It might be helpful for you to know that I am a nurse by training. I work at a community health centre for women in Manitoba, where for 25 years we've been dealing with the issues of drug and device safety, including tracking women with diethylstilbestrol or DES exposure for screening, raising questions about the relative value and potential harm of hormone replacement therapy, the impact of reproductive technologies on the lives and bodies of women, and other issues around drug regulation.
Currently we are working on a team developing sex- and gender-based analysis tools for systematic review, hoping to improve our knowledge base for decision-making, and we are involved in the development of the proposed drug effectiveness research network, which I believe you are aware of.
The CWHN is a national network working to improve the lives of women and girls in Canada by undertaking research synthesis and collecting and distributing information. We are in fact a knowledge broker.
I am lucky enough to have participated in the consultations Health Canada has had on their proposed progressive licensing regime and the life cycle approach. This is laudable and demonstrates that Health Canada is finally moving to update its regulatory infrastructure.
The department I think also should be congratulated on its increased efforts to engage the public and community groups in its processes and deliberations. The establishment of the Office of Consumer and Public Involvement is an excellent example.
I also particularly wanted to take this time to thank the government for its rigorous defence in the CanWest Global charter challenge to the existing direct-to-consumer advertising regulations. Although we, like other groups, feel strongly that there's more to be done in this area, we are delighted and grateful for your active work in this area. Preventing direct-to-consumer advertising is directly related to keeping manageable and fundable medicare.
Given the rich testimony before you, though, I don't want to repeat what's already been said but want more to say that we absolutely support the recommendations and observations made to you by PharmaWatch, the Canadian Medical Association, the Canadian Health Coalition, Women in Health Protection, and Drug Safety Canada. My remarks are to enhance those areas.
Firstly, post-marketing surveillance is increasingly important to women, and of particular interest because the implementation of our commitments to sex and gender analysis in health research and the evaluation of health products is still not yet routine.
For example, in the United States eight of ten prescription medicines that were withdrawn from the market between 1997 and the year 2000 caused more adverse effects in women than in men, and they found that only 22 participants in the clinical trials were in fact women. This lack of subgroup analysis by sex leads to potential for error and for harm at the regulatory area and at the practice area. That's improving. Post-marketing processes are critical building blocks for women and for men. I would also suggest that you always include the term vaccines in your deliberations.
However, this must be a transparent process, not one managed by the industry. Like the move to the public reporting of clinical trials and clinical trial results, post-market surveillance, including adverse reaction reporting, must be publicly managed and publicly accessible. We also need to be including the existing products that are on the market, not just new products. This is really important because of the level of evidence for the evaluation of these products.
As you identified in your report “Opening the Medicine Cabinet”—one of my favourite documents of all time—increasing the capacity of Health Canada, and I would add of other infrastructures, is going to be absolutely essential. People cannot do this on the side of their desks. This includes supporting the proposed drug research and effectiveness network and expanding the work of CADTH, the Canadian Agency for Drugs and Technologies in Health. As well, as you have heard, there is an important and critical role for patients in adverse drug reporting and post-marketing surveillance, and infrastructure for outreach to them is needed.
However, improving post-marketing surveillance is only one component. I am, however, extremely fearful and worried that strengthening post-market surveillance will be used as an excuse, if not a smokescreen, for lowering the standard of evidence for the requirements of new health products.
There are already many problems for women, children, and the elderly. I would suggest that the current standards for the approval of a drug need to be nuanced and made more robust. We need products to be tested on the populations that are actually going to be using them. I know it sounds like a radical thought, but there you go. We need a framework, one that recognizes that standards for safety and effectiveness need to be different, depending on the goal of the product. Products that large numbers of Canadians use for prevention, such as hormone replacement therapy for women, or statins, need a different order of evidence from those used in life-threatening conditions. Drugs used by the elderly and Canadians who use multiple drugs need to be tested on those populations before they come on the market. If Canadians are going to be research subjects, I believe we have an ethical duty to tell them so.
As we evaluate drugs, we think it is important to include at the outset information about head-to-head trials and real-world effectiveness. We don't want to be doing this at the end. Developing a process for researchers, consumers, and citizen engagement in the approval of clinical trials, and in the anticipated pre-application consultations that will be put in place before a formal notice of compliance, would be a way to go.
We recognize that there are huge pressures on you as parliamentarians for drugs to be approved faster. Everybody lives that reality. However, I think there is now some evidence that the time requirements placed on Canadian and American reviewers is creating harm. A recent study has shown that safety problems in new drugs are very much tied to the timelines for their approval. I have the details of this study, but I won't take time to explain them now.
My next point is one that probably is predictable. It is improving the management of health products, incorporating sex and gender analyses into the regulations and legislation that you will be working on. Sex and gender are not just intellectual concepts at this point. We now know that sex and gender matter in ways involving the basic science, the basic genetic level. They manifest in many, many different ways. The pharmacokinetics and the pharmacodynamics of drugs are important. Examples include the effect of the menstrual cycle on the metabolism and use of drugs, and the way in which genetic expression and sex are linked. For example, for some reason, boys are particularly vulnerable to risks for cancer, asthma, birth defects, and learning and behaviour disorders. Women seem to have an increased risk of immune disorders and a higher risk of gene immune suppression disorders than men. We're at the very early stages of understanding this.
We also know there are big differences in the way in which women and men experience health services and health utilization. I won't reprint the front page articles from The Globe and Mail on the experiences of women and men when seeking hip replacement surgery.
We are learning more, but we have a long way to go. I think it is critical, and I would beg you to actively consider enshrining into legislation and regulation a policy that requires a sex and gender analysis in all aspects of the drug review and management process. The United States has moved to do so. Here in Canada we've made some good steps. We've had a guideline for almost a decade. But guidelines are only guidelines and the real money is in the regulation and the legislation.
I'm hoping we can talk a little bit more about that.
How am I doing for time?
Good morning, Madam Chair and committee members. I'm a clinician at the Children's Hospital in Vancouver, and I would like to speak to you today about post-market surveillance from the standpoint of somebody who works daily with patients in the Canadian health care system, and about what I think can be done about this system to make it even better.
Adverse drug reactions are a major cause of morbidity and mortality in this country and other countries around the world. Adverse drug reactions or drug side effects are the fifth leading cause of death in North America. If it were up to me, I would ban the term “side effects” from the lexicon and change it completely to “adverse drug reactions”.
We need to understand the fact that this is a major public health issue, and we need to address it. The difficulties, however, are that idiosyncratic response--the response that one person has to a drug that is an effective remedy for a particular ailment when for another it's actually harmful--make it very difficult to factor into regulatory change these kinds of issues.
We have a post-market surveillance system in this country. Most countries around the world do. Some are mandatory, some are voluntary. In either case, mandatory or voluntary, they predominantly don't work. In Canada, 95% of adverse drug reactions are never reported to regulators. Again, making it mandatory won't change that number--95% incomplete--significantly.
What we need is a system that's directed at solutions, at solving adverse drug reactions, not just at collecting reports. We need a solution-directed approach, and unfortunately with so few reports coming in and those that come in actually being incomplete, not having sufficient detail, it is very difficult to analyze the reports and to come up with meaningful solutions to these safety problems.
As an academic, I can tell you that one of the key examples of this is the methodology. You don't just collect reports of adverse drug reactions. You have to collect reports of people who took the drug and didn't have an adverse reaction so you can compare the two. That's not done. That's part of the problem.
What's the solution? One possible solution is to look at human genetics and the role it plays in drug biotransformation. Drugs are transformed in the body. They are not just consumed and then eliminated as the same product that you took by mouth, or took intravenously, or injected another way. Drugs are transformed, and in these transformations there is a variety of many steps for most drugs. Each of these steps is controlled by genes. Some of these genes are expressed when you are a young child, and some are expressed later in adulthood, which means that for children, an age-based approach, bearing in mind Madeline's comments about gender as well, is also important.
Pharmacogenomics can help by looking at how genes control the biotransformation of drugs, and whether some of those biotransformation products are toxic or not.
About four years ago, Michael Hayden, a geneticist in Vancouver, and I began a $10 million study to look at the genetic basis of drug reactions in children. To date we have more than 9,000 cases from Canada and controls from Halifax to Vancouver that we've captured with our surveillance network. We built a post-marketing surveillance system that could allow us to do the work that we wanted to do, since we didn't have one in Canada that we could use.
That system has proven remarkably effective. It has 13 paid clinicians, whom I pay, from across the country from Halifax to Vancouver at all the children's hospitals that are the tertiary referral centres. We have Halifax, Sainte-Justine in Quebec, the Hospital for Sick Children in Toronto, etc. There are eight sites. We're adding nine additional sites this year.
The goal is to find cases of adverse drug reactions, to find matched patients who haven't had adverse drug reactions but who took the drug, and to look at the genetic differences between them. I can report from this work today that we have found the genetic basis, we believe, according to preliminary data, for three serious and fatal drug reactions, and we will be on the quest for many more in the coming years.
I wanted to tell you a little bit about what we've discovered, and then also provide some forward thinking on where we are going to go next. The first report I wanted to tell you about was codeine.
Tylenol 3 is an over-the-counter non-prescription pain reliever that is very effective. Tylenol 3 actually has codeine in it. Codeine is a weak narcotic. When it is biotransformed in the body, it becomes morphine, which of course is a much stronger narcotic. We discovered a case of a child who died, presumably of sudden infant death syndrome, in Ontario about two years ago. We reported this case in The Lancet, the British medical journal.
In this case the child was found dead of presumed sudden infant death syndrome. This is a diagnosis of exclusion, meaning that if there isn't any other reason for the child's death, that would be the diagnosis. A follow-up toxicology screen by the Ontario coroner revealed that this child actually had lethal levels of morphine in the bloodstream. How does a 13-day-old child get morphine in the bloodstream? There was no apparent reason for that.
We analyzed the breast milk of the mother and found twenty times the level of morphine that one would expect in her breast milk. The reason is actually genetic. It was basically two gene variants that she possessed that caused the death of this child through breastfeeding, one of the worst possible events that I can imagine for a patient.
These genes are actually fairly common variants. If you've ever taken Tylenol 3 or you know people who have, you know that there are big differences between how people respond. Some people say that if they take one of those tablets, it knocks them out cold; some people say that if they take two or three of those--that would be me--they don't feel anything different.
These are genetic differences. This mother had this kind of response. She actually had constipation and somnolence. She was very, very tired from this medication. Those effects are well-known opiate effects from drugs like morphine and codeine. She went to her physician; the dose was reduced by half, and it still killed her baby.
This a major issue. What we've now come up with is a way to predict in whom these reactions are likely to occur and thus to avoid using the drugs in those patients, or at least to use them in much, much smaller doses.
That's one example of where we're heading.
We've done some follow-up work with Motherisk, the pregnancy and breastfeeding information line in Canada, with women who have called about codeine, and we're publishing those results, we hope, in the coming months. We've submitted them for publication.
The next reaction I want to talk about is cisplatin. Cisplatin is the drug of choice for ovarian cancer and many solid tumours in children and adults. It's a very effective anti-cancer agent. It's been around since the 1950s. It has an 80% to 85% success rate in inducing remission or cure.
Unfortunately, it causes deafness. In pediatrics this is well understood and well accepted. In adults, it isn't even monitored. I believe that it is a problem in adults as well as a problem in children. I want the effective outcomes, and I think hearing is a reasonable sacrifice for life, but I would really like to save people's lives without any loss of hearing and without causing another problem.
We've begun a quest to find out if there's a genetic difference. We've found a gene that is 100% predictive of severe deafness, deafness at the level at which a cochlear implant or hearing aid needs to be placed. This relationship is very strong.
Cardiovascular disease and cholesterol are linked. We all know that. We've been told this many times. The link is an odds ratio, a statistical calculation of about 1.7. In the case of cisplatin and deafness, the gene that we found is an odds ratio of infinity, because it is 100% predictive: it only occurs in people with severe hearing loss. It doesn't occur in anybody else. An odds ratio of infinity is quite substantially greater, obviously, than even the link between cardiovascular disease and cholesterol.
The third reaction I want to talk to you about is anthracyclines. Anthracyclines are the drugs of choice for leukemias and many other cancers. They are used as extra drugs for many types of cancer treatment. In the anthracyclines doxorubicin, daunorubicin, and epirubicin are many names of these drugs in this chemical class. They are very effective--in 80% to 85% of cases, they induce remission or cure--but again they have a limiting toxicity. That's cardiotoxicity, heart toxicity. About 3% of the children we treat at B.C. Children's Hospital end up dying of their cardiovascular complications from their anti-cancer drug. About 8% of our children end up on the cardiac transplant list in British Columbia.
There is a 61% mortality rate for this particular reaction. Again, we found the gene for this particular reaction. It's a membrane transporter that's responsible for removing anthracyclines from the cardiac cell. In the cardiac cell, once the drug gets in there it can't get back out and causes cell death. That's the mechanism we believe is responsible.
Again, these are preliminary results with a very high odds ratio of about 20, meaning you would be 20 times more likely to have cardiotoxicity if you had this particular gene than if you didn't. These are very significant findings and show that when you combine clinical pharmacology and the biotransformation of drugs with human genetic profiles, you can actually predict in whom reactions are likely to occur. And that's where we are heading, predictive testing.
The last thing I wanted to say is that we need many more of these kinds of predictive tests. I think Canada can actually lead the world. I've spent 20 years of my life studying post-market surveillance and running systems in two different countries to try to improve the quality of what we're doing. I can actually do a post-market surveillance system finding the genes, as I've described to you, for about $1.5 million a year. This is not an expensive process. This is about getting the right people engaged and the right attitudes in place to actually make a difference.
What this has enabled me to do is to get other clinicians involved. When you show people that reporting so we can have a solution makes a difference, they'll report, they'll participate. They don't want to see regulation for the purpose of regulation. It's great to talk about improving safety of drugs for Canadians, but we need solutions not just great frameworks.
Lastly, I'd like to say that it's like building a car. Start with a Kia, not a Cadillac. Start with something a little less impressive perhaps than what you ultimately want to create in terms of a post-market surveillance system. I would suggest drug-safety-focused, solution-directed. Pick one drug you want to find a solution to, or two or five, but just a few, and move from there.
That's an excellent question, and I think it's one of the reasons why I suggested that we keep vaccines in the drug and health product field. Right now they run in a separate.... They come from a separate history in medicine, and because we are now using them so much more regularly.... The last time it was hypertension, and the report before that was one on nicotine, a vaccine for smokers. So we're going to see a lot more of these kinds of products come on the market, and I think we are going to need to develop different frameworks.
I would say that in the past, as with any other pediatric drug, it's not been unusual as common practice for drugs, devices, and vaccines to be studied on one population and then used on another. The ethics involved here were particularly, to be honest, because of the unique nature of what they were doing. They were testing for HPV in vaginas, and to do that on young girls is problematic. So I am very sympathetic to the struggles ethically.
This vaccine does look like it could be a fabulous thing. Our position at Women's Health Network is that we would have preferred to have seen more research, better modelling. We don't, for example, really know the prevalence of the HPV vaccines that have caused harm in our backyard. In the backyard I'm in, it doesn't look like 16 and 18 are the big majority that they are in other countries. That's very important if we're going to start telling people that they're protected from something when they're not.
We're also very concerned that we know only that this vaccine lasts for about six years. It's been in clinical trials for only six years. If we look to our experience with chickenpox and mumps, we know the vaccines wear off. This is extremely worrying for those of us in the sexual and reproductive health game, because we may give this vaccine to a nine year old, but they become sexually active around age 16, 18, 19, as we see with our chlamydia rates, which are a really good example of what's going on there, despite what we say about protected sex.
So if we have a vaccine that's wearing off precisely when people are becoming sexually active, and we know from our experiences with chickenpox and other vaccines that wear off that, in fact, you can become sicker, what does that mean from an infectious virus perspective? I don't have the answer for that. I don't have the answer for that for the mothers and women who want to talk to me, and we need to know that.
The system is 95% incomplete, so there has to be a massive increase in reporting, and the quality reports have to be there.
I favour a model in which we train clinicians, who are responsible for the recognition and reporting of adverse reactions, to do the work, and not just increase public awareness of reporting. It's great to have consumer reporting; there's nothing wrong with that, and I encourage it. But to get the substance of the reports we need, we really need dedicated professionals to monitor and evaluate drug responses. That's the information that will be most helpful.
In Spain it is a criminal misdemeanour to not report an adverse drug reaction, but it hasn't changed reporting. Vioxx was removed from the market because of Merck's own trial that confirmed the cardiovascular risk. No surveillance system in the world--mandatory or voluntary--picked up that risk, despite the fact it was the most frequently prescribed drug in the history of the world.
I suggest that surveillance systems run by governments traditionally haven't accomplished the goal of helping us identify significant risk in many cases. They can help in many ways, but I think we have to look to science to help us understand better ways to informed solutions. If we can have safety solutions we'll get reporting, because clinicians want safety solutions.
When I started my work I went to the oncologists at the Children's Hospital in Vancouver and told them what I was proposing to do. The head of the medical oncology unit said, “You know, it's an interesting study looking at the genetic basis of adverse drug reactions. We don't have adverse drug reactions in oncology.” That's either a sign of ignorance or arrogance, but it's neither; it's nomenclature. She doesn't think about reactions that are expected, like hearing loss and heart toxicity, as being adverse. She thinks of them as being a consequence of using the drug.
Now that they see that we can actually predict in whom the most serious toxicities are likely to occur, that's where reporting, funding, and support comes from. That's the way to get reporting. Maybe it's to mandate it, but it's to get individuals who are responsible for capturing these reports and individual institutions.
Sure. I'll start this time.
On the issue of other jurisdictions, in the United States the National Institutes of Health has a program called the pediatric pharmacology research units, or PPRUs. These were a result of modernization of the food and drug regulations, the FDAMA, the Food and Drug Administration Modernization Act, and a pediatric rule that was created particularly to allow for more testing. They created, really, an incentive for pharmaceutical manufacturers to do more pediatric testing early on in the drug development, and that has created a bunch of research units across the country to help produce better information about the kinetics of drugs.
Unfortunately, it's very much limited to the pharmacokinetics of drugs, pharmacokinetics being the way the drugs are absorbed, distributed, metabolized, and excreted from the body. It doesn't link in genetics at this point, although there's interest in doing that.
I think where Canada can add value to other jurisdictions is in areas like pharmacogenomics, in which we clearly are leading. I know we're leading because FDA came to see us in October. Along with seven of the major pharma companies, they formed a non-profit in the United States called the serious adverse events consortium.
Drug safety is one of those issues that pharmaceutical manufacturers definitely want to take on, now that Vioxx has been removed from the market. The reason they want to take it on is that they recognize it's a risk to their products and to their financial viability if drugs are pulled by them or by governments and safety concerns are identified. If they see a solution-directed approach, they seem to be interested. That's what they've created with the FDA: this way of taking all of these patients they have heard about or they may have collected information on and collectively look at whether there's a genetic reason or other common reasons that might be responsible.
They came to look because we have this embedded national network and they're interested in how we've done that. They can't do that in the United States. In the United States the hospitals compete with each other, even within the city. The international review team, when we began our work, told us that we'd never get this network set up even in Canada, and if we did we wouldn't find any biomarkers of drug risk. Well, we stopped looking after six months because we found three.
We did get the network set up. It took 18 months, but we did it. We feel with all the privacy issues, all the ethical concerns across the country, that every ethics review committee at every hospital and university in every province has to approve this, and that's all been done.
I think we have a unique value here by embedding such networks in the health care system that we can add to other jurisdictions, which other jurisdictions just simply can't do.
I'll start, and then I'll let you comment, Madeline.
Very quickly, I've spent a lot of time working with Health Canada, many years, and also the provincial governments. I have been profoundly shocked, perhaps, on the lack of progress in many issues. We seem to have the same meetings with the same discussions time and time and time again.
There was a meeting in March, a stakeholder consultation, a Health Canada round on progressive licensing. I missed that. I told them I would come to talk to them about what I've done. I met David Lee, the lead senior counsel there, and Maurica Maher, who's head of the progressive licensing framework. I actually think those guys have the right attitude to this, but what they need to do is focus on solutions. It's great to have a framework, a legislative framework, but it has to be solution-directed.
If you want safer drugs for women, pick a drug, pick a group of women to test the safety and the new surveillance system on. It's the same with children, the same with men—let's not forget men. These safety issues are for all patients and are important. There are gender and age issues that are important, but it's important that we look to decide which safety solutions we would like to come up with first. So have solutions in place that you're aiming for, not just a framework for licensing. It's great, but it looks a little bit like a Cadillac from, frankly, a car dealer who hasn't ever really built anything like that before.
They need to recognize that we need to have very specific objectives to improve the safety. Maybe it's about a vaccine like the HPV vaccine, to understand the determinants of the deaths that have occurred or other risks that exist. There are many, many drugs and many reactions to choose from. We just need to pick two or three and get our feet wet.
There are two points. One is the incomplete nature of reporting, and the other is the quality of the reports, which is what we're talking about.
So the first is incomplete reporting. Why don't people report? There are lots of reasons that people have cited. I believe, after having studied this for 20 years, that the reason people don't report is that there's no reason to report. What happens if I report an adverse reaction? Health Canada already knows about that one. This is well accepted. Those are some of the things that I hear from clinicians. They're not reporting reactions because they recognize that somebody already knows about them. They don't understand the purpose of surveillance. The purpose of surveillance isn't to uncover whether a drug is responsible. It really should be to uncover whether there's a solution to the drug safety problem that can be produced as a result.
In 2004, a group of researchers in Toronto in Canada found that for toxic epidermal necrolysis, the most serious form of skin reactions that occur from drugs like Bactrim or cotrimoxazole, actually where the skin turns black and falls off in very large sheets--it's largely fatal in most cases, an awful condition--most of the patients end up in Canadian burn centres. There is almost no non-drug reason for that particular reaction to occur. So they went to Canadian burn centres and said, “How many of these cases have you treated in the last five years?” I think that was the length of time. They found only 4% of those cases were actually reported to Health Canada.
So I think part of the problem is that people don't see a reason to report in terms of helping them find a solution to these problems. It's just another report of a reaction that's idiosyncratic, from the Greek idios meaning “compound” or “mixture” of reasons. We don't know why. So I want to find a reason why.
The second question you asked was about the quality of reports. Why are the reports that come in not complete? And it's not just my reports. It's the ones in Health Canada, the ones I've seen through the Canadian pediatric surveillance program, the ones I've seen for the network I've built in the United States. The reason they're not complete is the physicians tell you the information they think you want to know. So if they think the purpose of reporting is to link drug and reaction, they'll report “Paxil: suicidal thinking”, and then sign their name. They don't provide all of the other information that's useful to determine the biological reason for the response, because they don't understand how you're going to use that information or how it's being used.
So I think that's part of the problem. We have to do more than just sell clinicians on reporting for the public good. We have to show them why it's useful--because we can get solutions.
I found when I built the network across the country that oncologists didn't want to participate in it initially. But once you start showing high odds ratios, high risks associated with a particular gene trait, they start to listen. The arms become uncrossed and they begin to listen and move to the edge of their chair and provide funding. Once they see a solution possibility, they begin to report. So I think those are the reasons why.
Vis-à-vis the HPV issue, as I said before, this could be the best thing since sliced bread. Our position at the clinic has been that it's premature to have put it into the population base until we knew how long it lasted and whether or not the viruses that are in it actually are the ones that women and men are being exposed to. We have some sense in Manitoba that they may not be.
Those are big issues, because if it wears off, what are we going to do? If we take the model of chicken pox and others, you actually get sicker when the vaccine wears off. And as you may know, repeat vaccination after school in adults is totally related to socio-economic issues; that is, people who are poor and the children of people who are poor are much less likely to revaccinate or to become vaccinated. It's a health equity issue, and the reason that's important in sexual and reproductive health is that the other burdens of problems with sexual and reproductive health also are borne by people of lower socio-economic areas.
What we know about access to cervical cancer.... And we have made such a huge impact. The rates of death in Canada have plummeted. In Manitoba, we have about eight to eleven deaths a year right now. Of those women, the vast majority were in care but didn't have a Pap test in that timeframe. How can that be?
I would plead that some of that investment needs to go to places that are women-friendly, that provide female physicians, that do outreach to women to get them into care. That's what I meant by “They died of a lack of care”. They saw a doctor; they just didn't get what was needed. Women with disabilities, poor women, and women with addictions are particularly challenged in this area.
Regarding the info highway, I have two pieces I can speak to on that—which gets me to the part I didn't even get to talk about. How convenient is that?
It is true, the electronic medical record will help us with this. These investments that are being made to help develop these systems will help.
The other piece is an electronic reporting process itself—not a web-based one, but in the same way that physicians can use a Palm Pilot to send off a bill to every provincial government, they could fill this out as well.
I hope I answered that piece. But I also wanted to talk a little about increasing Canadians' capacity in drug policy.
Canadians believe right now that if it's approved for use, it's a great drug and should be on a provincial formulary—I'm sure, if you talk to your provincial counterparts. They can't believe and they don't believe, if it's approved for use, that it is much of a risk for them, because they believe that has happened.
So we have a huge problem in what our patients understand an “approved” drug to be and what it means. This means increasing their ability to be thoughtful consumers and understand what's going on in their own bodies.