Back to 2026 Abstracts
A Statistical Fragility Analysis of Randomized Controlled Trials on Biological Therapies in Diabetic Foot Ulcer Management
Pushti Shah
*, Jacquelyn Roth, Sidharth Addepalli, Ishan Patel, Seth Noorbakhsh, Mark Granick, Edward Lee
Division of Plastic Surgery, Department of Surgery, Rutgers New Jersey Medical School, Newark, NJ
Background: Diabetic foot ulcers (DFUs) drive over 80% of lower-extremity amputations, yet biological therapies cost thousands per application. While existing RCTs show statistical significance favoring biologics, significance alone does not reflect robustness, making fragility analysis essential to assess whether conclusions withstand minor outcome changes.
Methods: PubMed, Scopus, CENTRAL, and Web of Science were searched. Outcomes included wound closure, adverse events, and recurrence. Fragility index (FI) and reverse fragility index (rFI) were calculated using Fisher's exact test and represent the number of patient outcome changes required to reverse/achieve significance; fragility quotients (FQ/rFQ) standardize these by sample size (e.g., FQ of 0.05 = 5 changes per 100 patients). Data are reported as median[Q1-Q3].
Results: Of 33 studies (N=3,459), only 48.5% reported power analyses with a mean loss to follow-up of 6.46 ± 4.88 patients. Patients received dermal matrices (N=1,302), placental membranes (N=606), or standard of care (SOC, N=545). Biologics improved wound closure in 13/23 trials, but findings were highly fragile (FI=6[3-8], FQ=0.08[0.02-0.13]). Nonsignificant trials were equally fragile (rFI=4[3-4], rFQ=0.11[0.10-0.14]). Meta-analyses favored dermal matrices (p<0.001; FQ=0.05) and amniotic membranes (p<0.001; FQ=0.11) over SOC, with 5% and 11% patient changes reversing significance (Figure 1). Direct amniotic membrane vs dermal matrix comparison showed no difference in wound closure (p=0.09; rFI=1; rFQ=0.01). Biologics yielded fewer complications (p<0.001; FQ=0.02) and similar recurrence rates (p=0.19; rFQ=0.04) vs. SOC, though neither finding was robust.
Conclusion: Evidence supporting biologics is highly fragile, with only 6 outcome changes (8%) required to negate wound-closure significance - fewer than the mean loss to follow-up. This raises concern for the overestimation of treatment benefits. Given their substantial cost, adoption of biologics should be limited to indications supported by statistically robust, adequately powered trials.
Models adjusted for BMI, tissue expander size, and axillary irradiation. OR > 1 indicates higher odds with early exchange.
Back to 2026 Abstracts
Models adjusted for BMI, tissue expander size, and axillary irradiation. OR > 1 indicates higher odds with early exchange.
