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  1. CDER Center for Clinical Trial Innovation (C3TI)

C3TI Demonstration Program Proposal Submission

CDER Center for Clinical Trial Innovation (C3TI)

Content and Format of the C3TI Demonstration Program Proposal

The C3TI Demonstration Program proposal should include the information below and not exceed 10 pages. The sponsor should indicate in their proposal if any items listed below do not pertain to their proposal. C3TI Demonstration Program proposals that do not adhere to these format and content requirements will not be considered.

If a proposal is accepted, the information provided in the proposal submission will be used as a basis for guiding subsequent steps and potential discussions.

Proposals should be submitted electronically to the relevant application (i.e., pre-IND, IND) with “C3TI Demonstration Program” and the name of the specific demonstration project (e.g., Bayesian Supplementary Analysis, Selective Safety Data Collection, Streamlined Trials Embedded into clinical Practice) in the subject line. Review the information that describes providing regulatory submissions in electronic format.

In addition, please send an email to CDERclinicaltrialinnovation@fda.hhs.gov providing notification that your proposal has been submitted to the relevant application.

  1. Product name
  2. pre-IND or IND Application Number
  3. Proposed indication(s) and context of product development (e.g., evidence generation for new or expanded labeling claim or to meet post-marketing requirement)
  4. Brief history of the development program, status of product development, and relevant summaries of pertinent information from prior trials.
  5. Timeline for trial conduct (e.g., target start and end date)
  6. A list of topics/questions for discussion with CDER staff, specifically regarding elements related to the applicable demonstration project, and a rationale explaining that additional communication or interactions with CDER staff would benefit trial design and implementation.
  7. Brief overview of whether the trial will be subject to review by other regulatory agencies and any other relevant details.
  8. Brief overview of trial design, conduct, and analysis methods. The information relevant to each demonstration project, regarding study design, data sources, and proposed analyses, is described below. Sponsors should decide what information to include that is most relevant to their proposal.

    Bayesian Supplementary Analysis (BSA) Demonstration Project

    • Proposed primary analysis plan: principal features of the statistical analysis plan, including the anticipated sample size and methods for analyzing primary and key secondary endpoints.
    • Proposed Bayesian supplementary analysis plan: methodology; prior distributions and supporting rationale; sensitivity analyses.

    Selective Safety Data Collection (SSDC) Demonstration Project

    • Summary of factors contributing to the sponsor’s conclusion that the safety profile of the drug is sufficiently characterized to justify selective safety data collection: mechanistic factors; clinical safety database; similarity of the planned clinical trial to previous trials; clinical pharmacology; non-clinical data; post-authorization data.
    • Proposed implementation of selective safety data collection: protocol; monitoring plan; statistical analysis plan.
    • If the proposed methods of safety data collection are not consistent for all participants in a trial or are not consistent throughout the duration of a trial: proposed methods for aggregating the data within the protocol and associated analysis plans.

    Relevant FDA guidance: E19 A Selective Approach to Safety Data Collection in Specific Late-Stage Pre-Approval or Post-Approval Clinical Trials

    Streamlined Trials Embedded into clinical Practice (STEP)​ Demonstration Project

    • Attributes of trial design that make it appropriate for this demonstration project: objectives; design architecture, including those elements that the sponsor considers to be pragmatic (e.g., broad eligibility criteria; setting for trial conduct in a healthcare setting; treatment of interest, comparator, and concomitant therapies; primary and key secondary endpoints).
    • Potential data sources: whether from trial-based procedures or other sources (e.g., electronic health records, medical claims, registries, and/or other); data reliability and relevance; additional data collection (e.g., linkage to other data sources).
    • Proposed primary analysis plan: anticipated sample size; analytic plan for primary and key secondary endpoints; definition of follow-up period; handling of intercurrent events, missing or misclassified data, and multiplicity, if applicable.
  9. Elements of the proposed trial design or analysis plan, as detailed in this proposal, the sponsor considers non-disclosable, along with a rationale for exclusion.  
    • If the proposal is accepted, details provided in the proposal will be considered for disclosure unless specified otherwise. Shared details would aim to reflect general principles and innovative aspects, while maintaining the necessary confidentiality of proprietary or sensitive information.
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