FDA unveils draft guidance on REMS logic models

The US Food and Drug Administration (FDA) has released a draft guidance outlining the agency’s risk evaluation and mitigation strategy (REMS) logic model.

FDA described a REMS logic model as a framework recommended by the agency that is a “systematic, structured approach to the design, implementation, and evaluation of a REMS” with a goal of having the applicants’ goals, objectives, and strategies line up with intended outcomes. Examples of a REMS include a communication plan, a package insert for a patient, a medication guide, and technologies associated with packaging and safe disposal for a drug at risk of abuse or overdose. They noted the draft guidance does not focus on the relationship between REMS or risk management and the benefit-risk assessment for a drug, nor does it focus on when the use of a REMS is necessary to determine when the benefits of a drug outweigh its risks.

While various scientific frameworks exist and could be applied to REMS assessments, FDA said it chose a logic model for REMS program design and evaluation, citing the ability to create a road map for program development and exploring the relationship between key elements of a program in a single unifying framework as reasons for its adaptation. “Through creating a visual representation of the relationships between program inputs, activities, outputs, and outcomes, a logic model makes explicit the scientific evidence, assumptions, and underlying logic that support the program and the various processes behind it,” the agency wrote.

“Leveraging this type of systematic approach is a critical aspect to the success and effectiveness of programs,” they said in a Federal Register notice.

FDA’s REMS logic model consists of a design phase, implementation phase, and evaluation phase. “The REMS logic model, although described in sequential steps, is an iterative process that involves moving back and forth or toggling between steps and phases to address uncertainties, validating assumptions, incorporating new information, and refining the program,” FDA said.

The design phase is separated into two steps, which involves assessing the situational context and developing a clear program goal. These two steps have subtasks; the situational context step includes a risk assessment and care gap assessment, while the program goal has subtasks of setting goals and objectives and determining the level of prevention of the REMS. “The purpose of this phase is to identify the problem(s) associated with a serious risk that a REMS may be able to address and to determine what the REMS aims to achieve,” FDA wrote.

In the implementation phase, steps include identifying inputs, selecting activities, and identifying and developing outputs for the program. The input step of the implementation phase involves identifying the strategies and resources associated with the REMS. Subtasks for the activity step of the implementation phase includes organizing activities related to communication, mitigation, and surveillance. The program’s outputs include whether the strategies and activities of a program are being delivered, received, and reached as intended.

The evaluation phase assesses the short-term, long-term and impact of the program. Short-term and long-term program outcomes include those that affect knowledge, safe-use behavior, and risk characterization and/or mitigation. In the evaluation phase, a REMS should also examine the impact the program is having. “For a REMS, impact generally aligns with the health outcome or a serious adverse event the REMS intends to mitigate,” FDA wrote. “Applicants should propose measures for assessing the impact of the REMS in mitigating the risk in the postmarketing setting.”

FDA also highlighted the limitations of using a REMS logic model, noting that it is not static, is not a guarantee for delivering the intended result, and does not preclude other models or theories. “The REMS logic model is flexible and adaptive, and other theories and frameworks can be complementary and simultaneously incorporated into an applicant’s decision-making process,” they said.

The agency said it plans to release additional guidances for industry and staff on REMS design and REMS assessment.

Draft guidance

Federal Register notice

FDA unveils draft guidance on REMS logic models

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