Bart’s Corner: REMS Update

Dec 22, 2014

Pharmacovigilance, Drug Safety and Regulatory Affairs Author & Expert

Bart's Corner: REMS Update

In September 2014 FDA issued a paper on Standardizing & Evaluating Risk Evaluation and Mitigation Strategy (REMS).

A REMS is put in place for those products to ensure that benefits outweigh the risks. REMS may require additional measures above and beyond the usual post-marketing safety surveillance by the sponsor.

This report has been released as part of FDA’s commitments, as required by the Prescription Drug User Fee Act reauthorization of 2012 (called PDUFA V) to continue to improve REMS to better protect the public health. FDA promised to develop techniques to standardize REMS by getting stakeholder input. The goal is to reduce the burden of REMS on practitioners, patients and others in the health care settings. Five areas are being looked at: providing patient benefit-risk information, prescriber education, pharmacy systems, and practice settings.

Three FDA working groups were set up to comply with the law’s requirements:

  1. The Policy Work Group: This group is developing a guidance on how FDA intends to use the statutory criteria to determine whether a REMS is needed or not.
  2. The Evaluation Work Group: This group is working to develop an evidence-based approach to assessing the effectiveness and burden of REMS and developing a guidance for assessing REMS’s effectiveness.
  3. The Design and Standardization Work Group: Identify the best practices to incorporate into future REMS design, tools and their integration into the US healthcare delivery system.

FDA held multiple public meetings in 2013 and issued this report in September 2014.

The feedback and high level findings include (my comments in italics):

  • Many health care stakeholders have successfully implemented REMS at the institution level in the six years since REMS have been in place. The best results, not surprisingly, seem to be at institutions where the drugs in question are prescribed frequently and the REMS requirements are routinized.
  • Stakeholders are not uniformly impacted by REMS requirements. Some stakeholders have noted that the heaviest burden for knowing about the REMS and implementing them has fallen on the pharmacists there. Many institutions charge the pharmacy department with setting up and monitoring the REMS and its compliance. Some physician stakeholders indicated that the presence of a REMS deters them from prescribing that drug.
  • Communication about REMS requirements should be improved. This seems to be a widespread complaint from the stakeholders in terms of knowing the requirements and how to divide them amongst all the personnel involved in an institution. There also seems to be a lack of clarity as to the specific risk the REMS is to mitigate. Some patients complained that the REMS is “simply an extra step in an already complicated and stressful medical care and drug procurement process.” This is a bit surprising as the goal of the REMS is usually clearly stated in the REMS document itself posted on the FDA website.
  • There should be flexibility to implement a REMS program based on the nature and variety of healthcare settings. A not surprising request to avoid a one size fits all approach.
  • REMS are vital tools that will be increasingly necessary, and content delivery must be streamlined without compromising the content itself. However, it would be good to show, with evidence-based data that REMS do work.
  • FDA should standardize REMS across platforms, media, and delivery technologies and work to fully integrate them into healthcare systems. Another fairly obvious suggestion that the IT component of REMS should be standardized. Easy to say, hard to do across the country, however.
  • FDA should use human factor evaluation approaches like Failure Mode and Effects Analysis (FMEA) to support and standardize REMS program design. This is complex and sometimes expensive and time-consuming methodology to analyze failure or potential failure with the goal of avoiding it in the future. It is common in industry and manufacturing but less so in service industries.
  • FDA can improve REMS assessments with a variety of tools and techniques. This covers to a degree the issues of moving to electronic health records and other methodology being developed in the US healthcare system that is not necessarily directly related to pharmaceuticals.
  • FDA should structure and standardize REMS information. This is following on the footsteps of the Structured Product Labeling initiative that is underway by FDA and is very reasonable.

Four key projects were defined and put in place:

  1. Providing better patient benefit-risk information under REMS by improving tools for prescriber to patient counseling
  • Conduct research into current REMS patient counseling tools and other tools and literature to identify the state of the art and best practices.
  • Get feedback from experts, HCPs, Advisory Committees and others on how to improve the counseling tools.
  • Develop a report of findings and proposals to improve the tools.

Author’s comment: This is indeed a laudable and necessary project not only for REMS but also for medical communication in general. When a patient fills a prescription he or she will often get (whether in the pharmacy or by mail) either the professional package insert (PI) or a long, single spaced, small font highly technical document largely derived from the PI. Some are hard to read even for the HCP, let alone the patients. With the arrival of social media and patient oriented websites, one hopes we will see significant new and improved means of getting the key risks (and benefits) across to patients perhaps by tweets, SMS or other modern means.

  1. Providing prescribers better continuing education on REMS
  • A proposal to accredit REMS information so that prescribers will get CME credit for reviewing this information.
  • For new drugs, determine when the best time for education will be (pre or post approval).
  • Figure out how to do the CE.
  • Try to determine the time and resources need to develop and use REMS CE.

Author’s comment: Certainly reasonable but not sure that this is the best or only way to get the education points across. Perhaps many of the tools in the first project on patient counseling can be adapted for HCPs. Again, maybe social media will have a big role.

  1. Standardizing REMS information for inclusion in pharmacy systems using Structured Product Labeling (SPL)
  • FDA is proposing to develop SPL for REMS content and a structured method to share and communicate REMS content with all stakeholders.
  • Provide a single source of comprehensive information on all REMS.
  • Facilitate the REMS information into pharmacy systems and health information technology.
  • Have FDA receive REMS information from sponsors in a consistent format.
  • Catalog the similarities and differences between REMS programs.

Author’s comment: Again highly laudable and quite workable. It is rather complex and time consuming for the labeling of all US products. As there are fewer REMS, this should be more doable in a shorter length of time. Standardization of content and format is something that governments are generally quite adept at. Getting agreement amongst the parties, including the information technology requirements, may be a bit harder if systems must be redone at significant cost.

  1. Provide a central source for REMS information for practice settings
  • Investigate a centralized, standardized, user–friendly source of what stakeholders must do in each REMS.
  • Help stakeholders learn about and comply with requirements.
  • Allow comparison of requirements across REMS to minimize confusion if one must comply with multiple REMS.

Author’s comment: Laudable and should be fairly easy to do.

If you wish to see more about each of these projects, have a look at the document itself. It is a very positive sign that FDA is clearly not frozen in place with REMS as they currently exist, and is collecting input from stakeholders with the goal of making the whole concept and process better.

As the engineers say, “if you can measure it, you can fix it”. It certainly seems that we can measure outcomes of some or most of the REMS to see whether they are really working. From this there will be lessons to be learned and changes to be made. The only mildly disquieting issue (to me at least) is the time involved in all of this. REMS have been in place for a number of years. It took FDA all of 2013 to get this feedback and then about a year to write this report on only one of the working groups. One would hope that the process can be sped up (presuming that the will and the funding to do so are available).



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