Pfizer, Groton, Connecticut (B.H., E.T.).
Stanford University, Stanford, California (L.T.).
Ann Intern Med. 2020 Sep 1;173(5):368-374. doi: 10.7326/M20-0104. Epub 2020 Jul 7.
In comparative studies, treatment effect is often assessed using a binary outcome that indicates response to the therapy. Commonly used summary measures for response include the cumulative and current response rates at a specific time point. The current response rate is sometimes called the probability of being in response (PBIR), which regards a patient as a responder only if they have achieved and remain in response at present. The methods used in practice for estimating these rates, however, may not be appropriate. Moreover, whereas an effective treatment is expected to achieve a rapid and sustained response, the response at a fixed time point does not provide information about the duration of response (DOR). As an alternative, a curve constructed from the current response rates over the entire study period may be considered, which can be used for visualizing how rapidly patients responded to therapy and how long responses were sustained. The area under the PBIR curve is the mean DOR. This connection between response and DOR makes this curve attractive for assessing the treatment effect. In contrast to the conventional method for analyzing the DOR data, which uses responders only, the above procedure includes all patients in the study. Although discussed extensively in the statistical literature, estimation of the current response rate curve has garnered little attention in the medical literature. This article illustrates how to construct and analyze such a curve using data from a recent study for treating renal cell carcinoma. Clinical trialists are encouraged to consider this robust and clinically interpretable procedure as an additional tool for evaluating treatment effects in clinical studies.
在比较研究中，通常使用二分类结局来评估治疗效果，该结局表明对治疗的反应。常用的反应汇总指标包括特定时间点的累积反应率和当前反应率。当前反应率有时也称为响应概率（PBIR），仅当患者目前已达到并保持反应时，才将其视为有反应者。然而，实际中用于估计这些比率的方法可能并不合适。此外，虽然有效的治疗方法预计会产生快速和持续的反应，但在固定时间点的反应并不能提供关于反应持续时间（DOR）的信息。作为替代方法，可以考虑构建整个研究期间的当前反应率曲线，该曲线可用于观察患者对治疗的反应速度以及反应持续的时间。PBIR 曲线下的面积是平均 DOR。这种反应与 DOR 之间的联系使得该曲线成为评估治疗效果的理想选择。与仅使用有反应者分析 DOR 数据的传统方法相比，上述方法将研究中的所有患者都包括在内。尽管在统计文献中广泛讨论，但在医学文献中，对当前反应率曲线的估计却很少受到关注。本文使用最近治疗肾细胞癌的研究数据说明了如何构建和分析这种曲线。鼓励临床试验人员考虑这种稳健且具有临床可解释性的方法，作为评估临床研究中治疗效果的附加工具。
