FDA: New logic model sets structured approach to REMS development

The US Food and Drug Administration’s (FDA) proposed risk evaluation and mitigation strategy (REMS) logic model is not meant to be a “cookie-cutter” approach for manufacturers to follow in designing their REMS programs. Instead, the model is meant to take a holistic and structured approach in evaluating a drug’s safety profile, said Gerald Dal Pan, the director of the Office of Surveillance and Epidemiology within the agency’s drug center, at a recent meeting sponsored by the Food and Drug Law Institute in Washington, DC.

At the meeting, industry representatives expressed their support for the REMS logic model, saying that it is outcome driven, formalizes the process and “shows the work” in developing a REMs. The REMS logic model was proposed in a draft guidance released earlier this month. (RELATED: FDA unveils draft guidance on REMS logic models, Regulatory Focus, 6 May 2024)

Examples of a REMS include a communication plan, a package insert for a patient, and a medication guide.

Dal Pan told the meeting that the logic model “is really exciting.” The model, he said, “is not a template, it is not a cookbook, it’s not a one size fits all where you plug things in. It’s a way of thinking about how to develop and implement and assess a REMS. I think lots of people have probably been doing parts of this either instinctively, intuitively, or deliberately, but this sets forth a structured approach on how to think about it.”

Del Pan said the model contains design, implementation, and evaluation elements. The design piece looks at REMS planning, the implementation process evaluates the process, and the evaluation phases looks at the outcomes.

For example, in the planning phase, sponsors can look at the context of the REMS and the risk they are evaluating. In this phase, the setting of care is evaluated and whether the drug will be administered in the ICU, operating room, or an outpatient setting. From there, sponsors evaluate what is in place to control the risk and whether something is missing in the setting of care for patients and practitioners.

Dal Pan said that once the planning phase is over, “You understand the situation in what you’re managing” the risk. The next step is to establish clear goals and objectives for the REMS and the level of care needed to control this. It could be primary prevention, secondary prevention, preventing the risk altogether, or tertiary prevention.

The implementation phase looks at the inputs, strategies and resources to manage the REMS. “Are you going to have communications or are going to have certain mitigation measures or are you going to have surveillance measures, things like that,” he said. “Given the goals and the context, which of these things do I need and what resources do I need to do that? Are the labs available and things like that.”

The outcomes stage, or the activities phase, looks at “what people actually do.”

Dal Pan noted that “the idea of the REMS logic model is to design the program holistically so that you can go from the risk characterization, from the planning all the way to the health outcomes.”

Before this model, many of the metrics used in REMS were primarily driven by “process metrics,” which evaluated how many letters were sent out and how many people registered for the REMS.

The industry representatives on the panel expressed their support for the logic model. Jamie Wilkins, senior director and head of the risk management center for excellence at Pfizer, said that “for those of us that touch and feel REMS every day, we were ecstatic to see this.”

She added that “everyone can sit and articulate a structure of a REMS, but this puts it to paper.”

Wilkins noted that the model gets away from process metrics and instead focuses on health outcomes. Pfizer was using the RE-AIM (Reach, Effectiveness, Adoption, Implementation, Maintenance) model, but plans to now switch to the REMS logic model.

Brian Malkin, the associate general counsel for regulatory law at Teva said the model puts into one place a set of best practices for developing a REMS.

“If you are a start-up company and you have never done a REMS, you have a lot of learning to do, this is a good starting place for that.”

Wilkins also discussed how the industry decided to form the REMS Industry Consortium (RIC) in September 2021 to discuss and establish a set of best practices for drugs that are subject to a REMS. She said the consortium was formed to an interest among industry to meet more frequently to address REMS practices.

“If you rewind back to 2018 there was one REMS meeting a year that happened in January where everyone that worked on REMS came together to talk as much as humanly possible in three days, and everyone left wanting to talk some more but there were antitrust concerns. From that hunger was born the RIC,” she said.

RIC currently has 25 companies participating and discussions are “devoid of antitrust concerns.” The meetings focus on conceptual matters related to REMs development. There are currently 69 active REMS programs for various medications.

FDA: New logic model sets structured approach to REMS development

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