For Gene Haislip, a former official of the U.S. Drug Enforcement Agency, the
perennial debate over Ritalin, the stimulant commonly prescribed for children
with "attention deficit hyperactivity disorder (ADHD)," is an aching reminder of
a moral battle he fought - and lost - to big drug companies.
years, the now retired director of the DEA´s Office of Diversion Control set
production quotas for controlled substances like methylphenidate (MPH), the
federally restricted stimulant commonly known as Ritalin. During that time, he
fought hard to raise public awareness about over-prescribing of stimulants to
children, about the drug's high rate of street diversion, and about its
long-term health impact on young patients.
"This affects the most
sensitive part of our population," says Haislip, now a consultant for drug
companies on issues of compliance to federal law. "When I was at the DEA, we
created awareness about this issue. But the bottom line is we didn't succeed in
changing the situation because this - prescribing methylphenidate, for example -
"A few individuals in government expressing concern can't
equal the marketing power of large companies," he adds. "I have doubts that the
truth is driving this issue. It seems that market forces and money is behind
As public scrutiny of drug companies grows, so do questions about
what critics say is a vast over-prescribing of MPH, especially as more adults
are taking other MPH-based medicines such as Concerta. According to the DEA,
production of the central nervous system stimulant, which is pharmacologically
similar to amphetamines, grew from 5,000 kilograms in 1993 to 20,967 kilograms
in 2002 - probably the largest ever prescribing explosion for a controlled
substance, says Haislip.
Echoing the sentiments of many in and outside
the scientific community, Haislip says he suspects the dubious marketing tactics
of big drug money have fueled the spiraled use of MPH. Specifically, he suspects
the compromise of a small group of prolific ADHD researchers whose work is
funded by corporate producers of ADHD drugs. He also suspects that one or more
ADHD patient advocacy groups that receive drug company donations have
essentially become fronts to push the prescribing of stimulants to
And evidence suggests Haislip may be right.
Like A Whitewash"
Enter Dr. William Pelham, director of the Center
for Children and Families at State University of New York at Buffalo
A leading ADHD researcher for 30 years, Pelham is a former member
of the scientific advisory board for McNeil Pharmaceuticals, which produces
Tylenol and markets Concerta, a popular stimulant medication trademarked by Alza
Corp. of Mountain View, Calif. Over his career, Pelham has penned over 250
research papers on ADHD, many with industry grants. In 2002, he was given a
lifetime achievement award by the world's largest ADHD patient advocacy group,
Children and Adults with Attention Deficit/Hyperactivity Disorder
In interviews with AlterNet, Pelham provided glimpses into the
dubious methods drug maker McNeil-Alza uses to ensure that studies it funds
produce favorable results for its ADHD medications.
Between 1997 and
1999, he was paid by McNeil to conduct one of three studies used to get FDA
approval. The company currently uses the three studies to claim that 96 percent
of children taking Concerta experience no problems in appetite, growth, or
sleep. But Pelham says the studies were flawed. The original intent of the
studies was to measure both side effects and main effects of the drug. But two
of the three studies, including Pelham's, required that the subjects had to
already be taking MPH and responding well to it in order to enter the study. In
other words, by stacking the studies with patients already successfully taking
stimulants, McNeil ensured the subjects would be unlikely to register side
effects, Pelham says.
"It's really misleading and
I'm surprised the FDA is letting them use the studies to advertise no side
effects," he says. "They had no side effects because they took only people with
only a positive history of medication. This is really pushing meds without
telling the full picture."
There was also pressure from the company to
tweak the findings, he says. Part of Pelham's study involved "providing parent
training to parents, having a simple behavioral program in place on Saturday lab
days, and establishing simple behavioral programs in the children's regular
school classrooms." When his paper was in the galley proof stage at the medical
journal Pediatrics, Pelham says he joined a conference call with a number of
senior people from the corporation who lobbied him to change what he had written
in the paper.
"The people at Alza clearly pushed me to delete a paragraph
in the article where I was saying it was important to do combined treatments
(medication and behavioral)," he says, adding that they also pushed him to water
down or eliminate other sentences and words that did not dovetail into their
interests. "It was intimidating to be one researcher and have all these people
pushing me to change the text."
McNeil offered no direct response to the
"We cannot comment on unsubstantiated allegations," says
Gary Esterow, a spokesman for McNeil Consumer & Specialty Pharmaceuticals,
in a written statement. "The protocols and full study reports for these clinical
trials were reviewed by the FDA, and provided the basis for FDA approval. Prior
to publication, there was ample opportunity for full discussion of the data
among the investigators. Publication of the findings reflect the prevailing
opinion of the authors and is further supported by the peer review process of
the scientific journals in which these studies appear."
McNeil didn't stop there. The company commissioned a follow-up study on the
conversion study mentioned above. This time McNeil did the data analysis and
coordinated the paper writing. "I insisted on seeing the analyses and having
major inputs into the manuscript and it was like pulling teeth to get wording
and analyses changed," he says. "It was like a whitewash, a praise to
Pelham says the company submitted the paper twice to the
Journal of the American Academy of Child and Adolescent Psychiatry. Drafts were
sent to Pelham several times but he says he never returned anything with his
signature. In the end, however, he says the paper was accepted without his
knowledge and published with his name on it.
Besides pressuring researchers they fund, companies also
seem to pepper their direct-to-consumer marketing materials with only the
science that favors their products.
Makers of stimulant medications fight
hard to downplay several longstanding theories.
One theory is that
consistent use of stimulants suppresses a child's growth. Concerns increased in
April when the journal Pediatrics published a federally-funded study, the
largest yet investigating the long-term health impact stimulants have on
children. That study, funded by the National Institutes of Mental Health and
known as the MTA Follow Up Study, found that consistent use of the stimulants
stunts growth in children at a rate of about one inch every two years. The study
also questioned a theory, apparently one still promoted by drug companies, that
children make up lost growth over time.
Yet some seven months after the
study was published, neither Novartis, the maker of Ritalin, nor McNeil mention
the study in their web-based marketing materials.
An information document
for prescribing physicians found on the Concerta web site tells doctors that
Concerta causes "no clinically significant impact on growth with long-term
Likewise, the Ritalin website says stimulants may cause "initial,
mild slowing of growth," but tells consumers the effect is temporary, that
children will make up the lost growth and eventually reach their normal
"We used large, well-designed studies to provide factual
easy-to-understand information to readers," says Denise Brashear, a spokeswoman
for Novartis. "There are hundreds of studies conducted regarding methylphenidate
treatment making it difficult to include every study on each
In their written statement
to AlterNet addressing questions for this article, McNeil officials did not
respond to a question regarding the MTA Follow Up Study.
damaging to stimulant sales is that medications like Ritalin may not work over
the long run and that behavioral modifications may serve just as
According to Pelham, who is on the steering committee for the MTA
studies, much of his research, as well as data gleaned from the MTA studies,
shows the efficacy of medication declines over time.
"No drug company in
its literature mentions the fact that 40 years of research says there is no
long-term benefit of medications," he says. "That is something parents need to
The pharmaceutical industry has long
donated money to patient advocacy groups that critics say become conduits for
spreading industry-friendly information.
In the world of ADHD advocacy,
CHADD, based in Landover, MD, is an 800-pound gorilla, claiming 20,000 members
and 200 affiliates, even offering members a CHADD Visa Card. Though the
organization, which also engages in lobbying, claims to provide "science-based,
evidence-based information about ADHD" to parents and the public, critics say
CHADD basically promotes stimulant medications manufactured by its corporate
donors. Pharmaceutical companies - including Novartis and McNeil - donated a
total of $674,000 in fiscal year 2002-2003, making up 17 percent of the group's
budget, according to CHADD financial documents posted on its
Pelham, who is currently listed by CHADD as a member of its
professional advisory board, came face to face with what he says are the group's
glaring conflicts of interest.
In 2002, after he received the CHADD Hall
of Fame Award, he was subsequently interviewed for Attention!, the
organization's magazine. In the interview, Pelham said, among other things, that
stimulant drugs have serious limitations when employed alone and at high doses.
He also pointed out that psychosocial treatments should be the treatment of
first choice in ADHD, with adjunctive medication when necessary.
eight months later, after CHADD's board of directors tried to quash the article,
CHADD published Pelham's interview - but with large swaths cut out, particularly
his comments about the limitations of the stimulants.
"In recent years, I
have come to believe that the individuals who advocate most strongly in favor of
medication - both those from the professional community, including the National
Institutes of Mental Health, and those from advocacy groups, including CHADD -
have major and undisclosed conflicts of interest with the pharmaceutical
companies that deal with ADHD products," Pelham wrote in a foreword to the
unedited version of the article he provided AlterNet. "I believe that parents of
ADHD children and the public at large should be made aware of this situation.
That is one of the points that I was attempting to make in my interview. As I
think is clear from examining the edited sections, the CHADD CEO and board of
directors did not share my concerns."
Chadd officials say their board is
not involved in any aspects of the magazine and that some of Pelham's claims
"were not scientifically supported."
"CHADD did not withhold information
because of pressure from pharmaceutical companies," says Phyllis Anne Teeter
Ellison, who chairs the editorial advisory board for the magazine. "After
extensive review and consultation with the scientific community, CHADD took a
responsible position by not publishing some of Dr. Pelham's unsubstantiated
claims that were not supported by available data and were not supported by his
colleagues on the MTA group."
But some drug makers no doubt find the
magazine interesting: Peg Nichols, CHADD's director of communications and
executive editor of Attention!, confirmed that Shire Pharmaceuticals, makers of
the stimulant medication Adderall, buys 65,000 of the 100,000 copies each print
run. Shire sales representatives, in turn, place them in doctors'
Pelhams suspects his comments in the article, while edited
heavily, were still "conservative" enough to cause problems with his
pharmaceutical industry contacts. For several years, Pelham has hosted a
conference on treatment for childhood mental health disorders for which drug
companies, including McNeil and Shire, have provided educational grants. Since
the article ran, he says his former contacts have not underwritten the
Other types of organizations
are also targets for pharmaceutical industry contributions. Concerta.net, for
example, references guidelines issued by the American Academy of Pediatrics and
the American Academy of Child & Adolescent Psychiatry that recommend
stimulant medications like Concerta as the first choice of treatment for
children with ADHD.
Those prominent trade groups also have links to Big
Pharma. McNeil, according to a document from The American Academy of Pediatrics,
has given at least $25,000 in donations to the academy. It could not be
confirmed if AACAP receives direct donations but links do exist. Dr. Graham J.
Emslie, a professor at the University of Texas Southwestern Medical Center and a
consultant for McNeil, serves on the corporate contributions and research
committee for the AACAP, according to the Center for Science in the Public
industry-funded research is growing. But drug companies dismiss claims of
conflicts of interest, saying industry needs experts and has long turned to them
for clinical trials. Moreover, says Brashear of Novartis, "when the results of
the trial are published or presented, there is transparency about the
But conflicts can clearly arise, especially
with something so controversial and hard-to-define as ADHD.
Barkely, considered by some to be the world's leading ADHD expert, says he has
taken money from drug companies and that problems can occur when financial
connections run too deep. "Whenever there is a financial arrangement between
people or organizations, there always exists the potential for a conflict of
interest and to influence the outcome of that arrangement," he says. "That is
just human nature. It does not mean that one always does exist or that the
products of such arrangements are always biased adversely in some
Barkely recognizes potential conflict of interest can arise when
findings from the study don't merge perfectly with the commercial interest of
the drug company. But many researchers, he says, insist on "unrestricted" grants
that give researchers a green light to conduct the study and promote the results
in ways that don't just advance the company's financial
"Nevertheless, if the researcher wants subsequent grants from a
drug company, there may be an indirect conflict of interest for researchers
here," says Barkely. "But so long as consumers want drug companies to produce
state-of-the-art, safe, and well-tested drugs for disorders, you cannot then
restrict drug companies from having access to the world's leading researchers to
help them in providing such products."
For Barkely, the real test is a
matter of degree, that is the percentage of a researcher's income that's
directly derived from grants or consulting arrangements, not simply whether or
not such an arrangement exists.
"I consult for four or five drug
companies a year, yet I derive less than 10 percent of my income from such
consultations and speaking engagements for them," he says. "It is the degree of
support that can raise the specter of a conflict of interest and not just the
existence of a relationship. And we especially want to know if the researcher
has stock options, royalties, or other financial arrangements with the company
such that results which are favorable to the drug in a research project result
in a proportionate and direct financial advancement of the
Most scientific journals, Barkely points out, require
researchers to say in their articles what, if any, financial arrangements they
have with a commercial interest that supported the research or may be mentioned
in the article.
"The results from drug company-funded research are not
essentially different from federal studies," says Eugene Arnold, an ADHD expert
and Ohio State University researcher who has taken money from drug companies.
"Much of the new research funding surge has been for development of better
products, such as longer-lasting delivery formulations. In order to obtain FDA
approval, the companies have to sponsor research to demonstrate efficacy and
safety. Naturally, they turn to experts in the disorder and its treatment to
help do that research."
Arnold says that all
researchers heavily involved in new product research take money from drug
companies. But he points out that research supporting efficacy of MPH,
amphetamine, and other FDA-approved drugs for ADHD was originally done in the
1930s, '40s, and '50s without drug company support and even now some studies are
done solely with federal funding.
Sam Goldstein, a clinical neurologist
and member of the faculty at the University of Utah who has in the past served
as a general consultant for drug companies and authored educational materials
for them, says the profit motive can hurt research in other ways. "The nature of
our capitalist system is such that if there is a profit to be made it is much
more likely a treatment will be investigated," he says. "There are many good
psychosocial treatments that with sufficient research would probably benefit
children with ADHD. No one is going to fund them because there is no profit to
be made. I don't think this is a bad thing. It is just the way the system
Goldstein notes that the system of industry funding has produced
medications that have dramatically in a positive way altered the lives of
millions of people.
"For me the issue is not so much ethics but the fact
that only those treatments that stand to lead to profit are funded for
research," he says.
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