Frequently Asked Questions

1.  What is the NIH Common Fund?

The NIH Common Fund is a funding entity within NIH that supports bold scientific programs that catalyze discovery across all biomedical and behavioral research. These programs create a space where investigators and multiple NIH Institutes, Centers, and Offices collaborate on innovative research expected to address high priority challenges for NIH as a whole and make a broader impact in the scientific community.

2. What does the NIH Common Fund do?

• We make substantial investments in time-limited, goal-driven programs in order to change significantly the trajectory of biomedical research.
• Our programs accelerate emerging science, enhance the biomedical research workforce, remove research roadblocks, and support high-risk high-reward science in ways that no other entity is likely or able to do.
• We gather diverse input from NIH leadership, staff, and the broad biomedical research community to plan our programs.
• We assemble consortia of multidisciplinary, innovative researchers who collaborate to tackle a shared, ambitious goal.
• We manage our programs in partnership with nominated experts from the NIH Institutes and Centers
• We design our programs so that each deliverable will spur subsequent biomedical advances that otherwise would not be possible without our strategic investment.
• For more information on the Common Fund, visit: https://commonfund.nih.gov/about 

3. What are New Approach Methodologies (NAMs)?

NAMs are laboratory (in vitro and in chemico) or computer-based (in silico) research approaches intended to more accurately model human biology, and complement, or in some cases, replace traditional research models. NAMs provide alternative, and in some cases, more advanced methods of modeling human health and disease. NAMs, which broadly span in chemico, in vitro, and in silico approaches, have proven to be valuable tools in fundamental, translational, clinical, and toxicological research, and are being used to study human biology and in risk assessments for efficacy and toxicity of novel therapeutics. NAMs are sometimes referred to as Novel Alternative Methods or Non-Animal Methods.

4. What is the NIH Common Fund’s Complement Animal Research In Experimentation (Complement-ARIE) Program?

The NIH Common Fund’s Complement Animal Research In Experimentation (Complement-ARIE) program will accelerate the development, standardization, validation, and use of human-based New Approach Methodologies (NAMs).

NAMs are laboratory (in vitro and in chemico) or computer-based (in silico) research approaches intended to more accurately model human biology, and complement, or in some cases, replace traditional research models. The Complement-ARIE program will build upon ongoing efforts in the field related to NAMs, while identifying opportunities for innovation and coordination amongst the various collaborators.

Complement-ARIE will significantly advance understanding of human health and disease by providing a range of mature and/or validated and standardized biomedical research models. Developing these models will require multi-disciplinary expertise in disease research, personalized medicine, and in screening therapeutics for safety and effectiveness.

5. What is the goal of the Complement-ARIE Program?

The overall Complement-ARIE program goal is to catalyze the development, standardization, validation, and use of human-based NAMs that will transform fundamental, translational, and clinical sciences. The program goals include: 

• Better model and understand human health and disease outcomes across diverse populations. 
• Develop NAMs that provide insight into specific biological processes or disease states. 
• Validate mature NAMs to support regulatory use and standardization. 
• Complement traditional models and make biomedical research more efficient and effective. 

6. How did the NIH arrive at these scientific and operational needs to advance NAMs?

Common Fund strategic planning is undertaken regularly to identify research areas that address key roadblocks in biomedical research or that represent emerging scientific opportunities ripe for Common Fund investments. NAMs were identified as an area of research that would benefit from Common Fund investment for a variety of reasons:

• The past decade has seen dramatic advances in areas such as complex in vitro systems, bioengineering technologies, human data, and computational methods.
• Existing programs in the Common Fund Data Ecosystem and others represent a wealth of data to support and enable complementary NAMs.
• We are at a watershed moment in the history of drug discovery and development where the FDA Modernization Act 2.0 is a gamechanger in legislating that drugs may be registered without animal studies.

Simultaneous to early planning stages of the Complement-ARIE program, the NIH sought the assistance of the Advisory Committee to the Director (ACD) on catalyzing the development and use of Novel Alternative Methods to Advance Biomedical Research to identify areas in which the development and use of novel alternative methods will provide the most value to biomedical research. 

• The ACD working group recommendations are aligned with Complement-ARIE program goals and have been incorporated into the program planning structure.

7. What are major components for the Complement-ARIE Program and what are the goals of these components?

The Complement-ARIE Program consists of three major initiatives: 

• NAMs Comprehensive Technology Development Centers
• NAMs Data Hub and Coordinating Center (NDHCC)
• Validation and Qualification Network (VQN)

Complement-ARIE will also have a component on strategic engagement with key partners from other federal agencies including regulatory bodies, industry, non-profits, and other non-governmental organizations (NGOs) to advance emerging opportunities in development and use of NAMs in basic, translational, and clinical research.

The goal of the NAMs Comprehensive Technology Development Centers is:

• To stimulate the development of combinatorial NAMs to support the areas of greatest need, with emphasis on increased biological complexity and throughput, innovative combinatorial approaches, and data sharing according to FAIR principles. Training and outreach components will be required to facilitate dissemination, capacity building, and adoption.
• Components of Technology Development Centers
  • Integrated NAMs Technology Development
    • NAMs technology development
    • Technology pilot projects
  • Center Core Facilities
    • Administration
    • Data collection and bioinformatics
    • Resources
  • Technical Characterization
  • Training and Outreach
    • Workforce development and training
    • Community and collaborator engagement research
    • Ethical, Legal, and Social Implications (ELSI)

The goal of the NAMs Data Hub and Coordinating Center (NDHCC) is: 

• To create integrated data structures and a central data hub, establish standards for data reporting and model credibility, enhance the FAIRness (Findability, Accessibility, Interoperability, and Reusability) of NAMs-relevant data, develop strategies for interoperability and data reuse, build a searchable repository for New Approach Methodologies (NAMs), develop tools for data analytics, dissemination, and sharing, and foster community collaborations. 
• Facilitate NAMs data submissions from tech dev centers and other sources, including those coming from the VQN and partner organizations
• Establish common data elements:
  • Data standards and annotations
  • Data analyses and visualization tools
• Identification and integration of relevant preclinical and clinical datasets 
• Reference, training, and validation datasets

The goal of the Validation and Qualification Network (VQN) is: 

• To work with regulatory authorities, industry partners, and other collaborators to establish and apply validation/qualification frameworks and develop a framework to evaluate use cases from the technology development centers and the collaborator community that encourages adoption of NAMs for regulatory, industrial, and biomedical research use.
• Accelerate deployment and implementation of NAMs in both research and regulatory contexts.
• Develop standardized reporting and common data elements for preclinical, clinical, and safety performance.
• Perform conformity assessments and develop quality management systems.
• Work with collaborators for commercial market entrance and surveillance.

The goal of strategic engagement is: 

• To identify emerging gaps and opportunities, workforce development needs, (including training and community engagement) in the development of novel and/or combinatorial NAMs to catalyze the development, standardization, validation, and use of human-based NAMs through innovative technologies and partnerships. Strategic engagement activities will support programmatic gap areas and allow Complement-ARIE to dynamically respond to any emerging opportunities that surface throughout the duration of the program.    

8. How will the Complement-ARIE components interact with each other?

Program Flow Diagram: The diagram illustrates the key components of the Complement-ARIE program including technology development, centralized data resources, validation and qualification along with key training and dissemination activities to provide a fluid conduit from collaborator engagement to implementation.

9. How long will the program last?

The first phase of the Program was cleared at the January 2024 Council of Councils  for five years. If the first phase is successful, there will be a proposal for a second phase to be considered by the Council of Councils.

10. Where can I find more information?

Announcements and regular updates will be posted on the program website:  https://commonfund.nih.gov/complementarie

11. Who should I contact with questions?

• General inquiries can be sent to [email protected]. Scientific and Research contacts for individual Notice of Funding Opportunity (NOFO) are indicated in each announcement. These individuals should be your first contact for questions related to the NOFO. 
• In addition, the Common Fund Complement-ARIE Program is administered via a team of NIH program experts. The NIH Complement-ARIE Program Working Group members and their affiliations are listed at: https://commonfund.nih.gov/complementarie/members
• You can also sign up for the Complement-ARIE listserv to stay up to date on future announcements.

12. What type of NAMs will Complement-ARIE support?

Complement-ARIE will support the development, standardization, and validation of NAMs in the following categories:

• Complex in vitro models, such as microphysiological systems (MPS), organoids and other advanced 3-D models using human-derived cells and tissues that emulate human organ structure, function and response to study both normal physiology and disease pathology.  
• In silico multi-scale systems simulating and modeling healthy/diseased individuals through approaches such as physiological-based pharmacokinetic (PBPK) modeling and digital twin approaches.
• In chemico cell-free systems capturing dynamic changes to assess chemical toxicity, chemical hazard and risk assessment, and inform adverse outcome pathways (AOP).
• Integrated findable, accessible, interoperable, and reusable (FAIR) datasets and artificial intelligence (AI)-engines to generate testable predictions (i.e., patient digital twin with tissue chips (MPS) and avatar approaches).
• Combinatorial approaches that combine two or more of the above approaches.