Molecular, Genetic and Population Health Sciences, The University of Edinburgh Medical School, Edinburgh, UK
Department of Surgery, University Digestive Health Care Center, Clarunis, University Hospital Basel, Basel, Switzerland.
BMJ Open. 2024 Aug 24;14(8):e089587. doi: 10.1136/bmjopen-2024-089587.
The reporting of randomised controlled non-inferiority (NI) drug trials is poor with less than 50% of published trials reporting a justification of the NI margin. This is despite the introduction of the Consolidated Standards of Reporting Trials (CONSORT) extension on reporting of NI and equivalence in randomised trials. It is critical to set the appropriate NI margin as this choice dictates the conclusions of the trial. Methods to estimate the margin are heterogeneous but generally based on clinical judgement and statistical reasoning, and hence tailored to each clinical situation. Yet an appraisal of NI in clinical trials has not been undertaken. Therefore the aim of this systematic review is to assess the reporting and methodological quality of defining the NI margin. Surgical NI trials have been chosen as our prototype to assess this.
We will conduct a systematic review of published randomised controlled trials in abdominal surgery that use an NI design. Key eligibility criteria will be: surgical intervention in at least one trial arm; adult patients and a sample size of 100 or more. Ovid MEDLINE, EMBASE and the Cochrane Central Register of Controlled Trials will be searched from inception until the date of the search. Identified studies will be assessed for reporting according to the CONSORT recommendations. The outcomes are the description of the methods for defining the NI margin, and the robustness of the NI margin estimation. The latter will be based on simulations using alternative assumptions for model parameters. The results of the simulation will be compared with the trial authors' conclusions.
The review will describe and appraise the design and reporting of surgical NI trials including shortcomings thereof and allow a comparison with pharmaceutical trials. These findings will inform researchers on the appropriate design and pitfalls when conducting surgical randomised controlled trials with an NI design and promote thorough and standardised reporting of study findings.
Ethical approval is not required and any changes to the protocol will be communicated via the registration platform. The final manuscript will be submitted to a journal for publication and the findings will be disseminated through conference presentations to inform researchers and the public.
随机对照非劣效性（NI）药物试验的报告质量较差，少于 50%已发表的试验报告了 NI 边界的合理性。尽管 CONSORT 扩展报告了 NI 和随机试验等效性，但情况仍然如此。设定适当的 NI 边界至关重要，因为这一选择决定了试验的结论。估计边界的方法多种多样，但通常基于临床判断和统计推理，因此针对每个临床情况进行了定制。然而，临床试验中的 NI 评估尚未进行。因此，本系统评价的目的是评估定义 NI 边界的报告和方法学质量。我们选择了外科 NI 试验作为原型来评估这一点。
我们将对使用 NI 设计的腹部外科随机对照试验进行系统评价。主要纳入标准为：至少在一个试验臂中进行手术干预；成年患者，样本量为 100 例或更多。将从 Ovid MEDLINE、EMBASE 和 Cochrane 中央对照试验注册库中搜索从成立到搜索日期的文献。确定的研究将根据 CONSORT 建议进行报告评估。结果是描述定义 NI 边界的方法和 NI 边界估计的稳健性。后者将基于替代模型参数假设的模拟。模拟的结果将与试验作者的结论进行比较。
该综述将描述和评估外科 NI 试验的设计和报告，包括其不足之处，并允许与制药试验进行比较。这些发现将为研究人员提供有关在进行具有 NI 设计的外科随机对照试验时的适当设计和陷阱的信息，并促进对研究结果进行彻底和标准化的报告。
不需要伦理批准，任何对方案的更改都将通过注册平台进行沟通。最终手稿将提交给期刊发表，并通过会议演示传播研究结果，以告知研究人员和公众。
