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Five tenets for advancing evidence-based precision medicine

Nature Medicine (2026)Cite this article

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Abstract

Precision medicine for complex diseases uses individual-level characteristics to improve prediction of risk, therapeutic response and prognosis. Many precision medicine studies leverage existing data types and analytic methods to reveal new insights; however, beyond oncology, there has been limited success in translating precision medicine research for complex diseases into clinical practice. Thus, there is a need to identify areas for improvement, particularly in translation-oriented analytical methods and study designs. In this perspective article, we outline five fundamental tenets to enhance the efficient clinical translation of precision medicine research. These tenets focus on addressing (1) heterogeneity in risk, response and prognosis; (2) signal robustness; (3) structured statistical benchmarking against key performance indicators; (4) precision trial designs; and (5) risks and benefits to individuals and society. Our intention is to promote clinically meaningful, reproducible, scalable and equitable health outcomes through precision medicine, beyond those possible through contemporary approaches.

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Fig. 1: Precision and contemporary approaches in medicine and healthcare.
Fig. 2: Responders and nonresponders in the SELECT trial.
Fig. 3: Benchmarking nested models with or without cluster allocations.
Fig. 4: Precision trial designs.

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Acknowledgements

A.J.D. is supported by the National Institutes of Health (NIH)/National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK; K23 DK140643). M.S.U. is supported by NIH/NIDDK (U01DK140757 and U54DK118612) and the Doris Duke Foundation (grant 2022063). D.E.C., L.M.C., G.N.G., E.R.P. and P.W.F. were supported by grants from the European Commission (IMI SOPHIA, 875534), Swedish Research Council, Novo Nordisk Foundation, Vinnova and Swedish Foundation for Strategic Research (LUDC-IRC, 15-0067) and Exodiab (2009-1039). D.E.C. was supported by an EFSD/Lilly research grant.

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Author notes

  1. These authors contributed equally: Daniel E. Coral, Jennifer L. Sargent.

Authors and Affiliations

  1. Genetic & Molecular Epidemiology Unit, Department of Clinical Sciences, Lund University, Helsingborg, Sweden

    Daniel E. Coral, Luis M. Coral, Giuseppe N. Giordano & Paul W. Franks

  2. Diabetic Complications Unit, Department of Clinical Sciences, Lund University, Malmo, Sweden

    Daniel E. Coral

  3. Heidelberg Institute of Global Health, Heidelberg University, Heidelberg, Germany

    Jennifer L. Sargent

  4. School of Public Health, Imperial College London, London, UK

    Jennifer L. Sargent

  5. Precision Healthcare University Research Institute, Queen Mary University of London, London, UK

    Julia Carrasco-Zanini & Paul W. Franks

  6. Diabetes Unit and Center for Genomic Medicine, Massachusetts General Hospital, Boston, MA, USA

    Aaron J. Deutsch & Miriam S. Udler

  7. Programs in Metabolism and Medical & Population Genetics, Broad Institute of MIT and Harvard, Cambridge, MA, USA

    Aaron J. Deutsch & Miriam S. Udler

  8. Department of Medicine, Harvard Medical School, Boston, MA, USA

    Aaron J. Deutsch & Miriam S. Udler

  9. McMaster University, Hamilton, Ontario, Canada

    Guillaume Pare

  10. School of Medicine, University of Dundee, Dundee, Scotland

    Ewan R. Pearson

  11. Julius Center for Health Sciences and Primary Care, Department of Data Science and Biostatistics, University Medical Center Utrecht, University of Utrecht, Utrecht, The Netherlands

    Maarten van Smeden

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Contributions

D.E.C. and P.W.F. conceived the core ideas described in this study. D.E.C., J.L.S. and P.W.F. wrote the initial draft of the manuscript. All authors contributed to the ideas described herein and reviewed and edited the manuscript before submission.

Corresponding authors

Correspondence to Daniel E. Coral or Paul W. Franks.

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Competing interests

M.S.U. has consulting activity and research supported in collaboration with Novo Nordisk. J.L.S. has received consulting fees from the World Health Organization, University of Bergen, University of Heidelberg, Lund University, Karolinska University, Springer Nature, ABC Labs and European Diabetes Forum; travel support from University of Tubingen, University of Silensia, and European Association for Study of Diabetes; she is also founder of BabelFiskAB, which provides consulting services in global public health. P.W.F. has received consulting fees from Novo Nordisk and Zoe Ltd, and travel support and speaker fees from Menarini Group. P.W.F. has received research grants (paid to his institution) from Boehringer Ingelheim, Novo Nordisk, Medtronic, Pfizer and Lilly as part of the Innovative Health Initiative of the European Union. The remaining authors declare no competing interests.

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Coral, D.E., Sargent, J.L., Carrasco-Zanini, J. et al. Five tenets for advancing evidence-based precision medicine. Nat Med (2026). https://doi.org/10.1038/s41591-026-04309-6

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