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[sSRI-Research] Experimental Drug Kills 4 Year Old Boy

 

Experimental Drug Kills 4 Year Old Boy

 

http://www.canada.com/search/story.html?id=æ130be6-9175-42f1-aaa1-4f4229c470c4

 

Research turns deadly

 

Four-year-old Ryan died at an Ottawa hospital from an experimental drug

given at 25 times the proper dose

 

Margaret Munro

CanWest News Service

 

Thursday, February 26, 2004

 

Four-year-old Ryan Lucio survived the first four drug overdoses. The last

two killed him.

 

Ryan's liver, heart and lungs began to fail. He began bleeding severely and

hallucinating. He died at an Ottawa hospital, two weeks after starting

treatment with an experimental drug which was administered at 25 times the

correct dose.

 

The little boy from Sault Ste. Marie had been diagnosed in early 2002 with

neuroblastoma, a rare and deadly form of cancer. The cancer appeared to be

in remission when his parents, Peter and Maria, learned their only child had

been selected by doctors to participate in an international clinical trial

underway at eight research centres across Canada. They agreed to enrol Ryan

in the Ottawa arm of the trial, hoping the treatment would cure him.

 

Instead, Ryan's death on Sept. 30, 2002, stands as a tragic reminder of how

dangerous clinical research can be. And, as a CanWest investigation has

found, it illustrates how U.S. health authorities are more likely than

Canadian agencies to blow the whistle on scientific and ethical misconduct

involving Canadian researchers.

 

" I am startled by the lack of reaction by Health Canada, " says Professor

Jocelyn Downie, director of the Health Law Institute at Dalhousie

University, whose view is echoed by many of her colleagues.

 

U.S. health authorities, on the other hand, were so concerned they sent an

investigator to Ottawa in January, 2003, to find out how things could have

gone so terribly wrong with a trial funded by the prestigious U.S. National

Cancer Institute.

 

Patricia Murphy, a U.S. Food and Drug Administration inspector, spent a week

at the Children's Hospital of Eastern Ontario in January, 2003, combing

through binders of notes kept on Ryan and the other children who received

the experimental interleukin-2 treatment.

 

Her conclusion, summarized in a letter sent by the FDA to the lead Ottawa

investigator, Dr. Jacqueline Halton, was devastating:

 

" You failed to protect the rights, safety and welfare of subjects when you

administered overdoses of the study drug interleukin-2 that were 22 to 25

times higher than the dose specified in the protocol. "

 

The letter, dated April 14, 2003, goes on to say Ryan died " as a result of

the overdoses, " and another child " suffered adverse events. "

 

The other child, who became ill from the treatments but ultimately survived,

might have served as a warning to the Ottawa researchers that something was

terribly wrong. After receiving 22 times the correct dose during his first

round of four treatments beginning on July 23, 2002, the boy became feverish

and lethargic and developed a skin rash so severe doctors discontinued his

treatment, the FDA notes.

 

But the Ottawa doctors, who had grossly miscalculated how much drug to give

their young charges, failed to realize their error. When Ryan arrived at the

hospital six weeks later, they again miscalculated the dose. This time, the

consequences were deadly.

 

After completing its investigation, the FDA posted the letter castigating

Dr. Halton on its Web site; an unusual move.

 

In contrast, Health Canada has said virtually nothing about the death on its

home turf. Nor did it conduct its own on-site investigation. Indeed, Health

Canada officials are reluctant to discuss the case at all. They would only

answer queries for this story through Krista Apse, a media relations

officer. But Health Canada confirms Ryan's trial and seven related cancer

trials across Canada were, through much of 2002, violating its regulations

that require federal approval of trials before they can begin.

 

Department officials learned in March, 2002, -- seven months before Ryan's

death -- that the trials " had not been authorized by Health Canada, " Ms.

Apse says.

 

Officials discussed stopping the trials but ultimately allowed them to

continue, since the trials had been reviewed and approved by U.S.

authorities. Still, they urged the Canadian researchers to quickly complete

the Canadian approval process.

 

Health Canada officials fired off a letter on March 20, 2002, to Dr. Mark

Bernstein, a children's cancer specialist at Ste. Justine Hospital in

Montreal, who was representing the Canadian researchers running the

unauthorized trials. It advised Dr. Bernstein the eight trial centres were

violating federal regulations and asked him to file the necessary clinical

trial application within four to eight weeks.

 

Dr. Bernstein failed to meet the deadline but did finally deliver the

application on July 24. It was missing what Health Canada describes as

" critical information " about the drug being tested on the children. Memos

between Health Canada officials and Dr. Bernstein continued through the

summer of 2002, which is when the first overdose occurred.

 

Under Health Canada regulations, investigators must report serious,

unexpected, adverse reactions to the department in a bid to catch problems

with experimental drugs early. The Ottawa doctors did not report the fever,

lethargy and a skin rash the first child developed, Ms. Apse says, because

the child's reaction was " initially interpreted as a normally expected side

effect. " The doctors running the trials did, however, consult among

themselves and decided to discontinue the child's treatment, according to

the FDA report.

 

Then the Ottawa researchers made their lethal errors.

 

On Friday, Oct. 4, Health Canada learned Ryan had died. That same day,

officials found out the same group of cancer researchers had " activated "

more clinical trials, once again without submitting applications to Health

Canada for approval.

 

Health officials decided then, seven months after learning of the group's

first set of unauthorized trials, to have a " face-to-face meeting " with the

cancer researchers.

 

The following week, details of Ryan's overdose and death were made public in

an emotional news conference by doctors at the children's hospital, who took

full responsibility for his tragic overdose. No mention was made that the

trial was violating Health Canada regulations.

 

After Ryan's death, the doctors involved in the cancer trials requested

" provisional clinical trial approval " for the trials, Health Canada

documents say. The department refused.

 

Ms. Apse says Health Canada officials did meet with the cancer researchers

after Ryan's death. She says the doctors suspended enrolment of patients in

the unauthorized trials " of their own accord " while completing the

long-overdue authorization process. The trials were finally authorized on

Oct. 25, 2002, more than seven months after they started and a month after

Ryan died.

Health Canada says it saw no need to send an investigator to the hospital

located a short drive from the department's Ottawa headquarters. On-site

inspection " was not deemed necessary, " as the children's hospital supplied

all the information needed by e-mail, fax and telephone, Ms. Apse says.

 

Dr. Bernstein and the co-chairs of the Children's Oncology Group (COG),

which helps co-ordinate the trials -- Dr. Max Coppes, director of the

children's cancer program at Alberta's Children's Hospital in Calgary and

Dr. Victor Blanchette, chief of hematology and oncology at the Hospital for

Sick Children in Toronto -- declined requests for interviews. But in

e-mails, Dr. Bernstein and Dr. Coppes suggested trials undergo a rigorous

approval process in the United States and indicated more approvals by Health

Canada delays trials.

 

" We strongly believe that COG clinical trials need to be available to

Canadian children without undue delay, " Dr. Coppes said in an e-mail.

 

" Other jurisdictions, such as New Zealand and Australia, allow for mutual

recognition of multinational studies that have been reviewed by competent

authorities such as the U.S. Food and Drug Administration and the Cancer

Treatment and Evaluation Program without requiring further review, " Dr.

Bernstein writes.

 

The researchers may be making a valid point that Canadian rules should be

changed, but it does not excuse their decision not to comply with existing

rules. Moreover, Prof. Downie thinks Health Canada has made a big mistake in

failing to enforce its own rules.

 

By letting the cancer researchers break the rules for so long, Prof. Downie

says, Health Canada sent a message to the research community that " not much

happens if you don't comply. "

 

Fourth in a Series; Tomorrow: Rubber-stamping medical trials.

© National Post 2004