Boehringer-Ingelheim Pharma GmbH&Co. KG, Biberach/Riss, Germany.
Stat Med. 2011 Dec 20;30(29):3373-86. doi: 10.1002/sim.4379. Epub 2011 Sep 23.
A reliable determination of progression is of key importance in determining progression-free survival in oncology trials. An independent review of tumour assessments made by investigators is often implemented with the aim of reducing a possible bias. Often, the independent review is performed in a prespecified but retrospective fashion by reviewing a patient after all assessments have been performed. It has been discussed that this mechanism can lead to informative censoring with respect to independent review. This is caused by the fact that often no further assessments are available after the investigator has declared the patient to be progressive, possibly leading to a considerable amount of patients being judged progressive by the investigator and being censored by independent review. We introduce and investigate a model for the error in assessment with the aim of quantifying the bias in independent review. The model is based on single error probabilities at each assessment time-point that are independent from each other but dependent on the time to the true progression time-point. The bias introduced for the independent review is described and quantified. We show that the investigator assessments of progression can lead to less bias for progression-free survival than the results for independent review. Results show that a within-arm discordance rate is not necessarily correlated with the bias in independent review. Finally, we propose an approach for a sensitivity analysis that is a useful tool to sandwich the true underlying distribution by the results for independent review itself and the described sensitivity analysis.
在肿瘤学试验中，可靠地确定疾病进展对于确定无进展生存期至关重要。通常会进行独立的肿瘤评估审查，以减少可能的偏倚。独立审查通常是在回顾所有评估后，以预定但回顾性的方式进行的，目的是评估研究者的评估。有人讨论过，这种机制可能会导致独立审查的信息性删失。这是因为在研究者宣布患者进展后，通常没有进一步的评估可供使用，这可能导致大量患者被研究者判断为进展并被独立审查删失。我们引入并研究了一种评估错误的模型，旨在量化独立审查中的偏倚。该模型基于每个评估时间点的单一错误概率，这些概率彼此独立，但与真实进展时间点的时间有关。描述并量化了独立审查中引入的偏差。我们表明，与独立审查的结果相比，研究者对疾病进展的评估可以导致无进展生存期的偏差更小。结果表明，臂内不一致率不一定与独立审查中的偏倚相关。最后，我们提出了一种敏感性分析方法，该方法是通过独立审查本身和描述的敏感性分析来夹在真实潜在分布的有用工具。
