Measuring upper limb function in MS: Which existing patient reported outcomes are fit for purpose?

Area of Science:

• Clinical trial methodology
• Patient-reported outcomes research
• Neurology

Background:

• Multiple Sclerosis (MS) clinical trials increasingly focus on progressive disease and upper limb function (ULF).
• Patient-Reported Outcomes (PROs) are crucial for quantifying clinical variables and meaningfulness of change in trials.
• Regulatory bodies like the FDA mandate PROs be 'fit-for-purpose': well-defined, reliable measures for specific contexts.

Purpose of the Study:

• To identify existing PROs measuring ULF from scientific literature.
• To determine if these PROs meet scientific and regulatory requirements for clinical trials.

Main Methods:

• Systematic literature screening of PubMed/Web of Science.
• Evaluation of PRO suitability using established criteria.
• Assessment of PRO development papers against Consensus Standards for Measurement Instruments (COSMIN) criteria.

Main Results:

• 3619 articles were screened, identifying 24 distinct ULF PROs across 485 studies.
• None of the identified ULF PROs met the scientific and regulatory 'fit-for-purpose' criteria.
• No PRO was found to be a well-defined measure of a clearly defined construct within a specific clinical context.

Conclusions:

• Current ULF PROs in MS research are inadequate for clinical trial use.
• Development of new measures requires enhanced patient engagement, robust theoretical frameworks, and rigorous qualitative research.
• Without improved PROs, clinical trials risk misrepresenting treatment efficacy by failing to capture meaningful patient-level changes.