FDA finalizes guidance on complex innovative trials designs
The US Food and Drug Administration (FDA) on Wednesday finalized guidance for sponsors on interacting with the agency on complex innovative trial designs (CID) for drugs and biologics.The nine-page final guidance comes just over a year after the draft version was released for comment and two years after the agency launched its CID pilot program. (RELATED: FDA launches pilot program in support of complex trial designs for drugs and biologics, Regulatory Focus 29 August 2018).
The aim of the CID program is to facilitate the use of novel and innovative trials, including complex adaptive and Bayesian designs that often feature simulation. FDA explains that “there is no fixed definition of CID because what is considered innovative or novel can change over time,” and that the guidance is intended to apply to trail designs “that have rarely or never been used to date to provide substantial evidence of effectiveness” in new drug applications (NDAs) or biologics license applications (BLAs).
While FDA’s CID pilot program is set to run through September 2022, the agency explains that sponsors may present and discuss CID proposals through existing pathways for interaction, though the pilot program offers sponsors the opportunity for additional meetings with FDA review staff and senior decision-makers.
“Novel clinical trial designs call for clear communication between sponsors and FDA on aspects of the design, including the purpose, execution, and operating characteristics (such as the chance of producing erroneous conclusions) of the design, and how the trial will be analyzed and presented,” FDA writes. While the guidance includes examples of trial designs, including study designs that formally borrow information or controls from previous studies and master protocols, FDA explains that determinations on the appropriateness of study designs for a given use will be made on a case-by-case basis.
“A CID proposal that may be appropriate for one product class in one indication may not be appropriate for another product class or in another indication,” FDA explains.
When it comes to discussing CID proposal with the agency, FDA says sponsors should generally stick to existing pathways for interaction, such as feedback on investigational new drug (IND) amendment submissions and Type B or Type C meetings. For early-phase studies with novel design elements, FDA says that pre-IND meetings could be an appropriate time to discuss a CID proposal. In any case, FDA says that sponsors should be considerate of the time available to review meeting packages and stick to topics that are relevant to the stage of development.
For proposals that feature “extensive computer simulations,” FDA says it may grant additional Type C meetings. FDA also encourages sponsors to explain how their CID proposal meshes with their overall development program and how it may improve the efficiency or generalizability of a study or its results versus a conventional clinical trial design.
The guidance goes on to provide recommendations for common elements to be included in CID proposals, recommended elements that should be included in proposals featuring Bayesian designs and examples of potential CIDs, including ones that were accepted to the CID pilot program.
FDA