Veterans Affairs Committee on Nov. 3rd, 2016

[The Chair, Liberal, Neil Ellis]

Everybody, I'd like to call the meeting to order.

Pursuant to Standing Order 108(2), we are conducting a study of mental health and suicide prevention among veterans. Today we have three different groups joining us. From the Department of National Defence, we have Brigadier General Hugh MacKay, surgeon general and commander of the Canadian Forces Health Services Group; and Lieutenant Colonel Andrew Currie, section head of the communicable disease control program, and the director of Force Health Protection. From the Department of Health, we have Dr. John Patrick Stewart, director general of the marketed health products directorate in the health products and food branch. From the Public Health Agency of Canada, we have Dr. Barbara Raymond, interim director general of health security integration in the health security infrastructure branch.

Thank you, everybody, for joining us today. We'll start with a panel, and each of you will have up to 10 minutes for testimony and then we'll have questions.

We'll start with the Department of National Defence.

Good afternoon.

[Brigadier-General Hugh MacKay, Surgeon General, Commander, Canadian Forces Health Services Group, Department of National Defence]

Mr. Chair, and members of the Standing Committee on Veterans Affairs, thank you for the opportunity to present specifically on the use of medications for the prevention of malaria within the Canadian Armed Forces.

Canadian Armed Forces personnel can deploy to areas of the world where malaria presents a significant threat to individual health and to mission success. Malaria is a significant infectious disease transmitted by a very determined mosquito vector that requires us to use multiple approaches to prevent disease.

The World Health Organization estimated that globally in 2015, there were 214 million cases of malaria and around 438,000 deaths attributed to this infection. In addition to personal protective measures, which are vulnerable to penetration and difficult to sustain in operational settings, it is critically important to provide the additional protection of malaria chemoprophylaxis, or medications. When used appropriately, chemoprophylactic medications can safely reduce the risk of malaria by more than 90%.

In developing our approach to malaria prevention and treatment in addition to our own assessment, we seek the advice and guidance of experts in this field, such as the Canadian Committee to Advise on Tropical Medicine and Travel. This committee has developed evidence-based clinical guidelines.

Those best medical practices address the very real threat that malaria presents, while taking into consideration the safety and effectiveness of the medications involved. This committee, along with similar authorities such as the United States Centers for Disease Control and Prevention, Public Health England and the World Health Organization, recommend several medications, including mefloquine, as suitable drugs for the prevention of malaria, depending on the regional susceptibility of the malaria and appropriate patient screening.

The Canadian Armed Forces, following the advice of the Canadian Committee to Advise on Tropical Medicine and Travel and other expert bodies, has included mefloquine as one of the suitable options available to patients to prevent malaria for several decades. Our other two main options at this time include doxycycline and a combination of atovaquone and proguanil, also known by trademark as Malarone. Each of these medications has its own advantages and disadvantages as well as potential side effects.

The selection of a potential anti-malaria medication for each mission involves an assessment by our Directorate of Force Health Protection to determine the risk of malarial infection and identify medication resistance in the region. Clinicians then work with the patients to discuss the risk of malarial infection along with a discussion of the advantages, disadvantages, and potential side effects and precautions of each of the medication options and a screening for potential contraindications before an informed choice is made by the patient as to the medication that fits their preferences and the situation.

The potential for medication side effects can impact the patient and their operational readiness, which is why it is so important that we appropriately educate and medically screen Canadian Armed Forces personnel. We want our people to make an informed and medically supported choice when selecting a drug to protect themselves against malaria.

In the Canadian Armed Forces, we have seen a decrease in the selection of mefloquine during the last decade. In the early 2000s, mefloquine was the most often used antimalarial. This started changing in the mid-2000s, and now mefloquine is our least often selected medication. It accounts for about 5% of our current antimalarial prescriptions, whereas atovaquone/proguanil, first licensed in 2002, now accounts for about 80%. The remainder of prescriptions are for doxycycline.

More than 17,000 Canadian Armed Forces personnel and tens of millions of people worldwide have received mefloquine since it was first licensed to prevent and treat malarial infection. We are aware of the potential short-term side effects of mefloquine; however, even given this extensive use of mefloquine, severe neuropsychiatric adverse effects have very rarely been associated with its use.

We are also aware of the assertions of some regarding their theories that mefloquine might cause long-standing neurological damage and mental health issues, which they themselves suggest requires more research to support. Our assessment of their assertions, at this time, is that they are not sufficiently supported through direct scientific evidence for us to remove mefloquine as an option for patients to protect themselves from malarial infection, particularly if they have used it safely in the past.

This assessment is consistent with the recommendations with respect to malaria chemoprophylaxis of the Canadian Committee to Advise on Tropical Medicine and Travel, the U.S. Centers for Disease Control and Prevention, Public Health England, and the World Health Organization.

As you are likely aware, mefloquine remains an option for malaria prevention for many militaries around the world. We do, however, remain vigilant and open to assessing any new evidence related to mefloquine and other antimalarial medications.

We also have confidence that our drug regulator and the Canadian Committee to Advise on Tropical Medicine and Travel will update their advice in a timely and appropriate way if or when new and credible scientific and medical evidence emerges.

We will, accordingly, update our approach to malaria prevention in a scientifically sound manner and with an emphasis on critical appraisal of the evidence.

Thank you for the opportunity to appear before the committee today.

[The Chair, Liberal, Neil Ellis]

Thank you.

Next, we'll call upon the Department of Health.

Dr. John Patrick Stewart.

[Dr. John Patrick Stewart, Director General, Marketed Health Products Directorate, Health Products and Food Branch, Department of Health]

Thank you.

Good afternoon, everyone.

Thank you for the opportunity to appear today. I'm pleased to be here today to speak on the regulatory history of mefloquine.

Malaria is a serious life-threatening illness. Even with modern effective treatments and intensive-care support, as many as 20% of patients die when affected with the most severe form of malaria. Over the past three years, there have been approximately 65 cases of severe malaria per year in Canada. Preventing the infection is an important strategy for reducing malaria's impact on travellers.

Mefloquine is a prescription medication that is recommended as one of the few options for malaria prevention by the Public Health Agency of Canada's expert advisory Committee to Advise on Tropical Medicine and Travel, CATMAT, and by most public health and travel medicine authorities around the world. Mefloquine is a tablet taken by mouth and its once-weekly dosing may help with compliance, compared with other drugs that must be taken every day. These other available options, which include Malarone, doxycycline, and primaquine, are generally as effective in preventing malaria but have serious side effects as well. The benefits and risks of each option should be considered by the prescriber, and ultimately the decision on which drug to prescribe to a particular patient rests with the physician in discussion with the patient.

I would like to now speak about how Health Canada has monitored the safety profile of mefloquine since it came to market in 1993, and how it took steps to update, when needed, mefloquine's safety profile in the Canadian “Product Monograph”, the document listing information about uses, dosing, and side effects.

The side-effect information in the monograph is obtained from clinical trials as well as from market experience with the drug. Rare adverse events are usually only detected after a drug is launched onto the market as more patients are exposed to it. Health Canada relies on several sources of information, including its Canada Vigilance Adverse Reaction Online Database , the published literature, and communications from other regulatory authorities to monitor the safety of marketed drugs.

Through mefloquine's life-cycle, its safety information has been continuously monitored by Health Canada. As such, it has been periodically assessed to determine if current labelling appropriately reflects the drug's safety profile. The original monograph, introduced in 1993, included a warning to advise that patients with a past history of psychiatric disturbance or convulsions should not be prescribed mefloquine for malaria prevention. As a result of post-market adverse drug reaction reports, in January 1997 these warnings were moved into the contraindication section of the monograph.

In 1998, an article was published in Health Canada's Canadian Adverse Reaction Newsletter, describing four reports of neuropsychiatric adverse events with mefloquine use.

This action was followed in 1999 by a safety review that examined all Canadian adverse events in association with mefloquine, which resulted in an addition of suicidal thoughts as a listed side effect. Health Canada also decided at that time to assess all adverse events associated with mefloquine every six months.

Additional information on neurologic and psychiatric adverse events associated with mefloquine, including that they may continue long after mefloquine has been stopped, was added to to the monograph in 2003. This included the addition of a patient-information section as well as a wallet card describing the neurologic and psychiatric side effects and advising patients to consult a physician should these effects emerge. These changes were prompted by a similar update carried out by the U.S. Food and Drug Administration.

In 2005, two related public advisories, a “Dear Healthcare Professional” letter and a “Dear Pharmacist” letter, were issued by the manufacturers of mefloquine in collaboration with Health Canada.

The safety profile and product labelling were formally assessed again in 2006. This review concluded that no additional risk minimization measures were required. The department has since then continued to monitor the safety of mefloquine in a standard manner.

As mentioned before, Health Canada also monitors and assesses the actions taken by other regulatory authorities. In 2013, the U.S. Food and Drug Administration published a risk communication highlighting a boxed warning on neurologic and psychiatric adverse events in the U.S.'s mefloquine prescribing information. Health Canada reviewed the safety data at that time and determined that the safety issues were already adequately labelled in the product monograph.

In 2014, Health Canada introduced its plain language labelling initiative, setting out a new format for the Canadian product monograph. Following this, Health Canada requested that the sponsor update the mefloquine monograph to reflect this new format. The update was completed in August 2016, allowing for a clearer presentation of information. For example, the new product monograph and wallet card now include more prominent boxed warnings indicating that mefloquine may cause neurological and psychiatric adverse reactions that can persist after the product has been discontinued. The box warnings also state that if psychiatric or neurological symptoms occur, mefloquine should be discontinued and an alternative medicine substituted.

To conclude, malaria is a serious, life-threatening infection with a mortality rate of 20% in patients with severe malarial infection. Mefloquine is a very effective antimalarial drug when it's tolerated by travellers and when the drug is prescribed and taken as directed in the product monograph. Health Canada will continue to monitor its risks and take steps to address the safety issues in a timely manner. The benefit/risk profile of mefloquine for malaria prevention based on current information is considered positive.

I would like to thank the committee for the opportunity to speak to you today.

I will now turn to Barbara Raymond, from the Public Health Agency of Canada, to provide her remarks.

[The Chair, Liberal, Neil Ellis]

Thank you.

Dr. Raymond, the floor is yours.

[Dr. Barbara Raymond, Interim Director General, Health Security Integration, Health Security Infrastructure Branch, Public Health Agency of Canada]

Good afternoon, and thank you for the opportunity to speak specifically about the Committee to Advise on Tropical Medicine and Travel, CATMAT, and its role and process in developing medical, scientific, and public health advice relating to tropical disease and health risks associated with international travel.

The committee, more commonly referred to as CATMAT, is an expert advisory body to the Public Health Agency of Canada and is made up of health professionals, all volunteers, in the fields of tropical medicine, travel medicine, travel health, infectious disease, and epidemiology. Also included are liaison members from relevant associations, including the Association of Medical Microbiology and Infectious Disease Canada and the Canadian Paediatric Society. In addition, we have ex officio representatives from Health Canada and the Department of National Defence who participate in the committee's activities.

In developing its guidelines, the committee undertakes a very thorough review of the scientific literature and also reviews recent research and international and national epidemiological data to tailor its recommendations to the Canadian context. Influencing factors in its recommendations include the drugs available for use in Canada, Canadian-specific travel patterns, and related disease epidemiology or patterns of disease.

CATMAT considers the need for protection and weighs that against the potential for adverse effects that could be associated with treatment or prevention therapies and the values and preferences of Canadian travellers and health care providers. CATMAT regularly reviews and updates its guidelines as new information becomes available so that Canadian health care providers have the information they require to provide appropriate guidance to individual travellers.

With respect to the “Canadian Recommendations for the Prevention and Treatment of Malaria”, these were last developed and published by CATMAT in 2014. CATMAT includes in that edition mefloquine along with doxycycline, atovaquone, and proguanil as drugs of choice for the prevention of malaria in travellers to regions that have strains of malaria that are resistant to chloroquine, another drug that is used to treat some strains of malaria.

The current CATMAT guidelines advise that mefloquine is generally well tolerated and that severe reactions are rare. They stipulate that individual risk assessments are required prior to use, and the Public Health Agency of Canada advises travellers who are going to malaria-affected destinations to discuss the benefits of taking antimalarials with their health care professionals, preferably six weeks before departure.

As part of its regular review schedule, CATMAT is currently reviewing the recommendations for the use of antimalarials, including mefloquine. The review of CATMAT's malaria guidelines is expected to be completed in 2017, and at that point, the Public Health Agency of Canada will review its advice to Canadian travellers based on those updated recommendations.

Thank you for your attention, and I return the floor.

[The Chair, Liberal, Neil Ellis]

Thank you.

We'll start with questions now.

I'll turn the floor over to Mr. Kitchen.

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

Thank you, Mr. Chair, and thank you all for coming today. I appreciate your comments.

I come from a military family, and my father was the military attaché to Pakistan, Afghanistan, and Iran, with the high commission there. When we were sent there, I was just a teenager. Basically, we were told that when you're going there, you have to take malaria pills.

When my two sons travelled to Africa, one son talked to his doctor, a South African doctor who was very aware of malaria and suggested he take doxycycline. The other son was given mefloquine. It happens: doctors give out what their preferred drug may be.

My question is really dealing with informed consent. General, can you describe to us what the informed consent process would be for our soldiers when they go into theatre?

[BGen Hugh MacKay]

The current process is dependent on the size and nature of the deployment.

If we have small numbers of people going off as UN military observers, for example, they would have a briefing with a preventative medicine technician about the risks of the region they're going to, which would include the risk of malarial infection, if it were there. Then those small groups of individuals would have a face-to-face encounter with a physician or a pharmacist at which there would be discussion about all of the options available in the region to which they are going to combat malaria.

That discussion would include the medications available, the advantages, the dosing schedules of each of those types of available medications, as well as a discussion of the risks of adverse effects and the types of adverse effects they might experience with the medications being considered. Then, in a discussion with them about what their preferences would be with respect to advantages and disadvantages and the potential for adverse effects, they'll make a decision about which medication to go with.

If there are larger groups, there will probably be a larger presentation to a company-size or platoon-size group given by a medical provider, probably a pharmacist. They wouldn't have that individual session up front, although they would fill in a questionnaire that identifies the risk factors we need to consider for each of the medications, and there would then be a review of what they report with respect to their risk factors and the antimalarial they might want to select. We will then have them sit down with a health care provider to receive these medications.

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

And were these policies in place all the way back to Somalia?

[BGen Hugh MacKay]

I can speak to having this policy in place since 2004. I can't speak to the exact policy that was in place back to the time of the deployment to Somalia. I think, though, that there have been reviews by the Auditor General and the commission of inquiry for Somalia that have identified that those processes were not in fact followed at that time.

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

What sort of documentation would there be to support that? Is it still in existence today? Is it archived? Is it in medical records?

[BGen Hugh MacKay]

I'm not sure what information they used to generate their evaluations in reports. If there has been an encounter with a health care provider with respect to counselling on a medication and a prescription, it should end up in a medical record, and it would have been a policy that a record be made in the health record at that point in time.

Specific to malaria prophylaxis discussions, I'm not sure what the policy was.

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

I might be able to go back into the archives to find out what medication I took back in 1972-73, because I can't remember. Records are available, possibly archived.

[BGen Hugh MacKay]

Medical records are possibly archived, yes.

[The Chair, Liberal, Neil Ellis]

You have one minute.

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

Very quickly Dr. Raymond, in public health there are issues with civilians dealing with mefloquine, because it is a drug out there for civilians as well as for our veterans. We are hearing about people having serious side effects.

Would it be of interest for the Public Health Agency to do a long-term national study and keep records of these side effects to see exactly what is going on with the medication?

[Dr. Barbara Raymond]

The Public Health Agency's role with respect to this is to develop the guidance and the recommendations for health care practitioners to use when they are prescribing for individuals, taking into account all the issues that relate to that individual and so forth. The agency does not engage in long-term studies monitoring drug use or adverse events over time.

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

Dr. Stewart, would there be an interest by Health Canada in that?

[Dr. John Patrick Stewart]

That type of information would be very helpful. The mandate, as defined under the Food and Drug Act and regulations, is that Health Canada doesn't carry out research. It may support research through funding through CIHR, the Canadian Institutes of Health Research, but as far as practice guidelines and so forth are concerned, generally that type of research is carried on outside of Health Canada. Sponsors will come in with information to update their monographs, so they may do individual studies, but currently that's not part of the mandate of Health Canada.

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

Thank you.

[The Chair, Liberal, Neil Ellis]

Mr. Bratina.

[Bob Bratina, Liberal, Hamilton East—Stoney Creek, ON]

Thank you.

We have following comment by General MacKay:

We are also aware of the assertions of some regarding their theories that mefloquine might cause long-standing neurological damage and mental health issues, which they themselves suggest requires more research to support. Our assessment of their assertions, at this time, is that they are not sufficiently supported through direct scientific evidence for us to remove mefloquine as an option for patients....

Dr. Raymond, does that statement by General MacKay sound reasonable?

[Dr. Barbara Raymond]

As I noted, the CATMAT committee undertakes a very rigorous review of the scientific evidence that is available, and if that scientific evidence is available, it would be accounted for in their recommendations.

At this point, the balance of information does not allow for that conclusion to be drawn.

[Bob Bratina, Liberal, Hamilton East—Stoney Creek, ON]

In our committee we have heard some disturbing testimony regarding the effects on our veterans, and the veterans of course are our concern in this committee.

Anecdotally it was interesting for me to hear from a person in uniform at a military event that, yes, they had been in malarial areas and had taken mefloquine and decided after three or four times that they didn't like the bad dreams, or words to that effect.

General MacKay, has there been consistent feedback on how different people react to things such as mefloquine, in this particular case? Do you get the sense that some people go through their military careers and have been in malarial settings and taken drugs and didn't get malaria and some have had terrible side effects, which apparently have been lasting, according to the testimony we heard, but for others, it's not been so. Does that coincide with your understanding of this issue?