Health Committee on April 15th, 2008

[The Vice-Chair, Liberal, Lui Temelkovski]

I call the meeting to order.

Pursuant to Standing Order 108(2), we are continuing our study on post-market surveillance of pharmaceutical products.

Today we have with us Alan Cassels, a pharmaceutical policy researcher, School of Health Information Sciences, University of Victoria; Mary Wiktorowicz, chair and associate professor, School of Health Policy and Management, York University; and have Robyn Tamblyn, science director, McGill Clinical and Health Informatics, Department of Medicine, McGill University.

We will start with ten-minute opening remarks from each presenter, and then we will go into our question and answer session.

I thank you for coming here and bringing all of your good information. We will start with Mr. Cassels.

[Alan Cassels, Pharmaceutical Policy Researcher, School of Health Information Sciences, University of Victoria]

Thank you very much for having me here. I'm surprised there's no snow here. Usually when I come to Ottawa, I like to gloat about how difficult it is back in Victoria, where we're wading through the cherry blossoms and the daffodils.

My name is Alan Cassels. When I told my family last week that I was coming to Ottawa, my 11-year-old daughter, a budding environmentalist, said to me, “Dad, are you going to be increasing greenhouse gases to travel all the way to Ottawa for a ten-minute speech?” I had to explain to her that every day in our country people are being harmed or die because they are taking perfectly legal prescribed drugs. I told her that I didn't want her or her brother, or anyone, for that matter, to die because they or their doctors didn't learn of the potential dangers of prescription drugs. I told her the story of Terence Young, who lost his own daughter when she took a drug they thought would help her. So my daughter said to me, “Okay, Dad, you can go to Ottawa.”

I've been doing drug policy research in British Columbia for 14 years. My research at the University of Victoria is funded by the Canadian taxpayer, mostly through grants from the Canadian Institutes of Health Research and the Ministry of Health. I've never held any stocks or shares in pharmaceutical companies, nor have I ever done any work for the pharmaceutical industry. I mention this specifically because I think it's important. As a researcher, I like to base my assertions on data, and my reading of the data tells me that most of the time, when patient groups—many of those groups, by the way, do vital and important work—have ties to the pharmaceutical industry, they will push for policies to improve the profits of the companies that fund them.

My reading of the data also tells me that the people you've heard from before who demand better transparency of drug information, better regulation, more careful safety screening of drugs, and better warnings are not receiving funding by corporations whose interests are in profits. Those who have gone before me, specifically Michelle Brille-Edwards, Terence Young, and those from the Canadian Women's Health Network, have made some very good suggestions. I support those suggestions, and I hope this committee acts on them.

I also want to tell you that I went to school not too far from here, in Kingston. I went to the Royal Military College of Canada. As an officer in the Canadian Forces, I was a parachutist, a military diver, and a ship's watch-keeping officer. I have two United Nations missions under my belt. I've faced the business end of an AK-47 assault rifle. I've faced minefields in Cambodia, and other sorts of near-death experiences on the high seas. I have two medals for my peacekeeping and one medal for 12 years of service in the Canadian Forces.

I only mention my military experience for one reason. It's because I've come to understand fear and how it tends to motivate people. Let me explain.

This drug that I hold up right now is the most prescribed drug in the history of the world. It's a drug to lower cholesterol, called atorvastatin. It also goes by the trade name Lipitor. Globally, the manufacturer sold $14 billion worth of this drug last year, and in Canada about 14 million scrips for atorvastatin were written for Canadians. In total, more than 20 million prescriptions for cholesterol-lowering drugs, or statins, get consumed in Canada every year, at a cost of over $1.5 billion. That's an awful lot of money for one class of drugs.

Let me tell you three things about high cholesterol.

First of all, high cholesterol is not a disease. It is a risk factor for a disease, but it is treated as a disease in and of itself.

Secondly, taking a drug to lower your cholesterol may save your life. If you are a man and have had a heart attack, it can help prevent another one. The benefit of the drug in these high-risk men is about 3%, which is to say that even in high-risk men, over 90% of the men who swallow these drugs every day for five years will see no benefit in terms of living longer. There's evidence that the drug will not provide any benefits for women, and these drugs provide no benefit for the elderly.

The third thing I want to tell you is that taking a drug to lower your cholesterol could kill you. I don't want to be dramatic about this, because many people who take these drugs don't have any problem with them, but some people who do will experience terrible, severe, and sometimes intolerable adverse effects. The most well-known adverse effect is a disease called rhabdomyolysis. It's a muscle-weakening disease that can cause kidney failure and death.

Cerivastatin, a drug that went under the name Baycol, was very, very good at lowering cholesterol, but it also killed people. It was removed from the Canadian market on August 8, 2001.

Five years after Baycol went off the market, Health Canada issued a public advisory about the risks of rhabdomyolysis. That was on July 12, 2006. Did Canadian doctors read the warning? Did they even see it? Did consumers become concerned and stop taking their statin drugs? Not the way I read it; Canadians swallowed 22 million scrips for statins last year, and the number has risen steadily over the last decade.

Yesterday I searched the Canada Vigilance online database and found 1,173 adverse reports for this drug, atorvastatin. How many people are actually being hurt by this and other statins? The simple answer is that we don't know. Those 1,173 reports could represent between 1% and 10% of people injured by atorvastatin, which means to say that there could be between 11,000 and 111,000 Canadians injured by that one drug alone. There are seven statin drugs on the market in Canada right now.

The pharmaceutical industry spokespeople will tell you that they should be involved in the education of consumers about drugs, but let me show you how they choose to educate consumers. This “toe tag” ad appeared in many magazines and major newspapers across Canada. This one came from the National Post of February 20, 2004. It shows a toe tag hanging off a corpse with the headline, “What would you rather have, a cholesterol test or a final exam?” Here's another example, from Maclean's magazine, of the same ad.

These ads are probably the most egregious example of disease-mongering that this country has ever seen. The ads, which ran in both France and Canada, were the subject of a letter from the World Health Organization to the medical journal The Lancet, complaining that this kind of advertising is undoubtedly driving the inappropriate use of cholesterol-lowering drugs around the world.

How many of the 22 millions scrips for statins in Canada this year are prescribed for men at high risk? Probably three-quarters of those drugs are taken by women, the elderly, and low-risk men who would see no benefit.

The point I want to make is that in Canada we don't control the advertising and promotion of diseases, we don't control the definitions of disease, and we don't provide adequate impartial health or drug information to Canadians or to our physicians. We allow conflicted experts to sit on committees that decide the definitions of disease, and we allow our physicians to be educated by the pharmaceutical industry. This is an industry that spends in excess of $3 billion a year marketing their products directly to Canadian physicians.

So where does the poor patient end up in all of this? In my estimation, Canadians are naked in the pharmaceutical marketplace.

My recommendations for post-market surveillance revolve around stopping bad and misleading information from getting to patients and physicians, and ensuring that we have adequate data before drugs are released in the wider population. I have four recommendations.

First, I think we need a policy on disease-mongering. We need to maintain our current ban on the direct-to-consumer advertising of pharmaceuticals, but we need to go a bit further than that. We actually need more strict control of the advertising of diseases. I call it “disease-mongering” and the industry calls it “disease awareness”.

One place to start is to ask Health Canada some hard questions: What is your policy around disease-mongering? Can you collect data to see if disease-mongering is driving the inappropriate use of pharmaceuticals? What research into disease-mongering have you commissioned? What other steps is Health Canada taking to control it? Instead of trying to deal with patients who may be dying from prescription drugs, how can we stop people from taking drugs they don't need in the first place?

Secondly, we need better information for patients. After all, it's the patients who put drugs like this in their mouths every day. There's a dire need for Canadians to receive approved and regulated information about diseases and drugs provided by an independent, objective source that's free from profit-driven industries.

The Government of Canada recently showed its interest in objective consumer health information by killing funding for the Canadian Health Network, one source of quality, publicly funded information on the Internet. In terms of medical treatments, the Cochrane Database of Systematic Reviews is one of the best sources of independent research behind common health treatment.

A site licence for the Cochrane database, which the Canadian government currently won't fund, would cost about $500,000 per year, so that all Canadians--and not just people like me who work at universities--could access these reviews.

Other groups, like the Common Drug Review and the Canadian Agency for Drugs and Technologies in Health, need our full support and stable, long-term public funding.

The third thing is that we need better objective information and education for physicians. It's not just the patients who need independent information. It's time we recognize that leaving the education of our physicians to the pharmaceutical industry has some downsides. We need better education on prescribing, education that comes from an objective source, preferably one with public funding.

Australia has a national organization called the National Prescribing Service that does probably one of the best jobs in the world of providing physicians with useful, up-to-date, and unbiased information about drugs. Why can't we replicate that here on a national level and with input from the provinces? It would make a great first step in moving towards a national pharmacare plan in Canada.

The last thing is a point about progressive licensing. My suggestion would be that we should learn about drug safety from looking at how other industries operate. I personally think that post-market surveillance needs to be done and it needs to be done better. But to me, it's largely a sad, after-the-fact proposition. We have to do post-market surveillance because we do all the pre-market stuff so poorly.

Could you imagine another industry, say the nuclear industry or the airline industry, where we allow the manufacturer to rely on post-market surveillance for the safety of their airplanes or their nuclear plants? No one would accept the proposition of having the job of the regulator be to count the bodies afterwards and then decide if this is a good technology to expose to a wider population. We would never accept allowing the airline manufacturers to use people as test subjects in terms of the safety and effectiveness of its planes. We demand the nuclear and airline industries to take a zero-risk approach to their products, so why do we accept a lesser standard for products that people consume every day?

In terms of progressive licensing--and this is connected to Bill C-51--I have no idea where this will lead. But I'm left with one question about these current attempts to “modernize” the regulatory environment around drugs. How would a more modern drug licensing regime prevent another Vioxx, another Propulsid--the drug that killed Vanessa Young--or otherwise stop the thousands of Canadians who may be suffering adverse effects of cholesterol-lowering drugs?

Thank you.

[The Vice-Chair, Liberal, Lui Temelkovski]

Thank you very much, Mr. Cassels.

Now we'll move to Dr. Mary Wiktorowicz.

[Dr. Mary Wiktorowicz, Chair and Associate Professor, School of Health Policy and Management, York University]

I thank the committee for inviting me here today to engage in this dialogue.

Let me begin by saying that although pharmaceuticals are assessed for safety and efficacy at the pre-market stage, current pre-market evaluation is really recognized as incomplete. While the strength of randomized clinical trials, which is the primary evidence on which drugs are approved to be on the market, is the determination of short-term efficacy, safety is often unresolved within the limited controlled context of these pre-market randomized control trials. Their small size and short duration don't allow them to detect late-onset or less frequent adverse drug reactions. Patients with comorbid diseases are frequently excluded from such trials, and pregnant women and children. So pre-market randomized controlled trials really have limited generalizability. At the same time, these pre-market trials are essential to establish efficacy from an initial assessment perspective for safety before widespread population exposure. So we can think of pre-market randomized trials as necessary but woefully insufficient.

Canada's lack of systematic monitoring of marketed drugs means that adverse drug reactions are often not evident until years after a drug is on the market. As a result, many drugs with unacceptable harm-benefit ratios remain on the market for prolonged periods of time, thereby leaving Canadians exposed to unanticipated risks.

As representatives from the FDA noted in a publication--I believe it was The New England Journal of Medicine--the immense biological subtlety of human pharmaceuticals often cannot practically or adequately be detected in formal clinical studies. In the conclusion of that particular article they advised against taking a new medicine in the first two years in which it's marketed. I think that's a huge statement.

Researchers who have taken a look at the effect of adverse drug reactions have found that they are between the fourth and sixth leading cause of death in the U.S., contributing to more than 100,000 deaths and 1.5 million hospitalizations yearly. Since we have basically the same drugs in the Canadian market as in the U.S., we can extrapolate that in Canada the figure would be about 10,000 deaths annually due to adverse effects, or about 150,000 hospitalizations yearly. That means our current passive system of adverse event reporting--we do have a system in place, and it's after the fact--captures less than 5% of all of these adverse drug reactions. We're really only capturing the tip of the iceberg and not the whole picture.

The medicine digoxin offers a very good example. While the FDA received only 82 reports of adverse drug reactions annually, a post-market study that involved data-mining of hospital records found that it was associated with over 200,000 hospitalizations in seven years. So there were 82 reports from patients through their doctors, but 200,000 by taking a look at hospital records and seeing what hospitalizations were linked to that particular drug.

I find it very counterintuitive that just as a new drug enters the market and its use increases exponentially, its effects and patterns of use are no longer actively monitored. This is an oversight that could be ameliorated through a system of post-market surveillance.

I would like to share some insights with you from a comparative analysis that colleagues and I have done on how the U.S., Britain, France, New Zealand, Australia, Norway, and the European Medicines Agency approach pharmacosurveillance. I'm going to highlight the role that research networks can play, and how the knowledge they produce can be used by drug regulators to inform their regulatory decisions.

In these countries, two main approaches are used to look at the safety and efficacy of drugs after they're in the market. The first involves risk management plans. How these risk management plans work is that when a drug sponsor, a manufacturer, is about to have a product approved for the market, they negotiate the terms of the marketing and how they will assess risk on the market. The second involves developing a national network of research centres that can be commissioned or can submit proposals to conduct independent research. That could include observational studies that incorporate electronic health care databases.

Let me begin with the risk management plans. These currently are used by the European Medicines Agency, EMEA, in which the regulator requests drug sponsors to develop and implement a risk management plan to monitor each new drug's safety once it's on the market.

What we found is that the EMEA's risk management plans really lack transparency. What we can find about the plans is just a very brief summary on the Internet. More seriously, though, they don't involve the systematic approach to developing a study protocol. Instead, these protocols are developed on a case-by-case, ad hoc basis and they often don't entail any rigorous scientific method.

For example, they can involve developing a registry of patients who are taking a particular medication without any control group. The importance of having a control group is so you can monitor patients, but how will you know their level of adverse effects is higher than that of someone who is not taking it if you're just observing them? So you really need a control group, and that would be a far more rigorous approach. Alternatively, they can involve educational initiatives to physicians for patients, but as we all know, when industry is involved in promoting their medications, you don't necessarily get the full story on the risks and the benefits.

If we were to go that route in Canada, risk management plans should be informed by a process of risk assessment that precedes risk management, in which the magnitude of the harm is modelled by incorporating all pre-market data that's been generated and anticipating population exposure levels, so a far more rigorous approach. Unless Health Canada adopts a more systematic, rigorous approach to the risk management plans than the European Medicines Agency, including defined standards for research methods similar to the pre-market phase one, two, and three trials, and sets conditions regarding blinded assessments, alternate methods should be used to assess post-market safety and effectiveness. Such a study is developed and conducted by independent pharmaco-epidemiologic research centres.

In our study, we concluded the EMEA risk management plans are of limited value, even though they lend the impression of systematic surveillance. Just as a point of emphasis, they put something in place so the public is under the impression their drugs are being monitored, when often what is being done is not an effective approach to surveillance at all.

Reliance on drug company studies can also be imprudent, given the inherent conflict of interest, even when safeguards are incorporated. For example, in France, where they take a look at some of these risk management plans, they have an oversight committee to ensure industry adopts a scientific approach, but even those studies have weaknesses, because in the end, industry analyzes the data and interprets what they mean.

Getting industry to conduct these studies through the marketing process is an inadequate process. But at the same time, industry could still fund the research, as in the case of Italy, in which manufacturers contribute the equivalent of about 5% of their promotional budget to the Italian Medicines Agency to fund post-market research by university and clinical researchers. It would also allow studies of an entire drug class. And what I mean by that is often a pharmaceutical company will study a particular drug, and even though there are competing drugs on the market that address the same problem, they refuse to do a head-to-head comparison of one with another. So as a drug benefit plan, you're trying to decide which drugs to fund; as a physician you're trying to decide which drug to prescribe to your patient. If you don't have information on how the benefits of one drug compared to another are in an overall study framework, it's very difficult to know which one to choose.

Pharmaceutical companies have also been shown to report their research selectively, by either publishing studies with only positive results or finding a way to convey a positive outcome for those that have negative results. Recently, Turner et al. reported in 2008 that it would appear that 94% of trials for selective serotonin re-uptake inhibitors, SSRIs, were positive. In contrast, they conducted a separate analysis of the entire range of trial data submitted to the FDA and found that only half of those studies showed positive results. So again, industry can find a way to lend a positive approach even to studies that are negative.

These issues highlight the need for public oversight to ensure post-market studies address key research questions, that they are designed to produce valid results, and that they are reported accurately.

Minimizing study duplication is also likely to foster continued cooperation from doctors. A lot of these studies--these randomized controlled trials--involve working with physicians who prescribe the medication to their patients and then monitor how the patients are doing. If you're going to do separate little studies all over the place.... They found in France, where they're starting to do some of these observational studies, that physicians are starting to say they've done enough and that their patients are tired. The physicians just won't engage.

So if you're going to develop some kind of a strategy, you should use your resources, including physician time and patient time, in the best possible way.

The second approach to post-market surveillance that I would like to propose is an independent research network that creates a framework to allow oversight of study design, ensures validity, facilitates independence from commercial interests, and makes comparisons of drugs in the same class possible. Research would also be publicly available instead of being proprietary. Often we have a problem where the drug benefit plans in the provinces would like more information on the safety and efficacy of a particular product and Health Canada tells them it can't share that information because it's proprietary. So there's a problem with transparency in terms of getting the information to the drug plans and ultimately the physicians and patients who will be using that information. If we have research that's conducted in a public forum, then we will allow that data to be publicly accessible.

Several national regulators commission post-market studies from several centres. The U.S. has a research network called DEcIDE. New Zealand has a national pharmaco-vigilance centre. And in the European Union they are developing an EU-wide approach to commission international pharmaco-surveillance research from over 60 research centres across Europe. This is in the early stages of development.

Canada is well positioned to realize the potential for a national network of research centres. Our provincial health care plans have electronic health care records and pharmacy dispensing records that could be used to conduct observational research that would augment an activity already underway in Canada.

But a commitment and a will to support cooperation among provincial health care systems and Health Canada is essential to develop the infrastructure needed for pharmaco-vigilance and public health impact studies.

[The Vice-Chair, Liberal, Lui Temelkovski]

If you could wrap it up, please, I would appreciate it.

[Dr. Mary Wiktorowicz]

Sure.

So while national approaches are emerging, international coordination could also hold the potential to extend global resources and to address this policy challenge.

In order to be a global participant in this kind of international cooperation, it's in Canada's interest to explore the models of research networks that are emerging internationally and to develop an approach that optimizes our innovative research capacity to address public health concerns.

[The Vice-Chair, Liberal, Lui Temelkovski]

Thank you very much, Dr. Wiktorowicz.

We'll continue with Dr. Robyn Tamblyn, from McGill University.

[Dr. Robyn Tamblyn, Scientific Director, Clinical and Health Informatics Research, Department of Medicine, McGill University]

Thank you very much.

I'm delighted to be here, and I'm really delighted that our government is taking this initiative to examine progressive licensing and pharmaco-surveillance. I think it is such a low-hanging fruit, a sure-win proposition, that I'm just thrilled to be here.

I don't think I need to convince anybody here that this is a good thing to do, because drugs are like surgery--they can cure you and they can kill you. Surgeons get controlled by hospitals. They have to have privileges. They do morbidity-mortality reviews, that kind of thing. But drugs...well, drugs get to be prescribed by everybody. Actually, there are 50,000 physicians--25,000 of them are primary care physicians--and they prescribe basically 80% of all the drugs. So there aren't the same natural controls here. So I think pharmaco-surveillance is definitely going to be an exciting initiative and one that's surely overdue.

Not only that, but what I would like to talk to you about is how you're going to do it, because we have some unique advantages in Canada that no one else in the world has. That has to do with the fact that we have a socialized health care system, that we actually provide services—come one, come all—for every Canadian. By virtue of having to administer a system like that across the board, we are like a series of health maintenance organizations--one in each province--that provide complete population coverage. If you get bankrupted by your health, you're not tossed out and no longer visible to the system. We count every one and all.

I would say that the only other countries that have the kinds of administrative systems that keep track of what everybody is doing are Denmark and Iceland. Those are the only other groups that have that kind of deep, detailed information on what's happening.

Now, what's exciting about this is that you're doing that anyway, so you can leverage that in. In fact, Canadian researchers have leveraged that. They have become leaders in the world in terms of how they actually assess the risks and benefits of drugs, using these detailed health services records that are maintained in each and every province.

What Mary referred to, and what Dr. Laupacis referred to earlier, is a proposition that was put together by a group of regulators, drug benefit managers, and researchers to say, “We can build a network across this country that will allow the timely observation and surveillance of who is using the drugs, how much they are using, and what the outcome is of that information on a daily basis”. That's possible, on a daily basis, with the information we have.

We haven't leveraged this opportunity. The data sit there in large servers and computers. Why don't we do that? I really don't know.

We've put together a proposition, during the first time that people such as myself have collaborated in such a broad scale with everyone, to actually link together these data repositories in each and every province. We will be the envy of the world.

Iceland actually sold its data. Saskatchewan has actually, I would say, more or less sold its data to the industry to have this kind of information.

We can have this information as Canadians. A proposition has been put forward; it's on the Health Canada website. I think we should be excited about that as Canadians, because I think we could become world leaders. This will be the place where people should come to actually assess the risks and benefits of drugs, using this data.

The second investment that we have made, which is also exciting and actually provides us with the complementary tools, is essentially the investment that we've started to make in the electronic health record in Canada. Some $1.4 billion has been put aside for upgrading the electronic health record in Canada. As part of that investment, about $34 million was put aside to create a repository of all drugs, all people, in each and every province. That information flows when the drug is dispensed into a repository. All electronic prescriptions would flow to those repositories.

Why is that information critical? The information is critical because in fact by putting in place essentially electronic prescribing, computerized, drug management systems for each and every provider in this country, we have certain huge assets. Number one, you have information on each drug dispensed for every Canadian. Number two, you have the potential to say, if you make this a mandatory requirement, “Why was that drug prescribed?” So you begin to be able to monitor why drugs are being prescribed. Are they being prescribed for people on whom the drug was tested or not?

I think that is a critical question, because in various studies I looked at, anywhere between 30% and 90% of some drugs are being used in people who have not been tested. That is a risk management thing we can actually address by essentially collecting that information through what we've already invested, which is an electronic drug repository, drug management system.

The second thing that is important about that is that should we achieve the objective of widespread adoption that is present, let's say, in Denmark, the United Kingdom, and Scotland, we would see almost 100% of physicians using electronic health records to deliver care. The advantage we have is that this would mean that with the repositories that have been built through Canada Health Infoway, that information on all labs, all diagnostic images, and all drugs would be available, irrespective of who prescribed them.

That means that for the first time ever a physician will have a complete drug history when they're prescribing. What drugs have you taken? What drugs have been stopped because you've had adverse effects from them or you've been allergic to them? What drugs should not be prescribed because there is another drug that another physician has prescribed that you don't remember, because you're calling it the purple pill? It actually is a magenta colour and is long and oblong, and there are 400 pills that shape and size that you'll have to figure out on your own, thank you very much.

We have this opportunity of leveraging this incredible investment that has been made to build these repositories, to say to each and every physician in this country and each and every pharmacist in this country that they shouldn't be prescribing or dispensing unless they have information on all of the drugs a person is currently taking or has taken in their medical history. We will have that information. That is the most exciting piece.

The second piece is when problems are identified. As Mary and Alan have pointed out, when problems are identified a piece of information is sent, essentially, to a physician to join the other 900 pieces of information that arrive daily on his or her desktop. That piece of information, instead of being sent by paper, essentially could be linked to the drug in the repository, and every time that drug is prescribed an alert fires to say that drug has just killed 300 people. An advisory is on this drug: “For this treatment, the indication that is this is not a good thing to do.”

This is possible in this day and age. We've already made this investment, and what it requires now is really a strategic decision about how we are actually going to leverage our investment so that we have the tools to actually do daily day-to-day monitoring for all Canadians through these two very exciting opportunities, where we've already made deep investments in Canada.

On a final note, while information technology is probably going to revolutionize the way we deliver care, one area where I'd have to say we're weak--in fact, we're at the bottom of the pile--is that we've built fabulous state-of-the-art resources where information resides and can be identified very effectively and accurately as being your information, but we have not addressed what other countries have done in terms of how to get the practitioners in our country to use that information.

We have some strategic decisions we need to make in order to actually have all 50,000 physicians, 150,000 nurses, and 60,000 pharmacists in this country using that information, so that we no longer have deaths because someone actually got three anti-coagulants because they didn't recall taking the first two, or an excessive dose of digoxin, which happened because two physicians were prescribing for them. This happens every day in our country, and it simply is not necessary.

Once we have this information, it can be a mandatory requirement that all stop orders on drugs get attached for a reason. Adverse effects and treatment ineffectiveness account for 66% of all stop orders in this country. Secondly, you can actually make it a mandatory field to have treatment indications so you know when people are getting drugs that are what I call the grand social experiment: they're getting drugs for which they weren't tested.

I would beg you to consider some of the strategic policies that were put in place in other countries, which have succeeded in achieving an almost 100% uptake of computerized prescribing electronic health records: a policy for paying for quality; support for training and transformation of practitioners in adopting electronic health records; and most importantly, the delivery of value-added benefits to those practitioners who work daily against all odds with a very archaic information system and need these value-added tools at the bedside.

Thank you very much.

[The Vice-Chair, Liberal, Lui Temelkovski]

Thank you very much, Dr. Tamblyn.

Now we will continue with questions and answers, for seven minutes per questioner. We'll start with Madam Kadis.

[Susan Kadis, Liberal, Thornhill, ON]

Thank you, Mr. Chair.

Welcome to all our guests today for our continuing study of post-market surveillance.

Recently, as you probably heard, there was an announcement by the government, a consumer protection announcement. We do need a balance between protecting patients against harm and helping them to get life-saving drugs and medication as quickly as possible.

It would seem, based on the government's latest announcement, that we are going to rely more than ever on post-market surveillance, because the government appears to be fast-tracking drug approvals. Do you believe that this change is effective and will be beneficial for Canadians' health and well-being, or will this put patients and Canadians at more risk? We have heard some testimony concerned about risks. Will potentially harmful drugs, such as Vioxx, be prescribed to patients more quickly through that process? Also, they are proposing that hospitals and industry will, on a mandatory basis, report adverse drug reactions, but pharmacists or doctors will not.

I am interested in hearing your comments on the new announcement--if you think it will actually enhance the safety, health, and well-being of Canadians, or if there are concerns associated with that.

Here we are trying to strengthen, I believe, post-market surveillance and doing a very in-depth study. By the same token, I am concerned--and others have raised the issue--that we will have less rigorous standards for safety at the earlier stage of the pre-market trials.

[Dr. Mary Wiktorowicz]

I think the post-market aspect of this bill is important, because you need that capacity to be able to do the research, as my colleagues and I have pointed out. But when it comes to the pre-market portion of the bill, I get afraid. For example, as you mentioned with Vioxx, would Vioxx have been prevented if we lowered the standard for getting it on the market quicker? I don't think so. I think you're going to have more Vioxxes. Certainly we'll have post-market surveillance in place, but how that post-market surveillance will be done is very ambiguous right now. We don't know, actually.

It is great to set up a system of post-market surveillance, but right now there are a lot of questions as to how it will be done and the role that industry will play. So I would not lower the pre-market framework of phase one, two, and three trials. My sense is that there are consumer groups who step forward and say that patients want drugs at an earlier time, but I still think that there's a problem with getting them. They are not aware of the risks that are also associated with these drugs. The risk-benefit profile of these drugs is not completely clear. You're taking a much greater risk than I think is warranted.

Health Canada does take a longer time than other countries in reviewing drugs currently, and I think that is one of the pushes, but the fact is we have had a lower record of withdrawals than the United States and other countries have had. One of the reasons is that drugs are on the market in the U.S. and we get to see them, and when there's a Vioxx out there, we're not even going to approve it. We're not letting it out of the gate. Actually, I think that's a good thing. I'd rather be protected than take risks.

If you're talking about drugs that address life-threatening conditions like AIDS and cancer, we have a fast-track system already within Health Canada that allows those drugs to get on the market after only phase two trials, as far as I know. The drug companies are responsible for doing the post-market studies after the fact.

The problem with leaving industry in charge of the phase four trials, which are the post-market trials, is that there is no obligation for them to complete those trials. In the U.S. they found that less than half of the post-market studies that industry had agreed to conduct were ever begun. There is recent legislation, from the fall of 2007, that will give the FDA the power to compel industry to complete those phase four studies, but even in our current system, where we allow some fast-tracking, those studies are not necessarily completed, and there are no repercussions for industry; they just go on and market.

Just to summarize, I think I would not reduce the standards in the pre-market phase. We definitely need greater surveillance out there. So I laud the post-market portion of the bill, but the pre-market portion I would amend to strengthen it and not lower the standards.

[Dr. Robyn Tamblyn]

There are two issues there. One is what you ideally want if you are going to pay for a drug. If you're a drug benefits manager in a province, you want to know whether it's worth it for you to pay for the drug. You essentially want to know whether that drug is going to reduce your costs--your hospitalization costs, your emergency-visit costs, your treatment costs.

Unfortunately, many of the phase three trials have end points that don't allow that to be determined. For example, this is the reason British Columbia is running its own trial for the Alzheimer's drugs: to determine whether or not they delay nursing home admission, because that's their big cost, right? Whether the person does one point better on Mini-Mental status isn't really that helpful, because that's not really the end point that you care about.

That's one issue, and Canada can't really take that step alone. We're 2% of the drug market, so do we want to take that step alone? I think we should take it internationally and say that in phase three pre-market standards, we want to have disease end points and not intermediate proxy end points. That means the trials are going to be longer. They're going to be more expensive, and--let's not kid ourselves--the cost of those trials will be downloaded onto the price of the drug, so I think there's not just a simple answer to your question.

The second issue is that at the moment you cannot control off-label prescribing. Once a drug is out in the market, you can't say, “Don't prescribe it for kids and don't prescribe it for people who are taking more than three other drugs”, which is the group on which it was tested. The group on which it was tested is not necessarily the group in which the drug is going to be used.

That can again be a pre-market requirement. You can say you want the target population on which you test that drug to be just like the target population in which you're going to use that drug. A granny who is on 16 drugs and who has three other health problems is going to be pretty unpredictable, as you can imagine, and you're going to need a very large sample of people on which to test that new drug.

The third thing you really care about is whether this drug is any better than the other drugs on the market. That's what Mary was talking about. If you want to know that, you make it a pre-regulatory requirement that the trials get compared to current comparators on the market for treating the same treatment indication. Again, can Canada go it alone? I doubt it. I think we are a small portion of the drug market and I think that there would have to be an international agreement to do so.

In the end, you're still going to have some unknowns--the rare events that are going to happen, the off-label prescribing that's going to happen--and there you're going to get some unexpected outcomes for which you have to have a post-market surveillance. There's no other way of doing it.

So either you get international collaboration on getting the right end points before notice of compliance or you actually put in a robust system after the fact to say that it's conditional upon your meeting the following requirements in the first two years the drug is on the market, and you've got that information system behind you to say you can actually measure it--not on the people that you select to be in your study, but on each and every person who's on that drug.

[The Vice-Chair, Liberal, Lui Temelkovski]

Thank you very much, Madam Kadis.

Please go ahead, Madame Gagnon.

[Christiane Gagnon, Bloc, Québec, QC]

Thank you for your presentations, they are very informative and provide additional information on drug monitoring.

Mr. Cassels, you've addressed a number of interesting points. If others would like to answer my question, it might broaden the debate on prescription drug advertising. I don't really watch any advertising, because I do not take any specific drugs; I do not suffer from any illness requiring me to take drugs.

Let's take the example of Viagra. We get the impression that it is a harmless drug. However, in actual fact that is not the case. How could we amend the legislation to ban this type of advertising? You said there is no control over the definition of the illness and that marketing is inadequate. The individuals concerned who have erectile difficulties want to solve those problems. But this type of advertising is completely false when it comes to the effect the drug may have on health and the adverse events which could occur.

[Alan Cassels]

I'm sorry, but my military college French is not very good.

[Christiane Gagnon, Bloc, Québec, QC]

You may answer in English: I can hear the interpretation.

[Alan Cassels]

Then I will speak in English.

I have a couple of points.

When you said that some drugs are harmless and some drugs are dangerous, I think I would want to correct that to say that there's no such thing as a dangerous drug.

[Christiane Gagnon, Bloc, Québec, QC]

No, I referred to advertising.

[Alan Cassels]

Sure, there's the advertising, but the drugs themselves are inert in the sense that it's how they're used that influences whether they're being used wisely and safely or incorrectly and dangerously.

In terms of drug advertising, such as erectile dysfunction drugs and so on, what some manufacturers would say is that advertising the drugs provides information to consumers. The style of ad we see in the U.S. gives you information about the drug and provides some information about the side effects. That's a regime that's currently not allowed in Canada.

I forget the second part of your question.

[Christiane Gagnon, Bloc, Québec, QC]

How should we amend the legislation to ban all advertising? There is a great deal of drug advertising. We always get the impression when watching it, that the drugs are harmless and that they will solve our problems. Patients are seen to be happy. Earlier on you referred to cholesterol. I took the example of Viagra.

What should we do to prevent this type of advertising from appearing in newspapers or various advertising-driven media?

[Alan Cassels]

If I understand the question correctly, it is about what can be done so that these advertisements don't pop up in other media.

Currently we receive a lot of direct-to-consumer advertising of pharmaceuticals from the United States in magazines and so on. We have the ability to block ads from the U.S. if we want to. It seems that Health Canada or the regulatory environment is not that interested in blocking ads from the U.S. But we could do it if we wanted to.

The ad I referred to was not a drug ad; it was a disease ad. It's an advertisement for a condition. That's, I think, what companies are using in Canada to drive people to their doctors to seek the drug they're selling. In fact, they're selling the condition, not necessarily the drug.

The main point I was trying to make is whether we can at least try to curb the excesses of disease advertising. Of the many people who see those ads, perhaps some might go to their doctors and open up a conversation, and that might be a good thing. But many of those people are going to get worried. You're going to create a certain psychological anxiety in the population, and you'll drive those people to their doctors to ask for tests and drugs that they probably don't need.

I hope that answers your question.

[Christiane Gagnon, Bloc, Québec, QC]

Yes, you did answer my question. I was wondering what type of advertising or whom your comments were targeted to. You mentioned disease ads creating anxiety and a need for people to visit their health care professional to ask for a drug. It remains drug advertising. The end result of this process would be to get a drug.

[Dr. Mary Wiktorowicz]

I think the problem is, as Mr. Cassels mentioned, that the advertising comes from the United States. In Canada, companies are not allowed to do this. If you want to draw up new legislation, perhaps you should prohibit Canadian broadcasters carrying American programs from broadcasting such advertising here, in Canada. It is true that it is prohibited in Canada.

[Christiane Gagnon, Bloc, Québec, QC]

There still is advertising, though. They do circumvent the law. It is one way of circumventing the law.

[Dr. Mary Wiktorowicz]

Yes, that is what Alan showed. Companies are not allowed to associate a product to a condition, but they manage to do certain things without associating the drugs to the condition.