As noted in a previous UPDATE [here], on April 19, 2011 the U.S. Food and Drug Administration (FDA) announced requirements of their new Risk Evaluation and Mitigation Strategy (REMS) that will apply to all long-acting and extended-release (LA/ER) opioid medications. This multi-pronged program is intended to reduce the misprescribing, misuse, and abuse of opioid analgesics. However, as more details unfold, the Opioids-REMS initiative is looking much like a rather bold experiment with potentially confounding factors and unknown outcomes.
Manufacturers of the affected products have until August 17, 2011 to submit their proposed REMS plans to the FDA for approval. On May 16, 2011, manufacturers — who had banded together in an Industry Working Group, or IWG — met with the FDA to address questions from the group that had been submitted in advance of and during that meeting. Here are some of the meeting highlights that have just been released to the public…
- A first part of the Opioid-REMS program focuses on educating prescribers about proper pain management, patient selection and monitoring, and other aspects of opioid analgesic safety. The FDA is requiring manufacturers to work together in developing a framework of proposed educational content that will be approved by the FDA and serve as a “blueprint” for program creation.
- The blueprint will be turned over to independent, accredited continuing education providers for development of the final program and delivery to prescribers (in some fashion yet to be determined). Manufacturers will pay for all program costs and hire an independent auditor to select the education program providers.
- There will be no cost to opioid prescribers to receive the education and CME/CE credits. At this time, participation is voluntary; there is “no requirement that prescribers have completed this training before they write a prescription for a LA/ER opioid, or before such a drug is dispensed,” the FDA states.
- However, the FDA continues to seek legislation that would make prescriber education mandatory under the Controlled Substances Act (CSA) as a precondition for DEA registration. The agency further states: “If the voluntary program under the current REMS is found to be ineffective, FDA will also consider the possibility of developing a mandatory educational program or other measures under the Food and Drug Administration Amendments Act (FDAAA).”
Another way of stating this is that, if prescribers choose not to voluntarily participate, ways will be found to make them do so if they want to prescribe LA/ER opioid analgesics; either as a requirement of DEA registration or by further actions of the FDA. [This is our interpretation.]
- Prescriber education is envisioned as a two part program: First, a general section covering LA/ER opioids as a class and, second, more specific sections or modules on individual drug products. Asked about participant time investment in such training, the FDA said it “expects the training to take at least a couple of hours,” but the length will depend on how the continuing education providers develop the program. [It seems unrealistic that 2 hours of training would be sufficient time for even a cursory overview of all key aspects of proper and safe opioid prescribing.]
- Another major aspect of REMS requires prescribers to improve patient awareness about how to use opioids safely. The FDA wants manufacturers to develop a single, patient education sheet to assist prescribers in counseling patients. The prescriber also would be able to write-in any necessary product-specific information on this sheet. [Note: such a single-page information sheet is already available – here – at our Opioids911-Safety program site.]
- Additionally, new Medication Guides will be developed containing standard information on LA/ER opioids overall and information specific for each product. Presumably, these documents will be distributed by prescribers and also by pharmacies, who will need to keep an inventory of opioid-product Medication Guides on hand.
- Finally, the FDA notes that it is working on developing two versions of a model Patient/Prescriber Agreement (PPA) for opioids that can be used as appropriate or necessary. [Apparently, routine use of a PPA will not be mandatory; however, once the PPA versions are published by the FDA these may become an implicit standard of care compelling their use by every practitioner.]
COMMENTARY: Without question, the FDA serves a vital role in helping to safeguard public health, and the need to stem increasing misuse, abuse, and overdoses of opioid analgesics is imperative. There has been somewhat of an uproar in the U.S. Congress about these issues, with various bills introduced during recent months seeking to address the problems.
Therefore, it seems likely that FDA officials are under considerable political pressure to quickly pursue the Opioid-REMS initiative, even though many portions are only vaguely conceived and the entire approach has qualities of a rather bold experiment. Outcomes, and potential unintended consequences, are largely unknown; hence, the FDA is insisting that manufacturers work together in devising a strong data gathering and assessment component.
One of the most intriguing aspects of the Opioid-REMS program is an expectation — actually, more of a mandate — by a government agency that competing, publicly owned, corporations must band together and work toward a common goal. Repeatedly, the FDA refers to establishing a single shared system for developing, implementing, and assessing the REMS, along with an administrative and cost-sharing mechanism for accomplishing this.
For this purpose, most, but not all, affected pharmaceutical manufacturers joined the above-mentioned IWG to address the FDA’s mandates. Under normal circumstances these same, competing organizations would avoid any and all contact with each other to avoid any semblance of collusion or antitrust violations; yet, the FDA is telling them that they must collaborate, with the unstated understanding that if they fail in their mission there could be future repercussions in terms of added regulations or unknown requirements that might impact their businesses in some fashion.
It seems apparent in the questions submitted to the FDA by the IWG that manufacturers are concerned that monitoring and assessment requirements of the REMS might involve divulging information that is normally considered confidential and proprietary. For example, data regarding the number of product prescriptions written, by whom, to which patients, for what purpose, etc, might be gathered and disclosed to the FDA and members of the group. The competitive sensitivity of such data does not appear to be of concern to the FDA, as evidenced in their responses.
Furthermore, there could be significant costs to manufacturers for the REMS and added paperwork, including possibly more reporting, required of healthcare providers. No doubt the added economic burden will be passed along to consumers, and the further, time-consuming bureaucratization of medical practice may be a disincentive for some healthcare providers to continue prescribing the Opioid-REMS products.
If this REMS “experiment” is successful, lives might be saved while preserving access to vital opioid analgesics. If it goes awry, millions of patients with chronic pain today and in the future may be victimized and suffer needlessly.