School of Pharmacy and Pharmaceutical Sciences, University of California Irvine, Irvine, California, USA.
Kaiser Permanente Washington Health Research Institute, Seattle, Washington, USA.
Clin Pharmacol Ther. 2022 Jan;111(1):116-121. doi: 10.1002/cpt.2256. Epub 2021 May 2.
Concerns regarding both the limited generalizability and the slow pace of traditional randomized trials have led to calls for greater use of real-world evidence in the evaluation of new treatments or products. Real-world clinical trials or pragmatic trials often differ from traditional clinical trials in the use of open-label or nonblinded treatments delivered by real-world clinicians in community practice settings. Blinding and standardization of treatment may sometimes be necessary for internal validity, but they may also obscure or distort meaningful differences between treatments. When investigators consider whether blinding of clinicians, patients, or assessors is necessary, we suggest they consider several specific questions: Will clinicians, patients, and assessors have expectations or preferences regarding benefits or adverse effects? How might those expectations affect treatment uptake, treatment adherence, or assessment of outcomes? Will expectations differ in the settings where trial results will be applied? How would blinding of treatment reduce biases? How would blinding obscure true differences between treatments? How would procedures necessary for blinding reduce acceptability or increase risk of trial participation? When investigators consider how strictly treatments should be standardized, we suggest they consider several specific questions: How would treatment effectiveness or safety vary according to clinician experience or expertise? What level of experience or expertise is available in potential trial settings and settings where trial results would be applied? Is some level of standardization necessary for valid inference? Considering any special vulnerabilities of the study population, is some level of standardization necessary to assure participant safety?
人们对传统随机试验的推广性有限和进展缓慢感到担忧，这促使人们呼吁在评估新的治疗方法或产品时更多地使用真实世界证据。真实世界临床试验或实用临床试验在使用开放标签或非盲治疗方面通常与传统临床试验不同，这些治疗由真实世界的临床医生在社区实践环境中提供。为了内部有效性，有时可能需要对治疗进行盲法和标准化，但这也可能掩盖或扭曲治疗之间的有意义差异。当研究人员考虑是否需要对临床医生、患者或评估者进行盲法时，我们建议他们考虑以下几个具体问题：临床医生、患者和评估者是否会对治疗的益处或不良反应有期望或偏好？这些期望会如何影响治疗的接受程度、治疗的依从性或结局的评估？在将试验结果应用的环境中，期望会有所不同吗？治疗的盲法会减少哪些偏见？治疗的盲法会掩盖哪些真实差异？为了进行盲法而采取的程序会降低试验的可接受性还是增加参与试验的风险？当研究人员考虑应该如何严格地对治疗进行标准化时，我们建议他们考虑以下几个具体问题：根据临床医生的经验或专业知识，治疗效果或安全性会有何不同？潜在试验环境和将试验结果应用的环境中可获得何种经验或专业知识水平？是否需要一定程度的标准化才能进行有效的推断？考虑到研究人群的任何特殊脆弱性，是否需要一定程度的标准化来确保参与者的安全？
