Scientific Research Today - Part I - Long

[Guest guest]

can this post be shortened to one sentence so I wqon't have to read the

whole thing?

Jan

 

 

 

[Guest guest]

Disturbing information regarding the state of scientific research forwarded

in two parts This is Part I.

 

 

Why you can't trust medical journals anymore

Doctors Without Borders

 

By Shannon Brownlee

Source: Washington Monthly

 

<http://www.washingtonmonthly.com/features/2004/0404.brownlee.html>

http://www.washingtonmonthly.com/features/2004/0404.brownlee.html

 

With financial ties to nearly two dozen drug and biotech companies,

Dr. Charles B. Nemeroff may hold some sort of record among academic

clinicians for the most conflicts of interest. A psychiatrist, a

prominent researcher, and chairman of the department of psychiatry and

behavioral science at Emory University in Atlanta, Nemeroff receives

funding for his academic research from Eli Lilly, AstraZeneca, Pfizer,

Wyeth-Ayerst--indeed from virtually every pharmaceutical house that

manufactures a drug to treat mental illness. He also serves as a

consultant to drug and biotech companies, owns their stocks, and is a

member of several speakers' bureaus, delivering talks--for a fee--to

other physicians on behalf of the companies' products.

 

But it was just three of Nemeroff's many financial entanglements that

caught the eye of Dr. Bernard J. Carroll last spring while reading a

paper by the Emory doctor in the prominent scientific journal, Nature

Neuroscience. In that article, Nemeroff and a co-author reviewed

roughly two dozen experimental treatments for psychiatric disorders,

opining that some of the new treatments were disappointing, while

others showed great promise in relieving symptoms. What struck

Carroll, a psychiatrist in Carmel, Calif., was that three of the

experimental treatments praised in the article were ones that Nemeroff

stood to profit from--including a transdermal patch for the drug

lithium, for which Nemeroff holds the patent.

 

Carroll and a colleague, Dr. Robert T. Rubin, wrote to the editor of

Nature Neuroscience, which is just one of a family of journals owned

by the British firm, Nature Publishing Group, pointing out the

journal's failure to disclose Nemeroff's interests in the products he

praised. They asked the editor to publish their letter, so that

readers could decide for themselves whether or not the author's

financial relationships might have tainted his opinion. After waiting

five months for their letter to appear, the doctors went to The New

York Times with their story--a move that sparked a furor in academic

circles, and offered the public yet another glimpse into conflict of

interest, one of the most contentious and bitter debates in medicine.

 

In his defense, Nemeroff told the Times he would have been happy to

list his (many) relationships with private industry--if only the

journal had asked. " If there is a fault here, " he said, " it is with

the journal's policy, " which did not require authors of review

articles to disclose their conflicts of interest.

 

And that is pretty much where the debate over conflict of interest in

medical journals stands: Should research scientists who have financial

stakes in the products they are writing about be forced to disclose

those ties? To which the average person might reasonably respond, of

course they should. But the more pertinent question is why scientists

with financial stakes in the outcome of scientific studies are allowed

anywhere near those studies, much less reviewing them in elite journals.

 

The answer to that question is at once both predictable and shocking:

For the past two decades, medical research has been quietly corrupted

by cash from private industry. Most doctors and academic researchers

aren't corrupt in the sense of intending to defraud the public or harm

patients, but rather, more insidiously, guilty of allowing the

pharmaceutical and biotech industries to manipulate medical science

through financial relationships, in effect tainting the system that is

supposed to further the understanding of disease and protect patients

from ineffective or dangerous drugs. More than 60 percent of clinical

studies--those involving human subjects--are now funded not by the

federal government, but by the pharmaceutical and biotech industries.

That means that the studies published in scientific journals like

Nature and The New England Journal of Medicine--those critical

reference points for thousands of clinicians deciding what drugs to

prescribe patients, as well as for individuals trying to educate

themselves about conditions and science reporters from the popular

media who will publicize the findings--are increasingly likely to be

designed, controlled, and sometimes even ghost-written by marketing

departments, rather than academic scientists. Companies routinely

delay or prevent the publication of data that show their drugs are

ineffective. The majority of studies that found such popular

antidepressants as Prozac and Zoloft to be no better than placebos,

for instance, never saw print in medical journals, a fact that is

coming to light only now that the Food and Drug Administration has

launched a reexamination of those drugs.

 

Today, private industry has unprecedented leverage to dictate what

doctors and patients know--and don't know--about the $160 billion

worth of pharmaceuticals Americans consume each year. This is an

unsettling charge that many (if not a majority) of doctors and

academic researchers don't want to acknowledge. Once grasped, however,

the full scope and consequences of medical conflict of interest beget

grave doubts about the veracity of wide swaths of medical science. As

Dr. Drummond Rennie, deputy editor of The Journal of the American

Medical Association (JAMA), puts it, " This is all about bypassing

science. Medicine is becoming a sort of Cloud Cuckoo Land, where

doctors don't know what papers they can trust in the journals, and the

public doesn't know what to believe. "

 

Clinical trial and error

 

How did we get to this point? What effect is industry influence having

on the treatment of patients? And why are the medical journals not

more vigilant to weed out papers that have been distorted by conflict

of interest? The answers to these questions begin, oddly enough, with

an amendment to U.S. patent law called the Bayh-Dole Act. Passed in

1980, Bayh-Dole for the first time permitted universities to

commercialize products and inventions without losing their federal

research funding, the seed money for innovative research. The

brainchild of George Keyworth II, President Reagan's science advisor,

who was watching the United States get beaten in world markets by the

Japanese, Bayh-Dole was intended to stimulate advanced technological

invention and speed its transfer from university labs into private

industry, where it could be put to work spurring U.S. productivity.

 

It seemed like a win-win proposition. Indeed, Bayh-Dole has helped

launch the biotech industry and has propelled several life-saving

products to market. The basic research behind Gleevec, for instance,

an incredibly effective new anti-cancer drug, was done by a university

scientist. The drug's manufacturer, Novartis, stepped in and provided

additional funding for development. In 1984, private companies

contributed a mere $26 million to university research budgets. By

2000, they were ponying up $2.3 billion, an increase of 9,000 percent

that provided much needed funds to universities at a time when the

cost of doing medical research was skyrocketing.

 

That's the upside. The downside is that Bayh-Dole has also fostered

increasingly cozy relationships between the academics upon whom the

nation depends for unbiased medical information and Big Pharma,

private companies whose main goal, let's face it, is making a profit.

And we're talking serious money here. In addition to the salaries

built into company-sponsored research grants, academic clinicians at

medical schools can pad their already decent incomes with $1,000-a-day

consulting contracts with pharmaceutical companies, patent royalties,

licensing fees, and big-payoff stock options. Nemeroff stood to reap

as much as $1 million in stock from a company that manufactured one of

the products in his Nature Neuroscience paper. At many of the top

research universities and medical schools around the country, a

substantial percentage of the faculty enjoys the perks of industry

relationships. At MIT, 31 percent of the science and engineering

faculty has outside income; at Stanford Medical School, it's 20 percent.

 

What's in it for the pharmaceutical companies? Simple economics. It's

Marketing 101. By penetrating the wall that once existed around

academic researchers, drug companies have gained access to the

" thought leaders " in medicine, the big names whose good opinion of an

idea or a product carries enormous weight with other physicians.

Companies target academic KOLs, or Key Opinion Leaders, in the lexicon

of marketing, and woo them with invitations to sit on scientific

advisory committees, or to serve as members of speakers' bureaus,

which offer hefty fees for lending their prestige to a company and

touting its products at scientific meetings and continuing medical

education conferences. Of course, KOLs must be convinced of their own

impartiality, says Carl Elliott, a moral philosopher at the University

of Minnesota and author of Better Than Well: American Medicine Meets

the American Dream. " If they understood that they were being used as

industry mouthpieces, they would probably pull the plug on the whole

enterprise. " Drug companies encourage their KOLs to consult for

multiple companies so the appearance of objectivity can be maintained.

But the drug industry's most powerful means of boosting the bottom

line is funding research, which allows companies to control, or at

least influence, a great deal of what gets published in the medical

journals, effectively turning supposedly objective science into a

marketing tool.

 

" These are not benign people who are interested in helping people with

their new wonder drugs, " says Drummond Rennie. " The drug companies are

run by hard-nosed marketers, not by the physicians and the scientists.

They use what works, and money works. " Rennie, who has a thatch of

unkempt white hair and remnants of the accent of his native Leeds,

England, got a clear picture of the extent to which drug companies

will go to control the results of studies they fund in 1993, when a

colleague at University of California San Francisco tried to publish a

paper in JAMA in 1993 on the metabolic activity of four different

forms of thyroid hormone. Betty J. Dong, a pharmacologist, had been

contracted in 1987 by Flint Laboratories to run a clinical trial

comparing Synthroid, Flint's synthetic version of thyroid hormone, to

that of three competing formulations. At the time, Synthroid was the

market leader and the most expensive drug in its class. Dong and Flint

signed a lengthy agreement detailing the design of the study, and both

sides fully expected the results would show that Synthroid was superior.

 

But all four drugs turned out to be essentially equivalent. In 1990,

as Dong prepared a paper for JAMA, the company that was at first so

eager to solicit her help, launched a vigorous campaign to discredit

the study. Flint then rushed its own paper into press at a less

prestigious journal, concluding--surprise!--that Synthroid was

superior. After numerous attempts to address the company's criticisms,

Dong finally submitted her paper to JAMA, only to withdraw it three

months later when the firm threatened to sue for breach of contract.

It took the FDA and U.S. Department of Health and Human Services to

get the company to back down. Dong's paper did not see print in JAMA

until 1997.

 

In this case, it might seem as if the only real harm to the public

during the seven years that elapsed from the time Dong completed her

study to its publication was higher prices to patients and insurers.

To Rennie's way of thinking, the Dong imbroglio and others like it

have a more insidious effect by sending a chilling message to

scientists, namely, don't bite the hand that feeds you. In a recent

survey of clinical researchers, nearly 20 percent of respondents

admitted to delaying publication of their results by more than six

months at least once in the last three years to allow for patent

application, protect their scientific lead, or to slow the

dissemination of results that would hurt sales of their sponsor's

product--often without overt pressure from the company. " If you're

getting a lot of money from a corporate sponsor, it's easy to get the

impression that you'll get even more for future research if you don't

write up the negative results, " says Rennie--and that your funds will

dry up if you do.

 

The bottom line is that articles appearing in medical journals contain

a lot of happy talk about medical products. At least eight studies

have shown that industry-sponsored research that gets published tends

to produce pro-industry conclusions, according to a review by Yale

University researchers that appeared last year in JAMA. By reanalyzing

data from eight separate studies of the effect of conflict of interest

on 1,140 published scientific papers, the researchers found that

papers based on industry-sponsored research are significantly more

likely to reflect favorably on a sponsoring company's drug or device

than research that is supported by a non-profit entity or the federal

government.

 

How can this be? Isn't science, well, scientific, an objective search

for the truth? That's what many academic clinicians, especially those

who are mixed up with corporate sponsors, would have the public

believe. A typical comment comes from Niels Reimers, an early promoter

of industry-university ties, who told the Hartford Courant, " You may

think I'm a Pollyanna or something, but most people are honest. It's

sort of the ethos of academic research. " Here's Dr. Irwin Goldstein, a

Boston University urologist who has consulted for at least seven

companies developing impotence therapies: " Science is science. It

comes down to the bottom line. What the data shows, the data shows. "

 

Such statements reflect the ideal of science, not the reality, says

Dr. Marcia Angell, former editor in chief of The New England Journal

of Medicine. Public protestations aside, she says, " Clinicians know

privately that results can be jiggered. You can design studies to come

out the way you want them to. You can control what data you look at,

control the analysis, and then shade your interpretation of the

results. " Even the most careful research can be fraught with murky

results that require sifting and weighing, a measure of judgment that

the researcher hopes will bring him closer to the truth. Was this

patient's headache caused by the antibiotic you gave her, or does she

have a history of migraines? Is that patient's depression lifting

because of the drug you are testing, or because a kindly doctor is

actually listening to him?

 

Sometimes there isn't much that journal editors can do to separate

good science from that which has been weighed, sifted, and jiggered

according to a corporate sponsor's needs. Increasing numbers of

studies that get published are actually written by PR firms, " medical

communications " specialists, who then go out and recruit an academic

willing to put his name on the paper, for a fee. Other studies simply

omit data that detract from the sponsor's message. In September 2000,

for example, JAMA published a paper comparing the prescription

painkiller Celebrex to over-the-counter ibuprofen. The manufacturer of

the prescription drug, known as a selective Cox-2 inhibitor, launched

the study in order to show that Cox-2 inhibitors, a class that also

includes the prescription drug Vioxx and was already worth $3.5

billion a year, cause fewer instances of bleeding in the stomach and

intestine than either aspirin or ibuprofen. The huge study, which

looked at six months of data from more than 8,000 patients, produced

unambiguous results: There were fewer side effects among patients on

the Cox-2 drug.

 

A year later, news surfaced that patients had actually been followed

for 12-15 months at the time the JAMA paper came out, not six, and

that during the second half of the study, the group taking the Cox-2

drug suffered higher rates of gastrointestinal side-effects than

patients on the over-the-counter painkiller. To make matters worse,

patients on the Cox-2 developed serious heart problems three times

more often than those on ibuprofen. The authors of the paper--all of

them either consultants to the manufacturer or employees " defended

their decision to report only the first, positive, half of their

study, saying several patients who weren't taking the Cox-2 drugs

dropped out after six months, making the statistics more difficult to

analyze. But Dr. Catherine D. DeAngelis, JAMA's editor in chief, told

The Washington Post: " I am disheartened. We are functioning on a level

of trust that was, perhaps, broken. "

 

continued in part II

 

 

 

[Guest guest]

On Behalf Of Oaklandplants

Tuesday, January 10, 2006 1:16 PM

Re: Scientific Research Today - Part I -

Long

 

 

can this post be shortened to one sentence so I wqon't have to

read the

whole thing?

Jan

 

 

Unfortunately, no, Jan. Sometimes there is a lot of information and

explanation that needs to be absorbed and digested to really understand

things to have an informed opinion. And, understandably, sometimes a person

just doesn't seem to have the time to do this. Perhaps this is why things

have gotten so out of control (as presented in the long article) . . . We're

simply too busy to pay close attention.

 

Be Well,

Marcia Elston http://www.wingedseed.com

" Give thanks for a little and you will find a lot. " Hausa Saying from

Nigeria