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Regulatory Focus™ > News Articles > 2019 > 5 > Reassessing Benefit-Risk: FDA Preps for New Guidance

Reassessing Benefit-Risk: FDA Preps for New Guidance

Posted 16 May 2019 | By Zachary Brennan 

US Food and Drug Administration (FDA) and pharmaceutical industry experts gathered Thursday in Silver Spring, MD, to discuss how FDA assesses the benefits and risks of new drugs from the preclinical to postmarket phases.

The meeting was conducted as part of FDA preparations in drafting new guidance in FY 2020 on the benefit-risk assessment of new drugs and biologics.

Theresa Mullin, associate director for strategic initiatives at FDA’s Center for Drug Evaluation and Research (CDER), explained how the guidance will be an “articulation of our decision-making context” for benefit-risk assessments “throughout the lifecycle of a medical product.” She said the guidance will provide information to help companies communicate and submit data to FDA. And it will discuss how to more explicitly incorporate patient experience data that can be used to inform benefit-risk assessments.

Kerry Jo Lee, a medical advisor at FDA, also discussed new ideas that the agency is floating related to an updated integrated review template that FDA will use internally. She said fit-for-purpose testing is ongoing.



James Smith, a medical officer in CDER’s Office of New Drugs (OND), explained how much of the morning discussions at the meeting dealt with the common threads of early engagement between FDA and industry, incorporating the patient perspective and thinking about benefit-risk early in development.

He also explained how patient perspectives can be a double-edged sword, as there are situations where a patient can truly tell that a drug is having an effect, but, “We have plenty of examples of drugs where if you only looked at the treatment arm, with no control group, it would look like the drugs are working. An antidepressant is a classic example — often there’s a dramatic effect even in the placebo arm…but if every patient could truly tell if they were a responder or not, would we ever need controlled trials?”

Ellis Unger, director of the Office of Drug Evaluation-I in CDER, explained how FDA is “very interested in a patient coming in saying certain symptoms are worse and that can be used as an endpoint for certain trials, but we talk about it a lot and we don’t see it very often.”

Unger simplified the issue by dividing the world of benefit-risk into symptoms and harms.

“A lot of drugs approved to address symptoms but don’t address outcomes, and there are risks that are basically symptoms and others that are harms. If the benefit is a symptom and the risk is a symptom, we don’t really care…because we can put them in the label and patients and doctors can decide if they want to use them. If there’s a harm involved, that’s different, that’s not just a symptom,” Unger added.

He also later presented information on how to communicate benefits and risks.


“I can’t tell you how many times I see results expressed on a continuous scale where they don’t explain what the scale is or what the range is. If I told you there’s global warming on Mars and that average temperature is up .73 degrees on the Martian scale, you can’t interpret that,” he said.


Bob Temple, CDER's deputy center director for clinical science, also clarified that studies are often done based on mean results, where “you win if the mean result changes,” but “that’s not as informative as you’d like it to be. The distribution of results is more informative.” Unger also included a slide in his discussion to explain such an issue.


Meanwhile, Judith Zander, director of FDA’s Office of Pharmacovigilance and Epidemiology, further addressed in the afternoon sessions some of the postmarket considerations that FDA deals with.


Comments on the public docket to help inform the guidance can be submitted until 17 June.

Public Meeting: Characterizing FDA’s Approach to Benefit-Risk Assessment throughout the Medical Product Life Cycle


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