Centre for Statistics in Medicine, Nuffield Department of Orthopaedics, Rheumatology and Musculoskeletal Sciences, University of Oxford, Oxford, UK.
Medical Statistics Group, School of Health and Related Research, University of Sheffield, Sheffield, UK.
Health Technol Assess. 2019 Oct;23(60):1-88. doi: 10.3310/hta23600.
The randomised controlled trial is widely considered to be the gold standard study for comparing the effectiveness of health interventions. Central to its design is a calculation of the number of participants needed (the sample size) for the trial. The sample size is typically calculated by specifying the magnitude of the difference in the primary outcome between the intervention effects for the population of interest. This difference is called the 'target difference' and should be appropriate for the principal estimand of interest and determined by the primary aim of the study. The target difference between treatments should be considered realistic and/or important by one or more key stakeholder groups.
The objective of the report is to provide practical help on the choice of target difference used in the sample size calculation for a randomised controlled trial for researchers and funder representatives.
The Difference ELicitation in TriAls (DELTA) recommendations and advice were developed through a five-stage process, which included two literature reviews of existing funder guidance and recent methodological literature; a Delphi process to engage with a wider group of stakeholders; a 2-day workshop; and finalising the core document.
Advice is provided for definitive trials (Phase III/IV studies). Methods for choosing the target difference are reviewed. To aid those new to the topic, and to encourage better practice, 10 recommendations are made regarding choosing the target difference and undertaking a sample size calculation. Recommended reporting items for trial proposal, protocols and results papers under the conventional approach are also provided. Case studies reflecting different trial designs and covering different conditions are provided. Alternative trial designs and methods for choosing the sample size are also briefly considered.
Choosing an appropriate sample size is crucial if a study is to inform clinical practice. The number of patients recruited into the trial needs to be sufficient to answer the objectives; however, the number should not be higher than necessary to avoid unnecessary burden on patients and wasting precious resources. The choice of the target difference is a key part of this process under the conventional approach to sample size calculations. This document provides advice and recommendations to improve practice and reporting regarding this aspect of trial design. Future work could extend the work to address other less common approaches to the sample size calculations, particularly in terms of appropriate reporting items.
Funded by the Medical Research Council (MRC) UK and the National Institute for Health Research as part of the MRC-National Institute for Health Research Methodology Research programme.
随机对照试验被广泛认为是比较健康干预措施效果的金标准研究。其设计的核心是计算试验所需的参与者数量（样本量）。样本量通常通过指定感兴趣人群中干预效果的主要结局之间的差异幅度来计算。这种差异称为“目标差异”，应适合主要感兴趣的估计量，并由研究的主要目的决定。治疗之间的目标差异应被一个或多个主要利益相关者群体认为是现实的和/或重要的。
本报告的目的是为研究人员和资助者代表提供有关随机对照试验中样本量计算中使用的目标差异选择的实用帮助。
通过五个阶段的过程制定了差异诱导试验（DELTA）建议和意见，其中包括对现有资助者指南和最近方法学文献的两次文献综述；德尔菲（Delphi）过程以吸引更广泛的利益相关者群体；为期两天的研讨会；以及最终确定核心文件。
为确证性试验（III/IV 期研究）提供了建议。回顾了选择目标差异的方法。为了帮助那些对此主题不熟悉的人，并鼓励更好的实践，提出了 10 条关于选择目标差异和进行样本量计算的建议。还提供了在传统方法下报告试验提案、方案和结果文件的建议项目。提供了反映不同试验设计和涵盖不同情况的案例研究。还简要考虑了替代试验设计和选择样本量的方法。
如果研究要为临床实践提供信息，选择适当的样本量至关重要。试验中招募的患者数量需要足够回答目标；然而，数量不应高于必要的程度，以避免给患者带来不必要的负担和浪费宝贵的资源。在传统的样本量计算方法下，目标差异的选择是这一过程的关键部分。本文提供了关于这一方面的试验设计的建议和建议，以改进实践和报告。未来的工作可以扩展到解决样本量计算的其他不太常见的方法，特别是在适当的报告项目方面。
由英国医学研究理事会（MRC）和英国国家健康研究所资助，作为 MRC-英国国家健康研究所方法学研究计划的一部分。
