FDA Releases an Updated Guidance for Adaptive Trials
[Thursday, December 5, 2019]
Last week FDA released the final guidance document for adaptive trials for drugs and biologics and it contains mostly the same information as the previous guidance documents by the Agency on the topic with some small but critical recommendations. FDA expects the sponsors to include the statistical analysis plan, the Data Monitoring Committee (DMC) charter, and the Adaptation Committee (AC) charter along with the protocol, either included in the trial protocol or attached as separate documents; documents distinct from the clinical protocol are preferred for ease of review. The purpose of the above documents is that the FDA reviewers can evaluate (1) the rationale for the adaptive design, (2) the monitoring and adaptation plan including details of the planned interim analyses, (3) the role of the bodies such as DMC and AC involved in implementing the planned adaptation, and (4) the statistical methods and operational characteristics planned for the trial. Where simulations were used to justify the adaptive design, the FDA expects to see all aspects of the simulation provided with the clinical protocol as well. Detailed description of the processes followed to maintain data integrity at the planned interim analyses (IA) is also expected including information of the data management and statistical personnel involved in performing the IA and having access to results of the IA, and kind of information that will be disseminated after the IA. All processes are expected to be documented in detail. Similar information is expected in the marketing approval applications, particularly when the pivotal trials in support of a given market approval used adaptive design. FDA encourages sponsors to formal feedback prior to execution of adaptive trials via Type C meetings and Special Protocol Assessments. The new guidance document expands on well established practices for adaptive clinical trials that emphasize the importance of such trial design by the FDA. The document does not contain any new suggestions but would help list the key considerations for all developers of adaptive design trials.