Evidence map›Paper›PMID 28590373›Full record

ArticleEpidemiology (Cambridge, Mass.)2017

Nature as a Trialist?: Deconstructing the Analogy Between Mendelian Randomization and Randomized Trials.

Sonja A Swanson, Henning Tiemeier, M Arfan Ikram, Miguel A Hernán

Abstract readComparative Study
PubMed Full text at PMC Publisher
In one paragraph

Article in Epidemiology (Cambridge, Mass.), 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 125 papers, 5 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
125citing papers in PubMed, 5 pooled it
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

125 citing papers in PubMed, 5 syntheses or guidelines pooled it.

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65 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

4 authors.

Sonja A SwansonFrom the aDepartment of Epidemiology, Erasmus MC, Rotterdam, The Netherlands; bDepartment of Epidemiology, Harvard T. H. Chan School of Public Health, Boston, Massachusetts; cDepartment of Child and Adult Psychiatry, Erasmus MC, Rotterdam, The Netherlands; dDepartment of Psychiatry, Erasmus MC, Rotterdam, The Netherlands; eDepartment of Biostatistics, Harvard T. H. Chan School of Public Health, Boston, Massachusetts; and fHarvard-MIT Division of Health Sciences and Technology, Harvard University and Massachusetts Institute of Technology, Boston, Massachusetts.
Henning Tiemeier
M Arfan Ikram
Miguel A Hernán

Funding

Dynamic strategies for the clinical management of HIV diseaseR01AI102634 · NIAID · HARVARD SCHOOL OF PUBLIC HEALTH · PI HERNAN, MIGUEL · 2013 to 2017
$2.6M
NIAID NIH HHS R01 AI102634
6 · The paper itself

Abstract

Mendelian randomization (MR) studies are often described as naturally occurring randomized trials in which genetic factors are randomly assigned by nature. Conceptualizing MR studies as randomized trials has profound implications for their design, conduct, reporting, and interpretation. For example, analytic practices that are discouraged in randomized trials should also be discouraged in MR studies. Here, we deconstruct the oft-made analogy between MR and randomized trials. We describe four key threats to the analogy between MR studies and randomized trials: (1) exchangeability is not guaranteed; (2) time zero (and therefore the time for setting eligibility criteria) is unclear; (3) the treatment assignment is often measured with error; and (4) adherence is poorly defined. By precisely defining the causal effects being estimated, we underscore that MR estimates are often vaguely analogous to per-protocol effects in randomized trials, and that current MR methods for estimating analogues of per-protocol effects could be biased in practice. We conclude that the analogy between randomized trials and MR studies provides further perspective on both the strengths and the limitations of MR studies as currently implemented, as well as future directions for MR methodology development and application. In particular, the analogy highlights potential future directions for some MR studies to produce more interpretable and informative numerical estimates.

Indexed as

Mendelian Randomization AnalysisRandomized Controlled Trials as TopicGenetic VariationHumansTreatment Outcome

Identifiers

PMID28590373
PMCPMC5552969

What OpenQuestion holds

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Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.