Drugs

Complex Innovative Trial Designs Pilot Program

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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.

Goals of the CID Pilot Meeting Program

The CID Pilot 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 program, including trial designs for medical products that have not yet been approved by FDA.

Procedures and Submission Information

Under the CID 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. Meeting-granted and -denied decisions and notifications 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.

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

  1. Product name.
  2. Application number.
  3. Proposed indication(s) or context of product development.
  4. Background section that includes 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) should include several plausible hypothetical scenarios.
  10. Elements of the study design that the sponsor considers nondisclosable, 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 and a summarized list of next steps in the regulatory decision-making process along with any supporting data relevant to the discussion.

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:

  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 detailing the simulated type I error probability and power under various scenarios.
    4. 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.
  7. 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:

  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.

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.

For more information regarding a submission inquiry to CDER please use the subject line:
CID Pilot Meeting Program for CDER

For more information regarding a submission inquiry to CBER please use the subject line:
CID Pilot Meeting Program for CBER

Learn More about CID:

Adaptive Design Clinical Trials for Drugs and Biologics (PDF - 623KB)

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

 

Page Last Updated: 09/28/2018
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