University of Maryland School of Pharmacy, Baltimore, MD, USA.
Department of Clinical Pharmacy, School of Pharmacy, University of California-San Francisco, San Francisco, CA, USA.
BMC Med. 2021 Dec 6;19(1):307. doi: 10.1186/s12916-021-02176-1.
There have been ongoing efforts to understand when and how data from observational studies can be applied to clinical and regulatory decision making. The objective of this review was to assess the comparability of relative treatment effects of pharmaceuticals from observational studies and randomized controlled trials (RCTs).
We searched PubMed and Embase for systematic literature reviews published between January 1, 1990, and January 31, 2020, that reported relative treatment effects of pharmaceuticals from both observational studies and RCTs. We extracted pooled relative effect estimates from observational studies and RCTs for each outcome, intervention-comparator, or indication assessed in the reviews. We calculated the ratio of the relative effect estimate from observational studies over that from RCTs, along with the corresponding 95% confidence interval (CI) for each pair of pooled RCT and observational study estimates, and we evaluated the consistency in relative treatment effects.
Thirty systematic reviews across 7 therapeutic areas were identified from the literature. We analyzed 74 pairs of pooled relative effect estimates from RCTs and observational studies from 29 reviews. There was no statistically significant difference (based on the 95% CI) in relative effect estimates between RCTs and observational studies in 79.7% of pairs. There was an extreme difference (ratio < 0.7 or > 1.43) in 43.2% of pairs, and, in 17.6% of pairs, there was a significant difference and the estimates pointed in opposite directions.
Overall, our review shows that while there is no significant difference in the relative risk ratios between the majority of RCTs and observational studies compared, there is significant variation in about 20% of comparisons. The source of this variation should be the subject of further inquiry to elucidate how much of the variation is due to differences in patient populations versus biased estimates arising from issues with study design or analytical/statistical methods.
人们一直在努力了解如何以及何时可以将观察性研究的数据应用于临床和监管决策。本综述的目的是评估来自观察性研究和随机对照试验（RCT）的药物相对治疗效果的可比性。
我们在 PubMed 和 Embase 中搜索了 1990 年 1 月 1 日至 2020 年 1 月 31 日期间发表的系统文献综述，这些综述报告了来自观察性研究和 RCT 的药物的相对治疗效果。我们从观察性研究和 RCT 中提取了每个综述评估的每种结局、干预比较和适应证的汇总相对效应估计值。我们计算了来自观察性研究的相对效应估计值与 RCT 的比值，以及每对汇总 RCT 和观察性研究估计值的相应 95%置信区间（CI），并评估了相对治疗效果的一致性。
从文献中确定了 30 项来自 7 个治疗领域的系统综述。我们分析了来自 29 项综述的 74 对 RCT 和观察性研究的汇总相对效应估计值。在 79.7%的对中，RCT 和观察性研究的相对效应估计值没有统计学上的显著差异（基于 95%CI）。在 43.2%的对中存在极端差异（比值<0.7 或>1.43），在 17.6%的对中存在显著差异且估计值指向相反的方向。
总体而言，我们的综述表明，虽然与大多数 RCT 相比，观察性研究的相对风险比没有显著差异，但在大约 20%的比较中存在显著差异。这种差异的来源应该是进一步探究的主题，以阐明差异有多少是由于患者人群的差异，以及有多少是由于研究设计或分析/统计方法的问题导致的有偏估计。
