ORCID
- Jeremy Hobart: 0000-0002-2114-7920
Abstract
Background: Many clinical trials use patient-reported outcome (PRO) measures, which can influence treatmentdecision-making, drug approval and label claims. Given that many PRO measure options exist, and there areconceptual and contextual complexities with PRO measurement, we aimed to evaluate how and why specificPRO measures have been selected for pivotal multiple sclerosis (MS) clinical trials. Specifically, we aimed toidentify the reasons documented for PRO measure selection in contemporary phase III MS disease-modifyingtreatment (DMT) clinical trials.Methods: We searched for phase III clinical trials of MS DMTs published between 2015 and 2021 and evaluatedtrial protocols, or primary publications where available, for PRO measure selection information. Specifically, weexamined study documents for their clarification of clinical concepts measured, definitions of conceptsmeasured, explanations of which PRO measures were considered, why specific PRO measures were chosen, andtrade-offs in PRO measure selection.Results: We identified 1705 abstracts containing 61 unique phase III MS DMT clinical trials. We obtained andexamined 27/61 trial protocols. Six protocols were excluded: four contained no mention of PRO measures andtwo contained redacted sections preventing adequate assessment, leaving 21 protocols for assessment. For theremaining 34 trials (61–27), we retrieved 31 primary publications; 15 primary publications mentioned the use ofa PRO measure. None of the 36 clinical trials that mentioned the use of PRO measures (21 protocols and 15primary publications) documented clear PRO or clinical outcome assessment (COA) measurement strategies,provided clear justifications for PRO selection, or reasons why specific PRO measures were selected when alternatives existed.Conclusion: PRO measure selection for clinical trials is not evidence-based or underpinned by structured systematic approaches. This represents a critical area for study design improvement as PRO measure results directlyaffect patient care, PRO measurement has conceptual and contextual complexities, and there is a wide range ofoptions when selecting a PRO measure. We recommend trial designers use formal approaches for PRO measureselection to ensure PRO measurement-based decisions are optimised. We provide a simple, logical, five-stageapproach for PRO measure selection in clinical trials.
DOI Link
Publication Date
2023-08-01
Publication Title
Multiple Sclerosis and Related Disorders
Volume
76
ISSN
2211-0348
Acceptance Date
2023-06-01
Deposit Date
2023-08-15
Embargo Period
2023-08-16
Funding
Medical writing support for the review was funded by Novartis Pharma AG.
Keywords
Clinical assessment, Clinical measurement, Clinical outcome assessment, Clinical trial, Cost effectiveness research, Medical decision-making, Patient-reported outcome (PRO), PRO measure
Creative Commons License
This work is licensed under a Creative Commons Attribution 4.0 International License.
Recommended Citation
Hobart, J., Chitnis, T., Oh, J., Burke, L., King, M., Vo, P., Vandercappellen, J., & Lloyd, A. (2023) 'Do clinical trials prepare to fail by failing to prepare? An examination of MS trials and recommendations for patient-reported outcome measure selection', Multiple Sclerosis and Related Disorders, 76. Available at: 10.1016/j.msard.2023.104788
