11 th International EvidenceBased Health Care Symposium Interactions

11 th International Evidence-Based Health Care Symposium Interactions between HTA, coverage and regulatory processes Methodological Challenges and Alternatives to Assess Rare Diseases Treatments Alicia Granados MD Ph. D PH HTA Strategy Sanofi Genzyme

Outline • • • Determinants of patient access to treatments Methods used in HTA Methodological and Ethical Challenges of HTA for RD Alternative assessment and appraisal options for RDs Final reflections

Determinants of Patients Access to Innovations HTA Appraisal HTA Assessment • Safety & Efficacy Regulatory Filing • • Relative Safety Relative Efficacy Relative Effectiveness Cost- effectiveness Product Reimbursement

Quality of Scientific Evidence 5

The complex nature of causality The increasing understanding of the complex nature of causality of diseases and therapeutic effects and the multitude of actual influences on outcomes, as revealed by molecular biology (*) poses RCT and quantitative data alone, less capable of capturing the complexity effects(**) • • (*) On the nature of causation in complex systems George F R Ellis. Mathematics Department, University of Cape Town, 2006 Rondebosch, Cape Town 7701, South Africa (**) Yusuf S, Wittes J, Probstfield J, Tyroler HA. Analysis and interpretation of treatment effects in subgroups of patients in randomized clinical trials. JAMA. 1991; 266(1): 93 -98 |6

Avances Científicos y Tecnológicos Burrill&Company. Biotech 2012. 7

Variability in decision making treatments for RDs 8

HTA and RDs

Burning issues in HTA for RD • Genetic, metabolic rare disease patients are difficult to include in RCT studies…… given the limited patient population, the heterogeneity of disease, non-uniform disease progression and lack of clinical expertise • The best possible evidence available is judged against the same standards as other compounds addressed to larger populations (EBM, CEA/CUA) • Final oucomes vs surrogate are required by HTA, but is it ethical in RDs? • Decisions using cost/utility analyses and ICERs raise additional concerns 10

Burning issues in HTA for RD • CEA is currently used in reassessments of therapies for RD as criterion to recommend that they should no longer be funded (NL, SW) • To solve the issue of appropriateness of the outcome measure PROs are seen as responsive to modest intervention effects (i. e. statistical significance can be attained with relatively small sample sizes), . 11

Burning issues in HTA for RD • There is of lot a variability on the assessment/ appraisal of therapies for rare diseases • The main issues that HTAs reference assessing of orphan products are: – Poor quality of evidence (small sample size!!) for efficacy and safety – Scarcity of knowledge on specific rare diseases – Amount of time required to perform the assessment given the high dispersion of information – Orphan drugs do not usually prove to be cost- effective 12

Economic Evaluation of therapies for RDs Potential Ways Forward 13

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HTA Evidence for Rare diseases. Potential Ways Forward

Alternative Appraisal Framework of value of therapies for RDs 18

MCDA Framework 19

MCDA Framework helps Health Care in having an Explicit Ethical Thinking and Positioning 20

MCDA is a tool of Translating Ethical Positions into Criteria 21

Utilitarianism vs Egalitarianism in RDs • The scarcity of patients in rare diseases poses ethical dilemmas that should be assessed in a systematic way using moral enquiry. • There have been discussions since Plato’s era on what value is; no general consensus since then. • There are two competing ethical principles utilized in the interpretation of distributive justice (fair allocations of resources), in Health Care: Utilitarianism vs. Egalitarianism. • Some countries balances the conflicting demands of Utilitarianism and Egalitarianism in it’s approach to HTA assessments. (“Muddling through elegantly”) 22

In summary • It seems that best way to assess therapies for RDs is a multimetodological approach and • The most fair way to appraise treatments for RDs is the multicriteria approach, but making explicit the moral and ethical position of Health Care 23

Final reflections 24

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