PART 3

Excerpt:

Late last year, researcher Gretchen LeFever was placed on
administrative leave by Eastern Virginia Medical School, and computers
filled with her research were seized. In addition, she says, the school
terminated her latest ADHD project -- financed by a prestigious
government grant -- and banned her from presenting her findings at two
national conferences. Today, she says, she remains shut out of her
university office and restricted from even discussing her most recent
ADHD findings."

------------------------------­------------------------------­--
Attention Deficit Pays at Shire

By Melissa Davis
Senior Writer
5/11/2005 7:02 AM EDT

For a while, Gretchen LeFever was able to draw national television
coverage to her crusade: what she calls the excessive diagnosis and
treatment of attention deficit hyperactivity disorder.

The pediatric clinical psychologist made a name for herself after
studying the apparent prevalence of ADHD in her eastern Virginia
community. At one local school district, for example, LeFever found
that 17% of the children in grades two through five had been diagnosed
with ADHD. Moreover, she discovered that the vast majority of those
diagnosed with the disorder were being treated with prescription
stimulants like Ritalin and the next-generation drugs manufactured by
Eli Lilly (LLY:NYSE - news - research), Johnson & Johnson (JNJ:NYSE -
news - research) and Shire Pharmaceuticals (SHPGY:Nasdaq ADS - news -
research).

On average, only about 5% of the nation's children supposedly suffer
from ADHD. So LeFever's findings, representing the highest rates of
ADHD ever documented, led to stories by major news outlets including
CBS, CNN and NPR.

But soon enough, critics attacked her research. LeFever believes some
were actually bankrolled by the pharmaceutical industry. She says even
her employer, the financially strapped Eastern Virginia Medical School,
turned against her. The university failed to return a phone call from
TheStreet.com.

"I was one of the more notable researchers at the school," LeFever
says. "But suddenly, everything I did was under scrutiny."

Now, LeFever says she no longer feels surprised. After all, she has
come to realize, her research could threaten a major growth market for
the cash-rich drug industry.

In this third of five articles exploring apparent conflicts of interest
in the medical business, TheStreet.com examines how an increasingly
popular but still controversial diagnosis has paid off for big pharma
companies -- and how the industry might benefit from silencing
troublesome questions.

Booming Business

As LeFever fights to keep her job, pharmaceutical companies continue to
rake in huge sums for their ADHD drugs.

Last year, one of Eli Lilly's newest drugs -- the ADHD treatment
Strattera -- became one of its most popular as well. Sales of Strattera
rocketed 80% to $667 million, far outpacing the growth posted by every
other product line.

Johnson & Johnson also counts its ADHD drug Concerta, obtained through
an $11.8 billion purchase of Alza in 2001, as a particularly strong
performer. Even Novartis (NVS:NYSE ADR - news -research) continues to
make plenty of money on the old standby Ritalin.

But Shire now boasts the most popular ADHD drug of all. Last year,
sales of Adderall jumped 28% -- capturing one-fourth of the crucial
U.S. market -- as physicians wrote more and more prescriptions. Shire
is now banking much of its future on ADHD as it races to bring out four
new treatments for the disorder in 2005 alone.

"As the ADHD market develops, new choices of treatment are emerging,"
Shire CEO Matthew Emmens recently explained. And "Shire aims to have a
range of medicines in its ADHD portfolio."

Yet some believe the ADHD drug market has already grown too large.

William Pelham -- a prominent researcher involved with trials of both
Concerta and Adderall -- says a major government study, sponsored by
the National Institute of Mental Health, showed that behavioral therapy
often eliminates the need for ADHD drugs altogether. During that
one-year trial, he says, 75% of the children who relied on behavioral
treatments functioned well without ADHD drugs. Moreover, he adds, most
of those children remained off the drugs a full year later.

"What this means to me is that two-thirds of ADHD kids could be taken
off the medications," Pelham says. "I'm not saying the drugs are all
bad. They're useful for many children. But I do think they are grossly
overused as a first line of intervention."

Still, Pelham has battled to make his views known. Following the first
Concerta trial, he says, Alza "wanted whole paragraphs cut out" of a
journal article that highlighted the role of behavioral therapy in
treatment. Pelham ultimately won his fight to retain the material, but
he believes that other researchers -- without his stubbornness or
seniority -- often feel pressured enough to back down instead.

"That pressure, whether it is subtle or not so subtle, is always
something you have to deal with," he says. "The drug companies want to
emphasize medications. That is what they are selling."

Catching Conflicts

LeFever's research could hurt that goal.

So far, her opponents have only managed to nitpick. For example, they
pounced on the wording of a single question in one of her studies even
though it failed to influence her overall results. They also
highlighted research that showed much lower ADHD rates instead of more
recent studies that helped support her work.

Still, LeFever has felt herself battling an unimaginable force.

Russell Barkley -- a high-profile expert known to embrace the ADHD
drugs -- emerged with his familiar argument that, if anything, even
more children should be medicated for the disorder. His recent "Without
Boundaries" survey was spearheaded in 2004 by the World Federation for
Mental Health, in partnership with Eli Lilly.

Donald Lewis, a pediatrics professor at LeFever's own medical school,
also took aim at LeFever's work. Lewis did not respond to a phone
message from TheStreet.com. But like many researchers, he could be
answering to more than one boss. The school's directory says that Lewis
actually works for nearby Monarch Research. Notably, Monarch counts
dozens of drug manufacturers among its "collaborators" -- including
Alza, Eli Lilly, Novartis and Shire -- and currently operates four
clinical studies on ADHD treatments alone.

Pelham worries about potential conflicts in the industry and even
points to a shortcoming in his very own work. He believes that
researchers, including himself, should have disclosed their industry
ties when reporting on the big NIMH study of ADHD. Right now, he says,
the reports simply include a footnote -- running for roughly 40 lines
-- about the researchers involved in the study. He says that a second
footnote, exposing industry ties, would be about three times that long.

Pelham says he has tried, but failed, to see that addition made.

"I have argued for five years -- on every paper -- that we should have
a footnote listing those relationships," he says. "But pretty much
nobody else thinks that's necessary or important. ... I always get
outvoted."

Meanwhile, LeFever fears that other researchers -- influenced by their
industry ties -- feel compelled to halt her work.

If so, they seem to have succeeded. Late last year, LeFever says, the
school abruptly placed her on administrative leave and seized the
computers filled with her research. In addition, she says, the school
terminated her latest ADHD project -- financed by a prestigious
government grant -- and banned her from presenting her findings at two
national conferences. Today, she says, she remains shut out of her
university office and restricted from even discussing her most recent
ADHD findings.

LeFever feels like the victim of powerful academic intrusions that,
before, she never dreamed possible.

"This is research that's important for the public interest and the
public good, and they're interfering with that," she says. "It's wrong.
It's an injustice. And it's dangerous."

Shaping Studies

To be fair, others have attacked more mainstream ADHD research as well.

Indeed, scientists Jonathan Leo and David Cohen offered a direct
challenge. "Broken Brains or Flawed Studies?" they asked in a 2003
article published by the Journal of Mind and Behavior. They went on to
tear apart some of the most powerful studies used to support the
prescription of ADHD drugs. Those studies, they said, rely on imaging
tests that seem to show brain differences in normal children and ADHD
sufferers. But, they argued, those studies are faulty because they
compare a control group with children who have already been medicated
with ADHD drugs that could have actually caused the brain changes.

"After 25 years and 35 studies, there is not a single straightforward
experiment comparing typical unmedicated children with an ADHD
diagnosis to typical controls," they concluded. "We are perplexed."

Nor have scientists fully studied the long-term effects of popular ADHD
drugs.

Berkeley professor Nadine Lambert offers one of the more extensive --
and frightening -- reports available. Lambert set out to determine
whether children who take ADHD drugs go on to abuse other stimulants,
such as tobacco and cocaine, as adults. She found a troubling
correlation.

"Childhood use of CNS (central nervous system) stimulant treatment is
significantly and pervasively implicated in the uptake of regular
smoking, in daily smoking in adulthood, as well as ... diagnoses of
tobacco and cocaine dependence," she wrote.

But other experts, including Barkley, have criticized those results.
They call Lambert's study flawed and highlight other research that
contradicts her findings.

Andrea Arcona, a clinical psychologist and former colleague of
LeFever's, sees a pressing need for more extensive ADHD research. She
says that current "long-term" studies often stretch for just a few
months even though they involve drugs that may be taken by children --
beginning as early as preschool -- who will go on to use them for
decades.

"Does it really hurt when kids start taking a drug -- sometimes with
other drugs -- and stay on it for that long?" she asked. "Nobody knows.
The research is just not out there."

PART 4

Excerpt:

"Two years ago, Clinical Orthopedics and Related Research published an
entire report about ethical problems in the industry. The journal
complained that device makers offer surgeons generous gifts -- ranging
from ski trips to stock options to outright cash -- that could sway
them to use products that may not be in their patients' best
interests."

------------------------------­----------------------

Biomet Gains Hinge on Old Standby

By Melissa Davis
Senior Writer
5/12/2005 7:05 AM EDT

When some people look at implant makers like Biomet (BMET:Nasdaq - news
- research) and Zimmer (ZMH:NYSE - news - research), they see a lot to
complain about.

Every year, the medical device companies promote new joint implants and
surgical techniques aimed at improving hip and knee replacements.
Industry-sponsored studies typically show a high success rate for the
new procedures.

But critics say the industry is merely creating the illusion of success
by controlling scientific research and avoiding steps that would pool
independent data on surgery outcomes. These people say the industry has
been miserly in its research-and-development spending, and that as a
result implant science has advanced little in four decades. Yet even
amid these questions about how well their devices work, the companies
continue to make a bundle.

"Industry is proposing new designs and new technologies almost every
day, with increasing costs," Italian physician Paolo Gallinaro wrote in
the journal Orthopedics this year. "However, no real progress has been
made."

Zimmer didn't immediately return a call seeking comment, but Biomet's
founding CEO, Dane Miller, rejects the notion that the companies have
fallen short. He defends the durability and usefulness of his company's
products, as well as the industry's stance on data sharing.

Nonetheless George Cipolletti, who once oversaw knee implant research
for Johnson & Johnson (JNJ:NYSE - news - research), holds a similar
view to Gallinaro's.

"We all sell our products, to some extent, based on unsubstantiated
premises," says Cipolletti, who, together with two other Johnson &
Johnson alums, now runs a competing company, closely held Apex
Surgical. "If we had to base it on clinical data, there would be a lot
fewer designs out there."

In this fourth of five articles exploring apparent conflicts of
interest in the medical business, TheStreet.com looks at the implant
industry's marketing-intensive focus -- and the costs borne by patients
and taxpayers alike.

Catch Phrase

Right now, the new catch phrase -- especially at Zimmer -- is
"minimally invasive surgery."

Zimmer is, in fact, banking much of its future on the new technique.
Already, the company has spent large sums training hundreds of surgeons
to use MIS when implanting its devices. And in theory, at least, MIS
does sound attractive. After all, the procedure -- with its smaller
incisions -- seems like it would cause fewer complications than
traditional surgery. And industry-sponsored research has backed up such
assumptions.

But a rare independent study, conducted by orthopedic surgeons at
Stanford University Hospital, found no significant benefits to MIS at
all. Patients who underwent MIS spent about the same amount of time in
the operating room as those who opted for traditional surgery. They
experienced similar blood loss and transfusion rates. And they stayed
in the hospital just as long and felt about the same when they finally
did leave.

Moreover, the study found, MIS patients suffered more serious
complications. Following surgery, they proved more vulnerable to wound
problems. They also faced bigger setbacks -- such as poor implant
positioning and fit -- that could trouble them down the road.

The researchers saw clear reason for alarm.

"If other studies of the mini-incision technique also show more
component malposition and more serious post-operative complications
than the standard-incision technique, then the long-term results of the
mini-incision arthroplasty may be jeopardized," they wrote in the
Journal of Bone and Joint Surgery. "Until the safety and efficacy of
mini-incision total hip replacement are confirmed in the peer-reviewed
literature by other investigators, we are concerned about the
widespread use of the technique."

Popularity Contest

So far, at least, MIS has yet to achieve the popularity that some --
like Zimmer -- tend to celebrate.

Robert Bourne, chairman of the Canadian joint registry, says that fewer
than 10% of hip and knee replacements currently involve the new
technique. He also says that nobody really knows, yet, whether MIS
implants will perform as well or last as long as traditional devices.

"That will be very important data," he says. But right now, "there's a
lot of hype in the marketplace without a lot of substance."

As it stands now, however, the U.S. has limited access to scientific
data on joint implants in general. Despite recommendations to start a
joint registry here -- and a feasibility study launched years ago by
the American Association of Orthopedic Surgeons -- the U.S. remains
without one.

Bourne hopes to see that change. He says that joint registries have
helped other countries already. Since establishing the first joint
registry in 1979, he says, Sweden has seen its rate of "revision"
surgeries on senior citizens -- needed when original implants fail --
drop to just 6%. In contrast, he says, the revision rate on U.S.
Medicare patients remains three times that. That rate is also higher
than the revision rates in other countries, like Australia and Canada,
that have registries of their own.

"Just about every first-world country except the U.S. has one," Bourne
says. "I think it would be a great thing" if the U.S. followed suit.

But Miller of Biomet stops well short of endorsing a joint registry
that would document actual surgical outcomes.

"Unfortunately, the results of a registry could be misinterpreted if
people are not careful," Miller says. "I think we need to be careful
that a registry doesn't become a shopping list for plaintiffs'
attorneys."

Cipolletti, for one, sees other motives.

"There are very big dollar reasons for large companies to try to
prevent it," he says. "They have a real vested interest in keeping the
status quo the way it is."

Money Game

For one thing, industry insiders say, revision implants cost even more
than the originals.

Medicare pays a capped rate -- around $2,500 or so -- for primary
implants, they say. But it establishes no such cap, they say, for
revisions that often sell for at least $5,000 more.

"The companies make a lot more money on those," says a salesman for one
of the major implant makers. "It's all money-driven."

Others go so far as to claim that most popular implants are almost
designed to fail. When creating the devices, they say, most companies
rely very little on the science -- known as biomechanics -- that would
enable them to create an implant that actually matches a patient's true
physiological condition. Instead, they say, the companies crank out
devices that, if anything, work opposite of human joints.

Edmund Chao, director of the orthopedic biomechanics lab at Johns
Hopkins University, has highlighted this very problem. He says that
current implants are designed to place the "load" -- or the pressure of
a patient's weight -- on the inside of the bone instead of the outside
like normal anatomy. As a result, he says, the bone can remodel itself
in an effort to adapt to the new arrangement -- eventually wearing away
-- and cause the joint replacement to fail in the end.

Miller of Biomet says his company's products hold up extremely well.
Indeed, he puts their long-term success rate in the "upper 90% range."
He also says that Biomet has made a number of significant advances,
ranging from improved bone cementing to enhanced surgical techniques,
over the last few decades.

Still, few seem willing to discuss the science behind this apparent
problem.

"You would think that orthopedic surgery would have biomechanics as a
fundamental prerequisite, much like civil engineering is needed to
design a bridge," Cipolletti says. "Yet many surgeons have little or no
knowledge of the subject. This void could be filled by the implant
companies, but instead they inundate the surgeons -- and, now, the
patients -- with marketing hyperbole."

Ethics 101

To be sure, the big device makers have no problem selling their
implants. Increasingly, however, they have come under fire -- and
government scrutiny -- for some of the tactics they use. Orthopedic
surgeons themselves have actually raised concerns.

David Apple, a section editor at Orthopedics Today, worries about even
some routine practices in the industry. Specifically, he sees ethical
problems with certain contracts, inked by implant makers, that offer
surgeons financial rewards or suggest that they use specific products.

Two years ago, Clinical Orthopedics and Related Research published an
entire report about ethical problems in the industry. The journal
complained that device makers offer surgeons generous gifts -- ranging
from ski trips to stock options to outright cash -- that could sway
them to use products that may not be in their patients' best interests.

The Justice Department has since begun examining cozy relationships
inside the industry. And many insiders believe the government could
eventually uncover plenty.

Different Angle

Some companies, like Cipolletti's, do emphasize product design --
specifically based on biomechanics -- more than marketing.

Cipolletti says that he and his colleagues, all engineers, often felt
frustrated by the lack of focus on an implant's actual performance when
they worked for Johnson & Johnson. So, he says, when Johnson & Johnson
acquired DePuy -- and then moved the implant division to another city
-- the trio decided against relocating and launched Apex Surgical in
the late 1990s instead.

So far, Apex has yet to be in business the decade necessary to track
the long-term success rate of its products. However, Cipolletti says,
the company has seen its implants regularly escape a major problem --
dislocation -- that tends to surface early.

He calls dislocation an "awful" experience for the surgeon as well as
the patient. But, he says, at least one surgeon who uses his implants
has stopped worrying about the problem at all. Indeed, he says, all of
his customers have welcomed the company's new -- if less hyped --
design.

"The doctors who use it regularly -- although there are not very many
-- say they wouldn't change back," he says.

To be fair, Cipolletti says that other companies have relied on
biomechanics to design sound implants as well. However, he is still
waiting for the big players to follow suit and bring about real change.

"If a Stryker (SYK:NYSE - news - research) or a DePuy sold a device
like this, the adoption rate would be much faster," he says. "But 10
years from now, I really think that people will be asking, 'How did I
ever recreate hips properly before?'"

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