Roach Mack
Departments of Radiation Oncology and Urology, University of California, San Francisco, CA, United States.
Helen Diller Family Comprehensive Cancer Center, Medical Center, University of California, San Francisco, CA, United States.
Front Oncol. 2024 Jul 25;14:1379306. doi: 10.3389/fonc.2024.1379306. eCollection 2024.
In "Explanatory and Pragmatic Attitudes in Therapeutic Trials", Schwatrz and Lelouch describe two approaches to the design of trials, "… the first "explanatory", the second "pragmatic". They explained "… the biologist may be interested to know whether the drugs differ in their effects … the explanatory approach". Biologically endpoints might determine whether it was better to give androgen deprivation therapy (ADT) before or after external beam radiation (EBRT) (i.e., does the sequence of treatments matter). Alternatively, if the arms focus on a clinical endpoint, this is considered … "the pragmatic approach". An example of a clinically relevant endpoint is overall survival (OS). A real-world example of this are the two randomized controlled trials (RCTs) evaluating the role of prophylactic whole pelvic radiotherapy (WPRT) conducted by the Radiation Therapy Oncology Group (RTOG). RTOG 9413 evaluated possible interactions between the sequence of drugs and volume irradiated, while RTOG/NRG 0924 focuses on OS. There appears to be a common pattern of "what not to do", or "design errors" made by a number of investigators, that I call the "three sins". I posit that the prospects for a well-designed pragmatic RCT are likely to be high if these "three sins" are avoided/minimized. The "three sins" alluded to are: 1. You can't prove something doesn't work by treating people who don't need the treatment. 2. You can't prove something does not work if the treatment is not done properly. 3. You can't prove something does not work with an underpowered study.
在《治疗性试验中的解释性态度和实用性态度》一文中，施瓦茨和勒卢什描述了试验设计的两种方法，“……第一种是‘解释性的’，第二种是‘实用性的’。他们解释说：‘生物学家可能有兴趣了解药物在效果上是否存在差异……这就是解释性方法’。生物学终点可能会确定在进行外照射放疗（EBRT）之前还是之后给予雄激素剥夺疗法（ADT）更好（即，治疗顺序是否重要）。或者，如果试验组关注的是临床终点，这就被认为是……‘实用性方法’。一个与临床相关的终点的例子是总生存期（OS）。放疗肿瘤学组（RTOG）进行的两项评估预防性全盆腔放疗（WPRT）作用的随机对照试验（RCT）就是一个实际例子。RTOG 9413评估了药物顺序和照射体积之间可能的相互作用，而RTOG/NRG 0924则关注总生存期。许多研究者似乎存在一种共同的‘不该做什么’或‘设计错误’模式，我称之为‘三大罪过’。我认为，如果避免/最小化这些‘三大罪过’，精心设计的实用性随机对照试验成功的可能性就很大。提到的‘三大罪过’是：1. 对不需要治疗的人进行治疗无法证明某种治疗方法无效。2. 如果治疗实施不当，就无法证明某种治疗方法无效。3. 研究样本量不足就无法证明某种治疗方法无效。
