title: JCL roundtable: Risk evaluation and mitigation strategy.
abstract: Many factors enter into the decision by the Food and Drug Administration (FDA) to approve a new drug for use by physicians and other health care providers in treating diseases. Initially, the FDA authority was restricted to issues of safety and only later did the documentation of efficacy become part of the review process required for approval. However, all drugs have the potential for causing harm at some dose level to all and at lower doses in certain patients with vulnerability to the particular pharmacology of the agent. As new drugs have been designed to manage disorders that are uncommon, but of significant consequence, they may have adverse effects that are acceptable only because they are so uniquely beneficial to these specific conditions. The risk of these adverse effects may be acceptable since the benefit can outweigh the harm in most patients and the adversity can be predicted and managed. The approval of this category of drugs has grown rapidly since definition of a mechanism of action to manage and modify the risk has been provided by a process known as known as Risk Evaluation and Mitigation Strategy or "REMS." In 2007, the Food and Drug Administration Amendments Act (FDAAA) allowed the FDA to require postmarketing studies and the authority to mandate the implementation of a REMS for drugs with efficacy but documented potential for harm. Two relatively new drugs useful in the management of severe elevations of low-density lipoprotein cholesterol have been approved under a requirement for a REMS. These are lomitapide, an inhibitor of microsomal triglyceride transfer protein and mipomersen, an antisense oligonucleotide which reduces the synthesis of apolipoprotein B.
authors.affiliation: Emory University School of Medicine, Atlanta, GA, USA. Electronic address: wbrow925@bellsouth.net.
authors.forename: W Virgil
authors.initials: WV
authors.lastname: Brown
authors.affiliation: Heart & Lipid Institute of Florida, South Pasadena, FL, USA.
authors.forename: Dean A
authors.initials: DA
authors.lastname: Bramlet
authors.affiliation: University of Pennsylvania Health System, Philadelphia, PA, USA.
authors.forename: Joyce L
authors.initials: JL
authors.lastname: Ross
authors.affiliation: New York University School of Medicine, New York, NY, USA.
authors.forename: James A
authors.initials: JA
authors.lastname: Underberg
mesh_terms: D000924:Anticholesteremic Agents / Q000009:adverse effects* / Q000627:therapeutic use; D001055:Apolipoproteins B / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism; D001562:Benzimidazoles / Q000009:adverse effects / Q000627:therapeutic use; D002352:Carrier Proteins / Q000037:antagonists & inhibitors / Q000378:metabolism; D008078:Cholesterol, LDL / Q000097:blood; D017277:Drug Approval; D006801:Humans; D006937:Hypercholesterolemia / Q000188:drug therapy; D009841:Oligonucleotides / Q000009:adverse effects / Q000627:therapeutic use; D018570:Risk Assessment; D014481:United States; D014486:United States Food and Drug Administration
chemical_list: D000924:Anticholesteremic Agents; D001055:Apolipoproteins B; C473731:BMS201038; D001562:Benzimidazoles; D002352:Carrier Proteins; D008078:Cholesterol, LDL; D009841:Oligonucleotides; C106092:microsomal triglyceride transfer protein; C524142:mipomersen
keywords: Disease; LDL-C; Lomitapide; Mipomersen; Mitigation strategy; REMS; Risk evaluation