Clinical Trial Generalizability Assessment in the Big Data Era: A Review.


Clinical studies, especially randomized controlled trials, are essential for generating evidence for clinical practice. However, generalizability is a long-standing concern when applying trial results to real-world patients. Generalizability assessment is thus important, nevertheless, not consistently practiced. We performed a systematic review to understand the practice of generalizability assessment. We identified 187 relevant papers and systematically organized these studies in a taxonomy with three dimensions: (1) data availability (i.e., before or after trial [a priori vs a posteriori generalizability]), (2) result outputs (i.e., score vs non-score), and (3) populations of interest. We further reported disease areas, underrepresented subgroups, and types of data used to profile target populations. We observed an increasing trend of generalizability assessments, but less than 30% of studies reported positive generalizability results. As a priori generalizability can be assessed using only study design information (primarily eligibility criteria), it gives investigators a golden opportunity to adjust the study design before the trial starts. Nevertheless, less than 40% of the studies in our review assessed a priori generalizability. With the wide adoption of electronic health records systems, rich real-world patient databases are increasingly available for generalizability assessment; however, informatics tools are lacking to support the adoption of generalizability assessment practice.

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