Risk Evaluation & Mitigation

What is a REMS?

The primary goal of a Risk Evaluation and Mitigation Strategy (REMS) is to help patients and physicians understand the known or potential risks associated with a drug and to mitigate, or lessen, the chance that a serious adverse reaction might occur.

Beginning in 2008, the FDA has required these plans for certain drugs with potentially serious risks. REMS are intended to ensure that the benefits of a drug outweigh the risks.

In essence, REMS provides the FDA and drug companies with an iterative, stepped framework for managing risks. Which step a product will occupy depends on its specific risk, the tools to help lessen the risk, and whether or not the tool is required by the FDA for the product's benefits to outweigh its risks. Such an approach is not a single event, but a dynamic approach to managing risk throughout the product's lifecycle by increasing or decreasing the elements of the strategy.

When is a REMS Required?

FDA Amendments Act of 2007 provided the FDA with new authority to more effectively manage the risks of drugs, both before and after a medication's approval, including the ability to require Risk Evaluation and Mitigation Strategies (REMS), in certain circumstances.

There are a number of conditions in which REMS may be required. Most commonly, REMS are required when new safety information becomes available to make certain that the benefits of the medication outweigh its risks. The FDA may also require REMS for a group of medications that all have a similar risk - those from the same drug class, such as serotonin-reuptake inhibitors or anti-epileptic drugs. The FDA can also require REMS when a new medication is approved and there is a concern about a known or potential side effect.

Review a list of drugs deemed to have an approved REMS. This includes a list of REMS for all FDA approved drugs, including non-Lilly medications.

In regards to a medication, "new safety information" is defined as:

  • Information derived from a clinical trial
  • Spontaneous adverse event reports
  • A post-approval study
  • Peer reviewed biomedical literature
  • Other scientific data deemed appropriate about a risk or unexpected risk associated with the use of the drug.

"New safety information" is an important trigger in assessing a product's benefit/risk profile and making a determination on whether or not a REMS is needed.

What impact does REMS have on administration of the drug?

Drug information is provided in labels (package inserts) that accompany a drug product, which is reviewed and approved by regulatory agencies, such as the FDA. This information is the primary tool to describe the benefits and risks for physicians and patients.

The Medication Guide is used to help explain important risks to patients. For many years, the FDA has required Medication Guides for certain prescription drugs with serious risks. A part of REMS, the FDA can require a Medication Guide be provided so that patients can learn about a serious side effect or be reminded about special directions on how to take a drug for it to be most effective. Medication Guides, however, do not take the place of discussing a patient's medical condition and use of the drug with their healthcare provider. Patients should read the medication guide that is included with the prescription drugs to ensure they are aware of important risks.

A Medication Guide is an example of one tool that helps communicate risk as part of REMS. Other tools, such as Dear Healthcare Professional  letters, help inform healthcare providers as well. This information is shared with healthcare professionals to support them in providing information to patients.

For prescription drugs that have a very serious known risk, such as effects on a fetus, others special requirements may be included in the REMS. This may include a specific, mandatory laboratory test before a patient can receive the medication. REMS may require that a medication only be administered to a patient in a specific setting, such as a hospital. Healthcare providers are trained to administer these special requirements and will instruct patients on what to do when these programs are necessary to ensure appropriate management of serious risks.

What are the elements of REMS?

REMS may require any number of specific elements, such as:

  • A Medication Guide
  • Communication Plan with healthcare providers
    • Dear Healthcare Professional Letter
    • Introductory brochure for healthcare providers and/or patients,
    • Product website
    • Educational materials disseminated via professional associations and scientific meetings
  • Additional measures may be required, if necessary, to address serious known risks and assure safe use of a medication. These may be implemented to allow access to drugs proven effective but with associated risks. Without these interventions to assure safe use, these medications might not otherwise be made available to patients or withdrawn from the market. Additional requirements may include:
    • Healthcare providers who prescribe the drug have particular training or experience or are specially certified
    • Pharmacies, practitioners, or healthcare settings that dispense the drug are specially certified
    • The drug be dispensed only in certain healthcare settings, such as hospitals
    • The drug be dispensed to patients with evidence of safe-use conditions, such as laboratory test results
    • Each patient using the drug be subject to monitoring
    • Patients using the drug be enrolled in a registry

How does the FDA know if the REMS is working?

The legislation that gave the FDA the authority to require REMS also requires that pharmaceutical companies report to the FDA on a regular basis about their REMS. Three scheduled reports are required after the FDA approves the REMS: 18 months, three years and seven years. The drug company must report on the success of the REMS and whether the REMS need to be modified, based on the assessment.