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APS Bulletin • Volume 19, Number 3, 2009
President’s Message
Charles E. Inturrisi, PhD
Speaking for You: APS Develops and Promulgates REMS Position
In February 2009 the Food and Drug Administration (FDA) sent a letter to 18 manufacturers of certain extended release opioids and methadone indicating that Risk Evaluation and Mitigation Strategies (REMS) needed to be developed for these drugs to “ensure that the benefits of these drugs continue to outweigh the risks.” The risks as indicated by the FDA are misuse, abuse, addiction, and overdose deaths. In seeking REMS on these approved products, the FDA was exercising new authorities granted by Congress (FDAAA, 2007) which includes the power to remove a product from the market.
Months before, APS had become aware of the looming REMS issues through industry and FDA contacts. In May 2008 the FDA held a two-day meeting to obtain input from industry, healthcare providers, and patient advocates on REMS. Ed Michna, MD JD, chair of the Public Policy Committee, represented APS.
At the APS Mid-Year Board meeting in November 2008, the Board unanimously decided that APS should assume the role of patient/prescriber advocate. We committed ourselves to developing a position that struck a balance between the need to limit the risks associated with prescription opioid availability, and the possible unintended consequences of a REMS policy limiting access to opioids for patients who require these drugs as part of comprehensive pain management treatment. Board members David Craig, PharmD BCPS, and Greg Terman, MD PhD, agreed to prepare a REMs policy statement on behalf of APS. This statement was also intended to be the basis for a communication from APS to the FDA offering assistance and consultation on the REMS policy and its implementation.
The Pain Care Forum (a broad-based network representing patient advocates, nursing and physician associations, and medical institutes), of which APS is a member, prepared a position letter to be sent to the FDA concerning REMS and Drs. Craig and Terman both co-signed the Pain Care Forum letter and also sent a separate letter detailing the APS position.
In February 2009, just 4 days after the REMS letters were sent, the FDA sponsored a meeting discussing current regulatory processes for reviewing and approving opioid analgesics. Speakers at this meeting were largely federal agencies involved with opioid regulation and study (including the Drug Enforcement Administration, FDA, National Institute on Drug Abuse, and Substance Abuse and Mental Health Services Administration) and a number of individuals whose loved ones had been hurt by prescribed or diverted prescription opioids. APS was represented by Ed Michna and Greg Terman. That same week the APS/American Academy of Pain Medicine (AAPM) guidelines for opioid treatment for chronic noncancer pain were published in The Journal of Pain and copies of these guidelines were made available to the FDA in support of safe opioid prescription practices.
In May 2009 the FDA held a two-day meeting to obtain input from industry, healthcare providers, and patient advocate stakeholders concerning opioid REMS. Greg Terman gave testimony on behalf of APS highlighting five strong recommendations approved by the Board at the annual meeting earlier that month:
REMS should cover the entire class of opioid medications. Past experience has shown us that any attempt to regulate only a portion of the opioid class of medications will drive prescribers, users, and particularly misusers of these medications to other, less stringently regulated opioid medications, which may be less effective and in fact, pose greater addictive or toxicologic risks. Limiting REMs to certain opioids clearly will not significantly diminish opioid abuse or misuse and will almost certainly result in some patients not getting the medications that are most appropriate for their care.
There should be no registry requirements for patients using opioids included in the REMS. No evidence exists to suggest that a federal or state patient registry diminishes abuse or misuse of medications. Evidence does exist, however, showing that such an approach would stigmatize patients and impose significant burdens on all parties, resulting in stilted prescribing and, likely, inadequate pain management.
All implemented REMS components should be measurable and, when necessary, easily reversible. Whichever REMS elements are implemented should be designed so that they can be measured to determine their effectiveness in reducing opioid abuse, misuse, and overdose as well as their effects on appropriate access to opioids. APS provided specific recommendations—prepared by Aaron Gilson, MS MSSW PhD, and colleagues at the Board’s request—that identified metrics that could be used for assessing effects of any implemented REMS.
Demonstrated prescriber and dispenser knowledge concerning opioid pharmacology should be expected of all who seek DEA licensure as a component of REMS. It is appropriate that clinicians be required to demonstrate a requisite level of knowledge and competence that supports safe and effective prescribing or dispensing of opioids for therapeutic purposes. Steve Biddle, APS education director, Roger Fillingim, PhD, and the APS Education Advisory Committee (together with input from APS president-elect Seddon Savage, MD) developed an outline of an educational curriculum for prescribers and dispensers which could improve safe opioid treatment.
REMS education programs should be aimed at the public as well. Educating the public about the dangers of sharing opioid prescription drugs and other drug abuse behaviors should be implemented to reduce diversion. Public education— particularly targeted to the youth—should facilitate recognition of the urgent need for healthcare treatment for excessive sedation after opioid use. APS has also been working on the problem of proper and legal disposal of opioids no longer required by the patient.
These points are more fully clarified in documentation submitted to the official FDA docket (public docket 2009-N-0143) concerning opioid REMS during the summer. Unfortunately, the recently approved REMS accompanying the new opioid products Onsolis and Exalgo have largely ignored the REMS suggestions made by APS (and the rest of the Pain Care Forum) and will almost certainly lead to limited access to these drugs for patients in pain. This has led to an additional letter to the FDA reiterating our previous concerns and recommendations and a renewed vigor in monitoring each new action of the FDA concerning analgesic drugs.
APS recognizes the importance of the REMS issues to pain management and we will continue to implement a proactive approach that utilizes the multidisciplinary expertise of APS members to develop a policy that both informs the FDA and the public, provides solutions to some of the critical issues raised by REMs, and should allow the balanced response we all seek.
Thanks to Greg Terman for his helpful comments.
