Health Technology AHealth Technology ADise

Justice LeadJustice Lead

Albert FVice President Glo

Assessment and RareAssessment and Rare easeds to Accessds to Access

Farrugiaobal Access PPTA

www.pptaglobal.org

US Healthh Expenditures per Capita, 1960-2010

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FacIn Real

Thorpe K E He

ctors Accounting For The Rise l U.S. Per Capita Health Spending.

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ealth Aff 2005;24:1436-1445

Iron TrianIron TrianAcceAcce

CostCostSource: Adapted from Kissick WL. Medicine’s DilemmResources. Yale University Press, 1994

ngle of Health Carengle of Health Careessess

QualityQualitywww.pptaglobal.org

yymas – Infinite Needs Versus Finite

Health Te

“We shall use the term assessment

of a medical technology to denote

•

gy

any process of examining and

reporting properties of a medical

technology used in health care, such

as safety, efficacy, feasibility, and•

indications for use, cost, and cost

effectiveness, as well as social,

economic, and ethical consequences,

whether intended or unintended.”

(IOM 1985)(IOM 1985)

echnology Assessment (HTA)

Multidisciplinary research area aimed at

make “informed” health policy decisions

Institutional level,

Individual health organizations

Cli i l tiClinical practice

Through assessments

ClinicalClinical

Economical

Ethical

Legal

Organizational implications

www.pptaglobal.org

Health Tec

• The goal of HTA is to inform the

health policies that are patient fochealth policies that are patient foc

as defined by decision makers.

• HTA underpins decisions such as:

• Should treatment A be re

system?

• For which patients should it

• For how long should patientFor how long should patient

chnology Assessment (HTA)

e development of safe and effective

cused and seek to achieve best valuecused and seek to achieve best value

eimbursed in a national healthcare

t be provided?

ts receive the treatment?

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ts receive the treatment?

Health Tec

• Although the scientific assessment o

way in which a technology is appra

used to devise recommendations on

country to country.

• As a result, different decisions are ta

be provided, leading to variation in ac

• In socialized systems – cost effec

insurers etc)

• In USA, comparative effectivene

outcomes research (PCOR)

chnology Assessment (HTA)

of the available data may be similar, the

aised (that is, how the assessment is

its value in healthcare) may vary from

aken about which technologies should

ccess to treatments.

ctiveness analysis (but increasingly applied by

ess research (CER) and patient centered

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Health Tecthe evaluatio

• Efficacy and effectiveness: contribut

health status of the patient.

• Efficacy refers to benefits aris

conditions (for example under a

• Effectiveness considers the be

under normal conditions;

• Economic impact: assessment of costs

a single technology.

• Also considered by a macroec

systems and services reim

innovation and competitiveness

.

chnology Assessment: on of health technologiesion made by technology to improving the

sing from the use of technology in "ideal“

a clinical trial protocol).

enefit derived from the use of a technology

s, prices, levels of payment associated with

conomic point of view (analysis of financing

mbursement, policies for technological

www.pptaglobal.org

s …);

• Evidence

– RCTs

– Systematic reviews

Cost effecti eness• Cost effectiveness

– Total medical costs

– Role of Decision Analysis

Choices and d

s

www.pptaglobal.org

The

www.pptaglobal.org

RandoLimitati

Representativeness / Generalizability

• Patient selection / eligibility criteria

• Comparators

• MD/Patient adherence

• ‘Real world’ practice patterns / variations

• Intent-to-treat analysis

Data Limitations

• Outcomes assessed

Ti h i / F ll• Time horizon / Follow–up

• Clinically–relevant subgroups

• Resource use/ CostResource use/ Cost

Ethical and logistical barriers

omized Clinical Trials:ons RE: Effectiveness

www.pptaglobal.org

“The paradox of tThe paradox of tthat it is the beswhether an intewhether an inte

but arguably the wwho will benwho will ben

Mant. Lancet. 19

the clinical trial isthe clinical trial isst way to assesservention workservention works,orst way to assess

nefit from it ”nefit from it.999;353:743–746

www.pptaglobal.org

•“The benefit or harm• The benefit or harmin clinical trials can

fail to reveal the potentfail to reveal the potentsubstantial ben

little benefit flittle benefit fharm fo

R K i Milb– – R Kravitz, Milba

m of most treatmentsm of most treatmentsn be misleading andially complex mixture ofially complex mixture of nefits for some,for many andfor many, andor few.”

k Q l 2004ank Quarterly, 2004

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Why is HT

• HTA can provide information to sup

example:example:

• Health authorities thinking of

prevention programmes, such

• Health care payers deciding w

drugs) should be paid for;

• Health care organisations dec

new technologies such as mo

• Health care companies produea ca e co pa es p odu

demonstrate a level of benefit

TA important for patients?

pport a range of decisions, for

putting in place primary or secondary

h as screening programmes;

which technologies (e.g., operations,

ciding whether to exclude or implement

odern types of radiotherapy;

ucing new products that may need to

www.pptaglobal.org

uc g e p oduc s a ay eed o

t for the product to justify the cost.

HealthHealth

SocietySociety

PatientPatientPointPoint PatientPatient

PayorPayor

ProviderProvider

ofofViewView

Bombardier and Eisenberg, 1984.Bombardier and Eisenberg, 1984.

h Economic Analysish Economic Analysis

TypesTypesofofofofAnalysisAnalysis

Types ofTypes ofIntangibleIntangibleCosts and Costs and Benefits Benefits IncludedIncluded

ggProductivityProductivity

DirectDirect

www.pptaglobal.org

• “The principal objectiveobjective of the N

be to maximize the aggregate to maximize the aggregate

of the whole community.” Anth

• “The underlying premisepremise of CE

any given level of resources av

making jurisdiction involved) wwmaking jurisdiction involved) ww

aggregate health benefit confe

Stason (1977)Stason (1977)

Societal Perspective?

National Health Service oughtought to

improvementimprovement in the health status

ony J. Culyer (1997)

EA in health problems is that for

vailable, societysociety (or the decision-

wisheswishes to maximize the totalwisheswishes to maximize the total

erred.” 3M.C. Weinstein and W.B.

www.pptaglobal.org

Types of

• Cost effectiveness analysis (CEA): c

focused on a single natural unit, e.g

casescases

• Cost utility analysis (CUA): form o

into a unit of utility, e.g., quality-a

• Cost benefit analysis (CBA): costs w

aggregated into monetary unitsaggregated into monetary units

f Economic Studies

costs weighed against outcomes

., deaths, heart attacks, lung cancer

of CEA, outcomes aggregated

adjusted life-years (QALYs)

weighed against outcomes

www.pptaglobal.org

• Key features result in probwith rare chronic disorderswith rare chronic disorders

• Discounting of both costsgreatly the effectiveness ag yQALY

• Utility surveys with currenpatients with chronic disorbenefits, also resulting in

Cost Utility analysis

blematic results for patients sss and benefits decreases and increases the cost per p

nt instruments show that rders “underestimate” increased costs/QALY

www.pptaglobal.org

“There are three criteria which must be ful

• The human value principle; which unThe human value principle; which un

human beings and the integrity of eve

• The need and solidarity principle; w• The need and solidarity principle; w

precedence when it comes to reimbur

people with more severe diseases apeople with more severe diseases a

conditions.

The cost effectiveness principle; which• The cost-effectiveness principle; which

should be reasonable from a medical

perspective ”perspective.

In praise of lfilled if a medicine should be reimbursed:

nderlines the respect for equality of allnderlines the respect for equality of all

ry individual.

which says that those in greatest need takewhich says that those in greatest need take

rsing pharmaceuticals. In other words,

are prioritised over people with less severeare prioritised over people with less severe

h states that the cost for using a medicineh states that the cost for using a medicine

, humanitarian and social-economic

www.pptaglobal.orgSwedish Pharmaceutical Benefits Board 2007

HTA fo

• Nothing to fear

• Use ALL the evidence

• Reject dogma

• Involve patients

or PPTs and rare diseases

www.pptaglobal.org

• HTA includes health relate

• All aspects of health that a

the personthe person

• physical functi

• social and role

• mental health,

• general healthgeneral health

Quality of Life

ed quality of life (QoL)

are directly experienced by

ioning,

e functioning,

,

h perceptionswww.pptaglobal.org

h perceptions.

Pati

• QoL used to estimate

Year (QALY)

• Obtaining the cost of• Obtaining the cost of

about

• To estimate QoL – W

ents are CRUCIAL in HTA

e the Quality Adjusted Life

QALYs is what HTA isQALYs is what HTA is

We need patient input

www.pptaglobal.org

• Ask patients how they feel

(Q lit f Lif ) i(Quality of Life) using

questionnaires which scale the

state of health

• Get a benefit (utility) – 0 to 1 –( y)

from the scale

Estimating the QALY (1)

1 = perfect health

e

0 = dead

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• (Benefit) X (time in which it • Eg “On a scale of 1 (highes• Eg On a scale of 1 (highes

health?”• Lets say the answer is 0 5Lets say the answer is 0.5• Lets assume the person live• The person will generate 0• The person will generate 0.• Lets give the person a treat• Now the person answers 0• Now the person answers 0.• With the treatment, the pers

The person will now genera• The person will now genera

Estimating the QALY (2)

is in place) = QALYst) to 0 how do you rate yourst) to 0 how do you rate your

es another 40 years5 X 40 = 20 QALYS.5 X 40 = 20 QALYStment and ask the person again7 (The person feels better).7 (The person feels better)

son lives for another 50 yearsate 0 7 X 50 35 QALYS

www.pptaglobal.org

ate 0.7 X 50 = 35 QALYS

Wh

• Estimating the number of

HTA

• In CER, QALYs are comp

• Interventions which yield m

(hopefully)

hy is the QALY important?

QALYs is what is done in

pared

more QALYs are favored

www.pptaglobal.org

• A new wheelchair for elder• Increases quality of• Increases quality of • 10 years benefit• Gives 1 QALY• Gives 1 QALY

• Special post natal careQuality of life = 0 8• Quality of life = 0.8

• 35 years benefitGi 28 QALY• Gives 28 QALYs

• So…. which gets cho

QALYs allow comparisonOf Effectiveness

rlyf life = 0 1f life = 0.1

osen?www.pptaglobal.org26

Wh

• Estimating the number of

HTA

• In CEA, the COST/QALY

interventions

hy is the QALY important?

QALYs is what is done in

is used to rank health

www.pptaglobal.org

• A new wheelchair for elde• Increases quality of life = 0• 10 years benefit• Extra costs: $ 4,000 per life• QALY = Y x V(Q) = 10 x 0.QALY Y x V(Q) 10 x 0.• Costs are 10 x $4,000 = $4• Cost/QALY = 40,000/QALY

S i l t t l• Special post natal care• Quality of life = 0.8• 35 year35 year• Costs are $250,000• QALY = 35 x 0.8 = 28 QAL

C t/QALY 8 929/QALY• Cost/QALY = 8,929/QALY

• So…. which gets cho

QALYs allow comparisonOf Cost-Effectiveness

erly0.1

e year 1 = 1 QALY1 1 QALY

40,000Y

LY

www.pptaglobal.orgosen?

I t tiInterventionGM-CSF in elderly with leukemia

EPO in dialysis patients

Lung transplantation

End stage renal disease management

Heart transplantation

Didronel in osteoporosis

PTA with Stent

Breast cancer screeningBreast cancer screening

Viagra

Treatment of congenital anorectal malf

QALY league table

$ / QALY$ / QALY235,958139,623100,957

53,51346,775

Conventional cut off

32,04717,889

5 1475,1475,097

formations 2,778

www.pptaglobal.org

C

• Health outcomes are exprequality-adjusted life-years (quality adjusted life years (

• The cost of a QALY is then• Key features result in probKey features result in prob

for patients with rare chron– Discounting of both costg

decreases greatly the effe– Benefit estimates show t

chronic disorders “underechronic disorders undere

ost-Effectiveness Analysis

essed as (QALYs)(QALYs)n estimatedlematic resultslematic results

nic disorders: ts and benefits }ectivenessthat patients with

estimate” benefits

} Increase the costs/QALY

estimate benefits

www.pptaglobal.org

Benefit mea

Study Prophylay p yLippert 2005

0.760.70

Risebrough (2008) 0.95

asurements for prophylaxis vson demand in hemophilia

axis On Demand

0.750.66With target joint 0.905No target joint 0.875

www.pptaglobal.org

SF-36 D

Physcompo

Physicalfunction

Rolephysical

Bodilypain

Generalhealthfunction physical pain health

MenMencompo

Domains and Summary Scores

sicalonent

Sco es

Vitality Socialfunction

Roleemotion

Mentalhealthfunction emotion health

ntal

www.pptaglobal.org

ntalonent

Benefits discounte

Benefits discounte

Miners Haemophilia (2009), 15, 881–887

Effect of discountinged at 1.5%

What does this mean?

If th b fit i• If the benefit is

discounted by 1.5 %

instead of 3.5%

(NICE etc), the CE ed at 3.5% increases to

“acceptable” levelsp

Assuming a WTP of ₤30,000/QALY

www.pptaglobal.org

How thHow thAn example with α

hings can go wronghings can go wrongα1AT Augmentation

www.pptaglobal.org

Cochran

“Augmentation therapy with alpha-1 antitrypsin cannot be recommended, in view of the lack of evidence of clinical ,benefit and the cost of treatment”

e and A1AT Augmentation

www.pptaglobal.org

Alpha-1

• Report from husband/wife team

• Report methodology flawed• Report methodology flawed

• Ignores guidelines based on scie

disease and many observational

• Co-researcher Dirksen was lead

Cochrane MA

– Requested his name removed frRequested his name removed fr

– Claimed collaboration was not p

A t ti th i th lAugmentation therapy is the only

the lung disease asso

Foundation Statement on Cochrane Review 2010

– no AAT expertise

entific understanding of the

l studies

d investigator in studies cited for g

rom reportrom report

possible

il bl ifi t t t fwww.pptaglobal.org

y available specific treatment for

ociated with Alpha-1

“(1)basbas(2) disquaquaaugothwithwithdisconaugNHpat

) we model disease progression on the sis of data from the NHLBI Registrysis of data from the NHLBI Registry, we consider the impact of

scounting over time, the impact of ality of life and the incremental cost ofality of life, and the incremental cost of gmentation therapy compared with her pulmonary medications that patients h chronic obstructive pulmonaryh chronic obstructive pulmonary ease (COPD) commonly use, (3) we nsider the costs and benefits of

t ti th ( th b i fwww.pptaglobal.org

gmentation therapy (on the basis of HLBI Registry data) over the lifetime of tients”

• Found that α1AT Augmen(costs/QALY too high)(costs/QALY too high)

• But– Only used small part of ey p– Used 3% discounting of – Estimated QALYs withou

Strategy CostgyNO Treatment $92,091

Treatment for Life $895,243

ntation is not cost-effective

evidence (one patient registry)( p g y)the QALY

ut asking patients (asked doctors)

Effectiveness(QALYs)

Incremental Cost-effectiveness*( )

4.627.19 $696,933

www.pptaglobal.org

C

α1AT AugmentationUse all the evidence!!

www.pptaglobal.org

Chapman et al Journal of Chronic Obstructive Pulmonary Disease,2009; 6:177–184

Cost Effective

• Coalition of PPTA, treaters and patients

PPtreaters and patients

• Used latest best evidence for

U

effectiveness of prophylaxis U

• Used patient survey for benefit

S• Used modern concept for discounting

S(dpp

eness of prophylaxis vs on-demand treatment for hemophilia A

Payer Perspective

Cost Effectiveness

UK Prophylaxis is DOMINANT over On Demand

USA Cost/QALY is $68K (C$68K (Cost-effective)

S d P h l i iSweden daily rophylaxis)

Prophylaxis is DOMINANT over On Demand

www.pptaglobal.org

rophylaxis) On Demand

Farrugia et al Haemophilia in press 2013

Orange et al Clinical Im

Trough Levels in PIDDEffect on incidence of pneumonia

• The highest trough levels still do notstill do not prevent all cases of pneumonia!p

• Can we show that higher trough levels are cost-effective?

www.pptaglobal.orgmmunology (2010) 137, 21–30

MakingMaking Prophylaxis for

things rightthings rightlife in hemophilia A

www.pptaglobal.org

Cost e

Published cost per QALY esFVIII proph la is in children

Study

FVIII prophylaxis in children

yMiner 2009

Miner 2002

Roosendahl 2007

Ri b h 2008Risebrough 2008

Lippert 2005

Brian O'Mahony

effectiveness of prophylaxis

timates ofn

Cost per QALY estimate ($)

n

p ( )50,000

65,000,

300,000

420 000420,000

1.2m – 2.7m

www.pptaglobal.org43y 2011

Pha[FVIII] per wee

0 1 2 3 4 5 6 days

Bjorkman and Berntorp Clin Pharmacokinet 2001; 40 (11): 815-832

rmacokinetic dosage ek to maintain a trough level > 1% (IU/kg)

Daily Alternate Day Every Third Day

1 – 6 10 – 65 1 – 6 10 – 65 1 – 6 10 – 651 6 years

10 65 years

1 6 years

10 65 years

1 6 years

10 65 years

17 12 59 35 236 119

Collins et al 2010 JTH, 8: 269–275

www.pptaglobal.org

Cumulativepro

Gouw S C et al. Blood 2007;109:4648-4654

e incidence of inhibitor development : ophylaxis versus on demand

The RODIN Study

Difference only after 20exposure ddays

Gouw et al 2011 http://igitur-archive.library.uu.nl/dissertations/2011-1110-y200501/gouw.pdf

www.pptaglobal.org

Discounti

“Where the Appraisal Committee ha

undertake sensitivity analysis on the

treatment effects are both substantreatment effects are both substan

sustained over a very long period

Committee should apply a rate of 1.5

t ”costs.”

http://www.nice.o6 of the Guide6_of_the_Guide_

ing – New NICE position

as considered it appropriate to

effects of discounting because

ntial in restoring health andntial in restoring health and

(normally at least 30 years), the

5% for health effects and 3.5% for

rg.uk/media/955/4F/Clarification_to_section_5.to Methods of Technology Appraisals pdf

www.pptaglobal.org

_to_Methods_of_Technology_Appraisals.pdf

Outcom

Payer Perspective Cost QALYs IncrementalCost

USUSOD $4,140,275 19.42

$412,999Pro $4,563,274 25.48UK

OD £1 784 095 27 16OD £1,784,095 27.16- £280,866Pro £1,503,229 36.85

Sweden

OD SEK 22 101 124

17.87SEK22,101,124 SEK

5,331,051Pro SEK 27,432,176

28.87

Sweden (Daily Pro dosing)(Daily Pro dosing)

OD SEK 22,101,124

17.87- SEK

10,541,993Pro

SEK 11 559 131

28.87Pro 11,559,131

es of the cost-utility model

l Incremental QALYs Cost/QALY ICER

6.06$213,759

$68,109$179,097

£65 6889.69

£65,688Dominant

£40,798

SEK 1,236,77210.99 SEK 484,888

SEK 950,197

10.99SEK 1,236,772

DominantSEK 400,386

www.pptaglobal.org

HTA is here to stay

‘Nothing about us with

Find ways to contributeFind ways to contribute

Remember ‘distress is

Patient involvement me

We need PATIENTS to i

Conclusion

out us’

ee

not enough’

eans a two way process

influence QOL data

www.pptaglobal.org

WillinC

• Contingent Valuation Method

– Interview of 600 Swedish house

– Question: Would you pay [x EUR

can get Pro/OD treatment?

• Results

– Mean WTP

1. EUR 39 (OD) and EUR 65

– Cost/taxpayerCost/taxpayer

1. OD - EUR1.97 (95% CI 1.6

2 PRO EUR 5 56 (95% CI 42. PRO - EUR 5.56 (95% CI 4

Carlsso

ngness to pay for prophylaxisCost Benefit study in Sweden

eholds to measure WTP

R] so that patients with severe hemophilia

(Pro) [p<0.01]

69–2.26)

4 94 6 17)]

www.pptaglobal.org

4.94–6.17)]

on et al. 2004 Haemophilia (2004), 10, 527–541

• Focusing on the patient’

• Taking a patient’s persp

• Accommodating of the p

• Allowing patient particip• Allowing patient particip

• Building upon patient/ph

• Empowering the patienSource: Bridges J and Jones C (2007) Patient based health tecSource: Bridges, J and Jones C (2007) Patient based health tec

possible, International Journal of Technology Assessmen

A new vision for evaluation

’s problems

pective

patient’s preferences

pationpation

hysician partnerships

nt to improve their healthchnology assessment: A vision of what might one day be

www.pptaglobal.org

chnology assessment: A vision of what might one day be nt in Health Care. 23(1) pp30-35.

Patient-cen

DODO COS

The Patient –ntered outcomes research

NOT CONSIDERNOT CONSIDER ST-EFFECTIVENESS

www.pptaglobal.org

The

• “The principal objectiveobjective ofoughtought to be to maximize thto maximize thoughtought to be to maximize thto maximize thin the health status of the

• “The underlying premisepremiseThe underlying premisepremiseAnalysis in health problemof resources available, sosojurisdiction involved) wishwishaggregate health benefit c

M.C. Weins

patient or the community?

f the National Health Servicehe aggregate improvementhe aggregate improvementhe aggregate improvementhe aggregate improvementwhole community.”

Anthony J. Culyer (1997)y y ( )

of Cost Effectivenessof Cost Effectiveness ms is that for any given level cietyciety (or the decision-making eses to maximize the total conferred.”

www.pptaglobal.org

stein and W.B. Stason (1977)

In contin

Sometimes the good effects of

they easily compensate for all

considered as cost saving. Buconsidered as cost saving. Bu

high demands in order to

medicine is cost-effective

d t i ido not experience pain an

normal life through usingg g

enough for society to be

nued praise of

f a medicine are so great that

costs. Then the treatment is

ut we do not make suchut we do not make such

o consider if the use of a

e. That people get well,

d lind can live a more

g a medicine is important www.pptaglobal.org

g p

willing to pay for it.

Har

“and there shall be n

neither sorrow, nor cr

there be any more pa

things are passed aw

Revelatio

rold Roberts in Freemantle Australia October 1999

o more death,

rying, neither shall

ain: for the former

way”

ons Ch21

www.pptaglobal.org