Psych Diagnoses Fraud Leads to Pharmaceutical Prosecutions

NowPublic.com
Kevin Hall
October 8, 2012

Nearly all major psychiatric drug manufacturers have been convicted of illegal marketing and/or fraudulent claims. Several of these cases are linked below. Any that haven't been prosecuted, probably should be.

The reason behind this is simple. There are no medical tests to confirm or deny any mental disorder or diagnoses. A few decades back, psychiatrists "voted" that mental "illness" was caused by a "chemical imbalance of the brain." This is drug marketing, not science. Nobody votes in diabetes or cancer as medical disease and there are sound medical and lab tests for these and other medical diseases.

Psychiatric diagnoses is merely opinion of behavior. Psychiatrists simply vote on what is or is not a mental disorder and place these diagnoses into the American Psychiatric Association's "Diagnostic and Statistical Manual." Their controversial DSM5 is set to be released in 2013 and will likely lead to more pharmaceutical fraudulent marketing prosecutions and settlements.

The reason is simple. If there is no identifiable disease, there can never be a drug that will cure. In fact, there are no cures for any mental disorders. The drugs are generally uppers (ADHD drugs) or downers (anti-anxiety drugs and antipsychotics) that merely mask symptoms in some cases while having extremely dangerous side effects. The upper-type antidepressants have been proven to be very little, if any, more effective than a placebo (sugar pill) yet greatly increase sexual dysfunction while also increasing the likelihood of violence and suicide. Honest marketing would refer to them as anti-sex drugs.

The flow (explained and graphed here) is that psychiatrists create a disease by voting, then pharmaceuticals make the drug. Psychiatrists, usually at major universities, create fraudulent studies that the FDA approves on the word of the drug companies that funded the studies. Once they get approval for a certain condition (such as depression) and population (such as men over age 18, etc.), they get some paid-off psychiatrist to create and get published a study saying that the drug is helpful for other populations and diagnoses. This allows for what is termed off-label prescribing.

It's all fraud and all prosecutable.

The story printed below on Abbott Labs (Depakote) came out last week. It's the Virginia Attorney General's press release www.oag.state.va.us/Media%20and%20News%20Releases/News_Releases/Cuccinelli/100212_Abbott_Labs.html .
Here are some other links to recent settlements with:

GlaxoSmithKline (Paxil) http://www.justice.gov/opa/pr/2012/July/12-civ-842.html ;

Johnson & Johnson, (Risperdal, Invega) www.nytimes.com/2012/04/12/business/drug-giant-is-fined-1-2-billion-in-arkansas.html?_r=0, www.bloomberg.com/news/2012-08-30/j-j-will-pay-181-million-to-settle-risperdal-ad-claims.html, http://www.bloomberg.com/news/2012-08-31/j-j-loses-appeal-of-257-7-million-risperdal-verdict.html  ;

Pfizer, (Zoloft,Geodon, etc.) www.msnbc.msn.com/id/32657347/ns/business-us_business/t/pfizer-pay-record-billion-penalty/#.UHLjXVF_P1U ;

Astrazeneca, (Seroquel) www.azcentral.com/business/articles/2010/04/27/20100427astra-zeneca-settlement.html ;

Bristol-Myers Squibb (Abilify) www.justice.gov/opa/pr/2007/September/07_civ_782.html ;

Eli Lilly (Zyprexa) www.justice.gov/opa/pr/2009/January/09-civ-038.html .

Maybe it is time that some of the psychiatrists creating the fraudulent diagnoses and studies start getting criminally prosecuted for fraud?


Commonwealth of Virginia
Office of the Attorney General


For media inquiries only, contact:  Brian J. Gottstein
Email: bgottstein@oag.state.va.us (best contact method)
Phone: 804-786-5874

Sentencing in Abbott Labs Depakote case: Judge approves $1.5 billion settlement to resolve complaints of off-label promotion of drug

~ Virginia-led investigation was largest state Medicaid fraud investigation in U.S. history ~

ABINGDON, VA (October 2, 2012) - As part of the largest Medicaid fraud case ever led by a state, Attorney General Ken Cuccinelli announced the sentencing of global health care company Abbott Laboratories Inc. in the United States District Court in Abingdon, Va., today. The court approved the $1.5 billion settlement reached on May 7, 2012, among Abbott, Virginia, the United States government, and 48 other states and the District of Columbia, in which Abbott pled guilty to a criminal charge and admitted civil liability for the company's unlawful promotion of the prescription drug Depakote for uses not approved as safe and effective by the Food and Drug Administration (FDA). 

The attorney general's Medicaid Fraud Control Unit (MFCU) was the lead investigative agency in the case, partnering with the prosecutors and civil attorneys from the U.S. Attorney's Office for the Western District of Virginia. This was the largest Medicaid fraud recovery in U.S. history resulting from a state-led investigation, with the Virginia MFCU spending more than four years on the investigation, traveling to 26 states to conduct interviews and sifting through more than one million records looking for evidence.

When it pled guilty in May, Abbott agreed to pay $1.5 billion to resolve its criminal and civil liability pertaining to government health care programs that were defrauded based on reimbursements paid for Depakote due to Abbott's illegal marketing practices. The settlement that was approved today includes a criminal fine and forfeiture totaling $700 million and civil settlements with the federal government and the states totaling $800 million. The civil settlement includes $270 million for the federal government's share of the Medicaid program; $239 million for the states' share of the Medicaid program; and $291 million for Medicare and other federal programs. Abbott will also pay a $500 million fine to the federal government, $198.5 million in criminal asset forfeiture penalties, and $1.5 million to Virginia MFCU to cover investigative costs. Virginia's share of the Medicaid civil settlement is $4.2 million. 

Abbott must also agree to the terms of a Corporate Integrity Agreement with the Office of the Inspector General for the Department of Health and Human Services.

"I've made fighting Medicaid fraud a priority in Virginia by increasing the size of our fraud team by adding 30 new people over the last two years," said Cuccinelli. "I'm committed to ensuring that money intended for medical services for the poor isn't stolen from them and the taxpayers through fraud. Medicaid dollars are limited, and fraud deprives people in true need of necessary medical care."

He continued, "This settlement will allow 49 states, the District of Columbia, and the federal government to recover money fraudulently taken from Medicaid, Medicare, and other health care programs." Louisiana is pursuing separate litigation.

On May 7, Abbott pled guilty to misbranding Depakote by promoting the drug to control agitation and aggression in elderly dementia patients and to treat schizophrenia when neither of these uses was FDA approved. In an agreed statement of facts filed in the criminal action, Abbott admitted that from 1998 through 2006, the company maintained a specialized sales force trained to market Depakote in nursing homes for the control of agitation and aggression in elderly dementia patients, despite the absence of credible scientific evidence that Depakote was safe and effective for that use. In addition, from 2001 through 2006, the company marketed Depakote in combination with atypical antipsychotic drugs to treat schizophrenia, even after its clinical trials failed to demonstrate that adding Depakote was any more effective than an atypical antipsychotic alone for that use.

The FDA is responsible for approving drugs as safe and effective for specified uses. Under the Food, Drug and Cosmetic Act (FDCA), a company in its application to the FDA must specify each intended use of a drug. A company's promotional activities must be limited to only the intended uses that are FDA approved. Promotion by the manufacturer for other uses - known as "off-label" uses - renders the product misbranded, and is illegal.

 For more information on the history of the Abbott Labs settlement, please click here.

Virginia's role in the Abbott case

In September 2007, the Virginia attorney general's Medicaid Fraud Control Unit (MFCU) was contacted with allegations of off-label drug marketing by Abbott Pharmaceuticals.

Although neither the whistleblowers nor the defendant in this case were located in Virginia, the whistleblowers came to Virginia because the MFCU has a national reputation for successfully investigating major national cases, such as the Purdue Pharma Oxycontin case, the Octagon case, and others.

Following Virginia MFCU's initial investigation, the unit contacted the U.S. Attorney's Office for the Western District of Virginia because of their history of working together on such cases. They then began a joint investigation.

On October 31, 2007, the first qui tam ("whistleblower") suit was filed in the United States District Court in Abingdon, Va., against Abbott Laboratories for marketing the drug Depakote for off-label uses. Three other qui tam complaints from other relators were subsequently filed.

MFCU investigators operating out of the attorney general's offices in Roanoke and Abingdon were assigned to the investigation full-time and spent more than four years and 38,000 man-hours on the investigation, traveling to 26 states to conduct interviews and sifting through more than one million records looking for evidence.

The investigation uncovered that Abbott illegally marketed Depakote for non-approved uses, including as an alternative to antipsychotics to treat dementia patients in nursing homes, and for schizophrenia. The investigation also revealed that Abbott paid rebates to health care professionals and long-term care pharmacies for increasing their off-label use of Depakote. 

Attorney General Cuccinelli would like to thank Randall "Randy" Clouse, Director and Chief of Health Care Fraud and Elder Abuse section, and the following MFCU investigators and attorneys for their work in this case: Erica Bailey, Mary Blackburn, Steve Buck, Beverly Darby, Harold Erwin, Elizabeth Fitzgerald, William Clay Garrett, Doug Johnson, John Johnston, Kristy Knighton, Adele Neiburg, John Peirce, and Joey Rusek.

Virginia's MFCU: A history of stopping Medicaid fraud

The Virginia MFCU was established in 1982 within the attorney general's office to investigate and prosecute insurance fraud against the federally funded Medicaid program for indigent health services. MFCU employs a professional staff of criminal investigators, auditors, and several assistant attorneys general who are experienced in commercial and financial investigations. MFCU works regularly with federal and state law enforcement agencies, as well as private insurance companies operating within Virginia.

Over the past 30 years, prior to the Abbott case, Virginia's MFCU had recovered nearly $800 million by tracking down and prosecuting Medicaid fraud offenders. This fiscal year alone, MFCU has recovered more than $22 million. MFCU was also involved in the recovery of more than $634 million after a joint criminal investigation revealed that Purdue Pharma Company fraudulently misbranded the drug OxyContin by marketing the drug to physicians as a slower release -- and thus less addictive -- drug than other prescription opioids. 

From 2010 to today, Attorney General Cuccinelli increased the number of Medicaid fraud and elder abuse staff by more than 50 percent (from 56 to 86) to better combat fraud in Virginia's Medicaid program and to protect the elderly from individuals who abuse and neglect them in nursing homes and health care facilities. It is the only section of the office that he has grown significantly during his tenure, while he has maintained a smaller general fund budget allocation than when he came into office.

Elderly patients over-prescribed antipsychotic drugs

New York Post
Friday, December 02, 2011

In the United States, elderly patients with dementia are too often prescribed antipsychotic drugs to calm their disruptive behavior, a costly and risky practice that should end, experts said Wednesday
Instead, more care should be taken to determine why dementia patients may be acting up and treat those underlying causes, lawmakers were told at a hearing of the Senate Committee on Aging.
"As the baby boomer generation ages, it is imperative to address the overuse and misuse of antipsychotic drugs among nursing home patients," said Daniel Levinson, Health and Human Services Inspector General.

Levinson said recent government audits have raised concerns about the use of antipsychotics by elderly people with dementia in nursing homes, raising their risk of death and wasting money for the US healthcare system.
For instance, more than half of such prescriptions were wrongly paid for in 2007 by government Medicare because the patients did not exhibit symptoms of schizophrenia or bipolar disorder, amounting to about 230 million dollars in waste.
One audit showed 14 percent of nursing home residents had Medicare claims for antipsychotic drugs, he said.
But another panel member, Toby Edelman, senior policy attorney in the office of the Center for Medicare Advocacy, said that audit's estimate was low because it only included some kinds of anti-psychotics.
"Nursing facilities' self-reported data indicate that in the third quarter of 2010, 26.2 percent of residents had received antipsychotic drugs in the previous seven days. That is approximately 350,000 individuals," she said.
"Facilities reported they gave antipsychotic drugs to many residents who did not have a psychosis, including 40 percent of patients at high risk because of behavior issues."
Edelman also pointed out that this issue is far from new, and that the same Senate committee had issued a report on the misuse of drugs in nursing homes back in 1975, and held a workshop on the topic two decades ago.
The practice persists, even though it is against federal law, because of serious understaffing in nursing facilities, high turnover of staff, and "aggressive off-label marketing of anti-psychotic drugs," she said.
The pharmaceutical giant Eli Lilly in 2009 paid a nearly 1.5 billion dollar settlement, in which it admitted no wrongdoing, for off-label promotion of its drug Zyprexa as a treatment for dementia. The drug is FDA-approved for bipolar disorder and schizophrenia.
According to Tom Hlavacek, executive director at Alzheimer's Association's southeastern Wisconsin chapter, elderly people with dementia are sometimes prescribed these potent drugs for behaviors that have other causes.
Urinary tract infections, tooth decay, arthritic pain, or simply moving a patient from one place to another can lead to agitated behaviors.
"Our experience indicates that these care transitions can exacerbate behaviors and often lead to escalating drug treatments," he told lawmakers.
Experts said solutions could include creating stronger penalties for inappropriate prescribing, and a renewed focus on trying non-pharmacological approaches to a problem first.
"Most doctors treat unwelcome behavior in all settings as a disease that requires medication. These drugs are used as chemical restraints," said Jonathan Evans, a doctor who specializes in caring for frail elders.
"Behavior is not a disease. Behavior is communication. And in people who have lost the ability to communicate with words, the only way to communicate is through behavior," he added.
"Good care demands we figure out what they are telling us and help them."

Hurting Pharma Targets Alcoholics

Out of New Diseases and Blank Checks from Insurers, Pharma Targets Alcoholics

By Martha Rosenberg
August 2011

The gravy train of the 2000's is over for Pharma reports yesterday's Wall Street Journal. New drugs made the drug industry $11.8 billion in 2005 and only $4.3 billion last year-- almost two-thirds less.

Why? There are several reasons, says the Journal. Doctors have a "growing fear of prescribing new drugs with unknown side effects," the government is continuing to crackdown on Pharma's illegal marketing, and private and government insurers are becoming less willing to "cough up money for an expensive new drug--particularly when a cheap and reliable generic is available." Could the change be retroactive, some wonder?

It's gotten so bad, AstraZeneca, whose controversial Seroquel still makes $5.3 billion a year, now conducts "payer excellence academies" to teach reps to sell insurers and state health care systems on its latest drugs (if there's any more government money to loot, that is, or if private premiums can go any higher.)

Maybe that's why Pharma is now targeting the nation's millions of alcoholics and drugs addicts as its new revenue source. Like energetic kids who are really hyperactive and people with normal life problems who are really depressed, alcoholics and drug addicts, we are now told, really have a brain disease!

"Sixty percent of people with a substance abuse disorder also suffer from another form of mental illness, says an article in this week's New York Times' Science Times. (Another? ) They are "wired differently" and may have a "developmental brain disorder," says the article, next to a photo of Amy Winehouse, lest anyone miss The Point. But luckily, scientists are cracking the code and beginning to "find answers," says Science Times.
Pharma is mongering the "dual diagnosis" of alcoholics and addicts--they have both an addiction and a psychiatric illne$$ --with so much unbranded advertising and Madison Avenue spin, nationally known major rehab centers are telling their patients they have "co-occurring disorders," in a repudiation of basic recovery theory.
Getting the millions in bars and on street corners on antidepressants and other psychoactive drugs for their putative lack of "dopamine receptors," would certainly help Pharma through its slump as it runs out of people to call sick. But Nora D. Volkow, director of the National Institute on Drug Abuse, has bigger ideas: Let's give alcoholics and drug addicts vaccines, she said at last year's American Psychiatric Association's meeting in New Orleans. Rehabilitation professionals fell out of their seats.
Not only do we know the brains of alcoholics and addicts are different from normal people, say psychopharmacology buffs and brain researchers, not only do we know their addictions are progressive, with a little help (and more federal money) we can even identify who is At Risk. Just like we identify those with pre-asthma, pre-diabetes, pre-schizophrenia and pre-osteoporosis. Treat 'em early and often.
Let's use those gigantic government primate centers! Let's concoct more unnecessary vaccines. Let's help Pharma's decade of the biologic drug. Let's cement government/industry incest. Let's pimp the nation's alcoholics and addicts!
There's only one problem with Pharma's new buzz campaign and intended demographic. Alcoholics and addicts are neither mentally ill or suffering from a vaccine deficiency. They recover perfectly with the help of each other in self-help groups for free (a painful word for Pharma) and have done so for almost eighty years. More importantly, for alcoholics and addicts, drugs are the problem not the solution!

Martha Rosenberg is columnist and cartoonist based in Chicago.
Copyright � 2002-2011, OpEdNews

Mass. General disciplines three psychiatrists

Boston Business Journal
by Eric Convey
July 1, 2011

Massachusetts General Hospital on Friday disclosed sanctions against three psychiatrists for violating hospital ethics guidelines by failing to adequately report, internally, seven-figure payments they received from drug companies.

In a statement to colleagues provided by the hospital upon request from the Business Journal, Drs. Joseph Biederman, Thomas Spencer and Timothy Wilens said the disciplinary actions include:

• They must refrain from "all industry-sponsored outside activities" for one year.

• For two years after the ban ends, they must obtain permission from Mass. General and Harvard Medical School before engaging in any industry-sponsored, paid outside activities and then must report back afterward.

• They must undergo certain training.

• They face delays before being considered for "promotion or advancement."

The three doctors came under the political microscope in June 2008 during remarks Sen. Charles Grassley, R-Iowa, made to a committee investigating conflicts of interest involving clinicians.

The three Harvard doctors "are some of the top psychiatrists in the country, and their research is some of the most important in the field," Grassley said, according to an online version of the Congressional record. "They have also taken millions of dollars from the drug companies." The senator complained that Biederman and Wilens took money from drug giant Eli Lilly (NYSE: LLY) at the same time they were being paid by the National Institutes of Health to study an Eli Lilly drug.

Grassley went on to say he had requested conflict-of-interest forms from the hospitals, and they "were a mess."

"My staff had a hard time figuring out which companies the doctors were consulting for and how much money they were making," he said.

When the hospitals asked the doctors to clarify the matter, Grassley continued, "things got interesting."

"Dr. Biederman suddenly admitted to over $1.6 million dollars from the drug companies," Grassley said. "And Dr. Spencer also admitted to over $1 million. Meanwhile, Dr. Wilens also reported over $1.6 million in payments from the drug companies."

"We have learned a great deal from (the in-house investigation)," the doctors wrote in their joint statement released Friday. "And we profoundly hope that our mistakes will benefit our colleagues by bringing clarity and attention to these important issues."

They wrote earlier in the letter: "We always believed that we were complying in good faith with the institutional policies and that our mistakes were honest ones."

In its own statement, the hospital wrote: "A committee at Massachusetts General Hospital that has been looking into conflict-of-interest questions involving three MGH child psychiatrists has completed its review. Appropriate remedial actions have been taken by the hospital to address specific issues."

Beware pf ghost(writer)s of medical research, Well placed journal articles sell more pills than sales staff do

Straight Goods News
by Dr. Marc Andre Gagnon and Dr. Sergio Sismondo
June 28, 2011

The medical research world has been concerned about the problem of ghostwriting for more than a decade. The issue has been repeatedly raised in the mainstream media over the past few years, with most of the commentary focused on the ethics of academics serving as authors on papers they did not write and on some of the most egregious actions by pharmaceutical companies.

Big Pharma firms spend twice as much on promotion as on research and development (R&D).
But these efforts miss the ways in which Big Pharma has developed new forms of medical research to serve its own interests.

Big Pharma firms spend twice as much on promotion as on research and development (R&D). Worse, more and more medical R&D is organized as promotional campaigns to make physicians aware of products. The bulk of the industry's external funding for research now goes to contract research organizations to produce studies that feed into large numbers of articles submitted to medical journals. Internal documents from Pfizer, made public in litigation, showed that 85 scientific articles on its antidepressant Zoloft were produced and coordinated by a public relations company. Pfizer itself thus produced a critical mass of the favourable articles placed among the 211 scientific papers on Zoloft in the same period. Internal documents tell similar stories for Merck's Vioxx, GlaxoSmithKline's Paxil, Astra-Zeneca's Seroquel, and Wyeth's hormone-replacement drugs.

To promote the now-notorious Vioxx, Merck organized a ghostwriting campaign that involved some 96 scientific articles. Key articles did not mention the death of some patients during clinical trials. Through a class action lawsuit against Vioxx in Australia, it was discovered that Elsevier had created a fake medical journal for Merck — the Australasian Journal of Joint and Bone Medicine — and perhaps 10 other fake journals for Merck and other Big Pharma companies.
In another example, GlaxoSmithKline organized a ghostwriting program to promote its antidepressant Paxil. According to internal documents made public in 2009, the program was called "Case Study Publication for Peer-Review", or CASPPER, a playful reference to the "friendly ghost". Such strategies are not exceptions; they are now the norm in the industry.

Most new drugs with blockbuster potential are introduced accompanied by 50, 60, or even 100 medical journal articles. Any firm that refused to play this game in the name of ethics would likely lose market share. Profits in the pharmaceutical industry depend on companies' capacity to influence medical knowledge and create market share and market niches for their products.
In 2008, research showed that pharmaceutical companies systematically failed to publish negative studies on their SSRIs, the Prozac generation of antidepressants. Of 74 clinical trials, 38 produced positive results and 36 did not: 94 per cent of the positive studies were published, but only 23 per cent of the negative ones were, and two-thirds of those were spun to make them look more positive. Physicians reading the scientific literature got a biased view of the benefits of SSRIs. This helps to explain the huge number of antidepressant prescriptions, in spite of the fact that, according to a meta-analysis in JAMA in January 2010, for 70 per cent of people taking SSRIs, the drug did not bring more benefits than a placebo. Compared to placebos, however, SSRI antidepressants can result in serious adverse drug reactions.

There we see one of the problems with the ghost management of medical research and publication. Pharmaceutical companies want upbeat reports on their drugs. They design, write, and publish studies that are likely to show their drugs in positive lights — and there are myriad ways to do so. Ghosts sometimes bend the truth, and sometimes even commit fraud, with grave results.

Why do academics serve as authors on scientific articles they did not write, using research they did not perform? Because they are rewarded, both by their universities and by their colleagues for how much they publish and for its prominence. Pharmaceutical companies and their agents are very good at placing articles in prestigious journals, and then make them even more prominent by having their armies of sales reps circulate them and talk them up.
Researchers who serve as authors on studies and analyses (perhaps scientifically correct) that are favourable to the industry can expect to see these articles increase their prestige and influence, and possibly even funding.

What happens, however, when a researcher produces studies and analyses (also scientifically correct) showing that some products are dangerous or inefficient, as some did about Vioxx before the scandal broke? Reading Merck's internal e-mails, revealed during the class lawsuit, it was exposed that the company drew up a hit list of "rogue" researchers who needed to be "discredited" or "neutralized" — "seek them out and destroy them where they live," reads one e-mail. Eight Stanford researchers say they received threats from Merck after publishing unfavourable results.

In the ghost management of research and publication by drug companies we have a new model of science. This is corporate science, done by many unseen workers, performed for marketing purposes, and drawing its authority from traditional academic science. The high commercial stakes mean that all of the parties connected with this new corporate science can find reasons or be induced to participate, support, and steadily normalize it. It also biases the available science by pushing favourable results and downplaying negative ones — and sometimes through outright fraud. As long as pharmaceutical companies hold the purse strings of medical research, medical knowledge will serve to market drugs, not to promote health. And as long as universities grovel for more partnerships with these companies, the door will remain wide open to proceed with the corruption of scientific research.

Dr Marc-André Gagnon is assistant professor with the School of Public Policy and Administration at Carleton University. He is also an expert advisor with EvidenceNetwork.ca, a comprehensive and non-partisan online resource designed to help journalists covering health policy issues in Canada. Dr Sergio Sismondo is professor of Philosophy and Sociology at Queen's University. His current research is on the pharmaceutical industry's relationships with academic medicine and practicing physicians.

This article previously appeared in Troy Media.

Former Glaxo Lawyer Charged With Obstruction of Probe

The Wall Street Journal
November 2010
By THOMAS CATAN And PETER LOFTUS

Federal prosecutors charged a former GlaxoSmithKline PLC attorney with lying to obstruct a U.S. investigation into whether the pharmaceutical company illegally marketed an antidepressant as a weight-loss drug.

The Department of Justice on Tuesday indicted Lauren Stevens, a former vice president at the drug company, with four counts of making false statements to the Food and Drug Administration, as well as obstructing its investigation and withholding documents.

The indictment reflects a new U.S. effort to hold company executives legally accountable for criminal wrongdoing, rather than simply fining the companies for violations.

"This indictment shows that we will investigate those responsible for unlawful acts done on a company's behalf," said Richard DesLauriers, a special agent at the Federal Bureau of Investigation.

Ms. Stevens's lawyer said she did nothing wrong.

"Lauren Stevens is an utterly decent and honorable woman," Brien O'Connor said. "Everything she did in this case was consistent with ethical lawyering and the advice provided her by a nationally prominent law firm retained by her employer."

The indictment didn't identify the company or drug involved, but Glaxo confirmed that Ms Stevens formerly worked in its U.S. legal department and that the investigation involved its antidepressant Wellbutrin SR. It declined to comment further.

In its 2009 annual report, Glaxo disclosed that the government was inquiring about the company's response to an October 2002 letter from the FDA. The letter asked for information on the company's "alleged promotion of Wellbutrin SR for off-label use," meaning a use for which the drug didn't have FDA approval. Antidepressants have at times been associated with weight loss, though also with weight gain.

The U.S. attorney's office in Massachusetts has been leading a long-running investigation into Glaxo's marketing of several products between 1997 and 2004, including Wellbutrin SR, Glaxo has disclosed.

Glaxo first disclosed the existence of the investigation in 2004, and last year said it was taking a $400 million charge in relation to the probe, in a possible sign that it was approaching a settlement.

The Justice Department, acting on behalf of the FDA, has recently reached a slew of recent legal settlements with pharmaceutical companies for various violations, many of them prompted by information from whistleblowers.

Last month, GSK pleaded guilty to charges that it knowingly sold adulterated drugs made at its factory in Puerto Rico, paying $750 million in fines. The previous month, Allergan Inc. pleaded guilty to charges that the company actively promoted its top-selling product, the wrinkle-smoothing drug Botox, for unapproved medical uses such as treating headaches and pain. It paid $600 million to resolved the charges.

No individuals were indicted in those cases. To have an effective deterrent effect, the Justice Department has emphasized that it wishes to prosecute individual executives involved in corporate wrongdoing, so that the fines aren't simply seen as a cost of doing business.

The Wall Street Journal reported in March that the Food and Drug Administration planned to increase prosecutions of industry executives and corporate counsel.

Tuesday's indictment alleged that Ms. Stevens made a series of false statements and deliberately withheld potentially incriminating evidence from investigators. For example, she allegedly decided not to submit presentations made on the company's behalf by doctors who promoted the drug for unapproved purposes, prosecutors said.

A memorandum she requested to help decide whether she should hand over the slide sets warned that such a move would provide "incriminating evidence about potential off-label promotion of [the drug] that may be used against [the company] in this or in a future investigation," the indictment said.

Instead of providing the slides, Ms. Stevens wrote that the company's responses to the FDA's requests were "final" and "complete." The indictment says a company employee reported the alleged off-label promotion of the drug and sent the FDA some of the missing slides.
—Jeanne Whalen and Alicia Mundy contributed to this article.

Write to Thomas Catan at thomas.catan@wsj.com and Peter Loftus at peter.loftus@dowjones.com

NAMI State Chapters and Pharma Funding

Pharmalot
By Ed Silverman
April 28th, 2010

The latest chapter in the saga involving the National Alliance on Mental Illness, or NAMI, and the amount of money accepted from the pharmaceutical industry has millions being contributed to NAMI state chapters. And Chuck Grassley, the ranking Republican on the Senate Finance Committee, who has been probing the relationship between patient groups and drugmakers and how this may influence the practice of medicine, wants to know what the national organization is doing to make the state chapters more transparent, and how the money is used.

You may recall that a majority of donations made to NAMI, a big advocacy group, have come from drugmakers in recent years. And the disclosure comes after protracted criticism of NAMI for coordinating lobbying efforts with drug makers and pushing legislation that also benefits the pharma industry. NAMI subsequently promised to accept less pharma funding (background). Until recently, NAMI refused for years to disclose specifics of its fund-raising. But according to Grassley, between 2006 and 2008, drugmakers contributed nearly $23 million to NAMI, or about three-quarters of its donations.

Now, in an April 26 letter to NAMI officials, he notes that state chapters are also big beneficiaries. California’s chapter received $632,000 last year (see here), while the Ohio chapter got $623,000 from drugmakers. Looked at another way, Lilly ponied up $2.2 million, AstraZeneca donated $1.6 million and Bristol-Myers Squibb gave $1.3 million. All three drugmakers market antipsychotics. The info was obtained by querying each state chapter, although Grassley is miffed that the Alabama, Arizona, Connecticutt and Hawaii chapters ignored him.

Medicating the Military, Use of Psychiatric Drugs has Spiked, Concerns furface about suicide, other dangers

Army Times
By Andrew Tilghman and Brendan McGarry
Wednesday Mar 17, 2010

At least one in six service members is on some form of psychiatric drug.

And many troops are taking more than one kind, mixing several pills in daily “cocktails” — for example, an antidepressant with an antipsychotic to prevent nightmares, plus an anti-epileptic to reduce headaches — despite minimal clinical research testing such combinations.

The drugs come with serious side effects: They can impair motor skills, reduce reaction times and generally make a war fighter less effective. Some double the risk for suicide, prompting doctors — and Congress — to question whether these drugs are connected to the rising rate of military suicides.

“It’s really a large-scale experiment. We are experimenting with changing people’s cognition and behavior,” said Dr. Grace Jackson, a former Navy psychiatrist.

A Military Times investigation of electronic records obtained from the Defense Logistics Agency shows DLA spent $1.1 billion on common psychiatric and pain medications from 2001 to 2009. It also shows that use of psychiatric medications has increased dramatically — about 76 percent overall, with some drug types more than doubling — since the start of the current wars.
THE FULL INVESTIGATION:

• Could meds be responsible for suicides?

• Downrange: ‘Any soldier can deploy on anything’

• How drugs enter the war zone

Troops and military health care providers also told Military Times that these medications are being prescribed, consumed, shared and traded in combat zones — despite some restrictions on the deployment of troops using those drugs.

The investigation also shows that drugs originally developed to treat bipolar disorder and schizophrenia are now commonly used to treat symptoms of post-traumatic stress disorder, such as headaches, nightmares, nervousness and fits of anger.

Such “off-label” use — prescribing medications to treat conditions for which the drugs were not formally approved by the FDA — is legal and even common. But experts say the lack of proof that these treatments work for other purposes, without fully understanding side effects, raises serious concerns about whether the treatments are safe and effective.

The DLA records detail the range of drugs being prescribed to the military community and the spending on them:

• Antipsychotic medications, including Seroquel and Risperdal, spiked most dramatically — orders jumped by more than 200 percent, and annual spending more than quadrupled, from $4 million to $16 million.

• Use of anti-anxiety drugs and sedatives such as Valium and Ambien also rose substantially; orders increased 170 percent, while spending nearly tripled, from $6 million to about $17 million.

• Antiepileptic drugs, also known as anticonvulsants, were among the most commonly used psychiatric medications. Annual orders for these drugs increased about 70 percent, while spending more than doubled, from $16 million to $35 million.

• Antidepressants had a comparatively modest 40 percent gain in orders, but it was the only drug group to show an overall decrease in spending, from $49 million in 2001 to $41 million in 2009, a drop of 16 percent. The debut in recent years of cheaper generic versions of these drugs is likely responsible for driving down costs.

Antidepressants and anticonvulsants are the most common mental health medications prescribed to service members. Seventeen percent of the active-duty force, and as much as 6 percent of deployed troops, are on antidepressants, Brig. Gen. Loree Sutton, the Army’s highest-ranking psychiatrist, told Congress on Feb. 24.

In contrast, about 10 percent of all Americans take antidepressants, according to a 2009 Columbia University study.
Suicide risks

Many of the newest psychiatric drugs come with strong warnings about an increased risk for suicide, suicidal behavior and suicidal thoughts.

Doctors — and, more recently, lawmakers — are questioning whether the drugs could be responsible for the spike in military suicides during the past several years, an upward trend that roughly parallels the rise in psychiatric drug use.

From 2001 to 2009, the Army’s suicide rate increased more than 150 percent, from 9 per 100,000 soldiers to 23 per 100,000. The Marine Corps suicide rate is up about 50 percent, from 16.7 per 100,000 Marines in 2001 to 24 per 100,000 last year. Orders for psychiatric drugs in the analysis rose 76 percent over the same period.

“There is overwhelming evidence that the newer antidepressants commonly prescribed by the military can cause or worsen suicidality, aggression and other dangerous mental states,” said Dr. Peter Breggin, a psychiatrist who testified at the same Feb. 24 congressional hearing at which Sutton appeared.

Other side effects — increased irritability, aggressiveness and hostility — also could pose a risk.

“Imagine causing that in men and women who are heavily armed and under a great deal of stress,” Breggin said.

He cited dozens of clinical studies conducted by drug companies and submitted to federal regulators, including one among veterans that showed “completed suicide rates were approximately twice the base rate following antidepressant starts in VA clinical settings.”

But many military doctors say the risks are overstated and argue that the greater risk would be to fail to fully treat depressed troops.

For suicide, “depression is a big risk factor,” too, said Army Reserve Col. (Dr.) Thomas Hicklin, who teaches clinical psychiatry at the University of Southern California. “To withhold the medications can be a huge problem.”

Nevertheless, Hicklin said the risks demand strict oversight. “The access to weapons is a very big concern with someone who is feeling suicidal,” he said. “It has to be monitored very carefully because side effects can occur.”

Defense officials repeatedly have denied requests by Military Times for copies of autopsy reports that would show the prevalence of such drugs in suicide toxicology reports.
‘Then it’s over’

Spc. Mike Kern enlisted in 2006 and spent a year deployed in 2008 with the 4th Infantry Division as an armor crewman, running patrols out of southwest Baghdad.

Kern went to the mental health clinic suffering from nervousness, sleep problems and depression. He was given Paxil, an antidepressant that carries a warning label about increased risk for suicide.

A few days later, while patrolling the streets in the gunner’s turret of a Humvee, he said he began having serious thoughts of suicide for the first time in his life.

“I had three weapons: a pistol, my rifle and a machine gun,” Kern said. “I started to think, ‘I could just do this and then it’s over.’ That’s where my brain was: ‘I can just put this gun right here and pull the trigger and I’m done. All my problems will be gone.’”

Kern said the incident scared him, and he did not take any more drugs during that deployment. But since his return, he has been diagnosed with PTSD and currently takes a variety of psychotropic medications.

Other side effects cited by troops who used such drugs in the war zones include slowed reaction times, impaired motor skills, and attention and memory problems.

One 35-year-old Army sergeant first class said he was prescribed the anticonvulsant Topamax to prevent the onset of debilitating migraines. But the drug left him feeling mentally sluggish, and he stopped taking it.

“Some people call it ‘Stupamax’ because it makes you stupid,” said the sergeant, who asked not to be identified because he said using such medication carries a social stigma in the military.

Being slow — or even “stupid” — might not be a critical problem for some civilians. But it can be deadly for troops working with weapons or patrolling dangerous areas in a war zone, said Dr. John Newcomer, a psychiatry professor at Washington University in St. Louis and a former fellow at the American Psychiatric Association.

“A drug that is really effective and it makes you feel happy and calm and sleepy … might be a great medication for the general population,” Newcomer said, “but that might not make sense for an infantryman in a combat arena.

“If it turns out that people on a certain combo are getting shot twice as often, you would start to worry if they were as ‘heads up’ as they should have been,” Newcomer said. “There is so much on the line, you’d really like to have more specific military data to inform the prescribing.”

Military doctors say they take a service member’s mission into consideration before prescribing.

“Obviously, one would be concerned about what the person does,” said Col. C.J. Diebold, chief of the Department of Psychiatry at Tripler Army Medical Center in Hawaii. “If they have a desk job, that may factor in what medication you may be recommending for the patient [compared with] if they are out there and they have to be moving around and reacting fairly quickly.”
Off-label use

Little hard research has been done on such unique aspects of psychiatric drug usage in the military, particularly off-label usage.

A 2009 VA study found that 60 percent of veterans receiving antipsychotics were taking them for problems for which the drugs are not officially approved. For example, only two are approved for treating PTSD — Paxil and Zoloft, according to the Food and Drug Administration. But in actuality, doctors prescribe a range of drugs to treat PTSD symptoms.

To win FDA approval, drug makers must prove efficacy through rigorous and costly clinical trials. But approval determines only how a drug can be marketed; once a drug is approved for sale, doctors legally can prescribe it for any reason they feel appropriate.

Such off-label use comes with some risk, experts say.

“Patients may be exposed to drugs that have problematic side effects without deriving any benefit,” said Dr. Robert Rosenheck, a professor of psychiatry at Yale University who studied off-label drug use among veterans. “We just don’t know. There haven’t been very many studies.”

Some military psychiatrists are reluctant to prescribe off-label.

“It’s a slippery slope,” said Hicklin, the Army psychiatrist. “Medication can be overused. We need to use medication when indicated and we hope that we are all on the same page … with that.”

Combinations of drugs pose another risk. Doctors note that most drugs are tested as a single treatment, not as one ingredient in a mixture of medications.

“In the case of poly-drug use – the ‘cocktail’ — where you are combining an antidepressant, an anticonvulsant, an antipsychotic, and maybe a stimulant to keep this guy awake — that has never been tested,” Breggin said.

Newcomer agreed. “When we go to the literature and try to find support for these complex cocktails, we’re not going to find it,” he said. “As the number of medications goes up, the probability of adverse events like hospitalization or death goes up exponentially.”
Looking for answers

Pinpointing the reasons for broad shifts in the military’s drug use today is difficult. Each doctor prescribes medications for the patient’s individual needs.

Nevertheless, many doctors in and outside the military point to several variables — some unique to the military, some not.

A close look at the data shows that use of the antipsychotic and anticonvulsant drugs, also known as “mood stabilizers,” are growing much faster than antidepressants. That may correlate to the challenges that deployed troops face when they arrive back home and begin to readjust to civilian social norms and family life.

“The ultimate effect of both of these drugs is to take the heightened arousal — the hypervigilance and all the emotions that served you once you were deployed — and help to turn that back down,” said Dr. Frank Ochberg, former associate director for the National Institute of Mental Health and a psychiatry professor at Michigan State University who reviewed the Military Times analysis.

Dr. Harry Holloway, a retired Army colonel and a psychiatry professor at the Uniformed Services University of the Health Sciences in Bethesda, Md., said the increased use of these medications is simply another sign of deployment stress on the force.

“For a long time, the ops tempo has been completely unrelieved and unrestrained,” Holloway said. “When you have an increased ops tempo, and you have certain scheduling that will make it hard for everyone, you will produce a more symptomatic force. Most commanders understand that and they understand the tradeoffs.”

Connecting the Dots Between PhRMA and Congress

National Public Radio
February 22, 2010

The initial cost-cutting deal between PhRMA and Congress would have included $30 billion in savings related to the so-called doughnut hole in Medicare prescription-drug coverage.

The initial cost-cutting deal between PhRMA and Congress would have included $30 billion in savings related to the so-called doughnut hole in Medicare prescription-drug coverage.

Earlier this month, former congressman Billy Tauzin announced that he would step down from his position as president of the pharmaceutical industry's main lobbying group, the Pharmaceutical Research and Manufacturers of America — known by the shorthand PhRMA.

Last year, PhRMA spent $28 million lobbying in favor of a health care overhaul, after negotiating a deal with the White House and members of Congress. In that deal, the pharmaceutical industry pledged to reduce health care costs by $80 billion over 10 years.

By negotiating the secret deal, writer Paul Blumenthal explains, "the Obama administration got the biggest lobby in Washington and put them on the side of health care reform." Meanwhile, the pharmaceutical industry got a guarantee that "Congress would not legislate any cost-cutting measures that would make a dent in industry profits."

Blumenthal, a senior writer at the Sunlight Foundation, determined that Congress and PhRMA met dozens of times to negotiate that deal. He tells Terry Gross that he learned who attended the meetings by examining Federal Election Commission records, public visitor logs to the White House and the publicly available schedule of Sen. Max Baucus, the chairman of the Senate Finance Committee.

"The major people are President Obama, [Chief of Staff] Rahm Emanuel and Jim Messina," Blumenthal says. "Jim Messina is the former chief of staff and campaign manager to Sen. Max Baucus. You see Jim Messina pop up in meetings between pharmacy CEOs."

Blumenthal says that the CEOs of pharmaceutical giants Pfizer and AstraZeneca attended a series of meetings at the White House throughout the spring and summer, and agreed to spend more than $150 million on ads touting a health care overhaul. That spending and the subsequent lack of progress on the bill, Blumenthal notes, may be why Tauzin resigned.

"One of the key things to look at is the fact that pharmaceutical companies dumped $100 million to $150 million on ads and haven't gotten what they paid for," says Blumenthal. "They're not thrilled that they spent [that money] in ads, and this isn't going to pass."

Glaxo to Shift Away from Antidepressant Research CEO admits antidepressant research only based on subjective mood surveys

Wall Street Journal
By Jeanne Whalen
February 5, 2010

GlaxoSmithKline PLC said it will stop research into new antidepressants and focus on diseases for which it believes it can develop more valuable drugs, a major shift for a company that developed some of the biggest-selling antidepressants of the past 20 years.

Profits at the U.K. drug giant, which posted a 66% increase in fourth-quarter earnings Thursday, were long fueled by the antidepressants Paxil and Wellbutrin, which at their peak generated billions of dollars a year in sales. Similar medicines, such as Eli Lilly & Co.’s Prozac and Pfizer Inc.’s Zoloft, also generated big sales for those companies.

However, low-cost generic copies have eroded demand for name-brand antidepressants, which accounted for just 2.3% of Glaxo’s total sales last year, down from 14% in 2002. Chief Executive Andrew Witty said Thursday that the company thinks further investment in the market wouldn’t be prudent.

Part of the reason is financial risk. Clinical trials of antidepressants are among the “most expensive and highest-risk” of all drug trials, Mr. Witty said, because companies often don’t know until the end of very large studies whether a drug works. It is also hard to prove that a depression drug is working, he said, because patient improvement is measured by subjective mood surveys, and not by the clear-cut blood tests and biological measures used in other diseases.

That’s a drawback in an era when insurers and other health-care payers want to see clear value for their money, Mr. Witty said.

Payers “want big benefits to make it worth their while to invest their resources,” he said, adding that Glaxo would scrap research into pain drugs for the same reasons, focusing instead on diseases including Alzheimer’s, Parkinson’s, multiple sclerosis and a clutch of rare diseases.

AstraZeneca facing 26,000 suits over Seroquel

Bloomberg News
February 4, 2010
By JEF FEELEY and MARGARET CRONIN FISK

AstraZeneca PLC is facing as many as 26,000 lawsuits over its antipsychotic drug Seroquel as the drug maker prepares for its first jury trial over claims the medicine causes diabetes, according to court filings.

Attorneys for AstraZeneca, which has its U.S. headquarters in Fairfax, met with plaintiffs' lawyers in court-ordered mediation sessions last month to discuss a possible settlement, according to court filings. Consumers' lawyers said they had about 26,000 cases in their inventories, Stephen Saltzburg, a George Washington University Law School professor who served as mediator, said.

"I wish there were a magic wand that could be waved to settle all Seroquel cases instantly," Saltzburg said in the filing. "Such a wand does not exist."

In a Securities and Exchange Commission filing last week, AstraZeneca executives noted the company has paid about $656 million to defend itself in Seroquel cases. That's an increase of 28 percent, or $144 million, over last year's Seroquel defense costs, according to regulatory filings. The company said it had insurance of $521 million to cover Seroquel defense costs as of December.

The company said in the SEC filing it faces more than 25,000 claims that Seroquel caused diabetes. That's a 65 percent increase in cases over the number the company reported in a January 2009 regulatory filing. Many of the suits also claim AstraZeneca promoted Seroquel, approved for schizophrenic and bipolar patients, for unapproved uses.

Saltzburg said the two-day talks didn't generate a resolution, but he expects negotiations will take place at some point between the company and individual users' lawyers.

"The question is what is fair for plaintiffs and what is fair for AZ," the professor said in the report. "The parties are far apart at the moment on resolving that question."

AstraZeneca's stock fell last week after the drug maker's sales forecast and stock-buyback plan disappointed some analysts and fourth-quarter profit missed estimates. The company plans to buy back as much as $1 billion of shares this year, managers said Jan. 28.

A New Jersey judge has set a Feb. 16 trial date for the first of thousands of Seroquel cases filed in that state to go before a jury. Seroquel, which generated sales of $4.9 billion last year, is AstraZeneca's second-biggest seller after the ulcer treatment Nexium.

"The evidence, looked at fairly and fully, does not back up the allegations that Seroquel was responsible for the plaintiffs' alleged injuries," AstraZeneca spokesman Tony Jewell said in an e-mail.

In November, a judge in Florida who is overseeing all federal-court litigation over Seroquel ordered the company to meet with plaintiffs' lawyers and Saltzburg to discuss settlement.
U.S. District Judge Anne Conway in Florida, who is overseeing pre-trial proceedings in federal Seroquel litigation, said in November that she would ask a panel of judges to return the 6,000 cases consolidated before her to their home courts for trial.

Pfizer Broke the Law by Promoting Drugs for Unapproved Uses

Bloomberg News
November 9, 2009
By David Evans

Nov. 9 (Bloomberg) -- Prosecutor Michael Loucks remembers clearly when lawyers for Pfizer Inc., the world’s largest drug company, looked across the table and promised it wouldn’t break the law again.

It was January 2004, and the attorneys were negotiating in a conference room on the ninth floor of the federal courthouse in Boston, where Loucks was head of the health-care fraud unit of the U.S. Attorney’s Office. One of Pfizer’s units had been pushing doctors to prescribe an epilepsy drug called Neurontin for uses the Food and Drug Administration had never approved.

In the agreement the lawyers eventually hammered out, the Pfizer unit, Warner-Lambert, pleaded guilty to two felony counts of marketing a drug for unapproved uses.

New York-based Pfizer agreed to pay $430 million in criminal fines and civil penalties, and the company’s lawyers assured Loucks and three other prosecutors that Pfizer and its units would stop promoting drugs for unauthorized purposes.

What Loucks, who’s now acting U.S. attorney in Boston, didn’t know until years later was that Pfizer managers were breaking that pledge not to practice so-called off-label marketing even before the ink was dry on their plea.

On the morning of Sept. 2, 2009, another Pfizer unit, Pharmacia & Upjohn, agreed to plead guilty to the same crime. This time, Pfizer executives had been instructing more than 100 salespeople to promote Bextra, a drug approved only for the relief of arthritis and menstrual discomfort, for treatment of acute pains of all kinds.

Record High Fine

For this new felony, Pfizer paid the largest criminal fine in U.S. history: $1.19 billion. On the same day, it paid $1 billion to settle civil cases involving the off-label promotion of Bextra and three other drugs with the U.S. and 49 states.

“At the very same time Pfizer was in our office negotiating and resolving the allegations of criminal conduct in 2004, Pfizer was itself in its other operations violating those very same laws,” Loucks, 54, says. “They’ve repeatedly marketed drugs for things they knew they couldn’t demonstrate efficacy for. That’s clearly criminal.”

The penalties Pfizer paid this year for promoting Bextra off-label were the latest chapter in the drug’s benighted history. The FDA found Bextra to be so dangerous that Pfizer took it off the market for all uses in 2005.

Across the U.S., pharmaceutical companies have been pleading guilty to criminal charges or paying penalties in civil cases when the U.S. Department of Justice finds that they deceptively marketed drugs for unapproved uses, putting millions of people at risk of chest infections, heart attacks, suicidal impulses or death.

$7 Billion in Penalties

Since May 2004, Pfizer, Eli Lilly & Co., Bristol-Myers Squibb Co. and four other drug companies have paid a total of $7 billion in fines and penalties. Six of the companies admitted in court that they marketed medicines for unapproved uses.

In September 2007, New York-based Bristol-Myers paid $515 million -- without admitting or denying wrongdoing -- to federal and state governments in a civil lawsuit brought by the Justice Department. The six other companies pleaded guilty in criminal cases.

In January 2009, Indianapolis-based Lilly, the largest U.S. psychiatric drug maker, pleaded guilty and paid $1.42 billion in fines and penalties to settle charges that it had for at least four years illegally marketed Zyprexa, a drug approved for the treatment of schizophrenia, as a remedy for dementia in elderly patients.

In five company-sponsored clinical trials, 31 people out of 1,184 participants died after taking the drug for dementia -- twice the death rate for those taking a placebo. Those findings were reported in an October 2005 article in the Journal of the American Medical Association.

‘Don’t Respect the Law’

“Marketing departments of many drug companies don’t respect any boundaries of professionalism or the law,” says Jerry Avorn, a professor at Harvard Medical School in Boston and author of “Powerful Medicines: The Benefits, Risks, and Costs of Prescription Drugs” (Random House, 2004). “The Pfizer and Lilly cases involved the illegal promotion of drugs that have been shown to cause substantial harm and death to patients.”

The widespread off-label promotion of drugs is yet another manifestation of a health-care system that has become dysfunctional.

“It’s an unbearable cost to a system that’s going broke,” says Avorn, who heads the pharmacology economics unit of Brigham and Women’s Hospital in Boston. “We can’t even afford to pay for effective, safe therapies.”

10 Million Prescriptions

About 15 percent of all drug sales in the U.S. are for unapproved uses without adequate evidence the medicines work, according to a study by Randall Stafford, a medical professor at Stanford University in Palo Alto, California.

He estimates that doctors write more than 10 million such prescriptions each year.

As large as the penalties are for drug companies caught breaking the off-label law, the fines are tiny compared with the firms’ annual revenues.

The $2.3 billion in fines and penalties Pfizer paid for marketing Bextra and three other drugs cited in the Sept. 2 plea agreement for off-label uses amount to just 14 percent of its $16.8 billion in revenue from selling those medicines from 2001 to 2008.

The total of $2.75 billion Pfizer has paid in off-label penalties since 2004 is a little more than 1 percent of the company’s revenue of $245 billion from 2004 to 2008.

$36 Billion in Revenue

Lilly already had a criminal conviction for misbranding a drug when it broke the law again in promoting schizophrenia drug Zyprexa for off-label uses starting in 1999. The medication provided Lilly with $36 billion in revenue from 2000 to 2008.

That’s more than 25 times as much as the total penalties Lilly paid in January.

Companies regard the risk of multimillion-dollar penalties as just another cost of doing business, says Lon Schneider, a professor at the University of Southern California’s Keck School of Medicine in Los Angeles.

In 2006, he led a study for the National Institute of Mental Health of off-label use of drugs, including Zyprexa, for the treatment of Alzheimer’s disease.

“There’s an unwritten business plan,” he says. “They’re drivers that knowingly speed. If stopped, they pay the fine, and then they do it again.”

Shareholders Unmoved

Schneider has been paid both by Lilly as a consultant and by plaintiffs suing the company.

Big Pharma’s off-label transgressions didn’t trigger a rush for the doors by shareholders. From Jan. 26, when Pfizer announced that it would pay billions in penalties, to Oct. 12, Pfizer’s share price increased 9.3 percent, just shy of the 11.2 percent rise in the Standard & Poor’s 500 Health Care Index.

From Oct. 21, 2008, when Lilly said it would pay its penalties, to Oct. 12, the company’s stock value went up 0.6 percent; the S&P index gained 6.9 percent in that time.

In pushing off-label use of drugs, companies find ready and willing partners in physicians. Under the fragmented system of medical regulation in the U.S., it’s legal for doctors to prescribe FDA-approved drugs for any use.

The FDA has no authority over doctors, only over drug companies, regarding off-label practices. It’s up to the 50 states to oversee physicians.

“I think the physician community has to take some ownership responsibility and do their own due diligence beyond the sales and marketing person,” says Boston’s former U.S. Attorney Michael Sullivan.

Off-Label Benefits

Loucks says prosecutors realize that patients can benefit when doctors use drugs for off-label purposes based on science and not on false marketing claims.

Doctors generally don’t tell people that they’re prescribing drugs pitched to them by pharmaceutical salespeople for unapproved treatments, says Peter Lurie, deputy medical director of Public Citizen, a Washington-based public interest group.

Most physicians don’t keep track of FDA-approved uses of drugs, says Lurie, a physician who has published articles in “The Lancet” and the “Journal of the American Medical Association.”

“The great majority of doctors have no idea; they don’t even understand the distinction between on- and off-labeling,” Lurie says.

Pharmaceutical companies have showered doctors with cash to persuade them to use drugs off-label, according to their guilty pleas.

‘Buying Access’

Pfizer’s marketing program offered doctors up to $1,000 a day to allow a Pfizer salesperson to spend time with the physician and his patients, according to a whistle-blower lawsuit filed by John Kopchinski, who worked as a salesman at Pfizer from 1992 to 2003.

“By ‘pairing up’ with a physician, the sales representative was able to promote over a period of many hours, without the usual problems of gaining access to prescribing physicians,” Kopchinski says. “In essence, this amounted to Pfizer buying access to physicians.”

Pfizer spokesman Chris Loder says the company stopped what it calls “mentorships” in 2005. He says Pfizer paid doctors $250 per visit.

It used to be legal for companies to promote drugs for any use in the U.S. Congress banned the practice in 1962. The catalyst was Thalidomide, a morning sickness drug taken by pregnant women outside the U.S. that caused severe birth defects.

Recouping Investments

The 1962 law required pharmaceutical companies to prove their drugs were safe and effective for specific uses. Before that, a drug company could market an approved medicine for any illness.

If the law is clear, why do drug companies keep breaking it? The answer lies in economics. Pharmaceutical companies spend about $1 billion to develop and test a new drug. To recoup their investment, the companies want doctors to prescribe their drugs as widely as possible.

Pfizer’s Neurontin is a case in point. The FDA approved the drug as a supplemental medication in treating epilepsy in 1993. Pfizer took in $2.27 billion from sales of Neurontin in 2002. A full 94 percent -- $2.12 billion -- of that revenue came from off-label use, according to the prosecutors’ 2004 Pfizer sentencing memo.

Pfizer, which bought Wyeth on Oct. 15 for $68 billion, put itself at the center of illegal off-label drug marketing with an acquisition frenzy a decade earlier. From 1995 to 2005, Pfizer purchased more than 20 companies.

Guilty Pleas

Since 2004, companies that are now Pfizer divisions have pleaded guilty to off-label marketing of two drugs. Pfizer continued off-label promotions for these medications after buying the firms, according to Pfizer’s Sept. 2 guilty plea and FDA correspondence with Pfizer.

Pfizer first stepped into an off-label scheme in 1999, when it offered to buy Morris Plains, New Jersey-based Warner-Lambert Co. Prosecutors charged that Warner-Lambert marketed Neurontin off-label between 1995 and 1999.

Warner-Lambert admitted doing so for one year in a May 2004 guilty plea for which Pfizer paid $430 million in fines and penalties.

Neurontin, which was invented by Warner-Lambert, was first tested in humans in 1987. When the FDA approved it in 1993 to be used only along with other epilepsy drugs, the agency wrote that a side effect of the drug can be that it induces depression and suicidal thoughts in patients.

Whistle-Blower

Much of what prosecutors learned about Warner-Lambert’s marketing of Neurontin comes from a former employee.

David Franklin, who holds a Ph.D. in microbiology from the University of Rhode Island, left his job as a pediatric researcher at Harvard University’s Dana-Farber Cancer Institute in 1996 to work for the Parke-Davis unit of Warner-Lambert in Boston.

He says he hoped the salary boost -- to $55,000 annually from $18,000 -- would help him pay off student loans and better support his family.

Franklin’s title at Warner-Lambert was medical liaison. He says he soon realized his new employer viewed his doctorate as a badge that would allow him to strike up conversations with physicians.

Franklin, 48, says his job involved more salesmanship than science. He told doctors that Neurontin was the best drug for a dozen off-label uses, including pain relief, bipolar disease and depression.

‘What I Did Was Wrong’

“Technically, I had responsibility for answering physician questions about all of Parke-Davis’s drugs,” Franklin says. “In practice, my real job was to promote Neurontin for off- label indications heavily -- to the exclusion of just about everything else.”

Franklin, whose wife is a lawyer, says he knew such uses of the drug had no scientific support for effectiveness and safety.

“I was actually undermining their ability to fulfill the Hippocratic oath,” Franklin says, referring to a physician’s pledge to “first, do no harm.”

Franklin says he was horrified when he learned from a doctor that a child had a behavioral outburst at school for the first time after taking Neurontin.

“Don’t we have an obligation to tell physicians about this?” Franklin says he asked his manager, Phil Magistro. His boss tried to reassure him, Franklin says.

‘Total Disregard’

“‘Don’t worry about this stuff,’” he says Magistro told him. “‘It can never get back to us.’”

Franklin was stunned.

“I realized at that moment, looking into his eyes, that there was an absolute total disregard for the patient,” he says.

Magistro, who now works at drug marketing adviser Atom Strategic Consulting LLC in Randolph, New Jersey, didn’t return calls seeking comment.

Franklin saved phone messages from Magistro to his sales team urging them to market Neurontin for off-label uses, including pain relief. During one such call, on May 23, 1996, at 5:48 p.m. in Boston, Magistro told his staff, “You’re supposed to be pushing on Neurontin,” according to a transcript of the tape filed in federal court.

“When we get out there, we want to kick some ass. We want to sell Neurontin on pain,” Magistro said. “All right?”

Quit the Job

After working for Warner-Lambert for three months, Franklin grew concerned about his own liability. He quit the job and talked with Boston attorney Thomas Greene, who helped him file a lawsuit against the company.

Franklin acted as a whistle-blower, suing on behalf of taxpayers to recover money the government paid for illegally promoted drugs. Under federal and state whistle-blower statutes, he stood to collect as much as 30 percent of any settlement the company made with the government.

Franklin had to wait four years -- until 2000 -- before the Justice Department began a criminal investigation. In November 1999, Pfizer made its public offer to buy Warner-Lambert. In January 2000, a federal grand jury in Boston issued subpoenas to Warner-Lambert employees to testify about the marketing of Neurontin.

That March, Warner-Lambert’s annual report disclosed that prosecutors were building a criminal case. Undeterred, Pfizer bought Warner-Lambert in June for $87 billion. It was the third- largest merger in U.S. history.

‘Misleading and in Violation’

A year after the acquisition, the FDA discovered that Neurontin was still being marketed off-label. In a letter to the company on June 29, 2001, the agency wrote that Pfizer’s promotion of the drug “is misleading and in violation of the Federal Food, Drug and Cosmetics Act.”

The agency asked Pfizer to stop such promotions of Neurontin. The FDA said Pfizer had distributed brochures -- known as “slim jims” because they’re small enough to put in a jacket pocket -- improperly claiming that the drug could improve energy levels and memory.

“Immediately discontinue the use of this slim jim and any other promotional material or practices with the same or similar messages,” the FDA wrote.

Pfizer marketed Neurontin off-label after receiving that letter, agency records show. For 2001, Pfizer reported revenue of $1.75 billion from Neurontin sales, making it the company’s fourth-largest-selling drug that year, ahead of impotence pill Viagra, which Neurontin topped for four years.

Marketing Violated Rules

As Neurontin sales soared to $2.27 billion in 2002, the FDA found that Pfizer was improperly claiming that the drug was useful for a broader range of brain disorders than scientific evidence had established.

The agency sent a letter dated July 1, 2002, that said the company’s marketing practices were in violation of FDA rules. It asked Pfizer to stop using misleading promotions. Pfizer reported $2.7 billion in revenue from Neurontin in 2003. Overall, the drug has provided Pfizer with $12 billion in revenue.

In a response to Bloomberg News, Pfizer spokesman Chris Loder said, “Regarding the 2001 and 2002 FDA letters, we do not believe that they were suggestive of any continuing off-label promotion.”

For blowing the whistle on his employer, Franklin collected $24.6 million under the False Claims Act.

Prosecutors Loucks and Sullivan got involved in the case after Franklin filed his suit, relying on information from Franklin and their own investigation. Before 2004, prosecutions for off-label marketing were rare.

‘Everybody Does It’

“Until a couple of these cases became public, companies were probably saying, ‘Everybody does it this way,’” Sullivan says.

Loucks had a track record in off-label prosecutions. He gave up private practice at Choate Hall & Stewart LLP in Boston in 1985 to join the U.S. Attorney’s Office.

In 1994, he negotiated a $61 million settlement with Murray Hill, New Jersey-based C.R. Bard Inc., which pleaded guilty to promoting off-label use of a heart catheter that led to patient deaths.

In 2002, he co-authored, with Carol Lam, “Prosecuting and Defending Health Care Fraud Cases” (BNA Books).

In the January 2004 settlement negotiations with Loucks, Sullivan and two other prosecutors, Pfizer’s lawyers assured the U.S. Attorney’s Office that the company wouldn’t market drugs off-label.

‘Those Promises’

“They asserted that the company understood the rules and had taken steps to assure corporate compliance with the law,” Loucks says. “We remember those promises.”

What Pfizer’s lawyers didn’t tell the prosecutors was that Pfizer was at that moment running an off-label marketing promotion using more than 100 of its salespeople. They were pitching Bextra, a Pfizer sales manager admitted when she pleaded guilty to misbranding a drug on March 30, 2009.

Jeff Kindler, who became Pfizer’s general counsel in 2002, supervised the lawyers who made the promises to prosecutors. By 2004, Kindler increased the compliance budget 12-fold. He became chief executive officer in 2006. In Pfizer’s ethics guide, he says stories about misbehaving companies and executives abound.

“Pfizer truly stands apart,” he says. “I am proud of our record.” On Oct. 1, Kindler was elected to the board of the Federal Reserve Bank of New York. Kindler declined to comment.

Peapack, New Jersey-based Pharmacia & Upjohn Inc. developed Bextra, which was approved by the FDA only for the treatment of arthritis and menstrual discomfort in 2001.

Sales Manager Pleads Guilty

P&U and Pfizer had by then already crafted a joint marketing agreement to sell the drug. In November 2001, Mary Holloway, a Pfizer regional manager for the Northeastern U.S., began illegally training and directing her sales team to market Bextra for the relief of acute pain, Holloway admitted in a March 2009 guilty plea.

On Dec. 4, 2001, Pfizer executives sent Holloway a copy of a nonpublic letter from the FDA to the company. The agency had denied Pfizer’s application to market Bextra for acute pain. Clinical trials had shown Bextra could cause heart damage and death.

Pfizer bought Pharmacia & Upjohn in April 2003. From 2001 to the end of 2003, P&U, first as an independent company and then as a unit of Pfizer, paid physicians more than $5 million in cash to lure them to resorts, where salespeople illegally pitched off-label uses for Bextra, P&U admitted in its Sept. 2 guilty plea.

‘Golf, Massages’

“Pharmacia paid targeted physicians both airfare and two to three days’ accommodations at lavish resorts in the Bahamas, Virgin Islands and across the United States and further entertained these physicians with golf, massages and other recreation activities,” according to prosecutors’ findings.

In her guilty plea, Holloway said her team had solicited hospitals to create protocols to buy Bextra for the unapproved purpose of acute pain relief. Her representatives didn’t mention the increased risk of heart attacks in their marketing.

They told doctors that side effects were no worse than those of a sugar pill, Holloway admitted in her guilty plea.

In 2003, Holloway reported her unit’s off-label promotions of Bextra up the corporate ladder at Pfizer, according to a pre- sentencing memo to the judge written by Robert Ullmann, Holloway’s attorney. Top managers didn’t attempt to halt the illegal conduct, the memo said.

“Corporate tracked this information, and at no time did it inform Ms. Holloway that any of the reported protocols were inappropriate,” he wrote. “Instead, the instruction was to get more protocols.”

Blockbuster Status

By the end of 2004, Bextra reached blockbuster status, with annual sales of $1.29 billion. Holloway promoted Bextra until the FDA asked Pfizer in April 2005 to pull it from the market for all uses, evidence in her case shows.

The agency concluded that the drug increased the risk of heart attacks, chest infections and strokes in cardiac surgery patients. In June 2009, Holloway, 47, was sentenced to two years on probation and fined $75,000. She didn’t return phone calls seeking comment.

Ronald Rainero, a Pfizer district sales manager and employee for more than 20 years, says he was responsible for promoting Bextra in New York from 2001 to 2005. In September 2007, Rainero, 47, began cooperating with federal prosecutors on the Bextra case.

Hotel Meetings

He says he met monthly with his fellow managers at a Hilton hotel in Staten Island, New York, to discuss sales methods of promoting Bextra off-label. As a whistle-blower, Rainero was awarded $9.3 million as part of the September settlement.

In the same time period that Pfizer was marketing Bextra off-label, the company’s sales force was promoting another drug, Zyvox, improperly, Pfizer admitted at the time of its September plea agreement.

Zyvox was approved in 2000 by the FDA for treating MRSA- caused pneumonia and skin infections. Raniero told federal prosecutors that Pfizer began the Zyvox campaign in 2001. The company admitted to falsely claiming that the drug was better than other medications for treating MRSA pneumonia.

Pfizer told doctors to use Zyvox rather than vancomycin, a generic antibiotic that cost $18 a day. Pfizer sold Zyvox for about $150 a day. A table on page 30 of a 35-page fact book produced by Pfizer for Zyvox says the drug is less effective than vancomycin for MRSA pneumonia.

‘Misleading Promotion’

On July 20, 2005, the FDA sent a letter to Hank McKinnell, then Pfizer’s CEO, saying, “Your misleading promotion of Zyvox, and in particular your unsubstantiated implied claims regarding its superiority to vancomycin, poses serious health and safety concerns.”

The agency ordered the company to stop the promotion. In response, Pfizer told the FDA it would stop saying Zyvox was more effective against MRSA pneumonia than vancomycin.

Despite its 2005 pledge to the FDA, Pfizer continued to tell hospitals and doctors that Zyvox would save more lives than vancomycin, the company admitted in the September settlement.

By 2007, the criminal and civil cases against Pfizer, its employees and its subsidiaries had started to mount. The tally of drugs cited by federal prosecutors for off-label promotion reached six by 2009. In April 2007, P&U pleaded guilty to a felony charge of offering a $12 million kickback to a pharmacy benefit manager.

$2.2 Billion in Penalties

Pfizer paid a criminal fine of $19.7 million. Thomas Farina, a Pfizer district sales manager, was convicted in federal court in March 2009 for destroying records during the Bextra investigation. Farina, 42, was sentenced to three years on probation, including six months of home confinement. He didn’t return calls seeking comment.

Pfizer itself was called to account on Sept. 2, when it agreed to pay the $2.2 billion in fines and penalties. P&U pleaded guilty to a felony charge of misbranding Bextra with the intent to defraud. After the settlement, Pfizer general counsel Amy Schulman said the company had learned its lesson.

“We regret certain actions we’ve taken in the past,” she said. “Corporate integrity is an absolute priority for Pfizer.”

One reason drug companies keep breaking the law may be because prosecutors and judges have been unwilling to use the ultimate sanction -- a felony conviction that would render a company’s drugs ineligible for reimbursement by state health programs and federal Medicare.

“It’s potentially a death sentence for a drug company,” prosecutor Sullivan says.

Fig Leaf

A legal fig leaf allows a parent company to continue to participate in government programs even after its subsidiary has pleaded guilty.

Pfizer maintains its good standing with such agencies because its subsidiaries, Warner-Lambert and P&U, and not the corporation itself, entered the guilty pleas to felony charges.

A felony conviction of a pharmaceutical giant could lead to disaster for shareholders, Loucks says, adding that’s a step that may have to be taken for repeat offenders.

“I think it’s something the trigger will get pulled on,” he says from his ninth-floor office in the federal courthouse, with a sweeping view of Boston Harbor. “It’s just a question of when.”

At Pfizer’s Pharmacia sentencing on Oct. 16., U.S. District Court Judge Douglas Woodlock said companies don’t appear to take the law seriously.

“It has become something of a cost of doing business for some of these corporations, to shed their skin like certain animals and leave the skin and move on,” he said.

Eli Lilly

Lilly’s rap sheet goes back to 1985. That’s when the company pleaded guilty to 25 federal misdemeanor charges related to its misbranding of Oraflex, an arthritis drug.

Lilly stopped selling the drug four months after U.S. sales began in 1982, following the company’s failure to tell the FDA about illnesses and deaths tied to the medication. Lilly paid a $25,000 fine.

Twenty years later, in 2005, Lilly paid $36 million in a guilty plea to one federal misdemeanor for off-label marketing of Evista, a drug the FDA had approved for bone strengthening.

In 1997, the agency had rejected Lilly’s application to market the drug to reduce the risk of breast cancer. Yet beginning the next year, Lilly adopted an Evista marketing plan that included a seminar with doctors designed to appeal to women’s breast cancer concerns, Lilly admitted in its 2005 guilty plea.

In 2007, the FDA approved Evista for preventing breast cancer in two limited groups.

Back in Court

In January 2009, Lilly was back in federal court. Prosecutors in Philadelphia accused the company of earning hundreds of millions of dollars by illegally promoting its schizophrenia drug Zyprexa for the unapproved treatment of dementia from 1999 to at least 2003.

In 2001, Lilly’s senior management decided not to seek FDA approval for Zyprexa to treat dementia because of what they viewed as mixed results in clinical trials and safety risks, according to admissions by Lilly in its 2009 guilty plea. In its marketing, Lilly promoted the drug as effective.

Zyprexa has been Lilly’s best-selling drug for the past decade.

“Eli Lilly undertook this illegal off-label promotion for its own financial gain despite the potential risk to patients’ health and lives,” prosecutors wrote in their sentencing memo.

Lilly Chairman and CEO John Lechleiter said after the settlement that the company was devoted to acting responsibly.

‘Deeply Regret’

“We deeply regret the past actions covered by the misdemeanor plea,” he said. “Doing the right thing is nonnegotiable at Lilly.”

In a written response to questions from Bloomberg News, Lilly said, “Lilly entered into a very narrow guilty plea. Even though the company disagrees with and does not admit to the allegations, Lilly agreed to settle the dispute.”

Lilly paid $1.42 billion for a fine and penalties in the January settlement with federal and state governments. That included the largest criminal fine in U.S. history -- until Pfizer pleaded guilty in September.

The Justice Department could have charged Lilly with a felony. Prosecutors decided that it wouldn’t be fair to innocent Lilly employees, shareholders and pensioners to potentially shut down the company, according to the sentencing memo.

‘All the Factors’

“The government considered all the factors in its decision,” prosecutors wrote. “Those factors included other persons not proven personally culpable.”

Federal regulators have detected a similar pattern of dishonesty by other pharmaceutical firms. Schering-Plough Corp. drug salesmen pitched off-label uses of a cancer drug called Temodar at the American Society of Clinical Oncology’s annual conference in San Francisco in May 2001.

Schering-Plough representatives said Temodar compared favorably to a placebo in clinical trials for the off-label uses and was approved by the FDA for first-line use in treating brain tumors.

An FDA employee attending the conference took note. The next month, the FDA accused Schering of lying.

There had been no such clinical trials and the agency had not approved Temodar as the salespeople had claimed, the FDA said in a June 28, 2001, letter to Mary Jane Nehring, Schering’s senior director of marketed products. The agency ordered the company to immediately cease illegal promotion of Temodar.

Kenilworth, New Jersey-based Schering-Plough was quick to respond. On July 12, 2001, it wrote back to the FDA, assuring regulators that the San Francisco activity was an isolated incident.

‘Certainly Inconsistent’

“It was certainly inconsistent with the direction provided by the home office,” the drug company wrote, according to prosecutor’s records.

The FDA told Schering-Plough three weeks later that it had closed its investigation.

Schering-Plough didn’t stop pitching the drug for unapproved uses. At the direction of top management, Schering ordered widespread off-label marketing of Temodar and Intron A, another cancer drug, until December 2003, the company admitted in an August 2006 guilty plea.

Schering, which agreed in March to be acquired by Merck & Co., earned a pre-tax profit of $124.2 million from the illegal sales after promising the FDA in 2001 it would stop marketing for off-label uses, the company admitted.

Schering-Plough pleaded guilty in August 2006 to conspiring to make false statements to the FDA. The company agreed to pay $435 million to settle the case.

‘Upsetting to Me’

U.S. District Court Judge Patti Saris, who had presided over the Neurontin whistle-blower case before the Pfizer probe, accepted Schering’s plea in her Boston courtroom in January 2007. She expressed dismay with the drug industry.

“It’s been upsetting to me how many of the big pharmaceutical companies have engaged in what I view as clearly illegal behavior in terms of off-label marketing,” she said. “It almost seems as if the pharmaceutical companies said ‘Yeah, yeah, yeah’ to the FDA and then went and did it anyway.”

Brent Saunders, a Schering-Plough senior vice president, said after the settlement that his company had made great progress in putting integrity at the center of its work.

“With this agreement, we are putting issues from the past behind us,” he said. Schering declined to comment further.

As prosecutors continue to uncover patterns of deceit in off-label marketing by pharmaceutical companies, millions of patients across the nation remain in the dark. Doctors often choose the medications based on dishonest marketing by drug company salesmen.

‘A Morass’

“It’s a morass of undifferentiated information out there,” Public Citizen’s Lurie says. “And the doctors, let alone patients, aren’t able to distinguish the good from the bad.”

One thing all people should do, Lurie says, is ask whether their prescriptions are for FDA-approved uses, and if not, whether strong evidence supports using the drug, particularly if it can be dangerous.

Loucks says that putting an end to the criminal off-label schemes by the pharmaceutical industry is more difficult. As drugmakers repeatedly plead guilty, they’ve shown they’re willing to pay hundreds of millions of dollars in fines as a cost of generating billions in revenue.

The best hope, Loucks says, is that drug companies actually honor the promises they keep making -- and keep breaking -- to obey the law of the land.

To contact the reporter on this story: David Evans in Los Angeles at davidevans@bloomberg.net

Drug Makers Are Advocacy Group's [NAMI's] Biggest Donors

New York Times
By GARDINER HARRIS
October 21, 2009

WASHINGTON — A majority of the donations made to the National Alliance on Mental Illness, one of the nation's most influential disease advocacy groups, have come from drug makers in recent years, according to Congressional investigators.

The alliance, known as NAMI, has long been criticized for coordinating some of its lobbying efforts with drug makers and for pushing legislation that also benefits industry.

Last spring, Senator Charles E. Grassley, Republican of Iowa, sent letters to the alliance and about a dozen other influential disease and patient advocacy organizations asking about their ties to drug and device makers. The request was part of his investigation into the drug industry's influence on the practice of medicine.

The mental health alliance, which is hugely influential in many state capitols, has refused for years to disclose specifics of its fund-raising, saying the details were private.

But according to investigators in Mr. Grassley's office and documents obtained by The New York Times, drug makers from 2006 to 2008 contributed nearly $23 million to the alliance, about three-quarters of its donations.

Even the group's executive director, Michael Fitzpatrick, said in an interview that the drug companies' donations were excessive and that things would change.

"For at least the years of '07, '08 and '09, the percentage of money from pharma has been higher than we have wanted it to be," Mr. Fitzpatrick said.

He promised that the industry's share of the organization's fund-raising would drop "significantly" next year.

"I understand that NAMI gets painted as being in the pockets of pharmaceutical companies, and somehow that all we care about is pharmaceuticals," Mr. Fitzpatrick said. "It's simply not true."

Mr. Fitzpatrick said Mr. Grassley's scrutiny, which he described as understandable given the attention paid to potential conflicts of interest in medicine, had led his organization to begin posting on its Web site the names of companies that donate $5,000 or more. And he predicted that other patient and disease advocacy groups would be prodded by Mr. Grassley's investigation to do the same.

"Everyone I talk to wants to have more balanced fund-raising," Mr. Fitzpatrick said.

In a statement, Mr. Grassley praised the alliance for its disclosures. "It'd be good for the system for other patient groups to do what NAMI has done," he said.

Mr. Grassley's scrutiny has been unnerving for patient and disease advocacy groups, which are often filled with sincere people who are either afflicted with serious illnesses themselves or have family members who have been affected. Many join the groups in the hope of making sense of their misfortune by helping to find a cure or raising awareness of a disease's risks and frequency.

Drug makers are natural allies in these pursuits since cures may come out of corporate laboratories and the industry's money can help finance public service campaigns and fund-raising dinners. But industry critics have long derided some patient organizations as little more than front groups devoted to lobbying on issues that affect industry profits, and few have come under more scrutiny for industry ties than the mental health alliance.

For years, the alliance has fought states' legislative efforts to limit doctors' freedom to prescribe drugs, no matter how expensive, to treat mental illness in patients who rely on government health care programs like Medicaid. Some of these medicines routinely top the list of the most expensive drugs that states buy for their poorest patients.

Mr. Fitzpatrick defended these lobbying efforts, saying they were just one of many the organization routinely undertook.

The close ties between the alliance and drug makers were on stark display last week, when the organization held its annual gala at the Andrew W. Mellon Auditorium on Constitution Avenue in Washington. Tickets were $300 each. Before a dinner of roasted red bell pepper soup, beef tenderloin and tilapia, Dr. Stephen H. Feinstein, president of the alliance's board, thanked Bristol-Myers Squibb, the pharmaceutical company.

"For the past five years, Bristol-Myers has sponsored this dinner at the highest level," Dr. Feinstein said.

He then introduced Dr. Fred Grossman, chief of neuroscience research at Bristol-Myers, who told the audience that "now, more than ever, our enduring relationship with NAMI must remain strong."

Documents obtained by The New York Times show that drug makers have over the years given the mental health alliance — along with millions of dollars in donations — direct advice about how to advocate forcefully for issues that affect industry profits. The documents show, for example, that the alliance's leaders, including Mr. Fitzpatrick, met with AstraZeneca sales executives on Dec. 16, 2003.

Slides from a presentation delivered by the salesmen show that the company urged the alliance to resist state efforts to limit access to mental health drugs.

"Solutions: Play Hard Ball," one slide was titled. "Hold policy makers accountable for their decisions in media and in election," it continued.

The alliance's own slides concluded by saying, "We appreciate AstraZeneca's strong support of NAMI."

Mr. Fitzpatrick said that the alliance frequently had such meetings and that the organization would fight for better access to mental health drugs "even if we had no relationship with pharmaceutical companies."

Tony Jewell, an AstraZeneca spokesman, said that the company was "committed to improving health through partnerships with nonprofit organizations" and that "includes striving to ensure people can access our medicines through formularies managed by state Medicaid agencies."