Pre-announcement – RD internal call 2020 : Innovative Statistical Methodologies to Improve Rare Diseases Clinical Trials in Limited Populations

The European Joint Programme on Rare Diseases (EJP RD) will implement the present internal call for innovation projects to improve RD clinical trials methodologies in limited populations.

The ambition to foster RD clinical trial methodology will be implemented in an internal call (EJP RD partners) promoting collaborative projects. Three collaborative projects aiming to validate innovative statistical design and analysis methods in small population groups developed by Asterix, IDeAl and InSPiRe are currently being evaluated in the demonstration projects (call was closed on June 8th, 2020 and results were announced on July 2020). However, EJP-RD has recognized that these existing methods leave space for improvement and innovation in particular when population size is limited. Our focus now is to target rare and very rare diseases where the number of affected patients is rather low and the incidence is small as well, so that traditional methodologies to conduct clinical trials often fail. These innovation methodologies topics particularly include:

• Development of innovative trial endpoints covering PCOMs

• Validation of possible composite end points and surrogates • Retrieving efficacy and important safety information in cohorts of natural history studies to inform design and analysis of clinical trials.

• Develop methods to assess the level of evidence associated with randomization in limited populations • Efficient designing and analysis of bridging studies accepted in one regulatory region to another region (as defined in ICH E5) for RD

• Pharmacometric modeling for design and analysis in limited populations These calls intend to privilege support of collaborations among methodological experts or groups of experts consisting of different stakeholders including clinicians, patients and or industry who will jointly develop innovative methods to fill gaps of RD clinical trial methodologies. The aim is, to have ready to use methods, which will drive regulatory decision-making.

In preparation, partners who are interested can join the GA on the 16th of September 2020 where WP20 will present this new call and join a hackathon, which will be held on 30th of September 2020 aiming to bring people with interesting clinical questions together with methodologists to foster potential collaboration. Applicants for this call can be from institutions who are partners of the EJP-RD. The call is expected to be launched at the end of November 2020.

A networking meeting will be held on January 11th, 2021 to consolidate the collaborative networks. The call deadline will be confirmed around the end of February 2021. All proposals will undergo scientific external reviewers. Updated information can be found on the website of the EJP-RD. For any further information please contact the secretary under the email address