FDA Proposals Fail to Ensure Independent Drug Safety Assessment

FDA officials continue to ignore the public outcry about the agency’s failure to intervene–even as evidence shows that widely marketed drugs are linked to lethal effects that companies methodically conceal from the public and prescribing physicians.

The FDA’s response 5 months after the devastating report by the Institute of Medicine which gave the agency failing grades across the board on drug safety http://www.iom.edu/CMS/3793/26341/37329.aspx is to issue a series of proposals that would be under drug manufacturers' control. In essence the proposals merely change the seating arrangement on the deck of the sinking Titanic. 
   
At a press briefing this week, FDA announced that the agency will issue “report cards” about unexpected side effects that emerge within 18 months of a drug’s approval, and will monitor new drugs for safety problems.

However, FDA pronouncements do not necessarily translate into action in the public interest. As professor Alta Charo, a member of the IOM committee whose report made concrete recommendations for greater independence and transparency noted: "Crucial to our recommendation was that these postmarketing data be shared with an advisory committee made up of independent safety experts. [FDA’s] proposal would have the data remain internal,"

Indeed, FDA officials were hedging even as they announced that the agency “would regularly publish newsletters to summarize its safety reviews of older drugs and disclose emerging issues.” The Associated Press reports that FDA officials were speaking from the same page as the drug industry’s trade organization, PhRMA: Both expressed concern that broad disclosure of preliminary information about apparent safety problems could do more harm than good.

PhRMA is concerned about only one “harm” that may result from disclosure of drug risks—that is, reduction in sales:
"One thing we don't want to see happen is if patients get concerned and they decide to stop therapy and don't talk to their doctors," said Alan Goldhammer of the Pharmaceutical Research and Manufacturers of America (PhRMA), the drug industry’s trade group.

FDA’s failure to exercise its authority to protect the public from unsafe drugs whose risks have been deliberately concealed, has emboldened the industry to disregard patient safety and seek approval to market drugs with dubious safety profiles.

For example, Eli Lilly announced this week, that it intends to seek FDA approval for an long-lasting injectable form of Zyprexa (taken once a month). 
A long-lasting formulation of a highly toxic drug, such as Zyprexa, increases risks for patients who cannot tolerate the drug’s effects.
See: Reuters 2007 http://www.tiny.cc/vyNAw

Lilly has settled lawsuits with 26,000 plaintiffs for $1.2 billion in cases charging the company with concealing the drug’s lethal effects. Associated Press reports that the company's CEO told analysts during a conference call that more than 1,000 Zyprexa cases are still pending.

Furthermore, Lilly’s marketing of Zyprexa in its current, once-a-day formulation for unapproved uses is under investigation by numerous state Attorneys General.

It will be significant whether the FDA will approve Lilly's marketing of this toxic drug in an even more dangerous formulation before the Attorneys General investigations are complete.

Contact: Vera Hassner Sharav
212-595-8974
veracare@ahrp.org

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Associated Press
FDA Proposes Report Cards on New Drugs
By ANDREW BRIDGES
January 30, 2007

WASHINGTON — The public outcry over the withdrawal of the painkiller Vioxx is leading to closer government scrutiny of new drugs to identify and disclose late-developing safety problems.

As part of a pilot program, the Food and Drug Administration will issue drug "report cards" that would detail unexpected side effects that emerge within 18 months of a drug's approval. The reports also would include follow-up studies and details about how the drugs are being used.

The proposal is among more than a dozen initiatives the FDA unveiled Tuesday in response to a recent report by a committee of experts at the Institute of Medicine that criticized the agency's handling of drug safety in the wake of the Vioxx case. Nor will it be the last word, said FDA Commissioner Dr. Andrew von Eschenbach.

"It will be a continuous process of improvement. The initiatives we are announcing today are not the full story, nor are they the final chapter in that story," von Eschenbach told reporters.

Their release comes just days before Sens. Edward Kennedy, D-Mass., and Mike Enzi, R-Wyo., introduce legislation to overhaul how the FDA handles drug safety.  "Today's report is thoughtful and provides important recommendations for administrative action, but only legislation can give FDA the tools it needs to ensure that FDA is the gold standard for safety," Kennedy said in a statement.

The Institute of Medicine report was prompted in part by the 2004 withdrawal of Vioxx after research showed it increased risk of heart attacks and strokes. The report said the FDA needs more funding, people and authority to ensure it focuses on the safety of drugs while they remain on the market.

The FDA also hopes to step up its mining of large public and private health care databases to detect emerging safety problems, said agency drug chief Dr. Steven Galson. The Department of Veterans Affairs recently signed an agreement to share such information with the FDA.

The agency also said it would regularly publish newsletters to summarize its safety reviews of older drugs and disclose emerging issues. However, the newsletters would be scrubbed of whatever the FDA deemed confidential commercial and predecisional information, the agency said.

The Institute of Medicine, part of the federally chartered National Academy of Sciences, had pushed for even more public disclosure of that underlying information, said Alta Charo, a member of the committee that wrote the report who is also a University of Wisconsin professor of law and bioethics.  "Crucial to our recommendation was that these postmarketing data be shared with an advisory committee made up of independent safety experts. Their proposal would have the data remain internal," Charo said.

Both the FDA and the drug industry are concerned that broad disclosure of preliminary information about apparent safety problems could do more harm than good.
"One thing we don't want to see happen is if patients get concerned and they decide to stop therapy and don't talk to their doctors," said Alan Goldhammer of the Pharmaceutical Research and Manufacturers of America, a drug industry group.

The FDA did not address the Institute of Medicine report's specific recommendations for Congress, including its push for additional agency funding and authority.  Without that, the FDA's proposals amount to "small potatoes," said Bill Vaughan, a senior policy analyst at Consumers Union.

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http://www.tiny.cc/Hegpz
THE NEW YORK TIMES
January 31, 2007
F.D.A. Widens Safety Reviews on New Drugs
By GARDINER HARRIS

The Food and Drug Administration announced changes yesterday that were intended to ensure that marketed drugs are as safe as advertised, including the first effort to do a comprehensive assessment of the safety of drugs 18 months after introduction.
The agency also announced the creation of an advisory panel to improve the way it announces safety worries and a collaboration with the Veterans Health Administration to track how real patients fare after taking drugs.

The F.D.A. plan is the latest effort to fix the agency after a series of missteps. In September 2004, Merck withdrew its arthritis drug, Vioxx, after a study showed that it doubled the risks of heart attack. About the same time, the agency announced that antidepressants cause some teenagers to think more about suicide.

In both cases, the agency took years to acknowledge risks to millions of patients that had been apparent to some researchers. “We don’t see this as the only answer,” said Dr. Andrew C. von Eschenbach, the F.D.A. commissioner, at a news conference in Washington announcing the initiatives. “It’s merely a step as we continue a process of improvement that will be ongoing.”
Senator Christopher J. Dodd, Democrat of Connecticut, said in a written statement that far greater changes were needed at the agency. Mr. Dodd promised to introduce two bills today that would reorganize the F.D.A. and require drug makers to disclose the results of all clinical trials involving humans. The bills’ co-author, Senator Charles E. Grassley, Republican of Iowa, has called the agency far too “cozy” with drug makers.

In many cases, the date that the agency will begin the efforts announced yesterday is uncertain. For instance, Dr. Steven Galson, director of the agency’s drug center, said at the news conference that the pilot program to assess systematically a drug’s safety 18 months after its introduction would probably take about a year to put into place — with the assessment due 18 months after that.   “We’re just organizing that process to get started,” Dr. Galson said.

In a scathing assessment released in September, the Institute of Medicine concluded that the F.D.A. was rife with internal squabbles and hobbled by underfinancing, poor management and outdated regulations. The institute, the most important medical advisory organization in the country, suggested that the agency undergo 25 major changes, many of which would require Congressional authorization.

Alta Charo, a professor of law and bioethics at the University of Wisconsin and one of the authors of the Institute of Medicine’s report, described the F.D.A. announcement yesterday as “a good set of first steps towards improving the safety of the drug supply in the United States.”
Professor Charo said she was “disappointed” that the agency had failed to adopt some of the institute’s bolder recommendations, including one suggesting that the agency give greater authority to officials who assess the safety of drugs after they go on the market.  “We viewed that as critical,” she said.

Alan Goldhammer, deputy vice president for regulatory affairs for the Pharmaceutical and Research Manufacturers of America, praised the F.D.A.’s announcement as a “very thoughtful and comprehensive response” to the Institute of Medicine’s report. “The agency has made substantive and significant progress in improving and enhancing the drug safety system in the U.S.” said Mr. Goldhammer, whose organization represents drug makers.

Still, the plan does little to address a problem that nearly all agree underlies many of its woes: a chronic shortage of government money. As Dr. von Eschenbach noted at the news conference, the agency has regulatory authority over about a quarter of the American economy. After the Sept. 11 attacks, the agency was asked to increase its efforts to prevent bioterrorism. Despite having greater responsibilities, its budget has remained relatively flat for years.

There are now thousands of drugs in routine use. Figuring out which of these medicines may have undiscovered side effects will take a lot of money. The agency gets about $400 million of its $1.9 billion budget from fees assessed on drug makers. Under a formula negotiated with the drug industry, this money comes with strings attached. One restriction was that the F.D.A. could use little of the money to track the safety of approved drugs.

That deal between the F.D.A. and drug makers expires this year, and the drug companies have agreed to allow more of their money to be used for postmarket safety assessments. Whether those fees are enough, whether there should be any strings attached to them and whether that money should be coming from drug makers at all has become the subject of fierce debate.

“Drug makers clearly get their money’s worth with all this money,” said Dr. Sidney Wolfe, director of Public Citizen’s health research group. Dr. Wolfe and other consumer advocates say that the F.D.A.’s dependence on drug industry fees has softened its oversight.
 
Dr. Scott Gottlieb, who last week left his job as the F.D.A. deputy commissioner to return to the American Enterprise Institute, a free-market research group, said the real debate unfolding around the agency is between those who believe that it needs more money and tools to assess drug risks, and those who believe that the agency should begin regulating the practice of medicine. “I think we need to give the agency the resources it needs to get information about drug risks quickly,” Dr. Gottlieb said. “But we don’t need the government telling doctors and patients what to do.”
The F.D.A. plan promises to return the agency to its scientific roots. It once had robust laboratories that conducted original studies to assess drug risks on its own. Those laboratories were largely eliminated in the past decade to apply more money to the drug-approval process and the support of a bare-bones computer program to track side effects of drugs.

But in the past two years, the agency has begun an effort to improve the science of drug safety, making itself an active participant in scientific endeavors once left exclusively to drug makers and basic scientists.
The efforts announced yesterday included the creation of a database of genetic codes associated with bad drug outcomes, the development of a computer model to identify patients who are most likely to suffer liver injury, and the design of screening tests that would identify patients most at risk of general drug problems.

Copyright 2007  The New York Times Company

<http://www.kentucky.com/mld/kentucky/business/16589366.htm >
Associated Press Wed, Jan. 31, 2007
Earnings roundup 2: Eli Lilly, Media General, New York Times Co.
Lilly reports lower 4Q profit; adjusted results beat expectations

INDIANAPOLIS – The drugmaker Eli Lilly and Co. on Wednesday reported a sharply lower fourth-quarter profit, resulting mostly from a number of hefty charges and higher expenses. But its results excluding charges beat Wall Street estimates, and its shares rose nearly 2 percent. For the three months that ended Dec. 31, net income plunged to $132.3 million, or 12 cents per share, from $700.6 million, or 64 cents per share, a year ago.

Revenue rose 9 percent to $4.25 billion from $3.88 billion a year ago.
Excluding one-time items including charges for the closure of several manufacturing facilities and for a legal settlement over its top-selling drug Zyprexa, Lilly earned $929.6 million, or 85 cents per share. That compares with $871.6 million, or 80 cents per share, a year earlier. Wall Street expected 82 cents per share on revenue of $4.08 billion, according to a Thomson Financial poll.

The company took a fourth-quarter charge of $450 million, or 31 cents per share, for closing a manufacturing operation in Basingstoke, England, and research and development sites in Belgium and Germany. Lilly also stopped construction on an insulin manufacturing site in Prince William County, Va. Earlier this month, the company also announced that it will settle about 18,000 more lawsuits over its anti-psychotic drug Zyprexa. Lilly took a fourth-quarter settlement charge of $495 million, or 42 cents per share, for that.

Company President John Lechleiter told analysts during a conference call that more than 1,000 Zyprexa cases are still pending.

Zyprexa has been featured in a number of recent stories in The New York Times stating that Lilly downplayed the drug's risks and marketed it for unapproved uses. The company has denied that.

Lechleiter, Lilly's chief operating officer, said physician reaction to the articles has been "very muted."  "This does not seem to be a big concern," he said. "I think physicians who prescribe Zyprexa understand it well, the benefit/risk equation, and understand clearly the patients who stand to benefit most from the product. "We know that for many patients, Zyprexa is going to be the best choice."

For the year, Lilly's profit rose to $2.66 billion, or $2.45 per share, from $1.98 billion, or $1.81 per share a year ago. Sales rose 7 percent to $15.69 billion from $14.65 billion.

Five Lilly drugs crossed the billion-dollar sales mark in 2006. Zyprexa led the pack with $4.3 billion, a 4 percent increase over 2006, and was followed by Gemzar, Cymbalta, Humalog and Evista.

Company officials noted in a prepared statement that Cymbalta, which is used to treat depression and nerve pain, topped $1 billion in sales in its second full year on the market. It registered $1.3 billion.
Lilly on Monday completed the $2.3 billion acquisition of ICOS Corp., bringing the company's Cialis treatment fully in-house. The deal is expected to add to earnings in 2008.

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