Safety and Risks: February 2007 Archives

Recent problems at FDA can be attributed to the lack of consistent, long-term leadership; insufficient resources; and not enough authority to address safety issues, according to four former FDA commissioners who participated Wednesday in a panel discussion at the George Washington University School of Public Health and Health Services, the Newark Star-Ledger reports.

David Kessler, who served as commissioner from 1990 to 1997, criticized the pharmaceutical industry's use of mass-marketing techniques and direct-to-consumer advertising. "The notion that you can come up with a new drug and millions and millions of people take it safely -- the blockbuster -- that is what got us in trouble," Kessler said.

China will tighten the inspection of pharmaceutical products to prevent drug safety accidents, the country's drug watchdog said Tuesday, disclosing that the licenses of 353 medicines have been revoked since August 2006.

Wu Zhen, deputy director of the State Food and Drug Administration (SFDA), said about 3,049 applications for producing new drugs were turned down since last August to fend off shoddy manufacture of medicines.

Attending an online interview hosted by the central government's website, Wu said the administration has required its officials to leave offices to check whether the production conditions meet the description of the applications filed to the SFDA.

During the past several years, there has been a perceived drug safety crisis in the United States. The Institute of Medicine (IOM), recently released its final recommendations for reforming the U.S. drug safety system, but an editorial published in Health Economics by Tomas Philipson and colleagues at the University of Chicago finds little evidence of a drug safety crisis and no scientific evidence to back up the IOM's recommendations.

The current drug controversy is largely due to the withdrawal of Vioxx from the market, but the decrease in drug approval times thanks to the Prescription Drug User Fee Acts (PDUFA), and undue influence from the pharmaceutical industry that these acts may have invited have also played a role. Yet the scientific basis that too many unsafe drugs enter the market is lacking.

ZURICH (Reuters) -- U.S. regulators have asked for more data on Novartis AG's diabetes drug Galvus, potentially delaying any approval of the possible blockbuster by a year and sending shares tumbling.

The Food and Drug Administration has requested a further clinical study to show Galvus's safety and efficacy in patients with kidney impairment, Novartis (Charts) said Monday, but the drugmaker remains confident of getting approval for the medication.

"There are no details on the study requirements, but we would expect this study to take a minimum of 12 months to complete, taking likely U.S. approval beyond August '08," JPMorgan analyst Craig Maxwell said in a note.

The U.S. Food and Drug Administration (FDA) is facing renewed criticism over the process by which it approves drugs for market. Recent reports indicate many drugs are approved before they are proven safe, and problems with the agency's structure and processes prevent it from fulfilling its mission. Subsequently, Congress has started using its oversight powers to scrutinize the agency, and the clamor for FDA reform is growing louder.

The Federal Food Drug and Cosmetic Act requires FDA to ensure the safety of new drugs before the agency approves the drugs for market. However, operating within a provision of the law, FDA often approves drugs before safety is established. The agency then requires drug manufacturers to further study drugs while they are on the market. These "post-marketing commitments" serve to streamline the drug approval process.

Read the package and label of all over-the-counter medicines carefully. Look for the section called "Drug Interaction Precaution."

Make sure your doctor and pharmacist have a list of all the prescription and over-the-counter medicines, vitamins and herbal products you use every day or every so often. Keep a personal medication record and take it with you to doctor's appointments and pharmacy visits.

Consider using one pharmacy for all of your prescription and over-the-counter medicines.

The Food and Drug Administration yesterday warned consumers who ordered pills for depression, anxiety and insomnia over the Internet that they may have received an antipsychotic drug instead.

Haloperidol, a medicine for schizophrenia, was substituted for Sanofi-Aventis SA's Ambien, Pfizer Inc.'s Xanax, Forest Laboratories Inc.'s Lexapro, and Wyeth's Ativan, the FDA said.

Ambien is a sleeping pill. Xanax and Ativan are anti- anxiety treatments. Lexapro is used to treat depression.

By Jerry Avorn

A FEW BLOCKS from the high-rise casinos of Atlantic City, Merck & Co. Inc. is in the middle of a multi billion-dollar bet. A jury is about to decide whether the pharmaceutical giant knew that its blockbuster Vioxx could cause heart attacks, but then minimized that risk in the information it gave to doctors and patients. The decision could have implications for the prevention of future drug disasters more profound than all the tepid plans being discussed by Congress and the FDA.

Faced with thousands of patients assigned to her jurisdiction suing the drugmaker for Vioxx-related heart damage, Superior Court Judge Carol Higbee decided to first resolve a few over-arching issues, before getting to the details of each individual case. She'll instruct the jury first to determine whether the pain reliever could ever increase the risk of heart attack. Most experts agree that it does, and Merck took the drug off the market in 2004 when its own clinical trial proved it, but the company still does not fully acknowledge this fact. Next, she'll ask the jury a kind of pharmacological Watergate question: What did the company know, and when did it know it? And finally, did Merck misrepresent this risk in its promotional materials?

With a lot of fanfare, the Food and Drug Administration last week announced a first — its approval of a diet pill that can be bought without a prescription.

A lower-dosage version of the prescription drug Xenical, the over-the-counter medication will be marketed by GlaxoSmithKline and goes on sale this summer. Since nearly 130 million Americans are considered overweight, the drug is expected to be popular. Conservative estimates are that 5 million-6 million Americans will use the drug in its first year.

Since obesity has been identified as a worsening problem in the United States, this news could be greeted with optimism, except for the many "ifs" and "buts."

NEW YORK - February 13 - A U.S. District Court judge today refused Eli Lilly's request to ban a number of websites from publishing leaked documents relating to Zyprexa, Eli Lilly's top-selling drug. Although the judge rejected the First Amendment arguments made by a variety of individuals eager to publish the documents, the court concluded that "it is unlikely that the court can now effectively enforce an injunction against the Internet in its various manifestations, and it would constitute a dubious manifestation of public policy were it to attempt to do so."

The order is a victory for the Electronic Frontier Foundation (EFF), which represents an anonymous individual who was previously barred by the court's earlier orders from posting links to the Zyprexa documents on the zyprexa.pbwiki.com wiki.

by Jerry Avorn, MD

It has become fashionable to argue that if we just let the marketplace do its thing in healthcare, quality will rise, costs will plummet, and our patients -- I mean our customers -- will prosper. But this is a bad way to organize medical care delivery, and it's an even worse way to generate information about the medications we use.

The Food and Drug Administration does not test drugs itself, instead relying on manufacturers to design and conduct the clinical trials that determine whether their products are approved or not. The companies even pay the salaries of the FDA employees who make those approval decisions. The FDA has hardly any resources to conduct its own postmarketing safety studies of drugs. Instead, it asks the manufacturers to do them -- and most of the studies it requests are not done.^[1,2]

Unintentional deaths due to drug poisoning -- primarily with prescription drugs -- increased by 68 percent between 1999 and 2004, and is second only to motor vehicle crashes as a cause of death from unintentional injury in the US, investigators at the Centers for Disease Control and Prevention report.

Dr. L Paulozzi and Dr. J. Annest, both with the CDC in Atlanta, summarize the most current data from the National Vital Statistics System regarding accidental poisoning deaths in the CDC's publication Morbidity and Mortality Weekly Report.

The annual poisoning-death rate increased from 4.4 per 100,000 population in 1999 to 7.1 per 100,000 in 2004.

Of all sex, racial, and ethnic groups, the greatest increase was among non-Hispanic white females. The age group most affected was persons aged 15 to 24 years.

Scientists who have worked at the U.S. Food and Drug Administration and criticized agency decisions are now helping Congress fashion legislation to tighten product- safety rules.

The scientists include David Ross, who said in an interview that FDA supervisors forced him to retract a recommendation that the antibiotic Ketek, made by Sanofi-Aventis SA, was probably too dangerous to be used for treating two common respiratory infections. The drug was approved in 2004 and had $148 million in sales in 2005.

Ross is one of four current or former employees of the FDA who are working with Congress on bills intended to create more stringent drug safety rules. One change being proposed would create a new office to monitor the safety record of drugs after they're on the market. Next week, several of the critics will state their concerns at a congressional hearing into the FDA.

CHICAGO - A drug widely used to prevent excessive bleeding during heart surgery appears to raise the risk of dying in the five years afterward by nearly 50 percent, an international study found.

The researchers said replacing the drug -- aprotinin, sold by Bayer AG under the brand name Trasylol -- with other, cheaper medications for a year would prevent 10,000 deaths worldwide over the next five years.

The findings were more bad news for Trasylol: The same scientists found the drug raised the risk of kidney failure, heart attacks and strokes in a study published last year. Most of the deaths in the new study were related to those problems.

GeneEd, Inc., a leading provider of Continuing Medical Education (CME) accredited online learning for the life-science and healthcare professions, announced today the release of a Drug Safety: Adverse Event Reporting course.

The course discusses the reasons and mechanisms for adverse event collection during and following clinical studies. Key concepts and roles are defined and current and legacy terminologies used to report adverse events (AEs) in clinical trials are discussed. In addition, the reporting responsibilities of the sponsor and investigator are explored on both a national and global scale.