Patient-reported outcome measures in MS: Do development processes and patient involvement support valid quantification of clinically important variables?

Trishna Bharadia; Jo Vandercappellen; Tanuja Chitnis; Piet Eelen; Birgit Bauer; Giampaolo Brichetto; Andrew Lloyd; Hollie Schmidt; Miriam King; Jennifer Fitzgerald; Thomas Hach; Jeremy Hobart

doi:10.1177/20552173221105642

Patient-reported outcome measures in MS: Do development processes and patient involvement support valid quantification of clinically important variables?

Mult Scler J Exp Transl Clin. 2022 Jun 22;8(2):20552173221105642. doi: 10.1177/20552173221105642. eCollection 2022 Apr-Jun.

Authors

Affiliations

¹ Patient Author, Marlow, UK.
² Novartis Pharma AG, Basel, Switzerland.
³ Department of Neurology, Brigham and Women's Hospital, Boston, MA, USA.
⁴ National Multiple Sclerosis Center of Melsbroek, Flanders, Belgium.
⁵ Manufaktur für Antworten UG, Abensberg, Germany.
⁶ Associazione Italiana Sclerosi Multipla Rehabilitation Center, Genoa, Italy.
⁷ Acaster Lloyd Consulting Ltd, London, UK.
⁸ Accelerated Cure Project for Multiple Sclerosis, Waltham, MA, USA.
⁹ Peninsula Schools of Medicine and Dentistry, University of Plymouth, Plymouth, UK.

Abstract

Background: Patient-reported outcomes (PROs) are widely measured in multiple sclerosis (MS) studies. However, the quality of instrument development processes varies, raising concerns about the meaningfulness of associated data.

Objectives: To review the development of selected PROs commonly used in MS studies, including definitions of the concepts measured, use of conceptual frameworks, and degree of input from people living with MS (PlwMS). To gain insights and recommendations from PlwMS on their experience with these PROs.

Methods: We assessed 6 PROs (FSIQ-RMS, modified-FIS, MSQoL-54, Leeds 8-item MSQoL, MSIS-29 and EQ-5D) for alignment with regulatory and scientific requirements on PRO structure/development. PlwMS evaluated the degree to which the PROs reflect disease aspects they perceive important.

Results: Definitions, clarifications and conceptualisations of the measurement variables were often lacking. PlwMS were variably involved in PRO development. Ethnic diversity was rarely documented. PlwMS identified individualisation, ease of understanding, time burden, and mode of administration as factors affecting PRO usability.

Conclusions: To date, the PRO development process has consistently lacked clear definitions of concepts of interest, use of conceptual frameworks and patient involvement, thereby compromising the validity of data they generate. PRO instrument development must be conducted more robustly to maximise the value of pivotal clinical trials.

Keywords: Multiple sclerosis; fatigue; impact; insights; patient-reported outcomes; symptoms.