News Center

**INTRODUCTION **
This guidance document provides recommendations on the design and analysis of trials conducted under a master protocol as well as guidance on the submission of documentation to support regulatory review.

For the purpose of this guidance, FDA defines the following terms:

• Master protocol: a protocol designed with multiple substudies, which may have different objectives and involve coordinated efforts to evaluate one or more medical products in one or more diseases or conditions within the overall study structure.
• Substudy: the information and design features (e.g., objectives, design, methodology, statistical considerations) related to evaluation of a single medical product in a single disease, condition, or disease subtype in the master protocol.

Examples of trial types that could utilize a master protocol include the following:

• Umbrella trial: a trial designed to evaluate multiple medical products concurrently for a single disease or condition.
• Platform trial: a trial designed to evaluate multiple medical products for a disease or condition in an ongoing manner, with medical products entering or leaving the platform.
• Basket trial: a trial designed to evaluate a medical product for multiple diseases, conditions, or disease subtypes.

For the purpose of this guidance, the term master protocol sponsor refers to the person or organization who takes responsibility for and initiates the master protocol. In many instances individual drugs chosen for evaluation in the master protocol will also be evaluated under separate Investigational New Drug Applications (INDs) independent of the master protocol. A sponsor responsible for the investigation of an individual drug evaluated under the separate IND is referred to as the individual drug sponsor. The master protocol sponsor and the individual drug sponsor may or may not be the same entity. This guidance uses the term sponsor when providing general recommendations that may be relevant to both the master protocol sponsor and 49 individual drug sponsors.

The primary focus of this guidance is on randomized umbrella and platform trials that are intended to contribute to a demonstration of safety and substantial evidence of effectiveness of a drug. The concepts discussed may also be useful to consider for early-phase or exploratory umbrella and platform trials as well as those conducted to satisfy post-marketing commitments or requirements. The recommendations and considerations in this guidance do not apply to master protocols evaluating first-in-human drugs given the unique attributes from both a trial design and regulatory perspective that must be considered.

The considerations in this guidance apply to a range of therapeutic areas. Sponsors considering 60 master protocols in oncology should also consult Master Protocols: Efficient Clinical Trial Design Strategies To Expedite Development of Oncology Drugs and Biologics (March 2022).

Sponsors evaluating cellular and gene therapy products in early-phase development should consult the guidance for industry Studying Multiple Versions of Cellular or Gene Therapy Product in Early-Phase Clinical Trials (November 2022).

In general, FDA’s guidance documents do not establish legally enforceable responsibilities. Instead, guidances describe the Agency’s current thinking on a topic and should be viewed only as recommendations, unless specific regulatory or statutory requirements are cited. The use of the word should in Agency guidances means that something is suggested or recommended, but not required.

To continue reading this article please go to US FDA .