Public Servant or Private Marketer? NIH Seeks Inquiry of Alzheimer’s researcher conflicts of interest

NIH: Public Servant or Private Marketer? NIH Seeks Outside Inquiry of Alzheimer’s researcher conflicts of interest – LAT

Mon, 31 Jan 2005

A year after the Los Angeles Times published its first an in-depth investigative report documenting in detail evidence of major conflicts of interest by top scientists at the National Institutes of Health, [December 7, 2003] a follow-up investigtion [Excerpt below]– found that NIH scientists continue to violate regulatory ethical standards with impunity. [Excerpt of 12/ 2003 article at: http://www.ahrp.org/infomail/03/12/07.php ]

NIH receives $28 billion in taxpayer funding but is shown to have issued tainted medical guidelines and recommendations to physicians and the public. For example, 8 out of 9 NIH scientists who wrote the cholesterol-lowering guidelines recommending drugs such as Crestor had financial interests in the companies manufacturing these drugs.

The LAT reported that Dr. H. Bryan Brewer Jr., chief of the National Heart, Lung, and Blood Institute’s molecular disease branch, whose NIH salary is $187,305, supplemented it with $114,000 in consulting fees from four companies that make cholesterol lowering drugs, including $31,000 from the maker of Crestor.

“When Brewer praised Crestor in a medical journal in 2003, the article identified him as an NIH scientist, not as a paid consultant to the manufacturer. In marketing Crestor to doctors, the company cited Brewer’s findings without mentioning that he was on its payroll.” Furthermore, “Brewer also concluded that Crestor’s “benefit-risk profile … appears to be very favorable,” and that proved to be questionable.”

Furthermore, the LAT reports: “Brewer assured doctors there was no basis for worry about a muscle-wasting side effect called rhabdomyolysis, which can cause kidney failure and death. (Another anticholesterol drug, Baycol, was removed from the market in 2001 after at least 31 deaths related to rhabdomyolysis were reported.) Brewer wrote: “No cases of rhabdomyolysis occurred in patients receiving [Crestor] at 10 to 40″ milligrams.”

Another example is Dr. Trey Sunderland III, an Alzheimer’s disease researcher at the National Institute of Mental Health, accepted $508,050 from Pfizer without seeking permission or reporting the income to NIH as required. The LAT found that: “Sunderland’s NIH staff had begun providing Pfizer with samples of the spinal fluids in 1998 under terms of a material transfer agreement. “Sunderland’s paid services for Pfizer Inc. often overlapped with his government role. For instance, at the same time that Sunderland accepted consulting and speaking fees from Pfizer, he led a study of Alzheimer’s patients in which the company collaborated.” “On more than 80 occasions from 1999 to June 2004, Sunderland was paid by Pfizer for speaking appearances at conferences in the U.S. and overseas, documents show.”

“Sunderland also was a paid consultant to Eisai in recent years, according to information recently provided to the NIH by his attorney. The two companies jointly market a drug called Aricept, which is approved for treating the symptoms of mild to moderate Alzheimer’s. The once-a-day pill generated worldwide sales of $1.6 billion in 2003, making it the top-selling Alzheimer’s drug.”

“Sunderland endorsed the use of Aricept during a televised presentation at the NIH in September 2003. Viewers of the event, broadcast by C-SPAN, had no way of knowing about Sunderland’s affiliation with Pfizer or with Eisai.”

“Investigators are now examining whether Sunderland used vacation hours for all of his private appearances or whether he spoke for Pfizer while on government time, according to officials familiar with the inspector general’s probe.”

On January 28, 2005, the LAT reported that NIH ethics specialists have requested an outside investigation by the inspector general who has subpoena powers which internal agency investigators do not. Sunderland’s lawyer defended his client stating that throughout the NIH the monitoring of financial relationships between the government scientists and their outside employers has been characterized by “indifference, lack of enforcement and administrative shortcomings.”

Indeed, NIH administrators continue to turn a blind eye on its scientists’ “unabashed mingling of science and commerce” – invalidating numerous promises and pronouncements to Congress by Dr. Elias Zerhouni, the director of NIH.

A demonstration of NIH’s culture of entitlement is a letter signed by nearly 200 NIH researchers who protested to Zerhouni, claiming that a permanent ban would make the scientific staff – who are paid between $130,000 and $200,000 a year by the government – “second-class citizens in the biomedical community.” Such displays of greed and entitlement led Senator Pete Domenici to refer in disgust to NIH scientists as “pigs.” [http://www.ahrp.org/infomail/04/03/18.php ]

Contact: Vera Hassner Sharav
212-595-8974

http://www.latimes.com/news/nationworld/nation/la-na-nih28jan28,1,3197774.story?coll=la-headlines-nation

THE LOS ANGELES TIMES
NIH Seeks Outside Inquiry of Scientist

Agency ethics officials target an Alzheimer’s researcher who accepted more than $500,000 from a drug company and did not report it.

By David Willman
January 28, 2005

WASHINGTON – Ethics specialists at the National Institutes of Health have requested an outside investigation of an Alzheimer’s disease researcher who accepted more than $500,000 from a drug company without seeking permission or reporting the income to the agency as required, according to government officials familiar with the matter.

In response, the investigations unit of the inspector general’s office at the Department of Health and Human Services has opened an inquiry into the researcher, Dr. P. Trey Sunderland III, the officials said. Among the circumstances being investigated is whether Sunderland’s conduct violated federal conflict-of-interest law, they said. The inspector general’s office is empowered to subpoena documents and to question witnesses. It also may refer a matter for criminal prosecution to a local U.S. attorney’s office or to the Justice Department.

Based on interviews and public records, the Los Angeles Times reported last month that Sunderland’s paid services for Pfizer Inc. often overlapped with his government role. For instance, at the same time that Sunderland accepted consulting and speaking fees from Pfizer, he led a study of Alzheimer’s patients in which the company collaborated. In the spring of 1998, Sunderland’s NIH staff began providing the company with samples of spinal fluid that the government employees collected from elderly patients who had visited the agency’s research hospital in Bethesda, Md. The research collaboration with Pfizer spanned about five years. Sunderland, 53, has focused at the NIH on finding ways to detect Alzheimer’s disease before a patient develops pronounced symptoms. And Pfizer, along with a corporate partner, Eisai Inc., stands to gain billions of dollars in sales from the early-stage treatment of Alzheimer’s.

The Times article last month reported that Sunderland also was a paid consultant to Eisai in recent years, according to information recently provided to the NIH by his attorney. The two companies jointly market a drug called Aricept, which is approved for treating the symptoms of mild to moderate Alzheimer’s. The once-a-day pill generated worldwide sales of $1.6 billion in 2003, making it the top-selling Alzheimer’s drug.Sunderland endorsed the use of Aricept during a televised presentation at the NIH in September 2003. Viewers of the event, broadcast by C-SPAN, had no way of knowing about Sunderland’s affiliation with Pfizer or with Eisai. On more than 80 occasions from 1999 to June 2004, Sunderland was paid by Pfizer for speaking appearances at conferences in the U.S. and overseas, documents show.

Investigators are now examining whether Sunderland used vacation hours for all of his private appearances or whether he spoke for Pfizer while on government time, according to officials familiar with the inspector general’s probe.Sunderland’s attorney, Robert F. Muse, declined to comment for this article. In a letter last month to the director of the NIH ethics office, Muse said Sunderland had not tried to hide his dealings with Pfizer or other companies.

“Dr. Sunderland has committed no unethical acts,” Muse wrote. “His failures have been in the context of not keeping and filing proper paperwork.” Throughout the NIH, Muse wrote, the monitoring of financial relationships between the government scientists and their outside employers has been characterized by “indifference, lack of enforcement and administrative shortcomings.”

Internal NIH e-mails show that Sunderland was aware of agency conflict-of-interest rules that could ban him from taking consulting fees from a company, like Pfizer, that maintained a formal research agreement with the NIH. In e-mail exchanges in March 1999 that had not previously been made public, an NIH ethics officer, Olga Boikess, asked Sunderland about a lecture that he had delivered at a psychiatric conference. On March 23, 1999, Sunderland replied: “I can tell you that I have no CRADAs or MTAs with any European pharmaceutical company, so there should be no possible conflict of interest.” CRADA is shorthand for “cooperative research and development agreement.” An MTA is a material transfer agreement, an arrangement to exchange proprietary material or information.

In 1998, Sunderland’s NIH staff had begun providing Pfizer with samples of the spinal fluids under terms of a material transfer agreement. Pfizer pledged to provide analyses of the samples. Starting that year, and continuing through 2003, Pfizer paid Sunderland consulting and speaking fees totaling $508,050, records reviewed by The Times show. Related documents describe how Sunderland received fees from Pfizer as recently as June 3, 2004.

The NIH over the last decade has allowed employees who seek advance approval to enter into a wide variety of paid positions with pharmaceutical and biotechnology companies. However, NIH policies have consistently forbidden its scientists from accepting income from a company that is collaborating with their government laboratory.

Ethics specialists under the director of the NIH, Dr. Elias A. Zerhouni, requested the inspector general’s investigation of Sunderland, according to the officials familiar with the matter, who spoke on condition of anonymity. A deputy NIH director assigned by Zerhouni to oversee ethics matters, Dr. Raynard S. Kington, has said that he is not at liberty to discuss the specifics of any internal review or investigation.

However, an in-house newsletter at the NIH this month, paraphrasing Kington, said agency officials were “investigating every case that has come to light of inappropriate outside activities at NIH.” The newsletter quoted Kington as saying that “fairly soon, we’ll enter the penalty phase of these investigations…. Some employees have substantially violated rules and regulations.”

It has been nearly 13 years since an NIH scientist was prosecuted and convicted for an offense related to a conflict of interest. The scientist, Prem S. Sarin, repaid $25,000 to a German pharmaceutical company involved with AIDS research. A federal judge also sentenced him to two months of community service. He had faced a maximum sentence of about 20 years in federal prison, said his lawyer, W. Neil Eggleston.

http://www.latimes.com/news/nationworld/nation/la-na-nih22dec22,0,7519657.story?coll=la-home-headlines

THE LOS ANGELES TIMES
The National Institutes of Health: Public Servant or Private Marketer?

Doctors have long relied on the NIH to set medical standards. But with its researchers accepting fees and stock from drug companies, will that change? A continuing examination by The Times shows an unabashed mingling of science and commerce.

By David Willman
December 22, 2004

EXCERPT:

For 15 million Americans, it is a daily ritual: gulping down a pill to reduce cholesterol.

They do it because their doctors tell them to. Their doctors, in turn, rely on recommendations from the National Institutes of Health and its scientists, such as Dr. H. Bryan Brewer Jr.

Brewer, as a leader at the NIH, was part of a team that gave the nation new cholesterol guidelines that were expected to prompt millions more people to take the daily pill. He also has written favorably of a specific brand of cholesterol medication, Crestor, which recently proved controversial.

What doctors were not told for years is this: While making recommendations in the name of the NIH, Brewer was working for the companies that sell the drugs. Government and company records show that from 2001 to 2003, he accepted about $114,000 in consulting fees from four companies making or developing cholesterol medications, including $31,000 from the maker of Crestor.

Brewer was far from alone in taking industry’s money: At least 530 government scientists at the NIH, the nation’s preeminent agency for medical research, have taken fees, stock or stock options from biomedical companies in the last five years, records show.

NIH Director Dr. Elias A. Zerhouni has told Congress that outside work should be allowed if “the scientist is giving advice in an area … that is not part of his official duties.”

Information gathered by a congressional committee, in addition to company records and 15,000 pages of government documents obtained by the Los Angeles Times under the Freedom of Information Act, shows that NIH researchers have repeatedly crossed Zerhouni’s line.

For example:

  • Dr. P. Trey Sunderland III, a senior psychiatric researcher, took $508,050 in fees and related income from Pfizer Inc. at the same time that he collaborated with Pfizer – in his government capacity – in studying patients with Alzheimer’s disease. Without declaring his affiliation with the company, Sunderland endorsed the use of an Alzheimer’s drug marketed by Pfizer during a nationally televised presentation at the NIH in 2003.
  • Dr. Lance A. Liotta, a laboratory director at the National Cancer Institute, was working in his official capacity with a company trying to develop an ovarian cancer test. He then took $70,000 as a consultant to the company’s rival. Development of the cancer test stalled, prompting a complaint from the company. The NIH backed Liotta.
  • Dr. Harvey G. Klein, the NIH’s top blood transfusion expert, accepted $240,200 in fees and 76,000 stock options over the last five years from companies developing blood-related products. During the same period, he wrote or spoke out about the usefulness of such products without publicly declaring his company ties.

Announcing such ties is not required by the NIH. The agency has encouraged outside consulting, and has allowed most of its scientists to file confidential income disclosure forms.

Supported by the taxpayers at a cost this year of $28 billion, the NIH oversees research with a mission to extend healthy life and to reduce “the burdens of illness and disability.” The laboratories and offices of most NIH scientists are at the agency’s woodsy, 300-acre headquarters in Bethesda, Md., nine miles north of the White House.

The scientists at the NIH – seen by many outsiders as neutral government experts – advise federal regulators and write hundreds of articles for influential medical journals. Some travel the world encouraging doctors to prescribe a particular medication.

The flow of drug industry fees and stock options to NIH scientists was disclosed in December 2003 in an article in The Times. The article also explained the bureaucratic means by which most of the payments had been kept secret from Congress, the public and the nation’s doctors.

Subsequent inquiries this year by Congress have shown that even Zerhouni, the NIH’s director, did not know the extent to which agency scientists were being paid by industry.

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Other documents obtained this year by The Times, including programs of industry meetings for physicians that featured NIH scientists as speakers, reveal dozens more relationships not reported as approved by the agency. The companies, in marketing their products, have frequently cited the NIH’s reputation for high scientific standards. The cholesterol guidelines, for example, have been widely circulated by makers of anticholesterol drugs.

Dr. Curt D. Furberg, a former head of clinical trials at the National Heart, Lung, and Blood Institute and now a professor at Wake Forest University in North Carolina, explained how such information reached physicians: “The [company] reps tell the doctors, ‘You should follow these guidelines,’ implying that you’re not a good doctor if you don’t follow these guidelines.”

Often NIH involvement is featured, while the government researchers’ links to the companies go unmentioned. When Brewer, the cholesterol researcher, praised Crestor in a medical journal in 2003, the article identified him as an NIH scientist, not as a paid consultant to the manufacturer. In marketing Crestor to doctors, the company cited Brewer’s findings without mentioning that he was on its payroll. ……cut……..

As chief of the National Heart, Lung, and Blood Institute’s molecular disease branch since 1976, Brewer is one of the nation’s leading experts on cholesterol.

With his rimmed glasses and shock of sandy hair, he has the bearing of an accomplished scientist and the credentials to match. Born in Casper, Wyo., he gained his medical degree from Stanford University and received further training at Massachusetts General Hospital. Now 66, Brewer has a manner that is both authoritative and plain-spoken.

But when Brewer wrote a medical journal article in 2003 helping to introduce Crestor, he did not inform doctors about a potentially lethal safety risk. The product was about to be launched in the United States by AstraZeneca, a British company that had put Brewer on a scientific advisory board and paid him $31,000 from 2001 through 2003, according to NIH records.

In the Aug. 21, 2003, American Journal of Cardiology, Brewer wrote that Crestor “produced markedly greater reductions” in cholesterol levels than three established competitor drugs tested in clinical trials. That was true. But Brewer also concluded that Crestor’s “benefit-risk profile … appears to be very favorable,” and that proved to be questionable.

Brewer assured doctors there was no basis for worry about a muscle-wasting side effect called rhabdomyolysis, which can cause kidney failure and death. (Another anticholesterol drug, Baycol, was removed from the market in 2001 after at least 31 deaths related to rhabdomyolysis were reported.)

Brewer wrote: “No cases of rhabdomyolysis occurred in patients receiving [Crestor] at 10 to 40” milligrams. But eight cases of rhabdomyolysis were reported during clinical trials of Crestor. One of the case reports cited a patient who took the drug in 10-milligram doses, according to records filed with the Food and Drug Administration and reviewed by The Times under the Freedom of Information Act. Sales representatives for AstraZeneca have routinely provided copies of Brewer’s journal article about Crestor to doctors nationwide, a company spokeswoman confirmed last week.

The FDA received 78 reports of rhabdomyolysis among patients taking Crestor during its first year on the market, FDA records show. Two of those patients died.

In contrast to Brewer’s opinion in August 2003, an editorial two months later in the Lancet, the prominent British medical journal, said: “Physicians must tell their patients the truth about [Crestor] – that, compared with its competitors, [Crestor] has an inferior evidence base supporting its safe use.”

In March of this year, a U.S. consumer group, Public Citizen, called for banning Crestor based upon several cases of kidney failure or muscle damage. AstraZeneca defended its drug as safe and effective in print and television ads this fall, adding that FDA management agreed. But on Nov. 18, senior FDA epidemiologist Dr. David J. Graham told a Senate committee that the safety of Crestor needed reassessment.

Brewer told Zerhouni that he had not mentioned seven of the rhabdomyolysis cases because those patients had received doses of Crestor higher than the approved level. As for the patient who took the drug at 10 milligrams, “it was not possible to definitively conclude” that Crestor had caused her rhabdomyolysis, Brewer wrote. Other medical experts said reviewers should report such a serious event regardless of possible cause.

“Baycol had already been pulled for exactly that same side effect and it was a matter of great concern,” said Angell, the former editor of the New England Journal of Medicine. “If he knew about it, he should have mentioned it.”

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