Distinguishing between Exploratory and Confirmatory Preclinical Research Will Improve Translation

被引:156
作者
Kimmelman, Jonathan [1 ]
Mogil, Jeffrey S. [2 ,3 ]
Dirnagl, Ulrich [4 ,5 ,6 ,7 ,8 ]
机构
[1] McGill Univ, Studies Translat Eth & Med STREAM, Biomed Eth Unit, Montreal, PQ, Canada
[2] McGill Univ, Dept Psychol, Montreal, PQ, Canada
[3] McGill Univ, Alan Edwards Ctr Res Pain, Montreal, PQ, Canada
[4] Charite, Dept Neurol, Ctr Stroke Res Berlin, D-13353 Berlin, Germany
[5] Charite, Dept Expt Neurol, Ctr Stroke Res Berlin, D-13353 Berlin, Germany
[6] Charite, Excellence Cluster NeuroCure, D-13353 Berlin, Germany
[7] German Ctr Neurodegenerat Res DZNE, Tubingen, Germany
[8] Ctr Cardiovasc Dis DZHK, Munich, Germany
基金
加拿大健康研究院;
关键词
REPLICATION;
D O I
10.1371/journal.pbio.1001863
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
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.
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