le 17 juillet 2019


It has been more than a decade since the Food and Drug Administration Amendments Act (FDAAA) was signed into law in September 2007.1 The Act enabled the FDA to mandate Risk Evaluation and Mitigation Strategy (REMS) programs for products that are approved but require specific steps be taken to assure safe use. Since then, REMS programs have evolved in both scope and complexity but the use of new technologies to relieve the burden a REMS can place on prescribers, pharmacists, other healthcare providers (HCPs) and/or patients has not kept pace.


REMS modernization was one of the subjects of a Syneos Healthsponsored Leadership Forum for REMS executives, convened on October 3-4, 2018 in Austin, Texas. Participants discussed the state of REMS implementation today—what’s working and what’s not—and where to go from here to optimize the success of REMS by more effectively balancing risk mitigation with stakeholder burden.



What is—and is not—working

The first and foremost purpose of incorporating a strategy such as REMS is to ensure that the benefits of a drug outweigh its risks by managing known or potential serious risks, thus enabling patients to have access to the medicines they need. Almost since their inception, however, stakeholders have been concerned about the burdens REMS programs can place on prescribers, patients, pharmacists and the healthcare system overall—and as a result, about the degree to which REMS programs may limit patient access to needed therapies. This is especially the case as REMS programs have become increasingly more complex, a trend that is likely to continue.

To be sure, certain REMS fundamentals are working as intended. REMS are meeting statutory requirements, raising benefit/risk awareness among providers, and identifying individuals who are best positioned to mitigate risks. Perhaps most importantly, medicines are on the market helping patients today that would not be available without a REMS in place. Despite these benefits, some important aspects of REMS have not kept pace with the technological advances transforming the healthcare and information ecosystems in which these programs operate.

Pain Points and Opportunities

The amount of time and effort that a prescriber, pharmacist, other HCP, and/or patient must dedicate to fulfill REMS program requirements before a medication can be prescribed, dispensed and obtained may be considered a stakeholder burden. The burden can vary significantly from program to program. Some REMS are straightforward, simply calling for an informational website and a call center for providers, patients, caregivers or pharmacists who have questions. Complexity increases as a REMS calls for more involved Elements to Assure Safe Use (ETASU) (e.g., stakeholder certification/enrollment or restricted distribution). The number and type of ETASU, in addition to other elements and tools required, directly impacts stakeholder burden associated with the program.

  • Prescribers. The greatest burden of a REMS program is typically borne by prescribers, who often find that participation can take already-scarce time away from patient care. A prescriber may need to become certified to participate and then may be responsible for enrolling their patients appropriately, making sure the results of any mandatory testing requirements are entered into the REMS system, and facilitating any staff training needed. These logistical burdens multiply in larger group practice and health system settings, and the time all this takes is largely uncompensated.

For REMS to be carried out effectively, information must be regularly exchanged between prescribers and REMS administrators. Tools such as Web portals and integration with electronic health records are needed to seamlessly and efficiently manage REMS requirements within existing patient care workflows and healthcare systems, and to simplify prescribers’ interactions with REMS programs. Technologies are available—and becoming more accessible— to support multichannel, targeted and clinically relevant messaging to prescribers and integrate REMS requirements into clinical workflows and electronic medical record/electronic health record systems. These should be further evaluated and utilized in real-world REMS programs and key learnings more widely shared.

  • Patients. REMS programs attempt to place the least amount of burden possible on the patient. Beyond simple enrollment requirements, however, patients often must undergo additional testing before a drug is prescribed as well as during treatment. In some cases, the drug may need to be administered in an out-patient or hospital setting. Greater use of automated scheduling and reminders—for example, through mobile apps that can integrate information into patients’ daily lives—might not entirely eliminate these burdens but could make it easier for patients to navigate and adhere to program requirements.

In addition, patient education needs to be comprehensive, streamlined and coordinated, and ideally allow for customization based on the patient’s stage of therapy. Patients often have concerns about what a REMS means. There is an opportunity to improve patient adherence by producing patient-focused material that more effectively helps patients understand the benefits of the proposed medication as well as the associated risks, and the steps being taken to mitigate those risks. Making relevant information easy to understand and even easier to access via different channels, including Web-based formats (e.g., patient portals), may help improve the patient experience, treatment adherence and their overall success in the program.

  • Pharmacists. The third stakeholder that bears much of the burden in a REMS program is the pharmacist. Pharmacists have historically been relied upon to determine prescription qualifications although they may have limited access to helpful technology to aid in determining patient eligibility. To facilitate this, electronic telecommunication systems used for pharmacy claim adjudication (i.e., switch technology) has been utilized per the approval of the FDA for the last several years. The benefits of using such an established system are predominantly due to its integration with the standard pharmacy work flow and ability to leverage standardized technology and data standards already in place. One of the primary disadvantages of using such a system is that it was not designed with specific REMS program requirements in mind.

Another concern is that pharmacists often find themselves the primary healthcare professional answering questions about the drug, the REMS program, and what impact it may have. Patients should be able to supplement their interactions with pharmacists and prescribers with access to clear, actionable information to enhance their understanding of complex benefit/risk issues.

  • Manufacturers. Another area in need of modernization is the REMS assessment process, which is critical to ensuring that a program is working as intended to mitigate risk without limiting patient access or increasing burden on the healthcare system. As part of this process, manufacturers typically use surveys to evaluate patient and healthcare provider understanding of the serious risks associated with, and safe use of, the drug in question—a central objective of any REMS program. Acknowledging challenges in the survey process (e.g., survey recruitment, attaining sufficient sample sizes, survey fatigue, lack of standardized metrics) and the burden these place on stakeholders, the FDA has released various guidances over the last several years, most recently in April 2019 concerning REMS assessment and survey methodologies.2,3 More progress from a technological standpoint is needed to enable expanded, efficient access to and communication with providers, patients and prescribers as part of the REMS assessment process.

In addition, to reduce the considerable time and cost associated with making modifications to a program once it is fully operational, manufacturers are looking for ways to engage key stakeholders in REMS program design much earlier but without introducing significant delays in the REMS approval process. One option might be to consider the benefit from a program being piloted first, providing opportunity for adjustments based on stakeholder feedback and behaviors. This approach might take more time up front in the process and require even closer coordination with the FDA, but could be well worth the resources saved over time.

The Path Forward


The FDA recognizes that REMS is in need of modernization and has taken steps in this regard— for instance, announcing in 2015 the creation of the REMS Platform Standards Initiative4 to better integrate the design, implementation and assessment of REMS with electronic health records, and with its most recent guidance regarding REMS assessment and survey methodologies. While this work continues, it’s time for all those involved to take concerted action to modernize REMS program design and consider innovative ways to better implement and assess these critical programs. Priority should be placed on deepening dialogue and collaboration with the FDA, piloting new processes and technologies, and sharing best practices. Key stakeholders should take this opportunity to build coalitions capable of proactively bringing solutions forward, helping to ensure that patients will continue to have safe access to the drugs they need without undue burdens being placed on them or others involved in their care.


  1. U.S. Food and Drug Administration. Food and Drug Administration Amendments Act (FDAAA) of 2007. Available at: https://www.fda.gov/regulatory-information/selected-amendments-fdc-act/food-and-drug-administrationamendments- act-fdaaa-2007
  2. U.S. Food and Drug Administration. REMS assessment: planning and reporting. January 2019. Available at: https://www.fda.gov/regulatory-information/search-fda-guidance-documents/rems-assessment-planning-andreporting? utm_campaign=SBIA%3A%20FDA%20announces%20two%20draft%20Guidances%20on%20REMS%20 to%20improve%20the%20assessment%20of%20REMS%20programs&utm_medium=email&utm_source=Eloqua
  3. U.S. Food and Drug Administration. Survey methodologies to assess REMS goals that relate to knowledge. Available at: https://www.fda.gov/regulatory-information/search-fda-guidance-documents/surveymethodologies- assess-rems-goals-relate-knowledge?utm_campaign=SBIA%3A%20FDA%20announces%20 two%20draft%20Guidances%20on%20REMS%20to%20improve%20the%20assessment%20of%20REMS%20 programs&utm_medium=email&utm_source=Eloqua
  4. U.S. Food and Drug Administration. REMS platform standards initiative: needs assessment. Available at: https://www.fda.gov/media/106442/download
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