Efficiently matching patients to clinical trials is essential for advancing medical research and ensuring reliable outcomes. However, current matching methods face several challenges. These include data integrity issues from tampered records, privacy risks caused by weak anonymization, and manual processes that delay recruitment. In addition, centralized systems lack transparency, expose sensitive patient data to security vulnerabilities, and suffer from single points of failure that reduce resilience and trust. In this paper, we propose a blockchain and Large Language Models (LLMs)-driven solution for secure, trustworthy, traceable, decentralized, and transparent patient–clinical trial matching. Blockchain ensures data integrity, security, and transparency by eliminating single points of failure and enabling tamper-proof records. LLMs enhance patient–trial matching by automating the interpretation of complex eligibility criteria, improving accuracy, and significantly reducing the time required for manual review. Our approach uses Ethereum-based smart contracts to automate workflows such as trial registration, eligibility assessment, and consent tracking. We fine-tune GPT-4, T5, and Gemini on synthetic data derived from real clinical trial records and employ majority voting to ensure consistent and unbiased eligibility decisions. A prototype Gradio interface was developed as a minimum viable product (MVP) to demonstrate seamless interaction between LLMs and smart contracts. Performance evaluation based on accuracy (0.800), precision (0.733), recall (1.000), and F1-score (0.846) demonstrates reliable eligibility prediction. Cost analysis confirms affordability, and security evaluation verifies resilience against known threats. Comparison with existing solutions highlights the framework’s advantages in transparency, trust, and automation. The smart contract code is publicly available on GitHub.
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