Edition of 09 November 2020

In the aim of fostering existing rare diseases clinical trial methods in limited populations, an internal call will be launched in November 2020 by the European Joint Programme on Rare Diseases (EJP RD). Amongst the innovative methodologies for the internal call are the validation of composite end points and surrogates, the development methods to assess the level of evidence and randomisation in limited populations, the development of innovative trial endpoints, or the pharmacometric modeling for design and analysis in limited population. Applicants to the call must be from partners institutions of the EJP RD.

Three steps will be implemented: the dissemination of the latest development in trial methodology, the implementation and development of innovative and value methodologies to RD clinical studies and practical settings, and the identification of unmet needs for tailored methodologies.

Three other collaborative projects on innovative statistical and analysis methods in small groups were developed by partners of the EJP RD (Asterix, Ideal and InSPiRe). This follows the EJP RD call for proposal on the “demonstration projects on existing statistical methodology to improve RD clinical trials”. The call aimed to highlight the usability and capability of nine innovative statistical methodologies for clinical trials, including two types primary outcome variables (surrogate and co-primary), uncertainty evaluation (bias assessment), or three types of use of external information (historical control, extrapolation, and dose response profiles).

The call will be launched at the end of November 2020, and the experts will meet in January 2021 for further consolidation of efforts. The closing deadline for the call is the end of February 2021. All proposals will be reviewed by independent scientific external reviewers (a scientific committee). For more information, you should contact the secretary at the following email address (innovation.callsec@ejprarediseases.org). The calls are contributing to fostering collaboration among methodological experts (industry, patients, clinicians) to develop innovative methodological methods to drive regulatory decision-making.

Orphan drug designation was introduced in the European Union (EU) in 2000 to stimulate orphan drug development (ODD). ODD is currently still facing challenges. Authors explained in this paper the different characteristics of ODD, such as the general procedure leading to the development of ODD, including an application submitted to the European Agency that includes scientific literature, condition, and results of experimental and clinical studies. Three criteria, rarity, medical significant benefit and medical plausibility are central key for the application.

Pre-submission meetings, even though not mandatory, are recommended to sponsors by the European Medicines Agency (EMA) committee, prior to filing the application, as it was noticed that the mentioned meetings have a positive impact on the success of applications. The success of the translation of RD research into approved orphan drugs depends as well to other elements, including a clear medical justification, the prevalence, scientific output and class of the disease, and the OD market experience of the sponsor. Eligible sponsors benefit from orphan incentives, for instance, the assistance by the Committee for Orphan Medicinal Products (COMP), and 10-year market exclusivity.

Research was conducted on what could be a reasonable price for an orphan drug. Differences in patient population and the cost of research were taken into account by researchers. A general method based on rates of return of investment was proposed to establish a reasonable price for orphan drug. The authors state that rates should not be superior to the industry average, with a higher cost-effectiveness threshold (CET), that will help to adjust established payer versus Health Technology Assessment (HTA) body incremental CET. The proposed method intended to establish a just and affordable price for patients. The researchers note that decision-makers may wish to negotiate a lower price or refuse paying a premium.