Beyond mediators: A critical review and methodological path forward for studying mechanisms in alcohol use treatment research.

Understanding how treatments for alcohol use disorder (AUD) facilitate behavior change has long been recognized as an important area of research for advancing clinical care. However, despite decades of research, the specific mechanisms of change for most AUD treatments remain largely unknown because most prior work in the field has focused only on statistical mediation. Statistical mediation is a necessary but not sufficient condition to establish evidence for a mechanism of change. Mediators are intermediate variables that account statistically for the relationship between independent and dependent variables, whereas mechanisms provide more detailed explanations of how an intervention leads to a desired outcome. Thus, mediators and mechanisms are not equivalent. To advance mechanisms of behavior change research, in this critical review we provide an overview of methodological shortfalls of existing AUD treatment mechanism research and introduce an etiologically informed precision medicine approach that facilitates the testing of mechanisms of behavior change rather than treatment mediators. We propose a framework for studying mechanisms in alcohol treatment research that promises to facilitate our understanding of behavior change and precision medicine (i.e., for whom a given mechanism of behavior change operates and under what conditions). The framework presented in this review has several overarching goals, one of which is to provide a methodological roadmap for testing AUD recovery mechanisms. We provide two examples of our framework, one pharmacological and one behavioral, to facilitate future efforts to implement this methodological approach to mechanism research. The framework proposed in this critical review facilitates the alignment of AUD treatment mechanism research with current theories of etiologic mechanisms, precision medicine efforts, and cross-disciplinary approaches to testing mechanisms. Although no framework can address all the challenges related to mechanisms research, our goal is to help facilitate a shift toward more rigorous and falsifiable behavior change research.