目的:评估对间充质基质细胞(MSCs)治疗肌肉骨骼疾病的介入试验登记和报告结果的法定要求的遵守情况,并描述试验的临床和设计特点。
方法:对已发表的试验和提交给公共登记处的试验的系统评价。
方法:数据库Medline,科克伦图书馆和麦克马斯特;六个公共临床登记处。所有搜索都进行到2023年1月31日。
方法:提交给注册管理机构并在2021年1月之前完成的试验。发表在同行评审期刊上的前瞻性介入试验。
方法:第一作者搜索了那些(1)在公共注册表中发布了试验结果的试验,(2)在同行评审的出版物中介绍了结果,以及(3)在发布前向注册表提交了审前协议。其他提取的变量包括试验设计,参与人数,资金来源,随访持续时间和细胞类型。
结果:在登记处和文献数据库中发现了总共124项试验。膝关节骨性关节炎是最常见的适应症。在100项注册试验中,52项试验,共有2993名参与者既没有在注册登记中公布结果,也没有公布结果。52项注册试验回顾性地提交了协议。在已发表的67项试验中,有43项(64%)注册了审前方案。资金来源与遵守报告要求无关。在25项试验中的16项发现了注册和出版物中主要终点之间的差异。在28%的试验中,治疗组采用辅助治疗.只有39%的对照试验是双盲的。
结论:很大一部分试验不符合注册和报告结果的法定要求,从而增加了结果评估中偏差的风险。为了提高对MSCs在肌肉骨骼疾病中的作用的信心,注册管理机构和医学期刊应更严格地执行现有的注册和报告要求。
OBJECTIVE: 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.
METHODS: A systematic review of published trials and trials submitted to public registries.
METHODS: The databases Medline, Cochrane Library and McMaster; six public clinical registries. All searches were done until 31 January 2023.
METHODS: Trials submitted to registries and completed before January 2021. Prospective interventional trials published in peer-reviewed journals.
METHODS: 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.
RESULTS: 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.
CONCLUSIONS: 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.