Cholesterol Guidlines & American Heart Assoc. (Conflicts of Interest)

[Guest guest]

I hope the following Associated Press article will raise questions

in your mind about the politics, conflicts of interest, and profit

driven motives that exist when cholesterol and Food Pyramid diet

guidelines are written.

Beth

Tuesday, October 19, 2004 10:16 PM PDT

CHOLESTEROL GUIDELINES BECOME a MORALITY PLAY ABOUT CONFLICT of

INTEREST in MEDICINE

By: MARILYNN MARCHIONE - Associated Press

They led influential medical groups, starred at prestigious

meetings, published in top journals and were undisputed giants in

their field.

But when these famous doctors advised the government recently on new

cholesterol guidelines for the public, something else they had in

common wasn't revealed.

Eight of the nine were making money from the very companies whose

cholesterol-lowering drugs they were urging upon millions more

Americans. Two own stock in them. Two others went to work for drug

companies shortly after working on the guidelines. Another was a

senior government scientist who moonlights for 10 companies and even

serves on one of their boards.

Consumer groups and others now are questioning not only the advice

these doctors gave but also their fundamental ability to act in the

public's best interest.

It comes as some of these companies lobby the government to let

drugs at the center of this controversy -- statins such as Lipitor

and Zocor -- be sold over-the-counter. Prominent doctors with ties

to statin makers are urging approval.

There's little doubt that statins save lives or that too few people

take them now. But critics say the doctors' coziness with drug

companies compromises their credibility and undercuts their latest

advice that more people would benefit from these medications.

Conflicts of interest are increasingly common now that two-thirds of

medical research at universities is funded by private industry.

Twenty years ago, only one-third was.

Many people think that big corporations have too much power, but " we

have to live in the context of the country's structure, " said Dr.

Grundy, a Texas cardiologist who headed the cholesterol

panel. " The government is not producing drugs. All the big statin

trials have been paid for by the companies. "

Government has its own problems. A ban on private consulting was

lifted a decade ago, and recent years have seen one scandal after

another involving federal scientists taking money from companies

directly affected by their decisions.

Conflicts also have bedeviled trusted groups like the American Heart

Association, which rely on private cash for meetings and activities,

and the continuing medical education system, which often gives

doctors credits for attending drug-company-sponsored talks that

sometimes amount to paid commercials.

The drug industry spent $2 billion in 2001 on events for doctors --

double what it spent five years earlier, Dr. Jerome Kassirer, former

editor-in-chief of the New England Journal of Medicine, reports in

his new book, " On the Take. "

" The time has come to ask whether all of the money floating around

medicine has created a pattern of corruption, " he writes. " Clinical

advice, like votes, should never be bought. "

Some say it's naive to think a panel of true experts with no

industry ties could be assembled today.

Seymour, executive director of the National Lipid

Association, a group that promotes cholesterol control and is

largely funded by drug companies, has six of the nine guideline

panel members on his board.

" Who in America is going to write these guidelines if you don't go

to the thought leaders? Should I call Dr. X in the middle of Peoria?

What gives them credentials to be on my board? " he asked.

But at the University of Illinois in Peoria, they think quite a lot

of Dr. Gold, who in 30 years as a cardiologist has managed not

to take consulting or lecture fees from industry.

" I'm squeaky-clean, " he says, and " would jump at the opportunity " to

serve on a guidelines panel. " There are tons of people like me, and

they're even in places like Des Moines, Iowa. "

The statin flap reveals much about modern medicine and how industry

influences decisions that affect the health of ordinary Americans.

It involves drugs with so much science behind them and proven

benefits that doctors only partly joke about putting them in the

water supply.

More than half of American adults have high cholesterol, raising

their risk of heart attack. Doctors tell them to eat right and

exercise, but that takes time to work and usually produces only

modest improvement. Statins' ability to drop cholesterol

dramatically and almost overnight has made them the nation's top-

selling drugs.

The government's National Cholesterol Education Program periodically

asks experts to help set guidelines for controlling cholesterol. Not

surprisingly, rules issued in 2001 advocate aggressively curbing

this risk factor and using statins.

New studies prompted officials to convene a new panel to revise the

guidelines. Seven of its nine members had been on the previous one.

The newcomers -- Dr. Sidney C. Jr. of the University of North

Carolina in Chapel Hill and Dr. C. Noel Bairey Merz of Cedars-Sinai

Medical Center in Los Angeles -- were representatives of the heart

association and the American College of Cardiology, respectively.

These groups in July endorsed and published the new guidelines,

which set cholesterol limits even lower, encouraging statins for

millions more Americans.

A day later, the Center for Science in the Public Interest said the

advice was tainted by doctors' industry ties, which weren't

disclosed.

The financial ties ranged from long-ago grants to a doctor's

university to do research all the way up to stock ownership and

ongoing deals providing thousands of dollars in personal income from

statin makers.

The most complicated situation is that of Dr. H. Brewer, chief

of the molecular disease branch of the National Heart, Lung and

Blood Institute, which houses the federal cholesterol program.

He is on the scientific advisory board of Lipid Sciences Inc., a

private biotechnology firm developing cholesterol treatments, and

the National Lipid Association, the industry-backed group that

promotes cholesterol control.

Brewer also is a consultant or speaker for 10 companies, including

several statin makers. He even attended a meeting in July 2003 of a

federal Food and Drug Administration advisory committee debating

whether to recommend approval of Crestor, a statin made by

AstraZeneca -- one of the companies for whom he moonlights.

The meeting was on a Thursday, and it couldn't be determined whether

Brewer was there on government time. He refused requests for an

interview. In a memo to National Institutes of Health director Dr.

Elias Zerhouni, Brewer wrote that he was " only an observer and did

not participate " in the FDA meeting, which led to the drug's

approval a month later.

Zerhouni had gotten a complaint from Public Citizen's Dr. Sidney

Wolfe, who said Brewer had inaccurately analyzed Crestor's risks in

a medical journal article whose publishing costs were paid by

AstraZeneca.

What is conflict of interest today? Many think they know it when

they see it but have trouble defining its boundaries, especially as

times change and things once taboo become accepted as industry foots

more of the research bill.

" It is very much a continuum. I don't think there is a sharp line,

and that's where disclosure becomes so important, " said Dr.

Goldrich, chairman of the American Medical Association's council on

ethical and judicial affairs.

Consulting fees can range from a couple thousand dollars to $50,000

to $100,000 a year, said Mildred Cho, associate director of Stanford

University's Center for Biomedical Ethics.

" The concern is that when you get into these larger amounts, they're

not just for duties performed, " but for using clout to help market a

drug, she said.

Some guideline panel members talk candidly about their industry

ties. Grundy, a cardiologist at the University of Texas Southwestern

Medical Center in Dallas and former Heart Association president,

said he makes less than $10,000 a year in speaker fees from various

companies and refuses to promote a particular drug in a talk.

Dr. Neil J. Stone of Northwestern University Medical School in

Chicago, said he takes speaker fees to replace lost income when a

talk forces him to miss work and sometimes donates his fees to

universities.

" I have scrupulously avoided owning a share of stock in these

companies, " he said. " I don't want anybody to think I knew something

ahead of time. "

, also a former heart association president, said he owns about

$10,000 in stock in two companies with heart products, including

& , which has partnered with Merck & Co. to sell a

statin over the counter in England.

" I didn't even know I had it till I called the fellow that handles

the accounts, " said of his stock, adding, " Nobody volunteers

time for one of these committees because they think a small amount

of stock they may have in a retirement plan is going to benefit. "

Bairey Merz, the California cardiologist, listed stock in &

and seven other companies with heart-related business, plus

consulting, lecture or research money from nine, including several

statin-makers. She declined to be interviewed but said in a brief

written statement that she had not breached any ethics rules.

Grundy, the panel's leader, said he didn't know any members owned

stock. Although it wouldn't necessarily disqualify them, " I probably

would not allow that, " he said.

Efforts to interview three other panel members -- Dr. Luther T.

of State University of New York Downstate Medical Center in

Brooklyn, Dr. B. Hunninghake of the University of Minnesota

in Minneapolis, and Dr. C. Pasternak of Massachusetts

General and Harvard Medical School in Boston -- were unsuccessful.

Multiple requests to interview and Pasternak were unreturned

by spokespeople; Hunninghake could not be located through the

university.

Hunninghake quit before the guidelines were released to become a

full-time industry consultant, according to the cholesterol program.

Pasternak joined Merck soon after the guidelines came out.

Financial conflicts aren't the only danger. " Group think " can set in

when a panel doesn't include people who can look at the science with

different views than cardiologists.

" These folks made their careers on being aggressive on treating risk

factors, " but internal medicine doctors might feel differently, said

Dr. Harlan Krumholz, a Yale University cardiologist and

epidemiologist who runs a center for medical outcomes research. He's

been on dozens of guideline groups -- not this one -- and says

he's " pretty careful " about industry ties.

" When you've been spending your life trying to prove a hypothesis

and you believe in a certain thing, you're obviously seeing the

world through that perspective, " Krumholz said.

Indeed, many of the doctors making the case for statins helped

establish their effectiveness.

" Most of us did all the original trials of the statins, " said Stone

of Northwestern.

He had a personal reason -- his father was the first in his family

to live past 48, dying of heart disease in 1985 at age 68.

" He never got a chance to get a statin, " Stone said. " I'm actually

stunned that people who know the evidence don't see the enormous

value of this class of drugs. "

The only panel member with no financial conflicts -- the federal

cholesterol program's coordinator, Dr. Cleeman -- is upset by

attacks on the guidelines like the letter signed by 35 scientists

and doctors asking NIH to launch an independent review.

" They are science-based, " Cleeman said. " The public should have

confidence in them. I'm an unconflicted person, and I read the

science the same way. "

Meanwhile, moves are under way to curb conflict.

• The NIH is revising rules on outside consulting. Zerhouni

first said it would be banned only for top scientists but now wants

restrictions on all employees for two years. He altered his stance

after the Office of Government Ethics said this summer that NIH was

so full of conflict that across-the-board rules were needed.

• Pressure is growing on medical journals for more meaningful

disclosure of authors' conflicts -- not just fine print naming a

company without saying what it makes or does. Kassirer cites a June

2003 editorial describing its author as " having equity interests " in

a company when in fact he was its president and its product was the

subject of the article.

• Vermont, with the support of then-Gov. Dean, himself a

physician, passed a law in 2002 requiring doctors to disclose gifts

over $25 and listing them on the Internet.

• The heart association and College of Cardiology are about to

release an ethics report that will make broad recommendations on

physician behavior and patients' interests, said.

As for the statin mess, " I hope that the focus on a potential

conflict of interest does not overshadow the real problem that

patients are not receiving care which can prevent heart attack and

stroke, " said.

Stone agreed: " The science is out there for everybody to see. The

one thing that I'm very distressed about is these are evidence-based

guidelines ... this is not an opinion report. "

All the more shame, Kassirer says, that the authors' financial deals

make their advice appear biased.

" I'm just not sure what to believe, " he said. " That's the issue. "

Conflict aside, statins are wonder drugs that too few take

Perhaps no medicine today is so widely regarded as a wonder drug as

the cholesterol-lowering statin. From Zocor to Lipitor to Pravachol,

statins are top sellers in a country where half of American adults

have high cholesterol.

In Britain, they recently became available over the counter, and

there are efforts afoot in the United States to do the same.

This summer, a U.S. advisory panel set recommended cholesterol

levels even lower, encouraging millions more Americans to take

statins. But because all but one member of that panel receives money

from the makers of those drugs, some consumer advocates wonder about

the credibility of the latest advice.

Still, no one questions the overall value of these drugs, which

quickly and drastically lower the cholesterol that builds up in

blood vessels, thus preventing heart attacks and strokes.

The first statin, Mevacor, came on the market in 1987. Now there are

five others in the United States. About 13 million Americans take

statins -- roughly one-third of the number for whom they're

recommended.

The most famous recent example is former President Bill Clinton, who

was prescribed a statin for high cholesterol when he left office

several years ago but who stopped taking it at some point. On Labor

Day, he had a quadruple bypass operation for arteries so severely

clogged that doctors said he was in grave danger of a major heart

attack.

Proponents of statins, such as the National Lipid Association, a

largely industry-funded group, say Clinton's case shows the need for

educating more doctors to treat cholesterol more aggressively.

" How in the heck did he get something that could be prevented? The

president's doctors didn't even know how to manage lipids, " said the

group's executive director, Seymour.

A federally funded program, the National Cholesterol Education

Program, was formed in 1985 to help educate Americans about this

risk factor. Its revised guidelines, issued in July, have been

criticized by some as perhaps too aggressive for certain groups like

the elderly, women and people with diabetes.

They advise people at high risk of a heart attack to get their level

of LDL or " bad " cholesterol to 70, instead of 100, the previous

target. The guidelines urge people at moderate-to-high risk to aim

for 100 versus the previous target of 130.

The drugs and their makers are Merck's lovastatin (Mevacor) and

simvastatin (Zocor); Bristol-Myers Squibb's pravastatin (Pravachol);

Novartis Pharmaceuticals' fluvastatin (Lescol); Pfizer's

atorvastatin (Lipitor), and AstraZeneca's rosuvastatin (Crestor).

Side effects are very rare, but can include severe muscle weakness.

The federal Food and Drug Administration has warned doctors to be

careful about prescribing statins, particularly Crestor, in certain

patients at higher risk of complications, including certain Asians,

the elderly, and people with thyroid or kidney problems.

On the Net:

Center for Science in the Public Interest database on doctor

conflicts: http://www.cspinet.org/integrity/index.html

National Cholesterol Education Program's guidelines:

http://www.nhlbi.nih.gov/guidelines/cholesterol/

Disclosures by guideline panel members:

http://www.nhlbi.nih.gov/guidelines/cholesterol/atp3upd04--

disclose.h tm