Complex Innovative Trial Design Meeting Program

On this page

• Goals of the CID Paired Meeting Program
• Procedures and Submission Information
• Frequently Asked Questions
• Contact Us
• CID Paired Program Trial Design Case Studies
• Learn more about CID

As displayed in the Federal Register notice on October 20, 2022, FDA is continuing the Complex Innovative Trial Design (CID) Paired Meeting Program, originally established under PDUFA VI, to support the goal of facilitating and advancing the use of complex adaptive, Bayesian, and other novel clinical trial designs. The CID Paired Meeting Program fulfills a performance goal agreed to by the Prescription Drug User Fee Act (PDUFA) reauthorization for fiscal years (FYs) 2023-2027, known as PDUFA VII.

This paired meeting program offers sponsors whose meeting requests are granted the opportunity for increased interaction with FDA staff to discuss their proposed CID approach.

Meetings will be conducted by FDA’s Center for Drug Evaluation and Research (CDER) and Center for Biologics Evaluation and Research (CBER) during fiscal years 2023 to 2027. To promote innovation in this area, trial designs developed through the meeting program may be presented by FDA (e.g., in a guidance or public workshop) as case studies, including trial designs for medical products that have not yet been approved by FDA.

Advancing the Use of Complex Innovative Trial Designs (CID)

An introduction and overview of FDA’s CID Paired Meeting Program [Introduction Slides (PDF - 949 KB)]

Complex Innovative Trial Designs (CID) Paired Meeting Program Process

Learn about the CID Paired Meeting Program’s process and what to expect [Process Slides (PDF - 886 KB)]

Goals of the CID Paired Meeting Program

The CID Paired Meeting Program is designed to:

• Facilitate the use of CID approaches with emphasis in late-stage drug development.
• Promote innovation by allowing FDA to publicly discuss the trial designs accepted by the paired meeting program, including trial designs for medical products that have not yet been approved by FDA.

Procedures and Submission Information

CID Paired Meeting Program Quarterly meeting request submission deadlines
March 31	June 30	Sept. 30	Dec. 31

Applicants will be notified of eligibility to proceed to disclosure discussions within 45 days after submission deadlines.

Under the CID Paired Meeting Program, FDA will select 1-2 eligible and appropriate proposals per quarter each year (i.e. up to 8 per year). For each meeting request granted, FDA will conduct an initial meeting and a follow-up meeting on the same CID proposal. The second meeting will occur within approximately 90 days after receiving the briefing materials.

• Meeting requests should be submitted electronically to the relevant application (i.e., Pre-IND, IND) with “CID Program Meeting Request for CDER” (CDER applications) or “CID Program Meeting Request for CBER” (CBER applications) in the subject line.
• Review the information about providing regulatory submissions in electronic format.

Eligibility Criteria

• The sponsor must have a pre-investigational new drug (IND) application or IND number for the medical product(s) included in the CID meeting request with the intent of implementing the CID proposed in the meeting request.
• The trial is not a first-in-human study, and there is sufficient clinical information to inform the proposed CID.
• The sponsor and FDA are able to reach agreement on the trial design information to be publicly disclosed.

Selection for Participation

FDA welcomes submissions related to any eligible CID and will maintain the paired meeting program, selecting 1-2 eligible and appropriate proposals per quarter each year (i.e. up to 8 per year). 

FDA will select requests based on:

• Innovative features of the trial design, particularly if the innovation may provide advantages over alternative approaches. 
• Therapeutic need (i.e., therapies being developed for use in disease areas where there are no or limited treatment options).
• Priority will be given to trial designs for which analytically derived properties (e.g., type I error) may not be feasible and simulations are necessary to determine operating characteristics.
• Priority will also be given to proposed CIDs intended to provide substantial evidence of effectiveness to support regulatory approval of the medical product.

Submission Process

Sponsors may request to participate in the program on a rolling basis through June 30, 2027. Only those requests received by the last day of each quarter of the fiscal year will be considered for the following quarter. Proceeding to disclosure discussions notifications and meeting denied decisions will be made within 45 days after the quarterly closing date.

Meeting requests should be submitted electronically to the relevant application (i.e., Pre-IND, IND) with “CID Program Meeting Request for CDER” (CDER applications) or “CID Program Meeting Request for CBER” (CBER applications) in the subject line. Review the information about providing regulatory submissions in electronic format.

In addition, please send an email to CID.Meetings@fda.hhs.gov to provide notification that your CID meeting request application has been submitted to the program.

Content and Format of the Meeting Request

Include the following information in the meeting request (25 pages or less):

1. Product name.
2. Application number.
3. Proposed indication(s) or context of product development.
4. A background section that provides a brief history of the development program and the status of product development.
5. Trial objectives.
6. Brief rationale for the choice of the proposed CID.
7. Description of study design, including study schema with treatment arms, randomization strategy, and endpoints.
8. Key features of the statistical analysis plan including, but not limited to, the analyses, models, analysis population, approach to handling missing data, and decision criteria. These key features should include aspects of the design that may be modified and the corresponding rules for decisions, if adaptive.
9. Simulation plan, including the set of parameter configurations that will be used for the scenarios to be simulated and preliminary evaluation and discussion of design operating characteristics. Preliminary simulation results of the operating characteristics (e.g., type I error, power, etc.) should include several plausible hypothetical scenarios.
10. Elements of the study design that the sponsor considers non-disclosable, along with a rationale for exclusion.
11. A list of issues for discussion with FDA about the specific CID proposed approach for the applicable drug development program.

Disclosure

Within 45 days after the quarterly closing date, FDA will review the meeting requests, select up to two meeting requests each quarter to proceed to disclosure discussions, and notify sponsors of their status. Before FDA grants the initial meeting under the CID Paired Meeting Program, FDA and the sponsor must discuss and agree on the information that FDA may include in public case studies. The specific information to be disclosed will depend on the content of each CID proposal, but FDA intends to focus on information that is beneficial to advancing the use of CIDs, and those elements relevant to understanding of the CID and its potential use in a clinical trial intended to support regulatory approval. Generally, the Agency does not anticipate that the case studies will need to include information such as molecular structure, the sponsor’s name, product name, subject-level data, recruitment strategies, or a complete description of study eligibility criteria.  FDA does anticipate that the following information will generally be disclosed to facilitate discussion of the proposed CID:

Disclosure Categories:

1. Rationale for the selected design
2. Study design characteristics:
   1. Randomization
   2. Blinding
   3. Study schema
   4. Study endpoints
   5. Target population
   6. Sample size determination, including assumptions
   7. Choice of controls (external/historical, concurrent)
   8. Estimand(s) of interest
   9. Adaptive elements, including aspects of the design that can be modified
3. Analysis plan:
   1. Model(s), including underlying assumptions and any prior distributions
   2. Null and alternative hypotheses
   3. Statistical test(s)
   4. Approaches to handle missing data and multiplicity
   5. Decision criteria throughout the trial, including rules for adaptive decisions
4. Simulations:
   1. Objectives and assumptions
   2. Scenarios, including parameter configurations and the rationale for parameter values considered, and hypothetical examples of trials for a given simulation scenario
   3. Simulation results, including operating characteristics such as Type I error probability, power, expected sample size/duration, and estimation properties
5. Data access plan components and any other approaches to minimize impacts on trial integrity imposed by the innovative design 
6. Any modifications or amendments to any of the above that occur during interactions about the proposed CID between Submitter and FDA

Content and Format of the Meeting Information Package

Sponsors whose meeting requests are granted as part of the paired meeting program should submit a meeting information package electronically no later than 30 days before the initial meeting. The follow-up meeting will occur within approximately 90 days after receiving the follow-up meeting briefing materials.

Sponsors whose meeting requests are granted as part of the program should submit a meeting information package electronically with “CID Paired Meeting Program Package for CDER” (CDER applications) or “CID Paired Meeting Program Package for CBER” (CBER applications) in the subject line. 

The initial meeting package should include the following information:

1. Product name.
2. Application number.
3. Proposed agenda, including estimated times needed for discussion of each agenda item.
4. List of questions for discussion, along with a brief summary of each question that explains the need or context for the question.
5. Detailed description of the statistical methodology, including, but not limited to, the analyses, models, analysis population, approach to handling missing data, and decision criteria.
6. Detailed simulation report that includes the following:
   1. Example trials in which a small number of hypothetical trials are described with different conclusions.
   2. Description of the set of parameter configurations used for the simulation scenarios, including a justification of the adequacy of the choices.
   3. Simulation results including operating characteristics such as type I error probability, power, expected sample size/duration, and estimation properties under various scenarios.
   4. Simulation code that is readable, is adequately commented on, and includes the random seeds. The code preferably should be written in widely used programming languages such as R or SAS to facilitate the simulation review.
   5. Overall conclusions, including a brief summary of the simulated operating characteristics based on the design features and analyses and a discussion of the utility of the CID given the simulation results.

The follow-up meeting package should include the following information:

1. Product name.
2. Application number.
3. Updated background section that includes a brief history of the development program and the status of product development and clinical data to date, if applicable.
4. Proposed agenda, including estimated times needed for discussion of each agenda item.
5. List of questions for discussion with a brief summary of each question that explains the need or context for the question.
6. Updated programs/shells for simulations, if applicable.
7. Summary of new information that is available to support discussions.

A meeting summary will be sent to the requester within 60 days of each meeting.

Submission Assistance

To make a submission inquiry to CDER or CBER, please send an email to CID.Meetings@fda.hhs.gov and use the appropriate subject line: “CID Paired Meeting Program for CDER” or “CID Paired Meeting Program for CBER.”

Frequently Asked Questions

Visit Complex Innovative Trial Design Paired Meeting Program Frequently Asked Questions for more information about the program.

Contact Us

For submission assistance and inquiries about the CID Paired Meeting Program, email: CID.Meetings@fda.hhs.gov.
This mailbox is monitored daily and replies will be sent within two business days of receipt.

CID Paired Program Trial Design Case Studies

The description of each CID Paired Meeting Program case study focuses on the single clinical trial design that was the subject of the submission. The description does not discuss other potentially important aspects of the development program for the respective drug or biologic, such as any plans to conduct additional adequate and well-controlled trial(s) and/or to obtain confirmatory evidence to help establish substantial evidence of effectiveness. Please refer to draft guidance Demonstrating Substantial Evidence of Effectiveness for Human Drug and Biological Products (December 2019).

• EMAS Case Study (PDF - 95 KB)
• Multiple Sclerosis Case Study (PDF - 121 KB)
• Master Protocol Case Study (PDF - 123 KB)
• Lupus Case Study (PDF - 126 KB)
• DLBCL Case Study (PDF - 99 KB)

Learn More about CID

FDA Guidance

• Master Protocols for Drug and Biological Product Development Guidance for Industry
• Guidance Snapshot: Master Protocols for Drug and Biological Product Development Guidance for Industry
• Guidance Recap Podcast Transcript: Master Protocols for Drug and Biological Product Development
• Guidance Recap Podcast: Master Protocols for Drug and Biological Product Development
• Adaptive Design Clinical Trials for Drugs and Biologics Guidance for Industry
• Interacting with FDA on Complex Innovative Trial Designs for Drugs and Biological Products 
• Guidance Snapshot: Interacting with FDA on Complex Innovative Trial Designs for Drugs and Biological Products Guidance for Industry  
• Guidance Recap Podcast: Interacting with FDA on Complex Innovative Trial Designs for Drugs and Biological Products Guidance for Industry

Publications

• The U.S. Food and Drug Administration's Complex Innovative Trial Design Pilot Meeting Program: Progress to date

Public Meetings

• Advancing the Use of Complex Innovative Designs in Clinical Trials: From Pilot to Practice
• Promoting the Use of Complex Innovative Designs in Clinical Trials

Other Communications

• Impact Story: A Flexible Clinical Trial Design Suitable for Emerging Disease Outbreaks
• FDA in Brief: FDA launches new pilot to advance innovative clinical trial designs as part of agency’s broader program to modernize drug development and promote innovation in drugs targeted to unmet needs