Janiaud Perrine, Hemkens Lars G
Pragmatic Evidence Lab, Research Center for Clinical Neuroimmunology and Neuroscience Basel (RC2NB), University Hospital Basel and University of Basel, Basel, Switzerland; Department of Clinical Research, University Hospital Basel and University of Basel, Basel, Switzerland.
Pragmatic Evidence Lab, Research Center for Clinical Neuroimmunology and Neuroscience Basel (RC2NB), University Hospital Basel and University of Basel, Basel, Switzerland; Department of Clinical Research, University Hospital Basel and University of Basel, Basel, Switzerland; Meta-Research Innovation Center at Stanford (METRICS), Stanford University, Stanford, California, USA.
J Clin Epidemiol. 2024 Dec;176:111566. doi: 10.1016/j.jclinepi.2024.111566. Epub 2024 Oct 11.
Over half a century ago, the terms "pragmatic" and "explanatory" were introduced to biomedicine by Schwartz and Lellouch, presenting two distinct conceptual approaches to trial design. Today, we frequently say that there are pragmatic trials and there are explanatory trials. Pragmatic trials inform decision-making in practice, and explanatory trials aim to understand the mechanism of an intervention. They are often perceived as diametral extremes of a continuum. In this commentary, we argue that with the digitalization of health care and clinical research, ways for modern trial designs were paved and new avenues opened, and that there is no such continuum.
METHODS, RESULTS AND CONCLUSIONS: Since the groundbreaking work of Schwartz and Lellouch, new approaches and methods have become available that allow researchers to address pragmatic and explanatory questions in parallel in the same trial. Emerging availability of routinely collected "real-world" data, development of decentralized trial techniques, and creation of digital biomarkers allow to observe health outcomes with minimal or no interference in real-world care. This overcomes previous limitations to studying mechanisms of interventions in routine care and makes the idea of a continuum obsolete. We argue that pragmatism and explanatorism need to be understood as two distinct but compatible conceptual dimensions to open new perspectives for using novel technologies to design the most informative clinical trials and make better clinical and regulatory decisions. We base our argument on an analysis of the concept of a continuum and highlight its limitations. We review key trial design features and introduce a new concept that sees explanatory design features as fundamental, invasive or noninvasive, or sufficient or insufficient. We describe their impact on pragmatism and explanatorism and show how multidimensional pragmatic explanatory trials that are most useful are possible today.
半个多世纪前，施瓦茨（Schwartz）和勒卢什（Lellouch）将“务实的”和“解释性的”这两个术语引入生物医学领域，提出了两种截然不同的试验设计概念方法。如今，我们常说有务实性试验和解释性试验。务实性试验为实践中的决策提供信息，而解释性试验旨在了解干预措施的机制。它们常被视为一个连续统一体的两个极端。在本评论中，我们认为随着医疗保健和临床研究的数字化，为现代试验设计铺平了道路并开辟了新途径，而且不存在这样的连续统一体。
方法、结果与结论：自施瓦茨和勒卢什的开创性工作以来，已有新的方法和手段可供研究人员在同一试验中并行解决务实性和解释性问题。常规收集的“真实世界”数据的日益可得、去中心化试验技术的发展以及数字生物标志物的创建，使得能够在对真实世界医疗干预最小或无干扰的情况下观察健康结果。这克服了以往在常规医疗中研究干预机制的局限性，并使连续统一体的概念过时。我们认为务实主义和解释主义需要被理解为两个不同但兼容的概念维度，以便为利用新技术设计信息量最大的临床试验以及做出更好的临床和监管决策开辟新视角。我们的论点基于对连续统一体概念的分析，并突出其局限性。我们回顾关键的试验设计特征，并引入一个新概念，即将解释性设计特征视为基本的、有创或无创的，或充分或不充分的。我们描述它们对务实主义和解释主义的影响，并展示如今最有用的多维务实性解释性试验是如何成为可能的。
