Exploratory trials of complex public health interventions: development of guidance for researchers and funders

人们日益认识到，干预措施对改善饮食、体育活动和药物使用等健康行为具有潜在的公共卫生价值。鉴于这些行为的因果关系复杂，改善公共卫生往往需要复杂的干预措施，其中包括相互作用以产生变化的多个组成部分，其行动受到其与所涉环境相互作用的制约和促进。考虑到这些干预措施的成本和潜在的非预期伤害，利用有效的证据并严格评估有效性至关重要。在可行的情况下，随机对照试验（RCT）是检查有效性的最有力手段。然而，复杂的干预措施往往难以在多种环境和目标群体中以符合方案理论的方式实施，而在真实的环境中开展和解释随机对照试验具有挑战性。因此，在进行明确的评价之前，无论是随机的还是其他的，都需要注意建立干预计划和预期评价设计的可行性和可接受性。随着越来越多的研究描述了建立全规模试验可行性的目标，越来越多的人认识到需要仔细检查这些问题。这些研究被描述为“探索性试验”，“2期试验”或“试点和可行性”研究。然而，目前缺乏一致的指导，为研究人员准备此类工作的投标，或同行评审员或资助者，在这些研究中要解决的最重要的问题，解决这些问题的关键方法学考虑，当它或多或少适合在这个阶段使用随机化，以及决定是否以及如何进行全面最终评价的标准。因此，正如描述这些研究的术语范围所反映的那样，它们的实施和报告不一致，并且关于是否进行全面评估的结论的基础往往不明确。拟议的研究将通过审查当前实践和征求专家资助者和研究人员的意见，为探索性试验的实施制定指南，首先，使用系统性综述方法，确定描述了研究全规模试验（包括II期试验、探索性试验或可行性和试点研究）潜力的研究，以及关于其开展的现有指南。我们还将进行水平扫描练习，以确定在临床研究的其他领域的2期试验和试点和可行性研究的设计中的最新方法学发展，以确保指南从这些相关领域的最新发展中学习。然后将使用基于网络的德尔菲过程和共识会议来制定关于何时进行探索性试验的指南，他们应该解决什么样的研究问题，在进行此类研究时的关键方法学考虑因素，以及应该为进行全面最终试验的决定提供信息的标准范围。然后，该指南将积极传播给研究资助者，研究人员和期刊编辑，以最大限度地发挥其对复杂公共卫生干预措施探索性试验的委托，实施和报告的影响。

Recognition is growing of the potential public health value of interventions to improve health behaviours such as diet, physical activity and substance use. Given the complex causality of these behaviours, improving public health often requires complex interventions which comprise multiple components interacting to produce change, with their actions constrained and facilitated by their interaction with the settings into which they are introduced. Given the cost of such interventions and the potential for unintended harms, drawing on evidence of what works and rigorously evaluating effectiveness is crucial.Where feasible, randomised controlled trials (RCTs) represent the most robust means of examining effectiveness. However, complex interventions are often difficult to implement in a manner consistent with programme theory across multiple settings and target groups, whilst conducting and interpreting RCTs in real word settings is challenging. Hence, prior to committing to definitive evaluation, randomised or otherwise, attention is needed to establishing the feasibility and acceptability of intervention plans and intended evaluation designs.The need to carefully examine these issues is increasingly recognised, with an increasing number of studies describing an objective of establishing the feasibility of full scale trials. Such studies are described under terms including 'exploratory trials', 'phase 2 trials' or 'piloting and feasibility' studies. However, there is currently a lack of consistent guidance for researchers preparing bids for such work, or for peer reviewers or funders, on the most important questions to address in such studies, key methodological considerations in addressing these questions, when it is more or less appropriate to use randomisation during this phase, and the criteria on which decisions should be made regarding whether and how to progress to a full scale definitive evaluation. Hence, as reflected by the range of terms under which such studies are described, their conduct and reporting is inconsistent, and the basis on which conclusions regarding whether or not to progress to a full-scale evaluation are made often unclear.The proposed study will develop guidance for the conduct of exploratory trials through reviewing current practice and eliciting views of expert funders and researchers, beginning by using systematic review methodology to identify studies describing an intention to investigate the potential for a full scale trial (including phase 2 trials, exploratory trials or feasibility and pilot studies) and existing guidance on their conduct. We will also conduct a horizon-scanning exercise to identify recent methodological developments in the design of phase 2 trials and pilot and feasibility studies in other areas of clinical research, to ensure that the guidance learns from recent developments in these related areas.A web-based Delphi process and consensus meeting will then be used to develop guidance on when exploratory trials should be conducted, what research questions they should address, key methodological considerations in the conduct of such studies and the range of criteria that should inform a decision to proceed to a full scale definitive trial. The guidance will then be actively disseminated to research funders, researchers and journal editors to maximise its impact on the commissioning, conduct and reporting of exploratory trials of complex public health interventions.