Bolland Mark J, Grey Andrew, Gamble Greg D, Reid Ian R
Department of Medicine, University of Auckland, Auckland, New Zealand.
PLoS One. 2015 Oct 6;10(10):e0139975. doi: 10.1371/journal.pone.0139975. eCollection 2015.
Observational studies (OS) and randomized controlled trials (RCTs) often report discordant results. In the Women's Health Initiative Calcium and Vitamin D (WHI CaD) RCT, women were randomly assigned to CaD or placebo, but were permitted to use personal calcium and vitamin D supplements, creating a unique opportunity to compare results from randomized and observational analyses within the same study.
WHI CaD was a 7-year RCT of 1g calcium/400IU vitamin D daily in 36,282 post-menopausal women. We assessed the effects of CaD on cardiovascular events, death, cancer and fracture in a randomized design- comparing CaD with placebo in 43% of women not using personal calcium or vitamin D supplements- and in a observational design- comparing women in the placebo group (44%) using personal calcium and vitamin D supplements with non-users. Incidence was assessed using Cox proportional hazards models, and results from the two study designs deemed concordant if the absolute difference in hazard ratios was ≤0.15. We also compared results from WHI CaD to those from the WHI Observational Study(WHI OS), which used similar methodology for analyses and recruited from the same population.
In WHI CaD, for myocardial infarction and stroke, results of unadjusted and 6/8 covariate-controlled observational analyses (age-adjusted, multivariate-adjusted, propensity-adjusted, propensity-matched) were not concordant with the randomized design results. For death, hip and total fracture, colorectal and total cancer, unadjusted and covariate-controlled observational results were concordant with randomized results. For breast cancer, unadjusted and age-adjusted observational results were concordant with randomized results, but only 1/3 other covariate-controlled observational results were concordant with randomized results. Multivariate-adjusted results from WHI OS were concordant with randomized WHI CaD results for only 4/8 endpoints.
Results of randomized analyses in WHI CaD were concordant with observational analyses for 5/8 endpoints in WHI CaD and 4/8 endpoints in WHI OS.
观察性研究（OS）和随机对照试验（RCT）常常报告不一致的结果。在妇女健康倡议钙与维生素D（WHI CaD）随机对照试验中，女性被随机分配至钙与维生素D组或安慰剂组，但允许使用个人的钙和维生素D补充剂，这创造了一个在同一研究中比较随机分析和观察性分析结果的独特机会。
WHI CaD是一项针对36282名绝经后女性的为期7年的随机对照试验，每日服用1克钙/400国际单位维生素D。我们在一项随机设计中评估了钙与维生素D对心血管事件、死亡、癌症和骨折的影响，即将43%未使用个人钙或维生素D补充剂的女性中的钙与维生素D组和安慰剂组进行比较，同时在一项观察性设计中，将安慰剂组中44%使用个人钙和维生素D补充剂的女性与未使用者进行比较。使用Cox比例风险模型评估发病率，如果风险比的绝对差异≤0.15，则认为两种研究设计的结果一致。我们还将WHI CaD的结果与妇女健康倡议观察性研究（WHI OS）的结果进行了比较，后者采用了类似的分析方法且招募自相同人群。
在WHI CaD中，对于心肌梗死和中风，未调整以及6/8种协变量控制的观察性分析（年龄调整、多变量调整、倾向调整、倾向匹配）结果与随机设计结果不一致。对于死亡、髋部和总骨折、结直肠癌和总癌症，未调整和协变量控制的观察性结果与随机结果一致。对于乳腺癌，未调整和年龄调整的观察性结果与随机结果一致，但只有1/3的其他协变量控制的观察性结果与随机结果一致。WHI OS的多变量调整结果仅在4/8个终点与随机的WHI CaD结果一致。
WHI CaD中的随机分析结果在WHI CaD的5/8个终点以及WHI OS的4/8个终点上与观察性分析结果一致。
