Accelerating Growth in REMS Programs a Challenge for Oncologists

Daniel Denvir

April 2011, Vol 2, No 2 - ACCC Conference

Addressing the 2011 Association of Community Cancer Centers annual meeting attendees, Timothy Tyler, PharmD, FCSHP, Director of Pharmacy Services at the Desert Regional Medical Center Comprehensive Cancer Center, Palm Springs, CA, outlined the considerable demands and complications that have been added to oncology care with the introduction of the Risk Evaluation and Mitigation Strategies (REMS) program for high-risk drugs. Many of these are cancer drugs, Dr Tyler said, and the US Food and Drug Administration (FDA) has much work to do to calm provider fears and confusion.

“REMS presents very significant challenges for a lot of stakeholders,” said Dr Tyler. “Providers in community cancer centers have a fair number of these drugs.” He participated in a National Comprehensive Cancer Network (NCCN) working group on REMS, which developed a white paper on increasing concerns in the oncology community, including:

  • Increased and nonreimbursed workload for physicians, pharmacists, and nurses
  • A misleading focus on risks, not balanced against a discussion of benefits
  • Lack of clarity and plain language in patient communication
  • Concern that onerous REMS programs could make it potentially less likely for a provider to prescribe a drug and limit legitimate off-label use.

The NCCN group, however, also recognized the potential for improved patient safety, citing examples in recent years of major problems with prescription drugs (eg, Vioxx), which is lending a sense of urgency to drug safety. The FDA may now require manufacturers to develop REMS for both existing and new drugs.

Risk a Familiar Face in Oncology
The oncology community is uniquely well positioned to mitigate risk, despite the widespread use of oncology drugs for off-label indications, he said.

“The basic concern was that for years we’ve had black box warnings, we’ve had contraindications,” said Dr Tyler. “In the oncology community, because we tend to go off label, the incorrect or correct assumption was that we’re not paying attention. I would say that because of the toxicities of the agents we’re dealing with, and the fragility of the patients, we tend to be a little more in tune than other populations.”

Nurses and pharmacists, for example, already use a double-check system when administering chemotherapy. The high toxicity of oncology drugs means that providers are already experienced in discussing risks with patients.

The most common REMS requirement is medication guides. Drugs that pose a high-risk level can be required to include a communication plan for providers. And oncology pharmacy directors are now inundated with these. “I get a stack of those a month,” he complained, but “how else do you communicate with the prescribing community?” Dr Tyler asked. In the most high-risk cases, an element to assure safe use (ETASU) can be required, which can mandate prescriber training, certification, or credentials.

Manufacturers or Providers?
There is also concern that although the FDA can only exercise control over manufacturers, it is the providers who will actually implement REMS in the clinical setting. “They don’t really have any sticks or carrots. They’re just trying to do what’s best by the product. Their biggest concern is having their drug withdrawn from the market, which is the FDA’s ultimate trump card,” Dr Tyler noted.

In 2010, an FDA panel decisively rejected proposed REMS for opioids, insisting on a more exacting standard that required training and not merely education. The panel was responding to growing concern about the widespread abuse of drugs such as Oxycontin.

“The biggest drug category that’s been looked at is opioids,” Dr Tyler pointed out. “We use opioids like candy in the oncology community. There are problems, but what’s the best way to solve them?”

A Staggering Growth
The number of drugs subject to REMS is growing rapidly, from 136 in September 2010 to 177 in March 2011, covering 113 unique entities (Table).

All 177 drugs required a medication guide, 43 required a communication plan, and 21 required an ETASU. Of those requiring an ETASU, 12 are used in the cancer center setting; 11 are of vital interest to oncology; and all except interferon are oral medications.

All REMS were created or have been modified over the past 18 months. An additional 46 drugs are related to hematology/oncology, 18 of which have a place in infusion centers, and 25 include antibiotics.

“If you’re involved in outpatient care, you could see up to 82 of these at the present moment. That’s kind of a staggering number,” Dr Tyler pointed out.

Traditional chemotherapy has yet to be subjected to REMS, but it is possible that it could. This would pose serious challenges to the oncology community. “It is an overwhelming force coming at you. And in the physician office setting and the hospital setting, they don’t have a lot of slack,” he said.

Dr Tyler cited a report saying that 33% of new molecular entities and biologic products approved by the FDA in the first half of 2010 had REMS required.

“All the paperwork we need to do is not reimbursable. We might end up doing a lot to comply with the REMS, but there’s no added revenue. And I may spend an extra 2 to 3 hours on a patient,” Dr Tyler noted.

Streamlining the Process
Electronic medical records and web technology could play an important role in streamlining REMS. “Efficiencies become ever more important,” he said, so “electronic records, electronic information, is certainly one of those areas that is making it potentially easier for us to be compliant.”

The NCCN working group recommended streamlining the process and ensuring that the burden does not become overwhelming, calling on the FDA and manufacturers to standardize risk categories and accompanying REMS, and to deliver that information through an online clearinghouse.

Dr Tyler reports that the FDA seemed to understand the problems during a 2010 meeting. He suggests, however, that Congress may ultimately need to consider amending the FDA Amendments Act.

“It is realistic to think that REMS can help,” Dr Tyler said. “But as the number and complexity of these things start to skyrocket, challenges of both prescribing and dispensing drugs are going to increase.”