Saturday, July 24, 2010

FDA Committee Nixes Sensible Opioid-REMS Plan

FDA LogoLate last week a special U.S. FDA Advisory Committee considered the agency’s proposed Risk Evaluation and Mitigation Strategy (REMS) intended to stem the tide of problems associated with extended-release opioid pain relievers. By a large majority, the committee turned down the FDA’s sensible plans, saying a broader approach and more rigorous restrictions are needed; however, the wisdom of the Committee’s decision at this time might be questioned.

After 2-days of hearings on July 23-24, 2010, the FDA’s Advisory Committee voted 25 to 10 in favor of rejecting the agency's proposed plan to help prevent inappropriate prescribing, misuse, and abuse of extended-release (ER) opioid analgesics, saying the plan is not rigorous enough to stem the "public health crisis" of opioid addiction, overdose, and death. We have previously discussed the opioid-REMS initiatives [here] and, prior to the meeting, the FDA released a new and sensible REMS that would require drug companies that make ER opioids to develop educational programs guiding physicians in patient selection, dosing, and monitoring. Prescribers also would be trained in counseling their patients on how to safely store and dispose of opioids, and manufacturers would provide FDA-approved information sheets for physicians to use in their interactions with patients, along with "medication guides" highlighting safe use of opioids to be dispensed with the drugs. [See the FDA’s REMS proposal document available here.]

Also in advance of the meeting, the Industry Working Group — or IWG; a consortium of companies manufacturing ER-opioid analgesics — had proposed their own plan, which was consistent with essential elements of the FDA’s REMS. The IWG went a step further by recommending practical ways for how the REMS would be communicated to the field and implemented, while assuring access to those vital medications for patients who would benefit.

Still, the Advisory Committee was in universal agreement that the proposed REMS plans fell short of what is needed. Even the 10 panelists who voted in favor of the REMS said the plan might not do much to stem the growing abuse and misuse problems, but they said it was at least a start. Committee members conceded that the FDA could only do so much to curb widespread drug misuse problems and this is beyond the FDA's primary mission of assuring that medications are reasonably safe and effective if used as indicated. Many of the members endorsed a statement calling for Congress to pass a law to urge other government agencies — including the Drug Enforcement Agency (DEA) — to work together in stemming the growing problems.

The Committee’s decision was a tremendous set back, following months of work by the FDA, IWG, and various stakeholder organizations. While the FDA is not mandated to accept the conclusions or recommendations of its Advisory Committees, the 71% majority opinion in this case, rejecting the proposed REMS, is certain to have an impact. At this time, future actions by the FDA are still to be determined.

FURTHER OBSERVATIONS: In our opinion, the plans presented to the Advisory Committee by the FDA and IWG represented plausible and practical steps forward in addressing the problems, all of which could be implemented within a reasonable period of time. The Committee had been expanded by 24 temporary voting members for this opioids-REMS meeting but only 9 of them were involved directly in pain management. Overall, a majority of the Committee members (19 of 35) were not actively engaged in pain care or anesthesiology clinical practice and merely one member represented patients' interests. Yet, there were many criticisms of the opioid-REMS proposals.

For one, some members said it would be inappropriate for drugmakers themselves, by supporting development of the educational programs, to tell physicians how to prescribe their drugs. Quoted in a MedPage Today report on the meeting, Jeffrey Kirsch, MD — chairman of the combined Anesthetic and Life Support Drugs Advisory Committee and Drug Safety and Risk Management Advisory Committee — said, "I think the committee would feel more comfortable if the FDA created the program" [Walker 2010]. However, this seems to completely disregard the fact that an independent third party was intended to develop the education programs and having the FDA do it instead would involve a government agency in dictating the practice of medicine and clearly goes beyond the FDA’s mission.

Furthermore, the Committee was concerned that there were no assurances that opioid prescribers would voluntarily participate in the available training. Some members favored linking practitioner DEA registration to completion of an opioid-training program, an approach that is beyond the current purview of the DEA and would require approval via act of Congress. In our opinion, ensuring appropriate practitioner training for opioid prescribing might be better suited for State Medical Licensing Boards rather than intrusion of the federal government.

One Committee member, Roland Gray, MD, observed that one reason opioid use is so prevalent is because of unscrupulous doctors who are quick to dole out these drugs: "They don't need a course in writing prescriptions, they need a course in ethics. If they don't have a conscience, we can't give them that" The FDA can only go so far, agreed John Jenkins, MD, director of the FDA's Office of New Drugs, during a post-meeting press conference: "The REMS cannot address the entire scope of the problem of prescription abuse and misuse" [Walker 2010]. Or, to express it another way, more government regulations alone cannot guarantee “good behavior” by practitioners, patients, or the general public.

Another problem Committee members had with the FDA's proposal was that it governs only extended-release opioids. The panel felt that the REMS should include immediate-release (IR) opioids as well. Indeed, according to FDA data, in 2009 there were roughly 23 million prescriptions for ER-opioids compared with 234 million for IR-opioids dispensed from outpatient retail pharmacies in the U.S. The IWG, along with many stakeholder organizations, had long argued that a class-wide REMS covering all opioid analgesics would be most appropriate; however, the FDA’s insistence on only addressing ER-opioids might have been a reasonable and manageable beginning that could be later expanded.

RESOURCE: Walker EP. FDA Panel Wants Tougher Restrictions on Opioids. MedPage Today. 2010(Jul 23) [available here].