Restricted accessResearch articleFirst published online 2026-1
A Framework for Estimating Posttreatment Moderation of Treatment-by-Dosage Effects in Individual-Patient Meta-Analysis: An Illustration Using Project Harmony
Making causal statements regarding dose-response in treatments for posttraumatic stress disorder (PTSD) and alcohol/other drug use disorders (AODs; PTSD+AOD) is difficult because (a) dosage is rarely randomized and (b) self-selected dosage can be affected by treatment assignment. In the present study, we sought to clarify causal inferences regarding treatment-by-dosage interactions in PTSD+AOD treatment using Project Harmony, an individual-patient meta-analytic data set of behavioral, pharmacological, and combination PTSD+AOD treatments (k = 36; N = 4,046). Using propensity score weighting and moderated multilevel “net treatment difference” modeling, trauma-focused (TF) treatments, whether integrated or nonintegrated with AOD treatment, outperformed treatment as usual by greater margins on reductions in PTSD and alcohol use as dosage increased. Furthermore, appropriately treating dosage as a posttreatment covariate and moderator revealed effects for TF treatments on drug use that had not been detected in previous studies. Implications for approaches to increasing TF-treatment attendance and greater use of causal-inference methodologies with dose-response analyses are discussed.
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