With the FDA extending the public comment period on the development of a Risk Evaluation and Mitigation Strategy (REMS) for opioid drug products until October 2010, there's still time for physicians, pharmacists, and patients to make their voices heard.
By Diana Pichardo
With the FDA extending the public comment period on the development of a Risk Evaluation and Mitigation Strategy (REMS) for opioid drug products until October 2010, there’s still time for physicians, pharmacists, and patients to make their voices heard.
REMS are just one incarnation of a decades-long government initiative to curb the misuse and abuse of prescription drugs, but it comes at a critical time when more and more prescription drug overdoses are being reported, the number of prescriptions for controlled substances is increasing, and more prescription drugs are ending up in the wrong, unintended hands, according to the Centers for Disease Control and Prevention. The medical use of opioids has increased 10-fold in the last 15 years. Today, the CDC reports that opioid analgesics are responsible for more unintentional overdose deaths than cocaine and heroin combined. The need for REMS is clearly warranted, but just what the program should entail has drawn opinion and comments from all stakeholders in pain medicine.
Drugs and REMS Programs
The debate centers on whether a class-wide REMS program should be put in place—specifically for schedule II opioids—or whether each opioid or drug should have its own REMS program. So far, the FDA has required drug manufacturers to put in place their own REMS before receiving approval for new products. Exalgo, Onsolis, and Lyrica are examples of drugs that have met approval. Each of the three have REMS that satisfy the three main components required by the FDA: patient education, prescriber education, and patient-adherence follow-up measures.
Exalgo: Comes with a medication guide that will be glued to the bottle and packaging and will also be available through its website; healthcare providers will be trained and receive an education program kit. The drug manufacturer Covidien will submit REMS assessments to the FDA every six months.
Onsolis: Uses FOCUS (Full Ongoing Commitment to User Safety) as its REMS program. FOCUS requires that Onsolis be made available only through a restricted distribution program with prescriber, pharmacy distributor, and patient enrollment. The program provides training and educational materials to prescribers and pharmacies, and is designed to educate patients and provide counseling.
Lyrica: Also comes with a medication guide that is either glued to the bottle or inserted in the folding carton; pharmacies will also distribute medication guides. Pfizer will submit REMS assessments to the FDA 18 months after its original approval, then again after three years and seven years.
According to Bob Rappaport, MD, director of the Division of Anesthesia, Analgesia, and Rheumatology Products for the FDA’s Center for Drug Evaluation and Research, the FDA’s focus in creating REMS has been to address the following concerns:
• There are untreated chronic pain patients
• The drug overdose death rate in the United States is increasing due to abuse and misuse
Rappaport discussed these issues during a presentation at the American Pain Society’s 29th Annual Scientific Conference, in Baltimore, MD. He mentioned that the FDA will soon release a “strawman REMS,” a class-wide REMS proposal, and will await public comment in July. Rappaport emphasized that addressing the issues of prescription drug abuse must be a joint effort among physicians, patients, and drug manufacturers. Maintaining a balance between curbing potential dangers associated with opioid prescription drugs and ensuring the drugs are made available to those in pain is the top goal, he said, but it is one that cannot solely be achieved by the FDA.
Creating this balance and assessing the risks and benefits is the issue that most concerns physicians and their patients when it comes to REMS, Rappaport said.
Life with REMS
For Gerald Aronoff, MD, DABPM, FAADEP, the FDA’s initiative to take action against misuse and abuse through the creation of REMS is admirable, but like many physicians, he is concerned with the potential complications, hindrances, and actual effectiveness of the program. “On the one hand, it’s one thing to say that the government agencies are going to be more involved in directing what physicians can and can’t do in medicine, but what we need to do is recognize that there are a lot of patients suffering with chronic pain and we don’t want to make prescribing these medications so onerous that physicians won’t want to prescribe the medications,” says Aronoff.
Aronoff, who serves as the medical director of Carolina Pain Associates in Charlotte, NC, is a fellow of both the American Academy of Disability Evaluating Physicians and the American College of Pain Medicine, and is board certified in pain medicine, forensic medicine, and psychiatry. Aronoff says he takes an integrated approach to medicine, emphasizing not only treating the physical ailments or symptoms of chronic pain patients, but also their psychological functioning, and overall quality of life. Prescribing opiates has become a big part of the treating of chronic pain, he says. Though certainly not the only component, it does have a significant impact on helping patients. Aronoff says he agrees with the American Academy of Pain Medicine’s position that there should be a class-wide REMS program, rather than individual programs. “It seems to me that we need a comprehensive opioid REMS program and not a bunch of individual programs,” he says. “It’s almost as if the way this is being handled is punitive because it is so onerous that the prescribers are less willing to prescribe them.”
Some of the complicated strategies, such as the REMS program for Onsolis, that also contain ETASU (Elements to Assure Safe Use), may create more conflict, Aronoff says. Because physicians only have a certain amount of time during each visit in which they must write prescriptions and evaluate patients, they’re going to probably opt for prescriptions that do not include a rigorous REMS program, he says. To avoid this problem, Aronoff says there should be better access to, and development of databases of, patientprescription information, as well as further research into developing abuse-deterrent opioid drugs.
Kathryn H. Keller, PharmD, CPE, says that so far, the effects on prescribing recently approved drugs that include REMS programs are not readily apparent; especially since all REMS are unique to the product. But it seems the stricter the program is, the more
burdensome it may be to prescribe. “For at least one of the newly approved, rapid-onset opioids, the fentanyl buccal film, the REMS has presented a significant impediment to access due to its complex requirements and limited sources,” she says.
However, it isn’t known whether this is due to prescribers’ aversion to the complicated process or just the unfamiliarity with the process, she says. “If you look at some of the established REMS programs for non-opioids, with multiple-step programs requiring a patient registry and input of laboratory test results, for example, there was an initial drop in use of the drug, followed by a return to usual usage as clinicians and patients became familiar with the requirements and understood their purpose,” she says.
Keller says she sees the REMS initiative as a mixed blessing. Complying with REMS reinforces the pharmacists’ duty to counsel his or her patients, but executing the additional safe use features of the programs increases the financial and time investment. Still, she says, the process is worthwhile. “In my experience, juggling the additional tasks and expense is becoming an even greater challenge, but the patient contact is personally and professionally rewarding.”
The debate goes on
A number of consulting firms have joined the mix, including REMS Group, Biotrak, and others, and offered suggestions for creating a successful REMS program. REMS Group, a research-based consultancy and training institute, helps clients develop REMS for their products. Its goal is “to help pharmaceutical and biotech manufacturers maximize the benefit of a REMS program for their customers and patients,” according to Gerard Maher, chief operating officer. Maher has worked on two REMS programs that contained ETASU. While each REMS program is unique to the specific product, Maher says there are a few considerations that REMS Group keeps in mind when creating specific programs:
• The impact of the program on the patients and the healthcare providers
• How the program would help in mitigating the risks, or potential risks, that prompted the FDA to require the REMS program
Maher says his clients are concerned with “the potential effect on product sales,” as well as placing further burden on the healthcare system. “REMS is adding greater uncertainty to the drug approval process and is also an issue any time new safety information is released on a marketed product,” Maher says. “We have seen a REMS, or even the prospect of a product getting a REMS with elements to assure safe use, put a lot of fear in an organization and frustrate healthcare professionals. We believe most of the fear and frustration comes from the unknown of what effect REMS may have on financial resources.”
In terms of creating individual REMS or a classwide REMS program, the REMS Group identified two issues that need to be considered. The first issue is whether the risks that triggered the REMS are the same across all agents in the class. The second issue is the complexity of the REMS program. If the risks are the same for all agents across the class and the REMS program contains ETASU, Maher says the company believes “it would overwhelm the healthcare delivery system if each manufacturer in a drug class had their own REMS.” If one REMS program is used across a class of drugs, the question of how fairly the burden of developing, implementing, managing, and assessing a REMS program can be distributed among each manufacturer in that class becomes an issue. “Another consideration,” Maher says, “is what effect a REMS program might have on smaller branded and generic organizations that don’t have the financial resources to develop and implement a REMS. Will REMS potentially keep some important drugs or cheaper drugs off the market?”
Like many of the groups involved, Maher says that his company believes the FDA’s effort to improve patient safety is laudable, but how effective it will be at doing so while minimally impacting healthcare delivery and not impeding patient access remains unknown. “I believe healthcare providers need to have a stronger voice and exert greater influence on the issue of REMS,” he says. “In the end, they are the ones who will be left to implement REMS and they are ultimately responsible for the care provided to patients.”