C3TI Demonstration Program Frequently Asked Questions (FAQs)

General FAQs

1. What is the purpose of the Center for Drug Evaluation and Research (CDER) Center for Clinical Trial Innovation (C3TI) Demonstration Program?

• The C3TI Demonstration Program provides the opportunity to test, implement, and scale the integration of innovative approaches used in clinical trials through increased communication between CDER and selected sponsors in the pre-specified project areas.
• The program intends to support sponsors with timely, focused feedback from FDA review staff and subject matter experts as sponsors integrate innovative elements into trials intended to support new drug approvals or drug labeling changes.

2. Who can participate in the C3TI Demonstration Program?

• Sponsors planning clinical trials with innovative elements in one or more of the pre-specified project areas may be eligible to participate. The trial must be under an active pre-Investigational New Drug (IND) or IND for the product(s) included in the proposal and intended to support new drug approvals or changes to approved drug labeling.
• For eligibility criteria for each project area, please refer to the project-specific webpage:
  • Bayesian Statistical Analysis (BSA)
  • Selective Safety Data Collection (SSDC)
  • Streamlined Trials Embedded in clinical Practice (STEP)

3. Why should a sponsor participate?

• Participation in the program can support more efficient drug development by enabling earlier FDA engagement and feedback on key study design decisions and improve trial design and execution. Sponsors will receive feedback on the innovative elements of the clinical trial from CDER subject matter experts.

4. What project areas are included in the C3TI Demonstration Program?

• C3TI prioritizes three demonstration project areas, given their alignment with C3TI’s mission, their expected readiness of implementation and scalability, and their ability to generate case studies or best practices. The project areas are:
  • Bayesian Statistical Analysis – Aims to provide a structured opportunity to use Bayesian approaches for the pre-specified primary analysis, supplemental analysis, or monitoring of simple trials.
  • Selective Safety Data Collection – Aims to promote the adoption of SSDC principles into appropriate drug development programs.
  • Streamlined Trials Embedded in clinical Practice – Aims to promote the adoption of pragmatic design elements to integrate randomized trials into clinical practice.

5. What can a sponsor expect if their trial is accepted into the C3TI Demonstration Program?

• Sponsors of trials accepted into the program can expect to have enhanced communication and interaction with CDER staff, including review team members and relevant subject matter experts, to receive timely, focused feedback on the innovative trial elements.
• The nature and frequency of communication will vary based on the demonstration project area(s) and the specific innovations being applied. Typically, this will include a formal initial meeting to discuss the proposed trial and key design considerations, followed by a tailored engagement approach to support critical milestones such as protocol development and study start-up.
• Engagement may include an inspection process that is fit-for-purpose for the innovative design (i.e., focused on a quality-by-design approach).

6. Who from CDER is involved in the Demonstration Program?

• The review team responsible for the IND application, as well as subject matter experts and leaders from across CDER, are all involved in the Demonstration Program. Together, they assess proposals, participate in formal meetings, and provide feedback to sponsors. C3TI identifies and engages the appropriate subject matter experts and leaders from across CDER based on factors specific to each proposal, including the specific innovative trial approach being proposed.

7. Is the C3TI Demonstration Program limited to CDER products or would any products under other FDA Centers [e.g., Center for Biologics Evaluation and Research (CBER) or Center for Devices and Radiological Health (CDRH)] be eligible?

• C3TI and its Demonstration Program are CDER initiatives. For medical product development related to CBER, please visit Investigational New Drug Applications (INDs) for CBER-Regulated Products. For innovative medical device technology related to CDRH, please visit CDRH Innovation. More information about combination products (therapeutic and diagnostic products that combine drugs, devices, and/or biological products) is available here.

8. Are there opportunities to engage with C3TI outside of the C3TI Demonstration Program?

• Yes, C3TI offers unique opportunities for stakeholders to learn about clinical trial innovation. C3TI’s engagement activities are designed to build shared knowledge and advance the field of clinical trial innovation broadly.
  • Use C3TI Compass, C3TI’s knowledge management repository, which houses resources to support innovation in clinical trials in a streamlined, searchable platform. C3TI Compass connects users with FDA guidance documents, case studies, and other resources that support the implementation of innovative approaches in clinical trial design and conduct.
  • Subscribe to the C3TI newsletter for updates about clinical trial innovation at CDER and C3TI’s activities.
  • Ask for a C3TI expert to speak at a conference. To request a CDER employee to give a speech, make a presentation, or participate on a panel, meeting, or webinar related to clinical trial innovation, please submit a speaker request form.

Submitting a Demonstration Program Proposal

1. How can a sponsor determine if their trial is suited for C3TI’s Demonstration Program or another FDA program?

• Sponsors should review the project-specific pages on the C3TI Demonstration Program webpage, which include eligibility criteria for each project area. If a sponsor is unsure whether their trial is a good fit, they can reach out to CDERclinicaltrialinnovation@fda.hhs.gov.

2. What can a sponsor expect from the C3TI Demonstration Program proposal submission process?

• The C3TI Demonstration Program proposal submission process is designed to facilitate early engagement between sponsors and CDER staff. Here is an overview of what sponsors can expect:
  • Deciding to Submit: The first step is determining whether participation in the C3TI Demonstration Program is right for your trial. Sponsors should review the eligibility criteria for one or more project areas to confirm their planned trial may qualify. For eligibility criteria for each project area, please refer to the project-specific webpages:
    • Bayesian Statistical Analysis
    • Selective Safety Data Collection
    • Streamlined Trials Embedded in clinical Practice

If you have questions about the process or are unsure whether a trial falls within scope, reach out to cderclinicaltrialinnovation@fda.hhs.gov.

• Preparing Your Proposal: Information on the content and format of proposals, and instructions on how to submit, can be found on the C3TI Demonstration Program Proposal Submission webpage. Proposal content is intended to support early engagement, so a finalized protocol is not required at the time of submission, and proposals may be submitted at an early stage of planning.
• Deadlines for Submitting Your Proposal: Proposals are accepted on a rolling basis, meaning there is no set deadline for submission, and sponsors may submit at their discretion.
• After Proposal Submission: CDER staff will review the proposal and notify the sponsor of the decision (e.g., acceptance, denial) in writing within 60 days from submission. If accepted, in the acceptance correspondence, CDER will provide feedback on the innovative elements being proposed and the specific questions included in the sponsor’s proposal.

3. How will submitting a proposal potentially impact development timelines?

• The Demonstration Program is designed with development timelines in mind and may help sponsors identify clinical trial efficiencies. Proposals are accepted on a rolling basis, allowing sponsors to submit at the time that is most appropriate for their program. Sponsors receive a decision within an average of 60 days from proposal submission, and C3TI works to provide timely feedback throughout the program.

4. Why does FDA ask for a brief overview of whether the trial will be subject to review by other regulatory agencies in the proposal submission?

• FDA recognizes that many clinical trials are multi-regional. Understanding whether other regulatory authorities are involved and at what stage those discussions are helps FDA better contextualize the proposal.
• If it would be beneficial for FDA to engage with other regulators on the innovative elements in the trial, FDA is open to that dialogue where appropriate and where such avenues exist.
• To learn more about the proposal submission process for the C3TI Demonstration Program, visit C3TI Demonstration Program Proposal Submission.

5. What are the eligibility criteria for the C3TI Demonstration Program?

• The innovative elements should fit in one or more of the pre-specified project areas.
• The proposed trial must be under an active pre-Investigational New Drug (IND) or IND for the product(s) included in the proposal and intended to support new drug approvals or changes to approved drug labeling.
• The sponsor and FDA must be able to reach agreement on the trial design information to be publicly disclosed.
• Please see the Demonstration Program project-specific webpages for more information on specific eligibility criteria for each project area:
  • Bayesian Statistical Analysis
  • Selective Safety Data Collection
  • Streamlined Trials Embedded in clinical Practice
• To learn more about the proposal submission process for the C3TI Demonstration Program, visit C3TI Demonstration Program Proposal Submission.

6. What are disclosure requirements for participation?

• One goal of the Demonstration Program is to share lessons learned with the clinical trial community. Participating sponsors will receive a disclosure agreement clarifying what information will be considered for disclosure unless specified otherwise.
• Sponsors will be expected to share select details of their clinical trial innovations as these trials progress. This may include updates, lessons learned, and insights gathered during the trial.
• Shared details would aim to reflect general principles and innovative aspects while maintaining the necessary confidentiality of proprietary or sensitive information.
• To learn more about the proposal submission process for the C3TI Demonstration Program, visit C3TI Demonstration Program Proposal Submission.

7. Can the sponsor withdraw a proposal before or after it is accepted, or reapply if their proposal is not accepted?

• A sponsor can withdraw their proposal at any point in the process.
• Sponsors can reapply if their proposal was not accepted. Sponsors should carefully review the feedback provided on their initial proposal to understand why it was not accepted and address those considerations in their resubmission. Sponsors who intend to resubmit are encouraged to notify C3TI in advance via email.
• To learn more about the proposal submission process for the C3TI Demonstration Program, visit C3TI Demonstration Program Proposal Submission.

Proposal Review Process

1. Who reviews the submitted proposals?

• The review team responsible for the IND application to which the proposal is submitted, as well as relevant subject matter experts and leaders from across CDER, will review the proposal. C3TI identifies and engages the appropriate subject matter experts and leaders from across CDER based on factors specific to each proposal.

2. When will sponsors receive an FDA response on whether their proposal is accepted?

• The average response time is 60 days from proposal submission.

3. How will sponsors receive feedback on their proposal(s)?

• CDER staff will review the proposal and notify the sponsor of the decision (e.g., acceptance, denial) in writing within an average of 60 days from proposal submission. If accepted, in the acceptance correspondence, CDER will provide feedback on the innovative elements being proposed and the specific questions included in the sponsor’s proposal.
• To learn more about the proposal submission process for the C3TI Demonstration Program, visit C3TI Demonstration Program Proposal Submission.

4. Will a proposal be accepted if it is longer than 10 pages?

• Proposals should not exceed 10 pages. If you anticipate that the information required cannot fit within this page limit, please email C3TI prior to submitting your proposal. In your email, explain why the page limit cannot be met and provide an estimated number of additional pages anticipated and what information would require the extra space. C3TI will review your request and provide guidance before you submit.
• To learn more about the content and format of proposals for the C3TI Demonstration Program, visit C3TI Demonstration Program Proposal Submission.

Next Steps Following the Review Process

1. What can a sponsor expect if their proposal is accepted? What interactions can sponsors expect through Demonstration Program participation?

• Sponsors will receive a proposal acceptance letter outlining next steps along with preliminary feedback on their proposal.
• The nature and frequency of communication will vary based on the demonstration project area(s) and the specific innovations being applied. Typically, this will include a formal initial meeting to discuss the proposed trial and key design considerations, followed by a tailored engagement approach to support critical milestones such as protocol development and study start-up.
• CDER staff, including review team members and relevant subject matter experts, will participate in these discussions and provide timely feedback.