FDA proposes master control trial guidance that goes beyond COVID-19

The US Food and Drug Administration (FDA) this week published a draft guidance on the use of master protocols in clinical trials of drugs and biologics research that replaces a pandemic-era guidance on the topic.

On 21 December, FDA published a draft guidance replacing its 2021 master protocol guidance, which was issued during the COVID-19 public health emergency (PHE) to facilitate the use of master protocol designs in certain studies to make them more efficient.

A master protocol study design allows the use of several substudies that may have different objectives, and in which researchers simultaneously evaluate multiple products or diseases and conditions. Following the expiration of the PHE declaration, FDA revised the 2021 guidance to enable it to remain in effect until it could issue the new draft guidance on the topic.

FDA said the 2021 guidance has been withdrawn following the publication of the draft guidance, which was mandated in the 2022 Food and Drug Omnibus Reform Act (FDORA).

“FDA is issuing this draft guidance because many of the issues addressed in the 2021 guidance arise outside the context of the COVID-19 PHE,” said FDA. “The recommendations in this draft guidance apply to a range of therapeutic areas, not just COVID-19.”

FDA also said that the guidance is more comprehensive with regards to the designs and analysis topics compared to the previous guidance. Specifically, the new guidance delves deeper into issues such as randomization in master protocol trials, considerations for control groups and how to address informed consent. It also gives more details on FDA’s thinking on trial oversight of such complex studies, data sharing, information dissemination and what to include in premarket application.

“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,” said FDA. “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.”

An umbrella trial is defined by FDA as a trial that is designed to evaluate multiple products to treat a single disease or condition. A platform trial evaluates multiple products to treat a single disease or condition on an ongoing basis where products being evaluated can be added or taken off the trial.

“Well-designed and -conducted trials using master protocols can accelerate drug development by maximizing the amount of information obtained from the research effort,” said FDA. “Compared with stand-alone trials under separate protocols, a master protocol may offer certain advantages by leveraging a shared control arm and other shared protocol elements (e.g., visit schedule, measurement procedures), shared infrastructure (e.g., network of clinical sites, central facilities, central randomization system, data management systems), and shared oversight (e.g., steering committee, data review committee).”

“At the same time, master protocols add elements of complexity, which can increase startup time and can lead to design challenges such as ensuring adequate blinding to treatment assignment,” the agency added. “Additionally, master protocols involving multiple stakeholders will require a high degree of coordination.”

Stakeholders can comment on the draft guidance on www.regulations.gov under docket no. FDA-2023-D-5259 until 20 February 2024.

Master protocol draft guidance

FDA proposes master control trial guidance that goes beyond COVID-19

Related topics

Recommended content

Welcome to the new RAPS Digital Experience