Randomized Controlled Trials for the Prevention of Venous Thromboembolism in Trauma and Emergency General Surgery Patients: A Systematic Review of Sample Size Methodologies

INTRODUCTION: Trauma and emergency general surgery patients are at an elevated risk of developing venous thromboembolism (VTE). However, deviations from guideline-recommended thromboprophylaxis regimens persist. As such, improving thromboprophylaxis compliance has been deemed a high priority. However, the few trials evaluating VTE prevention regimens in these settings have important methodological limitations preventing clinical application. Thus, we conducted a systematic review to evaluate the sample size methodology and justification in randomized controlled trials (RCTs) examining VTE prevention in the trauma and emergency general surgery setting. METHODS: We searched two databases (Medline and EMBASE) from inception to February 17, 2025, for all English-language RCTs that enrolled adult trauma or emergency general surgery patients and evaluated an intervention aimed at preventing VTE. Citation screening, data extraction, and risk of bias were performed independently and in duplicate. RESULTS: We included seven studies involving 1358 patients. Most trials were single center (71.4%), assessing trauma patients (85.7%), with a primary outcome encompassing any VTE (71.4%). Only two of the six studies (33.3%) reporting sample size targets achieved their recruitment goals. None of the included studies met their prespecified VTE incidence or absolute risk reduction estimations. Furthermore, only one (14.3%) study incorporated prognostic enrichment in their methodological approach. The majority of studies (57.1%) were terminated early, citing futility of the intervention as the most common reason. CONCLUSIONS: This systematic review shows that RCTs assessing VTE prevention in the trauma and emergency general surgery population consistently demonstrate methodological limitations resulting in unrealistic treatment effect targets and inaccurate estimates of baseline risk. Future trials in this field should consider abandoning dichotomization with statistical analysis interpretation, as well as incorporating heterogeneity of treatment effect and prognostic enrichment in the study design.