Kris Oliver Jalusic1, David Ellenberger2, Paulus Rommer3, Alexander Stahmann2, Uwe Zettl4, Klaus Berger1. 1. Institute of Epidemiology and Social Medicine, University of Muenster, Muenster, Germany. 2. MS Forschungs- und Projektentwicklungs-gGmbH, German MS Register, Hannover, Germany. 3. Department of Neurology, University Medicine Rostock, Rostock, Germany/Department of Neurology, Medical University of Vienna, Vienna, Austria. 4. Department of Neurology, University Medicine Rostock, Rostock, Germany.
Abstract
BACKGROUND: Newly approved, drug-modifying therapies are associated with still unknown adverse events, although clinical trials leading to approval have strict inclusion and exclusion criteria and analyse safety and efficacy. OBJECTIVES: The aim of this study was to analyse the eligibility of multiple sclerosis (MS) patients treated in routine care into the phase III clinical trial of the respective drug. METHODS: In total, 3577 MS patients with 4312 therapies were analysed. Patients with primary-progressive MS were excluded. Inclusion and exclusion criteria of phase III clinical trials in relapsing-remitting MS were adopted and subsequently applied. A comparison in clinical and sociodemographic characteristics was made between patient who met the criteria and those who did not. RESULTS: 83% of registered patients would not have been eligible to the respective phase III clinical trial. Relapse was the single most frequent criterion not fulfilled (74.7%), followed by medication history (21.2%). CONCLUSION: The majority of MS patients treated in routine care would not have met clinical trials criteria. Thus, the efficacy and safety of therapies in clinical trials can differ from those in the real world. Broader phase III inclusion criteria would increase their eligibility and contribute to a better generalizability of the results in clinical trials.
BACKGROUND: Newly approved, drug-modifying therapies are associated with still unknown adverse events, although clinical trials leading to approval have strict inclusion and exclusion criteria and analyse safety and efficacy. OBJECTIVES: The aim of this study was to analyse the eligibility of multiple sclerosis (MS) patients treated in routine care into the phase III clinical trial of the respective drug. METHODS: In total, 3577 MS patients with 4312 therapies were analysed. Patients with primary-progressive MS were excluded. Inclusion and exclusion criteria of phase III clinical trials in relapsing-remitting MS were adopted and subsequently applied. A comparison in clinical and sociodemographic characteristics was made between patient who met the criteria and those who did not. RESULTS: 83% of registered patients would not have been eligible to the respective phase III clinical trial. Relapse was the single most frequent criterion not fulfilled (74.7%), followed by medication history (21.2%). CONCLUSION: The majority of MS patients treated in routine care would not have met clinical trials criteria. Thus, the efficacy and safety of therapies in clinical trials can differ from those in the real world. Broader phase III inclusion criteria would increase their eligibility and contribute to a better generalizability of the results in clinical trials.
Entities:
Keywords:
Multiple sclerosis; drug approval; drug safety; generalizability; multiple sclerosis disease therapy; pharmacoepidemiology; phase III clinical trials; registry
Authors: Lisa-Marie Ohle; David Ellenberger; Peter Flachenecker; Tim Friede; Judith Haas; Kerstin Hellwig; Tina Parciak; Clemens Warnke; Friedemann Paul; Uwe K Zettl; Alexander Stahmann Journal: Sci Rep Date: 2021-06-25 Impact factor: 4.379