HHS “Operation TrialBlazer” and the Future of U.S. Clinical Trial Access, Payment, and Infrastructure Reform

On June 22, 2026, the U.S. Department of Health and Human Services (HHS) announced “Operation TrialBlazer”, a coordinated, department-wide initiative to restore U.S. leadership in clinical research and development (the “Initiative”).¹ The Initiative spans multiple HHS divisions: the Food and Drug Administration (FDA), the National Institutes of Health (NIH) (including the National Center for Advancing Translational Sciences (NCATS) and the National Cancer Institute (NCI)), the Advanced Research Projects Agency for Health (ARPA-H), the Office of the National Coordinator for Health Information Technology (ONC), and the HHS Office of Inspector General (OIG).

At its core, the Initiative is a response to a competitiveness problem defined by speed and regulatory efficiency: as currently structured, the U.S. path from a pre-Investigational New Drug Application (IND) meeting to an enrolled patient can run well over a year, while jurisdictions that have streamlined their processes measure the same path in months. China is the clearest example cited in the Initiative: HHS notes that China surpassed the U.S. in its share of Phase 1 trials in 2021 and in total registered clinical trials in 2024.² Australia illustrates the same competitiveness issue from a different regulatory model, with HHS citing its faster, notification-based system for early-stage trials.³ The unifying theme is the reduction of what HHS sees as unnecessary delay, redundant requirements, and regulatory ambiguity across various federal government components that fund and regulate research.

Importantly, most of what HHS announced consists of proposals, non-binding draft guidance, requests for information (RFIs), and voluntary pilots, as opposed to final, binding law. Several announcements include opportunities for public comment, and we have summarized the public comment deadlines at the end of this Alert.

This Alert focuses on the HHS-wide components of Operation TrialBlazer—including actions from NIH, ARPA-H, ONC, and HHS OIG—and summarizes the FDA-specific reforms affecting human subjects research protections, with attention throughout to the legal status of each action and the key compliance questions it raises for clinical trial sponsors, academic medical centers (AMCs), research institutions, contract research organizations (CROs), and other stakeholders.

The FDA-specific reforms are summarized at a high level below and addressed in depth in our companion Alert.

1. HHS OIG: RFI on AKS Safe Harbors and Beneficiary Inducements CMP Exceptions for Clinical Trial Participant Remuneration

On June 22, 2026, HHS OIG, which administers the federal Anti-Kickback Statute (AKS) and Beneficiary Inducements Civil Monetary Penalty (CMP) regulations, issued an RFI exploring whether to create new AKS safe harbors and Beneficiary Inducements CMP exceptions for remuneration tied to clinical trial participation.⁴ An RFI is a fact-gathering exercise rather than a rule, proposed rule, or guidance document, and the AKS and Beneficiary Inducements CMP regulations continue to apply in their existing form until regulatory action is taken to revise the regulations. The RFI’s questions nonetheless track fraud and abuse issues that sponsors, trial sites, and CROs navigate regularly, and the RFI represents a meaningful opportunity to seek codified protection for arrangements that today rest on an analysis of an arrangement’s facts and circumstances.

The Two Statutes: AKS and Beneficiary Inducements CMP

The RFI addresses both the AKS safe harbor regulations at 42 C.F.R. § 1001.952 and the Beneficiary Inducements CMP exceptions to the definition of “remuneration” at 42 C.F.R. § 1003.110.

Briefly stated, the AKS prohibits the knowing and willful offering, paying, soliciting, or receiving of remuneration to induce or reward referrals or other business reimbursable by a federal health care program.⁵ The AKS is a criminal statute punishable by fines of up to $100,000 and up to 10 years’ imprisonment, and a violation may also give rise to CMPs, program exclusion, and False Claims Act (FCA) liability.⁶ HHS OIG has promulgated certain regulatory safe harbors to protect specified arrangements from AKS sanctions.⁷

The Beneficiary Inducements CMP separately prohibits the offering or transferring of remuneration to Medicare or state health care program beneficiaries that is likely to influence such beneficiaries’ selection of a provider, practitioner, or supplier.⁸ The Beneficiary Inducements CMP is a civil provision with a lower “knows or should know” standard for liability.⁹ HHS OIG has promulgated certain regulatory exceptions to protect specified arrangements from Beneficiary Inducements CMP liability.¹⁰

Current Protection for Clinical Trial Participant Remuneration

HHS OIG has issued several favorable advisory opinions over the last two decades permitting the waiver or subsidization of federal health care program cost-sharing obligations—copays, coinsurance, and deductibles—for clinical trial participants in specific scenarios. These opinions have largely focused on medical device trials that have some federal government involvement, such as approval by CMS of Medicare coverage for the investigational product and related services.¹¹ HHS OIG has not issued any opinion or guidance addressing other forms of support provided to clinical trial participants, such as transportation, childcare, or stipends, and an advisory opinion in any event protects only the requesting party rather than the broader research community.¹²

Issues Raised in the RFI

The RFI’s questions map closely to recurring issues that arise in clinical trial operations and clinical trial participant support programs:¹³

• Cost-sharing waivers for standard-of-care components. Subsidizing copays, coinsurance, or deductibles on routine care items billed to Medicare or Medicaid implicates both statutes. This is the area where the existing advisory opinions cluster and for which the RFI may lead to a codified safe harbor.
• Reimbursement versus stipends, time payments, and completion incentives. The RFI asks which categories and levels of remuneration are useful and which carry heightened risk, signaling that any safe harbor may distinguish documented expense reimbursement from payments that resemble inducements.
• Value caps and need-based limits. HHS OIG asks whether caps, demonstrated financial need, or reimbursement only for documented costs should be conditions of protection, an indication that any safe harbor may be conditional rather than blanket.
• Who may pay. The RFI asks whether eligibility to provide remuneration should be limited (e.g., to sponsors rather than investigators or sites), reflecting that payments from a treating physician or downstream supplier may raise more referral concerns than payments from a sponsor that does not directly treat patients.
• Steering outside the clinical trial. HHS OIG flags the risk that a compensated participant could be channeled to other reimbursable items or services offered by the payor, such as a pharmaceutical manufacturer or health care provider.
• Advertising of remuneration. The RFI identifies the advertisement of payments available to subjects as a risk factor for both clinical trial integrity and the inducement analysis.
• Phase and clinical trial-type gradient. HHS OIG asks whether remuneration is provided across all stages of development and whether different amounts or types of remuneration are needed for early- versus late-stage trials. The issue may differ by trial phase: one study found median compensation of $3,070 per Phase 1 healthy-volunteer trial, while later-phase therapeutic trials generally pay more nominal amounts.¹⁴ HHS OIG also asks whether particular categories of trials should or should not pay participants, including the pointed question of whether protection should be limited to government-sponsored trials.¹⁵

The RFI also asks what safeguards should accompany any new protection. Two questions are particularly important: (1) whether Institutional Review Board (IRB) review of the type, amount, frequency, and advertising of participant payments could serve as a safeguard against fraud and abuse, and (2) whether HHS OIG should proceed through formal rulemaking or instead issue sub-regulatory guidance, such as a Special Advisory Bulletin or FAQ.¹⁶ Only a final AKS safe harbor or Beneficiary Inducements CMP exception codified through rulemaking would provide the assurance associated with regulatory protection; sub-regulatory guidance would signal HHS OIG’s enforcement posture but would not itself create a safe harbor or exception.

Implications While the HHS OIG RFI Is Pending

Because the RFI does not change existing law, both statutes continue to apply in full while the RFI is pending. Sponsors and sites should continue to structure patient cost-sharing support and clinical trial participant compensation against the law as it currently stands and should consider submitting comments to shape any eventual rulemaking. Comments must be received no later than 5 p.m. on August 24, 2026.¹⁷

2. Cross-Agency Collaboration: Clinical Trial Participant-Facing Financial Barriers

HHS has acknowledged that expanding clinical trial access requires coordinated action, and FDA will work with the Centers for Medicare & Medicaid Services (CMS), HHS OIG, the Office for Human Research Protections (OHRP), and NIH to address financial barriers faced by clinical trial participants.¹⁸ This thread connects directly to the HHS OIG RFI discussed above and to coverage and reimbursement analysis, signaling that clinical trial participant compensation reform will require coordinated regulatory change rather than any single fix.¹⁹

The Initiative identifies three priorities for interagency work: (1) co-payment exposure for standard-of-care services delivered during a clinical trial, (2) unexpected tax liability for clinical trial-related compensation, and (3) the risk that clinical trial participation may jeopardize eligibility for federal health care programs such as Medicaid.²⁰ Compensation is already widespread but inconsistently structured: a 2025 analysis by the Office of the Assistant Secretary of Planning and Evaluation (ASPE) reviewed 7,648 U.S. clinical studies and found that roughly 60% of studies offered clinical trial participant compensation, with rates varying widely by trial phase and condition.²¹ This portion of the Initiative intersects with the HHS OIG RFI: federal policy has expanded routine-care-cost coverage across Medicare, Medicaid, and private payors, yet clinical trial participants may still face copays, deductibles, and out-of-network costs — precisely the remuneration the AKS and Beneficiary Inducements CMP reach when a sponsor or site steps in to subsidize it.²² Any expansion of permissible participant remuneration would therefore need to be reconciled with CMS coverage rules and program eligibility frameworks.

3. FDA: Single IRB Reform and Other TrialBlazer Initiatives at FDA

FDA’s reforms are among the most operationally significant components of the Initiative, targeting two related priorities: accelerating time to first-in-human trials and reducing later-stage administrative burden.²³ This Alert focuses on the human subjects and institutional implications of FDA’s single IRB proposal; the remaining FDA-specific reforms are summarized briefly below and are analyzed in depth in our companion Alert.

Single IRB Reform and Human Subjects Research Oversight

FDA plans to continue advancing rulemaking that would require a single IRB model for multi-site cooperative studies, under which one IRB would serve as the “IRB of record” for all sites.²⁴ This would build on FDA’s September 2022 proposed rule on cooperative research and would further align FDA’s regulations with the federal policy for the protection of human subjects (the “Common Rule”) and NIH policy, which already require single IRB review for most U.S.-conducted, federally funded, nonexempt human subjects research.²⁵

A mandatory single IRB regime would curtail duplicative review and could speed multi-site start-up, but it would also require institutions to revisit how reliance is documented and operationalized. If FDA ultimately mandates single IRB review for multi-site cooperative studies, AMCs, independent IRBs, and sites accustomed to conducting their own local review of FDA-regulated, non-federally funded multi-site studies will need to clarify how the IRB of record is selected, how local-context issues (including state law) are reviewed, how responsibilities are allocated among reviewing and relying institutions, and how recordkeeping and reporting obligations are handled. Those implementation questions are familiar from the Common Rule and NIH single IRB experience, but FDA-regulated studies raise distinct operational considerations because they often involve industry sponsors, commercial IRBs, investigational product oversight, and site contracting by commercial sponsors or CROs with multiple sites of diverse types across the country.

Other FDA Operation TrialBlazer initiatives include clarification of IND expectations, Chemistry, Manufacturing, and Controls and pharmacology/toxicology streamlining, expanded use of New Approach Methodologies, the proposed Expedited-IND Pilot Program and Qualified Research Institution concept, and revised draft guidance documents on substantial evidence of effectiveness and master protocols.²⁶ These FDA actions are at different procedural stages—including non-binding draft guidance, a proposed pilot, and ongoing rulemaking—and should be evaluated accordingly.

4. ONC: EHR/ClinicalTrials.gov Integration and Computable Protocols

ONC is exploring connecting patients to clinical trials through electronic health records (EHRs). ONC notes near universal EHR adoption (roughly 99% of hospitals and 90% of providers using certified EHRs) and indicates it “could propose” a certification capability allowing certified EHRs to integrate with the public ClinicalTrials.gov application programming interface (API) for preliminary eligibility screening at the point of care.²⁷ Separately, ONC highlights the development of “computable” protocols for automated eligibility screening, alongside emerging standards (ICH M11, the CDISC Unified Study Definitions Model, and HL7 FHIR-based protocols) to render protocols computable.²⁸ Any such capability would arrive only through a future Health IT Certification rulemaking and would carry binding force only once finalized.

EHR-based clinical trial participant recruitment raises several issues the Initiative does not address. Identifying and contacting eligible patients generally involves a use or disclosure of protected health information (PHI) under the Privacy and Security Rules of the Health Insurance Portability and Accountability Act of 1996 (HIPAA); an EHR-based matching capability sits adjacent to the information-blocking framework governing interference with access, exchange, or use of electronic health information; and certification obligations would fall in the first instance on EHR developers. A central open question—unresolved in the materials—is who bears compliance responsibility among EHR developers, provider organizations, and sponsors. In addition, the HHS Office for Civil Rights (OCR) is not mentioned in Operation TrailBlazer despite its importance in clarifying pathways for research recruitment under the HIPAA Privacy Rule, such as identifying when research recruitment may be performed by a business associate as a health care operation function.

5. NIH: Metrics, Rigor, Real-World Data, and Decentralized Trials

NIH’s workstreams—a clinical trial metrics RFI, expanded use of NIH networks and SMART IRB, greater use of real-world data (RWD), enhanced rigor and data-integrity policies, and decentralized/rural trials—point toward tighter expectations for federal awards and research funding compliance. Framing itself as a steward of taxpayer investment, NIH signals heightened scrutiny of underpowered or poorly designed trials.²⁹

NIH will issue an RFI, though it provides no timing for such issuance, to identify metrics for trial start-up efficiency, ongoing performance, and go/no-go decisions. NIH also plans to leverage existing networks—including the NCI-Designated Cancer Centers and the Clinical and Translational Science Awards—as platforms to test better clinical trial practices, including expanded use of SMART IRB, a framework for IRB reliance agreements designed to streamline IRB review for multi-site studies.³⁰

NIH also states that it is advancing RWD and causal inference methods, enhancing rigor through a semi-structured clinical trial application form, updating its 1998 Data and Safety Monitoring Policy, developing a new return-of-results policy, and expanding decentralized and hybrid trials in rural, tribal, and underserved communities.³¹ Separately, NCI is working with cancer centers, researchers, and other stakeholders to streamline trial activation and improve enrollment, while NCATS is building on gene-editing platform work that HHS describes as contributing to the first fully personalized CRISPR-based gene-editing treatment.³²

6. ARPA-H: Platforms, Predictive Models, and Advanced-Therapy Manufacturing

ARPA-H is a federal agency that funds high-risk, high-reward biomedical and health research aimed at producing breakthroughs in areas like disease prevention, diagnosis, and treatment. In coordination with FDA, the agency is using programmatic funding to target scientific and operational bottlenecks in early-stage drug development.

Specifically, in the Initiative, ARPA-H’s signal comes through specific programs: CATALYST, which supports predictive human and computational models to assess safety and efficacy before human testing; THRIVE, which explores platform- and umbrella-trial approaches for genetic medicines; and ENGINE and UNICORN, which focus on improving the consistency, scalability, and predictability of advanced-therapy manufacturing using computational and AI-enabled tools.³³ These programs suggest continued HHS interest in platform-based trial design, AI-enabled development tools, and more standardized approaches to complex therapies.

Key Dates and Opportunities to Engage

Current and expected engagement opportunities include the following:

• HHS OIG RFI Comments – August 24, 2026. Comments on potential AKS safe harbors and Beneficiary Inducements CMP exceptions for clinical trial participant remuneration are due.
• NIH Clinical Trial Metrics RFI – To be announced. NIH is expected to seek input on metrics for trial start-up efficiency, ongoing performance, early intervention, and go/no-go decisions.
• HHS Roundtables – To be announced. HHS plans roundtables on IND streamlining, clinical trial initiation, hospital contracting, IRB reform, Phase 1 acceleration, and participant/sponsor payment.

Conclusion

Operation TrialBlazer is best understood not as a single policy announcement, but as a coordinated signal of where HHS may be headed: faster early-phase trial development, more harmonized oversight, broader use of data and technology, and fewer clinical trial participant-facing barriers. Most components remain proposals, RFIs, draft guidance, or pilots, but the breadth of the initiative means that sponsors, AMCs, research institutions, CROs, and investors should monitor the comment process and developing guidance and assess how these reforms may affect trial operations, contracting, participant support, data strategy, and diligence.

Ropes & Gray will continue to monitor developments in these areas closely. If you have any questions about Operation TrialBlazer or recent HHS developments, please contact any member of Ropes & Gray’s health care or FDA regulatory practices or your usual Ropes & Gray advisor.