Kuchibhatla Maragatha N, Fillenbaum Gerda G
Center for the Study of Aging and Human Development, Duke University Medical Center, Durham, North Carolina, USA.
Am J Geriatr Pharmacother. 2011 Dec;9(6):483-94. doi: 10.1016/j.amjopharm.2011.09.001. Epub 2011 Oct 28.
The objective of this article was to determine whether, in drug intervention trials, growth mixture modeling (GMM) is able to identify drug-responsive trajectory classes that are not evident in traditional growth modeling approaches.
We reanalyzed acute phase (biweekly data up to 7 occasions) and longitudinal (12 months) data on the 469 patients in the SADHART-CHF study of the safety and efficacy of sertraline for depression in patients with heart failure. GMM was used to identify the trajectory classes present in the treatment and placebo groups, based on Hamilton Depression Rating Scale scores.
Two distinct trajectory classes were identified in the treatment group: (1) chronic depressives (12%), who remained depressed through the treatment phase; and (2) responders (88%), who had scores indicating nondepression at the conclusion of the acute phase. At baseline, chronic depressives were distinguished by higher Hamilton Depression Rating Scale scores, the presence of implantable cardioverter defibrillators, and a history of anxiety. During follow-up, they were more likely to have unstable angina. Only responders remitted (70%). Three distinct trajectories were identified in the placebo group: (1) moderating depressives (19%), (2) temporary improvers (13%), and (3) responders (68%). At baseline, the classes differed in mean Hamilton Depression Rating Scale scores, responders' scores falling between the other 2 classes, and the proportion with renal disease. Only remission differed at follow-up: responders (76%), moderating depressives (21%), and temporary improvers (3%). Where the traditional analytic approach found improvement from moderate to mild depression but no significant treatment effect, GMM found response in 20% more people in the treatment group than in the placebo group.
Unlike conventionally used, standard analytic approaches, which focus on intervention impact at study end or change from baseline to study end, GMM enables maximum use of repeated data to identify unique trajectories of latent classes that are responsive to the intervention.
本文的目的是确定在药物干预试验中,生长混合模型(GMM)是否能够识别出传统生长模型方法中不明显的药物反应轨迹类别。
我们重新分析了SADHART-CHF研究中469例患者的急性期(每两周一次的数据,共7次)和纵向(12个月)数据,该研究旨在探讨舍曲林治疗心力衰竭患者抑郁症的安全性和有效性。基于汉密尔顿抑郁量表评分,使用GMM识别治疗组和安慰剂组中存在的轨迹类别。
治疗组中识别出两种不同的轨迹类别:(1)慢性抑郁症患者(12%),在治疗阶段一直处于抑郁状态;(2)反应者(88%),在急性期结束时得分表明无抑郁。在基线时,慢性抑郁症患者的特点是汉密尔顿抑郁量表评分较高、存在植入式心脏复律除颤器以及有焦虑病史。在随访期间,他们更有可能发生不稳定型心绞痛。只有反应者缓解(70%)。安慰剂组中识别出三种不同的轨迹:(1)缓解性抑郁症患者(19%),(2)临时改善者(13%),(3)反应者(68%)。在基线时,这些类别在汉密尔顿抑郁量表平均得分上有所不同,反应者的得分介于其他两类之间,且肾病比例不同。在随访时只有缓解情况不同:反应者(76%)、缓解性抑郁症患者(21%)和临时改善者(3%)。传统分析方法发现从中度抑郁改善到轻度抑郁,但没有显著的治疗效果,而GMM发现治疗组中反应者比安慰剂组多20%。
与传统使用的标准分析方法不同,传统方法侧重于研究结束时的干预影响或从基线到研究结束的变化,GMM能够最大限度地利用重复数据来识别对干预有反应的潜在类别的独特轨迹。