Compliance with requirements for registration and reporting of results in trials of mesenchymal stromal cells for musculoskeletal disorders: a systematic review.

Abstract

To assess compliance with statutory requirements to register and report outcomes in interventional trials of mesenchymal stromal cells (MSCs) for musculoskeletal disorders and to describe the trials' clinical and design characteristics. A systematic review of published trials and trials submitted to public registries. The databases Medline, Cochrane Library and McMaster; six public clinical registries. All searches were done until 31 January 2023. Trials submitted to registries and completed before January 2021. Prospective interventional trials published in peer-reviewed journals. The first author searched for trials that had (1) posted trial results in a public registry, (2) presented results in a peer-reviewed publication and (3) submitted a pretrial protocol to a registry before publication. Other extracted variables included trial design, number of participants, funding source, follow-up duration and cell type. In total 124 trials were found in registries and literature databases. Knee osteoarthritis was the most common indication. Of the 100 registry trials, 52 trials with in total 2 993 participants had neither posted results in the registry nor published results. Fifty-two of the registry trials submitted a protocol retrospectively. Forty-three of the 67 published trials (64%) had registered a pretrial protocol. Funding source was not associated with compliance with reporting requirements. A discrepancy between primary endpoints in the registry and publication was found in 16 of 25 trials. In 28% of trials, the treatment groups used adjuvant therapies. Only 39% of controlled trials were double-blinded. A large proportion of trials failed to comply with statutory requirements for the registration and reporting of results, thereby increasing the risk of bias in outcome assessments. To improve confidence in the role of MSCs for musculoskeletal disorders, registries and medical journals should more rigorously enforce existing requirements for registration and reporting.