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Rationalizing Prescribing for Older Patients with Multimorbidity: Considering Time to Benefit

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Abstract

Given the growing number of older adults with multimorbidity who are prescribed multiple medications, clinicians need to prioritize which medications are most likely to benefit and least likely to harm an individual patient. The concept of time to benefit (TTB) is increasingly discussed in addition to other measures of drug effectiveness in order to understand and contextualize the benefits and harms of a therapy to an individual patient. However, how to glean this information from available evidence is not well established. The lack of such information for clinicians highlights a critical need in the design and reporting of clinical trials to provide information most relevant to decision making for older adults with multimorbidity. We define TTB as the time until a statistically significant benefit is observed in trials of people taking a therapy compared to a control group not taking the therapy. Similarly, time to harm (TTH) is the time until a statistically significant adverse effect is seen in a trial for the treatment group compared to the control group. To determine both TTB and TTH, it is critical that we also clearly define the benefit or harm under consideration. Well-defined benefits or harms are clinically meaningful, measurable outcomes that are desired (or shunned) by patients. In this conceptual review, we illustrate concepts of TTB in randomized controlled trials (RCTs) of statins for the primary prevention of cardiovascular disease. Using published results, we estimate probable TTB for statins with the future goal of using such information to improve prescribing decisions for individual patients. Knowing the relative TTBs and TTHs associated with a patient’s medications could be immensely useful to a clinician in decision making for their older patients with multimorbidity. We describe the challenges in defining and determining TTB and TTH, and discuss possible ways of analyzing and reporting trial results that would add more information about this aspect of drug effectiveness to the clinician’s evidence base.

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Acknowledgements

Holly M. Holmes is funded by a K23 from the National Institute on Aging, K23AG038476. Lillian Min is funded by the Agency for Healthcare Research and Quality (R21 HS017621) and career development awards from the University of Michigan Older Americans Independence Center (NIA) and the Hartford Foundation. Michael Yee is funded by the Medical Student Training in Aging Research (MSTAR), which is funded through the American Federation for Aging Research (AFAR). Ravi Varadhan is a Brookdale Leadership in Aging Fellow at the Johns Hopkins University School of Medicine. Dr. Boyd is funded by an R21 from the Agency for Healthcare Related Quality, “Improving Clinical Practice Guidelines for Complex Patients” HS018597-01, a Paul Beeson Career Development Award Program from the National Institute on Aging, 1K23AG032910, the American Federation for Aging Research, The John A. Hartford Foundation, The Atlantic Philanthropies, The Starr Foundation, and an anonymous donor. The authors’ work was independent of the funders.

Conflict of Interest

Dr. Holmes, Dr. Min, Mr. Yee, Dr. Varadhan, Dr. Basran, and Dr. Dale have no conflicts of interest to disclose. Dr. Boyd has served as an author for UptoDate on the topic of multimorbidity and has given a talk on multimorbidity to United Health Care’s Medicare Advisory Board.

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Authors and Affiliations

  1. Department of General Internal Medicine, UT MD Anderson Cancer Center, 1515 Holcombe Blvd, Unit 1465, Houston, TX, 77030, USA

    Holly M. Holmes

  2. Division of Geriatric Medicine, University of Michigan, Ann Arbor, MI, USA

    Lillian C. Min

  3. Pritzker School of Medicine, University of Chicago, Chicago, IL, USA

    Michael Yee

  4. Division of Geriatric Medicine and Gerontology, Department of Medicine, Johns Hopkins University, Baltimore, MD, USA

    Ravi Varadhan & Cynthia M. Boyd

  5. Division of Geriatrics, University of Saskatchewan, Saskatoon, Canada

    Jenny Basran

  6. Section of Geriatrics and Palliative Medicine, Department of Medicine, University of Chicago, Chicago, IL, USA

    William Dale

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  1. Holly M. Holmes
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  7. Cynthia M. Boyd
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Correspondence to Holly M. Holmes.

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Holmes, H.M., Min, L.C., Yee, M. et al. Rationalizing Prescribing for Older Patients with Multimorbidity: Considering Time to Benefit. Drugs Aging 30, 655–666 (2013). https://doi.org/10.1007/s40266-013-0095-7

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