FDA Quietly Ends a Major Risk-Management Program
FDA on April 13 ended the risk evaluation and mitigation strategy (REMS) program for erythropoiesis-stimulating agents (ESAs), a decision that caught some longtime users of the program off-guard.
At Ministry Saint Michael's Hospital, part of Ascension in Stevens Point, Wisconsin, a nurse's inability to look up a new prescriber's registration information at the REMS program's website was the first hint of change.
"That's when we noticed that the REMS program was no longer active," said Brook DesRivieres, director of pharmacy at the 50-bed hospital.
Known officially as the ESA APPRISE Oncology Program, the REMS program was approved in 2010 by FDA for two epoetin alfa products—Amgen's Epogen and Janssen's Procrit—and Amgen's darbepoetin alfa product, Aranesp.
The REMS plan was created to ensure that the benefits of the products exceed their risks when used as an alternative to red blood cell transfusion in cancer patients with anemia resulting from myelosuppressive therapy. The specific risks named in the REMS program were shortened overall survival time and an increased likelihood of tumor progression or recurrence in patients with cancer.
According to FDA, an assessment of the REMS program indicated that healthcare providers understand the risks and benefits of the products and are prescribing them in accordance with current clinical practice guidelines. The agency determined that continuing the REMS program offers no educational benefits beyond those provided in the products' labeling, which includes an FDA-required Medication Guide.
FDA attributed the improvements in prescribing largely to labeling revisions that predated the REMS program and a 2007 decision by the Centers for Medicare and Medicaid Services decision to limit reimbursement for ESAs when used for certain conditions unrelated to kidney disease.
Those actions, FDA stated, coincided with a decrease in the use of ESAs in patients undergoing cancer chemotherapy, an increase in the initiation of ESA therapy at a hemoglobin level of less than 10 g/dL, and an increase in the initiation of ESA therapy at dosages recommended in the products' labeling.
The ESA APPRISE Oncology Program included mandatory certification for prescribers and dispensers and other elements that FDA reserves for the most restrictive REMS programs.
"There were pharmacy components, prescriber components, supply chain components. It was a very robust program," DesRivieres said. "We spent a lot of time and resources complying with the program."
DesRivieres said her health system recently completed ESA REMS-related training and documentation for a newly opened cancer center but would not have done so had there been advance notice of the impending end of the REMS program.
Other than the decrease in administrative tasks, the ending of the program hasn't affected daily operations at the health system's outpatient cancer centers, DesRivieres said.
But at inpatient facilities, the end of the REMS program may cause complications.
Karen Whalen, drug information pharmacist at St. Joseph's Hospital Health Center in Syracuse, New York, said elements of the ESA REMS program are embedded in the inpatient electronic medical record (EMR) system.
"It's not so easy to turn the switch off," Whalen said.
One reason is that the REMS requirements applied to ESA use in patients undergoing cancer treatment but not other patients for whom ESAs are indicated.
"Our ordering process had extra layers in it to catch oncology patients," Whalen explained. "We have all kinds of patients at our hospital—oncology patients, nephrology patients, Jehovah's Witnesses. So our process had to address everybody."
Whalen said the pharmacy and therapeutics committee met about a week after the end of the REMS program and signed off on necessary changes to the order-entry process for ESAs. And a briefing for the purpose of getting the medical executive committee's expedited approval of those changes was in the works.
She said in late April that she planned to meet soon with an information technology colleague to discuss a time frame for completing necessary programming changes, which include altering order sets to allow pharmacists to process ESA requests the same way they manage orders for other medications.
Whalen said the hospital had struggled to comply with risk communication elements of the REMS program for "mixed oncology and nephrology patients" who had more than one indication for an ESA.
"We're happy not to deal with that now," she said.
But she noted that the elimination of the REMS program doesn't eliminate concerns about the appropriateness of ESA therapy for specific patients.
"The risk still exists. So we're just going to remind our prescribers that it's up to them to convey risks," Whalen said.
FDA similarly cautioned that the risks that the REMS program was intended to address remain and must factor into prescribing decisions.
[This news story appears in the June 1, 2017, issue of AJHP.]