An empirical evaluation of the impact scenario of pooling bodies of evidence from randomized controlled trials and cohort studies in medical research.

BACKGROUND: Randomized controlled trials (RCTs) and cohort studies are the most common study design types used to assess treatment effects of medical interventions. We aimed to hypothetically pool bodies of evidence (BoE) from RCTs with matched BoE from cohort studies included in the same systematic review. METHODS: BoE derived from systematic reviews of RCTs and cohort studies published in the 13 medical journals with the highest impact factor were considered. We re-analyzed effect estimates of the included systematic reviews by pooling BoE from RCTs with BoE from cohort studies using random and common effects models. We evaluated statistical heterogeneity, 95% prediction intervals, weight of BoE from RCTs to the pooled estimate, and whether integration of BoE from cohort studies modified the conclusion from BoE of RCTs. RESULTS: Overall, 118 BoE-pairs based on 653 RCTs and 804 cohort studies were pooled. By pooling BoE from RCTs and cohort studies with a random effects model, for 61 (51.7%) out of 118 BoE-pairs, the 95% confidence interval (CI) excludes no effect. By pooling BoE from RCTs and cohort studies, the median I2 was 48%, and the median contributed percentage weight of RCTs to the pooled estimates was 40%. The direction of effect between BoE from RCTs and pooled effect estimates was mainly concordant (79.7%). The integration of BoE from cohort studies modified the conclusion (by examining the 95% CI) from BoE of RCTs in 32 (27%) of the 118 BoE-pairs, but the direction of effect was mainly concordant (88%). CONCLUSIONS: Our findings provide insights for the potential impact of pooling both BoE in systematic reviews. In medical research, it is often important to rely on both evidence of RCTs and cohort studies to get a whole picture of an investigated intervention-disease association. A decision for or against pooling different study designs should also always take into account, for example, PI/ECO similarity, risk of bias, coherence of effect estimates, and also the trustworthiness of the evidence. Overall, there is a need for more research on the influence of those issues on potential pooling.

Evaluating agreement between bodies of evidence from randomized controlled trials and cohort studies in medical research: a meta-epidemiological study.

BACKGROUND: Randomized controlled trials (RCTs) and cohort studies are the most common study design types used to assess the treatment effects of medical interventions. To evaluate the agreement of effect estimates between bodies of evidence (BoE) from randomized controlled trials (RCTs) and cohort studies and to identify factors associated with disagreement. METHODS: Systematic reviews were published in the 13 medical journals with the highest impact factor identified through a MEDLINE search. BoE-pairs from RCTs and cohort studies with the same medical research question were included. We rated the similarity of PI/ECO (Population, Intervention/Exposure, Comparison, Outcome) between BoE from RCTs and cohort studies. The agreement of effect estimates across BoE was analyzed by pooling ratio of ratios (RoR) for binary outcomes and difference of mean differences for continuous outcomes. We performed subgroup analyses to explore factors associated with disagreements. RESULTS: One hundred twenty-nine BoE pairs from 64 systematic reviews were included. PI/ECO-similarity degree was moderate: two BoE pairs were rated as "more or less identical"; 90 were rated as "similar but not identical" and 37 as only "broadly similar". For binary outcomes, the pooled RoR was 1.04 (95% CI 0.97-1.11) with considerable statistical heterogeneity. For continuous outcomes, differences were small. In subgroup analyses, degree of PI/ECO-similarity, type of intervention, and type of outcome, the pooled RoR indicated that on average, differences between both BoE were small. Subgroup analysis by degree of PI/ECO-similarity revealed high statistical heterogeneity and wide prediction intervals across PI/ECO-dissimilar BoE pairs. CONCLUSIONS: On average, the pooled effect estimates between RCTs and cohort studies did not differ. Statistical heterogeneity and wide prediction intervals were mainly driven by PI/ECO-dissimilarities (i.e., clinical heterogeneity) and cohort studies. The potential influence of risk of bias and certainty of the evidence on differences of effect estimates between RCTs and cohort studies needs to be explored in upcoming meta-epidemiological studies.