Health Committee on April 29th, 2008

[Dr. Gerald Dal Pan]

I think a few things are involved in the adequate testing of a drug. One is the numbers of patients tested and another is the length of time to which they're exposed to the drug during the testing process. My colleagues who do the pre-approval testing can work with me to get information on this for you. We use standards for drugs that are going to be marketed for chronic use, and we can get those to you. I think it's important to understand, though, that many of the serious adverse events are also relatively rare, and even large clinical trials won't pick up all of them. So it's a balance we have here.

[The Chair, Conservative, Joy Smith]

Thank you, Dr. Dal Pan.

We'll now go to another member of our committee, Ms. Wasylycia-Leis.

[Judy Wasylycia-Leis, NDP, Winnipeg North, MB]

Thank you, Madam Chairperson.

Thank you, Mr. Dal Pan. I appreciate your input today.

I would like to go back to your comments about heparin and pursue the idea of inspection and proper surveillance of drugs that are produced overseas. In the case of heparin, I believe it was a factory in China that resulted in a batch of heparin being contaminated. What does the United States do now, in terms of inspection overseas, to ensure that drugs are safe and free of contaminants?

[Dr. Gerald Dal Pan]

This is obviously a very big topic here in the States right now. It's a topic of many congressional inquiries, including one this morning as we speak. As I said before, my office doesn't deal with the inspection of drugs coming into the country, so we can get you some detailed information on that. I wouldn't be the appropriate person to answer that question.

[Judy Wasylycia-Leis, NDP, Winnipeg North, MB]

Would you be able to tell us if it's a general policy of the government in your country to have overseas inspection capabilities? Is it all done at the border, or is it done only in reaction to problems arising?

[Dr. Gerald Dal Pan]

We'd have to get you an answer from the people who really implement those policies.

[Judy Wasylycia-Leis, NDP, Winnipeg North, MB]

Thank you. I may keep asking you questions that you may not be able to answer, but I'll try anyway.

A news story today suggests that in both Canada and the United States we have regulatory rules that allow companies to conduct secret science that tends to jeopardize the lives and health of hundreds of people who take part in clinical trials. What safety precautions do you have in place to deal with this development? What do you do to ensure that information that's considered proprietary is shared with your government and released for surveillance purposes?

[Dr. Gerald Dal Pan]

On the post-marketing side, we have regulations that require companies to report basically all the safety information they have on their drug, but not all of it in an expedited or timely way. So individual case safety reports of events that are both serious--and we have a regulatory definition of that--and not on the product's label have to come to us within 15 days. But most other things--like individual case safety reports that don't meet those serious, unexpected criteria, and reports of other kinds of studies that companies are doing--are only reported to us on a periodic basis, either quarterly for the first three years after approval, or annually thereafter.

We had an incident in the United States where we had an advisory committee meeting about a drug, and we were considering whether that drug had some serious adverse effects on the kidneys. We convened a public advisory committee, and it concluded that there were some effects on the kidneys, but the drug should remain on the market and we would change the label. A week after that advisory committee met, we learned that the company had embarked on a large observational study using these databases I described in my opening statements. It showed that not only were there problems with the kidneys, but there was excess mortality with this drug, which was a new finding. That caused quite a big stir here.

While the company is required to report it, it's only required to report it on an annual basis. So we are in the process of rewriting some of our safety rules. We put out a draft a few years ago on post-marketing safety, and we'd like to address some of these kinds of issues.

But our expedited reporting has largely been based on these individual case safety reports, and it's clear that drug safety is moving much beyond that.

[Judy Wasylycia-Leis, NDP, Winnipeg North, MB]

Thank you.

Can I pursue a bit of this whole agenda item? Take Vioxx as an example. It has been in the news recently in terms of the possibility of Merck Frosst not disclosing information that would have prevented some of these thousands of deaths as a result of using Vioxx.

What have you learned from that situation? What are you doing about drug companies that may not be either disclosing certain information that would be important for health and well-being or misrepresentation by drug companies of a risk and benefit profile of a particular drug?

[Dr. Gerald Dal Pan]

We learned quite a lot from Vioxx here at FDA. One of the things we learned is that the public wants to know when we know about something. As you may recall with Vioxx, there was a delay of over a year in adding information about heart attacks to the label.

We've started a program here in the last year or two through which.... When we are working on an important safety issue but before we've brought it to resolution, before it has been added to the product's label, we are issuing what we call “early communications of safety findings”, so the public can know this is something of concern to us, that we're working on it, or that we've concluded this and we will be adding it to the product's label. The way it was communicated to the public before was through the product's label. Now we are being proactive in communicating that earlier.

In addition, the legislation that was passed in September of 2007, the Food and Drug Administration Amendments Act, has provisions for us to work on a timeline with companies to get information about important new safety findings in a way that should preclude this long period before the information gets on the label.

So there are two things: the legislation that allows us to get this information to the label in a more timely fashion, and our own proactive public communications.

[The Chair, Conservative, Joy Smith]

Thank you, Dr. Dal Pan.

We'll now go to our next committee member, Mrs. Pat Davidson.

[Patricia Davidson, Conservative, Sarnia—Lambton, ON]

Thank you, Madam Chair.

Thank you, Dr. Dal Pan, for your presentation this morning and for being with us to answer our questions.

I want to go back for a moment, please, to the life-cycle approach. I think you said that in the United States--and it's true in Canada too--you balance the benefit and the risk of a drug before it's licensed, and that's some of the determination that goes into it. You also said, I think, that you learn about the drug during its life cycle.

I'm sure you're aware that there's legislation before our Parliament to introduce a life-cycle approach to the regulation of these products. Health Canada has said much the same thing. They indicate that the concept of this life-cycle approach is that over time there's a progression of knowledge in and about the drug.

Could you outline the difference between what you do and what we're proposing here with this new legislation?

[Dr. Gerald Dal Pan]

I have to be fully frank and say that I'm not aware of the details of the proposed legislation, so I couldn't make that kind of comparison for you.

[Patricia Davidson, Conservative, Sarnia—Lambton, ON]

And as far as the life-cycle approach goes? I think you made the comment that you learn about a drug during its life cycle. Do you in fact take that into account in your process?

[Dr. Gerald Dal Pan]

Yes, we do. One of the things we have is risk management for drugs. This starts before the drug is approved. We look at what it is about this drug that may cause problems when the drug is on the market and whether there are certain things, based on the drug's chemistry, biology, or certain findings in clinical trials, that we may want to keep a close eye on after the drug is approved.

We have a group in my office that works on risk management. We work with the parts of FDA that are responsible primarily for the pre-market review. And for certain drugs--not the majority, but for certain of them--we can institute risk management plans that will keep an eye on these things after a drug is approved and see if the risks and benefits are changing, post-approval. This is in addition to all our normal safety monitoring that goes on as part of a routine.

[Patricia Davidson, Conservative, Sarnia—Lambton, ON]

Thank you.

You mentioned, I think, in your presentation cooperation and collaboration with different countries. You talked about the World Health Organization. I'm wondering if there are specific mechanisms or structures that either are in place or that could be put in place to help regulation between Canada and the United States, since we're such close neighbours.

I live in a border community, and it's certainly very commonplace for people to drive across the border to get some drugs that are available there and that maybe are not available here, even across-the-counter drugs. Could you comment on putting mechanisms in place that would help coordinate between the two countries?

[Dr. Gerald Dal Pan]

We have a memorandum of understanding with Canada. It allows us and Health Canada to share information. We've found that very useful.

In the end, I think it's important to understand that each society may have its own different idea about risk and benefit. This may vary from one country to another, although I think Canada and the United States are probably pretty similar in these ideas.

In terms of risk management and other things, these involve many aspects of the health care system. They depend on the health care system structure as well as individual scientific determinations about risk and benefit. There are some harmonization procedures we have with Europe and Japan, such as the International Conference on Harmonisation, but those are in terms of clinical trial data, which is largely about format, number of patients, and things like that.

I don't know if that answers your question.

[Patricia Davidson, Conservative, Sarnia—Lambton, ON]

Yes, it does.

I'm interested to know what some of the largest challenges are for you in the United States when it comes to post-market surveillance. We've heard from a tremendous number of witnesses that it's not mandatory for the medical profession; it's not mandatory for the public. We've heard a lot of different testimony about who should be doing it, how they should be doing it. Are those some of the challenges you face? How are you dealing with them?

[Dr. Gerald Dal Pan]

We face all these challenges. I think our challenges are very similar.

In terms of reporting adverse events, we do not have a requirement in the United States for physicians, nurses, pharmacists, patients, or anyone else at the point of care to report an adverse event related to a drug to either the manufacturer or to the FDA. We understand that only a fraction of the adverse events that are really happening are reported. It's often quoted to be 1% to 10%. The real percentage is probably not known, but probably varies from drug to drug.

What's most important about these systems, though, isn't the number of reports you get, but the quality of reports you get. We get over 450,000 reports a year, but a lot of them are lacking the kind of critical information we'd need or want to make an accurate determination of what role, if any, the drug played in the adverse event. We can go back and get follow-up information. We can do that. That's very time-consuming and resource-intensive, and we don't have the resources for that.

With regard to other kinds of surveillance systems--these systems that rely on large databases of health care information and electronic medical records--FDA doesn't own them. The drug companies don't own them. These are owned by independent parties. In the United States, with a private health insurance system, they're often owned by health insurers or health plans. One of the challenges we're going to have is how to get everybody together: the FDA, other government agencies, the companies, the people who hold the data--health systems, hospital systems, practitioners, and academics who have the skill to look into these data. How do we bring all these people together--and handle important issues of patient privacy and confidentiality and things like that—to look at this data to see what's happening?

So FDA is just starting some initiatives.

[The Chair, Conservative, Joy Smith]

Thank you, Dr. Dal Pan. Your presentation today has been very helpful to our committee. I want to especially thank you for taking the time to come via video conference. I think this collaboration between our two countries is extremely important. As I said, we as a committee all want to thank you for your time. I would bid you good day, and I look forward to some more contact on the same issue in the future.

Thank you, Dr. Dal Pan.

[Dr. Gerald Dal Pan]

Thank you for having me here today. We'd be happy to answer any other questions you have in the future.

Thank you.

[The Chair, Conservative, Joy Smith]

Thank you so much.

Committee, we will take a two-minute break.

We have some food for you if you'd like to take this opportunity to get it, and we will resume in two minutes.

[The Chair, Conservative, Joy Smith]

We will resume our committee meeting now.

I would like to particularly welcome our witnesses. We have Jean-Pierre Ménard, attorney and specialist in medical law. We have Tom Brogan here as well. He's president and chief executive officer. And Julie-Kim Godin is here joining us, and I understand she is part of Mr. Ménard's group.

Welcome to all of you.

We give each organization ten minutes to speak, after which we go into committee questions, starting with seven-minute rounds.

Mr. Jean-Pierre Ménard, would you like to start?

[Jean-Pierre Ménard, Attorney and Specialist in Medical Law, Ménard, Martin, Avocats, As an Individual]

Good afternoon. I will be giving my presentation in French.

I will begin by introducing myself. I am a lawyer specializing in health law. I am first and foremost a practitioner. My practice is a bit special because it deals with approximately half of all health care-related legal cases in Quebec. We basically defend the rights of users and patients in all areas of the health care system. Today I will be presenting from the point of view of patients and patients' rights, since this is a very important factor when we are talking about oversight of drugs after they come on the market. It is an important issue for patient safety.

I would first say that my practice is not an ordinary one; it is not an American-style approach either. We promote certain values such as quality, safety and accessibility, in particular. My comments today will focus primarily on our commitment to safety.

I am very pleased to be here and I thank the committee for giving us this opportunity to express our views. It is important that the whole process be reviewed because, if we look at the current regulations, it is clear that they are extremely weak and limited from the standpoint of the public, consumers, and those taking these drugs. The regulations are based mainly on self-regulation by the pharmaceutical companies as to the undesirable effects of drugs put on the market. The only control is the obligation that companies have under section 16 of the regulations to indicate to Health Canada any cases where the drug is found to have had an undesirable effect.

Under the act, Health Canada can ask for analyses, etc., but the public has no concept of how the companies interpret the rules. In other words, are they using a restrictive interpretation, which would result in too few cases being reported? Moreover, the public has no idea whether Health Canada checks or validates how the companies interpret the information. And people do not really know what Health Canada does with all the reports. The department is empowered to do additional analysis and testing, but I personally have not seen any reports or documentation or anything else to show that those rules are actually implemented.

There is also the possibility of clinical trials being carried out in phase 4 as well. There are a lot of rules governing clinical testing in phases 1, 2 and 3, but practically none for phase 4 testing. So there is a problem. That aspect should be looked at in the legislation.

There is also a system of voluntary reporting by health professionals and the general public. This is a voluntary, administrative system that does not have any process set out for it. Likewise, there is no follow-up mechanism for these reports. So an ordinary citizen or a professional might report a problem, but what happens to that report? Nothing is known about what the process might be. I think that this is an important precaution, since it is a major issue for health safety, as I have said.

As one possible approach, I would mention the Quebec Health Safety Act passed in 2002. In Quebec, the legislation did get changed. It resulted from a case that was dealt with by my office. Steps were taken to amend the legislation, to change the rules governing the safety of care. The premise was that a certain number of health care accidents occur in our health system. Similarly, there are certain undesirable effects of drugs as well. Up to that point, they were often considered to be anecdotal incidents that were talked about and reported but there was never any follow-up. In 2002, the legislation was changed to make the reporting of health care incidents and accidents mandatory.

Under the Quebec act, drug side-effects are considered to be health care accidents. The legislation requires that they be reported within each health care institution. Incidents must be reported to an internal body called the Risk Management and Health Care Quality Committee, which the law requires to be set up. So disclosure must be made to patients whenever they suffer complications, and they must be given support or told what action will be taken if such a thing happens. The committee is required to investigate all incidents to determine what occurred, prepare reports and recommendations, and keep a registry.

So Quebec's health system already has a very structured legal framework. This legal framework would be extremely useful in this case for reporting the adverse effects of drugs, or for reporting any unexpected results linked to taking prescription medication.

If we generally consider what might be more useful for Health Canada, it might be a good idea to take into account Quebec's system without creating any overlap. I believe that the legislation in Quebec and Manitoba is fairly similar. These two provinces are ahead of the others in this regard. Whatever the case may be, what is important is that we now have an organized and accountable system that allows people to report accidents. These cases are handled by an organization that investigates and makes recommendations to improve the situation.

Today, the voluntary disclosure system is purely administrative. There has been a significant increase in the number of disclosures made. This system, which is not very well known by the public, involves a lot of red tape. Despite this fact, it received thousands of disclosures. It's unbelievable. Further, I believe this is only the tip of the iceberg. My impression is that in reality, if the system were better known, more user-friendly, tighter and more accountable, we would receive many more complaints. And if that was the case, we would certainly be in a better position to improve the safety of the public.

As I said, these statements are often perceived by doctors as being nothing more than more bloody paperwork. Even if they see things which should be reported, most of the time doctors don't do so because they can choose between making a report to the federal government, which is a lengthy process, or to treat the patient. That's often their dilemma. Further, people have no idea what happens after they send in their statement. Under a post-market surveillance system of pharmaceutical products, perhaps disclosure should be mandatory for health care professionals. But even under a mandatory system, people usually under-report any incidents. If they are not forced to do so, the under-reporting will be even greater.

I know that this information is not relevant to the committee's mandate, but it is estimated that only between 4% and 5% of post-vaccination accidents or complications are reported, despite the fact that there is a mandatory reporting process in place for post-vaccination incidents. So just imagine the very low number of cases which would be reported under a system where that is not mandatory. However, I think this is one solution that we should consider.

Perhaps we should also force manufacturers to do a bit more. The packaging of drugs provides information and medical terms. It also contains a package insert describing the risks and effects of the medication, and so on. Why should we not force manufacturers to also include a telephone number or an Internet address which people could access to report any adverse reaction or complication? That way, manufacturers would be more accountable to the people who take their drugs. They also could indicate what to do in case of an adverse effect. I think this would be the very least that should be done.

I also believe that the regulations, or even the act, should outline the disclosure process, so that people realize it is important. For now, it's a purely administrative issue. People might think that the information ends up somewhere, but they don't really know where. There should be some kind of organization within Health Canada to conduct follow-ups and people should know what the process involves, rather than hearing that there were 30, 40 or 50 other complaints without being able to in any way appreciate the significance of what has happened.

Regarding the management of risks and the safety of these medications, we should benefit from provincial experience. It's clear that from a marketing point of view, we can benefit from provincial health care systems, at least in the case of Quebec, where there is a system for managing health care accidents which is structured, regulated and organized. In order to avoid overlap and wasting time, it would be important to benefit from that experience.

It is all the more imperative to do this because there is growing pressure to shorten the time it takes to licence drugs. The same applies to the access to medication under the Special Access Programme, for example. There is the risk that we will see more drugs ending up on the market for which the trials during phases 1, 2 and 3 will not have been extensive enough. It therefore becomes all the more important to strengthen monitoring during phase 4, to implement a legal framework, and to create ethics oversight committees under phase 4.

At present, ethics committees get almost no legal supervision. Their makeup and operation varies. With regard to the object of the research, we know that these practices are not very reassuring. Clearly, this needs thinking about. Unfortunately, a number of these aspects also fall under provincial jurisdiction.

[The Chair, Conservative, Joy Smith]

Mr. Ménard, we're a little over time here. You will have lots of time to answer questions, and I thank you for your very insightful presentation.

Mr. Brogan.