Here, Kiddie, Kiddie

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http://www.alternet.org/drugreporter/20594/

 

Here, Kiddie, Kiddie

 

By Kelly Hearn, AlterNet. Posted November 29, 2004.

 

How drug companies are pushing ADHD drugs for children by funding

researchers and advocacy groups – and ignoring the studies which

question their claims.

 

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.

 

For 17 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 – is

spiraling.

 

" 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 it. "

 

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 children.

 

And evidence suggests Haislip may be right.

 

" It Was Like A Whitewash "

 

Enter Dr. William Pelham, director of the Center for Children and

Families at State University of New York at Buffalo (SUNY).

 

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 (CHADD).

 

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 allegations.

 

" 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. "

 

Pelham says 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 Concerta. "

 

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.

 

Sins of Omission

 

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 use. "

 

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 height.

 

" 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 topic. "

 

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.

 

Potentially most damaging to stimulant sales is that medications like

Ritalin may not work over the long run and that behavioral

modifications may serve just as well.

 

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 know. "

 

Front Groups?

 

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 website.

 

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.

 

But 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' offices.

 

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 conference.

 

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 Interest (CSPI).

 

Profitable Research

 

Criticism of 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 physician's involvement. "

 

But conflicts can clearly arise, especially with something so

controversial and hard-to-define as ADHD.

 

Dr. Russ 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 way. "

 

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 interest.

 

" 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 researcher. "

 

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 works. "

 

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.

 

Kelly Hearn is a correspondent for The Christian Science Monitor and a

former science and technology writer for UPI.