Another very interesting pharm article...

Take care,
 Celia

On 22 Nov 2002, Alexander Tsai wrote:
> 
> http://www.nytimes.com/2002/11/22/business/22DRUG.html
> 
> November 22, 2002
> Madison Ave. Plays Growing Role in Drug Research
> By MELODY PETERSEN
> 
> Dentists leafing through The Journal of the American Dental Association
l=
> ast
> May found a study concluding that a new drug called Bextra offered relief
> from one of their patients' worst nightmares =97 the acute pain that
foll=
> ows
> 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
pai=
> n
> drugs.
> 
> The new study helped light a fire under Bextra. Its sales soared 60
perce=
> nt
> 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,
o=
> ne
> of the world's biggest advertising companies.
> 
> Madison Avenue =97 whose television ads have helped turn prescription
> medicines like Viagra, Allegra and Vioxx into billion-dollar products
=97=
>  is
> expanding its role in the drug business, wading into the science of drug
> development.
> 
> The three largest advertising companies =97 Omnicom, Interpublic and WPP
=
> =97
> have spent tens of millions of dollars to buy or invest in companies like
> Scirex that perform clinical trials of experimental drugs. One
advertisin=
> g
> 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
Harvar=
> d
> 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 =97 or
a=
> s in
> Bextra's case even conduct =97 studies aimed at showing that the drugs
ha=
> ve
> the qualities patients most desire.
> 
> Armed with the results, ad agencies try to sway doctors' prescribing
habi=
> ts.
> 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,
of=
> ten
> at expensive dinners the physicians are paid a fee to attend.
> 
> "We provide services that go from the beginning of drug development all
t=
> he
> 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
sys=
> tem
> too slow. And ad agencies =97 having built a multibillion-dollar business
> selling drugs to consumers =97 pushed deeper and deeper into the process.
> 
> Federal law prohibits the promotion of drugs before they have been
approv=
> ed
> by the Food and Drug Administration, or the promotion of them for
unappro=
> ved
> 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
governm=
> ent
> approval and, later, to prompt physicians to prescribe drugs for
conditio=
> ns
> 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
contribut=
> ing
> 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
l=
> ast
> 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 =97 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 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
wit=
> h
> longer-acting versions.
> 
> Novartis had introduced Ritalin LA, its own once-a-day medicine. But
ther=
> e
> was no research to back up a crucial selling point: that the eight- to
> nine-hour impact of a dose =97 long enough to help at school, but not
too=
>  long
> to interfere with dinner and bedtime =97 was better for many children
tha=
> n the
> 12-hour action of a competitor's drug.
> 
> The drug company's advisers at Intramed, a medical education company
owne=
> d
> 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
t=
> o a
> transcript of the conversation obtained by The New York Times, "and then
> submit it to you for your =97 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
stud=
> y
> expected to provide scientific data showing Ritalin LA's advantages was
n=
> ot
> 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
t=
> old
> 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 =97 John S. Markowitz and Kennerly S. Patrick of the Medical
> University of South Carolina =97 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
s=
> he
> 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,
whi=
> le
> 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.
"W=
> hat
> I mind is advertising that calls itself education."
> 
> The ad agencies' medical education companies say that they neither toy
wi=
> th
> science nor ghostwrite articles that physicians use to make decisions
abo=
> ut
> 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
dictat=
> e
> what their paper should say. "No figure, no table, anything goes in
witho=
> ut
> our approval," Dr. Markowitz said. Dr. Patrick added that he thought,
bas=
> ed
> 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
w=
> as
> 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,
whic=
> h
> 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
dr=
> ug,
> for more than a dozen unapproved uses.
> 
> One document made public in a whistle-blower lawsuit against
Warner-Lambe=
> rt
> describes how Proworx, a company owned by the ad giant Omnicom, offered
t=
> o
> help write journal articles about using Neurontin to treat pain. Proworx
> planned to recruit doctors to be the named authors of the articles,
payin=
> g
> them a $1,500 fee.
> 
> Omnicom declined to comment on the matter.
> 
> Dr. Relman, the former editor of The New England Journal of Medicine,
sai=
> d
> there was no place in medical education for ad agencies.
> 
> "We don't get anywhere in medicine without objective data," he said.
"Tha=
> t's
> the coin of the realm. The whole purpose of medical research is lost if
y=
> ou
> 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
effectiv=
> e
> against acute pain, the research firm Scirex headed to central Texas,
whe=
> re
> 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
conclusi=
> ons
> was insignificant: that one dose of Bextra worked longer than a single
do=
> se
> 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, 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
part=
> ly
> owned by an ad agency.
> 
> "If this is where clinical research is headed, that would be a terrible
> negative trajectory," he said.
> 
> Dr. Topol =97 who drew attention last year with a finding that Celebrex
a=
> nd
> its competitor, Vioxx, appeared to raise the risk of heart attacks =97
sa=
> id
> 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
helpe=
> d
> Bextra's marketers shift attention away from the F.D.A.'s negative
findin=
> gs.
> Because of confidentiality rules, the F.D.A. cannot release any
informati=
> on
> about the earlier pain studies that failed to sway regulators.
> 
> "Even though the study lacked some important proof, the real problem is
t=
> hat
> in the dental literature, this will be read," Dr. Topol said. "And
dentis=
> ts,
> 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
behi=
> nd
> the design and conclusions of the Scirex studies. Pharmacia was not
tryin=
> g
> 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.
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
perc=
> ent
> went to academic institutions, while the rest went to investigators
worki=
> ng
> 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
t=
> he
> 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
Scire=
> x's
> research to produce positive results for drug company clients =97
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
eac=
> h
> 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,
o=
> ne
> need look no further than the introduction this summer of a new
> antidepressant called Lexapro by Forest Laboratories, a drug company
base=
> d
> in Manhattan.
> 
> 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 advertising.
> 
> 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
Fores=
> t
> invited Dr. Richard J. Brown, a Manhattan psychiatrist, and about 20 of
h=
> is
> peers to dinner at Daniel, one of Manhattan's most expensive restaurants.
> Besides dining on tournedos of beef and cabernet sauvignon, each doctor
w=
> as
> 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
mont=
> h
> not to give gifts or cash to doctors in an attempt to influence their
> prescribing =97 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
nig=
> ht
> to sit on Forest's advisory board. He said Daniel was not a restaurant
hi=
> s
> agency normally used. Intramed executives, he said, had scheduled the
din=
> ner
> 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
ot=
> her
> dinners he attended that were organized by Intramed and other drug
market=
> ing
> companies on behalf of their pharmaceutical clients.
> 
> "I think it's disgusting," said Dr. Brown, who organized a protest
outsid=
> e a
> similar dinner that Forest held at the Four Seasons last year. "This is
m=
> y
> 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
numbe=
> r
> 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
prod=
> uct
> 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 consulting firm.
> 
> Indeed, the drug industry relies far more heavily on behind-the-scenes
> promotion than on consumer advertising. Last year, just $2.8 billion of
t=
> he
> $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
vers=
> ion
> 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,
a=
> s
> 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 =97 a study that the company paid to
ha=
> ve
> 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
compan=
> y
> 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
pharmaceutic=
> al
> industry, reviewed the same clinical trials as Dr. Gorman and concluded
i=
> n
> 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 =97 as drug
companie=
> s do
> hundreds of other doctors =97 but did not pay him for the Lexapro
article=
> . In
> published research, he has acknowledged serving as a consultant or
receiv=
> ing
> 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
th=
> e
> country to New York for a two-day conference at Columbia. The students
we=
> re
> treated to two nights at the Plaza Hotel, three meals a day and tickets
t=
> o a
> Broadway show. Intramed coordinated the event, shuttling students from
pl=
> ace
> 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
promo=
> te
> Forest's drugs. Forest had simply donated money for the conference, he
sa=
> id.
> 
> The University of Rochester did not send a representative because some
> students expressed concern about the drug industry sponsorship. In a
lett=
> er
> to Columbia, Lenard I. Lesser, a Rochester medical student, said that
For=
> est
> would not have paid for the conference unless it expected a financial
> return.
> 
> "This is setting a bad precedent," Mr. Lesser said. "It is all about
> establishing relationships that will be profitable."
> 
> 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
dr=
> ug
> promotion as a private lawyer, is leading a review of regulations that
co=
> uld
> relax existing limits on behind-the-scenes marketing of drugs.
> 
> 
> ---
> You are currently subscribed to healthpolicy as: [log in to unmask]
> To unsubscribe send a blank email to
> [log in to unmask]
> 
> If you would prefer to receive a daily digest of this listserve, send an
> email to: [log in to unmask] Do not include a subject. In the body,
type:
> set healthpolicy digest.
>