How robust are clinical trials in primary and secondary ankle sprain prevention?

Objectives Determine the statistical stability of RCTs examining primary and secondary prevention of ankle sprains. Methods Databases were searched to August 2023. We included parallel design RCTs, using conservative interventions for preventing ankle sprain, reporting dichotomous injury event outcomes. Statistical stability was quantified using Fragility Index (FI) and Fragility Quotient (FQ). Subgroup analyses were undertaken to test if FI varied based on by study objective, original approach to analysis (frequency vs time to event), follow-up duration, and pre-registration. Results 3559 studies were screened with 45 RCTs included. The median number of events required to change the statistical significance (FI) was 4 (IQR 1–6). FI was similar regardless of study objective, original analysis, follow-up duration, and pre-registration status. Median (IQR) FQ was 0.015 (0.005–0.046), therefore reversing events <2 patients/100 would alter significance. In 80% of studies the number of patients lost to follow-up was greater than the FI. Conclusion RCTs informing primary and secondary prevention of ankle sprain are fragile. Only a small percentage of outcome event reversals would reverse study significance, and this is often exceeded by the number of drop outs. Robust reporting of dichotomous outcomes requires the use P values and key metrics such as FI or FQ.