National Institute for Health Research (NIHR) Biomedical Research Centre at University Hospitals Bristol NHS Foundation Trust and University of Bristol, Surgical Innovation Theme.
Medical Research Council ConDuCT-II Hub for Trials Methodology Research, Bristol Centre for Surgical Research, Population Health Sciences, Bristol Medical School.
Br J Surg. 2020 Aug;107(9):1114-1122. doi: 10.1002/bjs.11509. Epub 2020 Mar 18.
Placebo-controlled trials play an important role in the evaluation of healthcare interventions. However, they can be challenging to design and deliver for invasive interventions, including surgery. In-depth understanding of the component parts of the treatment intervention is needed to ascertain what should, and should not, be delivered as part of the placebo. Assessment of risk to patients and strategies to ensure that the placebo effectively mimics the treatment are also required. To date, no guidance exists for the design of invasive placebo interventions. This study aimed to develop a framework to optimize the design and delivery of invasive placebo interventions in RCTs.
A preliminary framework was developed using published literature to: expand the scope of an existing typology, which facilitates the deconstruction of invasive interventions; and identify placebo optimization strategies. The framework was refined after consultation with key stakeholders in surgical trials, consensus methodology and medical ethics.
The resulting DITTO framework consists of five stages: deconstruct treatment intervention into constituent components and co-interventions; identify critical surgical element(s); take out the critical element(s); think risk, feasibility and role of placebo in the trial when considering remaining components; and optimize placebo to ensure effective blinding of patients and trial personnel.
DITTO considers invasive placebo composition systematically, accounting for risk, feasibility and placebo optimization. Use of the framework can support the design of high-quality RCTs, which are needed to underpin delivery of healthcare interventions.
安慰剂对照试验在评估医疗保健干预措施方面发挥着重要作用。然而，对于包括手术在内的侵入性干预措施，设计和实施安慰剂对照试验具有挑战性。需要深入了解治疗干预措施的组成部分，以确定哪些应该作为安慰剂的一部分提供，哪些不应该提供。还需要评估对患者的风险和确保安慰剂有效模拟治疗的策略。迄今为止，尚无关于侵入性安慰剂干预设计的指南。本研究旨在制定一个框架，以优化 RCT 中侵入性安慰剂干预的设计和实施。
使用已发表的文献制定了一个初步框架，以扩展现有分类法的范围，该分类法有助于对侵入性干预措施进行分解；并确定安慰剂优化策略。该框架在与手术试验、共识方法学和医学伦理方面的主要利益相关者协商后进行了改进。
由此产生的 DITTO 框架包括五个阶段：将治疗干预措施分解为组成部分和共同干预措施；确定关键手术要素；去除关键要素；在考虑剩余组成部分时，考虑试验中剩余部分的风险、可行性和安慰剂的作用；并优化安慰剂以确保患者和试验人员的有效盲法。
DITTO 系统地考虑了侵入性安慰剂的组成，考虑了风险、可行性和安慰剂的优化。该框架的使用可以支持高质量 RCT 的设计，这对于提供医疗保健干预措施至关重要。
