LAUSR

Any mention of generalizability during a presentation is likely to induce narcolepsy amongst most clinicians. Randomized trials are invaluable and customarily supersede other study designs in guiding clinical decision-making. A timely, relevant, well-designed, properly executed randomized trial is golden. Which is exactly why internal validity and generalizability are more than semantic or statistical nerd chatter. They are critical to guide whether and how we should apply trial findings to patients and populations. Internal validity represents whether the trial was a fair test of the hypothesis versus being affected by study design, study conduct, bias, or random error. Consequently, trialists strive to create a fair comparison of experimental and control groups (eg, randomization, reduce contamination), minimize confounding (eg, no previous cancer treatment allowed, exclude patients with other active medications, centralized expert pathology/radiology review), and establish strict rules (eg, standardized monitoring, validated questionnaires, clear definition of endpoints). Due to severe contamination in the control arm, the Prostate, Lung, Colorectal, and Ovarian prostate cancer screening trial is a textbook example of poor internal validity [1,2]. Regrettably, it has helped inform public policy and population health [3]. External validity, also known as generalizability or applicability, is the appropriateness of applying the trial findings to other populations, either generally or specifically. Would the findings among the studied population likely be replicable in other cohorts that may differ by species (eg, animal studies), sex, race, ethnicity, germline DNA, age, comorbidities, geography, healthcare system, or socioeconomic status? For example, evaluation of a surgical