Evaluating Study Design Rigor in Preclinical Cardiovascular Research: A Replication Study

Methodological rigor remains a priority in preclinical cardiovascular research to ensure experimental reproducibility and high-quality research. Limited reproducibility diminishes the translation of preclinical discoveries into medical practice. In addition, lack of reproducibility fosters uncertainty in the public's acceptance of reported research results.

We evaluated the reporting of methodological practices in preclinical cardiovascular research studies published in leading scientific journals by screening articles for the inclusion of the following study design elements (SDEs): considering sex as a biological variable, randomization, blinding, and sample size power estimation. We screened for these SDEs across articles regarding preclinical cardiovascular research studies published between 2011 and 2021. We replicated and extended a study published in 2017 by Ramirez et al. We hypothesized a higher SDE inclusion across preclinical studies over time, that preclinical studies that include human and animal substudies within the same study will exhibit greater SDE inclusion than animal-only preclinical studies, and that a difference exists in SDE usage between large and small animal models.

SDE inclusion was low; with 15.2% of animal-only studies including both sexes as a biological variable, 30.4% including randomization, 32.1% including blinding, and 8.2% including sample size estimation. The incorporation of SDEs did not significantly increase over the ten-year timeframe in the screened articles. Randomization and sample size estimation differed significantly between animal and human substudies (corrected p=1.85e-05 and corrected p=3.81e-07, respectively.).

Evidence of methodological rigor varies depending on the study type and model organisms used. From 2011-2021, SDE reporting within preclinical studies has not increased, suggesting more work is needed to foster the inclusion of rigorous study design elements in cardiovascular research.