Improving preclinical studies through replications

Abstract

The purpose of preclinical research is to inform the development of novel diagnostics or therapeutics, and the results of experiments on animal models of disease often inform the decision to conduct studies in humans. However, a substantial number of clinical trials fail, even when preclinical studies have apparently demonstrated the efficacy of a given intervention. A number of large-scale replication studies are currently trying to identify the factors that influence the robustness of preclinical research. Here, we discuss replications in the context of preclinical research trajectories, and argue that increasing validity should be a priority when selecting experiments to replicate and when performing the replication. We conclude that systematically improving three domains of validity - internal, external and translational - will result in a more efficient allocation of resources, will be more ethical, and will ultimately increase the chances of successful translation.

Keywords: medicine; none; preclinical research; replication; reproducibility; science forum; translation; validity.

Figure 1.. Increasing different forms of validity (internal, external and translational) during a preclinical research trajectory.

This schematic shows that internal validity (green line) is higher than external validity (orange) and translational validity (blue) at the start of a preclinical research trajectory (left), and that evidence from different types of experiments can increase different types of validity. For example, evidence from exploratory studies can increase internal and external validity, and evidence from between-lab replications can increase translational validity. C1, C2 and C3 are decision points where researchers can decide to refine the current experiment (yellow arrow), stop the trajectory (red arrow), or proceed to the next experiment (green arrow).