November 22, 2008
Popular Radio Host Has Drug Company Ties
By GARDINER HARRIS
An influential psychiatrist who served as the host of public radio’s popular “The Infinite Mind” program earned at least $1.3 million between 2000 and 2007 giving marketing lectures for drug makers, income not mentioned on the program.
The psychiatrist and radio host, Dr. Frederick K. Goodwin, is the latest in a series of doctors and researchers whose ties to drug makers have been uncovered by Senator Charles E. Grassley, a Republican from Iowa. Dr. Goodwin, a former director of the National Institute of Mental Health, is the first media figure investigated.
Dr. Goodwin’s radio programs have often touched on subjects important to the commercial interests of the companies for which he consults. In a program broadcast on Sept. 20, 2005, Dr. Goodwin warned that children with bipolar disorder who are left untreated could suffer brain damage, a controversial view. “But as we’ll be hearing today,” Dr. Goodwin reassured his audience, “modern treatments mood stabilizers in particular have been proven both safe and effective in bipolar children.”
That very day, GlaxoSmithKline paid Dr. Goodwin $2,500 to give a promotional lecture for its mood stabilizer drug, Lamictal, at the Ritz Carlton Golf Resort in Naples, Fla. Indeed, Glaxo paid Dr. Goodwin more than $329,000 that year for promoting Lamictal, records given Congressional investigators show.
In an interview, Dr. Goodwin said that Bill Lichtenstein, the program’s producer, knew of his consulting activities but that neither he nor Mr. Lichtenstein thought that “getting money from drug companies could be an issue. In retrospect, that should have been disclosed.”
But Mr. Lichtenstein said that he was unaware of Dr. Goodwin’s financial ties to drug makers and that he called Dr. Goodwin earlier this year “and asked him point-blank if he was receiving funding from pharmaceutical companies, directly or indirectly, and the answer was, ‘No.’”
“The fact that he was out on the stump for pharmaceutical companies was not something we were aware of. It would have violated our agreements,” Mr. Lichtenstein said in an interview.
Margaret Low Smith, vice president of National Public Radio, said that N.P.R. will remove “The Infinite Mind” from its satellite radio service next week, the earliest possible date. Ms. Smith said that had N.P.R. been aware of Dr. Goodwin’s financial interests, it would not have aired the program.
Sarah Alspach, a spokeswoman for Glaxo, said, “We continue to believe that healthcare professionals are responsible for making disclosures to their employers and other entities, in this case National Public Radio and its listeners.”
“The Infinite Mind” is a weekly program that has won more than 60 journalism awards over 10 years and bills itself as “public radio’s most honored and listened to health and science program.” It has more than one million listeners in more than 300 radio markets. Mr. Lichtenstein said that the last original program aired in October, that reruns have been airing since and that “the show is going off the air.”
The program has received major underwriting from the National Institutes of Health and the National Science Foundation, both of which have policies requiring grantees to disclose and manage conflicts of interest. Mr. Grassley wrote letters to both agencies asking whether disclosure rules were followed for the grants. Spokespeople for both agencies said they were cooperating with the investigation.
Mr. Grassley is systematically asking some of the nation’s leading researchers and doctors to provide their conflict-of-interest disclosures, and Mr. Grassley is comparing those documents with records of actual payments from drug companies. The records often conflict, sometimes starkly.
In October, Mr. Grassley revealed that Dr. Charles B. Nemeroff of Emory University, one of the nation’s most influential psychiatric researchers, earned more than $2.8 million in consulting arrangements with drug makers from 2000 to 2007, failed to report at least $1.2 million of that income to his university and violated federal research rules. As a result, the National Institutes of Health suspended a $9.3 million research grant to Emory and placed restrictions on other grants, and Dr. Nemeroff relinquished his chairmanship of Emory’s psychiatry department.
In June, the senator revealed that Harvard University’s Dr. Joseph Biederman, whose work has fueled an explosion in the use of powerful antipsychotic medicines in children, had earned at least $1.6 million from drug makers between 2000 and 2007, failed to report most of this income to his university, and may have violated federal and university research rules.
Mr. Grassley’s investigation demonstrates how deeply pharmaceutical commercial interests reach into academic medicine, and it has shown that universities are all but incapable of policing these arrangements. As a result of these revelations, almost every major medical school and medical society is now reassessing its relationships with drug and device makers.
“We know the drug companies are throwing huge amounts of money at medical researchers, and there’s no clear-cut way to know how much and exactly where,” Mr. Grassley said. “Now it looks like the same thing is happening in journalism.”
Mr. Grassley has proposed legislation that would require drug makers to publicly post all payments of $500 or more made to doctors. Eli Lilly and Merck have promised to begin posting such payments next year.
Dr. Goodwin has authored an influential textbook on bipolar disorder and is an adjunct professor at George Washington University. In an extensive interview, Dr. Goodwin blamed a changing ethical environment for any misunderstandings between himself and Mr. Lichtenstein about his consulting arrangements.
“More than 10 years ago when he and I got involved in this effort, it didn’t occur to me that my doing what every other expert in the field does might be considered a conflict of interest,” Dr. Goodwin said.
He defended the views he expressed in many of his radio programs and said that, because he consults for so many drug makers at once, he has no particular bias.
“These companies compete with each other and cancel each other out,” he said. This view is dismissed by industry critics, who say that experts who consult widely for drug makers tend to minimize the value of non-drug or older drug treatments.
In the fine print of a study he authored in 2003, Dr. Goodwin reported consulting or speaking for nine drug makers. Mr. Grassley only asked for payment information from Glaxo. Dr. Goodwin said that in recent years Glaxo paid him more than other companies.
He said that he has never given marketing lectures for antidepressant medicines like Prozac, so he saw no conflict with a program he hosted in March titled “Prozac Nation: Revisited” that he introduced by saying, “As you will hear today, there is no credible scientific evidence linking antidepressants to violence or to suicide.”
That same week, Dr. Goodwin earned around $20,000 from Glaxo, which for years suppressed studies showing that its antidepressant, Paxil, increased suicidal behaviors.
Tom Rosenstiel, director of the Project for Excellence in Journalism, said that although concerns about media bias are growing, few people believe that journalists take money from those they cover. Disclosures like those surrounding Dr. Goodwin could change that, “so this kind of thing is very damaging,” Mr. Rosenstiel said.
To learn more about the marketing deceptions used by the pharmaceutical companies and how the evidence has been and is being purposely misconstrued, see this discussion that begins with excerpts from the already classic video of Tom Cruise on the Today Show.
June 27, 2007
Psychiatrists Top List in Drug Maker Gifts
By GARDINER HARRIS
WASHINGTON, June 26 As states begin to require that drug companies disclose their payments to doctors for lectures and other services, a pattern has emerged: psychiatrists earn more money from drug makers than doctors in any other specialty.
How this money may be influencing psychiatrists and other doctors has become one of the most contentious issues in health care. For instance, the more psychiatrists have earned from drug makers, the more they have prescribed a new class of powerful medicines known as atypical antipsychotics to children, for whom the drugs are especially risky and mostly unapproved.
Vermont officials disclosed Tuesday that drug company payments to psychiatrists in the state more than doubled last year, to an average of $45,692 each from $20,835 in 2005. Antipsychotic medicines are among the largest expenses for the state’s Medicaid program.
Over all last year, drug makers spent $2.25 million on marketing payments, fees and travel expenses to Vermont doctors, hospitals and universities, a 2.3 percent increase over the prior year, the state said.
The number most likely represents a small fraction of drug makers’ total marketing expenditures to doctors since it does not include the costs of free drug samples or the salaries of sales representatives and their staff members. According to their income statements, drug makers generally spend twice as much to market drugs as they do to research them.
“For the fourth year in a row, our analysis shows that there is a great deal of money being spent in our small state on marketing pharmaceutical products,” said William H. Sorrell, the Vermont attorney general.
Endocrinologists received the second largest amount, according to the Vermont analysis, earning an average of $33,730. Since the state identified the specialties of only the top 100 earners, these averages represent the money earned by only some of the state’s specialists. There were 11 psychiatrists and 5 endocrinologists in that top group of 100.
Still, a similar pattern was evident in a Minnesota database that was the subject of a series of articles in The New York Times this year. As in Vermont, psychiatrists earned on aggregate the most in Minnesota, with payments ranging from $51 to $689,000. The Times found that psychiatrists who took the most money from makers of antipsychotic drugs tended to prescribe the drugs to children the most often.
These and other stories have helped to fuel a growing interest among state and federal officials to document and restrict payments to doctors from drug makers. At a gathering last month at Columbia Law School in New York, state attorneys general from across the country discussed ways to get similar data for their states.
And today, the Senate Special Committee on Aging, which is led by Senator Herb Kohl, Democrat of Wisconsin, will hold the first of a series of hearings on the issue, which could lead to legislative proposals to restrict and require disclosure of payments and gifts to doctors from drug companies nationwide.
Several lawmakers on Capitol Hill have expressed interest in such legislation, including Senator Charles E. Grassley, Republican of Iowa. “A federal law requiring public disclosure of payments to doctors could be very effective if it was carefully monitored and consistently applied,” Mr. Grassley said.
Efforts to require disclosure of payments to doctors began almost by happenstance in 1993, when The Minnesota Legislature passed a law that restricts drug companies from giving doctors gifts valued at more than $100 in any given year. The legislation also required companies to report and make public any consulting fees paid to doctors.
Lee Greenfield, a former state representative in Minnesota and one of the law’s authors, said it passed with little fanfare or debate after legislators heard stories about doctors accepting gifts of great value from drug makers.
“Why do we want them bribing doctors to use what may not be the best or most cost-effective drug for the patient purely to get some hand-held TV, we all asked,” Mr. Greenfield said.
Still, compliance with the law has been spotty. Some companies never responded to the board’s requests for disclosures. Others did so fitfully. A few sent letters saying they did not collect that information and thus could not provide it.
Minnesota officials never cracked down. Such reports were put in file drawers and largely forgotten until this past year, said Cody Wiberg, executive director of the Minnesota Board of Pharmacy. Mr. Wiberg said he planned this year to pursue companies that fail to report.
Besides Vermont and Maine, more than a dozen other states have or are now considering similar legislation, said Sharon Anglin Treat, executive director of the National Legislative Association on Prescription Drug Prices.
Officials in Maine and Vermont said they would try to compare reports of payments to doctors with Medicaid records to explore how marketing practices might influence prescribing by doctors in ways that increased costs to taxpayers.
“What we want to be able to do is overlay the prescribing information that we have with the drug detailing information,” said Jude Walsh, special assistant to the governor of Maine, John E. Baldacci. “If we see that doctors in a certain southern county in the state are prescribing a lot of a drug and getting a lot of detailing for that drug, that could lead to some record reviews to see what’s happening.”
June 6, 2008
Researchers Fail to Reveal Full Drug Pay
by GARDINER HARRIS and BENEDICT CAREY
The Sunday New York Times
Child Experts Fail to Reveal Full Drug Pay
A world-renowned Harvard child psychiatrist whose work has helped fuel an explosion in the use of powerful antipsychotic medicines in children earned at least $1.6 million in consulting fees from drug makers from 2000 to 2007 but for years did not report much of this income to university officials, according to information given Congressional investigators.
NY Times photos, right: top: Senator Charles E. Grassley pushed three experts in child psychiatry at Harvard to expose their income from consulting fees. bottom: Dr. Joseph Biederman belatedly reported at least $1.6 million in consulting fees.
By failing to report income, the psychiatrist, Dr. Joseph Biederman, and a colleague in the psychiatry department at Harvard Medical School, Dr. Timothy E. Wilens, may have violated federal and university research rules designed to police potential conflicts of interest, according to Senator Charles E. Grassley, Republican of Iowa. Some of their research is financed by government grants.
Like Dr. Biederman, Dr. Wilens belatedly reported earning at least $1.6 million from 2000 to 2007, and another Harvard colleague, Dr. Thomas Spencer, reported earning at least $1 million after being pressed by Mr. Grassley's investigators. But even these amended disclosures may understate the researchers' outside income because some entries contradict payment information from drug makers, Mr. Grassley found.
In one example, Dr. Biederman reported no income from Johnson & Johnson for 2001 in a disclosure report filed with the university. When asked recently to check again, he reported receiving $3,500. But Johnson & Johnson told Mr. Grassley that it paid him $58,169 in 2001, Mr. Grassley found.
The Harvard group's consulting arrangements with drug makers were already controversial because of the researchers' advocacy of unapproved uses of psychiatric medicines in children.
In an e-mailed statement, Dr. Biederman said, "My interests are solely in the advancement of medical treatment through rigorous and objective study," and he said he took conflict-of-interest policies "very seriously." Drs. Wilens and Spencer said in e-mailed statements that they thought they had complied with conflict-of-interest rules.
John Burklow, a spokesman for the National Institutes of Health, said: "If there have been violations of N.I.H. policy - and if research integrity has been compromised - we will take all the appropriate action within our power to hold those responsible accountable. This would be completely unacceptable behavior, and N.I.H. will not tolerate it."
The federal grants received by Drs. Biederman and Wilens were administered by Massachusetts General Hospital, which in 2005 won $287 million in such grants. The health institutes could place restrictions on the hospital's grants or even suspend them altogether.
Alyssa Kneller, a Harvard spokeswoman, said in an e-mailed statement: "The information released by Senator Grassley suggests that, in certain instances, each doctor may have failed to disclose outside income from pharmaceutical companies and other entities that should have been disclosed."
Ms. Kneller said the doctors had been referred to a university conflict committee for review.
Mr. Grassley sent letters on Wednesday to Harvard and the health institutes outlining his investigators' findings, and he placed the letters along with his comments in The Congressional Record.
Dr. Biederman is one of the most influential researchers in child psychiatry and is widely admired for focusing the field's attention on its most troubled young patients. Although many of his studies are small and often financed by drug makers, his work helped to fuel a controversial 40-fold increase from 1994 to 2003 in the diagnosis of pediatric bipolar disorder, which is characterized by severe mood swings, and a rapid rise in the use of antipsychotic medicines in children. The Grassley investigation did not address research quality.
Doctors have known for years that antipsychotic drugs, sometimes called major tranquilizers, can quickly subdue children. But youngsters appear to be especially susceptible to the weight gain and metabolic problems caused by the drugs, and it is far from clear that the medications improve children's lives over time, experts say.
In the last 25 years, drug and device makers have displaced the federal government as the primary source of research financing, and industry support is vital to many university research programs. But as corporate research executives recruit the brightest scientists, their brethren in marketing departments have discovered that some of these same scientists can be terrific pitchmen.
To protect research integrity, the National Institutes of Health require researchers to report to universities earnings of $10,000 or more per year, for instance, in consulting money from makers of drugs also studied by the researchers in federally financed trials. Universities manage financial conflicts by requiring that the money be disclosed to research subjects, among other measures.
The health institutes last year awarded more than $23 billion in grants to more than 325,000 researchers at over 3,000 universities, and auditing the potential conflicts of each grantee would be impossible, health institutes officials have long insisted. So the government relies on universities.
Universities ask professors to report their conflicts but do almost nothing to verify the accuracy of these voluntary disclosures.
"It's really been an honor system thing," said Dr. Robert Alpern, dean of Yale School of Medicine. "If somebody tells us that a pharmaceutical company pays them $80,000 a year, I don't even know how to check on that."
Some states have laws requiring drug makers to disclose payments made to doctors, and Mr. Grassley and others have sponsored legislation to create a national registry.
Lawmakers have been concerned in recent years about the use of unapproved medications in children and the influence of industry money.
Mr. Grassley asked Harvard for the three researchers' financial disclosure reports from 2000 through 2007 and asked some drug makers to list payments made to them.
"Basically, these forms were a mess," Mr. Grassley said in comments he entered into The Congressional Record on Wednesday. "Over the last seven years, it looked like they had taken a couple hundred thousand dollars."
Prompted by Mr. Grassley's interest, Harvard asked the researchers to re-examine their disclosure reports.
In the new disclosures, the trio's outside consulting income jumped but was still contradicted by reports sent to Mr. Grassley from some of the companies. In some cases, the income seems to have put the researchers in violation of university and federal rules.
In 2000, for instance, Dr. Biederman received a grant from the National Institutes of Health to study in children Strattera, an Eli Lilly drug for attention deficit disorder. Dr. Biederman reported to Harvard that he received less than $10,000 from Lilly that year, but the company told Mr. Grassley that it paid Dr. Biederman more than $14,000 in 2000, Mr. Grassley's letter stated.
At the time, Harvard forbade professors from conducting clinical trials if they received payments over $10,000 from the company whose product was being studied, and federal rules required such conflicts to be managed.
Mr. Grassley said these discrepancies demonstrated profound flaws in the oversight of researchers' financial conflicts and the need for a national registry. But the disclosures may also cloud the work of one of the most prominent group of child psychiatrists in the world.
In the past decade, Dr. Biederman and his colleagues have promoted the aggressive diagnosis and drug treatment of childhood bipolar disorder, a mood problem once thought confined to adults. They have maintained that the disorder was underdiagnosed in children and could be treated with antipsychotic drugs, medications invented to treat schizophrenia.
Other researchers have made similar assertions. As a result, pediatric bipolar diagnoses and antipsychotic drug use in children have soared. Some 500,000 children and teenagers were given at least one prescription for an antipsychotic in 2007, including 20,500 under 6 years of age, according to Medco Health Solutions, a pharmacy benefit manager.
Few psychiatrists today doubt that bipolar disorder can strike in the early teenage years, or that many of the children being given the diagnosis are deeply distressed.
"I consider Dr. Biederman a true visionary in recognizing this illness in children," said Susan Resko, director of the Child and Adolescent Bipolar Foundation, "and he's not only saved many lives but restored hope to thousands of families across the country."
Longtime critics of the group see its influence differently. "They have given the Harvard imprimatur to this commercial experimentation on children," said Vera Sharav, president and founder of the Alliance for Human Research Protection, a patient advocacy group.
Many researchers strongly disagree over what bipolar looks like in youngsters, and some now fear the definition has been expanded unnecessarily, due in part to the Harvard group.
The group published the results of a string of drug trials from 2001 to 2006, but the studies were so small and loosely designed that they were largely inconclusive, experts say. In some studies testing antipsychotic drugs, the group defined improvement as a decline of 30 percent or more on a scale called the Young Mania Rating Scale - well below the 50 percent change that most researchers now use as the standard.
Controlling for bias is especially important in such work, given that the scale is subjective, and raters often depend on reports from parents and children, several top psychiatrists said.
More broadly, they said, revelations of undisclosed payments from drug makers to leading researchers are especially damaging for psychiatry.
"The price we pay for these kinds of revelations is credibility, and we just can't afford to lose any more of that in this field," said Dr. E. Fuller Torrey, executive director of the Stanley Medical Research Institute, which finances psychiatric studies. "In the area of child psychiatry in particular, we know much less than we should, and we desperately need research that is not influenced by industry money."
To learn more about the marketing deceptions used by the pharmaceutical companies and how the evidence has been and is being purposely misconstrued, see this discussion that begins with excerpts from the already classic video of Tom Cruise on the Today Show.
October 4, 2008
Top Psychiatrist Didn’t Report Drug Makers’ Pay
By GARDINER HARRIS
One of the nation’s most influential psychiatrists earned more than $2.8 million in consulting arrangements with drug makers from 2000 to 2007, failed to report at least $1.2 million of that income to his university and violated federal research rules, according to documents provided to Congressional investigators.
The psychiatrist, Dr. Charles B. Nemeroff of Emory University, is the most prominent figure to date in a series of disclosures that is shaking the world of academic medicine and seems likely to force broad changes in the relationships between doctors and drug makers.
In one telling example, Dr. Nemeroff signed a letter dated July 15, 2004, promising Emory administrators that he would earn less than $10,000 a year from GlaxoSmithKline to comply with federal rules. But on that day, he was at the Four Seasons Resort in Jackson Hole, Wyo., earning $3,000 of what would become $170,000 in income that year from that company 17 times the figure he had agreed on.
The Congressional inquiry, led by Senator Charles E. Grassley, Republican of Iowa, is systematically asking some of the nation’s leading researchers to provide their conflict-of-interest disclosures, and Mr. Grassley is comparing those documents with records of actual payments from drug companies. The records often conflict, sometimes starkly.
“After questioning about 20 doctors and research institutions, it looks like problems with transparency are everywhere,” Mr. Grassley said. “The current system for tracking financial relationships isn’t working.”
The findings suggest that universities are all but incapable of policing their faculty’s conflicts of interest. Almost every major medical school and medical society is now reassessing its relationships with drug and device makers.
“Everyone is concerned,” said Dr. James H. Scully Jr., the president-elect of the Council of Medical Specialty Societies, whose 30 members represent more than 500,000 doctors.
Dr. Nemeroff is a charismatic speaker and a widely admired scientist who has written more than 850 research reports and reviews. He was editor in chief of the influential journal Neuropsychopharmacology. His research has focused on the long-term mental health risks associated with child abuse as well as the relationship between depression and cardiovascular disease.
Dr. Nemeroff did not respond to calls and e-mail messages seeking comment. Jeffrey L. Molter, an Emory spokesman, wrote in an e-mail statement that the university was “working diligently to determine whether our policies have been observed consistently with regard to the matters cited by Senator Grassley.”
The statement continued: “Dr. Nemeroff has assured us that: ‘To the best of my knowledge, I have followed the appropriate university regulations concerning financial disclosures.’ ” On Friday night, Emory announced that Dr. Nemeroff would “voluntarily step down as chairman of the department, effective immediately, pending resolution of these issues.”
Mr. Grassley began his investigation in the spring by questioning Dr. Melissa P. DelBello of the University of Cincinnati after The New York Times reported her connections to drug makers. Dr. DelBello told university officials that she earned about $100,000 from 2005 to 2007 from eight drug makers, but AstraZeneca alone paid her $238,000 during the period, Mr. Grassley found.
Then in early June, the senator reported to Congress that Dr. Joseph Biederman, a renowned child psychiatrist at Harvard Medical School, and a colleague, Dr. Timothy E. Wilens, had reported to university officials earning several hundred thousand dollars each in consulting fees from drug makers from 2000 to 2007, when in fact they had earned at least $1.6 million each.
Then the senator focused on Dr. Alan F. Schatzberg of Stanford, president-elect of the American Psychiatric Association, whose $4.8 million in stock holdings in a drug development company raised concerns.
Mr. Grassley has sponsored legislation called the Physician Payment Sunshine Act, which would require drug and device companies to publicly list payments to doctors that exceed $500. Several states already require such disclosures.
As revelations from Mr. Grassley’s investigation have dribbled out, trade organizations for the pharmaceutical industry and medical colleges have agreed to support the bill. Eli Lilly and Merck have announced that they would list doctor payments next year even without legislation.
The National Institutes of Health have strict rules regarding conflicts of interest among grantees, but the institutes rely on universities for oversight. If a university fails, the agency has the power to suspend its entire portfolio of grants, which for Emory amounted to $190 million in 2005, although the agency rarely takes such drastic measures.
Dr. Nemeroff was the principal investigator for a five-year $3.9 million grant financed by the National Institute of Mental Health for which GlaxoSmithKline provided drugs.
Income of $10,000 or more from the company in any year of the grant a threshold Dr. Nemeroff crossed in 2003, 2004, 2005 and 2006, records show would have required Emory to inform the institutes and take steps to deal with the conflict or to remove Dr. Nemeroff as the investigator.
Repeatedly assured by Dr. Nemeroff that he had not exceeded the limit, Emory did nothing.
“Results from N.I.H.-funded research must not be biased by any conflicting financial interests,” John Burklow, a spokesman for the health institutes, said in the kind of tough statement that in the past has rarely been followed by real sanctions. “Officials at Emory are investigating the concerns.”
“Failure to follow N.I.H. standards” on conflict of interest, Mr. Burklow continued, “is very serious, and N.I.H. will take all appropriate action to ensure compliance.”
In 2004, Emory investigated Dr. Nemeroff’s outside consulting arrangements. In a 14-page report, Emory’s conflict of interest committee detailed multiple “serious” and “significant” violations of university procedures intended to protect patients.
But the university apparently took little action against Dr. Nemeroff and made no effort to independently audit his consulting income, documents show.
Universities, too, can benefit from the fame and money the deals can bring a point Dr. Nemeroff made in a May 2000 letter stamped “confidential” that he sent to the dean of Emory’s medical school. The letter, which was part of a record from a Congressional hearing, addressed Dr. Nemeroff’s membership on a dozen corporate advisory boards (some of the companies’ names have since changed).
“Surely you remember that Smith-Kline Beecham Pharmaceuticals donated an endowed chair to the department and that there is some reasonable likelihood that Janssen Pharmaceuticals will do so as well,” he wrote.
“In addition, Wyeth-Ayerst Pharmaceuticals has funded a Research Career Development Award program in the department, and I have asked both AstraZeneca Pharmaceuticals and Bristol-Meyers [sic] Squibb to do the same. Part of the rationale for their funding our faculty in such a manner would be my service on these boards.”
Universities once looked askance at professors who consulted for more than one or two drug companies, but that changed after a 1980 law gave the universities ownership of patents discovered with federal money.
The law helped give birth to the biotechnology industry and led to the discovery of dozens of life-saving medicines. Consulting arrangements soon proliferated at medical schools, and Dr. Nemeroff who at one point consulted for 21 drug and device companies simultaneously became a national model.
He may now become a model for a broad reassessment of industry relationships. Many medical schools, societies and groups are considering barring doctors from giving lectures on drug or device marketing.
For all his fame in the world of psychiatry, Dr. Nemeroff has faced ethics troubles before. In 2006, he blamed a clerical mix-up for his failing to disclose that he and his co-authors had financial ties to Cyberonics, the maker of a controversial device that they reviewed favorably in a journal he edited.
The Cyberonics paper led to a bitter e-mail exchange between Dr. Nemeroff and Claudia R. Adkison, an associate dean at Emory, according to Congressional records. Dr. Adkison noted that Cyberonics had not only paid Dr. Nemeroff and his co-authors but had also given an unrestricted educational grant to Dr. Nemeroff’s department.
“I can’t believe that anyone in the public or in academia would believe anything except that this paper was a piece of paid marketing,” Dr. Adkison wrote on July 20, 2006.
Two years earlier, unknown to the public, Emory’s conflict of interest committee discovered that Dr. Nemeroff had made more serious blunders, including failing to disclose conflicts of interest in trials of drugs from Merck, Eli Lilly and Johnson & Johnson.
His continuing oversight of a federally financed trial using GlaxoSmithKline medicines led Dr. Adkison to write Dr. Nemeroff on July 15, 2004, that “you must clearly certify on your annual disclosure form that you do not receive more than $10,000 from GSK.”
In a reply dated Aug. 4, Dr. Nemeroff wrote that he had already done so but promised again that “my consulting fees from GSK will be less than $10,000 per year throughout the period of this N.I.H. grant.”
When he sent that letter, Dr. Nemeroff had already earned more than $98,000 that year from GlaxoSmithKline. Three weeks later, he received another $3,844.56 for giving a marketing talk at the Passion Fish Restaurant in Woodbury, N.Y.
From 2000 through 2006, Dr. Nemeroff earned more than $960,000 from GlaxoSmithKline but listed earnings of less than $35,000 for the period on his university disclosure forms, according to Congressional documents.
Sarah Alspach, a GlaxoSmithKline spokeswoman, said via e-mail that “Dr. Nemeroff is a recognized world leader in the field of psychiatry,” and that the company requires its paid speakers to “proactively disclose their financial relationship with GSK, and we believe that healthcare professionals are responsible for making those disclosures.”
November 25, 2008
Research Center Tied to Drug Company
By GARDINER HARRIS
When a Congressional investigation revealed in June that Dr. Joseph Biederman, a world-renowned child psychiatrist, had earned far more money from drug makers than he had reported to his university, he said that his interests were “solely in the advancement of medical treatment through rigorous and objective study.”
But e-mail messages and internal documents from Johnson & Johnson made public in a court filing reveal that Dr. Biederman pushed the company to finance a research center at Massachusetts General Hospital, in Boston, with a goal to “move forward the commercial goals of J.& J.” The documents also show that the company prepared a draft summary of a study that Dr. Biederman, of Harvard, was said to have written.
Dr. Biederman’s work helped to fuel a fortyfold increase from 1994 to 2003 in the diagnosis of pediatric bipolar disorder and a rapid rise in the use of powerful, risky and expensive antipsychotic medicines in children.
Although many of his studies are small and often financed by drug makers, Dr. Biederman has had a vast influence on the field largely because of his position at one of the most prestigious medical institutions.
Massachusetts General said in a statement Monday that it took the accusations related to the research center “very seriously” and intended “to investigate these issues thoroughly.”
Johnson & Johnson makes a popular antipsychotic medicine called Risperdal, or risperidone. More than a quarter of its use is in children and adolescents.
Last week, a panel of federal drug experts said that medicines like Risperdal were being used too cavalierly in children and that regulators must do more to warn doctors of their substantial risks. Other popular antipsychotic medicines, also referred to as neuroleptics, are Zyprexa, made by Eli Lilly; Seroquel, made by AstraZeneca; Geodon, made by Pfizer; and Abilify, made by Bristol-Myers Squibb.
Thousands of parents have sued AstraZeneca, Eli Lilly and Johnson & Johnson, claiming that their children were injured after taking the medicines; they also claim that the companies minimized the risks of the drugs.
As part of the lawsuits, plaintiffs’ lawyers have demanded millions of documents from the companies. Nearly all have been provided under judicial seals, but a select few that mentioned Dr. Biederman became public after plaintiffs’ lawyers sought a judge’s order to require Dr. Biederman to be interviewed by them under oath.
In a motion filed two weeks ago, lawyers for the families argued that they should be allowed to interview Dr. Biederman under oath because his work had been crucial to the widespread acceptance of pediatric uses of antipsychotic medicines. To support this contention, the lawyers included more than two dozen documents, among them e-mail messages from Johnson & Johnson that mentioned Dr. Biederman. A judge has yet to rule on the request.
The documents offer an unusual glimpse into the delicate relationship that drug makers have with influential doctors.
In a November 1999 e-mail message, John Bruins, a Johnson & Johnson marketing executive, begs his supervisors to approve a $3,000 check to Dr. Biederman as payment for a lecture he gave at the University of Connecticut.
“Dr. Biederman is not someone to jerk around,” Mr. Bruins wrote. “He is a very proud national figure in child psych and has a very short fuse.”
Mr. Bruins wrote that Dr. Biederman was furious after Johnson & Johnson rejected a request that Dr. Biederman had made for a $280,000 research grant. “I have never seen someone so angry,” Mr. Bruins wrote. “Since that time, our business became non-existant (sic) within his area of control.”
Mr. Bruins concluded that unless Dr. Biederman received a check soon, “I am truly afraid of the consequences.”
A series of documents described the goals behind establishing the Johnson & Johnson Center for the study of pediatric psychopathology, where Dr. Biederman serves as chief.
A 2002 annual report for the center said its research must satisfy three criteria: improve psychiatric care for children, have high standards and “move forward the commercial goals of J.& J.,” court documents said.
“We strongly believe,” the report stated, “that the center’s systematic scientific inquiry will enhance the clinical and research foundation of child psychiatry and lead to the safer, more appropriate and more widespread use of medications in children.
“Without such data, many clinicians question the wisdom of aggressively treating children with medications, especially those like neuroleptics, which expose children to potentially serious adverse events.”
A February 2002 e-mail message from Georges Gharabawi, a Johnson & Johnson executive, said Dr. Biederman approached the company “multiple times to propose the creation” of the center. “The rationale of this center,” the message stated, “is to generate and disseminate data supporting the use of risperidone in” children and adolescents.
Documents show that Johnson & Johnson gave the center $700,000 in 2002 alone. Massachusetts General said in its statement on Monday that grant agreements indicated the center “was for scientific and educational purposes only and not for purposes of promoting, directly or indirectly, the products of Johnson & Johnson and its affiliates.”
A statement Monday from Janssen Pharmaceutica, a unit of Johnson & Johnson, said it helped finance the research center in 2002 “with an objective to conduct rigorous clinical trials to clarify appropriate use and dosing of Risperdal in children.”
A June 2002 e-mail message to Dr. Biederman from Dr. Gahan Pandina, a Johnson & Johnson executive, included a brief abstract of a study of Risperdal in children with disruptive behavior disorder. The message said the study was intended to be presented at the 2002 annual meeting of the American Academy of Child and Adolescent Psychiatry.
“We have generated a review abstract,” Dr. Pandina wrote, “but I must review this longer abstract before passing this along.”
One problem with the study, Dr. Pandina wrote, is that the children given placebos and those given Risperdal both improved significantly. “So, if you could,” Dr. Pandina added, “please give some thought to how to handle this issue if it occurs.”
The draft abstract that Dr. Pandina put in the e-mail message, however, stated that only the children given Risperdal improved, while those given placebos did not. Dr. Pandina asked Dr. Biederman to sign a form listing himself as the author so the company could present the study to the conference, according to the message.
“I will review this morning,” responded Dr. Biederman, according to the documents. “I will be happy to sign the forms if you could kindly send them to me.” The documents do not make clear whether he approved the final summary of the brief abstract in similar form or asked to read the longer report on the study.
Drug makers have long hired professional writers to compose scientific papers and then recruited well-known doctors to list themselves as the author. The practice, known as ghostwriting, has come under intense criticism recently, and medical societies, schools and journals have condemned it.
In June, a Congressional investigation revealed that Dr. Biederman had failed to report to Harvard at least $1.4 million in outside income from Johnson & Johnson and other makers of antipsychotic medicines.
In one example, Dr. Biederman reported no income from Johnson & Johnson for 2001 in a disclosure report filed with the university. When asked by Senator Charles E. Grassley, an Iowa Republican who is leading the Congressional inquiry, to check again, Dr. Biederman said he had received $3,500. But Johnson & Johnson told Mr. Grassley that it paid $58,169 to Dr. Biederman in 2001.
A Harvard spokesman, David J. Cameron, said Monday that the university was still reviewing Mr. Grassley’s accusations against Dr. Biederman. Mr. Cameron added that the university had not seen the drug company documents in question and that it was not directly involved in the child psychiatry center at Massachusetts General.
Calls to Dr. Biederman were not returned.
October 2, 2010
Side Effects May Include Lawsuits
By DUFF WILSON
FOR decades, antipsychotic drugs were a niche product. Today, they’re the top-selling class of pharmaceuticals in America, generating annual revenue of about $14.6 billion and surpassing sales of even blockbusters like heart-protective statins.
While the effectiveness of antipsychotic drugs in some patients remains a matter of great debate, how these drugs became so ubiquitous and profitable is not. Big Pharma got behind them in the 1990s, when they were still seen as treatments for the most serious mental illnesses, like hallucinatory schizophrenia, and recast them for much broader uses, according to previously confidential industry documents that have been produced in a variety of court cases.
Anointed with names like Abilify and Geodon, the drugs were given to a broad swath of patients, from preschoolers to octogenarians. Today, more than a half-million youths take antipsychotic drugs, and fully one-quarter of nursing-home residents have used them. Yet recent government warnings say the drugs may be fatal to some older patients and have unknown effects on children.
The new generation of antipsychotics has also become the single biggest target of the False Claims Act, a federal law once largely aimed at fraud among military contractors. Every major company selling the drugs — Bristol-Myers Squibb, Eli Lilly, Pfizer, AstraZeneca and Johnson & Johnson — has either settled recent government cases for hundreds of millions of dollars or is currently under investigation for possible health care fraud.
Two of the settlements, involving charges of illegal marketing, set records last year for the largest criminal fines ever imposed on corporations. One involved Eli Lilly’s antipsychotic, Zyprexa; the other involved a guilty plea for Pfizer’s marketing of a pain pill, Bextra. In the Bextra case, the government also charged Pfizer with illegally marketing another antipsychotic, Geodon; Pfizer settled that part of the claim for $301 million, without admitting any wrongdoing.
The companies all say their antipsychotics are safe and effective in treating the conditions for which the Food and Drug Administration has approved them — mostly, schizophrenia and bipolar mania — and say they adhere to tight ethical guidelines in sales practices. The drug makers also say that there is a large population of patients who still haven’t taken the drugs but could benefit from them.
AstraZeneca, which markets Seroquel, the top-selling antipsychotic since 2005, says it developed such drugs because they have fewer side effects than older versions.
“It’s a drug that’s been studied in multiple clinical trials in various indications,” says Dr. Howard Hutchinson, AstraZeneca’s chief medical officer. “Getting these patients to be functioning members of society has a tremendous benefit in terms of their overall well-being and how they look at themselves, and to get that benefit, the patients are willing to accept some level of side effects.”
The industry continues to market antipsychotics aggressively, leading analysts to question how drugs approved by the Food and Drug Administration for about 1 percent of the population have become the pharmaceutical industry’s biggest sellers — despite recent crackdowns.
Some say the answer to that question isn’t complicated.
“It’s the money,” says Dr. Jerome L. Avorn, a Harvard medical professor and researcher. “When you’re selling $1 billion a year or more of a drug, it’s very tempting for a company to just ignore the traffic ticket and keep speeding.”
NEUROLEPTIC drugs — now known as antipsychotics — were first developed in the 1950s for use in anesthesia and then as powerful sedatives for patients with schizophrenia and other severe psychotic disorders, who previously might have received surgical lobotomies.
But patients often stopped taking those drugs, like Thorazine and Haldol, because they could cause a range of involuntary body movements, tics and restlessness.
A second generation of drugs, called atypical antipsychotics, was introduced in the ’90s and sold to doctors more broadly, on the basis that they were safer than the old ones — an assertion that regulators and researchers are continuing to review because the newer drugs appear to cause a range of other side effects, even if they cause fewer tics.
Contentions that the new drugs are superior have been “greatly exaggerated,” says Dr. Jeffrey A. Lieberman, chairman of the psychiatry department at Columbia University. Such assertions, he says, “may have been encouraged by an overly expectant community of clinicians and patients eager to believe in the power of new medications.”
“At the same time,” he adds, “the aggressive marketing of these drugs may have contributed to this enhanced perception of their effectiveness in the absence of empirical evidence.”
Others agree. “They sold the story they’re more safe, when they aren’t,” says Robert Whitaker, a journalist who has written two books about psychiatric medicines. “They had to cover up the problems. Right from the start, we got this false story.”
The drug companies say all the possible side effects are fully disclosed to the F.D.A., doctors and patients. Side effects like drowsiness, nausea, weight gain, involuntary body movements and links to diabetes are listed on the label. The companies say they have a generally safe record in treating a difficult disease and are fighting lawsuits in which some patients claim harm.
The cases, both civil and criminal, against many of the world’s largest drug makers have unveiled hundreds of previously confidential documents showing that some company officials were aware they were using questionable tactics when they marketed these powerful, expensive drugs.
Such marketing, according to analysts and court documents, included payments, gifts, meals and trips for doctors, biased studies, ghostwritten medical journal articles, promotional conference appearances, and payments for postgraduate medical education that encourages a pro-drug outlook among doctors. All of these are tools that federal investigators say companies have used to exaggerate benefits, play down risks and promote off-label uses, meaning those the F.D.A. hasn’t approved.
Lawyers suing AstraZeneca say documents they have unearthed show that the company tried to hide the risks of diabetes and weight gain associated with the new drugs. Positive studies were hyped, the documents show; negative ones were filed away.
According to company e-mails unsealed in civil lawsuits, AstraZeneca “buried” — a manager’s term — a 1997 study showing that users of Seroquel, then a new antipsychotic, gained 11 pounds a year, while the company publicized a study that asserted they lost weight. Company e-mail messages also refer to doing a “great smoke-and-mirrors job” on an unfavorable study.
“The larger issue is how do we face the outside world when they begin to criticize us for suppressing data,” John Tumas, then AstraZeneca’s publications manager, wrote in a 1999 e-mail. “We must find a way to diminish the negative findings,” he added. “But, in my opinion, we cannot hide them.”
Tony Jewell, an AstraZeneca spokesman, said last week that the company had turned over all that material to the F.D.A. as part of the approval process and updated its label over the years to show the latest safety information.
Dr. Stefan P. Kruszewski, a Harvard-educated psychiatrist who once worked as a paid speaker for several drug makers, became a government informant and now consults for plaintiffs suing drug companies. Earlier in his career, he spoke at events for Pfizer, GlaxoSmithKline and Johnson & Johnson as an advocate of antipsychotics. He said one company offered him incentives of $1,000 or more every time he talked to an individual doctor about one of its drugs.
“When I started speaking for companies in the late 1980s and early ’90s, I was allowed to say what I thought I should say consistent with the science,” he recalls. “Then it got to the point where I was no longer allowed to do that. I was given slides and told, ‘We’ll give you a thousand dollars if you say this for a half-hour.’ And I said: ‘I can’t say that. It isn’t true.’ ”
Slides for one new antipsychotic drug contended that it had no neurological side effects. “They made it all up,” Dr. Kruszewski said. “It was never true.”
The antipsychotics found an easy route around regulations because of the leeway given to many big drug makers.
While drug companies are prohibited from promoting drugs for conditions for which they have not been proved safe and effective, their paid consultants, researchers and educators may do that for them verbally and in company-sponsored studies.
“They can give a small hint, and people will take the bait,” says Dr. Robert Rosenheck, a professor of psychiatry and public health at the Yale School of Medicine, who has received research support from drug makers and federal agencies. “Psychiatric disorders are vaguely defined enough that you can stretch definitions,” he says. “So many treatments are completely ineffective, people are willing to try anything.”
For their part, doctors are free to prescribe any approved drug for any medical condition they choose, even if the drug hasn’t been approved for that specific treatment. “Because they’re approved, they become an alternative for doctors who can’t think of what else to prescribe,” says Dr. Daniel J. Carlat, an associate professor of psychiatry at Tufts University. “Whether they’re useful or not is unclear.”
Analysts said that given the profits that were to be made, the murkiness of mental disorders, and holes in the regulatory regime, marketing excesses were bound to occur.
“If you have a lot of money on the table and you have clinical uncertainty over mental health conditions, where you don’t have a blood test or objective test for it, you see it’s kind of a combustible mixture,” says Dr. Mark Olfson, a Columbia University psychiatry professor and researcher.
DOCUMENTS produced in recent litigation and in Congressional investigations show that some leading academic doctors have worked closely with corporate benefactors to expand the use of antipsychotics.
The most well-known is Joseph Biederman, a Harvard medical professor and Massachusetts General Hospital researcher. His studies, examining prevalence of bipolar psychological disorders in children, helped expand practice standards, leading to a fortyfold increase in such diagnoses from 1994 to 2003. The increase was reported in a 2007 study by the Archives of General Psychiatry.
Between 2000 and 2007, he also got $1.6 million in speaking and consulting fees — some of them undisclosed to Harvard — from companies including makers of antipsychotic drugs prescribed for some children who might have bipolar disorder, a Senate investigation found in 2008.
Johnson & Johnson gave more than $700,000 to a research center that was headed by Dr. Biederman from 2002 to 2005, records show, and some of its work supported the company’s antipsychotic drug, Risperdal.
Dr. Biederman says that the money did not influence him and that some of his work supported other drugs.
“Dr. Biederman’s research does not promote a particular diagnosis or treatment,” his lawyer, Peter Spivack, wrote in an e-mail on Thursday.
The increase in pediatric bipolar diagnosis, the lawyer said, “cannot be attributed solely to Dr. Biederman’s work.” Treatment was expanded to help children and their families, he said.
Mr. Spivack said Dr. Biederman’s disclosure lapses were minor and inadvertent. A Harvard spokesman said they were still under review.
According to government investigators and plaintiffs’ lawyers, many of the studies of antipsychotics were conceived in marketing departments of pharmaceutical companies, written by ghostwriters and then signed by prominent physicians — giving the illusion that the doctors were undertaking their studies independently.
Such practices continue.
“The content is preplanned,” said one doctor who has worked as an uncredited medical writer for antipsychotic studies. Data is used selectively and interpreted for company benefit, said the doctor, who still works in medical writing and spoke on the condition of anonymity to preserve future job prospects.
“Review articles and original research articles have advertising messages in them,” the doctor said. “That’s part of the plan.”
Such papers influence medicine in many ways, as sales representatives show them to doctors and future research builds upon them.
ACCORDING to the Justice Department, drug companies trained sales reps to rebut valid medical concerns about unproved uses of antipsychotics. For example, the department says, Lilly produced a video called “The Myth of Diabetes” to sell Zyprexa, which became its all-time best-selling drug, even though evidence showed that Zyprexa could cause diabetes, as well as other metabolic problems.
Lilly salespeople also promoted a “5 at 5” drug regimen in nursing homes — 5 milligrams of Zyprexa at 5 p.m. to settle down agitated older patients for the night. A Lilly spokesman declined to say when those sales campaigns occurred. But in 2005, after a new analysis of 15 previous studies, the F.D.A. issued a public health advisory saying the use of antipsychotics to calm older dementia patients would increase risk of death from heart failure or pneumonia. The F.D.A. asked drug makers to add a special warning about that on packaging.
Over the years, as psychiatrists learned more about the drugs’ risks, companies promoted them more to family doctors, pediatricians and geriatricians. Pfizer paid more than 250 child psychiatrists to promote its antipsychotic, Geodon, at a time when it was approved only for adults, according to a government filing with the Pfizer settlement last year.
High-prescribing doctors pocketed extra money in the form of research payments, speaking fees, gifts, meals and junkets — some of which the government has specifically termed illegal “kickbacks.”
In its suit against AstraZeneca, the government produced documents showing that the company paid a Chicago psychiatrist, Dr. Michael Reinstein, nearly $500,000 over a decade to do research, travel and speak for it — even as he led a Medicaid practice he had described to the company as one of “the largest prescribers of Seroquel in the world.”
Dr. Reinstein and AstraZeneca have both denied any misconduct.
In April, AstraZeneca became the fourth major drug company in three years to settle a government investigation with a hefty payment — in its case, $520 million for what federal officials described as an array of illegal promotions of antipsychotics for children, the elderly, veterans and prisoners. Still, the payment amounted to just 2.4 percent of the $21.6 billion AstraZeneca made on Seroquel sales from 1997 to 2009.
LAST year, Eli Lilly and Pfizer settled investigations resulting in the largest criminal fines in United States history. Lilly paid a $515 million criminal fine as part of a broader, $1.4 billion settlement with the government. Pfizer later paid a $1.3 billion criminal fine as part of a broader, $2.3 billion settlement.
The Lilly case focused entirely on its antipsychotic drug Zyprexa, while Pfizer’s settlement included $301 million related to its antipsychotic, Geodon, along with marketing of other drugs.
In 2007, Bristol-Myers Squibb paid $515 million to settle federal and state investigations into marketing of its antipsychotic drug Abilify to child psychiatrists and nursing homes. Bristol-Myers Squibb, like AstraZeneca, denied any misconduct.
Johnson & Johnson is currently under investigation by the Justice Department, which says it paid kickbacks to induce Omnicare, the nation’s largest nursing home pharmacy, to recommend Risperdal, government filings show. Omnicare paid $98 million last November to settle civil charges.
J.& J. is fighting a government lawsuit and says in court filings that it was paying rebates — an argument endorsed in a filing by the industry trade group, the Pharmaceutical Research and Manufacturers of America.
Some officials at companies say they’ve made systemic changes to avoid illegal marketing of antipsychotics and other products.
“That was a blemish for us,” John C. Lechleiter, Eli Lilly’s chief executive, said in an interview. “We don’t ever want that to happen again. We put measures in place to assure that not only do we have the right intentions in integrity and compliance, but we have systems in place to support that.”
Jeffrey B. Kindler, Pfizer’s chief executive, voiced similar thoughts in an interview. “Never again,” he said. “I take this very seriously.”
Mr. Kindler is operating under Pfizer’s third corporate accountability agreement, a five-year promise to the federal government to reform sales behavior, monitor employees and disclose misconduct. The first was signed in 2002 for withholding rebates for Lipitor. The second, in 2004, was for illegal marketing of the seizure drug Neurontin. The third, last year, was for illegal marketing of the painkiller Bextra.
Pfizer officials say they inherited the first two situations with their acquisitions of two other companies, Warner-Lambert and Parke-Davis.
“It wasn’t our people,” says Douglas Lankler, a senior vice president and chief compliance officer at Pfizer.
Lew Morris, chief counsel for the inspector general of the Department of Health and Human Services, says he is serious about bolstering government efforts to reform or punish drug makers for illegal sales of antipsychotics.
“The message we want to send to the industry is it’s not just the same-old, same-old,” he said in an interview.
He agrees that few industry employees have gone to jail for white-collar crimes, but says this may change soon. “We’re targeting managers and executives who should have known,” he said.
Mr. Morris says some companies are “too big to debar” from government contracts, since doing so would just hurt patients needing medicine. But he says discussions are under way about forcing one health care company to sell off a subsidiary accused of fraud. And directors who ignore information may face more risk of shareholder suits, he says.
Over the next year, the government is adding at least 15 prosecutors and 100 investigators to pursue health care fraud.
The Pharmaceutical Research and Manufacturers of America, also strengthened its marketing code of conduct two years ago, banning gifts and meals, although salespeople can still bring meals to doctors’ offices.
Some companies are also disclosing their consulting and speaking payments, as required by the government agreements. And groups in charge of medical writing and postgraduate education have taken steps to disclose or reduce industry influence.
But more than 1,000 False Claims Act lawsuits are still under way, most of them focused on health care and many on lucrative antipsychotic drugs. For that reason alone, critics say they think the industry still hasn’t gone far enough to change questionable practices.
“The drug industry still rewards sales,” says Stephen A. Sheller, a lawyer who has represented whistle-blowers in the Lilly and AstraZeneca cases. “And it’s still easy to market these drugs to doctors who are rushed.”