Fragility of randomized controlled trials on treatment of proximal humeral fracture

Proximal humeral fracture represents an increasingly common pathology with evaluation and treatment often guided by evidence from randomized controlled trials (RCTs), but the strength of an RCT must be considered in this process. The purpose of this study was to evaluate the strength of outcomes in RCTs on the management of proximal humeral fractures using the fragility index (FI), a method used with statistically significant dichotomous outcomes to assess the number of patients that would change an outcome measure from significant (P ≤ .05) to nonsignificant if the patient outcome changed. We also aimed to correlate the FI with other measures of study strength.

A systematic review was performed using Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) guidelines to evaluate RCTs on the management of proximal humeral fractures. The PubMed, Ovid MEDLINE, Web of Science, and Embase databases were searched from database inception to May 2021. RCTs with at least 1 statistically significant (P ≤ .05) dichotomous outcome were included. The FI was calculated for each included trial using the Fisher exact test. The FI was correlated with the study sample size and journal impact factor.

Ten RCTs reporting on 656 patients and published between 2011 and 2020 were included. The median patient sample size was 67 (mean, 65.6; range, 40-86). Complications were the most commonly reported dichotomous statistically significant outcome. The median FI was 1 (mean, 2.6; range, 0-18), with 4 studies having an FI of 0. A median FI of 1 indicates that 1 patient experiencing an alternative outcome or having not been lost to follow-up could have changed the pertinent conclusions of the trial for a given outcome. The median number of patients lost to follow-up was 3 (mean, 4.9; range, 0-16) and exceeded the FI in 50% of studies. There was no correlation between the FI and sample size (Spearman coefficient = 0.0592, P = .865) or between the FI and journal impact factor (Spearman coefficient = -0.0229, P = .522).

In most studies of proximal humeral fractures, only 1 or 2 patients experiencing an alternative outcome or lost to follow-up would change the conclusions for the dichotomous outcome studied. Although the FI cannot be used to assess continuous variables, which are often the primary outcome variables of RCTs, it does offer an additional unique measure of study strength that surgeons should consider when evaluating RCTs.