Risk Minimization Planning

The primary goal of a Risk Minimization Plan (RMiP) is to develop activities that help patients and healthcare providers understand an important known or potential risk associated with a drug and to lessen the chance that a serious side effect might occur. The activities implemented by the drug company as part of this plan are called risk minimization activities. Regulators may require a risk minimization plan for a drug with a known or potential serious risk to ensure the benefit of the drug outweighs the risk. At the FDA, this plan is referred to a Risk Evaluation and Mitigation Strategy or REMS.

Implementing a RMiP consists of implementing risk minimization activity, assessing the usefulness of those activities, and using the assessment results to decide if the RMiP should remain in place as long as the drug is available for use.

When is a REMS or RMiP 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. Similar regulations are in place in Europe and other countries to allow the requirement for risk mitigation.

There are a number of conditions in which Risk Mitigation may be required. These could include activities associated with a new product available for patient use or when new safety information for existing medicines becomes available. Regulators may also require Risk Mitigation for a group of medications that all have a similar risk - those from the same drug class, such as different antidepressants with the same mechanism of action.

The FDA maintains a list of all drugs that require a REMS.

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

  • Information derived from a clinical trial
  • Spontaneous adverse event reports (patient, doctor and other reports of side effects)
  • A study conducted after the approval of a drug
  • Peer reviewed biomedical literature (scientists’ and doctors’ published research)
  • 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 additional risk minimization is needed.

What impact does Risk Minimization Activities 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. A Medication Guide can be part of label or could be a risk minimization activity. It is provided so that patients can learn about a serious side effect or be reminded about special directions on how to take a drug in order 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 doctor or other healthcare provider. Patients should read the medication guide that is included with their prescription drug to ensure they are aware of important risks.

Other risk minimization tools, such as Dear Healthcare Professional letters, help inform healthcare providers. This information is shared with doctors and other 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, other special requirements may be required for additional risk minimization. This may include a specific, mandatory laboratory test before a patient can receive the medication. There could be a requirement that a medication only be administered to a patient in a specific setting, such as a hospital. Doctors, pharmacists and other 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.

How does the FDA know if the Risk Minimization Activities are working?

The legislation that gave regulators the authority to require risk minimization also requires that pharmaceutical companies report to the regulator on a regular basis about the implementation and assessment of the risk minimization activities. For example, scheduled reports are required after the FDA approves the REMS. The drug company must report on the success of the risk minimization and whether the risk minimization plan needs to be modified, based on the assessment.