02/20/2001 – Drug Trials – Give us your children!

This situation is only getting worse and fast! This incredible article by the
Boston Globe shows us the dangerous potential in using our babies as guinea
pigs. As I said in my article “Our Next Generation of Medical Guinea Pigs –
Our Prozac, Zoloft, and Paxil Babies,” warning of this and written two years
ago, “If witnessing our children suffer like this is not enough to wake us up
to this nightmare, I DO NOT WANT TO SEE WHAT IT WILL TAKE TO WAKE US UP!!!!”

This time I made sure to include a link so that if the article is cut off,
you can go to the original Boston Globe site and finish reading it. Please
share this with your family and friends.

Ann Blake-Tracy, Executive Director,
International Coalition For Drug Awareness
www.drugawareness.org
__________________________________________

http://www.boston.com/dailyglobe2/049/nation/Dangerous_dosageP.shtml

Dangerous dosage

To make pediatric medicine safer, thousands of children are being used to
test drugs originally designed for adults. Tragically, the side effects can
sometimes prove deadly

By Alice Dembner, Globe Staff, 2/18/2001

First in a series of occasional articles on medical trials involving children.

Gage Stevens might have taken his first steps that bleak morning in November
1999. And by his first birthday, he would probably have outgrown his one
persistent ailment – acid reflux. Instead, he lay in the Allegheny County,
Pa., morgue.

His mother, Gretchen Stewart, had taken him to a specialist at Children’s
Hospital of Pittsburgh the spring before he died, seeking to ease the baby’s
crying as the acid irritated his esophagus. Dr. Susan Orenstein recommended
Gage enter a study she was running to find ”the safest, most effective
treatment for esophagitis in infants” using the ”best available”
medications, according to the consent form Stewart signed.

But the experimental treatment triggered a heart rhythm disturbance that
killed the 9-month-old, the coroner found. By that time, the key drug,
Propulsid, had also been linked to many adult deaths.

”They told me they were just trying to see how effective it was. Had I known
it was a dangerous drug, I would never have let him take it. Who in their
right mind would?” said Stewart of Homestead, Pa., who has filed a wrongful
death suit against the doctor, the hospital, and the drug’s maker, Janssen
Pharmaceutica.

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, according to an investigation by The Boston Globe. These
tragedies, ethicists suggest, are a harbinger of troubles ahead as a federal
push to test more medicines in children kicks into high gear this year.

An estimated 45,000 children are participating in industry-sponsored testing
of new drugs, up from about 16,000 in 1997, according to Christopher-Paul
Milne, senior research fellow at the Tufts University Center for the Study of
Drug Development. ”Although researchers are looking pretty hard at the
ethical issues, there’s greater risk if you increase the number of children
being studied,” he said.

The rush to experiment on children has been triggered by federal initiatives
intended to improve the safety of drugs for children. Three-quarters of the
medicines used in children have never been fully tested for safety and
effectiveness in them, including heavily prescribed drugs such as the asthma
medication Albuterol. And children have been hurt when doctors lacking that
information prescribed inappropriate doses of drugs marketed for adults.

In response to appeals from pediatricians, since late 1997, Congress has
offered drug companies a lucrative six-month extension of patents on drugs
already on the market if they test them on children. Also, as of last
December, Food and Drug Administration policy requires that any new drugs be
tested on children as well as adults.

Drug companies are already pouring an estimated $1 billion a year into
pediatric testing, according to CenterWatch of Boston, which tracks the
industry. The additional sales of a single blockbuster drug during an extra
six months without competition from cheaper generics could offset that entire
investment.

The increase in pediatric research, which builds on a longer tradition of
testing children in cancer and AIDS research, has brought some benefits.
Since 1997, 14 drugs have been newly labeled with instructions for use in
children as a result of the push, while studies on dozens more have been
completed and are awaiting review by the FDA. Many of the tests are safe and
ethical.

But an examination of research in children since 1994 shows that the potent
combination of vulnerable children, ambitious researchers, potential profits,
and weak oversight can hold great peril for those children. From deadly
infections in Memphis to a troubling misdiagnosis in Arkansas, children have
suffered in the name of science.

In the case of Propulsid, the manufacturer, the doctor, and Children’s
Hospital deny that the drug caused Gage’s death.

”We believe it’s not possible to establish a direct causal relationship with
the administration of the drug. We learned that the infant had been brought
to the ER several days prior [to his death] with serious respiratory
illness,” said Janssen spokesman Greg Panico.

However, county coroner Cyril Wecht is convinced that a reaction to the drug
– not a respiratory problem – killed the child. Although autopsy can never
prove arrhythmia, he said he ruled out all other possible causes.

”We’re satisfied that … we are not acting prematurely, unwisely, unfairly,
or unscientifically,” said Wecht, who is also a nationally known commentator
on high-profile cases.

Moreover, Propulsid was linked to potentially dangerous heart rhythm problems
even before it was approved for adult use in 1993. By 1997, as doctors
increasingly used their discretion to prescribe Propulsid to children despite
the lack of federal approval, the FDA stepped in. Armed with reports of
cardiac deaths of three young children taking Propulsid, regulators suggested
that Janssen test the drug in children or provide a stronger warning label.

Janssen provided the warning label but held off on its own large trials,
instead providing the drug free to researchers, including Dr. Orenstein in
Pittsburgh. Orenstein enrolled about 100 children in her study, which
compared Propulsid given with and without another drug, Tagamet, against a
placebo.

Neither Orenstein nor her lawyer responded to requests for interviews and
hospital officials declined to explain why the study was conducted in a way
that seemed contrary to the FDA warning that Tagamet might increase
Propulsid’s heart risk.

In the months after Gage’s death, the FDA received reports of more than 100
cardiac deaths in people taking Propulsid, including 19 children whose
doctors had prescribed it. Janssen pulled it from the market last July.

”The country is still learning how to study children ethically,” said
Robert Ward, chairman of the American Academy of Pediatrics Committee on
Drugs, stressing that he could not comment directly on the Propulsid case.

Cancer centers have been at the forefront of clinical testing in children,
with long-standing research programs for all forms of the disease. But even
they may not set the best example, despite good intentions.

Three children died of complications in an experiment at the internationally
known St. Jude Children’s Research Hospital in Memphis in 1998 and 1999, as
researchers tried to improve the five-year ”cure rate” for acute
lymphoblastic leukemia, normally one of the most treatable forms of the blood
cancer.

The children, whom the hospital declined to identify, died of infections or
seizures apparently caused by the first phase of the multifaceted drug and
radiation experiment, according to Dr. William Evans, the hospital’s
executive vice president. The death rate in the first phase of the trial,
three of 53 children, was double the usual rate.

Inspectors with the federal research protection office, acting on a
complaint, faulted the hospital for failing to report the deaths promptly
both to the government and to the hospital’s ethical review board, so they
could decide if other children’s lives were at risk.

An independent review, required by the government, later concluded that the
hospital did not unjustifiably delay reporting the deaths and tried to adjust
the experiment to make it safer. Nonetheless, with the deaths still
unexplained, the hospital abandoned the study and agreed to hire an ombudsman
for patients in future studies.

”We have since modified the treatment and had no problems,” said the lead
researcher, Dr. Ching-Hon Pui, who declined to talk in detail about what
happened, saying, ”I still feel bad and I don’t want to refresh my memory.”

Even when cancer researchers know that an experiment may increase the child’s
risk of death, it’s not clear that they always fully inform the children or
their parents.

Two children died suddenly and two more suffered life-threatening infections
in the first phase of a leukemia experiment conducted in 2000 – nine years
after researchers at Dana-Farber Cancer Institute in Boston warned of an
unusually high rate of death and infection in similar chemotherapy.

Among the first 32 children enrolled in the Pediatric Oncology Group study at
sites across the United States, Canada, and Europe, a 10-year-old girl died
from a fungal infection and a 5-year-old girl succumbed to a septic
infection. In addition, a 12-year-old went into shock and a 19-month-old
suffered a brain inflammation, according to a study report.

Researchers at Dana-Farber had warned about just such a tragedy from using
the same drug, dexamethasone, in a four-drug combination during the first
stage of treatment for acute lymphoblastic leukemia. ”The toxicity
associated with dexamethasone used during induction therapy outweighed its
potential benefits,” the Dana-Farber researchers wrote in the journal Cancer
last April, spelling out their earlier warning.

But doctors at the Pediatric Oncology Group, with the approval of the
National Cancer Institute, believed that a change in an antibiotic prescribed
along with dexamethasone would prevent a recurrence of the toxic reactions in
Boston.

Looking back, Dr. William Bowman, the study chairman, said he wasn’t sure
whether the children and their parents were told of the specific risk
suggested by the Boston study. They were warned, he said, about the usual
risk of death during the induction phase for this type of leukemia – about 2
percent. In this case, the death rate was three times higher.

Ultimately, the Pediatric Oncology Group substituted another drug for the
dexamethasone in the first phase. ”We didn’t want to take the risk any
longer,” Bowman said.

Today, other researchers are reluctant to criticize Bowman’s team, since
dexamethasone shows such promise against cancer. ”Part of our task is to
fine-tune how we use these drugs in an attempt to improve outcomes. Sometimes
very small changes have adverse outcomes and sometimes they have positive
outcomes,” said Dr. Stephen E. Sallan, chief of staff at Dana-Farber.

But Boston University medical ethicist Leonard Glantz said the doctors should
have spelled out the risks and alternatives for the parents. ”Certainly
parents should be told when you have a responsible medical authority who
thinks the risks of a particular regime are especially high. It appears there
were some alternatives that reasonable scientists would argue were less risky
for the children.”

There is strong reason to believe that deaths and injuries in research
involving children are more widespread than what is reported to government
offices that handle complaints. For one thing, parents of children with
serious diseases often see drug trials as their best option and are less
likely to complain later if something goes wrong. In addition, many parents
erroneously believe signing a consent form detailing the risks of the
experiment means giving up their right to a remedy.

”They think if something negative happened, `Well, I accepted it and I have
nothing to complain about,”’ said Abbey Meyers, president of the National
Organization for Rare Disorders, a patient advocacy group.

Adding to the difficulty of assessing the scope of research injuries, neither
drug companies nor the FDA typically release information about problems in
drug trials, unless the drug is approved. And even after approval, the FDA
drags its feet in releasing details of the trials. Moreover, there is no
national effort to track the testing of children or any central review of the
reports of side effects.

”It’s likely we wouldn’t be aware of it unless a patient or their parents
brought it to public attention or there was an investigation by [the US
Department of] Health and Human Services. Things could happen very easily and
no one would know about it,” said Dr. Ralph E. Kauffman, director of
research at Children’s Mercy Hospital in Kansas City, Mo., and a leader of
the movement to test drugs in children.

Kauffman, like many researchers, believes that the new testing program is
much safer than the current system in which doctors prescribe drugs without
knowing their effects. ”The risk to a child in a well-run clinical study is
much less than the risk of a child receiving that drug in a doctor’s office
without specific information on dosing,” he said.

For instance, the antibiotic chloramphenicol was widely used for infections
in premature infants until a study in 1959 discovered that babies were unable
to metabolize the drug and it was killing them. The drug had only been
approved for use in adults for infections resistant to penicillin.

Such problems led the American Academy of Pediatrics to campaign for testing
of drugs in children in the late 1970s. But drug companies resisted, citing
the difficulties of finding qualified researchers and parents willing to
volunteer their children as well as the legal liabilities. While a few
companies pursued the pediatric drug market, many saw no financial reason to
do so since drugs approved for adults could be legally prescribed to children.

But an act of Congress in 1997, giving companies financial incentives to test
drugs in children, has led to a flood of testing. Milne, of Tufts, estimates
600 industry-funded studies are underway, double the number in 1997.

The initiative has spurred the creation of a testing infrastructure,
including government-supported centers around the country. In New England,
Yale University houses one center, where 10 studies are ongoing. New England
is also home to two other big players in the private sector – Parexel
International of Waltham, a contract research organization that recently
established a pediatric division, and Kelson Pediatric Partners of Hartford,
which says it has developed a network of pediatric researchers with access to
a pool of 120,000 children. Boston’s academic medical centers have seen a
small increase in testing.

So far, there are no indications of abuses of the magnitude of those at the
Fernald State School in Waltham during the 1940s and 1950s when retarded
children were given radiation-spiked cereal in a test sponsored by MIT and
Quaker Oats.

But there are plenty of troubling examples of research that demonstrate weak
oversight of the burgeoning wave of studies.

In the case of Propulsid, the FDA finally took Dr. Orenstein to task for
numerous failings in her study. But its review came five months after Gage
Stevens died.

FDA investigators found she failed to report to her hospital review board a
number of earlier problems resulting from the drugs, including the case of a
baby who had to be hospitalized when he briefly stopped breathing.

In addition, the FDA noted egregious errors in the consent form that the
Stevens family signed, including the incorrect claim that Propulsid had been
approved for use in children and a failure to spell out known risks.

Stewart and her husband, Scott Stevens, filed a wrongful death suit last
September that also accuses

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12/29/2000 – Boston shooting – involvement of Prozac & other antidepressants

As so many of you have been asking since Tuesday, here is
the official data from the Boston Globe on the Prozac use and
use of other antidepressants in the shooting that took place
the day after Christmas in the Boston area. It is very rare that the
information about the drug use comes out to the public so quickly. Generally
it is kept quiet until the case goes to court. We must
commend the Boston Globe for continuing to have the courage
to educate the public about this group of very dangerous drugs.

In the highlighted paragraphs 12 and 13, Kevin Reddington, the
attorney, states that he will ask experts to consider whether
McDermott’s medication (Prozac & other antidepressants)
contributed to the rampage.

Ann Blake-Tracy, Executive Director,
International Coalition For Drug Awareness
www.drugawareness.org

http://www.boston.com/dailyglobe2/364/metro/Questions_and_grief+.shtml

Questions and grief

Police seeking clues to what set off rampage in Wakefield

By Brian MacQuarrie, Globe Staff and Ralph Ranalli Globe Correspondent,
12/29/2000

Three minutes before the shooting rampage that killed seven of his
co-workers, Michael McDermott received a brief telephone call in his work
cubicle at Edgewater Technology Inc.

A Chrysler Financial supervisor informed McDermott that his 1994 Plymouth
Acclaim would be repossessed, according to a source familiar with the call.

”I won’t be needing it; come pick it up,” answered McDermott, seemingly so
unconcerned that the supervisor made a note in her log.

It was 11:07 a.m. Tuesday. Three minutes later, the carnage began. Within 15
minutes, authorities say, McDermott had murdered seven people.

A law enforcement source said yesterday that State Police have heard of the
telephone call and are investigating its connection to the slayings.

The call may have been the final insult for a man squeezed by a tightening
vise of financial worries.

Already informed that the Internal Revenue Service would seize a large
portion of his pay for back taxes, McDermott had a tense confrontation last
week with an Edgewater accountant who rebuffed his plea for a cash advance
and pay raise. The accountant, Rose Manfredi, told McDermott to take his
concerns about money to Edgewater’s president.

Manfredi’s mother said yesterday that her daughter, who handled much of the
company’s billing and payroll, had been so unnerved by McDermott that she
shared her concerns with the family.

”She told me last week, `Mummy, he was kind of nervous,”’ Carmella Manfredi
said. ”She was scared of him.”

On Tuesday, McDermott heard that his car, with a book value of only $5,930,
would be seized for nonpayment of a 1997 loan.

Haverhill police told the Globe they checked McDermott’s Bartlett Street
apartment several times on Christmas Eve and early Christmas morning after
his car had been spotted close to a wooded area where gunshots were reported.

Police said two spent shotgun shells were found on the ground near where
McDermott’s car – with the distinctive license plate MUCKO – had been seen. A
young woman said she also saw a man closing the trunk of the car.

”It sort of sends shivers down my spine,” said Haverhill Police Sergeant
Stephen Brighi, who reported that police did not find McDermott at his
apartment that night.

Yesterday, McDermott’s lawyer said he will consider an insanity defense. The
attorney, Kevin J. Reddington, said he will ask experts to determine whether
McDermott’s medication, which sources have said includes Prozac and other
antidepressants, contributed to the rampage.

”The medication is an issue,” Reddington said. ”It will be explored in
this case.”

McDermott, 42, pleaded not guilty to seven counts of first-degree murder at
his arraignment Wednesday in Malden District Court. He is being held without
bail in Middlesex County Jail in Cambridge, pending a Jan. 31 court
appearance.

Last night, opposite the converted 19th-century mill that houses Edgewater
and other companies, about 800 people filled St. Joseph Catholic Church for
an ecumenical memorial service.

The methodical slaying of seven people at the Internet consulting company
ranks as one of the worst mass murders in Massachusetts history.

After allegedly shooting two people in the reception area and three employees
in Human Resources, McDermott reportedly reloaded and shot open the locked
door to the accounting office, authorities say.

There, he allegedly shot Paul Marceau, 36, of Melrose, three times in the
chest, as Marceau tried to scurry away on his back. Manfredi, 48, was hit
twice in the legs before a shotgun blast to the head ended her life. Another
woman in the room may have survived only because she hid underneath her desk
and behind a coat on her chair.

The other victims were Jennifer Bragg Capobianco, 29, of Brighton; Janice
Hagerty, 46, of Stoneham; Louis Javelle, 58, of Nashua; Cheryl Troy, 50, of
Beverly; and Craig Wood, 29, of Haverhill.

Manfredi, a Lexington resident who handed out paychecks every two weeks,
appears to have been a prime target. Investigators said McDermott allegedly
used both an AK-47 assault rifle and a shotgun to shoot her. A rare Spanish
handgun made in 1914 was tucked in his pants, authorities say.

Manfredi’s mother and one of her three sisters, Florence Holleran, said
McDermott and Manfredi ”had words.” Neither woman knew further details of
McDermott’s request.

”Rose said [McDermott] was perturbed at a lot of people when he heard the
IRS was after him,” according to Nat Manfredi, one of four brothers.
”Naturally, he would have gone to the accounting office Tuesday.”

At the arraignment, Assistant District Attorney Thomas F. O’Reilly said
Edgewater was preparing to garnishee McDermott’s wages at the direction of
the Internal Revenue Service. Under that plan, McDermott said, he would have
been left with only $275 in pay every two weeks, according to Middlesex
District Attorney Martha Coakley.

IRS officials said that they cannot comment on McDermott’s tax situation, but
that he should not have been surprised by the decision to take part of his
salary. They said McDermott should have received at least two notices, by
mail or in person, informing him that a portion of his wages would be seized,
according to IRS policy.

However, the IRS ensures that debtors are left with enough of their salary to
live on, said Peggy E. Riley, an IRS spokeswoman in Boston. Under IRS
regulations, McDermott also should have been offered an installment plan or
another way to pay off the debt.

Edgewater Technology began grief counseling sessions yesterday for its
employees, about 80 of whom were at work Tuesday. The company plans to
renovate the office and move the accounting department out of the area of the
shooting.

Shirley Singleton, the president and chief executive officer, said Edgewater
has donated $70,000 to create a foundation at Fleet Bank for the victims’
families. The company also has given each family an additional $5,000 for
immediate costs, a source said.

Outside the brick building yesterday, a makeshift memorial with flowers and a
teddy bear had been set up by co-workers and other mourners.

The concern also extended to Beacon Hill, where a spokesman for Governor Paul
Cellucci predicted that the state’s strict gun restrictions would be
tightened even more.

”We’re in general agreement and general support of strengthening our gun
laws,” said John Birtwell, the governor’s spokesman, who added that
solutions also should be sought on a national level.

Yesterday, the future seemed far away for the Edgewater worker who escaped
death by hiding under her desk. Her nightmare this week, however, was still
too close.

When approached at her home, where flowers and friends were trying to ease
the recent trauma, the woman greeted a reporter with a sad, slow shake of her
head.

”I’m not ready to talk about it,” she said. ”I don’t think I’ll ever talk
about it.”

Patrick Healy, Stephen Kurkjian, Farah Stockman, Rick Klein, Adam Pertman,
and Jamal Watson of the Globe Staff and Globe correspondent Regina Montague
contributed to this report.

This story ran on page A01 of the Boston Globe on 12/29/2000.
© Copyright 2000 Globe Newspaper Company.

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6/13/2000 – Quandary Over Prozac – Boston Globe Editorial

http://search.boston.com/globe.vts

A BOSTON GLOBE EDITORIAL

The Prozac Question

Eli Lilly, manufacturer of the highly successful antidepressant drug Prozac,
wants to have it both ways. While it has always insisted that the drug does
not cause even a tiny percentage of its users to contemplate suicide, it also
wants to sell an updated version of Prozac with a patent which states
specifically that one of its advantages over the original is that it is less
likely to cause suicidal thoughts.

Now the firm has been caught in this contradiction by a Houston lawyer whose
clients unsuccessfully sued Lilly after their father killed his wife and then
himself while on the drug. By the time of the trial last year, Lilly had
bought rights to the new patent, boasting of its superiority over Lilly’s
original Prozac, whose patents expire in 2004.

The lawyer says his clients would have gotten a fairer trial if Lilly had
come forward with that language, and he is now asking a federal court for a
new trial. His clients deserve that chance, and the Food and Drug
Administration should ask Lilly why, in light of the language in its new
patent, it is not warning current Prozac users about suicidal thoughts.

Even if it had been aware of the new patent language, the jury might still
have exonerated the drug manufacturer. Prozac is hailed by many health
professionals for treating often debilitating depression and actually
preventing suicides. And while a small percentage of Prozac users have
committed suicide, it is not easy to prove that it was the drug and not the
underlying illness that was the cause.

Lilly, for its part, notes that a separate company developed the new version
of Prozac and wrote the patent language for it before Lilly acquired the
patent. And Lilly says ”not all of the `side effects’ listed in the patent
are scientifically demonstrated facts.” But why should a patent have been
issued for a new version of Prozac if it does not reduce side effects like
suicidal thoughts?

The FDA should reopen the question of whether the patent language on the new
Prozac is not a warning that users and prescribers of the original Prozac
should have been receiving all along. The patent’s message should also be
conveyed to a jury in a second trial of the Houston lawyer’s case.

This story ran on page A26 of the Boston Globe on 6/13/2000.
© Copyright 2000 Globe Newspaper Company.

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4/16/2000 – More from Boston Globe on Drug Safety Issues

This story ran on page A10 of the Boston Globe on 5/15/2000.
© Copyright 2000 Globe Newspaper Company.

A BOSTON GLOBE EDITORIAL

Better drug reporting deal with a wide range of conditions, from depression
to osteoporosis, doctors are reaching increasingly for their prescription
pads. Patients who consume these drugs have faith that any side effects other
patients have had are carefully reported by physicians and monitored by
officials so that, if need be, warnings can be issued.

That faith is misplaced.

While the drug companies and the US Food and Drug Administration have a
system for maintaining an adverse-event database, doctors are not required to
report the serious problems patients have with a drug. As a result, there are
distinct limitations in the system to track bad reactions and then add new
warnings on the drug’s label or withdraw it altogether. Public Citizen, a
watchdog group in Washington, D.C., reports that actual surveys of medical
records turn up 10 times as many drug reactions as are reported voluntarily
by doctors.

Under current practices, drug companies are required to alert the FDA within
15 days of any severe reactions to drugs and within a year of less serious
reactions, but without more mandatory reporting by practitioners (hospitals
and nursing homes are required to make such reports), companies’ own
awareness of problems will be stalled.

If reporting by doctors of bad reactions were mandatory, both the FDA and Eli
Lilly and Co. would know more than they do about some of the problems
connected with Lilly’s popular antidepressant, Prozac. While Prozac and
similarly acting drugs have been hailed by both doctors and patients for
relieving symptoms that can often presage suicide, there have long been
reports of extreme agitation and anxiety among a small percentage of users.

One argument against mandated reporting of adverse reactions from doctors is
the extra paperwork this would entail. But, for the past several years, the
FDA has maintained a Web site that permits doctors – and patients – to make
online reports with little fuss. Closer monitoring could give both health
professionals and the public a greater awareness of what to be alert for as
they make use of the drugs that are changing American medicine.

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