Keith Tolley Director, Tolley Health Economics Ltd

WFH World Congress in Paris, July 8-12, 2012

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Personal background

Health Economist in academia, pharma and consultancy

Interest in economics of haemophilia (since mid 90’s) Worked with Royal Free Hospital, Haemophilia Unit (Christine Lee).

Involved in Miners (health economist) 2002 publication on the cost-effectiveness of prophylaxis in UK

Co-author of WHF booklet on health economics in haemophilia

Economic assessor for a UK HTA body - the Scottish Medicines Consortium (SMC)

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Pressures on the payers… Drug expenditures continue to rise

New drugs are rarely cost saving

New drugs for previously untreated conditions

Ageing, obesity, etc

Growing patient awareness

Budgets for health care becoming even more constrained

Always been constrained - Economic crises meaning becoming even more constrained

Health Technology Assessment (HTA) has been used as a tool to help reimbursement authorities and payers assess the added value new pharmaceuticals bring

To justify reimbursement and/or price desired

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Drug expenditure estimates 2007

UK - primary & secondary care = £6-7 billion

England – secondary/tertiary care Branded £1.6 billion Generics £300m

London – secondary/tertiary care All drugs £660m

HIV (antiretrovirals) £125m Cancer £ 96m Haemophilia £ 60m

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What tools?........ Health Technology Assessment

“a form of policy research that systematically examines the short- and long-term consequences, in terms of health and resource use, of the application of a health technology” (Henshall et al., 1997)

Cost-effectiveness, cost-utility, cost-benefit analysis

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Growth in Health Technology Assessment around the globe

Organisations assessing clinical and cost-effectiveness of new medicines

To aid decisions about reimbursement and funding of new products

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HTA organisations in Europe

All the following perform appraisals of new technologies:

National Institute for Health and Clinical Excellence (NICE)

Scottish Medicines Consortium (SMC)

TLV, Sweden

IQWiG, Germany

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Questions of ‘added value’………..over current practice Questions on clinical and cost-effectiveness:

Are the additional therapeutic benefits of a new drug or intervention worth paying for?

Does the new drug result in healthcare resource savings?

Does the new drug bring benefits to the wider society that are worth paying for?

Is an additional [healthcare] cost affordable?

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Demonstrating value – what data?

This varies across HTA systems:

Germany/France - Bleeds prevented

UK/Sweden - Quality Adjusted Life Years (QALYs)

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Condition Short and medium term clinical measures

Long run Outcome measure

Resource benefits

Type 2 Diabetes:

HbA1c reduction

Reduced CV events

Reduced mortality, improved QoL

QALY gain

Less CV event costs

Cancer: Progression free survival

Improved survival

QALY gain

None usually

Haemophilia: Bleeds prevented

Improved HRQoL

QALY gain

Reduced surgery

Cost-effectiveness metric used in UK The incremental cost per Quality Adjusted Life Year Gained

New treatment additional cost and QALY compared to current practice

Cost considered from a health care provider perspective

Outcomes measured by the QALY:

Life years weighted by a health related quality of life (HRQoL) index (on 0-1 scale)

Typical instrument for measuring HRQoL is the EQ 5D

In the UK decision makers/payers are generally willing to pay up to £30,000 per QALY gained, but depends!

UK HTA Benchmark incremental cost per QALY gained

Source: Rawlins and Culyer, BMJ 2005;329:224-227

A = <£20,000 per

QALY gained:

-Considered an

efficient use of NHS

resources

B = >£30,000 per

QALY gained

-Would need special

circumstances to

accept

Increasing cost/QALY (log scale)

Pro

babilit

y o

f re

jecti

on o

n

gro

unds

of

cost

infe

cti

veness

Patient-reported health status and quality of life

Mobility

Self-Care

Usual activities

Pain/ Discomfort

Anxiety/ Depression

100mm Visual analogue scale

100 = best assessment

0 = worst assessment

HTA questions in haemophilia

Prophylaxis with recombinant factor VIII reflects ‘best practice’ in treatment of bleeds associated with severe haemophilia in UK More expensive than on-demand, but improves health outcomes

(Manco-Johnson et al, 2007)

So, do the additional benefits outweigh the additional costs?

What is the cost-effectiveness of factor VIII prophylaxis vs use of on-demand treatment?

Are newer longer half life drugs more cost-effective than conventional factor VIII?

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Cost-effectiveness studies

A number of economic evaluations have been performed evaluating the cost per QALY gained for prophylaxis over on-demand treatment in severe haemophilia:

Miners, 2009 (UK) – €44K/QALY in children and adults over a lifetime.

Columbo, 2011 (Italy) – €40K/QALY in children and adults over a lifetime.

Risebrough, 2008 (Canada) – €320K/QALY for esculating dose prophylaxis children aged 0-6.

Lippert, 2005 (Germany) – €1 million/QALY in adults over 1 year.

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Miners, 2009: “Revisiting the cost-effectiveness of primary prophylaxis

with clotting factor for the treatment of severe haemophilia A” *Haemophilia, 2009, 1-7

Markov decision model with life time horizon, and societal perspective

Treatment doses: On-demand treatment with single dose of 31 IU/kg per bleed ( for 90% of

bleeds), with 10% of bleeds requiring two infusions Prophylaxis is 25-40 iu/kg (Malmo protocol with X 3 weekly infusion to

prevent trough clotting factor levels falling below 1IU/kg) Clotting factor requirement based on factor VIII half life of 12.2 hours, and

recovery rate of 2% per IU/kg

Clotting factor price of £0.325 /IU

Data on probability of surgery and higher quality of life due to fewer bleeds from published studies

Health outcomes measured in Quality Adjusted Life Years (QALYs) Costs and QALYs discounted at 3.5% p.a.

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Miners et al 2009 results for prophylaxis v on-demand in the UK Base case lifetime result of £38,000 per additional QALY:

On-demand mean lifetime cost of £644,000 for 14 QALYs

Prophylaxis mean lifetime cost of £858,000 for 19.5 QALYs

There is uncertainty in the cost/QALY results Miners found there was only a 13% chance that prophylaxis could

achieve a cost/QALY <£30K with the current evidence base

Results sensitive to frequency of bleeds, price of clotting factor, discount rate.

Discount QALYs at 1.5% per annum the probability rises to 60%

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Impact of Pharmacokinetics

A longer half life and higher recovery rate will reduce the dose of recombinant factor VIII required to achieve target trough clotting factor at >1 IU/dl.

And hence can reduce drug cost, and improve cost-effectiveness

So can new developments help achieve this: FVIII:Fc - t1/2 (h) 1.7 times longer than Advate

LongAte – once weekly product

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What impact can experiential evidence have?

The cost-effectiveness evidence is limited and inconclusive: The Miners model is the best one available, but needs updating with

new clinical evidence

Could be useful in countries outside the UK

A more holistic approach to HTA is being advanced, placing a value on: Unmet need, societal value, innovation

Key role here for patient organisations Lobbying for the holistic approach to HTA

Providing information to verify quality of life impacts 18

Conclusions

Limited HTA/health economic attention given to severe haemophilia – challenging area

HTA impact in haemophilia has so far been limited

Tendering in UK is maybe contributing to no formal UK HTA

Haemophilia patient organisations have a role in HTA

Understanding the language to engage with HTA decision makers.

Contributing the experiential case to counter the limitations in the health economic/HTA case.

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References Colombo, GL, Matteo SD, Mancuso ME, Santagostinino. Cost utility analysis of prophylaxis versus

treatment on demand in severe haemophilia. ClinicoEconomics and Outcomes Research 2011, 3: 55-61

Lee C. The use of recombinant factor VIII products in previously treated patients with haemophilia A: Pharmacokinetics, efficacy, safety and inhibitor development. Seminars in Thrombosis and Hemostasis 2002, 28 (3).

Lippert B, Berger K, Berntorp E, Giangrande P, van den BM, Schramm W et al. Cost effectiveness of haemophilia treatment: a cross-national assessment. Blood Coagul Fibrinolysis 2005; 16(7):477-485.

Manco-Johnson MJ, Abshire TC, Shapiro AD, Riske B, Hacker MR, Kilcoyne R et al. Prophylaxis versus episodic treatment to prevent joint disease in boys with severe hemophilia. N Engl J Med 2007; 357(6):535-544.

Miners AH, Sabin CA, Tolley KH, Lee CA. Cost-utility analysis of primary prophylaxis versus treatment on-demand for individuals with severe haemophilia. Pharmacoeconomics 2002; 20(11):759-774

Miners A. Revisiting the cost-effectiveness of primary prophylaxis with clotting factor for the treatment of severe haemophilia A. Haemophilia 2009; 15(4):881-887.

Nature - News: Hemophilia market awaits next generation therapies

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References Recht M et al. Clinical evaluation of moroctocog alfa (AF-CC), a new generation of BDD recombinant

factor VIII for the treatment of haemophilia A. Haemophilia 2009; 1-12

Risebrough N, Oh P, Blanchette V, Curtin J, Hitzler J, Feldman BM. Cost-utility analysis of Canadian tailored prophylaxis, primary prophylaxis and on-demand therapy in young children with severe haemophilia A. Haemophilia 2008; 14(4):743-752.

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