Madison Ave., Ghostwriters, and Marketing (3 articles)

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Madison Ave., Ghostwriters, and Marketing (3 articles)

Madison Ave. Plays Growing Role in Drug Research

November 22, 2002

By MELODY PETERSEN

Dentists leafing through The Journal of the American Dental Association last

May found a study concluding that a new drug called Bextra offered relief

from one of their patients' worst nightmares - the acute pain that follows

dental surgery.

Federal regulators had rejected that conclusion only six months before,

leaving Bextra's marketers, Pharmacia and Pfizer, hard pressed to sell it as

an advance over Celebrex, their earlier entry in a crowded market for pain

drugs.

The new study helped light a fire under Bextra. Its sales soared 60 percent

over the three months that followed, according to industry data. But the

research was not conducted by academics. Instead, the lead investigators

were from Scirex, a little-known research firm owned partly by Omnicom, one

of the world's biggest advertising companies.

Madison Avenue - whose television ads have helped turn prescription

medicines like Viagra, Allegra and Vioxx into billion-dollar products - is

expanding its role in the drug business, wading into the science of drug

development.

The three largest advertising companies - Omnicom, Interpublic and WPP -

have spent tens of millions of dollars to buy or invest in companies like

Scirex that perform clinical trials of experimental drugs. One advertising

executive calls it " getting closer to the test tube. "

Ad agency executives say they do nothing to distort the research process.

But critics worry that science is being sacrificed for the sake of

promotion. " You cannot separate their advertising and marketing from the

science anymore, " said Dr. Arnold S. Relman, professor emeritus at Harvard

Medical School and a former editor of The New England Journal of Medicine.

" Ad agencies are not in the business of doing science. "

In interviews, advertising executives say their intention is to work side by

side with scientists, directing research toward drugs the marketers think

could be big sellers. Their companies, they say, can help design - or as in

Bextra's case even conduct - studies aimed at showing that the drugs have

the qualities patients most desire.

Armed with the results, ad agencies try to sway doctors' prescribing habits.

Some agencies own companies that ghostwrite articles for medical journals.

They also create the continuing-education courses that doctors take to

maintain their licenses. As new drugs are about to go on sale, these

marketers recruit doctors to speak to peers about the drugs' benefits, often

at expensive dinners the physicians are paid a fee to attend.

" We provide services that go from the beginning of drug development all the

way to the launch of your products, " said Joe Torre, chairman and chief

executive of Torre Lazur-McCann Healthcare WorldWide, an Interpublic unit

that is among the biggest health care marketing companies.

Only a few years ago, drug research and education were the province of

universities. But with pharmaceutical companies counting on instant

blockbuster sales of their new drugs, executives found the university system

too slow. And ad agencies - having built a multibillion-dollar business

selling drugs to consumers - pushed deeper and deeper into the process.

Federal law prohibits the promotion of drugs before they have been approved

by the Food and Drug Administration, or the promotion of them for unapproved

uses. But published research and medical education are exempt from those

rules, and doctors are free to prescribe approved drugs for any purpose.

The critics say that marketers are exploiting the loopholes, to begin

building markets for expensive new medicines long before they win government

approval and, later, to prompt physicians to prescribe drugs for conditions

the medications are not approved to treat.

" Doctors are led to prescribe drugs that may not be necessarily worth the

money, may not be better than a generic that's already on the market and

that their patients don't need, " Dr. Relman said. " It's clearly contributing

to the rising costs of prescription drugs and health care. "

Moreover, critics worry that the success of drug makers and marketers in

spurring big sales shortly after a drug's approval means that millions of

patients may take a drug before all of its side effects are known. Just last

week, Pharmacia sent letters to thousands of doctors warning that Bextra can

cause a life-threatening skin rash.

Advertising executives note that scientific trials are tightly regulated and

that most medical journal articles get careful review. Doctors, they say,

are hungry for information about new drugs.

" The implication that we are going to accentuate the good things and may

bury the bad things - there would be nothing in it for us to do that, " said

Lloyd J. Baroody, managing director of Target Research Associates, a

research firm in New Providence, N.J., that Torre Lazur acquired in March.

" I can't imagine why anyone in my company would want to break the law or go

against F.D.A. regulations. "

Even before ad agencies became involved in research, experts had found

repeated cases in which the drug industry shaded the truth in its zeal to

produce blockbusters. In a May 2000 article in The New England Journal of

Medicine, Dr. Bodenheimer, a professor at the University of

California at San Francisco, cited numerous cases in which, he said, drug

companies manipulated results of clinical trials by controlling a study's

design or choosing to make public only positive data.

The problems can only grow worse, he said, with ad agencies involved.

" It introduces another bias into the whole clinical drug trial picture, " Dr.

Bodenheimer said, " so that the American public and the physicians in the

United States are not going to know, really, the true facts about the

drugs " .

******

THE GHOSTWRITER - Articles That Follow Marketers' Advice

Executives at Novartis, the Swiss drug maker, faced a marketing conundrum

last spring. They had watched sales slide for Ritalin, the company's drug

for attention deficit hyperactivity disorder, as competitors came out with

longer-acting versions.

Novartis had introduced Ritalin LA, its own once-a-day medicine. But there

was no research to back up a crucial selling point: that the eight- to

nine-hour impact of a dose - long enough to help at school, but not too long

to interfere with dinner and bedtime - was better for many children than the

12-hour action of a competitor's drug.

The drug company's advisers at Intramed, a medical education company owned

by the global ad giant WPP, had a solution. They would take an article,

commissioned from two university professors, that objectively surveyed a

wide range of drugs and rewrite it to emphasize the potential benefits of a

drug with the characteristics of Ritalin LA.

" We would like to help draft this manuscript, " Marcia Zabusky, a vice

president of Intramed, told the doctors in a conference call, according to a

transcript of the conversation obtained by The New York Times, " and then

submit it to you for your - for your editing and for approval. "

During the call, Shane Schaffer, a Novartis marketing executive, told the

doctors that the company wanted " a quick, down and dirty " article. A study

expected to provide scientific data showing Ritalin LA's advantages was not

scheduled to start until the following day, he said, but the lack of

research findings should not be an obstacle.

" Obviously, we have to stick within data limits of what's published

currently as well as what we know are factual about these products, " he told

the doctors. " But, of course, inferences can be made. "

One such " potential theoretical conclusion " of the article, Ms. Zabusky

added, was that a drug that worked for 9 hours might be better than a

12-hour drug.

The doctors - S. Markowitz and Kennerly S. of the Medical

University of South Carolina - agreed to what Intramed and Novartis

proposed. " I think we're quite clear on what you want the next manuscript to

look like, " Dr. said as the call concluded.

To produce the new draft, Intramed turned to Logdberg, who has a

doctorate in anatomy and has made her living the last 12 years as a

ghostwriter for Intramed and other medical marketing companies. Starting

with an outline approved by Intramed, Dr. Logdberg said that she produced a

new manuscript in a few days.

The assignment was one of her last ghostwriting tasks. Dr. Logdberg, who

recently took a job teaching biology to high school students, said that she

had become increasingly disenchanted with the process.

Typically, she said, her manuscript would be sent to the drug company for

approval before it was given to the doctors who were paid to be listed as

the authors. Some doctors fretted over each comma, Dr. Logdberg said, while

others made no changes at all. The marketing companies, she added, " will

drop a doctor if they don't think he will be particularly malleable. "

The result, Dr. Logdberg said, is marketing masquerading as science.

" I don't have any problem with medical advertising that states in a clear

way, either by format or by copy, this is an advertisement, " she said. " What

I mind is advertising that calls itself education. "

The ad agencies' medical education companies say that they neither toy with

science nor ghostwrite articles that physicians use to make decisions about

prescribing drugs.

" We make editorial suggestions, " said Jed A. Beitler, chairman of Sudler &

Hennessey, a division at WPP that includes Intramed. " The doctors are the

ultimate writers. "

Dr. Markowitz and Dr. agreed, saying that Intramed did not dictate

what their paper should say. " No figure, no table, anything goes in without

our approval, " Dr. Markowitz said. Dr. added that he thought, based

on past research, that a drug like Ritalin LA could be better for certain

children than other long-lasting drugs.

Neither the doctors nor the companies disputed the accuracy of the

transcript of their conference call.

Novartis said the article was not intended to conclude that one product was

better than the others. Instead, the company said, it was a review of the

available medications in which the authors could suggest theoretical

advantages.

Mr. Beitler said that Intramed was unhappy with the manuscript that Dr.

Logdberg produced and later gave the assignment to another writer. The

article has not been published.

A 1998 survey of named authors writing for some of the nation's top

journals, including The Journal of the American Medical Association, which

published the survey, found that 11 percent of the articles had been

ghostwritten. Some experts think the practice continues to grow, even as the

best journals take steps to prevent it.

Wyeth hired ghostwriters in promoting the diet drug combination fen-phen,

according to documents made public in litigation filed after it became

evident that fen-phen caused a potentially deadly heart-valve defect.

Evidence of ghostwriting has also surfaced in federal and state

investigations of Warner-Lambert's marketing of Neurontin, an epilepsy drug,

for more than a dozen unapproved uses.

One document made public in a whistle-blower lawsuit against Warner-Lambert

describes how Proworx, a company owned by the ad giant Omnicom, offered to

help write journal articles about using Neurontin to treat pain. Proworx

planned to recruit doctors to be the named authors of the articles, paying

them a $1,500 fee.

Omnicom declined to comment on the matter.

Dr. Relman, the former editor of The New England Journal of Medicine, said

there was no place in medical education for ad agencies.

" We don't get anywhere in medicine without objective data, " he said. " That's

the coin of the realm. The whole purpose of medical research is lost if you

don't tell the truth. "

**************

THE RIGHT RESULTS - Finding the Positive in Medical Studies

For Pharmacia and Pfizer's second run at proving that Bextra was effective

against acute pain, the research firm Scirex headed to central Texas, where

it recruited dozens of patients with impacted molars. In two studies, it

reached just the conclusion that the drug makers' sought.

But three doctors who reviewed the Scirex studies for The Times said the

research was not persuasive. All three said that one of Scirex's conclusions

was insignificant: that one dose of Bextra worked longer than a single dose

of a medicine containing oxycodone and acetaminophen, a combination often

sold under the brand name Percocet. Patients rarely receive just one dose of

that combination drug, the doctors said, because it wears off in four to six

hours.

One of the doctors, J. Topol, chairman of the Cleveland Clinic's

department of cardiovascular medicine, called the studies " a contrived

comparison " and said he found it " quite disquieting " that Scirex was partly

owned by an ad agency.

" If this is where clinical research is headed, that would be a terrible

negative trajectory, " he said.

Dr. Topol - who drew attention last year with a finding that Celebrex and

its competitor, Vioxx, appeared to raise the risk of heart attacks - said

the Bextra studies did not include enough patients to justify drawing a

broad conclusion. The average age of patients in the study, 23, did not

represent the population likely to take the drug, he added.

Yet through publication in the leading dental journal, the research helped

Bextra's marketers shift attention away from the F.D.A.'s negative findings.

Because of confidentiality rules, the F.D.A. cannot release any information

about the earlier pain studies that failed to sway regulators.

" Even though the study lacked some important proof, the real problem is that

in the dental literature, this will be read, " Dr. Topol said. " And dentists,

who have to deal with trying to prevent or modulate pain, will be

impressed. "

Judy Glova, a spokeswoman for Pharmacia, said the drug company stood behind

the design and conclusions of the Scirex studies. Pharmacia was not trying

to bypass the regulatory process, she said, adding that the company is in

discussions with regulators to have Bextra approved for acute pain.

Scirex executives did not return repeated phone calls.

Editors at The Journal of the American Dental Association said the Scirex

article was reviewed by at least three scientists. One reviewer, Dr. A.

, an associate editor of the journal, said the study was " carefully

designed and rigorously performed. "

But Dr. said he would have recommended that the journal reject the

paper had he known that Bextra was not approved for acute pain.

The Bextra episode is just one example of the changing face of drug

research. In the early 1990's, about 75 percent of the drug industry's

clinical research dollars went to universities, according to a study by

CenterWatch, a company that tracks clinical trials. By 2000, just 34 percent

went to academic institutions, while the rest went to investigators working

under the direction of either a private research firm like Scirex or a

pharmaceutical company.

Omnicom says it has no control over Scirex. " We have nothing to do with the

design of clinical studies, " said Pat Sloan, an Omnicom spokeswoman.

Yet when the ad agency paid $20 million for part-ownership of Scirex in

1999, a top Omnicom executive, L. on, said he expected Scirex's

research to produce positive results for drug company clients - results that

would help speed new-drug applications, or N.D.A.'s, to the F.D.A.

" Our goal, " he said, " is to help ensure that all clinical studies and each

patient accrued into a study can be assessed to support the N.D.A.

submission. "