1. How should we measure treatments for rare diseases?
Elad Shemesh1, Laura Deroma2, Bruno Bembi2, Carla Hollak3, Patrick B Deegan4, Neal J Weinreb,4 Timothy M Cox5
1…; 2University hospital Santa Maria della misericodia Udine, Italy; 3Academic Medical Center, Amsterdam, Netherlands; 4University of Miami, Miami, United States; 5University of Cambridge, Cambridge, UK Contact:
The brief history of orphan drugs and health economy
An opportunity to promote equity?
A well designed comparative efficacy analysis is a potential method to reduce treatment costs
National/international registries (long term follow-up) instead of RCTs?
Should orphan drugs be funded by governments? An independent evidence-based analysis may reduce geographical inequalities in patient access to treatment, by serving as a ‘standardized’
guideline
Kefauver- Harris Bill
Thalidomide crisis
ODA law
A new interest in rare diseases and the emergence of ‘blockbusters’
Public protection € € €
focus on common diseases
‘lack of efficacy’ and Criticism
1950s
1960s
1980s
Rare diseases: High impact on health-care systems
40% are misdiagnosed at least once
In the last 5 years, 1/3 of new drug approvals were for rare diseases, yet only 5% of rare diseases have approved treatments
EC regulation 141/2000: ‘patients suffering from rare conditions should be entitled to the same quality of treatment as other patients’ / unrestricted drug price
How much are we missing when conducting a classical Cochrane review? A simulation based on Pubmed database
Inclusion of non-RCT data in Cochrane analyses- proposed advisor
Score
Feature +1
Studies compare bio-similar drugs or different doses?
EMBASE search yields Non-RCT/RCT ratio greater than 3
Is the disease assessed considered ‘rare’? (US/European definition)
Primary analysis goal is to prove superiority / effectiveness (the ability of an intervention to produce a clinical benefit in actual practice)?
Gaucher disease
Pompe disease
Fabry disease
Why ‘gold-standard’ study designs, QALYs and meta-analytic ‘efficiency’ evaluations are likely to fail?
Small numbers (not surprising)
The mean time-to-diagnosis for rare diseases is ~5 yrs – when treatment is eventually applied, complete reversal of pathologies can not be expected
Neurological deterioration (a dominant feature of rare diseases) can be slowed- but often not cured
Very high heterogeneity- different geographical locations, ethnicities, study protocols
“RCT only” inclusion criteria- a selection bias?
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This study was supported in part by a grant from the UK Gaucher Association

2. Appendix: Methods for consolidating policy
recommendations in rare diseases
Embracing conceptual changes: Innovative trial designs
Equality of opportunity: Every member of the society should have the same opportunities to receive the best available treatment
No cure-no pay: Reimbursements will be paid only if measurable effects are produced (if not- costs will be reclaimed from the pharmaceutical companies)
Weighted QALY: Attach a higher value to the health gain of people with rare diseases
Utilitarianism: The best moral action is the one that maximizes utility (greatest good for the greatest number)
Cost effectiveness analysis / QALY per $: Quality-adjusted life years [1 year of life x 1 utility value = 1 QALY]
Favors proven efficacy-for-money Favors compassionate use