by Kathryn E. Heagerty, BSN, JD
Ms. Heagerty is a Risk Manager for PRMS, Inc.

Innov Clin Neurosci. 2012;9(3):27–29

This ongoing column is dedicated to providing information to our readers on managing legal risks associated with medical practice. We invite questions from our readers. The answers are provided by PRMS, Inc. (www.prms.com), a manager of medical professional liability insurance programs with services that include risk management consultation, education and onsite risk management audits, and other resources to healthcare providers to help improve patient outcomes and reduce professional liability risk. The answers published in this column represent those of only one risk management consulting company. Other risk management consulting companies or insurance carriers may provide different advice, and readers should take this into consideration. The information in this column does not constitute legal advice. For legal advice, contact your personal attorney. Note: The information and recommendations in this article are applicable to physicians and other healthcare professionals so “clinician” is used to indicate all treatment team members.

QUESTION

I have noticed that the subject of “REMS” is appearing more frequently in the news, scientific literature, and in professional conference agendas. In a concise format, please tell me what I need to know about REMS and why I need to know it.

ANSWER

A Risk Evaluation and Mitigation Strategy (REMS) is a plan the United States Food and Drug Administration (FDA) may require of manufacturers, pre- and post-approval, to ensure that a drug or biological product’s benefits outweigh its risks.[1] The genesis of REMS, and other drug safety measures, date back to the FDA’s response to recommendations made in the Institute of Medicine(IOM) report, The Future of Drug Safety: Promoting and Protecting the Health of the Public.[2] REMS are a product of the FDA’s commitment to monitor drug safety postapproval.[3]

As stakeholders in the drug safety system, physicians should be familiar with REMS in order to contribute to the safety of patients, minimize liability risks, and in some cases, maintain prescribing privileges.

REMS components. Through REMS, the FDA strives to balance the need to ensure patient safety with that of maintaining accessibility. To determine if a REMS is necessary, the FDA considers the following factors: size of population likely to use the drug, seriousness of disease or condition to be treated, expected benefit, expected or actual duration of treatment, seriousness of known or potential adverse events, incidence of such events in those likely to use the drug, and whether the drug is a new molecular entity.[4] The FDA may require a REMS preapproval or postapproval if new concerns arise regarding safety or efficacy.[5]

A REMS must include a timetable for assessing the strategy’s effectiveness. Although modifiable, assessments typically occurs at 18 months, three years, and seven years after initiation. A REMS may include any or all of the following components: label or package insert changes, medication guides, a communication plan, and elements to assure safe access.[6]

The medication guides use simple language to convey to patients the most important information. For example, the medication guide for olanzapine tablets informs patients that the most important thing they need to know is that the drug can cause serious side effects, such as an increased risk of death in elderly patients with dementia; increased blood sugar, cholesterol, and triglyceride levels; and weight gain in teenagers. The guide goes on to provide symptoms which, if experienced, warrant a call to the doctor.[7]

Communication plans may include sending letters containing important safety information to providers, pharmacies, and patients. Other plans may include utilizing the manufacturer’s staff and professional societies to disseminate the safety information.

The FDA may require some manufacturers to include elements to assure safe access. Prescriber and dispenser training or certification, dispensing restrictions, evidence of safe use conditions (lab test results), required patient monitoring, and patient registries are some of the elements that may be used. The REMS for buprenorphine and naloxone requires prescribers to document that safe use conditions have been met. Specifically, the prescriber must document that the patient meets diagnostic criteria, risks and safe storage have been discussed, and that a limited amount was prescribed at the first postinduction visit.[8] The natalizumab REMS requires prescriber certification and restricts distribution to hospitals and infusion centers.[9]

Opioid REMS. Addiction, abuse, and diversion of opioid medications are of great national concern. The FDA has been working with stakeholders to develop REMS for long-acting and extended-release opioid drugs. Presently, the FDA is accepting comments on its proposed content for prescriber education. Although not yet effective, this prescriber education is likely to be mandatory as a condition to prescribing and may even be required by some state licensing boards.[10]

Patient safety and professional liability risks. Enhancing patient safety and minimizing professional liability risks go hand in hand. The main purpose of REMS is to minimize the risks to patients taking prescription drugs. It follows that if a patient alleges an injury while taking a drug with a REMS, the REMS itself may likely be one factor used to establish the standard of care. Attorneys would likely scrutinize the REMS components and the physician’s compliance with them. Likewise, experts reviewing the case might compare the defendant physician’s actions to those recommended in the REMS. Defending a physician who failed to comply with REMS requirements may prove to be difficult.

Currently, approximately 122 medications have a REMS and chances are you prescribe one or more of them. To minimize liability risks and improve patient safety, frequently review the REMS for drugs you prescribe. The information can be quickly and easily accessed by entering “FDA” in your search engine and following the links to medication safety and REMS.[11] The site also indicates when a drug has been released from the REMS requirement and when new REMS have been added. The medication guides can be printed and used to educate patients and to guide informed consent discussions.

You may need to lower your tolerance for treatment nonadherence by your patients when prescribing drugs with REMS. In some situations, you may decide that you cannot safely continue to prescribe a medication to a patient. Consider that in the REMS for natalizumab, patient adherence is a prerequisite for receiving the next dose.[12] Additionally, in REMS with elements to assure safe use, your compliance may be necessary for continued prescribing. As a final note, documentation will be crucial to show adherence to the REMS and to support the exercise of one’s professional judgment.

References
1. 21 USCA § 355-1(West 2012)(codifying the Food and Drug Administration Amendments Act of 2007 which expanded the FDA’s authority to ensure drug safety).
2. National Research Council. Front matter. The Future of Drug Safety: Promoting and Protecting the Health of the Public; 153. Washington, DC: The National Academies Press, 2007.
3. FDA News Release: FDA reinforces commitment to drug safety. January 30, 2007. http://www.fda.gov/NewsEvents/Newsroom/PressAnnouncements/2007/ucm108833.htm?utm_source=fdaSearch&utm_medium=website&utm_term=FDA%20News%20Release:%20FDA%20reinforces%20commitment%20to%20drug%20safety.%20January%2030,%202007&utm_content=1. Accessed March 15, 2012.
4. 21 U.S.C.A. § 355-1(a)(1)(West 2011).
5. 21 U.S.C.A. § 355-1(a)(1)-(2)(West 2011).
6. 21 U.S.C.A. § 355-1(c)-(f)(West 2011).
7. US Food and Drug Administration Medication Guide. Zyprexa. http://www.fda.gov/downloads/Drugs/DrugSafety/UCM134700.pdf. Accessed March 15, 2012.
8. US Food and Drug Administration Medication Guide. Suboxone. http://www.fda.gov/downloads/Drugs/DrugSafety/UCM225677.pdf. Accessed March 15, 2012.
9. US Food and Drug Administration Medication Guide. Tysabri. http://www.fda.gov/downloads/Drugs/DrugSafety/ucm089809.pdf. Accessed March 15, 2012.
10. US Food and Drug Administration Opioid Drugs and Risk Evalutaion and Mitigation Strategies (REMS). www.fda.gov/Drugs/DrugSafety/InformationbyDrugClass/ucm163647.htm. Accessed March 15, 2012.
11. US Food and Drug Adminstration. Postmarket Drug Safety Information for Patients and Providers. http://www.fda.gov/Drugs/DrugSafety/PostmarketDrugSafetyInformationforPatientsandProviders/default.htm. March 15, 2012.
12. US Food and Drug Adminstration. REMS Tysabri. www.fda.gov/downloads/Drugs/DrugSafety/PostmarketDrugSafetyInformationforPatientsandProviders/UCM288126.pdf. Accessed March 15, 2012.

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