CIRCARE: Citizens for Responsible Care & Research
A Human Rights Organizaiton
mailto: veracare@...
''It is sad, sick and reprehensible that researchers, corporations or those
who call themselves healers would toy with children's lives as if they were
somehow less than human.'' An estimated 45,000 children participate in
industry-funded drug research this year, up from 16,000 in 1997.

Even before the recruitment initiative kicks into high gear, regulators are
finding violations of human protections at the nation's premier research
centers. Tragedies are bound to multiply because-- unlike the protections
afforded to laboratory animals under the Animal Welfare Act, 1966-- there
are no safeguards to protect children, nor penalties to deter researchers
from violating ethical standards.

Government oversight agencies are weakening current Federal regulations
rather than strengthening them. They are attempting to broaden the inclusion
criteria for children who have no medical condition to serve as research
subjects.

Lack of protection has already resulted in deaths. The Boston Globe reports
that researchers at the National Institutes of Health deceived families,
used undue pressure to get their children in a pacemaker experiment that was
unlikely to help them and ended tragically. The parents of a child who died
say they were misled into believing the child was getting the best care in
the nation, then they learned that government doctors betrayed their trust.
"Federal regulators later found that Fananapazir and other NIH doctors
overstated the potential benefits of pacemakers, downplayed the risks and
didn't offer enough information about alternatives." The family of another
child in the study also have filed suit, alleging that the pacemaker made
him sicker.

The Globe reports that the Government refused to provide public information
about the outcome of the experiment, including the number of children helped
and harmed. And the doctors involved are being shielded by Government
lawyers.

In another experiment at Yale, researchers are exposing children-- who have
no medical diagnosis-- to a powerful drug that may damage their brains. The
experiment is being conducted on the medically unsupportable THEORY that the
drug will prevent schizophrenia. Indeed, a Federal investigation "found
that psychiatrists failed to fully inform 32 children and adults about the
side effects of a schizophrenia drug that the subjects were given. In
addition, regulators faulted Yale's ethical review of the research."

Refering to the rationalization of deceptive recruitment practices, Paul
Gelsinger, whose son became an uwitting sacrificial lamb in a research
experiment that killed him, said:

''There's a lot of thinking that it's OK to sacrifice a few human beings for
the welfare of others. It's not right.''

CIRCARE is especially concerned about the trafficking of children for
profit: "About 25 percent of pediatric studies in 1999 advertised some
compensation for the children or parents, according to a survey by an NIH
researcher. Amounts typically ranged from $200 to $400, but occasionally
reached $1,000."

And who compensates the children or families when harm is done? Who is held
accountable when tragedies occur?
~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~



http://www.boston.com/dailyglobe2/079/science/Teddy_bears_and_veiled_threats
P.shtml


THE BOSTON GLOBE

Teddy bears and veiled threats
By Alice Dembner, Globe Staff, 3/20/2001

Second in an occasional series.


Jennifer Munger was literally dancing her way through life when a government
doctor convinced the little girl's parents that her rare heart condition was
likely to worsen if she didn't get a pacemaker immediately.


Victor and Lydia Munger say their daughter had virtually no symptoms from
the hypertrophic cardiomyopathy that made her vulnerable to heart failure.
With the defect controlled by medication, Jennifer was active, even taking
dancing lessons.
But Dr. Lameh Fananapazir of the National Institutes of Health persuaded the
family to enter Jennifer in an experiment in September 1994 in which she
would get the pacemaker to regulate her heartbeat instead of drugs.


Fourteen months later, the 8-year-old collapsed and died at her school
playground in Southbury, Conn. Only afterward did her parents find out that
exercise tests at the NIH in Bethesda, Md., showed she had been doing worse
with the pacemaker than without it.


''Fananapazir had his own set of rules,'' said Victor Munger, who, along
with his wife, has filed a federal lawsuit against the NIH and several
doctors, including Fananapazir. ''It doesn't appear that he was held to any
standards.''


Amid a rising wave of medical experiments involving children, there is
growing concern about the tactics some researchers are using to attract
parents and their children as test subjects. Regulators are increasingly
finding that some researchers sidestep protections and engage in outright
coercion.

Over the last three years, a Globe investigation has found, federal
regulators have cited more than three dozen hospitals and universities -
including some of the nation's most prestigious - for breaking research
rules protecting children.


Even when rules aren't broken, researchers often work in an ethical gray
zone by offering children or their parents gift certificates to McDonald's
or toy stores, or as much as $400 to take part in research that may expose
them to risk.
''It's a huge issue,'' said Brian P. O'Sullivan, a pediatrician who chairs
the human subjects committee at the University of Massachusetts Memorial
Hospital in Worcester. ''You don't want parents to make a profit by offering
their child as a guinea pig.''


For the Mungers, there is bitter irony mixed with their grief. They say they
took Jennifer to the National Institutes of Health believing they were
getting the best care in the nation, and the government failed them. Federal
regulators later found that Fananapazir and other NIH doctors overstated the
potential benefits of pacemakers, downplayed the risks and didn't offer
enough information about alternatives. The family of another child in the
study, Douglas Gray Jr., also have filed suit, alleging that the pacemaker
made him sicker.


Government lawyers said NIH would not comment about the case because of the
pending suits. But speaking to the broader issue of NIH's place at the
center of medical research, deputy director Michael Gotteson stated: ''We
should be the paragon of virtue. The requirements are complex and we try to
follow them. Most of the time we succeed.''


But following the rules ''most of the time'' may not be enough. As the Globe
reported on Feb. 18, medical experiments across the country appear to have
killed at least eight children and subjected hundreds more to harmful side
effects in the last seven years. Without stronger enforcement of the rules,
ethicists fear a jump in the number of tragedies as an estimated 45,000
children participate in industry-funded drug research this year, up from
16,000 in 1997.


Driving the increase is a federal initiative aimed at improving drug safety
that has made pediatric research quite lucrative. Companies may get a
six-month extension on patents for existing drugs in exchange for studying
their safety and effectiveness in children, potentially boosting drug sales
by hundreds of millions of dollars.
The federal effort is expected to improve children's health by providing
detailed information about which drugs are safest and work best for them.
But researchers say they are struggling to recruit enough children for their
studies, in part because of parents' resistance to any experimentation on
their children.


''The number one roadblock to pediatric research is recruitment of qualified
volunteers,'' said Kathleen Drennan, president of Drennan Healthcare
International, a Chicago-based consulting firm. ''It will be an expensive
endeavor that will require a lot of creativity.''


To solve the test subject crunch, some researchers are moving experiments
overseas, while others are enlisting help from specialists like Drennan.
Still others are resorting to unethical tactics.


Even before the initiative kicks into high gear, regulators are finding
violations of human protections at leading research centers. For instance,
regulators temporarily shut down all research at Duke University in North
Carolina after finding pervasive gaps in protections for patients of all
ages.


At Yale University, the federal Office for Human Research Protections found
that psychiatrists failed to fully inform 32 children and adults about the
side effects of a schizophrenia drug that the subjects were given. In
addition, regulators faulted Yale's ethical review of the research. Yale
subsequently overhauled its review process, paying special attention to the
children's rules.


''What good does it do us to have a set of protective regulations if they're
widely ignored,'' asked Dr. Peter Lurie, deputy director of Public Citizens
Health Research Group.


Today's protections for children were developed in response to historical
abuses, such as the 1970s case in which doctors used promises of a bed at
Willowbrook State School in New York City to get parents' permission to
inject their mentally retarded children with hepatitis in order to study the
disease.


The rules, which build on regulations governing all human experimentation,
recognize children's vulnerability - both to coercion and to physical harm.
Experimental drugs that may leave adults unscathed could slow the
development of children's growing brains and bodies. In addition, adults may
be able to weigh the risks of research, but most children cannot.


Thus, the rules reserve the most invasive research for the sickest children,
and allow risky tests only if researchers can show that they might help the
children. Both parents and children must agree to the research, and review
committees with pediatric expertise must scrutinize the experiments before
they begin.


But many believe the protections are flawed. Congress plugged a major
loophole last fall, extending the rules for the first time beyond
government-funded studies to most industry research as of this April. Still,
no rules require that tests be conducted first in adults. No rules
specifically cover the cash flowing to researchers or the gifts offered to
attract children to participate. And little protects parents of seriously
ill children for whom a clinical trial has come to symbolize hope.
''Without an education in the ethics and an understanding of how much money
is at stake, parents can't really make an informed decision about letting
their children take part,'' said Paul Gelsinger, whose son, Jesse, was
killed in a gene therapy experiment in September 1999.


University of Pennsylvania officials had decided the experiment was too
risky for children and required Jesse to wait until he turned 18 to
participate. But Paul Gelsinger, of Tuscon, Ariz., said the family didn't
learn of the true risks - including deaths in animal studies - or the
researchers' financial stake in the study until after Jesse's death.


''There's a lot of thinking that it's OK to sacrifice a few human beings for
the welfare of others. It's not right,'' he said.
University of Pennsylvania officials have said they have no intention of
sacrificing anyone, but have acknowledged serious problems with the
experiment, paying Gelsinger an undisclosed amount to settle his wrongful
death lawsuit.


In the pacemaker research, some parents say NIH doctors used undue pressure
to get their children in an experiment that was unlikely to help them and
ended tragically.


The researchers, led by Fananapazir, a cardiac surgeon, put pacemakers into
68 children between 1992 and 1996 to test whether the devices could treat or
cure an inherited disease called hypertrophic cardiomyopathy that can cause
thickening of the heart and sudden death. Because the theory was unproven,
the experiment - supported by pacemaker manufacturers - was supposed to
target children not helped by medication.


From the time of her diagnosis at 7 months, Jennifer Munger had been treated
successfully with drugs. She took weekly dance lessons from age 3 and was a
cheerleader for the local Pop Warner team. Her father, Victor, said that for
years they resisted Fananapazir's insistence that they enroll her in the
study because ''the only course for Jen was a pacemaker.'' Then, during a
checkup, Fananapazir said he detected an obstruction in her heart and told
them that if they waited much longer, a pacemaker would not be as effective
in improving her condition. Frightened, Victor and Lydia Munger agreed to
the pacemaker operation.

In their lawsuit filed after Jennifer's death, the Mungers question whether
Jennifer ever had an obstruction and say Fananapazir never discussed other
treatment options and never told them there were signs she was getting worse
with the pacemaker. ''We think her death could have been prevented,'' Victor
said, most likely by keeping her on the medication that had been working.

''Fananapazir had one mission - proving pacemakers worked'' for hypertrophic
cardiomyopathy, Victor Munger said. ''It seems there was a lot of
self-interest in his decisions.''


Douglas Gray Jr.'s parents say they were also stampeded into a pacemaker for
their son without even being told it was an experiment. Gray was 12 and
quite sick when Fananapazir told Gray's parents he would die if they didn't
act quickly, Judith Gray said.


Fananapazir offered three options, she said: Medications that already had
failed Doug, a heart-thinning operation that Fananapazir said might kill
him, and the pacemaker, which he presented as a terrific choice. When Gray
and her husband asked for time to consider the options, she said,
Fananapazir told them funding for the pacemakers was running out.
''He had my husband and me scared to death,'' she said.


After Fananapazir implanted the pacemaker, Gray became so weak he could
barely walk the 25 yards to the family's mailbox at their home in Roanoke,
Va. He was repeatedly hospitalized and had to be schooled at home, according
to the Grays' lawsuit. Finally, the couple took Douglas to another doctor,
who recommended heart-thinning surgery. Doug recovered quickly and, at 21,
now works full-time and enjoys long walks and other exercise.
''I know I was used,'' said Douglas Gray.


A government lawyer barred the NIH doctors from talking with the Globe. The
government also refused to provide public information about the outcome of
the experiment, including the number of children helped and harmed. In its
response to the suit, the government denies any coercion, negligence or
responsibility for Jennifer's death or Gray's ill health.


Today, Fananapazir is still conducting research at the NIH, although he was
demoted and subjected to greater scrutiny. According to the NIH Web site, a
version of the children's experiment is ongoing.


''Research in children should be treated with 10 times the level of caution
as research in adults,'' said Lisa Salberg, who resisted the NIH's attempts
to recruit her niece and daughter into the pacemaker study after her sister
died in a similar test.

''It is sad, sick and reprehensible that researchers, corporations or those
who call themselves healers would toy with children's lives as if they were
somehow less than human.''


Darcy Trick had a similar experience. When her 5-year-old daughter, Molly
Foley, was diagnosed with an inoperable brain tumor in March 1999, Trick
said an East Coast children's hospital, which she declined to name for fear
of retribution, pushed her to enroll Molly in a national experiment with the
drug taxotere.


''One doctor played hardball,'' said Trick, who lives in Virginia. ''He told
us if we didn't proceed immediately, Molly would die very quickly.


''I think they knew that what they were offering to Molly would not help
her. But there are so few children with brain tumors that they need to use
them - they need their bodies.''
Trick and her husband decided to spare Molly from the trial's ravaging
chemotherapy in her last days.


Theodore Zwerdling, the national director of the Children's Oncology Group,
acknowledged that the study was testing a long-shot treatment because
no