Background: Multiple Sclerosis (MS) clinical trials increasingly focus on progressive and advanced MS, with upper limb function (ULF) as a key outcome. Within clinical trials, Patient Reported Outcomes (PROs) quantify clinical variables and establish meaningfulness of changes. Scientific standards and regulatory criteria (from Food and Drug Administration [FDA]) require PROs be "fit-for-purpose": well-defined and reliable measures of specific concepts in defined contexts.
Objective: To identify, from literature, existing PROs measuring ULF and determine which satisfy scientific and regulatory clinical trials requirements.
Method: We screened PubMed/Web of Science using multiple relevant terms. Abstracts and full texts were screened using suitability criteria. PRO development papers were evaluated using recently expanded Consensus Standards for Measurement Instruments (COSMIN) criteria for content development.
Results: We identified 3619 articles; 485 used 24 different ULF PROs. No PRO satisfied scientific and regulatory requirements as a well-defined measure of a clearly defined construct in a specific clinical context.
Conclusions: Existing ULF PROs don't meet fit-for-purpose criteria. MS clinical trials require new measures with greater emphasis on patient engagement to derive theoretical frameworks, concepts of interest, and contexts of use followed by systematic literature searches, expert input, and qualitative research to support item generation. Until then, trials will miss aspects of meaningful within-patient change and thereby misrepresent (likely underestimating) treatment effects.
Keywords: Concept of interest; Context of use; Multiple sclerosis; Patient reported outcome; Upper limb/extremity measurement.
© 2020 The Authors. Published by Elsevier B.V.