European countries differ in their value assessment of new orphan drugs, but steps can be taken to create a more harmonized, comparable and rational evidence-based decision-making system in Europe, two experts from the London School of Economics Health reported at the Ninth Orphan Drug Congress 2018. The presentation by Aris Angelis and Panos Kanavos covered the outline policies, practices and incentives for orphan medicinal products (OMPs) and also the health technology assessment (HTA) models in context and dimensions of value.
“European countries differ in their value assessment of new orphan drugs, but steps can be taken to create a more harmonized, comparable and rational evidence-based decision-making system in Europe.”
Evidence was presented on HTA outcomes of 42 OMPs and across four countries, including the time of coverage, the outcome of the HTA process, clinical and economic evidence, uncertainties and judgments of social values. Comparing the frameworks and incentives for orphan drug development in the Organisation for Economic Co-operation and Development area, it was shown that the U.S. (introduced in 1993), Europe (in 2000), Australia (in 1990) and Japan (in 1993) all have an orphan drug framework defined, whereas Canada does not. Orphan drugs receive a market exclusivity of seven years in the U.S., 10 to 12 years in Europe, 10 years in Japan and eight years in Canada. All the mentioned countries provide regulatory assistance.
There are three different HTA models: the Clinical Benefit Assessment model (France, Germany), the model of Clinical and Cost Effectiveness (Sweden, Canada, Netherlands) and a Value-based Pricing Model (UK, Sweden, Italy). The comparison of different study values in different European countries showed that the status of severity of a disease burden is only mandatory in France, whereas countries such as Germany, Sweden, the UK or Spain see the severity of a disease burden as a recommended value.
Direct endpoints as well as studying of adverse events are mandatory for studies in all different presented countries (France, Germany, Sweden, UK, Italy, Netherlands, Poland and Spain). Clinical novelty must only be mandatorily presented in France and Poland; all other countries see clinical novelty as implicit but planned (Spain, Italy) or as optional value (Germany, Sweden).
Scientific and social value judgments taken into account
There is a direct budget impact as a socioeconomic value in Germany and Poland and an indirect budget impact in Sweden, Italy and Spain. Decisions for the HTA and coverage of orphan medicinal products are taken from two kinds of judgments.
On the one hand, the scientific judgments include the clinical and cost-effectiveness, the reliability and quality of the evidence-base, the appropriateness of sub-groups and the associated analysis, the generalizability in population and the handling of uncertainty.
On the other hand, there are social value judgments such as the severity of the disease, the end of life interventions, age and health inequalities. The social value judgments do not have always appropriate metrics; they can be revealed but can also be implicit judgments based on the treatment characteristics or the disease profile. HTA decisions are influenced by different factors such as the clinical effectiveness, health benefits, the extent of uncertainty, equality and diversity and different social value judgments.
Cancer vs. non-cancer drugs
Analysis was also carried out on the time between regulatory market access and reimbursement decisions of cancer versus non-cancer orphan drugs. It was shown that non-cancer orphan drugs need more months between regulatory market authorization and reimbursement than cancer orphan drugs throughout different HTA agencies, such as the Scottish Medicine Consortium (SMC) (26 versus 19 months), Pharmaceutical Benefits Advisory Committee (PBAC) (23 versus 16 months) or the Canadian Agency for Drugs and Technologies in Health (CADTH) (13 versus six months). Only the National Institute for Health and Care Excellence (NICE) has shown a longer time period for cancer orphan drugs than non-cancer orphan drugs (36 versus 24 months).
“… non-cancer orphan drugs need more months between regulatory market authorization and reimbursement than cancer orphan drugs throughout different HTA agencies.”
In conclusion, the study showed that there is a significant time difference between regulatory and funding decisions across agencies for cancer versus non-cancer orphan drugs. It demonstrated that most drugs get approved or are approved with restrictions plus risk sharing. Some of the studied drugs have already been rejected which impacts timing between regulatory and funding decisions. Surrogates are found mostly as primary endpoints and this has impact on a large number of prior rejections and significant timelines.
The data also show that a number of social value judgments are beyond cost and effects.
This article was excerpted from the author’s full coverage of the World Orphan Drug Congress, which was organized by Terrapinn in Barcelona, Spain, in November. Her report also covered sessions on:
- the importance of patient organizations in the process of a treatment evaluation and granting market access of a drug;
- new trends and perspectives on gene therapies for treatment of rare diseases;
- how organ-on-a-chip technologies are being used to model rare diseases; and
- how foundations can influence the search for a cure for a rare disease.
The full report on the World Orphan Drug Congress appears in Cortellis and is available here.