Risk Evaluation and Mitigation Strategies: FDA Guidances for Assessing Effectiveness
March 30, 2019
|Program outreach and communication||Measures of the extent to which the REMS materials reached the intended stakeholders.||Numbers of specific REMS materials that were distributed to, and the proportion of these that were subsequently opened or read by, the targeted audiences.|
|Program implementation and operations||Measures of the extent to which the intended stakeholders are participating in the program; how effectively the REMS program is being implemented, including the extent of use of REMS materials and compliance with REMS requirements; and any unintended consequences that could affect patient access or potential burden to the healthcare system related to the program operations.||Number of prescribers, health care settings, and/or pharmacies that have certified or undergone training in the REMS program; the number of contacts to the call center and a summary of the reason for the contact; number and results of audits of certified health care settings; and the number of shipments of the drug to non-certified settings.|
|Knowledge||Measures of the extent of stakeholders’ (e.g., patient/caregiver, prescriber, pharmacist) knowledge about the REMS-related risk or knowledge of any safe use conditions that are needed in order to mitigate the risk.||Stakeholder understanding of the risks and safe use of the drug; the draft guidance for industry “Survey Methodologies to Assess REMS Goals that Relate to Knowledge” provides further recommendations on using surveys to evaluate knowledge of REMS risks and safe use conditions.|
|Safe use behaviors||Measures of the extent to which safe use conditions are being adopted or followed (e.g., how often a required laboratory test is conducted prior to dispensing of the medication).||Evaluation of prescribing patterns and the proportion of patients who were counseled prior to initiating a drug, as evidenced by the use of a REMS material, such as a patient counseling tool or patient-provider agreement form.|
|Health outcomes and/or surrogates of health outcomes||Measures of the safety-related health outcome of interest (e.g., a reduction in the number of serious outcomes associated with a particular adverse event) or a surrogate of a health outcome (e.g., a reduction in the number or proportion of patients at greatest risk of an adverse event who are prescribed a drug).||Numbers and/or rates of a specific adverse event of interest such as rates of serious bleeds or severe neutropenia; surrogate metrics could include the number of inadvertent fetal exposures or the number of prevented fetal exposures to the teratogenic drug.|
One or more data sources may inform the different categories in a REMS Assessment Plan. Description and justification of the data source(s) and methodological approaches for assessing specific REMS goals and objectives should also be submitted to the FDA in support of the assessment plan. Some sources of data could include:
- Applicant’s REMS data
- Data may come from a database of certified/enrolled prescribers, dispensers, healthcare settings, distributors, or patients that may be required with the REMS.
- Drug utilization data
- If a drug utilization study is included in a REMS Assessment Plan, it should describe the source of the data, rationale for use of the data source, data collection methodology, design and analytical approaches, and any limitations.
- Postmarketing adverse event data
- Postmarketing adverse event data to be collected should be specified in the REMS Assessment Plan and focus on further characterizing the risk, capturing patient outcomes, and determining whether safe use conditions were met.
- Observational/epidemiology data
- This guidance does not recommend a specific pharmaco-epidemiology study design as FDA intends to exercise a flexible approach; however, any potential challenges and limitations should be clearly stated in the study proposal.
- Root cause analysis data
- FDA states that root cause analysis best practices consist of the development and use of a predefined protocol and a team-based reconstruction of each issue via retrospective review and interviews.
- Stakeholder outreach data
- The guidance states that data from key stakeholders, such as prescribers, pharmacists, other healthcare professionals, and patients can inform the applicant and FDA about the impact of the program on the healthcare delivery system, patient access to the drug, and opportunities for improvement.
Surveys are commonly used to evaluate provider and patient understanding of the serious risks associated with, and safe use of, the product.