In a letter to Senate Aging Committee Chairman Herb Kohl and Sen. Bob Corker on the Sunshine Act, the CME Coalition also highlights the role of CME in FDA’s Risk Evaluation Management Strategies (REMS). The letter notes that "the central component of the Opioid REMS program is an education program for prescribers (e.g., physicians, nurse practitioners, physician assistants) and patients... Under the Sunshine Act rules as proposed, however, funds given to CME providers to produce REMS-mandated CME would constitute a transfer of value and would have to be reported. This could be a huge disincentive to participate in a REMS program because many physicians would not want to appear on lists for attending such programs. Moreover, the publication of payments made by manufacturers to CME providers who are providing the FDA mandated REMS would suggest impropriety and brings into question the objectivity of the program, despite the fact that FDA has mandated the specific educational components." The full comments are available below.
As you are aware, the Food and Drug Administration Amendments Act of 2007 (FDAAA) created new section 505-1 of the Federal Food, Drug, and Cosmetic Act (FD&C Act), which authorizes FDA to require a risk evaluation and mitigation strategy (REMS) when necessary to ensure that the benefits of a drug outweigh the risks. FDA may now require REMS for any New Drug Application (NDA), Abbreviated New Drug Application (ANDA), or Biologic License Application (BLA) at any stage of the product lifecycle when the FDA determines that such a strategy is necessary to ensure that the benefits of the drug outweigh the risks.
Section 505-1 also authorizes FDA to require holders of covered applications approved without a REMS to submit a proposed REMS if the FDA becomes aware of new safety information as defined in 505-1(b)(3) and determines that such a strategy is necessary to ensure that the benefits of the drug outweigh the risks of the drug. Once the holder of an approved covered application is notified by FDA that a REMS is necessary, the holder must submit a proposed REMS within 120 days, or within such other reasonable time as FDA requires to protect the public health (section 505-1(a)(2)(B)). Once approved, the REMS create an enforceable obligation for the manufacturer and the FDA. Proposed REMS may contain any of the following elements:
· Medication Guide – Document written for patients highlighting important safety information about the drug; this document must be distributed by the pharmacist to every patient receiving the drug.
· Communication Plan – Plan to educate healthcare professionals on the safe and appropriate use of the drug and consists of tools and materials that will be disseminated to the appropriate stakeholders.
· Elements to Assure Safe Use (EASU) – These are strictly controlled systems or requirements put into place to enforce the appropriate use of a drug. Examples of EASUs include physician certification requirements in order to prescribe the drug, patient enrollment in a central registry, distribution of the drug restricted to certain specialty pharmacies, etc.
· Implementation Plan – A description of how certain EASUs will be implemented.
· Timetable for Submission of Assessments – The frequency of assessment of the REMS performance with regard to meeting the goal(s) and objective(s). FDA requires that assessments be conducted at 18 months, 3 years, and 7 years post-launch, at a minimum. Results of these evaluations must be reported to the FDA and will determine whether additional actions or modifications to the REMS program are required.
A drug’s REMS program may not require the provision of all the components above, as the specific components a REMS program employs will vary based on the severity of the risks, the population likely to be exposed, and other factors. Most common REMS only require the provision of a medication guide. While REMS components are not uniform, some do and will contain new provisions and requirements for physicians and other certified health care providers.
The strong connection between FDA, manufacturers and CME providers is clearly demonstrated by REMS. In fact, recently, FDA began requiring companies to fund CME for REMS education in long acting opioids. The central component of the Opioid REMS program is an education program for prescribers (e.g., physicians, nurse practitioners, physician assistants) and patients. The REMS notification letter expressed FDAʼs expectation that the training would be conducted by accredited, independent continuing education providers. FDA later elaborated its vision for prescriber education stating that it expected the CE training to be provided without cost to the healthcare professionals and that supporters would offer unrestricted grants to accredited CE providers to develop CE for the appropriate prescriber groups. FDA Commissioner Margaret A. Hamburg, M.D. asserted that, “the prescriber education component of this opioid REMS balances the need for continued access to these medications with stronger measures to reduce their risks.”
In the final Opioid REMS Blueprint, FDA provided an outline of the required prescriber education. The outline specified that the education must include information on weighing the risks and benefits of opioid therapy, choosing patients appropriately, managing and monitoring patients, and counseling patients on the safe use of these drugs. In addition, the education must include information on how to recognize evidence of, and the potential for, opioid misuse, abuse, and addiction. FDAʼs expectation is that the initial or basic REMS related CE that should be offered to all prescribers of long-acting and extended-release opioids should consist of a “core” content of about 2 to 3 hours.
Under the Sunshine Act rules as proposed, however, funds given to CME providers to produce REMS-mandated CME would constitute a transfer of value and would have to be reported. This could be a huge disincentive to participate in a REMS program because many physicians would not want to appear on lists for attending such programs. Moreover, the publication of payments made by manufacturers to CME providers who are providing the FDA mandated REMS would suggest impropriety and brings into question the objectivity of the program, despite the fact that FDA has mandated the specific educational components. However, concerns about improper influence or conflicts of interest in REMS programs should be misplaced, given the safeguards in place and the significant penalties companies can face. Failure to comply with FDA REMS can render the company’s drug misbranded. Penalties can range from $250,000 to$1 million cap per violation; $1 million to $10 million cap per proceeding.