Evidence of meeting #19 for Health in the 39th Parliament, 2nd Session. (The original version is on Parliament’s site, as are the minutes.) The winning word was women.
A recording is available from Parliament.
Conservative
The Chair Conservative Joy Smith
Good morning, and welcome back from the break. It's so good to see everybody here.
Committee business has started up, and we're really pleased to have our guests here today. But before we hear from our witnesses I would like to ask members of the committee to devote a few minutes at the end of today's meeting for consideration of committee business and the proposed meeting schedule. You will get that schedule following the witnesses' presentations this morning.
Madame Gagnon.
Bloc
Christiane Gagnon Bloc Québec, QC
I would like you to set aside some time to discuss certain points, because I will not be able to stay longer than an hour.
Bloc
Christiane Gagnon Bloc Québec, QC
I will have to leave after an hour. So if there is a vote on a proposed work plan, we should set aside some time to discuss it.
Conservative
David Tilson Conservative Dufferin—Caledon, ON
We all have difficulties with our schedules. If we are finished with our guests I have no problem with that, but if our guests are still here I think it would be most inappropriate to delay our guests simply for one member who's unavailable.
I appreciate that we all have those difficulties, but we've invited our guests to come here, and they have priority.
Conservative
Steven Fletcher Conservative Charleswood—St. James—Assiniboia, MB
Obviously the Bloc members are an important part of the committee. I wonder if we could move the future business to the next meeting where they could contribute.
Conservative
The Chair Conservative Joy Smith
I would like to present this to you. Our next meeting will be rather full, with little time. Today we have two witnesses, and if we get through the presentations and the questions and answers, we could get the business done a little earlier. But it's the will of the committee.
I'll go over the situation for some of the members. I said that at the end of the meeting today we have some committee business to do. We have two witnesses and we don't want to curtail their time or the questioning, because they have some very important things to share with us. Madame Gagnon has to leave early, and asked for the committee business to be dealt with earlier. At that point two members said we have to make sure we don't short-change the witnesses; we need to hear everything they have to tell us. Mr. Fletcher suggested we leave the committee business until another day.
If the witnesses are finished and the questioning is finished within the hour or so, should we go straight to committee business? Is everyone willing to do that?
Mr. Tilson.
Conservative
David Tilson Conservative Dufferin—Caledon, ON
I don't know how much business it's going to entail. The guests today have had no notice that they might be short-changed. The guests next week could be given notice that the regular meeting will end at a certain time.
We're killing all kinds of time right now blathering about this. My suggestion is that we put this business on for next week so Madame Gagnon will have an opportunity to participate in the business meeting. The guests next week can be put on notice.
Conservative
Conservative
The Chair Conservative Joy Smith
We will do that.
I would like to welcome today Ms. Madeline Boscoe, executive director of the Canadian Women's Health Network; and Dr. Bruce Carleton, senior clinician scientist from the University of British Columbia, Child and Family Research Institute, B.C. Children's Hospital.
I'd like to remind witnesses that you have ten minutes each to make your presentations. Following that we will have questions from all the committee members.
Ms. Boscoe, I would ask you to begin.
Madeline Boscoe Executive Director, Canadian Women's Health Network
I'm delighted to do that, and thank you very much for the opportunity to come today.
It's also great to see the number of Manitobans on this committee. I guess it says something about how seriously we take this aspect of Canadian culture.
Executive Director, Canadian Women's Health Network
I was going to bring a Jeannnie's cake, but just couldn't get it together. I'm sorry.
Conservative
Executive Director, Canadian Women's Health Network
Okay.
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?
Executive Director, Canadian Women's Health Network
I would say that my written remarks to you are going to deal a little more with lifestyle management and the whole concept of health information and access. As you may know, Madam Chair and members, I co-chaired the Minister of Health's advisory committee on the health info highway and consumer and public health information. I have some remarks on that.
Conservative
The Chair Conservative Joy Smith
Thank you, Ms. Boscoe.
Dr. Carleton, could you give us your presentation please?
Dr. Bruce Carleton Senior Clinician Scientist, Child and Family Research Institute, B.C. Children's Hospital, University of British Columbia
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.
Thank you.
Conservative
The Chair Conservative Joy Smith
Thank you so much.
If you permit me, committee, I'd like to ask one question before we start the committee.
I'm very interested in this heart drug. As you know, cancer patients who have very heavy chemotherapy are given a drug that could affect the heart quite adversely and that belongs to this family. How do you know? Right now what you're saying is that in Canada they don't test for this gene in the body.
In other words, what you're saying as a scientist is that even if the patient is forewarned, you could predict as a scientist whether or not the heart would be affected if we did that test. Is that correct?
Senior Clinician Scientist, Child and Family Research Institute, B.C. Children's Hospital, University of British Columbia
That's right, but we're the first to sort of couple these things together, and the results are preliminary. As you know, the best work that's done by scientists is that which is peer reviewed. We should get this published, and then we should move this into the commercial market.
Michael Hayden, the geneticist, and I were just awarded a commercialization grant from Genome British Columbia. We plan on bringing one of those three discoveries to the commercial market. I'm particularly interested in doing that quickly, for a couple of reasons. It's mostly because it can help to further endow the work we're doing. Doing this kind of work and getting the kinds of funds you need to run a national surveillance system is very difficult for an academic, and it requires continuous care and feeding. At the end of my three-year funding stint, which ends in December, I will have no funding. People begin leaving surveillance positions six to eight months before the funding runs out, to find other positions. It's critical that we endow this work so that we can continue to make it grow.