Healthy Skepticism Library item: 1285

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Publication type: news

Deadly clinical trial wasn't approved by Health Canada
CBC Radio 2003 Jun 12
http://www.cbc.ca/canada/ottawa/story/2003/06/12/ot_lucio20030612.html

Full text:

OTTAWA – CBC News has learned a clinical trial for a cancer drug that killed a four-year-old boy last year at the Children’s Hospital of Eastern Ontario wasn’t authorized by Health Canada.

Ryan Lucio died last year after he was given an overdose of the cancer drug Interleukin-2. He was given a dose 25 times what it should have been.
FROM OCT. 8, 2002: Drug error kills child with cancer
INDEPTH: A Matter of Trust: drug trials in Canada
Government documents obtained by CBC under the federal Access to Information Act reveal that, at the time of Lucio’s death, Health Canada allowed the clinical trial at CHEO to go ahead without the department’s legal approval.
ACCESS DOCUMENT: A chronology prepared for senior Health Canada officials after Ryan Lucio’s death – obtained through access to information (PDF file)
The hospital says it was under the impression that the trial had “conditional approval,” but there is no such thing as conditional approval under Health Canada’s regulations.
The trial at CHEO was one of several in Canada and the United States that treated children with a rare, and often fatal, form of childhood cancer called neuroblastoma.

When Ryan Lucio died, the hospital was quick to admit that it made the mistake.

ACCESS DOCUMENT: Talking notes prepared for Health Minister Ann McLellan – obtained through access to information. Note the declassified information at the end of page 2. (PDF file)
Dr. Simon Davidson spoke on the hospital’s behalf shortly after the death.
“As many as 15 professionals, many of different backgrounds, reviewed the protocols, and we had a system failure in which this young man was given too much [Interluekin-2],” said Davidson.

The hospital reviewed Ryan Lucio’s death and came up with a series of recommendations officials say will prevent similar incidents from occurring in clinical trials.

The U.S. Food and Drug Administration conducted its own investigation into the problems with CHEO’s clinical trials. It issued a warning letter to CHEO’s Dr. Jacqueline Halton saying, “We have determined that you violated regulations governing the proper conduct of clinical studies involving investigational new drugs.”

RELATED LINK: FDA warning letter sent to CHEO’s Dr. Jacqueline Halton, April 14, 2003

Health Canada sat in on the FDA investigation, but didn’t do its own.
Another boy named Ryan

But Ryan Lucio’s death is linked to the story of another boy with the same name and the same disease, who took part in the same clinical trial at CHEO.

DOCUMENTARY: Tragic Trials: Bob Carty’s documentary look at the unauthorized clinical drug trials at CHEO, from The Current (Runs 15:21) [Documentary transcript]
Last year at this time Ryan Carroll, now two and a half years old, was in cancer treatment. His mother Anne was hoping that the clinical trial at the Children’s Hospital of Eastern Ontario would keep him alive.
Then something went wrong.

“His body was covered in a rash. He was very clingy. He lost his appetite [and] he should have improved a lot more than he had,” says Anne.

It turns out that Ryan Carroll was accidentally given an overdose so severe-22 times greater than it should have been-that he had to be taken off Interleukin-2.

Those side effects should have been reported to Health Canada. But the sponsor of the trial, a North American network of researchers called the Children’s Oncology Group, didn’t do that for Ryan Carroll.

AUDIO: CBC reporter David McKie presents the story of the unauthorized trials on Ottawa Morning, with host Lucy van Oldenbarneveld [Runs 11:24]
“I don’t believe we had the information about that adverse reaction,” says Ken Moore, Health Canada’s risk process manager at the biologics and genetics therapies directorate.
The significance of the lack of reporting of adverse events and monitoring is not lost on Anne Carroll.

She and her husband wonder, ‘What if?’ What if her son’s adverse reaction had been reported to Health Canada? Would the overdose that cost Ryan Lucio his life have been prevented?

“I guess that will always haunt Michael and I, and the Lucios,” says Anne Carroll.

Health Canada and CHEO insist the lack of approval had nothing to do with Ryan Lucio’s death.

However, they concede that approval would have ensured the trial was monitored more closely.

The hospital looked into the death of Ryan Lucio, and made recommendations, but that investigation took place behind closed doors.

Dr. Alex MacKenzie, CHEO’s director of research, says they were charged with doing a system review, not a public investigation.

Despite that explanation, questions nag bio-ethicist Douglas Kinsella, a retired doctor who lives in Kingston. He’s also professor emeritus of Medical Bioethics at the University of Calgary.

Kinsella says CHEO had no right to conduct its investigation behind closed doors.

“[It] has been demonstrated for 40 years that people don’t learn very well from that kind of a system. So it should be public. Absolutely,” says Kinsella. “And I think it not only should be public, I think that the government should consider the question of regulating, by legislation, human research in this country.”

Kinsella says greater transparency by institutions running clinical trials is the best way to ensure that patients desperate to survive are treated fairly and humanely.

The Canadian representative for the trial’s sponsor, Dr. Mark Bernstein of Montreal’s Sainte-Justine Hospital, suggested to the CBC it was more important to offer the drug trials to the children than to meet Health Canada’s requirements.

“The question is what does that do to the availability of these trials to children with cancer, sometimes advanced cancer, who need that therapy,” said Bernstein.