Re-Designing Clinical Trials: Understanding the Federal Push to Modernize Clinical Research

Part 1 of a Three-Part Series

Clinical trials are the foundation for determining the safety and effectiveness of new drugs and treatments. Yet bringing a new product through clinical development, especially in today’s landscape of immunotherapies, gene and cell therapies, and other Advanced Therapy Medicinal Products (ATMPs), remains a lengthy, expensive, and fragmented process. The U.S. government is now signaling that the domestic clinical-trial process needs an overhaul.

In June 2026, the U.S. Department of Health and Human Services (HHS) launched Operation TrialBlazer, a department-wide initiative to strengthen U.S. leadership in clinical research. The roadmap reflects growing concern that early-stage research is moving overseas, and that unnecessary delays, redundant requirements, and regulatory ambiguity are slowing and discouraging U.S.-based development.^1,2

Rather than centering on a single new program or organization, Operation TrialBlazer treats clinical development as an interconnected challenge that requires change across the entire federal research and regulatory environment.

Several initiatives launched since the announcement already illustrate this incremental, collaborative approach. In Part 1 of this three-part series, we will:

• Outline how Operation TrialBlazer sets the broader federal direction

• Introduce ARPA-H and its approach through the new SURPASS program

• Explain how complementary projects addressing trial activation, data infrastructure, and patient navigation fit into the larger effort to modernize the clinical-trial ecosystem

Operation TrialBlazer: The Broader Federal Strategy

Announced on June 22, 2026, Operation TrialBlazer brings together efforts across several HHS divisions, including the Food and Drug Administration (FDA), the National Institutes of Health (NIH), and the Advanced Research Projects Agency for Health (ARPA-H), to reshape clinical development.¹

Six Priority Areas for Action

HHS identifies six priority areas for action:¹

• Modernizing regulatory requirements and processes

• Improving transparency for regulated entities

• Encouraging adoption of more efficient practices

• Ensuring federal dollars support adequately powered and well-designed trials

• Making better use of existing data and technologies

• Improving patient and participant access while addressing disincentives to health-care worker participation

Rethinking Early-Phase Development

HHS plans to advance these objectives through several strategies. Early roadmap efforts focus on early-phase research, with the potential to shorten submission timelines by 6 to 12 months.¹

TrialBlazer aims to do more than accelerate FDA review. It also examines whether all work traditionally completed before an Investigational New Drug (IND) application is necessary at that stage. Final FDA guidance on streamlined nonclinical testing could reduce conventional pre-Phase 1 requirements for certain investigational products while preserving a risk-based safety standard.

Modernization Efforts Already Underway

Across HHS, agencies have already begun turning the roadmap into action:¹

• Clarifying early-development expectations: FDA’s updated Phase 1 resources clarify phase-appropriate, risk-based Chemistry, Manufacturing, and Controls (CMC) and pharmacology/toxicology expectations, so sponsors submit only what is needed at this stage.

• Testing a faster path to first-in-human studies: FDA’s Expedited IND Pilot pairs sponsors with qualified research institutions and reviews completed IND components on a rolling basis, shortening the path from drug identification to Phase 1 trials.

• Bringing research closer to participants: Federal efforts are advancing decentralized and technology-enabled trial models to expand access for rural and underserved communities.

NIH: Strengthening Trial Infrastructure and Research Tools

NIH and its institutes are modernizing the oversight, infrastructure, and scientific tools that support clinical research:¹

• Reducing duplicative ethics review: NIH is expanding SMART IRB, a national reliance agreement and platform that helps institutions use a single IRB for multisite studies.

• Modernizing trial oversight: NIH is updating its data and safety monitoring policy, first issued in 1998, to reflect today’s trial designs and oversight needs.

• Accelerating cancer trials: The National Cancer Institute (NCI) is working with cancer centers, researchers, and other stakeholders to streamline trial activation and improve enrollment.

• Speeding rare-disease therapies: The National Center for Advancing Translational Sciences (NCATS) is applying lessons from the first fully personalized CRISPR gene-editing treatment to accelerate future therapies for rare diseases.

• Advancing alternatives to animal testing: In September 2026, as part of a related HHS effort to reduce reliance on animal testing, NIH announced more than $88 million for 10 research-infrastructure projects, plans for an NIH Clinical Center laboratory integrating human organoid models, robotics, and artificial intelligence, and a challenge offering more than $7 million in awards for quantum-enabled measurement tools.

Measuring Trial Performance

HHS reports that NIH plans to seek public input on measures of clinical-trial performance, including the time required to activate, enroll, complete, and report results. These metrics would help assess whether federally funded trials produce timely, meaningful evidence and use public funds effectively.¹

The Bigger Picture

Taken together, these efforts point to something larger than making individual trials move faster. The federal strategy targets multiple bottlenecks in clinical development—from regulation and study design to data, technology, participation, and trial operations. This context is essential to understanding the role of ARPA-H.

ARPA-H: Taking a Different Approach to the Problem

Origins and Funding

Although ARPA-H is a relatively new agency, it was not created as part of Operation TrialBlazer. Congress authorized ARPA-H through the FY2022 Consolidated Appropriations Act, signed into law on March 15, 2022, with an initial $1 billion in funding, and later codified the agency in 2023.^3,4 The agency received a budget of $1.5 billion in both 2025 and 2026.⁵

Addressing a Gap in Federal Research Funding

ARPA-H was proposed to address a specific gap. Federal research funding through the NIH relies largely on investigator-initiated, consensus-driven peer review, a process that some evidence suggests is less likely to support high-risk, high-reward projects.⁶

To fill that gap, ARPA-H was modeled on the Defense Advanced Research Projects Agency (DARPA), known for developing ARPANET (the internet’s predecessor), and the Advanced Research Projects Agency-Energy (ARPA-E). Like those agencies, ARPA-H relies on:⁶

• Minimal organizational hierarchy

• Program Managers who serve limited terms and have substantial autonomy

• Awards tied to defined milestones

ARPA-H leverages NIH’s expertise and infrastructure but functions as a separate funding agency, with a Director who reports to the HHS Secretary. It has no laboratories of its own and directs most of its funding to external teams nationwide.³

Starting With the Problem

ARPA-H was established to take on ambitious health challenges that traditional approaches may struggle to solve. Instead of beginning mainly with questions proposed by investigators, it begins with a clearly defined problem. This approach is now being applied to challenges within the broader effort to modernize clinical development.

In general, the process follows four steps:⁷

1. An ARPA-H Program Manager defines a difficult health challenge.

2. ARPA-H funds several multidisciplinary teams, known as performers, to pursue different solutions.

3. Performers are assessed throughout the program; promising approaches move forward, while those that fall short can be discontinued.

4. Projects that solve the challenge “graduate” to engaged partners that can scale the solution.

This model is not a replacement for NIH, NCI, or the existing federal clinical-research infrastructure. Rather, it adds a mechanism for addressing problems that demand coordinated expertise, technology, operational capabilities, and measurable results.

A Rapidly Expanding Portfolio

ARPA-H’s portfolio has grown quickly and now spans a wide range of health challenges. Notable milestones include:

• ARPANET-H (2023): A national health innovation network with hubs in Washington, D.C.; Cambridge, Massachusetts; and Dallas, Texas. ARPA-H used the Dallas hub opening to announce Advancing Clinical Trial Readiness (ACTR), an early initiative to help more Americans join clinical trials close to home.⁸

• NITRO (March 2024): For its first program, the agency selected five performer teams to develop approaches that enable joints damaged by osteoarthritis to heal themselves.⁸

• 2024–2025 programs: A $100 million Sprint for Women’s Health; PROSPR (age-related disease); RAPID (faster rare-disease diagnosis); and GIVE (RNA-based medicine manufacturing).⁸

• 2026 programs: New launches accelerated, including 1-CURE (low-cost radiotherapy for all cancers), Delphi (wearable biosensors), CIRCLE (AI-guided critical care), STOMP (microplastics in the body), and SPECTRA (precision care for autism).^9,10

• Drug-development programs: CATALYST applies computational modeling to predict drug safety and efficacy before clinical trials begin, while FASTPASS seeks to verify the quality and safety of medicines within the supply chain.^11,12

In September 2026, ARPA-H applied this model to the structure of clinical trials itself with the launch of SURPASS.

SURPASS: Challenging the Traditional Clinical-Trial Model

On September 30, 2026, HHS, through ARPA-H, launched SURPASS (Simulation-augmented, Real-time Platform Adaptive Seamless Trials), a program that asks whether the traditional clinical-development model can work differently.^13–15

The Problem SURPASS Targets

ARPA-H’s assessment of today’s clinical-development environment is stark: developing drugs and biologics often takes more than a decade, costs $1–2 billion and fails 90% of the time. The agency describes the current paradigm as fragmented and inefficient, relying on:^13–15

• Separate clinical phases

• Repeated trial startups

• Static designs

• Duplicated operational infrastructure

SURPASS Proposal & Goals

Rather than treating every investigational therapy as requiring its own sequence of static trials (and repeatedly rebuilding the supporting infrastructure) SURPASS seeks to develop persistent adaptive platform trials. These platforms would combine:¹³

• Predictive computational models

• Shared trial infrastructure

• Common control groups

• Real-time analysis to support earlier decision-making as evidence accumulates

ARPA-H’s goal is to determine whether drugs and biologics can be evaluated faster, at lower cost, and with fewer participants than conventional approaches. The program even poses the question of whether clinical-trial timelines could ultimately be shortened from more than a decade to less than four years.¹³

Perhaps more consequential is the question SURPASS poses to a long-standing assumption in clinical research: Does every development program need to rebuild so much of the underlying trial infrastructure from scratch?

SURPASS challenges a long-standing feature of clinical development: the need to build a largely separate trial infrastructure for each investigational therapy and development phase. The program asks whether shared, persistent platforms could safely reuse certain operational, data, and control-group resources across multiple studies—reducing repeated startup work, cost, and delay.

Modernization Takes More Than a New Trial Design

Trial design is only one source of delay. Even the most sophisticated adaptive platform still relies on:

• Sites that can activate studies

• Clinical data that are accessible

• Patients who can find and take part in research

• Operational systems that can support the research

Reflecting these dependencies, ARPA-H announced three projects that complement SURPASS.^14,15

STACK: Streamlining Trial Activation

Standardized Trial Activation through Composable Knowledge (STACK) focuses on trial activation. ARPA-H states that STACK will create a governance framework, establish a Trial Activation Consortium, and develop a navigator network to streamline and modernize clinical trials. Evidence Health Inc. received an award of up to $41.18 million.¹⁶

Potential impact: Faster trial designs can only deliver their full value if studies can be activated efficiently. By targeting trial activation, STACK is intended to address an operational barrier that contributes to delays in clinical development.

COMMONS: Strengthening the Data Foundation

Connected Outcomes through a Multi-institutional Observational, National System (COMMONS) focuses on the data foundation for clinical research. The project aims to create a consent-governed national real-world data resource by aggregating patient data through lawful channels, harmonizing records to a common data model, and enabling privacy-protected research access. It is designed to include rural, community, and safety-net providers.¹⁴

Potential impact: By creating a standardized, privacy-protected national real-world data resource, COMMONS could accelerate clinical research, broaden participation across the research ecosystem, and strengthen the data foundation supporting evidence generation.

CINCH: Guiding Patients Through Cancer Care and Research

Cancer Intelligence for Navigation, Care and Health (CINCH) focuses on helping adults with cancer understand and navigate their own cases. Awarded to Courage Health Inc. for up to $8.95 million, CINCH will gather a person’s cancer records, assess whether they contain enough information to guide diagnosis and treatment decisions, and provide clear, oncologist-reviewed findings that patients and their local care teams can use. Its initial focus is adults in rural and underserved communities.¹⁷

Potential impact: A more efficient clinical-research ecosystem also depends on patients having access to the information needed to navigate complex care. By turning fragmented cancer records into clear, actionable guidance, CINCH could help patients and local care teams make more informed decisions, particularly in rural and underserved communities.

Summarizing the Modernization Initiatives in the Clinical Trial Ecosystem

Although HHS does not formally organize these initiatives this way, viewing them together clarifies the distinct problem each one addresses:

Initiative	What It Addresses
Operation TrialBlazer	The broader HHS roadmap for strengthening and modernizing U.S. clinical research1
SURPASS	The traditional structure of clinical development, through persistent, adaptive platform trials13
STACK	Trial activation infrastructure16
COMMONS	The data environment supporting clinical research14
CINCH	The patient-facing challenge of navigating information, care, and research opportunities14

Viewed together, these initiatives show that clinical-trial modernization cannot be achieved through a single program or through trial design alone. Faster trial designs still depend on sites that can activate studies, data that can move between organizations, patients who can find research opportunities, and operational infrastructure that does not have to be rebuilt for every study. Of these, SURPASS will focus on the need for shared infrastructure.

SURPASS Is Still a Vision Being Built

SURPASS is not an established national adaptive clinical-trial network, nor is it planning to become one. As of October 22, 2026, ARPA-H lists the program as “Accepting Submissions.” Its open solicitation, ARPA-H-SOL-26-164, seeks cross-disciplinary teams with capabilities spanning statistics, artificial intelligence, clinical-trial design, operations, and regulation to pursue three coordinated technical areas:¹³

1. Building faster trials with fewer patients

2. Developing a continuous-inference capability for faster decisions

3. Creating an agentic operations layer intended to reduce time and cost

ARPA-H has defined the challenge and the goals, but the teams and approaches that will build SURPASS platforms are still being evaluated and selected.

Looking Ahead: From Vision to Reality

Operation TrialBlazer sets the federal imperative: strengthen U.S.-based clinical research by reducing unnecessary barriers while maintaining rigorous safety, privacy, ethical, and scientific standards.¹ SURPASS goes further, asking not only how conventional clinical development can move faster, but whether the clinical-trial model itself can be redesigned.

That shift raises a new set of questions:

Who actually builds a SURPASS platform? Why would organizations that ordinarily compete collaborate around shared infrastructure? And how will ARPA-H fund, evaluate, and scale the models that succeed?

In Part 2, From Vision to Reality: How ARPA-H Plans to Build the SURPASS Clinical Trial Model, we will take a closer look at how the SURPASS Innovative Solutions Opening is structured, how multidisciplinary Core Platform Teams fit into the model, and why ARPA-H is asking traditionally separate parts of the clinical-development ecosystem to solve this challenge together.

References

1. U.S. Department of Health and Human Services. Operation TrialBlazer: A Roadmap to Strengthen U.S. Clinical Research. June 2026. Operation TrialBlazer roadmap

2. AllSci. “HHS Launches Operation TrialBlazer to Reverse Offshoring of Early-Phase Clinical Research.” 2026. HHS Launches Initiative to Reverse Offshoring

3. Advanced Research Projects Agency for Health. “Frequently Asked Questions.” ARPA-H FAQs

4. Sekar K, Gallo ME. Advanced Research Projects Agency for Health (ARPA-H): Overview and Selected Issues (R47568). Congressional Research Service; May 23, 2023. CRS Report R47568

5. Advanced Research Projects Agency for Health. FY 2026 ARPA-H Operating Plan. 2026. FY 2026 Operating Plan

6. Congressional Research Service. Advanced Research Projects Agency for Health (ARPA-H) (R47074). CRS Report R47074

7. Advanced Research Projects Agency for Health. “The ARPA-H Model.” ARPA-H Model

8. Advanced Research Projects Agency for Health. “Timeline.” ARPA-H Timeline

9. Research!America. ARPA-H Initiatives at a Glance: Major Projects and Project Objectives as of June 2026. ARPA-H Initiatives at a Glance

10. U.S. Department of Health and Human Services. “ARPA-H Launches SPECTRA to Transform Autism Diagnosis and Precision Care.” Press release, September 17, 2026. SPECTRA press release

11. Advanced Research Projects Agency for Health. “Programs.” ARPA-H Programs

12. Beth Israel Deaconess Medical Center Translational Research Hubs. “New ARPA-H Research Programs and Initiatives (Updated 8/28/2026).” BIDMC ARPA-H programs update

13. Advanced Research Projects Agency for Health. “SURPASS: Simulation-augmented, Real-time Platform Adaptive Seamless Trials.” SURPASS program page

14. Advanced Research Projects Agency for Health. “HHS Launches SURPASS and New Efforts to Accelerate Faster, Smarter Clinical Trials.” September 30, 2026. ARPA-H SURPASS announcement

15. U.S. Department of Health and Human Services. “HHS Launches SURPASS and New Efforts to Accelerate Faster, Smarter Clinical Trials.” Press release, September 30, 2026. HHS SURPASS press release

16. Advanced Research Projects Agency for Health. “STACK: Standardized Trial Activation through Composable Knowledge.” Award, September 29, 2026. STACK award

17. Advanced Research Projects Agency for Health. “CINCH: Cancer Intelligence for Navigation, Care and Health.” Award, September 21, 2026. CINCH award

About the Author