By Margaret Munro CanWest News Service
The critically ill patients, many of them struggling for breath as tiny sacs in their lungs filled with fluid, were in no shape to quibble with the Vancouver doctors who recruited them into an experiment.
The patients, and their legal guardians, willingly agreed to have catheters inserted into their bodies and extra fluids left in their lungs as part of an international study comparing treatments for acute respiratory distress syndrome – a baffling and often fatal inflammatory lung condition The patients were not informed, however, that joining the experiment might hasten their death, U.S. health officials later concluded. Or that it might cause kidney failure or brain injury, and impair the recovery of their lungs if they survived.
The project was funded by the U.S. National Institutes of Health and conducted at the University of British Columbia and more than a dozen U.S. medical centres. The huge trial proved so controversial that it was suspended in 2002, and the U.S. Office for Human Research Protections launched a nine-month investigation.
In the end, all the research centres were reprimanded for not properly informing patients of the risks.
UBC received an 11-page letter from the agency last July saying the university failed both to conduct a proper ethical review of the study and to inform the “highly vulnerable” patients of the risks of joining the study.
The UBC component of the trial was led by Dr. James Russell, who received $405,000 in funding for the project, at Vancouver’s Saint Paul’s Hospital. The patients, often so ill they were on ventilators and heavily sedated in intensive care, were asked to undergo experimental treatments that involved manipulating lung pressures and fluid therapy in order to discover which techniques had higher and lower death rates.
American authorities say UBC’s ethics review board, like its counterparts at the U.S. centres, “failed to receive or request sufficient information” to adequately assess the risks and benefits to patients before approving the trial.
They say UBC’s ethics board also failed to ensure that patients and their legal guardians were properly informed of the risks. Consent forms approved by the university’s review board “did not include a statement that the subject could have a higher risk of death depending on which of the experimental groups he or she was assigned to.”
The U.S. authorities note that “the language throughout the informed consent documents would not have been understandable to most subjects or their representatives. In particular, the descriptions of the research interventions, the alternatives and the risks and discomforts in general were confusing and difficult to understand.”
The letter sent to the UBC is posted on the Internet by the Office for Human Research Protections, which encourages discussion of problems that arise in research.
Russell declined to be interviewed, deferring to Dr. Indira Samarasekera, UBC’s vice-president of research. She said U.S. investigators found no problem with the actual study design.
“The long and the short of it is that the consent forms of many of the centres that were involved in the trials needed improvements and they have been improved,” said Samarasekera, noting that UBC has made “major improvements” in its ethics review process since 2001. UBC investigators, like their U.S. counterparts, can now re-apply to resume the study, she said.
McMaster University in Hamilton, Ont., also ran afoul of U.S. health authorities. A U.S. investigation, which started in the late 1990s and ended in 2001, centred around experimental children’s cancer treatments at McMaster funded by a U.S. agency.
According to letters released to CanWest News Service, U.S. investigators found that McMaster’s research ethics board, which is meant to protect patients and ensure families are informed of the risks of experimental therapies, had been failing to properly review experimental protocols and assess the experiments as they progressed. They also found consent forms given to the guardians of the children were incomplete, hard to understand, and tended to minimize the potential risks while overstating the potential benefits.
The research was headed by cancer researcher Dr. Ronald Barr. McMaster was required to provide the U.S. Department of Health and Human Services with a “corrective action plan” that included expanded ethics review policies and procedures. U.S. investigators stressed that failure to comply “may result in suspension” of McMaster’s co-operative project assurance, which is needed for the university to quality for funding from U.S. government agencies.
In January 2001, the U.S. authorities said they were satisfied that with the way McMaster had overhauled its ethics review procedures and closed the file.
“We worked diligently to make changes, and those issues were resolved to everyone’s satisfaction,” says Dr. John Capone, McMaster’s associate dean of research.