Complex Innovative Trial Design Pilot Meeting Program
As displayed in the Federal Register notice on August 29, 2018, FDA is conducting a Complex Innovative Trial Design (CID) Pilot Meeting Program to support the goal of facilitating and advancing the use of complex adaptive, Bayesian, and other novel clinical trial designs. The CID Pilot Meeting Program fulfills a performance goal agreed to under PDUFA VI, included as part of the FDA Reauthorization Act of 2017.
This pilot 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 2019 to 2022. To promote innovation in this area, trial designs developed through the pilot 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.
Complex Innovative Trial Designs Brochure (PDF - 438KB)
Advancing the Use of Complex Innovative Trial Designs (CID): Introduction Slides (PDF-889KB)
Complex Innovative Trial Designs (CID) Pilot Meeting Program: Process Slides (PDF-723KB)
Goals of the CID Pilot Meeting Program
The CID Pilot Meeting Program is designed to:
- Facilitate the use of CID approaches in late-stage drug development.
- Promote innovation by allowing FDA to publicly discuss the trial designs considered through the pilot meeting program, including trial designs for medical products that have not yet been approved by FDA.
Procedures and Submission Information
CID Pilot Meeting Program Quarterly meeting request submission deadlines |
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March 31 | June 30 | Sept. 30 | Dec. 31 |
Applicants will be notified of eligibility to proceed to disclosure discussions approximately 45 days after submission deadlines.
Under the pilot meeting program, FDA will accept two primary meeting requests and two alternates per quarter. For each meeting request granted as part of the pilot, FDA will conduct an initial meeting and a follow-up meeting on the same CID and medical product within a span of approximately 120 days.
- The sponsor must have an Investigational New Drug (IND) or pre-IND number for the medical product in the CID proposal.
- The proposed CID is intended to provide substantial evidence of effectiveness to support regulatory approval of the medical product.
- 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.
FDA welcomes submissions related to any eligible CID. However, given that FDA expects to grant up to two meeting requests per quarter as part of the pilot program, FDA will select requests based on:
- Innovative features of the trial design, particularly whether the innovation may provide advantages over alternative approaches. Initial priority will be given to trial designs for which (1) analytically derived properties (e.g., type I error) may not be feasible and (2) simulations are necessary to determine operating characteristics.
- Therapeutic need (i.e., therapies being developed for use in disease areas where there are no or limited treatments).
Sponsors may request to participate in the program on a rolling basis through June 30, 2022. 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 Pilot Program Meeting Request for CDER” (CDER applications) or “CID Pilot Program Meeting Request for CBER” (CBER applications) in the subject line. Please review the information about providing regulatory submissions in electronic format.
In addition, please send an email to CID.Meetings@fda.hhs.gov providing notification your CID meeting request has been submitted to the relevant application.
Include the following information in the meeting request (25 pages or fewer):
- Product name.
- Application number.
- Proposed indication(s) or context of product development.
- Background section that includes a brief history of the development program and the status of product development.
- Trial objectives.
- Brief rationale for the choice of the proposed CID.
- Description of study design, including study schema with treatment arms, randomization strategy, and endpoints.
- 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.
- 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) should include several plausible hypothetical scenarios.
- Elements of the study design that the sponsor considers nondisclosable, along with a rationale for exclusion.
- A list of issues for discussion with FDA about the specific CID proposed approach for the applicable drug development program and a summarized list of next steps in the regulatory decision-making process along with any supporting data relevant to the discussion.
Within 45 days after the quarterly closing date, FDA will review the meeting requests, select up to four meeting requests each quarter (two primary and two alternates) to proceed to disclosure discussions, and notify sponsors of their status. Before FDA grants the initial meeting under the CID pilot 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 meeting request and associated CID. FDA intends to focus on information that is beneficial to advancing the use of CIDs, and those elements relevant to the understanding of the CID and its potential use in a clinical trial intended to support regulatory approval. FDA intends to include the following categories regarding the proposed CID in a disclosure agreement with sponsors before they can be accepted into the pilot program.
Disclosure Categories:
- Rationale for the selected design
- Study design characteristics:
- Randomization
- Blinding
- Study schema
- Study endpoints
- Target population
- Sample size determination, including assumptions
- Choice of controls (external/historical, concurrent)
- Estimand(s) of interest
- Adaptive elements, including aspects of the design that can be modified
- Analysis plan:
- Model(s), including underlying assumptions and any prior distributions
- Null and alternative hypotheses
- Statistical test(s)
- Approaches to handle missing data and multiplicity
- Decision criteria throughout the trial, including rules for adaptive decisions
- Simulations:
- Objectives and assumptions
- Scenarios, including parameter configurations and the rationale for parameter values considered, and hypothetical examples of trials for a given simulation scenario
- Simulation results, including operating characteristics such as Type I error probability, power, expected sample size/duration, and estimation properties
- Data access plan components and any other approaches to minimize impacts on trial integrity imposed by the innovative design
- Any modifications or amendments to any of the above that occur during interactions about the proposed CID between Submitter and FDA
Sponsors whose meeting requests are granted as part of the pilot program should submit a meeting information package electronically no later than 30 days before the initial meeting and no later than 90 days before the follow-up meeting. Include “CID Pilot Program Meeting Package for CDER” (CDER applications) or “CID Pilot Program Meeting Package for CBER” (CBER applications) in the subject line.
The initial meeting package should include the following information:
- Product name.
- Application number.
- Proposed agenda, including estimated times needed for discussion of each agenda item.
- List of questions for discussion, along with a brief summary of each question that explains the need or context for the question.
- Detailed description of the statistical methodology, including, but not limited to, the analyses, models, analysis population, approach to handling missing data, and decision criteria.
- Detailed simulation report that includes the following:
- Example trials in which a small number of hypothetical trials are described with different conclusions.
- Description of the set of parameter configurations used for the simulation scenarios, including a justification of the adequacy of the choices.
- Simulation results detailing the simulated type I error probability and power under various scenarios.
- Simulation code that is readable, is adequately commented on, and includes the random seeds. The code should be written in widely used programming languages such as R or SAS to facilitate the simulation review.
- Overall conclusions, including a brief summary of the simulated operating characteristics based on 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:
- Product name.
- Application number.
- 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.
- Proposed agenda, including estimated times needed for discussion of each agenda item.
- List of questions for discussion with a brief summary of each question that explains the need or context for the question.
- Updated programs/shells for simulations, if applicable.
- 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.
For more information regarding a submission inquiry to CDER please use the subject line:
“CID Pilot Meeting Program for CDER”
Frequently Asked Questions
Visit Complex Innovative Trial Design Pilot Meeting Program Frequently Asked Questions for more information about the program.
Contact Us
For submission assistance and inquiries about the CID Pilot Meeting Program, email: CID@fda.hhs.gov.
This mailbox is monitored daily and replies will be sent within two business days of receipt.
New! CID Pilot Program Trial Design Case Studies
The description of each CID Pilot Meeting Program case study focuses on the single clinical trial design that was the focus of the Pilot Program 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).
Learn More about CID
- New!Publication: The U.S. Food and Drug Administration's Complex Innovative Trial Design Pilot Meeting Program: Progress to date
- 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
- Impact Story: A Flexible Clinical Trial Design Suitable for Emerging Disease Outbreaks
- Adaptive Design Clinical Trials for Drugs and Biologics Guidance for Industry
- Public Meeting: Promoting the Use of Complex Innovative Designs in Clinical Trials
- 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
- Interacting with FDA on Complex Innovative Trial Designs for Drugs and Biological Products