Important informations

JAMA and BMJ publish new reporting guidelines for observational studies in epidemiology using Mendelian randomization

A team of international researchers and experts is describing the development of the STROBE-MR Statement, a set of guidelines to assist researchers in reporting their Mendelian randomization (MR) studies clearly and transparently, in a special communication published in both JAMA and BMJ.

Mendelian randomization is a statistical method that uses measured variation in genes to test for or estimate the causal effect of exposure to an agent or risk factor on a health outcome. It aims to reduce bias from reverse causation, where the cause is said to be the effect (and vice versa), and from confounding, where a third variable or factor influences both the independent and dependent variables, causing to wrongly estimate the relationship between these variables.

Mendelian randomization has gained traction as a method for establishing or estimating causality without having to conduct a traditional randomized controlled trial – the gold standard in epidemiology. “Yet, despite the increasing relevance and popularity of Mendelian randomization studies, empirical evidence indicates that their reporting is often incomplete or of inadequate quality, which may limit their credibility,” says Dr. Brent Richards, senior investigator at the Lady Davis Institute’s Centre for Clinical Epidemiology at the Jewish General Hospital, who led the papers.

The development of the STROBE-MR Statement followed the Enhancing the Quality and Transparency of Health Research (EQUATOR) methodological framework for guideline development and used the STROBE (Strengthening the Reporting of Observational Studies in Epidemiology) Statement as a starting point to draft a checklist tailored to Mendelian randomization studies. The checklist comprises 20 items and 30 sub-items that should be addressed when reporting a Mendelian randomization study, to ensure clarity and comprehensiveness.

“The guidelines apply to studies that use properties from genetic variation in germ cells (genetic changes in cells, which when fully developed become sperm or ova, that can be passed on to offspring) to test for the causal effect of exposure to a risk factor on a health outcome,” states Dr. Richards. “They are tailored to such studies that use an instrumental variable estimation (i.e., variable used to account for unexpected behavior between variables). They cover both 1-sample and 2-sample Mendelian randomization studies that assess one or multiple exposures and outcomes and those that follow a genome-wide association study and are reported in the same article. The STROBE-MR guidelines do not apply to genome-wide association studies, sequencing studies, expression studies, or the traditional observational epidemiology studies.”

The STROBE-MR Statement is intended to guide authors in reporting on Mendelian randomization studies, to support editors and reviewers considering such studies for publication, and to help readers decide whether the results are valid and useful. It is not an instrument to evaluate the quality of Mendelian randomization research and should not be used for this purpose, emphasizes Dr. Richards.

“The publication of the STROBE-MR Statement, together with a comprehensive Explanation and Elaboration document, is a first step toward implementing these reporting guidelines,” says Dr. Richards. “We hope the final guidelines will serve the entire community and contribute to improving the reporting of MR studies in the future. Next steps include encouraging journals to endorse and support adherence to these guidelines, translating the guidelines into various languages and keeping them updated to address new and existing challenges.”

Skrivankova VW, Richmond RC, Woolf BAR, et al. Strengthening the Reporting of Observational Studies in Epidemiology Using Mendelian Randomization: The STROBE-MR Statement. JAMA. 2021;326(16):1614–1621. doi:10.1001/jama.2021.18236.

Skrivankova V W, Richmond R C, Woolf B A R, Davies N M, Swanson S A, VanderWeele T J et al. Strengthening the reporting of observational studies in epidemiology using mendelian randomisation (STROBE-MR): explanation and elaboration. BMJ 2021; 375 :n2233 doi:10.1136/bmj.n2233.