Risk Evaluation and Mitigation Strategy (REMS)
3/23/2009
On March 3, 2009, the FDA met with representatives from companies that manufacture extended-release opioid medications to begin discussion about mapping out new strategies to minimize the risk of adverse drug events, such as an emerging trend of misuse or abuse, while maximizing safe use. This is a step to begin developing what’s expected to be a new, class-wide Risk Evaluation and Mitigation Strategy (REMS) program. The REMS program will have a direct affect on clinicians, pharmaceutical companies, and patients. The goal of REMS, broadly speaking, is to ensure that the benefits of certain products outweigh the risks: misuse, abuse, and overdose, both accidental and intentional. One of the key elements distinguishing REMS from the previous risk minimization action plans, called RiskMAPs, is the requirement for ongoing evaluation of the efficacy of a program, both by the FDA and the sponsor of the drug. This is so that adjustments can be made to ensure that risk-mitigation goals are being met.
So what will the new program look like? The devil, of course, is in the details. In a webinar on February 9th, 2009, John Jenkins, M.D., Director of the FDA's Office of New Drugs, stressed that the new REMS would be a "relatively massive” new program, and that developing it would entail gathering input from multiple stakeholders, including patient and consumer advocates, pain and treatment communities, and other health professionals. He declined, however, to speculate on the shape the final program might take, leaving plenty of unanswered questions. Will the FDA issue guidance for creating individual, product-specific REMS using an approach similar to past practices, or will the Agency require that companies work together to develop a single, class-wide REMS for all extended-release opioids? If, as some have suggested, the new program adopts some elements from the iPLEDGE program for the acne treatment isotretinoin to eliminate fetal exposure to the drug, how might this differ? While no one can answer these questions right now, it might help to look at the issue through the lens of the transition from RiskMAP to REMS. In the case of opioid medications, the FDA has concluded that strategies for minimizing risk – which have included the RiskMAP – need to be more effective. As the FDA has stated, “Despite these efforts, the rates of misuse and abuse, and of accidental overdose of opioids, have risen over the past decade.” Given iPLEDGE as a potential model for the new REMS program, raising the bar for efficacy of the program will likely mean companies working more closely with diverse constituencies to mitigate risk. That includes physicians, pharmacists, patients – everyone along the continuum of care. To ensure that every link in the chain is strong, companies must take a comprehensive, integrated approach. And to make sure that risk-mitigation goals will be met, companies must build in ways of continuously, scientifically measuring the relative success or failure of their efforts. In short, they must facilitate the FDA’s goal of monitoring and reducing risk on a “real-time” basis, to the degree that is possible, without denying opioid medications to appropriate patient populations. It would be difficult to overstate the enormity and complexity of the challenges that lie ahead for the companies that manufacture these medications. To develop a REMS that moves beyond yesterday's RiskMAPs companies need to figure out the best way to build on past strategies to address the diversion, misuse, and abuse problems that persist. Critically, they have to devise a strategy for measuring the impact of their initiatives over time. And, to meet requirements for compliance, they must act swiftly, potentially in cooperation with one another as well as the FDA, to complete the REMS on time and keep their products available to the public. There is now little doubt that the program will require: - Ongoing, opioid-specific training and possibly certification for clinicians and pharmacists
- A higher level of clinician vigilance than previously required
- Expanded use of doctor-patient opioid agreements
- Detailing the responsibilities of both clinician and patient
- Including review of the Medication Guide
- Information about the safe and appropriate use of opioid medications
- The dangers of sharing medications
- A plan that outlines continued monitoring of these initiatives to ensure that goals are being met
From a clinical perspective, these requirements have important implications. In designing a system for training clinicians, it’s critical that we avoid the unintended consequence of denying patients, en masse, the medications that may be most effective for treating their pain. To do that, we need to ensure that training is as cost-effective, convenient, and “friction-free” as possible.
History tells us that if an undue burden is placed on health care providers, clinicians may tend to migrate towards methods and treatment plans that do not interrupt workflow, don’t entail more paperwork, or require increased expenditure of time and money. In a society where more of us are living longer lives, and many with chronic pain, a poorly designed program, along with a perception of undue burden, runs the risk of lowering the quality of care, leading to under-treatment of pain and needless patient suffering. References |
