Advancing patient-centered research using meta-analysis of individual patient data to identify clinically significant trajectories of PTSD/SUD and recovery outcomes

PROJECT SUMMARY/ABSTRACT Substance use disorders (SUD) are globally prevalent and costly, and polysubstance use is more common than single-substance use. The public health consequences of SUD are compounded by co-occurring posttraumatic stress disorder (PTSD), with several associated outcomes linked to increased mortality, To date, PTSD/SUD treatment evidence syntheses have been repeatedly criticized for “low quality” evidence due in part to several methodological limitations: study-level predictors do not always mirror individual-level effects, study- level measurement bias cannot be corrected in conventional meta-analytic methods, covariates are not always appropriately managed, and few syntheses estimate comparative effect sizes for distinct PTSD/SUD treatment approaches against common controls. Additionally, SUD and PTSD/SUD treatment outcome research has historically emphasized reduction in substance use and clinical severity, not psychosocial recovery, despite the importance of recovery-oriented outcomes to patients seeking treatment. The current project addresses these limitations of the PTSD/SUD treatment literature by using meta-analysis of individual-patient data (MIPD) combined with Integrative Data Analysis (IDA; to adjust for PTSD and SUD measurement error), propensity score weighting (PSW; to mitigate against confounding that can result when “mixing and matching” treatment arms across multiple trials), and contemporary approaches to quantifying clinically significant change (CSC; instead of mean group differences) to test the comparative efficacy of pharmacological, behavioral, and combination treatments for PTSD/SUD on clinical severity and psychosocial recovery outcomes. Thus, in response to RFA-DA-22-037, we propose three Specific Aims. Aim 1: Conduct new analyses on recovery-focused outcomes to evaluate comparative effects of behavioral, pharmacological, and combination treatments for PTSD/SUD. Aim 2: Expand MIPD/IDA methodologies to individual-level statistical inferences regarding the proportion of patients with clinically significant improvement/deterioration across treatment classes. Aim 3: Update and extend MIPD comparative effectiveness analysis of PTSD severity, SUD/AUD consumption, and recovery outcomes to an expanded 60-trial, 8000+ participant PH dataset. The novel integration of CSC into a patient-centered MIPD will yield results that, instead of comparative effectiveness of treatments on average, will give providers information on optimal patient/treatment matches— through greater precision in the expected probabilities for meaningful improvement or deterioration on PTSD, SUD, and recovery outcomes. If successful, this project will yield a synthesis of evidence in short order for the impact of existing PTSD/SUD treatments on clinical and recovery outcomes.