Part 1: Overview and Assessment Design
Since March 2008, the U.S. FDA has taken action on its new authority under the FDAAA act requiring a Risk Evaluation and Mitigation Strategy (REMS) when necessary to ensure that the benefits of a drug outweigh the risks. A REMS Program falls into one or more of following three categories:
- Elements to Assure Safe Use (ETASUs)
- Health care professional communication plan
- Patient medication guide and patient package insert
The effectiveness of a REMS requiring a health care professional communication plan, patient medication guide, or patient package insert in mitigating drug risks will require a formal assessment. REMS assessment measures the effectiveness of the REMS tools and elements in achieving the goals of the REMS (mitigating drug risks). The FDA uses the word tool to describe a process or system designed to implement one or more REMS elements. In some cases, an element itself, such as a Medication Guide, may be viewed as a tool.
Designing a REMS Assessment
In designing and conducting a REMS assessment, the pharmaceutical industry faces several key challenges:
- What is an acceptable measurement instrument and will it be a reliable predictor of the REMS program performance?
- What are the acceptable and practical methods for stakeholder recruitment and assessment?
- What are the acceptable and practical methods for prescriber recruitment and assessment?
- What is an appropriate sample size?
- How is sample bias minimized?
- How will the data collected be used to predict the effectiveness of the REMS program and inform changes, if necessary?
When developing a REMS assessment protocol, it is essential to continually reexamine the objective of the assessment: that is, to measure program effectiveness of the REMS tools in achieving the goals of the REMS. For new drug applications deemed to require a REMS, the FDA will want the REMS assessment plan or protocol prior to approval. It also is preferable to submit the stakeholder assessment survey at that time. For approved drugs identified as needing a REMS, the timeline for protocol submission will be communicated by the FDA.
The measurement vehicle is most often a stakeholder survey or pharmacoepidemiologic study or both. In this article, I will be discussing REMS assessment survey considerations. The aim of the REMS assessment survey is to measure program effectiveness as defined by individual domains of interest relating to the REMS goals and the elements. Domains refer to statistical groupings of questions that comprise a specific measurement. An example of domains of interest for a patient medication guide assessment might include:
- Knowledge and understanding of key drug risks
- Knowledge and understanding of appropriate medication use
- Actions to be taken in the event of a drug related adverse event
- Distribution reach of the Medication Guide
For health care provider surveys, we may have a similar set of domains to measure effectiveness of a health care provider communication plan. With this in mind, let’s review specific techniques for developing and implementing a REMS assessment protocol, including:
- Description of the stakeholder sample
- Sample recruitment methods
- Rationale for the sample size
- Description of how sample bias will be minimized
- Statistical analysis and reporting metrics
- Performance targets
- The survey instrument
We will continue to examine the above protocol components in Part 2 of this feature article series