FDA Guide on Late-stage Safety Data Trials

FDA has released a guidance on “Determining the Extent of Safety Data Collection Needed in Late-Stage Premarket and Postapproval Clinical Investigations” to help sponsors understand how much safety data are needed from Phase 3 clinical trials, studies of new uses and  long-term outcomes. The document discusses a “selective approach” to safety data collection during late-stage premarket development or during the postapproval stage based on what is already known about a drug’s safety profile. It provides recommendations on “when to consider selective safety data collection and how to do so to maintain a balance between eliminating the collection of data that will not be useful and collecting sufficient data to allow adequate characterization of the safety profile of a drug,” according to the agency.

 

The guidance notes that some recommendations may not align with non-U.S. regulatory agency expectations, which it says may lead to difficulty in implementing this guidance in some clinical investigations. “However, we believe this guidance will give sponsors the flexibility to design and implement protocols with selective safety data collection where appropriate,” it says.

 

Because non-serious adverse events may have already been well-characterized through data collection in earlier clinical trials, the guidance says it may be appropriate to use a selective approach to safety data collection for these in late-stage trials. “For example,” it says, “if safety data already collected on hundreds of patients indicate that 17% reported a headache when on drug treatment compared with 10% on placebo, collection of similar data in thousands of additional patients in a large phase 3 trial would minimally refine this value and would require extensive resource utilization, while providing no important new information. In this situation, a limited collection of safety data may be appropriate.”

 

The document also says that in some cases, collecting data that do not contribute to better characterizing a drug’s safety profile may have negative consequences. “For example, there is growing interest in larger, simpler trials to obtain outcome data, data on long-term effects of drugs, and data on comparative effectiveness and safety,” it says. “Excessive safety data collection may (1) discourage the conduct of these types of trials by increasing the resources needed to perform them and (2) be a disincentive to investigator and patient participation in clinical trials.”