Analyzing Phase III Studies in Hospice/Palliative Care. A Solution That Sits Between Intention-to-Treat and Per Protocol Analyses: The Palliative-Modified ITT Analysis
Analyzing Phase III Studies in Hospice/Palliative Care. A Solution That Sits Between Intention-to-Treat and Per Protocol Analyses: The Palliative-Modified ITT Analysis
复制标题
DOI：
10.1016/j.jpainsymman.2011.10.028
复制
发表时间：
2012-10-01
影响因子：
4.7
通讯作者：
Abernethy, Amy P.
中科院分区：
文献类型：
--
作者：
Currow, David C.;Plummer, John L.;Abernethy, Amy P.
意向性治疗（ITT）分析是评价随机对照试验（RCT）的标准方法，以尽量减少与一个研究组未完成率差异相关的I类错误。姑息治疗患者通常因疾病进展而早于预期死亡，其中一些人将参加RCT，因此，他们将退出或在随机分组后因与干预无关的原因死亡。在其他临床学科中，这种退出比例在统计学上可以忽略不计，但在临终关怀/姑息治疗中很常见，从而产生了偏离真实效果的系统性偏倚。在临终关怀/姑息治疗中，ITT分析认为所有退出都是治疗失败，或者从恶化的参与者中插补数据，系统地低估了干预的益处，降低了这些研究的功效。同样不可接受的是排除随机化后所有退出的符合方案分析，因为这将低估毒性。在ITT分析和符合方案分析之间的连续体上，需要一种改良的分析方法。为了解决随机化后因死亡或恶化而退出率高的数据，标准需要包括：1）原始方案中预先规定的; 2）临床上绝对是疾病进展的结果; 3）由设盲的独立数据监查委员会确定为与干预无关; 4）在研究CONSORT图中说明。此类数据不应纳入主要结局分析。本文的目的是定义一种更好的方法来平衡I型和II型错误的临终关怀/姑息治疗RCT分析使用姑息性改良ITT分析。可以说，姑息性改良ITT分析应该是临终关怀/姑息治疗III期研究的主要评价，但至少应该是常规的关键敏感性分析。J Pain Symptom Manage 2012;44：595-603. (C)2012年美国S.癌症疼痛缓解委员会。爱思唯尔公司出版All rights reserved.
Intention-to-treat (ITT) analyses are the standard way to evaluate randomized controlled trials (RCTs) to minimize Type I errors related to differential rates of noncompletion from one study arm. People in palliative care often die sooner than predicted as a direct result of disease progression, some of whom will be participating in RCTs and who will, therefore, withdraw or die after randomization for reasons unrelated to the intervention. This proportion of withdrawals is statistically negligible in other clinical disciplines, but commonplace in hospice/palliative care, creating a systematic bias away from the true effect. ITT analyses in hospice/palliative care that deem all withdrawals to be treatment failures or that impute data from deteriorating participants systematically underestimate the benefits of interventions, reducing the power of these studies. Equally unacceptable would be a per protocol analysis that excludes all withdrawals after randomization as this will underestimate toxicity. A modified analytic approach is needed on a continuum between ITT and per protocol analyses. To address data after randomization where there is a high rate of withdrawals because of death or deterioration, criteria need to include being: 1) prespecified in the original protocol; 2) clinically absolutely the result of disease progression; 3) identified by the blinded Independent Data Monitoring Committee as being unrelated to the intervention(s); and 4) accounted for in the study's CONSORT diagram. Such data should not be included in the analysis of the primary outcome. This article aims to define a better way of balancing Type I and Type II errors in hospice/palliative care RCT analyses using the palliative-modified ITT analysis. Arguably, the palliative-modified ITT analysis should be the primary evaluation of hospice/palliative care Phase III studies but, as a minimum, should routinely be the key sensitivity analysis. J Pain Symptom Manage 2012;44:595-603. (C) 2012 U. S. Cancer Pain Relief Committee. Published by Elsevier Inc. All rights reserved.