The fragility of statistically significant results from clinical nutrition randomized controlled trials

Summary Background & aims Recently, a parameter called “Fragility index” (FI) has been proposed, which measures how many events the statistical significance relies on. The lower the FI the more “fragile” the results, and thus more care should be taken when interpreting the results. Our aim in this study was to check FI of nutritional trials. Methods We conducted a systematic review of human clinical nutrition RCTs that report statistically significant dichotomous primary outcomes. We searched the EMBASE, MEDLINE, and Scopus databases. The FI of primary outcomes using the Fisher exact test was calculated and checked the correlations of FI with the number of randomised trials, the p-value of primary outcomes, the publication date, the journal impact factor and the number of patients lost to follow-up. Results The initial database search revealed 5790 articles, 37 of which were included in qualitative synthesis. The median (IQR) FI for all studies was 1 (1–3). 28 studies (75.7%) had an FI lower or equal to 2, and in 12 (32.43%) articles, the FI was lower than the number of patients lost to follow-up. No correlations were found between FI and the study characteristics (number of randomized patients, p value of primary outcome, event ratio in experimental group, event ratio in control group, publication date, journal impact factor, lost to follow-up). Conclusion The results of RCTs in nutritional research often rely on a small number of events or patients. The number of patients lost to follow-up is frequently higher than the FI calculation. Formulating recommendations based on RCTs should be done with caution and FI may be used as auxiliary parameter when assessing the robustness of their findings.