Screening patients for clinical trial eligibility remains a manual, time - consuming, and resource-intensive process. W e present a secure, scalable proof-of - concept system for Artificial Intelligence ( AI)- augmented patient - trial matching that addresses key implementation challenges: integrating heterogeneous electronic health record (EHR) data, facilitating expert review, and maintaining rigorous security standards. Leveraging open-source, reasoning-enabled large language models (LLMs), the system moves beyond binary classification to generate structured eligibility assessments with interpretable reasoning chains that support human-in - the - loop review. This decision support tool represents eligibility as a dynamic state rather than a fixed determination, identifying matches whe n available and offering actionable recommendations that could render a patient eligible in the future . The system aims to reduce coordinator burden, intelligently broaden the set of trials considered for each patient and guarantee comprehensive auditability of all AI - generated outputs. Introduction Applications of artificial intelligence (AI) in healthcare are increasingly focused on improving administrative efficiency and optimizing clinical workflows . Identifying relevant trials and screening them for a particular patient is traditionally manual, time - consuming, and heavily reliant on clinical expertise.

We present ClinicalTrialsHub, an interactive search-focused platform that consolidates all data from ClinicalTrials.gov and augments it by automatically extracting and structuring trial-relevant information from PubMed research articles. Our system effectively increases access to structured clinical trial data by 83.8% compared to relying on ClinicalTrials.gov alone, with potential to make access easier for patients, clinicians, researchers, and policymakers, advancing evidence-based medicine. ClinicalTrialsHub uses large language models such as GPT-5.1 and Gemini-3-Pro to enhance accessibility. The platform automatically parses full-text research articles to extract structured trial information, translates user queries into structured database searches, and provides an attributed question-answering system that generates evidence-grounded answers linked to specific source sentences. We demonstrate its utility through a user study involving clinicians, clinical researchers, and PhD students of pharmaceutical sciences and nursing, and a systematic automatic evaluation of its information extraction and question answering capabilities.

This work presents the development and evaluation of an NLP-enabled probabilistic classifier designed to estimate the probability of technical and regulatory success (pTRS) for clinical trials in the field of neuroscience. While pharmaceutical R&D is plagued by high attrition rates and enormous costs, particularly within neuroscience, where success rates are below 10%, timely identification of promising programs can streamline resource allocation and reduce financial risk. Leveraging data from the ClinicalTrials.gov database and success labels from the recently developed Clinical Trial Outcome dataset, the classifier extracts text-based clinical trial features using statistical NLP techniques. These features were integrated into several non-LLM frameworks (logistic regression, gradient boosting, and random forest) to generate calibrated probability scores. Model performance was assessed on a retrospective dataset of 101,145 completed clinical trials spanning 1976-2024, achieving an overall ROC-AUC of 0.64. An LLM-based predictive model was then built using BioBERT, a domain-specific language representation encoder. The BioBERT-based model achieved an overall ROC-AUC of 0.74 and a Brier Score of 0.185, indicating its predictions had, on average, 40% less squared error than would be observed using industry benchmarks. The BioBERT-based model also made trial outcome predictions that were superior to benchmark values 70% of the time overall. By integrating NLP-driven insights into drug development decision-making, this work aims to enhance strategic planning and optimize investment allocation in neuroscience programs.

Matching patients to clinical trial options is critical for identifying novel treatments, especially in oncology. However, manual matching is labor-intensive and error-prone, leading to recruitment delays. Pipelines incorporating large language models (LLMs) offer a promising solution. We conducted a systematic review of studies published between 2020 and 2025 from three academic databases and one preprint server, identifying LLM-based approaches to clinical trial matching. Of 126 unique articles, 31 met inclusion criteria. Reviewed studies focused on matching patient-to-criterion only (n=4), patient-to-trial only (n=10), trial-to-patient only (n=2), binary eligibility classification only (n=1) or combined tasks (n=14). Sixteen used synthetic data; fourteen used real patient data; one used both. Variability in datasets and evaluation metrics limited cross-study comparability. In studies with direct comparisons, the GPT-4 model consistently outperformed other models, even finely-tuned ones, in matching and eligibility extraction, albeit at higher cost. Promising strategies included zero-shot prompting with proprietary LLMs like the GPT-4o model, advanced retrieval methods, and fine-tuning smaller, open-source models for data privacy when incorporation of large models into hospital infrastructure is infeasible. Key challenges include accessing sufficiently large real-world data sets, and deployment-associated challenges such as reducing cost, mitigating risk of hallucinations, data leakage, and bias. This review synthesizes progress in applying LLMs to clinical trial matching, highlighting promising directions and key limitations. Standardized metrics, more realistic test sets, and attention to cost-efficiency and fairness will be critical for broader deployment.

Objectives: With accurate estimates of expected safety results, clinical trials could be better designed and monitored. We evaluated methods for predicting serious adverse event (SAE) results in clinical trials using information only from their registrations prior to the trial. Material and Methods: We analyzed 22,107 two-arm parallel interventional clinical trials from ClinicalTrials.gov with structured summary results. Two prediction models were developed: a classifier predicting whether a greater proportion of participants in an experimental arm would have SAEs (area under the receiver operating characteristic curve; AUC) compared to the control arm, and a regression model to predict the proportion of participants with SAEs in the control arms (root mean squared error; RMSE). A transfer learning approach using pretrained language models (e.g., ClinicalT5, BioBERT) was used for feature extraction, combined with a downstream model for prediction. To maintain semantic representation in long trial texts exceeding localized language model input limits, a sliding window method was developed for embedding extraction. Results: The best model (ClinicalT5+Transformer+MLP) had 77.6% AUC when predicting which trial arm had a higher proportion of SAEs. When predicting SAE proportion in the control arm, the same model achieved RMSE of 18.6%. The sliding window approach consistently outperformed direct comparisons. Across 12 classifiers, the average absolute AUC increase was 2.00%, and absolute RMSE reduction was 1.58% across 12 regressors. Discussion: Summary results data from ClinicalTrials.gov remains underutilized. Predicted results of publicly reported trials provides an opportunity to identify discrepancies between expected and reported safety results.

Clinical trials are critical for advancing medical treatments but remain prohibitively expensive and time-consuming. Accurate prediction of clinical trial outcomes can significantly reduce research and development costs and accelerate drug discovery. While recent deep learning models have shown promise by leveraging unstructured data, their black-box nature, lack of interpretability, and vulnerability to label leakage limit their practical use in high-stakes biomedical contexts. In this work, we propose AutoCT, a novel framework that combines the reasoning capabilities of large language models with the explainability of classical machine learning. AutoCT autonomously generates, evaluates, and refines tabular features based on public information without human input. Our method uses Monte Carlo Tree Search to iteratively optimize predictive performance. Experimental results show that AutoCT performs on par with or better than SOTA methods on clinical trial prediction tasks within only a limited number of self-refinement iterations, establishing a new paradigm for scalable, interpretable, and cost-efficient clinical trial prediction.

Digital individual participant data (IPD) from clinical trials are increasingly distributed for potential scientific reuse. The identification of available IPD, however, requires interpretations of textual data-sharing statements (DSS) in large databases. Recent advancements in computational linguistics include pre-trained language models that promise to simplify the implementation of effective classifiers based on textual inputs. In a subset of 5,000 textual DSS from ClinicalTrials.gov, we evaluate how well classifiers based on domain-specific pre-trained language models reproduce original availability categories as well as manually annotated labels. Typical metrics indicate that classifiers that predicted manual annotations outperformed those that learned to output the original availability categories. This suggests that the textual DSS descriptions contain applicable information that the availability categories do not, and that such classifiers could thus aid the automatic identification of available IPD in large trial databases.

Clinical trials drive improvements in cancer treatments and outcomes. However, most adults with cancer do not participate in trials, and trials often fail to enroll enough patients to answer their scientific questions. Artificial intelligence could accelerate matching of patients to appropriate clinical trials. Here, we describe the development and evaluation of the MatchMiner-AI pipeline for clinical trial searching and ranking. MatchMiner-AI focuses on matching patients to potential trials based on core criteria describing clinical "spaces," or disease contexts, targeted by a trial. It aims to accelerate the human work of identifying potential matches, not to fully automate trial screening. The pipeline includes modules for extraction of key information from a patient's longitudinal electronic health record; rapid ranking of candidate trial-patient matches based on embeddings in vector space; and classification of whether a candidate match represents a reasonable clinical consideration. Code and synthetic data are available at https://huggingface.co/ksg-dfci/MatchMiner-AI . Model weights based on synthetic data are available at https://huggingface.co/ksg-dfci/TrialSpace and https://huggingface.co/ksg-dfci/TrialChecker . A simple cancer clinical trial search engine to demonstrate pipeline components is available at https://huggingface.co/spaces/ksg-dfci/trial_search_alpha .

Cancer clinical trials often face challenges in recruitment and engagement due to a lack of participant-facing informational and educational resources. This study investigated the potential of Large Language Models (LLMs), specifically GPT4, in generating patient-friendly educational content from clinical trial informed consent forms. Using data from ClinicalTrials.gov, we employed zero-shot learning for creating trial summaries and one-shot learning for developing multiple-choice questions, evaluating their effectiveness through patient surveys and crowdsourced annotation. Results showed that GPT4-generated summaries were both readable and comprehensive, and may improve patients' understanding and interest in clinical trials. The multiple-choice questions demonstrated high accuracy and agreement with crowdsourced annotators. For both resource types, hallucinations were identified that require ongoing human oversight. The findings demonstrate the potential of LLMs "out-of-the-box" to support the generation of clinical trial education materials with minimal trial-specific engineering, but implementation with a human-in-the-loop is still needed to avoid misinformation risks.

New medical treatment development requires multiple phases of clinical trials. Despite the significant human and financial costs of bringing a drug to market, less than 20% of drugs in testing will make it from the first phase to final approval. Recent literature indicates that the design of the trial protocols significantly contributes to trial performance. We investigated Clinical Trial Outcome Prediction (CTOP) using trial design documents to predict phase transitions automatically. We propose CTP-LLM, the first Large Language Model (LLM) based model for CTOP. We also introduce the PhaseTransition (PT) Dataset; which labels trials based on their progression through the regulatory process and serves as a benchmark for CTOP evaluation. Our fine-tuned GPT-3.5-based model (CTP-LLM) predicts clinical trial phase transition by analyzing the trial's original protocol texts without requiring human-selected features. CTP-LLM achieves a 67% accuracy rate in predicting trial phase transitions across all phases and a 75% accuracy rate specifically in predicting the transition from Phase~III to final approval. Our experimental performance highlights the potential of LLM-powered applications in forecasting clinical trial outcomes and assessing trial design.