Detecting Heterogeneous Treatment Effects to Guide Personalized Blood Pressure Treatment: A Modeling Study of Randomized Clinical Trials.
Detecting Heterogeneous Treatment Effects to Guide Personalized Blood Pressure Treatment: A Modeling Study of Randomized Clinical Trials.
复制标题
DOI：
10.7326/m16-1756
复制
发表时间：
2017-03-07
影响因子：
39.2
通讯作者：
Hayward RA
中科院分区：
文献类型：
--
作者：
Basu S;Sussman JB;Hayward RA
最近的两项随机试验在测试降低心血管疾病（CVD）患者血压（BP）治疗的益处和危害时产生了不一致的结果。进行一项理论建模研究，以确定患者之间获益和损害的较大的临床重要差异（异质性治疗效应[HTE]）是否可能隐藏在达标治疗BP试验中，并解释这些试验之间的不一致结果。微观模拟。比较标准（收缩压目标<140 mm Hg）与强化（收缩压目标<120 mm Hg）BP治疗的2项试验的结果以及来自国家健康和营养检查调查（2013 - 2014）的数据。美国成年人5年社交血压治疗。CVD事件和死亡率。临床上重要的HTE可以解释两项强化BP治疗试验之间结局的差异，特别是每种额外BP药物的获益减少（例如，添加第二种药物可降低CVD风险[风险比，0.61]，但在第三种药物中添加第四种药物没有获益），并且在低舒张压下增加危害。尽管样本量很大（n > 20 000），但传统的达标治疗试验设计检测HTE的统计功效很差（<5%），并且产生了有偏差的效果估计。相比之下，尽管样本量较小（n = 3500），但序贯随机化至更强化治疗的试验获得了大于80%的把握度和无偏HTE估计值。仅探索了作为BP剂数量的函数的HTE。由于无法获得个体参与者数据，因此将试验的模拟汇总数据用作模型输入。在传统试验设计中，BP强化治疗效果的临床重要异质性仍然无法检测到，但可以在序贯随机试验设计中检测到。美国国立卫生研究院和美国退伍军人事务部。
Two recent randomized trials produced discordant results when testing the benefits and harms of treatment to reduce blood pressure (BP) in patients with cardiovascular disease (CVD). To perform a theoretical modeling study to identify whether large, clinically important differences in benefit and harm among patients (heterogeneous treatment effects [HTEs]) can be hidden in, and explain discordant results between, treat-to-target BP trials. Microsimulation. Results of 2 trials comparing standard (systolic BP target <140 mm Hg) with intensive (systolic BP target <120 mm Hg) BP treatment and data from the National Health and Nutrition Examination Survey (2013 to 2014). U.S. adults. 5 years. Societal. BP treatment. CVD events and mortality. Clinically important HTEs could explain differences in outcomes between 2 trials of intensive BP treatment, particularly diminishing benefit with each additional BP agent (for example, adding a second agent reduces CVD risk [hazard ratio, 0.61], but adding a fourth agent to a third has no benefit) and increasing harm at low diastolic BP. Conventional treat-to-target trial designs had poor (<5%) statistical power to detect the HTEs, despite large samples (n > 20 000), and produced biased effect estimates. In contrast, a trial with sequential randomization to more intensive therapy achieved greater than 80% power and unbiased HTE estimates, despite small samples (n = 3500). The HTEs as a function of the number of BP agents only were explored. Simulated aggregate data from the trials were used as model inputs because individual-participant data were not available. Clinically important heterogeneity in intensive BP treatment effects remains undetectable in conventional trial designs but can be detected in sequential randomization trial designs. National Institutes of Health and U.S. Department of Veterans Affairs.