Prescribing

Outlook

National Developments

2013

A resource for the NHS to help with budget setting,

prescribing planning and medicines management

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Foreword……………………………………………………………………………...3 Abbreviations and acknowledgements…………………………………………….6 Drug related exclusions in the 13/14 tariff…………………………………………7

1. GASTROINTESTINAL SYSTEM 10 Patent expiries ............................................................... 10 Inflammatory Bowel disease (IBD) ................................ 10 Diarrhoea and constipation ............................................ 12 Dyspepsia and gastro-oesophageal reflux disease (GORD) .......................................................................... 13 Other gastro-intestinal related conditions ...................... 14 2. CARDIOVASCULAR DISEASE 15 Patent expiries ............................................................... 15 Hypertension .................................................................. 15 Lipid modification ........................................................... 16 Acute coronary syndrome [ACS - unstable angina and myocardial infarction (MI)] & chest pain ........................ 17 Heart failure (HF) ........................................................... 20 Ischaemic stroke & atrial fibrillation (AF) ....................... 24 Peripheral arterial disease (PAD) .................................. 27 Venous thromboembolism (VTE) ................................... 27 3. RESPIRATORY SYSTEM 30 Patent expiries ............................................................... 30 Asthma ........................................................................... 30 Chronic Obstructive Pulmonary Disease (COPD) ......... 31 Other respiratory conditions ........................................... 33 4. CENTRAL NERVOUS SYSTEM 34 Patent expiries ............................................................... 34 Hypnotics and sedation ................................................. 35 Schizophrenia ................................................................ 35 Conduct disorders .......................................................... 36 Bipolar disorder .............................................................. 37 Depression ..................................................................... 38 Autism ............................................................................ 39 Obesity ........................................................................... 40 Pain ................................................................................ 41 Nausea and vomiting ..................................................... 43 Epilepsy ......................................................................... 43 Substance dependence ................................................. 44 Alzheimer’s disease & dementia .................................... 46 Other mental health and CNS related guidance ............ 47 5. INFECTIONS 48 Patent expiries ............................................................... 48 General strategy ............................................................ 48 Infection in children ........................................................ 49 Respiratory infections .................................................... 50 Hepatitis B ...................................................................... 51 Hepatitis C ..................................................................... 52 Hepatic encephalopathy ................................................ 52 Other infection-related developments and guidance ..... 53 6. ENDOCRINE SYSTEM 54 Patent expiries ............................................................... 54 Diabetes ......................................................................... 54 Osteoporosis .................................................................. 58 Fertility ........................................................................... 60

7. OBSTETRICS, GYNAECOLOGY AND URINARY TRACT DISORDERS 61 Patent expiries ................................................................ 61 Incontinence ................................................................... 61 Benign prostatic hyperplasia (BPH) ............................... 63 Contraception ................................................................. 63 Antenatal and intrapartum care ...................................... 64 Renal .............................................................................. 65 9. NUTRITION AND BLOOD 67 Anaemia ......................................................................... 67 Platelet disorders ............................................................ 67 Nutrition .......................................................................... 68 10. MUSCULOSKELETAL AND JOINT DISEASES 70 Patent expiries ................................................................ 70 NSAIDs ........................................................................... 70 Rheumatology ................................................................ 71 Spasticity ........................................................................ 73 Osteoarthritis (OA) ......................................................... 75 Gout ................................................................................ 76 11. EYE 77 Patent expiries ................................................................ 77 Macular oedema ............................................................. 77 Age related macular degeneration (AMD) ..................... 79 Choroidal neovascularisation (CNV) .............................. 80 Vitreomacular traction (VMT) ......................................... 81 13. SKIN 83 Patent expiries ................................................................ 83 Psoriasis ......................................................................... 83 Wound care .................................................................... 84 Eczema .......................................................................... 85 Extemporaneous Specials ............................................. 85 PATENT EXPIRIES due 2013-2015 86

Contents

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Foreword

Managing new medicines Underpinning the strategic direction for managing new medicines is the Department of Health's report Innovation Health and Wealth, Accelerating Adoption and Diffusion in the NHS document (2011, updated 2012) . It sets out the Government’s support for the NHS to embrace innovation to meet current and future healthcare challenges and outlines the importance of early adoption and diffusion of clinically and cost effective innovative practices, including medicines. Horizon scanning is essential at many organisational levels so that new medicines that improve patient outcomes can be planned for and adopted. Since April 2013, NHS England Area Teams have a strategic medicines management role and are responsible for commissioning the majority of high cost drugs as well as all cancer chemotherapy. The detail of the operational mechanisms underpinning these responsibilities is yet to be fully outlined although a number of interim commissioning documents relevant to medicines have been published including: Individual funding requests (IFRs) – for when drugs are

not routinely commissioned.

Implementation and funding of NICE guidance

Experimental and unproven treatments

On-going treatment following a NHS England funded trial

On-going treatment following non-commercially funded clinical trials

On-going access to treatment following a trial of treatment

On-going access to treatment following industry sponsored clinical trials or funding

Specialised Services Commissioning Innovation Fund (SSCIF)

The cancer drug fund (CDF), set up to facilitate patient access to cancer treatments that fail to get NICE approval, is being managed by NHS England until the end of 2013. The most recent list of drugs funded by the CDF can be accessed via the NHS England website. The intention is that the CDF will cease as value based pricing (VBP) is implemented in January 2014. Under VBP, different pricing strategies will apply to different indications for drugs based on the assessed ‘value’ for each indication. The mechanism for VBP is still to be decided but NICE will have a central role in the process and be responsible for the full value assessment of medicines (see terms of reference). There are already situations where the same medicine has a different price for different indications. This is especially true for medicines that have an orphan designation. In this case, the medicine will have a different brand name for non-orphan and orphan indications. The majority of developments highlighted in this document are due to be launched in 2014 and beyond. Their launch will be affected by VBP reimbursement negotiations, but exactly how is currently uncertain. For high cost new medicines that are in the NICE work programme manufacturers have the option to submit a proposal for a Patient Access Schemes (PAS). This allows NICE to recommend treatments that it might

otherwise not have been found to be cost effective. PAS are either cost (discounts, free stock etc) or outcome (price variation linked to patient outcomes) based. A list of NICE technologies with an approved PAS can be viewed on the NICE website. In Prescribing Outlook

current PAS schemes are highlighted if they are relevant to a new medicine in the same therapeutic area, and, although this will not give an indication of the likely cost of the new medicine, it suggests that subsequent treatment options will have to be competitive. The role of NICE is expanding to include support for implementation of NICE guidance. Where relevant, links are provided in Prescribing Outlook to NICE pathways, commissioning guidance and quality standards. Quality standards are designed to drive and measure quality improvements within a particular area of care and be reflected in commissioning frameworks. NICE implementation tools for launched drugs include costing templates and these may provide relevant information for drugs yet to be launched. The NICE Medicines and Prescribing Centre (MPC) has produced good practice guidance on developing and updating local formularies in response to Innovation Health and Wealth, Accelerating Adoption and Diffusion in the NHS. It advises that local systems and processes for accessing medicines support innovation where appropriate and recommends horizon scanning is included as a standing agenda item in local formulary decision-making meetings It is estimated more than 70% of the secondary care drugs bill can be accounted for by ‘high cost’ drugs excluded from the Payment by Results (PbR) tariff, the national system for paying trusts for activity. Standard tariff prices do not always allow fair reimbursement of some interventions so a list of drugs and services excluded from the tariff has been developed. The majority of drugs appearing on this list (previously known as ‘PbR exclusions’, now referred to as ‘Specified high cost drugs’) are likely to be commissioned by NHS England via specialised commissioning systems but the detail of exactly which drugs and how the funding streams operate is awaited. The Manual outlining which services (and treatments) are commissioned by NHS England has been published but will be updated shortly. As of April 2013 the Department of Health is no longer responsible for managing PbR; Monitor has been charged with this and has consulted on the future direction of the Tariff. There are few changes for the 2013/14 PbR tariff (see tab 19 for high cost drugs detailed list) but payment mechanisms for high cost drugs in 2014/15 could be influenced by the outcome of the consultation. In previous editions of Prescribing Outlook an ‘educated guess’ as to the potential tariff positioning of each new medicine has been made. Current uncertainty now makes this difficult. In the absence of additional guidance for 2014/15, estimates of tariff positioning in this document are based on historical assumptions. An ‘educated guess’ is also made on the likely commissioning route for individual medicines to take into account new commissioning arrangements outlined above.

For the pharmaceutical industry, the cost of bringing a new drug to the market is high. It is inevitable that more

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effort is being put into looking for new uses for, or new formulations of, currently licensed products. Applications for licence extensions are processed through licensing systems faster than those for new drugs as less safety and technical data are required. Data collection of pipeline licence extensions and new formulations has also improved over recent years. As a result an increased number of potential licence extensions appear in this document. This year, to manage this, there are two types of monograph; a full monograph with all the information previously included and an abbreviated entry (highlighted in blue) containing basic information for those drugs with an anticipated launch date in 2015 or beyond. This enables us to highlight drugs near and slightly further away from launch in the same therapeutic area. As in previous editions of Prescribing Outlook, drugs with patents due to expire in the near future are highlighted as they are then open to generic competition. It is important that the possibility of generic options is considered as part of the wider medicines management agenda, hence their inclusion in this document together with an ‘educated guess’ as to which have the potential for generic competition and an indication whether generic product licence applications are currently in progress in the EU. For the first time we have included a separate section on biosimilar drugs. Although there are a small number of biosimilar drugs already on the market there are many more in the pipeline that could have a potentially cost saving impact on medicines budgets. It is estimated about 50% of the current UK market for biological medicines spend may be subject to biosimilar competition by 2019

.1

1 Anon. What are biosimilars and are they important? Drug and Therapeutics Bulletin

2013; 51(5): 57-60.

There are a number of regulatory schemes that impact on the availability of new medicines. Those that allow earlier access to medicines in the EU and UK include ‘individual patient supply’ and ‘conditional approval’. Where relevant, and if known, details of these are included in this document. Details of a scheme which would allow patients access to new medicines prior to licensing were put out for consultation by the Medicines and Healthcare products Regulatory Agency (MHRA) in July 2012. The intention of the scheme is to widen access to "promising new medicines that will treat, diagnose or prevent life threatening, chronic or seriously debilitating conditions without adequate treatment options". The outcome of the consultation is awaited.

About the Prescribing Outlook series The content of this series is based on the views of the authors and does not constitute NHS or government policy.

The aim of the annually published Prescribing Outlook

series produced by UK Medicines Information (UKMi) is to assist NHS organisations in planning, implementing and budgeting for new medicines or licence extensions and national guidance. It provides support to commissioners and providers by highlighting new medicines and service developments that may require dialogue about financial and operational resource implications. The Prescribing Outlook series is produced

for primary and secondary care NHS organisations and has a national perspective. This document is the first in the series that comprises Prescribing Outlook - New Medicines and Prescribing Outlook - National Developments, and is supported by an electronic Cost Calculator. All available at http://www.ukmi.nhs.uk/. The

component documents of the Prescribing Outlook series are published each autumn in line with annual budget planning timeframes and key outputs from NICE. Updates on the progress of individual medicines at other times throughout the year can be found on the UKMi New Drugs Online database.

The content and presentation of the Prescribing Outlook series has evolved following consultation with users. These documents they are all now only published electronically but are formatted to make them suitable for printing. Further specialist medicines information not included in the series can also be obtained from local and regional medicines information centres. See www.ukmi.nhs.uk.

Prescribing Outlook – National Developments is

produced by the UKMi. It estimates the impact of national

guidance, such as NICE guidance and the outcome of

major clinical trials on clinical practice and prescribing

budgets. It is intended to inform discussions between

commissioners and providers, and highlight issues around

implementation of national guidance. Access is via

www.ukmi.nhs.uk. There will be additional, unquantifiable,

local factors that influence implications for the NHS such as

local demographics and prescribing preferences which

cannot be accommodated in a national document. In view of

the changes in commissioning of high cost medicines from

April 1st 2013, this year’s PO – National Developments

focuses on medicines where the responsible commissioners

are Clinical Commissioning Groups (CCGs).

Other UKMi horizon scanning resources

Prescribing Outlook – New Medicines aims to provide

advance information about new medicines (and new

licensed indications or formulations) with anticipated market

launches in the next 18 to 24 months. In addition, brief

details of drugs launched in the last 12 months are included

as this is often useful for local planning purposes. The

content is not comprehensive but focuses on medicines with

the potential for significant clinical or financial impact on the

NHS. Estimates of potential uptake, patient, service and

financial implications are included where possible.

Reference is made to relevant national guidance and links

to in-depth independent reviews are included, where

available. Access is via www.ukmi.nhs.uk.

Prescribing Outlook – Cost Calculator is an Excel

spreadsheet tool to facilitate estimates of potential

prescribing changes for a local population. Access is via:

www.ukmi.nhs.uk

New Drugs Online (NDO) database includes information on medicines in clinical development from phase

II trials to product launch and includes links to evaluated

information on medicines up to one year post launch. This

database is maintained by UKMi and forms the basis of the

content of Prescribing Outlook – New Medicines. This

dynamic horizon scanning tool is updated daily and can be

used to produce reports based on a number of criteria

including possible launch date, stage of clinical development

or pharmaceutical company. Access is free to all with an NHS

email address via www.ukmi.nhs.uk but requires

individual registration. Access is. Limited access is also freely available to non-NHS users via Evidence search (www.evidence.nhs.uk).

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VAT statement

Where the costs are available for a licensed drug, cost

estimates are based on BNF or Drug Tariff prices and

exclude VAT. Where the cost has been estimated – this

should be taken indicatively and local interpretation is

advised.

How can you help?

The editors of Prescribing Outlook proactively seek

information from front-line staff to identify developments

that impact locally as most resources used in the horizon

scanning processes have an international or national

perspective. Developments that are having or expected

to have significant financial or service impact in one

organisation are likely to affect other organisations

similarly. Please contact the editor of this publication

directly with information you feel is relevant e.g. clinical

trials you have been involved with, licensed drugs used

for an unlicensed indication in your organisation or

repeated individual funding requests your organisation

has received.

Key Authors of this document:

Devika Sennik, Pharmacist - London and South East Regional Medicines Information Centre, Guy’s and St.

Thomas’ NHS Foundation Trust (GSTfT)

David Erskine, Director - London and South East Regional Medicines Information Centre, GSTfT

Please direct comments on Prescribing Outlook – National Developments and the Cost Calculator to: Devika Sennik or

David Erskine, London and South East Medicines Information Centre, Guy’s and St. Thomas’ NHS Foundation Trust.

Email: devika.sennik@gstt.nhs.uk, david.erskine@gstt.nhs.uk

Please direct comments on Prescribing Outlook – New Medicines to the editor: Helen Davis, North West Medicines

Information Centre. Email: helen.davis@lrippu.nhs.uk.

Please direct comments and enquiries on New Drugs Online to: Alexandra Denby, London Medicines Information

Service-Northwick Park. Email: nwlh-tr.medinfo@nhs.net

Horizon scanning and new medicines support materials are available via www.ukmi.nhs.uk

The information in these resources is the best available at the time of publication but is subject to significant change with time.

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Abbreviation Definition ACD Appraisal Consultation Document.

ACEI Angiotensin Converting Enzyme Inhibitor

ARB Angiotensin II Receptor Blocker

BAD British Association of Dermatologists

BSG British Society of Gastroenterologists

CABG Coronary artery bypass graft

CCB Calcium Channel Blocker

CCG Clinical Commissioning Group

CHD Coronary Heart Disease

CHMP Committee for Medicinal Products for Human Use

CMO Chief Medical Officer

CVD Cerebrovascular disease, cardiovascular disease

DH Department of Health

DVLA Driver and Vehicle Licensing Agency

DVT Deep vein thrombosis

ECG Electrocardiogram

EMA European Medicines Agency

FAD Final Appraisal Determination

FEV1 Forced expiratory volume in 1 second

HPA Health Protection Agency

HSCIC Health and Social Care Information Centre

LNDG London New Drugs Group

MHRA Medicines and Healthcare Regulatory Authority

MI Myocardial infarction NICE National Institute for Health and Clinical Excellence

NPC National Prescribing Centre

NHSC National Horizon Scanning Centre

NSAID Non steroidal anti inflammatory drug

NSTEMI Non-ST segment myocardial infarction

PbR Payment by Results

PCI Percutaneous coronary intervention

PE Pulmonary embolism

QIPP Quality, Innovation, Productivity, Prevention

RCP Royal College of Physicians

PPI Proton pump inhibitor

TBC To be confirmed

SNRI Serotonin and noradrenaline reuptake inhibitors

SSRI Selective serotonin reuptake inhibitors

STEMI ST segment myocardial infarction

UFH Unfractionated heparin

UKMi United Kingdom Medicines Information group

VTE Venous thromboembolism

Abbreviations used in the document

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Table 1: High Cost Drug related PbR exclusions in the 13/14 National Tariff . Note: From 14/15, the DH is no longer responsible for PbR. Monitor is reviewing the PbR payment system therefore this list is subject to change.

Key: Addition/amendment in 13/14 BNF category followed by a “>” symbol means that only that drug or drug sub category is excluded Drugs with ^ have been excluded for non-chemotherapy indications - chemotherapy is dealt with separately

Exclusions for 13/14 Exclusions categorised by BNF category Existing NICE guidance?

Future NICE guidance?

Cykotine inhibitors

1.5.3 >Drugs affecting the immune response>Cytokine Modulators^ 10.1.3 >Cytokine Modulators^ (includes Teduglutide and Tofacitinib)

Vasodilator antihypertensive drugs/ Primary pulmonary hypertension (PPH)

2.5.1 >Ambrisentan 2.5.1 >Bosentan 2.5.1 >Iloprost "2.5.1 >Sildenafil * *(Sildenafil excluded only when used for Pulmanory Arterial Hypertension)" 2.8.1 >Epoprostenol "7.4.5 >Tadalafil (excluded only when used for PAH) (Includes Macitentan, Nitric Oxide, Riociguat and Treprostinil sodium)

Fibrinolytic drugs 2.10.2 >Alteplase** **(Alteplase is dealt with as an adjustment under PbR)

Blood related products 2.11> Blood Products

Allergen immunotherapy 3.4.2> omalizumab

Allergic emergencies 3.4.3 >Angioedema (Includes Conestat alfa and Ecallantide)

Pulmonary surfactants 3.5.2 >Beractant 3.5.2 >Poractant alpha

Mucolytics 3.7 >Dornase alfa 3.7 >Mannitol (when delivered via nebulisation/inhalation) (Includes Ivacaftor)

Hypnotics and anxiolytics 4.1.1 >Sodium oxybate

Non-opioid analgesics 4.7.1 >Ziconotide

Neurodegenerative Conditions 4.9.1 >Co-careldopa internal tube intestinal gel*** ***(Only when used as intestinal gel with internal tube) Includes Tafamidis

Torsion dystonias and other involuntary movements

4.9.3 >Riluzole 4.9.3 >torsion dystonias and other involuntary movements

Antibacterial Drugs 5.1.2.3 >Aztreonam**** 5.1.4 >Tobramycin**** 5.1.7 >Colistimethate sodium**** ****(only when delivered via nebulisation/inhalation)

Antifungals

5.2.1 >Triazole antifungals >Posaconazole 5.2.1 >Triazole antifungals >Voriconazole 5.2.3 >Polyene antifungals >Amphotericin >lipid formulations 5.2.4 >Echinocandin antifungals >Anidulafungin 5.2.4 >Echinocandin antifungals >Caspofungin 5.2.4 >Echinocandin antifungals >Micafungin

AIDS/HIV antiretrovirals 5.3.1 (Includes Cobicistat, Dolutegravir, Elvitegravir, Elvitegravir + Cobicistat + Emtricitabine + Tenofovir, Rilpivirine and Vicriviroc)

Cytomegalovirus infection 5.3.2.2 >Cytomegalovirus infection

Viral hepatitis (B&C) & Respiratory syncytial virus (RSV)

5.3.3 5.3.5 8.2.4 >interferon alfa (Includes Alisporivir, Faldaprevir, Motavizumab and Simeprevir)

Growth hormone & growth hormone receptor antagonist

6.5.2 >Tolvaptan 6.5.1 >Anterior pituitary hormone>growth hormone receptor antagonist 6.5.1 >Anterior pituitary hormones>growth hormone 6.7.4 >Mecasermin (includes Tesamorelin and Lixivaptan)

Drugs affecting bone metabolism 6.6.1 >teriparatide 6.6.1 >Parathyroid hormone

Antineoplastic drugs 8.1.5 >Bevacizumab^ 8.1.5 >Bortezomib^ 8.1.5 >Cetuximab^

Protein kinase inhibitors 8.1.5 >Protein kinase inhibitors^

Corticosteroids and other immunosuppressants

8.2.2 >Basiliximab Daclizumab (no BNF category available)

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Exclusions for 13/14 Exclusions categorised by BNF category Existing NICE guidance?

Future NICE guidance?

Myelodysplastic Syndrome 8.1.3 >Azacitadine^ Decitabine^ (no BNF category available)

Immunomodulating drugs

8.1 >Dexrazoxane 8.1.3 >Cladribine^ 8.2.4 >Interferon alfa>interferon alfa 8.2.4 >Interferon beta 8.2.4 >Aldesleukin 8.2.4 >Glatirimer 8.2.4 >Lenalidomide^ 8.2.4 >Natalizumb 8.2.4 >Thalidomide^ 8.2.4 >Fingolimod (Includes Dimethyl fumarate, Laquinimod, Rilonacept^ and Teriflunomide)

Somatostatin analogues 8.3.4.3 (includes Fibroblast growth factor 1 gene therapy)

Paroxysmal nocturnal haemoglobinuria

9.1.3 >Eculizumab

Drugs used in hypoplastic, haemolytic, and renal anaemia’s

8.2.2 >Antilymphocyte globulin 9.1.3 >Antithymocyte Immunoglobulin 9.1.3 >Iron Overload (For chronic iron overload)

Drugs used in neutropenia 9.1.6^

Drugs used in metabolic disorders

8.2.4 >Canakinumab 9.4.1 >Sapropterin 9.8.1 >Carnitine deficiency 9.8.1 >Fabry's disease 9.8.1 >Gaucher's disease 9.8.1 >Mucopolysaccharidosis 9.8.1 >Nephropathic cystinosis 9.8.1 >Pompe Disease 9.8.1 >Tyrosinaemia type I 9.8.1 >Urea cycle disorders 9.8.1 >Other metabolic disorders BNFc 9.8.1 >Betaine (Includes Eliglustat, Human Arginate and Taliglucerase alfa)

Gout and cytotoxic-induced hyperuricaemia

10.1.4 >Hyperuricaemia associated with cytotoxic drugs Pegloticase (no BNF category available)

Retinal disorders Afamelanotide (no BNF category available)

Subfoveal choroidal neovascularisation

11.8.2 >Pegaptanib 11.8.2 > Ranibizumab 11.8.2 >Verteporfin (Includes Aflibercept and Microplasmin)

Drugs affecting the Immune response

8.2.3 >Belatacept 8.2.3 >Alemtuzumab^ 9.1.7 >Plerixafor 10.1.3 >Belimumab 13.5.3 >Efalizumab 13.5.3 >Ustekinumab (includes Vedolizumab)

Intravenous/subcutaneous human normal immunoglobulins

14.5 >Normal immunoglobulin>for intravenous use 14.5 >Normal immunoglobulin>for subcutaneous use

Platelet Disorder Drugs 9.1.4 >Eltrombopag 9.1.4 >Romiplostim

Parenteral Nutrition 9.3 >Parenteral Nutrition (after 14 days or when the patient is receiving parenteral nutrition prior to admission)

Bone morphogenetic protein No BNF Category available (includes Dibotermin Alpha and Eptotermin alpha)

Poisoning Emergency treatment of poisoning >Other poisons >Ethylene glycol and methanol >Fomepizole

Macular Oedema 11.4.1 >Dexamethasone intravitreal implant Fluocinolone acetonide (only when used as an intravitreal implant)

Neuromuscular Disorders 10.2.1 >Amifampridine phosphate 10.2.1 >Fampridine

Enzymes 10.3.1 >Collagenase (only when used in outpatients)

Skin Conditions 13.5.1 >Alitretinoin Afamelanotide (no BNF category available)

Pulmonary Fibrosis Pirfenidone (no BNF category available)

Drug related device exclusions include insulin pumps and pump consumables and intrathecal drug delivery pump Drugs which are excluded from the tariff when used for chemotherapy may also have other purposes. When used for non-

chemotherapy purposes they may or may not continue to be excluded.

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Table 2: Useful published QIPP case studies and Cochrane QIPP summaries – list correct as at August 2013

Therapeutic area Relevant

BNF Chapter

QIPP Topic (hyperlinked)

QIPP case studies

Diabetes 6 Diabetes inpatient care: ThinkGlucose programme

Haematology 9 Giving intravenous iron in patients’ homes and community hospitals

Nutrition 9 Prevention and treatment of adult malnutrition: appropriate prescribing of oral nutritional supplements

Nutrition 9 Oral nutritional supplement prescribing review: to reduce number of patients with malnutrition

Haematology 2 Warfarin loading protocol: to improve patient safety

Musculoskeletal 10 Early use of oral prednisolone for Bell’s palsy

Respiratory 3 Hospital at home for patients with acute exacerbations of Chronic Obstructive Pulmonary Disease

Respiratory 3 Specialist oxygen review and prescription services

Hypertension 2 Implementing NICE hypertension guidelines

Sexual Health 7 Long acting reversible contraception (LARC)

Nutrition 9 Implementation of NICE clinical guideline on nutrition support in adults

Respiratory 3 Community based teams for management of chronic obstructive pulmonary disease

Mental Health 4 Appropriate prescribing of medication for patients with Alzheimer’s disease

Cochrane Quality and Productivity topics – these aim to help the NHS identify practices that could be significantly

reduced or stopped completely, releasing cash and/or resources without negatively affecting the quality of NHS care.

Liver 1 Ursodeoxycholic acid for cystic fibrosis-related liver disease

Respiratory 3 Inhaled corticosteroids for cystic fibrosis

Infection 5 Beta-lactam antibiotic monotherapy versus beta-lactam–aminoglycoside antibiotic combination therapy for sepsis

TIA/Stroke 2 Oral anticoagulants versus antiplatelet therapy for preventing further vascular events after transient ischaemic attack or minor stroke of presumed arterial origin

Sub-arachnoid haemorrhage

2 Calcium antagonists for aneurysmal subarachnoid haemorrhage

IBD 1 Aminosalicylates for induction of remission or response in Crohn's disease

IBD 1 Oral budesonide for induction of remission in ulcerative colitis

Diabetes 6 Long-acting insulin analogues versus NPH insulin (human isophane insulin) for type 2 diabetes mellitus Constipation 1 Lactulose versus polyethylene glycol for chronic constipation

Infection 5 Antibiotics for the common cold and acute purulent rhinitis

Infection 5 Antibiotics for treating salmonella gut infections

Pain Control 4 Single dose oral codeine, as a single agent, for acute postoperative pain in adults

Hypertension 2 Antiplatelet agents and anticoagulants for hypertension

IBD 1 Azathioprine and 6-mercaptopurine for maintenance of remission in ulcerative colitis

Pain Control 4 Single dose oral gabapentin for established acute postoperative pain in adults

Infection 5 Antibiotics for acute laryngitis in adults

ENT 3 Antihistamines and/or decongestants for otitis media with effusion (OME) in children

Respiratory 3 Anti-leukotriene agents compared to inhaled corticosteroids in the management of recurrent and/or chronic asthma in adults and children

Skin & Infection 5 Minocycline for acne vulgaris: efficacy and safety

Mental Health 2 & 4 Statins for the treatment of dementia

Mental Health 4 Selective serotonin reuptake inhibitors (SSRIs) for autism spectrum disorders

Full list available at: http://www.evidence.nhs.uk/documents/qipp/p-quality-productivity-1-qipp-collection-tracking-master-list-of-published-qipps-qipp-published-case-studies-v1.29-published-30082013.xls

Disease or Indication: National targets and guidance

Epidemiology, potential financial implications for a population of 100,000 and other comments

National spend in primary care (£) Apr 2012-Mar 2013 (Epact England data) plus limited data on secondary care prescribing

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1. Gastrointestinal system Patent expiries According to Prescribing Outlook New Medicines 2013, the following

patent expiries (which may have a significant impact on prescribing costs) are due within the next couple of years: Infliximab (Feb 2015).

Inflammatory Bowel disease (IBD)

NICE Quality Standard on IBD (Ulcerative colitis and Crohn's disease), expected date TBC

NICE guideline on the management of

Crohn’s disease, issued Oct 2012 A NICE Bites summary of this guideline is available.

NICE clinical guideline on the management of ulcerative colitis (UC), issued Jun 2013

A NICE Bites summary of this guideline is available. NICE pathway also available.

NICE guidance on the use of infliximab, adalimumab and golimumab for the second line treatment of moderately to severely active UC expected Feb 2015

This is an area of moderate financial risk

This Quality Standard topic has been referred to NICE and is at an early stage of development. The NICE clinical guideline on the management of Crohn’s disease in adults and children with the condition covers clinical issues such as drug treatment, enteral nutrition, surgical management, and monitoring. The guideline addresses the use of corticosteroids, aminosalicylates, antibiotics, immunomodulators (azathioprine, mercaptopurine and methotrexate) and tumour necrosis factor (TNF) alfa inhibitors.

The NICE costing statement suggests that implementation of the recommendations in the guideline will not have a significant national resource impact, as no significant change in prescribing practice is anticipated. Additionally, the use of enteral nutrition is unlikely to change.

This clinical guideline offers evidence-based advice on the care and treatment of adults, children and young people with a diagnosis of ulcerative colitis (UC). The costing template and report focus on the recommendations that are considered to have the greatest resource impact, they are: - using a high induction dose of an oral aminosalicylate and adding oral

beclometasone dipropionate to induce remission in adults - adding oral beclometasone dipropionate to an oral aminosalicylate to

induce remission in children and young people - adding oral tacrolimus to oral prednisolone to induce remission - using oral mercaptopurine to maintain remission - monitoring bone health in children and young people

The costing template estimates that the medicines based recommendations above could result in an additional spend of ~ £12,000 per 100,000 population per year. This guidance is at an early stage of development but will provide recommendations on the treatment of UC after the failure of conventional therapy.

Data from the HSCIC show that in 2012 the NHS in England spent a total of £216.5m on etanercept (a decrease of 0.5% on the previous year), £121.7m on infliximab (an increase of 9.5% on the previous year), £265.7m on adalimumab (an increase of 18% on the previous year) and £11m on golimumab (a 5-fold increase on the previous year). Usage is not separated by indication.

Disease or Indication: National targets and guidance

Epidemiology, potential financial implications for a population of 100,000 and other comments

National spend in primary care (£) Apr 2012-Mar 2013 (Epact England data) plus limited data on secondary care prescribing

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IBD cont’d

NICE guidance on the use of infliximab, adalimumab and golimumab for the second line treatment of moderately to severely active ulcerative colitis cont’d

Proposed appraisal referred to NICE: Vedolizumab for the second line treatment of moderate to severe active UC

TA140 did not recommend infliximab for sub-acute manifestations of UC and TA262 (adalimumab for moderate to severe UC) was terminated as an evidence submission was not received from the manufacturer. All three biologics are licensed for the treatment of moderate to severe UC in adults who have had an inadequate response to conventional therapy including corticosteroids and 6-mercaptopurine or azathioprine, or who are intolerant to or have medical contraindications for such therapies.

The NICE guideline on UC states that the condition has an incidence in the UK of approximately 10 per 100,000 people annually, and a prevalence of approximately 240 per 100,000. This amounts to around 146,000 people in the UK (or 231 people per 100,000 population) with a diagnosis of UC. The costing template for this guideline assumes 85% of adults have mild to moderate disease, therefore if it is assumed that: - 15% of adults have moderate to severe disease (or 35 people per 100,000 population) - 50% of these might be eligible for treatment with infliximab, adalimumab or golimumab (~18 people per 100,000 population) following failure of standard treatment - Adalimumab if used as per dosing in its SPC (40mg alternate weeks) costs around £10,900 per patient per year and infliximab costs around £13,400 per patient per year (drug costs only). The dosing for golimumab has not been updated in its SPC but the cost is likely to be comparable to adalimumab. - 50% of patients receive adalimumab or golimumab and 50% receive infliximab

This could result in additional costs of around £220,000 per 100,000 population. This cost excludes any service delivery costs and does not cover the cost of adalimumab if dosing frequency is increased to weekly in those experiencing a decrease in response.

Vedolizumab is a monoclonal antibody – it is a first in class alpha4-beta7 integrin antagonist and is administered as an i/v infusion. It is not currently licensed in the UK, although it has been filed for approval. If licensed, vedolizumab may provide an alternative treatment option for patients resistant or intolerant to conventional therapies, including anti-TNF agents. NICE has been invited to appraise the clinical and cost effectiveness of vedolizumab within its licensed indication for treating moderately to severely active UC in adults who are intolerant of, or whose disease has had an inadequate response or loss of response to conventional therapy. Vedolizumab will compete with infliximab, adalimumab and golimumab (which are also being appraised) and the cost is likely to be a substitution.

Disease or Indication: National targets and guidance

Epidemiology, potential financial implications for a population of 100,000 and other comments

National spend in primary care (£) Apr 2012-Mar 2013 (Epact England data) plus limited data on secondary care prescribing

12

Actions/ issues which may be considered by commissioners and providers

Demand management through service redesign may mean more patients are treated in primary care for certain gastrointestinal conditions such as IBS using condition specific protocols instead of being referred to secondary care.

Cytokine modulators, such as TNF-inhibitors, are listed as exclusions in the National Tariff for 13/14. A decision on funding will need to be agreed locally for these agents for indications outside NICE guidance. Drug exclusions under Payment by Results 13/14 . As of April 2013, NHS England is the responsible commissioner when theses agents are used in children (aged 18 years or younger). CCGs are the responsible commissioners for use of these agents in adults.

New commissioning arrangements from April 2013 mean that these drugs are commissioned nationally by NHS England for paediatrics and locally commissioned by CCGs for adults. Ensure that any local policies for children are in line with national guidance.

Diarrhoea and constipation QIPP indicator for laxative use NICE guidance on the use of

methylnaltrexone for opioid induced bowel dysfunction in advanced illness or palliative care, terminated appraisal

NICE guidance on the use of lubiprostone for treating chronic idiopathic constipation, expected Oct 2014

A set of comparators has been developed to support the QIPP medicines use and procurement workstream. The aim of the comparators is to support organisations and prescribers to review the appropriateness of prescribing, revise prescribing where appropriate and monitor implementation.

The “laxatives” comparator considers the total number of average daily quantities (ADQs) for laxatives per STAR-PU.

NICE is unable to recommend the use in the NHS of methylnaltrexone for treating opioid-induced bowel dysfunction in people with advanced illness receiving palliative care because no evidence submission was received from the manufacturer of the technology. It is unlikely that this agent will have a significant resource impact. The SMC accepted restricted use of methylnaltrexone within NHS Scotland for the treatment of opioid-induced constipation in advanced illness in patients who are receiving palliative care, where a response to usual laxative therapy has not been sufficient. Negligible drug costs were estimated in the SMC guidance (£7K across Scotland in Year 1 rising to £59K in year 5). Lubiprostone is a prostone, a bicyclic fatty acid and a locally acting chloride channel activator that enhances the secretion of chloride-rich intestinal fluid without altering electrolyte concentrations in the serum. This increase in intestinal fluid secretion results in softening of the stool, promotion of spontaneous bowel movements, and a reduction in abdominal discomfort/pain and bloating. It is administered orally.

Disease or Indication: National targets and guidance

Epidemiology, potential financial implications for a population of 100,000 and other comments

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13

Diarrhoea and constipation cont’d

NICE guidance on the use of lubiprostone for treating chronic idiopathic constipation, cont’d

NICE guidance on the use of

lubiprostone for treating opioid induced constipation, expected Oct 2014

NICE Quality Standards on

- Constipation in children and young people expected May 2014

- Faecal incontinence, expected Feb 2014

Lubiprostone is licensed to treat chronic idiopathic constipation and associated symptoms in adults when response to diet and non-pharmacological treatments are inappropriate. Lubiprostone will provide an additional treatment option for this patient group. The NHSC briefing for this drug estimates that between 2.5-12.5 million people in the UK are affected by chronic idiopathic constipation (or ~ between 4,000-20,000 per 100,000 population). If it is assumed:

- 10,000 people per 100,000 population are affected - Lubiprostone will be similarly priced to prucalopride (~£40 per patient per month) - 70% will present to their GP for treatment (or 7,000 per 100,000 population) - 20% will fail the first laxative and therefore try a second laxative (or 1,400 per 100,000 population) - Of these, 50% fail second laxative and 10% (or 70 per 100,000 population) might try lubiprostone. This could result in an additional cost of ~ £34,000 per 100,000 population per year. The licence for use of lubiprostone in opioid induced constipation (non-cancer pain related) is expected in Q4 2013. Again, lubiprostone will provide an additional treatment option for this patient group. The scope for this guidance states that approximately 32,000 people (or 60 people per 100,000 population) receive strong opioids (for cancer and non-cancer pain) in England. If it is assumed that: - 50% of this use is for non-cancer pain (or 30 people per 100,000 population) - 50% try at least 2 other laxatives and fail (or 15 people per 100,000 population) and therefore might be eligible for lubiprostone. This could result in an additional cost of ~£7,000 per 100,000 population. Quality Standards are under development for these topics.

Dyspepsia and gastro-oesophageal reflux disease (GORD)

NICE Quality Standards on GORD and GORD in children, expected date TBC

These Quality Standard topics have been referred to NICE and are at an early stage of development.

Disease or Indication: National targets and guidance

Epidemiology, potential financial implications for a population of 100,000 and other comments

National spend in primary care (£) Apr 2012-Mar 2013 (Epact England data) plus limited data on secondary care prescribing

14

Dyspepsia and GORD cont’d

NICE guideline for the management of dyspepsia and GORD, expected date TBC

NICE guideline on the management of

GORD in children and young people, expected Oct 2014

This is a partial update of ‘Dyspepsia’ (NICE clinical guideline 17, published in 2004) and will also include some new areas that were not previously covered, such as specialist pharmacological management of dyspepsia, heartburn, other symptoms of reflux and GORD. The guideline is at an early stage of development, however, it is unlikely to have a significant financial impact on medicines spend. This guideline will cover the recognition, diagnosis and management of GORD in children and young people. The guideline will consider the effectiveness of treatments for GORD in this setting. It is unlikely that the guideline will have a significant financial impact on medicines spend.

Other gastro-intestinal related conditions

NICE Quality Standard on acute upper gastrointestinal bleeding, issued Jul 2013

The following Quality Standards have been referred to NICE (expected date TBC): - Diverticular disease - Irritable bowel syndrome - Pancreatitis - Coeliac disease

NICE guideline on coeliac disease, expected Jun 2015

This quality standard covers the management of acute upper gastrointestinal bleeding in adults and young people (16 years and older). This guideline will provide recommendations on the recognition, assessment and management of coeliac disease. The guideline will include advice on the dietary management strategy for people with coeliac disease, including the use of calcium, vitamin D and vitamin B12. It will also cover the management of refractory coeliac disease, for example, with corticosteroids azathioprine, cyclosporin, infliximab, cladribine, autologous stem cell transplant, and nutritional support. The guideline is at an early stage of development.

Actions/ issues which may be considered by commissioners and providers

NICE has issued a Commissioning Guide for faecal continence services. NICE estimates that the standard benchmark rate for a referral into a faecal continence service is 0.1%, or 100 per 100,000, of the adult population

(aged 15 years or older) per year. For a standard primary care trust population of 250,000 (around 200,000 people are aged 15 years or older), the average number of people requiring referral into a faecal continence service would be 200 per year.

NICE has issued a Commissioning Guide for the upper GI endoscopy service. NICE estimates that the benchmark endoscopy rate should be 0.75%, or 750 endoscopies per 100,000 population per year. This includes

all diagnostic endoscopies and follow-up endoscopies. For a standard primary care trust population of 250,000, the number of endoscopies required would be expected to be 1875 per year.

Disease or Indication: National targets and guidance

Epidemiology, potential financial implications for a population of 100,000 and other comments

National spend in primary care (£) Apr 2012-Mar 2013 (Epact England data) plus limited data on secondary care prescribing

15

2. Cardiovascular disease Patent expiries

According to Prescribing Outlook New Medicines 2013, the following patent expiries (which may have a significant impact on prescribing costs) are due within the next couple of years: telmisartan (December 2013), bivalirudin (August 2015)

Hypertension QIPP indicator for ACEi

NICE Quality Standard on hypertension, issued Mar 2013

NICE Quality Standard on hypertension in pregnancy, issued Jul 2013

NICE Quality Standard on the

secondary care management of malignant hypertension, expected date TBC

According to QoF data for 12/13, the raw prevalence rate for hypertension in England is 13.7%.

This area is unlikely to have any major cost implications for prescribing

A set of comparators has been developed to support the QIPP medicines use and procurement workstream. The aim of the comparators is to support organisations and prescribers to review the appropriateness of prescribing, revise prescribing where appropriate and monitor implementation. The renin angiotensin system drugs comparator measures the number of prescriptions for ACE inhibitors (ACEi) as a % of the total number of prescriptions for all drugs affecting the renin-angiotensin (RAS) system excluding aliskiren.

This quality standard covers the management of primary hypertension in adults, including diagnosis and investigations, treatment to reduce risk of cardiovascular disease, monitoring of treatment efficacy, and specialist referral. This quality standard covers pre-pregnancy advice for women with pre-existing hypertension, as well as the antenatal, intrapartum and postnatal care of women at risk of or with hypertensive disorders of pregnancy. This Quality Standard topic has been referred to NICE and is at an early stage of development.

Calcium channel blocker costs: £112.7m (or £212,000 per 100,000 population). This represents a 6% decrease on the previous year despite a 4% increase in prescription numbers. The decrease in spend is probably due to a reduction in the price of generic CCBs.

Diuretic costs (total): £56.2m (or £106,000 per 100,000 population). This is a 3.4% increase on the previous year’s figures and a 2% drop in prescriptions items. Beta blocker costs: £68.4m (or £128,800 per 100,000 population). This represents an 8% increase in spend on the previous year, and a 4% increase in prescription numbers.

Actions/ issues which may be considered by commissioners and providers

As there are now several generically available ARBs, commissioners should agree which ARB will be used where patients can not tolerate an ACEi due to cough.

Disease or Indication: National targets and guidance

Epidemiology, potential financial implications for a population of 100,000 and other comments

National spend in primary care (£) Apr 2012-Mar 2013 (Epact England data) plus limited data on secondary care prescribing

16

Lipid modification QIPP indicator for lipid modification

drugs

NICE Quality Standard on familial

hypercholesterolaemia (FH), issued Aug 2013

NICE Quality Standard on lipid

modification, expected date TBC

NICE guidance on the use of

mipomersen for the prevention of CV events in people with homozygous or severe heterozygous familial hypercholesterolemia, development suspended

NICE guideline on lipid modification

(update of previous guideline), expected date Jul 2014

This is an area of low financial risk - the patent for atorvastatin expired in May 2012.

According to QoF data for 12/13, the raw prevalence rate for CHD in England is 3.3%. The percentage prevalence for primary prevention of CVD increased from 1.7% in 11/12 to 2.2% in 12/13.

A set of comparators has been developed to support the QIPP medicines use and procurement workstream. The aim of the comparators is to support organisations and prescribers to review the appropriateness of prescribing, revise prescribing where appropriate and monitor implementation. Two comparators relating to lipid modifying drugs have been developed which cover prescribing of ezetimibe and high-cost statins to ensure it is in line with NICE guidance: (i) The number of prescription items for generic statin preparations (listed under category M in part VIII of the Drug Tariff) as a % of the total number of prescription items for all statins, plus the total number of prescription items for combination of simvastatin/ezetimibe, plus total number of prescription items for ezetimibe alone. (ii) The number of items for ezetimibe and ezetimibe/simvastatin combinations as a percentage of the total number of prescription items for all statins, plus the total number of prescription items for combination of simvastatin/ezetimibe, plus total number of prescription items for ezetimibe alone. This quality standard covers the identification and management of heterozygous familial hypercholesterolaemia (FH) in adults, young people and children. This Quality Standard topic has been referred to NICE and is at an early stage of development. Development of NICE guidance is currently suspended as the CHMP recently re-examined its initial negative opinion for mipomersen and has confirmed the refusal of the marketing authorisation. This guidance is therefore unlikely to have an impact on medicines spend. This guideline updates the previous guideline on cardiovascular risk assessment and the modification of blood lipids for the primary and secondary prevention of CVD. It is unlikely to have a significant financial impact on medicines use as it updates previous guidance.

Data for 2012 from the HSCIC show that the NHS in England (primary and secondary care) spent approximately £171.5m on atorvastatin (~£323,000 per 100,000 population – a decrease of 46% on 2011 – note: generic availability in 2012), £1.4m on fluvastatin (£2,600 per 100,000) – a decrease of 15% on 2011, £7.2m on pravastatin (£13,600 per 100,000 population) – an increase of 10%, £50.4m on rosuvastatin (£95,000 per 100,000 population) – a decrease of 7%) and £61.4m on simvastatin – excluding combinations - (£115,000 per 100,000 population) – a decrease of 3%). A total of £63m was spent on ezetimibe (excluding combinations, or £119,000 per 100,000 population), representing a 13% decrease on 2011.The majority of spend for these drugs occurred in primary care. Total statin costs: £197m (£371,000 per 100,000 population). This represents 51% decrease in spend on the previous year despite a 5% increase in prescription numbers. Nb: Atorvastatin’s patent expired in May 2012 and the decrease in spend can be attributed to its generic availability.

Atorvastatin: £91m (or £172,000 per 100,000 population). This is a 69% decrease in spend and a 21% increase in prescription numbers on the previous year. Nb: Generic availability. Rosuvastatin: 44.4m (or £83,400 per 100,000 population). Spend and prescription numbers have both decreased by 10%.

Disease or Indication: National targets and guidance

Epidemiology, potential financial implications for a population of 100,000 and other comments

National spend in primary care (£) Apr 2012-Mar 2013 (Epact England data) plus limited data on secondary care prescribing

17

Lipid modification cont’d

Review rosuvastatin prescribing

NICE guidance on the use of ezetimibe for the treatment of primary (heterozygous-familial and non-familial) hypercholesterolaemia (review of TA132), expected Jan 2016

and Reviewing use of ezetimibe

A total of £44.4M was spent on rosuvastatin in England in 12/13 (or ~£84,000 per 100,000 population). If it is assumed that 50% of this use is inappropriate and is reviewed, this could result in a saving of £42,000 per 100,000 population. This guidance is unlikely to have a significant financial impact as it updates previous guidance. However, a DTB editorial questioned the NHS spend on ezetimibe and highlighted that the evidence on effectiveness of ezetimibe is based largely on surrogate outcomes and there is a lack of published data to show that ezetimibe reduces mortality or morbidity. Ezetimibe spend (including the simvastatin combination product) totalled ~£60m (or £111,000 per 100,000 population) in primary care in England in 12/13. If this could be reduced by 25%, this could result in savings of approximately £28,000 per 100,000 population.

Ezetimibe: £55.6m (£104,800 per 100,000 population). This represents a 13% decrease in spend and a 12% decrease in prescriptions numbers. Ezetimibe/simvastatin combination (Inegy®): £3.5m (£6,500 per 100,000 population). This represents a 33% decrease in spend and prescription numbers on last year. Current NICE guidance on ezetimibe recommends that when treating with ezetimibe co-administered with a statin, ezetimibe should be prescribed on the basis of lowest acquisition cost.

Actions/ issues which may be considered by commissioners and providers

Three statins are now available generically. Organisations should review prescribing of lipid modifying agents in line with the QIPP comparators and agree which statin is a reasonable 2

nd line option. Recent outputs from the

MHRA concerning interaction between simvastatin and amlodipine and use of rosuvastatin and ezetimibe should be reviewed as these agents have patents in place until 2017.

Establish local agreement on pathway to achieve suggested cholesterol levels in patients with established CHD. NICE has not set lipid targets for the primary prevention of CVD. Ensure NICE recommendations on statin choice

in this setting (simvastatin 40mg daily or pravastatin where there are contraindications/drug interactions) are implemented. Current practice in some areas indicates that clinicians are treating to target and switching patients to more potent, non-generic statins. Audit use of the other non-generic statins locally for this indication.

Acute coronary syndrome [ACS - unstable angina and myocardial infarction (MI)] & chest pain

NICE Quality Standards on: - acute coronary syndromes (including MI) - secondary prevention of MI and cardiac rehabilitation - Risk assessment of modifiable cardiovascular risk factors expected dates TBC for these

This is an area of moderate financial risk

These Quality Standard topics have been referred to NICE and are at an early stage of development.

Disease or Indication: National targets and guidance

Epidemiology, potential financial implications for a population of 100,000 and other comments

National spend in primary care (£) Apr 2012-Mar 2013 (Epact England data) plus limited data on secondary care prescribing

18

ACS & chest pain cont’d NICE clinical guideline on the acute

management of MI with ST-segment elevation, issued Jul 2013

NICE pathway available.

NICE clinical guideline on secondary prevention of MI in primary and secondary care (update), expected Nov 2013

NICE guidance on prasugrel with

percutaneous coronary intervention for the treatment of ACS (review of TA182), expected Aug 2014

This guideline provides recommendations on the management of patients with spontaneous onset of myocardial infarction (MI) with ST-segment elevation (STEMI). In terms of medicines use, one of the key priorities is for organisations to “Offer fibrinolysis to people with acute STEMI presenting within 12 hours of onset of symptoms if primary PCI cannot be delivered within 120 minutes of the time when fibrinolysis could have been given.” The guideline encourages use of more primary PCIs. The costing template and costing report for the guideline focus on the recommendations that are considered to have the greatest resource impact, in this case increased PCIs vs. no reperfusion strategy. The costing report notes that primary PCI is a nationally commissioned service, via NHS England’s Specialised Services Commissioning. Expert clinical opinion indicated that, after implementation of the guidance, the proportion of people who have no reperfusion strategy could decrease from 29% to around 20% of people after a STEMI. It is assumed that there is a corresponding 9% increase in the number of people who have a primary PCI. It is assumed that the proportion of people that have fibrinolytic treatment remains at 5% and that those with an unclear treatment strategy remains at 1%. The total cost of implementing this change is given as £1.15M across England (or ~£2,000 per 100,000 population).

Nb: An increase in the number of PCIs will result in additional use of

antiplatelet drugs; however, this is not accounted for within the costing tools. If generic clopidogrel is used, the cost impact of this is likely to be negligible. This guideline is unlikely to have a significant financial impact as it updates previous guidance. A draft version contains new recommendations for secondary prevention in people who have had a MI, following the advent of primary PCI and to reflect new findings on enhancing people’s uptake of cardiac rehabilitation, antiplatelet therapy in people with an additional indication for anticoagulation, omega-3 fatty acid supplementation, ACEIs and beta-blockers. The guideline does not support the use of omega-3 fatty acid capsules or omega-3 fatty acid supplemented foods to prevent another MI, which is a change to the previous version and therefore could result in some savings. In 12/13 the NHS spend on omega-3 marine triglycerides and ethyl esters in primary care in England totalled ~£13m, or £25,000 per 100,000 population.

This guidance will review NICE recommendations on prasugrel issued in 2009. It is unlikely that the revised guidance will have further significant financial implications. It should be noted that during development of the original guidance, clopidogrel was not generic and as such, the new guidance may or may not have significant financial implications with the use and availability of prasugrel.

Antiplatelet drugs: £64m (or £120,600 per 100,000 population). There was a 1.4% increase in spend (prescription items remained similar) on antiplatelets compared to the previous year. Clopidogrel: £12.9m (or £24,200 per 100,000 population). Expenditure on clopidogrel in primary care increased by 16% on last year’s figures and prescription numbers increased by 25%. Prasugrel: £5.4m (or £10,000 per 100,000 population). This represents a 34% increase in spend and items on the previous year. Ticagrelor: usage was negligible in 11/12 in primary care. In 12/13 there was a spend of £2.6m (or £5,000 per 100,000 population). Prescription numbers increased from 758 items in 11/12 to 53,000 in 12/13. NICE guidance on the use of ticagrelor post ACS was issued in October 2011.

Disease or Indication: National targets and guidance

Epidemiology, potential financial implications for a population of 100,000 and other comments

National spend in primary care (£) Apr 2012-Mar 2013 (Epact England data) plus limited data on secondary care prescribing

19

ACS & chest pain cont’d

NICE guidance on rivaroxaban for the prevention of adverse outcomes in patients after the acute management of ACS, expected Mar 2015

A NICE Evidence Summary is available for this drug/indication.

The anticoagulant rivaroxaban was approved in the EU for the prevention of atherothrombotic events in adult patients after an ACS in May 2013. The EMA approved licensing for a new strength of rivaroxaban (2.5mg), which is expected to be launched in 2014. The licence covers rivaroxaban (2.5mg twice daily) co-administered with acetylsalicylic acid (ASA) alone or with ASA plus clopidogrel or ticlopidine, for the prevention of atherothrombotic events in adult patients after an ACS with elevated cardiac biomarkers. A phase III study found that the use of rivaroxaban (added to standard medical therapy - including low-dose aspirin +/- a thienopyridine) for a mean of 13 months following an ACS event reduced the risk of a composite of death from cardiovascular causes, myocardial infarction, or stroke, compared to placebo. The risk of major bleeding and intracranial haemorrhage was increased with rivaroxaban, but not the risk of fatal bleeding. Rivaroxaban was used at a dose of 2.5mg or 5mg twice daily and this would represent an additional cost in this population. The NICE evidence summary indicates that only the 2.5 mg twice-daily dose of rivaroxaban is licensed for the ACS secondary prevention indication. A NHSC briefing on this topic states that the company estimates the cost of rivaroxaban will be between £100 and £1,000 per annum for ACS (assume per patient). Using epidemiology data from the costing template for NICE guidance on ticagrelor if it is assumed there are 455 ACS patients per 100,000 population each year and a third receive rivaroxaban at a cost of £50 per month (or £600 per patient for 1 year), this could result in an additional drug cost of £91,000 per 100,000 population per year. This excludes additional costs due to increased admissions from complications of treatment (e.g. bleeding) or savings from events avoided.

Actions/ issues which may be considered by commissioners and providers

There are now three antiplatelet agents recommended by NICE post ACS. Commissioners and providers should agree locally on the place in therapy for each of these (i.e. generic clopidogrel vs. prasugrel vs. ticagrelor) and the duration of therapy for audit purposes. This information should be communicated appropriately across the interface.

Audit and monitor use of prasugrel and ticagrelor locally. Agree local policy on the use of these drugs for unlicensed indications not covered by the NICE guidance, for example, use in patients with “clopidogrel resistance” or intolerance, or use in combination with PPIs, as these will increase the cost implications.

Agree the place in therapy locally of rivaroxaban for the secondary prevention of ACS. A systematic review found that the increase in major bleeding events associated with use of new-generation oral anticoagulants in patients receiving dual anti-platelet therapy following an ACS probably outweigh their ischaemic benefits in this setting.

Users may wish to refer to the NICE Commissioning Guides on Integrated Commissioning for the prevention of cardiovascular disease (May 2012) and Cardiac Rehabilitation (October 2011).

Disease or Indication: National targets and guidance

Epidemiology, potential financial implications for a population of 100,000 and other comments

National spend in primary care (£) Apr 2012-Mar 2013 (Epact England data) plus limited data on secondary care prescribing

20

Heart failure (HF) National HF audit results, published

Nov 2012

NICE Quality Standard on acute heart

failure, expected date TBC NICE guidance on the use of

ivabradine for heart failure, issued Nov 2012

This area is unlikely to have any major cost implications

According to QoF data for 12/13, the raw prevalence rate for HF in England is 0.7%.

The 5th

report of the National HF audit (April 2011-March 2012) collected data on 37,076 heart failure admissions over the period 1 April 2011 and 31 March 2012. It supports analysis from previous years and in particular, continues to highlight that access to specialist cardiology input and the prescription of recommended treatments are associated with prolonged survival and better outcomes for heart failure patients. As observed in previous years, prescription rates for ACE inhibitors/ARBs, beta blockers and mineralocorticoid receptor antagonist (e.g spironolactone or eplerenone) are all higher when patients are admitted to cardiology wards, as opposed to general medical or other wards. This Quality Standard topic has been referred to NICE and is at an early stage of development. Ivabradine was approved for use in chronic heart failure in March 2012. The licence covers use in NYHA II to IV class chronic heart failure with systolic dysfunction, in patients in sinus rhythm and whose heart rate is ≥ 75 bpm, in combination with standard therapy including beta-blocker therapy or when beta-blocker therapy is contraindicated or not tolerated. Ivabradine will be add-on therapy or could be used in patients intolerant of beta-blockers. The usual recommended starting dose of ivabradine is 5 mg twice daily. The dose can be titrated up to 7.5mg twice daily or down to 2.5mg twice daily according to heart rate.

This guidance recommends ivabradine as an option for treating chronic HF for people: - with New York Heart Association (NYHA) class II to IV stable chronic HF with systolic dysfunction and - who are in sinus rhythm with a heart rate of 75 beats per minute (bpm) or more and - who are given ivabradine in combination with standard therapy including beta-blocker therapy, ACEIs and aldosterone antagonists, or when beta-blocker therapy is contraindicated or not tolerated and - with a left ventricular ejection fraction of 35% or less

It is recommended that ivabradine should only be initiated after a stabilisation period of 4 weeks on optimised standard therapy with ACEIs, beta-blockers and aldosterone antagonists.

Disease or Indication: National targets and guidance

Epidemiology, potential financial implications for a population of 100,000 and other comments

National spend in primary care (£) Apr 2012-Mar 2013 (Epact England data) plus limited data on secondary care prescribing

21

HF cont’d NICE guidance on the use of

ivabradine for heart failure, cont’d

Licence extension for eplerenone –NYHA class II HF (not currently included in the NICE work plan)

Dose titration and monitoring should be carried out by a HF specialist, or in primary care by either a GP with a special interest in HF or a HF specialist nurse.

The costing template for this guidance estimates for England that: - The prevalence of HF due to left ventricular dysfunction is 0.41% (n=326 per 100,000 population) - Of these, 80% have NYHA class II to IV HF (n=261 per 100,000 population) -Of these, 12.2% have left ventricular ejection fraction of 35% or less, sinus rhythm and resting heart rate of 70 bpm or more (n= 32 per 100,000 population) - Of these, 63.8% have a resting heart rate of 75 bpm or more would be eligible for treatment with ivabradine and that currently none of these are receiving the drug (or 20 per 100,000 population) - Of these, 50% (or 10 people per 100,000 population) will take up ivabradine in the future at year 5.

Based on these assumptions NICE predict that the total drug and initiation cost for ivabradine will be £6,122 per 100,000 population per year at year 5 of implementation. Once savings from reduced costs due to hospital admissions are taken into account, the total cost falls to £4,393 per 100,000 population per year. It is assumed that uptake will be 10% in year 1, resulting in drug and initiation costs of ~£1,200 per 100,000 population. Eplerenone’s licence was extended in April 2012 to cover the treatment of adults with NYHA class II chronic HF and left ventricular systolic dysfunction (LVEF 30%) in addition to standard optimal therapy. The licence extension is based on the results of the EMPHASIS-HF study, which found that the addition of eplerenone (up to 50mg daily) to standard therapy reduces the risk of death and hospitalisation among patients with systolic HF and mild symptoms. It is unknown whether substituting spironolactone would produce similar results in these patients (at significantly lower cost). The manufacturer estimates that approximately 230,000 patients in the UK (or 370 patients per 100,000 population) may fall within NYHA class II and that half that number could be eligible for eplerenone for this indication. However, based on previous uptake of the drug, they anticipate only a small proportion of patients may be prescribed it. If it is assumed that 25% of these patients (93 patients per 100,000 population) receive eplerenone 50mg daily at an additional cost (over spironolactone) of £40.87 per patient per month, this could increase costs by ~ £45,000 per 100,000 population per year. The SMC accepted eplerenone for use in chronic HF in line with the product licence in July 2012. The manufacturer estimated the population

Renin angiotensin system (RAS) drug costs: Total RAS spend: £205.9m (or £387,700 per 100,000 population) ACEIs: £72.9m (or £137,300 per 100,000 population). This represents a 2.3% decrease on last year’s costs and a 2% increase in prescription numbers. Angiotensin receptor antagonists (ARBs): £131.5m (or £247,600 per 100,000 population). This represents a 31% decrease on last year’s costs. The number of prescriptions for these agents increased by 3% on the previous year. The decrease in spend can be attributed to the availability of generic ARBs, such as candesartan and losartan. Overall 64% of spend on RAS drugs is for ARBs. Prescriptions for ACEis comprise 71% of total ARB +ACEi prescriptions. Eplerenone: £9.3m (£17,500 per 100,000 population). This represents a 30% increase on last year’s spend, and a 32% increase in prescription numbers.

Disease or Indication: National targets and guidance

Epidemiology, potential financial implications for a population of 100,000 and other comments

National spend in primary care (£) Apr 2012-Mar 2013 (Epact England data) plus limited data on secondary care prescribing

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HF cont’d

Licence extension for eplerenone –NYHA class II HF (not currently included in the NICE work plan)

Proposed appraisal referred to NICE: Serelaxin for acute, decompensated HF

NICE clinical guideline on acute heart failure, expected Sep 2014

eligible for treatment in Scotland to be 7,457 in year 1 and 7,536 in year 5. Based on an estimated uptake of 5% in year 1 (349 patients or 7 patients per 100,000 population) rising to 15% in year 5 (1,057 patients or 20 patients per 100,000 population ), the impact on the medicines budget was estimated at £194.1k in year 1 (or £3,800 per 100,000 population) and £588.6k in year 5 (or £11,700 per 100,000 population) with no adjustment to the price to reflect that eplerenone is assumed to become generic in year 3. The manufacturer provided a further estimate showing an anticipated reduction in list price of eplerenone in years 3 to 5 due to the anticipation that it will become generic, in which the impact on the medicines budget would be £194.1k in year 1 (or ~£3,800 per 100,000 population) and £147.2k in year 5 (or ~ £2,700 per 100,000 population). Serelaxin is a peptide hormone with cardiorenal function-enhancing properties that is administered intravenously. NICE has been invited to appraise the clinical and cost effectiveness of serelaxin within its licensed indication for treating acute decompensation of heart failure. It has been filed for approval in the EU and its launch is expected in Q2 2014. A NHSC briefing on the drug states that serelaxin is intended to be administered in addition to IV diuretic treatment in patients hospitalised with acute HF, with normal to elevated blood pressure and mild to moderate renal impairment. Currently used IV vasodilators are associated with known restrictions such as intolerance, contraindications or uncertainty about long-term safety. The cost of serelaxin is not yet known. The NHSC briefing estimates that there were 60,000 admissions for heart failure (ICD10 I50) in 2010-11 in England. Approximately half of which were for acute HF (or 56 admissions per 100,000 population). If it is assumed that: - 20% of patients might be suitable for treatment (or 11 patients per 100,000 population) - Serelaxin is given intravenously over 48 hours and - It costs an additional £300 compared to standard treatment this would result in an additional cost impact of £3,300 per 100,000 population. This excludes any service related costs. This guideline will cover the diagnosis and management of acute heart failure in adults and will discuss pharmacological management. It is unlikely that this guideline will result in significant financial impact.

Disease or Indication: National targets and guidance

Epidemiology, potential financial implications for a population of 100,000 and other comments

National spend in primary care (£) Apr 2012-Mar 2013 (Epact England data) plus limited data on secondary care prescribing

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Actions/ issues which may be considered by commissioners and providers

A Cochrane Review concluded that in patients with symptomatic HF and systolic dysfunction or with preserved ejection fraction, ARBs compared to placebo or ACEIs do not reduce total mortality or morbidity. ARBs are better tolerated than ACEIs but do not appear to be as safe and well tolerated as placebo in terms of withdrawals due to adverse effects. Commissioners and providers should agree which ARB will be used where patients can not tolerate an ACEI due to cough. A number of ARBs are now available as generic preparations and the price has reduced considerably.

The Cochrane Review also found that adding an ARB in combination with an ACEI does not reduce total mortality or total hospital admission but increases withdrawals due to adverse effects compared with ACEI alone. Commissioners and providers should agree the place (if any) in therapy of this combination in HF.

Commissioners may wish to refer to the guide developed by NICE on commissioning services for people with chronic HF.

Many commissioners are redesigning services for HF so that more care is provided in the community through community HF clinics. Education and training requirements should be identified for practices providing community management of heart failure and appropriate protocols should be developed for medicines optimisation.

Serelaxin has been proposed as a high cost drug (formerly PbR excluded Drugs) for 2014/15 in the National Tariff consultation. It is unclear at this stage who the responsible commissioner will be for this drug (i.e. NHS England or CCGs).

Disease or Indication: National targets and guidance

Epidemiology, potential financial implications for a population of 100,000 and other comments

National spend in primary care (£) Apr 2012-Mar 2013 (Epact England data) plus limited data on secondary care prescribing

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Ischaemic stroke & atrial fibrillation (AF) New oral anticoagulants (NOACs)

NICE guidance on the use of apixaban for the prevention of stroke and systemic embolism in people AF, issued Feb 2013

MHRA advice – bleeding risks with NOACs, Oct 2013

NICE clinical guideline on the

management of AF, expected Jun 2014

This is an area of high financial risk

According to QoF data for 12/13, the raw prevalence rate for stroke in England is 1.7% and for AF it is 1.5%.

The new oral anticoagulants (NOACs) dabigatran, rivaroxaban and apixaban will have implications for existing anticoagulant services. Unlike warfarin, there is no need to monitor anticoagulant effect with the NOACs, however, reversing the anticoagulant effect is difficult. These agents will compete with each other for the same market. The NOACs are considerably more costly than warfarin, even when monitoring cost is taken into account. The three agents will compete with each other and hence the cost is likely to be a substitution.

NICE supports the use of apixaban as an option for preventing stroke and systemic embolism within its marketing authorisation, that is, in people with non-valvular AF with 1 or more risk factors such as: - prior stroke or transient ischaemic attack - age 75 years or older - hypertension - diabetes mellitus - symptomatic heart failure The costing statement for this guidance states that apixaban provides an alternative treatment option at a comparable cost to other NOACs and therefore it is anticipated that there will not be a significant cost impact from implementing this guidance. The MHRA previously advised (July 2012) that the contraindications for dabigatran had been clarified to include a range of clinical conditions where the patient is at significant risk of major bleeding, as well as in combination with other anticoagulant agents. Because similar risks are associated with the other new oral anticoagulants (apixaban and rivaroxaban), these contraindications have been applied across all three new oral anticoagulants for all indications and doses. NICE will be partially updating their previous guideline on the management of AF (2006). The guidance for NOACs is likely to be incorporated into the update guideline but implementation will already be underway for these. It is therefore unlikely that the update will result in a significant resource impact to the NHS.

NOAC drugs: £5.7m (or £10,700 per 100,000 population). Rivaroxaban: £1.6m (or £3K per 100,000 population) Apixaban: negligible Dabigatran: £4m (or £7, 700 pr 100,000 population) Nb: Use not separated out by indication.

Disease or Indication: National targets and guidance

Epidemiology, potential financial implications for a population of 100,000 and other comments

National spend in primary care (£) Apr 2012-Mar 2013 (Epact England data) plus limited data on secondary care prescribing

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Ischaemic stroke & AF cont’d

NICE guideline on rehabilitation after stroke, issued Jun 2013

NICE guidance on the use of vernakalant for the treatment of recent onset atrial fibrillation (≤7 days), expected date TBC

NICE Quality Standard on AF , expected date TBC

This guideline focuses on the long-term rehabilitation and support of people post stroke. The costing template and report focus on the recommendations that are considered to have the greatest resource impact. These are not medicines related and as an example include early supported discharge and support for rehabilitation in care homes and nursing homes. Vernakalant represents a low financial risk

The development of this guidance is currently suspended following information received from the manufacturer regarding the timings of the launch of the product in the UK. Vernakalant (Brinavess®) was approved in the EU in for rapid conversion of recent onset AF to sinus rhythm in adults in September 2010. The product has not yet been launched in the UK. In September 2012 the company holding the global marketing and development rights for both the IV and oral formulations of vernakalant made a business decision to return them to Cardiome Pharma Corp. In March 2012, Merck decided to discontinue further development of the oral formulation of vernakalant based on "an assessment of the regulatory environment and projected development timeline." Data indicates vernakalant could be 10 times more expensive than amiodarone, which is available generically at about £20. If it is assumed that:

- the overall incidence of acute AF is 170 per 100,000. - Vernakalant will compete with amiodarone injection for rapid conversion - 10% of patients are eligible for i.v amiodarone (17 per 100,000). - 50% of these patients receive vernakalant in preference to amiodarone and the cost is in the region of £200

This could result in a minor additional cost implication of £1,700 per 100,000 population. This Quality Standard topic has been referred to NICE and is at an early stage of development.

Disease or Indication: National targets and guidance

Epidemiology, potential financial implications for a population of 100,000 and other comments

National spend in primary care (£) Apr 2012-Mar 2013 (Epact England data) plus limited data on secondary care prescribing

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Actions/ issues which may be considered by commissioners and providers

NICE has recommended apixaban, dabigatran and rivaroxaban as options for the prevention of stroke and systemic embolism within their licensed indications in people with non-valvular AF. Organisations should agree how NICE guidance will be implemented at a local level and the place in therapy for each agent. The introduction of the NOACs will raise significant issues for commissioners, in particular the need to transfer funding from warfarin monitoring services in order to at least partially off set the increased cost of the new agents. Consideration should be given to scoping existing services and assessing the total budgetary impact of switching to a drug which might cost between £800 to £1000 per year but not require the same level of clinical monitoring. Savings through reduced monitoring may offset some of the cost of the drug.

When agreeing arrangements for commissioning the NOACs, ensure that bleeding management protocols are incorporated too as these agents lack a reversal agent.

Clarify current anticoagulant service provision and capacity i.e. self monitoring vs. community pharmacy/GP clinics vs. hospital clinics.

Primary care rebate schemes (PCRS) are contractual arrangements offered by pharmaceutical companies, or third party companies, which offer financial rebates on GP prescribing expenditure for particular branded medicine(s). These schemes have been developed for the NOACs. Organisations should develop robust local decision making processes for considering such schemes. Legal advice sought by the London Procurement Project (LPP) suggests that such schemes are not unlawful and are within the powers of commissioners to agree to, provided they meet certain requirements. If organisations agree to implement these schemes, they could result in savings in this area.

Readers may wish to refer to the following NICE Commissioning Guides: Anticoagulation therapy and service for the diagnosis and initial management of acute stroke, and transient ischaemic attacks (TIA).

Following publication of NICE guidance on the use of dipyridamole and clopidogrel for the prevention of vascular occlusive events (2010), clinicians may want to consider reviewing patients currently prescribed combination dipyridamole and aspirin and switch to generic clopidogrel in view of the savings associated with its use. Although unlicensed for TIA, the Royal College of Physicians National Clinical Guideline for Stroke (2012) supports the use of clopidogrel post TIA. This helps to reduce the pill burden for the patient and is cost saving.

Disease or Indication: National targets and guidance

Epidemiology, potential financial implications for a population of 100,000 and other comments

National spend in primary care (£) Apr 2012-Mar 2013 (Epact England data) plus limited data on secondary care prescribing

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Peripheral arterial disease (PAD)

NICE Quality Standard on peripheral arterial disease, expected Jan 2014

MHRA advice – cilostazol – indication

restricted, Apr 2013

This is an area of low financial risk but has been given more prominence as indicators for PAD are now included in the QOF. The indicators include the use of antiplatelets and blood pressure & cholesterol control

This Quality Standard will cover the diagnosis and management of lower limb PAD in adults aged 18 years and over. It does not cover acute ischaemia of the lower limb. A review of the benefits and risks of cilostazol was triggered by reports of adverse reactions (mainly cardiac and haemorrhagic), and by the potential for drug interactions. As a result, cilostazol is now restricted to second-line use in patients for whom life-style modifications and other appropriate interventions have failed to sufficiently improve their symptoms. Additionally, cilostazol is now contraindicated in patients with any of the following: (i) Unstable angina, recent myocardial infarction or coronary intervention (within 6 months) (ii) a history of severe tachyarrhythmia (iii) those receiving two or more other antiplatelet or anticoagulant treatments

Actions/ issues which may be considered by commissioners and providers

Commissioners and providers should assess the current provision of services for secondary prevention of cardiovascular disease in people over 60 years old with PAD and the varying needs of people with PAD in order to assess the potential costs of implementing recommendations made within the NICE guideline.

Review prescribing of drugs for PAD to ensure use is in line with NICE guidance issued in May 2011. Small cost savings could be possible in this area.

Venous thromboembolism (VTE) NICE Quality Standard on the

diagnosis and management of venous thromboembolic diseases, issued Mar 2013

Acute trust CQUIN schemes – VTE

The NOACs could have major implications on the delivery of anticoagulant services in this group of patients.

This quality standard covers the diagnosis and treatment of venous thromboembolic diseases in adults, excluding pregnant women. VTE is a national Commissioning for Quality and Innovation (CQUIN) target that applies to acute service providers and aims to reduce avoidable death, disability and chronic ill health from VTE. There are two indicators – the first measures the % of all adult inpatients who have had a VTE risk assessment on admission to hospital using the national tool. The second measures the number of root cause analyses (RCAs) on confirmed cases of pulmonary embolism (PE) or deep vein thrombosis (DVT).

Disease or Indication: National targets and guidance

Epidemiology, potential financial implications for a population of 100,000 and other comments

National spend in primary care (£) Apr 2012-Mar 2013 (Epact England data) plus limited data on secondary care prescribing

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VTE cont’d

NOACs for the treatment and long term secondary prevention of VTE

NICE guidance on the use of rivaroxaban for treating PE and preventing recurrent VTE, issued Jun 2013

NICE guidance on the use of dabigatran etexilate for the treatment of acute venous thromboembolic events, date expected TBC

NICE guidance in the use of dabigatran for the treatment and secondary prevention of DVT and/or PE, expected Oct 2014

Rivaroxaban is licensed for use in the treatment of DVT and PE, and prevention of recurrent DVT and PE following an acute DVT in adults (secondary prevention). Rivaroxaban is also licensed for the prevention of VTE in adult patients undergoing elective hip or knee replacement surgery (10mg strength).

Apixaban and dabigatran are not currently licensed for the treatment of DVT/PE in this patient group but are undergoing phase III trials. Dabigatran has been filed in the EU for VTE treatment and prevention. The NOACs will compete with each other in this setting.

NICE recommends rivaroxaban as an option for treating PE and preventing recurrent DVT and PE in adults. The costing template estimates that implementing the guidance will result in an additional cost of ~£20K per 100,000 population per year from year 5 of implementation. Costs of ~£9,500 per 100,000 population are estimated for year 1. These estimates include various assumptions for future practice set out in the costing template, including: (i) All those with active cancer still receive LMWH for 6 months (ii) 80% of people without cancer choose rivaroxaban and 20% choose dual therapy with a LMWH and warfarin (iii) Of these, 29% receive treatment for 6 months, 19% for 12 months (iv) The costing model assumes that as many as 50% of people who have a PE go on to receive 'lifelong treatment' with a drop-out rate each year of 13.5%. The costing model makes this assumption to year 5 following implementation of the guidance. Dabigatran is not currently licensed for the treatment of acute thromboembolic events. A NHSC review on the use of dabigatran for acute symptomatic VTE notes the drug would be intended for the treatment of the acute VTE event and prevention of recurrent VTE events during the treatment period, as a substitute for currently used anticoagulants (e.g. warfarin). The RE-COVER trial reported in December 2009. It investigated whether oral dabigatran (150mg twice daily) is (non-inferior) to warfarin (INR 2.0-3.0) for 6 months treatment of acute symptomatic VTE, following initial treatment (5-11 days) with a parenteral anticoagulant. The results found dabigatran was non-inferior to warfarin at preventing recurrent venous VTE (p<0.001). In terms of safety (secondary outcome), dabigatran demonstrated a 37% reduction in major or clinically relevant non-major bleeding (p=0.002). Major bleeding was comparable for dabigatran and warfarin. Dabigatran will compete with rivaroxaban in this setting and the cost is therefore likely to be a substitution. Dabigatran is not currently licensed for this indication. However, it will compete with the already NICE approved rivaroxaban in this setting and the cost is therefore likely to be a substitution.

Disease or Indication: National targets and guidance

Epidemiology, potential financial implications for a population of 100,000 and other comments

National spend in primary care (£) Apr 2012-Mar 2013 (Epact England data) plus limited data on secondary care prescribing

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VTE cont’d

NICE guidance on the use of apixaban for the prevention of VTE in acute medical illness, expected date TBC

NICE guidance on the use of rivaroxaban for the prevention of VTE in people hospitalised for acute medical conditions, suspended

The results of the phase III ADOPT study found that an extended course of thromboprophylaxis with apixaban is not superior to a shorter course of enoxaparin, in medically ill patients. The study compared apixaban 2.5mg twice daily for 30 days with enoxaparin 40mg once daily for 6-14 days. The primary outcome was a composite of VTE and VTE-related death during 30 day’s follow-up. VTE events occurred in 2.7% randomised to apixaban and 3.1% randomised to enoxaparin (p=0.44). Major bleeding by day 30 was seen in 0.47% (apixaban) vs. 0.19% (enoxaparin), p=0.04. The primary safety outcome of total bleeding showed no significant difference between apixaban (7.7%) and enoxaparin (6.8%).

Apixaban will compete with low molecular weight heparins and dabigatran (licence pending) for this indication. The cost of a 30 day course of apixaban at 2.5mg twice daily is approximately £100 per patient vs. a cost of around £30-50 per patient for LMWH (excluding administration costs). The costs associated with this guidance are likely to be similar to those provided in NICE guidance on the use of rivaroxaban for the treatment and prevention of recurrent DVT and will represent a substitution of one for the other. The development of rivaroxaban for this indication has been discontinued and as a consequence NICE has suspended this appraisal on its current work programme.

Actions/ issues which may be considered by commissioners and providers

Locally agree which agents will be used for the prophylaxis of DVT in the different patients groups covered by the updated NICE VTE guideline.

It is likely that there will be significant interest in the use of the NOACs for the treatment of acute VTE and long term secondary prevention. Organisations will need to consider their place in therapy vs. parenteral anticoagulants if service redesign in this area is being discussed. Consideration should also be given to what is currently covered under existing contracts with providers as some commissioners may have block contracts in place for warfarin, which include associated services, such as phlebotomy and district nursing.

Commissioners should confirm whether local tariffs charged by providers for VTE prevention in certain patient groups, for example post surgery or in maternity patients, include LMWH. There are increasing requests for prescribing of these anticoagulants to be continued in primary care and such requests may be inappropriate.

Disease or Indication: National targets and guidance

Epidemiology, potential financial implications for a population of 100,000 and other comments

National spend in primary care (£) Apr 2012-Mar 2013 (Epact England data) plus limited data on secondary care prescribing

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3. Respiratory System Patent expiries

According to Prescribing Outlook New Medicines 2013, the following patent expiries (which may have a significant impact on prescribing costs) are due within the next couple of years: Tiotropium (Sep 2015)

Asthma

QIPP area for high dose inhaled corticosteroids

NICE Quality Standard on asthma,

issued Feb 2013

NICE clinical guideline on diagnosis and monitoring of asthma, expected Jun 2015

This is an area of low financial risk

According to QoF data for 12/13, the raw prevalence rate for asthma in England is 6%. A set of comparators has been developed to support the QIPP medicines use and procurement workstream. The aim of the comparators is to support organisations and prescribers to review the appropriateness of prescribing, revise prescribing where appropriate and monitor implementation. Although there isn’t a specific indicator for this comparator, it is recommended that organisations: Review the use of ICS routinely in people with asthma Step down the dose and use of ICS when clinically appropriate in

people with asthma This quality standard covers the diagnosis and treatment of asthma in adults, young people and children aged 12 months and older This guideline will cover adults, children and young people who are being investigated for suspected asthma, or who have been diagnosed with asthma and are having their condition monitored. According to the final scope, the guideline will not discuss treatment of asthma but will consider objective tests such as spirometry/flow volume loop, peak expiratory flow (PEF) variability. It will also consider the use of tele healthcare as a route for assessment, monitoring adherence and inhaler technique.

Combination inhaler costs (Symbicort Seretide and Fostair): £239m (or £450,200 per 100,000 population). This figure represents a 4% increase in spend on the previous year and a 7% increase in prescription numbers. Long acting beta agonists (salmeterol and formoterol): £37.6m (or £71,000 per 100,000 population). This figure is 10% lower than the previous year and prescription numbers have decreased by 9%. This may reflect the increasing trend for prescription of combination inhalers. Inhaled corticosteroids (ICS) costs: £611.8m (or £1.2m per 100,000 population). This figure represents a 3% increase on last year and includes combination inhaler spend. Prescription numbers increased by 4%. Spend on combination inhalers makes up 40% of overall ICS spend. Usage can not be separated out by indication.

Disease or Indication: National targets and guidance

Epidemiology, potential financial implications for a population of 100,000 and other comments

National spend in primary care (£) Apr 2012-Mar 2013 (Epact England data) plus limited data on secondary care prescribing

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Actions/ issues which may be considered by commissioners and providers

Use of high dose steroids (for example the Seretide 250mcg inhaler in asthma) should be audited as there are concerns over excessive use. Agree local policy on the use of high dose ICS, to ensure patients are appropriately reviewed and stepped down, which could achieve savings in this area.

Locally agree place in therapy of Flutiform (fluticasone/formoterol) combination inhaler and whether switch programmes will be implemented as this combination inhaler may be cost saving against alternative combination inhalers. Flutiform was launched in September 2012 and is indicated for the regular treatment of asthma when a combination inhaler is appropriate. The NICE Evidence Summary for flutiform highlights that the company estimates that switching every person from Seretide to Flutiform could result in savings of up to £167,473 per year for an average primary care organisation’s population (339,000) or ~£50,000 per 100,000 population. These savings do not take into account the costs of the activity required to switch patients.

A DTB article highlighted that many healthcare professionals do not know how to use inhalers properly and are therefore not in a position to educate and counsel patients on the use of these devices. Healthcare professionals should be appropriately trained in checking inhaler technique and local guidance should also address this and promote the use of spacer devices where appropriate. These simple measures could prevent progression to more advanced treatment (e.g. LABA/ICS) and therefore be cost saving in the long run.

Develop local criteria for appropriate use of Symbicort SMART regimen - where Symbicort is used as both a maintenance and reliever treatment. The DTB reviewed this strategy in November 2011 and concluded, “In theory, use of the SMART regimen might help by reducing the number of inhalers required. However, patients using this approach would need a clear action plan and close monitoring of the number of inhalations that they are taking. Consequently, its place in practice remains unclear.” Opinion suggests that the SMART regimen has a limited place in therapy for some STEP 3 patients only.

Chronic Obstructive Pulmonary Disease (COPD)

Systematic review and meta-analysis - tiotropium Respimat® inhaler in COPD, Oct 2012

This is an area of increased activity and moderate financial risk

COPD is a clinical domain in the QOF and recent QoF data for 12/13 suggest a raw prevalence rate of COPD in England of 1.7%.

A systematic review and meta-analysis published in Thorax found a possible increased risk of all-cause mortality and death from cardiovascular causes associated with tiotropium administered by the Respimat device, when compared with placebo and other inhaled treatments for COPD. These increased risks were not present in all analyses and not seen with tiotropium administered by the HandiHaler device. In contrast a LABA plus ICS combination, tiotropium HandiHaler and LABAs had relatively safer profiles, with LABA-ICS having the lowest risk of overall death in patients with COPD. The higher risk was derived from doses that were higher than the currently licensed doses of Respimat. The MHRA provided information and advice for healthcare professionals in 2010 advising that patients with COPD who use tiotropium should be reminded not to exceed the recommended once-daily dose. The MHRA also advised that Respimat should be used with caution in patients with known cardiac rhythm disorders.

Tiotropium: £160.3m (or £302,000 per 100,000 population). This figure represents a 12% increase on last year. Prescription numbers increased by 10%.

Disease or Indication: National targets and guidance

Epidemiology, potential financial implications for a population of 100,000 and other comments

National spend in primary care (£) Apr 2012-Mar 2013 (Epact England data) plus limited data on secondary care prescribing

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Actions/ issues which may be considered by commissioners and providers

The way in which COPD services are delivered is being redesigned in many areas so that more care is commissioned in the community enabling “frequent flyers” to be identified and treatment targeted appropriately. An article in the HSJ (2010) estimated that a proactive approach to care pathway management could save England over £800m (or £1.5m per 100,000 population) on COPD inpatient care alone.

It has been estimated that 40% to 50% of patients on COPD registers still smoke. Since stopping smoking is one of the single most effective interventions for COPD, the use of smoking cessation products should be prioritised locally in this population.

There is debate about the place in therapy and cost effectiveness of triple therapy (LABA + LAMA + ICS) as recommended in the revised NICE guideline for COPD vs. pulmonary rehabilitation. A DTB review found that smoking cessation is the most effective intervention for patients with COPD. The review also suggests that there is insufficient evidence to show that any further benefit is gained from the use of triple therapy.

Use the commissioning guide developed by NICE on commissioning services for people with COPD when planning services for this patient group. The Department of Health also published a commissioning toolkit for COPD as a resource to help to implement the Outcomes Strategy for COPD and Asthma.

The NHS Improvement team has produced a basic guide covering ten key principles to adopt to provide good COPD care. Key principles covered within the guide include checking inhaler technique at every opportunity and ensuring clinically appropriate and cost effective prescribing of oxygen. The team has also produced a report on improving home oxygen.

It should be noted that the only licensed preparations containing corticosteroids for the treatment of COPD are the combination inhalers. For Seretide™ preparations, only the 500mcg accuhaler device and for Symbicort the 200mcg and 400mcg strengths of the combination inhaler are licensed for use in COPD.

Commissioners and respiratory teams should consider the good practice guide from Primary Care Commissioning for assessment and review of home oxygen as there are potential savings to be made in this area. The guide covers the development and commissioning of good assessment and review services for all home oxygen patients.

A Quality Standard for COPD was published in July 2011.

Disease or Indication: National targets and guidance

Epidemiology, potential financial implications for a population of 100,000 and other comments

National spend in primary care (£) Apr 2012-Mar 2013 (Epact England data) plus limited data on secondary care prescribing

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Other respiratory conditions

Bronchiolitis

NICE Quality Standard on bronchiolitis, expected date TBC

Cystic Fibrosis (CF)

NICE Quality Standard on cystic fibrosis , expected date TBC

Idiopathic Pulmonary Fibrosis (IPF)

NICE Quality Standard on IPF, expected date TBC

NICE clinical guideline on IPF,

expected Jun 2013

This Quality Standard topic has been referred to NICE and is at an early stage of development. Commissioning for CF and IPF now rests with NHS England. However quality standards and clinical guidelines will assist CCGs in defining the standards of care for these patient groups.

This Quality Standard topic has been referred to NICE and is at an early stage of development. IPF is a rare, progressive chronic interstitial lung disease (ILD).

This Quality Standard topic has been referred to NICE and is at an early stage of development. This guideline will cover the diagnosis and management of suspected IPF in adults (18 and older).

Actions/ issues which may be considered by commissioners and providers

Monitor use of the CF inhaled drugs in primary care. These agents are now commissioned through NHS England Specialised Services and therefore prescribing responsibility should remain with the specialist centre.

Disease or Indication: National targets and guidance

Epidemiology, potential financial implications for a population of 100,000 and other comments

National spend in primary care (£) Apr 2012-Mar 2013 (Epact England data) plus limited data on secondary care prescribing

34

4. Central nervous system Patent expiries According to Prescribing Outlook New Medicines 2013, the following patent

expiries (which may have a significant impact on prescribing costs) are due within the next couple of years: Montelukast (Feb 2013), Memantine HCl (Apr 2014), escitalopram oxalate (May 2014), paliperidone (Oct 2014), almotriptan (Dec 2014), aripiprazole (Apr 2015), eletriptan (Dec 2015) and frovatriptan (Dec 2015).

Anxiety NICE guideline on social anxiety

disorder, issued May 2013 NICE pathway available.

NICE Quality Standard on anxiety disorders , expected Feb 2014

This guideline covers the recognition, assessment and treatment of social anxiety disorder in children and young people (from school age to 17 years) and adults. It includes a recommendation on the treatment of specific phobias that updates and replaces the section of NICE TAG 97 (computerised cognitive behavioural therapy for depression and anxiety) that deals with phobia. The costing template and report for this guideline focus on the recommendations that are likely to have the greatest resource impact. This includes the following medication related recommendations:

1st line medication: For adults who decline individual CBT and express

a preference for a pharmacological intervention, offer a SSRI escitalopram or sertraline

Individual CBT plus medication: For adults whose symptoms have only partially responded to individual CBT, ass in sertraline or escitalopram

2nd

line medication: For adults whose symptoms have not responded or who cannot tolerate the side effects of first-line medication, and who have declined individual CBT the alternatives NICE recommends fluvoxamine or paroxetine or the SNRI venlafaxine

3rd

line medication: For adults whose symptoms have not responded to an alternative SSRI or an SRNI NICE recommends either phenelzine or moclobemide

The guideline also states that botulinum toxin should not be offered to treat hyperhidrosis in people with social anxiety disorder. This is because there is no good-quality evidence showing benefit from botulinum toxin in the treatment of social anxiety disorder and it may be harmful.

An estimated cost range of £324.00 to £651.00 per person for 26 weeks treatment with recommended medication.

The costing report states that because of the variation in both current practice and prevalence estimates of social anxiety disorder, the cost impact of implementing the guidance will vary locally depending on current practice and service provision, hence no overall cost impact figure per 100,000 population is provided.

Actions/ issues which may be considered by commissioners and providers

Commissioners and providers should locally agree a treatment pathway for social anxiety disorder, specifying where agents fit in.

Disease or Indication: National targets and guidance

Epidemiology, potential financial implications for a population of 100,000 and other comments

National spend in primary care (£) Apr 2012-Mar 2013 (Epact England data) plus limited data on secondary care prescribing

35

Hypnotics and sedation

QIPP area for hypnotics

A set of comparators has been developed to support the QIPP medicines use and procurement workstream. The aim of the comparators is to support organisations and prescribers to review the appropriateness of prescribing, revise prescribing where appropriate and monitor implementation. The hypnotics comparator considers the total number of average daily

quantities (ADQs) for benzodiazepines (indicated for use as hypnotics) and ‘Z’ drugs per Star-PU.

Actions/ issues which may be considered by commissioners and providers

Sodium oxybate is listed as an exclusion in the National Tariff for 13/14. A decision on funding will need to be agreed locally for this agent. Drug exclusions under Payment by Results 13/14

Schizophrenia NICE guideline on psychosis and

schizophrenia in children and young people, issued Jan 2013

NICE pathway available.

NICE guideline on psychosis and

schizophrenia in adults, expected Feb 2014

This guideline is concerned with the recognition and management of psychosis and schizophrenia in children and young people up to the age of 18. It incorporates TA 213 (‘Aripiprazole for the treatment of schizophrenia in people aged 15 to 17 years’). The guideline notes that although the mainstay of treatment for psychosis and schizophrenia has been antipsychotic medication, there is limited evidence of its efficacy in children and young people. The guideline discusses use of antipsychotics for the treatment of a first episode of psychosis and for recurrences; however no specific antipsychotic is recommended. It is advised that the choice of antipsychotic medication should be made by the parents/carers of younger children, or jointly with the young person and their parents/carers, and healthcare professionals. Age appropriate information should be provided and the likely benefits and possible side effects of each drug discussed. Clozapine is recommended for those who have not responded adequately despite the sequential use of at least two different antipsychotics given in adequate doses, and augmentation with a second antipsychotic can be considered if there is an inadequate response.

With respect to cost implications, the costing report and template note that there is considerable variation in the configuration and integration of child and adolescent mental health services (CAMHS). Therefore NHS organisations and local authorities are encouraged to consider local services in order to calculate the costs or savings associated with implementing the guideline. Regular monitoring throughout treatment with antipsychotic medication is noted to possibly result in more appointments than are currently provided. The cost of this is estimated between £5,000 and £8,000 per 100,000 population per year. This guideline will cover the treatment and management of psychosis and schizophrenia and related disorders in adults (18 years and older) with psychosis or schizophrenia with onset before age 60 years. This guidance is an update of the NICE guideline published in March 2009 and will replace it. This update is therefore unlikely to have additional significant resource impact on medicines use.

Antipsychotics: £138m (or £260,000 per 100,000 population). Spend has decreased by 43% and prescription numbers by 3%, compared to the previous year. The availability of generics, such as olanzapine, has led to the reduction in cost. Antipsychotic depot injections: £7.2m (or £14,000 per 100,000 population). Spend has increased by 8% and prescription numbers have fallen by 2%, compared to the previous year. Data for 2012 from the HSCIC show overall spend across primary and secondary care in England on aripiprazole was £54.7m (or £103,000 per 100,000 populatrion) - an increase of 14% on the previous year. The majority of this prescribing was in primary care.

Disease or Indication: National targets and guidance

Epidemiology, potential financial implications for a population of 100,000 and other comments

National spend in primary care (£) Apr 2012-Mar 2013 (Epact England data) plus limited data on secondary care prescribing

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Schizophrenia cont’d

MHRA learning module on antipsychotics

NICE Quality Standard on

schizophrenia, expected sate TBC

The MHRA launched a learning module on antipsychotics that identifies their most important hazards and informs on actions health professionals can take in order to anticipate, minimise and manage the risks. This Quality Standard topic has been referred to NICE and is at an early stage of development.

Actions/ issues which may be considered by commissioners and providers

Users may wish to refer to the NICE commissioning guide on an effective service for the treatment and management of schizophrenia in adults

Develop local protocols for the use of newer antipsychotic drugs such as aripiprazole and paliperidone. Agree a place in therapy for the injectable second-generation antipsychotic formulations and monitor and audit their use.

Conduct disorders NICE guideline on conduct disorders

in children and young people, issued Mar 2013

This guideline provides advice on the recognition and management of conduct disorders in children and young people. Conduct disorders, and associated antisocial behaviour, are the most common mental and behavioural problems in children and young people. They are characterised by repetitive and persistent patterns of antisocial, aggressive or defiant behaviour that amounts to significant and persistent violations of age appropriate social expectations. The guideline covers a range of interventions including treatment, indicated prevention and selective prevention. In terms of pharmacological interventions, methylphenidate or atomoxetine are recommended for the management of co-existing ADHD (as per NICE clinical guideline 72 on ‘Attention deficit hyperactivity disorder’). The short-term use of risperidone (with careful evaluation) is recommended as an option for the management of severely aggressive behaviour, in young people with a conduct disorder who have problems with explosive anger and severe emotional dysregulation. The costing template and report for this guideline focus on the recommendations likely to have the greatest resource impact. This doesn’t include medicines related recommendations. The report states that because of the variation in current practice and uncertainty about future practice, it is not possible to quantify the national cost impact of implementing the guidance.

Disease or Indication: National targets and guidance

Epidemiology, potential financial implications for a population of 100,000 and other comments

National spend in primary care (£) Apr 2012-Mar 2013 (Epact England data) plus limited data on secondary care prescribing

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Bipolar disorder

NICE Quality Standards on bipolar disorder in (i) Adults and (ii) Children and young people, expected date TBC

NICE guidance on the use of aripiprazole for bipolar disorder in adolescents, issued Jul 2013

NICE guidance on loxapine for schizophrenia or bipolar disorder, terminated May 2013

NICE guideline on bipolar disorder

(update), date expected TBC

DTB review: Asenapine for bipolar I disorder

These Quality Standard topics have been referred to NICE and are at an early stage of development. NICE recommends aripiprazole as a possible treatment (for up to 12 weeks) for moderate to severe manic episodes in young people aged 13 and older with bipolar I disorder. The costing statement for this guidance does not consider that the guidance will result in a significant resource impact because of the limited change to current practice anticipated.

NICE is unable to recommend the use in the NHS of loxapine inhalation for treating acute agitation and disturbed behaviours associated with schizophrenia and bipolar disorder because no evidence submission was received from the manufacturer. This agent is therefore not expected to have a significant financial impact.

This is an update of Bipolar disorder (NICE clinical guideline 38; July 2006). The final scope notes that some important steps in the treatment pathway and the treatment approaches most likely to lead to benefit have been published since the current guidance was issued. In terms of management, the guideline will consider psychological and social interventions, information and communication technologies, nutritional supplements (e.g. fish oil, folic acid, zinc, co-enzyme Q), pharmacological interventions, combined interventions, and physical treatments (including ECT). This guidance is at an early stage of development and no estimate of its likely cost impact is available.

A DTB review considered the evidence for and practical implications associated with use of sublingual asenapine for treatment of moderate to severe manic episodes associated with bipolar I disorder in adults. The review concluded there is currently insufficient evidence to be able to determine its place in therapy.

Disease or Indication: National targets and guidance

Epidemiology, potential financial implications for a population of 100,000 and other comments

National spend in primary care (£) Apr 2012-Mar 2013 (Epact England data) plus limited data on secondary care prescribing

38

Depression

QIPP area for antidepressants

NICE guidance on the use of

vortioxetine for treating major depressive disorder, expected Aug 2014

MHRA: Updated guidance on liver function monitoring with agomelatine, Oct 2012

NICE Quality Standard on depression in children and young people, issued Sep 2013

A set of comparators has been developed to support the QIPP medicines use and procurement workstream. The aim of the comparators is to support organisations and prescribers to review the appropriateness of prescribing, revise prescribing where appropriate and monitor implementation. Two antidepressant related comparators have been developed: Antidepressants ADQ/STAR-PU: the total number of average daily

quantities (ADQs) of all antidepressant prescribing per STARPU Antidepressants first choice % items: the number of prescription items

for ‘1st choice’ generic SSRIs as a percentage of the total number of

prescription items for selected ‘other antidepressants’.

Vortioxetine is a bimodal oral antidepressant that is thought to work through a combination of reuptake inhibition of serotonin and modulation of serotonin receptor activity. It is not yet licensed in the UK but it has been filed with the EMA. The NHSC briefing for the drug notes that it is intended for the treatment of major depressive disorder as a first line treatment, a substitute in patients with no or an inadequate response to SSRIs or SNRIs, and for patients who are difficult to treat using existing pharmacological options. The comparators for vortioxetine in the clinical trials include duloxetine, agomelatine, venlafaxine and placebo. It is administered orally, once daily as monotherapy.

The NICE clinical guideline on the management of depression in adults recommends that people with moderate or severe depression should be provided with a combination of antidepressant medication and a high-intensity psychological intervention (CBT or IPT). The draft scope for this guidance states that in the UK, the prevalence of major depressive disorder ranges from 5% to 10% of people seen in primary care settings and 10% to 14% of medical inpatients. If it is assumed that there is a 10% prevalence (or 10,000 per 100,000 population) and of these 50% are considered for drug treatment (or 5,000 per 100,000 population). If 1% (50 people per 100,000) of these are prescribed vortioxetine first line at an additional cost (vs. citalopram) of £29/month (assume cost of vortioxetine will be £30/month/patient), this could result in a cost implication of around £17,000 per 100,000 per year. Use as a sequential antidepressant agent will have further cost implications – these have not been modelled here.

The MHRA has provided updated information about the risk of dose-related hepatotoxicity (including hepatic failure) associated with use of agomelatine. This quality standard covers the diagnosis and management of depression in children and young people aged 5 up to their 18th birthday

Antidepressants: £200m (or £377,000 per 100,000 population). Spend has decreased by 14% and the number of prescriptions has increased by 6% on the previous year. SSRIs: £70m (or £132,000 per 100,000 population) – a 39% decrease in cost and a 5% increase in prescription item numbers compared to the previous year. The price of generic preparations has fallen over the past year, which has contributed to the fall in spend.

Disease or Indication: National targets and guidance

Epidemiology, potential financial implications for a population of 100,000 and other comments

National spend in primary care (£) Apr 2012-Mar 2013 (Epact England data) plus limited data on secondary care prescribing

39

Actions/ issues which may be considered by commissioners and providers

Define the place of vortioxetine in the pathway for the treatment of major depressive disorder (e.g line of therapy, monotherapy or combination with other treatments)?

Develop local guidelines to define the place in therapy of agomelatine for the treatment of depression. NICE announced the termination of its appraisal of agomelatine for the treatment of major depressive episodes in adults in 2011, as the manufacturer did not make an evidence submission.

Autism

NICE guideline on autism in children and young people, issued Aug 2013

NICE pathway available.

NICE Quality Standard on autism in children, young people and adults expected Jan 2014

This guideline covers the management and support of children and young people on the autism spectrum. The guideline contains recommendations on pharmacological interventions and a key priority for implementation involves using pharmacological interventions for behaviours that challenges. Specifically, the guideline recommends that antipsychotic medication is considered for managing behaviour that challenges in children and young people with autism when psychosocial or other interventions are insufficient or could not be delivered because of the severity of the behaviour. Treatment should initially be prescribed and monitored by a paediatrician or psychiatrist. Additionally: Anticonvulsants, antidepressants and antipsychotics should not be

used for the management of core features of autism in children and young people

Psychosocial and pharmacological interventions should be offered for the management of coexisting mental health or medical problems in children and young people with autism in line with NICE guidance for children and young people, including the NICE guideline on ADHD (CG 72)

A pharmacological intervention to aid sleep should not be used unless sleep problems:

- persist despite following the sleep plan - are having a negative impact on the child or young person and their

family or carers. The costing statement for this guideline notes that there might be costs involved in implementing the guidance. However, because of the variation in current practice, the costs can only be assessed at a local level. Organisations are advised to assess the resource implications of this guidance locally. The statement highlights potential areas for additional costs and these do not include the use of medicines. This Quality Standard is under development.

Methylphenidate: £22.7m (or £43,000 per 100,000 population). Compared to the previous year, spend increased by 9% and the number of prescriptions increased by 10%. Atomoxetine: £6m (or £11,400 per 100,000 population). Compared to the previous year, spend increased by 2.5% and the number of prescriptions increased by 5%.

Actions/ issues which may be considered by commissioners and providers

Users may wish to refer to the NICE Commissioning Guides on services for the diagnosis and management of ADHD in adults and in children and young people.

Agree local place in therapy for lisdexamfetamine, which is licensed as a 2nd

line option after methylphenidate for the treatment of ADHD in children aged 6 years and over.

Disease or Indication: National targets and guidance

Epidemiology, potential financial implications for a population of 100,000 and other comments

National spend in primary care (£) Apr 2012-Mar 2013 (Epact England data) plus limited data on secondary care prescribing

40

Obesity NICE guidance on lorcaserin

hydrochloride for obesity, suspended NICE guidance on phentermine (with

topiramate) for obesity, suspended NICE guideline on the management of

obesity in adults and children (update), expected date TBC

NICE Quality Standards for obesity in

(i) adults (ii) children [public health] and (iii) adults [public health], expected date TBC

These drugs are unlikely to result in significant resource impact for the NHS.

This appraisal has been suspended as the manufacturer has informed NICE that they have withdrawn their licensing application for this indication. Development of this appraisal has been suspended as the CHMP confirmed the refusal of the marketing authorisation for this product in February 2013. This follows an initial negative opinion issued by the CHMP in October 2012. This guideline is at an early stage of development but will update the previous guideline (2006) in this area. It is unlikely to have further significant impact on NHS resources. These Quality Standards have been referred to NICE and are at an early stage of development.

Orlistat: £12.8m (or £24,000 per 100,000 population). Compared to the previous year, both spend and prescription numbers dropped by ~47%. This decrease is probably linked to a supply issue with orlistat during 2012.

Actions/ issues which may be considered by commissioners and providers

Users may find the NICE bariatric surgical service commissioning guide useful

Disease or Indication: National targets and guidance

Epidemiology, potential financial implications for a population of 100,000 and other comments

National spend in primary care (£) Apr 2012-Mar 2013 (Epact England data) plus limited data on secondary care prescribing

41

Pain Update of clinical guideline on the

pharmacological management of neuropathic pain in adults in non-

specialist settings, expected Nov 2013

NICE pathway available.

In March 2010, NICE published a clinical guideline on the management of neuropathic pain conditions in adults in primary and secondary care, in non-pain specialist settings. This recommended pregabalin or amitriptyline (unlicensed use) as options for first-line treatment, except in the case of painful diabetic neuropathy, where duloxetine should be offered (or amitriptyline if this is contra-indicated).

Due to ongoing concerns about the cost-effectiveness of some of the recommended treatment options, NICE is fully updating this guideline. For neuropathic pain (excluding trigeminal neuralgia), the draft version of this guideline now recommends: Either choice of amitriptyline, gabapentin or nortriptyline as initial

treatment for neuropathic pain (except trigeminal neuralgia). If the initial treatment is not effective or not tolerated, offer another of 1

these 3 treatments instead. If initial treatment is not effective, is not tolerated or is contraindicated

with all 3 of amitriptyline, gabapentin and nortriptyline, consider switching to duloxetine or pregabalin.

Consider tramadol only if acute rescue therapy is needed while the person is waiting for a referral appointment

Consider capsaicin cream for people with localised neuropathic pain who wish to avoid, or who cannot tolerate, oral treatments

The draft guideline does not recommend the use of cannabis sativa extract, capsaicin patch, lacosamide, lamotrigine, levetiracetam, oxcarbazepine, topiramate or venlafaxine for the treatment of neuropathic pain in non-specialist settings. The guideline also provides recommendations on the management of trigeminal neuralgia. The costing statement accompanying the original guideline noted that estimated 28-day prescribing costs associated with the different drug treatments for neuropathic pain ranges from £0.84 for amitriptyline to £64.40 for pregabalin. Gabapentin at a maximum dose of 3.6g daily in divided doses costs £10.13 for 28 days (assuming 400mg capsules used; based on Drug Tariff prices Oct 2013). The DTB published a two-part (part 1 and part 2) update on the treatment of neuropathic pain in October and December 2012 reviewing the available evidence for antiepileptics, antidepressants, opioids, tramadol, and topical agents. The author notes current guidance recommending a tricyclic antidepressant, gabapentin or pregabalin first-line, and concludes that the lowest cost agents should be used first, due to the absence of overwhelming evidence of superiority of one drug over another.

Pregabalin: £172m (or £324,000 per 100,000 population). Compared to the previous year, spend increased by 17% Usage can not be separated by indication.

Disease or Indication: National targets and guidance

Epidemiology, potential financial implications for a population of 100,000 and other comments

National spend in primary care (£) Apr 2012-Mar 2013 (Epact England data) plus limited data on secondary care prescribing

42

Pain cont’d

Update of clinical guideline on the pharmacological management of neuropathic pain in adults in non-

specialist settings, cont’d

NICE clinical guideline on the early

management of persistent non-specific low back pain (update), expected date TBC

European review of codeine for

analgesia in children, Jul 2013

NICE Quality Standards on (i) Low

back pain and (ii) Pain management (young people and adults), expected date TBC

Many organisations are reviewing the use of pregabalin in neuropathic pain. In 12/13 ~£172m was spent by the NHS in England on pregabalin in primary care. Although usage can not be separated by indication, if it is assumed that a third was in neuropathic pain (£57.4m, or £108,000 per 100,000 population) and that use could be reduced by 25% following review, this could result in savings of around £27,000 per 100,000 population. This guideline will update previous guidance in this area (2009) and therefore it is not anticipated that it will have further additional significant resource impact on medicines use. A European review of the safety of codeine-containing medicines licensed for pain relief in children (age 0–18 years) was started in October 2012 and concluded in July 2013. The review was triggered by concerns of an increased risk of morphine toxicity when susceptible children receive codeine for pain after surgery. The review concluded that codeine should only be used to relieve acute moderate pain in children older than 12 years and only if it cannot be relieved by other painkillers such as paracetamol or ibuprofen alone. Furthermore, a significant risk of serious and life-threatening adverse reactions has been identified in children with obstructive sleep apnoea who received codeine after tonsillectomy or adenoidectomy (or both). Codeine is now contraindicated in all children younger than 18 years who undergo these procedures for obstructive sleep apnoea. These Quality Standards have been referred to NICE and are at an early stage of development.

Actions/ issues which may be considered by commissioners and providers

Locally agree the approach to the management of neuropathic pain, including the role of pregabalin – based on the draft content of the revised guideline, there are opportunities for cost savings in this area.

Disease or Indication: National targets and guidance

Epidemiology, potential financial implications for a population of 100,000 and other comments

National spend in primary care (£) Apr 2012-Mar 2013 (Epact England data) plus limited data on secondary care prescribing

43

Nausea and vomiting

EMA review – metoclopramide and risk of neurological effects, Aug 2013

The EMA completed a review into the benefits and risks of metoclopramide. The review was undertaken at the request of the French medicines regulatory agency (ANSM), following concerns over side effects and efficacy. The review confirmed the well known risks of neurological effects such as short-term extrapyramidal disorders and tardive dyskinesia. The conclusion of the review was that these risks outweigh the benefits in long-term or high-dose treatment. The EU review has recommended changes that include a restriction to the dose and duration of use to help minimise the risk of potentially serious neurological adverse effects. The risk of acute neurological effects is higher in children than in adults. In children, age 1–18 years, metoclopramide should only be used as a second-line option for prevention of delayed chemotherapy-induced nausea and vomiting, and for treatment of established postoperative nausea and vomiting Use of metoclopramide is contraindicated in children younger than 1 year.

Epilepsy NICE Quality Standards on epilepsy in

adults and children, issued

Phenytoin capsules price increase

According to QoF data for 12/13, the national prevalence of epilepsy across England is 0.8% (based on patients aged over 18 years old) These sets of Quality Standards cover the diagnosis and management of the epilepsies in (i) adults (aged >18 years) and (ii) children and young people aged up to 18 years. Flynn Pharma took over the manufacture and distribution of Epanutin capsules (now marketed as Phenytoin Sodium Flynn hard capsules) in September 2012. The list price for a 28-pack of the 25mg capsules is now £15.74 – this compares to a previous price of £0.66 for the same quantity of Epanutin capsules (with a similar 24-fold increase in the other capsule strengths). Although other forms are available, capsules account for around 85% of the market. An article in the Telegraph estimated that the extra cost to the NHS for phenytoin as a result of the price increase is £44m or £83,000 per 100,000 population. The price increase occurred in October 2012.

Actions/ issues which may be considered by commissioners and providers

Users may wish to refer to a NICE Commissioning Guide on an effective service for the accurate diagnosis of the epilepsies in adults.

Commissioners and providers should locally agree which treatments will be used at each line of therapy for patients with epilepsy. This may include the use of shared care protocols.

Disease or Indication: National targets and guidance

Epidemiology, potential financial implications for a population of 100,000 and other comments

National spend in primary care (£) Apr 2012-Mar 2013 (Epact England data) plus limited data on secondary care prescribing

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Substance dependence Smoking Cessation NICE public health guidance on harm

reduction approaches to smoking, issued Jun 2013

NICE public health guidance on harm

reduction approaches to smoking, cont’d

NICE Quality Standard on supporting people to stop smoking, issued Aug 2013

This public health guidance will consider various tobacco harm-reduction approaches, which is an alternative option for people who are unable to (or do not want to) quit smoking in one step, or at all. The guidance will consider use of pharmacotherapies licensed for such use, other non-tobacco nicotine-containing products (e.g. electronic cigarettes), behavioural support/counselling, and self-help. The guidance recommends raising awareness of licensed nicotine containing products and that NRT products should be offered to people who smoke, as part of an overall harm-reduction strategy. All types of NRT should be on offer and should be used alone or in combination, depending on preference and level of dependence. NRT products should also be offered as necessary to prevent relapse among those who have quit and those who have reduced the amount they smoke. People should be advised that licensed nicotine-containing products can be used as long as they help reduce the desire to smoke (indefinitely if necessary). Although some nicotine-containing products (e.g. electronic cigarettes) are not currently regulated by the MHRA, and therefore their quality and safety cannot be assured, patients should be advised that they are likely to be less harmful than cigarettes. Unlicensed products that are currently being marketed, such as electronic cigarettes, and products new to the market will need a medicines licence once the European Commission's revised Tobacco Products Directive comes into effect in the UK (this is expected to be in 2016). Recommendations on the prescribing of NRT for patients who need or want to abstain temporarily are also given. The costing report and template for this guidance provides unit costs but do not provide an overall cost impact for implementing it. However, the report notes that the recommendations considered to have the greatest financial impact are: Behavioural support Supplying licensed nicotine-containing products Follow-up appointments Commissioning stop smoking services The report discusses the potential costs and savings that need to be considered locally. Implementing the guidance may increase the number of people accessing services. This may lead to a corresponding increase in the number of people using licensed nicotine-containing products as part of a tobacco harm reduction approach. This Quality Standard covers smoking cessation, which includes support for people to stop smoking and for people accessing smoking cessation services.

Nicotine: £26m (or £49,000 per 100,000 population). Spend decreased by 9% and prescription numbers decreased by 15% compared to the previous year. Bupropion: £0.9m (or £1,700 per 100,000 population). Spend and prescription numbers have decreased on the previous year by 18% and 14% respectively. Varenicline: £27m (or £50,000 per 100,000 population). Both spend and prescriptions numbers have decreased by 10% compared to the previous year. These decreases may reflect increased supply of nicotine products and varenicline through other routes, such as PGDs or voucher schemes.

Disease or Indication: National targets and guidance

Epidemiology, potential financial implications for a population of 100,000 and other comments

National spend in primary care (£) Apr 2012-Mar 2013 (Epact England data) plus limited data on secondary care prescribing

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Substance dependence cont’d Smoking Cessation

NICE public health guidance on smoking cessation in secondary care - acute, maternity and mental health services, expected Nov 2013

NICE public health guidance on smoking cessation (update), expected date TBC

Statistics on smoking - England, Aug 2013

Alcohol Misuse

NICE Quality Standard on preventing and managing alcohol misuse, expected date TBC

This guidance aims to support smoking cessation, temporary abstinence from smoking and smokefree policies in all secondary healthcare settings. Recommendations in the draft guidance include: identifying people who smoke and referring them on for support helping people admitted to secondary care to abstain temporarily if they

do not want to stop smoking completely providing and advising on stop smoking pharmacotherapies adjusting drug treatments for people who have stopped smoking hospital pharmacies (supply and stock of smoking cessation products)

This guidance is at an early stage of development but will update previous public health guidance (2006) in this area. Latest statistics from the HSCIC for England show: In 2012/13, there were just over 2.2 million prescription items to help

people stop smoking, a decrease since last year when there were there were over 2.5 million prescription items.

The Net Ingredient Cost (NIC) of all prescription items used to help people quit smoking was just over £58.1 million. This is a decrease of 10% on the £64.6 million spent in 2011/12.

There were approximately 1.6 million hospital admissions in 2011/12, among adults aged 35 and over with a primary diagnosis of a disease that can be caused by smoking. The annual number of admissions has been rising steadily since 1996/97, when the number of such admissions was 1.1 million.

Current smokers smoked an average of 12.7 cigarettes per day This Quality Standard has been referred to NICE and is at an early stage of development.

Actions/ issues which may be considered by commissioners and providers

Users may wish to refer to the NICE commissioning guides on effective needle and syringe programmes using a harm-reduction approach, effective smoking cessation service for people having elective surgery, services for quitting smoking during pregnancy and following childbirth, and services for the identification and treatment of hazardous drinking, harmful drinking and alcohol dependence in children, young people and adults

The Tobacco Return on Investment Tool developed by NICE and Brunel University will help support commissioners and policy makers count the cost of tobacco-related harm in their communities and estimate the longer-term cash savings that they can expect by putting tobacco control strategies in place.

Due to changes in the configuration of the NHS from April 1st 2013, commissioners will need to ensure

engagement with Public Health Teams is maintained in order that these areas are addressed collaboratively. Health and Wellbeing Boards are ideally placed to ensure this occurs.

Disease or Indication: National targets and guidance

Epidemiology, potential financial implications for a population of 100,000 and other comments

National spend in primary care (£) Apr 2012-Mar 2013 (Epact England data) plus limited data on secondary care prescribing

46

Alzheimer’s disease & dementia NICE social care Quality Standard on

supporting people to live well with dementia, issued Apr 2013

QIPP area for low dose antipsychotics

in people with dementia Acute trust CQUIN schemes –

dementia

This quality standard covers the care and support of people with dementia. It applies to all social care settings and services working with and caring for people with dementia. It should be read alongside the NICE Dementia quality standard. A set of comparators has been developed to support the QIPP medicines use and procurement workstream. The aim of the comparators is to support organisations and prescribers to review the appropriateness of prescribing, revise prescribing where appropriate and monitor implementation. Although no specific comparator is available for this area, organisations are advised to review and, if appropriate, revise prescribing of low-dose antipsychotics in people with dementia, in accordance with the NICE/Social Care Institute for Excellence (SCIE) clinical guideline and the NICE quality standard on dementia, and the Alzheimer's Society best practice guide. Dementia is a national Commissioning for Quality and Innovation (CQUIN) target that applies to acute service providers. It aims to: incentivise the identification of patients with dementia and other causes of cognitive impairment alongside their other medical conditions, prompt appropriate referral and follow up after they leave hospital and ensure that hospitals deliver high quality care to people with dementia and support their carers.

Drugs for dementia: £56.7m (or £107,000 per 100,000 population). Spend has decreased by 35% on the previous year (reflecting generic availability and a drop in prices), and prescription numbers increased by 23%. This could be a reflection of increased shared care in this area. Data from the HSCIC indicate that in 2012, overall spend across primary and secondary care in England on: - donepezil was £49.5m (a decrease of 37% on the previous year) - memantine was £16m (an increase of 103% on the previous year) - rivastigmine was £19.4m (an increase of 16% on the previous year) - galantamine was £18.1m (a decrease of 6% on the previous year)

Actions/ issues which may be considered by commissioners and providers

Users may wish to refer to the NICE tool providing support for commissioners of dementia care (2013). Review and, where appropriate, revise prescribing of low dose antipsychotics in people with dementia, in

accordance with NICE/SCIE guidance and the NICE Quality Standard on dementia. There are opportunities for

cost saving if prescribing in this area is reduced.

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Other mental health and CNS related guidance

NICE clinical guideline on antenatal and postnatal mental health (update), expected Jan 2015

NICE clinical guideline on head injury,

expected Jan 2014 NICE clinical guideline on challenging

behaviour and learning disabilities, expected May 2015

CQC annual report for 2012 on the

safer management of controlled drugs, Aug 2013

This will be a partial update of Antenatal and postnatal mental health (NICE clinical guideline 45). It will cover the care of women who have, or are at risk of, mental health disorders during pregnancy and the postnatal period, in the same healthcare settings as the original NICE guideline. Treatments to be covered include psychological interventions, pharmacological, electroconvulsive therapy and combined interventions, and the balance of risk and benefit for the mother, foetus and baby. This guideline is at an early stage of development, no information on the likely cost impact is available. This will be a partial update of the current NICE guideline on Head injury and will cover the triage, assessment, investigation and early management of adults, young people and children presenting with a suspected or confirmed head injury. Key issues that will be covered include selection of patients for specialist neuroscience care and for imaging, diagnosis of cervical spine injury using CT and MRI, and information for patients and carers on discharge. This guideline update is unlikely to have a significant impact on medicines spend.

This guideline will provide recommendations on interventions for people with learning disabilities whose behaviour challenges. The interventions covered in the guideline will include environmental, psychosocial and pharmacological. The draft scope notes that medication is the most common intervention used to manage behaviour that challenges and it is considered overused by most professionals, e.g. antipsychotics. This guideline may lead to a reduction in the use of anti-psychotics in this group of people, however, the guideline is at an early stage of development and it is therefore difficult to assess its impact.

This sixth annual report from the CQC covers the regulation of controlled drugs in England and relates to the year ended 31 December 2012. In 2013, changes were made to the regulations governing controlled drugs to align them with the new NHS architecture and this report is the last under the 2006 regulations.

Actions/ issues which may be considered by commissioners and providers

Users may with to refer to the NICE commissioning guides for antenatal and postnatal mental health services and commissioning stepped care for people with common mental health disorders

Tafamidis is an orphan drug licensed in the EU for the treatment of transthyretin familial amyloid polyneuropathy (FAP). According to Prescribing Outlook New Medicines 2012, FAP has a prevalence of 1 in 100,000 in the EU, and liver transplantation is currently the only treatment option. Although tafamidis is likely to be expensive, it may prevent or delay liver transplantation. Tafamidis is listed as an exclusion in the National Tariff for 12/13 and a decision on funding will need to be agreed locally. Drug exclusions under Payment by Results 12/13.

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5. Infections Patent expiries

According to Prescribing Outlook New Medicines 2013, the following patent expiries (which may have a significant impact on prescribing costs) are due within the next couple of years: efavirenz (Nov 2013); zanamivir (Feb 2014); abacavir (Jun 2014); moxifloxacin (Jun 2014); nelfinavir mesylate (Oct 2014); lopinavir/ritonavir (Dec 2015)

General strategy QIPP area – antibiotic prescribing

Latest Public Health England primary care infection guidance

Annual Report of the Chief Medical Officer - Infections and the rise of antimicrobial resistance, Mar 2013

UK 5 Year Antimicrobial Resistance

Strategy 2013 to 2018, Sep 2013

A set of comparators has been developed to support the QIPP medicines use and procurement workstream. The aim of the comparators is to support organisations and prescribers to review the appropriateness of prescribing, revise prescribing where appropriate and monitor implementation. The following antibacterial prescribing QIPP comparators are available:

“Antibacterial items/STAR PU” (number of prescription items for antibacterial drugs (BNF 5.1) per STAR-PU)

“Cephalosporins and quinolones % items” (number of prescription items for cephalosporins and quinolones as a percentage of the total number of prescription items for selected antibacterial drugs).

“3 days trimethoprim ADQ/item” (total number of average daily quantities per item for trimethoprim 200mg tablets)

Minocycline ADQ/1000 patients (total number of average daily quantities for minocycline per 1000 patients)

In April 2013 the DTB published an article discussing the decline in the prescribing of minocycline relating to its serious adverse effects and lack of clinical advantage over existing therapies for acne.

The latest version of Public Health England’s “Management of infection guidance for primary care” can be adapted for local use.

This CMO report highlights that, while a new infectious disease has been discovered nearly every year over the past 30 years, there have been very few new antibiotics developed leaving the armoury depleted as diseases evolve and become resistant to existing drugs. In addition to encouraging development of new drugs, the report highlights that preserving the current supply of antibiotics is equally important. This includes better hygiene measures to prevent infections, prescribing fewer antibiotics and making sure they are only prescribed when needed. The report makes 17 recommendations and suggests antimicrobial resistance is placed on the national risk register.

This cross-government UK strategy aims to slow the development and spread of antimicrobial resistance by focusing activities around 3 strategic aims: (i) improve knowledge and understanding of antimicrobial resistance; (ii) conserve & steward the effectiveness of existing treatments; (iii) stimulate development of new antibiotics, diagnostics and novel therapies.

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General strategy cont’d Antimicrobial prescribing and

stewardship competencies, Oct 2013

Fidaxomicin for Clostridium difficile

The DH and PHE have published these competencies for all independent prescribers to help improve the quality of prescribing practice. There are 5 overarching competencies: Infection prevention and control Antimicrobial resistance and antimicrobials Prescribing antimicrobials Antimicrobial stewardship Monitoring and learning

Actions that independent prescribers can take for each competency are outlined within the document.

Fidaxomicin (Dificlir®) is the first in a new class of macrocylic antibiotics recently licensed in the EU and launched in the UK for the treatment of Clostridium difficile infection (CDI). A DTB review (November 2012) discusses its place in therapy and concludes that there is insufficient evidence to allow it to be recommended as a first-line treatment for all cases of CDI. However, it may provide an option for some patients based on specialist advice. Local protocols should be agreed to ensure that fidaxomicin is only used following specialist advice from a microbiology service. A NICE new medicines evidence summary on fidaxomicin is also available.

Actions/ issues which may be considered by commissioners and providers

Review and, where appropriate, revise current prescribing practice and use implementation techniques to ensure prescribing is in line with guidance from Public Health England and in line with the Department of Health Strategy.

Benchmark and review the total volume of antibiotic prescribing and the prescribing of quinolones, cephalosporins, trimethoprim and minocycline against local and national data.

Infection in children

NICE guideline on feverish illness in children (update), issued May 2013

NICE pathway available.

NICE guideline on bronchiolitis in children, expected Apr 2015

This guideline updates and replaces a previous guideline in this area (2007). The guideline evidence-based advice on the care of young children (aged < 5 years) with feverish illness. New and updated recommendations are included in areas relating to assessment and initial management in children younger than 5 years with no obvious cause of feverish illness. The guideline makes recommendations on the use of antipyretics and notes that antipyretic agents do not prevent febrile convulsions and should not be used specifically for this purpose. Advice is also provided on using ibuprofen and paracetamol in children with fever. The costing statement for this guideline states that there are no recommendations in the guideline which are anticipated to have a significant resource impact.

This guideline will cover the diagnosis and management of bronchiolitis in children and will include recommendations on specific treatments – antibiotics, inhaled therapies (including epinephrine, salbutamol, corticosteroids, ipratropium bromide), systemic corticosteroids, nebulised hypertonic saline, heliox (combined helium and oxygen), combined bronchodilator and corticosteroid therapy and montelukast. The guideline is

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Infection in children cont’d

NICE Quality Standards on (i) feverish illness in children and (ii) antibiotics for neonatal infection, expected date TBC

NICE Quality Standard on UTI in children (<16 years), issued Jul 2013

at an early stage of development. These Quality Standards are at an early stage of development. This Quality Standard covers the care of infants, children and young people under 16 years with a first or recurrent upper or lower UTI and without known underlying uropathy

Respiratory infections Tuberculosis (TB)

NICE guideline on TB (update), expected date TBC

PHE annual TB report, Aug 2013

NICE Quality Standard on TB, expected date TBC

Pneumonia

NICE guideline on Pneumonia - including community acquired expected date TBC

This guideline will cover the clinical diagnosis and management of TB, and measures for its prevention and control. It will update and replace previous guidance in this area (2011). With respect to the treatment of active TB, the guideline will consider when treatment should deviate from the 'standard recommended regimen', taking into account factors such as the site and severity of the disease, and individual patient characteristics including age and the presence of co-morbidities such as HIV, renal or liver disease and drug dependency. Identification and treatment of multi-drug resistant (MDR) TB and treatment of latent TB infection will also be included. It is unlikely that this guideline will have further significant resource implications for The latest annual TB report states that rates of TB have stabilised in the UK over the past seven years, following the increase in the incidence from 1990 to 2005. However, despite considerable efforts to improve TB prevention, treatment and control, the incidence of TB in the UK remains high compared to most other Western European countries, with 8,751 cases reported in 2012, an incidence of 13.9 per 100,000 population.

The proportion of TB cases with resistance to any first line drug (7.4 %) was slightly lower in 2012 than in 2011, while the proportion of MDR TB cases (1.6 %) remained stable. The majority of cases with MDR TB (89%) were born outside the UK. The proportion of cases who had completed treatment by 12 months continued to improve gradually, accounting for 82.9% of cases notified in 2011. This Quality Standard has been referred to NICE and is at an early stage of development. This guideline will cover the diagnosis and management of community- acquired pneumonia (CAP) and hospital-acquired pneumonia (HAP) in adults. Its purpose will be to determine evidence-based, cost-effective best practice to reduce mortality and morbidity from pneumonia and maximise

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Respiratory infections cont’d

Pneumonia

NICE guideline on Pneumonia - including community acquired expected date TBC

NICE Quality Standard on pneumonia, expected date TBC

resources. Topics to be covered include diagnostic and microbiological investigations, use of severity assessment tools, pharmacological treatment (antibiotics [choice, when to start, duration of therapy] and glucocorticoids), gas exchange management, monitoring of response, safe discharge and the provision of patient information.

The guideline apply to adults only and will not consider the management of those with ventilator-associated pneumonia, pneumonia acquired in intensive care, pneumonia complicating bronchiectasis, cases where pneumonia is considered a terminal event, and immunocompromised patients. It will also not consider the management of specific identified pathogens, prevention strategies (e.g. vaccination), or other management strategies such as complementary and alternative treatments, statins, or G-CSF.

This Quality Standard has been referred to NICE and is at an early stage of development.

Hepatitis B

NICE guideline on chronic hepatitis B issued Jun 2013

NICE Quality Standard on hepatitis B, expected Jul 2014

This guideline covers the diagnosis and management of chronic hepatitis B in children, young people and adults. The guideline updates and replaces recommendations 1.2 to 1.4 in NICE guidance on the use of adefovir dipivoxil and peginterferon alfa-2a for the treatment of chronic hepatitis B (2006). NICE TAG 173 (tenofovir; 2009), TAG 154 (telbivudine; 2008), TAG 153 (entecavir; 2008), recommendation 1.1 of TAG 96 (adefovir and peginterferon alfa-2a; 2006) have been incorporated into the guideline. With respect to medicines related key priorities for implementation, the guideline provides advice on the treatment sequence in adults with HBeAg-positive/negative chronic hepatitis B and compensated liver disease. It also makes recommendations for prophylactic treatment during immunosuppressive therapy and women who are pregnant or breastfeeding.

The costing template does not include additional medicines related costs – the costs focus on assessing liver disease in secondary specialist care. Note: Although the drugs considered within this guideline are now commissioned through NHS England, the guideline’s content will be useful for CCGs and hospital Trusts.

NICE is developing a Quality Standard on chronic hepatitis B.

Actions/ issues which may be considered by commissioners and providers

Drugs for hepatitis B are listed as an exclusion in the national Tariff for 13/14. From April 2013, the responsible commissioner for the hepatitis B drugs in England is NHS England. Drug exclusions under Payment by Results 13/14

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Hepatitis C NICE guideline on hepatitis C,

expected date TBC HPA annual hepatitis C report, Jul

2013

This guideline will provide advice and recommendations on the diagnosis and management of hepatitis C. The guideline will cover treatment and monitoring of peginterferon with ribavirin or in combination with boceprevir or telaprevir It will cover: Peginterferon alfa-2a with ribavirin versus peginterferon alfa-2b with

ribavirin When to start or delay hepatitis C treatment Monitoring of treatment efficacy and how to guide treatment duration

(response-guided therapy) Defining a sustained virologic response When to stop treatment The guideline is at an early stage of development, however as many of the medicines related aspects are already being implemented, it is unlikely to have an additional significant resource impact on medicines use in this area. Note: Although the drugs being considered within this guideline are now commissioned through NHS England, the guideline’s content will be useful for CCGs and hospital Trusts. The latest annual report from the HPA on hepatitis C estimates that around 215,000 individuals are chronically infected in the UK. Most of this infection (~90%) is genotype 1 and genotype 3. Hospital admissions from HCV-related end stage liver disease and hepatocellular carcinomas are continuing to rise and there has been an overall increase in registrations for liver transplants for post-hepatitis C cirrhosis. Injecting drug use continues to be the most important risk factor for HCV infection.

Actions/ issues which may be considered by commissioners and providers

Drugs for hepatitis C are listed as exclusions in the national Tariff for 13/14. From April 2013, the responsible commissioner for the hepatitis C drugs in England is NHS England. Drug exclusions under Payment by Results 13/14

Hepatic encephalopathy NICE guidance on rifaximin for hepatic

encephalopathy, expected Jan 2014

Rifaximin (Targaxan

®) has been launched for the reduction in recurrence of

episodes of overt hepatic encephalopathy in patients ≥ 18 years of age. It is licensed at a dose of 550mg twice daily. This guidance will appraise the clinical and cost effectiveness of rifaximin for use within its licensed indication. Hepatic encephalopathy is a neuropsychiatric syndrome seen in hepatic insufficiency associated with acute or chronic liver disease. It is associated with diminished health-related QOL, impaired daily function, decreased work activity and frequent hospitalisation for the treatment of acute episodes, and 1- and 3-year survival rates after experiencing an episode are 42% and 23%, respectively. The estimated prevalence of hepatic encephalopathy in the UK in 2008 was 1.4 per 100,000.

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Hepatic encephalopathy cont’d

NICE guidance on rifaximin for hepatic encephalopathy, cont’d

The aim of treatment is to reduce the production of ammonia in the gut, as the condition is thought to be caused by an inability to remove ammonia from the bloodstream. Current management involves antibiotics (e.g. neomycin) for acute episodes, to inhibit ammonia-producing bacteria, and disaccharides (e.g. lactulose) to convert soluble ammonia to insoluble ammonium (the latter may also be used for prophylaxis).

Rifaximin decreases intestinal production and absorption of ammonia. It has been studied in combination with lactulose for the treatment of adults with liver cirrhosis who have had prior acute episodes of hepatic encephalopathy. The SPC for the product notes that in the pivotal study, 91% of the patients were using concomitant lactulose.

Draft NICE guidance (ACD) issued in July 2013 does not recommend rifaximin as per its licensed indication. If final NICE guidance remains as per the draft, this guidance is unlikely to have additional resource impact on medicines use in the NHS. However, if it is supported by NICE, rifaximin 550mg bd costs £259.23 for 1 month’s treatment. The SMC accepted rifaximin for use in this indication in September 2013. The submitting company estimated the population eligible for treatment to be 1,102 (or 22 people per 100,000 population) in all 5 years, with an estimated uptake rate of 8% in year 1 and 40% in year 5. Based on an uptake of 8% in year 1 (or 2 people per 100,000 population) the budget impact is estimated at £298K in year 1 (or ~£6,000 per 100,000 population). This rises to £1.5m (or £30,000 per 100,000 population) in year 5 where a 40% uptake is estimated. These costs are based on 6 months treatment. The SPC notes that clinical benefit was established from a controlled study in which subjects were treated for 6 months.

Other infection-related developments and guidance

NICE Quality Standard on surgical site infection, issued Oct 2013

NICE Quality Standard on infection control, expected Apr 2014

NICE Quality Standard on urinary tract infections, expected Apr 2014

Good practice recommendations for

OPAT: UK consensus statement, issued May 2012

This Quality Standard covers the prevention and treatment of surgical site infection for adults, children and young people undergoing surgical incisions through the skin, in all healthcare settings These Quality Standards are under development. These good practice recommendations provide pragmatic guidance on the development and delivery of outpatient parenteral antimicrobial therapy (OPAT) services, looking at all aspects of service design, care delivery, outcome monitoring and quality assurance, with the aim of ensuring that OPAT services provide high-quality, low-risk care, whatever the healthcare setting. They will provide a useful resource for teams developing new services, as well as a practical set of quality indicators for existing services.

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6. Endocrine system Patent expiries According to Prescribing Outlook New Medicines 2013, the following patent

expiries (which may have a significant impact on prescribing costs) are due within the next couple of years: strontium ranelate (Aug 2015)

Diabetes

QIPP area – diabetes

This is an area of major financial risk depending on rate of uptake of newer therapies and the anticipated rise in the number of cases over the next few years.

According to QoF data for 12/13, the raw prevalence rate of diabetes in England is 6% (based on patients aged over 17 years old).

A set of comparators has been developed to support the QIPP medicines use and procurement workstream. The aim of the comparators is to support organisations and prescribers to review the appropriateness of prescribing, revise prescribing where appropriate and monitor implementation. The following diabetes related comparators have been developed:

Prescribing of metformin and sulfonylureas in line with the NICE guideline. This indicator measures the number of prescriptions for metformin and sulfonylureas as a percentage of the total number of prescription items for all antidiabetic drugs.

Prescribing of long acting insulin analogues. The indicator measures the number of prescriptions for the long acting human analogue insulins detemir and glargine as a percentage of the total number of prescription items for all long acting and intermediate acting insulins excluding biphasic insulins.

Self monitoring of blood glucose (SMBG): although this area does not currently have a QIPP comparator available, this is an identified area for the QIPP programme. It is recommended that organisations review and, where appropriate, revise local use of SMBG in type 2 diabetes mellitus to ensure that it is in line with NICE guidance. The former NHS Diabetes published a report (now archived) on SMBG, including recommendations on self-monitoring for all people with Type 2 diabetes.

For Group 2 drivers (buses and lorries) with diabetes, the DVLA has recommended that when treated with medication, other than insulin, which carries a risk of inducing hypoglycaemia (including sulfonylureas and glinides), the driver must show adequate control of the condition by regular blood glucose monitoring, at least twice daily and at times relevant to driving. A rapid review from the former NPC clarifies the DVLA requirements and advice for the monitoring of glucose.

Drugs used in diabetes (incl. monitoring): £706m (or £1.3m per 100,000 population). Spend is similar to last year. Prescription numbers have increased by 5%. Anti-diabetic drugs: £253m (or £476,000 per 100,000 population). Spend decreased by 3% with a 6% increase in prescription numbers. The decrease in spend is most likely due to a drop in price of generically available products. Insulins: £295m (or £556,000 per 100,000 population). An increase of 2% in spend and 3% in prescription numbers on the previous year.

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Diabetes

NICE Quality Standards on diabetes in (i) children and young people, and (ii) pregnancy, expected dates TBC

National diabetes audit 11/12 (report 1) published Oct 2013

National diabetes inpatient audit (NaDIA) 2012, published Mar 2013

NICE guidance on the use of

dapagliflozin in combination therapy for the treatment of type 2 diabetes, issued Jun 2013

These Quality Standard topics have been referred to NICE and are at an early stage of development. Report 1 of this year’s audit covers care processes and treatment targets. Over half of patients diagnosed with type 1 diabetes did not receive all diabetes checks (56.8 per cent, or 117,800 out of 207,570) and over a third of patients with type 2 diabetes did not receive all checks (37.4 per cent, or 819,980 out of 2.2 million). Treatment targets for glucose control and blood pressure control are less likely to be achieved in people with type 1 diabetes than people with type 2 diabetes. When combined with their longer average durations of diabetes, this predicts higher levels of future complications for people with Type 1 diabetes. The report also shows wide variation in achieving the 140/80 blood pressure target between CCGs and Local Health Boards (LHBs). Some CCGs and LHBs met this target in 53% of cases but in others it was met in less than 44% of cases. NaDIA 2012 was carried out by diabetes teams in acute hospitals in England on a nominated day between the 17 and 21 September 2012. The majority of patients included in this year’s inpatient audit (65.6 %) were admitted for medical reasons other than diabetes with only 8.2 % of patients admitted specifically for the management of their diabetes. People in hospital with diabetes were older than other patients; the median age of 75 years for inpatients with diabetes compared to 68 years for all inpatients. The median length of stay for inpatients with diabetes was 8 nights. Those admitted to hospital as an emergency had a longer median length of stay (8 nights) than patients admitted electively (5 nights). Findings from this year’s audit suggest that 39.8 % of patients included in the audit experienced at least one diabetes medication error while in hospital. Patients with medication errors were more than twice as likely to experience a severe hypoglycaemic episode (16.8 %) compared to patients who did not have a medication error (7.5 %).

Dapagliflozin is a once-daily oral medication that is a first in class selective and reversible inhibitor of sodium-glucose co-transporter 2 (SGLT2). It works independently of insulin and blocks the reabsorption of glucose in the kidneys and promotes excretion of excess glucose in the urine. Dapagliflozin is licensed for adults with type 2 diabetes as: (i) Monotherapy - when diet and exercise alone do not provide adequate glycaemic control in patients for whom use of metformin is considered inappropriate due to intolerance.

Breakdown of costs:

Gliptins: £71.3m (or £134,000 per 100,000 population). Spend increased by 36% and prescription numbers by around 38% on last year.

Pioglitazone: £20.4m (or £38,000 per 100,000 population). Spend decreased by 67% and prescription numbers by 15%. The fall in spend can partly be attributed to generic availability and also safety concerns surrounding the use of this agent. Exenatide (inc. long acting): £19.7m (or £37,000 per 100,000 population). Spend and items increased by 8% on the previous year. Liraglutide: £32.2m (or £61,000 per 100,000 population). Both spend and prescriptions numbers increased by 43% on the previous year. Lixisentaide: Negligible prescribing in 12/13 as newly licensed. Insulin glargine: £72m (or £135,691 per 100,000 population). A decrease in spend of 1% on the previous year and a 1% increase in prescription numbers. Insulin detemir: £38.7m (or £73,000 per 100,000 population). An increase in spend and prescription numbers of 4% on the previous year. Glucose testing reagents for diabetes: £151.8m (or £286,000 per 100,000 population). This represents a 4% increase in spend on last year. Prescription numbers increased by 2%. Spend on glucose testing reagents makes up 21.5% of overall spend on diabetes.

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Diabetes cont’d NICE guidance on the use of

dapagliflozin in combination therapy for the treatment of type 2 diabetes, cont’d

NICE guidance on the use of

canagliflozin in type 2 diabetes, expected Jun 2014

NICE guidance on the use of buccal

insulin for the management of type 1 diabetes, expected date TBC

(ii) Add-on combination therapy - in combination with other glucose-lowering medicinal products including insulin, when these, together with diet and exercise, do not provide adequate glycaemic control The recommended dose is 10 mg once daily. NICE recommends dapagliflozin as an option for treating type 2 diabetes under the following circumstances: in a dual therapy regimen in combination with metformin, only if it is

used as described for dipeptidyl peptidase-4 (DPP-4) inhibitors in type 2 diabetes: the management of type 2 diabetes (NICE clinical guideline 87).

in combination with insulin with or without other antidiabetic drugs

The guidance does not recommend dapagliflozin in a triple therapy regimen in combination with metformin and a sulfonylurea. It also does not cover the use of dapagliflozin in a dual therapy regimen with a sulfonylurea or use as monotherapy. The costing template for this guidance estimates an additional cost of ~£23,000 per 100,000 population per year. The manufacturer's submission included an assumption of uptake of 4.3% of eligible people after 5 years. For second-line treatments it was anticipated that the drugs displaced would primarily be those from the DPP-4 class (gliptins), rather than pioglitazone, with a ratio of around 85% to 15% respectively. For insulin treatments (third and fourth line) there were no assumptions around which forms of insulin were most likely to be displaced. The expected level of uptake was split proportionately between the treatments used. Canagliflozin is the second SGLT2 under development. It was given a positive opinion recommending it’s approval by the EMA’s CHMP in September 2013. Approval was recommended as monotherapy and add-on therapy (including insulin) in adults aged 18 years or over. Canagliflozin is likely to b similarly priced to dapagliflozin. If NICE approve its use as per dapagliflozin, the two drugs will compete with each other for the same market, the cost is therefore likely to be a substitution. According to the UKMi New Drugs Online database, buccal insulin is currently in phase II and III trials and a predicted UK launch date is not yet available. This guidance is therefore at an early stage of development.

Liraglutide: £22.5m (or £42,390 per 100,000 population). Both spend and prescriptions numbers doubled on the previous year. The costing template for NICE guidance on liraglutide (Oct 2010) estimated that implementation of the guidance would lead to an overall annual cost implication of £4,200 per 100,000 population. However, spend data for 12/13 indicate that spend predicted by NICE is being exceeded. At ~ £42,000 per 100,000 population, current spend is ten times

the NICE estimate.

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Diabetes cont’d

Review of NICE clinical guidelines on: - the diagnosis and management of diabetes (type 1 and 2) in children and young people, expected date TBC - diabetes in pregnancy, expected date TBC - the diagnosis and management of type 1 diabetes in adults, expected date TBC

Review of NICE clinical guideline on

the management of type 2 diabetes in adults, expected date TBC

NICE guideline on prevention and

management of foot problems in people with diabetes, expected date TBC

EMA safety review of GLP-1 based

therapies for diabetes, Jul 2013

These three guidelines will review and update previous versions and are unlikely to result in further additional significant resource impact on medicines use.

This review is at an early stage of development but the final scope indicates that the review will include the pharmacological management of blood glucose levels, target values for blood glucose control, self-monitoring of blood glucose levels for blood glucose control, antithrombotic therapy and drug therapy for erectile dysfunction. This guideline will update and replace all of NICE clinical guidelines 10 (footcare in type 2 diabetes) and 119 (inpatient management of footcare problems) and will replace the recommendations on foot care in NICE clinical guideline 15 (type 1 diabetes). This update is being undertaken to bring together all NICE diabetic foot guidance into one guideline. The guideline will consider the use of wound dressings, antibiotic and antimicrobial regimens and other adjunctive treatments (such as dermal or skin substitutes). The guideline unlikely to result in further additional impact on medicines resource use for the NHS. The EMA started an investigation in GLP-1 based treatments for diabetes (DPP-4 inhibitor and GLP-1 agonists) following the publication of a study that suggested an increased risk of pancreatitis and a possible link to pancreatic cancer in patients with type-2 diabetes treated with these agents. The EMA review concluded that presently available data do not confirm these concerns.

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Actions/ issues which may be considered by commissioners and providers

The redesign of diabetes services is underway in many CCGs so that more care is provided in the community setting instead of referral into secondary care. Ensure that the medicines related aspects are included in any redesign - this may include insulin and exenatide/liraglutide start groups, for which agreed protocols should be developed.

Monitor and audit the use of dapagliflozin (and other SGLT2 inhibitors when available) to ensure that use is within NICE recommendations. This includes both starting and stopping criteria. Many specialists are approaching this drug with caution in view of the adverse effects observed in clinical trials, such as urinary tract and genital infections (which have been linked to the drug’s mechanism of action).

Insulin pumps and consumables are listed as an exclusion in the National Tariff for 13/14. A decision on funding will need to be agreed locally for these for indications outside NICE recommendations. Drug exclusions under Payment by Results 13/14 . Commissioners and providers should agree local prices for insulin pumps and consumables, and choice of pump and put in place local arrangements for monitoring activity. It should be noted that NHS England is the responsible commissioner for paediatric insulin pumps where the pump is provided through an approved specialised centre. If the centre is not an approved specialised centre, the funding will rest with the CCG.

Locally agree which statin will be used after NICE 1st line recommended simvastatin when treating lipids in people

with diabetes. Atorvastatin is off patent and the price has reduced considerably. Ensure local policy not only provides guidance on when to initiate the newer treatments for type 2 diabetes in line

with the NICE recommendations, but also when to stop them. This should be audited to ensure NICE criteria for stopping treatments are being followed.

Develop local guidance on self-monitoring of blood glucose by patients with type 2 diabetes. A recent UKMi Medicines Q&A document summarises the current available data in this area.

Commissioners may wish to refer to the following commissioning guides produced by NICE in relation to diabetes: insulin pump services, patient education programmes for type 2 diabetes, and foot care services.

To support commissioners, the Parliamentary and Stakeholder Diabetes Think Tank published a briefing which brings together examples of best practice, and sets out recommendations on how local QOF and CQUIN schemes can deliver for local patients with diabetes.

Organisations may find the “How to Why to” guide from the NHS Technology Adoption Centre (NTAC) useful when setting up an insulin pump service.

Map of Medicine has produced a “Productivity Considerations” briefing for those designing diabetes services. The document highlights various interventions to help achieve productivity improvements while maintaining the quality and safety of clinical care.

Osteoporosis

Addition of osteoporosis related

indicators to QOF

This is an area of low financial risk

Three osteoporosis indicators were introduced in the QOF (OST1, OST2 and OST3) in 2012/13. Although these are likely to lead to increased diagnosis and treatment, they are unlikely to result in significant additional spend on drugs for osteoporosis as both alendronate and risedronate are now available generically.

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Osteoporosis

NICE guideline on falls in older people (update of previous guideline), issued Jun 2013

NICE guideline on the assessment and management of complex fractures, expected Jun 2015

NICE guideline on the diagnosis, management and follow up of fractures (non-complex), expected Jun 2015

NICE Quality Standards on (i) fractures (exc. head and hip), (ii) falls in a care setting, (iii) complex fractures and (iv) osteoporosis, under development, expected dates TBC

This guideline extends and replaces previous NICE guidance in this area. New recommendations have been added about preventing falls in older people during a hospital stay. The costing statement for this guideline states that the section of the guideline on preventing falls in older people living in the community was originally published in 2004, and the content is unchanged. It will result in new costs only if organisations have failed to implement it previously. The new inpatient section of the guideline is unlikely to have a significant cost impact for the NHS, as most components of multifactorial assessment and multifactorial intervention (assessing mobility and continence) are already standard practice.

In October 2012 the National Osteoporosis Society and Age UK launched the Falls and Fractures Declaration. Every organisation that has signed the Declaration has agreed to join the new Falls and Fractures Alliance, which is committed to reducing the rate of hip fractures and falls related injuries in older people over the next five years. These two guidelines are part of 5 being developed by NICE relating to trauma. With respect to prescribing, both will discuss pain relief (opioids and non-opioids). The complex fractures guideline will also discuss wound management of open fractures (including dressings). These guidelines are unlikely to have additional significant impact on medicines spend. These Quality Standard topics have been referred to NICE and are at an early stage of development.

Actions/ issues which may be considered by commissioners and providers

Organisations may wish to refer to a briefing document from the NHS Confederation on new approaches to integrated falls prevention services (May 2012).

The costing statement for the NICE denosumab guidance suggests that the initial prescribing will be started in secondary care via a hospital outpatient appointment. It will subsequently be delivered almost exclusively in primary care. However, it is acknowledged that GPs may be cautious about administering a new therapy, particularly a monoclonal antibody, in a primary care setting following initiation in secondary care. If denosumab is not administered in primary care after the initial dose, commissioners will have recurring costs due to additional outpatient activity. Develop appropriate protocols for denosumab to enable GPs to take on continued prescribing in the primary care setting (e.g. shared care). A recent DTB article reviewed the evidence base for the use of denosumab in postmenopausal osteoporosis.

The patent for zoledronic acid expired in May 2013 and generic preparations are now available. Savings are possible in this area and commissioners should ensure any tariffs that include this drug have taken any price reductions/discounts into account.

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Fertility NICE guideline on fertility (review),

issued Feb 2013

This is an area of moderate financial risk

This clinical guideline updates and replaces the previous NICE guideline on fertility (February 2004). New and updated recommendations have been included in areas of diagnosis and treatment for fertility problems. The revised guideline increases uptake of IVF as it raises the age limit to 42 years for one cycle of IVF and supports provision of the 3 full cycles of IVF to women under 40 years, provided certain criteria are met. The guideline does however note that if the woman reaches the age of 40 during treatment, the current full cycle should be completed further full cycles should not be offered. The previous guideline had recommended that couples in which the woman is aged 23-39 years at the time of treatment and who have an identified cause for their fertility problems or who have infertility of at least three years' duration should be offered up to three

stimulated cycles of IVF treatment.

The costing template and report for this guideline focus on the recommendations within the guideline likely to have the most significant resource impact. This includes the revised criteria for referral for IVF: “In women aged under 40 years who have not conceived after 2 years of regular unprotected intercourse or 12 cycles of artificial insemination (where 6 or more are by intrauterine insemination) offer 3 full cycles of IVF, with or without intracytoplasmic sperm injection (ICSI).”

The costing report states that if commissioners move to being consistent with access to IVF services across the NHS, in line with the previous NICE guideline, there is likely to be an increase in the annual recurrent cost of around £129,000 for IVF treatment per 100,000 population once a steady state is reached. It is anticipated that implementation of the recommendations may occur over 3 years and that it would take this time to reach a steady state. The total cost of offering IVF treatment to women aged 40–42 years in line with the recommendations is not included in the costing model. Based on expert opinion, women aged 40–42 years do not currently receive NHS-funded IVF treatment and it is anticipated that only a small number of women will become eligible to receive such treatment.

Actions/ issues which may be considered by commissioners and providers

Use the costing template for the fertility guidance to assess whether there is a cost implication locally of providing IVF to women in the higher age bracket (aged 40-42 years).

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7. Obstetrics, gynaecology and urinary tract disorders Patent expiries According to Prescribing Outlook New Medicines 2013, the following patent

expiries (which may have a significant impact on prescribing costs) are due within the next couple of years: ulipristal acetate (Jun 2014); darifenacin (Mar 2015)

Incontinence

NICE guidance on mirabegron for overactive bladder, issued Jun 2013

NICE guideline on urinary incontinence in women (update), issued Sep 2013

NICE pathway also available.

NICE supports the use of mirabegron (a beta-3-adrenoceptor agonist) as an option for treating the symptoms of OAB only for people in whom antimuscarinic drugs are contraindicated or clinically ineffective, or have unacceptable side effects. The costing template for this guidance estimates an annual cost of ~£41,000 per 100,000 population per year. This is made up of £33K from the increased use of mirabegron and ~£8K from increased specialist consultations and is based on 20% of eligible people receiving mirabegron. This guideline updates and replaces the previous NICE guideline on urinary incontinence in women (October 2006). Lifestyle interventions (including physical therapies) should be tried before moving onto pharmacological agents, e.g. pelvic floor muscle training. With respect to medicines, the recommendations include: Prescribe the lowest recommended dose when starting a new

overactive bladder (OAB) drug treatment Offer one of the following choices first to women with OAB or mixed UI:

o oxybutynin (immediate release), or o tolterodine (immediate release), or o darifenacin (once daily preparation)

Do not offer oxybutynin (immediate release) to frail older women If the first treatment for OAB or mixed UI is not effective or well-

tolerated, offer another drug with the lowest acquisition cost (from the following drugs: darifenacin, fesoterodine, oxybutynin (immediate release), oxybutynin (extended release), oxybutynin (transdermal), oxybutynin (topical gel), propiverine, propiverine (extended release), solifenacin, tolterodine (immediate release), tolterodine (extended release), trospium and trospium (extended release)

Offer a transdermal OAB drug to women unable to tolerate oral medication

Offer a face-to-face or telephone review 4 weeks after the start of each new OAB drug treatment

The guideline also makes recommendations relating to the use of botulinum toxin A bladder wall injection. It recommends that bladder wall injection with botulinum toxin A should be offered to women with OAB caused by proven detrusor over activity that has not responded to

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Incontinence cont’d NICE guideline on urinary

incontinence in women (update), cont’d

NICE Quality Standards on lower

urinary tract symptoms (LUTs), issued Sep 2013

NICE Quality Standard on Urinary

incontinence in women, expected date TBC

conservative management (including OAB drug therapy).

The costing statement for this guideline notes that many of the variables could not be estimated and because there is considerable variation in local practice in a number of the areas where recommendations have been changed. For example, prescribing patterns for drugs treating OAB; the cost of these drugs; the increase in the use of botulinum toxin A, and the decrease in the use of sacral nerve stimulation will all depend on local circumstances. NICE therefore encourages organisations to evaluate their own practices against the recommendations in the NICE guideline and assess costs locally.

With respect to pharmacological treatment, the statement suggests that it is anticipated that the recommendations on prescribing OAB drugs are likely to lead to savings on medicines spend in most areas. It anticipates that the guidance will increase the use of botulinum toxin A, which is likely to involve additional spend. Based on the health economic model developed alongside the guidance update, treatment with botulinum toxin A costs £493, with additional drug cost for 200 units of £276. Each nursing review costs £70, and botulinum toxin A is expected to last around 6–12 months. An average total treatment cost is around £1100 per person treated, per annum.

Using the mirabegron costing template: If it is assumed a proportion of people failing mirabegron will be

considered for botulinum toxin A (as they would have already been considered for antimuscarinincs)

The template estimates 144 people per 100,000 population may try mirabegron

Of these 99 people per 100,000 population will discontinue treatment If 25% of these (or 25 people per 100,000 population) go on to try

botulinum toxin A at a cost per person per annum of £1100

Then this could result in an additional cost of £27,500 per 100,000 population per year. Some of this activity may already be occurring, therefore users should try and estimate this where possible. This Quality Standard covers the diagnosis and management of LUTS in men (18 years and older). This Quality Standard topic has been referred to NICE and is at an early stage of development.

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Actions/ issues which may be considered by commissioners and providers

The patent for sildenafil expired in June 2013 and generic preparations are now available. The price reduced in October 2013. In view of this agree a local policy on choice of PDE5 agents for the treatment of erectile dysfunction.

NICE has published commissioning guides aimed at helping health professionals in England to commission the following: an effective service for the conservative management of urinary incontinence in women an effective paediatric continence service an effective service for the management of lower urinary tract symptoms in men

Botulinum toxin is listed as an exclusion in the national Tariff for 13/14. A decision on funding will need to be agreed locally for this agent for use outside NICE recommendations. Drug exclusions under Payment by Results 13/14

Benign prostatic hyperplasia (BPH) NICE guidance on tadalafil for benign

prostatic hyperplasia, suspended

Tadalafil 5mg was approved in the EU for once-daily treatment of the signs and symptoms of benign prostatic hyperplasia in adult males, including those with erectile dysfunction, in October 2012. The manufacturer of tadalafil has informed NICE that they will not provide an evidence submission for this appraisal, and it has therefore been suspended. This is therefore unlikely to result in any cost impact over the next year.

Contraception NHS Information Centre annual report

on contraceptive services, Oct 2012 NICE Quality Standard on

contraceptive services (including emergency contraception), expected date TBC

MHRA reminder – oral retinoids and

pregnancy prevention programme, Jun 2013

The NHS Information Centre has published an annual report on NHS community contraceptive clinics (excludes GP and outpatient clinics). This notes that there were 2.5 million attendances made by 1.4 million individuals (decrease of 4% and increase of 7%, respectively, since last year), and that oral contraception remains the most common primary method (45% of women attending). Use of LARC continues to increase, accounting for 28% of primary methods (same as 2010/11, up from 26% in 2009/10); there were 1.3 million prescriptions overall. Emergency hormonal contraception was dispensed at community contraceptive clinics on 128,000 occasions (decrease of 5% on 2010/11) – this number has been steadily declining since it became available over the counter. This Quality Standard topic has been referred to NICE and is at an early stage of development. The MHRA reminded healthcare professionals that the risk of foetal malformation with oral retinoids is extremely high, even when used at a low dose or for a short time during pregnancy. Women of child-bearing potential should have pregnancy excluded before starting treatment. While taking these medicines, one - or preferably two - different forms of contraception must be consistently used.

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Antenatal and intrapartum care NICE guideline on ectopic pregnancy

and miscarriage, issued Dec 2012

NICE guideline on intrapartum care, expected Oct 2014

NICE guideline on pre-term labour and

birth, expected date TBC

NICE Quality Standard on intrapartum

care, expected date TBC

This guideline covers the diagnosis and management of ectopic pregnancy and miscarriage in early pregnancy (up to 13 completed weeks of pregnancy). The guideline includes some brief recommendations on pharmacological interventions, such as methotrexate as a management strategy in ectopic pregnancy. The costing report and template for this guideline focus on the recommendations likely to have a significant resource impact. This includes the recommendation to offer systemic methotrexate as a first-line treatment to women with ectopic pregnancy who are able to return for follow-up and fit the specified criteria in the recommendation. The report notes that use of methotrexate is not anticipated to result in a change in practice for most services, notably large centres where woman have 24-hour access to care. The report adds that an increase in the use of methotrexate is likely to result in savings locally (vs. open or laparoscopic surgery) and that these savings should be estimated locally. This guideline will focus on the care of healthy women and their babies during childbirth. The final scope indicates that some pharmacological interventions will be covered (such as pain control and the use of oxytocin), however the guideline is unlikely to have a significant financial impact on medicines spend. This guideline is at an early stage of development, but the final scope states that the following pharmacological strategies will be included: Antenatal antibiotic prophylaxis for women diagnosed with preterm

pre-labour rupture of membranes Use of progesterone/progestogens for women with suspected or

diagnosed preterm labour to improve the outcomes of preterm labour. Use of tocolytic agents (e.g. beta-sympathomimetics, oxytocin receptor

antagonists, calcium channel blockers, cyclo-oxygenase enzyme inhibitors, NSAIDs, nitroglycerin, magnesium sulphate) for women with suspected or diagnosed preterm labour to improve the outcomes of preterm labour

Interventions to improve neonatal outcomes including maternal corticosteroids for fetal lung maturation and magnesium sulphate for preterm neonatal neuroprotection

This guideline is unlikely to result in a significant financial impact on medicines spend. This Quality Standard topic has been referred to NICE and is at an early stage of development.

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Renal NICE guideline on acute kidney injury,

issued Aug 2013 NICE pathway available. NICE guideline on chronic kidney

disease (update), expected Jul 2014

This guideline offers advice on the prevention, detection and management of acute kidney injury (AKI; formerly known as acute renal failure) up to the point of renal replacement therapy. It is well established that assessment of acute kidney injury in the UK is often suboptimal, and the purpose of this guideline is to address variations in care.

The guideline includes advice on investigations for AKI, for example in patients on potentially nephrotoxic drugs, such as NSAIDS or ACE inhibitors/ARBs. With respect to pharmacological management of AKI, the guideline states that loop diuretics and low dose dopamine should not be routinely offered to treat AKI. Loop diuretics may be considered for treating fluid overload or oedema while: - an adult, child or young person is awaiting renal replacement therapy or - renal function is recovering in an adult, child or young person not receiving renal replacement therapy.

The costing statement for this guideline acknowledges that there is considerable variation in the recognition, assessment, initial treatment and referral for AKI. Commissioners should review local practice. However, it is it is anticipated that implementing the guideline would improve detection of AKI and thus significantly decrease costs associated with complications. The size of the overall saving is dependent on local practice and is not quantified.

This guideline will cover the early identification and management of chronic kidney disease (CKD) in adults in primary and secondary care, and will be a partial update of the current guideline (NICE clinical guideline 73).

The following areas in the original guideline will be updated:

Classification and investigation of CKD (measurement of kidney function and markers of damage, and frequency of monitoring)

Self management (e.g. dietary interventions The choice of renin-angiotensin-aldosterone system antagonists

including aldosterone antagonists for blood pressure control Efficacy and safety of antiplatelet and antithrombotic therapy for

reducing cardiovascular disease in people with CKD. Uric acid lowering therapy in people with CKD. Vitamin D supplementation in the management of renal bone disease

in people with CKD.

In addition, the guideline will discuss for the first time: the management of acidosis with bicarbonate supplementation, and the risk of developing CKD after an episode of AKI. The guideline is at an early stage of development and no information on its likely cost impact is available. However, as this is an update of previous guidance, it is unlikely to result in a significant additional impact on medicines spend in this area.

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Renal cont’d

NICE Quality Standard on acute kidney injury, expected Oct 2014

NICE Quality Standard on renal

replacement therapy services, expected date TBC

This Quality Standard is currently under development. This Quality Standard topic has been referred to NICE and is at an early stage of development.

Actions/ issues which may be considered by commissioners and providers

Users may wish to refer to the NICE commissioning guide on the early identification and management of chronic kidney disease in adults (July 2012)

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9. Nutrition and blood Anaemia NICE clinical guideline on anaemia

management in people with CKD, expected date TBC

This is an area of low financial risk

This guideline is at an early stage of development, but will review and update the previous guideline in this area (2011). It is unlikely that this review will result in a in a significant change in resource use in the NHS. Note: Although NHS England is now the responsible commissioner for erythropoietins in CKD, the guideline’s content will be useful for CCGs and hospital Trusts.

Platelet disorders NICE guidance on the use of

eltrombopag for the treatment of chronic (immune) ITP, issued Jul 2013

This is an area of moderate financial risk

This guidance reviewed previous guidance (2010) on the use of eltrombopag within its licensed indication for the treatment of refractory chronic idiopathic (immune) thrombocytopenic purpura (ITP). The previous NICE guidance did not recommend eltrombopag for ITP.

However, this updated guidance now supports the use of eltrombopag as an option for treating adults with chronic (immune) ITP within its marketing authorisation (in adults who have had a splenectomy and whose condition is refractory to other treatments, or as a second-line treatment in adults who have not had a splenectomy because surgery is contraindicated), only if: (i) their condition is refractory to standard active treatments and rescue therapies OR (ii) they have severe disease and a high risk of bleeding that needs frequent courses of rescue therapies and the manufacturer provides eltrombopag with the discount agreed in the

patient access scheme

The costing statement for this guidance states that NICE does not expect implementation to result in a significant impact on NHS resources. This is because the number of people eligible for treatment is small. Eltrombopag is an alternative treatment option to romiplostim. Any newly diagnosed people may be treated with either drug and some eligible people who are already receiving romiplostim may choose to continue on that treatment.

.

Actions/ issues which may be considered by commissioners and providers

Eltrombopag and romiplostim are listed as exclusions in the National Tariff for 13/14. A decision on funding will need to be agreed locally for these agents if used outside NICE recommendations. Drug exclusions under Payment by Results 13/14

As there are now two agents supported as an option by NICE for the treatment of ITP, commissioners and providers should agree a treatment pathway detailing place in therapy of each treatment and whether sequential therapy will be supported.

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Nutrition

National spend on oral nutrition products

NICE guideline on the use of intravenous fluid therapy in hospitalised adult patients, expected Dec 2013.

NICE guideline on the management of hyperphosphataemia in patients with stage 4 or 5 CKD, issued Mar 2013

This is an area of moderate financial risk (service implications and oral nutritional supplements)

Spend on oral nutrition products increased by 6% in 12/13 compared to the previous year although prescription numbers decreased. This is an area NHS organisations could make savings on working collaboratively across primary and secondary care. This guideline is unlikely to have a significant impact on medicines spend. It will, however, aim to improve safety by advising on how prescribing errors could be reduced in this area

The draft version of this guideline notes that recommendations are provided about general principles for managing I/V fluids, and applies to a range of conditions and different settings. It does not include recommendations relating to specific conditions. The aim of the guideline is to help prescribers understand: The aim of the guideline is to help prescribers understand the: physiological principles that underpin fluid prescribing pathophysiological changes that affect fluid balance in disease states

indications for IV fluid therapy reasons for the choice of the various fluids available and principles of assessing fluid balance

It is hoped that the guideline will lead to better fluid prescribing in hospitalised patients, reduce morbidity and mortality, and lead to better patient outcomes. This guideline offers best practice advice on the care of adults, children and young people with stage 4 or 5 CKD who have, or are at risk of, hyperphosphataemia. The guideline considers phosphate binders (sevelamer hydrochloride, lanthanum carbonate, magnesium/ calcium carbonate combinations, aluminium-based phosphate binders) in adults and children and also covers dietary restriction of phosphate (efficacy and adherence). The costing report and template for the guideline focus on the recommendations that are likely to have the greatest resource impact and therefore require the most additional resources to implement or can potentially generate the biggest savings. In terms of medicines, these include: For children and young people, offer a calcium-based phosphate binder

as the first-line phosphate binder. For adults, offer calcium acetate as the first-line phosphate binder

Oral nutrition: £286.6m (or £540,000 per 100,000 population) – includes £89m spend on foods for special diets. This figure represents a 6% increase in spend and a 5% decrease in prescriptions on the previous year.

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Nutrition cont’d

NICE guideline on the management of hyperphosphataemia in patients with stage 4 or 5 CKD, cont’d

NICE Quality Standard on nutrition support in adults, issued Nov 2012

NICE Quality Standards on i/v fluids in children, i/v fluids in hospitalised adults, TPN in neonates, and nutrition in hospital under development, expected dates TBC

MHRA – suspension of licences for

hydroxyethyl starch (HES) intravenous infusion, Jun 2013

The report notes that implementation of the guideline is likely to reduce the number of people being prescribed sevelamer hydrochloride or lanthanum carbonate. The potential savings per person arising due to changes in prescribing are: - Changing from sevelamer hydrochloride to either calcium carbonate or calcium acetate will result in annual savings of £2,186 or £2,096 per person respectively in adults - Changing from lanthanum carbonate to either calcium carbonate or calcium acetate will result in annual savings of £1,806 or £1,716 per person respectively in adults. However, due to the small number of patients who would be affected by the guidance, commissioners are advised to calculate costs on a case by case basis and use the local costing template to ascertain the resource impact for their population. Note: Although NHS England is now the responsible commissioner for

sevelamer and lanthanum in CKD, the guideline’s content will be useful for CCGs and hospital Trusts. This quality standard covers adults (18 years and older) in hospital and the community who are at risk of malnutrition or who have become malnourished, and adults who are receiving oral nutrition support, enteral or parenteral nutrition.

These Quality Standard topics have been referred to NICE and are at an early stage of development. Results from large randomised clinical trials have reported an increased risk of renal dysfunction and mortality in critically ill or septic patients who received HES compared with crystalloids. The MHRA concluded that the risks of HES products for plasma volume expansion outweigh the benefits in all patient groups and clinical settings. The licences for all HES products have therefore been suspended.

Actions/ issues which may be considered by commissioners and providers

Develop local policy on the use of enteral nutrition feeds and consider commissioning arrangements across primary and secondary care for the provision of nutritional support feeds and supplements.

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10. Musculoskeletal and joint diseases Patent expiries According to Prescribing Outlook New Medicines 2013, the following patent

expiries (which may have a significant impact on prescribing costs) are due within the next couple of years: infliximab (Feb 2015)

NSAIDs

QIPP area – NSAIDs EMA and MHRA – diclofenac

contraindications strengthened, Jun 2013

A set of comparators has been developed to support the QIPP medicines use and procurement workstream. The aim of the comparators is to support organisations and prescribers to review the appropriateness of prescribing, revise prescribing where appropriate and monitor implementation. The NSAID area suggests that prescribers should: (i) review the appropriateness of NSAID prescribing widely and on a routine basis, especially in people who are at higher risk of both gastrointestinal and cardiovascular morbidity and mortality (for example, older people) (ii) If an NSAID is needed, use ibuprofen (1200 mg per day or less) or naproxen (1000 mg per day or less). (iii) Review and, if appropriate, revise prescribing of etoricoxib to ensure it is in line with MHRA advice and the NICE clinical guideline on osteoarthritis The following comparators are available for this QIPP area: ADQ/STAR-PU: the total number of average daily quantities (ADQs) of

all NSAIDs prescribed per Specific Therapeutic Group Age-sex weightings Related Prescribing Unit (STAR-PU).

Ibuprofen & naproxen % items: the total number of ibuprofen and naproxen items prescribed as a percentage of the total number of all NSAID prescription items.

The EMA’s Pharmacovigilance Risk Assessment Committee (PRAC) recommended updates to the treatment advice for diclofenac in view of findings from a Europe-wide review of the cardiovascular safety of NSAIDs. The review found further evidence that the arterial thrombotic risk with diclofenac is similar to that for the selective COX-2 inhibitors. Consistent with COX-2 inhibitors, diclofenac is now contraindicated in those with: ischaemic heart disease; peripheral arterial disease; cerebrovascular disease; or established congestive heart failure (New York Heart Association [NYHA] classification II–IV). The new treatment advice applies to systemic formulations (i.e., tablets, capsules, suppositories, and injection available both on prescription and via a pharmacy, P); it does not apply to topical (i.e., gel or cream) formulations of diclofenac.

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Rheumatology

Rheumatoid Arthritis (RA)

NICE Quality Standard on RA, issued Jun 2013

NICE Quality Standard on

seronegative arthropathies, expected date TBC

NICE guidance on the use of

abatacept for the treatment of RA only after the failure of conventional DMARDs (review), issued Apr 2013

NICE guidance on the use of tofactinib in RA after the failure of DMARDs, suspended

This is an area of moderate financial risk

This quality standard covers the diagnosis and management of rheumatoid arthritis in adults (16 years and older). This Quality Standard has been referred to NICE and is at an early stage of development.

NICE recommends abatacept in combination with methotrexate as an option for treating RA in adults whose disease has responded inadequately to 2 conventional disease-modifying anti-rheumatic drugs (DMARDs), including methotrexate, only if: it is used in accordance with the recommendations for other biological

DMARDs set out in NICE TAG 130 (first line biologic therapy) and the manufacturer provides abatacept with the discount agreed in the

patient access scheme The costing statement acknowledges that the guidance is not expected to have a significant impact on NHS resources as it only represents a further treatment option amongst many other existing treatments after the failure of conventional DMARDs for people with RA. There are now several biologic agents approved for use in RA where: 1. the disease has responded inadequately to conventional DMARDs

only, including methotrexate and/or 2. for the treatment of RA in adults whose RA has responded

inadequately to other DMARDs, including a TNF inhibitor - i.e. sequential use, where rituximab is not appropriate – that is response is inadequate, or it is contraindicated/not tolerated

As usage is likely to be a substitution of one agent for another, it is unlikely that there will be a significant impact on spend in this area

(as long as NICE criteria for initiating and stopping the drug are being adhered to). Organisations should agree which agents will be preferred based on locally negotiated discounts. Tofacitinib (Xeljanz

®) is an orally administered selective inhibitor of the

Janus kinase (JAK) family of kinases, including JAK1 and JAK3 and acts as a targeted immunomodulating agent. This guidance is indefinitely suspended following a negative opinion and refusal of a marketing authorisation for the drug from the CHMP. Tofacitinib is unlikely to have a financial impact in this area over the next year.

Data from the HSCIC show that in 2012 the NHS in England spent a total of £216.5m on etanercept (a decrease of 0.5% on the previous year), £121.7m on infliximab (an increase of 9.5% on the previous year), £265.7m on adalimumab (an increase of 18% on the previous year), £11m on golimumab (more than a 5-fold increase on the previous year), £12m on certolizumab (a 56% increase on the previous year), £14.5m on tocilizumab (almost double last year’s spend) and £3.2m on abatacept (a 70% increase on 2011). Usage is not separated by indication. Total spend on these agents was approximately £644.6m (or £1.21m per 100,000 population). This represents an overall 12.5% increase on the previous year. The report notes that adalimumab incurred the greatest cost in hospitals. It does not include anakinra, which received a negative NICE appraisal. Spend on rituximab totalled £121.7m (an increase of 14% on the previous year). It is not possible to separate usage by indication for rituximab.

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Rheumatology cont’d RA cont’d

NICE guidance on the use of adalimumab, etanercept, infliximab, certolizumab pegol and golimumab for the treatment of RA, expected date TBC

This guidance will review previous sets of guidance in this area and it is therefore unlikely to result in a significant impact on NHS resources.

Ankylosing spondylitis (AS) NICE guidance on adalimumab,

etanercept infliximab and golimumab for treating AS and non-radiographic axial spondyloarthritis (including review of previous guidance - TA143 and TA233), expected Jan 2015

This guidance is at an early stage of development. However, as it will review previous guidance in this area, it is unlikely to have further additional significant impact on NHS resources.

Psoriatic Arthritis (PsA) NICE guidance on the use of

ustekinumab for the treatment of active and progressive PsA, expected May 2014

Ustekinumab was approved for use in PsA in September 2013. The exact licensed indication covers its use alone or in combination with methotrexate for the treatment of active PsA in adult patients when the response to previous non-biological DMARD therapy has been inadequate. NICE guidance already supports the use of adalimumab, etanercept, infliximab (TA199) and golimumab (TA220) in PsA, provided certain criteria are met. Ustekinumab will compete with these agents and therefore costs are likely to be a substitution of one agent for the other.

Actions/ issues which may be considered by commissioners and providers

Cytokine modulators, such as TNF-inhibitors are listed as exclusions in the National Tariff for 13/14. A decision on funding will need to be agreed locally for these agents for indications outside NICE guidance. Drug exclusions under Payment by Results 13/14 . As of April 2013, NHS England is the responsible commissioner when anti-TNFagents are used in children (aged 18 years or younger). CCGs are the responsible commissioners for use of these agents in adults.

There are now several biologics approved by NICE for the treatment of RA. Commissioners and providers should locally agree a treatment pathway in these patients, including preferred choices for 1

st and sequential line use.

Similarly, locally agree treatment pathway for JIA, AS and PsA including use of biologic agents. Some organisations have included the use of sub-cutaneoues methotrexate prior to progressing to biologics in

their treatment pathways as this step could delay the need for TNF inhibitors in some patients and therefore reduce costs.

Commissioners may wish to refer to the commissioning guide produced by NICE for the use of biologic drugs for the treatment of inflammatory disease in rheumatology, dermatology and gastroenterology to aid these decisions. NICE has also produced a guide for Support for Commissioning for RA

Trusts should consider auditing this area of prescribing to ensure that any variations to the drug regimens recommended in the NICE guidance are appropriate

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Spasticity

NICE clinical guideline on the management of multiple sclerosis in primary and secondary care (update), expected Oct 2014

This area could have a moderate financial impact

A review of the NICE Clinical Guideline on the management of multiple sclerosis (MS) in primary and secondary care is underway and advice on Sativex will be included in the remit of the guideline. The final scope includes the pharmacological management of spasticity using baclofen, tizanidine, gabapentin, dantrolene, benzodiazepines, botulinum toxin, pregabalin and Sativex.

Sativex is licensed as add on therapy for symptom improvement in patients with moderate to severe spasticity due to MS who have not responded adequately to other anti-spasticity medication and who demonstrate clinically significant improvement in spasticity related symptoms during an initial trial of therapy.

Whilst there are legitimate questions about the strength of the evidence base to support to this form of treatment costs around £4,200 per year to treat a patient started on Sativex and therefore it does represent a potential cost pressure.

A LNDG review on Sativex estimates: - There are approximately 100,000 patients with MS in the UK, and of these, 84% (84,000) are affected with spasticity - Of these, 28,500 have either moderate (17%) or severe/total (17%) spasticity and 21,134 will use medication (69% and 79% respectively). - Combination therapy is used by 33% of patients with moderate and 46% of patients with severe/total spasticity (11,567) - It is assumed that 50% of these (5,784) will use Sativex. This equates to approximately 9 users per 100,000. Sativex costs £375 for 3x10ml sprays, or a cost per spray of £1.25. If 9 patients were initially treated for 1 month, and 50% continued on therapy at a cost per patient of £375 per month, the annual cost impact would be around £22,000 per 100,000 population. The Peninsula Health Technology Commissioning Group (December 2010) concluded that although the clinical case for Sativex is supportable, it is not cost effective and therefore should not be routinely commissioned for that geographical region. The Group note that there are no robust long term efficacy data, with the longest trial lasting four months in duration. Similarly, in October 2010, the NETAG (legacy website) concluded that Sativex® should not be used within NHS North East as clinical evidence for its efficacy was considered to be of low quality and demonstrated a modest but clinically unclear benefit. In addition, the high acquisition cost of Sativex® made it unlikely to meet conventional cost-effectiveness criteria. The SMC was unable to recommend Sativex in NHS Scotland as no submission was received from the marketing holder.

Sativex: £829K (or ~£1,600 per 100,000 population). Note: this is spend in primary care only and is similar to the previous year.

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Spasticity cont’d

NICE guidance on the use of collagenase clostridium histolyticum for treating Dupuytren's contracture, expected Jan 2015

This area could have a moderate financial impact

Collagenase clostridium histolyticum (Xiapex®) is licensed for the treatment

of Dupuytren's contracture in adult patients with a palpable cord. Dupuytren’s disease, also known as palmar fibromatosis, is a benign, slowly progressive condition of unknown origin. The disease is characterised by a thickening of the connective tissues in the palm, which form nodules and fibrous bands (cords). Most people with Dupuytren’s disease are affected in both hands. It can cause difficulty in extending the fingers leading to fingers fixed in a bent position which cannot be straightened and in that case it is called Dupuytren’s contracture. Treatment seeks to restore hand function and surgery is widely used and can be an effective treatment for hand impairment. Collagenase clostridium histolyticum is a fixed ratio mixture of two purified collagenolytic enzymes isolated from the bacterium Clostridium histolyticum. The collagenase breaks up the collagen fibres, which weakens and disrupts the cord, sometimes with the help of finger extension procedures. It is administered by intralesional injection. It costs £780 per injection (inc. VAT). Collagenase is administered as a 580mcg intralesional injection into the palpable cord. If necessary this can be repeated at intervals of approximately 4 weeks, maximum of 3 injections per cord. Only one cord may be treated at a time. Clinical study experience with collagenase is currently limited to up to 3 injections per cord and up to 8 injections in total. The final scope for this guidance notes that in the UK, the prevalence of Dupuytren’s disease ranges from 0.2-30%, varying widely with geographical location possibly due to genetics, environment, or a combination of both. It is more common in men than women, and is most commonly found in people of northern European descent. About 1 in 6 men in the UK over the age of 65 have some degree of Dupuytren's contracture. Hospital episode statistics data show that on average there were approximately 13,000 admissions for Dupuytren’s contracture per year between April 2003 and March 2008 in England and Wales (or 23 per 100,000 population per year). A NETAG review (legacy website) for collagenase states that it is likely to be considered as an alternative treatment option to surgical intervention for moderate to severe Dupuytren’s contracture. Evidence from clinical studies indicates that patients require an average of two injections per case. If collagenase is used in 25% of cases (or 6 patients per 100,000 population) and two injections are used per case, this would result in a drug cost of £9,360 per 100,000 population. The NETAG note that collagenase will incur outpatient admission costs for administration and subsequent digital extension. The cost is therefore estimated at nearly £2,000 per case

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Spasticity cont’d

NICE guidance on the use of collagenase clostridium histolyticum for treating Dupuytren's contracture, cont’d

when this is factored in. However, collagenase (when used at 2 injections or less) could result in savings vs. surgery. If 3 or more injections are used then collagenase is likely to be less cost-effective than surgery. the net cost impact of collagenase could be optimised by directing treatment at patients who will be expected to require fewer injections, for example patients with only one or two affected joints.

In May 2012 the SMC accepted collagenase for restricted use in NHS Scotland. Use is restricted to restricted for use as an alternative to limited fasciectomy in adult patients with Dupuytren’s contracture of moderate severity (as defined by the British Society for Surgery of the Hand (BSSH), with a palpable cord and up to two affected joints per hand, who are suitable for limited fasciectomy, but for whom percutaneous needle fasciotomy is not considered a suitable treatment option. Based on an estimated uptake of 16% (21 patients) in year 1 and 80% (104 patients) in year 5, the total impact on the Scottish medicines budget was estimated at £25k in year 1 (or £500 per 100,000 population) and £124k (or £2,500 per 100,000 population) in year 5.

Actions/ issues which may be considered by commissioners and providers

Botulinum toxin and collagenase (when used in outpatients) are listed as exclusions in the National Tariff for 13/14. A decision on funding will need to be agreed locally for these agents. Drug exclusions under Payment by Results 13/14

Sativex is not listed as an exclusion in the National tariff for 13/14. Commissioners and providers should agree the place in therapy locally for Sativex and if/how it will be commissioned. Shared care protocols should be developed where it is agreed that general practices will be asked to take on prescribing of this drug.

Osteoarthritis (OA)

NICE guidance on the use of diacerein for the treatment of OA, expected date TBC

NICE clinical guideline on the management of OA (update), expected Feb 2014

This guidance is unlikely to impact over the next year

Diacerein is not currently licensed in the UK. It acts differently from traditional NSAIDs which inhibit prostaglandin synthesis, leading to adverse gastrointestinal effects. It has been proposed that diacerein acts as a slow-acting, symptom-modifying and perhaps disease-structure modifying drug for OA. In November 2013 the EMA ‘s PRAC recommended suspension of diacerein-containing medicines in the EU following concerns over gastro-intestinal side effects (severe diarrhoea) and liver toxicity. This guidance is therefore not expected to have an impact on NHS resources. This guideline is unlikely to have a significant financial impact on medicines spend

This guideline will update the currently available version and with respect to medicines the final scope confirms that the updated guideline will cover:

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OA cont’d

NICE clinical guideline on the management of OA (update), cont’d

NICE Quality Standard on OA, expected date TBC

Glucosamine and chondroitin hyaluronan intra-articular injections etoricoxib NSAID and proton pump inhibitor fixed combination therapy paracetamol (especially adverse events)

With respect to pharmacological treatment, new recommendations in the draft version of this guideline include: Do not routinely offer paracetamol for the management of OA

(identified as a key priority). Be aware of the potential side effects and limited clinical benefit. If paracetamol is prescribed, prescribers should: - use it at the lowest effective dose for the shortest possible period

of time and - use cautiously if prescribing in combination with an oral NSAID

Do not offer intra-articular hyaluronan injections for the management of osteoarthritis

Do not offer glucosamine or chondroitin products for the management of osteoarthritis

The draft guideline also states that acupuncture should not be offered for the management of OA.

This Quality Standard topic has been referred to NICE and is at an early stage of development.

Gout

NICE guidance on the use of canakinumab in gouty arthritis attacks and reduction in frequency of subsequent attacks, terminated Apr 2013

NICE guidance on the use of pegloticase for treating severe debilitating chronic tophaceous gout, issued Jun 2013

This is an area of low financial risk

NICE is unable to recommend the use in the NHS of canakinumab for treating gouty arthritis attacks and reducing the frequency of subsequent attacks because no evidence submission was received from the manufacturer of the technology. NICE does not recommend pegloticase for treating severe debilitating chronic tophaceous gout in adults who may also have erosive joint involvement and in whom xanthine oxidase inhibitors at the maximum medically appropriate dose have failed to normalise serum uric acid, or for whom these medicines are contraindicated. The costing statement notes that as pegloticase is not recommended, it is unlikely to result in a significant change in resource use in the NHS.

Actions/ issues which may be considered by commissioners and providers

Pegloticase is listed as an exclusion in the National tariff for 13/14. A decision on funding will need to be agreed locally for this agent for use outside NICE recommendations. Drug exclusions under Payment by Results 13/14

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11. Eye Patent expiries According to Prescribing Outlook New Medicines 2013, the following patent

expiries (which may have a significant impact on prescribing costs) are due within the next couple of years: verteporfin (Jul 2014), and brinzolamide (Dec 2014).

Macular oedema

NICE guidance on the use of ranibizumab for the treatment of macular oedema caused by retinal vein occlusion (RVO), issued May 2013

NICE guidance on the use of ranibizumab for the treatment of diabetic macular oedema, issued Feb 2013

This is an area of major financial risk

NICE recommends ranibizumab as an option for treating visual impairment caused by macular oedema: following central retinal vein occlusion (CRVO) or

following branch RVO (BRVO) only if treatment with laser photocoagulation has not been beneficial, or when laser photocoagulation is not suitable because of the extent of macular haemorrhage and

only if the manufacturer provides ranibizumab with the discount agreed in the patient access scheme

The costing template for this guidance estimates a total recurrent additional cost of £114,000 per 100,000 population per year (based on the list price for ranibizumab and the incident population). The total cost includes and additional recurrent cost of £89,000 per 100,000 population per year for the drug and an extra £8,000 per 100,000 population for administration and monitoring costs. The total cost also includes a small saving of £500 per 100,000 population due to a change in adverse event related costs for people changing from dexamethasone to ranibizumab. It is assumed that 10% of people will be treated for 3 years, 29% each for 6 months, 1 year and 2 years respectively.

The costing template assumes that in the future 95% of eligible people will receive ranibizumab for this indication and 5% intravitreal dexamethasone and 0% bevacizumab. NICE recommends ranibizumab as an option for treating visual impairment due to diabetic macular oedema only if: the eye has a central retinal thickness of 400 micrometres or more at

the start of treatment and

the manufacturer provides ranibizumab with the discount agreed in the patient access scheme

The costing template for this guidance estimates additional recurrent costs of £100,000 per 100,000 population per year once steady state is achieved (assumed from year 4 onwards in the incident population, drug costs make up £90,000 per 100,000 population). The recurrent additional cost in year 1 is estimated at ~£52,000 per 100,000 population.

Data from the HSCIC show that in 2012, the NHS in England spent approximately £194m on ranibizumab (or ~£365,000 per 100,000 population). This represents an increase of 25% on the previous year. Data from the HSCIC show that in 2012 the NHS in England spent a total approximately £6.2m on intravitreal dexamethasone implant (~£12,000 per 100,000 population) – this is a more than 5-fold increase from the previous year. Data from the HSCIC show that in 2012, the NHS in England spent approximately £785K on verteporfin (~ £1,500 per 100,000 population) – a decrease of 19% from the previous year.

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Macular oedema cont’d

NICE guidance on the use of ranibizumab for the treatment of diabetic macular oedema, cont’d

NICE guidance on the use of

aflibercept treatment of macular oedema caused by central retinal vein occlusion, expected Apr 2014

NICE guidance on the use of fluocinolone acetonide intravitreal implant for treating chronic diabetic macular oedema after an inadequate response to prior therapy (rapid review of technology appraisal guidance 271), issued Nov 2013

A total non-recurrent cost of £341,000 is estimated over the 3 years after implementation. When the guidance is implemented, the prevalent population will become eligible. People may be treated over the next 3 years following the treatment regimen for ranibizumab, thus incurring non-recurrent costs. After this point, it is anticipated that only recurrent costs from treating the incident population will be incurred. The non-recurrent costs in year 1 are estimated at ~£168,000 per 100,000 population, taking the total year 1 costs for implementing this guidance to ~£220,000 per 100,000 population. In years 2 and 3 the total cost (recurrent and non-recurrent) is estimated at £178,000 and £173,000 per 100,000 population respectively.

The costs assume that in the future 15% of eligible people will be treated with laser treatment and 75% with ranibizumab, 5 % receive combination laser and ranibizumab treatment and 5% receive no active treatment. Overall 90% of patients are expected to respond positively to ranibizumab and are expected continue beyond 3 injections of treatment.

These costs do not take into account the Patient Access Scheme, and therefore, costs would be expected to be less than this.

This guidance will provide recommendations on the use of aflibercept 1st

line in patients with macular oedema caused by CRVO. The licence extension for aflibercept in this indication was launched in October 2013. Aflibercept will compete with ranibizumab and dexamethasone in this indication. If a patient access scheme is involved, the drug cost is likely to be similar between ranibizumab and aflibercept. Savings are possible through reduced service delivery costs (administration and monitoring) vs. ranibizumab.

In January 2013 NICE did not recommend the use of fluocinolone acetonide intravitreal implant for the treatment of chronic diabetic macular oedema considered insufficiently responsive to available therapies (TA271). However, after publication, the manufacturer agreed a patient access scheme with the Department of Health and submitted revised analyses to be considered in a rapid review of the original guidance. The updated guidance now recommends fluocinolone acetonide intravitreal implant as an option for treating chronic diabetic macular oedema that is insufficiently responsive to available therapies only if: the implant is to be used in an eye with an intraocular (pseudophakic)

lens and

the manufacturer provides fluocinolone acetonide with the discount agreed in the patient access scheme

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Macular oedema cont’d

NICE guidance on the use of fluocinolone acetonide intravitreal implant for treating chronic diabetic macular oedema after an inadequate response to prior therapy cont’d

SMC guidance on nepafenac (Nevanac) for postoperative macular oedema following cataract surgery in patients with diabetes

The costing template for this guidance estimates a net cost impact in England of £8.6 million in year 1 (or ~£16,000 per 100,000 population), £1.2 million in year 2 (or ~£2,300 per 100,000 population) and £1.3 million in year 3 (or ~£2,500 per 100,000 population). These costs are based on the list price of the drug (not the revised price from the patient access scheme, which is commercial in confidence). The unit cost of the implant is taken as £5,500 within the template. The Year 1 costs consist of: - Increased cost of fluocinolone acetonide intravitreal implant £7.85m - Increased cost of vitreous retinal procedures £544K - Increased cost of outpatient follow up appointments £244K The template assumes that: - 10% of people have chronic diabetic macular oedema insufficiently

responsive to other therapies (n=6,216) - Of these, ~61% have chronic diabetic macular oedema (n= 3,767) - Of these, 43% have had an intraocular (pseudophakic) lens (n= 1,586) In year 1, 90% of this population (n = 1,427) will receive the fluocinolone acetonide. There will be ongoing costs of outpatient follow up attendances which continue for 3 years after the procedure. The SMC accepted nepafenac (Nevanac®) for use in NHS Scotland, for the reduction in the risk of postoperative macular oedema associated with cataract surgery in diabetic patients. In the drug summary, the SMC states that approximately 5,219 patients in Scotland would be eligible to receive the drug in year 1, with an increase to 5,859 patients per year in year 5 (at a cost of £16,000 in year 1, and £52,000 in year 5), equating to 52,745 patients and 59,213 respectively in England, or 99 and 111 patients/100,000 population respectively. This equates to a cost of £300 per 100,000 population in year 1, and £985 per 100,000 population in year 5.

Age related macular degeneration (AMD)

NICE guidance on the use of aflibercept for wet age-related macular degeneration, issued Jul 2013

This is an area where savings may be achievable due to reduced service delivery costs.

NICE recommends intravitreal aflibercept as an option for treating wet AMD only if: it is used in accordance with the recommendations for ranibizumab in

NICE technology appraisal guidance 155 (re-issued in May 2012) and

the manufacturer provides aflibercept with the discount agreed in the patient access scheme.

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AMD cont’d

NICE guidance on the use of aflibercept for wet age-related macular degeneration, cont’d

NICE guideline on the diagnosis and management of macular degeneration, expected Jul 2015

The costing template for this guidance estimates an annual saving of £10,000 per 100,000 population, based on the standard assumptions in the model, once a steady state is reached (year 5 onwards). The savings are due to fewer appointments for monitoring and treatment. Drug costs are expected to remain the same. It is assumed that the prevalent population are receiving current standard treatment (if eligible) with ranibizumab. This is because people with the condition would usually begin treatment immediately after diagnosis to avoid sight loss. As both aflibercept and ranibizumab are soluble vascular endothelial growth factor (VEGF) receptor inhibitors, people previously treated with ranibizumab may not benefit from switching to aflibercept as a second-line treatment (the same would apply to people who start treatment with aflibercept); therefore there are no non-recurrent costs or change in costs associated with the prevalent population. The model assumes that currently 100% of people receive ranibizumab, and in the future (year 5 onwards), 30% will receive aflibercept and 70% ranibizumab. This guideline is at an early stage of development and no information on content or impact is currently available.

Choroidal neovascularisation (CNV)

NICE guidance on the use of ranibizumab for treating CNV associated with pathological myopia, issued Nov 2013

This is an area of low financial risk

NICE recommends ranibizumab as an option for treating visual impairment due to CNV secondary to pathological myopia when the manufacturer provides ranibizumab with the discount agreed in the patient access scheme. The costing statement for this guidance notes that the guidance means that ranibizumab is an option for treating CNV associated with pathological myopia. The guidance is unlikely to result in a significant change in resource use in the NHS as the estimated eligible population per year is small. Ranibizumab is an alternative treatment option to verteporfin photodynamic therapy (vPDT) and bevacizumab. The statement notes that any people newly diagnosed with CNV associated with pathological myopia who are eligible for treatment can be treated with ranibizumab, vPDT or bevacizumab. Commissioners and healthcare providers are reminded that the manufacturer of ranibizumab has agreed a patient access scheme with the Department of Health, in which a confidential discount is applied to all invoices.

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Vitreomacular traction (VMT) NICE guidance on the use of

ocriplasmin in VMT, issued Oct 2013

Ocriplasmin is a non-surgical treatment for VMT, (intravitreal injection). NICE recommends ocriplasmin as an option for treating VMT in adults, only if: an epiretinal membrane is not present and

they have a stage II full-thickness macular hole with a diameter of 400 micrometres or less and/or

they have severe symptoms.

The annual cost associated with implementing the guidance is estimated at £2million for England, based on assumptions in the costing template (or ~£3,800 per 100,000 population). For patients with macular hole, the costing template estimates: - that 100% of eligible patients (listed for surgery) will receive ocriplasmin before surgery. - Of these, 40% will achieve macular hole closure by day 28 of ocriplasmin treatment. - The condition will not be resolved in ~60% of patients (and these would therefore presumably be considered for surgery). For patients with VMT without macular hole, it is assumed: - 45% will be managed through “watch and wait” - 45% will be listed for surgery and will receive ocriplasmin before surgery. Of these, ~30% will experience a resolution of their VMT and 70% will not (and would therefore presumably go onto have surgery). - 10% will have severe symptoms but are not listed for surgery and will receive ocriplasmin. Of these 70% will not experience resolution of their symptoms. Although the costing template notes that there may be savings through reduced surgical procedures, ocriplasmin does represent an additional step and therefore cost where it is used but fails to resolve the VMT. These patients are still likely to go onto surgery. The recommended dose is 0.125 mg (0.1 ml of the diluted solution) to the affected eye once as a single dose. Repeated administration in the same eye is not recommended. The cost of one injection is £3000 (inc. VAT). The administration cost for ocriplasmin is give as £177 in the costing template. As repeat injections are not recommended, this is the cost for a full treatment course.

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Actions/ issues which may be considered by commissioners and providers

Locally agree pathways for various ophthalmology indications. For example, there are now 3 agents approved by NICE for use as options in macular oedema. Work should be undertaken to understand local pathways and agree place in therapy of these drugs (including whether sequential use will be accepted).

Aflibercept, bevacizumab, dexamethasone intravitreal implant, fluocinolone acetonide intravitreally, ocriplasmin, pegaptanib, ranibizumab and verteporfin are listed as exclusions in the National Tariff for 13/14. A decision on funding will need to be agreed locally for these agents for indications outside/not covered by NICE guidance. Drug exclusions under Payment by Results 12/13. . CCGs are the responsible commissioners for use of these drugs.

Commissioners may wish to refer to the commissioning guide produced by NICE on commissioning a service for people at risk of developing glaucoma.

Some centres are assessing the role of bevacizumab for AMD and other eye conditions such as CNV in view of the lower cost associated with its use. However, there have been some safety concerns about its use in this way. Although bevacizumab costs much less than other agents such as ranibizumab, it is unlicensed for any indication in the eye. Determine whether it is appropriate to support centres that are using intravitreal bevacizumab instead of the licensed products available to treat AMD and other eye related conditions and agree a commissioning decision in this area.

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13. Skin Patent expiries According to Prescribing Outlook New Medicines 2013, the following patent

expiries (which may have a significant impact on prescribing costs) are due within the next couple of years: infliximab (Feb 2015)

Psoriasis NICE guideline on psoriasis, issued

Oct 2012 NICE pathway available.

This clinical guideline covers the management of adults and children with psoriasis. Topical treatments are discussed first-line and the guideline recommends a particular sequence of prescribing deemed to be the most cost-effective according to health economic modelling: a potent corticosteroid; combined potent corticosteroid and vitamin D, and then a vitamin D analogue. Phototherapies and systemic non-biological agents (such as ciclosporin, methotrexate and acitretin) are discussed in the second-line setting and systemic biological therapies for third-line treatment. The latter incorporates existing NICE guidance on the use of ustekinumab (TAG 180), adalimumab (TAG 146), infliximab (TAG 134), and etanercept (TAG 103) where relevant. The guideline reviewed the literature for the use of a second biological drug and recommends that this can be considered in cases of primary or secondary failure, or where the first biological cannot be tolerated or becomes contraindicated. The costing report notes that two of the three recommendations estimated to have the greatest resource impact are treatment-related – the changes in topical prescribing sequence and the use of a second biologic drug. These could potentially lead to cost savings of around £15,000 and £730, respectively, per 100,000 people. There is significant regional variation and these are estimates only - the costing template should therefore be used to estimate local impact. The estimate regarding use of a second biological drug assumes that the proportion of patients not responding to first-line biological therapy who go on to receive a second biological increases from 70% to 90%, as expert opinion suggested that the majority of commissioners may already be implementing this guidance. The costing template assumes a 1.75% prevalence of psoriasis and that 2.5% are treated with a first-line biologic; 42.7% of these do not respond to a first course (around 19 per 100,000 population). It is not known how many patients currently received a second-line biological and current practice is likely to vary. The worst case scenario, assuming that this is currently not commissioned and that this will increase to 90% (17 per 100,000 population), then at an average cost of £10,527 per year, this would result in an increase spend on biologicals of £179,000 per population per year.

Data from the HSCIC indicate that in 2012 the NHS in England spent a total of £216.5m on etanercept (a decrease of 0.5% on the previous year), £121.7m on infliximab (an increase of 9.5% on the previous year), £265.7m on adalimumab (an increase of 18% on the previous year) and £22.8m on ustekinumab (an increase of 83% on the previous year). It is not possible to separate usage by indication.

Disease or Indication: National targets and guidance

Epidemiology, potential financial implications for a population of 100,000 and other comments

National spend in primary care (£) Apr 2012-Mar 2013 (Epact England data) plus limited data on secondary care prescribing

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Psoriasis cont’d NICE guideline on psoriasis cont’d Proposed appraisal referred to NICE:

secukinumab (1st or 2nd line) in moderate to severe plaque psoriasis

NICE Quality Standard on psoriasis,

published Aug 2013

It is expected that the resultant increase in response to treatment (estimated that 50% would respond) will result in reduced secondary care activity which may outweigh these increased costs. Overall the recommendations are expected to direct treatment from secondary to primary care. However additional assessment for co-morbidities may increase demand on related outpatient services. NICE has been invited to appraise the clinical and cost effectiveness of secukinumab for moderate to severe plaque psoriasis in people for whom other systemic therapies have been inadequately effective, not tolerated or contraindicated. Secukinumab is not currently licensed in the UK (licensing expected during 2014). The draft scope notes that the drug is a monoclonal anti-human interleukin-17A (IL-17A) antibody of the IgG1/kappa isotype. It is administered by subcutaneous injection and administered as five weekly loading doses then monthly maintenance doses (150 or 300mg). Secukinumab is likely to be similarly priced to and will compete with other biologic agents used in psoriasis, therefore costs are likely to be a substitution of one agent for the other. This quality standard covers the assessment and management of psoriasis in children, young people and adults

Wound care QIPP area - wound care

NICE guideline on the prevention and

management of pressure ulcers expected May 2014

A set of comparators has been developed to support the QIPP medicines use and procurement workstream. The aim of the comparators is to support organisations and prescribers to review the appropriateness of prescribing, revise prescribing where appropriate and monitor implementation.

The wound care products comparator considers the cost (NIC) per item.

This guideline is unlikely to result in a significant impact on medicines spend

This clinical practice guideline covers the prevention, assessment and management of pressure ulcers in all age groups and all settings (secondary, primary and community care). It will update and replace two previous clinical guidelines: ‘Pressure ulcers’ (clinical guideline 29; 2005) and ‘The use of pressure relieving devices’ (clinical guideline 7; 2003). It will also update recommendations on pressure ulcers in the clinical guideline on multiple sclerosis (clinical guideline 8, 2003). A draft version of this guideline was published for consultation in November 2013 and includes recommendations on debridement (including larval therapy), pressure-redistributing devices, nutritional interventions, antimicrobials and antibiotics, wound dressings, management of heel pressure ulcers and other therapies.

Disease or Indication: National targets and guidance

Epidemiology, potential financial implications for a population of 100,000 and other comments

National spend in primary care (£) Apr 2012-Mar 2013 (Epact England data) plus limited data on secondary care prescribing

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Wound care cont’d NICE Quality Standard on Pressure

Ulcers, expected date TBC

This Quality Standard has been referred to NICE and is at an early stage of development.

Eczema

NICE Quality Standard on atopic eczema in children, published Sep 2013

This quality standard covers the management of atopic eczema in children from birth up to the age of 12 years

Extemporaneous Specials British Association of Dermatologists

(BAD) specials list

This is an area in which significant cost savings may be realised

The British Association of Dermatologists (BAD) published an updated rationalised list of dermatology specials (2008) that may be manufactured for the treatment of dermatological conditions. It is hoped that these proposals will rationalise the present situation and improve reliability of supply. They may decrease costs overall.

Actions/ issues which may be considered by commissioners and providers

Demand management through service redesign may mean more patients are treated in primary care for simple dermatological conditions using condition specific protocols instead of being referred to secondary care.

Review use of wound care products locally and develop local guidelines, including community nursing services. This has the potential for releasing savings through a reduction in the inappropriate use of dressings, such as silver dressings.

Cytokine modulators, such as TNF-inhibitors are listed as exclusions in the National Tariff for 13/14. A decision on funding will need to be agreed locally for these agents for indications outside NICE guidance. Drug exclusions under Payment by Results 13/14 . As of April 2013, NHS England is the responsible commissioner when anti-TNFagents are used in children (aged 18 years or younger). CCGs are the responsible commissioners for use of these agents in adults.

Alitretinoin is listed as an exclusion in the National Tariff for 13/14. Drug exclusions under Payment by Results 13/14 A decision on funding will need to be agreed locally for this agent for indications outside NICE guidance.

Users may wish to refer to the NICE commissioning guide on biologic drugs for the treatment of inflammatory disease in rheumatology, dermatology and gastroenterology (2012).

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Patent expiries due 2013-2015

Key: * Drugs which have the greatest potential for generic/biosimilar preparations becoming available. ** Drugs where generic/biosimilar products are in later stages of EU licensing or are licensed in EU # Patent extended by 6 months (paediatric extension)

Month of patent

expiry

Year and drug

2013

2014

2015

January

February

Montelukast # Fosphenytoin sodium Ganirelix

Alemtuzumab Temoporfin Zanamivir *

Infliximab *

March

Dorzolamide plus timolol ** Zidovudine plus lamivudine Daclizumab

Somatropin (synthetic hGH)

Darifenacin Tegafur/ uracil

April

Basiliximab Memantine HCl Aripiprazole # *

May

Nelarabine Tirofiban Zoledronic acid** #

Anakinra Escitalopram oxalate

Clofarabine Glatiramer Insulin glargine #

June

Capecitabine** Nevirapine** # Sildenafil**

Abacavir Hydroxyethyl starch Moxifloxacin Ulipristal acetate*

Nepafenac Tenecteplase

July Etonogestrel Trastuzumab Verteporfin

Etanercept # Rasburicase

August

Raloxifene HCl** Rizatriptan** # Clopidogrel hydrogen Sulphate #

Palivizumab Bivalirudin Strontium ranelate

September

Cetuximab* Panitumumab

Etoricoxib Nateglinide Sirolimus Tiotropium *

October

Irbesartan plus hydrochlorothiazide

Aripiprazole* Nelfinavir mesylate Paliperidone

Alitretinoin

November

Efavirenz Rituximab*

Insulin glargine Icatibant acetate

Palonosetron Pimecrolimus

December

Telmisartan** Almotriptan Bevacizumab Brinzolamide* Omalizumab

Eletriptan Frovatriptan Lopinavir/ ritonavir Pemetrexed