By Edward C. Li, PharmD, BCOP, Drugs and Biologics Editor
It is widely accepted that patients with cancer often experience chronic pain that must be managed with opioids. The National Comprehensive Cancer Network® (NCCN®) provides recommendations on the appropriate use of opioids in the management of cancer-related pain through the NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines™) Adult Cancer Pain. Unfortunately, the abuse of opioids is an increasing concern in the United States, and the US Food and Drug Administration (FDA) is placed in a difficult position of establishing regulations that minimize drug diversion while still allowing access to patients who require opioids for pain control. As part of a larger strategy to combat prescription drug abuse in the US, the FDA recently announced a plan to require a Risk Evaluation and Mitigation Strategy (REMS) for all long-acting opioids.
While oncology providers will agree that any additional requirements placed on them will increase the administrative burden of caring for patients, there is a silver lining to this situation. Rather than require the strictest mitigation strategy available (i.e., a restricted distribution system), the FDA decided to focus the REMS program on the education of opioid prescribers. Thus, the FDA is requiring that manufacturers of long-acting opioids do the following: 1) ensure that opioid prescribers receive education/training on opioids; 2) provide opioid prescribers with patient education materials that they can give to patients; and 3) communicate to opioid prescribers that their product has a REMS and therefore they need to undergo training.1
The content for the clinician education and training program must include specific information outlined by the FDA. Specifically, the education program must provide education about safe opioid prescribing, product specific information, and patient counseling points. Safe opioid prescribing points would focus on proper patient selection and assessment (e.g., determining abuse potential), pharmacokinetic considerations, and initiating and modifying the dosing of opioids (including concepts for how to convert from one opioid to another and titrate therapy). Examples of product specific information include the pharmacokinetic properties and product-specific toxicity information. Clinicians will also be educated on what patients should be told, such as adherence to the dosing regimen, reporting adverse events, discontinuation of the opioid, risks of sharing the drug, and proper storage and disposal. Of note, the education programs will discuss the use of "Patient-Provider Agreements," which is likely to be a contract between the patient and provider regarding terms to which both parties agree to adhere.1
It appears that the FDA established this class-wide REMS with some consideration of minimizing provider burden. For example, they are encouraging the use of a "single, shared system to implement the REMS for all members of the class." Additionally, the FDA explicitly states that opioid education/training should be conducted by "accredited, independent CME providers," likely enabling providers to obtain continuing education credit while undergoing this training.1 Of note, the standardization of REMS programs and utilizing CME providers as part of training programs are two recommendations provided by an NCCN REMS Work Group convened last year.
While it remains a certainty that the list of drugs requiring a REMS will continue to expand, it seems that the FDA has heard the concerns regarding provider burden by including some of the recommendations offered by NCCN and other groups into the design of the class-wide opioid REMS. Moving forward, questions still remain as to the details of this program, including how the "single, shared implementation system" for this class-wide REMS will look.
To aid oncology practitioners in staying current with REMS, NCCN maintains a REMS resource page. This resource page lists agents used in oncology care that have an FDA-approved REMS, including those used for active treatment and supportive care indications. This page is continually updated to reflect recent FDA approvals and REMS updates. For more information, please visit: www.nccn.org/rems.
1US Food and Drug Administration. Letter sent to Opioid Manufacturers Outlining Opioid REMS Implementation. Available at: http://www.fda.gov/downloads/Drugs/DrugSafety/InformationbyDrugClass/UCM251595.pdf. Accessed May 11, 2011.