Feb 1 -- The Food and Drug Administration (FDA or Agency) is announcing the availability of a draft guidance for industry entitled “Considerations for the Design and Conduct of Externally Controlled Trials for Drug and Biological Products.” FDA is issuing this draft guidance as part of a series of guidance documents under its Real-World Evidence (RWE) Program and to satisfy, in part, a mandate under the Federal Food, Drug, and Cosmetic Act (FD&C Act) to issue guidance about the use of RWE in regulatory decision-making. This draft guidance includes recommendations to sponsors and investigators considering the use of externally controlled trials to provide evidence of the safety and effectiveness of a drug product. The draft guidance also describes considerations related to communicating with FDA and ensuring access by the Agency to data from an externally controlled trial.
Submit either electronic or written comments on the draft guidance by May 2, 2023 to ensure that the Agency considers your comment on this draft guidance before it begins work on the final version of the guidance.
FDA is announcing the availability of a draft guidance for industry entitled “Considerations for the Design and Conduct of Externally Controlled Trials for Drug and Biological Products.” This draft guidance provides recommendations to sponsors and investigators considering the use of externally controlled trials to provide evidence of the safety and effectiveness of a drug product. In an externally controlled trial, outcomes in participants receiving the test treatment according to a protocol are compared to outcomes in a group of people external to the trial who had not received the same treatment.
The draft guidance addresses considerations for the design and analysis of externally controlled trials to study the effectiveness and safety of drugs, including discussion of threats to the validity of trial results from potential bias. Although various sources of data can serve as the control arm in an externally controlled trial, this draft guidance focuses on the use of patient-level data from other clinical trials or from real-world data (RWD) sources, such as registries as well as electronic health records and medical claims. The draft guidance also describes considerations related to communicating with FDA and ensuring access by the Agency to data from an externally controlled trial.
This draft guidance does not address other types of external controls, such as using summary-level estimates instead of patient-level data. This draft guidance does not discuss details of the design and analysis of a natural history study, nor the reliability and relevance of various sources of RWD that could be used in an externally controlled trial. Finally, this draft guidance also does not discuss considerations for using external control data to supplement a control arm in a traditional randomized controlled clinical trial.
This draft guidance is being issued consistent with FDA's good guidance practices regulation (21 CFR 10.115). The draft guidance, when finalized, will represent the current thinking of FDA on “Considerations for the Design and Conduct of Externally Controlled Trials for Drug and Biological Products.” It does not establish any rights for any person and is not binding on FDA or the public. You can use an alternative approach if it satisfies the requirements of the applicable statutes and regulations.
Draft Guidance:
https://www.fda.gov/regulatory-information/search-fda-guidance-documents/considerations-design-and-conduct-externally-controlled-trials-drug-and-biological-products
FRN:
https://www.federalregister.gov/d/2023-02094
