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Medical Journal Calls for a New Drug Watchdog
The United States needs a better system to detect harmful effects of drugs already on the market, and it should be independent of the Food and Drug Administration and the drug industry, medical researchers and journal editors said yesterday.
Arguing that it was unreasonable to expect the same agency that approves drugs to "also be committed to actively seek evidence to prove itself wrong," the editors of The Journal of the American Medical Association recommended that the nation consider establishing an "independent drug safety board" to track the safety of drugs and medical devices after they were approved and in widespread use.
The idea has been proposed several times, usually after a spectacular drug imbroglio like the recent withdrawal of the popular arthritis drug and painkiller Vioxx after it was linked to heart attacks. But the earlier proposals went nowhere.
This time around, as in the past, the industry and the drug agency reacted by challenging the need for a new safety board.
"It is not at all clear that there is need for change," Jeff Trewhitt, a spokesman for PhRMA, the trade group for drug makers, said.
Dr. Sandra Kweder, deputy director of the Office of New Drugs at the F.D.A., said a safety board was not necessary because "we consider our office of drug safety independent of the office of new drugs."
But both also left open the possibility of change in the future, depending on the findings of a study to be conducted by the Institute of Medicine, a branch of the Congressionally chartered National Academy of Sciences, which conducts scientific reviews for the government.
An act of Congress would most likely be needed to establish an independent board to evaluate the safety of drugs after they reach the market. The recommendation for a new safety board appeared in an editorial and in one of several articles that were scheduled for the Dec. 1 issue of the journal but were published online yesterday at www.jama.com.
The articles were released early because of their relevance to recent events: the Vioxx withdrawal and the addition of a strong warning to antidepressants because of evidence that they may raise the risk of suicidal thinking or suicide attempts in teenagers.
Those actions led to Congressional hearings last week and complaints that the drug agency was not moving quickly enough to get dangerous drugs off the market or to warn consumers about risks that emerged after drugs were approved.
Senator Charles E. Grassley, the Iowa Republican who led the hearings, favors an even stronger separation between the F.D.A.'s offices of new drugs and drug safety, a spokeswoman said yesterday. Mr. Grassley could not be reached for comment on the proposal for a new safety board.
The nation's current system for tracking drug side effects, called Medwatch, is rife with inadequacies, the editors of the journal wrote. The major problem, they said, is that drug makers are the ones who collect and evaluate most of the information on side effects from their own products and then report it to the F.D.A.
The companies "may be tempted to conceal" unfavorable data, the editors wrote, and they and the drug agency may be too slow to order studies to follow up hints of trouble.
Another flaw the editors cited is the system's reliance on voluntary reports from doctors, which means that most adverse effects probably go unreported. In addition, they said, most of the reports are of poor quality and cannot be used to determine how common side effects are or whether particular problems resulted from medicines or from the illnesses they were meant to treat.
The reports can be used as red flags, particularly if they concern rare conditions that would be hard to explain as anything other than a drug effect. But researchers say a passive system like Medwatch cannot be expected to pick up a drug-related increase in a disease that is already very common, like heart attacks or stroke. Carefully controlled studies are required to detect such problems - and they are not done often enough, researchers say.
The journal editors also noted that although drug companies have agreed to conduct postmarketing studies as a condition of approval for certain drugs, fewer than half the promised studies have been completed and many have not even been started.
Dr. Kweder, of the F.D.A., said, "We have very little authority to make sure those postmarketing commitments are carried out." Legislation would be needed to give the agency that power, she said.
But she said she did not see the need for an independent safety agency, given the separation between the Office of Drug Safety and the Office of New Drugs.
"We believe there is a healthy tension between those offices and there should be," Dr.. Kweder said. But, she added, "We are certainly willing to consider what alternatives there might be or how to facilitate that separation further."
That openness to change, she said, is why the drug agency asked the Institute of Medicine to evaluate its ability to track drug safety.
Mr. Trewhitt, the PhRMA spokesman, also said the F.D.A.'s Office of Drug Safety was independent enough, and noted that it would be doubling its staff by adding 106 officers over the next few years. He said "it would be wise" to wait for the Institute of Medicine's recommendations before making any changes in postmarket safety monitoring.
Other articles in the journal included a contentious exchange between doctors and a lawyer for Bayer over the company's drug Baycol, a cholesterol-lowering statin drug that was taken off the market in 2001 because it caused muscle breakdown in some patients.
The doctors, who acted as expert witnesses for plaintiffs suing Bayer, relied in part on company documents that became public during the case to conclude that Bayer had withheld or delayed releasing data that would have revealed the problems with Baycol and might have led to an earlier withdrawal.
"My judgment is that pharmaceutical companies may have too high a threshold for taking action in a timely fashion to protect the health of the public," one of the experts, Dr. Bruce M. Psaty, a professor of medicine and epidemiology at the University of Washington, said in an interview.
In a published response in the journal, Bayer's lawyer, Joseph D. Piorkowski Jr., denied that Bayer had acted too slowly, and said that the company had acted responsibly by withdrawing the drug voluntarily.
Bayer also issued a statement that said, in part, "The company believes the article is unscientific, lacking in fair balance and objectivity," and questioned the doctors' objectivity because they had worked for the plaintiffs suing the company.
Like the journal editors, Dr. Psaty recommended that an independent safety board be formed, perhaps appointed by Congress, to decide when drugs should be taken off the market.
Not all researchers agree. In another article in the journal, Dr. Brian L. Strom of the University of Pennsylvania School of Medicine said, "Our F.D.A. colleagues can be trusted to do the job, given sufficient resources."
But Dr. Alastair Wood of Vanderbilt University, an expert on drug research and regulation, who did not contribute to the journal, said he thought an independent board was needed.
Dr. Wood said: "When we have a drug problem it's analogous to a plane crashing off the coast of New York City, and being investigated by the air traffic controllers who controlled the flight and the airline flying the plane. They're not bad people, but it's not the way we do things in this country."
Los Angeles Times
September 24, 2004
Lawmakers Take FDA to Task on Antidepressants
A House subcommittee says the agency held back data on the drugs' risks to children.
By Elizabeth Shogren,
Times Staff Writer
WASHINGTON - Members of Congress on Thursday accused the Food and Drug Administration of suppressing information, for as long as eight years, about the increased risks of suicidal thought and behavior in children and teenagers taking antidepressants.
"There is something terribly rotten at the FDA," said Rep. Peter Deutsch (D-Fla.). "No agency charged with protecting public health should have behaved with such indifference."
During a House subcommittee hearing on the FDA review of clinical trials involving the widely prescribed drugs, the legislators also criticized FDA officials for withholding information from clinical trials about the lack of benefit for children from most antidepressants.
"The FDA knew about the lack of efficacy in these clinical trials several years ago, and nothing has been done to change labels to inform doctors, patients and parents," said Rep. Greg Walden (R-Ore.), chairman of the hearing of the House Energy and Commerce oversight and investigations subcommittee.
FDA officials defended their decisions to keep data gathered in clinical trials from the public.
"The higher-ups felt the data weren't ripe for presentation," said Dr. Robert Temple, a director at the FDA's center for drug evaluation and research.
Temple said agency officials were worried about scaring young patients away from the drugs.
"Having untreated depression is risky too," he said.
About 1,600 teens - many of them suffering from depression - commit suicide each year, according to the FDA.
The FDA is under intense congressional scrutiny for its failure to move more quickly to warn doctors and parents about the increased risk of suicidal behavior in children on antidepressants. Two FDA advisory committees recommended last week that the agency order drug companies to place prominent warnings on drug packaging and on the prescribing information that goes to physicians.
"We don't want children taking an antidepressant drug if there appears to be quite a bit of evidence that not only does it not help them, but in some cases it actually hurts them by increasing the risks" of suicidal thought, said Rep. Joe Barton (R-Texas), chairman of the Energy and Commerce Committee.
Doctors last year wrote about 15 million prescriptions of nine antidepressants for children and teens, according to an analysis from the FDA and from IMS Health, a pharmaceutical information and consulting company.
Fluoxetine hydrochloride, marketed by Eli Lilly & Co. as Prozac, is the only antidepressant approved by the FDA for use in children because it has met the agency's standard of effectiveness in clinical trials. But because they are not prohibited from doing so, physicians regularly prescribe other similar drugs to young patients.
In Thursday's daylong hearing, legislators questioned a decision by senior FDA officials to prevent an agency researcher, Dr. Andrew Mosholder, from presenting his analysis of data from clinical trials of antidepressant use by children to two FDA advisory committees in February. His report showed that children taking the drugs were almost twice as likely to exhibit serious suicide-related behavior as those taking placebos.
Mosholder presented his findings at last week's advisory committee meeting, but only after news of his report had leaked to the media and a reexamination of the data by a Columbia University team and another FDA researcher had confirmed his conclusions.
Mosholder analyzed data on Prozac, Zoloft, Celexa, Effexor, Luvox, Paxil, Remeron, Serzone, Wellbutrin and Lexapro. All but Lexapro were included in the reexamination of the clinical trials.
The legislators also grilled FDA officials about documents from as early as 1996 that suggested a possible connection between antidepressants and suicidal tendencies in children.
In March 1996, Dr. James F. Knudsen, an FDA researcher, wrote to an executive at Pfizer Inc. that "there appears to be an increased frequency of reports of suicidality in the pediatric/adolescent patients exposed to" the company's antidepressant, Zoloft, in clinical trials.
But Dr. Thomas Laughren, the FDA team leader who supervised Knudsen, told the hearing that he analyzed the data referred to in the letter and concluded that they did not "represent a signal of risk."
He said there was no reason the question of whether the drugs caused suicidal tendencies in children should have been on the agency's "radar screen" between 1996 and last year, when Mosholder's analysis revealed the possible link.
But legislators on the panel were not convinced.
HEARING on FDA's Role in Protecting the Public Health: Examining FDA's Review of Safety & Efficacy Concerns in Anti-Depressant Use by Children Subcommittee on Oversight and Investigations took place at 11:00 AM, September 23, 2004 at 2123 Rayburn House Office Building, Washington, D.C.
A sweeping mental health initiative will be unveiled by President George W Bush in July. The plan promises to integrate mentally ill patients fully into the community by providing "services in the community, rather than institutions," according to a March 2004 progress report entitled New Freedom Initiative (www.whitehouse.gov/infocus/newfreedom/toc-2004.html). While some praise the plan's goals, others say it protects the profits of drug companies at the expense of the public.
Bush established the New Freedom Commission on Mental Health in April 2002 to conduct a "comprehensive study of the United States mental health service delivery system." The commission issued its recommendations in July 2003. Bush instructed more than 25 federal agencies to develop an implementation plan based on those recommendations.
The president's commission found that "despite their prevalence, mental disorders often go undiagnosed" and recommended comprehensive mental health screening for "consumers of all ages," including preschool children. According to the commission, "Each year, young children are expelled from preschools and childcare facilities for severely disruptive behaviours and emotional disorders." Schools, wrote the commission, are in a "key position" to screen the 52 million students and 6 million adults who work at the schools.
The commission also recommended "Linkage [of screening] with treatment and supports" including "state-of-the-art treatments" using "specific medications for specific conditions." The commission commended the Texas Medication Algorithm Project (TMAP) as a "model" medication treatment plan that "illustrates an evidence-based practice that results in better consumer outcomes."
Dr Darrel Regier, director of research at the American Psychiatric Association (APA), lauded the president's initiative and the Texas project model saying, "What's nice about TMAP is that this is a logical plan based on efficacy data from clinical trials."
He said the association has called for increased funding for implementation of the overall plan.
But the Texas project, which promotes the use of newer, more expensive antidepressants and antipsychotic drugs, sparked off controversy when Allen Jones, an employee of the Pennsylvania Office of the Inspector General, revealed that key officials with influence over the medication plan in his state received money and perks from drug companies with a stake in the medication algorithm (15 May, p1153). He was sacked this week for speaking to the BMJ and the New York Times.
The Texas project started in 1995 as an alliance of individuals from the pharmaceutical industry, the University of Texas, and the mental health and corrections systems of Texas. The project was funded by a Robert Wood Johnson grant—and by several drug companies.
Mr Jones told the BMJ that the same "political/pharmaceutical alliance" that generated the Texas project was behind the recommendations of the New Freedom Commission, which, according to his whistleblower report, were "poised to consolidate the TMAP effort into a comprehensive national policy to treat mental illness with expensive, patented medications of questionable benefit and deadly side effects, and to force private insurers to pick up more of the tab" (http://psychrights.org/Drugs/AllenJonesTMAPJanuary20.pdf).
Larry D Sasich, research associate with Public Citizen in Washington, DC, told the BMJ that studies in both the United States and Great Britain suggest that "using the older drugs first makes sense. There's nothing in the labeling of the newer atypical antipsychotic drugs that suggests they are superior in efficacy to haloperidol [an older "typical" antipsychotic]. There has to be an enormous amount of unnecessary expenditures for the newer drugs."
President George W. Bush established the President’s New Freedom Commission on Mental Health in April 2002 as part of his commitment to eliminate inequality for Americans with disabilities. The President directed the Commission to identify policies that could be implemented by Federal, State and local governments to maximize the utility of existing resources, improve coordination of treatments and services, and promote successful community integration for adults with a serious mental illness and children with a serious emotional disturbance.
From June 2002 to April 2003, the 22 Commissioners met monthly to analyze the public and private mental health systems, visit innovative model programs across the country and hear testimony from the systems’ many stakeholders, including dozens of consumers of mental health care, families, advocates, public and private providers and administrators and mental health researchers. The Commission received feedback, comments and suggestions from nearly 2,500 people from all 50 states via personal testimony, letters, emails and a comment section on this website. In addition to public comment, the Commission consulted with nationally recognized professionals with expertise in diverse areas of mental health policy. The Commission established 15 subcommittees to examine specific aspects of mental health services and offer recommendations for improvement. The Commissioner page contains the Commission’s Membership Roster and the Subcommittee page displays the separate subcommittees and their report summaries.
The Commission will submit the final report to the President in May 2003, and the White House will, in turn, release the report soon thereafter. Once released, you will be able to access the final report on the "Reports" page of this website. The Commission wishes to thank all those who participated in this critical and historic effort. The final report to the President offers a vision of hope and recovery for people with a serious mental illness and their families.
PASADENA, Calif. -- On the September morning Merck pulled its blockbuster pain medicine Vioxx from the market, a group of lawyers was busy taking a deposition from the drug maker's former chief medical officer.
The news stunned those inside the offices of that prominent Philadelphia law firm. Then, the deposition quickly resumed, as attorneys probed for facts to make their case that Vioxx, a $2.5 billion seller, caused heart attacks and strokes.
Yesterday, with the litigation storm intensifying, hundreds of plaintiffs' attorneys from around the country gathered at the plush Ritz-Carlton Hotel here to receive a $795 crash course on the liability issues Merck faces in Vioxx.
"We are here in the wake of the largest pharmaceutical withdrawal in history," said Andy Birchfield, a prominent lawyer from Alabama whose firm is involved in a number of the oldest Vioxx lawsuits.
"The purpose of this meeting is to share what we know about Vioxx, and we actually know a lot because a handful of firms have been involved in this for three years."
In lawyer's parlance, Vioxx is a fast-breaking tort, which could ultimately generate in excess of 50,000 plaintiffs. By some estimates, Merck faces liability of as much as $18 billion in cases that stretch from New Jersey to the West Coast.
A California judge recently asked a group of attorneys litigating one of the older Vioxx cases, "Just how big is this going to get?" The attorneys looked at each other and shrugged, said David Bigelow of Los Angeles, one of the lawyers.
That has professional organizations scrambling to turn scheduled educational conferences into daylong sessions on Vioxx.
Lawyers who started taking cases as early as 2001 find themselves in a position of providing insights on everything from how the drug works to how to select cases -- without revealing too much of their own strategy.
In May 2003, New Jersey court officials designated a group of roughly 50 lawsuits as a mass tort and assigned the case to state Superior Court Judge Carol Higbee, who has presided over Atlantic and Cape May counties since 1993.
The case involves nearly 200 lawsuits today -- and the number continues to grow.
"New Jersey is the battleground, the epicenter," said Chris Seeger, one of the lead attorneys in the litigation.
Lawyers in the New Jersey case have gathered 4 million documents, many of which Merck is fighting to keep confidential. Those documents will be a key part of the effort to prove the drug was to blame for their clients' heart attacks, strokes and, in some cases, their deaths.
In a statement, Whitehouse Station-based Merck said it "believes the appropriate place to try proceedings against the company is in the court of law, not through the news media."
"None of the documents can obscure the fact that Merck acted responsibly and appropriately as it developed and marketed Vioxx. When questions arose about the safety, Merck took steps to investigate and address those issues," the company said.
But lawyers say there's proof to suggest otherwise.
"It's going to be difficult, if not impossible, to defend Merck's conduct," Kline said. The cases will turn on proving the drug caused the plaintiffs' injuries.
"That challenge is to take cases that are real, serious cases where it can be proved that the drug caused the stroke or the heart attack," David Jacoby, another lawyer representing cases in the mass tort litigation, said.
Big Changes Ahead for Technology-Based Pharmaceutical Detailing
Broader Applications Call For a Shift in Sales and Marketing Strategy
NEW YORK, Nov. 10 /PRNewswire/ -- Electronic detailing, or "edetailing" -- the practice of providing pharmaceutical information and promotional material to physicians using technology-continues its rapid evolution. A new study from
Manhattan Research, LLC (http://www.manhattanresearch.com ), a healthcare marketing information and services firm, finds that using technology to support the interaction between the physician, pharmaceutical company, and detail representative, which itself is just a few years old, has already broken the boundaries of its traditional definition.
"Electronic detailing has rapidly moved beyond physicians using a static website for product information," says Mark Bard, president of Manhattan Research. "It is now more accurately described as technology-supported detailing -- a way to engage, educate and incorporate physician preferences, including how and when they want to learn over time."
The study, the Technology-Supported Detailing Research Module, is based on an analysis of data collected from two nationally representative physician research studies, ePharma Physician(R) v4.0 and Taking the Pulse(R) v4.0. It explores all aspects of physician adoption of edetailing, including use, satisfaction, relevance, relative channel mix, response rates, and the pharma
and vendor competitive landscape.
The study finds that:
-- Of the physicians invited to participate in edetailing, an estimated three-quarters are participating today. Additionally, about half of all physicians not currently participating indicate future interest in doing so.
-- Physicians, on average, spend less than 10 percent of their overall time accessing pharmaceutical information through edetailing. To achieve an optimal channel mix, physicians expect their time spent accessing edetailing to increase by almost 66 percent in the near future.
-- The types of edetailing sessions with the highest response rates are a Flash animation detail and a self-service website.
-- In rank order, the top seven pharma companies in reaching physicians with edetailing are Pfizer, AstraZeneca, Novartis, GSK, Aventis, Merck, and Lilly.
-- Vendor platforms analyzed in this research include Physicians Interactive, Medscape, Lathian (a.k.a. My Drug Rep), MarketRx, Medsite, Aptilon, IQLearning and DotCom Advisors.
"With its flexibility and convenience, technology-supported detailing continues to be an effective and highly economical way to communicate with physicians," says Ashley Wendus, Senior Analyst, at Manhattan Research. "It offers a supplemental channel to build on existing relationships with high-
prescribing physicians and a primary channel to connect with hard-to-reach physicians." At the same time, despite top-line growth in users, physicians are becoming more selective about when and where they will participate in technology-based detailing when invited. They are seeking to optimize their information mix, including reallocating where they pull information.
Today's options for physicians include accessing a self-service
information site, participating in Web-based seminars, interacting with a remote rep by video stream, and meeting with sales reps who use mobile device detail aids. On the horizon are more choices based on different lengths of details, interactive learning that enables physicians to proceed at their own speed and pace, and close-loop analytics that can monitor physician users over
time tailoring new offerings based on their historical trends.
As physicians continue to spend less time with pharma detail reps and seek alternative information channels, pharma sales executives must rethink their approach, the study concludes. Pharma companies can take one of two paths-
The Technology-Supported Detailing Research Module is available
exclusively to Manhattan Research clients and is immediately available for purchase. To attain more information on gaining client-level access to the research findings and to sign up for a webinar on Monday November 15 at 3:00 P.M. EST or on Tuesday November 16 at 12:00 P.M. EST, visit http://www.manhattanresearch.com/edetailing.htm or contact Nicole D'Angelo at
ABOUT MANHATTAN RESEARCH, LLC
Manhattan Research, based in New York, helps healthcare and life sciences organizations adapt, prosper, and maximize pportunities in the networked economy. The company seeks to serve as a strategic positioning system for clients, helping them use industry expertise, robust proprietary data sets, and insight to maximize the value of their overall business strategy.
Manhattan Research's clients include global pharmaceutical and biotech companies, nonprofit health organizations, technology vendors, health content
providers, and health plans.
Big Pharma's Report Card
These are anxious times for the drug giants, which are uncomfortably aware that the first outfit to restock its pipeline will surge ahead of the pack.
The third quarter of 2004 hasn't been kind to the major U.S.-based pharmaceutical companies. In a period in which several of the players are already struggling with a dearth of new product launches, declining sales of key products, and looming patent expirations, Merck's (MRK ) surprise market withdrawal of Vioxx , its COX-2 inhibitor pain medication, was the biggest blow. The withdrawal meant not only the vaporization of $2.5 billion in annual sales, but also the beginning of a long product-litigation nightmare for the company.
NEW ORLEANS - This morning, Pfizer was blindsided as The New York Times reported information about a reanalysis of old data that say the drug giant's Bextra, which is similar to Merck's Vioxx, increased the risk of heart attacks and strokes.
That's not been proved yet. The study may well be flawed, and even its author says it falls short of the "gold standard" of clinical trial design. But even so, Pfizer (nyse: PFE - news - people ) executives should start thinking about Bextra as a lost cause, partly because it will make it easier for the company to defend Celebrex, which is Bextra's chemical cousin and one of Pfizer's best-selling drugs.
Garret FitzGerald, a pharmacologist at the University of Pennsylvania, dropped the information into a lecture he was giving here at the American Heart Association's annual meeting. The presentation had not been reviewed by the AHA, and FitzGerald released only a tease of data about his study. He started with two studies of Bextra pills, plus an injectible version, in patients undergoing open-heart surgery, and added other data taken from a reanalysis of Bextra studies, by the University of Connecticut's William White, of arthritis patients that took a placebo. When taken together, the data showed a doubling of the risk from heart attacks and strokes.
But it was already well known that the open heart surgery data showed an increased risk of heart attack and stroke in those patients. Pfizer disclosed information about those studies in letters to doctors on Oct. 15.
"We don't have any idea what Dr. Fitzgerald actually did," says Mitch Gandelman, a Pfizer vice president. "We're at a loss."
FitzGerald and two colleagues used statistical methods to try to make sure that he wasn't mixing apples and oranges by adding data about patients with arthritis, but he says the risk was certainly driven by the open heart surgery patients. In the first open heart surgery paper, patients were 3.5 times more likely to have heart attacks than those on a sugar pill. In the second, the risk was 2.88 times higher. In the third study, of arthritis patients, the risk was 1.77 times higher, according to slides presented by FitzGerald.
"What we're not saying is that people who have arthritis without cardiovascular risk should stop taking [Bextra]," FitzGerald said in an interview. He noted that his ideas, which he has been developing since Cox-2 drugs hit the market, would mean that only long-term users need to worry about Cox-2 heart risk. When his wife was taking pain medications, he said, she took Vioxx -- and that was when FitzGerald was talking very publicly about the potential for these drugs to cause heart disease.
Pfizer issued a statement defending Bextra, noting in its defense the same meta-analysis from which FitzGerald drew his arthritis data. Gandelman said, "Pfizer stands by the cardiovascular safety profile of Bextra established in studies up to one year for arthritis."
Other cardiologists reached for comment said that since they hadn't seen the data, they couldn't say anything. Eric Topol of the Cleveland Clinic worried that FitzGerald's analysis could easily be off-base, even though he believes that the heart surgery studies are "the real deal" and indicate a cardiovascular problem for Bextra. (It is easy to argue about these after-the-fact analyses. FitzGerald believes an early paper Topol co-wrote about Vioxx's heart risk was "right for the wrong reasons.")
Even if Pfizer managed to prove Bextra is safe for the heart in most populations, the drug's sales could still be severely limited. Pfizer revealed in a regulatory filing that it is likely to get a prominent warning about a skin reaction from the FDA, and analysts on Wall Street have speculated that the open heart surgery studies will also be cited in the drug's label.
Analysts at Prudential Equity Group and Goldman Sachs (nyse: GS - news - people ) have said that the black box warning could impair sales. Certainly it seems unlikely that Bextra, which was on the cusp of blockbuster status, is going to keep growing at a fast rate, and, given this controversy, sales may shrink. In a note to investors this morning, Winton Gibbons at William Blair & Co. wrote that in recent weeks there's been a market shift from Bextra to Celebrex.
FitzGerald does not think Bextra should be pulled from the market. He says his personal belief is that the drug should get a significant warning label for patients at risk of heart attacks and strokes. His theories about the mechanism by which Cox-2 drugs cause heart problems would also implicate Celebrex. Defending that drug, which has been studied in many patients without a clear signal of risk, will be much easier once issues relating to Bextra have been settled. The faster Pfizer gets this painful job out of the way, the better it will look.
Early next year, the U.S. Food and Drug Administration will convene a panel of academics to discuss the risks of these medicines, known as Cox-2 inhibitors, in causing heart disease. The more Pfizer can solely focus on how Celebrex might be different, the better.
WASHINGTON -- It was surely one of the most awkward moments of a long career at the top of one of America's best-known companies.
Raymond Gilmartin, chairman and chief executive of Merck, sat in front of the Senate Finance Committee and a C-Span television audience and listened for two hours as his company got hammered.
One Food and Drug Administration scientist accused Merck of ignoring early signs that Vioxx, a painkiller taken by 20 million people, doubled the risk of heart attacks and strokes. Behind the senators hung posters with excerpts from internal documents obtained by the committee, many still under court seal.
As the last witness, the 63-year-old executive who earned $7.9 million last year, took his seat in a leather arm chair at a table covered in red fabric and bathed in bright spotlights. Then he calmly explained why Merck abruptly pulled Vioxx off the market Sept. 30.
For one moment, his voice went beyond a monotone as he read a passage about his personal stake in the matter.
"Mr. Chairman, Merck believed wholeheartedly in Vioxx," he said as several hundred people in Room 216 of the Hart Senate Building listened. "I believed wholeheartedly in Vioxx.
"In fact, my wife was using Vioxx up until the day we withdrew it from the marketplace."
The rest of his hourlong testimony stuck mostly to the same script: Merck yanked the drug as soon as it realized it might be dangerous, he said.
Gilmartin said earlier studies of Vioxx did not show a risk of heart problems. He said Merck withdrew the product six days after the company's research chief called him with the news that a large clinical trial had found safety problems for those who took Vioxx more than 18 months.
Sen. Charles Grassley (R-Iowa), the committee chairman who has been spearheading the investigation, asked Gilmartin about an estimate earlier in the session from David Graham -- an FDA epidemiologist -- that Vioxx may have caused more than 100,000 heart attacks during its five years on the market.
Gilmartin said heart attacks "occur throughout the population" and that just become someone took Vioxx and had a heart attack doesn't mean the painkiller caused the heart attack. The FDA has determined the "risk for any one individual was very small" and there is "no way to make any reliable estimates," he said.
In one of the few efforts to press Gilmartin, Grassley asked how he could object to the estimates by Graham and others.
Gilmartin said they were "just speculation."
Speaking to reporters afterward, Grassley said there were "a lot of red flags that should have raised more questions. "But Mr. Gilmartin obviously disagrees with that," Grassley said.
Not everybody on the panel was so critical. Sen. Orrin Hatch (R-Utah), a longtime supporter of the pharmaceutical industry, said Gilmartin "acted responsibly" and noted that it is "a very difficult time for you."
When it was over, and the senators finished asking their questions, Gilmartin strode quickly out of the room before the hearing was officially adjourned.
Pharma stocks under pressure; five popular drugs "dangerous"
Friday, November 19, 2004 4:52:52 AM ET
NEW YORK, November 19 (newratings.com) – Various leading pharmaceutical companies witnessed sharp downside pressure on their share prices, after a veteran drug-safety official with the FDA warned of serious side-effect risks with five widely used drugs.
David Graham, an Associate Director with the Office of Drug Safety, testified before a Senate committee inquiring into the recent withdrawal of the arthritis drug, Vioxx, saying that five other popular drugs should be either withdrawn or restricted since they posed the risk of dangerous side effects. The official said that the FDA was sometimes incapable of stopping the dangerous drugs from coming into and staying on the market. While listing the five dangerous drugs, David Graham said that AstraZeneca's (AZN.ISE) cholesterol-reducing drug, Crestor, poses risks of kidney failure and a rare muscle disease; Abbot Laboratories' (ABT) weight-loss drug, Meridia, is of little use and has cardiovascular side effects; Roche's acne medication, Accutane, can cause birth defects if consumed during pregnancy; Pfizer's (PFE) painkiller, Bextra, poses cardiovascular risks similar to Merck's (MRK) Vioxx and GlaxoSmithKline's (GSK) asthma medication, Serevent, increasing the risks of dying of asthma. The makers of all five drugs later defended their respective products in separate statements.
THURSDAY, Nov. 18 (HealthDayNews) -- U.S. Food and Drug Administration officials defended their record on drug safety Thursday in the face of attacks from both inside and outside the agency.
Drug giants also found themselves with their feet held to the fire during a Senate Finance Committee hearing.
Dr. David Graham, an FDA reviewer who initially recommended the arthritis drug Vioxx be taken off the market, told committee members that the blockbuster medication may have caused up to 160,000 heart attacks and strokes, or 1 percent of the entire state of Florida.
"I would argue that the FDA, as currently configured, is incapable of protecting America against another Vioxx," the Associated Press quoted Graham as saying. "We are virtually defenseless."
The drug's maker, Merck & Co., voluntarily withdrew Vioxx in late September after its own studies found an unacceptable cardiovascular risk. The FDA did not force the recall.
Sen. Jeff Bingaman (D-N.M.) pointed to the FDA's own inner workings as the culprit. "The culture within the FDA, being one where the pharmaceutical industry -- which the FDA is supposed to regulate -- is seen by the FDA as its client instead," he said.
Dr. Sandra Kweder, director of the Office of New Drugs at the FDA's Center for Drug Evaluation and Research, spoke up for her agency. The "FDA worked actively and vigorously with Merck to inform public health professionals of what was known regarding cardiovascular risk with Vioxx, and to pursue further definitive investigations to better define and quantify this risk," she said. "Indeed, the recent study findings disclosed by Merck, leading to its decision to voluntarily withdraw Vioxx from the marketplace, resulted from FDA's vigilance in requiring these long-term outcome trials to address our concerns."
The drug has had a somewhat checkered history. The FDA approved Vioxx in May 1999. In 2002, labeling changes were required to highlight an increased risk in cardiovascular events, especially at the higher, 50-milligram dose.
Raymond Gilmartin, Merck's chairman and CEO, said the company "puts patients first," according to prepared testimony. He told the panel that Merck had conducted many studies on Vioxx both before and after its approval, and the research had found the results at best safe and at worst contradictory. He said he was surprised by the results of the study that led to its withdrawal. "Merck believed wholeheartedly in Vioxx," he said. "In fact, my wife was a user of Vioxx until the day we withdrew it."
Graham was the lead author on one study, which involved almost 1.4 million Kaiser Permanente patients. According to the AP, the study found high doses of Vioxx tripled the risk of heart attacks and sudden cardiac death.
Graham also testified that at least five other drugs are on the market today should be looked at seriously to see whether they should remain there, the AP reported. He cited the acne drug Accutane,made by Hoffmann-La Roche Inc. (Roche); the weight-loss drug Meridia, made by Abbott Labs; the anti-cholesterol drug Crestor, made by AstraZeneca; the pain reliever Bextra, made by Pfizer Pharmaceuticals; and the asthma drug Serevent, made by GlaxoSmithKline.
According to the AP, Graham has testified that his bosses pressured him to downplay his Vioxx conclusions. A statement issued Wednesday by Dr. Lester Crawford, acting commissioner of the FDA, said that "the project officer voluntarily chose to revise his conclusions, and he did so, in his own words, 'without compromising my deeply held convictions.'"
According to Crawford, that "project manager," assumed to be Graham, did not submit a draft report requested by his superiors until after Vioxx had been voluntarily withdrawn from pharmacy shelves. "Senior drug experts in [the] FDA did not have this report or the underlying data prior to that time," Crawford said. Crawford also alleged that Graham had submitted his findings to The Lancet without going through the "long-established peer-review and clearance process established for scientific papers submitted by FDA scientists."
Both Crawford and Kweder emphasized that additional steps are being undertaken by the FDA to strengthen its mission to protect the public's health. This included a "five-step plan to strengthen its drug safety program," Kweder pointed out, and three guidances designed to "assist pharmaceutical firms in identifying and assessing potential safety risks not only before a drug reaches the market but also after a drug is already on the market."
Pfizer Hit With Bextra Lawsuit
11/16/2004 4:13 PM EST -
Thursday November 11, 6:35 pm ET
By Mary Ellen Egan
GSK, which is spending $30 million on this campaign, is also trying to put a human face on the company. In one TV commercial Ann Saunders, a company researcher, discusses losing her grandmother to Alzheimer's. She says she is now determined to find a cure. In another spot, created by ad agency Publicis of Dallas, part of Publicis Groupe, GSK researcher Eliot Ohlstein talks of losing his father to heart disease while Ohlstein toiled for 20 years to develop Coreg. "When it takes that long, you draw your inspiration from two things: the millions you can help and the one you couldn't," he intones to the strains of heart-yanking music.
Drug companies are coming out of the shadows to fight for their reputations--and profits.
Drug companies are also starting to realize they need to seem like gentle giants, particularly as information about some of their shabby practices comes to light. Pfizer agreed to pay $430 million in May after its Warner-Lambert division was accused of marketing the epilepsy drug Neurontin for off-label use. And last August GSK settled a suit filed by New York Attorney General Eliot Spitzer, who accused the company of failing to publish negative studies about unapproved use of its antidepressant Paxil. The glare of bad publicity hit Merck & Co. in September when it pulled its heavily advertised anti-inflammatory drug Vioxx off the market because of an increased risk of heart attacks and strokes in patients. Around the same time Chiron, one of the world's largest vaccine suppliers, announced it couldn't ship 4 million doses of flu vaccine because they didn't meet sterility standards.
GlaxoSmithKline's Michael Szap is on the lecture circuit. "People complain about the cost of their medications," the senior district sales manager says, his voice rising. "But the money goes back into research and development." It's a point Szap repeats eight times in a 45-minute presentation to 12 pharmacy students and staffers at Woodhull Medical Center in Brooklyn, N.Y. And it's a message he and more than 9,000 GSK foot soldiers will deliver this year to as many as 500,000 prescription drug customers--professionals and patients--in intimate and informal gatherings across the country. "Medicines save lives," Szap also says repeatedly to these same groups.
The face time is part of a grand campaign by GSK, the world's second-largest pharmaceutical company, to combat a tide of resentment against its industry. Some politicians are talking about government cost controls. A lot more are openly advocating the next-worst thing for a vendor of patented medicines, the importation of prescription drugs from cheaper overseas markets. And then there are the tort lawyers, descending on the drug companies with billion-dollar class actions claiming that potentially dangerous drugs like antidepressants and Vioxx have been all too eagerly marketed.
Pfizer has a strategy for deflecting criticism: do-goodism. It recently announced a drug discount program targeting uninsured and poor consumers. It offers free Lipitor, the cholesterol-lowering drug, and Viagra, the erectile-dysfunction treatment, among others, to families with incomes under $31,000. Discounts are available for all uninsured families. TV ads touting the program feature Pfizer Chief Executive Henry McKinnell, in an unusual turn for a pharmaceutical boss.
(A Class I recall is a situation in which there is a reasonable probability that the use of or exposure to a violative product will cause serious adverse health consequences or death.)
If you believe your pet suffered any reaction to ProHeart 6, you may contact the attorney who has filed a class action lawsuit at:
For the latest information regarding the ProHeart 6 class action lawsuit, go to:
RECALLS AND FIELD CORRECTIONS: VETERINARY MEDICINE - CLASS I
Fort Dodge ProHeart 6 (moxidectin) Sustained Release Injectable for Dogs, Sterile Vehicle 17 ml. to be used to constitute moxidectin microspheres, 10% w/w moxidectin microspheres, packaged in 5- and 10-unit packs 20/5-packs per case and 10/10-packs per case, RX, NADA 141-189. Recall # V-004-5.
CODE All lots within expiry.
REASON FDA requested due to serious health concerns.
VOLUME OF PRODUCT IN COMMERCE
Nationwide and Internationally.
END OF ENFORCEMENT REPORT FOR November 24, 2004
In testimony Thursday before the Senate Finance Committee, Food and Drug Administration reviewer David Graham cited Meridia, Crestor, Accutane, Bextra and Serevent. Drug makers defended the use and safety of their products.
Graham contended the country is "virtually defenseless" against a repeat of the Vioxx debacle. Dr. Steven Galson of the FDA rejected that comment as having "no basis in fact."
Merck & Co. pulled Vioxx from the market on Sept. 30 after a study indicated the popular painkiller doubled the risk of heart attacks and stroke when taken for longer than 18 months.
The committee chairman, Sen. Charles Grassley, suggested an independent board of drug safety may be needed to ensure the safety of medications after FDA approval. An "awful lot of red flags" were raised before Vioxx was withdrawn, said Grassley, R-Iowa., and the agency disdained, rather than listened to, its own reviewers.
Graham contended that FDA has an inherent conflict of interest that triggers "denial, rejection and heat" when safety questions emerge about products it has approved.
In his view, the five most worrisome drugs that demand speedy action:
Meridia, a weight-loss drug. He said the agency should consider whether its benefits outweigh the risks of higher blood pressure and stroke among people taking it. "I don't think Meridia passes that test," Graham said.
Crestor, an anti-cholesterol drug. He said the government should evaluate the occurrence of renal failure and other serious side effects among people taking Crestor. Two of three other statin competitors prevent heart attack and stroke and do not cause renal failure, he said.
Accutane, an acne drug linked to birth defects. Graham said the drug represents a 20-year "regulatory failure" by the FDA and sales should be restricted immediately.
Bextra, a painkiller. Graham said the drug poses the same heart attack and stroke risk as Vioxx. He recommended designing studies to look at the drug's cardiovascular risks.
Serevent, an asthma treatment. He said the drug was shown, with 90 percent certainty in a long-term trial in England, to cause deaths due to asthma. GlaxoSmithKline, told by the FDA to do a large, clinical trial, begged off. "We've got case reports of people dying, clutching their Serevent inhaler," Graham said. "But Serevent is still on the market."
Galson, acting director of the FDA's Center for Drug Evaluation and Research, said the agency already has taken steps to alert consumers to those drugs' safety concerns. That includes heightened warnings for Serevent; a tougher risk-management plan to ensure pregnant women don't use Accutane; and an upcoming advisory committee hearing regarding Bextra.
"Each of these do have special safety issues, but they're under evaluation and we're watching them carefully," Galson said.
Tim Lindberg, a spokesman for Abbott Laboratories, said "science continues to support the safe use of Meridia to treat obesity."
AstraZeneca PLC, maker of Crestor, has confidence in the drug, spokeswoman Emily Denney said. "To date, the FDA has not given us any indication of a major concern regarding Crestor," she said.
Carolyn Glynn, spokeswoman for Roche Holdings AG, a maker of Accutane, acknowledged that the drug carries risk and said it is reserved for serious cases. "This drug is extremely beneficial as long as it's used safely and appropriately," she said.
Susan Bro, a Pfizer spokeswoman, said Bextra did not increase the risk of serious cardiovascular events in a recent analysis of nearly 8,000 arthritis patients who took the drug from six weeks to 52 weeks. She said Bextra has been found to be safe and effective when used as indicated.
GlaxoSmithKline, maker of Serevent, issued a similar statement about its product.
In his testimony, Graham said the FDA's Office of New Drugs unrealistically maintains a drug is safe unless reviewers establish with 95 percent certainty that it is not.
That rule does not protect consumers, Graham told the Senate committee. "What it does is it protects the drug," he said.
Grassley accused the FDA of attempting to intimidate Graham. Sen. Jeff Bingaman, D-N.M., urged President Bush to name a new leader at the FDA, where Lester Crawford is the acting commissioner.
Graham said he fears continued intimidation.
"I was frightened before," he told reporters after the hearing. "Senior management at the FDA did everything in their power to intimidate me prior to my testimony," he said.
May my beloved partner ROMI rest in peace - no matter wherever her bits and pieces/frozen carcass may be held hostage.
[what's in YOUR "urn" ?]