A Systematic Review of Testing and Evaluation of Healthcare Applications of Large Language Models (LLMs)

Importance Large Language Models (LLMs) can assist in a wide range of healthcare-related activities. Current approaches to evaluating LLMs make it difficult to identify the most impactful LLM application areas. Objective To summarize the current evaluation of LLMs in healthcare in terms of 5 components: evaluation data type, healthcare task, Natural Language Processing (NLP)/Natural Language Understanding (NLU) task, dimension of evaluation, and medical specialty. Data Sources A systematic search of PubMed and Web of Science was performed for studies published between 01-01-2022 and 02-19-2024. Study Selection Studies evaluating one or more LLMs in healthcare. Data Extraction and Synthesis Three independent reviewers categorized 519 studies in terms of data used in the evaluation, the healthcare tasks (the what) and the NLP/NLU tasks (the how) examined, the dimension(s) of evaluation, and the medical specialty studied. Results Only 5% of reviewed studies utilized real patient care data for LLM evaluation. The most popular healthcare tasks were assessing medical knowledge (e.g. answering medical licensing exam questions, 44.5%), followed by making diagnoses (19.5%), and educating patients (17.7%). Administrative tasks such as assigning provider billing codes (0.2%), writing prescriptions (0.2%), generating clinical referrals (0.6%) and clinical notetaking (0.8%) were less studied. For NLP/NLU tasks, the vast majority of studies examined question answering (84.2%). Other tasks such as summarization (8.9%), conversational dialogue (3.3%), and translation (3.1%) were infrequent. Almost all studies (95.4%) used accuracy as the primary dimension of evaluation; fairness, bias and toxicity (15.8%), robustness (14.8%), deployment considerations (4.6%), and calibration and uncertainty (1.2%) were infrequently measured. Finally, in terms of medical specialty area, most studies were in internal medicine (42%), surgery (11.4%) and ophthalmology (6.9%), with nuclear medicine (0.6%), physical medicine (0.4%) and medical genetics (0.2%) being the least represented. Conclusions and Relevance Existing evaluations of LLMs mostly focused on accuracy of question answering for medical exams, without consideration of real patient care data. Dimensions like fairness, bias and toxicity, robustness, and deployment considerations received limited attention. To draw meaningful conclusions and improve LLM adoption, future studies need to establish a standardized set of LLM applications and evaluation dimensions, perform evaluations using data from routine care, and broaden testing to include administrative tasks as well as multiple medical specialties. Key Points ### Competing Interest Statement The authors have declared no competing interest. ### Funding Statement This study did not receive any funding ### Author Declarations I confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained. Yes I confirm that all necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived, and that any patient/participant/sample identifiers included were not known to anyone (e.g., hospital staff, patients or participants themselves) outside the research group so cannot be used to identify individuals. Yes I understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance). Yes I have followed all appropriate research reporting guidelines, such as any relevant EQUATOR Network research reporting checklist(s) and other pertinent material, if applicable. Yes All data produced in the present study are available upon reasonable request to the authors