The Statistical Fragility of Platelet-Rich Plasma as Treatment for Achilles Tendinopathy: A Systematic Review and Meta-Analysis

Abstract

Category: Basic Sciences/Biologics; Hindfoot; Sports Introduction/Purpose: Randomized controlled trial (RCT) outcomes reaching statistical significance, frequently determined by p<0.05, are often used to guide decision-making. Noted lack of reproducibility of some RCTs has brought special attention to the limitations of this approach. In this meta-analysis, we assessed the robustness of RCTs evaluating platelet-rich plasma (PRP) for the treatment of Achilles tendinopathy (AT) by using fragility indices. Methods: RCTs comparing outcomes after PRP injection versus alternative treatment in patients with chronic AT were evaluated. Representative datasets were generated for each reported continuous outcome event using summary statistics. The fragility index (FI) and continuous FI (CFI) were determined for dichotomous and continuous outcomes, respectively, by manipulating each dataset until reversal of significance (a=0.05) was achieved. The corresponding fragility quotient (FQ) and continuous FQ (CFQ) were calculated by dividing FI/CFI by sample size. Results: Of 432 studies screened, 8 studies (52 outcome events) were included in the present analysis. The 12 dichotomous outcomes had a median FI of 4.5 (FQ: 0.111), and the 40 continuous outcomes had a median CFI of 5 (CFQ: 0.154). All 52 outcome events included lost-to-follow-up data, and 12 (23.1%) indicated a greater number of patients lost to follow-up than the FI or CFI. Conclusion: Our findings suggest that RCTs evaluating PRP for AT therapy lack statistical robustness, since changing only a small number of events may alter outcome significance. Given the importance of RCTs in clinical decision-making, fragility indices should be reported alongside p-values to indicate the strength of statistical findings. It is paramount that future RCTs be designed with consideration of sample size from both recruitment and retention perspectives to maximize protocol robustness and determine the true therapeutic effect of PRP in AT.