Overview

The Forum for Collaborative Research’s Data and Analysis Center (DAC) at the University of California Berkeley (UCB) School of Public Health (SPH) is a neutral venue for data sharing and analysis. Our mission is to advance clinical research by making secondary research data useful beyond its original purpose.

The Placebo Arm Database (PDB) is an integrated patient-level / participant-level database from completed phase 2 and phase 3 Metabolic Dysfunction-Associated Steatohepatitis (MASH) clinical trial studies. We aim to answer key scientific questions through the PDB to advance regulatory science by improving the quality, efficiency, and output of clinical trials to accelerate drug development.

Data sharing enables broader collaboration among sponsors, academic institutions, and regulatory agencies. This allows researchers to pool insights and validate findings across diverse trial populations. It reduces duplication of effort, maximizes existing clinical data value, and supports the development of more robust benchmarks and endpoints for trial design. Ultimately, data sharing fosters greater transparency, accelerates evidence generation, and strengthens the foundation for regulatory decision-making.

Regulatory Challenges

Despite recent improvements in the clinical development process, more than one-third of new drugs fail between Phase 3 and launch. Clinical trials for MASH face serious regulatory challenges: currently accepted surrogate endpoints are still histology based. Non-invasive biomarkers are in the qualification pipeline but not yet qualified. Additional challenges include recruiting patients into long-term clinical trials (e.g., competition for study participants in a rapid development space) and the rapid pace of development of non-invasive diagnostics to confirm disease status and entry/exclusion criteria.

Strategy

By pooling placebo arms from completed phase 2 and phase 3 MASH studies and by applying novel analytic methods, we can decrease the number of patients in placebo control arms, reduce the need to maintain patients in a placebo control arm long term, and establish a framework for biomarker identification and evaluation. Furthermore, regulators and industry members endorsed the formation of a “Pooled Placebo Arm Database” as a unique contribution complementing other types of observational cohorts, such as TARGET MASH (managed by TARGET Real-Word Evidence (RWE)) and MASH Clinical Research Network (MASH CRN). The PDB is distinctive in that it includes patients meeting specific inclusion/exclusion criteria, intensive follow-up, paired biopsy data, and standard plus investigational biomarkers.

Projected Benefits

By increasing the utility and analytical potential of individual and pooled datasets, the Forum anticipates that fewer patients will be needed to demonstrate efficacy in clinical trials. In economic terms, replacement or reduction in the size of a placebo arm conveys significant economic benefit. Estimated costs per patient in clinical trials range from $25,000 to $70,000, and in the MASH space, the cost can be considerably higher. Thus, eliminating even 100 patients from a clinical trial may save $2.5 to $7 million.

Partners

• Regulatory Agencies: Regulatory experts from these agencies will have input at each stage of discussion and project development:
        ○ United States Food and Drug Administration (US FDA), including
              ▪ Center for Drug Evaluation and Research (CDER): Division of Hepatology and
                Nutrition (DHN)
              ▪ Office of New Drugs (OND)
              ▪ Office of Translational Medicine (OTM)
              ▪ Center for Devices and Radiological Health (CDRH)
        ○ European Medicines Agency (EMA)
• Berkeley Center for Targeted Machine Learning and Causal Inference (CTML): The center brings the rigor and power of classical statistics together with advances in data mining and machine learning to accelerate the development and dissemination of causal inference methods. These can provide robust insight and evidence to help answer important public health questions.
• Industry: Participating Forum members will share data with the DAC through a standardized data transfer and use agreement (DTUA) from the University of California, Berkeley.
• Other groups: The PDB will collaborate with other relevant groups such as the Non-Invasive Biomarkers of Metabolic Liver Disease (NIMBLE in the USA) and the Liver Investigation: Testing Marker Utility in Steatohepatitis (LITMUS in Europe) consortia.

Leadership

The Forum’s PDB Project is led by its Steering Committee, consisting of an Executive Committee, industry partners who have contributed data, scientific experts, and the Forum’s DAC Leadership. The Executive Committee provides scientific leadership, general feedback on project development, sustainability, new directions, and help identifying areas of focus. The Steering Committee will review and approve research proposals and analyses requested by industry partners.

Neutrality and objectivity constitute foundational principles of the PDB Project. The Steering Committee will adhere to a collaborative process, with representation and active engagement of scientific experts from all stakeholder groups, including academia, industry, patient organizations, and regulatory agencies.

Database Security and Infrastructure

The PDB Project includes anonymized data, and it is housed on a secure platform, called the DAC Platform, that complies with the highest security standard (Protection Level 4, or P4) at UCB. The DAC Platform allows researchers to work with protected health information (PHI) and other data that are regulated by the Health Insurance Portability and Accountability Act (HIPAA), General Data Protection Regulation (GDPR), or similar data security standards. This P4 environment has security controls that far exceed those required for anonymized, de-identified, or limited datasets.

Access to all data from the PDB Project will be limited to those on the DAC Team who need to interact with the data for the Project. Regulatory agencies may be granted access to the database directly for purposes of their analyses as needed to inform regulatory processes.

Working Groups

Working groups carry out the work of the PDB Project by addressing priority areas identified by both the Executive Committee and Steering Committee project members. Expected outcomes of the working groups include recommendations, position papers, reports, peer-reviewed publications, and presentations at conferences to disseminate findings. Throughout the year, working groups communicate and collaborate by conference calls, email, in-person meetings, and workshops as needed. There is no minimum time requirement for participation; however, working group members are expected to be active participants and participate in as many calls and activities as possible.

Current working groups include:

1. MASH Placebo-Arm Working Group (co-Leads: Dr. Michael Cooreman and Dr. Manal Abdelmalek): This working group will further advance the field to answer key questions such as investigating the natural history, progression, and correlation of liver-related fibrosis and potentially clinical events of MASH.
2. Statistics & Analysis Working Group (Lead: Dr. Margot Yann): This group provides leadership within the Forum and the MASH PDB Project by applying, interpreting, and innovating statistical methodologies and machine learning techniques to address data challenges inherent in clinical trials and research. The group will focus on critical questions such as: How can we use statistical and machine learning methods to improve the design, execution, and analysis of MASH clinical trials? How can we apply these methods to better understand disease progression, treatment response, and patient stratification, particularly when linked to complex real-world data and the placebo arm database? How can these methods help identify patient subgroups that may benefit from specific interventions? The group will also work toward standardizing these advanced practices across different research initiatives and promoting transparency in reporting these methods. This group is composed of Forum statisticians and statisticians from the FDA, academia, and industry. Additional outputs of this working group will include annual closed-door statistical workshops.

Data Contribution/Sharing Opportunities

Please contact Alice Kang, DAC’s Senior Project Manager, at This e-mail address is being protected from spambots. You need JavaScript enabled to view it if you are interested in participating and contributing data to the MASH PDB Project.

Sponsorship Opportunities

Sponsorships are based on data and/or funding contributions. Please contact Jordan Cathey, Director of Business Operations and Development, at This e-mail address is being protected from spambots. You need JavaScript enabled to view it for information on how to become a sponsor.

 

 

References

1) Thompson, A., & Parekh, A. (2021). Value of Data Sharing to Advance Drug Development: A Regulatory Perspective. Therapeutic Innovation & Regulatory Science, 1-3.

2) Galson, S., Austin, C. P., Khandekar, E., Hudson, L. D., DiMasi, J. A., Califf, R., & Wagner, J. A. (2020). The failure to fail smartly. Nature reviews. Drug Discovery.

3) 2025 August: FDA accepted a letter of intent (LOI) to qualify Liver stiffness measurement by Vibration-Controlled Transient Elastography (VCTE) or Fibroscan as a reasonably likely surrogate endpoint.

4) 2025 December: FDA accepted LOI from Liver stiffness measurement by MRE as reasonable likely surrogate endpoint in non-cirrhotic MASH with F2 -F3 fibrosis.