Design of placebo-controlled randomized trials of anticancer agents: Ethical considerations based on a review of published trials
Design of placebo-controlled randomized trials of anticancer agents: Ethical considerations based on a review of published trials
复制标题
抗癌药物安慰剂对照随机试验的设计：基于对已发表试验的回顾的伦理考虑
DOI：
10.1177/17407745211052474
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发表时间：
2021
期刊：
影响因子：
2.7
通讯作者：
C. Grady
中科院分区：
文献类型：
--
作者：
A. Doussau;Isha Agarwal;T. Fojo;I. Tannock;C. Grady
背景关于安慰剂对照癌症试验设计的信息有限。通过对2013年发表的试验的系统回顾，我们描述了在测试抗癌药物的随机试验中使用安慰剂的情况，并分析了增加试验方案暴露的策略。方法试验分为附加试验(安慰剂与标准治疗相结合)或仅服用安慰剂。审查了允许超过一半的参与者接受实验方案的策略。如果主要结果的差异显著(p ≤ 0.05)，则认为接受试验剂的风险-收益比是有利的，如果主要结果没有显著的差异且试验剂没有增加实质性毒性，则认为是中性的，否则认为是不利的。结果共纳入80个试验(32,694人)。大多数试验是附加试验(69%)。在52%、32%和16%的单纯安慰剂试验和25%、53%和22%的附加试验中，风险-收益结果是有利的、中性的和对实验药物不利的。有四种策略增加了对实验方案的暴露：单向交叉(23%)、不均匀随机(21%)、三臂(13%)和随机停药设计(4%)；这些策略在仅使用安慰剂的试验中使用更频繁。结论少数受试者单独服用安慰剂，并普遍采用增加实验性暴露的策略。只有不到一半的研究取得了良好的结果，从而为在没有既定治疗的情况下使用安慰剂对照进行了辩护。增加患者接触实验药物而不是安慰剂的策略可能会使他们接触无益的、有时是有毒的实验药物。
Background Limited information exists about the design of placebo-controlled cancer trials. Through a systematic review of trials published in 2013, we describe placebo use in randomized trials testing anticancer agents and analyze strategies that increase exposure to the experimental regimen. Methods Trials were classified as add-on (placebo in combination with standard treatment) or placebo-only. Strategies to allow more than half of the participants to receive the experimental regimen were reviewed. The risk–benefit ratio of receiving the experimental agent was considered favorable if the difference in primary outcome was significant (p ≤ 0.05), neutral if there was no significant difference in the primary outcome and the experimental agent did not add substantial toxicity, and unfavorable otherwise. Results Eighty trials were included (32,694 participants). Most trials were add-on (69%). The risk–benefit outcome was favorable, neutral, and unfavorable to the experimental agent in 52%, 32%, and 16% of placebo-only trials and 25%, 53%, and 22%, respectively, of add-on trials. Four strategies increased exposure to the experimental regimen: one-way crossover (23%), uneven randomization (21%), three-arms (13%), and randomized discontinuation design (4%); these strategies were used more often in placebo-only trials. Conclusion A minority of participants received placebo alone and strategies to increase experimental exposure were used commonly. Fewer than half of the studies had favorable outcomes, thus defending the use of placebo controls, when there is no established treatment. Strategies that increase patient exposure to experimental agents rather than placebo may expose them to non-beneficial, sometimes toxic, experimental agents.