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
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
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
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
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
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
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
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. Thomas 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
"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."
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
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
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 - John S. Markowitz and Kennerly S. Patrick 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.
Patrick said as the call concluded.
To produce the new draft, Intramed turned to Linda
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
The result, Dr. Logdberg said, is marketing masquerading as
"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. Patrick 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. Patrick 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
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.
the former editor of The New England Journal of Medicine,
said there was no place in medical education for ad
"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
One of the doctors, Eric 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,
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
"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
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. Paul A. Moore, an associate
editor of the journal, said the study was "carefully
designed and rigorously performed."
But Dr. Moore 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
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, Thomas L.
Harrison, 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
"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."
The Invisible Hand
Courting Doctors With Food and Cash
To see just how successful the invisible hand of Madison
Avenue can be, one need look no further than the
introduction this summer of a new antidepressant called
Lexapro by Forest Laboratories, a drug company based in
Competitors like GlaxoSmithKline, the maker of Paxil, and
Pfizer, which makes Zoloft, have each spent tens of
millions of dollars for television and print ads promoting
their antidepressants. But Forest, a current darling of
Wall Street, does not spend its money on consumer
Instead, it relies on WPP's Intramed and other companies to
organize expensive dinners for physicians where research
studies, many paid for by Forest, are discussed.
Just days after the F.D.A. approved Lexapro in August,
Intramed and Forest invited Dr. Richard J. Brown, a
Manhattan psychiatrist, and about 20 of his peers to dinner
at Daniel, one of Manhattan's most expensive restaurants.
Besides dining on tournedos of beef and cabernet sauvignon,
each doctor was paid $500 for attending.
The industry's ethics rules say that any free meal for
doctors must be at a restaurant considered modest by local
standards. As for the $500, the federal government warned
drug companies in guidelines proposed last month not to
give gifts or cash to doctors in an attempt to influence
their prescribing - a practice it said would be illegal.
Mr. Beitler, the WPP executive, said the dinner and the
$500 checks were appropriate because the doctors had been
hired as consultants for the night to sit on Forest's
advisory board. He said Daniel was not a restaurant his
agency normally used. Intramed executives, he said, had
scheduled the dinner at another restaurant that closed
three days before the Lexapro meeting.
Dr. Brown, who is retired, said he did no consulting that
night, or at other dinners he attended that were organized
by Intramed and other drug marketing companies on behalf of
their pharmaceutical clients.
"I think it's disgusting," said Dr. Brown, who organized a
protest outside a similar dinner that Forest held at the
Four Seasons last year. "This is my profession, and I hate
to see this happening."
Two weeks after the dinner at Daniel, analysts at J. P.
Morgan called Forest's introduction of Lexapro "an instant
success." Based on the number of prescriptions written in
Lexapro's first weeks on the market, the analysts said that
Forest appeared on its way to one of the best new product
launches in the industry's history.
"This market does respond to promotion," Kenneth E.
Goodman, Forest's president, said in a conference call with
Wall Street analysts on Oct. 15. Forest invested so much in
promotion that Lexapro was the subject of 63 percent of all
industry-sponsored meetings that primary care doctors
reported attending in an October survey by ImpactRx, a
Indeed, the drug industry relies far more heavily on
behind-the-scenes promotion than on consumer advertising.
Last year, just $2.8 billion of the $11.8 billion the drug
industry spent on marketing was aimed at consumers; the
rest paid for everything from dinner meetings with doctors
to sales calls and medical education, according to
Verispan, a health-care information company.
For Forest and its ad agency partners, selling doctors on
Lexapro is crucial.
Lexapro is not an entirely new drug, but rather a
chemically refined version of Celexa, an antidepressant
that accounts for 70 percent of the company's sales. Wall
Street is counting on Forest to persuade doctors to switch
Celexa users to Lexapro, because the older drug will lose
its patent protection in 2004. Once the patent expires,
Celexa sales will plummet, as generic companies begin
offering low-priced versions of the drug.
But Forest can point to just one study concluding that
Lexapro offers patients an advantage over Celexa - a study
that the company paid to have published, and has promoted
at dinners like one Dr. Brown attended at a Manhattan
steakhouse, just two weeks after the meal at Daniel.
The paper, by Dr. Jack M. Gorman, until recently a
professor at Columbia University and now on the faculty of
the Mount Sinai School of Medicine, pooled the results of
three studies and concluded that Lexapro "may have a faster
onset" than Celexa. Dr. Gorman's paper was published in CNS
Spectrums, a medical journal he edits.
Forest said that it paid Medworks Media, a small medical
marketing company that publishes the journal, to print Dr.
Gorman's article in a special supplement.
Other researchers find the data less convincing. The
Medical Letter, a nonprofit newsletter respected for its
independence from the pharmaceutical industry, reviewed the
same clinical trials as Dr. Gorman and concluded in
September that Lexapro had not been shown to be better than
any other antidepressant, including Celexa.
Dr. Gorman said that Forest paid him as a consultant - as
drug companies do hundreds of other doctors - but did not
pay him for the Lexapro article. In published research, he
has acknowledged serving as a consultant or receiving
payments from a dozen other drug makers.
Last month, Forest and Intramed turned their attention to
fourth-year medical students who will begin writing
prescriptions next year.
On Oct. 18, Forest paid to fly one student from each
medical school in the country to New York for a two-day
conference at Columbia. The students were treated to two
nights at the Plaza Hotel, three meals a day and tickets to
a Broadway show. Intramed coordinated the event, shuttling
students from place to place and helping conference
speakers with their presentations.
Dr. Gorman, who helped organize the conference for
Columbia, gave a brief presentation on his Lexapro study
during a speech about antidepressants. He said the
conference's purpose was to get medical students interested
in psychiatric research and in residency positions at
Columbia, not to promote Forest's drugs. Forest had simply
donated money for the conference, he said.
The University of Rochester did not send a representative
because some students expressed concern about the drug
industry sponsorship. In a letter to Columbia, Lenard I.
Lesser, a Rochester medical student, said that Forest would
not have paid for the conference unless it expected a
"This is setting a bad precedent," Mr. Lesser said. "It is
all about establishing relationships that will be
The tide does not appear to favor Mr. Lesser's stance. In
Washington, the F.D.A.'s new chief counsel, Daniel E. Troy,
who fought restrictions on drug promotion as a private
lawyer, is leading a review of regulations that could relax
existing limits on behind-the-scenes marketing of drugs.
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