[Recorded by Electronic Apparatus]
Thursday, December 7, 1995
.0914 
[Translation]
The Chairman: Good morning, and welcome to the second hearing of the round table on compassionate access to experimental drugs.
Today, we wish to review Canada's process for regulating drugs. We are particularly interested in the Emergency Drug Release Program, and the Special Access Program which Health Canada recently proposed.
We would also like to know what impact clinical trials and compassionate access have upon the drug evaluation and approval process.
.0915
[English]
We will proceed as follows. First, all participants of groups will be given a maximum of ten minutes to present their views on the issue, then the members of the subcommittee will have the opportunity to ask their questions to witnesses. Finally, there will be a round table discussion involving both members and participants.
[Translation]
We will begin this morning by hearing from witnesses from the Health Department:
[English]
Mrs. Beth Pieterson, the chief, submission and information policy division; Dr. Tomasz Uscinowicz, manager, clinical trials and special access program, drugs directorate;
[Translation]
and Dr. Jacques Bouchard, who is the Acting Chief of the AIDS and Viral Diseases Division, Bureau of Human Prescription Drugs.
Welcome to our subcommittee. Please go ahead.
[English]
Dr. Tomasz Uscinowicz (Manager, Clinical Trials and Special Access Program, Drugs Directorate, Department of Health): Thank you very much.
Ms Beth Pieterson (Chief, Submission and Information Policy Division, Department of Health): I'm going to begin with a brief overview of the regulatory process in Canada. We don't have an overhead projector so you have the hard copies in front of you. I'll just take you through those. The package I'm starting with is the one that has the drugs directorate mission statement.
After I give you a brief overview of the regulatory process and the way the drugs directorate fits into it, Dr. Uscinowicz and Dr. Bouchard will describe the special access program and our role in the clinical trials.
The drugs directorate mission: Our main role in drug regulation is to assure that drugs available in Canada are safe, effective and of high quality. We do this by assessing continually, effectively and efficiently the benefits and risks of drugs, by managing the risks appropriately and by developing and disseminating information that encourages their optimal use.
I've included a definition of ``drug'', mostly because in previous presentations there were some questions about exactly what is considered a drug. So this is a definition out of the Food and Drugs Act. As you can see, it's a very broad definition. I'll read it out. It's a:
- Substance or mixture of substances manufactured, sold or represented for use in:
b) restoring, correcting or modifying organic functions in human being or animals, or
c) disinfection in premises in which food is manufactured, prepared or kept.
There are three main types of drugs that we regulate: radiopharmaceuticals, biologicals and pharmaceuticals. Biologicals are vaccines, products that are made from blood, and also products derived from tissues or human organs; radiopharmaceuticals are pharmaceuticals that have radioactive components; and pharmaceuticals are all the other drugs.
The next page is an organizational chart of the drugs directorate, just to give you a picture of how we actually operate. Dann Michols is the executive director, at the top. The four boxes under him are offices that report to him and that support the drugs directorate.
The next four boxes are the main reviewing bureaux in the drugs directorate: the bureau of human prescription drugs; the bureau of non-prescription drugs, and they also review generic drugs there; the bureau of biologics; and the bureau of drug surveillance, which is responsible for the post-market surveillance of drugs.
Underneath that are three other bureaux: the bureau of pharmaceutical quality, which is responsible for the chemistry and manufacturing review component of drug submissions; the drug policy and coordination bureau, which my division is part of; and the bureau of drug research.
Hopefully the next slide I included will show you where the drugs directorate fits into the drug development process and give you an overview of the drug development process. I think, again, this was in response to some questions that were raised at previous presentations to you. I hope it clarifies the process.
Members from industry, please pardon my ranges and averages if they've changed. This may be slightly out of date.
The first step is the pre-clinical testing, research and development. The range of times for this is one to three years. This is when the drug is actually synthesized and animal testing starts. This is obviously done by the pharmaceutical industry research and in research areas.
.0920
After that, the clinical research and development of the drug starts. You'll note the crossbarring at that phase. The drugs directorate does have a role, which Dr. Uscinowicz will go into, and that is where we do review protocols for clinical trials. The range of time is about 2 to 10 years for clinical research and development. I believe the average is 7 to 10 years in Canada now.
Then the next major step here, which is the drugs directorate responsibility, is the new drug submission review process. The average time right now for the last six months for new drug submissions in the bureau of human prescription drugs was 17 months for approval. Then after the drug is approved and on the market, there's post-market surveillance. Although this is a clear - not hatched - tine, we are involved in this. The drugs directorate does have responsibility to monitor continuously adverse drug reactions.
I wanted to point out that we do have a priority review policy in the drugs directorate. The criteria to be accepted for priority review is that - and I'll read this out, this is the definition from the policy:
- If the drug is intended for the treatment of an immediately life-threatening or other serious
disease where no comparable drug is marketed in Canada.
Drugs that are released through the special access program or emergency drug release are those released prior to the post-market surveillance period, obviously. So those drugs that are either in the clinical research and development phase or when they're under review in the new drug submission process are the ones that are released through special access. The vast majority of drugs released through that program are in either phase III trials or under review in the drugs directorate.
The last slide you have there is a very simplistic overview of the drug review process for a new drug submission in the drugs directorate. I must emphasize that this is very simplistic. Obviously, it's not a simple process whatsoever. A new drug submission contains vast amounts of data. We received one this week that had over 800 volumes. That's an exceptionally large one. Normally it's 200 to 300 volumes. But they contain a great deal of data.
I'll just take you through the chart.
Obviously, the sponsor's the manufacturer. They submit it to us. We screen all submissions before we accept them for review to find that all the necessary information is there before they actually enter the review process. Then there are two main review processes. There's a clinical and manufacturing review that examines the full preparation of the drug substance, plus the finished dosage form, the stability of the dosage form, the packaging material, all related aspects of chemistry manufacturing are examined. And then there is a clinical review that looks at all the results: clinical trials, toxicology studies, microbiology. It's an in-depth examination of all the results that you saw in the previous phase prior to this submission to us.
After those two reviews, the drugs directorate makes the decision either to issue a notice of compliance, which is the marketing approval, or if the submission is deficient in one way we either issue a notice of non-compliance or a notice of deficiency. If one of the latter two is issued, the notice of non-compliance or notice of deficiency, the manufacturer has the opportunity to resubmit the data that is missing to us and we look at the submission again. Then it goes through the same process again. We either issue a notice of compliance after that second review phase, meaning then, again, that's marketing approval, or we withdraw the submission, meaning that the submission is still not acceptable. They can reapply, but then they start off at the beginning when they've completed the necessary additional research, or whatever's required.
That's the end of my presentation. I'll pass you over to Dr. Uscinowicz.
.0925
Dr. Uscinowicz: I thank you very much, Mr. Chairman, ladies and gentleman.
Before I focus on the issue of emergency drug release or the special access program proposal, I would like to elaborate a little bit on the process of IND review. If you would kindly turn to this package, you will see there is a delineation of types of clinical trials and types of steps we are reviewing during the drug development.
As Ms Pieterson already alluded to, there are four basic phases of development. They contain different types of clinical trials, starting from establishing basic safety, tolerance and dose range to the therapeutic activity at phase II. Phase III, double-blind randomized treatment control, tries to establish safety and efficacy and a therapeutic effect in the target population. Post-marketing trials, if they are needed, establish safety and efficacy on a much broader scale.
We have a new process in the drugs directorate that started November 1. It includes two phases of interaction with the industry. The first phase is the pre-IND phase, and IND stands for investigation of new drug submissions. According to the Food and Drugs Act, no clinical research can be done without the permission of HPB, which is based on the review of appropriate submissions from the manufacturer, which in that case would be IND.
We introduced the possibility of the pre-IND phase in order to ensure successful filing of the IND submission later on and to give a platform to the manufacturer to resolve issues and possible controversies in the drug development process prior to the investment of money and energy from the manufacturer.
These manufacturers start by submitting an information package, which is a very brief summary of the data and development plans the company has. This may be followed by a meeting between the company and the HPB to identify the issues and resolve them. It's then followed by the formal IND submission.
The submission is reviewed, and it may be objected to or we may have no objections. A very frequent situation is that we do, or the manufacturer does, amend the protocols that were already approved.
I would like to ask Dr. Bouchard to give you a real-life example of the drug development program. I think it will be timely. This is the 3TC development program.
Jacques.
[Translation]
Dr. Jacques Bouchard (Acting Chief, AIDS and Viral Diseases Division, Bureau of Human Prescription Drugs, Department of Health): With your permission, I will provide a brief overview of the development of 3TC.
In 1989 and 1990, we were involved in the preliminary evaluation. There was a meeting with the manufacturer, Biochem Pharma, and then there was an agreement with Glaxo, whose representative is here, to go ahead with the clinical development of the drug.
In 1991, the first true clinical trials were carried out with human beings. First of all, the phase I pharmacokinetics trials were held, mainly in Europe, and then the phase I and phase II safety/efficacy trials were held. The monotherapy studies were done in Europe, Canada and the United States; they ended in July 1994.
In the meantime, pediatric studies began in 1992, and they are still underway in the United States.
In 1993, Glaxo Canada came to us to present the drug development plan. This plan included studies of clinical trials in combination with AZT, and these were the clinical trials that were used to introduce the new drug.
.0930
In September 1993, a compassionate access study was presented. I do not want to reveal any secrets, but other clinical indications were also submitted by Glaxo Canada for the development of this drug at the IND level.
Now we are in 1995. The pediatric studies are still in development. The studies which led to the introduction of the new drug have ended. Other studies are under way. The presentation of the new drug was submitted on July 18, and it is still being reviewed.
[English]
Dr. Uscinowicz: Thank you very much.
I will focus now on the emergency drug release program and its proposed reform.
We all know that to meet certain emergency needs or for quality of life considerations, Canadians may require access to a drug not yet approved or not currently marketed in Canada. The emergency drug release program has been designed to meet these needs by authorizing the manufacturer to make a specific product available to physicians. Sale of a drug under the program is exempt from the provisions of part I of the Food and Drugs Act and regulations.
The sale of a new drug for emergency treatment may be done providing that the practitioner provides the HPB with the details of the medical emergency for which the drug is required, data on the use of the drug and on safety and efficacy, details of the institution and any other information that may be required by the branch. The practitioner also has to agree to provide the manufacturer with reports on the use of the drug, particularly adverse reactions, and account for the quantities of the drug.
In practical terms, the current situation is that the physician, the practitioner, establishes the need for the patient and then contacts the drug directorate, particularly the emergency drug release program, and puts his request forward. Should it be a first request, consideration is given to that from the safety point of view, and then the drug directorate issues to the manufacturer an authorization for sale, at the same time informing the physician about this decision.
The authorization is for the given patient, for the given physician and for the amount of drugs prescribed in the request. Should it happen that the physician requires more drugs to maintain the patient, he will need to call it back and pose the second request, and that will be granted in the same way of authorization.
This process is very labour-intensive for us as well as time-intensive for the physician. It doesn't contribute much to the process, and at the same time it looks as though we are approving the drugs, which really we aren't. The only thing the government does is provide legal access to the drug; it never endorses the actual safety of the drug at this stage.
With that concern taken into account, we put forward the proposal - which is still a proposal, and it has been circulated to stakeholders - for a new process for what we now call the special access program. The process takes into consideration two facts of life: that patients may be in a true emergency situation and that the drug may be needed for other aspects, such as quality of life. We would like to distinguish between the involvement of the government in those two scenarios.
If you would kindly turn to the next page, I have the proposed definition of an emergency situation for the purpose of the special access program. It says an emergency situation is when a patient is seriously ill with a condition from which serious deterioration of the patient is reasonably likely to occur or from which premature death is reasonably likely to occur, both conditions in the absence of immediate or early treatment.
With that in mind, we look at the process we now have, and some elements are the same. The physician needs to establish the need for the patient to be treated with the unmarketed drug and the manufacturer has to release the drug to the physician. However, we feel the involvement of the government should be withdrawn from that situation so as not to interfere with the speed with which the access to this drug may be provided in an emergency situation. We only require that ex post facto we be notified about the use of the drug.
.0935
The other situation is a little bit different. It is not for emergency situation cases. We still have the situation where the patient is sick and in need of a drug that is not marketed in Canada. Then the practitioner will contact the manufacturer, not the government, and request the information on the possible use of the drug as well as its availability. The manufacturer has to agree to release the drug to the practitioner and then we would request authority from the government to release it.
The difference between the foreseen process and the current process is that we will release the drug not for single use but for the first 50 patients. Should that be requested, the information provided by the manufacturer would be enough to assess the safety of the drug in the one situation. The 49 similar situations should not be reported to us directly. That will be left to the manufacturer and practitioner to establish.
If the number of 50 authorizations is exhausted, then the manufacturer should come to us again and ask for repeated authorization. At that time, we may discuss with the manufacturer the need for the clinical trial instead of having the single-use releases of the drug.
There are other elements of this special access program that we feel are superior to the current situation. One, which I mentioned already, is that it devolves the government from the emergency situation when we really don't need to be there. The patient should be treated by the physician and everything should be done to provide the drug to the patient in need without any interruption.
We will require a less labour-intensive relationship between the manufacturer and us and the physician. We will centre on the physician-patient relationship. We will require as a new element that the patient be well informed about the use of the drug and we will ask the physician to obtain informed consent prior to the administration of the drug.
Last but not least, the release of the drug will be dependent on the knowledge we have of the drug and the adequacy of the information provided by the manufacturer both to us and to the physician so we can judge that the manufacturer has enough information to allow the physician to make the risk-benefit decisions. We would also like to have authority to deny access to the drug, not in the emergency situation, but as a tool in order to prevent the manufacturer from abusing the system.
That basically concludes my presentation. Thank you.
[Translation]
The Chairman: Thank you very much.
I will now give the floor to Ms. Lise Pineault, who is the coordinator of COCQ-sida. Ms. Pineault, please go ahead.
Ms. Lise Pineault (Coordinator, COCQ-sida): I would mainly like to ask some questions. Would you rather I waited until the time for questions?
The Chairman: You will be able to ask questions at the end of the round table.
[English]
Mr. Shedden from the Nova Scotia AIDS Coalition.
Mr. James Shedden (Nova Scotia AIDS Coalition): The comments I have to make will be brief. I don't have a prepared statement.
.0940
From what I understand, the changes to the emergency drug release program are very positive, and I think it's time it was overhauled. I know there have been a number of difficulties: physicians our organization works with have had real difficulties in getting drugs released from the EDRP; the time that it takes to release drugs; and the bureaucracy that's involved in the EDRP. So I'm really glad to see those changes being considered.
I think that the physician-patient relationship is a priority - and I appreciate the speed of changes being made with that - and that resources need to be better utilized.
The question that I would have involves the drug manufacturer. I wonder if they would still have the ultimate say in whether to release the drugs or not.
The Chairman: Mr. Shedden, what we're going to do is, if there are questions to the panellists, have them at the end in a round table. After the questions from the members of Parliament, I will allow questions between all the panellists, if all agree. Is that fine?
Mr. Shedden: That's fine.
The Chairman: Okay, great.
Now we'll hear from Dr. Bill Cameron from the Clinical Trials Network, please.
Dr. Bill Cameron (Assistant Professor, University of Ottawa at the Ottawa General Hospital; and Director, Ontario Region Canadian HIV Clinical Trials Network ): Thank you.
I'll speak here primarily for myself as a physician. Although I'm identified with the Clinical Trials Network, I have not had the opportunity to let everyone there disagree with what I have to say.
This session, I understand, is on drug regulation, and my perspective of the regulatory process is hierarchic. First, we had a provision that safety was the primary mission of this process, which is nice from a physician's point of view; we would like to think that we will do no harm, first.
Secondly, the effectiveness of new drugs is part of that mission. Imposed on that system, in the health protection branch, we witnessed a new component of their job, which was to facilitate the development of new drugs. This, I believe, has been achieved, but I have not seen any attribution of that achievement to an increased allocation of resources to the people who do that work.
Third, another job has been imposed on this process, which is to facilitate early access to drugs under development, and which I believe may bring the regulatory process into conflict with its first and second functions at times if it is not done well.
I'll go to my written statement, which has been circulated, I hope. I speak as a physician, first, in this.
The very sick seek three things: comfort, hope, and real help. A would-be provider of health care would like to give real help to the catastrophically ill, but this is not often possible. The invention of new therapies pursued through new drug developments by industry offers hope for the future, but our patients' needs are now. How can we use the small steps in progress to provide hope presently, if not real help, to those whose needs are immediate?
Cooperation between players - which I see as advocates of the affected and afflicted, health care providers, payers of health care, independent academic investigators, the pharmaceutical industry and regulators - can provide hope to the desperately ill through providing promising, if unproven, treatments in advance of licensure in a compassionate manner. This is more than passing a drowning man a straw at which to grasp. Not only does it offer hope to the afflicted, but the act of compassion offers comfort. Those three things - comfort, hope and real help - are all the rights and needs of the desperately ill.
The focus on access to experimental medications by individuals who are catastrophically ill is a small fragment of the real health care rights and needs. Hopeful but unproven therapies may displace treatments of known benefit and risk in favour of the unknown benefits and risks of the experimental. Desperate use of anti-HIV drugs and futile salvage treatment may breed drug-resistant virus, precluding later effective treatment in that person and in others, and offer false hope and no real help. We must accompany our hopeful provision of experimental therapies with the best evidence-based and proven management that can be offered. This is the first right of the catastrophically ill, which must not be lost among the other pressing wants, needs and rights of the afflicted and the affected.
The providers of health care in this have two roles. First is to identify the clients' wants and needs, to communicate, recommend and provide the options in a useful and timely manner. The second is to use the system to serve their client. The health care provider has divided roles, as employees of the health care payers, the ``market'' of pharmaceuticals, subject to regulation, and to the advocacy of the afflicted, as well as the competing professional commitment to a single, dependent and vulnerable afflicted person.
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To understand that drug access, even without confidence of concrete help, is compassionate, it is necessary to take a passport to Susan Sontag's ``Kingdom of the Sick'' in Illness as Metaphor. From there we can see the benefit of comfort and hope separately from effective treatment. The road to cure provides us with the opportunity to comfort, through the provision of hope to the desperate. This is our real mission.
There are obstacles. The narrow-minded self-interest of any individual player, whether ``me first'' in advocacy, therapeutic nihilism in health care workers, institutional rejection of principles, or simple despair in isolation, must all be overcome. By defeat or conversion, replacement or renewal, subversion or recruitment, as necessary to make a real partnership, we players can make a part of the problem become a part of the solution.
Expansion of huge, open, compassionate access trials of medications close to registration as pre-licence or market penetration exercises play industry against health care providers and regulators, as happened with didanosine and 3TC. Widespread access to drugs early in development may slow evaluative drug development, as happened with zalcitabine. That drug arrived shortly after AZT and was known in terms of its benefits and risk many years later - many years.
Rapid drug development is also an ethical pursuit. A confusion of experimental therapies may displace the real help to be had from proven ones, in favour of misuse and false hope, as may happen with non-nucleoside reverse transcriptase inhibitors and proteinase inhibitors. Experimental drug lotteries are perceived as forced or, even worse, cynical and perfunctory exercises that may disappoint many people. An experimental drug lottery is random. It should not be confused with fairness. It is neither compassionate nor real access. These may be a mistake.
The pursuit of a patient's interests by a physician may force the subversion of this system, which may leave the would-be provider in conflict and at professional risk. I refer to the falsification of documents, in placing what is necessary and good above what is correct and true.
Real treatment for all of our patients is like justice - treatment delayed is treatment denied. All of the real obstacles can be overcome by our commitment and partnership. This process will make us a better country.
The Chairman: Thank you, Dr. Cameron.
[Translation]
Dr. Mark Wainberg (Canadian Association for HIV Research): Thank you, Mr. Chairman. Good morning, ladies and gentlemen.
The Canadian Association for HIV research believes that people who are seriously ill must have access to experimental drugs through compassionate access programs.
In the past decade, patients have gained access to drugs such as AZT, DDI, DDC, D4C, delarvidine, nevarapin and saquinavir thanks to a variety of labelling mechanisms. The availability of these drugs gives hope to HIV-positive individuals and has provided valuable information about the toxicity and effects of these drugs.
I must stress that 3TC, an important drug, was initially developed in Canada before it was made available to patients in several countries through randomized clinical trials and open access programs. Several individuals have received combinations of AZT and 3TC through compassionate access programs, which has also added to the amount of information available about this particular combination.
These programs were even useful for the approval process, which lead to the FDA in the United States approving the combination of 3TC and AZT. Approval by Canadian regulators is imminent.
[English]
I am proud to be the scientist to first identify the anti-viral activity of 3TC, in collaboration with scientists from Biochem Pharma in Montreal. I believe that in time this drug may be recognized as Canada's most important drug contribution since insulin 75 years ago. I believe Canadians everywhere should take pride in the success of our HIV/AIDS research programs.
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As we contemplate the end of the national aids strategy in March 1998, the membership of Canadian Association for HIV Research is concerned about what mechanisms will be in place to ensure that Canada does not lag behind in the fight against AIDS, or fail to take advantage of the capacity for HIV/AIDS research that has been established in this country. Permit me to be crass for a moment and to speak in terms that are normally only appropriate for a Minister of Finance or his subsidiaries in Treasury Board.
If the expectations that we have of 3TC prove correct, Canadian taxpayers may save tens of millions of dollars during the next decade through reduced hospitalization costs. What better proof that investments in research can pay big dividends?
As president of the Canadian Association for HIV Research, I urge this committee to strongly consider the need to maintain a strong research environment in Canada so that people living with AIDS, and people inflicted with all kinds of dreaded disease, may look forward to the benefits of good science.
Speaking personally, I can have no greater satisfaction than the knowledge that work done in my laboratory in collaboration with Biochem Pharma and Glaxo Wellcome has contributed to the development of a drug that has already enabled tens of thousands of people to live longer and higher-quality lives than would otherwise have been the case. This is in part a reflection of the availability of 3TC and other drugs through compassionate release programs. While these programs have not been an integral part of the whole process of compounds, neither have these programs hindered the process of approval. This system, which has worked well for most of the past decade, should not be interfered with.
[Translation]
The Chairman: Thank you very much, doctor Weynberg.
[English]
Dr. Ken Logue (Individual Presentation): I introduced myself yesterday, but for those members who weren't here, I represent primary care physicians. I'm a primary care physician from Toronto and I've been involved in both hospital-based and community-based research. So my opinions come from that perspective, although, as Dr. Cameron stated, I certainly don't represent the entire group.
Facilitating the enrolment of large numbers of people in compassionate access programs without the concomitant conduct of sound clinical trials should not be considered a primary goal. Indeed, without ongoing trials conducted in a sound scientific fashion, the future availability of drugs to patients at all stages of illness, whether immediately life-threatening or not, will obviously be compromised.
Further to this argument, the enhancement or streamlining of regulatory approval will also not only speed access to potentially effective treatments, it will go further to provide more rapid delivery of efficacious treatments to all Canadians. Having stated that I believe the government can do more to provide enhanced treatment options to Canadians with life-threatening illness by both increasing the opportunities and feasibility to conduct clinical trials and by adopting measures to speed the regulatory process - there are significant and notable exceptions.
Persons with progressive fatal illness who are not responding to or who are suffering intolerable side effects from existing treatments, and are unable to participate in clinical trials due to lack of availability or failure to meet inclusion criteria, represent the obvious example in HIV disease. Further, patients who have exhausted all treatment options feel coerced into entering clinical trials because of the potential of being being randomized to a standard therapy arm, which they're presently receiving and failing on.
The desire and the demand to new drug access outside a controlled clinical trial, and the ethical justification for making suitable arrangements for such access, are best represented by the recent 3TC open access trial that has recruited such tremendous patient numbers. Indeed, the combination of 3TC and AZT has arguably become the standard of treatment, prior to receiving a notice of compliance.
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The argument of clinical treatment predating or preceding regulatory approval will again be witnessed after approval. Patients who have a CD4 count above 300, who do not qualify for the existing protocol, will likely be offered 3TC in given clinical situations no matter what the label indications state.
I reviewed yesterday some of the difficulties in conducting large compassionate programs for primary care physicians in Canada. Briefly, they are the difficulty of ethics approval for physicians not affiliated with an institution, and the tremendous administrative burden that these trials represent to MDs, especially those with a practice load that is significantly represented by HIV disease.
I feel that Health Canada needs to take a more active role in promoting the expanded access of drugs at a defined developmental stage. I agree with the Clinical Trials Network and community group opinions of having compassionate release on all drugs beyond a phase II. A process similar to parallel-track, which exists in the United States, would be an obvious improvement.
Evidence of collaboration among HIV-infected persons, researchers, and health care providers is now evident in Canada. I truly hope that the collaboration and further involvement with regulatory authorities continues. Thank you.
The Chairman: Thank you, Dr. Logue.
Dr. MacFadden, please.
Dr. Doug MacFadden (Individual Presentation): Having just received this document yesterday, I don't have a formal statement prepared. I have a number of suggestions and comments, but I think they will probably come out better in the question period. But have no fear; I will come back to them.
The Chairman: That's fine.
From the Community AIDS Treatment Information Exchange, Ms Dierdre MacLean.
Ms Dierdre MacLean (Clinical Trails Counsellor, Community AIDS Treatment Information Exchange): Hello, I'm Dierdre MacLean. I'm actually the clinical trials counsellor, not the community liaison coordinator, at the Community AIDS Treatment Information Exchange. My thanks to the committee for the invitation to participate in this round table.
I will give you the background for my comments about the document: Discussion Paper - Renewal Project D-10: Special Access Program. Let us remember that AIDS is not a disease; one doesn't get AIDS. AIDS is the acronym for acquired immune deficiency syndrome, the consequence of infection with the human immunodeficiency virus.
HIV, more than any other infectious agent, reminds us that we are each unique individuals. HIV disease does not progress at a predictable rate with predictable manifestations that allow accurate generalizations to be made about people living with the virus.
Measurable efficacy of a new drug in the test tube, with select cell lines, is never easily translated into measurable efficacy in the extraordinarily complex human body. The presence of the remarkably mutable HIV makes such a task even more difficult.
At the moment, there is no single effective agent that can control the progress of HIV infection for more than periods of months. At the moment, there are no combinations of effective agents that can control the progress of HIV infection for more than periods of months. At the moment, there are no effective agents, singly or in combination, that we can anticipate getting access to in the next several years that will be able to control the progress of HIV infection for more than periods of months.
Furthermore, these anti-HIV drugs are highly toxic. People who use them must often choose between seeing short-term benefit, as judged by surrogate markers, while experiencing adverse clinical events, ranging from neutropenia, bone marrow suppression and myopathy, to the usual offenders: nausea, vomiting, and diarrhea.
Finally, the cost of marketed HIV drugs is prohibitive. It would seem that soon-to-be-marketed drugs promise to be exorbitant in price. In short, there is no insulin for AIDS.
Part of my job involves providing treatment information to people living with HIV through our toll-free number. Callers from across the country often request information about unmarketed drugs sometimes, because they like to keep up to date in developments and sometimes because media hyperbole inflates hope for treatment.
.1000
Sometimes there is sufficient information about such products to satisfy the caller's needs, and that information can be translated into plain language. Sometimes the callers can be directed to a trial site. Very often, callers do not meet the criteria that would permit them to take part in a controlled clinical trial. We in the HIV community-based organizations truly do believe that the only reason anyone should take part in controlled clinical trials must be altruism.
If there were such a thing as insulin for AIDS, that would be possible. In the real world, however, there is no effective, long-term, highly tolerable treatment for HIV infection, and we must recognize that people enter trials seeking treatment. Standard-issue, randomized, double-blind, controlled clinical trials do not equal treatment. People with HIV desperately need compassionate access to new drugs.
It is with that background that I reviewed the proposal for a special access program. Unfortunately, I only received the document a couple of days ago.
I don't know if I should continue on here or address comments and questions. I think I might prefer that, but I wanted the people to know where I was coming from.
The Chairman: Thank you very much, Ms MacLean.
From the Pharmaceutical Manufacturers Association of Canada, Dr. Fourie and Dr. Levy.
Dr. Michael Levy (Vice-President, Medical Sciences, Glaxo Wellcome; Pharmaceutical Manufacturers Association of Canada): Good morning, Mr. Chair.
The PMAC was pleased to have the opportunity yesterday to provide this committee with our thoughts on compassionate access for patients with catastrophic illness. Today we would like to address the health protection branch's proposal to revamp the emergency drug release program.
I'll begin by making a few general comments on the health protection branch's proposal, then Dr. Fourie will address a number of key points.
The PMAC concurs that an effective program enabling access to experimental therapies is essential and that the process to achieve that end needs careful review. We also note that significant steps have been taken to streamline the process and to separate the authorization process between true emergencies and ongoing non-emergency use.
We believe that the proposal is a significant improvement for the drugs directorate and for industry, even though the recording and reporting requirements will be more onerous for the industry.
We also would suggest again a clear statement that compassionate access is not an alternative to proper regulatory review and timely market access for new and valuable therapies.
While we concur with the general direction of the policy, we're nonetheless obliged to note our concerns over process-related issues in the proposal. The concerns can be summarized in, but not limited to, a number of lines: first, the need for clarity and the delineation of responsibilities among the main stakeholders in the process, such as the HPB itself and practitioners in the industry; second, the absence of a clear right to refuse availability on appropriate grounds by the industry; third, clarity in certain definitions, for example, emergencies and suspected serious adverse events; fourth, total patient numbers and treatment periods; fifth, time lines for reporting; sixth, compliance issues regarding serious adverse event reporting; and seventh, expectations regarding regulatory processes, such as information packages and audit procedures.
Dr. Fourie will address all of these points in more detail.
In conclusion, the PMAC supports the basic principles of this proposal. We believe that with further elaboration and clarification of the points noted in this response, the new policy will lead to a more effective implementation of compassionate access for all the stakeholders concerned.
The Chairman: Dr. Fourie.
Dr. Sophia Fourie (Vice-President, Medical and Regulatory Affairs, Pharmacea and Upjohn Inc.; Pharmaceutical manufacturers Association of Canada): Good morning, Mr. Chair.
I just have a few brief comments touching on some of the points Dr. Levy made. We feel that it should be acknowledged in the proposed new procedure that the program would remain one of request for access, and that the manufacturer should retain the authority of not granting the request for access for a variety of reasons, including safety, lack of information, lack of availability, which are some of the issues we discussed yesterday.
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I'm relating this also to a comment Dr. Uscinowicz made earlier, where the approval from the HPB would be not an approval. It would not be an approval based on sanctioning the safety of the drug in the specific indication or usage. It's providing a legal vehicle to make the drug available.
Consequently, we feel the safety aspects really have to be considered as we discussed yesterday in the context of doing no harm and having certain expectations of what the drug can actually do in these life-threatening diseases.
We suggest all serious, unexpected adverse events be reported by the manufacturer within a specified timeframe of receipt of information on the adverse event from the practitioner.
Regarding patient informed consent forms, the proposal states the provision of signed informed consent is the responsibility of the manufacturer. We think this is not appropriate since it's on the request of the practitioner that the drug is indeed made available and the results/outcome of the administration of the drug is rarely provided to the manufacturer.
We believe it is the practitioner who should be responsible for the administration of the drug and hence administration of the consent regarding the use of the drug. The release of the drug to the practitioner should be dependent upon the receipt of the signed consent form for the patient. These consent forms will require ethical board review approval.
We think there is greater potential in the new proposal for increasing the time lag between the request and the receipt of the drug under this program. We would suggest mechanisms be put in place to ensure that bureaucratic delays can be curtailed as far as possible to prevent this from happening.
Manufacturers should be permitted to deny resupply of investigational products to practitioners who fail to comply with appropriate drug usage and responsible safety monitoring. Under the current program, some practitioners do not report outcomes or adverse events. Yet the HPB continues to issue authorizations. This situation can place a manufacturer in a difficult position.
The new proposal shifts more responsibility to the manufacturer. We feel there should be further clarification and details concerning auditing procedures and record-keeping. For example, are electronic or paper records acceptable? What will be audited? Will summary records be sufficient or will the drugs directorate review shipping invoices, case report forms? All of these details need to be specified in the new procedure.
In conclusion, the issue of the manufacturer charging for the drug has not been addressed in this proposal. We talked a little about that yesterday. The workload and resource usage that will be placed upon the manufacturer in administering these programs certainly have to be addressed and provided for in the new proposal.
With that, I conclude my comments.
The Chairman: Thank you, Dr. Fourie.
Now that we have completed hearing our witnesses, we will proceed by having a first round of questioning from the members of Parliament, starting with the Bloc Québécois, then the Reform Party and the Liberals. After that, we'll have a coffee break for five or ten minutes. Then we'll have a full discussion between the participants and the members of the subcommittee.
[Translation]
Mr. Ménard, please go ahead.
Mr. Ménard (Hochelaga - Maisonneuve): I'm going to make an observation and then ask four questions.
I think that this morning we are witnessing a somewhat historical event, because I'm sure that there have not been any events that brought together people from the Department of Health, a member of the scientific community who was closely associated with the discovery of 3TC's antiviral effects and the company that marketed it.
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My first question is for the official from the Department of Health. Will there be a recommendation to the government of Canada that compassionate access be made mandatory once research protocols have been approved? If so, how would the various stages work? If the House of Commons were to pass a bill that made compassionate access mandatory, how would that work in terms of each stage that you have suggested to us?
My second question is for Dr. Cameron, who is here this morning as the representative, in a way, of the Canadian HIV Trials Network, even though that was not the title he used when he introduced himself. What would you like to tell the committee members about the HIV Trials Network? How could it be improved? If you had the opportunity to highlight things that should be said about the HIV Trials Network, which things would you highlight? I would really like to hear your views on that particular matter.
My third question certainly is the most sensitive one, and I will ask this question as diplomatically as I can, being careful not to insult anyone and assuming that everyone is certainly being sincere, unless there is proof to the contrary.
Given all the tools that Health Canada has, why was 3TC first approved in the United States rather than in Canada? What went wrong? Why did I have to ask three good questions in the House, questions that I am rather proud of, all in all? Perhaps it's a question of insufficient resources, but as a committee, let's try to find out this morning what went wrong and what resources you need so that we can produce a very specific report and make sure that you get the resources you need to do your work effectively.
My last question is for Dr. Levy, because I always like to finish off by asking him a question. This time, I'm going to try to take him by surprise. I'm not going to talk to him about the profits made by drug companies, but rather, I'll ask him about his firm. Did Glaxo look at the impact of 3TC first being approved in the United States? Did it look at what this meant for the Canadian scientific community and people living with HIV? Do you want to say anything about that, and do you have information about what that means for Canadians living with HIV and for Canada's scientific community?
Those are my four questions, Mr. Chairman.
The Chairman: Thank you. I congratulate you on keeping your questions brief.
[English]
Ms Pieterson.
Ms Pieterson: In your first question you asked if you should make a recommendation to legislate compassionate access. Is that correct?
[Translation]
Mr. Ménard: If ever we were to recommend to the government of Canada that no clinical trial should be carried out in Canada unless there is compassionate access, what would that mean for the various stages that must be gone through? For instance, do you have the regulatory means to force drug companies to do that or to influence the approval of a compassionate access protocol?
[English]
Ms Pieterson: Currently we have no legislative authority to enforce compassionate access under the existing regulations. As you know, if a manufacturer doesn't want to provide a drug, we do not have the legislative authority to force him to provide the drug or set up a compassionate access of a clinical trial.
Now, should you? That's for the committee to decide based on the results of the hearing. No, we don't have the legislation authority now.
Dr. Uscinowicz: I have on additional comment. It is the Food and Drugs Act and regulations, and not the trade legislation. Therefore, that's where we're lacking the mechanism to force a manufacturer, should it be desirable to do so.
The manufacturers' prerogative is still to refuse the drug if they wish to do so. What we're doing is providing the legal vehicle to do that. I don't believe I can recall any situation when the government said no, unless there was a very serious public health hazard, which is a very rare situation.
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So from our point of view, we're not trying to obstruct the process. But this situation is very complex, as we heard from all the other witnesses, and we are only a part of it.
[Translation]
Mr. Ménard: Perhaps I express myself poorly. Of course, as a parliamentarian, I know you don't have any legislative power, otherwise I'd be terribly naive. You see the research protocols that are being conducted by the Canadian HIV trials network. When you have to make a decision, you have a research protocol for drug experimentation. Up until now, you've described the various steps involved in this research protocol.
If we made compassionate access compulsory, what would that imply in terms of standards and the process to be followed? Do you have any views on that?
I know that also implies giving some thought to the bureaucratization of the process, because our witnesses, particularly those from the medical community, told us that there was already considerable bureaucratic burden involved in conducting clinical trials.
Of course I don't want us to recommend something that would increase the bureaucratic burden, but what would this mean in terms of the steps to be followed if we were to make a communitarian access compulsory?
Dr. Bouchard: Of course, you would have to consult all the parties involved in this area if you really want to change the legislation to make it as efficient as possible in that regard.
I think that's the only solution. We have no more solutions to give you.
Mr. Ménard: Is this something that appears plausible from Health Canada standpoint?
Dr. Bouchard: I can't comment on that.
Mr. Ménard: Your caution is almost ministerial.
[English]
The Chairman: Dr. Cameron, for the second question.
Dr. Cameron: Thank you. I'm invited to make comments on behalf of the Clinical Trials Network. In the two minutes I've had to organize my thoughts, I have several things to say.
The Clinical Trials Network is a capable player in a five-year experiment of funding and has managed to produce a series of world-class contributions to the health care and health maintenance of people with HIV and AIDS. This has been done with infrastructure funding and a fair bit of poker playing with the actual payers of the conduct of these studies in the interests of new drug development.
In the United Kingdom, the Medical Research Council - that is, MRCUK - conducts randomized clinical trials not necessarily of new drug development but of medical health maintenance. These trials are conducted with operating funds, which give the MRCUK autonomy, almost academic autonomy, from the agenda of industry or the agenda of the payers of health care. Their contributions are great.
INSERM has the same privilege. In the United States, the AIDS clinical trials group was founded much as an experiment like the Clinical Trials Network but with one important distinction. It had money. The CTN needs, I believe, to develop a little bit of autonomy from industry. This is provided through operating funds. We need to answer more in the way of clinical management questions for health care, not just participate in new drug development processes that are also important.
We have the opportunity to offer given resources, pivotal re-evaluation of new and old drugs independent of proprietary interest, the lack of interest or the active disinterest of the owner of that compound or that therapy.
If we only serve to facilitate the pharmaceutical agenda, we answer only their questions. These are more drug-related than health-related at times and not necessarily in the best interests of the afflicted, the affected, the public and our country.
In short, the Clinical Trials Network is capable and competent and has been a successful experiment as it stands. It can make much larger contributions with the autonomy to use even the existing resources it's allocated for operations as opposed to infrastructure and collaboration with industry. At least, let us do that. At best, we need to operate like the ACTG, in which we have a mandate and the means to fulfil that mandate.
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The Chairman: Thank you, Dr. Cameron. The third question from the government is about the 3TC homologation in the United States prior to being homologated here in Canada.
[Translation]
Dr. Bouchard: 3TC, which is called Epivir in the United States, was submitted to American authorities on the FDA on June 29, 1995. Here in Canada, we received a comparable presentation on July 18th. So there was a three-week delay there. It's important to know that when we're referring to completely different legislation and sovereign countries, it's difficult to draw comparisons.
The size of the two regulatory bodies is also very different. The FDA is about a hundred people to examine drugs, compare to five people here in Canada. With regard to resources, it's always possible to obtain additional resources to examine presentations of new drugs.
Should a drug that was developed in a given country be approved in that country first? That question remains to be determined. Scientifically and clinically, I fail to see how we could justify that Canada be forced to approve its own drugs first, for example. I don't think that the country of origin of a drug should be the primary factor in the examination of applications.
Mr. Ménard: Doesn't this have an impact on access? Someone from the outside may naively assume that the country that approves a drug is ahead of the game as far as future marketing is concerned, and that marketing implies the availability of the drug for infected people.
Dr. Bouchard: That could happen in cases where the quantity of the drug is limited at the outset.
Mr. Ménard: In the scenario that concerns us, there's first and foremost the issue of resources. We have to know this. We can't ask a government agency with five people and another with 100 people to conduct the same initiatives. It's just a minimum display of intellectual honesty to say so publicly.
In the case of 3TC, which appears like a light at the end of the tunnel for infected individuals, do you, as a public servant with experience in these matters, feel that the fact that it was approved in the United States first means that it will be marketed and available to Americans first, before it is available to Canadians, even though the drug was discovered here?
Dr. Bouchard: It is a fact that the drug is marketed in the United States right now. It was approved on November 20th of this year. It is a fact that the drug is currently available in the United States.
Mr. Ménard: Thank you.
[English]
The Chairman: Dr. Levy, on the fourth question about the summary impact.
Dr. Levy: Mr. Ménard, I appreciate your saving a question for me again. I note you've not asked me about profits or other commercial matters of which I have no expertise. So thank you.
Of course, as Canadians, we are all very proud 3TC was discovered in Canada and we share Dr. Wainberg's sentiments that this is probably the most important Canadian medical discovery since insulin 75 years ago. In fact, we are very hopeful 3TC will be approved imminently. It would be wonderful if it could be approved some time today.
If in fact 3TC is approved imminently, as we hope, then we'll be very pleased with the health protection branch's speedy and efficient approval. The approval will have come in less than six months, which I believe would be the quickest approval of a new drug through the fast-track process.
The fact that it has been approved two weeks earlier in the United States is not a significant difference, especially when you consider the FDA has a huge bureaucracy at its disposal and that the HPB has a relatively small bureaucracy. In fact, I hope Dr. Bouchard's presence here today doesn't mean the process has come to a complete stop and that we can still look forward to an approval.
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[Translation]
Mr. Ménard: I have a question for Dr. Levy.
You obviously know that my question on profits has simply been postponed. I promise I will ask you that question during your next visit, because I know you will have the information then. You are an honourable man; and that's a well-known fact!
Why did your firm submit to the protocol for the product to be licensed in the United States rather than Canada?
I thought both had been submitted at once, but we found out to that three weeks passed between the two submissions. Why did your firm submit it in the United States first rather than in Canada?
[English]
Dr. Levy: In fact, it's not at all unusual that there's a small variation in when submissions are put in to different countries around the world. I believe the time difference is actually 13 days between when it was submitted in the United States and when it was submitted in Canada.
Canada has some very unique requirements, unique in the whole world in terms of formatting and in terms of the kinds of summaries that the health protection branch likes to look at in order to approve new drugs. In order to prepare these summaries and this special formatting, we have to wait until we prepare the dossier for the rest of the world. We then take it and modify it and add the extra components to make it acceptable to the health protection branch.
Typically, that process takes us four months to do, and for all of our other large drug submissions it has taken us four months to take a submission that we used in the rest of the world and convert it into a format for the unique Canadian requirements.
In the case of 3TC, we had special dispensation from the health protection branch on a number of these requirements, but nonetheless it still took us, with a team of 25 people working around the clock, two weeks to do these formatting changes and to put in place these summaries for them. That's why there was a delay.
The Chairman: Thank you, Dr. Levy.
Mrs. Hayes.
Mrs. Hayes (Port Moody - Coquitlam): I have fairly brief questions. There are a lot of other good questions and discussions that we'll look forward to, I'm sure.
I'd be interested to know what some of the uniqueness in requirements might be for submission in Canada as opposed to the United States, if the committee wants to comment on that.
To do with that would be, what drugs in fact have been fast-tracked in the last while? You said that generally five per year or so have been. Can we get a list, or do you know which ones have been fast-tracked in the last little while?
Those are my first questions. I have another two, but maybe I'll pose them one at a time, if that's all right.
The Chairman: That's fine.
Ms Pieterson: I think the uniqueness is based on the summaries. We require a cross-referenced, comprehensive summary in our submissions. We require this because we have fewer resources and it speeds up our review process.
The American process is often considered a bottom-up approach. They look at all the data from all the trials in detail, whereas we say we have a bottom-down approach. We look at a summary and base our review and our approval, or not approval, on the summary. That is, I believe, the requirement that's being addressed specifically.
With international harmonization of regulatory requirements, I think a lot of the differences in submissions to different agencies throughout the world are gradually disappearing. I think they will get better - we will get better - in our differences in the future.
I don't know off the top of my head the drugs that have been fast-tracked. I think probably Jacques could say the AIDS ones, and Tomasz the ones that have gone through his division. I can certainly provide you lists for the past couple of years, later. I don't have them off the top of my head - less than five, though, on average.
Jacques, do you know what has been fast-tracked?
Dr. Bouchard: On the AIDS drugs, we can say that ddI was really the first one that was fast-tracked; ddC was fast-tracked too. Another drug called Mepron was fast-tracked; 3TC was fast-tracked -
There's another drug now under review, our priority review. The drug is called Invirase. It's a proteinase inhibitor.
The Chairman: The second question, Mrs. Hayes?
Mrs. Hayes: Are those all specific to AIDS, then?
Dr. Bouchard: Yes.
Mrs. Hayes: Okay. Are those basically the ones that are fast-tracked, then, or are there others for other diseases -
Dr. Bouchard: Yes, there are others for other diseases in other divisions. I am not aware of the -
Ms Pieterson: As I said, I don't know them off the top of my head. Betaseron was recently approved. It was fast-tracked. That's a drug for multiple sclerosis.
Tomasz, do you know any?
Dr. Uscinowicz: I don't recall any names at this moment, but I'd be more than happy to be more specific.
Ms Pieterson: I can get you names if you're interested.
Mrs. Hayes: Okay, if you could, I would be interested.
Ms Pieterson: I'll get them for you.
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Mrs. Hayes: Okay. Actually, there was a comment in one of the presentations - and I have my notes here but it might take me a minute - that in fact with the fast-track process difficulties have come up afterwards with one or two of them. Has pretty much every one that has been fast-tracked eventually been entered into an approval process? What has been the experience with fast-tracked drugs?
Ms Pieterson: I think the experience has been fine. It means that it gets the same review, but it doesn't have to wait in line to be reviewed. When we issue an approval for that product, it has had the same depth of review; it just has not waited in line to be picked up. The same depth of safety has been considered. I don't believe there have been any serious problems.
Dr. Uscinowicz: There is one case I am aware of where the drug was fast-tracked but the presentation of the submission was not satisfactory, so a decision was reached within the prescribed time of 180 days and the drug was not approved at that time because of the failure to show its effects, efficacy and safety. It was resubmitted, and I think it was approved after that.
So it's not automatically that a fast-track drug is not complicated, or that we review it superficially. We go with the same scrutiny to all of them, but as Ms Pieterson said, the bureaucratic time is taken away.
Mrs. Hayes: I have one more question - because of time - which is on the emergency drug release program.
Has there been or do you think there might be a problem with the definition of emergency with regard to how that is actually played out in practice? Who determines whether there's an emergency drug release circumstance?
Dr. Uscinowicz: I thank you very much for the question, because this is a very important element of the program. As I stated, the material we circulated, which you have seen, is only the initial proposal. We realize very much that this is a very complex issue and that it's not only a government-industry issue; it's an issue of much broader prominence.
We sent it for the initial comments. I received the summary of those comments not long ago. I should admit that I didn't review them carefully, but I haven't seen any comments on the definition itself.
Maybe you would appreciate that when we look into the proposal we try to look at what other countries are doing in the same situation. We particularly looked at the special access scheme in Australia, and basically the definition we use now, for the first point of discussion, is modelled on the Australian definition.
It's open, like everything else in this proposal; however, we feel we need to have at least an extra consultation step with everyone involved before we even start the more detailed work on it. This is a crucial point, and I appreciate it.
Mrs. Hayes: Has it been a problem in the past?
Ms Pieterson: That's what I think, yes.
Mrs. Hayes: Will your proposals address that?
Ms Pieterson: I think the name now is not really accurate. It's called the emergency drug release program, while in fact there are very few true emergencies for which drugs are released through the program. I think that's why we're changing the name to call it special access. One of the reasons is to make the name more appropriate.
Is that what you wanted to know?
Mrs. Hayes: Yes.
Ms Pieterson: When the regulations came into effect, that section of the Food and Drugs Act - heavens, it was years ago; in the 1970s, I think - the use of drugs was far less, and different types of drugs. It has changed tremendously.
Mrs. Hayes: Okay.
Ms Pieterson: So in regard to the name, it's not an emergency. We don't require an emergency to release the drug now at all, if that's what you're asking. It has nothing to do with an emergency.
Mrs. Hayes: Right. I'm asking if you've experienced problems in your directorate with that definition in the past and how that will be affected by what you're proposing now.
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Dr. Uscinowicz: The current legislation does not contain a definition of emergency. It says the the practitioner should provide the details of the medical emergency, and it's not defined. So basically if we're going to devolve ourselves from the process, we need to define from what part of the process we're going to do it, and there is a medical justification for us that, within this definition, will not interfere at all.
Mrs. Hayes: So a key part of the job of this round table is to determine a definition for special access: what is it that makes it appropriate or not appropriate?
Dr. Uscinowicz: That would be very much appreciated.
The Chairman: Thank you.
Ms Fry.
Ms Fry (Vancouver Centre): Thank you very much. I want to congratulate one of our witnesses today, Dr. Cameron, because I think that he, in his presentation, really pulled together the essence of what we're doing here. He balanced carefully all of the problems - the issue of compassionate access, which is a very important human issue; the issue of scientific rigour, which has to be balanced; the issue of accountability. I really wanted to thank him for that. His presentation brought out the fact that we must, as a committee, eventually balance these many aspects.
I realize that Mrs. Hayes has asked some of the questions that I wanted to of Health Canada, but I wanted to ask, when you are considering the new enhanced special access program that you're thinking about, if you are devolving some of your accountability, who will eventually be accountable legally and, in the end, ethically? If it is going to be devolved simply to the physician to do this on a physician-patient basis - which is appropriate - who would keep the scientific rigour going?
Dr. Cameron pointed out that this has two side effects, and I wondered if you'd considered them. One is that it will increase the amount of work that the clinical practice physician has to do in the office. Secondly, how will you ensure that scientific rigour is met in terms of the physician doing record-keeping and all those other kinds of things?
Dr. Uscinowicz: I think that even in the current situation, the responsibility for administering drugs to the patient still lies with the physician and the provincial regulatory bodies. We do not regulate that, and that is the practice of medicine. The fact that the physician has used an approved drug or a not-approved drug makes no difference in that regard.
What we're trying to do here is first of all speed up the process of release of the drug to the patient in the true emergency situation - this is one thing - and there is a need for the physician to communicate this need to someone. In the current process, he or she communicates to us; then we go to the manufacturer; then the manufacturer communicates with the physician; then the shipment is provided.
What we're trying to do for the true medical situation is just withdraw ourselves from the process so the physician will call the manufacturer directly and say, ``I need the drug for an emergency situation.''
Ms Fry: Yes, I understand the process. I'm saying that if you enhance this new access you're talking about, I don't believe it's good enough to say that the physician should - if the physician has time - give back information. I think there has to be a process. Sometimes one develops programs without looking at the process and consulting with the various players. I would like to know if, say, physicians and patients have been consulted on this.
Ms Pieterson: The CMA has been consulted. We usually consult through the main organizations such as the Canadian Medical Association. We haven't finished the consultative process. It has been brought up in comments we've received back. It's not the first time we've heard this.
Ms Fry: Well it's important to find some feedback.
Ms Pieterson: We do recognize it's important. Right now, we have voluntary reporting of adverse drug reactions. Because we don't regulate physicians, only manufacturers, we do have difficulty. But it's a balance. We recognize the physician is overburdened with paper and yet we require - We're open for suggestions.
Ms Fry: I think the suggestion is accountability, which seems to be lacking in many processes. That's what I hope will be built into the process, or maybe we can make some suggestions for accountability.
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My second question, if I have a moment, is to Dr. Levy. It has to do with the fact that, as you know, at the moment many companies belong to PMAC. Some companies do allow compassionate access and other companies do not. Can you tell me what percentage of companies within PMAC do give compassionate access and what percentage don't?
Secondly, why would the ones that do not give compassionate access at this point in time not give it? If the reason, as I've heard in the past, is legal, how many people have been sued in the past or how many have had legal action brought against them, amongst the ones that gave compassionate access?
Dr. Levy: You've asked me a difficult question. I'm not sure how many companies within the PMAC do give compassionate access. It was my understanding that the vast majority, if not almost all, do provide compassionate access. So I'll need to go back and check to see what the answer to your question is. I'll have to do that for you.
Ms Fry: We will be hearing from you with that answer? It's important to the decision-making here today.
The Chairman: I will allow one more question.
I'll go with Dr. Logue, and after that we'll stop for about five or ten minutes for a coffee break and then resume with a round table among the panellists.
Dr. Logue.
Dr. Logue: I want to follow up on some comments Dr. Fry made regarding accountability and then make comments specifically to HPB.
The existing situation for accountability is unfeasible and unrealistic. As I stated yesterday, over 50% of my patients are on experimental therapies. I physically cannot, with my staff and support, do adverse drug reporting, and I do not.
The Gagnon report stated and the background document indicated that I believe it was 40% to 60% are reported. I strongly doubt that's actually the case. In fact, adverse reporting is abysmal and very poor.
Dr. Levy is well aware that in Toronto, with the primary care group, we essentially en masse refused to fill out any more 3TC forms over the past year, because we said this is administratively ridiculous and unrealistic. We cannot do it.
Subsequent to that we sat down with them, and through cooperative discussions they agreed to help fund existing infrastructure to pay for data collectors to come into our office. So that was a small regional solution in Toronto only, which the pharmaceutical company participated in.
But the existing situation across the country is very piecemeal and it's administered inconsistently. It's simply not realistic or feasible to report side effects. We are not doing it and we are not going to be able to do it.
Ms Fry: Thank you, Dr. Logue. I wanted to highlight that there is a big gap and a big problem that needs to be addressed somewhere or somehow.
I hope Dr. Levy will bring the information to the next session. Thank you.
Dr. Logue: If I can make one further comment, the problem is that these compassionate access programs, as I think most of us have come to realize, represent a failure of some of the science. We can talk about ethical and scientific rigour, but this represents a failure of being able to offer good, scientific, evidence-based choices to our patients.
We've gone from the position of assuming that emergency drug release is going to be a small percentage of patients to realizing that in fact our treatments in HIV disease pre-date regulatory approval in half or sometimes the majority of cases. We have huge numbers of patients on these pre-market drugs.
It's untenable to practice that way. We need speedier approval of these drugs or a look at how we can manage these compassionate access programs in a more feasible way. They are not manageable right now on a primary care basis, and they are going to worsen. We now have innumerable antivirals coming up, and the more research gives us these choices, the more difficult it's going to be.
Dr. Fourie: I want to comment on Dr. Logue's remarks. From a manufacturer's viewpoint, these are areas of great concern both for physicians as well as for us with regard to patient safety and the proper collecting of safety information. It is absolutely critical that this indeed be addressed. These issues are addressed and the data collection occurs in the clinical trial setting. Outside of that there are big problems, and we really have to address this.
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I would just like to make a brief comment with regard to Dr. Fry's question. It may not be that meaningful to look at the 65 member companies of PMAC and then see how many of them have expanded access programs. Not all of them may have drugs that would be in question or requested for such use.
So it may be more appropriate to look at specific examples, and then we have to go back to the basis of manufacturers' decisions along these lines: safety and proper information need to be available as a basic point before you can go ahead and agree to an expanded access program.
Ms Fry: I would like to suggest that my questions are appropriate, and the witness should not tell me what is an appropriate question or not.
I would like to get those answers, please.
The Chairman: Dr. Logue.
Dr. Logue: Yes, I'd just like to make one further point. I must underscore the point that we as practising physicians want this information about the safety of these drugs as much as anyone else.
We feel that the pharmaceutical industry wants them for a drug for which they're trying to get approval. The patients who are the consumers obviously want them in order to make informed decisions. We obviously want the information in order to counsel that patient about an informed decision.
It is not because of a lack of desire to get this information. However, for a pre-market drug that has not been approved yet, where we're participating as so-called ``co-investigators'' - but certainly we're just participating in an expanded access rather than a real scientific, rigorous trial - we feel it's the responsibility of the pharmaceutical company and it's part of drug development that this information is collected.
We are participating in these compassionate access programs and being paid under a provincial plan. There are some dictates in these programs, for example, when they are telling us how often to do blood work and how often we should be ordering tests within a provincial plan.
If you look at it that way, some of that drug development cost is being passed on to the province and taxpayer. I feel this is drug development, and we have to be clear about that. We have to be clear about whom we assign responsibility for collection of this data. If this data is subsequently used to apply for approval of the drug, then it is not the responsibility of the physician providing that drug to collect that data.
The Chairman: Thank you. We're going to stop now for about five or ten minutes, and we're going to come back to the round table.
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[Translation]
The Chairman: We will resume the discussion between participants and members of the subcommittee. This is a very opened formula. Panelists can put questions to other panelists and MPs can also put questions in response to questions from panelists.
I would like to begin with Dr. Michael Levy, who has a brief answer for Dr. Logue.
Dr. Levy, please.
[English]
Dr. Levy: Thank you. I just wanted the opportunity to make a quick response to Dr. Logue's comments before the break, and to mention that the Pharmaceutical Manufacturers Association of Canada strongly disagree that emergency drug release is a normal part of the drug research and development process. We strongly disagree that the data gathered is valuable to the manufacturer in seeking a speedy approval for new therapies.
Emergency drug release is plainly and clearly patient therapy, albeit patient therapy under difficult conditions, conditions that arise from a failure of the system to make drugs readily available. Dr. Logue has already told us that he doubts whether even basic data - critical data such as serious adverse events - are gathered, and he cited the example of himself and his colleagues.
Emergency drug release places a large burden on all the stakeholders, including the health protection branch, physicians in the industry, but it places an especially large burden on the industry, which has to manufacture the drug at an early stage, distribute the drug and put in place measures to try to collect the appropriate data.
For example, in a case which I'm familiar with, the case of 3TC, which Glaxo has been making available through the emergency drug release program, the costs to us - purely the financial costs - have been several million dollars a year in Canada just to put in place a distribution system, let alone the cost of manufacturing the drug or collecting the data. We do this because of the huge demand from patients and physicians such as Dr. Logue to make this drug available for therapy. But this is clearly not research and development.
The Chairman: Thank you, Dr. Levy.
Now, any panellist who would like to ask a question, you just -
[Translation]
Ms Pineault: My question is for the representatives of Health Canada, following the very interesting questions asked by Mrs. Fry.
According to my understanding of the process of the new emergency release program, an attempt is being made to eliminate some of the burden by putting doctors directly in contact with the manufacturers.
That's interesting, but one can only wonder how this will work. This is something we had looked a bit with activists last April.
Earlier, all this seemed to be described as a brief letter or phone call between a doctor and a pharmaceutical company. There's a little consent form, but it will surely be more elaborate than that.
Compassionate access to 3TC would have necessitated very heavy paper burden. As a matter of fact, doctors have discussed this at length. For my part, I'm concerned about the equity of this type of process throughout Canada. Not all doctors groups have the lobbying power of certain Toronto or Montreal clinics to convince pharmaceutical companies to support them.
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That's surely won't be the case in Rimouski, Sudbury, Blind River or elsewhere. So we could end up with a rather unfair system. Will every pharmaceutical company have its own emergency access program, with its own emergency access form? How will information be disseminated to doctors and how will doctors and patients be trained? In this whole issue of HIV, empowerment of patients is very important, specially in the regions, because they are often the ones who'll give their doctors information on new research.
Essentially, my first question is about the weighthyness of the process and doctors' responsibility in that process. What will doctors and their patients do when the company says no? Who will help them?
The Chairman: Thank you for your question. Which of the Health Canada panelists would like to answer?
[English]
Dr. Uscinowicz: With pleasure. The first question is on the paper burden. It's true that there are responsibilities for the physician, but I think that in the new proposal most of the responsibility, most of the work, is rather going to the industry. Maybe we would all find it informative if I highlighted the responsibilities of the industry and the physician, as we see it.
So, for example, under the new system, prior to the first sale of the drug, the manufacturer would be responsible for supplying the directorate with information concerning the condition of sale, recommendations on use of the drug and all information respecting risk, adverse reactions, warnings and precautions respecting the use of the drug. The information would be presented in summary form on data sheets, and would include relevant references. This is, of course, a proposal.
The manufacturer will supply physicians with the summary information and set up a mechanism to respond to physicians' questions regarding the drug. So there is a pipeline to exchange the information.
The manufacturer will maintain a detailed record of all drugs sold, including quantities, number of patients given the drug, dates of sale and the physicians' names. Annually or upon request, and within a given timeframe, the manufacturer will supply the drugs directorate with these detailed records of sale.
If requested by the directorate, the manufacturer may be asked to provide justification on why the drug cannot be sold in compliance with the Food and Drugs Act and regulations. Some of the drugs we've had in our program will most likely never receive regulatory approval or be pursued, but we want to know the reason the manufacturer reached such a decision.
The manufacturer also will be required to have in place and ensure its physicians have in place a recall procedure capable of immediately contacting all the patients involved with the program. This is viewed as a safety net.
The manufacturer must require that each physician will immediately report any new information respecting serious or unexpected adverse reactions. We would, in turn, report them to the drugs directorate. The manufacturer must not advertise or detail any drug that is sold under the new program.
Let me turn to the physician's role, which is to maintain records on the patient and medical situation, the intended dose regimen and the quantity of drugs supplied. This record must be provided to the manufacturer upon request.
I believe that to some extent this is also what any physician is doing at this time for the records. You put the name of the drug, the dosage you want to use and the quantity of the drug. You then report the outcome of the use of the drug and any serious or unexpected adverse reactions.
I would like to put emphasis on the serious or unexpected adverse reactions, and inform each patient receiving the drug made available under the program about the drug and the mechanism used to obtain it. So that's all for the physician.
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So we can see that most of the burden is still with the industry, with the new program, and the physicians practically do a lot of the things that are required in the current practice.
The issue of reporting adverse reactions is, of course, the crucial one, and we understand that. There are ways of elevating the time intensity for that.
Maybe we should favour templates for reporting adverse reactions. Maybe we will only require those that are serious or unexpected. This will be in line with the International Committee on Harmonization guidelines: to report adverse reactions in clinical trials. So we may expand those guidelines to the emergency drug release program.
So that's basically the proportion of duties under the new program. I should say these are all proposals. Everything is in the open. I welcome every comment that will improve the drug and I will see that we will give it very serious consideration, particularly when it comes from the committee.
The second question is on communication, and that's the most important aspect for us. It's much easier when we establish a policy that affects industry only. We have a mechanism to communicate with the pharmaceutical industry, and it's much easier to obtain input as well as establish the rules.
In this moment we at SAP and the government will have an impact on that, on the ethics board and on the physicians. Whenever the program is finalized we plan to have an extensive communication campaign. We understand that the way we communicate about the emergency drug release program now would not be sufficient for that process. Thank you.
The Chairman: Thank you, Dr. Uscinowicz.
Mrs. MacLean.
Ms MacLean: Thank you. I have three questions and one comment.
The comment is probably just a rhetorical question. Unfortunately the draft document does not address the problem of our branch plant economy in Canada. I mention this because in the past 18 months I've been in contact with several pharmaceutical manufacturers in the country, mostly to ask about the status of the new drug submission or the status of a compassionate access program. That includes Syntex Canada, Glaxo Canada, Burroughs Wellcome Canada, Serono Canada, and Boehringer Ingelheim (Canada).
I've had these responses: I don't know the answer, the Americans - or fill in the blank for the home office - won't tell us; we want to do a compassionate access trial, but the home office won't let us; we're ready to submit for an NOC, but the home office says we have to wait. Hearing such answers to my questions so often makes me think either they're telling the truth, or this is part of a learned response that all pharmaceuticals have when dealing with Canadian activists.
That's a comment.
My concern about the program itself in this draft form is that, as has been mentioned, there doesn't seem to be anything to encourage, much less compel, the manufacturers to participate in it. I mean, what if we give a program and nobody comes?
As part of that I would suggest that possibly an encouragement might be to require the inclusion of the information, of the data that must be collected, as safety in following up these compassionate access requests. This data must be included as part of the new drug submission for the NOC, and appropriate weight must be given to that data as safety data when consideration is being done for an NOC.
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I don't know if that's been considered, rejected, or I'm getting too picky. Perhaps somebody from either PMAC or Health Canada could comment on that one.
As for the item on information dissemination, there's a statement made about sufficient and current information to a practitioner. Well, what about the patient?
Reference is made to an appropriate consent form. There is no standard established for such forms in terms of completeness of information, accuracy of information or readability of information. This is a gap that must be filled; otherwise, the consent may well be given, but it is not informed.
Finally, regarding the evaluation of a program, no provision is made for anyone who might receive a drug through this program to evaluate the program or supply their comments on it.
The suggestion is made that questionnaires ought to be sent to physicians, to practitioners, to receive their input. A provision ought to be made for people who benefit or who do not benefit, but who have participated in the program one way or another. That will get you efficient feedback from the people who use it.
I don't know if there are any comments from either the manufacturers or from Health Canada.
The Chairman: Thank you.
Does anyone volunteer to answer the first question?
Ms Pieterson: I don't know if I actually picked up all your points - and I apologize - but I'll just comment on the ones I got.
On the one about consideration of safety data, if there is safety data that's reported from use of a drug that's given out through the emergency drug release program, and it's a serious adverse effect, it would be included. The manufacturer is not required to submit all adverse drug reactions. It would be submitted and considered.
Ms MacLean: I'm not merely thinking only of adverse drug reaction; I'm also thinking in terms of safety. This might add to the weight of patient days safely seen on a drug, and to the bulk of the safety data I assume one uses to judge the results of a phase II/III study. I assume you have to accumulate a certain number of patient days on drug in order to illustrate that, yes, this is safe for this number of conditions. I feel this ought to be given that weight.
Dr. Bouchard: It all depends on the drug. It's a case-by-case scenario for certain drugs.
Ms MacLean: They are safer than others?
Dr. Bouchard: It's true, but so also is the fact that the indication sought by the company may not be the one that is actually used in the open-label arm, the compassionate arm or for the emergency drug release program. So in that case you won't have to wait for the result, because you know that it might not be that relevant to the indication per se.
Ms MacLean: That only adds to the argument that control trials are not a real-world situation. Certainly in the case of HIV-related drugs, we know that people will not necessarily be taking them strictly as they were studied in the trials. Through a compassionate access program the opportunity to observe what happens in the case of multiple drug interventions that perhaps do not apply in a control trial could perhaps, in this case, be noted, commented on, and be with the information.
Dr. Bouchard: I think nobody's perfect, and obviously in the past -
Ms MacLean: I just wonder if that could possibly be included as part of the - It's not a criticism -
Dr. Bouchard: No, but in the past, for some of the first open-label drugs there were treatment trials basically. But now the actual open-label arms are more realistic with respect to the real-life situation, where the use of other drugs is allowed. You really compare that with the real-life situation.
The Chairman: Are there any other questions?
Ms Pieterson: You asked about the consent form, the difference between the consent form and informed consent.
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Part of the new program is to promote the information flow between all parties involved. One of our requirements is to see the information package the manufacturer will give the physician with the intent that the physician will then have enough information to make a good decision about prescribing this drug, but also be able to discuss the prescribing choice with the patient.
The informed consent form is an issue. I realize they have to be legible for the patient, and I think it's an area that's lacking in this proposal and there are a lot of suggestions coming out. PMAC has made some proposals about how to resolve that, but your input would appreciated.
Ms MacLean: I hope so, because having been asked to comment on a number of these forms and documents by pharmaceuticals proposing to produce trials for people with HIV/AIDS, and having received the comments in return from people who are taking part in the trials, all of us in community-based organizations would welcome a standard format.
The Chairman: Are there any questions? Does PMAC have anything to add to this?
Dr. Fourie: Going back to what Dr. Levy said, expanded access programs are not part of the drug registration process, but we are required to and we do submit all available safety data in our applications for registration. That is a requirement, and we do do that. We discussed earlier that there are gaps and holes in the collecting of safety information with the programs as they are now, but the information that would be available is included in the submissions.
Dr. Wainberg: I would like to make an additional comment because I think I neglected to say something in my statement this morning.
First, I'd like to thank the committee for the invitation to be here. This is the first time I've ever testified before a committee of this type. It has been an important personal and educational experience to witness how this group functions, and to understand how it impacts on the decision-making process in our system.
The point I would like to make that perhaps I did not adequately underline this morning is that the randomized clinical trial is the linchpin of our understanding of how drugs work and how well they work. While I understand the delicate balances this committee needs to understand in rendering judgment about the proper compassionate release procedure for drugs in Canada, I think that process cannot be one that limits the ability of Canadian clinicians and academics to direct and participate in properly randomized clinical trials.
I make this statement both personally and as president of the Canadian Association for HIV Research, with the backing of the organization's membership. It goes without saying that if we are to remain a competitive country, competitive in terms of our pharmaceutical industry's ability to continue to develop new compounds, and competitive with regard to the ability and efforts of Canadian academic clinicians and scientists to participate in clinical research of excellence, the randomized clinical trial must be protected.
I make this statement while being cognizant of Dr. Logue's remarks about the pressures on clinicians to complete perhaps too many forms in a manner that may take them away from their intended purpose. I am cognizant as well of Dr. Cameron's excellent comments regarding the complexities of the issues at hand.
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I cannot profess to have expertise with regard to allotment of clinician time, or the competing pressures on the approval process with regard to the need to protect Canadians while ensuring adequate, speedy and judicious approval of drugs. However, I do know that in seeking the balances that impending legislation must try to do, randomized clinical trials, as mainstays of drug development and the Canadian academic community's competitiveness on an international scale, must be protected.
Dr. Cameron: Thanks for the opportunity to add my two bits' worth.
In my opinion, the randomized clinical trial in drug development is well protected, because nothing else delivers the goods in terms of comparative risks and benefits and information as to the comparative costs of one health maintenance management over another.
I agree with Dr. Levy that expanded drug release programs or compassionate access programs are not drug development, although I acknowledge that it may become a part of the registration process, if we can distinguish between the registration process and drug development.
The EDRP or open-label compassionate access programs are tightly linked to patient participation in development trials, but the need not only for open-access medications but treatment, once proven, is much wider than the participation in clinical trials. The most ethical pursuit to bring the best treatment to the most people is rapid drug development. Nothing must interfere with this process. Speed is like justice - delay is denial of treatment. Nothing must interfere with the rapidity of drug development.
We've tried to streamline that process by saddling the health protection branch with a second task, and that is to facilitate the process of rapid drug development in these catastrophic illnesses. With additional tasks, not only safety and efficacy but facilitated development and now open and compassionate access programs, the HPB is smaller than it used to be. The tasks have tripled. Who is accountable in this? If we want the HPB to have an accountable role in this, it must have the means by which to be accountable for such tasks as they are assigned.
Who is liable in this? Everybody is liable. We see informed consent forms - patient information sheets - that sometimes include information as to waivers of liability by a person who might be asked to take an experimental medication. I'm not a lawyer but I do not believe it's possible to sign away one's civil right to sue anybody except, in time of war, the Crown. We don't have a system that waives that kind of liability.
I believe liability is tied to a person's ability to give informed consent, which is never perfect and usually imperfect. We cannot attribute liability to one place or another while the informed consent process is never adequate. Who's really liable? Everybody is on their own here, and we should all try to be responsible and recognize, if not subscribe to, the competing interests that are there.
Who pays for this? That is like asking which budget this goes on. The answer is that we all pay for it. Whatever budget it goes on, we all pay for it.
Dr. Logue: I want to add a comment. I'm a little distressed that Dr. Levy and I might seem more antagonistic than perhaps we are. I believe the pharmaceutical industry's contribution has not been small, and I acknowledge that its participation in and funding for compassionate programs is extremely costly.
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We're left in a quandary. If the pharmaceutical industry states this information is not valuable and is not useful in getting a drug licensed and we cannot prescribe this drug and it isn't licensed, we're left in the situation of asking if this is actually treatment. Clearly it isn't; it isn't a licensed drug. Is it drug development? To a certain extent it is. But I agree with his arguments that the information is not wholly used for licensing.
The issue is the size of these programs and the unwieldy situation that's been created. I think it's completely wrong to say this is active treatment if it's unlicensed. Yet that's what patients are demanding, and in some cases we're certainly feeling it is treatment.
On the other hand, it is also a part of drug development if some of that information is collected and used subsequently in reporting of adverse events. So a case can be argued either side. Health Canada has to delineate a mechanism whereby this can be feasibly done and to recognize these compassionate access programs are certainly not an ideal level of care and represent a situation that is a fall-back and an inadequacy of science delivering things more quickly.
To do that we need to have more rapid approval. We need to have harmonizing of international regulations. We need to have perhaps conditional approvals. We need to see an embellishment or an encouragement of more research that can be done more rapidly.
From our discussions it's clear we're in a situation where we're going to be continually opposed, even though I recognize the pharmaceutical companies are a huge partner and contribute a lot to these compassionate programs. But on our own we are not going to solve this without some intervention from someone like Health Canada.
The Chairman: Thank you, Dr. Logue.
Dr. MacFadden.
Dr. MacFadden: I have a comment and a suggestion, but first I have a question. The requirement for authorization for release of any experimental drug appears to require a fair amount of effort on the part of the pharmaceutical manufacturer to submit it for authorization and also to set up a structure whereby dissemination of information and monitoring can take place.
I'm wondering what your feeling is as to how this would impact on bringing drugs in from outside of Canada from manufacturers who don't have facilities in Canada. I've accessed a number of HIV drugs from the current EDRP program this way. I'm wondering how the new regulations might affect this situation, because I know EDRP does not have this kind of system in place for those specific drugs.
Ms Pieterson: The new proposal may - and I think it was recognized - increase the burden on the manufacturers. Most manufacturers have the systems already set up to record adverse drug reactions. They have medical departments that provide information. For their ongoing drugs that are under development they already have information readily available. I don't think that will be such an onerous increased responsibility for manufacturers.
With regard to the importation of drugs, this doesn't address that. You can import a drug for personal use. That is outside this part of the regulations and this won't affect that. Any physician import a drug for a patient.
Dr. MacFadden: Good. Thank you.
The Chairman: Did you have a question also?
Dr. MacFadden: Actually, she had answered the question. Thank you.
The Chairman: Thank you very much for these interesting remarks.
Mrs. Hayes, Mr. Ménard, and we'll finish with Madame Pineault.
Mrs. Hayes: Thank you. My question is very brief, actually. I listened to Dr. Logue and realized the amount of activity or involvement, certainly in his office, in this issue. Who would have an idea about the number of primary care givers or percentage of the population who are involved in compassionate access applications? Across the board, is it a large or a small percentage? Would there be many with the same type of use that you have? You say 50% or 60% of your patients are involved in this type of activity. Is that typical?
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Dr. Logue: First of all, I'll answer the second part. I am a member of the Toronto HIV primary care group and an ex-co-chair. There are about 50 members in our group, which treats about 60% of the HIV population in Ontario.
For some members in the group, HIV is almost the only disease they treat. In fact, a couple of members within the group have practices exceeding the size of any hospital-based clinic in Canada. That's unique and that's unusual, but it exists and it's noteworthy. Perhaps 20 individuals have a very significant number, if not a majority, of patients who are HIV-represented. I would think the same situation exists in Montreal and Toronto.
One of the problems is that the treatment of HIV disease has unfortunately been focused on small numbers of physicians. But it has expanded. One of the limitations of expanding that has been the discouragement to get involved in it. First, it's academically challenging; second, it's very political; third, there's a huge amount of paperwork; and fourth, other physicians don't get into it.
The brief answer is that I'm not representative of the entire group. There are certainly people who have more. I'm not unique. There is a large number, and that's just in one city. It's represented elsewhere in Canada. It's probably going to increase in other disease areas. The issues that are key in this situation are representative of other issues that will come up in other disease areas, for instance, in breast cancer perhaps.
Mrs. Hayes: In reply to that or by way of another question, in terms of paperwork, as you're part of a group, then, would it be a suggestion of the paper burden - if this type of compassionate care work is concentrated in an identifiable group, would it make sense to have support for a group for that particular part? We have already established that feedback is important.
Dr. Logue: We have in fact done that. That infrastructure does exist and came from an initiative within our group, and it's being replicated across Canada.
Funding for data collectors who go from physician's office to physician's office is partly provided by the Ontario ministry and partly by pharmaceutical companies. It comes under the auspices of the project centre in Toronto that distributes anti-viral drugs. So there is a mechanism and an infrastructure that we can access. Without that, we would not be able to carry on as we have.
I should mention one of my earlier points. After I met with Dr. Levy and some of his colleagues, they tapped into that resource and are funding that resource and contributing to it. They are helping with data collectors in that situation. There are obvious advantages. It relieves this paper burden and it should guarantee some consistency of case report forms and some reliability of the data, which is obviously in everyone's interest.
Presently, that is being funded partly by the Ontario Ministry of Health and partly by pharmaceuticals. That's one situation in one city. It's not consistently applied across the country and there certainly is not any formal mechanism that can be addressed by any physician. Some physician in London, Ontario, is simply out of luck.
Mrs. Hayes: This type of burden tends to cluster, you're saying, in a group. Maybe I could ask the directorate. Are there applications for compassionate access throughout the population or does it tend to cluster in specific groups?
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Dr. Bouchard: I don't have specific numbers, but I think it's a matter of 10,000 in question here. It's in that range. It's more than 10,000 a year. I must say that within the emergency drug release program most of them are not for AIDS patients, a large majority of them.
Ms Pieterson: We're mixing up compassionate arms of clinical trials and emergency drug release. They're different things.
One is a set protocol that the company establishes in a clinical trial, which is a compassionate access arm. The next is individual release of a drug through the EDRP program. They are different.
Mrs. Hayes: Good.
Dr. Uscinowicz: There are also some differences in the situations between physicians. We're now talking about primary care physicians, but we also get a lot of requests for drugs from physicians who are practising within the institutions where the problem of paper burden is different because of different resources.
The number of requests is enormous, but we cannot at this moment tell you how many of these requests are falling onto the physicians from the primary care set-up and how much is done by the institutional people.
[Translation]
Mr. Ménard: Mr. Chairman, there was something missing in the exercise we went through this morning. We received a great deal of information, but it would have been interesting to review various steps involved in the drug submission and examination process in order to better understand it and to found out what they imply in terms of the documentation to be filled out. Perhaps we should ask our clerk to provide us with that information.
For example, if we do a quick review of this exercise, we see that the applicant presents a file. Let's take the example of Glaxo and Biochem and must take the situation where they want to get a drug approved. We get back to clinical trials even either of the approaches involve clinical trials, if I've understood correctly.
The applicant presents a request for licensing of what will become a drug. During the first step, there's a verification. For the purposes of this verification, what is required as documentation and what exactly is being verified? Is there an attempt right at the outset to verify the toxicity of the drug?
Dr. Bouchard: No, at this stage, we verify the documentation as such. That will be discovered during the process itself.
Mr. Ménard: So when people talk about bureaucracy in the licensing process, are they referring to this stage where too many documents are required? What is required?
It would be a good idea for us parliamentarians to see, lets say in a file, what this means in concrete terms and what information is required at the verification stage. Could this burden be lightened? Or do we have the feeling that everything that is required is rigorously justified and that nothing less could be required?
All this is very abstract as long as we can't see it physically. Since this session will be rebroadcast, I'm sure that for the people listening to us at home, none of this will mean very much if we can't see the documents, Mr. Chairman. I would like to see them once in my life. I will not be called upon to fill them out. I'm not a doctor. I would like to determine what amount of information is involved here.
Next there is another stage involving chemistry and manufacturing review. Are there more forms to fill out at that stage? What does it mean in concrete terms?
Dr. Bouchard: The application per say has been presented. The review is a critical analysis of what has been presented.
Mr. Ménard: When you call a stage "chemistry and manufacturing review", that's what you're verifying at that stage.
Dr. Bouchard: Yes.
Mr. Ménard: We're talking about laboratory tests dealing with the manufacturing and chemistry of the drug to be licensed.
Dr. Bouchard: We're not talking about tests as such. Sometimes we request tests. Generally speaking, if a test is missing, the company will have to provide the results of the test. It can happen that we conduct them ourselves eventually. But that's not the usual case.
Mr. Ménard: Let's take an example so that I can understand this properly. Glaxo or Biochem submits a drug licensing application. You told us that there was a verification of all the information they submit. I as a parliamentarian would like to see these forms in the coming days.
We have never seen them and we have to report on something we have never seen. To avoid having to talk about something we don't know, we would like to find out what we should recommend to you. You have a step here entitled "chemistry and manufacturing review". If this is not clerical in nature, it's experimental.
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[English]
Ms Pieterson: If you want to know about forms - I'm not quite sure if you want to know the type of data we request or the forms - we do have bureaucratic forms for the manufacturer to fill out. But the manufacturer has a prescribed list. Actually, I have a structure of a human new drug submission here, which I can give to you if you want. It's basically a guideline for industry and outlines the type of data to be submitted in a new drug submission.
The paperwork associated with the review is connected to reviewers' reports internally and production of reports based on the dossier the manufacturer submits. Is that what you're asking?
[Translation]
Mr. Ménard: Yes. I've been hearing about this for a year now and it interests me a great deal. We went to meet with you and the department and I think I understand the theoretical aspects of the process. However, as parliamentarians, we will be undertaking something extremely important. As a matter of fact, last night we were told that, ultimately, the availability of these drugs were a matter of life and death.
I would like to be able to fully understand the non-theoretical aspects of the process. I would like to sit down with somebody from the Department of Health and see these forms. I would like to understand on what we can base our recommendations, as members of Parliament, to lighten some of the bureaucracy without becoming overly simplistic.
I know full well that this entire process cannot be simple, but I would like our clerk to find way to make it less theoretical. I want to see the documents and the type of date that's requested. Why is it that since last night, we've been hearing reoccurring demands for the bureaucracy to be simplified?
I would also like to ask questions concerning clinical trial. I'll get back to that later.
Do you understand what I'm feeling as an individual? I don't want to get existential here, but it,s important for us, members of Parliament, to understand what this documentation implies for those who have to fill out the forms.
[English]
Ms Pieterson: In the past, when we have given similar types of explanations, we recommend you see a new drug submission. Maybe it would be worth while, with permission of a manufacturer, to show you the volumes that come in. As I said, I got one with 800 volumes this week. I could show you the mountain of books in my office and you could actually look through the section.
[Translation]
Mr. Ménard: No, not that one.
[English]
Ms Pieterson: No, you don't want to. Also, we can take you right through the EDRP process, with a physician calling in to talk to us, the forms that are filled out at our end, the forms the physician has to fill in, the call to the manufacturer, the form he fills in, and shipment of the drug at that end. We can arrange to have that done.
[Translation]
Mr. Ménard: Ever since I've become interested in the work of this committee, my obsession has been a the Canadian HIV Trials Network. If the Deputy Minister was here she could tell you what an obsessive person I am. I've always understood that in Canada, there were two major problems: the first was that the Canadian HIV Trials Network was suffering from a lack of funding, which is something we won't discuss here this afternoon because it's another issue; and the second is that this network, which has five operating satellites, is imposed certain types of research by the pharmaceutical industry because it's the industry that provides the funding.
We parliamentarians will have to comment on that second problem. But you, as public servants, you see research protocols for each of the clinical trials conducted by the network, according to my understanding. Were told that there have been 40 since the network came into existence.
An activist from AIDS Action Now, Brian Farlinger, was now deceased, came to tell us what the Canadian government could do. That was the point of my earlier question, when we did not understand each other. The activists came and told us that when a research protocol is approved by the Canadian government, we as legislators can force the party submitting it to include a compassionate access provision.
Would this be possible, yes or no? I know that under current legislation, that's not the case. But I do understand that you see each of the authorized protocols that be the subject of experiments by the Canadian HIV Trials Network. You state your position on the merit of the protocol. It would be possible for us as parliamentarians to present a resolution requesting that the Food and Drug Act be amended, if that's the legislation that must be amended, so that authorized public servants are forced to make consent for a protocol or a research project contingent on compassionate access. Would that be possible?
That will be the second major question we will have to answer. Once the ethical questions are settled, we parliamentarians must decide if we want to recommend to the Canadian government that any protocol approved by the sections concerned, in this case your own, be conditional upon compassionate access.
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Do I understand the situation correctly when I present it this way or am I completely off the track?
Dr. Bouchard: Let me say that you're not off the track. I would add also that you're very welcome, if you want to come and spend the day reviewing drug. We will accept you; there's always room.
Mr. Ménard: The Liberals will say that I have to swallow my pencil, you understand?
Dr. Bouchard: There's no problem. We could make the necessary arrangements with the company.
Let's get back to your second point. If you eventually want to change the legislation, it will be up to you to thoroughly consider all the aspects of the problem, because it doesn't only apply to the subject that is your main interest here today, namely aids and HIV.
Don't forget that the legislation will also apply to all drugs and diseases. You must also remember that it will apply to large companies as well as small ones. I'm not sure that small companies will be able to afford to provide the kind of sustained effort that you will demanding.
The other point that has to be taken into consideration is that although Canada is very large, it is probably not the main market for most pharmaceutical companies. The effort that is being deployed right now in the fight against HIV and aids is international. Increasingly, we are seeing that protocols, even though submitted to the Canadian HIV Trials Network, are international in scope. The network has very little to say about -
Mr. Ménard: It's important to know that these are international protocols. We were told that. The people from the Canadian HIV Trials Network told us that the main strong point of the network was to encourage international research. We are on the same wavelength. I've always had the feeling that very little in-house research was done.
When an international protocol is conducted by the Canadian HIV Trials Network, do you see it? Do you have a say in it?
Dr. Bouchard: Yes.
Mr. Ménard: How much scope do you have in terms of your freedom to grant an authorization or not?
Dr. Bouchard: Our scope is extremely limited; either you grant permission, or no clinical trials are done in Canada in this area. Let be honest here. When the drug is available in the United States under trial and with compassionate access, if you don't agree to the same thing in Canada, you're creating serious problems for the Canadian company and to patients in Canada.
Mr. Ménard: I think it's very important that this committee make an effort to make this whole issue concrete, otherwise it can remain purely conceptual. I'm not a doctor. I may have chosen the wrong career, but I'm a member of parliament, and if my question is not answered in a very concrete way, we won't be able to make recommendations. Do you understand?
There is a dimension missing in this dialogue. For us, and I'm sure it's not a matter of bad faith, every member of parliament must understand exactly and in detail what it means to authorize a research protocol. This is imperative otherwise we cannot do our work properly.
Dr. Bouchard: I think you are going to come to see us, because this goes well beyond what we can do here.
Mr. Ménard: That's true.
The Chairman: Ms Pineault, one last question, please.
Ms Pineault: My question is the same as last time. The answers I was given concerning the weigthyness of the process have not alleviated my concerns. I did read the documents that were sent this week and I had read the information provided to me by representatives of the federal government.
My question was more of the type of confrontation that was conducted or that may not have been conducted with regard to access to emergency drugs. What kind of consultation are we considering? Or is this committee the only place where members of the government can gather information?
All the comments we made were answered with a great deal of good faith. We are prepared to accept suggestions, but we can't agree - we have to be realistic - to make very concrete suggestions here this morning. I'm still concerned that were putting a great deal of weight on the backs of manufacturers, which are not humanitarian organizations but profit-making corporations.
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This is not a bad thing. They try to play a social role, but they are profit-making organizations and not humanitarian ones. Were asking them to play a role that may not correspond to what they're all about. Some accommodation may be possible to ensure that these requirements correspond to what these corporations are all about. I would like to know what consultation process is being considered, if there is any, and when it will take place.
[English]
Dr. Uscinowicz: Of course, this is just the beginning of the consultation process and the beginning of the process in general. This is a discussion paper, and I would really like to emphasize that.
We're talking about the concept at a high level. We're not talking about the specifics here, although any comments on the specifics are welcome. We have sent this paper for initial consultation to the manufacturers of Canada, the pharmaceutical industry, both PMAC and generic associations; the Canadian Nurses Association; the Canadian Medical Association; the Canadian Pharmaceutical Association; some provincial governments; the Canadian Society of Hospital Pharmacists; and the Collège des médecins du Québec.
This is the initial process only. We envisage that at some moment, when we have a vision of the system, most likely we will try to publish that in the Canadian Medical Association Journal and/or other relevant journals to obtain broad input from the involved parties. It is already in our plans to do that.
However, that is the initial part only, and actually, at the time when we were talking about it, we did not know we would be invited by this committee and be privileged to hear your comments. This is just an additional enhancement that came to us.
[Translation]
Dr. Wainberg: I would like to add a point with regard to clinical trials implemented by the Canadian HIV Trials Network.
In addition to being President of the Canadian Association for HIV research, I'm also President of the scientific committee of the Canadian HIV Trials Network.
I must admit that a significant part of the clinical trials conducted in Canada are Phase I clinical trials; that is when we study a new drug to have an idea about its toxicity etc., and not necessarily to gain a better understanding of its antiviral effects.
[English]
Secondly, I would like to make the point that many of the trials considered by the HIV Trials Network are in fact investigator-driven. That is to say, the ideas for these trials really do originate with individual clinical scientists. For example, Dr. Cameron, who's sitting next to me, has himself proposed over the years a number of very important trials to the HIV Trials Network.
I believe there is a mechanism in place to consider both clinical trials that are investigator-driven as well as clinical trials that perhaps it could be said have been initiated at a certain level, at least in terms of when they reached the Canadian HIV Clinical Trials Network, by multinational pharmaceutical companies.
But even in the case where clinical trials have been initiated by multinational pharmaceutical companies, it's fair to point out that in most cases those trials in fact may well have originated with individual university- or hospital-based clinician scientists. They may not necessarily be in Canada. They may be in the United States or in Britain, but we as an international society have a country in which we must participate at an international level as well as on a national level in certain trials.
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The fact that a trial comes to the network under the sponsorship of a pharmaceutical company does not necessarily mean that the trial did not originate at the level of a university or hospital-based clinician scientist somewhere. I think that's an important point to make and an important distinction to underline.
The Chairman: Thank you, Dr. Wainberg.
Dr. Logue, quickly, please.
Dr. Logue: I have two small points. One is a procedural question.
I recognize in the documents with the proposal for the new program that there's a subtle difference in accessing emergency drug release. Currently, the policy is that the practitioner makes a request directly to the drugs directorate. In the new proposed process it's amended to being the practitioner communicating directly with the manufacturer.
I'm interested in knowing why that has been proposed. I know in certain situations that I would get useful information, if I'm requesting emergency drug release, if I contacted the drugs directorate first, because they can give me information as to whether or not they've made applications for that drug previously, whether it's been turned down, what the status of it is or whether there is an IND, etc.
So I'm not sure why there's the proposed change. I think in certain situations it would prove to be more difficult for physicians. We may contact drug companies but we may simply spend a great deal of time trying to track down the correct person to speak with.
The second question is regarding education and communication about the entire process. It may impact on how the process is subsequently assessed or evaluated.
The Canadian HIV Clinical Trials Network has a program in which they're staging a forum in Toronto in the new year for patients and primary care physicians. They're trying to address global, generic concepts such as what informed consent is, how to read a protocol, and the advantages and disadvantages of compassionate access versus a randomized control trial. It's things like that. I think that's very useful information for patients and physicians alike in order to make informed decisions. I think it's a fabulous program that was initiated by the CTN.
I'm just wondering if you, as a part of Health Canada, feel that could be a role that you could also serve. Is that a part of your mandate? Do you see that useful? Would you like to participate in programs such as that?
Dr. Uscinowicz: I'll answer the first question, if I may.
That directorate is a very small organization. We have no more than 500 personnel to handle all our functions delivered from our mandate and mission.
About two years ago we initiated a renewal process in which we looked at every activity of that directorate and tried to find a better way of handling them from many different points of view, but also from the point of view of resources. That's the first issue I would like to highlight.
The second one is that it's still the prerogative of the industry to make a final decision to release the drug or not. We can agree, but the final say is still with the pharmaceutical company. So we found it would be most appropriate for the process to include the manufacturer first.
This is expected, particularly in the emergency scenario, to enhance the timeliness of the drug shipment to the physician for his patients.
Those are the basic three reasons for it.
Ms Pieterson: I'll just add that we will still provide information. If you're a physician and you want to know if company X is making available a drug, you can call us. We would still provide you with that information. We aren't stopping that. We'll have a list of companies and what drugs they're providing.
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Dr. Logue: I wasn't clear about the summary of the special access program. In the second paragraph of the draft you indicate that the manufacturer will be permitted to release the drug to a practitioner in an emergency situation without pre-authorization from the drugs directorate.
Ms Pieterson: Right.
Dr. Logue: When you present your flow diagram, the implication -
Ms Pieterson: That's assuming the physician already knows that the manufacturer - If the physician doesn't know, we would provide the information.
Dr. Logue: On the same page, under authorization to release, it's indicated that the manufacturer would be the contact point for the practitioner and would be permitted to release a drug for up to 50 patients to a practitioner upon receipt of an authorization for release from the drugs directorate. So in one indication you state that they can release it without your pre-authorization, and in the other paragraph you're indicating -
Ms Pieterson: There are two different situations. The true emergency situation is the one where they don't need pre-authorization from us to release it, because we don't want to add that time element into it. So if the physician determines that it's a true emergency, the manufacturer can provide it directly. The other situation is the non-emergency situation where the company must have pre-authorization from us.
Dr. Logue: But in either case the physician could initiate inquiries with your branch.
Ms Pieterson: That's right.
Dr. Logue: Typically, in the small number of cases that are true emergencies and we're requesting a given drug for a one-off situation, the existing program works well, and we're initiating that with you. With these large programs we're usually trying to see if we can get expanded access, and we're initiating those discussions with the manufacturer.
So whether a case is a true emergency or not is debatable, but in either case we can contact your bureau directly.
Ms Pieterson: That's right.
Dr. Logue: The second question is in terms of education. The forum that the CTN is proposing - do you feel that's part of your mandate? Would you like to participate in forums like that?
Dr. Bouchard: We have been invited to participate. We have received three invitations. If not me, then one person from our bureau will go to the meeting.
Dr. Logue: I'm glad you'll be there, but is your role passive or as a participant? Would you like to see that expanded? Would you like to fund things such as that? Do you think that's an enhancement of patient choices and decisions? Is that part of your mandate or is that too big a question?
Dr. Uscinowicz: I think it's too big a question and it's outside of our mandate to decide on money. The drugs directorate evaluates submissions for safety and efficacy, and that is our core activity.
Ms Pieterson: You must recognize that there is a conflict with our funding any kind of studies for drugs that we're approving. I don't think anyone would want us to do that.
Dr. Logue: As a regulatory body you obviously don't want to do that, but this would be funding a program where you're allowing Canadians to make better choices about certain treatment options.
Dr. MacFadden: This is a comment, not a question. I was concerned when Mr. Ménard brought up the suggestion, and it has been bandied about before, of possibly compelling companies to add a compassionate arm to clinical trials.
We should never mandate that type of activity. It will be counter-productive. It's difficult enough to get pharmaceutical companies to do trials in Canada, since most of the major pharmaceutical companies are U.S.-based. Even with the development of a very good infrastructure for doing clinical trials, the pharmaceutical companies are mostly U.S.-based. If we add one more deterrent - and it would be a deterrent - to their doing trials in Canada, we might even prolong the period of time before we get compassionate access to that drug.
Dr. Cameron: I agree with Dr. MacFadden. Second, if the mandatory attachment of compassionate release or parallel arms to clinical trials conducted by the Clinical Trials Network could be attached, give us the means and we'll do it.
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The Chairman: Thank you, Dr. Cameron.
[Translation]
I wish to thank all our panelists. We are very pleased with this meeting. The discussions were very open and passionate.
We will meet again next Wednesday at 3:30 p.m. At that time, we will be discussing ethical and legislative considerations.
Thank you very much and good day.
This meeting stands adjourned.