Evidence mapPaperPMID 34280545Full record

ArticleAnnals of epidemiology2022

Generalizability of heterogeneous treatment effects based on causal forests applied to two randomized clinical trials of intensive glycemic control.

Sridharan Raghavan, Kevin Josey, Gideon Bahn, Domenic Reda, Sanjay Basu, Seth A Berkowitz, Nicholas Emanuele, Peter Reaven, Debashis Ghosh

Open access · greenAbstract read
In one paragraph

Article in Annals of epidemiology, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 9 papers.

0numbers the graph read from it
0cells of the map it votes in
9citing papers in PubMed
3.8field-weighted citation impact, top 6% of its field
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

9 citing papers in PubMed, 21 citations in OpenAlex.

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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

9 authors at 6 institutions in 1 country.

Sridharan RaghavanDepartment of Veterans Affairs Eastern Colorado Healthcare System, Aurora, CO; Division of Hospital Medicine, University of Colorado School of Medicine, Aurora, CO; Colorado Cardiovascular Outcomes Research Consortium, Aurora, CO. Electronic address: Sridharan.raghavan@cuanschutz.edu.
Kevin JoseyDepartment of Veterans Affairs Eastern Colorado Healthcare System, Aurora, CO; Department of Biostatistics and Informatics, Colorado School of Public Health, Aurora, CO.
Gideon BahnDepartment of Veterans Affairs Hines VA Hospital, Hines, IL.
Domenic RedaDepartment of Veterans Affairs Hines VA Hospital, Hines, IL.
Sanjay BasuCenter for Primary Care, Harvard Medical School, Boston, MA.
Seth A BerkowitzDivision of General Medicine and Clinical Epidemiology, University of North Carolina School of Medicine, Chapel Hill, NC; Cecil G. Sheps Center for Health Services Research, University of North Carolina at Chapel Hill, Chapel Hill, NC.
Nicholas EmanueleDepartment of Veterans Affairs Hines VA Hospital, Hines, IL.
Peter ReavenDepartment of Veterans Affairs Phoenix VA Medical Center, Phoenix, AZ.
Debashis GhoshDepartment of Biostatistics and Informatics, Colorado School of Public Health, Aurora, CO.
Edward Hines, Jr. VA Hospital · USColorado School of Public Health · USHarvard University · USPhoenix VA Health Care System · USUniversity of North Carolina at Chapel Hill · USVA Eastern Colorado Health Care System · US

Funding

Pilot and Feasibility ProgramP30DK092926 · UNIVERSITY OF MICHIGAN AT ANN ARBOR · 2025 to 2025
$779k
CSRD VA IK2 CX001907NCI NIH HHS R01 CA129102NIDDK NIH HHS K23 DK109200NIDDK NIH HHS P30 DK092926
6 · The paper itself

Abstract

Purpose Machine learning is an attractive tool for identifying heterogeneous treatment effects (HTE) of interventions but generalizability of machine learning derived HTE remains unclear. We examined generalizability of HTE detected using causal forests in two similarly designed randomized trials in type II diabetes patients. Methods We evaluated published HTE of intensive versus standard glycemic control on all-cause mortality from the Action to Control Cardiovascular Risk in Diabetes study (ACCORD) in a second trial, the Veterans Affairs Diabetes Trial (VADT). We then applied causal forests to VADT, ACCORD, and pooled data from both studies and compared variable importance and subgroup effects across samples. Results HTE in ACCORD did not replicate in similar subgroups in VADT, but variable importance was correlated between VADT and ACCORD (Kendall's tau-b 0.75). Applying causal forests to pooled individual-level data yielded seven subgroups with similar HTE across both studies, ranging from risk difference of all-cause mortality of -3.9% (95% CI -7.0, -0.8) to 4.7% (95% CI 1.8, 7.5). Conclusions Machine learning detection of HTE subgroups from randomized trials may not generalize across study samples even when variable importance is correlated. Pooling individual-level data may overcome differences in study populations and/or differences in interventions that limit HTE generalizability.

Indexed as

Cardiovascular DiseasesDiabetes Mellitus, Type 2Machine LearningBlood GlucoseGlycated HemoglobinGlycemic ControlHumansHypoglycemic AgentsRandomized Controlled Trials as TopicTreatment OutcomeBlood GlucoseGlycated HemoglobinHypoglycemic AgentsBMI, Body mass indexeGFR, Estimated glomerular filtration rateGeneralizability, Glycemic control, Causal forests, Heterogeneous treatment effects. Abbreviations: ACCORD, Action to Control Cardiovascular Risk in Diabetes StudyHbA1c, Hemoglobin A1cHGI, Hemoglobin glycation indexHTE, Heterogeneous treatment effectsVADT, Veterans Affairs Diabetes Trial

Identifiers

PMID34280545
PMCPMC8748294
OpenAlexW3185777382

What Socratic holds

Textmetadata
LicenceTDM
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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 Socratic graph.