The cortical scene processing network emerges in infancy, prior to independent navigation experience.

The push for appropriately governed secondary data use is accelerating as healthcare stakeholders seek to harness diverse health system datasets to optimize patient care (). Health technology developers (HTDs) and health technology assessment (HTA) bodies are utilizing real-world evidence (RWE) to inform clinical assessments and economic models (–). For example, descriptive RWE studies are used to characterize the local population, care and treatment pathways, qualitatively evaluate the external validity of clinical trial findings for the HTA body’s population of interest, and verify assumptions in economic modeling (;). In rarer instances, real-world data (RWD) is used as an external control to estimate comparative efficacy or benchmark trial results (;). RWE can also be used post-launch to evaluate a range of decision-relevant uncertainties (–). A major challenge in the use of RWE is internal validity (i.e., the extent to which the results of an RWE study accurately reflect the true situation in the specific population being studied, free from systematic errors (bias) or the effects of chance ()). Since RWE comparative effectiveness studies are not randomized, researchers must control for potential confounding to demonstrate the true effect of a therapy. Substantial work has outlined best practices for addressing internal validity challenges (e.g., HTA body guidance). External validity (or “the extent to which the results of a given study can be applied outside the original study context, such as to another target population of interest” ()) is another key challenge, but has been given less attention. Although local evidence is ideal, HTA bodies are increasingly receiving submissions that include RWE generated from other countries (). This is often driven by the lack of high-quality local data for the specific clinical application or due to small sample sizes for rare conditions and/or small populations or limited HTA capacity. RWE is recognized for its superior external validity, as it incorporates diverse patient populations and reflects contemporary clinical practice. However, when such studies are conducted outside the target jurisdiction, HTA bodies may question the relevance of the findings for their specific local population.