Distinguishing between exploratory and confirmatory preclinical research will improve translation

PLoS Biol. 2014 May 20;12(5):e1001863. doi: 10.1371/journal.pbio.1001863. eCollection 2014 May.

Abstract

Preclinical researchers confront two overarching agendas related to drug development: selecting interventions amid a vast field of candidates, and producing rigorous evidence of clinical promise for a small number of interventions. We suggest that each challenge is best met by two different, complementary modes of investigation. In the first (exploratory investigation), researchers should aim at generating robust pathophysiological theories of disease. In the second (confirmatory investigation), researchers should aim at demonstrating strong and reproducible treatment effects in relevant animal models. Each mode entails different study designs, confronts different validity threats, and supports different kinds of inferences. Research policies should seek to disentangle the two modes and leverage their complementarity. In particular, policies should discourage the common use of exploratory studies to support confirmatory inferences, promote a greater volume of confirmatory investigation, and customize design and reporting guidelines for each mode.

MeSH terms

  • Animals
  • Drug Evaluation, Preclinical / methods*
  • Humans
  • Practice Guidelines as Topic
  • Research Design / legislation & jurisprudence*
  • Translational Medical Research / methods*
  • Translational Medical Research / organization & administration

Grant support

This work was funded by Canadian Institutes of Health Research (EOG 111391). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.