P234: Advancing Drug Development for Rare Diseases: An Update on the Rare Disease Clinical Outcome Assessment Consortium
Poster Presenter
Lindsey Murray
Executive Director, Rare Disease COA Consortium
Critical Path Institute United States
Objectives
To describe how the Rare Disease Clinical Outcome Assessment Consortium (RD-COAC) is advancing drug development by leveraging expertise in COAs, rare disease clinical trials, regulatory science, and clinical experience to overcome challenges in clinical trial conduct for rare diseases.
Method
The RD-COAC is a multi-stakeholder, precompetitive collaboration aimed at identifying scientifically sound tools and methodologies for collecting clinically meaningful outcomes data in treatment trials for rare diseases.
Results
The Rare Disease Clinical Outcome Assessment (COA) Resource was launched in September 2023. The first iteration focuses on assessment of gross motor function, fine motor function, self-care, and communication/language in pediatric, non-oncologic populations. The Resource is expanding to include COAs measuring pain interference, pain severity, sleep disturbance, and sleep impact. The RD-COAC is advancing solutions for methodological and measurement challenges in rare disease, including best practices for leveraging qualitative data in rare disease clinical trials, crafting endpoints for gene therapy trials, best practices for patient engagement, and in collaboration with the eCOA Consortium, developing best practices for capturing and implementing video-based COAs in rare disease clinical trials. A Pediatric Cognition Working Group was launched in March 2025 which aims to generate a framework to better define and measure cognition in pediatric rare disease clinical trials. The RD-COAC also launched a "Rare Disease Discussion Session" series to promote education and share learnings among consortium members to expedite innovations in rare disease clinical trial measurement science. This internal learning series capitalizes on the pre-competitive environment by promoting collaborative learnings from real-world experiences conducting rare disease clinical trial research. Some of the session topics covered have included discussions on how a “most bothersome symptom” framework could be implemented in a rare disease trial with a focus on the statistical implications, presentations from patient advocacy groups on their registry programs, presentations from NIH colleagues on comparing ability and norm-referenced scores, including growth scale values to interpret results from a COA commonly used in pediatric clinical trials, and presentations from other C-Path rare disease consortia to ensure connectivity, promote data sharing, and prevent duplicative efforts.
Conclusion
The launch of the Rare Disease COA Resource is the first database of its kind. It is a cost-free, publicly available database of COAs that have been selected by consensus from industry, clinical experts, regulatory experts, and patient/caregiver representatives, reviewed against current regulatory evidentiary expectations, and specifically identifies COAs that may potentially support endpoints in clinical trials across multiple rare diseases. The cost (e.g., time, expenditure) of identifying relevant COAs for a single domain per disease can easily exceed $200,000 (USD); thus, the Rare Disease COA Resource may reduce efforts for COA identification by individual pharmaceutical companies, researchers, and patient advocacy groups and provides a selection of COAs that have been selected by a multi-stakeholder group of experts. Furthermore, results of the available evidence and gap analysis for each tool have been formatted in a way that information needed to populate a COA dossier for a regulatory submission can be easily downloaded.
The success of the RD-COAC lies in its ability to bring scientific thought leaders together to enact change in the rare disease research field. The importance of incorporating the patient voice into rare disease clinical trials toward the development of meaningful outcomes necessitates continued collaboration among patient advocacy, regulatory bodies, academia, and government/industry sponsors. These efforts will be important given the number of new treatment modalities (e.g., anti-sense oligonucleotides, immunology, and gene therapies) that have the potential to alter the disease course, improve life expectancy, and modify the background therapy of future clinical trials. The RD-COAC will continue to tackle existing methodologic challenges and address new opportunities for COA-based measurement to meet the ongoing evolution of regulatory science.
