The Rare Disease COA Resource provides information on published COAs that have the potential to be used to support efficacy endpoints in treatment trials for rare diseases. The Resource is an initiative of the Critical Path Institute’s Rare Disease Clinical Outcome Assessment (COA) Consortium, a public-private partnership focused on optimizing COA selection during drug development for rare diseases.

COAs included in the Rare Disease COA Resource represent the tools that are the most commonly used in current rare disease research and tools which have been published in the literature and were available to examine against evidentiary criteria. The Rare Disease COA Resource, therefore, only captures existing tools and may not include COAs that have been developed recently, but which lack publications to support their use. The Rare Disease COA Resource will be updated periodically to identify new tools that may warrant inclusion. Additionally, some historical COAs have been included because although they may not meet all evidentiary standards, they are the standard of care and allow for comparisons between individual rare disease populations and normative data.

The Rare Disease COA Resource is NOT a core outcome set. Core outcome sets are an agreed upon, standardized set of measures that should be gathered and reported as a minimum in all clinical research in specific areas of health or health care (https://nationalhealthcouncil.org/blog/blog-core-outcome-sets-what-are-they/). For each domain, multiple COAs have been identified. This is because the COAs selected for individual research programs still need to be carefully considered based on the suitability for the target population, coverage of concepts, applicability of the concept to the anticipated mechanism of action for the investigational product, abilities of each trial population, etc. Good measurement science principles still need to be applied to selection of the COAs from the Rare Disease COA Resource to ensure the optimal match with research targets can be met.

Clinical outcome assessment (COA): Assessment of a clinical outcome can be made through report by a clinician, a patient, a non-clinician observer or through a performance-based assessment.

Types of COAs

(as defined by https://www.ncbi.nlm.nih.gov/books/NBK338448/)

There are four types of COAs. The FDA-NIH BEST Glossary defines them as:

Clinician-reported outcome (ClinRO): A measurement based on a report that comes from a trained health-care professional after observation of a patient’s health condition.

Patient-Reported outcome (PRO): A measurement based on a report that comes directly from the patient (i.e., study subject) about the status of a patient’s health condition without amendment or interpretation of the patient’s response by a clinician or anyone else.

Observer-reported outcome (ObsRO): A measurement based on a report of observable signs, events or behaviors related to a patient’s health condition by someone other than the patient or a health professional.

Performance outcome (PerfO): A measurement based on standardized task(s) actively undertaken by a patient according to a set of instructions.

By identifying multiple existing COAs per domain, the considerable time and cost associated with identification of relevant COAs is dramatically reduced and available to all. Evidence from the extensive gap analysis on each COA included in this resource can be viewed for each tool individually or in comparison across several tools in a domain to aid with appropriate COA selection for an individual research program. The Rare Disease COA Resource can also inform patient advocacy groups of COAs available to measure outcomes of interest in patient registries and natural history studies.

The first iteration of the Rare Disease COA Resource focuses on the assessment of daily function subdomains of gross motor function, fine motor function and self-care and communication/language in pediatric, non-oncologic populations.

A literature review of available COAs measuring the daily function subdomains of pain interference, pain severity, sleep disturbance and sleep impact is in process. Other subdomains will be added over time.