In 2007, the Food and Drug Administration requested that manufacturers of all approved gadolinium-based contrast agents (GBCAs), drugs widely used in magnetic resonance imaging, use nearly identical ...text in their product labeling to describe the risk of nephrogenic systemic fibrosis (NSF). Accumulating information about NSF risks led to revision of the labeling text for all of these drugs in 2010. The present report summarizes the basis and purpose of this class-labeling approach and describes some of the related challenges, given the evolutionary nature of the NSF risk evidence. The class-labeling approach for presentation of product risk is designed to decrease the occurrence of NSF and to enhance the safe use of GBCAs in radiologic practice.
Pharmaceutical companies typically perform prospective, multicenter phase 3 clinical studies to support approval of a new imaging agent by the U.S. Food and Drug Administration (FDA). In uncommon ...situations, the FDA has approved imaging agents based solely, or in large part, on the clinical study experience described in published reports, including reports of exploratory (i.e., phase 1 or 2) studies performed at a single clinical site. We performed a survey of published reports to assess the potential of the reported information to support FDA approval of a commonly cited investigational imaging agent. Our survey revealed critical data limitations in most publications, all of which reported exploratory clinical studies. Here we summarize the precedent for FDA approval of imaging agents using effectiveness data from publications, FDA guidance, and our experience in reviewing publications. We also present a key-data checklist for investigators to consider in the design, conduct, and reporting of exploratory clinical studies for publication. We encourage editors and peer reviewers to consider requiring these key data when reviewing these reports for publication.
On June 30, 2009, the United States Food and Drug Administration (FDA) approved ferumoxytol (Feraheme™ injection, AMAG Pharmaceuticals), an iron‐containing product for intravenous (IV) ...administration, for the treatment of iron deficiency anemia in adult patients with chronic kidney disease (CKD). The safety and efficacy of ferumoxytol were assessed in three randomized, open‐label, controlled clinical trials. Two trials evaluated patients with nondialysis dependent CKD and a third trial assessed patients undergoing hemodialysis. Randomization was either to ferumoxytol or oral iron. Ferumoxytol was administered as two 510 mg IV injections, separated by 3–8 days. Oral iron, Ferro‐Sequels®, was administered at a dose of 100 mg twice daily for 21 days. In all three clinical trials, ferumoxytol administration increased the mean blood hemoglobin (Hgb) concentrations by ∼1.0 g/dL over the 35 day period, a mean increase that was greater than what was observed in patients receiving oral iron. Patients receiving ferumoxytol also had increases in blood transferrin saturation (TSAT) and ferritin values. For the proposed ferumoxytol dosing regimen, 4.9% of patients had serum ferritin ≥800 ng/mL and TSAT ≥50% post‐treatment. The most important ferumoxytol safety concerns were hypersensitivity reactions and/or hypotension. Anaphylaxis or anaphylactoid reactions were reported in 0.2% of subjects, and other adverse reactions potentially associated with hypersensitivity (e.g., pruritus, rash, urticaria, or wheezing) were reported in 3.7%. Hypotension was observed in 1.9%, including three patients with serious hypotensive reactions. Ferumoxytol administration may transiently affect the diagnostic ability of magnetic resonance imaging and the drug label provides further information regarding this effect. Am. J. Hematol. 2010. Published 2010 Wiley‐Liss, Inc.
Navigation with fluorescence guidance has emerged in the last decade as a promising strategy to improve the efficacy of oncologic surgery. To achieve routine clinical use, the onus is on the surgical ...community to objectively assess the value of this technique. This assessment may facilitate both Food and Drug Administration approval of new optical imaging agents and reimbursement for the imaging procedures. It is critical to characterize fluorescence-guided procedural benefits over existing practices and to elucidate both the costs and the safety risks. This report is the result of a meeting of the International Society of Image Guided Surgery (www.isigs.org) on February 6, 2015, in Miami, Florida, and reflects a consensus of the participants' opinions. Our objective was to critically evaluate the imaging platform technology and optical imaging agents and to make recommendations for successful clinical trial development of this highly promising approach in oncologic surgery.
Learning Objectives
After completing this course, the reader will be able to:
Describe the mechanism of action of eculizumab in PNH.
Discuss the efficacy findings upon which the approval of ...eculizumab was based.
Manage the safety concerns surrounding the use of eculizumab for the treatment of patients with PNH.
Discuss the efficacy and side effect profile of eculizumab.
This article is available for continuing medical education credit at CME.TheOncologist.com
On March 16, 2007, eculizumab (Soliris®; Alexion Pharmaceuticals, Inc. Cheshire, CT), a humanized monoclonal antibody that binds to the human C5 complement protein, received accelerated approval by the U.S. Food and Drug Administration for the treatment of patients with paroxysmal nocturnal hemoglobinuria (PNH) to reduce hemolysis. Eculizumab was studied in a randomized, double‐blind, placebo‐controlled clinical trial in 87 RBC transfusion–dependent adult PNH patients and in a supportive single‐arm study in 96 patients. The eculizumab dose was 600 mg as a 35‐minute i.v. infusion administered weekly for the first 4 weeks followed by 900 mg (week 5) then 900 mg every 14 days thereafter. Hemoglobin stabilized in 21 of 43 (48.8%) eculizumab‐treated patients, compared with none of 44 placebo‐treated patients. Eculizumab‐treated patients required significantly fewer RBC transfusions than placebo‐treated patients (median, 0 versus 10 units). There was also a significant reduction in the serum lactate dehydrogenase area under the curve with eculizumab compared with placebo treatment. Results of the phase II supportive study were similar to those of the phase III study. The safety database included 196 adult patients with PNH. Significant findings included the development of human anti‐human antibody responses in three patients and serious meningococcal infections in three patients. Patients should undergo meningococcal vaccination at least 2 weeks prior to receiving the first eculizumab treatment and have revaccination according to current medical guidelines. Patients must be monitored and evaluated immediately for early signs of meningococcal infections and treated with antibiotics as indicated.
Reported are the results of two studies of eculizumab in patients with paroxysmal nocturnal hemoglobinuria. Eculizumab appears to be generally safe and effective for the treatment of paroxysmal nocturnal hemoglobinuria patients with transfusion‐dependent hemolysis.
The safety and efficacy expectations for U.S. Food and Drug Administration (FDA) approval of diagnostic radiopharmaceuticals (DRs) are described in laws that broadly apply to all prescription drugs ...and biologic products. These laws also outline efficacy expectations that are unique for DRs. The FDA regulations and guidance documents elaborate on DR efficacy expectations for clinical uses of the drugs, such as the delineation of anatomy, the characterization of a physiologic process, or the diagnosis of disease. As described in the FDA regulations, the approval of a DR necessitates that the imaging drug has the ability to provide clinically useful information. Here we cite approved DRs to illustrate how the imaging performance of the drugs was characterized in clinical studies and the clinical usefulness of the imaging information described in drug labels.
Judging the safety of aprotinin Mangano, Dennis T; Rieves, R Dwaine; Weiss, Karen D
The New England journal of medicine,
2006-Nov-23, Volume:
355, Issue:
21
Journal Article
PDF
