Evaluating agreement between individual nutrition randomised controlled trials and cohort studies - a...

In nutrition research, randomised controlled trials (RCTs) and cohort studies provide complementary evidence. This meta-epidemiological study aims to evaluate the agreement of effect estimates from individual nutrition RCTs and cohort studies investigating a highly similar research question and to investigate determinants of disagreement.

MEDLINE, Epistemonikos, and the Cochrane Database of Systematic Reviews were searched from January 2010 to September 2021. We matched individual RCTs to cohort studies based on population, intervention/exposure, comparator, and outcome (PI/ECO) characteristics. Two reviewers independently extracted study characteristics and effect estimates and rated the risk of bias using RoB2 and ROBINS-E. Agreement of matched RCTs/cohort studies was analysed by pooling ratio of risk ratios (RRR) and difference of (standardised) mean differences (DSMD).

We included 64 RCT/cohort study pairs with 4,136,837 participants. Regarding PI/ECO similarity, 20.3% pairs were "more or less identical", 71.9% "similar but not identical" and 7.8% "broadly similar". Most RCTs were classified as "low risk of bias" (26.6%) or with "some concerns" (65.6%); cohort studies were mostly rated with "some concerns" (46.6%) or "high risk of bias" (47.9%), driven by inadequate control of important confounding factors. Effect estimates across RCTs and cohort studies were in high agreement (RRR 1.00 (95% CI 0.91-1.10, n = 54); and DSMD - 0.26 (95% CI - 0.87-0.35, n = 7)). In meta-regression analyses exploring determinants of disagreements, risk-of-bias judgements tend to have had more influence on the effect estimate than "PI/ECO similarity" degree.

Effect estimates of nutrition RCTs and cohort studies were generally similar. Careful consideration and evaluation of PI/ECO characteristics and risk of bias is crucial for a trustworthy utilisation of evidence from RCTs and cohort studies.