CANADA: UBC Broke Federal Ethics Rules By Failing To Adequately Warn Patients
University fixed drug-trial breach after discovering shortcomings

Margaret Munro
CanWest News Services

Wednesday, February 25, 2004

The University of British Columbia for years broke federal ethics rules and failed to warn patients of all the dangers
and side-effects associated with its medical experiments and drug trials, CanWest News Service has learned.

Federal officials were so concerned about the breach, which was not fully resolved until late last year, they
threatened to freeze funding and suspend patient enrolment for many of the affected projects at UBC and its affiliated
hospitals, according to documents obtained in response to an Access to Information request.

In all, 523 projects, funded variously by industry, non-profit agencies and Canadian and U.S. government agencies, and
involving treatments for everything from dementia to cancer, were not properly approved before they went ahead. Of
these, 399 were still going on when the federal government was told of the breach in March 2002.

In one study, patients were not told an experimental drug might increase the risk of cancer. In another project,
patients were not informed a drug might cause fertility problems, the documents say.

The federal agencies now say they are satisfied that UBC "recognized the significance of the breach," and in the end no
trials -- most of them in the faculty of medicine -- were shut down.

But officials at the Canadian Institutes of Health Research (CIHR) and the Natural Sciences and Engineering Research
Council (NSERC), the country's two largest research funding agencies, were so concerned when they learned of the
problem they threatened to freeze funding for the 44 projects they were financing if UBC did not respond to their
concerns "within two weeks."

They also scolded UBC officials for taking 10 months to report the breach and for appearing to be more concerned about
research funding than patient safety. "Your priority order appears to be inappropriate," said a letter to UBC co-signed
by senior officials from the two federal agencies.

It emphasized the need to make patient safety the priority.

Meanwhile, Health Canada was pressing UBC to quickly review projects involving new drugs, most of which were industry
funded. "Should this review not be conducted, Health Canada will be required to contact clinical trial sponsors to stop
further enrolment in the approved trials at the UBC clinical trial site," Dr. Robert Peterson, a Health Canada
official, told UBC on May 21, 2002. He gave the university six weeks to complete the reviews.

UBC had discovered a year earlier, in May 2001, its research ethics board had been cutting corners for years. The
board, which must approve projects before they can start, tended to only look at brief project summaries. The practice
violated federal rules that say ethics boards must review detailed project protocols, which can run for more than 100
pages. The protocols are considered key because they often reveal problems with experiments and risks for patients.

Dr. Indira Samarasekera, UBC vice-president of research, said in a recent interview the university acted quickly once
the problem was discovered. It revamped its ethics review process and dug out the full protocols to determine if any
risks had been missed. She says she waited 10 months to inform then Health Minister Anne McLellan because it took time
to determine how many projects had not been properly reviewed.

Federal officials didn't buy it.

"Although I acknowledge that the workload must have been (and remains) huge, the argument for not informing us earlier
is not convincing!," NSERC official Isabelle Blain wrote in an e-mail to colleagues at CIHR shortly after Samarasekera
informed McLellan of the breach.

Other documents show officials were concerned UBC had still not completed the re-review of the trials more than a year
after the problem was discovered. "Attitudes seem to be hardening" at Health Canada, says one memo. "Their lawyers are
getting very nervous about slowness in response."

Samarasekera says in the end only 399 trials needed to re-reviewed for risks -- "side-effects like a headache or a
rash," she said. No studies had to be cancelled. But consent forms needed to be amended in 37 studies. In only two
cases did patients have to be "reconsented," says Samarasekera, who said she did not know the specifics of the two
cases.

Documents released by CIHR show that, in all, 523 trials were affected, but 124 were not re-assessed because the
studies were over, did not enrol patients or the protocol was no longer available. Of the 399 projects re-reviewed, 215
were deemed to have "potential ethical issues." The most common problem, found in 126 studies, was "missed risks." Most
of the studies were no longer enrolling patients, so in only 37 cases did consent forms have to be amended. Seventeen
studies had potential long-term risks -- "cancer etc." -- that might occur even after the intervention had stopped.
UBC's re-review committee decided that in only two studies did patients need to be asked to sign a revised consent
form.

In one study, which appears to have been an experimental cancer treatment, patients had not been told the drug might
cause "some forms of cancer." In another study, patients were not told an experimental drug had the "potential to
produce fertility problems."

Federal granting agencies can freeze funding to universities that violate the federal ethics policy, known as the "tri-
council" policy statement, which requires ethics boards to look at full protocols. The agencies work in confidence with
institutions and do not publically report on problems.

Samarasekera's March 7, 2002, letter to McLellan generated a blizzard of paper in Ottawa, as officials at Health
Canada, the CIHR and NSERC tried to decide what do about the "most serious" breach.

Officials at the research councils seemed dismayed at the approach taken by UBC, which receives more than $300 million
worth of research grants each year, much of it from federal agencies and industry.

"You learned of the noncompliance issue in late August 2001. Why did you not inform us until March 2002?" CIHR and
NSERC officials asked in a letter sent to UBC shortly after they learned of the problem. They added: "Have you
considered informing the subjects involved in the trials? If not, why not?"

In a follow-up letter on May 17, 2002, the same officials said they would permit funding for affected projects to
continue as long as UBC responded to their concerns "within two weeks."

"We want to emphasize the seriousness that we attach to the problems identified at UBC," the letter said. It stressed
the need to complete the re-review "as rapidly as possible" and to ensure " maximum protection to the subjects of these
trials."

Of "great concern" to officials was UBC's decision to re-review industry-funded projects first, government-funded
trials second and UBC's in-house studies last, a decision officials said seemed to indicate UBC was more concerned
about "the source of funding, rather than the risk to the subjects." The letter went on to say: "In this respect, your
priority order appears to be inappropriate."

But the next week, Health Canada's Peterson fired off a letter to Samarasekera informing her the university had to
complete the re-review of projects involving new drugs within six weeks, or sponsors would be told and enrolment of new
patients would be stopped. He makes no mention of the need to inform patients enrolled in the trials.

Samarasekera initially told health officials the re-review would be complete by July 2002 but it took until November
2002. The university did not file its final report with the federal government until November 13, 2003, saying "follow-
up with principal investigators took some additional time."

The federal documents also raise serious questions about UBC's re-review. They show UBC was in such a hurry to try to
fix things it continued to break federal rules until November 1, 2001, six months after the problem was discovered.
This is because UBC failed to include two people "with broad relevant research experience" on the ethics board that was
reviewed the projects, as required by federal regulations.

Another memo released by CIHR said "it is vital that U.S. funding agencies be advised of UBC's difficulties with its
REB (research ethics board) process. This is not only important for UBC's reputation but also for the entire Canadian
process and the reciprocity which it enjoys with U.S. regulators." U.S. granting agencies that fund research in Canada
accept approvals from Canadian ethics boards as equivalent to those done by ethics boards in the U.S.

Other documents suggest UBC should not have been left solely in charge of the re-review. "Some form of independent
external audit of the re-review results would have brought greater openness and accountability to the process," says
one memo.

But lawyers and ethicists say UBC's problems point to serious failings with Canada's ethics review system, which is
supposed to ensure medical experiments and drug trials are scientifically and ethically sound and that people
volunteering are informed of all the potential risks.

It is estimated up to 1.8 million Canadians, many of them chronically ill, enrol in clinical trials each year.

They say the government needs to be much more proactive and open about identifying problems and resolving them in a way
that instills public confidence and enables the research community to learn from mistakes.

"The system is broken," says Prof. Jocelyn Downie, director of the Health Law Institute at Dalhousie University, whose
view is echoed by many medical ethicists.

They also say UBC's problems are not unique. "We know that several institutions across the country are non-compliant
with the tri-council policy," says Downie.

- - -

FEDERAL OFFICIALS RAISED PATIENT-SAFETY QUESTIONS

In March 2002 the federal government learned that the University of British Columbia had not observed federal ethics
rules and failed to warn patients of all the dangers and side-effects associated with its medical experiments and drug
trials. A correspondence ensued and excerpts are shown here:

March 19, 2002

Therese Leroux, director of Canadian Institutes of Health Research ethics office, writes to the University of British
Columbia (individual recipient blacked out by government officials in document released under freedom of information
law; full page shown at far right) questioning how the university was responding to the discovery of "partial
compliance" with ethics protocols. The university is asked whether it considered informing subjects involved in the
trials.

May 1

Replying to March 19 letter, a UBC representative (name blacked out) writes to Leroux explaining why the university
thought trial subjects would be harmed more by information about risks than by the actual possibility of new risks.

May 2

E-mail from Isabelle Blain of the Natural Sciences and Engineering Research Council (NSERC) to Leroux raises concerns
about non-compliance. Extract shows one of six points raised.

May 17

Leroux, in a letter to UBC (individual's name blacked out), raises concerns about perception that the university was
more concerned about risks to funding than about the safety of individuals participating in the trial.

May 21

Robert Peterson, director general of the federal Therapeutic Products Directorate, writes to Indira Samarasekera, UBC's
vice-president of research. He demands that UBC re-review trials approved when UBC's research ethics board "did not
reflect" requirements.

Third of a Series

SOURCE: The Vancouver Sun
http://tinyurl.com/2qyuy

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