Comments on Standardization of Risk Evaluation and Mitigation Strategies

November 24, 2014

Division of Dockets Management (HFA-305)
Food and Drug Administration
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Comments of members of the Patient, Consumer, and Public Health Coalition on the draft report
Standardization of Risk Evaluation and Mitigation Strategies
Docket No. FDA-2013-N-0502

We are writing as members of the Patient, Consumer, and Public Health Coalition to comment on the draft report Standardization of Risk Evaluation and Mitigation Strategies. As part of its PDUFA V commitments, the Food and Drug Administration agreed in closed door meetings with industry “to explore greater standardization of REMS…with the aim of reducing the implementation burden of REMS for practitioners, patients, and others in various health care settings.”[1]

Several organizations that are members of the Coalition supported REMS as part of the Food and Drug Administration Amendments Act (FDAAA) of 2007 (PDUFA IV), although we were concerned that mitigation strategies might be insufficient to make up for approving drugs with substantial risks.  The draft report indicates that the FDA wants to maintain the lower standards for approval while also weakening the REMS.  This is not acceptable.

Standardizing the process must not weaken one of the primary purposes of REMS, which is “to ensure that the benefits of a drug or product outweigh its risks.”1  REMS are designed to allow patients to have access to drugs with serious risks that would otherwise be unavailable to them.[2]  The REMS restrictions—that some stakeholders now consider too burdensome—were part of the trade off as part of FDAAA to allow patients to have access to drugs that have serious risks: “The REMS authority enables FDA to approve, and patients to have access to, certain drugs whose risks would otherwise exceed their benefits and may not be approvable.”[3]  The FDA has also stated, “By their nature, all REMS impose some burden on the healthcare system.”3  It should also be noted that the report’s recommendations that would lessen burdens on industry and other stakeholders would increase the burdens on the FDA without providing needed resources and would increase burdens on patients to understand the implications for their own health of the risks shown in scientific studies.

In the report, the FDA has identified four priority projects regarding REMS standardization. Our comments on each of the four projects are below.


Project 1: Patient Benefit/Risk Information under REMS

Providing Patient Benefit/Risk Information by Improving Tools for Prescriber-to-Patient Counseling

The purpose of Project 1 is to improve the communication of “serious risks relative to benefits associated with drugs with REMS programs.” The FDA notes that stakeholders have stated that REMS “are seen as potentially deterring providers from prescribing, and patients from taking, drugs that may, on balance, be appropriate for them simply because the product has a REMS.”1 However, the report also notes that, “the burden of a REMS is often subjective (i.e., perceived or suspected), or based on anecdotal information.”  We do not believe there is credible scientific evidence to support the statement that REMS are deterring providers from prescribing drugs that are the best choices for patients.  The FDA should not make changes to the REMS program based on anecdotes but rather make decisions based on scientific evidence.  Moreover, we agree with the FDA’s assessment that “there are limitations… to which the Agency will be able to identify, standardize and enable the provision of specific benefit and risk counseling information to patients.”1


Project 2: Health Care Provider Education Under REMS

REMS and Continuing Education (CE) for Health Care Providers

Project 2 would examine “the feasibility of including REMS-related CE as part of the training module for NDAs and BLAs for single products.”

We have two major concerns with this project.  The FDA does not have the resources to develop and run a continuing education program for REMS. FDA notes that its “previous effort to develop and implement a class-wide REMS-based CE training module proved to be a lengthy and intensive process.”1 In this report, the FDA listed eight significant barriers to implementing a CE program including curriculum development, accreditation, and limitations found in the Federal Food Drug and Cosmetics Act. Unless user fees are increased to cover all of the costs of this program, we urge the FDA not to engage in this resource-intensive program.   And, we are particularly concerned with drug sponsors’ “desire to offer CE for individual drugs with REMS.”1 Pharmaceutical companies currently support the vast majority of CE programs, and as a result, these “educational” efforts are often more promotional than evidence based, and clearly biased because of conflicts-of-interest.


Project 3: Pharmacy Systems Under REMS

Standardizing REMS information for Inclusion into Pharmacy Systems Using Structured Product Labeling (SPL) under REMS

Using Structured Product Labeling (SPL) could address the alleged problems of “unclear and inconsistent REMS-related information,” since industry and FDA are both familiar with SPL. However, we want to see evidence or examples of unclear or inconsistent REMS information.  This report does not show us the scope of the problem.

Again, we are concerned that scarce FDA resources will be used to implement the SPL program. The Agency stated that it has “determined that the most efficient strategy is for FDA, rather than individual applicants, to index the information received in SPL.”[4] We want the FDA to specify how many FDA staff will be needed to develop and implement SPL for REMS. Moreover, because “SPL indexing elements are not intended to be used by clinicians in lieu of the full prescribing information,” we are concerned that SPL could end up being a shortcut used by prescribers that usurps REMS.  This would undercut the safeguards that REMS are supposed to provide to patients.  If the FDA decides to include REMS information in SPLs, it would be necessary for the FDA to establish a study and a monitoring system to determine how well (if at all) REMS materials are communicated through SPLs.  Again, it would be necessary to increase user fees to pay for this.


Project 4: Practice Settings Under REMS

Providing a Central Source of REMS Information for Practice Settings under REMS

We support the FDA enhancing its existing REMS Web page. Making the site more user-friendly and providing answers to frequently asked questions about REMS should be a priority. The Web page should also provide specific information restrictions that apply to REMS products (how they may be prescribed, dispensed or administered).  Again, any costs should be added to user fees.



The REMS program was established to make it possible for the FDA to approve drugs that were known to have high risks for some well-defined groups of patients.  Unfortunately, REMS have not been effective, and the proposed efforts to standardize and streamline REMS are likely to further weaken the program.  This report recommends changes to the REMS program based on anecdotal evidence and fails to address the need for additional resources to develop and implement a REMS CE program or implement an SPL program or even to update the FDA’s REMS Web site.

We agree with the report’s conclusion, which states that safety is “a core element of the FDA mission” and that REMS is “an essential tool in augmenting FDA’s drug safety capacities.”1  REMS was designed to be a bit of a burden to physicians and patients.  It was designed to make physicians and other stakeholders slow down and think twice to ensure that the benefits of a high-risk medication outweigh its risks.  The proposed changes would shift that burden to patients and to the FDA.


Annie Appleseed Project
Breast Cancer Action
Center for Medical Consumers
Connecticut Center for Patient Safety
Jacobs Institute of Women’s Health
Mothers Against Medical Error
National Center for Health Research
National Organization for Women
The TMJ Association
Center for Science and Democracy, Union of Concerned Scientists

The Patient, Consumer, and Public Health Coalition can be reached through Paul Brown at (202) 223-4000 or at


[1] The Food and Drug Administration (September 2014). Report: Standardizing and Evaluating Risk Evaluation and Mitigation Strategies.

[2] The Food and Drug Administration (September 2009).  Draft Guidance for Industry: Format and Content of Proposed Risk Evaluation and Mitigation Strategies (REMS), REMS Assessments, and Proposed REMS Modifications.…/Guidances/UCM184128.pdf

[3] Food and Drug Administration (July 2013). PowerPoint presentation, FDA Public Meeting [on] Standardizing and Evaluating Risk Evaluation and Mitigation Strategies (REMS).

[4] Food and Drug Administration (June 2008) Guidance for Industry: Indexing Structured Product Labeling.