Regulation and Risk


Table 1: Risk Evaluation And Mitigation Strategy Communication Tools1,8,9


Tool/Element Medication guide What It May Include


• Required to conform to specifications noted in title 21, Code of Federal Regulations


Patient package insert


may be included in REMS if it helps mitigate a serious risk of the drug Communication plan


• Information for one specific drug or entire classes of drugs • FDA approval • FDA approval


Considering that the vast majority of REMS have MedGuides only or MedGuides with communication plans, one would assume that there is evidence to show these communication tools are effective as risk mitigation strategies. However, as much as MedGuides have been used (and some may argue overused), published studies evaluating these tools do not show a great deal of support for the use of MedGuides or other written patient materials as an effective intervention, particularly when used alone in mitigating product risks.


• Distribution of letters to healthcare providers


• Dissemination of educational information to professional societies


FDA = US Food and Drug Administration; REMS = risk evaluation and mitigation strategy.


Table 2: Medication Guides and Other Patient Communication Tools10,11


Consumer Medicine Information Not FDA-approved Information summary


Provided to the patient from the pharmacy Pharmacy receives the information from content vendors Dispensing is left to the discretion of the pharmacist


Medication Guide FDA-approved


Written by manufacturer Distributed by pharmacist


Contains information for patients on how to safely use a drug Must conform to specifications noted in the Code of Federal Regulations Not always required (required for drugs that pose a ‘serious and significant public health concern’)


Also required if: patient labelling could help prevent serious adverse events; the drug product has serious risk(s) relative to benefits of which patients should be made aware because information concerning the risk(s) could affect patients’ decision to use or continue to use the product; or the drug product is important to health and patients adherence to directions for use is crucial for drug effectiveness10


Patient Package Insert FDA-approved, but optional Written by manufacturer Not always required


Contains information for patients on how to safely use a drug Dispensing is left to the discretion of the pharmacist unless US state laws require otherwise10,11,14


Patient Information Leaflet Not FDA-approved


Computer-generated general information Often for a class of drugs, rather than a specific drug Dispensing is left to the discretion of the pharmacist


Patient Information Sheet Produced by FDA (beginning in 2005) Focused on risk information Intended for the consumer


FDA links new safety alerts to patient information sheets Available on the FDA website Not dispensed through the pharmacy


FDA = US Food and Drug Administration.


The intention of MedGuides is to disseminate critical product information to patients, including major risks and recommendations for performing or avoiding certain behaviours to reduce risks. There is, however, general confusion by patients surrounding the wide array of patient information materials available in addition to a MedGuide (mostly paper), including: consumer medicine information (CMI), PPI, patient information leaflet (PIL) or patient information sheet (PIS), see Table 2.10–13


In addition to confusion over the numerous types of information leaflets, MedGuides also face issues related to length, complexity and content, including the presentation of balanced descriptions of benefits versus risks, while effectively communicating the important risk concepts. The increasing numbers of MedGuides required by the FDA has also raised concerns regarding cost shifts from manufacturers to pharmacies and the additional burden placed on pharmacies in dispensing MedGuides to patients.11


The use of


outmoded (paper) distribution mechanisms of patient information has created a rising need for physical storage for a growing number of pre-printed leaflets. There is a concern that some REMS may create an added workload via distribution of MedGuides and the resulting provider-patient counselling conversations.9


MedGuides in the Pharmacy Setting In 2007, an FDA public hearing11


presented the results of the 2005 FDA


National Assessment and indicated that the assessment showed low pharmacy compliance levels.11


Results showed that 70% of


responding pharmacists were familiar with the term MedGuide, but only 30% of those (20% of the total) knew that they were required for all new and refill prescriptions. Only 30% of pharmacists thought that MedGuides effectively communicated risks. The results of this survey indicate that pharmacists share consumer confusion in terms of MedGuide definition, content and requirements.


MedGuide-only Risk Evaluation and Mitigation Tools In 2009, an RPM Report (Regulation Policy Market Access) noted that many REMS are MedGuide-only (meaning the MedGuide is the sole safety requirement of the REMS).3


products) require both a MedGuide and communication plan. Only 12 products (10.1%) at the time of writing this article have required all REMS elements, including ETASU.8


This report raised questions as to


whether (or not) Congress will be satisfied that the FDA is using the FDAAA effectively to improve safety if it is solely relying on MedGuides for the majority of REMS.


The FDA itself has been quoted as saying it does not think that MedGuides are working as intended, and noted: “It isn’t at all clear that people are getting the information they need”.3


In fact, “the FDA


has considered switching to a universal patient leaflet to replace MedGuides as part of a REMS because the guides don’t effectively


22 DRUG DEVELOPMENT


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