Evidence of meeting #119 for Veterans Affairs in the 42nd Parliament, 1st session. (The original version is on Parliament’s site, as are the minutes.) The winning word was mefloquine.
A recording is available from Parliament.
Conservative
Consultant Public Health Physician, As an Individual
In specific conditions it could be given to individual patients who could then be watched very carefully. I understand that somehow 900 soldiers came under this category and went off to Somalia and took it with disastrous consequences, of course, as we know.
Conservative
Cathay Wagantall Conservative Yorkton—Melville, SK
They were required to take it, first of all. It wasn't licensed at the time, and there was actually no study done because it didn't fit the criteria. They indicated that, basically, the theatre did not work for that, yet they went ahead and administered the drug anyway. I'm not a researcher, but if you're given the job to look at a drug and you don't do that and then still administer it, where does that fit ethically?
Consultant Public Health Physician, As an Individual
I understand that's been looked at already. I believe the Auditor General of Canada did his own investigation of that and was very critical of that in 1999. All I can do is reiterate what the Auditor General of Canada said, without knowing the exact details.
Consultant Public Health Physician, As an Individual
To just give a mass of people a drug and then tell them to go off and really have no provision for monitoring them carefully—as this was the whole rationale for giving the drug in advance of its licensing—seems to be a weird way of carrying out a study.
Liberal
Doug Eyolfson Liberal Charleswood—St. James—Assiniboia—Headingley, MB
Thank you, Mr. Chair.
Thank you both for coming.
Dr. Croft, I want you to expand on your statement that this drug is “uniquely dangerous” for soldiers. What is the level of evidence that leads you to that conclusion?
Consultant Public Health Physician, As an Individual
The side effect profile of the drug is one that focuses on the neuropsychiatric side, whereas with, say, doxycycline, it's a side effect profile that is more weighted toward the gastrointestinal and dermatological side. I think soldiers can put up with a bit of—
Liberal
Doug Eyolfson Liberal Charleswood—St. James—Assiniboia—Headingley, MB
No, I understand that. I'm wondering what kinds of studies you're looking at. Are you looking at the numbers of soldiers who were exposed to this, those who developed symptoms, those who didn't...?
I'm a physician, and I also did some medical research before medical school. We have levels of evidence that we get from the laboratory. We have levels of evidence when we look at the biochemistry of it. To make a trend to say “this drug does this”, of course we need large trials. What studies can you cite to give you this certainty that a soldier is much more likely to develop neuropsychiatric problems with this drug versus others?
Consultant Public Health Physician, As an Individual
Right. Perhaps I could go back to 1995 and a pivotal study. It was a control study involving n equals two, or two individuals. This was the Wittes and Saginur paper, which I remember reading then and was very struck by.
I'll have to expand on this a bit. This was a study where two geologists went to Tanzania. I'm sure you remember this. One of them was from Ottawa, in fact. They shared a tent for eight weeks. I think both geologists were in their forties. They were young and healthy guys. One of the geologists—
Liberal
Doug Eyolfson Liberal Charleswood—St. James—Assiniboia—Headingley, MB
I'm sorry to cut you off, but maybe you could provide the reference for that later. I have very limited time and I have other questions.
Consultant Public Health Physician, As an Individual
I did send an advance copy.
Liberal
Doug Eyolfson Liberal Charleswood—St. James—Assiniboia—Headingley, MB
Thank you. We'll look at that.
Liberal
Doug Eyolfson Liberal Charleswood—St. James—Assiniboia—Headingley, MB
Yes.
I have a 2018 article here from the American Journal of Tropical Medicine and Hygiene. This looked at the use of anti-malarial medications in U.S. veterans of the wars in Iraq and Afghanistan. This was a study of almost 19,500 veterans. They looked at all the different symptoms that they developed and the different drugs they were on. Again, we're talking almost 20,000 veterans here.
Basically, this was the conclusion of this very large study:
These data suggest that the poor physical and [mental health] outcomes reported in this study population are largely because of combat deployment exposure.
It said that in this very large study, when you corrected for combat deployment exposure, there was no association or no difference that they could see in these numbers of neuropsychiatric effects among those who received mefloquine versus those who didn't.
Do you have any large studies that refute that?
Consultant Public Health Physician, As an Individual
Right. I'll come back to a randomized controlled trial, but before giving the details of that, I need to point out to the chairman that what you're describing is an observational study. Observational studies are by definition weak sources of evidence. The fact that it's large doesn't make it powerful. It just means it's likely to be more weak. I don't think we can put too much credence in that. We must focus on the—
Liberal
Doug Eyolfson Liberal Charleswood—St. James—Assiniboia—Headingley, MB
What are the other studies? If the other ones aren't observational...because, as we've said, if you have something that's going to cause neuropsychiatric effects, ethically right now we couldn't do a randomized controlled trial.
Liberal
Doug Eyolfson Liberal Charleswood—St. James—Assiniboia—Headingley, MB
What kinds of studies are these that you're citing that aren't observational?
Consultant Public Health Physician, As an Individual
In 1995, I carried out two randomized controlled trials with British troops in Kenya, because my superiors told me to. The first one was a bit unsatisfactory. The soldiers were not taking their tablets and they admitted to not complying. I put on a second trial, and this time we said to them, “Look, please take your tablets. It's very important.” We put it in the orders and made every effort to make sure they complied.
The results were surprising. There were 600 soldiers in the study. They were randomized to take either mefloquine or chloroquine and proguanil, which is an obsolete combination now. About 280 were taking mefloquine and about 280 were taking the other regimen. It was double-blinded. We had two critical events among the soldiers. One of the soldiers became psychotic. He was getting auditory delusions and had to be airlifted out back to England to a mental hospital. His career was wrecked as a soldier. Shortly after the trial ended, we had a soldier who committed suicide. When the code was broken, it was found that he also was on mefloquine. Those were two very, very severe events.
Liberal
Doug Eyolfson Liberal Charleswood—St. James—Assiniboia—Headingley, MB
This was 600 soldiers. They were randomized.
Liberal
Doug Eyolfson Liberal Charleswood—St. James—Assiniboia—Headingley, MB
It was two soldiers out of 300 having developed psychotic symptoms.
