# Strengthening the Evidence-Base for Drug-Disease Interactions in Older Adults

> **NIH NIH R01** · RUTGERS, THE STATE UNIV OF N.J. · 2020 · $561,369

## Abstract

Drug-disease interactions (DDSIs) occur when drug effects, such as risks for rare but severe adverse
effects, are altered by a preexisting disease. DDSIs affect up to 50% of older adults and have been associated
with increased mortality and use of health services. DDSIs are of particular concern in older adults because
both polypharmacy and chronic illness become progressively more prevalent with advanced age. Although
drug labels, treatment guidelines, and drug information compendia include warnings and contraindications for
many thousands of drug-disease combinations, extremely little evidence and research exists on their clinical
relevance. DDSI guidance generally relies on case reports, pharmacological mechanism, or structural similarity
to related drugs, and thus commonly represents untested hypotheses rather than evidence from well-designed
population-based studies. As a result, physicians and their patients are often unable to distinguish between
warnings for clinically relevant DDSIs that should be followed to avoid increased risk for adverse drug effects,
and warnings for purely theoretical DDSIs that should be ignored in order to allow initiation of treatment with
the otherwise indicated drug of choice. Better evidence on DDSIs is thus urgently needed to allow physicians
to recommend evidence-based personalized therapy for their patients. Using existing data resources on
millions of patients from Medicare (US) and the Clinical Practice Research Datalink (UK), the proposed study
will use four carefully selected examples of highly prevalent drugs to demonstrate a new methodological
framework for the systematic assessment of DDSIs from large observational datasets: Metformin and renal
impairment increasing risk of lactic acidosis (Aim 1), Z-drugs and osteoporosis increasing risk of hip fracture
(Aim 2), systemic corticosteroids and peptic ulcer disease increasing risk of gastrointestinal bleeding (Aim 3),
and allopurinol and renal impairment reducing risk of dialysis or kidney transplant (Aim 4). These examples
were selected considering a number of explicit criteria including severity of the adverse outcome, disagreement
about relevance in the literature and clinical practice, ability to measure disease and adverse clinical outcome
in the databases, and availability of therapeutic alternatives that do not share the hypothesized DDSI. We
included interactions across a spectrum of prevalence and expected effect sizes to evaluate the performance
of the proposed approach in different situations and sought some effects very likely to be absent (Aim 1) or
present (Aim 2) to show we can reproduce expected findings, and uncertain effects (Aims 3 and 4). The
proposed study puts forward a novel framework that comprehensively classifies DDSIs according to their
underlying biological mechanisms and represents the first systematic attempt to apply modern epidemiological
and statistical methods to the examination of DDSIs. Its results will begin a line ...

## Key facts

- **NIH application ID:** 9970387
- **Project number:** 5R01AG061092-02
- **Recipient organization:** RUTGERS, THE STATE UNIV OF N.J.
- **Principal Investigator:** Tobias Gerhard
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $561,369
- **Award type:** 5
- **Project period:** 2019-07-15 → 2024-02-29

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9970387

## Citation

> US National Institutes of Health, RePORTER application 9970387, Strengthening the Evidence-Base for Drug-Disease Interactions in Older Adults (5R01AG061092-02). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/9970387. Licensed CC0.

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