A promising Canadian stroke drug has received a rare waiver of consent that allows Toronto paramedics to use the drug on patients without their permission.
Next January, the medication, called NA-1, will be administered intravenously to patients destined for Sunnybrook Health Sciences Centre, a major force in stroke care in the city. NoNO Inc., the privately funded company that makes the drug, has also applied for similar dispensation at hospitals in Peel Region and Vancouver, where clinical trials using EMS services will also take place next winter. It's a double-blinded experiment, meaning that there will be a placebo used as well.
The trial, called FRONTIER, will mark the first time in Canada that a stroke drug will be tried out on a large number of patients before they reach a hospital. Success could mean that for the first time since insulin, the country would be home to a blockbuster pharmaceutical. The risk in any pivotal trial is that there is no guarantee that a drug will be effective. Over the past two decades, more than a thousand stroke drugs have failed to show efficacy. In previous NA-1 trials involving mice, primates and a small number of humans, however, the intravenous drug demonstrated positive results and did not have any serious side effects on people.
Many view the exception granted by Sunnybrook's research ethics board last week as a watershed moment for Canadian research and emergency care. "It is a really, really big deal," said Merril Pauls, director of Ethics and the Humanities at University of Manitoba's Faculty of Medicine, where he is also an associate professor of emergency medicine. "It's very important that they go ahead with it. All the studies show many benefits with little risk."
NA-1 belongs to a class of drugs called neuroprotectants. Its unique proposition is that it inhibits the behaviour of PSD-95, a potentially insidious protein that, in the event of stroke, helps turns brain cells into a cesspool of lethal toxins.
A stroke kills two million cells a minute, and in the absence of intervention, the likelihood of a positive outcome decreases 10 to 20 per cent every half hour. In Canada, someone has a stroke every seven minutes, around 50,000 people a year – with a social cost of $3.6-billion per annum and an incalculable emotional, physical and financial toll on patients and families.
To date, only one medication is on the market, tPA, a clot-buster with a long list of disqualifiers. In Canada, it reaches only eight out of 100 patients. The lack of treatment options is one of several reasons ethicists feel it is important to proceed with NA-1, a complementary medication that would buy the brain time before the patient reaches the hospital and possible tPA treatment.
Referring to a critical Canadian research guideline called the Tri-Council Policy Statement, ethicists say the decision is justifiable on many levels, beginning with patient safety. Brain cells are dying at a ferocious rate, which means the need for swift intervention should trump consent. "The longer you wait, the more negative the outcome will be," explains Brian Murray, who is chair of Sunnybrook's research ethics board.
Aphasia, or the difficulty in articulation and comprehension as a result of stroke, also presents a challenge to consent. The guideline stipulates that patients who lack the ability to consent should not be unfairly excluded from the potential benefits of research.
Beyond the guideline, Dr. Murray emphasized that grounded medical research is imperative to the future of medicine, even if the outcome of the drug's effects on people is unknown. "If we don't make these exceptions, this kind of work would always be stymied," he said. "We'd still be using leeches."
Laurie Morrison, the trial's point-person between the hospital and EMS, says that while EMS can perform many interventions with cardiac issues, a paramedic can do little for stroke patients. "There's not much they can do except drive fast," said Dr. Morrison, the Robert and Dorothy Pitts Chair in Acute Care and Emergency Medicine at St. Michael's Hospital.
In the upcoming trial, which will involve 518 patients, the EMS team will consult with an on-call physician at Sunnybrook. After ascertaining that a stroke has taken place, they will inject the drug and then bring the patient to the hospital stroke centre. "It gives you goosebumps," Dr. Morrison said, "And in science, you don't get a lot of goosebumps."
Clarification: The original print version and an earlier online version of this article gave an incorrect title for Merril Pauls, director of Ethics and the Humanities at University of Manitoba's Faculty of Medicine, where he is also an associate professor of emergency medicine. This online version includes the change.