How statistically fragile are randomized controlled trial outcomes of balloon kyphoplasty for vertebral compression fractures?

Abstract

Randomized controlled trials (RCTs) are essential for guiding the treatment of vertebral compression fractures with kyphoplasty, yet the statistical robustness of their findings has not been thoroughly evaluated. This systematic review assessed the fragility of dichotomous outcomes in kyphoplasty RCTs using the fragility index (FI), reverse fragility index (rFI), and fragility quotient (FQ). A comprehensive search of PubMed, Embase, and MEDLINE identified eligible RCTs, yielding 282 dichotomous outcomes for analysis. The overall median FI was 4 (interquartile range [IQR], 4-5), corresponding to a median FQ of 0.020 (IQR, 0.013-0.040). Statistically significant outcomes (n=18) demonstrated greater fragility, with a median FI of 2 (IQR, 1-4) and FQ of 0.015 (IQR, 0.011-0.029), compared with nonsignificant outcomes (n=264; FI, 5 [IQR, 4-5]; FQ, 0.020 [IQR, 0.013-0.041]). Subgroup analyses revealed that pain and complication outcomes had median FIs of 4 and 5, respectively, with FQs ranging from 0.016 to 0.025. Cement leakage outcomes were the most fragile (FI, 4; FQ, 0.048). More than half of the analyzed outcomes involved a greater number of patients lost to follow-up than their corresponding FI, underscoring the need for cautious interpretation of kyphoplasty trial results and supporting the inclusion of fragility metrics in future trial reporting to better inform clinical decision-making.