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Generating and Communicating HEOR Evidence to Demonstrate Pharmaceutical Products’ Value: Recommendations for Chinese Payers on Evidence submission guidelines

ISPOR ASIA PACIFIC ANNUAL MEETING IN TOKYO | SEPTEMBER 9, 2018

• Xin (Cindy) Gao, PhD, Principal & Asia-Pacific Regional Lead, Pharmerit International, Bethesda, MD, USA & Shanghai, China • Rong Shao, Ph.D., Professor, Social and Administrative Pharmacy, China Pharmaceutical University, Nanjing, China• Shanlian Hu, MSc, MD, Professor, Fudan University and Shanghai Health Development Research Center, Shanghai, China;

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Agenda

Dr Cindy Gao

Prof. Shanlian Hu

Prof. Rong ShaoTranslated by Xiaoyu Xi

All

• Introduction of emerging and established frameworks• Review the latest European Network for Health Technology Assessment (EUNetHTA) Submission Template and the Academy of Managed Care Pharmacy (AMCP) Format for formulary submission in the US

• Recommendations based on the existing HTA frameworks and submission guidance

• Current use/lack of use of HEOR evidence in reimbursement and pricing negotiations and decision making in China

• Introduction of the current drug procurement bidding process in China • HTA data use in drug reimbursement and procurement process in China

• Recommendations and open discussions

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Overview (1)Increased health care resources and costs lead to the trend of evidence-based medicine and value-based reimbursement decisions.

Health technology assessments (HTAs) play a critical role in demonstrating the value of pharmaceutical agents and medical devices. Many value assessment frameworks have been developed around the world in recent years.

In Mainland China, HTA-related activities have been ongoing since the 1990s• Research based and no formal guidelines and policies• In general, no HTA data are required in the NRDL review• In the 2013/ 2014 and recent 2017/2018 NRDL reviews (and in the recent price negotiation

process) for the Provincial Reimbursement Drug List (PRDL), pharmaceutical companies were allowed to submit HTA data for certain premium-priced innovative drugs

• The draft version of Basic Health Care and Health Promotion Law in China in 2017 indicated that reimbursement negotiation process should be based on the results of evidence-based medicine and economic evaluations

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Confusions in Pharmaceutical Industryabout HTA data submission in China

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Aims of This WorkshopTo discuss key components in the submission guidelines and provide recommendations to Chinese policy makers and payers on developing efficient HTA framework and submission guidance

• Focus on frameworks that demonstrate value for payers.

• Review the newly developed EUNetTHAframework and well-established AMCP Format for Formulary Submission

• Overview the current role of HTA in reimbursement decision making and in healthcare institutions’ drug procurement bidding process in China

• Provide recommendations based on the evaluation of other assessment frameworks and their development process

HTA Frameworks and Submission Templates/Format

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ISPOR Special Task Force Report EUNetHTA and AMCP Format

IntroductionVA LU E A S S E S S M E N T F R A M E WO R K S F O R P H A R M AC E U T I C A L E V I D E N C E S U B M I S S I O N F O R H TA

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American College of Cardiology (ACC)/American Heart Association (AHA)

American Society of Clinical Oncology (ASCO)

Institute for Clinical Economic Review (ICER)

Memorial Sloan Kettering Cancer Center

National Comprehensive Cancer Network (NCCN)

European Society for Medical Oncology (ESMO)

Original Panel on Cost-Effectiveness

AMCP Format for Formulary SubmissionsSecond Panel on Cost-Effectiveness

SMART Vaccines

US Preventive Services Task Force

European Network for Health Technology AssessmentNational Institute for Health and Care Excellence

Avalere/FasterCures

Advisory Committee on Immunization Practices

Expanded health technology assessment

Institute of Medicine

Premera Blue Cross

Value Assessment FrameworksRecent US Frameworks

as Examples of Previous and

On-going Frameworks

Source: Neumann PJ, et al. A Health Economics Approach to US Value Assessment Frameworks—Introduction: An ISPOR Special Task Force Report (1). Value Health. 2018;21(2):119-123.

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EUnetHTA was established to create an effective and sustainable network for HTA across Europe; In partnership with 80+ organizations and 29+ countries

European Network for Health Technology Assessment (EUnetHTA)

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The EUNetHTA Core Model® (1)Domain Definition Full REA Rapid REA

Health problem and current use of technology (CUR)

• Health problem and target population• Epidemiology and burden of disease on individuals and

society • Availability, patterns of use, life cycles, and regulatory status • Alternatives to the technology

Description and technical characteristics of technology (TEC)

• Overview of the technology• When it was developed and for what purposes• Who will use the technology, how, and at which level of health

care• Material requirements, premises, equipment and staff• Training and information needs

Safety (SAF) • Direct and indirect harms for patients, staff and environment• How to reduce the risk of harm

Clinical effectiveness (EFF) • Beneficial health effects and quality of life• Effectiveness and safety

REA: Relative Effectiveness Assessment

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The EUNetHTA Core Model® (2)Domain Definition Full REA Rapid REA

Costs and economic evaluation (ECO)

• Identifies, measures, values and compares the costs and outcomes of technologies as a basis for value-for-money judgements and priority-setting between different health technologies

• Resource utilization, unit costs, indirect costs, outcomes/consequences, and incremental cost-effectiveness

Ethical analysis (ETH) • Considers prevalent social and moral norms and values relevant to the technology

• Ethical questions about the technology and the consequences of implementation and non-implementation

• Identifies the moral and ethical issues inherent in the HTA process

Organizational aspects (ORG) • Delivery models of the technology• Analyzing processes, resources, management and cultural issues• Understanding organizational aspects

Patient and social aspects (SOC)

• Considerations, worries and experiences before, during, and after the implementation of the technology for patients and significant others

• Where the patient uses the technology (hospitals, general practitioner, everyday life, homes, schools, and workplace),

• What specific meanings people give to the technology

Legal aspects (LEG) • Basic rights of patients, such as autonomy, informed consent, privacy and confidentiality

• Legal requirements, such as authorization, guarantee, and regulation of market

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JA Examples

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JA ExamplesPTJA02: Regorafenib (Stivarga©) indicated as monotherapy for the treatment of adult patients with hepatocellular carcinoma (HCC) who have been previously treated with sorafenib: Information on the implementation/uptake for this assessment (11 usage).

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EUnetHTA Submission Templates

Evidence submission templates were developed to support production of core HTA information and rapid assessments

• Long-form• Short-form

Details are provided in the “Joint Action 2 on HTA 2012-2015: Evidence submission templates to support production of core HTA information and rapid assessments: report. October 2015”

WP 7 Lead Partner: Haute Autorité de Santé (HAS)

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AMCP Format for Formulary Submission

Support informed selection of drugs, tests, and devices• Identify evidence• Standardize synthesis and

organization of evidence• Provide opportunity to

communicate• Supports government requirments• Requires models and projected

product impact • Encourages clear, transparent,

two-way communication

Improve information sharing• Timeliness• Scope• Quality• Relevance• Impact on clinical outcomes, value,

economic consequences

Streamlines evidence acquisition and review process• Manufacturers: Provides

consistent direction• Health systems: evaluate

for completeness and tailor to needs

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Evolution of AMCP Format for Formulary SubmissionsAMCP v2.0

2002

Sections did not change substantially from v1.0

Revisions provided additional clarity and

made document more user-friendly

AMCP v3.0

2009

Section 1.0 was completely changed to an Executive

Summary including a brief summary of the value of

the product

(previously found in section 4.0 of v2.1)

AMCP v2.1

2005

Evidentiary requirements were streamlined

Section added to describe evidence requirements for

biologics

More transparent presentation of economic

models

Differentiated requirements for budget impact vs. cost-

effectiveness models

AMCP v3.1

2012

Added companion diagnostic tests (CDT) –

initially added as an addendum

Added Comparative Effectiveness Research -

(starting 3.1, but reinforced in 4.0, adding meta analysis)

Specialty pharmaceuticals included

AMCP v4.0

2016

Biosimilars now included

More detailed CDT section

Medical devices included

Section 2: added description of how product may impact quality

measures

Section 3: expanded to add real-world evidence: clinical trial data for efficacy and real-world data

for effectiveness

Section 6: new patient information section and material safety data sheet for the product

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Keys to Effective Submission FormatE VO LU T I O N O F T H E A M C P F O R M AT

Communication• Added executive summary• Improved presentation structure• More transparency in model requirements

Evidence Integration• Integrate PE and clinical evidence, model and other evidence drafted by separate teams

Trends in Drug Development and HEOR• Increasing evidence for biologics, additional of biosimilars• Addition of medical device, companion diagnostic test, and specialty Rx

Evolving Needs and Advancement in HTA• Addition of comparative effectiveness info (e.g., MA, SLR)• Decisions based on multiple attributes or criteria instead of only on conventional CEA and

ICER

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Comparisons of EUNetHTA and AMCP Dossier Submission Requirements (1)

EUNetHTA: Long Form EUNetHTA: Short Form AMCP Dossier

Abbreviations Abbreviations Abbreviations

1.0 Executive Summary: Clinical and Economic Guidelines

1. Description and Technical Characteristics of the Technology

1. Description and Technical Characteristics of the Technology

2.0 Product Information and Disease Description

1.1 Characteristics of the technology 1.1 Characteristics of the technology 2.1 Product description

1.2 Regulatory status of the technology 1.2 Regulatory status of the technology

2. Health problem and current clinical practice

2. Health problem and current clinical practice

2.2 Place of the product in therapy

2.1 Overview of the disease or health condition

2.1 Overview of the disease or health condition

2.2.1 Disease Description

2.2 Target population 2.2 Target population

2.3 Clinical Management of the disease or health condition

2.3 Clinical Management of the disease or health condition

2.2.2 Approaches to treatment

2.4 Comparators in the assessment 2.4 Comparators in the assessment 2.1.1 Product comparison

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Comparisons of EUNetHTA and AMCP Dossier Submission Requirements (2)

EUNetHTA: Long Form EUNetHTA: Short Form AMCP Dossier 3. Current use of the technology and comparators

3 Current use of technology 5.1 Clinical practice guidelines

3.1 Current use of the technology 3.1 Current use of technology

3.2 Reimbursement and assessment status of the technology

3.2 Reimbursement and assessment status of the technology

3.3 Current use of the comparators 5.1 Clinical practice guidelines

4. Investments and tools required 4. Investments and tools required

4.1 Requirements to use the technology 4.1 Requirements to use the technology

4.2 Procedures required to use the technology

4.3 Investments, disinvestments and changes in service organization

4.2 Investments, disinvestments and changes in service organization

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Comparisons of EUNetHTA and AMCP Dossier Submission Requirements (3)

EUNetHTA: Long Form EUNetHTA: Short Form AMCP Dossier

5. Clinical Effectiveness and safety 5 Clinical effectiveness and safety 3.0 Clinical Evidence

5.1 Identification and selection of relevant studies 5.1 Identification and selection of relevant studies

5.2 Relevant studies 5.2 Relevant studies 3.1 Study Summaries

5.3 Main characteristics of studies 5.3 Main characteristics of studies

5.4 Individual study results (clinical outcomes) 5.4 Individual study results (clinical outcomes)

5.5 Individual study results (safety outcomes) 5.5 Individual study results (safety outcomes)

5.6 Subgroups

5.7 Risk of bias at study level: randomized controlled trials

5.8 Risk of bias at outcome level: randomized studies

5.9 Risk of bias: non-randomized studies

5.10 Methods of evidence synthesis

5.11 Results of evidence synthesis

5.12 Conclusions 5.6 Conclusions

5.13 Strengths and limitations 5.7 Strengths and limitations

5.14 Safety risk management

4.0 Economic Value and Modeling Report

5.0 Additional Supporting Evidence

References References 6.1 References

Example presentation of a search strategy Example presentation of a search strategy

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RecommendationsH TA F R A M E WO R K / G U I D E L I N E A N D S U B M I S S I O N F O R M AT I N C H I N A

Framework• HTA to be implemented at a central level BUT consider separate clinical (can be at central level) and

economic evidence (at provincial/local level)• Reflect trends in drug development and HEOR; include from start, but may evolve over time (e.g.,

multiple-decision criteria, gene therapy, biosimilars, companion diagnostic tests)

Submission Format Guide• Chinese payers and policy makers should recognize the value of a standardized process for efficient and

transparent evidence submission; As EUNetHTA is a positive step towards faster market access and a more unified approach to drug reimbursement in Europe, China may need a similar unified approach for provincial reimbursement submission process

• Streamline evidence presentation using 1 document for 1 joint submission• As learned from the AMCP format evolution, key considerations include concise communication, complete

clinical and economic evidence integration, and attention to evolving needs and advancement in HTA• Should be used as a tool allowing certain flexibility to support both national and regional HTA needs

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Present Situation of Health Technology Assessment in China

Shanlian Hu. MD. Msc. ProfessorSchool of public health, fudan university

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China Guidelines of Pharmacoeconomic Evaluation

A D R A F T E D G U I DA N C E O F H E A LT H T E C H N O LO G Y A S S E S S M E N T H A S N OT B E E N I S S U E D Y E T

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11th China Health Technology Assessment Forum in Shanghai in 2017

The First China Health Technology Assessment Conference will be held in Beijing on October 26, 2018

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Mapping of HTA Instrument

U S I N G P RO F E S S O R W I JA O O R T W I J N ’ S F R A M E WO R K

Institutionalization Identification Priority setting Assessment Appraisal Reporting Dissemination of findings Implementation in policy

ContentsGovernment attitude, public input, legislation and international support

Horizon scanning, information transparency

Evidence-based, literature review, outcome evaluation

Comparator, content, methods and generalization

Repeatability, stakeholder involvement, appeal mechanism

Report specification, relevant to health insurance

Timeliness of dissemination, channel & platform

Regulatory compulsory, planning & supervision

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Standardized Scores Comparison

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China Middle income High IncomeCountries Countries

Institutionalization

Identification

Priority setting

Assessment

Appraisal

Reporting

Dissemination of findings

Implementation in policy

S A M P L E S I Z E : 3 P ROV I N C E S , 2 2 2 S TA K E H O L D E R S I N T E RV I E W S U RV E Y ( Y I N YAO C H E N 2 0 1 7 )

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China Has Three Big Issues in HTA

H T T P : / / W W W. C H I N A M E D - C E . C O M / H TA 2 0 1 7

Shortage of decision making

Lack of institutionalization arrangement

Absence of HTA review system

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17 innovative anticancer drugs, such as Herceptin, Rituximab and Bortezomib (Velcade), etc. have conducted price negotiationThe average price reduction was 57%Medical insurance funds have paid 15.9 billion RMB ($2.34 billion USD)

16 out of 18 anticancer negotiated drugs were imported onesWhich cover a wide range of cancers, including NSCLC, colorectal cancer, renal cell carcinoma, melanoma, lymphoma, chronic myeloid leukemia, multiple myeloma, etc

New Round of Anticancer Drug Negotiations

2017 2018

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Current Use of China Model in Price Negotiations

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Establishing a Medical Insurance Drug Evaluation System

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ion

syst

em

shou

ld b

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tabl

ishe

d • Efficacy• Safety• Ability to pay• Economic

benefit ratio

To e

nsur

e dr

ug s

afet

y

• Before new drug launching to the market

• Clinical trials should be conducted in Chinese patients

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Negotiation Requirements for High Value Medical Consumables

PilotProducts

Drug coated coronary artery stent Artificial hip Prosthesis Implantable cardioverterdefibrillator (ICD) series Cardiac Resynchronization Therapy (CRT) series

Declaration materials

Application formsPower of attorney negotiation Application for negotiation Product information file Application for submission of negotiation materials

Enterprise declarationqualification

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Key MessagesChina needs to have submission guidelines for listing drug reimbursement & price negotiation

The concept of HTA and value-based pricing has been accepted by multi-sectoral policy makers

Evidence-based pharmacoeconomic evaluation, budget impact analysis and HTA capacity building remain importance in China

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HTA in Price Negotiation in China

Rong Shao, PhD, ProfessorThe Research Center of National Drug Policy Ecosystem, China Pharmaceutical University

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1. 2017 Review for The National Reimbursement Drug List (NRDL) U P DAT E TO T H E N R D L I N J U LY 2 1 S T 2 0 1 7

• It was the forth update to the NRDL since the establishment of Medical Insurance System of new China and was eight years from the previous update.

• More drugs were added to the list than expectation and the update was implemented in a proactive way, which fit perfectly with the bidding agenda.

• Price negotiation of innovative drugs and drugs for major critical diseases was carried out, with the to-be-negotiated varieties following behind. Special attention was given to pediatric drugs and ethnic drugs.

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2. Price Negotiation ProcessNATIONAL HEALTH COMMISSION OF THE PEOPLE’S REPUBLIC OF CHINATHE RESULT OF NATIONAL PRICE NEGOTIATION

Tenofovir Disoproxil Fumarate Icotinib Hydrochloride Tablets Gefitinib Tablets

67% 54% 55%

Price negotiation has greatly reduced the price！

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2. Price Negotiation ProcessM I N I S T R Y O F H U M A N R E S O U R C E S A N D S O C I A L S E C U R I T Y O F T H E P E O P L E ' S R E P U B L I C O F C H I N A ( M O H R S S ) T H E R E S U LT O F N AT I O N A L P R I C E N E G OT I AT I O N

• In 2017, 36 drugs were added to the list out of 44 drugs on the negotiation table, bringing an average deduction of 44% with the highest deduction being 70%.

• Before the negotiation, details of international drug price and reference price need to be collected, the inclusion standard of the drugs as well as the exemplified list of drugs should be made. Besides, pharmacoeconomics evaluation and model method could also be used to provide reference for negotiation.

• In 2018, there are 18 varieties under negotiation, and all the pharmaceutical companies have submitted the HTA report.

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2. Price Negotiation ProcessE X P E R I E N C E S U M M A R I Z AT I O N — I N N OVAT I O N A N D B R E A K T H RO U G H

The inclusion of negotiation varieties should be clinical-oriented.

Channels for dossier submission should be opened for pharmaceutical companies.

Big data and expert think tank could be used to provide technical support.

Health technology assessment tools could be used to support your decision

The process of application, evaluation and negotiation should be divided.

Encourage investment in major innovative drugs

Price negotiation serves as an important method for drugs to be included in drug list

of medical insurance

Future revolution: Standardize the negotiation routine；Provide institution and legislation support

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2. Price Negotiation ProcessCore Elements Future Direction

Subject1.Division of work—independent negotiation institutes or organizations

2.Disclose partial information of medical insurance market

Content1.Explore the mechanism on which the decisions of the interest-related parties are based.2.Diversify the standards to evaluate the negotiation (economy-oriented/efficacy-oriented)3.Establish risk sharing mechanism

Rules

1.Establish a scientific inclusion standard2.Safeguard the legal status of medical insurance negotiation

3.Switch between application for bids and invitation for bids

Process1.Form a dynamic evaluation system2.Set ways to save the negotiation when it fails.3.Set multiple access for inclusion

Supporting materials1.Establish the big data platform of information on what drugs should be used to treat what disease.2.Issue guidelines on the use of health technology assessment3.Set the price of drugs and coordinate among purchasing departments

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3.The New Bidding System — Cases of Provinces with Innovative PatternsProvince Quality

(grouping standard)

Price & Price competing

Wining the bid(hospital bargaining)

Medical insurance serving as the leverage(payment standard)

Anhui Refer to 2012 and 2014;Dynamic Adjustment

Hospital bargain with pharmaceutical companies while making quantity purchase

For drugs whose manufacturing companies refuse to provide medical insurance payment reference price, the amount of money which exceeds 40% of the purchase volume of the previous year shall be calculated with a deducted price.

Fujian Noncompetitive catalogue:branded drug;generic drugs

Lowest price all over the country

3-rounds

Set the online price, encourage hospital organizations to bargain while making quantity purchase

For drugs included in the noncompetitive catalogue, the part of money which is not covered by the basic medical insurance scheme shall be paid by the patients, while for drugs in the competitive catalogue whose price is generally bellow the price covered by the medical insurance scheme, the part of money saved shall be awarded to the hospital (encourage hospitals to negotiate the price).

Chongqing 3 levelsThe 2nd level:branded drugs, separate pricing drugs…

Average of entry price of all provinces

Set the online price, allowing the hospitals to bargain and negotiate autonomously

Set the medical insurance payment reference price according to the bidding price of the previous year and the bidding price of other provinces. The amount saved shall be awarded the hospital.

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Food for Thought and Future DiscussionWhat evidence and

corresponding studies should pharma

companies invest to collect and implement?

Will the patient voice have an increasingly bigger role in payer

assessments?

Is a format template/guide (e.g., EUNetHTA , AMCP) an effective way to facilitate faster

market access and a more unified approach to drug reimbursement in China?

Do current payer requirements for evidence define drug value in the

real world?

Are economic arguments such as the ICER fully able

to justify price?

How can we ensure that we prove important comparative claims linked with the most important benefits?

What are the current payer requirements for evidence that can be used to define

drug value?

Backup slides

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Real-World EvidencePatient engagement

Digital health

Drug PipelinesNew innovations in therapy (e.g. I-O, CAR-T…)

Companion diagnostics

Biosimilars

HTAValue based pricing

Accelerated drug approvals

EU HTA directive

Criteria decision analysis

Will the patient voice have an increasingly bigger role in payer assessments?Do current payer requirements for evidence define drug value in the real world?Role of HTA in pricing: Are economic arguments such as the ICER fully able to justify price?Decision made based on multiple attributes or criteria or conventional ICER with QALY as patient outcome measure?Considering evidence relevant to medical device, biosimilars, companion diagnostics

Future Considerations for Guideline Update

Key Trends Issues to Consider

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Key Challenges in China

Policy obstacles/Lack of official and clear framework and submission guidance

Great variance in regional situation (wealth inequity, regional budgets//should be different ICER/criteria be used)

On-going main focus on price-constrained approach

Within industry, lack of aligned evidence submission; sending mixed messages to payers by multiple groups within the company (e.g., market access, medical/HEOR, policy/GA)

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