Health Committee on April 8th, 2008

[The Chair, Conservative, Joy Smith]

Good morning, everyone. Welcome to the health committee. We're so happy to see you here today. We have had some very good discussion on post-market surveillance of pharmaceutical products, and the committee is very happy that you have joined us today.

Before we begin hearing from our witnesses today, I'd like to ask for the committee's agreement that at the end of the meeting we set aside 15 minutes to discuss a request from two delegations, from Germany and the Czech Republic, and also to determine the guidelines for the natural health products meetings on May 8. Can I have a show of hands? Is that agreeable, that 15 minutes?

[David Tilson, Conservative, Dufferin—Caledon, ON]

At the end of the meeting?

[The Chair, Conservative, Joy Smith]

At the end of the meeting.

[David Tilson, Conservative, Dufferin—Caledon, ON]

At one o'clock?

[The Chair, Conservative, Joy Smith]

No, at a quarter to one, before the end of the meeting, the last fifteen minutes.

[David Tilson, Conservative, Dufferin—Caledon, ON]

Okay.

[The Chair, Conservative, Joy Smith]

Is it agreed?

[Some hon. members]

Agreed.

[The Chair, Conservative, Joy Smith]

Thank you, members.

Now pursuant to Standing Order 108(2), I'd like to welcome our guests, our witnesses today, to our meeting. We have three witnesses today. We have Mr. Andreas Laupacis, and you're a doctor, I believe, are you?

[Dr. Andreas Laupacis, Executive Director, Li Ka Shing Knowledge Institute, St. Michael's Hospital]

That's correct.

[The Chair, Conservative, Joy Smith]

Dr. Laupacis, welcome today. I understand you're from St. Michael's Hospital in Toronto. We're very pleased to have you here today.

Dr. Steve Morgan from the University of British Columbia is here as well. Welcome.

And Mr. Patrick Orr, who is a lawyer, I believe--is that correct, Mr. Orr? And you're from Ottawa?

[Patrick Orr, Lawyer, As an Individual]

That is correct.

[The Chair, Conservative, Joy Smith]

Good.

I want to tell you that each of the presenters has 10 minutes to present. Following that, we will be asking the committee members to come forward with their questions.

Could we start with Dr. Laupacis, please?

[Dr. Andreas Laupacis]

Thank you very much. Good morning, everybody.

Thanks for the opportunity to talk with you about the post-marketing surveillance of pharmaceuticals.

By way of introduction, I'm a patient who consumes drugs, a physician who prescribes them, a researcher who studies their benefits and side effects, and a drug policy advisor. I'm also one of the authors of the proposal to establish a real world safety and effectiveness network, which is currently being considered by Health Canada.

Let me start by saying that Canada and the rest of the world would benefit greatly from a more robust mechanism of post-marketing surveillance of pharmaceuticals, for a number of reasons.

First, some important harms are not detected in the studies that are currently conducted for licensing, either because the harms are so rare that not enough patients are studied in the initial randomized trials to be able to detect them or because the side effects occur after prolonged use.

Second, the benefits and harms of drugs in the real world can be different from the benefits and harms found in the randomized trials conducted for licensing. Those trials tend to enrol patients who are healthier and more likely to take their drugs than the average patient, and the patients are cared for by health care providers who can offer closer follow-up than is usually the case in actual practice. Thus the benefits and harms in the real world may differ from those in the trials done for a licensor.

And third, some drugs are currently licensed on the basis of so-called surrogate markers--for example, a decrease in cholesterol--with no clear evidence about their impact upon the outcomes that matter to patients, such as whether the decrease in cholesterol leads to a decrease in heart attacks or death.

Post-marketing studies have the potential to provide information about the outcomes that matter to all of us. Currently there's no systematic approach to post-marketing surveillance in this country, which is why I enthusiastically support the establishment of the real world safety and effectiveness network, which has been submitted to Health Canada.

This independent network would bring together clinicians who prescribed drugs, patients who benefit from and are harmed by drugs, Health Canada, which approves drugs, the provinces and territories that pay for them, and researchers who can analyse the databases, the forum--that basis of post-marketing surveillance. Such a network would provide important information that is not currently routinely available, particularly if it is well linked with other such networks across the world.

I've been asked to say a few words about Health Canada's proposal for progressive licensing.

As I understand it, the idea is to allow some drugs to reach the market relatively early, on the basis of promising but not conclusive evidence of an attractive benefit-to-harm ratio. This initial licensing would be conditional upon the performance of post-marketing studies to determine if the initial promising results are substantiated when the drug is used in actual practice.

The idea is attractive in one way. It would allow patients who are suffering from a severe disease for which there is no good therapy a chance to try a drug with promise. However, there are also considerable downsides to this approach. There is a reason that randomized trials are the gold standard for the evaluation of new drugs. Because of the process of randomization, in which patients essentially receive the new drug, or standard therapy based upon the flip of a coin, those who receive the new drug are virtually identical to those who receive the current best therapy. This means that one can be quite certain that any differences between the two groups, either in benefits or harms, are likely due to the drug.

Patients are rarely randomized in post-marketing studies, so that those who do and do not get the new drug in the real world are often very different in their underlying characteristics, which can make it very difficult to conclusively determine the drug's benefits and harms.

Although judicious use of progressive licensing in limited circumstances seems reasonable to me, it would be important that post-marketing studies are not used as an excuse not to do the high-quality randomized trials that we need. As well, the legal and political framework must be in place to allow Health Canada to withdraw the drug from the market or limit its prescribing on the basis of negative post-marketing results.

It's important that the committee is aware that post-marketing surveillance will not be a panacea. As I've mentioned, these studies can be difficult to interpret, and there's a relatively small group of researchers in Canada who are skilled in their execution. That is why our network proposal contains a substantial component for the training of young researchers.

I believe that inappropriately withdrawing a drug from the market because of an inaccurate result is just as bad as inappropriately allowing a drug on the market with inadequate information about its benefits and harms. Therefore, the results of post-marketing studies in one jurisdiction should be confirmed by studies in other jurisdictions. That is why the network proposal indicates that our post-marketing network must be well linked with networks around the world.

Because post-marketing studies can be expensive, decisions will need to be made about which studies need to be done and which we can do without. That is why our network proposal suggests a priority-setting committee with representation from numerous stakeholders and a strong scientific director to make the judgment calls about how our limited funds should be spent.

Every beneficial drug causes side effects. Therefore, patients and physicians will always need to weigh the benefits of a drug with its harms. I have an elevated cholesterol level, and although I am otherwise healthy, this morning I took an Aspirin and a statin, a drug to lower my cholesterol, in an attempt to decrease my chance of having a heart attack. By so doing, I realize that I am accepting the small chance of a very severe side effect, such as a major bleeding ulcer caused by the Aspirin.

Another person in precisely my situation and as aware of the same information as I am might decide that the risks of these drugs are not worth the benefit. The important point is that we should both be fully aware of the drug's risks and benefits and should make the decisions that are right for us.

There's an urgent need for all Canadians to have access to the kind of information that I'm lucky enough to have because I'm a physician. Canadians deserve complete and unbiased information about the benefits and harms of drugs, in a form that is understandable to all. Currently, this does not happen.

The information that drug companies provide to the Therapeutic Products Directorate of Health Canada is kept secret, as is Health Canada's assessment of that information. Canadians deserve access to that information, and if legislative change is needed to make that happen, so be it.

There is also a need to produce information about drugs that is written in a language and provided in formats that are accessible to all Canadians. Current warnings from Health Canada about a drug's side effects are long, technical, and difficult to understand for physicians, let alone patients.

Health Canada should borrow from the pharmaceutical industry, which excels at communicating its message clearly and succinctly. The network that we have proposed could also play a role by providing accessible independent information about the benefits and harms of drugs.

In closing, let me thank you for taking the time to consider this important issue. Establishing a more robust post-marketing surveillance system in Canada, although it will not remove all uncertainty, will be a major step forward.

I look forward to your questions, and thanks very much.

[The Chair, Conservative, Joy Smith]

Thank you very much, Dr. Laupacis.

Could you send your presentation, please, to the clerk when you leave today to make sure it's translated? We'll distribute it to all of the members of the committee.

Thank you for a very insightful presentation.

[Dr. Andreas Laupacis]

Sure. Thanks.

[The Chair, Conservative, Joy Smith]

Dr. Morgan, could we hear from you next, please?

[Dr. Steve Morgan, Assistant Professor, Centre for Health Services and Policy Research, University of British Columbia]

Thank you very much for the invitation to speak on this important matter.

My name is Steve Morgan. I'm an assistant professor at the University of British Columbia's Centre for Health Services and Policy Research. CHSPR, as it's known, is one of Canada's academic repositories for administrative health care data. By tracking the use of medicines, physician services, hospital care, and other services in the health care domain, our research centre is one of the centres in Canada that's able to study the organization and delivery of health care and its impact on the health of populations.

This is an example of what I will refer to as the Canadian advantage in post-market evaluation of the safety and effectiveness of medicines, and I'll return to that Canadian advantage in a minute.

In addition to being a member of the centre's faculty, I am the lead of the program on pharmaceutical policy. Our program is an interdisciplinary collaboration among researchers, trainees, and even policy-makers who are interested in pharmaceutical policy across the entire life course of pharmaceuticals.

[The Chair, Conservative, Joy Smith]

Dr. Morgan, can I just interrupt you for one moment? Could you slow down just a bit for our interpreters? They can't quite keep up to your interesting dialogue.

[Dr. Steve Morgan]

For sure.

Our research program spans the life course of pharmaceutical policy, from factors that influence pharmaceutical innovation and research and development, including the location thereof, through to factors that were associated with the coverage of pharmaceuticals, the design of public insurance plans, and, finally, through the analysis of the population's use of medicines, its outcomes both on health status and on the health care system.

I want to thank this committee for its continued investment in the Canadian Institutes of Health Research and other federal granting agencies in health and other scientific domains. I bring this up in this particular forum because some individuals will tie the regulatory policies around medicines to industrial development and innovation policy.

My program at UBC has been studying innovation in pharmaceuticals for several years now. We've learned through this program of research that the way to foster innovation and the way to foster economic development is not through continuing to cut taxes for research investments; it is not to reduce regulatory requirements, which are both factors that will affect profits of industry but not necessarily innovation or the location of their investment. The best thing governments can do to affect innovation and to attract investment is through the direct and strategic investment in scientific personnel, capacity, and networks. This is a conclusion drawn by the C.D. Howe Institute, a reputable research institute in Canada; the Conference Board of Canada; and many others.

To paraphrase Michael Porter, a professor at Harvard who is an expert in what is referred to as industrial clusters, the best policy approach is to be a tough customer for any given sector while at the same time investing strategically in the capacities that would make your research environment a fertile ground for that sector to invest in. Therefore, my group has reached the conclusion that government in Canada is best to invest in organizations like the CIHR to foster research, to foster clinical trials in basic science that lead to innovation, while at the same time being a tough customer, so to speak. And that is, in some sense, the business of this particular committee's hearings today. Being a tough customer at some level also relates to post-market surveillance.

I've been fortunate enough to be collaborating with Mary Wiktorowicz, who will, I understand, be speaking before this committee next week on a cross-national study of post-market surveillance in several countries around the world. One of the key messages, which I am sure Mary will speak to you about at length next week, is that no country has truly succeeded in achieving post-market surveillance by leaving it to the pharmaceutical industry on a voluntary basis.

I don't say this is an accusation of industry. I think it's important to acknowledge that business is business and that pharmaceutical companies are not the agents in this sector whose primary responsibility is to ensure the safety of a population and value for money of the medicines used. The agents for whom that is a primary responsibility are us. It is policy-makers, it is health care professionals, and it is individuals like me, who are academics, who are publicly funded to do research on policy and practice.

You have heard from many individuals who have testified to this committee about gaps in evidence concerning post-market surveillance. I will not repeat this, other than to say it is a natural phenomenon in this sector that there will be evidence gaps at the point a product reaches the market. You've also heard, I think, a variety of conflicting reports around the value of adverse drug reporting.

It is true that few systems in the world attract all adverse drug events that occur, whether they're mandated adverse reporting systems or voluntary reporting systems. It is nevertheless still the case that ADRs, adverse drug reaction reports, are the basis on which roughly half of drugs that are withdrawn from markets around the world are eventually investigated and pulled from market. It is therefore an important signal and not one that should be abandoned because of concerns about the time constraints of practitioners and individuals involved in the reporting.

There are systems in which you can improve ADR reporting. You, as a committee, have heard from Bruce Carleton, who talks about active monitoring and an active system of surveillance for in-hospital reporting. In the hospital setting, it is possible to allocate dedicated personnel to tracking, documenting, and monitoring potential adverse events. Dr. Carleton's network of centres in children's hospitals across Canada is an example of an excellent system for tracking such ADRs. But all the ADR information in the world is going to be of little or no value unless we are tracking who is using medicines, who is not using medicines, and the effects of these phenomena.

Various representatives who have spoken before this committee have made mention of Canada's information systems for tracking drug utilization. Representatives of the pharmacy profession specifically mentioned British Columbia's PharmaNet data system.

PharmaNet is a system in which every prescription written in the province of British Columbia must be entered into a computer system at the point where it is dispensed by a pharmacy. This system tracks safety in a number of ways, the first of which is at the point of retail sale. When a patient fills the prescription, no matter the pharmacy and no matter the doctor who filled the prescription, the pharmacist has access to information that will allow them to identify potential adverse interactions between that drug and the other drugs the patient is receiving.

The second stage of value from systems like this is that every patient who fills a prescription is entered into a database, with the date of the prescription, the type of drug, and an identifying number that allows you to link it to their use of hospital and medical services and to important vital statistics, such as death and the causes thereof.

These kinds of information systems can be used for active and prospective post-market surveillance. Andreas Laupacis, who just spoke, was the former CEO of the Institute for Clinical Evaluative Sciences in Toronto. It is an exemplary institution in terms of the state of science for post-market surveillance using such databases.

The committee has also heard concerns about Canada's lack of an electronic prescription record, and I think this is an important concern. In 2006, the U.S.-based foundation, The Commonwealth Fund, did a survey of general practitioners in eight countries around the world. They found that over 80% of doctors in Australia, the Netherlands, New Zealand, and the U.K. routinely had access to electronic systems that flagged potential problems with drug doses or interactions for the drugs they were about to prescribe to patients.

In Canada, only 10% of doctors report having access to such systems. This is an abysmal failure of our system, given the fact that an investment in it would prevent adverse reactions or poor prescribing well in advance of the actual event. If you can stop a contraindicated drug or an adverse drug reaction before the prescription is written, the patient is more likely to leave the practitioner's office with the right drug in the right dose for their treatment.

There is no panacea, as Andreas has just said. In fact, in order to engage in post-market surveillance appropriately and to have real world drug safety and effectiveness monitored and managed in the way that optimizes our investment in care, we need a variety of approaches. In addition to adverse drug reaction reporting, we also need the prospective and active monitoring of data systems and the development of those data systems. But we will also need to fund new things, such as new head-to-head clinical trials—which manufacturers just don't have an interest in funding, yet are vital to engaging in the gold standard of scientific investigation of which drugs are best for our population.

We may need to do prospective cohort studies, where we collect primary data, possibly including genetic information, such as Bruce Carleton spoke of before this committee. And we may have to do what some refer to as pragmatic trials, or some others refer to as “designed delays”, where we in fact allow some populations of the country to access medicines randomly by choosing postal codes or other mechanisms, while holding the drug back for six months or a year for other populations, to get a form of quasi-randomization in the real world evaluation.

These are complex phenomena. There are many investments that need to be made; therefore, it is important to have sustained and substantial investment in post-market surveillance. Andreas Laupacis has referred to a business case and a proposal for a national network. I would encourage the members of this committee to read the business case and to speak further with the individuals involved with that network.

I want to put the investment into perspective, though. Canadians spend approximately $21 billion on prescription drugs every year. If we were to invest $21 billion as individuals in our retirement savings plans through mutual funds, or whatnot, we could expect to pay the fund managers approximately 2% for managing our return on investment. With all due respect to the managers of the funds, they're just managing financial matters. In the pharmaceutical sector, what we need, in some sense, is a fund manager who is not just managing for return on investment in terms of value for money, but also in terms of the population's health and safety. If you were to translate a 2% investment into monitoring post-market safety, effectiveness, and quality use of medicines in Canada, it would amount to $420 million a year invested in this activity every year, forever.

Now, I don't propose that the government immediately jump from zero to 60 in one moment, but it is quite probable, and I think it is quite important that we seriously consider the fact, that we have under-invested in systems such as electronic health records and such as a coordinating mechanism—which Andreas has talked about—with respect to prioritizing the allocation of scarce human resources toward researching and studying post-market surveillance.

So I would encourage you to carefully consider the investments that could be made, both in increasing the amount of resources available within Health Canada to do due diligence pre-market and outside in the community.

Finally, I want to stress, as you've heard from several members—

[The Chair, Conservative, Joy Smith]

Dr. Morgan, you've run out of time, so I need you to wrap up your presentation.

[Dr. Steve Morgan]

This is my last point.

I just want to stress, as you've heard from several witnesses before this committee, that however important—and perhaps essential—post-market surveillance and vigilance is, it is not a substitute for due diligence pre-market. It would not be acceptable to lower the bar before medicines come to market simply because we think we have a safety net in the real world environment.

Thank you.

[The Chair, Conservative, Joy Smith]

Thank you, Dr. Morgan.

You've given a very insightful presentation, and we'd like copies of it. I understand you're reading from your computer, which I often do. If you could provide the clerk with your presentation, we will ensure that it gets distributed to all committee members. It was a very good presentation, so we value it very much.

Thank you.

Now I'd like to hear from Mr. Patrick Orr.

[Patrick Orr]

Thank you very much for the opportunity to speak to the committee today.

I am a legislative lawyer in private practice here in Ottawa. I have been writing legislation for governments in Canada and outside Canada for over 20 years in private practice, and a few years before that with the Government of the Northwest Territories in Yellowknife. I am also consulting counsel on a number of class action lawsuits against Health Canada for regulatory negligence in relation to illegal and harmful medical devices allowed on the market. I should make it quite clear that I am a critic of Health Canada, and that will come clear in my presentation. These court cases also involve serious allegations of negligent post-market surveillance.

After the thalidomide disaster, the role of Health Canada was legislatively strengthened to protect the public from harmful drugs. People think this disaster cannot happen again. Recently, in a CBS report on Trasylol, they reckoned there are 1,000 deaths per month from that drug in the United States. I don't think we are in a position where we've learned many lessons from the past.

There's much I could speak about, but I understand this committee's focus is on post-market surveillance, so I'll restrict my comments to that.

The purpose of post-market surveillance is to protect the public. Health Canada's new commitment to reducing protection of the public through progressive licensing means that more dangerous products will be allowed on the market earlier. This means that post-market surveillance will be even more essential to protect the public.

In my view, post-market surveillance requires four essential things to work. I say this as a lawyer who designs regulatory systems for government. I do it for the Government of Canada, governments in the north, and provinces, as well as foreign governments. The first is that a legislative scheme has to be created to require it. Second, politicians and departmental management have to have the will to actually do it. Third, there has to be adequate staff and budget to do it. Fourth, the involvement of physicians, hospitals, and the public have to be included in the scheme.

In my view, none of these things are present today. Post-market surveillance is an illusion, and unfortunately a very sad illusion, for the public that is relying on it. I make no apology for being a bit gloomy on this, but I will explain my comments one by one.

First, on the legislative scheme, there is no legislative obligation for Health Canada to conduct post-market surveillance. There should be. I understand that a bill has just been introduced, or is about to be introduced today, requiring greater product safety recall powers. We'll have to see what it is, but this could be the beginning of a solution to this problem. I will speak about what I think should be in such legislation for proper post-market surveillance.

At a minimum, the legislation should define an adverse reaction as follows. An adverse reaction occurs when a drug, including its inactive or non-active ingredients, is suspected of causing any of the following: no therapeutic benefit; no diagnostic benefit; no prophylactic benefit; no effect at all; and finally, any injury to the patient. We are hearing about antidepressants that have no effect at all, not even a placebo effect. That should be an adverse report.

There should be mandatory reporting of adverse incidents, both within Canada and outside. There should be mandatory recall of adverse drug products, and mandatory public notice of adverse drug products should be required.

I have spoken with Dr. Ed Napke, who is a physician who was formerly in Health Canada, and he established the original adverse reaction reporting system in Canada. It's one of the first in the world. He insists that drugs must be defined as consisting of both active and inactive ingredients.

There is no obligation to label the inactive ingredients, even though these chemicals will affect the efficacy and safety of the drug product. This committee may not be aware, but Parliament unanimously passed a motion in 1989 asking the government to require complete labelling of all active and inactive ingredients in drugs, but no action has been taken 19 years later.

One example currently in Ottawa is Flomax, a prostate drug. The inactive ingredients in its formulation were changed to allow time release. It now swells up into a hard, glutinous substance about the size of a walnut. If it gets stuck in your esophagus, you can die. And those aren't the active ingredients; they're the “inactive” ingredients.

In my view, the current food and drug regulations are not adequate for post-market surveillance. It's only mandatory for industry to report a serious, unexpected adverse drug reaction, which means a serious adverse drug reaction that is not identified in nature, severity, or frequency in the risk information set out on the label of the drug. If the manufacturer says 5% of the people who take this will be seriously harmed, and in fact 5% of the people are harmed, the industry has no obligation to report that 5%.

There is no mandatory recall of drugs by industry. If a drug starts killing people, the industry is not obliged to recall the product. There is no power for government to order the recall of a drug. It seems very Canadian to just rely on the word “please”--“Please recall the drug. Take it off the market.”

There is no mandatory public notice of harmful or ineffective drugs. Instead, we have self-inspection by industry. There is even no need for industry to report any complaints they receive or investigation about drugs to Health Canada. If people are complaining directly to the drug companies, they do not have to report this to Health Canada. They are expected to keep a record of the complaint, but only for one year after the expiry of the drug lot.

Next I'd like to speak about political and management will. Even if there's a good legislative scheme, there must be will, of course, in the government to act to protect the public. In my view, the department has lost its way on this point.

The department is developing a corporate risk profile to identify management challenges, and I'll quote the following from the department:

The department is developing its corporate risk profile to identify management challenges with respect to the potential corporate risks--e.g. financial, technology, property, etc.--that may impact the realization of its corporate objectives.

So for the department, risk protection is not protection of Canadians from risk, but protection of the department from risk of the public.

The priority of the department is to improve access to drugs and medical devices. Look at their therapeutics access strategy. This is a complete about-face from the original purpose of the department, which was to protect the public.

The 2002 Speech from the Throne advocated speeding up the regulatory process for drug approvals to ensure Canadians have faster access to the safe drugs they need. In my view, this means that more dangerous products will get on the market, requiring even better need for post-market surveillance.

Health Canada refers in its literature to the drug industry as its client. In my own experience with litigation over a temporomandibular joint implant, Health Canada argued in court repeatedly that it owes no duty of care to the public. I repeat, it owes no duty of care to the public. And lawyers for Health Canada argue that if there is gross negligence in the department, even admitted gross negligence, there is no remedy except to vote out the politician. So the only remedy for bureaucratic negligence, lawyers for the department argue, is voting out the minister. I cannot stress too much the profound shift in the philosophy of the department.

I've been working with governments for a long time. I know that no government likes enforcement inspectors who go in and cause trouble, who raise problems with stakeholders. So there's a very strong tendency in government--and it's natural--to reduce inspections because they just cause problems. The inspector goes in, says, “You have this illegal product, take it off the market, or do something about it”, the minister or the deputy minister gets a call, and everyone's life is miserable. We have to take steps to deal with that.

In my own TMJ case, the department has resisted for nine years advising the public of a catastrophic medical device allowed on the market by Health Canada. Nine years it's fought us in court, saying it has no obligation to inform the public on this device.

Last week we finally, after repeated motions, got the court to order Health Canada to do a public notice campaign to advise the public that there's a catastrophic.... Now, this is a medical device, but this is the philosophy of the department--they owe no duty to inform the public.

I see that my time--

[The Chair, Conservative, Joy Smith]

Mr. Orr, your time is up now. Can you just wrap up quickly?