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Distinguishing between Exploratory and Confirmatory Preclinical Research Will Improve Translation

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  • Jonathan Kimmelman
  • Jeffrey S Mogil
  • Ulrich Dirnagl

Abstract

: Kimmelman and colleagues argue that the key to improving preclinical research lies in distinguishing between two different modes of research: exploratory vs. confirmatory. 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.

Suggested Citation

  • Jonathan Kimmelman & Jeffrey S Mogil & Ulrich Dirnagl, 2014. "Distinguishing between Exploratory and Confirmatory Preclinical Research Will Improve Translation," PLOS Biology, Public Library of Science, vol. 12(5), pages 1-4, May.
    • Handle: RePEc:plo:pbio00:1001863
    DOI: 10.1371/journal.pbio.1001863
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    4. Valerie C Henderson & Jonathan Kimmelman & Dean Fergusson & Jeremy M Grimshaw & Dan G Hackam, 2013. "Threats to Validity in the Design and Conduct of Preclinical Efficacy Studies: A Systematic Review of Guidelines for In Vivo Animal Experiments," PLOS Medicine, Public Library of Science, vol. 10(7), pages 1-14, July.
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    1. Mark Yarborough & Annelien Bredenoord & Flavio D’Abramo & Nanette C Joyce & Jonathan Kimmelman & Ubaka Ogbogu & Emily Sena & Daniel Strech & Ulrich Dirnagl, 2018. "The bench is closer to the bedside than we think: Uncovering the ethical ties between preclinical researchers in translational neuroscience and patients in clinical trials," PLOS Biology, Public Library of Science, vol. 16(6), pages 1-9, June.

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