HHS Launches Operation TrialBlazer to Restore US Leadership in Clinical Research

The US Department of Health and Human Services (HHS) has announced Operation TrialBlazer, a coordinated effort across multiple federal agencies aimed at strengthening the United States' position as the global leader in clinical research.¹

The initiative combines regulatory reforms at the FDA, new National Institutes of Health (NIH) investments, and programs across several HHS agencies, all focused on reducing unnecessary barriers and accelerating the path from drug discovery to patient access.

According to an article in The Hill, China surpassed the US in total clinical trials registered for the first time in 2024, accounting for 39% of global trials. China's Phase I trial share overtook the US as far back as 2021, driven by lower costs, streamlined regulation, and government subsidies that are difficult for other countries to match.²

"America should be the best place in the world to develop new medicines, yet we have built a system that drives too much clinical research overseas," said HHS Secretary Robert F. Kennedy Jr. in a press release. "HHS is launching a coordinated department-wide effort to restore America's leadership in clinical research, remove unnecessary barriers, and bring more clinical research and investment back to the United States."

Acting FDA Commissioner Kyle Diamantas framed the stakes similarly. "We've been witness to a growing share of Phase I clinical trials moving overseas, delaying opportunities for American patients and weakening the nation's position as a global leader in biomedical research," he said, according to The Hill.

FDA actions targeting early-stage development

The FDA's contributions to Operation TrialBlazer focus on compressing early development timelines and reducing regulatory complexity for sponsors, particularly smaller companies without large regulatory teams.³

A proposed Expedited Investigational News Drug (IND) pilot program would allow drug sponsors to partner with qualified research institutions—such as academic medical centers or CROs—to develop Phase I IND submissions through a rolling platform designed to minimize clinical holds and increase submission quality. The FDA is soliciting public comment before initiating the program.

Alongside the pilot proposal, the agency has updated its Chemistry, Manufacturing, and Controls (CMC) IND webpage to clarify phase-appropriate requirements for first-in-human Phase I trials. The change addresses a pattern of sponsors submitting more data than necessary at early stages—a practice that, according to the FDA, can add six to 12 months of unnecessary development time.

A new Phase I Contact Center has also been established, offering real-time responses to questions about clinical protocols and regulatory requirements, with the ability to connect sponsors to subject matter experts within the agency when needed.

Reforms at the late stage

On the late-stage side, the FDA has revised its guidance on demonstrating substantial evidence of effectiveness, clarifying that one rigorous, adequate, and well-controlled pivotal trial—supported by confirmatory evidence—will generally be sufficient for drug approval in many cases.

The agency has also updated its master protocol guidance to address basket, umbrella, and platform trial designs, which can reduce duplicative infrastructure and accelerate evidence generation across multiple indications simultaneously.

The FDA had historically required two late-stage trials to establish safety and efficacy, but has been moving toward greater flexibility in recent months.

Expert perspective: Designing for the new regulatory reality

In April, Applied Clinical Trials spoke with Mwango Kashoki, MD, MPH, SVP and global head of regulatory strategy at Parexel, in an exclusive interview covering the FDA's plausible mechanism framework.⁴

Kashoki explained that the framework represents a fundamental change in how early development is structured for individualized therapies in ultra-rare disease settings. Under the framework, the first-in-human study now has the potential to serve as the pivotal trial for approval—a possibility that pushes evidentiary planning much earlier in the process than sponsors have historically needed to consider.

"The FDA is now more formally encouraging and assisting companies to design their initial trials as the pivotal trials," Kashoki said. "For sponsors of genome editing and other types of individualized therapies, this means that even earlier in development, they have greater clarity on the nature and scope of clinical, CMC, and non-clinical data necessary to support approval."

Kashoki emphasized that early engagement with the FDA is critical, as is investment in robust nonclinical programs and biomarker qualification. Adaptive trial designs that allow sponsors to move quickly to the right dose and population are also important, as are plans for external control data in what are typically single-arm trials.

"The key is making sure it's clear from the very start that the framework is intended to be leveraged," Kashoki said, "and being clear on not only the clinical trial design but that package of confirmatory evidence that would provide the robustness of data for the agency to make the determination that there is indeed substantial evidence of effectiveness."

References

1. HHS Launches Unprecedented Department-Wide Effort to Restore American Leadership in Clinical Trials. HHS. News release. June 22, 2026. Accessed June 23, 2026. https://www.hhs.gov/press-room/hhs-launches-clinical-trials-reform-initiative.html

2. Health officials launch clinical trial reforms to counter China threat. The Hill. June 22, 2026. Accessed June 23, 2026. https://thehill.com/policy/healthcare/5934886-us-china-clinical-trial-competition/

3. FDA Actions to Accelerate and Modernize Early and Late-Stage Clinical Development. FDA. Accessed June 23, 2026. https://www.fda.gov/industry/fda-actions-accelerate-and-modernize-early-and-late-stage-clinical-development

4. Designing for Approval from Day One: Q&A with Mwango Kashoki, MD, MPH, Parexel. Applied Clinical Trials. April 21, 2026. Accessed June 23, 2026. https://www.appliedclinicaltrialsonline.com/view/designing-approval-mwango-kashoki-parexel