[Recorded by Electronic Apparatus]
Wednesday, December 6, 1995
.1545 
[Translation]
The Chairman: Hello again, everyone. I'm very pleased, as Chairman of the Sub-committee on HIV/AIDS of the Standing Committee on Health of the House of Commons, to welcome you here today in the context of our national round table on compassionate access to experimental drugs.
The members of the subcommittee and I sincerely wish to thank all those who travelled here in order to take part in this first sitting of the round table.
[English]
[English]
Before we embark on our session today on compassionate access to experimental drugs, I would like to briefly recall how the parliamentary Sub-Committee on HIV/AIDS was established.
[Translation]
Our subcommittee was created by the Standing Committee on Health in November 1994, following unanimous agreement by all MPs. The mandate of the subcommittee was as follows: to study the spread of HIV and the prevention, treatment and support of persons infected by HIV/AIDS, with special attention to the role of poverty and discrimination on the aforementioned matters.
At their first meeting, members of the subcommittee agreed to examine the role the federal government plays in the fight against HIV/AIDS. We held several public hearings and listened to a great number of witnesses.
I am pleased to announce that the first report of the subcommittee, which deals essentially with the National AIDS Strategy, is now completed and was tabled earlier today in the House of Commons.
[English]
At its first meeting the subcommittee also decided to examine how poverty and discrimination could hinder the delivery of AIDS education and prevention initiatives as well as the treatment and support to those affected by HIV and AIDS. These aspects of poverty and discrimination will be the subject of a study by the subcommittee in the coming months.
[Translation]
Moreover, in the course of its deliberations, the subcommittee was informed that compassionate access to experimental drugs was an important factor in the treatment of HIV-positive individuals. That is why a decision was made to hold a national round table on compassionate access to experimental drugs.
Let us recall that compassionate access refers to the delivery of a drug whose sale has not yet been approved by Health Canada for patients who, in consultation with their physician, feel that this treatment may offer them some hope of saving life, restoring health or alleviating pain.
[English]
Compassionate access to experimental drugs is therefore a vast and complex issue that raises human, medical and ethical concerns and questions about regulation and responsibility.
Our purpose is to delve into these complicated issues and identify the constraints and proposed solutions that will result in a more liberalized form of compassionate access that is acceptable to all those concerned.
[Translation]
This is why the round table has been separated into five different half-day sessions.
Today, we will begin the process with the opening session aimed at gaining some knowledge and understanding of the views of the groups most affected by the issue of compassionate access.
Tomorrow's session will deal with the drug regulatory process, with an emphasis on the impact on clinical trials and compassionate access on this process.
The third and fourth sessions will be held next week. We will examine ethical and legal considerations and the issue of responsibility as it pertains to patients, physicians, pharmaceutical manufacturers and government.
The fifth and final session will be held in February of 1996 with a view of establishing a consensus amongst all the parties affected by compassionate access to experimental drugs.
[English]
The purpose of today's session is to better understand the opinions of those concerned with compassionate access to experimental drugs.
One of the questions to be resolved is whether compassionate access to experimental drugs could compromise the quality of data obtained in clinical trials. Another important issue relates to obstacles that may hinder compassionate access. Further, it will be interesting to learn about other countries' experience with respect to compassionate access.
[Translation]
I hope that the participants who have gathered at this round table will be able to provide some answers to these questions, and many more. I thank you for accepting our invitation and with that, you have the floor.
This is how we will proceed today. All the participants this afternoon will have ten minutes. The participants have been divided into three groups: the first is made up of representatives of the catastrophically ill.
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We have with us Lise Pinault, Coordinator for COCQ-sida; James Shedden, Coordinator of the Nova Scotia AIDS Coalition; Susan Conrad, who is here to make an individual presentation; Ahmed Hassan, who is also here as an individual; Pat Kelly, Member of the Burlington Breast Cancer Support Group; Sharon Batt, Member of the Canadian Breast Cancer Network; also, Lorraine Parsons, Member of the Ottawa Chapter of the Canadian Haemophilia Society.
After this period, there will be a discussion and members of the subcommittee may ask questions.
I would just like to tell you that at 4:05 approximately, MPs will have to leave to go and vote in the House of Commons. This vote will last approximately 15 minutes. There will be a pause at that point and we will continue our deliberations afterward.
So I now give the floor to Ms Lise Pinault, the Coordinator for COCQ-sida. Ms Pinault.
Ms Lise Pinault (Coordinator, COCQ-sida, Representative for the Catastrophically Ill): Good afternoon, and thank you for your invitation.
COCQ-sida brings together community organizations and community shelters in Quebec. We represent all of the organizations, approximately 35 community groups.
The opinion that we want to put forth today is based on many discussions we've had with our colleagues in other provinces, mostly people with HIV/AIDS.
These reflections are mostly made up of excerpts of documents from Canadian activist organizations such as, for instance, AIDS Action Now!, from Toronto. Compassionate access occurs at the same time as clinical trials allowing a greater number of people with HIV/AIDS to have access to drugs that are being developed. Pharmaceutical manufacturers carry out clinical trials mainly in these three big Canadian cities, Vancouver, Toronto and Montreal. It is therefore impossible for a person suffering from the illness who lives outside of these big cities to take part in clinical trials.
We have discussed this problem many times with certain representatives of the pharmaceutical companies, and it would seem that the cost and difficulties with monitoring keep them from spreading the trials.
On the other hand, we've noticed that, more and more, people who are HIV-positive or who have AIDS go back to their home area. These two observations only reinforce the idea that there should be a compassionate arm to each clinical trial carried out in Canada, or even elsewhere.
The pharmaceutical companies' reluctance concerning the development of compassionate access is based on two main reasons which we won't go into, but which, I think, are quite logical: the cost, and the fear that they will have difficulty recruiting volunteers for the clinical trials.
We think that the only reason for taking part in a therapeutic trial should be altruism, giving of yourself for science so as to help discover effective treatment. When the only reason for a person's participation in a trial is to obtain a new molecule, the results are very often distorted. That person will give up more easily if he does not get the hoped-for results.
In the case of double-blind testing, patients will often do everything they can to find out whether they are taking the real agent or placebo. They do so by tasting the tablet of a partner or a friend. If the tablet doesn't have the same taste, they go to the laboratory to assess what's in the tablet and they sometimes also alter the dosage, take more, take less, because their interest isn't necessarily in the clinical trial.
There are certain advantages for pharmaceutical companies in developing compassionate access. The compassionate efforts can generate data on the safety and the effectiveness of a product, data that can then be used to bolster a request for marketing approval. Some companies have carried out verifications that show that the data from their compassionate arms are as reliable and precise as the data from their scientific arms.
A request for accelerated approval will have more chances of being approved if the treatment has been administered without endangering many thousands of people rather than many hundreds.
Thanks to the setting up of compassionate arms, trial participants will be motivated by the desire to help science move forward and not because it is their only way to get access to treatment.
By offering compassionate access, the company fulfils its obligation to act as a good citizen, and that attitude is the source of goodwill and good public relations within the HIV community. This behaviour will probably lead to regular sales and profits for the company.
We think that the federal government has the authority to regulate and require that companies develop compassionate access when they reach phase II of clinical trials.
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The second part of my presentation is an overview of draft guidelines which Canadian activists agreed on during the year 1994-95.
Firstly, in any phase II or III protocol the company should include a statement of intention with respect to compassionate access to the experimental agent.
The statement should include the following information: an estimate of the demand in Canada for the experimental agents from the date of application to the anticipated date of marketing approval, on a monthly or a quarterly basis; the dates when the company intends to make the agent available to the emergency drug release program and the compassionate arm of the clinical trial; if the agent is not to be made available to anyone who requests it, the eligibility criteria for compassionate access. And if the agent is not to be made available free of charge to the patients, the price which the company intends to charge.
In assessing the reasonablemess of the proposed compassionate access, the Health Protection Branch may request further information from the company, on a confidential basis, notably the particulars on the production process, including the costs, for instance, of beginning production for the anticipated compassionate demand, the rationale for excluding some people from compassionate access, the basis for the companies' demand estimates and the particulars on the financial capability of the company to satisfy compassionate demand.
If the HPB is not satisfied that the company has provided sufficient information, or is not satisfied that the company intends to provide reasonable access to the experimental therapy, it may refuse to approve the phase II or phase III trial.
In assessing the reasonableness of the proposed compassionate access, the HPB may consider all relevant factors including: the potential usefulness of the agent in alleviating suffering, prolonging survival, improving quality of life and treating or preventing a medical condition; whether people whose conventional and alternate therapies have failed have any other options; the affordability of any price established by the company; the cost of producing the experimental agent and the financial capability of the company.
If during the course of the clinical trial there is a material change in the demand for the experimental agent, the HPB may request that the company file a revised and reassessed statement of intention, compassionate, etc...
Then there is reference to certain regulations of the HPB which may be changed in the light of tomorrow's suggestions. So I'll just state them. We could always reinclude them in another form.
The Health Protection Branch may request a statement, under the terms of subsection (1) from any company developing or studying an experimental agent outside of Canada.
The HPB may request further relevant information, including the information referred to in the first subsection. If the HPB is not provided with adequate information, or is not satisfied that the company intends to provide reasonable compassionate access, the HPB may revoke the license or the patent on any drug.
Those are our recommendations. This isn't very developed. I think that my colleagues will be able to go a bit further. Thank you.
The Chairman: Thank you very much, Ms Pinault. We'll now give the floor to Mr. James Shedden.
[English]
Mr. Shedden is a coordinator for the Nova Scotia AIDS Coalition.
Mr. James Shedden (Coordinator, Nova Scotia AIDS Coalition): I'd like to first take this opportunity to thank the subcommittee for extending their invitation to me to attend this national round table. In the face of this catastrophic and at times divisive disease, it is gratifying as a community-based AIDS worker to be asked to participate in this forum.
I've been involved in the issue of HIV and AIDS in different capacities for close to ten years. As countless others, I have lost people close to me in my community and continue to see the devastation that this illness brings to thousands of individuals and their families and friends each year.
For the past four years I have worked for the AIDS Coalition of Nova Scotia, a community-based AIDS service organization funded in part by the AIDS community action program. My specific duties during this time have included the coordination and dissemination of HIV and AIDS treatment information to persons living with HIV and AIDS and their caregivers, including medical professionals interested in accessing reliable, understandable and up-to-date information on the treatments available for HIV and AIDS.
In the fall of 1994 I completed a needs assessment entitled ``Taking The Next Steps'', which asked people involved in the AIDS movement in Atlantic Canada what specific needs there are surrounding treatment for HIV and AIDS. The answer, while not surprising to anyone, was that relatively few persons with HIV knew a great deal about clinical trials in Atlantic Canada.
.1600
For the people I spoke with and work with, experimental medical care is a luxury that can be taken advantage of only after their basic needs have been met. For PHAs in my region, this is a luxury that is often never achieved.
For those who access clinical trials and wish to obtain the most up-to-date medical care, there are still a number of obstacles that must be overcome to access adequate levels of care surrounding compassionate access to drugs and therapies.
In the interest of time I would ask the round table to consider some pressing needs that people face in deciding about experimental care. The first is accessibility.
Atlantic Canada has historically been and continues to be an area that struggles for recognition and assistance and is routinely ignored and allocated few resources from governments and private industry. This is also true for pharmaceutical manufacturers. The Atlantic provinces are comprised of rurally based communities and as such represent an unnecessary cost for pharmaceutical companies and stretch the small budgets of hospitals and AIDS organizations to the breaking point.
Travel, accommodation and childcare are financial considerations. Just as important, the stress of constant travel for those PHAs who do not live in the few urban centres that house infectious disease clinics or clinical trials reduces the number of individuals who may wish to access these trials.
Since the number of people involved in trials is smaller, the pharmaceutical companies and others see little return on their investment, and many trials are simply not run here and occur in larger centres with more active PHA populations such as Toronto and Vancouver. This puts pressure on hospitals and clinical trial sites to maintain higher numbers of individuals in trials.
I am aware of a situation in Halifax where if a person diagnosed with HIV wishes to access the services of the infectious disease clinic and receive specialized medical care, they must wait for a minimum of two months before being allowed to access service. If, however, they choose to enter a clinical trial, they may access the services of the ID clinic immediately. For the newly diagnosed individual, grappling with the many issues associated with HIV and AIDS, this is a hard decision to make.
Accessibility to the different communities is also an issue. Women, persons of colour, persons in later stages of illness, gay men and others have particular considerations that are overlooked or not adequately addressed in participating in clinical trials. One example is asking women to practice two or three types of birth control if they enter into a clinical trial.
While I previously mentioned some areas of financial concern, I cannot stress strongly enough what an important aspect this is to the lives of persons living with HIV and AIDS in Atlantic Canada. The four Atlantic provinces, while not unique in this concern, suffer increasingly under that burden.
With cutbacks and downsizing of facilities becoming the norm across this country, people with HIV and AIDS find an increasingly difficult time in accessing adequate medical care or the leading edge in medical care. PHAs are substituting experimental medical care for their primary care because they are not guaranteed access to specialists and facilities that they would normally not be entitled to.
We in the activist community have been part of a trend over the last few years of recognizing that access to compassionate arms of clinical trials and catastrophic rights has been changing.
An example of this is the well-publicized saquinavir study. Individuals wishing to partake in this trial have had to submit to a lottery to apply for compassionate access to this drug. Information about this lottery has been hard to come by. Individuals must apply for a set allotment of this drug through a lottery and, even when they have been chosen, have at times not received the drug when specified. Some individuals I know in my region have still not received their allotment, although they have been promised as such.
The work of the Clinical Trials Network has helped to distribute the number of clinical trials across Canada, but it is woefully inadequate. Underpublicized and not really well known in our region, the CTN has no budget to complete the large volume of paperwork that is necessary for an individual to partake in a trial. As such, it places a greater burden on the individual to find out information about the trial and the trial nurses who need to fill out forms to allow the individual to access the chosen drug. Given the scope of stress that an individual has after their positive diagnosis, these financial considerations are another stress that the PHA simply does not need to have.
What we in the AIDS community are witnessing is a lack of services and options for people living with this illness and an erosion of the basic rights and individual freedoms that a person living with HIV experiences. This is simply not compassionate access. In the words of one PHA whom I spoke with, this is simply holding people hostage to access the kind of medical care they wish to receive.
On the rights of the individual, Canada as a nation encourages its citizens to practice their right to make individual choices that will govern how they live. The AIDS movement has also been built upon an individual movement of empowerment, an empowerment to take control over and direct their own lives and actions.
We who are close to this movement have been inspired by many people who live with HIV, who have taken control of their lives and live proud, full and independent lives in the face of such a devastating illness.
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This model of empowerment is seriously eroded, however, when one attempts to take control over one's health care. We are faced with a strict medical model that tells us to sit down, shut up and let other people make decisions for our lives. In the background documentation I have read, I am struck over and over again by the language used to explain the fate of people living with HIV and AIDS.
Pharmaceutical manufacturers and governments worry that people with HIV will not enter into a trial if a compassionate arm is offered, that they would rather not participate in a trial. The reason individuals take part in clinical trials is very complex. While some individuals take part in trials to access high-quality care, most PHAs take part in trials for very personal reasons and hope to make a difference in this world by offering one of the few things they are able to willingly give - themselves.
We in eastern Canada are labouring years behind the rest of this country in terms of treatment issues and access to information. People living with HIV and AIDS need more access to information and resources to make well-informed choices about their health care and to recognize that catastrophic rights are theirs in the face of this disease.
As a community-based AIDS worker, I implore the partners sitting around this table to recognize the rights of individuals living with HIV and AIDS to be able to access the treatment they wish to receive, with ongoing education and resource allotment for community-based organizations and partners providing health care.
Among the recommendations I would bring to this table are the following.
We need to continue to work with governments and pharmaceutical manufacturers to provide opportunities for PHAs to live strong and productive lives. PHAs must be recognized as important players in this process, and their lives are at stake. I am heartened at the evolving relationship between pharmaceutical companies and AIDS activists in reaching compromises that benefit as many people as possible.
Pharmaceutical companies and governments must recognize the needs of different regions of Canada and formulate policies and procedures accordingly to ensure an individual PHA can be guaranteed a high standard of care, regardless of where he or she chooses to live in this country.
Allow for geographic guarantees of allotments of upcoming drugs and therapies.
Provide for community-based trials across the country. While there has been an interest in community-based trials in eastern Canada, we have had no opportunity to explore these other options in health care.
It saddens me deeply that I cannot come to you today and tell you anything new, that I cannot shed more light on this subject than numerous others have in the past. We in the AIDS movement have been telling you for some time that more is needed - more access to information and resources, more openness to trials and truly compassionate access to all persons living with HIV and AIDS.
The individual rights of those persons infected with the AIDS virus are more important than anything else, least of all the profits of pharmaceutical manufacturers and cutbacks in basic government services.
Thank you.
The Chairman: Thank you very much, Mr. Shedden.
We're going to stop now because we have to go for a vote in about a minute and a half. We'll be back in about fifteen minutes.
[Translation]
The meeting is adjourned until we come back from the vote. Thank you.
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The Chairman: The Sub-committee on HIV/AIDS will now resume its work. I now give the floor to
[English]
Susan Conrad, please, as an individual.
Ms Susan Conrad (Individual Presentation): I am using a different microphone. I hope everyone can hear me.
I am a human rights lawyer who was diagnosed with ALS two months after being admitted to the Ontario bar in the spring of 1988. Since that time I have been working in the field of patient advocacy, human rights, capacity and consent, with a particular focus on medical and ethical issues involving vulnerable adults. For the past three years I've been working in a senior policy position at the Ontario Advocacy Commission. It is within the context of my background, knowledge, skills, and experience that the following comments are submitted.
The starting point for any discussion involving the drug regulatory system is to consider the underlying public policy rationale. Whenever the state chooses to involve itself at the federal level in the lives of private citizens and private sector companies, the justification for doing so must be clear and compelling. It is generally accepted that the federal government must assume the lead responsibility for ensuring that drugs approved for public consumption are both safe and effective.
Canada's existing drug approval system works well, requiring the highest standards in clinical testing and in its requirements for clear and accurate product information. The chief limitation to the existing system is the length of time needed to move forward from theory to proof of the theory and finally to successfully navigating the formal licensing process. Manufacturers must spend enormous sums of money on research and development, testing, analysing data, preparing paperwork, and sorting out the logistics of gearing up for mass production of new products.
From the perspective of the general public, the checks and balances are both reassuring and necessary. So long as catastrophic illness is an abstraction, the timing of research and drug regulatory approval is assumed to be under control.
People fighting catastrophic illnesses have a different view of the existing system. The most consistently repeated comment I have heard from people in this position is best summed up by the following question. Is it acceptable to sacrifice the needs of people who are seriously ill for the benefit of hypothetical future sick people? If the answer to that question is yes, then these hearings are unnecessary. If the answer is unclear, then it becomes essential to look at all of the arguments with an open mind.
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Drug manufacturers do not have a monopoly on truth, people who earn their living by studying ethics do not have a monopoly on morality, and patients do not have a monopoly on virtue.
When Woodward and Bernstein began examining the facts around what came to be known as Watergate, they were given valuable guidance by an anonymous source. This source told the reporters to follow the money. In the context of discussions involving the safety and effectiveness of the drug regulatory system, all of the issues raised ultimately involve financial concerns. As you listen to all of the statements made by everyone making a presentation before this panel, I ask you to consider whether the justifications for leaving this system as it is are all equally valid and all equally necessary. The threshold test should be whether it is possible to protect the drug research system and the needs of the general public without sacrificing people who are already ill.
Although there are differences between each catastrophic illness, what all of these illnesses share is that the people who have them understand that time is their enemy. For healthy Canadians, it is beneficial to take as long as possible testing and retesting new drugs. The goal is to keep products off the shelf until everyone in authority is confident there is no risk in allowing the drug to be distributed.
People with catastrophic illnesses by necessary definition have a different frame of reference in balancing benefit and risk. With any unproven drug, there are three possibilities. It could improve the condition, it could make the condition worse, or it could make no difference either way. For healthy people, it would make no sense to try a drug under those conditions.
The fundamental distinction between members of the general public and people who are fighting catastrophic illnesses is that for those who have these illnesses, the implication of doing nothing is a 100% chance of death. Viewed from that reference point, a 33% chance of benefit is reasonable on a cost-benefit analysis. It is dangerous to assume that serious illness renders people incapable of rationally considering benefits and risks. People who are ill are no more or less likely to behave irrationally than people who are not.
A 33% chance at becoming sicker as a result of taking a drug sounds considerably less intimidating when viewed from the perspective of having been written off by the medical system. Resist the temptation to assume that people fighting catastrophic illnesses do not know what is best for them and must therefore be protected from making their own decisions. We live in a country where mentally capable adults have the legal right to make fundamental choices affecting their lives. This includes choices others may disagree with.
A workable policy on compassionate drug access is needed in this country because there are thousands of people today who are sicker than they need to be. This is a direct consequence of a drug approval system that was not created to address situations where time is of the essence. It is common for academics and others to rationalize the sacrifice of the ill for the benefit of the healthy. It is also a dangerous thing to do, in that it institutionalizes a hierarchy of value among citizens.
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When a manufacturer decides to provide compassionate access to a new drug, the system works smoothly. The problems arise when a manufacturer decides, for whatever reason, to say no. Under the present system the patient has no recourse and the manufacturer is not required to provide reasons. We are all familiar with the efforts of patients to draw attention to situations in which they believe the manufacturer is behaving inappropriately. The media dutifully report the sit-ins, the hunger strikes, or the boycotts. Problem-solving by means of confrontation is always stressful, usually exhausting both mentally and physically, and in many cases is unsuccessful in resolving either the immediate problem or the broader issue.
Can compassionate access co-exist with effective drug testing? I believe we need to rethink the appropriateness of using double-blind testing as the primary research tool in the context of catastrophic illness. The adoption of an alternative testing protocol is a matter that needs to be discussed by the academic and research communities, in consultation with legal and ethical experts, as well as patient advocates.
Given the complexity of the issue, it will take considerable time and resources for the matter to receive the attention it needs. In the interim, regardless of how this debate over the universality of double-blind drug testing is resolved, I ask that you direct your attention to the possibility of amending section C.08.009 of the regulations to the Food and Drugs Act. This regulation provides for an objective review, on a case-by-case basis, in circumstances in which a manufacturer consents to compassionate access and the federal authority does not agree.
The function of the review is to determine whether or not the refusal to provide access was made on an arbitrary basis. The administrative law principles of natural justice and procedural fairness guide the review. It should not constitute undue hardship to ask that manufacturers be required to meet the same onus as the federal government in the context of justifying a refusal to consider the option of compassionate access.
At present, drug manufacturers would seem to bear no accountability for the decisions they make prior to a formal petition for licensing approval so long as they base their decisions on the importance of preserving the double-blind testing process. The goal of drug testing is to serve the needs of people who are ill. If double-blind testing serves the needs of the healthy at the expense of the ill, then this type of testing is by definition hostile to anyone fighting a catastrophic illness.
Our compassionate access drug policy could and should be there to prevent abuse and arbitrariness. An amendment to the relevant provisions under the Food and Drugs Act would be one step toward addressing the challenge posed by catastrophic illness. Another option would be to require evidence of a demonstrated good faith effort to provide the option of compassionate access as a prerequisite to filing a formal licensing petition.
Many manufacturers argue that compassionate access cannot be given to people outside drug studies because it would be unfair and unethical to give the experimental drug to some people but not to everyone. This argument ignores the fact that if it is unfair and unethical to offer the drug to some and not to all, then by definition a double-blind drug study is unfair and unethical. If participants in double-blind drug trials believe the trials to be fair and reasonable, there should be no reason for them to be dropping out, regardless of whether the drug is made available on a compassionate basis.
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Similarly, if the people responsible for administering these trials are confident that double-blind trials are fair and reasonable in the context of catastrophic illnesses, they should have no reason for doubting the continued cooperation of the participants.
The option of compassionate access could be made available to people who are outside the eligibility criteria for the drug trials. Whether it takes one year, three years, or longer before conclusive results are available, the data arising from these trials may not apply to people who are outside the eligibility criteria for the studies. It is unclear whether there is a viable compromise that would be of benefit to people who are outside the studies but eligible for inclusion.
Due to the nature of these illnesses, the timing of any attempt at medical intervention is critical. Unless the people who are outside the parameters of the studies are allowed the option of compassionate access, they will, for practical purposes, be abandoned entirely. Having this option would not compromise the viability of high-quality drug testing. The drug would only be available on a case-by-case basis to people who would not be eligible to participate in any existing studies. Informed consent and a waiver of liability should be mandatory.
What about false hope? A recurring theme in discussions relating to catastrophic illnesses is the danger of raising false hope by agreeing to compassionate access. This argument against false hope is arrogant and profoundly disturbing. It also raises an obvious question. Do the people who believe that hope is an unreasonable response to catastrophic illness believe instead that giving up all hope is appropriate? If that is what they believe, then by necessary implication they must support assisted suicide.
People with cancer, AIDS, and heart disease are not generally told to abandon all hope, in spite of the fact that there are no universally acknowledged effective treatments for any of these illnesses. The disproportionate number of people with ALS who have been fighting in the media and the courts for the right to choose the timing of their deaths bears testimony to the ramifications of intentionally extinguishing all hope.
[Translation]
The Vice-Chairman (Mr. Ménard): Will you allow me to ask a question?
Do you intend to read your text till the end?
Up until now, we've been quite lenient. I must say, however, out of respect for the other witnesses here, that I'm afraid there will be an imbalance in time allocated. If you could conclude in three or four minutes, we could then give the floor to the next witness.
The important thing is for us to take advantage of this opportunity to exchange views.
[English]
Ms Conrad: I think it is important to make note of the fact that there is nothing any manufacturer can do to insulate itself from the possibility of being sued. Lawsuits are filed every day, and there is no particular reason to believe that people who have signed waivers are more likely not to sue than anyone else. The best protection the company can have is to act in good faith in all of its dealings, and to provide sufficient information to the patient to support an argument that there was informed consent.
The drug companies will have their profits. The researchers will have their Nobel Prizes. The government will have its regulations respected. It is the responsibility of the federal government to fight with all the resources at its disposal so that the people living with catastrophic illnesses have the right to make their own choices and have the information and resources necessary to carry these choices out.
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If a workable solution is not readily apparent, I would strongly recommend that all of the relevant parties undertake to seek the guidance of an experienced mediator. There is any number of options for how to cover the costs associated with providing compassionate access. What is needed is a commitment to assume responsibility for trying to find a way.
[Translation]
The Vice-Chairman (Mr. Ménard): Thank you. In my short time as a parliamentarian, I've seen that sometimes lawyers tend to go beyond their time. I imagine there isn't any real link between that and one's profession. Your presentation was very interesting, and we will have an opportunity to exchange views with you during the time allotted for questions.
And now we will give the floor to the person beside you, Mr. Ahmed Hassan, who will have between 10 and 12 minutes. I don't want to be overly strict, but please remember that it is important for the members of the subcommittee to have time to ask questions.
[English]
Mr. Ahmed Hassan (Individual Presentation): Thank you for having me come to speak.
Multiple sclerosis is believed to be an autoimmune illness - the cause is unknown - where the immune system attacks the central nervous system and causes demyelination in the brain and the nerves in different parts of the body, creating havoc in the communication between the brain and various parts of the body. Luckily it rarely attacks the autonomic nervous system, or MS would be a fatal disease the majority of the time as opposed to occasionally.
I have applied for Linomide, which is an immune modulator. It's an experimental drug recently developed to treat MS. It stops the immune system from demyelinating the nervous system, and it has been approved by the emergency drug release program. However, the pharmaceutical company that manufactures it, Pharmacia Inc., has refused to release it for me.
I was going to ask my attendant to read some for me, but I think I'm just going to read some statements from Gerry McCready and Bruce Couper, two people with multiple sclerosis on the MS society computer bulletin board who sent me material when I asked if any people had anything they would like heard at this round table.
The following is from Gerry McCready.
Most MS people are extremely frustrated by the slowness of the system. Most of the neurology research will not be complete before the people retire and we are under the sod. When we have a new drug to try, those wanting it should be permitted to do so.
The medical community in Canada is often far too timid to explore new treatments under the medical model edict of ``Do not harm''. But in the meantime, severely disabled people are getting worse and might benefit from a new treatment approach that the doctors want to test for five to ten years first. We need shorter evaluation cycles.
These feelings are not just idle comments. The proof of the timidity of the system has been shown in the case of Betaseron, which has just been approved for use in Canada and has been available in the United States for eight years. Other drugs have followed similar slow development patterns: i.e., COP-1; Solumedrol, etc. Meanwhile, the disabled sit and wait.
With regard to Pharmacia's actions - or inactions - some different views have been expressed to me on this subject that I want to share with everyone.
Pharmacia may be frightened of doing something contrary to the norm of Canadian and American drug introduction protocol. In this way, they avoid taking on the risk of alienating the tradition-bound medical fraternity, who they will be selling to for a long time.
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Another viewpoint expressed is that Pharmacia may not have a lot of confidence in their research data, which shows mainly positive outcomes and few negative outcomes. They may be scared that letting some of it out for evaluation other than in controlled settings may open up the door for a big lawsuit if the recipient has a negative reaction.
That was from Gerry McCready.
The following is from Bruce Couper.
EDRP: emergency drug release program. ``Emergency'', noun; an unexpected situation or occurrence that demands immediate action. It is easy to see why AIDS patients fit this definition. Surely the prospect of an early and certain death qualifies as an emergency. But what about the folks with multiple sclerosis? What of all the little deaths we face? What of those who have found and who yet will find the losses so profound and devastating that they must choose death rather than live a life they find devoid of quality? What of the folks with multiple sclerosis who will hold on and fight so hard as their control slips away? What of their prospects for that thing alluded to by a sadly simple phrase that rolls so easily off the tongues of those who cannot know: ``quality of life''?
Surely, folks who face so much loss - too much loss - deserve to make their own decisions, assume risks unreasonable to others but terribly reasonable to them.
In the case of Linomide, the risks are not so very great, according to the literature to date: the trial at Brigham Women's Hospital in Boston, Massachusetts, where the patients on Linomide remained stable, with the lesions in their brain improving, and those on the placebo deteriorated. Two of the most serious side effects were pericarditis and arthritis-like joint pain. Pericarditis is an inflammation of the tissue surrounding the heart. It is not fatal and can be treated. It is also not sure whether the patient who had pericarditis already had it.
That the manufacturer, Pharmacia of Sweden, is unwilling to assume any liability is understandable. Not so understandable is Pharmacia's unwillingness to consider accepting a proposal to absolve them of any liability if they agree to make Linomide available for release through the EDRP. Perhaps they are not sufficiently apprised of both EDRP and of the urgency felt by so many people with multiple sclerosis.
That was from Bruce Couper.
The following is a very personal statement. This is my story.
I trace my multiple sclerosis to 1978, but I was not diagnosed until 1987. It was a long, frustrating journey from my first symptoms to my diagnosis. At my diagnosis I was told to go home and wait for the cure. That was my lightening bolt of wake up, go home and do what? Wait for your phone call, I suppose. I'm sure we're going to find it within your lifetime.
Here's what I lost.
Sexual function: in the fall of 1979 when I first experienced sexual dysfunction I thought it had more to do with the relationship between me and the person I was with.
The story goes on.
Incontinence: I was working as an accompanist at New York University in the fall of 1982. I was getting ready for my next class when I experienced incontinence. It took me so completely by surprise that I had absolutely no idea what was going on.
It goes on.
Blurring vision: in 1986 I started having blurred vision in my right eye. I went to the optometrist. I asked him to check my eyes. He could find nothing. He gave me an eye test. He told me my vision was 20:20.
It goes on.
Walking: I used to walk and walk and walk. I think part of my entertainment was walking. My first symptoms were tingling down the back of my legs in 1978. I was walking with ever-increasing difficulty until 1990, and you can see me here right now. This is how I get around.
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Fine motor functions: in my adult life I chose percussion as my vocation and, like my walking, was doing it with ever-increasing difficulty and had to give up accompanying dance classes this year. Cooking is something that I gave up. I love cooking, but I can't do it; it's too dangerous. Sharp knives, hot stoves - forget it. It's dangerous for me. I can't write any more, either.
I used to work, but I can't any more. Just being here today is very taxing and will take something out of me. It will take me a long time to recover from just being here speaking to you. I may not get back to the level I was at yesterday.
We people who are living with MS want to be treated as adults who think and decide what they want to do in the face of a disabling illness. We have intelligence and we can interpret information. We want to hear about all the factors associated with taking any medication, not just experimental ones. If there are other side effects that they are not releasing, we want to hear about them. Beyond that, we want to know the most effective dosage and to get on with the treatment. I'm talking about Linomide. What is the effective dosage that you are using? We want to take that.
That treatment could be going on at the same time as the double-blind tests taken by people who are consenting to the trial. We could be monitored just as closely and offer additional information as to the long-term effects of the drug. As far as I understand, it is only the long-term effects that Pharmacia, Health Canada and the FDA are missing to release this drug.
In summary, first, if there is a medication that could be used to treat multiple sclerosis, I want to be given the option of deciding whether or not I want to take it, even if it is still in an experimental stage.
Two, I would want the dosage that has shown the best results. I can be subjected to the same monitoring that the people on the clinical trials are being subjected to.
Three, in the case where the medication is in oral tablet form and I would be taking the medication with my own hand and putting it in my own mouth, I would be the one who is liable, taking the risks that have been shown to date.
Four, double-blind tests are necessary and important, but all patients going into a double-blind should be going in aware that they may be taking a placebo. I do not want to spend two years on a placebo, deteriorating to prove that I should have been on Linomide all along. At the very least, patients in a more advanced state of the illness should be allowed the risk of taking the medication in concurrent drug testing.
In my case, my emergency drug release program was approved. I stopped at the gates of the pharmaceutical company.
Thank you very much.
The Chairman: Thank you very much, Mr. Hassan.
Now we're going to go to Ms Kelly from the Burlington Breast Cancer Support Group.
Ms Pat Kelly (Member, Burlington Breast Cancer Support Group): Thank you, and thank you to the committee for the invitation to appear here today.
I have tabled with the clerk a series of articles that were written by women who were seeking access to drugs - Taxol and Taxotere - at a time when they were dealing with advanced breast cancer and metastatic disease.
I've chosen to present a prepared brief today that addresses the need for compassionate access to information about drugs, as I see this as a major priority.
In the early 1960s, a movement that had been characterized as a consumer revolt in attitudes and behaviours began to gain momentum and influence. Social movements dedicated to civil rights - women's rights, gay rights, consumer rights, human rights - contributed to a growing interest in medical matters and preventive health care. Each of these initiatives helped to frame a new way of thinking about and managing our health, and nurturing the idea that we can have a hand in our own destiny.
The North American consumer movement that began in the 1960s has contributed and continued to have a substantial impact on diverse elements in society, from manufacturing and service delivery to government policy.
The Canadian AIDS movement achieved critical mass when AIDS activists took to the streets with their lovers and their families and successfully lobbied for funding for research, education and support.
I recall that in the mid-1980s, as a research technologist at McMaster University in Hamilton, I admired the achievements of AIDS activists who had influenced the MRC to issue a request for proposals into research for their disease.
Some young researchers saw this as an opportunity to secure their labs and their futures, and AIDS activists got some of what they needed because those affected by the disease and those who cared for them and cared about them became obnoxious and persistent and would not die quietly.
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When I was diagnosed with breast cancer in 1987 and learned first hand that Canada had no groups, that treatments hadn't changed in fifty years, and, worst of all, that governments, charities and research bodies that were supposed to champion this cause were tolerant of the status quo, I was angry.
Because I had the example of Canadian AIDS activists and the emerging breast cancer movement in the United States, I was confident that change was possible. I set about the task of changing my future, and that of my daughters, as a woman radicalized by my disease.
In searching for models of grassroots organizations that effectively provided services of support, education and information, I found groups such as: DES Action; CATIE, the Community AIDS Treatment Information Exchange; the Consumer Health Information Service; Health Sharing in Canada; and the Boston Women's Health Collective in the United States. These organizations took the lead in providing health information that assisted consumers to make their own choices and enter into a more participative professional-client relationship.
A remarkable model of consumer-driven health information services is that of the CATIE model, the Toronto-based Community AIDS Treatment Information Exchange, and ATIS, the AIDS Treatment Information System, which is funded by Health Canada.
The major goals for CATIE are to provide information about health care options for HIV infection and to monitor and evaluate health care options and approaches. There are numerous books, journals, abstracts, indexes, computer databases, electronic bulletin boards, and information services that allow organizations and individuals to make large amounts of rapidly changing and complex information available in electronic form very quickly.
So we now have a situation in which government regulations that attempt to limit access to prescription drug information or clinical trials have been rendered ineffective by consumers and their organizations armed with modems.
Further evidence of government regulations having been rendered toothless are the direct-to-consumer advertisements that have begun to appear in no less a venerable daily than the The Globe and Mail. Consider such ads that appear as patient testimonials about the effectiveness of drug therapy for one young man treated for depression, or a full-colour glossy insert asking inhaler users to show your true colours, or even the appeal of new and more effective treatments for schizophrenia. Are these not a direct challenge to legislative effectiveness?
They most certainly indicate the shift toward recognizing that the consumers of the 1990s are extremely well educated, sophisticated and interested in being in charge of their lives and their decisions, particularly when they are affected or threatened by ill health.
Or take the case of Prozac. Consumers seek cosmetic pharmacology, not to treat disease, but to lend social ease, business acumen, energy, flexibility and sexual appeal. It's ``better living through pharmaceuticals of our own choosing''.
We are also increasingly being forced by government to take responsibility for our health, both individually and collectively, at the community level. Informed consumers who enter into decisions with their health care are seen as essential to the reform of the health care system. However, consumerism in the area of professional services has continued to be problematic, in part because of the difficulties consumers have in obtaining information they need to make choices and to judge the quality and appropriateness of services offered.
The consumer health movement has broadened its mandate in recent years through the activities of many social groups, organizations and agencies. The potential benefits of building an educated and responsible consumer group may include a better utilization of health services, an improved quality of care, and even improved health outcomes.
A great deal of health information is available from commercial publishers, voluntary organizations, pharmaceutical manufacturers, and government, but it is difficult for consumers to find out about any of these sources to judge their quality and to find the information they really need in a language and literacy level that makes sense to them.
Although libraries have a mandate to provide access to the kinds of information that consumers may be seeking, hospital and medical school libraries do not generally serve consumers, and public libraries have been cautious in the past about providing information that might be seen as infringing on the knowledge domains of the powerful professions, such as medicine and law.
This may account for the observation by Dr. Joanne Marshall, assistant professor in the Faculty of Information Studies at the University of Toronto that the evolution of health information services for consumers still lags far behind the services available to health care providers.
What about the role of the federal government in regulating the drug industry and, ultimately, the drug-related health of its citizens? It would appear that most government regulations are inadequate, inappropriate or outdated.
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According to Dr. Juanne Clarke, professor of sociology and former chair of the department at Wilfred Laurier University in Waterloo, Ontario, in her 1990 text ``Health, Illness and Medicine in Canada'':
- However stringent the laws, the government cannot guarantee that any drug is safe for all the
uses to which it may be put.
For example, some drugs react negatively when taken in conjunction with alcohol. We know from Canada's Health Promotion Survey, Technical Report 1988 that 82% of all Canadians drink alcohol. Untold problems result from drug-alcohol interactions. In addition, a number of drug-related problems or side effects are only discovered after long-term use. For these and other reasons, government drug regulations are inadequate, and clearly it is time to revisit the legislation.
There exist now many factors that can contribute to significant changes in providing drug information directly to consumers. These factors include a critical mass of sophisticated, educated, and demanding citizens; near unlimited and unregulated access to information technology exchange; and a political will to engage consumers as stakeholders in the new multi-sectoral partnerships.
As we begin to strategize about the best way to undertake this process, it is critical for the issues that have created traditional consumer reluctance to work directly with the pharmaceutical industry to be addressed.
These smart, new consumers are well aware of the scandals of thalidomide and DES. We have read about the audit of the Grady report on depo-provera's safety and the OMA report on death suspected to be associated with NSAIDs.
We followed, with interest, the story about Canada's retail pharmacist who launched a battle against one of the country's largest charities, The Arthritis Society, after learning that the group had formed a fund-raising partnership with a company that sells prescription drugs by mail.
We are well aware that the pharmaceutical industry is one of the most profitable manufacturing activities in Canada. High profitability and predictions of consistent growth in view of long-term demographics provide reason for continuing optimism.
In the past, the pharmaceutical industry has succeeded in maintaining its profitable position, through strategies that sometimes appear to be in opposition to health consumer interests, including: the absence of price competition; production of brand name rather than generic products; drug distribution, or dumping, as it's called in the third world; and excessive advertising and promotion that pressures physicians to prescribe, may exaggerate the effectiveness or gloss over the dangers of drugs, or tries to downgrade the competition, while costing at least 20% of sales revenue.
As Jim Harding suggests in Health and Canadian Society, the pharmaceutical industry is an outgrowth of the interlocking petrochemical industry, which produces pesticides, herbicides and fertilizers.
Toxins from the petrochemical industry have been responsible for environmental health calamities, such as what occurred with Union Carbide in Bhopal.
At the same time, as consumers, we have benefited enormously by advances made through drug and vaccine treatments used to manage and prevent disease. Smallpox and polio no longer threaten our children. In the cancer movement, many of us are aware of the remarkable advances made in the treatment of pain and chemotherapy-induced nausea and childhood leukemia.
Children and adolescents with leukemia 25 years ago faced a mortality rate of 90%. Of those affected today, fully 90% can expect complete recovery due to advances made in chemotherapeutic agents.
What is now needed in order for drug manufacturers to ethically access the new stakeholders, are guidelines, such as the code of marketing practices developed for health care professionals.
The proposed guidelines, based upon community development principles, would form a framework for the Pharmaceutical Manufacturers Association of Canada and its member companies to identify how to work together to achieve common goals.
In summary, I would caution you not to estimate the new breed of persons with disease and consumers of health care. We are very different from those of even a decade ago. We expect to live. We demand to live. Instead of resigning ourselves submissively, or even bravely, to the fates, we have set about fighting doggedly for our lives. We are forming groups, lobbying government, and owning and operating information technology and services.
We organize because while illness motivates us to be keen learners, it also threatens our capacity for comprehension and analytical reasoning. Thus, the role of competent and resourceful groups will become increasingly important in the fueling of the health consumer movement.
In closing, I offer the following statement from poet and politician Vaclav Havel:
- Hope is an orientation of the spirit, an orientation of the heart. It is not the conviction that
something will turn out well, but the certainty that something makes sense no matter how it
turns out.
Governments, doctors, drug companies, patients and consumer groups - we are all in the business of selling hope to vulnerable persons. Our public policy decisions must be based on appropriate scientific data and accountability to compassionate social action.
Thank you.
The Chairman: Thank you very much, Ms Kelly.
Sharon Batt, please.
Ms Sharon Batt (Member, Canadian Breast Cancer Network): Ninon Bourque, who is also with the network, will be available to answer questions during the question period.
Breast cancer is a catastrophic illness. Well over 5,000 Canadian women and about 40 men die every year of breast cancer, and the numbers are rising. Not all women with breast cancer become catastrophically ill, however. One-half to two-thirds of the 17,700 Canadians diagnosed this year will die of something else. I currently live symptom-free, with no immediate threat of death. My good fortune could change tomorrow, however, if the cancer spreads. Our community consists of a large number of women who are healthy and who may or may not remain so, and a smaller but numerically large proportion who are catastrophically ill.
The question of compassionate rights and catastrophic access to drugs is most pertinent to those diagnosed with metastatic disease, extensive lymph node involvement or extremely aggressive tumours. If we adopt a narrower definition of catastrophic illness, that is, a subgroup who no longer respond positively to standard therapy, we exclude a large number of women who beat the odds and remain active despite their advanced disease.
Unlike the AIDS activists, our community has not extensively debated the ethics of compassionate access and its effects on clinical trials. One likely reason for this is that most experimental treatments for breast cancer throughout the 1970s and 1980s were variations on standard toxic treatments that had limited benefits for dying women. Demands for access have more often been for alternative treatments such as Essiac or 714X. As well, women with breast cancer have a long history of silence. The well wanted to believe they would stay well, and those who were sick did not know how numerous they were.
Changes in breast cancer treatment and the evolution of our community have brought the issue of compassionate access forward. Women with breast cancer are now more organized. We participate in policy discussions. Those with advanced disease have shown they want improved access to investigational treatments such as high-dose chemotherapy, the chemotherapy agent Taxol, and the monoclonal antibody HER/2-neu. Silicone breast implants also provoked discussion about compassionate access, and the demand for unorthodox treatments has not abated.
Before I present our conclusions, I'll outline two of these examples, and I'll skip several others that are in the written text.
High-dose chemotherapy, used with various techniques to regenerate the bone marrow, is a drastic life-threatening treatment, but it's designed to achieve cures, something unheard of with past treatments for metastasized breast cancer. High-dose chemotherapy is very costly and still experimental. Only select cancer centres in Canada have treatment programs. These programs typically do not use a randomized trial design. Accessibility is blocked by the fact that the centres that do have programs have too few spaces to meet the demand generated by medical and media hype of a profitable but as yet unproven therapy.
Women with terminal diagnoses do research to find out which bone marrow transplant program has the lowest mortality rate and best suits their situation, and that may be in another province or in the United States. They look to their oncologists and politicians to get them in. They appeal to their provincial health departments to cover the costs. They are angry and dismayed if they are refused entry. They feel betrayed by Canada's commitment to universal access.
Some women offer to pay for the treatment and are still refused. Government payment policies are not clear, nor are the criteria by which experimenters choose or refuse women to their programs. The absence of clinical trial data, the media hype and the endorsements of medical enthusiasts confound women's efforts to obtain accurate risk-benefit information.
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The HER/2-neu antibody is another example, and this is the first breast cancer treatment to inspire an AIDS activist-style lobby for an open arm in clinical trials. This experimental treatment is targeted against a protein involved in tumour growth, a receptor called Her/2-neu. Many believe the HER/2-neu antibody could be the first of a new generation of anti-cancer treatments, precisely targeted to correct the problem at the cellular level.
This drug is intended only for a select group of women - the 20% whose breast tumours make the protein in question. Preliminary studies suggest that the HER/2-neu antibody could temporarily stop tumour growth or shrink these women's tumours for up to 16 months.
A year ago, when the San Francisco-based company Genentech was preparing to launch phase three trials of the HER/2-neu antibody, a member of the San Francisco breast cancer group Breast Cancer Action was dying and could not obtain the drug, although her tumour produced HER/2-neu. This experience led members of Breast Cancer Action to examine the issue of compassionate access. They teamed up with the AIDS group ACT UP/Golden Gate to stage a demonstration aimed at persuading Genentech to include a compassionate use policy in the phase three clinical trials. Genentech has recently agreed in principle to a compassionate use open arm. One of the open-arm study sites may be in Canada.
I'll move on to my observation and questions.
The Canadian Breast Cancer Network has not yet developed a formal position on the issue of compassionate rights and access to drugs. Instead of making recommendations, I'll conclude with a number of observations and pose questions to provoke discussion.
First, with an annual 5,800 breast cancer deaths, a large number of Canadian women are candidates for compassionate access to drugs, whether experimental or unapproved.
How can regulations and practices about access to experimental drugs for breast cancer treatments, including payment practices, be made open and accessible to all patients?
Second, cutting-edge treatments such as bone marrow transplants and Taxol are expensive and in limited supply. The question of who pays and the issue of universal access therefore loom very large.
How do financial costs act to limit compassionate access to current investigational breast cancer treatments? Can all women be assured access if these treatments prove effective? Should ethics committees be obliged to consider potential treatment costs when evaluating a trial? That is, is it ethical to conduct clinical trials on a treatment that, if it works, will be too expensive to provide to all patients who might benefit?
Third, breast cancer treatments, both standard and experimental, can drastically reduce quality and length of life. Women with breast cancer put a high premium on quality of life, including the emotional, social and spiritual dimensions. Information on those dimensions is typically not available with respect to treatment drugs, or is very limited.
How can women be given more appropriate quality of life information to help them make treatment decisions? Is the open arm in a clinical trial a suitable opportunity to gather qualitative data?
Fourth, drug companies and other agencies have historically been less than frank in revealing side effects of breast cancer treatments. Potential benefits are often exaggerated.
How can patients with advanced breast cancer be assured accurate information about treatments, risks and benefits? What are the roles and responsibilities of the Canadian Cancer Society, cancer specialists, governments and the media in disseminating information about investigational treatments?
Fifth, response to breast cancer treatments, including the standard ones is notoriously variable. Some women have a positive response to an intervention, while others die from the same treatment.
Is random assignment to clinical trials the best way of evaluating a new treatment when responses vary so much? How can women be helped in making decisions about treatments that have such unpredictable effects?
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Sixth, care for breast cancer patients who are dying is inadequate. Issues that need to be addressed alongside compassionate access to drugs include pain control, emotional support, individual and family counselling, and hospice care.
A number of questions need to be considered. How can treatment research be encouraged without slighting the issues surrounding the care of dying patients? Does compassionate access prevent patients from facing the issues of dying? Does the medical system focus on treatments at the expense of providing adequate palliative care?
Finally, women with breast cancer have seldom discussed, among ourselves or with other stakeholders, the issues related to compassionate access to drugs.
There are more questions. How can awareness of these issues be raised in the breast cancer community? Can the phase 3 HER/2-neu new trials be observed to assess the effect of the proposed open arm on accrual and on the quality of the trial?
I'd like to thank you for giving the CBCN the opportunity to open this dialogue. In concluding the presentation, I'd like to name three members of our board who have died in the past eight months: Jan Morrow of Kelowna; Shelly Achs-Reimer of Saskatoon; and Leah Lovestead of Coquitlam.
The Chairman: Thank you, Mrs. Batt.
We'll move now to Ms Lorraine Parsons.
Ms Lorraine Parsons (Member, Ottawa Chapter, Canadian Haemophilia Society): Thank you for allowing me to present today. As the mother of a haemophiliac who was infected with AIDS through the blood system, I am very aware of the direct impact of government policies and programs on the lives of individuals.
Since my family and my extended family have been so devastated by AIDS, we have reached out for support and to give support, not only to the haemophilia community, but also through working with other AIDS communities in Ottawa-Carleton.
I am proud to have been a board member of the AIDS Committee of Ottawa and to be working with the addictions community to provide much needed support services to women with AIDS and addictions.
I am also honoured to be here today because any policy on compassionate access to experimental drugs will directly affect members of the Canadian Haemophilia Society who have HIV or AIDS.
The large majority of our members who have HIV and are still living were infected with the AIDS virus before 1985. A few were infected in 1987 when Armour processed and the Red Cross distributed tainted products.
Many of our members are becoming seriously ill and may have haemophilia-related complications due to treatments for AIDS symptoms. Many are facing the end of their lives, and yet they continue to live in hope - that hope rests on new drugs and new therapies - and, like many, they dream of the ultimate cure for all people living with AIDS.
Yet there is a paradoxical relationship between the rights of these individuals whose health is seriously compromised and the goals of the pharmaceuticals and the regulatory agencies. The individual wants access to experimental drugs in the hope of prolonging his or her life at a quality level. They are often eager, and should have the choice, to try experimental drugs. The pharmaceuticals want the trials to be effective so they can get licensing, and get on with marketing their product. The regulatory agencies are concerned with limiting access to the trials because of liability and cost concerns.
We propose that this committee look at the rights of the terminally ill individual to compassionate access as separate from the issue of the pharmaceutical concerns for clinical trials. This will allow a broader scope to your creativity in finding ways to expand access.
We propose that you consider those people who have other complicating factors, such as haemophilia, as a subgroup in any trials if they cannot be included in the trials themselves.
What is important is that they get access to the drugs. These subgroups will tell subgroup members and other affected haemophiliacs about the impacts of these experimental drugs on their haemophilia as well as on their AIDS.
Governments and pharmaceuticals will have to determine cost-recovery mechanisms for these trials. Open-arm access is one mechanism, but perhaps another more practical option may be to expand the emergency drug release program.
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Criteria should always be drawn up to make access as wide a possible. Price tags to consumers will have the effect of severely restricting access, and, in our opinion, should not even be considered.
Just to move to the roles of the physicians, we have two concerns in this area: education and the liability for prescriptions.
First, outside major treatment centre physicians are sometimes the last to know about experimental HIV therapies. Thus they are not in a position to consider these therapies as possible options for their clients with HIV or AIDS.
This leads to many people with HIV being excluded from trials virtually by default. Where is the guiding hand that ensures physicians' ongoing education? Who has the responsibility to ensure that physicians have access to ongoing information on new trials and therapies?
We believe the process of education should be formalized and widely publicized among doctors. There should be prescribed roles for the drugs directorate, the College of Physicians and Surgeons, the Canadian Medical Association, the Pharmaceutical Manufacturers Association, and other groups.
Second, physicians are solely liable for prescriptions under EDRP - a situation that creates a significant barrier to emergency drug release. A thorough examination and recommendations for change to the liability aspects would lead to wider access to experimental drugs.
We want to encourage Health Canada to strategically seek out ways to ensure that Canadians are included in drug trials beyond our borders. It is a sad truth that drug trials are sometimes complete in the United States - sometimes the drug is even being marketed in the United States - before the trials are even begun in Canada. DDAVP and, I believe, 3TC are just such cases.
Ill-conceived policies that seek to exclude, rather than include, can ravage and destroy. Health Canada has an obligation to people living with hemophilia, to all people living with AIDS, and to all Canadians to ensure that access to drug trials is as wide as possible and not limited only to those individuals who are relatively healthy. We believe that the NHRDP should refuse to endorse drug trials that do not have a wide access.
In addition, we believe that Health Canada should be encouraged to look at its regulatory process with an eye to speed. It is intolerable to us, for example, that Factor IX, a highly purified product for hemophilia, is still not licensed in Canada.
People from the AIDS community, as dependent as they are on traditional medicines, are also benefiting from alternative therapies. Some choose to use these therapies exclusively, while some of these include drugs and others do not. We urge this subcommittee to consider these therapies under a wider definition of your mandate. These therapies could be made available both through clinical trials and through EDRP.
To conclude, I want to stress once again that people living with HIV have hopes and dreams. I want to quote from a song that my son David wrote, and I call the chorus, the chorus of dreams:
It says:
Sleepy town of early morn,
You're so sheltered from the storm.
Soon your people will awake under the morning sun.
Soon your people will awake; their dreams have just begun.
My son's 15-year-old sister told the Canadian Blood Agency that her dream was to share with her brother all the joys of their lifetimes when they are both old and grey. That is my hope too.
I believe that as broad and free an access that we can have to experiment with drug therapy is today one of the best hopes we have to keep people with AIDS alive and full of dreams until there is a cure.
Thank you.
[Translation]
The Chairman: Thank you very much, Ms. Parsons.
Now we are going to take 10 or 15 minutes to ask questions. Each party will have five minutes. We will begin with the Official Opposition, represented by Mr. Ménard of the Bloc Québécois. Then we will move on to Ms Hays, and then to our colleague from the Liberal Party.
Mr. Ménard (Hochelaga-Maisonneuve): Mr. Chairman, I thought it was going to be15 minutes per person. I see that you have compressed the schedule a bit. So I will try to be fast.
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I have four questions. First of all, Mr. Chairman, I would like to remind everyone that the first person who came before us to tell us about this problem with access to emergency drugs was Brian Farlinger. Perhaps some of you know him. He was an activist with AIDS Action Now! who is now deceased. I certainly remember how his testimony raised the awareness of our committee.
My first question is for Ms Pinault. But first, I would like to remind the committee that when we met with the Canadian HIV Trials Network, which under the current strategy has been allocated 2.9 million dollars over five years, we were told that the research protocol for each experiment included the establishment of a committee that people with HIV would sit on. I wanted to hear from the witnesses to ensure that that is really so.
Mr. Chairman, perhaps I could ask my four questions, and then let the witnesses respond. However, I would like to ask Ms Pinault my first question, because I do know she works closely with the Network, so that the parliamentarians can be quite sure that things are being done in this way. Ms Pinault, if you have any other information about this, it would be useful for us.
Mr. Shedden, you were telling us that it was difficult to conduct trials in the Maritimes. Unless I'm mistaken, you were saying that the community there is less active, and that it is more difficult to get access to experimental drugs. Could you explain to us what could encourage the Canadian HIV Trials Network to conduct more clinical trials in the part of the country that you represent? What are the problems? Are there not enough people to take part in these trials? Is the information not getting through? I would like to hear your opinion on that.
My next question is for Ms Susan Conrad, who asked us to consider Section c.08.009. I really didn't understand exactly what you wanted to draw the committee's attention to. Perhaps you could remind us of the amendment you would like made so that when we are drafting the report, we will know exactly what has to be changed in that section.
Pardon me for the joke I made about lawyers. It wasn't directed at you personally.
As well, Mr. Chairman, the witnesses revealed something that's rather troubling on three occasions. Ms Kelly mentioned it, Ms Batt mentioned it, and Ms Parsons also mentioned it. It would appear that end users are having a hard time obtaining up-to-date and relevant information about available treatments. In the case of AIDS, there is a national treatment centre subsidized by the federal government, which was nearly set up in Montreal, but was in the end established in Toronto.
How can we make recent information available? By creating another national structure with people paid by the federal government whose work would be to distribute this information? One after another, you have all told us that it is very difficult for people who may wish to try possible treatments to get access to relevant, up-to-date information that is suited to their needs, and I find that troubling.
Those are my four questions, Mr. Chairman.
Ms Pinault: Yes, I have something to say. Yes, the Canadian HIV Trials Network listens to people living which HIV, because they are well represented on its board. Furthermore, some pharmaceutical companies have already set up advisory committees that people living with HIV sit on. More and more clinics that carry out clinical trials have HIV-positive people or their representatives help establish the ethics and the operations of the clinical trial itself. At least, that's how it is in Quebec, but I couldn't speak for all of Canada.
Mr. Ménard: Are you satisfied with what we know?
Ms Pinault: Yes.
[English]
The Chairman: Mr. Shedden, do you have the answer to his question?
Mr. Shedden: I think the simplest answer I can give is that there is a lack of facilities in our region. There are only three sites for undertaking clinical trials in four provinces and there are as many sites for infectious disease centres. With a large part of our population living out of urban centres, it's very difficult for people to travel back and forth to clinical trials. Doctors in rural communities are very unaware of the issues surrounding HIV and AIDS, so a large number of people don't even have the access to larger centres.
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For people who do live in urban centres, there's a dramatic lack of information and lack of resources. We're working with cutbacks to the AIDS Community Action Program. In Nova Scotia, for example, at one time we had three or four different AIDS organizations and we're now being merged into one organization for an entire province, which is very difficult because we rely on funding from the federal government.
I think there's a lack of support. As I said earlier, we're years behind where other places in the country are in terms of developing support networks for people living with HIV, and that tends to take away their comfortability and confidence in accessing services that are available.
The Chairman: Thank you, Mr. Shedden.
Ms Conrad.
Ms Conrad: The reason why I brought up that particular regulation is that in all of my discussions with members of HPB, they indicated that the main problem was not in being able to provide early access approval from the federal end. The problem occurs with individual manufacturers making decisions on a case-by-case basis and with the Canadian authorities having no knowledge or input into the public policy behind what they are doing.
The difficulty seems to be that when the feds say no, there is provision for an administrative review of that decision to evaluate whether the decision was made on an arbitrary basis. When the manufacturer says no, there is nothing under the current system requiring the manufacturer to give reasons to the feds, physicians, and patients directly affected. If the feds began keeping records of the reasons given for saying no, it would help everyone involved to better understand whether the problem is liability, safety, logistics, something else, or a combination of all these things. Having a better sense of why they say no when they do is not the complete answer to the problem, but it is an important and necessary first step.
The Chairman: Thank you, Ms Conrad.
Who would like to answer the fourth question? Ms Kelly.
Ms Kelly: With regard to the information issue, I first presented the presentation I gave to the first Consumer Education Day, sponsored by the Pharmaceutical Manufacturers Association. What came out of that panel presentation was a consensus within the industry and the representatives there that there needed to be an information service and the development of some kind of guidelines for working directly with consumer groups.
As a result of that, I was asked to prepare a proposal, which I presented to Madam President at PMAC, Judy Erola, just a week ago, and I don't want to speak for her but I can say that there was a positive response.
Her recommendation was that it come to the federal government as a way...the government's role of bringing equitable participation to a discussion about how the pharmaceutical industry, the federal government, consumer organizations, pharmacists, etc., can work together to provide basically one-stop shopping for health information, either through taped health messages.... It's happening now in the insurance industry; the technology exists.
So my recommendation would be that there is a need for Health Canada or the federal government, in some aegis, to bring these various players together to look at how this information can be delivered cost-effectively, in a timely way, and with the appropriate level addressed to education, literacy and multicultural concerns.
I could provide you with a copy of that proposal.
The Chairman: I'd be very pleased. Please leave it with the clerk.
Mrs. Hayes.
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Mrs. Hayes (Port Moody - Coquitlam): I found the presentations most fascinating and very personal, and I thank you all for sharing them with us. I'm looking forward to the dialogue between the group members.
A couple of themes that seemed to be recurring are themes of liability and expense. That then goes into the ethical questions that surround who does what and when and where. I have three specific questions. I don't have a specific person to ask them to, but they're all to do with criteria.
First, what would be the criteria, say, for a primary care physician in trying to assess a patient claim for this type of compassionate access? How would you suggest a physician judge whether one person should have access and another not? At what level would that happen?
Secondly, if a pharmaceutical company had a demand put to them for a compassionate care type of drug, what kind of criteria would they use to determine where they would invest their time and money?
The third one is the criteria the government would use as far as including these things in a medical care regime. The term ``universal access'' has come up once or twice in the discussion. How would a government determine what qualified for that type of thing?
These are all ethical, philosophical questions, but they're real on all three levels. I'm wondering if someone could just comment on that.
The Chairman: I think all...[Inaudible - Editor]...because you're talking about pharmaceutical...government, and also doctors in relation to criteria.
Mrs. Hayes: But they may be slightly different depending on which...the doctor is an individual having to decide, the government is the policy. I don't know. Does anyone want to tackle the questions, anyway?
The Chairman: Sure.
[Translation]
Ms Pinault: Most physicians who treat HIV diseases live in the major centres. These physicians are able to analyze a person's health and to see if the person would be a suitable participant in a clinical trial, or they can apply for compassionate access for certain drugs.
The problem is outside the major centres, where physicians do not treat a great many HIV patients. Often they do not know very much about possible access to clinical trials, particularly compassionate access. Clinical trials outside of large cities are very difficult, because there may not be enough information to make a proper assessment. So these physicians are not necessarily making mistakes; they do not make referrals.
There also is a second problem that greatly affects people with these health problems, and I suppose people with other conditions have the same problem: I am speaking of all the forms that physicians have to fill out to register one of their patients for a compassionate access trial.
Sometimes physicians become disheartened when they think about all the paperwork they have to fill out, and they tell patients, ``I don't think it would be useful for you to try this medication, because it's too complicated or too awkward.''
[English]
The Chairman: Would anyone else like to contribute? Ms Kelly.
Ms Kelly: On the boards I sit on right now we talk a lot about patient-centred models of decision-making. I think the basic human right to decide what you can do to provide hope or treatment has to be left to an informed, educated patient in a discussion with their primary caregiver. If you don't know you have options, how would you know to initiate that discussion? You must rely on your physician. As difficult as it is, the physician is also obligated, through professional guidelines, to say, this is your decision, these are your options. Many patients will want guidance or may choose to leave the decision-making up to their physician. But we have a right to make a conscious choice.
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Mrs. Ur (Lambton - Middlesex): I will be short on the preamble so that I can have a few more questions.
Do you see a better venue out there than clinical trials, another alternative that would be more productive than clinical trials?
Some of the presenters this afternoon said Canadians should be deciding what drugs are best and most appropriate for their conditions, but other people ask why we can't have freer access in Canada if it's available in the United States. Where does that lie with some of the presenters?
Do you feel that one of the major concerns with compassionate access to drugs is the possibility of liability for doctors, that this may be one of the hindrances when it comes to accessibility to compassionate drugs?
To Mr. Shedden, is geography a major concern in Nova Scotia in terms of information and health care?
Women with advanced breast cancer have seldom discussed among themselves or other stakeholders the issues related to compassionate drug access. What has turned this around for women suffering from breast cancer?
On a more personal note regarding clinical trials, there appears to be a positive-negative reaction to people taking drugs and clinical trials, whether they are a placebo or whatever. My family is experiencing a clinical trial and they are pleased to be taking part in it. The patient doesn't know what he's taking, but he says if it doesn't help him it may help someone else. Could I have a few answers on those?
Mr. Shedden: Geography is certainly an important issue, as is economics - we need money, we need money, we need money. I think economics is our most pressing concern in terms of access and resource allotment for people living with HIV.
In response to your first question on clinical trials, I'm very supportive of the Clinical Trials Network in this country. It does a lot of really good work and gets a lot of support from our communities, but the funding it receives is dismal when compared to other countries. As you read in the background documentation, it gets no money at all for the organizational work, the paperwork that must be completed. So I would like to see an increase in that funding and an increase in the availability of sites. We only have three sites in Atlantic Canada at this time.
Ms Conrad: With your permission, I'll try the liability one. Based on my professional experience, I can state that there is nothing that physicians, or anyone else for that matter, can do to insulate themselves against the possibility of being sued. Patients reserve the right to file suits at any time, both before and after a drug is formally licensed. The best protection physicians have against the possibility of being sued is to obtain genuinely informed consent. This is only possible where physicians have general knowledge of all of the information that is available and the ability to explain that in plain language.
I've noticed that the specialists I've had contact with have a very tough time keeping up to date on new research developments, with periodicals often remaining in in-baskets for long periods of time. On the other hand, the family practitioners I have dealt with are much more open to reading new information and much more willing to pursue clarifying information where that would be needed as a prerequisite to being able to make an informed decision.
A good working relationship between a physician and a patient requires clear communication on both sides. It also requires that physicians talk with, rather than to, their patients.
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The Chairman: Thank you, Ms Conrad.
Before we pass to our second set of guests this afternoon, Mrs. Hayes has just reminded me that our guests didn't answer all her questions. They mainly answered on the criteria for doctors, but she would like to have some comments about the government and the pharmaceutical criteria. Would anyone like to answer? Go ahead, Mrs. Hayes.
Mrs. Hayes: I could focus that a little more because of the answers I had concerning physicians and their responsibility of how they would make the decision.
If we were to decide, say, that it's simply by patient request or if a patient feels this is something they want then they should have it, how would that fit into our medical system? Right now we have a medical funding program that in some provinces pays for regular casts but doesn't pay for plastic casts, for instance. There are certain things that are deemed appropriate and others more than necessary or whatever.
How would compassionate access and the costs involved - and some of these treatments described are very expensive - work within our medical system, or how would the government decide?
Ms Batt: I see a real problem with that in breast cancer treatments and I don't know how to get around it because the treatments are so expensive. Things like bone marrow transplants are hundreds of thousands of dollars. Whether you have the individual paying or the government paying, to say that somebody has access to this treatment in theory is no good unless there's some way of paying for it. I just don't see how to get around that as long as the costs are so high. I really think the costs of those treatments have to be reduced or there's no point in even investigating them.
Ms Kelly: I certainly support what Sharon is saying and I'd like to add, as it should be in any decision-making process that looks at research, that it should be data driven, outcome driven. I believe the best supportive care, which in many cases will be no care versus an active treatment...if you can measure that there is a difference for that patient in terms of quality or length of life, there is a benefit then to the system in not prolonging that life, but improving the quality of that life.
I'm going to give an example. In the treatment of lung cancer, physicians have for years offered patients best supportive care, which is no treatment, or surgery or chemotherapy, knowing from a professional point of view that chemotherapy is a very brutal treatment and will not prolong the life of that individual. When surveyed themselves, what would they do if it were them? Best supportive care. What would they do for the patient? Treatment.
What would the patient do if the patient knew that there was a choice and what those outcomes were? We don't know, because they didn't get that option. I would suggest looking at these as a comparison trial...what happens, what is the benefit, and being able to track the benefit.
The Chairman: Thank you, Ms Kelly.
We're going to pass to our second list of guests here this afternoon representing the medical profession. We're going to start with Dr. Ken Logue.
[Translation]
Mr. Ménard: Shouldn't we have a short break, Mr. Chairman, because eating and listening to witnesses...
[English]
The Chairman: It's up to our witness. You could wait a little bit and we'll get a longer one after.
[Translation]
Mr. Ménard: If you put it to a vote, I think you would be outnumbered.
[English]
The Chairman: Dr. Logue.
Dr. Ken Logue (Individual Presentation): Thank you very much, first of all, for asking me to speak here today. I very much appreciate the opportunity. I'm a primary care physician from Toronto. My practice is made up of a significant portion of HIV patients. I also have experience with clinical research and am involved in clinical trials, both in a hospital-based and a community-based setting.
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When I was a little more naive I used to think that the whole issue of experimental treatments, promising treatments, versus standard care could be easily subdivided. I felt it could be simply divided into standard of care, and if that's inadequate, possible participation in a clinical trial, and if that's inadequate, looking at options through an expanded release program of some sort.
The longer I'm involved in this the more inadequate I realize that simplistic model is. Perhaps 60% of my patients are involved in or are actively taking an experimental drug as part of my standard of care to them. Particularly in HIV disease, standards of care change rapidly and there's a blurring between what is experimental, what is potential and what is a standard proven treatment. I think that's the crux of the issue.
It's easy to look at expanded or compassionate release to someone who has a catastrophic life-threatening illness and there are no other options, but when they've exhausted other options, when the standards have been used up or exhausted and new drugs that will be licensed shortly are not available, there is a huge ethical if not logistical problem.
I thought it would be best to highlight four examples of expanded access that I've been involved in as a primary care practitioner over the last couple of years. Each highlights different issues from both the patient's and the doctor's perspective. Each of these examples concerns pre-market drugs, and pre-market drugs are what's referred into the special access program documentation. This is clearly where the focus of attention should be and where any significant recommendations should be directed.
My first example is compassionate use of rifabutin, which is an antibiotic that has been licensed as a prophylaxis or prevention of a significant opportunistic infection in AIDS. Prior to the licensing, that is, when phase 2 and 3 studies were ongoing and a significant amount of clinical knowledge was known about the drug, there was a widespread compassionate access program. Unfortunately, community physicians and people in my position who in some cases treat significant numbers of the HIV patient load did not fall under any ethics approval for a compassionate program.
In this particular example, ethics approval was not only from out of our jurisdiction, but from out of the country. It was from the United States. So a compassionate program was set up by the pharmaceutical company prior to their licensing. The drug was made available, but unfortunately the administration of the compassionate program was hindered by the lack of proper informed consent participation from the primary care physicians and an ethics approval that was completely out of our jurisdiction.
The second example is more timely, I think, and that's of 3TC. As everyone knows, 3TC has just been licensed in the States and will probably soon be licensed in Canada. 3TC has shown us two or three problems with compassionate access.
Approximately 40% of my patients are on 3TC, through a compassionate access program. This presents a huge administrative burden when up to 50% of your patients are on a compassionate access program. An analogous situation would be if your cardiologist or surgeon, for 50% of the procedures they perform, has to either have an understanding of a new drug that is over and above the standard base of knowledge or an understanding of the compassionate access protocol. They need a good understanding of informed consent and must be able to administer that and discuss that with the patient. Administratively, this is very difficult.
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These are some of the reasons why there are difficulties in recruiting physicians to treat HIV patients, and I think some of the other speakers have hinted that it's also a problem geographically and in other areas. Huge compassionate programs like this where they set up administrative problems, if not ethical problems, will certainly worsen that.
The third example that I think points out another significant problem that we encounter is that of saquinavir, another antiretroviral produced by Roche Pharmaceuticals. They have a compassionate access program and participated a great deal in communication with both physicians and community activists in setting up a compassionate program.
However, their supply is vastly limited. I believe they initially released drugs for 96 patients across Canada and have subsequently released drugs for another 200. So they've released 296 allotments of drug for patients, and clearly on a day-to-day basis we're confronted with patients who have few or no other choices for antiretrovirals and who would likely benefit from compassionate access to this drug, a drug for which we have considerable phase 2 and phase 3 clinical knowledge and which will likely be licensed.
Yet we're unable to provide it. In defence of the pharmaceutical company in this case, the situation is simply one of supply and manufacturing. I think it's been reasonably well-presented and is a legitimate case.
Despite the fact that patients certainly would like this drug and that we as physicians feel they would benefit, our hands are tied for other reasons that are completely out of our control.
The fourth example I wanted to bring up is that of nevirapine, another antiretroviral. Community groups have recently approached the pharmaceutical company that produces this drug requesting - or demanding, if you will - compassionate access. This is a drug that a lot of physicians have limited clinical knowledge of.
I think it's an example where a patient group would certainly be ahead by requesting this drug and presenting it to physicians, a majority of whom would not have a clear understanding of potential side effects, interactions and problems with this drug. I'm bringing that example up as a clear indication that there is a definite need for communication on all levels, as some of the other speakers have highlighted - communication not only to patient groups but to physicians.
I think each of these examples highlights some of the controversies in HIV disease. In the case of 3TC the perceived slow approval of accessing a new or promising HIV treatment is highlighted. The standard of treatment in treating HIV disease is often experimental or about to become approved. We certainly need a process whereby the regulatory process can be hastened if the science is at a position where we can confirm a treatment is effective or at least predictably effective.
Limited access to some existing compassionate release programs is a huge problem, as is whether or not pharmaceutical companies will agree to provide the drug at their cost or will agree to administer a compassionate program. The example of saquinavir, where they simply cannot produce the drug or don't have the drug, is a very important consideration and I don't think we have any easy solutions to that.
I think there's also a perceived and real unequal distribution of drug and compassionate release. I think it exists geographically. It exists because of communication problems with different groups and it also exists simply because of the nature of a limited supply. In addition, I think there is a perception of coercion to enter some trials, and I think in this area the need for definition and a better understanding is very much the key.
We have compassionate use, we have emergency drug release, we have orphan drugs, we have treatment I and D, we have parallel tracks, etc. A lot of these overlap and a lot of them are completely different in very significant ways.
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I think lost in all of this lack of definition is when is something treatment and when is something a potential treatment? Unfortunately, the consumer or patient perspective, perhaps rightly so, would like to attribute a potential treatment as something to which they require access, and we as physicians would in fact like to hasten that.
But the problem is really lack of understanding and a lack of definition of some of these issues and some of these means of providing emergency access.
In summary, I would like to just give five or six points of when I believe compassionate release programs are appropriate. In areas where clinical trials of new drugs are ongoing, number one, I feel that compassionate release programs are appropriate, providing preliminary studies have delivered grounds to believe this drug will be safe and efficacious. Whether that means the phase 2 trial or a phase 2-3, I have purposely not indicated this, and I think it's a very debatable point.
Number two, compassionate release is organized in a fashion that will not threaten the viability of controlled clinical trials of a new drug. I think this not only serves the interest of the pharmaceutical company, but also ultimately all patients.
Number three, compassionate release is structured in a way that will not discourage drug companies from continuing work on new drugs. I think in the area of HIV disease there are tremendous examples where pharmaceutical companies simply will not participate in certain drug trials in certain jurisdictions because of limiting enrolment and problems with compassionate release.
Number four, the compassionate release program offers a fair and equitable access according to stage of severity of disease.
Number five, the compassionate release program does not in its conditions of access entail compulsion on persons with HIV disease to enter into clinical trials of the new drug.
Number six, from my narrow self-interest, I think the administration of these huge compassionate access programs needs to be addressed. What HIV disease has done to a certain point is shifted a lot of dynamics in medicine and shifted a lot of dynamics between patients and physicians.
One of the changing dynamics in medicine is it shifted some of the access to early compassionate, experimental treatments from a university-based setting to a primary care setting. So they've shifted from an area where there has been a great deal of support, administratively, to where there is very little.
I think those issues are not only important from the point of view of recruiting new physicians into this disease area, but also in other disease categories.
The Chairman: Thank you, Doctor. We're going to pass now to Dr. Doug McFadden.
Dr. Doug McFadden (Individual Presentation): I work as a physician and an immunologist primarily in the HIV field, but also in autoimmune disease, such as multiple sclerosis.
I only found out last night that I was a member of the panel, so as per Monsieur Ménard's suggestion, we'll keep this very short, and it will be even shorter because I think Dr. Logue was looking at my notes, so that shortens down the number of things I wanted to say here.
When we're talking about humanitarian access I think that's a given among everybody around the table. In a very tolerant, compassionate Canadian society, that's a given. I don't think there are any arguments there. We haven't achieved it. The questions are the following. Why haven't we? Why should we? We know why we should. How can we?
Making access as wide as possible shouldn't necessarily be the only goal. What are the risks of providing drugs on a compassionate basis?
I'm going to say a few things today that may initially make people think I'm saying something contradictory to my opening statement. That's not the case, so wait until I finish.
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There are tremendous risks for providing drugs on a compassionate basis, and we've seen tremendous examples of those risks. I'll go through a couple of them later, but one of the major risks is this: when are we going to release the drugs? Dr. Logue suggested phase 2. He didn't quote me correctly. I had phase 3 down here.
The bottom line is if you allow it in phase 3, people are going to ask for it in phase 2-3, phase 2, and then phase 1. As has any other physician around this table, I have had requests for drugs that are pre-clinical. In the process of drug development you have pre-clinical and clinical stages, and I've been asked for drugs in the pre-clinical stage. We have to figure out where we're going to draw the line, so let's approach it in a reasonably logical way.
I'll preface that by saying humanitarian access shouldn't be thought of solely as the release of experimental drugs. Whether you talk about humanitarian or compassionate access doesn't matter. It's not necessarily release of experimental drugs. We have people in this country who have a disease that is treatable with well-documented and released antibiotics and cannot receive treatment because of the cost. So if we're going to talk about compassion, we should keep in mind the possibility of increased access to drugs for patients who can't afford them. We're talking about approved drugs, drugs that have received their NOC and are on the market.
Let's get back to the point. I want to address a few issues. I think safety is number one. There are well-defined, well-documented dangers in taking experimental drugs. That's why they're called experimental drugs. We're not talking about drugs that have a long history. If we're talking about phase 2 drugs, perhaps only 100 or 200 people have taken the drug. In phase 3, sometimes only 300 to 400 people will be taking that drug at that time.
Chloramphenicol, which is only available with great difficulty in Canada, was pulled off the list in the 1940s because the wife of a well-known physician developed aplastic anaemia. It occurs 1 in 40,000 times. If you're testing a drug on only 300 people, when are you going to get to that one person who's going to be killed? We're also talking about life-threatening illness. That brings up the topic of risk.
As a physician, my basic philosophy is if it won't hurt you, take it. If I don't know whether it's going to hurt you, it's up to you. If I know it's going to hurt you, don't take it. Not all patients listen, but that's my basic philosophy.
``Do no harm'' was mentioned earlier. That's the physician's basic mandate. Many people around the table have told us not to worry about that, that they as patients will assume the liability. That's fine, but if you're the physician who is giving that drug to the person, it's hard to sleep at night when you know you killed that patient with the drug.
Let's go back to compassion. Thalidomide was mentioned before. It's a damned good drug. It has wonderful properties, unless you're a pregnant female. Over the past twenty years I have not been able to access Thalidomide for children with giant aphthous ulcer diseases. That's like a cold sore that fills your entire mouth. You can't eat, drink or swallow. Thalidomide is not necessarily a curative, but it sure does a lot of good.
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It's only been the last six to eight months that we've been able to access Thalidomide for HIV disease. Even for an 80-year-old man I could not get Thalidomide. Don't get me wrong. I am not knocking EDRP. They have done a wonderful job. They've accessed drugs that I couldn't get any other way, but I've seen the benefits and I've seen the downside too.
In the 1920s, giving arsenic was compassionate. It was a great treatment for syphilis. Are we going to use that now? I doubt it. Sometimes history provides lessons that we really need to learn.
That brings me back to my original point, that I don't want to be the physician giving a drug to kill somebody. I'd at least like some information. The people who enter the double blind, placebo-controlled, randomized clinical trials - those are the people who are taking the risk, and they know the risk they're taking. They're the people who should be congratulated.
There is no replacement for clinical trials. Compassion should not replace common sense. It's those trials that tell us what drugs are good and what drugs are bad. It keeps Thalidomide off the market for pregnant women.
I'll go on to another point. The tremendous amount of work and effort in expanded release programs is not a small issue. I dealt with the FDA in trying to get a compassionate release trial of a drug going. They said sure, we will give you one physician IND, and we will allow expanded access among 25 patients and eight pages of documentation per patient per month. Physicians who see those patients find that difficult to take, but it wasn't an unreasonable request because they want to know about the safety of the drug. Whose head is on the chopping block when they release a drug that kills people, when they haven't looked at the safety aspects of it?
That brings up another point: the cost to the pharmaceutical company. In an expanded access program, the pharmaceutical company only gets safety data. That's all. They can't use it to help get the drug approved, so it's costing a phenomenal amount of money to get safety data. They get that in phases 3 and 4 anyway. That is not to say the pharmaceutical companies in Canada have not shown great compassion; they most definitely have.
The problem is that it is not cheap, and where is the money going to come from? A lot of good drugs are developed by small pharmaceutical companies. They don't have the money. Some of these drugs are horrendously expensive. They don't need the safety data; they know they can do that in the next phase of the trial.
We've been told that the patient takes the risk, but you won't find a pharmaceutical company without liability insurance if they're giving a drug to somebody. That's not common sense. No matter what documents the patient signs, there is always a way to get around it legally. Everybody around the table knows what litigation costs, even if they don't win.
Who's going to take the cost? The consumer? HPB? I don't think the PMAC will to do it, and with our recent budgetary situation, I doubt Health Canada will do it either. That's a difficult problem and I don't have an answer to it.
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I will say, though, to a couple of the criticisms that have been made with regard to HPB and EDRP, we have to think of them in a slightly different way. There is an imbalance, country to country, in what drugs are available. Salbutamol, or ventolin, the prime drug for the treatment of asthma, was available in Canada sixteen years before it was approved in the U.S., and a lot of people died in the U.S. by not getting it. That substantiates compassionate release, doesn't it?
Let me make a couple of suggestions.
There's been the suggestion, not just here but many times in many conferences, of parallel trials. That's fine, but those trials need to be done with the same intensity and the same scrutiny as the arms of the conventional trial itself, the placebo and the drug arm. They have to be absolutely strictly controlled and not have the loose access we have now, which simply provides safety data.
The second suggestion is actually a question, and that is, what are the guidelines for allowing people into compassionate release? Dr. Logue actually touched on this subject. What if you have only fifty slots? But even if you have 20,000 slots, should we not have certain guidelines that will allow us to determine who has failed conventional therapy? Should people not go through conventional therapy first?
I and all other physicians around the table have had many patients who want to jump immediately over the conventional therapy hurdle and go directly into experimental therapy. I try to explain the balance, saying ``We know this works and we don't know anything about the other'', but they still choose the other. It's like going to Las Vegas. We need very firm guidelines as to who gets in.
The financial aspects I've talked about. The downside is safety and cost.
Should there be compassionate release? We all agree and I agree, going back to my very first statement...you may misinterpret some of the things I've said, but yes, I'm in favour of expanded access and compassionate release.
Thank you very much, Mr. Chairman.
The Chairman: Thank you very much, Dr. McFadden.
Now we're going to ask
[Translation]
Ms Diane Filion, who is the Nursing Coordinator for clinical trials at the Ottawa General Hospital. Ms Filion, you have the floor.
Ms Diane Filion (Nursing Coordinator, Clinical Trials, Ottawa General Hospital): Actually, I'd just like to point out that I'm the coordinator for the entire clinic, not just for the clinical trials.
Over the next few days, people will be testifying before your committee, discussing the issue of distributing drugs for compassionate purposes. These people will be tackling the problem from different angles, depending on whether they are scientists, drug manufacturers or health care workers, depending on whether or not they use such drugs, depending on whether they have the disease or not.
I don't intend to discuss this problem from a scientific point of view, but rather, from a humanistic point of view, by showing the impact of the distribution of these drugs in a practical context, such as the one I work in daily as the nursing coordinator of an immunodeficiency clinic that provides multidisciplinary care to people living with HIV.
The distribution of drugs for compassionate purposes is an integral part of our pharmaceutical service. This is what the current situation is: often, a drug that has not yet been approved in Canada is identified as being crucial for a person's survival. While bearing in mind that human compassion is an inherent part of health care, immediate access to a drug is necessary if the physician who has prescribed this drug can justify emergency use of it as well as its impact on the patient's condition.
However, in chronic illnesses like HIV and AIDS, the immediate health gains for an individual are not always clear and are often difficult to identify at that time. This calls into question the accelerated access to a drug the beneficial effects of which can only be indirectly assessed in the patient.
Since this disease is of specific interest to the media, health care providers are confronted with repeated demands on the part of users who want easier access to investigational drugs which will not do anything to improve the state of their health and which could be harmful and even contraindicated in some cases.
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These same professionals must constantly justify their position because of the close and personal relationship they have with the clients they serve. They are sometimes accused of lacking compassion for their clients, which results in ethical and professional dilemmas for health care providers.
The distribution process for compassionate drugs and clinical trials are not interchangeable, although they complement each other. Clinical trials must safeguard the safety of the patient while protecting him from the harmful secondary effects which may appear during the course of a drug trial. We must maintain rigorous scientific methods for assessing the therapeutic value of the drug under study.
Controlling the use of compassionate drugs must, in my view, allow for the collection of data which will help establish and assess the effectiveness and the side effects of the drug while contributing to the treatment.
I would like to draw your attention to a very important point. Eligibility criteria for certain drugs seem contradictory, as generally, these drugs are being distributed to patients who are too ill to benefit from the therapeutic properties of the drug, when the drug is destined to treating patients who are at a less advanced stage of the disease. These are often the same people who suffer from the harmful side effects and the toxicity of these drugs, given the very precarious state of their health.
Our colleagues from outlying regions will tell you that it is impossible to get access to clinical trials outside large centres. Accessibility to certain drugs certainly takes on greater importance, as it enables patients to benefit more quickly from advances in medical research in which they cannot directly participate.
By distributing its drugs free of charge on a large scale, the pharmaceutical industry is building up a clientele which will continue to take the drug after it has been put on the market. In this way, it is also collecting a considerable amount of data which will enrich the information collected during the clinical trials.
Pharmaceutical companies are often unable to meet the demand for certain products. Eligibility criteria are often modified to counter production difficulties, thus creating waiting lists, but to a greater extent, causing uncertainty among patients.
The random process for providing access to a drug is an aberration of human compassion. The very idea of a lottery is unfair, not to say antidemocratic. Will the people who actually receive the drug be those who need it the most?
Under the pretext of offering hope to people whom we know don't have much time left, it sometimes seems easier to favour the humanitarian side of things and to distribute ineffective drugs.
We must keep in place a systematic way of controlling the quality of these drugs by maintaining a balance between emotion and clinical judgment, which is the reason why people consult health care professionals and physicians.
Canadian legislation and the Department of Health must, in turn, enforce the necessary safety standards. However, when a drug seems promising and safe, government authorities must use their influence to make the process fair for beneficiaries by favouring the interests of the patient.
For users, time is short. People with an incurable disease or in a very advanced stage of HIV infection often call upon health care professionals for guidance in using advanced therapies. They need the professional expertise of the people who provide the care they need, especially when the loss of autonomy associated with the disease makes them vulnerable to people selling miracle cures.
The people directly involved in providing health care services need the support of researchers and legislative bodies in order to help and support patients in this process.
In short, compassionate-use drugs must be distributed. The data collected lead to parallel clinical studies which must not be substituted for basic and formal clinical research.
The process must be clear and fair, as the health and lives of human beings are the ultimate concern. Thank you.
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The Chairman: Thank you very much, Ms Filion.
We will now hear an individual presentation from
[English]
Dr. Christos Tsoukas, please.
Dr. Christos Tsoukas (Individual Presentation): Thank you very much for inviting me to this meeting.
In terms of background, I'm an internist trained in clinical immunology. I have been treating people with HIV for the last thirteen years, and in the last ten years I've been a director of what is known as the Immune Deficiency Treatment Centre of the Montreal General Hospital.
In the past ten years I have either conducted as principal investigator or have been site investigator on at least seventy clinical trials. Currently we have ten antiretroviral therapies with three compassionate arms.
Based on these statements, my point of view should be that of a clinical researcher and not as a treating physician. At the onset, prior to reading my statement, I must say that I share many of the views expressed by my colleagues, in particular Dr. Logue as a treating physician.
In terms of what Dr. McFadden stated about the risks involved in treating persons with unproven therapies, in late 1984 the first patient I treated with a drug died of the side effects of that medication, and this is a drug that has yet to be licensed in Canada.
In its simplest format, the compassionate release of medication for HIV or AIDS means that an individual has a mechanism to obtain and thus the ability to take any medication that he or she believes may improve or prolong life.
This act of taking a drug is not simply an issue of swallowing a pill or receiving an injection. This is an active process where a person becomes motivated to take action either to self-medicate or with the assistance of a physician to be treated with a medication currently not available for sale in Canada.
There are numerous implications to this process. A variety of issues arise that have ethical, legal, social, medical, epidemiologic, regulatory and economic aspects that must be evaluated.
For the individual patient, the issue is often simple. He or she should receive what he or she wants. It's their life, after all. Why should any restrictions exist when the consequences of no treatment for AIDS are clear?
For those of us who treat persons with HIV and its complications, the personal wants of our patients may be obvious but the medical needs may not always be. It is true that this illness affects young individuals who in the prime of their life have a potentially fatal illness.
The chronicity and the variation in individual clinical expression of HIV disease make it difficult to generalize when it comes to therapy. Pressure for release and use of unproven therapies is generally the direct result of the anxiety and despair that individuals feel who have or are perceived to have significant or rapid disease progression. These feelings may be compounded by the frustration and helplessness of their treating physicians in such situations. Certainly this was true a decade ago prior to the development of any antiretroviral drug therapies.
Are the medical issues relating to compassionate release the same today as they were eight to ten years ago? I'll try to briefly review and outline the evolution of some of these issues.
First, since there is no cure for AIDS, and we must all hope for a cure, this hope often implies that a silver bullet will be found. Not having access to a particular drug because it has not yet been licensed has often been equated with potentially being deprived of this evasive silver bullet.
Secondly, the issue of compassionate access to medications often implies choice and independence, with the individual having the ability to choose between no therapy and proven or unproven treatments. The individual thus attains a feeling of empowerment and control. These feelings are usually quite powerful and may result in additional and sustained patient efforts to fight this illness. Thus compassionate access therapies may contribute to an improvement in the patient's clinical status, despite the potential access and use of a marginally effective medication.
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The urgency for compassionate release of drugs is dependent on and proportionate to the perceived potential for benefit of a particular treatment. This was clearly the case when AZT was being tested in 1987. This was an era of enormous expectations associated with the first anti-AIDS drug, the first perceived silver bullet. Recently the discovery of a new class of compounds, the protease inhibitors, has resulted in the same type of expectations and urgency.
Today, from a medical-therapeutic perspective, the issues are much more complex than they were a decade ago. It is unlikely that a single drug will have a dramatic impact on HIV disease progression. The reasons for this likelihood are based on recent data suggesting that the average patient has approximately two billion HIV particles produced and destroyed in their body daily. A single drug would have to decrease this amount of virus by 99.99999% to be clinically effective in the long term. In addition, HIV is also known to mutate rapidly. Drug-resistant strains arise quickly, thus rapidly negating any benefit, even from a very potent antiretroviral drug.
Given these two scientific facts, what hope would a single drug obtained through compassionate release have in providing therapeutic efficacy? A single drug may simply buy some time rather than be the silver bullet.
Given the usual lack of detailed data on combined use of unlicensed therapies, a lone drug obtained through a compassionate access program cannot with confidence be used to treat specific individuals. For instance, some drugs can cause antagonistic actions, that is, against each other, or drug interference, or potentiation of side effects, or of effect. Examples are the raising of blood levels of prophylactic antibiotics by antiretroviral agents, thus making the use of prophylactic antibiotics more toxic to the individual.
Although it has often been said that compassionate release impacts on the ability of clinical researchers to recruit and maintain individuals in clinical trials, this may only partly be the case today. Recruitment for clinical trials will become more difficult with time, not because of competing interest for a specific drug by individuals, but because of the potential for the creation of future ineligibility for clinical trials for such individuals, thus depriving them of potential future benefit.
Because there are more antiretrovirals available and more to come, it becomes important to maintain certain standards of therapy and to develop treatment algorithms that currently do not exist. The end result of not having guidelines in an era of multiple-drug availability may be the chaotic and futile switching between drugs based purely on empiric criteria.
Clinical trial recruitment involves a process of informed consent, which usually outlines current therapeutic options. This process gives the individual an opportunity not only to enrol in a trial, but also to decline enrolment. In the process of declining enrolment in such a clinical trial, the same individual, through the information they obtain via the recruitment process, and specifically from the consent form data, ultimately results in a better-informed individual with respect to what is currently available in terms of experimental drugs.
Compassionate release in the form of an open-dose comparative study may or may not provide similar background drug information. Emergency release of drugs outside of a defined protocol usually provides little to no information for the individual or his physician.
In both instances, in return for providing drugs, the patient, through the physician, is usually expected to provide safety data to the company supplying the drug and to the HPV. The individual may have scant monitoring during the time of therapy. The potential for disease acceleration also exists, either through the direct effects of the medication on the immune system or indirectly through its failure to adequately control viral replication.
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An example of how this may happen recently arose with the testing of certain protease inhibitors. Although these drugs are very potent inhibitors of HIV, they suffer because of low bioavailability, that is, low absorption by the body.
When a medication is provided within clinical trials, great efforts are made to ensure compliance with appropriate drug dosing. The medication must usually be given in high doses and frequently through the day. Uncontrolled access and an inability to maintain dosing compliance can lead to complications.
In certain cases too much drug may cause painful side effects, while low doses may not only not suppress the virus, but can facilitate the appearance of drug-resistant virus strains such that increasing the dose later may be futile. Drug-resistant strains may also be cross-resistant to other drugs in the same class, that is, other drugs the patient has not yet taken. Not only does the patient lose out, but society might lose out as well, given the potential for an increase in drug-resistant strains that may be transmitted sexually.
Protease inhibitors are not readily available at present because of supply problems and, to some degree, the cost of production. AIDS activists often believe the compassionate release of drugs is not in the interest of the pharmaceutical companies because of the potential competition for recruitment in company-sponsored clinical trials.
In fact, the compassionate release of drugs that have good therapeutic potential provides a mechanism to make physicians familiar with these medications prior to their licensing. Once licensed, the marketing of these drugs becomes simple because the user-physician group has been identified and has become familiar with the clinical use of the medication. It can thus be argued that it is economically important in the long term for a drug company to have an early compassionate release program.
Although most medications are traditionally provided free of charge by large pharmaceutical companies, at times small firms have charged for their products. This may no longer hold true since some large companies are also beginning to charge for drugs released through these programs. If drugs are to be made available but only with payment, the potential exists to have a two-tiered system of access to these agents, where those who can pay have access and those who cannot do not have access.
The major challenge of the future will not be to enable compassionate access to medications; it will be to ensure the rational and optimal use of combination therapies. We know that the potential for benefit from new management protocols utilizing currently available and licensed drugs exists today, yet this potential has not yet been fully realized.
As more drugs become licensed in this country, Health Canada, the pharmaceutical industry, patients and physicians should focus their efforts on setting standards and maximizing combination therapies, including those involving immunotherapies. Drug cost issues, along with management modalities, will determine the future of today's HIV-infected Canadians. We should be collectively addressing these problems now, as a major threat to therapeutic effects may result from the lack of affordable rather than available drugs.
I don't have typed recommendations but I'd like to read some specific recommendations that relate to today's meeting.
The pharmaceutical industry should be encouraged to institute compassionate release programs similar to those in the U.S. parallel track program. If they do so they should receive acknowledgement for fast-tracking the review of their submissions when that time arrives, while maintaining the appropriate review standards that have been set forth by the HPB.
Second, a program of accelerated approval, otherwise known as conditional approval, should be instituted using a modification of the current U.S. program and be tied to the availability of compassionate access through parallel tracking.
I was part of this review process for the Food and Drug Administration, with the approval of ddC and ddI in the U.S. I'm very familiar with this process, and I think it is something we should seriously look at in Canada.
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Companies should be encouraged to provide drugs through open-label, easy access programs, rather than on a one-on-one basis through the emergency drug release program.
I'm very much against the emergency drug release program for a number of reasons. I believe we can have a much better access through open-label programs, and these programs should be designed to provide dosing and safety data. The dose used should not be homeopathic but should ensure that there is potential for benefit. Oftentimes in the past the doses used in these programs were far from adequate.
Other points that should be looked at in these programs is the effect of using once-a-day or twice-a-day dosing. This is currently not the case for many drugs being given in this country where we provide these three times a day, and many patients have to take up to thirty pills in a given day. We have an urgent need to provide a humane, simplified way for people to take drugs so that we do not interfere with their daily lives.
I applaud the new tariffs being charged for the review of drug submissions by the HPB. I think this is a step forward. These funds should provide much needed resources for internal and external reviews and therefore expedite the review process.
Standardized case report forms have not been in existence in a universal format, and I think they should be. They should be designed to capture the basics in any compassionate release program. This format should ensure that only the simplest of demands are made on a physician's time or the nurse's time in enrolling patients in this program. So far this has not been the case.
We should provide monetary compensation to the physicians who complete these case report forms. This could be accomplished quite easily through the existing provincial health programs. We currently fill out forms for welfare or for other medical acts that we perform and we are reimbursed for these acts often by the provincial health programs.
Since the provinces as a rule provide antiretroviral drugs once they are licensed, payment could come from the provinces, with the federal government sharing the whole process along with industry. Why should industry share the process? Because one could tie this in with clinical trials research. A successful clinical trials program could ensure that part of the money that normally goes to run these trials, if recruitment is done within a short period of time, could be contributed to this kind of program.
Lastly, we have a real need to maintain a national ethics review board such as the one the Canadian Clinical Trials Network has established, also known as NERC.
I think I've made some very specific recommendations, and I really think that unless we act soon we will still be discussing these problems ten years from now.
The Chairman: Thank you very much, Dr. Tsoukas.
We are going to pass now to Mrs. Mary Grondin, the nursing coordinator for Wellsley Health Centre. Mrs. Grondin.
Ms Mary Grondin (Nursing Coordinator, Wellsley Health Centre): Thank you for the invitation to speak here today. I work in Toronto in a large urban centre where information about the availability of drugs for compassionate release is readily available.
I was wondering what happens to patients whose physicians and pharmacists are in smaller and rural areas who are not affiliated with a large urban medical teaching centre or a provincially funded HIV clinic.
Having listened to previous speakers I am now aware that there are people with HIV and other catastrophic diseases who may not be accessing treatments because they may not even know these drugs are available. In some cases it is the patient who hears of the drug and does the research. For instance, it could require a person to be on line to the Internet to have access to this information, or a person may be so well connected within the AIDS activist community that he or she knows more about this drug than the average patient or perhaps most family physicians.
The patient then takes the information to their physician, who then makes the request to EDRP for the release of the drug. This brings to question the whole idea of equity of access if one needs a personal computer and access to Internet in order to learn about new possible treatments for a particular disease.
When a request is made for a drug that is not known to EDRP or perhaps has never been requested before, someone has to do some additional investigating on the availability of the drug.
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I can remember having to call a pharmaceutical company in Maryland to determine if a drug could be made available, because this drug had never been used by someone with HIV before. The EDRP gave me the name and contact information for the company. But I had to call the company, get the okay, then call EDRP back, so that EDRP could call Maryland, so that then Maryland could release the drug to our patient.
When ordering drugs that are easily available for compassionate release, a physician must receive authorization for each and every individual patient, and the drug has to be re-ordered through EDRP, usually every month.
In a busy practice where a physician may have 100 patients with HIV, or in our health centre - we have close to 300 patients with HIV - this can result in a lot of phone calls and/or paperwork every month. In our centre we have nurses on staff to do the phone calls, but independent practitioners in the community, as outlined by Ken Logue earlier, do not have this type of support.
If a company and the EDRP are willing to release a particular drug to a physician for 10, 15, or 20 patients, why not simply authorize individual doctors instead of each individual patient? This way a physician would report that there are a certain number of individuals needing a drug each month and a supply would be sent based on that number versus having to call in each repeat. Let's face it, not everyone in a doctor's practice requiring, say, foscarnet, which is a treatment for CMV retinitis, has an appointment with that physician on the same day of the month. With adequate record-keeping in each doctor's office, the drugs would be distributed appropriately.
In some instances, why not have the drug released directly to a pharmacy dispensing other HIV treatments? The pharmacy could keep a stock, check monthly for side effects, and information could be kept on the computer to better watch for possible drug interactions. This, of course, does not apply to drugs just for HIV, but it could also be for other diseases, especially when it is for a long-term or lifelong therapy.
When a drug has reached the point of development to begin a phase 3 trial, the manufacturer should be encouraged, or perhaps even compelled, to make the drug available for compassionate release and through clinical trials. Clinical trials give a patient the opportunity to get a drug free, but what if someone doesn't live in a city where the trial is available, or what if someone is not eligible to enrol?
Take, for example, the drug saquinavir, a protease inhibitor developed by Hoffmann-La Roche. The patients enrolling in this trial have to be a fairly naive population. In order to qualify, AZT is the only antiretroviral therapy allowed for subjects. The latest research from Europe and the U.S. is showing that combination therapy may be the wave of the future. This involves using AZT with either ddC or ddI, and perhaps in addition to saquinavir. There are also patients who cannot tolerate AZT, or have strains of HIV resistant to AZT, and therefore have had to use other antiretrovirals. These people are then ineligible to enrol.
In all fairness to Hoffmann-La Roche, saquinavir is available on a limited basis through the compassionate access. How do we guarantee this is always the case in the future, especially when a well-informed AIDS activist told me that more and more lately EDRP is saying yes and the drug companies are saying no to requests for release on compassionate grounds?
There is no requirement for a company to release a drug for compassionate access. Pressure may have to be put on companies that don't comply with requests. There needs to be legislation or regulations that compel a company to justify a refusal. But this would only apply to Canadian companies. What about foreign companies? Individuals or activist organizations can't exert any pressure on a company situated outside of Canada. I don't have an answer to that one.
Another problem for patients trying to access some treatments is cost. Canadian companies can't charge for drugs released for compassionate access, but foreign companies can. People have to pay up to $1,000 for a month's supply of a drug called Thymesin.
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Ottawa must send a clear message to companies that there will be an increased demand for drugs, especially in treatment for AIDS. Companies willing to invest money to take a drug into a phase 3 trial need to increase their manufacturing capacity to meet the compassionate demands.
I believe well-informed patients would be only too happy to sign releases so that companies wouldn't be liable. Patients are aware and there are no other options.
A government body such as a bureau for human prescription drugs could facilitate the waiver of responsibility with companies for compassionate release. The demand is only going to increase as more drugs for HIV treatment are fast-tracked, and people with other catastrophic diseases are borrowing tactics from AIDS activists to ensure that they too can access drugs for compassionate release.
The Chairman: Thank you very much, Ms Grondin.
Monsieur Ménard.
[Translation]
Mr. Ménard: I'm a bit concerned, because the participants in the first group spoke out very clearly, but their comments were significantly moderated by the second group of participants.
I will start by asking two general questions. Am I to understand that there are three types of considerations in your reservations as to how the members of the committee should examine the issue of experimental drugs?
The first was addressed by Lise Pinault, who talked about bureaucratic considerations. I think that you and Dr. Logue are more open in that respect. You even told us that there were pharmaceutical companies that refused to participate in clinical trials if compassionate access is mandatory. You have quite clearly illustrated the bureaucratic reality involved. I wonder if this is not the aspect over which the committee has the most control. So the first type of consideration is bureaucratic.
There's a second type which is more worrisome for the committee, because I am not sure we have much control over it as parliamentarians. These are the issues relating to ethics and professional liability.
However, I cannot help wondering, as all three of you asked the same question: at what point is the doctor in a position to authorize participation in clinical research? I think that the response came unanimously from the other side.
When a person is infected, when a person is ill, when a person's life is being foreshortened, I feel that the decision must be up to that person. We must go on the assumption that when an individual - this does not call into question the issue of informed consent - is aware and wants to use an experimental drug, we have to go in that direction. It would perhaps be interesting for you to tell us if there are any "corporate" concerns, and I use this word for lack of a better term, because some physicians among you fear being exposed to subsequent legal action.
The Canadian Clinical Trials Network appeared before us as a committee and explained that during its short existence, 40 clinical trials had been conducted. It would be interesting to know what impact these 40 clinical trials had on the individuals involved.
The second-last witness referred to a drug which, after being used, had lethal consequences. In this case as well, it would be interesting to have more information on what that means in terms of past experience. That's the first area where I have a lot of questions.
I will conclude, because I feel you're getting a bit impatient, but it would be useful for the committee to have the information. In addition, it was Dr. Logue who referred to the costs of conducting clinical research for a pharmaceutical company. If I understood correctly, as we speak, data relating to the safety or the toxicity of a drug is easily accessible, and we could compare these data.
What problems do you see or what apprehensions do you have internally regarding the collection of information by pharmaceutical companies?
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Mind you, later on in this session, we will have the opportunity to ask the same question of Dr. Levy and his team.
[English]
The Chairman: Dr. Logue, do you want to answer his second question?
Dr. Logue: Yes. First of all, I'm having trouble sorting out a specific question because you've brought up a number of issues.
I think you mentioned earlier that I was commenting that some pharmaceutical companies refuse to carry on compassionate programs because of fear of either cost or inhibiting a given clinical trial. I think that's a very legitimate concern, but as Dr. Tsoukas has pointed out, there is a strong argument for the pharmaceutical companies to do that. In fact, a number of them have demonstrated a very strong willingness and a strong participation to do that in Canada, and I think both the 3TC and the saquinavir compassionate programs are examples of that.
I think what we need to be careful of is implementing a wide access that does inhibit ongoing clinical research for drugs that are earlier on...with little proven clinical benefit.
I think, again, we're getting into the difficult position of what is proven treatment or potential treatment versus what is completely experimental and unproven. As I stated in my address, I think drugs that have shown very strongly in preliminary studies to be safe and efficacious should be released compassionately and there should be wide compassionate programs.
I also agree with Dr. Tsoukas that release of programs individually through EDRP does not serve anyone. Large open-access programs enable us to collect safety data that otherwise we would not be able to collect. If we do collect any efficacy data from it, it's a benefit, but that's certainly not one of the roles of the compassionate access.
The Chairman: Thank you.
Dr. Logue: I don't know if I answered your last question.
The Chairman: Dr. Tsoukas, how about the first question?
[Translation]
Dr. Tsoukas: I do not think there is any difference between the legal liability of physicians who treat patients as part of a clinical trial and the liability of those who treat patients under another compassionate program. The physician and the pharmaceutical companies always have the same individual liability. So from a legal perspective, having a program or not will not change anything: the physician is always legally liable for care provided to patients.
Mr. Ménard: If someone dies as the result of an authorization issued by a physician, the physician is not liable in the corporate sense of the term and it does not expose him to legal action. For example, if one of your patients says that he wants to take a drug that has not been tested or approved in Canada and in the end he dies, as in the case you referred to in your presentation, that does not expose you, as a medical body, to possible legal action.
Dr. Tsoukas: There may be a difference with respect to the judgment of one body as compared to another, however the fact remains that the patient is entitled to launch legal proceedings. If we use the drugs that are currently on the market and that have been approved by the HPB, there are fewer risks. But there are always risks when we use higher dosages of an approved drug or a drug that has not been proven effective.
The Chairman: Thank you.
[English]
Mr. Jackson.
Mr. Jackson (Bruce - Grey): Thank you very much, Mr. Chairman. I have one comment and then I have two questions.
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It's very interesting to sit here as a government member and listen to the classic discussion where you have people asking for government intervention. On the one hand, you have desperate people who are ailing from a disease and really would like a cure, and I'm sure we'd all like to do that and ask for as many resources as we can put at it. On the other hand, we have the physicians and the pharmaceutical people telling us that there are cautions and there are routine things that you have to do. One of the doctors asked whose neck is going to be on the line when the drug is used and somebody gets killed, and that's usually the government's. I think it should be the doctor's or the pharmaceutical's, not ours.
We spend a lot of money sometimes, and it's usually the lawyers one way or the other who get that money, whether it's the doctors who are sued or the pharmaceuticals.
Right now we have the Krever inquiry. It usually ends up on our lap. A lot of those resources should actually be going towards trying to find cures for the drugs...or from that department.
So we have to approach this with caution and we have to make sure we do the right thing and the trials have procedures and so on, and I think it's well-documented by the medical profession represented here today.
I think education is extremely important. We heard that from people who are sick and they're saying to us that in some cases they live in rural areas where the information isn't there. We also know the information could be available through the Internet, through various sources and in their focus groups, and I think this is something that's lacking. They should have global communication with regard to where all the experiments are taking place, what kinds of drugs are available, what the side effects are of these drugs, what are the kinds of risks, and that information probably should get to the patients and the doctors.
I'd like to ask my first question. Is that an adequate educational program alone, or how could we help in making sure it gets across...? I think that's extremely important.
My second question has to do with the role of the government. Our resources are limited. We'd like to put in as much money as we can. Obviously, the Department of Health has a finite budget and part of the budget is placed into this category of the various kinds of diseases that were mentioned that are very hard to find a determinant in terms of curing them.
To that degree should it be outcome-based? Should it be the cure? Should it be the quality of life for the patients? Somebody mentioned algorithms, and I don't know if algorithms and outcomes are the same.
Dr. Tsoukas: Given the fact that the previous government and the current government have done everything in their power to destroy any progress that was ever made here in terms of therapies for AIDS, I think it is a sad fact that we are in desperate need now of programs that could have existed five years ago.
There is no funding for clinical trials operation in this country. The only funding comes from private pharmaceutical companies. It's totally inadequate.
I'm involved in the NIH process that reviews grants for the Clinical Trials Network in the U.S. We divide a budget of $330 million. I doubt very much that in the last five years we've even spent a hundredth of that amount in terms of clinical research on therapeutic drugs in this country in terms of operating costs. That does not exist. All we have is a Clinical Trials Network that is totally incapable of conducting research in this country because it cannot support the costs involved in doing drug trials.
So it's not a matter of education. It's a matter of putting some money to make these studies happen in Canada and to make available drugs for the average Canadian that cannot be done through the graces of pharmaceutical companies.
Mr. Jackson: The second question was what kind of yardstick should the government be using with regard to these resources. There are people, whether it's in research and development or what have you, who would take our funds and funnel it in all kinds of stuff. There probably would be no outcome. How do we measure them?
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Dr. Tsoukas: Mr. Chair, we have a system, and it's very easy to fund that system. As a point of fact, I'm the chairman of the subcommittee of the Canadian Clinical Trials Network on Vaccines and Immune Therapies. We currently have only one study that is being completed in terms of vaccines - one, and only one - and it is by a private pharmaceutical firm being funded by U.S. funds. We are a G-7 country that spends nothing in terms of vaccine development for HIV outside the private sector. We have to depend on companies in Canada such as Connaught, Pasteur, Mérieux to do the development. We do nothing in clinical development. The rest of the world depends on countries such as Canada to develop a vaccine to stop this epidemic. We have not spent a penny in that regard.
Mr. Jackson: I'm sorry, Doctor, but you have given me a political speech. I asked you about how you can measure the outcomes but you're telling me we don't have the resources. I heard you say that once, so you don't have to say it twice. If I'm going to give you any money, I want to know why I am giving you that money and how we are to measure it. That's what I'm asking you. I'm ignorant to that fact.
Dr. Tsoukas: We have a population that requires experimental therapies in this country. We have a substantial scientific base that can generate trials and studies that can be of benefit to citizens of this country. We have no money to carry out these studies. We have no money for this purpose. Even if we wanted to provide drugs from small pharmaceutical companies that may benefit one single individual, we have no mechanism by which this can be done through federal government resources.
Mr. Jackson: So we're back to money. I'm sorry, but you didn't answer my question.
The Chairman: Ms Fry.
Ms Fry (Vancouver Centre): Thank you very much, Mr. Chair. I just wanted to direct my question to Ms Pinault in regard to her written brief.
In recommendation 2, with regard to compassionate access, you've said that if the HPB is not provided with adequate information or the company does not show that it intends to provide reasonable compassionate access, there are two things that one could do. One would be to revoke any licence to market any therapy that the company holds in Canada. I wondered whether or not you felt this would have an impact on access to drugs by other people in Canada who may or may not be terminally ill, but who may in fact eventually die because they don't get treatment if you cut off the pipeline of treatment to other folks. Do you think that would happen?
[Translation]
Ms Pinault: No, I do not think that it is a risk, because I do not think that pharmaceutical companies would go that far. It is a threat, but I do not think that pharmaceutical companies would go as far as to refuse compassionate access and in so doing, risk losing their licence to market the product in Canada.
Pharmaceutical companies are in a position to offer compassionate access. It is a question of their willingness. For them to be very willing to do so, we have to help them a bit. The government has what it needs to help them.
[English]
The Chairman: Thank you.
We're going to pass now to PMAC, the Pharmaceutical Manufacturers Association of Canada. With us this evening is Dr. Sophia Fourie, vice-president of medical and regulatory affairs for Pharmacia and Upjohn, Inc.; Dr. Michael Levy, vice-president for medical science at Glaxo Wellcome; and Mr. William Milligan, vice-president of the biomedical business unit of Hoffmann-La Roche Limited.
I understand you're sharing your time. Who wants to speak, and are you speaking on behalf of the group?
Dr. Sophia Fourie (Representative, Pharmaceutical Manufacturers Association of Canada): Thank you very much for the invitation to participate today. We are indeed here on behalf of the Pharmaceutical Manufacturers Association of Canada. I would like to say we have not prepared a formal brief due to the short notice of this meeting, as we've already discussed with the chair.
I would also like to restate, as we did at the previous PMAC appearance before this committee, that the best kind of access is indeed provided through timely approval by the health protection branch so that the drug is indeed truly available.
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I would also like to state openly that we absolutely share with patients and physicians a desire to have life-saving and life-extending drugs available in the hands of physicians as soon as possible to treat their patients.
We would like to make strong representations for the continued streamlining of the drug approval process. We think that adequate resources absolutely must be provided toward this goal.
There are many possible ways to shorten the drug review process. For example, the use of external reviewers or of joint reviews with the FDA are certainly possible ways to shorten the review process. Conditional approval, which Dr. Tsoukas referred to earlier, is certainly another avenue to consider in Canada. We currently do not have this vehicle available. In the U.S. they do.
As referred to earlier by Ms Pinault, our companies do indeed have communications with patient groups and we do consult with them, but these ties certainly should be and must be strengthened so that we can come to a better understanding of each other's concerns and difficulties.
I'm also grateful for the acknowledgement that I have heard pertaining to the pharmaceutical industry and our compassionate outlook on having access to experimental therapies. The question of compassionate access is indeed fraught with many issues we have heard about this afternoon, which concern ethics, science and medicine as well as human compassion.
We look forward to learning as much as we can to ensure that appropriate balance of these important factors is achieved.
Thank you again for the opportunity to speak.
The Chairman: Thank you, Doctor.
Dr. Levy.
Dr. Michael Levy (Representative, Pharmaceutical Manufacturers Association of Canada): Thank you, Mr. Chair, for the opportunity to participate today in these round table discussions.
I'm here with Dr. Fourie and Mr. Milligan to represent the Pharmaceutical Manufacturers Association of Canada. In that capacity I'd like to take the opportunity to support all of the comments that Dr. Fourie has already made for us today. In particular, I'd like to echo her sentiment that we are all grateful for the opportunity to be here to listen and most importantly to learn from others about the role of compassionate access in meeting the needs of patients with catastrophic illnesses.
Today we are hearing about a number of issues regarding the compassionate access process in Canada, issues that I know we'll be discussing in more depth during tomorrow's session.
However, I think it would remiss of me not to mention that there have been a number of successes here in Canada. For example, in my roles as vice-president of medical sciences and chief medical officer at Glaxo Wellcome, I've had the privilege over the past few years of supporting the team conducting the clinical research to determine the safety and efficacy of 3TC, which is a new and novel anti-HIV therapy.
I'm proud to say that over the past few years about 2,900 people living with HIV/AIDS in Canada have been treated with 3TC prior to its approval. Most of these patients were treated through the compassionate access program while others received the drug through the clinical trial program itself. This is a very significant number when you consider that in total there are about 7,500 people receiving treatment for HIV/AIDS in Canada. I know that Mr. Milligan has other success stories that he'd like to share with us tonight.
Finally, I'd like to reiterate the remarks I made to this subcommittee in March of last year: the best access to new drugs is achieved by means of a speedy and efficient drug approval system. By its very nature emergency drug release is only meant as a stopgap measure and not as a substitute for making drugs available through the ordinary channels.
Mr. Chair, thank you very much. I look forward to the round table discussion tomorrow.
The Chairman: Mr. Milligan.
Mr. William Milligan (Representative, Pharmaceutical Manufacturers Association of Canada): Thanks, Dr. Levy. In addition to Dr. Levy's comments and Dr. Fourie's comments, I'm here to comment on some other success stories when it comes to compassionate access to investigational drugs.
A lot of the issues related to investigational drug release prior to approval have already been covered by some of the medical presenters and by my colleagues. However, at this time there are three compassionate programs that have been announced for the newest entry into the treatment-of-HIV market, and again those are the protease inhibitors that were referred to by our medical colleagues. There have been announcements by all three companies that manufacture these protease inhibitors that they will have compassionate access programs. Hoffmann-La Roche, Merck Frosst and Abbott have all provided information relating to saquinavir, indinavir and ritonavir compassionate access programs respectively. Saquinavir has been made available to about 4,000 patients worldwide and has been made available here in Canada. Most recently, there was an announcement made today to over 400 patients.
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Saquinavir is a member of the new class of antiretroviral agents. It blocks the activity of proteinase, an enzyme critical to the replication of HIV, the virus that causes AIDS. In vitro studies show it is effective. In vivo, the clinical phase 3 trials are still in progress. Clinical trials have shown improvements in the number of circulating CD4s - you know these as surrogate markers - although endpoint survival data are not available at this point.
The saquinavir compassionate access program was developed as part of an international compassionate access program and it was developed in close collaboration with the AIDS community and AIDS-treating physicians, as well as through the CTN. It will initially be used in a tiered system for the people most in need because of the issues we heard about earlier pertaining to the availability of the drug. An equal chance selection system is employed only when the quantity of drug is not sufficient for the number of patients in the given tier.
As additional saquinavir has become available over the last few months, the eight-person committee, including CTN, patients and treating physicians, has increased the number of patients who would have access to saquinavir. Very soon, perhaps this week, in the United States saquinavir may receive approval from the FDA. This will again create some urgency with the Canadian regulatory authorities to try to make the product available to Canadian patients on a broader basis.
Abbott has announced this week the global compassionate provision of ritonavir, and there will be more details to follow shortly. In addition, Merck Frosst has announced that a global compassionate access program is being developed right now for indinavir, and details on that will also be announced in the near future.
As Dr. Tsoukas alluded to earlier, there are questions about resistance, sequence and the point about algorithms as to when to use these drugs. Do they create problems for other drugs? Do they prevent additional opportunities for treatment for the drug? A lot of these are still question marks and they add to the complexity of some of the discussions we've been having.
Thank you for your opportunity to comment on these programs.
The Chairman: Thank you, Mr. Milligan.
[Translation]
Mr. Ménard: Mr. Chairman, you have allowed time to be used very liberally. I hope that we will have as much dialogue as possible.
I have three questions and one comment. First of all, I hope that by the end of our work, we will have gotten to know one another. I also hope that the people from PMAC will be convinced of the merit of compassionate access, since they started off by telling us that the best access was approval, and I agree with that, but if the compassionate access program is inevitable, in their view, what is the ideal form for it?
It would also be interesting to have additional information on the three suggestions made by the first speaker in order to improve the approval process. I think that it should be in the form of a written document, if they have the necessary expertise, because they have made three innovative suggestions that none of the witnesses made during our parliamentary work.
The three suggestions are as follows: first, use external assessments; second, conduct a joint review with the FDA; third, provide conditional approval.
My third question is much more nosy, but I will ask it anyway, because I am somewhat impudent. Would it be possible to find out how much profit pharmaceutical companies under PMAC have made? I ask this while paying homage to Dr. Levy, who is before our committee for the second time. I will always remember how proud he was when Brian Farlinger displayed a document in which he stressed the wonderful work accomplished by the pharmaceutical company Dr. Levy represents.
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However, this must not prevent us from remembering that between the time you appeared and now, 3TC has been commercialized in the United States, but not in Canada.
Those are my questions. I would like us to go on the assumption that the approval process must be improved. But when we weigh the pros and cons, we must also accept that the committee must make a very strong recommendation on the inevitability of compassionate access.
The Chairman: Was your question for Dr. Levy?
Mr. Ménard: It was for whoever wanted to respond. We can save the question on profits for the end.
The Chairman: You will not get an answer on the profits.
[English]
Dr. Fourie: I will respond first to what I think was a question about the three suggestions. Pardon my inability to address you in French. Even though I have a French name, I've lost the ability to use the language.
I would like to say these initiatives are not new and novel. They are certainly there, and although they have not been used specifically in the AIDS area as much, they have been used in other areas such as joint reviews, external reviews and more importantly the issue of adequate resources at the health protection branch.
If you look at the process and the improvements made since the Gagnon report, I think there is still room for improvement. And unfortunately, we are again back to resources and we are back to money. I think with very limited resources the HPB is doing the best job they can at the moment.
Certainly resources are constrained. One can look at the process of how drugs are evaluated, especially in the AIDS area. Companies are coming forward with breakthrough drugs and with significant advances and asking for priority review. When this happens it really absorbs a lot of local resources and reviewer time at the HPB. We need adequate exploitation of true joint review ability, where you really are saving time because part of a review would be done by the FDA and you would capitalize on this. We need adequate exploration of this avenue. We need to look critically at the resources actually in the HPB right now. We need to seriously consider the external review process and what can be gained from experts in this field. We need to employ them also in the review process.
I think without seriously looking at all of these things, the expedited reviews will not be as significant as they could be.
I will pass your second question to Dr. Levy.
Dr. Levy: Mr. Ménard, you've asked me specifically about the profits of the pharmaceutical industry. I think you were focusing on HIV/AIDS. I have to say you've caught me a bit by surprise because I came here today prepared to speak about compassionate use and about making drugs available to people living with HIV/AIDS and other people with catastrophic illnesses.
I have to confess I am more expert in the drug research and development process than I am with the commercial side of the business. But I'll take your question to heart. I will endeavour to check with my commercial colleagues and get back to you with an answer.
The other thing I should say, of course, is this kind of information is not shared among companies within PMAC. It is proprietary information held confidentially. I doubt there is anyone within a particular company who is in a position to speak of the profits or the profitability of the different companies in our organization.
One comment I could make, though, is I've had the opportunity to participate in the national AIDS forum planning committee over the past few months. At our last session a few weeks ago here in Ottawa we did some calculations on the back of an envelope to look at how big the HIV/AIDS market is in Canada. We discussed the common misconception that this is a very large market or a very lucrative market for pharmaceutical companies. Our very rough back-of-the-envelope calculations, which I think are probably generally correct, were that the HIV/AIDS market makes up less than 1% of the total pharmaceutical market in this country. So you'll see that it's not a very large market, and companies do research in this area because of their duty to do so, rather than because of the expectations of huge profits.
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I think it's also worth mentioning at this stage that - of course, I know you are aware because you are expert in this area - the drug research and development process is very lengthy and very expensive. A recent study by Tufts University showed that it cost about $270 million, on average, to develop a new drug.
The process is also very risky. It's a commonly stated fact that of all the new molecules tested, only one in 10,000 actually ever gets to the marketplace.
So when you consider all this information, you realize that the pharmaceutical company has a lot of investment to make in the R and D process to bring a new drug to the patients and people living with HIV/AIDS who need these new drugs, but it is not particularly a very profitable business.
The Chairman: Rose-Marie.
Mrs. Ur: Thank you, Mr. Chairman.
A few quick questions. When a pharmaceutical company receives a compassionate access request, what are the criteria they use in applying for the decision-making on it? Does compassionate access pose public relations advantages or disadvantages to the manufacturers?
We've heard from various presenters here this afternoon and this evening who are suffering from various diseases. How do you put priorities, or do you have priorities, within the manufacturing of drugs? Is there a push for one area, or do you have specifics?
Dr. Fourie: I'll take a stab at it and then my colleagues can join in.
I think the general statement I can make is that pharmaceutical companies in today's environment are really focused on getting their drugs to the market as quickly as possible. In an effort to do that, obviously, in the first definition of your development strategy, right there would be the issue of expanded access and at which point to consider this. I think this prominently features in all of the development plans.
There are various avenues that you could go down. You could, for instance, decide that you want to throw all your resources.... We heard it takes about $270 million in total to develop a drug. So when I'm talking about resources, I am talking about development money, resources, and people put toward a program that would get you to the market the soonest, so that indeed physicians can have the drug in their hands to treat their patients.
Many times, that means you curtail the phase 2 program. You compress it quite a bit. So you have the bare minimum of the safety and effect data that would allow you to go into registration studies.
You would then put up one registration study. Two studies, if you intend to register in the U.S., are still mandated. You would really focus on doing those studies well and setting up tight criteria, because you do not have a broad safety base. You would be doing a lot in your registration studies in the way of safety monitoring and exploring other efficacy effects that by rights you would have had if you had done a conventional, which is what we call phase 2, program, before you embark into phase 3, which is the registration studies.
You compress that. You do bare minimum safety and effects data. You get into registration trials. Then you file, hopefully, with a breakthrough drug, now being able to ask for priority review. That, in a very brief summary, would be the way in which you would proceed.
At which time do you put in expanded access? I think this would certainly depend on decisions regarding the trials you're running and the competition for patient numbers and patients who would be entering your studies. The idea is to do the studies, get the patients in, analyse the data, and file. Obviously, you don't want to interfere at any point there in jeopardizing your studies.
The other issue is that at some point you will reach a point at which you will have adequate safety data that would indeed allow you to make an estimation of risk benefit, at which point an expanded access program would become justifiable. We want to be sure that we do indeed balance the safety profile versus the effects that can reasonably be expected to benefit the patient. You don't have a large enough safety basis right up front to do that. So I think if I have to generalize across companies, it's really the two factors that would be driving those decisions.
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The Chairman: Thank you.
Mr. Milligan: Could I take the question on how you have patients enrolled in compassionate trials? I'll just give some feedback relating to the saquinavir compassionate access trial that's been running since June of this year.
There's an eight-person committee developing the plan for making the drug available on compassionate bases. The committee consists of one infectious disease specialist, one general practitioner, a medical ethicist, a non-medical representative of the Canadian HIV Trials Network and four HIV-positive individuals. The four individuals representing the HIV-positive community at large are also affiliated with large AIDS community organizations.
There are also two representatives of Hoffmann-La Roche who sit on that committee and they're responsible for running the compassionate access program and identifying individuals for compassionate use.
[Translation]
Mr. Ménard: As you may recall, when we heard from Catherine Hankins of the Canadian Association for HIV Research, whom you hold in high esteem, unless I am mistaken, and the Canadian Clinical Trials Network, as well as the Canadian Public Health Association, we were under the impression that pharmaceutical research was conducted in Canada or abroad by large companies; at least that's what I remember.
Earlier, in listening to the panel of physicians, I got the feeling that there were difficulties that could arise for pharmaceutical companies. The small size of some of them was mentioned. Are there apprehensions? Should the members of the committee pay particular attention to the possibility of making compassionate access mandatory for small pharmaceutical companies which are renowned for their research?
I apologize if my question concerning profits bothered any of the panelists. But Dr. Levy knows how terribly predictable I am becoming with age. I could perhaps tell him right away that I am going to ask him the same question tomorrow.
[English]
Dr. Fourie: Again, I'll take a stab at this. I'm not sure exactly which examples are being referred to. I can again make a general statement: usually small companies would tend to partner and team up with bigger companies. In this day and age of joint ventures and of mergers, I do not see that being a small company with a really exciting and advanced potential treatment.... You would be stuck and not able to do research.
I think if you have something that you can put on the table based even on pre-clinical data that would point toward a promising outcome, the partners would be there to assist you. Again, I'm making a general comment. I'm talking about the private sector. There may be specific examples that I'm not taking into account. Again, I think of the 3TC example. Michael can say a few words about that, but 3TC is a Canadian discovery, a success story. So where are we today with this drug? Maybe he can just take us briefly through this history of that. I think that may illustrate what I'm trying to say.
Dr. Levy: I think Dr. Fourie makes a good point. Currently there's good synergy among all of the interested parties in terms of doing HIV/AIDS research to bring new drugs to the people who need them. There's synergy among the community, the physicians and, I hope, the pharmaceutical companies and the regulators, and even the members of Parliament here today.
But to answer your question in particular, there has always been good synergy between the small research boutiques, as we call them, and the larger multinational pharmaceutical firms. It's a synergy that works very well. The small research boutiques have a need to access the expertise and the resources to develop their drugs and to bring them forward to the marketplace. And, of course, the larger companies are always looking for the opportunity to support good and novel ideas.
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I think the case of BioChem Pharma in Montreal and Glaxo Wellcome, originally Glaxo, are ideal examples. BioChem is a true Canadian success story. They started off 10 years ago with a small number of employees. Today they have over 1,000 employees and a large part of their success is predicated on their partnership with Glaxo Wellcome to develop 3TC. There was good sharing of individual expertise to make sure this drug was available for the people who needed it, and at the same time the partnership puts Canada in the limelight for contributing to this disease on an international basis.
The Chairman: Dr. Tsoukas, do you want to answer?
Dr. Tsoukas: Actually, I want to ask a question, because this is an issue that comes up very frequently. It's wonderful to be proud of the success story of one particular company that has developed a drug. Unfortunately, one of the problems we have with drug development in this country is as soon as there is some potential for some firm to develop a particular product here, the development potential leaves this country until the drug gets into phase 2 and 3 studies.
One of the big problems I think we face here is we do not have a history of developing drugs in phase 1 studies. What can the Canadian pharmaceutical industry do to foster these types of approaches for newer drugs developed in this country in the pre-clinical stage?
The Chairman: Go ahead, Dr. Levy.
Dr. Levy: In fact, you'll be pleased to know some of the phase 1 work with 3TC was done here in Canada. It wasn't all done abroad. As you know, the number of patients involved in phase 1 trials is very small. Typically the trials consist of perhaps 12 to 24 volunteers. The phase 2 trials are much larger, involving hundreds of people, and the phase 3 trials involve thousands of people.
So there is really very small opportunity for any particular country to participate heavily in phase 1 trials. But specifically in the case of 3TC, there was some involvement in Canada.
I think, though, one thing we could do as a country is improve the regulations to make it easier to do these trials in Canada. Currently Canada has some of the most rigorous regulations in the world, if not the most rigorous, in terms of beginning new drug trials. This means lengthy delays and lengthy submissions to the government in order to begin this kind of research in Canada, which make it very unattractive to the pharmaceutical manufacturers, who have the opportunity to conduct it in other countries where the government is more supportive of doing early phase research.
The Chairman: Do you have a short comment, Dr. Fourie?
Dr. Fourie: I absolutely endorse what Dr. Levy is saying, having had personal experience. I think what you have to know is in other areas as well but in the phase 1 area in particular there are people out there in Europe and elsewhere who make it their business to do phase 1 work. They're set up. They have the units. Their drug regulatory process is such that you can virtually go in and do your study.
In fact, this happened to us early on in the development of our drug. I was given the opportunity to try to place a phase 1 study in Canada. I hunted around until I found the unit that could accommodate it. This was unfortunately going to have to be an in-house, in-hospital phase 1 study. We needed a unit of 12 to 18 beds, and there were several things complicating the study. Anyway, by the time I identified the unit that could accommodate this and we were ready to file, I was notified Spain already had their approval ready and you could just walk in there and do it. So we lost out.
I think really we have to look at the paperwork, at the process, at what is required and how we can speed this up. I absolutely agree with you. We have top-notch expertise and yet we do not have the volume of phase 1 work we should have in Canada.
Mr. Milligan: I will just add an additional comment, if I may.
We've had a history in Canada where the vision has not been to create a country supporting basic research. I think there's been a motivation from the medical community and the academic community. However, in an environment of compulsory licensing for almost 18 years, it's understandable companies looking at markets for opportunities for continued growth and development chose other countries to develop the necessary infrastructure.
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I'll take a Roche example. In the United States, there are centres of excellence for many of the diseases we're talking about today. The reason these centres of excellence have developed there, many of them with talented Canadians who have gone south to join those organizations, is a result of the environment we've had here in the pharmaceutical industry for the last two decades.
The Chairman: Thank you. Last question, Dr. Logue.
Dr. Logue: I just wanted to make two comments. The first was I would like to underscore some of Dr. Tsoukas' comments. After hearing the pharmaceutical representatives discuss the compassionate access programs now existing in Canada, and the benefits of them, I certainly applaud this and am appreciative of it.
However, I think one of Dr. Tsoukas' points was compassionate access programs of a marginally effective, ineffective, possibly ineffective or yet to be proven effective drug are not replacements for a trial for rapid approval of a drug that is effective.
Following up on the discussion of 3TC, 3TC is now licensed in America. It has very strong demonstrated clinical benefit. There is much discussion around the initiation and the Canadian content in research for this drug, yet today it is approved in the United States and not in Canada.
I access the drug through a compassionate program administered by Glaxo Wellcome in the United States. I think it would be interesting for the committee members to perhaps pose a question to the pharmaceutical representatives. Would it not have been a speedier access for my patients for this drug had there been in place some of the recommendations you and Dr. Tsoukas have made regarding approval of the drug? By this I mean a a joint review with HPB and FDA in the United States, or a contingent approval.
Dr. Levy: I think you are absolutely right about the most important thing being to make sure we have the speediest and most efficient approval process possible in Canada in order to ensure there is good access to the important new drug discoveries.
In the case of 3TC in particular, though, we're very pleased with the collaboration we've had with the health protection branch. Approval of the drug for general use in Canada is imminent. If in fact this comes about as we hope, the HPB will have reviewed and approved the drug in about five months, which is a record for them under the fast-track system they put in place.
I think when you look at the resources available to a very large bureaucracy like the FDA, and you look at the limited resources available to a comparatively small bureaucracy like the HPB, we have to be impressed and pleased they've been able to go through essentially the same amount of documentation and the same amount of material to bring about this approval. The fact it is approved a couple of days or even a couple of weeks earlier in one country or the other isn't all that significant. I think this is one case where we can be proud of the efforts they've made.
Dr. Logue: May I be permitted to make one further comment. I don't think a short time period is that significant. But at the same time, if I were a patient I would be interested. If the framework of drug approval and drug development is multinational, if the existing studies for 3TC are multinational and conducted in the States and Canada and elsewhere, and if the information from those studies and the scientific data are being presented to two regulatory bodies simultaneously, why would I as a patient in Canada not expect as expedient an approval process as south of the border? It is the same information. Why would I not expect, as a patient or consumer, that we would do everything possible to ensure there would be joint communication in the multinational study to allow for quick approval?
The Chairman: Mr. Milligan.
Mr. Milligan: I think it's an excellent question. Dr. Tsoukas alluded to two examples where we were very effective in having parallel reviews with ddI and ddC about two and a half years ago. I believe they did hit the market per se in both countries in the same week. So there are success stories in our history. As to why we haven't been able to achieve this more recently, it's a question mark.
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[Translation]
The Chairman: Thank you very much for participating in this long half-day session. I would like to thank all of the panelists and the people who came to meet the members of the Sub-committee on HIV/AIDS.
We are going to resume our work tomorrow morning at 9:00 a.m., in Room 253-D. I wish you all a safe trip back and a good evening. Thank you very much.
The meeting is adjourned.