Why is it so difficult to estimate the value of orphan drugs indicated for the treatment of rare diseases? There are a variety of reasons, but a scoping review by Grand et al. (2024) provides a good summary of these topics. Key challenges include small sample sizes for almost all parameters and lack of data in general. More specifically, key issues identified in the document include:
- Natural history of disease.: Unclear epidemiological data (e.g., incidence, prevalence), unclear disease trajectories, frequent delays in diagnosis or misdiagnoses; Challenges in creating disease registries
- Clinical effectiveness. Trials are usually short in duration and with small samples; few or poorly validated surrogate endpoints; difficulty in comparing treatments due to heterogeneity in treatment regimens and study designs.
- Costs. Limited data on the economic burden of diseases and indirect costs; Transferability of cost inferences between studies is challenging due to variations between countries.
- Quality of life: There are few studies on HRQOL and those that are carried out have a small sample size; few disease-specific quality of life metrics; HRQoL was measured at limited time points, making it difficult to map nonlinear disease trajectories; limited focus on informal care
- Cost effectiveness. Few previous studies; numerous biases (e.g., publication bias, sponsorship bias); limited transferability of ACE results due to inconsistent results of differences between healthcare settings; frequent use of assumptions; failure to report discount rate assumptions; heterogeneity of input parameters; little patient level data
- Budget impact. Few BIM studies published for a given disease; frequent use of unproven assumptions; failure to report drug-related care
- Value/refund. Country-specific CEA thresholds for rare diseases vary dramatically between countries; Values framework requirements vary by country; reference prices may prevent launches in low-income countries; The use of ADMC may overcome some limitations of CEA, but produces others (e.g., transparency, consistency between treatments).
To overcome these barriers, the authors propose a number of solutions including working directly with patient advocacy groups, creating disease registries, and considering outcome-based payment/risk-sharing arrangements. It is helpful to work with patient advocates to collect data and create disease registries; On the other hand, while outcome-based payments would solve the problem of uncertainty, they may be cost-prohibitive, as the largely fixed cost of establishing and administering these arrangements may not be worth it if spread over very few patients.
You can read more details about the challenges and opportunities in economic evaluations of rare diseases. here.
