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As discussed in our last blog, with advances in medical science and new data sources, study design complexity is on the rise. The US FDA continues to show interest and support for these new and innovative science and clinical trial designs, initiating programs and guidance to assist research organizations. This is the second of three blogs on the topic of Complex Innovative Trial Designs. You can read the first blog, “Complex Innovative Trial Design (CID) to Facilitate Innovation” here.

In the last quarter of 2019, the FDA issued two important documents relating to complex clinical trials:

  • Draft Guidance for Industry: Interacting with the FDA on Complex Innovative Trial Designs for Drugs and Biological Products, dated September 2019
  • Guidance for Industry: Adaptive Designs for Clinical Trials of Drugs and Biologics, dated November 2019

This blog will discuss the draft guidance for interacting with the agency and the final blog in the series will cover the November guidance for adaptive design trials.

Draft Guidance for Industry: Interacting with the FDA on Complex Innovative Trial Designs for Drugs and Biological Products

This document offers guidance to sponsors on how to interact with the agency regarding complex innovative trial designs (CID). It discusses the types of qualitative and quantitative information that sponsors should consider preparing for agency review. It also discusses how they can obtain feedback on complex simulation and modeling issues.

The guidance illustrates the agency’s willingness to consider novel clinical trial designs. In fact, it notes that they purposely don’t define CID because “what is considered innovative or novel can change over time.” The agency encourages early interactions through existing regulatory procedures (Type A, B, C meetings, IND amendments, pre-IND meetings). The guidance also references the CID Pilot Program that was announced in the Federal Register on August 29, 2018 and referenced in our previous blog.

In interacting with the agency, it is important to note that the increased complexity may require additional, in-depth discussions with relevant agency representatives. For example, extensive computer simulations, possible adaptations, and methods for ensuring trial integrity all require clear and effective communication. For a Bayesian CID, the FDA will be concerned about prior distribution and the study decision criteria for primary and secondary endpoints.

The guidance also notes Sequential Multiple Assignment Randomized Trials (SMARTs) as:

“A SMART is comprised of multiple intervention stages, and each stage corresponds to one of the critical decisions involved in the adaptive intervention. In a SMART, patients move along multiple stages and are randomly assigned to one of several treatment options at each stage.”

For this type of trial, the FDA will expect to discuss statistical questions/hypotheses, stages, and interventions. In some cases, flow diagrams may be useful to illustrate the patient pathway.

The guidance introduces a core set of common items that should be submitted to the agency to initiate discussion and planning. These include statistical analysis considerations, description of how the trial design fits into the larger development plan, adaptation plan, prior information, instruction for Data Monitoring committee and data access and integrity plan.

The key takeaways from this guidance are:

  • The FDA is encouraging innovative science and clinical trial design
  • There are multiple avenues (new and existing) for sponsors to seek input from the agency
  • Sponsors should be prepared for early and often communication to ensure success of their complex innovative design program.

As sponsors seek to implement complex innovative trial designs, they will require flexible technology solutions that reflect the same degree of innovation and enable them to swiftly adapt to the requirements of novel and evolving study designs. The iMednet unified platform is purpose-built to support varied trial designs with a simple and consistent user experience. Its broad functionality delivers capabilities for all study types and phases. Contact us to learn more or schedule a demo.