Third-Variable Effects: Tools to Understand Who, When, Why, and How Patients Benefit From Surgical Prehabilitation

Prehabilitation is a new field of research that aims to optimize modifiable surgical risk factors before surgery to improve patient-oriented outcomes preoperatively and postoperatively. As with any new intervention, the pressing questions that arise include what interventions work, for whom they work, and when do they work best? Given that prehabilitation can be resource intensive, and that preoperative patient characteristics are likely to produce variation in response to treatment, establishing answers to these questions is critical for successful implementation of prehabilitation in clinical practice. The objective of this review article is to describe the illuminating potential of including "third-variable effects" into the integration of research design; by planning for and including measurements of mediators, moderators, and confounders in the design and analysis of prehabilitation research, we can begin to answer practical, clinically relevant questions.