By Kimberly Chew and Odette Hauke

The FDA recently announced two proof-of-concept real-time clinical trials (RTCTs) with AstraZeneca and Amgen and issued a request for information (RFI) for an AI-enabled early-phase trial pilot expected to launch this summer.^1,2 The objective is compelling: faster early-phase decisions, stronger safety monitoring, reduced gaps between trial phases, and a path toward continuous clinical trials. The FDA also reported that it had already received and validated real-time signals from AstraZeneca's trial through Paradigm Health, suggesting that the technical framework is no longer theoretical.¹

The initiative deserves serious support. Clinical development remains slow, expensive, and fragmented, and technology can help regulators and sponsors identify safety and efficacy signals earlier. But real-time regulatory visibility also changes the risk profile for sponsors, especially smaller biotechnology companies. Large pharmaceutical companies may be able to absorb continuous monitoring, vendor oversight, cybersecurity controls, and market volatility. Single-asset or resource-constrained sponsors often cannot. Without safeguards, RTCT could create a two-tier system: a faster pathway for companies with the infrastructure to tolerate increased vulnerability and a more perilous pathway for innovators that cannot.

Five issues should be addressed before the pilot expands. The goal is not to slow modernization but to ensure that speed does not come at the expense of data integrity, confidentiality, sponsor fairness, or market stability.

1. Data Quality Before Regulatory Visibility

Traditional trials rely on data review, query resolution, source data verification, medical coding, and database lock before key analyses reach regulators. These steps can be slow, but they serve an essential purpose: ensuring that regulatory decisions are based on accurate, complete, and contextualized data. ICH E6(R3) supports modern trial designs, data sources, and technology, while emphasizing quality by design, data governance, participant protection, and reliability of results.³

RTCT compresses that quality control sequence. A miscoded lab value, duplicated adverse event, or site entry error could look like a meaningful safety signal before basic review is complete. In a conventional workflow, that error might be caught during cleaning; in an RTCT workflow, it may be visible to FDA almost immediately. The FDA should clarify what data are visible in real time, what minimum checks must occur first, how corrections will be labeled, and whether preliminary signals can trigger regulatory action before verification. Real time should not mean raw, uncontextualized, or uncorrected.

2. Intellectual Property And Confidentiality Exposure

Clinical trial data can reveal far more than safety and efficacy. It may expose dosing strategy, biomarker thresholds, enrollment criteria, response patterns, protocol assumptions, and go/no-go decisions. Paradigm Health has described its platform as automating data collection and analysis and streamlining the reporting of key safety and efficacy signals to trial sponsors and the FDA.⁴ That architecture raises practical questions about third-party access, vendor personnel, data segregation, audit trails, breach response, and competitor separation.

Existing protections for trade secrets and confidential commercial information, including FOIA Exemption 4, the Trade Secrets Act, and the FDA's public information regulations, remain important.⁵ But those protections were developed around traditional submissions not continuous data flows through technical intermediaries. Sponsors need clear contractual, technical, and regulatory assurances before sensitive development information moves through a shared platform. The FDA should also clarify how RTCT records will be treated if requested under FOIA and how sponsors will be notified and allowed to object to disclosure.

3. The "FDA Flag" Problem And Market Disruption

Real-time monitoring may create new market-moving moments before the underlying facts are understood. A preliminary signal, FDA inquiry, safety pause, or clinical hold can be significant for a public company, particularly a single-asset biotechnology company whose valuation and financing depend on one trial. SEC Form 8-K Item 8.01 permits reporting of events a registrant deems important to security holders, and Regulation Fair Disclosure can affect how companies manage selective disclosure.⁶ Even when disclosure is not mechanically required, sponsors may feel pressure to disclose quickly to avoid investor, analyst, or enforcement risk.

That pressure is dangerous if the signal later proves to be a site error, incomplete data artifact, or transient imbalance that disappears after review. The FDA should develop a materiality and communications framework that distinguishes routine data queries, preliminary unverified signals, and formal regulatory actions, such as clinical holds. Moreover, developing a rapid correction process is essential for false alarms, including a mechanism for the FDA to clarify when a signal has been withdrawn, corrected, or determined not to reflect a safety issue.

4. Operational Burden And Hidden Cost

RTCT may reduce some delays, but it can also add new burdens. Sponsors may need cross-functional monitoring teams, rapid medical and statistical review, regulatory and securities law support, enhanced site training, vendor oversight, cybersecurity controls, and integrations among EHRs, trial systems, and FDA-facing platforms. These requirements may be manageable for large companies; for smaller sponsors, they can be disproportionate.

The RFI asks what infrastructure is needed, what FDA support should be provided, and how the pilot can accommodate varying levels of AI maturity across participants.² Those questions should be answered with sponsor size in mind. If the pilot is populated mainly by companies that already have sophisticated data, compliance, and legal infrastructure, the FDA may learn too little about whether RTCT is scalable across the broader innovation ecosystem.

5. Regulatory Uncertainty And Endpoint Integrity

The FDA has stated that it met with sponsors to establish criteria for real-time signal reporting, but those criteria are not yet public.¹ Sponsors need to know how reportable signals are defined, whether they are patient-level or aggregate, how endpoint and signal definitions are documented, and whether the FDA may modify criteria after observing interim data.

This is not a technicality. Adaptive and innovative trial designs depend on prospectively defined rules and careful control of bias. The FDA's adaptive design guidance emphasizes prespecified adaptation rules and control of trial integrity; similar discipline should apply here.⁷ RTCT should not become a mechanism for moving analytical goalposts in response to emerging data. Sponsors also need clarity on voluntariness, appeals, interactions with non-U.S. regulators, and trial types that may not fit real-time review, including rare disease studies, pediatric trials, and long-term survival endpoints.

Practical Safeguards

These risks are solvable. The FDA should consider the following six safeguards before expanding RTCT beyond the proof-of-concept stage.

First, create verification gateways. Critical values and safety signals should undergo basic validation before they are treated as actionable, except where immediate patient protection requires otherwise. Corrections should be time-stamped, auditable, and visible to both the FDA and the sponsor. A short verification window, such as 48 to 72 hours for nonemergent signals, would preserve speed without sacrificing reliability.

Second, require a confidentiality framework for platform providers. This should include data segregation, role-based access, audit logs, cybersecurity standards, breach notification, conflict of interest controls, and confirmation that confidential commercial information remains protected in RTCT workflows. Sponsors should know exactly who can access their data, for what purpose, and under what safeguards.

Third, establish a materiality and false alarm protocol. Routine data queries should not be treated like formal regulatory action. Preliminary signals should have a defined investigation window, and FDA should be able to issue rapid clarifications when a signal is withdrawn, corrected, or determined not to reflect a safety issue.

Fourth, scale requirements by sponsor capacity. Large companies may be able to support continuous safety and efficacy review. Smaller sponsors may need staged participation, longer response windows, FDA technical assistance, or safety-only participation at the outset and defer efficacy assessments until they build capacity.

Fifth, require binding prespecified signal and analysis plans. Signal definitions, thresholds, escalation rules, and change control procedures should be agreed before trial launch and protected against post-hoc modification. Any changes after data observation should require documentation, justification, sponsor-FDA agreement, and an assessment of whether the change affects interpretability or statistical validity.

Sixth, evaluate the pilot rigorously. The FDA's RFI asks for metrics on trial efficiency, decision quality, participant safety, data integrity, AI system performance, trustworthiness, and operational feasibility.² Those metrics should also include cost, sponsor burden, false-positive signals, correction timelines, market disruption, and representation across sponsor size and therapeutic area. An independent assessment would help ensure the pilot is evaluated on evidence rather than enthusiasm alone.

Conclusion

RTCT could become an important modernization of clinical development. It could shorten avoidable pauses, improve safety surveillance, and help promising therapies reach patients faster. But speed is not the only measure of success. The system must also be accurate, confidential, fair, operationally feasible, and resilient when early signals are wrong.

The May 29, 2026, comment deadline gives stakeholders a narrow but meaningful opportunity to shape the pilot before selection criteria are finalized in July and pilot selections are completed in August.^1,2 With careful safeguards, the FDA's initiative can support innovation without making real-time trials available only to the largest and best-resourced sponsors.

References:

1. U.S. Food & Drug Administration, FDA Announces Major Steps to Implement Real-Time Clinical Trials (April 28, 2026).
2. FDA, AI-Enabled Optimization of Early-Phase Clinical Trials Pilot Program; Request for Information, 91 Fed. Reg. 23100 (April 29, 2026).
3. FDA, E6(R3) Good Clinical Practice (GCP): Guidance for Industry (September 2025).
4. Paradigm Health, Paradigm Health Announces Collaboration with the FDA to Transform Regulatory Review of Clinical Trial Data (Apr. 28, 2026).
5. 5 U.S.C. § 552(b)(4); 18 U.S.C. § 1905; 21 C.F.R. § 20.61.
6. SEC Form 8-K, Item 8.01; 17 C.F.R. §§ 243.100-243.103.
7. FDA, Adaptive Design Clinical Trials for Drugs and Biologics: Guidance for Industry (December 2019).

About The Authors:

Kimberly Chew is senior counsel in Husch Blackwell LLP’s virtual office, The Link. Chew is a seasoned professional with a background in biotech research, leveraging her experience to guide clients through the intricate landscape of clinical trials, FDA regulations, and academic research compliance. As the cofounder and co-lead of the firm’s Psychedelic and Emerging Therapies practice group, Kimberly is inspired by the potential of psychedelic therapeutics to address mental health conditions like PTSD. Her practice encompasses regulatory due diligence and intellectual property enforcement, particularly in patent infringement and validity. She can be reached at kimberly.chew@huschblackwell.com.

Odette Hauke is a global regulatory affairs consultant supporting regulatory strategy across clinical development and registration, with an emphasis on clear regulatory narratives and submission strategies that meet heightened evidentiary expectations. She has 12+ years’ experience directing IND/CTA/NDA/BLA/MAA work across the U.S., EU, U.K., Japan, Canada, APAC, and Latin America, and is experienced in integrating AI/ML-enabled regulatory intelligence into decision-making. Previously, she served as associate director of regulatory affairs at AtaiBeckley, leading global regulatory strategy for first-in-class psychedelic and neuropsychiatric programs including VLS-01 (DMT) and EMP-01 (MDMA), navigating novel endpoints, complex trial operations, Schedule I requirements, and evolving global guidance. Earlier, at Memorial Sloan Kettering Cancer Center, she managed 200+ oncology IND submissions and maintained regulatory documentation for 30+ clinical trials, including pediatric research. She holds an M.S. in regulatory affairs and a B.S. in epidemiology.