Department of Biostatistics and Bioinformatics, Rollins School of Public Health, Emory University, Atlanta, Georgia.
Department of Psychiatry and Behavioral Sciences, Emory University School of Medicine, Atlanta, Georgia.
Depress Anxiety. 2018 Oct;35(10):992-1000. doi: 10.1002/da.22832. Epub 2018 Sep 7.
Definition of response is critical when seeking to establish valid predictors of treatment success. However, response at the end of study or endpoint only provides one view of the overall clinical picture that is relevant in testing for predictors. The current study employed a classification technique designed to group subjects based on their rate of change over time, while simultaneously addressing the issue of controlling for baseline severity.
A set of latent class trajectory analyses, incorporating baseline level of symptoms, were performed on a sample of 344 depressed patients from a clinical trial evaluating the efficacy of cognitive behavior therapy and two antidepressant medications (escitalopram and duloxetine) in patients with major depressive disorder.
Although very few demographic and illness-related features were associated with response rate profiles, the aggregated effect of candidate genetic variants previously identified in large pharmacogenetic studies and meta-analyses showed a significant association with early remission as well as nonresponse. These same genetic scores showed a less compelling relationship with endpoint response categories. In addition, consistent nonresponse throughout the study treatment period was shown to occur in different subjects than endpoint nonresponse, which was verified by follow-up augmentation treatment outcomes.
When defining groups based on the rate of change, controlling for baseline depression severity may help to identify the clinically relevant distinctions of early response on one end and consistent nonresponse on the other.
在寻求建立治疗成功的有效预测因素时,反应的定义至关重要。然而,研究结束时或终点的反应仅提供了与预测因素检验相关的整体临床情况的一个视角。本研究采用了一种分类技术,旨在根据受试者随时间变化的速度对其进行分组,同时解决控制基线严重程度的问题。
对来自评估认知行为疗法和两种抗抑郁药(依他普仑和度洛西汀)在重度抑郁症患者中的疗效的临床试验的 344 名抑郁患者样本进行了一系列潜在类别轨迹分析,其中纳入了症状的基线水平。
尽管很少有与反应率特征相关的人口统计学和疾病相关特征,但先前在大型遗传药理学研究和荟萃分析中确定的候选遗传变异的综合效应与早期缓解以及无反应显著相关。这些相同的遗传评分与终点反应类别之间的关系不太一致。此外,研究治疗期间持续的一致无反应与终点无反应不同,这通过后续的增效治疗结果得到了验证。
当根据变化率定义组时,控制基线抑郁严重程度可能有助于识别早期反应和持续无反应的临床相关区别。