The number of orphan drug (OD) approvals has increased sharply in Europe. In Germany, all ODs are initially subject to a limited assessment after market access. Their added benefit over the standard of care is accepted as established upon EU approval; a regular health technology assessment (HTA) is performed only in certain cases.

We assessed whether the increase in OD approvals has led to improvements in patient-relevant outcomes as supported by the evidence submitted by market authorization holders (MAHs) for HTA in Germany. We also examined the extent to which these ODs address unmet medical needs.

The results of limited assessments and regular HTAs of ODs in Germany (January 2011–September 2021, plus January–December 2023) were analyzed to determine their added benefit based on MAH-submitted dossiers. Added benefit was reported separately for each research question generated from the EU-approved therapeutic indications and any sub-indications (e.g., different subpopulations or control interventions) specified for HTA in Germany.

Eighty-nine ODs (limited assessments: sixty-nine; regular HTAs: twenty) were evaluated in 175 research questions (limited assessments: ninety-seven; regular HTAs: seventy-eight). The added benefit granted in limited assessments was non-quantifiable in nearly eighty percent of the ninety-seven questions. In regular HTAs, no proof of added benefit was shown in fifty-four percent of the seventy-eight questions, mainly due to insufficient comparative data with the standard of care. Established treatments were available for fifty-eight percent of the seventy-eight questions; more than half of which addressed oncology indications (although these account for only eight percent of rare diseases).

Due to evidence gaps in post-approval HTA, many ODs approved in the EU lack proof of added benefit in terms of improving patient-relevant outcomes. Moreover, most approved ODs are indicated for diseases with established treatments and oncology indications, while many unmet medical needs remain. Incentives are required to encourage research in areas of unmet medical need and to generate comparative data with the standard of care.

Out of 185 orphan medicinal products (OMPs) registered in 2015–2021, a mere 110 (59 percent) were available to Czech patients, and only 54 (29 percent) were officially reimbursed. Moreover, this proportion has steadily decreased over time. After years of public debate induced by this unsatisfactory OMP patient access, the national viewpoint shifted toward creating a special pathway for the reimbursement of OMP. Thus, a rigorous pricing and reimbursement procedure with strict timelines and elaborated methodology has been recently adopted in Czechia.

The innovative legislation follows the recommendations for value assessment and funding processes for rare diseases and incorporates additional elements of value, such as the societal perspective. First, the application with clinical evidence, cost-effectiveness, and budget impact analyses is submitted to the governmental health technology assessment (HTA) agency by the Marketing Authorization Holder or a Health Insurance Fund. Moreover, professional associations and patients’ organizations are rightful participants in the proceeding, providing evidence and comments. Then, the HTA agency performs the assessment/appraisal of the evidence. It subsequently publishes the assessment report summarizing available information. The report is then forwarded to the Ministry of Health and its advisory body consisting of patients, clinical experts, health insurance funds, and the State. They critically evaluate the documents and issue a binding opinion following prespecified decision-making criteria. Based on this binding opinion, the decision is issued by the HTA agency. Thus, the role of the advisory body in this process is crucial.

We believe that this novel approach may offer satisfactory patient access to orphan drugs. Moreover, it serves as a real-world example of “value-based” decision making.

This study aimed to identify different criteria for priority setting of rare diseases to help policy makers in making evidence-informed decisions.

A scoping review was conducted to comprehensively examine the existing various methods and criteria for prioritizing orphan drugs and rare diseases. We performed searching in Scopus, PubMed, Embase, and websites of health technology assessment (HTA) agencies, 2000–21, and data were extracted.

From the 1,580 identified publications, eleven articles were included. Multicriteria decision analysis was the most frequent method (seven out of eleven studies) used for priority setting. The extracted criteria for priority setting of orphan products were analyzed based on six main categories as follows: health outcomes and clinical implications (six subsets which showed clinical implications), economic aspects (four subsets that indicated the economic effects of orphan drugs and rare diseases), disease and population characteristics (six subsets that included the characteristics of the rare diseases), therapeutic alternatives and uniqueness of orphan technologies (two subsets which discussed the alternatives and uniqueness of orphan technologies), evidence (three subsets which regarded the quality and availability of evidence), and other criteria (three subsets dealing with social and organizational criteria). Cost-effectiveness, budget impact, and disease severity were the most frequent criteria in the studies.

Because of the high price of orphan drugs and limitations of using HTA for reimbursement of them, it is critical to explore them by precise technical methods like multiple criteria decision making in priority setting.