Office Of Drug Safety Research Articles

Insulin Sensitizers and Heart Failure: An Engine Flooded with Fuel

Since the FDA approved rosiglitazone in May 1999, there have been concerns about adverse lipid effects, edema and increased cardiovascular risk.[1] Nissen and Wolski’s 2007 meta-analysis of 42 clinical trials drew special attention to increased death and disability from cardiovascular complications in patients treated with rosiglitazone; thus many questions have been raised regarding the safety of this drug.[2] In 2007, the FDA revealed similar results in a separate meta-analysis showing a statistically significant increase in cardiovascular risk with the use of rosiglitazone.[3] The manufacturers of rosiglitazone therefore felt compelled to release an interim analysis of the RECORD Trial in 2007, with final results published in 2009. The RECORD Trial supports that the addition of rosiglitazone to glucose-lowering therapy in people with type 2 diabetes does indeed increase the risk of heart failure. However, the data were inconclusive about any possible effect on myocardial infarction, and it suggested no increased risk of overall cardiovascular morbidity or mortality in those treated with rosiglitazone compared with standard glucose-lowering drugs.[4] The RECORD Trial was criticized as being underpowered and flawed by the publication of unblinded, preliminary data.[5] In June 2009, the FDA therefore mandated an adequately powered cardiovascular outcomes study for rosiglitazone known as the TIDE Trial. In July 2010, the FDA’s Endocrinologic and Metabolic Drugs Advisory Committee joint meeting with the Drug Safety and Risk Management Advisory Committee convened. At this meeting, Dr. Nissen (Cardiovascular Medicine Chairman of the Cleveland Clinic) presented an updated meta-analysis which again demonstrated an increased risk of AMI associated with rosiglitazone.[6] In addition, Dr. Graham (Associate Director of the FDA’s Office of Drug Safety) presented the results of the retrospective cohort study discussed here, also suggesting adverse cardiovascular events associated with the use of rosiglitazone. A representative from the manufacturers of rosiglitazone was also present at the joint meeting to defend its product utilizing results from the RECORD Trial. One week following the advisory committee meeting, the FDA announced that the TIDE Trial has been placed on partial clinical hold, with no new patients eligible for enrollment until further notice. In addition, the FDA has instructed the manufacturers of rosiglitazone to update their investigators, institutional review boards and ethics committees involved in the TIDE Trial regarding any new safety information, along with information concerning the deliberations and votes of the FDA joint advisory committee meeting. The FDA is currently still evaluating all available information on rosiglitazone’s safety, in conjunction with discussions of the recent advisory committee meeting, and will update the public on the outcome of its review and its implications for both the TIDE Trial and rosiglitazone.

FDA PANEL VOTES IN FAVOR OF AVANDIA

AN ADVISORY PANEL of the Food & Drug Administration voted on July 14 to keep the controversial diabetes drug Avandia (rosiglitazone) on the market, despite evidence linking the drug to an increased risk of heart disease. The panel did, however, recommend tightening warning labels and restricting sales of the drug. FDA Commissioner Margaret A. Hamburg will now have to decide what action to take. The agency is under pressure to move swiftly from members of Congress and advocacy groups, who claim that Glaxo-SmithKline (GSK), the maker of Avandia, hid data relevant to the safety of the drug. Congress is also looking closely at this case to determine whether FDA’s office of drug safety is in need of reform. The Senate Finance Committee, in particular, has been investigating the safety of Avandia since 2007. In a report released in February, the committee found that GSK promoted the drug despite studies suggesting serious health risks. Committee ...

A Need for Reorganization of the Food and Drug Administration

The associate director for science and medicine in the Office of Drug Safety at the Food and Drug Administration (FDA), Dr. David Graham, reported that the FDA was incapable of protecting Americans from unsafe drugs. In testimony to the Senate Finance Committee, he stated that the FDA has let the American people down and betrayed public trust. Drastic changes and measures within the FDA must be made to ensure the safety of American consumers of drugs, products, and medical devices. Efforts such as the introduction of the Grassley-Dodd Bill, allowing the FDA to order immediate drug recall or increased risk warnings, followed by the FDA Safety Act of 2007, are still not enough to ensure the safety and efficacy of drugs, biological products, and medical devices that the American public use every day. In this report, we describe past and present efforts by congressional leaders, FDA representatives, and American citizens to effect changes within the FDA in order to protect America from unsafe drugs and medical devices. We describe our own struggles in passing a citizen’s petition to ban cornstarch in medical gloves, and the lack of response and responsibility that the FDA has displayed.

FDA Panel: Ban 2 Popular Asthma Drugs

A PANEL OF ADVISORS TO THE US Food and Drug Administration (FDA) recommended that the agency ban the marketing of 2 popular asthma drugs that have been associated with an increased risk of rare but serious adverseeventsand, insomecases,death. The panel was charged with assessing the risks and benefits of certain asthma treatments, specifically the longacting -agonist (LABA) drugs formoterol and salmeterol and combination products containing both a LABA and an inhaled corticosteroid (formoterol plus budesonide and salmeterol plus fluticasone). Previously, the FDA’s Office of Drug Safety and the agency’s pulmonary and allergy drug products division had made contradictory recommendations concerning LABAs. The panel, which consisted of members from 3 committees that advise the FDA on drug safety, pediatric issues, and pulmonary and allergy drugs, recommended that the agency ban the marketing of products containing a LABA only (formoterol or salmeterol) as asthma treatments in all age groups. However, they also recommended the continued sale of combination products (formoterol plus budesonide for adults and adolescents or salmeterol plus fluticasone for all ages) for treating this disorder, noting that these drugs appeared to be less risky. The agency typically follows the recommendations offered by its advisory committees. “What we have come to learn is that LABAs, when used alone, are associated with more deaths [among asthma patients],” said Marsha D. Rappley, MD, dean of the College of Human Medicine atMichiganStateUniversity inEastLansing.Rappleyservesaschairof theFDA’s pediatric advisory committee. As part of its deliberations, the committee reviewed a new FDA metaanalysis of data from 110 clinical trials of LABA products used to treat asthma;

First do no harm

The Hippocratic Oath extols physicians “to first do no harm.” So, doctors weigh the risks of using a drug—including its side effects—against its benefits for an individual patient. However, as medicines have become more powerful, the risk of side effects has increased: the number of serious and fatal drug‐related events reported to the US Food and Drug Administration (FDA; Bethesda, MD, USA) increased 2.6‐fold and 2.7‐fold respectively, between 1998 and 2005. Furthermore, the number of serious events increased four times faster than the volume of prescriptions (Moore et al , 2007). These developments—together with a recent spate of highly publicized drug withdrawals—raises several fundamental questions. How can patients be sure that the drugs they take are as safe as is practicable? Do regulating authorities and companies act as quickly as possible to address safety problems that emerge after a drug has been approved? What could be done to improve the regulatory system to better protect patients? > …as medicines have become more powerful, the risk of side effects has increased… The withdrawal of Vioxx® (rofecoxib; Merck, Whitehouse Station, NJ, USA)—a selective cyclo‐oxygenase (COX) 2 inhibitor—provided a wake‐up call for regulatory authorities (Greener, 2005). After the FDA approved Vioxx in 1999, around 80 million people worldwide used the drug to treat arthritis and other conditions characterized by chronic pain. In September 2004, Merck withdrew the drug following evidence that long‐term use of Vioxx increased the risk of heart attack and stroke. David Graham, Associate Director for Science and Medicine at the FDA's Office of Drug Safety, estimates that Vioxx caused between 88,000 and 138,000 additional heart attacks or sudden cardiac deaths in the USA, and that 30–40% of patients who suffered cardiovascular problems because of Vioxx probably died. As Graham famously told the US Senate in 2004: “If there were an average …

FDA Overhaul Needed to Ensure Drug Safety, IOM Says

FDA Overhaul Needed to Ensure Drug Safety, IOM Says

FDA Criticized On Drug Safety Monitoring

FDA lacks clear and effective processes for making decisions about and providing management oversight the safety of approved prescription drugs, states a report from the Government Accountability Office. Two FDA offices, the Office of Drug Safety and the Office of New Drugs, are involved in tracking the safety of drugs after they are on the market. ODS, however, cannot pull drugs from the market or ask manufacturers to put warnings on drug labels. It acts primarily as a consultant to OND. Often, ODS personnel are not even invited to testify at FDA's advisory committee hearings at which safety issues are being discussed, the report says. In addition, certain data constraints impede FDA's ability to evaluate the safety of drugs after they are approved, GAO says. Two-thirds of the postmarket safety studies that the agency asks drugmakers to conduct are never even started. The Drug Safety Oversight Board, which ...

FDA ponders cardiovascular risks of ADHD drugs

Drug regulators are grappling with how to investigate reports of cardiovascular adverse events associated with drugs used to treat attention-deficit/hyperactivity disorder (ADHD). FDA has received reports of 25 deaths associated with use of ADHD medications, according to agency safety reviewers. But, said Kate Gelperin, a medical officer in FDA’s Office of Drug Safety, cardiovascular signals in ADHD-drug-related adverse events reported to the agency were “not conclusive.” A federal advisory panel on February 9 voted 8–7, with one abstention, to add a black-box warning to the labeling of ADHD stimulants to alert prescribers about cardiovascular risks associated with use of the drugs. The Drug Safety and Risk Management Advisory Committee also recommended that FDA require makers of ADHD stimulants to develop medication guides, which pharmacists would distribute when dispensing the medications, to inform patients about cardiovascular risks in ADHD medication use. Panelists decided to exclude from the voting the ADHD medication atomoxetine, or Strattera, which is a selective norepinephrine-reuptake inhibitor made by Eli Lilly and Company.

IOM panel mulls over adverse-event reporting

While many health systems, insurers, and government agencies have developed various reporting programs for gathering adverse-drug events (ADEs), the nation lacks a successful model for collecting ADEs and turning the data into actionable information. Anne Trontell, deputy director of FDA’s Office of Drug Safety, acknowledged before an Institute of Medicine (IOM) panel in November that although the agency’s adverse-event-reporting system has over 3 million reports collected from manufacturers, health care providers, and consumers, the figure reflects only a small portion of actual events that occur. In fact, said Daniel E. Troy, a partner at the Washington, D.C., law firm of Sidley Austin Brown & Wood and a former FDA chief counsel, regulators assume that only 1 in 10 ADEs is reported to the government. With increasingly tightened patient schedules, physicians have little incentive to report ADEs to FDA’s program, known as MedWatch, and other reporting systems, he told IOM’s Forum on Drug Discovery, Development, and Translation, which met for two days in November to discuss the role that consumers and health care providers play in reporting adverse events.

Opening Pandora’s Pillbox: Using Modern Information Tools To Improve Drug Safety

How the Food and Drug Administration (FDA) responds to criticism of its drug safety process will determine whether drug safety actually improves. Propping up the Office of Drug Safety with more bureaucratic prominence or adding new requirements to the preapproval process will add to the cost of drug development and not make drugs safer. New information tools can dramatically improve postmarketing surveillance and collection of data on safety. This information could then be used to reach more definitive regulatory conclusions sooner. New incentives will be needed to entice payers and product developers to work on building a broader, more robust system for collecting data on drug safety.

Update on the Office of Drug Safety at the US FDA

Update on the Office of Drug Safety at the US FDA