AI-Enabled Optimization of Early- Phase Clinical Trials Pilot Program; Request for Information

BullFrog AI, Inc. strongly supports the proposed pilot program for AI-enabled optimization of early-phase clinical trials. The company argues that integrating advanced AI technologies, such as automated data harmonization and causal inference, can significantly reduce development timelines, minimize patient risk, and improve regulatory decision-making.

Three academic researchers and industry experts (from Columbia University, Tulane University, and NouStarX LLC) support the FDA's pilot program for AI-enabled clinical trials. They argue that successful real-time clinical trials require a "Computational Evidence Infrastructure" that prioritizes data interoperability, human oversight, and continuous validation over just the implementation of AI technology.

Medrio, a software and services vendor for clinical trial technology, supports the FDA's pilot program for AI-enabled optimization of early-phase clinical trials. They advocate for including technology vendors as formal collaborators, establishing clear regulatory guardrails for data privacy and signal response, and ensuring that AI remains a tool to inform human clinical judgment rather than replace it.

Wicked Problem Wizards, an advisory firm focused on clinical trial data quality, supports the pilot program but emphasizes that it requires robust Risk-Based Quality Management (RBQM) and pre-competitive cross-industry collaboration to be successful. They argue that the FDA should act as a regulatory anchor in existing industry working groups (like BRAVE) to help develop validation frameworks for generative and agentic AI.

The International Consortium for Innovation and Quality in Pharmaceutical Development (IQ) supports the proposed pilot program and provides detailed recommendations on its design, metrics, and operational structure. They advocate for a multi-tiered approach to AI integration, emphasizing the need for clear validation, pre-competitive collaboration, and specific metrics to measure safety, efficiency, and model performance.

QuantHealth, a clinical-AI company, supports the FDA's pilot program to examine AI-enabled optimization of early-phase clinical trials. They argue that patient-level simulations can improve decision quality, enhance participant safety by identifying risks before enrollment, and eventually provide a framework for accelerated approval and simulated control arms.

Evalion, an AI-native clinical research organization, supports the proposed pilot program and recommends requiring evidence-based reliability for AI agents in consequential roles. They propose a specific framework involving offline evaluation, continuous online monitoring, expert-in-the-loop grading, and transparent reporting to ensure participant safety and data integrity.

BioinvestGPT ApS, a biotechnology company, supports the pilot program by proposing a specific "tool class" for evaluation: independent, prospective, and patient-data-free mechanistic predictions of drug effect sizes. They argue that these predictions can improve Phase 1 to Phase 2 go/no-go decisions and provide a ten-element evidentiary standard for qualifying such tools.

Sovereign Harbor, a regulatory intelligence and quantitative advisory firm, supports the FDA's initiative to advance real-time clinical trials using AI. They argue that the pilot program must mandate pre-specified decision rules, rigorous statistical frameworks (such as group-sequential designs), and standardized data infrastructure to ensure that real-time data leads to valid clinical decisions rather than acting on noise.

Representatives from Indiana University Health, the Indiana University School of Medicine, and the Regenstrief Institute provide a detailed technical response to the FDA's Request for Information. They support the pilot program but argue that it must prioritize a multimodal data foundation, multi-step decision evaluation for agentic AI, continuous supervisory monitoring, and independent evaluation infrastructure to be successful and safe.