Importance: The Fragility Index (FI) is the minimum number of participants in a randomized clinical trial (RCT) whose status would have to change from a nonevent (not experiencing the primary end point) to an event (experiencing the primary end point) required to turn a statistically significant result to a nonsignificant result. The FI measures the robustness (or fragility) of the results of an RCT and is an important aid to the clinician's interpretation of RCT results. It has now been recognized that RCTs, which provide the foundation for treatment guideline recommendations, may not be robust.
Observations: Most RCTs in surgery and general medicine are fragile (with a low FI score), in contrast to those in cardiac disease and heart failure, where most RCTs are robust (with high FI scores). For clinical trials of trauma, we identified that the median (interquartile range) FI score was 3 (1-8), which means that adding 3 events to the opposite treatment arm in a given RCT eliminated statistical significance. The median Fragility Quotient (the FI score divided by the total study sample size) was 0.016 (0.0043-0.0408).
Conclusions and relevance: The provision of high-quality, evidence-based clinical care in surgery for optimal patient outcomes requires a foundation of robust clinical research evidence, and knowledge of the FI will assist in future surgical RCT design. We strongly recommend the routine reporting of FI scores for all future trauma and surgical RCTs to assist in appropriate and optimal decision making in the care of patients who have experienced trauma and/or need surgery. We also recommend the routine inclusion of the FI score in the development of clinical guidelines to assist the clinician in ascertaining whether guideline recommendations are robust. Surgeons should be aware to particularly exercise caution when considering a potential change in clinical practice based on RCTs with a low FI score.