Gap Analysis of Swine-Based Hemostasis Research: "Houses of Brick or Mansions of Straw?"

Abstract

Introduction: Hemorrhage control is the top priority in far-forward care. Preclinical studies are essential for determining safety and efficacy before novel therapeutics can be tested in humans. Unfortunately, poor methodological quality jeopardizes translational potential.

Methods: We systematically reviewed 136 recent publications describing swine models of hemostasis and hemorrhage reduction to assess compliance with established standards for scientific reporting. Quality measures were summarized by descriptive statistics; randomization was assessed by using baseline group differences to test the uniform distribution assumption for observed P-values.

Results: Most articles did not report information essential to assess study validity and reliability of experimental results. Studies claiming random allocation showed clear evidence of systematic bias. Sample sizes were small, but nearly all studies reported statistically significant effects in the direction of "benefit." Excessive hypothesis testing increased the risk of false positives.

Conclusions: Methodological quality was poor. Although funding agencies actively promote good scientific practice, investigators have been slow to comply. Poorly executed and reported animal research is an ethical and translational issue, wasting animals and potentially harming patients. To properly assess the therapeutic benefit of novel interventions, investigators must rely less on rote hypothesis testing, develop skills in experimental design and quantitative analysis, and comply with best-practice reporting guidelines.