The Fragility of Statistically Significant Results in Gynaecologic Surgery: A Systematic Review.

OBJECTIVE: To use the fragility index (FI) to evaluate the robustness of gynaecologic surgery trials that report statistically significant results. The FI defines the minimum number of patients who must have an alternative outcome to alter statistical significance.

DATA SOURCES: We searched MEDLINE, Web of Science, Embase, and ClinicalTrials.gov from 2011 to 2021 to identify gynaecologic surgery randomized controlled trials (RCTs).

STUDY SELECTION: A total of 4775 trials were screened for eligibility. All included studies evaluated benign gynaecologic surgery interventions or peri-operative medical interventions. Only 2-arm RCTs with statistically significant dichotomous primary outcomes were included. Ninety-three trials were ultimately included for analysis.

DATA EXTRACTION AND SYNTHESIS: Data from the included studies, including sample size, loss to follow-up, and number of events, were recorded. The FI of each study was calculated using a predefined technique. The overall FI and FIs by subgroup (clinical subspecialty, country of origin, and statistical test used) are reported as medians alongside their interquartile ranges (IQRs). The Kruskal-Wallis test was applied to find possible statistically significant relationships between FI and the nominal subgroups. Among this cohort, the median FI was 3 (IQR 1-7). The FI was 0 in 13 trials (14%), and in 39 trials (42%), the number of patients lost to follow-up was greater than the FI. The median FI within clinical subspecialty groups (general gynaecology, anaesthesia, urogynaecology, and fertility) did not differ (P = 0.122).

CONCLUSION: Statistically significant results of RCTs in gynaecologic surgery are fragile, suggesting that clinicians should interpret results with caution. This is particularly true when the number of patients lost to follow-up is greater than the FI. The FI serves as a quality metric that can be used to evaluate robustness of results when applying the outcomes of RCTs to clinical practice or guideline development.