FDA moves to accelerate US clinical development as OIG weighs new protection for trial participant remuneration

HHS is targeting speed. The department is saying that the U.S. is losing early-stage research to China and has a critical window to act “measured in years, not decades.” Operation TrialBlazer comes on the heels of recent congressional concerns about the pace of clinical research in China and other covered nations, as we wrote about here.

FDA sets the stage for accelerated U.S. clinical development

FDA announced a set of actions it is taking spanning the investigational new drug (IND) phase through late-stage pivotal trials. The early-stage items are the most concrete and several are actionable today.

• Expedited IND pilot program RFI. FDA is seeking public feedback before launching a pilot in which sponsors will partner with “qualified research institutions” (QRIs), such as academic medical centers, to develop and review Phase 1 IND “components” via a rolling submission platform, aiming to accelerate first-in-human studies.

Beyond pilot mechanics, FDA poses questions with direct commercial and compliance stakes, such as whether a QRI serving in a “dual capacity as both an IRB and regulatory advisor” needs additional safeguards to manage conflicts of interest and whether the pilot could “create inequitable access favoring well-resourced sponsors over smaller companies.” FDA also requests information about which product types (small molecules, biologics, cell and gene therapies, etc.) are best suited to the pilot and how to protect confidential and trade-secret information on the rolling platform. One practical wrinkle: FDA expects sponsors to pay fees directly to QRIs, with FDA not involved in setting or collecting them.

QRI input is advisory only. FDA retains full authority to make regulatory decisions, impose clinical holds, disqualify investigators or IRBs, and conduct inspections. Comments are due July 22, 2026, under Docket No. FDA-2026-N-4699.

• Clarification of Phase 1 CMC requirements. FDA updated its CMC IND webpage for CDER-regulated drugs to clarify phase-specific CMC requirements for first-in-human Phase 1 INDs, emphasizing that certain data—such as clinical-lot stability data, full-duration stability data, analytical method validation, and non-safety-related process controls—generally may be deferred until later development. FDA frames the clarification as phase-appropriate flexibility intended to prevent sponsors from over-submitting CMC information at the initial IND stage while preserving FDA’s ability to assess quality and patient safety. This can save 6 to 12 months of development time, according to FDA.
• Phase 1 contact center. FDA established a staffed line and email address offering real-time responses on protocols, regulatory requirements, and early-phase questions. FDA frames it as a complement to, not a replacement for, product-specific pre-IND meetings.
• QSP/MABEL dose-selection draft guidance. FDA issued a new draft guidance on the appropriate use of a quantitative systems pharmacology (QSP)-based approach for determining minimum anticipated biological effect level (MABEL) dose in first-in-human, Phase 1 trials, part of FDA's broader move away from animal-toxicology-driven dose selection.
• Substantial evidence of effectiveness revised draft guidance. FDA issued revised draft guidance clarifying how a single adequate and well-controlled trial plus confirmatory evidence can support approval and outlining FDA’s authority to exercise “regulatory flexibility” in certain circumstances. This new guidance builds on FDA’s earlier single-trial initiatives, including its 2023 guidance, Demonstrating Substantial Evidence of Effectiveness With One Adequate and Well-Controlled Clinical Investigation and Confirmatory Evidence. In addition, when comparing the new draft guidance to the 2019 draft guidance, FDA reorganizes the confirmatory-evidence framework by dividing it into two routes—a single trial plus a source of strong confirmatory evidence (e.g., related-indication data) and a highly persuasive single trial plus early-phase confirmatory evidence. It also highlights factors that determine evidentiary strength—including trial design, conduct, statistical persuasiveness, and overall program context—and retains regulatory flexibility in certain settings while framing that flexibility as a balance between evidentiary uncertainty and timely patient access. FDA directs sponsors to seek agency alignment on a single-trial approach by the end of Phase 2, a more specific timing expectation than the 2019 draft’s general call to consult FDA in advance. Comments are due September 22, 2026, under Docket No. FDA-2019-D-4964.
• Master protocols revised draft guidance. FDA issued revised draft guidance on master protocols, or single overarching trials with multiple substudies. The 2023 draft guidance focused primarily on umbrella and platform trials, while the revision adds recommendations on basket trials, including a new framework for evaluating a drug’s effects across multiple disease subpopulations and for borrowing information across substudies. The remaining changes are clarifying in nature (e.g., on randomization, choice of control, and informed consent). FDA’s guidance aims to identify opportunities for greater trial efficiency. A shared control arm and shared infrastructure and oversight can reduce the duplication of standalone trials, according to the agency. Comments due August 24, 2026, under Docket No. FDA-2023-D-5259.
• Real-time status tracker. FDA says it plans to build so sponsors can see when FDA has reviewed a protocol amendment and determined that no further action is required, rather than waiting on a formal FDA communication.

The direction is clear. FDA is signaling that it wants to move clinical development faster, and sponsors who engage early will help set the terms.

OIG probes the need for a new safe harbor, exception, or guidance

Separately, but relatedly, OIG issued an RFI asking whether it should add or modify an AKS safe harbor or exception to the Beneficiary Inducements CMP to protect payments to clinical trial participants, or whether sub-regulatory guidance such as special advisory bulletin, FAQ, or other would suffice. OIG frames the effort as “seeking visibility into” the value, risks, and necessary safeguards of such payments.

As the RFI notes, OIG has issued several favorable advisory opinions touching on the narrow issue of subsidizing or waiving the cost-sharing obligations that participants—including federal health care program beneficiaries—would otherwise owe for trial-related care. Another favorable opinion addressed participant stipends for time and effort in a government-funded, non-commercial study. Those favorable outcomes rested largely on OIG’s analysis of the facts and circumstances, and it has not addressed other categories of support.

Among the RFI’s fourteen questions, several are particularly relevant to manufacturer sponsors:

• Does remuneration facilitate trial participation, and is the AKS/CMP a barrier? OIG seeks feedback on whether remuneration to clinical trial participants will meaningfully enhance clinical trial participation and whether the AKS or Beneficiary Inducement CMP are viewed as a barrier to such remuneration and why.
• Which types of remuneration facilitate participation, at what caps, and who may pay? OIG identifies several categories of remuneration that may facilitate clinical trial participation, including transportation, lodging, childcare, meals, stipends, and enrollment and completion incentives. OIG also solicits feedback on whether the risk of fraud and abuse varies based on who provides the remuneration—the clinical trial site, sponsor, or others.
• What safeguards may be necessary? OIG asks whether IRB review of payments is a meaningful safeguard, how to prevent steering to the offeror’s non-trial products, and whether to limit advertising of remuneration provided to clinical trial participants.
• Should trial phase or trial type change the analysis? OIG solicits feedback on whether different amounts or types of remuneration are necessary for different stages of development or whether remuneration should be limited to government-sponsored trials.

Comments are due August 24, 2026 (refer to file code OIG-2602-N).

Where to start with Operation TrialBlazer

Two separate comment windows are in play, so triaging them is the first order of business. FDA’s expedited IND pilot RFI has a deadline of July 22, 2026, the nearer of the two, while OIG’s participant-payment RFI has a deadline of August 24, 2026.

Both agencies are explicitly soliciting data, so internal enrollment, retention, and cost-related barriers that affect participation could directly shape the categories, caps, and safeguards in any eventual OIG safe harbor, exception, or guidance as well as the design of the FDA pilot.

On FDA’s pilot, the questions worth engaging are those with commercial and competitive stakes, including conflict-of-interest handling by QRIs (especially where one entity is both IRB and regulatory advisor), protection of confidential and trade-secret information on the rolling submission platform, and product-type eligibility. Larger sponsors may also want to contest the premise that the pilot favors well-resourced sponsors, since accepting it could invite access caps or small-sponsor prioritization.

For the OIG RFI, manufacturers should consider engaging on the potential limitations to government-sponsored trials and the scope of permissible payors, since either one, if adopted, could constrain industry-sponsored trials or sponsor-funded remuneration models.

The revised draft guidances remain non-binding drafts, so there is nothing to implement today. But they signal the direction of FDA’s thinking, and sponsors weighing single-trial programs, master-protocol designs, or MABEL-based dose selection should factor that trajectory into near-term development planning. The one item available to act on now is FDA’s updated Phase 1 CMC webpage, which clarifies what data is phase-appropriate for a first-in-human IND and may relieve the submission burden for some programs.

We are tracking each of these workstreams and the comment deadlines that come with them. Please reach out to the authors or your usual Hogan Lovells contact to help you decide where a comment is worth the effort and for assistance in drafting one.

Authored by Robert Church, Heidi Gertner, Eliza Andonova, Eman Al-Hassan, Bryan Walsh, and Ashley Grey.