Hardening Local SHA-256 (Secure Hash Algorithm 256-Bit) Chained Clinical Trial Logs Against Post-Hoc Manipulation Using Separated Seed Custody

• Ahmed M. El Sayed

  Faculty of Science, Department of Mathematics and Computer Science, Damanhour University, Egypt

  Author

• Tarek R. Mostafa

  Department of Biostatistics and Health Informatics, Faculty of Medicine, Alexandria University, Egypt

  Author

• Khaled S. Nour

  Department of Computer Science, Faculty of Computers and Artificial Intelligence, Cairo University, Egypt

  Author

The evidentiary integrity of randomized controlled trials (RCTs) depends upon maintaining an immutable, tamper-evident audit record of treatment allocations. To achieve operational transparency without relying on complex enterprise infrastructure, recent clinical trial informatics frameworks have introduced local, lightweight allocation prototypes utilizing recursive SHA-256 (Secure Hash Algorithm 256-Bit) hash chaining. However, when hash verification digests and pseudorandom generator seeds reside on the same local filesystem as the execution runtime, the resulting audit trail remains vulnerable to sophisticated post-hoc tampering. In this investigation, we execute an exhaustive empirical vulnerability benchmark evaluating 2,000 simulated clinical trial allocation logs subjected to four distinct adversarial tampering modalities: single-entry arm flipping, row deletion, clear_log() truncation, and full downstream hash-chain recomputation. We demonstrate that while baseline single-file architectures achieve 100% detection against naive arm flips and row deletions, they exhibit complete blindness (0% detection sensitivity) against full downstream hash-chain recomputation and file truncation attacks. To eliminate this critical vulnerability, we implement and benchmark a separated-seed-custody architecture, decoupling sequence generation from cryptographic seed management via an independent custody verification enclave. Utilizing 1,000-resample bootstrap confidence intervals and paired permutation tests (10, 000 iterations) adapted from the PSF-Med statistical evaluation protocol, we prove that separated seed custody restores tamper-detection sensitivity to 100.0% (95% CI: [99.85%, 100.0%]) across all attack classes, including full downstream hash recomputation (p < 0.0001), with negligible latency overhead (< 1.8 ms per allocation). Our findings provide a rigorous, mathematically verified blueprint for deploying regulatorily compliant, tamper-proof allocation logging across decentralized clinical trials.

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