Mitigating Multiple Sources of Bias in a Quasi-Experimental Integrative Data Analysis: Does Treating Childhood Anxiety Prevent Substance Use Disorders in Late Adolescence/Young Adulthood?

Psychiatric epidemiologists, developmental psychopathologists, prevention scientists, and treatment researchers have long speculated that treating child anxiety disorders could prevent alcohol and other drug use disorders in young adulthood. A primary challenge in examining long-term effects of anxiety disorder treatment from randomized controlled trials is that all participants receive an immediate or delayed study-related treatment prior to long-term follow-up assessment. Thus, if a long-term follow-up is conducted, a comparison condition no longer exists within the trial. Quasi-experimental designs (QEDs) pairing such clinical samples with comparable untreated epidemiological samples offer a method of addressing this challenge. Selection bias, often a concern in QEDs, can be mitigated by propensity score weighting. A second challenge may arise because the clinical and epidemiological studies may not have used identical measures, necessitating Integrative Data Analysis (IDA) for measure harmonization and scale score estimation. The present study uses a combination of propensity score weighting, zero-inflated mixture moderated nonlinear factor analysis (ZIM-MNLFA), and potential outcomes mediation in a child anxiety treatment QED/IDA (n = 396). Under propensity score-weighted potential outcomes mediation, CBT led to reductions in substance use disorder severity, the effects of which were mediated by reductions in anxiety severity in young adulthood. Sensitivity analyses highlighted the importance of attending to multiple types of bias. This study illustrates how hybrid QED/IDAs can be used in secondary prevention contexts for improved measurement and causal inference, particularly when control participants in clinical trials receive study-related treatment prior to long-term assessment.