The statistical fragility of randomised controlled trials evaluating tranexamic acid against a saline control in total hip arthroplasty

Abstract

Introduction:

This study applied the fragility index (FI), reverse fragility index (rFI), and fragility quotient (FQ) to evaluate the statistical fragility of outcomes reported in RCTs evaluating TXA against a saline control in total hip arthroplasty (THA).

Methods:

PubMed, Embase, and MEDLINE were searched for RCTs on TXA in THA compared to a saline control. FI and rFI were calculated for dichotomous outcomes, representing the number of outcome reversals required to alter significance.

Results:

32 studies were included. Across 69 total outcomes, the median FI was 3.0 (IQR 2.0–6.0) with an associated median FQ of 0.031 (IQR 0.020–0.053), suggesting that 3 outcome event reversals would alter significance for 50% of all outcomes. 18 outcomes were statistically significant, with a median FI of 3.0 (IQR 1.0–5.0) and a median FQ of 0.026 (IQR 0.017–0.036). 51 outcomes were non-significant, with a median rFI of 4.0 (IQR 2.5–7.0) and a median FQ of 0.032 (IQR 0.020–0.066). Results designated as primary outcomes were more fragile (median FQ = 0.025, n = 20) than non-primary outcomes (median FQ = 0.032, n = 49).

Conclusions:

The efficacy of TXA use during THA from RCTs is statistically fragile, particularly among significant outcomes and those related to blood or platelet transfusion rates. We recommend combined reporting of p-values with FI and FQ metrics to help interpret clinical findings in RCT involving TXA use during THA.