Observational Studies Analyzed Like Randomized Experiments An Application to Postmenopausal Hormone Therapy and Coronary Heart Disease
Observational Studies Analyzed Like Randomized Experiments An Application to Postmenopausal Hormone Therapy and Coronary Heart Disease
复制标题
DOI：
10.1097/ede.0b013e3181875e61
复制
发表时间：
2008-11-01
期刊：
影响因子：
5.4
通讯作者：
Robins, James M.
中科院分区：
文献类型：
--
作者：
Hernan, Miguel A.;Alonso, Alvaro;Robins, James M.
背景：妇女健康倡议随机试验发现，接受雌激素/孕激素治疗的女性患冠心病（CHD）的风险高于接受安慰剂的女性。此前的观察性研究曾表明激素使用者患冠心病的风险降低。
方法：利用来自观察性护士健康研究的数据，我们模拟了随机试验的设计和意向性治疗（ITT）分析。该观察性研究被概念化为一系列“试验”，其中符合条件的女性被分为雌激素/孕激素治疗的起始者和未起始者。
结果：起始者与未起始者相比，冠心病的ITT风险比（HRs）（95%置信区间）在最初2年为1.42（0.92 - 2.20），在整个随访期间为0.96（0.78 - 1.18）。在绝经10年内的女性中，ITT HRs为0.84（0.61 - 1.14），在其他女性中为1.12（0.84 - 1.48）（交互作用P值 = 0.08）。这些ITT估计值与妇女健康倡议的结果相似。由于ITT方法会导致严重的治疗错误分类，我们还通过逆概率加权估计了依从性调整后的效应。在最初2年，HRs为1.61（0.97 - 2.66），在整个随访期间为0.98（0.66 - 1.49）。在绝经后10年内的女性中，HRs为0.54（0.19 - 1.51），在其他女性中为1.20（0.78 - 1.84）（交互作用P值 = 0.01）。我们还对这些估计值与先前报道的护士健康研究估计值进行了比较。
结论：我们的研究结果表明，妇女健康倡议和护士健康研究的ITT估计值之间的差异在很大程度上可以由绝经后的时间分布和随访时间长度的差异来解释。
Background: The Women's Health Initiative randomized trial found greater coronary heart disease (CHD) risk in women assigned to estrogen/progestin therapy than in those assigned to placebo. Observational studies had previously suggested reduced CHD risk in hormone users.Methods: Using data from the observational Nurses' Health Study, we emulated the design and intention-to-treat (ITT) analysis of the randomized trial. The observational study was conceptualized as a sequence of "trials," in which eligible women were classified as initiators or noninitiators of estrogen/progestin therapy.Results: The ITT hazard ratios (HRs) (95% confidence intervals) of CHD for initiators versus noninitiators were 1.42 (0.92-2.20) for the first 2 years, and 0.96 (0.78-1.18) for the entire follow-up. The ITT HRs were 0.84 (0.61-1.14) in women within 10 years of menopause, and 1.12 (0.84-1.48) in the others (P value for interaction = 0.08). These ITT estimates are similar to those from the Women's Health Initiative. Because the ITT approach causes severe treatment misclassification, we also estimated adherence-adjusted effects by inverse probability weighting. The HRs were 1.61 (0.97-2.66) for the first 2 years, and 0.98 (0.66-1.49) for the entire follow-up. The HRs were 0.54 (0.19-1.51) in women within 10 years after menopause, and 1.20 (0.78-1.84) in others (P value for interaction = 0.01). We also present comparisons between these estimates and previously reported Nurses' Health Study estimates.Conclusions: Our findings suggest that the discrepancies between the Women's Health Initiative and Nurses' Health Study ITT estimates could be largely explained by differences in the distribution of time since menopause and length of follow-up.