Use of pragmatic randomized trials in multiple sclerosis: A systematic overview - Hirt, J.; Janiaud, P.; Dublin, P.; Nicoletti, G. J.; Dembowska, K.; Nguyen, T. V. T.; Woelfle, T.; Axfors, C.; Yaldizli, O.; Granziera, C.; Kuhle, J.; Kappos, L.; et al. (Mult Scler, 2024)
BACKGROUND: Pragmatic trials are increasingly recognized for providing real-world evidence on treatment choices. OBJECTIVE: The objective of this study is to investigate the use and characteristics of pragmatic trials in multiple sclerosis (MS). METHODS: Systematic literature search and analysis of pragmatic trials on any intervention published up to 2022. The assessment of pragmatism with PRECIS-2 (PRagmatic Explanatory Continuum Indicator Summary-2) is performed. RESULTS: We identified 48 pragmatic trials published 1967-2022 that included a median of 82 participants (interquartile range (IQR) = 42-160) to assess typically supportive care interventions (n = 41; 85%). Only seven trials assessed drugs (15%). Only three trials (6%) included >500 participants. Trials were mostly from the United Kingdom (n = 18; 38%), Italy (n = 6; 13%), the United States and Denmark (each n = 5; 10%). Primary outcomes were diverse, for example, quality-of-life, physical functioning, or disease activity. Only 1 trial (2%) used routinely collected data for outcome ascertainment. No trial was very pragmatic in all design aspects, but 14 trials (29%) were widely pragmatic (i.e. PRECIS-2 score ⩾ 4/5 in all domains). CONCLUSION: Only few and mostly small pragmatic trials exist in MS which rarely assess drugs. Despite the widely available routine data infrastructures, very few trials utilize them. There is an urgent need to leverage the potential of this pioneering study design to provide useful randomized real-world evidence.
Keywords: journalArticle; (1) advisory board and consultancy fees from Actelion, Novartis, Genzyme, and F; (2) speaker fees from Biogen and Genzyme-Sanofi; (Research Center for Clinical Neuroimmunology and Neuroscience Basel) is; *Multiple Sclerosis/drug therapy/therapy; *Pragmatic Clinical Trials as Topic; Basel, Free Academy Basel, Swiss Multiple Sclerosis Society, Swiss National; Consulting, Minoryx, Novartis, F. Hoffmann-La Roche Ltd, Senda Biosciences Inc.,; ECTRIMS/MAGNIMS, University of Basel, Pro Patient Stiftung University Hospital; Foundation (320030_189140/1), University of Basel, Biogen, Celgene, Merck,; G.J.N. declares no competing interests. K.D. declares no competing interests; Hoffmann-La Roche Ltd; Humans; Multiple sclerosis; Neuroimmunology and Neuroscience Basel) have received and used exclusively for; Neuroimmunology and Neuroscience Basel) is supported by Foundation Clinical; Neuroimmunology and Neuroscience Basel; Neuroimmunology and Neuroscience Basel. O.Y. received grants from; Neuroimmunology and Neuroscience Basel. P.D. declares no competing interests; Neuroimmunology and Neuroscience Basel. T.W. declares no competing interests; Novartis, Octave Bioscience, Roche, and Sanofi. L.K. has received no personal; RC2NB (Research Center for Clinical Neuroimmunology and Neuroscience Basel) is; Randomized Controlled Trials as Topic; Sanofi and Biogen. C.G. as the employer of the University Hospital Basel (USB); Sanofi, Santhera, Shionogi BV, TG Therapeutics, and Wellmera, and license fees; Science Foundation and advisory board/lecture and consultancy fees from Roche,; Serono, Genentech, Glaxo Smith Kline, Janssen, Japan Tobacco, Merck, MH; also received speaker honoraria and travel funding by Novartis. J.K. received; and (3); by the Progressive MS Alliance, Swiss MS Society, Swiss National Research; compensation. His institutions (University Hospital Basel/Stiftung; declares no competing interests. RC2NB (Research Center for Clinical; for Neurostatus-UHB products; from: Actelion, Bayer, BMS, df-mp Molnia & Pohlmann, Celgene, Eli Lilly, EMD; grants from Novartis, InnoSuisse, and Roche. L.G.H.; has received the following fees which were used exclusively for research support:; participation, consultancy services, and participation in educational activities; potential conflicts of interest with respect to the research, authorship, and/or; pragmatic clinical trial; publication of this article: J.H. declares no competing interests. RC2NB; randomized controlled trial; research support by F. Hoffmann-La Roche Ltd. Before my employment at USB, I have; research support payments for steering committee and advisory board; routinely collected health data; speaker fees, research support, travel support, and/or served on advisory boards; supported by Foundation Clinical Neuroimmunology and Neuroscience Basel. C.A.; supported by Foundation Clinical Neuroimmunology and Neuroscience Basel. P.J.; supported by Foundation Clinical Neuroimmunology and Neuroscience Basel. T.V.T.N.