Benchmarking ChatGPT-3.5 and OpenAI o3 Against Clinical Pharmacists: Preliminary Insights into Clinical Accuracy, Sensitivity, and Specificity in Pharmacy MCQs

<b>Objective:</b> This proof-of-concept study aimed to evaluate and compare the clinical performance of two AI language models (ChatGPT-3.5 and OpenAI o3) in answering clinical pharmacy multiple-choice questions (MCQs), benchmarked against responses from specialist clinical pharmacists in Jordan, including academic preceptors and hospital-based clinicians. <b>Methods:</b> A total of 60 clinical pharmacy MCQs were developed based on current guidelines across four therapeutic areas: cardiovascular, endocrine, infectious, and respiratory diseases. Each item was reviewed by academic and clinical experts and then pilot-tested with five pharmacists to determine clarity and difficulty. Two ChatGPT models-GPT-3.5 and OpenAI o3-were tested using a standardized prompt for each MCQ, entered in separate sessions to avoid memory retention. Their answers were classified as true/false positives or negatives and retested after two weeks to assess reproducibility. Simultaneously, 25 licensed pharmacists (primarily from one academic institution and several hospitals in Amman) completed the same MCQs using validated references (excluding AI tools). Accuracy, sensitivity, specificity, and Cohen's Kappa were used to compare AI and human performance, with statistical analysis conducted using appropriate tests at a significance level of <i>p</i> ≤ 0.05. <b>Results:</b> OpenAI o3 achieved the highest accuracy (83.3%), sensitivity (90.0%), and specificity (70.0%), outperforming GPT-3.5 (70.0%, 77.5%, 55.0%) and pharmacists (69.7%, 77.0%, 55.0%). AI performance declined significantly with increasing question difficulty. OpenAI o3 showed the highest accuracy in the cardiovascular domain (93.3%), while GPT-3.5 performed best in infectious diseases (80.0%). Reproducibility was higher for GPT-3.5 (81.6%, κ = 0.556) than OpenAI o3 (76.7%, κ = 0.364). Over two test rounds, GPT-3.5's accuracy remained stable, whereas OpenAI o3's accuracy decreased from 83.3% to 70.0%, indicating some variability. <b>Conclusions:</b> OpenAI o3 shows strong promise as a clinical decision-support tool in pharmacy, especially for low- to moderate-difficulty questions. However, inconsistencies in reproducibility and limitations in complex cases highlight the importance of cautious, supervised integration alongside human expertise.