Department of Family Medicine, College of Human Medicine, Michigan State University, East Lansing, MI, USA.
Pharmacoepidemiol Drug Saf. 2012 May;21 Suppl 2:121-9. doi: 10.1002/pds.3242.
To propose methods for the quantitative assessment of the applicability of evidence from a trial to a target sample using individual data.
Demonstration was with a trial of drug therapy to prevent mortality and an accompanying registry of people with heart failure. Principal components analysis with biplots did not identify measurement discrepancies. Multiple imputation with chained equations addressed missing predictor values. A proportional hazards model with interaction term, including graphical interpretation and a multivariate interaction test, identified heterogeneity of treatment effect. An interval of homogeneity of treatment effect was the interval of the baseline risk of outcome in which no two treatment effects were statistically significantly different. Absolute risk reduction for individuals was estimated for both benefit and harm outcomes and presented in a bivariate treatment effects scatterplot.
Overall, the trial evidence applied to most of the registry according to overlapping distributions of estimated benefit and harm. However, 52% of trial and 33% of registry participants were estimated to have net benefit, and 14% of trial and 36% of registry participants were estimated to have strong net harmful treatment effect, that is, the individual estimate of harm was more than twice the estimate of benefit.
The proposed methods provide quantitative assessment of the applicability of trial evidence to a target sample. They combine the strengths of different study designs, namely, unbiased effects estimation from trials and representation in observational studies, while addressing the practical challenges of combining information, namely, measurement discrepancies and missing data.
提出使用个体数据定量评估试验证据对目标样本适用性的方法。
通过一项预防死亡率的药物治疗试验和心力衰竭患者登记处的伴随研究进行演示。主成分分析和双标图未发现测量差异。链式方程的多重插补解决了预测值缺失的问题。包含交互项的比例风险模型，包括图形解释和多变量交互检验，确定了治疗效果的异质性。治疗效果同质区间是指结果基线风险区间，在此区间内，两种治疗效果没有统计学上的显著差异。个体的绝对风险降低被估计为获益和伤害结果，并在双变量治疗效果散点图中呈现。
总体而言，根据估计获益和伤害的重叠分布，试验证据适用于登记处的大多数患者。然而，52%的试验参与者和 33%的登记处参与者被估计有净获益，14%的试验参与者和 36%的登记处参与者被估计有强烈的净有害治疗效果，即个体估计的伤害是获益的两倍多。
所提出的方法提供了对试验证据对目标样本适用性的定量评估。它们结合了不同研究设计的优势，即试验的无偏效应估计和观察性研究中的代表性，同时解决了合并信息的实际挑战，即测量差异和缺失数据。
