Introduction
The Foundation for the National Institutes of Health (FNIH) Biomarkers Consortium, founded in 2006, unites leaders from the National Institutes of Health (NIH), US Food and Drug Administration (FDA), Centers for Medicare & Medicaid Services, academia and more than 70 life sciences companies and nonprofit organizations to advance precompetitive initiatives (Supplementary Fig. 1). This public–private partnership has been instrumental in driving innovation and transforming how biomarkers and other decision-making tools are developed, validated and applied in clinical and regulatory settings — ultimately accelerating therapeutic development and improving patient care.
The Biomarkers Consortium is structured around four steering committees — cancer, inflammation and immunity, metabolic disorders and neuroscience — each charged with identifying unmet needs and driving high-impact projects. To date, these efforts have yielded more than 35 scientifically validated methods, materials or measures for use in clinical trials and patient care (Supplementary Table 1). Collectively, these initiatives have supported more than 20 new or expanded FDA drug approvals across multiple therapeutic areas, contributed to 10 FDA guidance documents and championed the FDA’s Innovative Science and Technology Approaches for New Drugs (ISTAND) Pilot Program.
Since a publication in this journal in 2019 on the impact of the Biomarkers Consortium1, the field has seen the rise of multi-component biomarker application, multiple FDA biomarker qualifications, artificial intelligence (AI)-driven discoveries and expanded use of real-world evidence (RWE). Nevertheless, considerable challenges remain in achieving the level of evidentiary rigour and regulatory alignment necessary for broad implementation in drug development and clinical practice.
Here, we illustrate the consortium’s contributions in advancing biomarkers that have supported drug approvals, informed safety monitoring and expanded scientific and clinical knowledge.
Biomarkers supporting drug approvals
The consortium’s impact on drug approvals includes the FDA’s acceptance of two biomarkers as surrogate endpoints: pathologic complete response (pCR) as part of the I‑SPY 2 master trial protocol and measurable residual disease (MRD) in acute lymphoblastic leukaemia (ALL)2,3.
The I‑SPY 2 trial, a master protocol aimed at advancing breast cancer drug development, stands out as a model of innovation. Conducted in the neoadjuvant setting for women with high-risk, locally advanced breast cancer, this study used a Bayesian adaptive platform model to match multiple investigational therapies to specific breast cancer subtypes through biomarker-driven stratification. A key breakthrough was that I-SPY 2 incorporated pCR as an early endpoint to predict long-term outcomes. The trial showed that achieving pCR correlates strongly with improved survival across disease subtypes, supporting its use as a surrogate endpoint. With the support of the consortium, this project informed two FDA guidance documents on master protocols (Supplementary Table 2).
The project on MRD in ALL not only standardized and validated key testing methodologies — flow cytometry and next-generation sequencing — but also helped establish MRD as a clinically meaningful endpoint that has informed regulatory decisions and guided treatment strategies for more than a decade. For example, MRD as an endpoint has supported multiple FDA approvals, including those for inotuzumab ozogamicin, tisagenlecleucel and blinatumomab. Blinatumomab specifically received accelerated approval for the treatment of MRD-positive ALL, with achievement of undetectable MRD serving as a key part of the evidence of efficacy, and later gained full approval based on confirmatory trials. With the FDA recognition of MRD’s clinical utility, the endpoint is expected to continue accelerating patient access to new therapies.
In infectious disease, the consortium contributed to the development of clinical endpoints for use in trials targeting bacterial infections. These efforts informed three FDA guidance documents (Supplementary Table 2) and played a role in drug approvals for conditions including acute bacterial skin and skin structure infections (ABSSSI), community-acquired bacterial pneumonia (CABP), hospital-acquired bacterial pneumonia and ventilator-associated bacterial pneumonia. The 2024 approval of ceftobiprole for ABSSSI and CABP is a recent example that highlights the downstream impact of tools driven by the consortium on regulatory decisions and patient access.
Safety biomarkers
The consortium’s Kidney Safety Biomarker Project Team and the Critical Path Institute’s Predictive Safety Testing Consortium Nephrotoxicity Working Group collaborated on the development and FDA qualification of a multi-component kidney safety biomarker. Since its qualification in 2008, the biomarker has been applied in more than 150 clinical studies. The successful development of this biomarker highlighted the importance of understanding the analytical, clinical, regulatory and statistical considerations of each component — both individually and collectively — of a multi-component biomarker. This collaborative effort, also involving the FDA, led to the development of a user guide to support its implementation in clinical trials.
Current projects
The consortium is addressing key challenges in validating and integrating emerging technologies, such as next-generation sequencing and AI, while navigating evolving policy developments that shape biomarker use and patient-centric decision-making. Emerging initiatives, such as the FDA’s focus on new approach methods for product testing, are providing further opportunities for nonclinical biomarker development. Current efforts span epigenomic, blood-based and digital biomarkers, while also addressing cross-cutting issues such as analytical validation in the context of AI, harmonization of assay platforms and development of multi-component biomarkers and surrogate endpoints. A few ongoing projects are highlighted below, with more examples provided in the Supplementary information.
Standardizing liquid biopsy assays in cancer. The consortium addressed variability in circulating tumour DNA (ctDNA) assays by creating well-characterized reference materials that enable cross-platform comparisons, support analytical validation, and equip regulators and sponsors with tools to harmonize ctDNA applications globally. As a result, this project has increased confidence in the clinical utility of ctDNA for applications such as treatment monitoring and early cancer detection. This work is summarized in a white paper by the International Liquid Biopsy Standardization Alliance4.
Bone mineral density (BMD) measured by low-dose X-ray imaging as a surrogate endpoint for trials of new anti-osteoporosis drugs. The Study to Advance BMD as a Regulatory Endpoint (SABRE) project assembled and analysed existing data (representing more than 150,000 participants from 52 osteoporosis clinical trials) and demonstrated a strong association between increased hip BMD and reduced fracture risk. These findings provided robust evidence that a change in BMD can reliably demonstrate the effectiveness of osteoporosis drugs used in clinical trials. With support from the American Society for Bone and Mineral Research, and the FDA, the investigators expanded the original study to seek formal approval for the surrogate endpoint through the FDA Biomarker Qualification Program. This is the first surrogate endpoint biomarker accepted into the programme, and it is currently under review by the FDA.
Non-invasive biomarkers of metabolic liver disease (NIMBLE). This project evaluated the diagnostic performance of five blood-based biomarker panels in an observational cohort with metabolic dysfunction-associated fatty liver disease. The NIMBLE project identified blood-based and imaging biomarkers that outperformed current standards, enabling diagnosis of patients at risk for progressing to cirrhosis, improving trial recruitment and potentially supporting future regulatory approvals. Data generated from NIMBLE, publicly shared through letters to the FDA and peer-reviewed publications, were helpful in developing FDA’s approach to the application of non-invasive tests in clinical trials for metabolic dysfunction-associated steatohepatitis.
Other impacts. FDA guidance documents informed in part by cross-sector initiatives, including the Biomarkers Consortium, have addressed emerging areas such as structural endpoints for osteoarthritis, validation strategies for digital health technologies and comprehensive frameworks for biomarker qualification (Supplementary Table 2). The consortium has convened numerous public workshops — several co-hosted with the FDA — designed to foster regulatory dialogue and incorporate lived patient experience. The convening function of the FNIH strengthens alignment between scientific progress and regulatory acceptance while providing a venue for shared learning and knowledge dissemination.
Outlook
The Biomarkers Consortium provides a neutral forum to generate rigorous data, establish best practices and accelerate regulatory alignment across therapeutic areas. With a portfolio of more than 200 peer-reviewed publications that have collectively received more than 11,000 citations, the consortium’s contributions to biomarker science and therapeutic development are substantial and enduring.
Looking ahead, priority areas include developing multi-component biomarkers that integrate multiple data streams, leveraging RWE and digital health technologies, increasing inclusion of representative populations, and pursuing regulatory acceptance of fit-for-purpose biomarkers and other decision-making tools. By remaining aligned with the FDA BEST (Biomarkers, EndpointS, and other Tools) framework and integrating patient-centred outcomes, the consortium will continue to serve as a catalyst for innovation, translating scientific advances into high-impact tools that guide diagnosis, treatment and decision-making — transforming what is possible in medicine while remaining grounded in what is essential: better outcomes for patients.
