Address correspondence to Erik Fernandez y Garcia, M.D., M.P.H., Assistant Professor of Clinical Pediatrics, Department of Pediatrics, University of California—Davis, School of Medicine, 2516 Stockton Blvd., Ste. 341, Sacramento, CA 95817; e-mail: firstname.lastname@example.org. Hien H. Nguyen, M.D., M.A.S., Associate Clinical Professor, is with the Division of Infectious Diseases, University of California—Davis, School of Medicine, Sacramento, CA. Naihua Duan, Ph.D., Professor of Biostatistics (in Psychiatry), is with the Departments of Psychiatry and Biostatistics, Columbia University, New York, NY. Erik Fernandez y Garcia, M.D., M.P.H., and Nicole B. Gabler, M.P.H., M.H.A., are with the Center for Healthcare Policy and Research, Sacramento, CA. Richard L. Kravitz, M.D., M.S.P.H., Professor and Co-Vice Chair, Research, is with the Division of General Medicine, University of California—Davis, Sacramento, CA.
Assessing Heterogeneity of Treatment Effects: Are Authors Misinterpreting Their Results?
Article first published online: 19 NOV 2009
© Health Research and Educational Trust
Health Services Research
Volume 45, Issue 1, pages 283–301, February 2010
How to Cite
Fernandez y Garcia, E., Nguyen, H., Duan, N., Gabler, N. B. and Kravitz, R. L. (2010), Assessing Heterogeneity of Treatment Effects: Are Authors Misinterpreting Their Results?. Health Services Research, 45: 283–301. doi: 10.1111/j.1475-6773.2009.01064.x
- Issue published online: 8 JAN 2010
- Article first published online: 19 NOV 2009
- Heterogeneity of treatment effects;
- HTE analysis;
- subgroup analysis;
- individualized care;
- interaction analysis
Objective. To determine whether investigations of heterogeneity of treatment effects (HTE) in randomized-controlled trials (RCTs) are prespecified and whether authors' interpretations of their analyses are consistent with the objective evidence.
Data Sources/Study Setting. Trials published in Annals of Internal Medicine, British Medical Journal, Journal of the American Medical Association, Lancet, and New England Journal of Medicine in 1994, 1999, and 2004.
Study Design. We reviewed 87 RCTs that reported formal tests for statistical interaction or heterogeneity (HTE analyses), derived from a probability sample of 541 articles.
Data Collection/Extraction. We recorded reasons for performing HTE analysis; an objective classification of evidence for HTE (termed “clinicostatistical divergence” [CSD]); and authors' interpretations of findings. Authors' interpretations, compared with CSD, were coded as understated, overstated, or adequately stated.
Principle Findings. Fifty-three RCTs (61 percent) claimed prespecified covariates for HTE analyses. Trials showed strong (6), moderate (11), weak (25), or negligible (16) evidence for CSD (29 could not be classified due to inadequate information). Authors stated that evidence for HTE was sufficient to support differential treatment in subgroups (10); warranted more research (31); was absent (21); or provided no interpretation (25). HTE was overstated in 22 trials, adequately stated in 57 trials, and understated in 8 trials.
Conclusions. Inconsistencies in performance and reporting may limit the potential of HTE analysis as a tool for identifying HTE and individualizing care in diverse populations. Recommendations for future studies on the reporting and interpretation of HTE analyses are provided.