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February 17, 2021

New Directions in Research on Heterogeneity of Treatment Effects for Major Depression

Author Affiliations
  • 1Department of Statistics, University of Washington, Seattle
  • 2Vaccine and Infectious Disease Division, Fred Hutchinson Cancer Research Center, Seattle, Washington
  • 3Department of Health Care Policy, Harvard Medical School, Boston, Massachusetts
JAMA Psychiatry. 2021;78(5):478-480. doi:10.1001/jamapsychiatry.2020.4489

In this issue of JAMA Psychiatry, Maslej et al1 carried out a meta-analysis of placebo-controlled trials to investigate whether systematic individual differences exist in antidepressant medication (ADM) response. To our knowledge, this is the fifth meta-analysis of the same data set.2-5 All 5 have compared outcome score variances, since larger variance in the treatment group than control group cannot occur in the absence of heterogeneity of treatment effects (HTE). The 5 studies differed in effect size measures. Basing a comparison on a simple variance ratio in the earliest reports led to the conclusion that no meaningful HTE exists.2,3 Correcting for between-group outcome mean differences in a subsequent report4 led to the conclusion that HTE may exist, but that article was retracted based on the finding that evidence for HTE disappears when the association between the outcome mean and variance is estimated rather than assumed to be either 0 (the implicit assumption when making the simple variance comparison) or 1 (the implicit assumption when adjusting for mean differences).5 The Maslej et al report1 updates the data set with more recent trials and again finds a negative result based on this regression-based estimation method.

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