Veterans Affairs Committee on Oct. 25th, 2016

[Dr. Remington Nevin]

Yes, I am aware of multiple suits, either completed or pending. I've been involved as a consultant or expert in a number of successful cases in the United States. I've been involved in the same capacity in a number of cases overseas, and I do expect in the coming years that the number of claims against prescribers, against the governments that oversaw the prescribing of this drug, are going to face significant financial consequence.

In the United States, our military is protected from claims of liability due to something called the Feres Doctrine. Before the meeting, I was discussing this issue with my colleagues. My understanding is that Canada has no such immunity from torts, so I do think it's important for governments to examine their exposure on this issue.

[Colin Fraser, Liberal, West Nova, NS]

Thank you.

Go ahead, Dr. Ritchie.

[Dr. Elspeth Ritchie]

If I may add, I agree with everything Dr. Nevin just said. The analogy in the United States is Agent Orange, the defoliant that was used in Vietnam. Really, mefloquine is one of a number of toxic exposures but it's the one we're focused on today. The Agent Orange analogy was, “Oh, that was nothing, it's all in your head.” Now I see Vietnam-era patients all the time. They've been exposed to Agent Orange. It's part of what is in their disability. It's part of what the VA compensates. And I would not be at all surprised if 30 years from now, or sooner, we will see mefloquine as the Agent Orange for this generation of Somali and Afghan veterans.

[Colin Fraser, Liberal, West Nova, NS]

Thank you.

Perhaps I can ask Mr. Passey a quick question. You talked about nightmare Fridays. Dr. Ritchie mentioned nightmare Mondays, or something akin to that. I'm sorry if this is a dumb question, but is that simply because if you're taking the drug once a week, it's on the day you take it that you have really bad nightmares? Is it only on that day, or are there other effects throughout the week too?

[Dr. Donald Passey]

Certainly you can have effects throughout the week, but the highest concentration, the highest frequency, is on the day you actually take the medication. It's simply the way the medication is absorbed etc. Pretty much most people are guaranteed vivid if not full-out nightmares on that day. When I was overseas it was Fridays. It could have been Mondays for somebody else, but definitely it was on that particular day.

[Colin Fraser, Liberal, West Nova, NS]

Thank you, Doctor.

[The Chair, Liberal, Neil Ellis]

Thank you.

Mr. Kitchen.

[Robert Gordon Kitchen, Conservative, Souris—Moose Mountain, SK]

Thank you all for coming today.

I have a whole bunch of questions. I've not taken as many notes in a long time. I'll try to get in as many as I can in this short period of time.

Dr. Nevin, can you comment on what trials might have been done prior to this drug being put on the market? From an understanding that someone doesn't simply come up with the idea, then here it is, there is research done before it's put out there and is used. From your research, can you comment on that?

[Dr. Remington Nevin]

It's important to understand mefloquine's development in context. This is just the latest in a series of quinoline drugs that the U.S. military, which developed mefloquine, had quite a bit of experience with. I have always thought it would be reasonable for the U.S. military to have expected that mefloquine would have many of the same side effects that it had seen previously with other synthetic quinoline drugs, including atebrin, used in World War II.

In fact, I found a paper from the World War II era that described atebrin causing symptoms of anxiety, depression, restlessness, and confusion and these symptoms predicting the development of a more serious psychosis or what I refer to as an encephalopathy. It's that very language that seems to have been echoed in the product insert when Roche finally marketed the drug. I do believe that during marketing of the drug, there was knowledge of these effects.

Certainly looking back on some of the studies that were done, it's remarkable that they didn't see as much of this as we see today in studies. It was either tremendous luck on the part of the investigators to not have observed these effects, or it was something else.

One important point I think we should emphasize is that Canada's first experience with this drug was part of a safety study that was conducted in the early 1990s and through which the Department of National Defence gained access to large quantities of mefloquine for use during the early months of the Somalia mission. It was not a licensed drug in 1992 and into the first weeks of 1993 when many service members started taking the drug and deployed to Somalia.

The Department of National Defence's access to that drug was contingent on participating in a safety study that should have informed the licensing of the drug, should have informed the content of the product label, should have informed physicians of the side effects that would be experienced with regular use of that drug.

You ask what studies were done. The study that should have been done on military personnel was not done, and the drug was licensed without the benefit of what, in retrospect, probably was very important information.

[Robert Gordon Kitchen, Conservative, Souris—Moose Mountain, SK]

We're aware that the gold standard, an RCT, is difficult to do in such situations, but the situation is as you mentioned. We know that soldiers follow orders, and when they're told, they do; and their families follow orders.

My father served and was in Gagetown and was subjected, as Dr. Ritchie mentioned, to the issue of Agent Orange in testing that was done in Canada. Likewise, we lived in Pakistan and we were told we'd take malaria medication and this was the medication we would take, end of story.

Just to go on more of a scientific bent, we're always looking for concrete data to try to say how it is, and it's very tough to come up with concrete data when we're dealing with neuropsychiatric disorders. We're talking about liver toxicity, brain stem toxicity, limbic toxicity.

Dr. Passey, you mentioned blood tests. I'm wondering if you could explain some more about that and just enlighten the committee on some of those tests that may be evident, if they are or not, and how experimental they are.

[Dr. Donald Passey]

Dr. Mark Gordon has been working on this area for about 19 years in the U.S. He's been working with U.S. veterans including Green Berets, Navy Seals, Army Rangers, etc. He was looking at traumatic brain injuries particularly, but he's also found that with post-traumatic stress disorder there are certain metabolic pathways when individuals have got brain trauma. I think of PTSD very differently. It's actually trauma to the brain. It's secondary to extreme stress or cumulative stress, but it actually causes dysfunction in the brain. I don't like the whole mental health thing.

He has basically established that there are these metabolic pathways, and I'm in the process of doing all the reading and trying to get up to speed to pass this exam, so I can actually start doing this in Canada. When you correct those, it's not by using drugs. It's actually by using precursors and compounds that are normally found within the body. When you correct those pathways, then it corrects the symptoms.

Very quickly, there's a thing called cortisol steal. Under a lot of stress, people have to produce cortisol. When they do that, the other pathway is to testosterone. That ends up not being produced. A lack of testosterone in the brain will cause things such as anxiety, insomnia, irritability, and concentration problems. So when he treated those pathway disorders in an individual, Andrew Marr, who he actually treated, his symptoms all settled and he got off all his psychiatric medication. That's the direction I think we need to start going.

[The Chair, Liberal, Neil Ellis]

Thank you.

Ms. Jolibois, you have three minutes, and then we are going to do one quick round of three minutes each, and that will take us to the conclusion.

[Georgina Jolibois, NDP, Desnethé—Missinippi—Churchill River, SK]

Thank you.

Dr. Ritchie, I know what your answer is in terms of the use of mefloquine.

In the Canadian system currently, can you describe more, so that I have a better understanding, if we cease to use this or continue to use this?

[Dr. Remington Nevin]

I'm sorry, could you restate the question? I'm not sure I understood.

[Georgina Jolibois, NDP, Desnethé—Missinippi—Churchill River, SK]

In our Canadian system my understanding is that it's still being used, so how can we ensure that we have further discussion to continue using versus not to continue using?

[Dr. Remington Nevin]

If I may, Mr. Chair, the policy changes that we've seen in other country's militaries—in the United States, in the United Kingdom—they have generally followed or have reflected regulatory re-evaluation of the drug.

In the United States, around the time that the U.S. military formally declared it a drug of last resort, the FDA was adding the boxed warning to the medication. Similarly, in the U.K., some years ago a similar warning was added across Europe and now the Ministry of Defence has declared it a drug of last resort.

I do think that any substantive policy re-evaluation here in Canada should be informed by an updated mefloquine product label. The Canadian product label for mefloquine does not state that the drug can cause permanent effects. The Canadian drug label does not state, as it does in other countries, that you should immediately stop taking the drug at the onset of nightmares or abnormal dreams.

I would argue that an update to the label should probably precede a policy re-evaluation. That being said, if the Department of National Defence and others feel there is sufficient information, even in the absence of that update, to warrant action, then of course adopting a policy that reflects that seen in other countries would, in my opinion, be entirely reasonable.

[Dr. Elspeth Ritchie]

Perhaps I could add to it. I think both Dr. Nevin and I would be happy to advise or consult with a group, if you pulled one together to look at this issue, and that's often where it starts, with a review of the science.

There is sometimes bias. In some cases people do feel, again, that this is a hysterical reaction. In part of the work we're doing at the VA, the neurologist told us outright that he didn't believe in mefloquine toxicity, and he had told that to a patient and his wife, who became very upset. You need to have some people who are academic, independent.

In the U.S. we have, for example, the Institute of Medicine, as a body that can pull together thinkers. And I would recommend some kind of pulling together, and that's going to be epidemiologists, people who do research on malaria.

I'll go back to the other question about testing. One important thing to think about is that neuropsychological testing can be very helpful, and as part of that it's just to get to know what tests are useful.

[The Chair, Liberal, Neil Ellis]

Thank you.

We'll start the next round with three minutes each, and we're going to go with Ms. Wagantall first.

[Cathay Wagantall, Conservative, Yorkton—Melville, SK]

I appreciate what I just heard about the offer to be part of dealing with this issue in Canada, and lending your expertise and being part of that dynamic.

Clearly, then, we would have the people prepared to come and do the studies. What we need is the people to be studied. Would you see an outreach program to our veterans being a significant part of that whole process so that we get the clarity that we need here in Canada? These are the people we are concerned about on this issue.

Dr. Nevin.

[Dr. Remington Nevin]

If I may, that's the idea of a specific outreach to veterans who may have been affected. This is a consistent request by veterans groups internationally. We've seen this request articulated in Ireland, in the United Kingdom, in the United States, and in Australia.

I think the implementation of that kind of outreach program is very helpful. It would demonstrate acknowledgement of the problem by the government, either by the military or by the Department of Veterans Affairs. This is critical. It has been critical in the United States where for many years mefloquine was sort of like a Lord Voldemort, it was that-which-shall-not-be-named. One could not ascribe ill effects to the drug. Now clinicians, who for many years have suspected their patient may have been injured by the drug, feel more comfortable coming forward now that there are tangible steps being taken to sponsor studies.

I think a formal outreach program has the benefit of clearly articulating to the military, to veterans workers, and to clinicians that the government takes this seriously, that the government will support you when you propose that an individual soldier may have been injured by the drug. Also, it has the practical benefit of giving veterans and soldiers information they may not have heard. Social media and regular media go only so far. I think many more veterans could be reached through such a program.

[Dr. Elspeth Ritchie]

And quickly, if I could add, it would reach the family members. It's often the family members who are very concerned, very affected, and likely would be very interested in such an outreach.

[The Chair, Liberal, Neil Ellis]

You have 30 seconds.

[Cathay Wagantall, Conservative, Yorkton—Melville, SK]

Can you talk briefly to the fact that they may be treated for PTSD at the same time? How does that complicate whatever medications they're taking for that treatment when it may not be PTSD?

Sorry, that's not a 30-second question.

[The Chair, Liberal, Neil Ellis]

Okay, where do we want to send it? One person, then.

[Cathay Wagantall, Conservative, Yorkton—Melville, SK]

Who would like to take that? Dr. Passey?