Epidemiology Unit, Health Research Institute-Fundación Jiménez Díaz University Hospital, Universidad Autónoma de Madrid, E-28040, Madrid, Spain.
Meta-Research Innovation Center at Stanford (METRICS), Stanford University, Stanford, CA, 94305, USA.
BMC Med. 2018 Apr 3;16(1):49. doi: 10.1186/s12916-018-1038-2.
Pragmatic randomized controlled trials (RCTs) mimic usual clinical practice and they are critical to inform decision-making by patients, clinicians and policy-makers in real-world settings. Pragmatic RCTs assess effectiveness of available medicines, while explanatory RCTs assess efficacy of investigational medicines. Explanatory and pragmatic are the extremes of a continuum. This debate article seeks to evaluate and provide recommendation on how to characterize pragmatic RCTs in light of the current landscape of RCTs. It is supported by findings from a PubMed search conducted in August 2017, which retrieved 615 RCTs self-labeled in their titles as "pragmatic" or "naturalistic". We focused on 89 of these trials that assessed medicines (drugs or biologics).
36% of these 89 trials were placebo-controlled, performed before licensing of the medicine, or done in a single-center. In our opinion, such RCTs overtly deviate from usual care and pragmatism. It follows, that the use of the term 'pragmatic' to describe them, conveys a misleading message to patients and clinicians. Furthermore, many other trials among the 615 coined as 'pragmatic' and assessing other types of intervention are plausibly not very pragmatic; however, this is impossible for a reader to tell without access to the full protocol and insider knowledge of the trial conduct. The degree of pragmatism should be evaluated by the trial investigators themselves using the PRECIS-2 tool, a tool that comprises 9 domains, each scored from 1 (very explanatory) to 5 (very pragmatic).
To allow for a more appropriate characterization of the degree of pragmatism in clinical research, submissions of RCTs to funders, research ethics committees and to peer-reviewed journals should include a PRECIS-2 tool assessment done by the trial investigators. Clarity and accuracy on the extent to which a RCT is pragmatic will help understand how much it is relevant to real-world practice.
实用随机对照试验（RCT）模拟了常规临床实践，对于在真实环境中为患者、临床医生和决策者提供决策依据至关重要。实用 RCT 评估现有药物的有效性，而解释性 RCT 评估研究药物的疗效。解释性和实用性是一个连续体的两个极端。本文旨在评估并提供建议，以根据当前 RCT 格局来描述实用 RCT。这篇辩论文章的依据是 2017 年 8 月进行的 PubMed 搜索结果，该搜索在标题中检索到 615 项自我标记为“实用”或“自然主义”的 RCT。我们重点关注了其中 89 项评估药物（药物或生物制剂）的试验。
这 89 项试验中有 36%是安慰剂对照的，在药物获得许可之前进行，或者在单一中心进行。在我们看来，这些 RCT 明显偏离了常规护理和实用性。因此，使用“实用”一词来描述它们，向患者和临床医生传达了一个误导性的信息。此外，在 615 项被标记为“实用”并评估其他类型干预的试验中，许多其他试验可能并不十分实用；然而，对于读者来说，如果没有获得完整的方案和试验实施的内部知识，就不可能知道这一点。实用性的程度应该由试验研究者自己使用 PRECIS-2 工具进行评估，该工具包含 9 个领域，每个领域的得分从 1（非常解释性）到 5（非常实用）。
为了更准确地描述临床研究的实用程度，向资助者、研究伦理委员会和同行评议期刊提交 RCT 时，应包括试验研究者进行的 PRECIS-2 工具评估。明确和准确地说明 RCT 的实用程度将有助于理解其与现实实践的相关性。
