The Role of Mobility Endpoints in Marketing Authorisation of Drugs: What Gets the EMA Moving?

Abstract

Background: Mobility is defined as the ability to independently move around the environment and is a key contributor to quality of life. The aim of this study was to evaluate the use of mobility as a decisive outcome for the marketing authorisation of drugs by the European Medicines Agency (EMA). Methods: Fifteen therapeutic areas which commonly lead to mobility impairments and alter the quantity and/or the quality of walking were selected: two systemic neurological diseases, four conditions primarily affecting exercise capacity, seven musculoskeletal diseases, and two conditions representing sensory impairments. European Public Assessment Reports (EPARs) published by the EMA up to September 2020 were examined for mobility endpoints included in their ‘main studies’, defined as those which were decisive for EU approval. Clinical study registries and primary scientific publications for these studies were also reviewed. Findings: 484 EPARs yielded 186 relevant documents with 402 ‘main studies’. The EPARs reported 153 primary and 584 secondary endpoints which considered mobility; 70 different assessment tools (38 patient-reported outcomes, 13 clinician-reported outcomes, 8 performance outcomes, and 13 composite endpoints) were used. Importantly, only 15·7% of those tools distinctly informed on patients’ mobility status. 105/402 (26·1%) of the ‘main studies’ did not have any mobility assessment and none of these studies included a digital mobility outcome. The supplementary review of study registries and primary publications revealed only five uses of mobility assessments not reported by EPARs. Interpretation: For conditions with a high impact on mobility, distinct mobility assessment was given little consideration in the marketing authorisation of drugs by the EMA. Where mobility impairment was considered to be a relevant outcome, questionnaires or composite scores were predominantly used. Reporting biases for such outcomes presents challenges for the interpretation of study results. Funding: Mobilise-D (Innovative Medicines Initiative) and Robert Bosch Stiftung, Germany. Declaration of Interest: SJ is partly supported by the Robert Bosch Stiftung Stuttgart. MW reports grants from HORIZON2020 IMI No. 820820, during the conduct of the study. DS reports grants from HORIZON2020 IMI No. 820820, during the conduct of the study. MC reports personal fees from Takeda Pharmaceuticals, during the conduct of the study; personal fees from Takeda Pharmaceuticals, outside the submitted work. JK reports grants from HORIZON2020 IMI No. 820820, during the conduct of the study. JGA reports grants from HORIZON2020 IMI No. 820820, and from AstraZeneca, Chiesi, Esteve, outside the submitted work. WM receives or received funding from the European Union, the German Federal Ministry of Education of Research, Michael J. Fox Foundation, Robert Bosch Foundation, Neuroalliance, Lundbeck and Janssen. He received speaker honoraria from Abbvie, Bayer, GlaxoSmithKline, Licher MT, Rolke Pharma and UCB, was invited to Advisory Boards of Abbvie, Biogen, Lundbeck and Market Access & Pricing Strategy GmbH, and is an advisory board member of the Critical Path for Parkinson's Consortium. He serves as the co-chair of the MDS Technology Task Force. MP reports grants from HORIZON2020 IMI No. 820820, outside the submitted work. MS is supported by the Robert Bosch Stiftung Stuttgart and reports grants from HORIZON2020 IMI 2 Mobilise D, during the conduct of the study, and grants and non-financial support from Green Cross WellBeing Co. Ltd., Gilead Sciences Inc., Robert Bosch GmbH, and CORAT Therapeutics GmbH , as well as other from Agena Bioscience GmbH, outside the submitted work. CB disclosed consultation from E. Lilly and speaker fees from Amgen, Nutricia and Pfizer reports grants from HORIZON2020 IMI No. 820820, during the conduct of the study. RT, BS, LL, LR, SCR declare no competing interests.