Evaluation of large language models’ ability to identify clinically relevant drug-drug interactions and generate high-quality clinical pharmacotherapy recommendations
Abstract
Purpose Large language models (LLMs) are promising artificial intelligence (AI) tools to support clinical decision-making. The ability of LLMs to evaluate medication regimens, identify drug-drug interactions (DDIs), and provide clinical recommendations has undergone limited evaluation. The purpose of this study was to compare the performance of 3 LLMs in recognizing DDIs, determining clinical relevance, and generating management recommendations. Methods A total of 15 patient cases with medication regimens were created; each contained a commonly encountered DDI. Two separate study phases were developed: (1) DDI identification and determination of clinical relevance; and (2) DDI identification and generation of a clinical recommendation. The primary outcome was the ability of the LLMs (GPT-4, Gemini 1.5, and Claude 3) to identify the DDI within each medication regimen. Secondary outcomes included the ability of the LLMs to identify the clinical relevance of each DDI and generate a recommendation of high quality relative to ground truth. Results Claude 3 identified all DDIs, followed by GPT-4 (14/15, 93.3%) and Gemini 1.5 (12/15, 80.0%). All LLMs were significantly more likely than clinical experts to categorize the DDI as clinically relevant (P Conclusion While LLMs demonstrate promising potential to identify DDIs, application to clinical cases requires ongoing development. Findings from this study may assist in future development and refinement of LLMs for clinical decision-ma…
Integrity signals
Registry
Cites
Statistics
Claims the paper makes
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
ChatGPT-3 generated only 2 identical responses across 9 questions over four repeated time points.
“In another study, ChatGPT-3 generated only 2 identical responses across 9 questions over four repeated time points.66”
From Large Language Models in Pharmacist-Led Direct Patient Care: A Rapid Review of Published Evaluations (2026) · cites this paper as [66]
Another study reported that ChatGPT-3 performed poorly on tasks requiring proprietary clinical data that were not publicly available.
“Another study reported that ChatGPT-3 performed poorly on tasks requiring proprietary clinical data that were not publicly available.66”
From Large Language Models in Pharmacist-Led Direct Patient Care: A Rapid Review of Published Evaluations (2026) · cites this paper as [66]
LLM response reproducibility refers to the consistency of its outputs to the same query and has been shown to differ on repeat assessment.
“LLM response reproducibility refers to the consistency of its outputs to the same query and has been shown to differ on repeat assessment.58,59,66”
From Large Language Models in Pharmacist-Led Direct Patient Care: A Rapid Review of Published Evaluations (2026) · cites this paper as [66]
Cites
Wong, A., Otles, E., Donnelly, J. P., Krumm, A., McCullough, J., DeTroyer-Cooley, O., Pestrue, J., Phillips, M., Konye, J., Penoza, C., et al. (2021) · JAMA Internal Medicine · doi:10.1001/jamainternmed.2021.2626 · Cited by 995 · see citing works
Harnessing the power of llms in practice: a survey on chatGPT and beyond
Yang, J., Jin, H., Tang, R., Han, X., Feng, Q., Jiang, H., Zhong, S., Yin, B., & Hu, X. (2024) · ACM Transactions on Knowledge Discovery from Data · doi:10.1145/3649506 · Cited by 644 · see citing works
Flagged first, then by citations
Cited by
Sorted by citations
Large language models management of complex medication regimens: a case-based evaluation
Chase, A., Most, A., Xu, S., Barreto, E., Murray, B., Henry, K., Smith, S., Hedrick, T., Chen, X., Li, S., et al. (2025) · Frontiers in Pharmacology · doi:10.3389/fphar.2025.1514445 · Cited by 14 · see citing works
Self-citationDomián, B. M., Ashraf, A. R., Fittler, A. T., Káplár, M., & Vida, R. G. (2025) · Exploratory Research in Clinical and Social Pharmacy · doi:10.1016/j.rcsop.2025.100655 · Cited by 6 · see citing works
Large Language Models in Pharmacist-Led Direct Patient Care: A Rapid Review of Published Evaluations
Yakob, R. A., Bamgboje-Ayodele, A., Collins, J. C., & Aslani, P. (2026) · Research in Social and Administrative Pharmacy · doi:10.1016/j.sapharm.2026.09.007
- Authors
- Chase, A., Most, A., Sikora, A., Smith, S. E., Devlin, J. W., Xu, S., Liu, T., & Murray, B.
- Affiliations
- Augusta University Health (US)
- University of Georgia (US)
- Brigham and Women's Hospital (US)
- University of Colorado Skaggs School of Pharmacy , Aurora, CO ,
- ORCID
- Venue
- American Journal of Health-System Pharmacy
- Publisher
- Oxford University Press (OUP)
- Published
- 2025-07-01
- Volume
- 83
- Issue
- 13
- Pages
- e494-e500
- ISSN
- 1079-2082 (ISSN-L)
- 1535-2900
- OpenAlex
- W4411846992
- Cited by
- 11
- References
- 2
- Citations by year
- 2026: 7 · 2025: 4
- FWCI
- 2.63
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- American Journal of Health-System Pharmacy (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Agency for Healthcare Research and Quality (R21HS028485, R01HS029009)
- Topics
- Health Sciences › Medicine › Health Informatics › Artificial Intelligence in Healthcare and Education
- Health Sciences › Medicine › Geriatrics and Gerontology › Pharmaceutical Practices and Patient Outcomes
- Health Sciences › Health Professions › Health Information Management › Electronic Health Records Systems
- Keywords
- large language models, drug-drug interactions, clinical decision support, GPT-4, Gemini 1.5, Claude 3, AI-generated recommendations, patient harm
- MeSH terms
- Clinical Decision-Making, Clinical Relevance, Large Language Models, Artificial Intelligence, Drug Interactions, Humans
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review