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Prevalence of diabetes treatment effect modifiers: the external validity of trials to older adults

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Abstract

Background and aims: Potential treatment effect modifiers (TEMs) are specific diseases or conditions with a well-described mechanism for treatment effect modification. The prevalence of TEMs in older adults with type 2 diabetes mellitus (DM) is unknown. Objectives were to 1) determine the prevalence of pre-specified potential TEMs; 2) demonstrate the potential impact of TEMs in the older adult population using a simulated trial; 3) identify TEM combinations associated with number of hospitalizations to test construct validity. Methods: Data are from the nationally- representative United States National Health and Examination Survey, 1999–2004: 8646 Civilian, non-institutionalized adults aged 45–64 or 65+ years, including 1443 with DM. TEMs were anemia, congestive heart failure, liver inflammation, polypharmacy, renal insufficiency, cognitive impairment, dizziness, frequent mental distress, mobility difficulty, and visual impairment. A trial was simulated to examine prevalence of potential TEM impact. The cross-sectional association between TEM patterns and number of hospitalizations was estimated to assess construct validity. Results: The prevalence of TEMs was substantial such that 19.0% (95% CI 14.8–23.2) of middle-aged adults and 38.0% (95% CI 33.4–42.5) of older adults had any two. A simulated trial with modest levels of interaction suggested the prevalence of TEMs could nullify treatment benefit in 3.9–27.2% of older adults with DM. Compared to having DM alone, hospitalization rate was increased by several combinations of TEMs with substantial prevalence. Conclusions: We provide national benchmarks that can be used to evaluate TEM prevalence reported by clinical trials of DM, and correspondingly their external validity to older adults.

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Authors and Affiliations

  1. Division of Geriatric Medicine & Gerontology, 7th Floor Center Tower, 5200 Eastern Avenue, Baltimore, MD, 21224-2734, USA

    Carlos O. Weiss MD, MHS, Cynthia M. Boyd & Bruce Leff

  2. Department of Health Policy & Management, Baltimore, MD, USA

    Jennifer L. Wolff

Authors
  1. Carlos O. Weiss MD, MHS
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  2. Cynthia M. Boyd
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  3. Jennifer L. Wolff
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  4. Bruce Leff
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Correspondence to Carlos O. Weiss MD, MHS.

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Weiss, C.O., Boyd, C.M., Wolff, J.L. et al. Prevalence of diabetes treatment effect modifiers: the external validity of trials to older adults. Aging Clin Exp Res 24, 370–376 (2012). https://doi.org/10.1007/BF03325268

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  • DOI: https://doi.org/10.1007/BF03325268

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