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European Journal of Heart Failure Advance Access originally published online on January 22, 2009
European Journal of Heart Failure 2009 11(3):256-263; doi:10.1093/eurjhf/hfn048
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Published on behalf of the European Society of Cardiology. All rights reserved. © The Author 2009. For permissions please email: journals.permissions@oxfordjournals.org.

Years-needed-to-treat to add 1 year of life: a new metric to estimate treatment effects in randomized trials

Wayne C. Levy1,*, Dariush Mozaffarian2, David T. Linker1, Kenneth W. Kenyon1, John G.F. Cleland3, Michel Komajda4, Willem J. Remme5, Christian Torp-Pedersen6, Marco Metra7, Philip A. Poole-Wilson8 on behalf of the COMET Investigators

1 Division of Cardiology, University of Washington, Box 356422, 1959 NE Pacific Street, Seattle, WA 98177, USA
2 Brigham and Women's Hospital and Harvard Medical School, Harvard School of Public Health, Boston, MA, USA
3 University of Hull, Kingston upon Hull, UK
4 La Pitié-Salpétrière Hospital, Paris, France
5 Sticares Cardiovascular Research Institute, Rhoon, The Netherlands
6 Bispebjerg University Hospital, Copenhagen, Denmark
7 Cattedra di Cardiologia, Università di Brescia, Italy
8 Imperial College School of Medicine, London, UK

* Corresponding author. Tel: +1 206 221 4507, Fax: +1 206 221 6835, Email: levywc{at}u.washington.edu


   Abstract

Aims: A standard metric to estimate absolute treatment effects is numbers-needed-to-treat (NNT), which implicitly assumes that all benefits reverse at trial-end. However, in-trial survival benefits typically do not reverse until long after trial-end, so that NNT will substantially underestimate lifetime benefits.

Methods and results: We developed a new concept, years-needed-to-treat (YNT) to add 1 year of life, that quantifies the expected average life expectancy for two treatments including the estimated years of life remaining post-trial. Numbers-needed-to-treat and YNT were calculated in the COMET trial, in which carvedilol vs. metoprolol tartrate resulted in 17% lower mortality over 4.8 years. A multivariate Cox model was used to predict survival. Remaining years of life were estimated using the mortality-life-table method. At trial-end, survival was 9% higher in the carvedilol arm. Assuming that patients remained on the same therapy post-trial, the average total years of life for carvedilol vs. metoprolol were 10.63 ± 0.19 vs. 9.48 ± 0.18 (P < 0.0001) or 1.15 (95% confidence interval 0.64–1.66) additional years of life. The YNT was 9.2, indicating that 9.2 person-years of treatment added 1 person-year of life, compared with NNT of 59.

Conclusion: Compared with NNT, the YNT method more accurately accounts for potential long-term benefits of interventions in randomized trials.

Key Words: Heart failure • Prognostication • Outcomes • Epidemiology • Gompertz • Beta-blocker • Number-needed-to-treat • Years-needed-to-treat

Received July 21, 2008; Revised November 11, 2008; Accepted November 11, 2008


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