The fragility of statistically significant findings from randomized trials in head and neck surgery

Abstract

Objectives: The Fragility Index (FI) is a novel tool for evaluating the robustness of statistically significant findings in a randomized control trial (RCT). It measures the number of events upon which statistical significance depends. We sought to calculate the FI scores for RCTs in the head and neck cancer literature where surgery was a primary intervention.

Data sources: Potential articles were identified in PubMed (MEDLINE), Embase, and Cochrane without publication date restrictions.

Review methods: Two reviewers independently screened eligible RCTs reporting at least one dichotomous and statistically significant outcome. The data from each trial were extracted and the FI scores were calculated. Associations between trial characteristics and FI were determined.

Results: In total, 27 articles were identified. The median sample size was 67.5 (interquartile range [IQR] = 42-143) and the median number of events per trial was 8 (IQR = 2.25-18.25). The median FI score was 1 (IQR = 0-2.5), meaning that changing one patient from a nonevent to an event in the treatment arm would change the result to a statistically nonsignificant result, or P > .05. The FI score was less than the number of patients lost to follow-up in 71% of cases. The FI score was found to be moderately correlated with P value (ρ = -0.52, P = .007) and with journal impact factor (ρ = 0.49, P = .009) on univariable analysis. On multivariable analysis, only the P value was found to be a predictor of FI score (P = .001).

Conclusions: Randomized trials in the head and neck cancer literature where surgery is a primary modality are relatively nonrobust statistically with low FI scores. Laryngoscope, 128:2094-2100, 2018.

Keywords: Fragility Index; Randomized control trials; clinical epidemiology; head and neck cancer; lost to follow-up; research methodology; statistical significance.