ARPA-H Launches SURPASS to Advance Simulation-Augmented, Real-Time Adaptive Clinical Trials

Technical Objectives/Capability Areas

SURPASS is structured around three integrated technical areas that each Core Platform Team must address. ARPA-H will evaluate teams on the integrated clinical and technical performance of the complete platform, rather than on isolated completion of individual technical area activities.

Technical Area 1: Phaseless Design Engine

Technical Area 1 requires a simulation-based design environment for adaptive, seamless platform trials. The design engine must support integrated planning across first-in patient, efficacy, and, where proposed, confirmatory development rather than optimizing conventional clinical phases separately. Required capabilities include representation of the adaptive platform design, shared controls, in silico method integration, operating characteristic estimation, platform-level performance assessment, tools for qualified nondeveloper trialists, and reproducible, auditable workflows.

The solicitation calls for in silico capabilities that may include digital twins, synthetic controls, disease progression models, multimodal longitudinal models, PK/PD models, predictive safety and toxicity models, and models of patient eligibility, recruitment, enrollment, and retention. Each model must have a defined platform role, specified data inputs, an identified decision it informs, and computational performance compatible with clinical operations timelines.

Technical Area 2: Continuous Inference

Technical Area 2 focuses on a continuous inference and adaptation validity engine that enables clinically meaningful decisions as data accumulate without compromising inferential validity. ARPA-H specifies that “continuous” or “real-time” inference does not permit unrestricted or undocumented review of trial data; analyses and adaptations must occur through authorized, reproducible, and auditable procedures established in the Master Protocol, arm-specific appendices, and Statistical Analysis Plan.

The technical approach may use adaptive platform methods, anytime-valid approaches, group-sequential methods, Bayesian methods, or other inferential frameworks. The system must support arm additions and removals, seamless safety-to-efficacy and confirmatory transitions, and integration of prognostic scores, digital-twin outputs, and other in silico information. Proposed teams must also define prespecified adaptation rules, independent Statistical Analysis Committee procedures, DSMB reporting, blinding plans, safety operations, and version-controlled records sufficient to reconstruct interim analyses and resulting trial changes.

Technical Area 3: Agentic Operations

Technical Area 3 seeks AI enabled operational systems and an integrated clinical operations framework to allow platforms and their intervention arms to start, enroll, execute, adapt, and generate decision ready data rapidly while preserving participant safety, data integrity, regulatory compliance, quality, and inspection readiness.

ARPA-H identifies a broad operational scope, including Master Protocol and arm-specific document management; new-arm feasibility and onboarding; contracting and site activation; regulatory and IRB workflows; participant prescreening; data collection, reconciliation, cleaning, and analysis ready dataset construction; enrollment monitoring; safety reporting; clinical supply; vendor oversight; Trial Master File management; and implementation of adaptations approved through Technical Area 2. The solicitation emphasizes that AI enabled automation does not transfer or replace the responsibilities of sponsors, investigators, clinical sites, statistical committees, DSMBs, IRBs, or regulatory authorities.

Program/Solicitation Overview

SURPASS is a five-year program divided into two stages:

ARPA-H intends to negotiate multiple Other Transaction agreements. Each Core Platform Team must establish a platform trial in a single disease area and must propose at least three drug or biologic intervention arms. At least two proposed interventions must not be approved for any indication, including at least one drug or biologic with no prior human data. Teams also should include at least two for profit drug or biologic sponsors, one of which must be a startup or small company.

The platform must use a Master Protocol capable of evaluating multiple simultaneous interventions and adding new interventions over time. It must be randomized and controlled, designed to share control information across arms where appropriate, and use a seamless design that supports each arm from first-in patient safety evaluation through preliminary efficacy evaluation. For an ultra-rare disease, the proposed design must encompass Phases 1, 2, and 3 and be capable of supporting registration, unless commercial drug supply makes that approach infeasible and the proposer explains the limitation and proposes an alternative.

Proposers may select any disease area if they demonstrate substantial unmet patient need, suitability for a self-sustaining adaptive platform, and ability to meet all program requirements. ARPA-H identifies neurodegenerative diseases as being of particular interest, while noting that teams in those areas must still demonstrate that the proposed platform can achieve its objectives within the program timeline.

Teams must establish a multi-site clinical network, open the first site by Year 2, and include at least six clinical sites by the end of the program. One site must hold the Master Protocol IND and Statistical Analysis Plan. The team must identify a lead platform operator with the expertise, infrastructure, authority, and long-term incentive to sustain a multi-sponsor platform after the program concludes; ARPA-H states that a disease expert clinical institution or comparable durable organization is preferred.

Continuation from Stage I to Stage II requires FDA authorization to proceed for both the platform Master Protocol IND and at least one investigational arm by the end of Stage I. ARPA-H states it will consider fully funding trial expenses associated with the first three intervention arms and may consider partial funding for the fourth and fifth arms. The agency does not anticipate funding intervention arms beyond the fifth.

Key Dates & Submission Timeline

• October 15, 2026, 12:00 to 1:00 p.m. ET: Informational webinar, online.
• November 2, 2026: Deadline for questions submitted to [email protected].
• November 6, 2026, 9:00 a.m. to 5:00 p.m. ET: Proposers’ Day, Day 1, offered in person in Washington, DC, and virtually.
• November 9, 2026, 9:00 a.m. to 12:00 p.m. ET: Proposers’ Day, Day 2, virtual.
• November 30, 2026, by 5:00 p.m. ET: Solution Summary due date and ISO closing date.
• January 22, 2027, by 5:00 p.m. ET: Estimated Solution Pitch Package due date.
• February 1 to 5, 2027: Estimated virtual Solution Pitches.

The estimated Pitch Package and Pitch dates are subject to confirmation in Solution Summary feedback letters. Questions must be submitted to [email protected]; ARPA-H plans to post answers to the program webpage rather than respond directly except when appropriate. Solution Summaries and Pitch Packages must be submitted through the ARPA-H Solutions site.

Funding Overview

ARPA-H anticipates making multiple Other Transaction agreements under SURPASS. The agency will select solutions for negotiation that it determines are most advantageous to the Government, considering innovation, feasibility, and scientific and technical merit in the context of the program requirements. Awards will be negotiated at reasonable prices.

The initial submission is a Solution Summary limited to four narrative pages, excluding the cover page, rough order of magnitude and basis of estimate, and references/citations. The narrative must address the proposed disease area, intervention arms, potential sponsors, patient population, platform trial design and conduct, related experience, innovations under all three technical areas, regulatory strategy, economic sustainability after SURPASS, and the reasons the solution is better than competitors’ approaches.

Teams invited to submit a Solution Pitch Package must provide a 21 slide or fewer pitch deck, Excel Gantt chart, preliminary Master Protocol with detailed adaptive design and statistical content, two-page description of in silico and AI models, Scope of Work, Cost Workbook, and, if applicable, an optional appendix of relevant regulatory documents that have been developed and shared with regulators.

Eligible proposers must initiate System for Award Management registration and possess a Unique Entity Identifier for a Solution Pitch Package to be considered conforming; active SAM registration is required for award eligibility. All responsible sources may submit, subject to the solicitation’s eligibility rules. Federally Funded Research and Development Centers and government entities are generally prohibited from participating as prime or subperformers, except in limited circumstances considered by ARPA-H.

Building a Reusable Clinical Development Platform

SURPASS positions platform trial infrastructure, simulation, continuous inference, and AI enabled operations as mutually dependent capabilities rather than separate technology demonstrations. For organizations with the requisite clinical, statistical, regulatory, modeling, operational, sponsor, and site network resources, the solicitation requires a proposal that demonstrates operational readiness as well as a credible path to sustained multi-sponsor use after ARPA-H support concludes.

As contractors and life sciences organizations assess SURPASS, the central capture task is to align the clinical platform, intervention arm strategy, governance model, FDA engagement plan, technical architecture, site network, and long-term sustainability case with the solicitation’s integrated performance expectations.