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Kenneth L. Kehl

Publications and source records attributed to Kenneth L. Kehl.

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MatchMiner-AI: Open-source, Privacy-preserving Cancer Clinical Trial Matching using Artificial Intelligence

Background: Clinical trials are essential to advancing cancer treatments, but fewer than 10% of adults with cancer enroll in therapeutic trials. Open-source AI trial matching tools could democratize access to trial options. Methods: We created MatchMiner-AI, co-developed with practicing clinical oncologists and trained on synthetic electronic health record (EHR) data. It uses open-weight LLMs to summarize patient histories from unstructured EHR text and extract target populations from trial eligibility documents. Embedding and re-ranking models were distilled to retrieve and rank trial and patient suggestions. Multifaceted evaluation was performed, including retrospective quantification of distillation fidelity; applying a closed-source LLM as judge of patient summarization and matching; and evaluation of candidate matches by oncologists. Results: Across retrospective evaluations of distillation fidelity, the pipeline outperformed a baseline text-embedding model, improving mean average precision (MAP) at 20 from 0.44 (95% CI 0.44-0.45) to 0.95 (95% CI 0.95-0.96) for trial-enrolled patients and from 0.38 (95% CI 0.37-0.38) to 0.94 (95% CI 0.93-0.94) for patients who received standard of care therapies. In a 50-patient sample selected for comparison between MatchMiner-AI and a rules-based tumor genomic trial matching algorithm, MatchMiner-AI retrieved trials for all patients, as opposed to 19 patients (38%) who had tumor genomic data available. Among those 19 patients, 80% of 256 trial suggestions retrieved by MatchMiner-AI were deemed reasonable considerations by a frontier LLM, vs 53% of 113 suggestions retrieved by the rules-based approach. Conclusion: MatchMiner-AI is an open-source, open-weights, clinical trial matching AI pipeline for oncology. Synthetic training data, model weights, inference tools, and demonstration frontends are publicly available.

cs.AI

Assessing Delayed Treatment Benefits of Immunotherapy Using Long-Term Average Hazard: A Novel Test/Estimation Approach

Delayed treatment effects on time-to-event outcomes have often been observed in randomized controlled studies of cancer immunotherapies. In the case of delayed onset of treatment effect, the conventional test/estimation approach using the log-rank test for between-group comparison and Cox's hazard ratio to estimate the magnitude of treatment effect is not optimal, because the log-rank test is not the most powerful option, and the interpretation of the resulting hazard ratio is not obvious. Recently, alternative test/estimation approaches were proposed to address both the power issue and the interpretation problems of the conventional approach. One is a test/estimation approach based on long-term restricted mean survival time, and the other approach is based on average hazard with survival weight. This paper integrates these two ideas and proposes a novel test/estimation approach based on long-term average hazard (LT-AH) with survival weight. Numerical studies reveal specific scenarios where the proposed LT-AH method provides a higher power than the two alternative approaches. The proposed approach has test/estimation coherency and can provide robust estimates of the magnitude of treatment effect not dependent on study-specific censoring time distribution. Also, the proposed LT-AH approach can summarize the magnitude of the treatment effect in both absolute difference and relative terms using ``hazard'' (i.e., difference in LT-AH and ratio of LT-AH), meeting guideline recommendations and practical needs. This proposed approach can be a useful alternative to the traditional hazard-based test/estimation approach when delayed onset of survival benefit is expected.

stat.ME