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

Artificial Intelligence (AI) is rapidly transforming drug development by enabling more efficient data analysis, predictive modelling, and evidence-based decision-making. Early-phase clinical trials, particularly Phase 1 studies, represent one of the most challenging stages of drug development due to uncertainties surrounding dose selection, patient recruitment, safety monitoring, and progression decisions. Improving the efficiency of these trials has the potential to accelerate the development of safe and effective therapies while reducing time and resource requirements.

Recognizing these opportunities, the U.S. Food and Drug Administration (FDA) has issued a Request for Information (RFI) on the proposed AI-Enabled Optimization of Early-Phase Clinical Trials Pilot Program. The initiative seeks public input on how AI-enabled technologies can improve the speed, quality, and efficiency of early clinical trial decision-making while maintaining FDA's rigorous scientific and regulatory standards. The pilot will also explore how trustworthy AI principles can be integrated into regulatory decision-making for future drug development. Comment Period Ended: Jun 29, 2026

Why This Initiative Is Important

Early-phase clinical trials are a critical gateway in medicine development, providing the first opportunity to evaluate the safety, dosing, pharmacology, and preliminary effectiveness of investigational products. However, these studies often face significant challenges, including limited patient populations, uncertainty in dose selection, lengthy timelines, and complex decision-making regarding whether development should continue.

The FDA's proposed pilot program aims to evaluate whether AI technologies can improve these processes by supporting faster, data-driven decisions while maintaining participant safety, data integrity, and scientific reliability. The agency also intends to ensure that AI systems used in clinical trials remain transparent, accountable, and aligned with established risk management principles.

Challenges in Early-Phase Clinical Trials

The FDA highlights several limitations associated with current early-phase clinical development. Sponsors frequently encounter uncertainty when selecting appropriate dose levels, evaluating early safety signals, and determining whether sufficient evidence exists to advance a product into later-stage clinical development.

Additional challenges include recruiting suitable participants, managing limited patient populations, collecting high-quality clinical data, and balancing the need for rapid development with robust scientific evaluation. These factors contribute to extended development timelines and increased research costs.

Potential Role of Artificial Intelligence

The proposed pilot explores multiple opportunities for AI to improve clinical trial efficiency. AI-enabled technologies may assist with participant recruitment, optimize dose escalation strategies, strengthen safety monitoring, improve biomarker identification, support adaptive trial designs, enhance patient stratification, validate clinical endpoints, and facilitate earlier Phase 1 to Phase 2 progression decisions.

By improving data analysis and supporting more informed regulatory and sponsor decisions, AI has the potential to reduce uncertainty while increasing the overall efficiency of early clinical development.

Trustworthy AI and Regulatory Oversight

The FDA emphasizes that AI implementation must remain consistent with principles of trustworthy AI. The proposed pilot aligns with the National Institute of Standards and Technology (NIST) AI Risk Management Framework, promoting AI systems that are valid, reliable, safe, secure, explainable, accountable, privacy-protective, and fair.

The agency also intends to apply considerations described in its existing draft guidance on the use of AI to support regulatory decision-making for drugs and biological products. These principles aim to ensure that AI enhances regulatory decision-making without compromising scientific integrity or patient safety.

Pilot Program Design

The FDA proposes recruiting sponsors conducting or planning early-phase clinical trials submitted through the Center for Drug Evaluation and Research (CDER), the Center for Biologics Evaluation and Research (CBER), and the Oncology Center of Excellence (OCE).

Through this Request for Information, the agency seeks stakeholder feedback on several aspects of pilot implementation, including appropriate trial types, therapeutic areas, AI applications, participant selection criteria, collaboration models, regulatory support, technical infrastructure, pilot timelines, and mechanisms for knowledge sharing while protecting confidential information.

Measuring Success

The guidance proposes evaluating the pilot using a broad range of scientific and operational metrics. These include improvements in trial efficiency, participant recruitment, study timelines, decision quality, participant safety, data integrity, AI model performance, transparency, fairness, and regulatory reliability.

The FDA also seeks input on methods for comparing AI-supported trials with traditional clinical trial approaches and assessing stakeholder confidence in AI-enabled clinical development.

Public Participation

As part of the Request for Information, the FDA invites comments from pharmaceutical companies, biotechnology organizations, technology developers, academic institutions, investigators, patient groups, and other stakeholders.

The agency is seeking recommendations on how AI can be responsibly integrated into early-phase clinical trials, what governance structures should be adopted, how pilot participants should be selected, and how the success of AI-enabled clinical trial approaches should be evaluated. Public feedback will help shape the final design of the pilot program and future regulatory approaches for AI-supported clinical research.

By exploring how AI can improve trial efficiency, participant safety, dose optimization, and regulatory decision-making while adhering to trustworthy AI principles, the initiative aims to modernize early clinical research without compromising scientific rigor. The Request for Information provides stakeholders with an opportunity to help shape the future use of AI in drug development and contribute to more efficient, evidence-driven clinical trials.

References

• FDA Request for Information: AI-Enabled Optimization of Early-Phase Clinical Trials Pilot Program (Docket No. FDA-2026-N-4390)