The medical community recently has raised concerns about the Food and Drug Administration’s (FDA’s) use of Risk Evaluation and Mitigation Strategy (REMS) to ensure the safe use of drugs.
Since 2008, if FDA believes a drug’s risks may outweigh its benefits, or that the drug potentially poses serious risks to patients, it mandates that the manufacturer develop a REMS. FDA instituted a REMS for erythropoeisis stimulating agents (ESAs) in February 2010.
In light of concerns that the REMS requirements are burdensome and may be a barrier to accessing needed drugs for some patients, FDA is taking a second look at the REMS program. The agency convened a public hearing on the issue in July. ASN Public Policy Board Chair Thomas Hostetter, MD, FASN, testified on behalf of the American Society of Nephrology.
Roughly 100 REMS exist, but the components of the REMS (such as Medication Guides or monitoring programs) vary by drug. As part of the REMS for ESAs, physicians must provide a five-page Medication Guide about ESAs to all patients receiving the medication—including patients with kidney disease—when an ESA is dispensed. Doctors who give ESAs to patients with cancer must, in addition, train and enroll in the ESA APPRISE (Assisting Providers and cancer Patients with Risk Information for the Safe use of ESAs) Oncology Program and document that they discussed the risks of ESAs with each patient prior to the initiation of each new course of ESA therapy.
Hostetter—who served on three panels at the FDA meeting—focused his remarks on the effect of REMS on patients on dialysis. While applauding the goals of REMS in promoting patient safety, Hostetter raised concerns about the Medication Guide’s current content balance and sensitivity level.
For example, the ESA Medication Guide begins with the question “What is the most important information I should know about Aranesp?” and the answer “Using Aranesp can lead to death or other serious side effects.” (See Figure 1). Many nephrologists are troubled that this strong introductory statement, followed by a detailed review of the risks of ESAs (with scant information on their benefits) may frighten patients away from a medication that is crucial to preserving their vitality and quality of life. Hostetter emphasized to FDA that REMS should present information on the benefits as well as the risks of therapies in a sensitive manner.
Excerpt from page one of ESA Medication Guide: therapeutic options
Citation: Kidney News 2, 9
The frequency of distribution and review of the Medication Guide with patients—once per month—may also be misguided for this patient population, Hostetter said. Unlike cancer patients, who are treated for a relatively short amount of time, dialysis patients will receive ESAs for the rest of their lives, or until they receive a transplant. Monthly review of the dangers of ESAs may not constitute the best use of time for patients or nephrologists and, over time, may create undue concern about the drugs among some patients.
Hostetter further emphasized that “REMS should be administered on a schedule that best facilitates patient attention to their content, depending on how often the drugs are administered or dosages changed.” A less frequent distribution schedule, such as biannually, may be more reasonable for the kidney disease population. Yet, recognizing the importance of dialog between nephrologists and their patients about ESAs, Hostetter said that in the dialysis environment, physicians (or qualified nurse practitioners and physician assistants), should be responsible for administering and reviewing REMS for ESA with patients.
“We are also concerned about how to evaluate the effectiveness of REMS in this group,” Hostetter said. It is important that FDA make sure this program is meaningful and effective, but efforts to evaluate the effectiveness of a REMS involving patients—such as a follow-up survey or phone call—should be respectfully designed, ensuring that evaluation efforts do not cause alarm. Patients should also be involved in development and evaluation of any REMS program, Hostetter said.
FDA has yet to finalize its guidance regarding REMS, but will take testimony presented at the July meeting into account. The agency has not proposed expanding the APPRISE program from the oncology to the nephrology arena. ASN will continue to monitor FDA’s activity in this area and advocate for decisions that promote informative, sensitive, and safety-conscious programs.
