Dr. William Pelham, a leading ADHD researcher for 30 years, is the latest

[Guest guest]

ALLIANCE FOR HUMAN RESEARCH PROTECTION (AHRP)

Promoting Openness and Full Disclosure

www.ahrp.org

 

FYI

 

A newly released report by the Center for Disease Control-Health US

2004--reveals how effective the pharmaceutical industry is in

marketing its

drugs-whether or not they are beneficial; whether or not they cause severe

harm--they sell. Antidepressants showed the largest increase in

use-prescriptions for children of both antidepressants and

psychostimulants

soared. See: http://www.cdc.gov/nchs/hus.htm

 

Confessions by insiders and an examination of the evidence leave little

doubt that the that the promoters of these drugs claims are

unsubstantiated,

that integrity of medicine and the biomedical literature have been

systematically corrupted thanks to collaborative efforts of the

pharmaceutical industry and their paid prominent academic consultants.

 

Dr. William Pelham, a leading ADHD researcher for 30 years, is the latest

insider to come forward: " 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. "

 

Dr. Pelham was paid by McNeil to conduct one of three studies used to get

FDA approval for Concerta, a stimulant prescribed for ADHD. But when the

evidence was not favorable, he recounted in an interview with AlterNet,

McNeil-Alza engaged in dubious methods to ensure that the published

reports

would be favorable for Concerta. He said " 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. 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. "

 

Dr. Pelham notes: " It's really misleading and I'm surprised the FDA is

letting them use the studies to advertise no side effects. 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. "

 

Pressure was also brought to bear to shape Dr. Pelham's written

report: 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). " 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. " In the end, Dr. Pelham says, they published a report

with

his name penned to it without his authorization.

 

Last week, the New York Times referred to the pillars of American

psychiatry

as " data-deprived academic researchers " when caught issuing an

unsubstantiated report claiming that antidepressants do not increase the

risks of suicide in children. These " data-deprived " researchers represent

psychiatry's elite research establishment-including a former director

of the

National Institute of Mental Health. The report was issued by the

prestigious American College of Neuropsychopharmacology (ACNP)-whose

members

are by invitation only. Their dominance in psychiatric research

practices--

and their influence on practice guidelines and public policy cannot be

overstated.

 

The Alliance for Human Research Protection calls upon medical journal

editors to disinfect the scientific literature by putting these authors'

other published reports through rigorous re-assessment-not by the authors'

collegial peers--but by independent scientists. Otherwise journals such as

JAMA may be accused of publishing " junk science. "

 

See: Leo J and Cohen D. Broken Brains of Flawed Studies? Journal of

Mind and

Behavior, Winter, 2003, Vol 24, pp 29-56, available online at:

http://psychrights.org/research/Digest/NLPs/criticalreviewofadhd.pdf

 

*Dr. David Cohen is a member of the board of directors of AHRP.

 

Contact: Vera Hassner Sharav

212-595-8974

veracare

 

 

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

AlterNet

Here, Kiddie, Kiddie

By Kelly Hearn

Posted on November 29, 2004, Printed on December 3, 2004

 

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.

 

© 2004 Independent Media Institute. All rights reserved.

 

FAIR USE NOTICE: This may contain copyrighted (© ) material the use of

which

has not always been specifically authorized by the copyright owner. Such

material is made available for educational purposes, to advance

understanding of human rights, democracy, scientific, moral, ethical, and

social justice issues, etc. It is believed that this constitutes a 'fair

use' of any such copyrighted material as provided for in Title 17 U.S.C.

section 107 of the US Copyright Law. This material is distributed without

profit.