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Successful drug discovery is like finding oases of safety and efficacy in chemical and biological deserts. Screens in disease models, and other decision tools used in drug research and development (R&D), point towards oases when they score therapeutic candidates in a way that correlates with clinical utility in humans. Otherwise, they probably lead in the wrong direction. This line of thought can be quantified by using decision theory, in which ‘predictive validity’ is the correlation coefficient between the output of a decision tool and clinical utility across therapeutic candidates. Analyses based on this approach reveal that the detectability of good candidates is extremely sensitive to predictive validity, because the deserts are big and oases small. Both history and decision theory suggest that predictive validity is under-managed in drug R&D, not least because it is so hard to measure before projects succeed or fail later in the process. This article explains the influence of predictive validity on R&D productivity and discusses methods to evaluate and improve it, with the aim of supporting the application of more effective decision tools and catalysing investment in their creation.


Journal article


Nature reviews drug discovery


Nature Research (part of Springer Nature)

Publication Date



Duncan Richards, University of Oxford, Nuffield Department of Orthopaedics, Rheumatology, and Musculoskeletal Sciences, University of Oxford, Botnar Research Centre, Oxford, Oxford, OX3 7LP, Oxfordshire, Jack W. Scannell, University of Edinburgh, Science, Technology, and Innovation Studies, Edinburgh, Scotland, James Bosley, Nova Discovery, South Africa, John A Hickman, University of Manchester, School of Biological Sciences, Manchester, United Kingdom, Gerrard R. Dawson, P1vital Ltd, Manor House, Wallingford, Oxford, Oxfordshire, OX10 8BA, United Kingdom, Hubert Truebel, The Knowledge House GmbH, 363 Rider Ave 3rd floor,, New York, NY 10451, United States, Guilherme S. Ferreira, 3D-PharmXchange, Maidstone 48a, 5026 SK Tilburg,, Tilburg, North Brabant, Netherlands, J. Mark Treherne, Talisman Therapeutics Ltd, Jonas Webb Building Babraham Research Campus, Cambridge, CB22 3AT, United Kingdom


Drug Discovery