[Recorded by Electronic Apparatus]
Wednesday, December 13, 1995
.1532 
[Translation]
The Chairman: Good afternoon, ladies and gentlemen. Welcome to this third Round Table on Compassionate Access to Experimental Drugs. Our subject for today will be ethics and the law.
It is my pleasure, as Chairman of the Sub-committee on IHV/AIDS and on behalf of all members, to welcome you all to this National Round Table on Compassionate Access to Experimental Drugs.
[English]
The round table started last week. During the first session held on Wednesday, December 6, we discussed the particular needs of the catastrophically ill with respect to compassionate access to experimental drugs.
The second session was held on December 7 and dealt with the possible impact of compassionate access and the drugs evaluation and approval process as well as with the results of clinical trials.
[Translation]
We will proceed today with the third session of this round table and we will be dealing with concerns relating to ethics and the law. We are looking at several issues. For example, what would be the implications in the area of legal liability if the government were to legislate some form of compassionate access? Are pharmaceutical companies ethically obligated to allow compassionate access to their drugs by the catastrophically ill? Is written consent of patients sufficient to protect the government, medical practitioners, clinicians and drug companies against legal action?
Do patients who signed an informed consent form have legal obligations?
[English]
Our intention today is to proceed as follows. First, all participants of groups will be given five minutes to a maximum of ten minutes to present their views on the issue depending on the group. Then the members of the subcommittee will have an opportunity to ask their questions. Finally, there will be a round table discussion involving both members and participants.
[Translation]
Before we begin, I want to thank all of you for appearing before us this afternoon. I want to mention that the bells will start ringing at 5 p.m. There will be a vote in the House at 5:15 and we will have to leave here around 5:05. But we will be back after the vote.
Before giving the floor to our first witness, Mr. Ménard wants to move a motion.
Mr. Ménard (Hochelaga-Maisonneuve): I have two motions, Mr. Chairman, one of which I gave to the clerk, dealing with the Summit on Research, which I would like to have translated and to be considered tomorrow. I also have a second motion that I would like to read and move now.
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I move that the Sub-committee on HIV/AIDS send its most sincere congratulations to the pharmaceutical companies Glaxo Wellcome and Biochem Pharma for their discovery and distribution of the drug 3TC. I move that the committee express its congratulations to these companies which have always shown a great interest for people with HIV/AIDS.
Mr. Chairman, you will realize that this is quite in line with our subject of today.
The Chairman: Thank you.
Our first witness this afternoon will discuss legal liability. Mr. Mario Simard, from Justice Canada, is Senior Legal Counsel, Legal Services, at Health Canada.
Mr. Simard, please.
Mr. Mario Simard (Justice Canada, Senior Legal Counsel, Legal Services, Health Canada): Thank you. I have prepared a two page written summary of my presentation today.
[English]
My presentation will be very short. I've been asked to limit it to five minutes. I've divided it into two parts. In the first part I'm going to try to give you a summary of the general principles applicable with regard to crown liability. In the second part, with you, I will look at the provisions that are currently under the Food and Drugs Act with a view to determining what is the duty of care that is imposed upon government.
[Translation]
Regarding the general principles of Crown liability, it is a well established principle under the Crown Liability Act that the government is responsible for the wrongs of its agents. For our purposes here, elements of negligence that would have to be proven for the government to be held liable are of two kinds.
It would have to be shown that the government had a statutory duty of care. Therefore, to establish whether there is a duty of care, one needs to read the relevant act or regulation in order to determine the nature of the government's duty. One needs also to look whether there is a relation of proximity between the government and the person harmed, in order to determine whether it was reasonably foreseeable that failure to meet the obligation could cause injury to that person. This will allow to establish what duty of care the government carries. I will get back to this in the second part of my presentation.
The second element of negligence requires to show that the government failed to exercise due diligence in its operations. I should emphasize that the government is not a public insurer. The government does not insure the public against any damage but it has a duty to take reasonable steps to protect the public when such a duty is imposed by statute.
The following comments are of an incidental nature but will shed some light, I think, on some of the issues raised in the letter of invitation sent to the Department of Justice. First of all, I should stress that the government cannot be held liable for the exercise of a legislative or adjudicative authority.
For example, the making of a regulation does not result in a Crown liability. In the same way, policy decisions involving allocation of resources according to social needs, policy orientations and economic means will not be reviewed by the courts.
In your letter of invitation you asked if it is possible to immunize the government against any liability. Yes, it is possible. Since the liability of the Crown is based on the Crown Liability Act, Parliament could, by legislation, declare that the government cannot be held liable in a given area.
However, I should add that the courts tend to interpret such provisions in a restrictive way and to look for loopholes in order to hold the government liable. The trend also seems to be to make the government more and more accountable for its actions, rather than the reverse.
But to immunize the government in such a way, Parliament must pass a legislation. It cannot be done by regulation. You asked if the consent of the victim could contribute to immunize the government. Theoretically, the answer is yes.
But the problem for Health Canada in this regard is that for consent to have any worth, it needs to be given in a valid fashion, and to be validly given the person who signs needs to have all the information required to assess the risk. You need to show that the person was in an intellectual and emotional position to give valid consent.
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But Health Canada is not there when consent is given since the doctor is alone with the patient at that time. Therefore, Health Canada has no means to verify the validity of the consent.
[English]
Having established the general principles, which as you can see are pretty simple and pretty straightforward, let's look now at what the food and drug regulations say with a view to determining what the duty of care is that is imposed upon government. I've divided it into three parts.
First, I've looked at the duty of care in the situation where there is a submission for a notice of compliance for a new drug. In that case, the government is responsible for anything having to do with the safety and the efficacy of the product. In other words, the minister must satisfy herself that the product is safe or must at least take reasonable steps to ensure that.
If you look at pre-clinical submissions you realize that the duty of care is much more limited. I've listed here in a summary fashion what the department is asked to look at.
Nowhere is the minister asked to satisfy herself about the safety of the drug. The department has to look at the composition of the drug, the protocols for research, and the manufacturing process to make sure the drug will be used for clinical trials only, but the extent of the duty of care is much more limited than it is with a straight application for notice of compliance.
As for emergency drug release, when the government is asked to authorize the use of a drug for emergency treatment, you realize that the responsibility of the government, the duty of care, is even more limited because in that case we have to establish that there is a patient-practitioner relationship, that there is a medical emergency, and, based on the data provided by the practitioner, that the product is safe and efficacious - and I insist on repeating the fact that this is based on the data provided by the practitioner. We also have to look at what institutions will use the product and we have to ensure that there will be proper reporting of adverse reactions and so forth.
In conclusion, I will say that it is basically the legislation that determines what duty of care is imposed on government and consequently what the potential for liability is. Also, in the case of emergency drug release, as it stands now the potential is relatively limited compared to other functions that the government exercises.
On that note I will terminate my presentation. If you have any questions, I will be glad to answer them.
[Translation]
The Chairman: Questions will be asked at the end of this first part of the round table.
[English]
Now we have Dr. Sophia Fourie, the vice-president of medical and regulatory affairs from Pharmacea and Upjohn, and Dr. Michael Levy, vice-president, medical sciences, Glaxo Wellcome.
Dr. Sophia Fourie (Vice-President, Medical and Regulatory Affairs, Pharmcea Uphohn Inc., Pharmaceutical Manufacturers' Association of Canada): Good afternoon, Mr. Chair. Thank you for this opportunity. We have divided our comments. I will deliver a few comments on the legal liability issue and then Dr. Levy will talk about some of the ethical aspects.
We first need to look at liability of three parties - the government, the physician and the manufacturer - and at the responsibility of the patient. The purpose of HPB approval under the revamped emergency drug release procedure, the newly proposed special access program, is strictly limited to providing the legal vehicle to release experimental drugs prior to approval.
HPB approval under the SAP is not based on the assessment of safety, risk or possible clinical benefit and the government makes no recommendations for it. Manufacturers cannot delegate or distance themselves from liability for the use of their products. Under the current system, the patient always has the right to sue the physician, the institution or the manufacturer.
With specific reference to early access to experimental drugs, the onus remains on the manufacturer to assess all available information on the drug with the aim of reaching a level of assurance that indeed no harm will be done and that there is a reasonable expectation of net benefit to the patient. The issue is that patients and physicians may desire access to a drug before this information is available, and even before basic scientific questions are answered, such as dosing schedule.
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It might be possible to provide legal options that would delineate liability of manufacturers in the setting of early release of experimental drugs. These options do not currently exist and they should be explored before implementing a new system.
Research on human subjects is guided by international and local rules on the ethical conduct of investigations; for example, the Helsinki code, FDA, HPB, and MRC guidelines. Full disclosure of information on known and potential risks and benefits must be provided so indeed the patient can make an informed decision on exposure to the drug. This provides protection for patients, physicians, and manufacturers. The duty of disclosure is indeed higher in the case of research than in medical treatment.
The current system is based on informed consent and signing informed consent forms. The issues are summarized as follows. First, there may be insufficient information to provide to the patient for the patient indeed to give informed consent. Informed consent even under optimum conditions does not provide protection from lawsuits for a physician or a manufacturer.
In summary, the underlying legal framework, in particular the liability issues, must be addressed by the government before responsibility is delegated to physicians and manufacturers.
The Chairman: Thank you, Dr. Fourie.
Dr. Michael Levy, please.
Dr. Michael Levy (Vice-President, Medical Sciences, Glaxo Wellcome, Pharmaceutical Manufacturers' Association of Canada): I support the comments by Dr. Fourie. I'll reserve my comments until a later part, when we get to the topic of ethics.
The Chairman: Thank you.
We are going to pass to our next witness, from the McGill Centre for Medicine, Ethics and the Law, Mr. Trudo Lemmens.
Mr. Trudo Lemmens (Member, McGill Centre for Medicine, Ethics and the Law): I'm a researcher in law and bioethics at McGill University and also at Université de Montréal. I'm a member of the research ethics committee at the Montreal General Hospital.
I was invited to provide comments on the proposed policy as a member of the Canadian HIV-AIDS Legal Network. I must say, though, the members of the network did not discuss the drug release policy and have taken no official position on this issue. I'm solely responsible for the following remarks.
Debating the drug release policy is a very sensitive task. It involves careful consideration of several interests and values. First, we want to ensure catastrophically ill people receive the best treatment currently available. This could sometimes include giving them access to promising non-approved drugs.
Second, vulnerable individuals, such as those who are catastrophically ill, deserve at least as much protection against potential harm as others. The notion of consent should not be an excuse to allow exposure to whatever physical and financial harm. To say people with HIV and AIDS have nothing to lose is obviously incorrect.
Third, drug approval systems exist not only to protect individuals against harm. They also serve to ensure efficacy and safety and a positive risk-benefit ratio for a drug. This is of major importance for future patients who might need a drug and for the entire population, who pay for the use of drugs. Spending money on worthless or even harmful drugs is depriving patients of other care. Our resources are definitely limited.
I was asked to comment on the impact of the proposed policy on the liability of the HPB, pharmaceutical companies, and physicians who prescribe a non-approved drug. Although more research is needed on the subject, it seems to me legal liability is not the central issue. Solving legal liability is clearly not sufficient to create an ethically sound system.
Tort law aims at compensating people for damage resulting from breach of a duty of care. It does more than that. By creating a system of financial liability...people are also urged to act carefully toward others. The duty to inform patients of potential harm further obliges physicians and pharmaceutical companies to respect people's self-determination.
.1550
Under the proposed policy the duty of physicians to inform patients should resemble the researchers' duty towards research subjects. Warning them that the drugs are not approved, explicitly mentioning that HPB cannot guarantee the efficacy and safety of the drug, mentioning all the potential risks and so on might be sufficient to prevent serious liability claims. However, the system of liability law has not been considered sufficient to protect the interests of patients and the population at large.
A system of drug approval has been created, but we believe that the economic pressure to commercialize drugs quickly because of the desperation of people who are terminally ill, the sometimes naive belief of researchers and manufacturers in a new drug and so on might sometimes jeopardize the health of individuals.
While the deterrent aspect of liability claims might prevent some harm, appropriate protection requires a more a priori approach, especially when health is at stake. This is particularly true, I would say, for vulnerable populations who could easily be convinced to use a drug whatever the side effects and potential harm. People have a right to the best available treatment, but they also have to be protected against harm.
Moreover, drug approval also ensures that scientifically valid studies are conducted on the efficacy and safety of a drug. The conduct of these scientifically valid trials is of major importance for people with HIV and AIDS. We have to be careful that a policy, while offering only an appearance of immediate benefit, doesn't harm the entire HIV and AIDS population in the long run.
Therefore, I would simply say that the following issues might need further consideration. First is the issue of payment for non-approved drugs. Pharmaceutical companies should not use the system to introduce drugs before approval in order, for example, to recoup a part of the production costs.
Patient payment for non-approved drugs might have to be prohibited. This issue is also essential in the context of HIV and AIDS in order to avoid a two-tiered system of health care. We have always rejected this in Canada for obvious reasons of justice. Such a system would affect people who are already stigmatized in society, such as drug users with HIV and AIDS, who would be unlikely to be capable of paying for novel treatments. Drugs are either valuable and should be freely offered to all, or they are not.
A second point that would need further consideration is the procedure for emergency release. The protection of terminally ill patients and the interests of society require more safeguards for medical research, HPB counts and local research ethics boards to control the ethical and scientific validity of research. These research ethics boards consist of representatives of the community, such as physicians, nurses, lawyers, anesthetists and so on.
A similar system of approval for emergency drug release could be developed. The HIV and AIDS community should be involved in that. Individual patients should not be left to their own, sometimes desperate, decision-making but should be represented and assisted by people who understand their interests. The current means of communication would make it possible for physicians in isolated regions, for example, to obtain help from communities in urban centres.
These are only some of the issues that should be addressed in order to find a reasonable balance between the interests of the catastrophically ill and society at large. It should be clear that these interests are not necessarily conflicting. A basic control on the release of drugs is in the interests of both people with HIV and AIDS and the community at large.
Thank you.
[Translation]
The Chairman: Thank you very much, Mr. Lemmens. Since we have now heard all presentations dealing with legal liability, we will have a question period of about 15 minutes where questions will be asked by members of the sub-committee. Mr. Ménard, please.
Mr. Ménard: On a practical level, if Parliament were to legislate compassionate access for clinical purposes, what would be the duty of care of the government and the manufacturer in this specific instance, in your view? Would it mean that every time a research protocol of the Canadian HIV Trials Network would be submitted to the government, it would not be able to approve this protocol under the national strategy on AIDS or under some other policy unless the protocol includes compassionate access? This is the ideal situation we are aiming at.
If this were to become a legislative requirement, could you tell us how you would view the duty of care of each of the parties? By parties I mean the manufacturer of the drug and the government.
Mr. Simard: It is difficult to answer this question in the abstract. In essence, the duty of care will be determined by the requirements set out in the legislation. In my view this raises the problem of the obligation of companies to distribute the product.
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This scenario raises two issues in my mind. The first has to do with liability. If a company does not want to give access to a product but the government compels it to do so, if eventually the product causes harm, somebody will have to pay damages and you cannot hold the company liable if it dit not want to distribute the product. The liability of the government would potentially be increased in such a case. But it would always depend on how the legislation has been written and on the exact duties imposed on the government.
Mr. Ménard: But you understand this is precisely what we are discussing. Our thinking is based on the presentation of one of our first witnesses, from AIDS Action Now, who expressed what seemed at the time very radical views. He said that the government should never authorize protocols for clinical trials that do not include compassionate access.
Compassionate access means that a doctor who makes a request - since this is how the system presently works under the emergency drug release program - because he has reasons to believe that this might prolong the patient's life, will be able to obtain this experimental substance that is not yet considered to be a therapy.
The decision we have to make in this committee is whether to recommend to the government to make compassionate access compulsory as a condition of approving any research protocol.
But you are telling us that we should always have in mind that the voluntary or compulsory nature of the distribution of a drug by the manufacturer changes the level of liability. But you cannot tell us precisely what the level of liability would be if it were compulsory.
Mr. Simard: No, I can't, since I don't have a precise text in front of me. I have tried to show in my presentation that the level of responsibility would depend on the precise language of any legislation.
Mr. Ménard: Okay.
Mr. Simard: So, this raises a first issue regarding liability. I will raise another for which I have no answer. To compel a manufacturer to distribute a drug would require amending the Food and Drugs Act. Such an amendment would completely change the philosophy of this legislation. The Food and Drug Act comes under the criminal law powers of the federal Parliament since it aims at prohibiting the sale of products considered to be dangerous and establishes a regulatory scheme for controlling distribution of these products. This is part of criminal law.
If we start compelling companies to distribute information documents, are we still in the realm of criminal law? Are we still within federal jurisdiction or are we not stepping into the area of pharmaceutical or medical practice? I don't have the answer. We will need to look at this very closely before making an amendment.
Mr. Ménard: Indeed, we will have to determine the level of liability. You are making me aware of the difference between civil law and criminal law. Obviously, there is a difference in the burden of proof.
At the McGill Centre for Medicine, Ethics and the Law, about which I have been hearing for several months and which I intend to visit some day, how do you generally view the functioning of the emergency drug release program?
You probably know that changes are on the way, flowing out of the Gagnon Report, in order to facilitate more direct links between doctors and manufacturers and to try to give the government a less prominent role. What do you think of the program as it is presently set up? If you had the possibility to influence its reform, what would you recommend?
Mr. Lemmens: I will say it in English since I am a bit more proficient in this language.
[English]
In general, I've read the proposal for the new emergency drug release program. I don't think it's a bad idea to put more power in the hands of physicians to decide what the appropriate treatment should be and whether a new promising drug could indeed help people with HIV and AIDS.
.1600
At the same time, I think it might be dangerous not to involve other people in the scientific community and the community at large when those decisions have to be made. As I said in my proposal, maybe the use of research ethics committees and the system of approval through research ethics committees could be of a lot of assistance in such a new system.
I'm a little afraid that the system as it is proposed now would lay a very heavy burden on an individual physician to assess the scientific validity of new drugs and the efficacy and harm of new drugs.
[Translation]
Mr. Ménard: Mr. Chairman, have you seen the movie Médecins de coeur with Réjean Thomas? It is about a doctor concerned with ethics who's asking himself a lot of questions about the relationship between science and medicine. Would you have a short definition of ethics to propose?
[English]
Mr. Lemmens: It's a system of moral rules, I would say, upon which the community can agree that determines our relations with each other and governs the way we act ethically toward each other.
[Translation]
Mr. Ménard: I will remember that.
[English]
The Chairman: You can ask our panellist your next question afterwards.
[Translation]
Mr. Ménard: Yes, I think he had an interesting definition, Mr. Chairman, but I will get back to this later.
[English]
The Chairman: Mrs. Hayes, please.
Mrs. Hayes (Port Moody - Coquitlam): Thank you, Mr. Chair.
While we're addressing our witness from McGill and the AIDS network - you're representing both, in a sense. You mentioned that you feel these drugs should be freely available for all because that would only seem fair and right and would treat all people the same.
Who do you suppose, ethically, should bear the cost, if that is your stand? Depending on who would bear the cost, would that perhaps not stifle the accommodation of that particular part of the process if they found this was costing them more and more as time went on? Would they not draw back from participating in such a program - whether it was the doctors, the pharmaceutical companies or whatever - if the cost landed on them?
Mr. Lemmens: I'm not sure whether I completely understand your question. I didn't say whatever drug it is should be available to all. I stressed the fact that we really should not allow whatever drug it is to enter the market without any control by the scientific community, by the community at large.
I said if a drug is really promising and we really can agree that it could help people with HIV and AIDS, we should not make it available only to those who can pay for it. If we make such a decision, we have to make it available to all. At that time it would be up to the health care system to provide for these drugs.
It would not be fair to create a system where some promising new drugs were available only to those who could pay for them and not to others. We have to be very careful. I'm not saying we should quickly release drugs as soon as there is an indication that they might give something. I think we really have to protect those vulnerable populations who are at risk and probably desperate to try all kinds of drugs.
Mrs. Hayes: Aren't you in a way reiterating the whole purpose of the health protection branch and the process it goes through in making sure a drug is efficacious and safe to those it's given to? In a sense, you are just repeating the process we already have, so things would reach the point where they are condoned by the health department. Are you not including experimental, pre-clinical, or any of those kinds of drugs in that comment?
Mr. Lemmens: I would say the necessity of this emergency drug release program seems to be that certain drugs - experimental drugs, for example, that show great promise - should be more quickly released than they are now.
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I would say if such a system were really necessary, perhaps decisions could be made on the release of these drugs locally - by hospitals, for example. By hospitals I mean ethics committees of hospitals.
Mrs. Hayes: Would they enter into that definition of being paid for by the public system? They wouldn't qualify for being tested the way you said.
Mr. Lemmens: It wouldn't necessarily be by the community at large. If pharmaceutical companies were willing to pay and make these drugs available, that would be very good, of course. If, before final approval has been given, drug companies that have developed a promising drug were willing to make it available to those who request it, that would be even better.
Mrs. Hayes: Maybe I should clarify - I probably should know this but I don't. Is the full cost of those drugs presently condoned or accepted by the health protection branch automatically covered by our health care system?
Mr. Lemmens: It doesn't cover all the drugs. I'm not so aware of the financial aspects of the recovery of costs for many of the prescription drugs.
Mrs. Hayes: As of today a new drug, 3TC, has been passed by the health protection branch. Does that mean the cost of it is covered in the public system as well as AZT? Do you know whether those two drugs are covered by public health care dollars?
Mr. Lemmens: I'm not sure. I imagine they may not be. I would say people with HIV and AIDS should have access to these drugs if they're really promising.
Mrs. Hayes: I have a quick question for our legal counsel, Mario Simard.
Where does the potential for the greatest liability lie? We've had recommendations for the new proposals for special access and emergency access to experimental drugs. Will the impact be greatest on the physician, the pharmaceutical company or the government if those proposals go ahead? I presume you've studied that.
Mr. Simard: Which proposal do you mean? The proposal of the drugs directorate or the proposal -
Mrs. Hayes: I mean the new proposals of the drugs directorate for special access and emergency access. Has that been looked into?
Mr. Simard: Quite frankly, when I was preparing to come here I had intended to look at this project to see whether I could make the same kind of evaluation. I found the details have not been carved out to a level where I can really determine in what sense it increases or decreases the duty of care.
My feeling is that it would not change it substantially. It may put some more responsibilities on the manufacturer, but that will remain to be seen. I don't think it's a fundamental change in terms of potential liability.
Mrs. Hayes: So liability at all three levels may come out approximately the same, but it may fall more to the manufacturer, potentially. But that has not been decided yet.
Mr. Simard: The liability may be more in the sense that the manufacturer will be issuing the drugs on a case-by-case basis, as opposed to HPB. All of that will depend on the wording of the regulations.
Mrs. Hayes: Okay. Thank you.
The Chairman: Mr. Jackson.
Mr. Jackson (Bruce - Grey): I have two questions for our guests. First, in the event that the government legislated some form of compassionate access as a precondition to drug evaluation or fast-tracking, how would the liability concerns change? Second, what action could the government take to indemnify itself?
Mr. Simard: As I said earlier, it depends on the legislation you adopt. If you decide to amend the Food and Drugs Act to provide for a provision like that, and at the same time add a clause stating the government is immune from liability, then presumably the government would be immune from liability. As I said, those clauses are always interpreted very restrictively.
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To a certain extent it's in your hands as members of Parliament to decide what level of liability will rest with the government.
Having said that, there's an issue of logic at some point. If the manufacturer tells you it is not ready to release a certain drug, not to the general public but outside the strictly clinical trials, and you force it to do so, you obviously cannot hold the manufacturer responsible if there's a problem with the drug. So somebody else will likely be held liable, and chances are it would be the government in a case like that.
Again, I'm sorry to repeat it, but it all depends on what you parliamentarians put in the legislation.
Mr. Jackson: Our dilemma is that as a government people ask us to intervene, and we know these people are extremely sick. We've already been told these trials are very precise and there are precise thumb prints they go through in order to have the drug approved. What we're hearing is that if the drugs are used incorrectly or prematurely they could cause the bug to mutate faster and create other kinds of problems.
I note with interest the Krever commission on blood. I know it was more of a Red Cross matter, but this government is spending millions of dollars and it seems to be a kind of Frankenstein monster that's growing. Notwithstanding the fact we want to help sick people, we sure don't want to spend our dollars in that particular direction.
We're trying to establish a legal framework so if we do this through compassion and the goodness of our hearts, we don't end up being dragged into the quagmire.
Mr. Simard: As I said earlier about the other issue, the question is whether the federal Parliament has constitutional jurisdiction to adopt a provision like that.
The Chairman: Merci, monsieur Simard. Monsieur Robinson, s'il vous plaît.
Mr. Robinson (Burnaby - Kingsway): Thank you, Mr. Chairman. I have two brief questions.
My first question is for Mr. Simard and is about the issue of informed consent. Is Mr. Simard aware of any legal precedents in Canada around the issue of informed consent, particularly if a patient who has signed an informed consent form later initiates legal proceedings, suggesting that either he or she wasn't given full information, or he or she had diminished capacity or something of that nature?
I've certainly heard from people living with HIV, and AIDS particularly, who are very sick. They say ``If I want to sign a consent form, if my doctor has something that may actually make a difference - we don't know but it might make a difference - for God's sake let me accept the responsibility for that, together with my doctor''. What's the legal implication of that?
In the interest of time, I'll put my second question to the representatives of PMAC, Dr. Fourie or Dr. Levy. To what extent does the PMAC, at present, have any kind of institutional consultation with people living with HIV and AIDS? What sort of communication is there? Is there any kind of an advisory group?
Obviously, as an industry you are in a position to affect profoundly the lives of people living with HIV and AIDS. What kind of communication and cooperation presently exists between your industry and people living with HIV and AIDS, and groups representing those people?
[Translation]
The Chairman: Could you repeat the first part of the question, please, Mr. Simard?
[English]
Mr. Simard: As to lawsuits that may have been made against the government with regard to an emergency drug release, I must say I'm not aware of any such action in the past. Before I came here I asked some of my colleagues at the office. I made a quick verification and I don't think there has ever been a lawsuit as a result of the emergency drug program. On a daily basis we receive actions, but not on that particular point. So in that context, the issue of informed consent has never presented itself.
I don't want to speak for other people, but I think so far it has probably been an issue primarily between the practitioner and the patient, and possibly the manufacturer and the patient, rather than the government and the patient.
I said earlier, to require the patient to provide a consent form for the release of a drug may be a good thing to have, but it does not resolve all of the problems from the point of view of government because we have no means of verifying whether the patient was well informed and emotionally and intellectually able to make that decision. Only the person who was sitting with that patient when he signed it would know that.
Mr. Robinson: But there has never been a law suit that you know of?
Mr. Simard: There has never been one I know of against the government.
The Chairman: Would you like to speak on the second part of the question for PMAC,Dr. Levy?
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Dr. Levy: The PMAC has just recently put in place a new HIV/AIDS committee. The mandate of that committee is to put together a strategy on behalf of the whole industry in trying to meet the needs of all the stakeholders concerned with HIV/AIDS. So far, to date, the companies within the PMAC have relied on their own individual advisory panels with the industry.
I can speak best about my own case with Glaxo Wellcome. We have had in place an advisory panel for a number of years now, and we've been meeting with that panel, which includes people from the community, in order to get their advice on our drug development programs.
Mr. Robinson: This is the first time since the epidemic started that the industry itself has established any kind of coordinated committee?
Dr. Levy: The industry previously had a committee a number of years ago, and that committee didn't meet as regularly as we would like within the industry. It's recently been rejuvenated under the guidance of Dr. Fourie, and we all have great hopes that it will become much more active and play a much more active role.
Mr. Robinson: It will be working with people with HIV and AIDS?
Dr. Levy: Yes, that's the aim.
The Chairman: Mrs. Ur.
Mrs. Ur (Lambton - Middlesex): Does liability insurance go up for practitioners who deal solely with HIV/AIDS patients? That's just a general question. At what level does a person who is living with HIV/AIDS have the right to compassionate access to drugs? Is there a judgment level that this person can apply? Has there ever been a signed consent by a patient sufficient to protect the government or practising physicians from any legal ramification if something went wrong in the treatment process?
It appears in your statement this afternoon that we have the government in the middle trying to help HIV/AIDS patients who are living with HIV/AIDS and we have the drug companies on the other side. The government are the bad people no matter which way we turn. How can we best rectify or paint a more positive situation for the patient as well as the drug companies so that we can be productive in what is obviously a very serious situation?
Mr. Simard: If I can start with your second question, at what point does a patient have access to the drug, I think if you look at the way the emergency treatment provisions are drafted right now, to a large extent it's very much a decision that's made by the practitioner. Health Canada essentially relies on the information that's provided by the practitioner to determine whether there's an emergency situation and so forth. That's pretty much where the decision is made.
As to the liability insurance for the practitioner, I'm not the best person to answer that because I don't represent doctors. I would doubt very much if the practitioner would deal out drugs if he's not insured. I would assume that they are still covered. I cannot answer that definitely.
Mrs. Ur: I think, sir, that you perhaps misunderstood my question. Is it more costly for a physician, because of the liability insurance, to deal solely with HIV/AIDS patients because there are so many differences in compassionate access to drugs, emergency drug relief, etc.? Are there more legal obligations or technicalities for doctors to endure in that position?
Mr. Simard: I cannot answer that question. There are doctors here. Maybe they know better than me.
The Chairman: I think we're going to get someone from the insurance business as a witness tomorrow. As a personal opinion, I don't think it makes a difference.
Mrs. Ur: Thank you, Mr. Chair.
The Chairman: Now we're going to go to a second part with our witnesses. We're going to address the ethics. Our first guest this afternoon is Mr. Arn Schilder from the B.C. People with AIDS.
Mr. Schilder, please.
Mr. Arn Schilder (Vice-Chair, B. C. People with AIDS): We received notice of this rather late, and it does take us some time to go through a consensus process. However, we have prepared a response to the questions that have been asked. I will go through the responses to each question as they correspond to the original fax we received.
On the issue of pharmaceutical companies being ethically obligated to extend compassionate access, yes, they are. Releasing a drug to someone who is catastrophically ill is a human rights issue. The pharmaceutical industry has the moral obligation on humanitarian grounds to respond by providing access to an experimental drug. Release of a compound on compassionate grounds means that a small amount of the drug is required only for a small number of people. If the supply is available, there is no justifiable grounds for not providing the drug to people who are catastrophically ill.
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My response to the second question, what criteria should drug companies use to determine whether they should or should not charge for an unproven therapy, is that it is the government's responsibility in earnest consultation with affected consumer populations to establish universal criteria that the pharmaceutical industry must apply. Otherwise, only the financial interest of an individual company will dictate whether or not they charge and how much.
Our position is that people living with HIV and AIDS contribute almost already a profound investment in the pharmaceutical industry through their participation. Without the collaboration of the consumer group, the pharmaceutical company would be unable to effectively carry out their research. If somebody is catastrophically ill they should have access to any therapy they believe could benefit them, free of charge. We do not believe that it is ever ethical to charge for an experimental therapy.
Thirdly, do catastrophic rights have defined limits? Yes. Someone who is catastrophically ill is facing imminent death. A more precise working definition in the context of AIDS is a person having fewer than 50 CD4 cells, plus one AIDS-defining illness as defined by the CDC or LCDC. Being catastrophically ill gives a person the right on humanitarian grounds to try anything that could prolong their life or relieve suffering.
Fourth, what are the rights of catastrophically ill people voluntarily enrolled in double-blind controlled studies? As with anybody enrolled in any of the clinical trials, they should have the right to withdraw at any time without compromising their standard of care. If there is a change for the worse in their health, they should have the right to try the experimental drug.
People who are catastrophically ill do not usually enter into a double-blind study. What they do is usually access therapeutic options and a better standard of care than they could otherwise receive. If compassionate access were made consistently available, people would be able to exercise their right to try an experimental compound free of charge without in any way compromising the quality of the study or putting their already tenuous health at greater risk.
Fifth, in the event of a positive result, when should patients receiving a placebo be switched to the test agent? In a crossover trial, there are standard time limits set so that eventually everybody in the trial tries an experimental therapy. In a non-crossover clinical trial, a person should be given the experimental therapy at the standard point when improvements should be seen in the course of an illness. If anybody is ill and not responding to the placebo they should automatically be given the experimental drug.
Sixth, is it ethical to extend compassionate access to asymptomatic HIV positive people when the unproven drug should diminish the quality of life and hasten death? No, it is not ethical. The concept of compassionate access was designed specifically for people who have very limited or no options, thus it should be reserved for people who are symptomatic or in otherwise catastrophic health situations.
The seventh question is at what point during the clinical trial should a promising agent be considered a candidate for compassionate access? The answer is once enough data has been obtained from the efficacy stage of the trial, either phase 1, 2 or 3, depending on the structure of the trial and whether the analysis demonstrates an acceptable balance between efficacy and toxicity.
The eighth question is at what point can research clinicians and news media ethically call an experimental drug promising? In light of recent announcements this is timely. The answer is when, after or during the efficacy stage, phase 2 or 3 or phase 3, the drug proves not to be physically harmful while positive benefits are observed to be clinically significant. This point could also be defined as when investigators are confident enough in the product that they are ready to conduct trials comparing the experimental therapy against an already approved therapy.
It is the government's responsibility to set criteria for the pharmaceutical industry about when it is appropriate to release research findings. In the field of mining, it is illegal to announce false assays. There should be parallel legislation for the pharmaceutical research industry.
Thank you.
The Chairman: Thank you, Mr. Schilder. Now from the
[Translation]
Medical Research Council of Canada, we have Dr. Michel Denis. Dr. Denis, please.
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[English]
Dr. Michel Denis (Scientific Officer, Medical Research Council of Canada): I am a scientific officer with the Medical Research Council. The MRC is funded by the federal government to promote, assist and undertake basic applied and clinical research in Canada in the health sciences arena.
MRC carries out its mandate by funding health research and research training in Canadian universities. In its quest to assure that all research in Canada meets rigorous moral and ethical standards, the council has assisted in the development and dissemination of guidelines on research involving human subjects.
The council requires that all MRC-funded research complies with these guidelines and strongly encourages non-MRC-funded researchers to respect the same protocol via their local research ethics board. From an MRC perspective, it is difficult to divorce the ethics from the scientific facets of the issue, when the issue of compassionate access is discussed.
For example, compassionate access to a drug could imply that drugs are distributed to patients before researchers have proven a drug's efficacy and/or safety. One should never underestimate not only the dangers, but also the potential lack of ethics in providing medication in the absence of rigorous scientific evidence related to its use in humans.
One possible outcome of the provision of compassionate access could be the reduction of patient participation in clinical trials. Clinical trials are a building block of our knowledge of safe, effective cures for a variety of diseases. On the other hand, access to potentially promising therapies for patients with life-threatening diseases should be pursued very vigorously.
Alternatives include having statements of intention on compassionate access presented with all protocols for all phase 1, 2 and 3 trials. The statement could provide the rationale for the presence or absence of a compassionate arm, with appropriate ethical and scientific justification.
Alternatively, trials may be designed to allow crossover of patients from placebo to the therapy. In addition, pharmaceutical companies and/or researchers may consider trials with an open arm, which allows people who do not wish or do not qualify to obtain the experimental therapy.
The issue of compassionate access of drugs brings to the forefront the need to delineate clearly the responsibilities of drug companies and government regulators as well as those of the patients. The issue of compassionate access to experimental drugs is complex and problematic.
Council has committed itself to ensuring that our research guidelines on the morality and ethics of research reflect the shifting views of society. As a representative of MRC, I welcome the opportunity to gain insights into your concerns on this important subject.
The Chairman: Thank you very much, Dr. Denis.
We now welcome from the National Council on Bioethics in Human Research, Mr. Derek Jones. Mr. Jones, please.
Mr. Derek Jones (Director, National Council on Bioethics in Human Research): Mr. Chairman and members of the House of Commons subcommittee, on behalf of the National Council on Bioethics in Human Research, I wish to thank you for inviting us to participate in deliberations.
After I introduce the national role of NCBHR and the history of our involvement on this issue, I shall convey the remarks of the chair of the NCBHR clinical trials panel, who is absent. Unfortunately, Professor Benjamin Freedman of McGill University was made ill last night and was unable to appear today.
The National Council on Bioethics in Human Research was established in the late 1980s, following in part from the conclusions of an international summit on bioethics held in Ottawa in 1987. The summit convened under the theme ``Towards an International Ethic for Research with Human Beings''.
Shortly thereafter, in 1989, NCBHR was founded to support the interpretation and implementation of ethical guidelines on research involving human subjects. We are supported by Health Canada, the Medical Research Council of Canada, the Natural Sciences and Engineering Research Council, the Royal College of Physicians and Surgeons of Canada and the Social Sciences and Humanities Research Council.
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NCBHR consists of an interdisciplinary group of some twenty experts from the health professions and the ethics, philosophy, law, humanities and lay communities across Canada. Over the years NCBHR has hosted national workshops, released discussion documents, and otherwise embarked on a variety of activities to assist researchers, granting agencies and government in meeting their ethical obligations involving research with human beings. These activities foster dialogue and education within the Canadian research ethics community.
Of vital importance in this dynamic dialogue are the working relations with the research ethics boards, those entities across Canada that are charged with reviewing the ethics of proposed research. For years NCBHR has provided a query service, that is, responses to written requests from REBs and others for information or advice on national research ethics issues. The service is intended to assist REBs in ensuring the protection of human research participants and the ethical conduct of research.
It is in these contexts that NCBHR has discussed some of the ethical questions surrounding compassionate access to experimental medications.
In 1989 NCBHR first addressed compassionate access during a national workshop on the ethical aspects of pharmaceutically based clinical investigation. During that workshop three potentially conflicting ethical obligations were identified: one, the protection of seriously ill patients; two, respect for the autonomy of patients with life-threatening illnesses; and three, the conduct of sound scientific research for the benefit of future patients.
A consensus emerged to the effect that:
- ...[t]erminally ill patients for whom there are extremely limited treatment options should have
early access to investigational drugs, provided this (a) does not compromise the scientific
validity of ongoing research on that illness and, (b) does not subvert drug evaluation in trials for
non-life-threatening situations.
For your convenience, we have included in appendix A of our testimony a copy of the response. That response emerged from our panel on clinical trials of which Benjamin Freedman of McGill University is the chair. I again convey my regrets for his absence.
Also, he asked me to convey some of his remarks. I'd like to begin to do so by emphasizing four points. First, the issue of patient access to experimental drugs is commonly understood as centring about new and promising drugs under development for diseases such as HIV/AIDS. The issue is broader, however. We need to consider as well the implications of any reform for drugs with no evidence on their behalf or for drugs that have been scientifically and clinically discredited. We must also focus upon the new dosages or treatment schedules or combinations of available drugs, keeping in mind the many influences upon drug safety and efficacy.
Secondly, because discussion of expanded access to experimental drugs is broader than a question of HIV/AIDS, we might look at other diseases for the lessons of history. Cancer is a good model, both because of its often catastrophic implications and because of our knowledge and long experience in studying it. The vast majority of promising anti-cancer agents introduced in phase 1 testing do not proceed to phase 3 testing, and the vast majority of cancer patients in phase 1 testing never experience clinical benefit from their experimental treatment. The lessons of cancer research tend to undercut generic claims that there are powerful, secret remedies for illnesses made unavailable by bureaucratic restriction.
Thirdly, patients who are desperately ill sometimes consent to research believing they have nothing to lose. This may be a mistaken belief, for even the most dreadful disease can be made worse by the inept application of an experimental treatment.
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Fourth, compassionate access to experimental drugs is an issue that falls between medical treatment and research. While the nature of the intervention is research, the patient requesting an experimental drug and the physician seeking to satisfy the request share a therapeutic intent to provide benefit.
These facts and cautions evoke certain ethical considerations. We've heard to some extent this afternoon about informed consent and autonomy, which flows from the basic ethical principle of respect for persons. The principle of beneficence requires that patients and subjects seeking medical attention should be helped, or should at least not be harmed. We've also heard about justice.
These principles, however, apply differently in research and in treatment. Before treating a patient, a doctor obtains informed consent on the basis of disclosure of risks, benefits, alternatives, side effects, etc. Information is certainly not available in the same way in the research context, nor does research carry the same warrant of benefit as does treatment. Issues of justice in research often focus on the relative positions of persons on and off trial.
There is also an important difference in the potential for a conflict of interest. A doctor treating a patient is understood to have as his or her main object the best interests of the patient. A clinical investigator enrolling a subject faces, of necessity, a mixture, if not a conflict, of interest in considering the scientific integrity of the trial as well as the physical integrity of the subject. When a research study is designed by a pharmaceutical company, the investigator's ability to attend to a patient's sole and individual interest may be further compromised.
For these reasons, the procedures taken to ensure that ethical principles are respected cannot be the same in research as in treatment. In treatment, autonomy within a doctor-patient relationship is primary. After-the-fact control is exercised by medical committees that review medical misadventure or potential lawsuits. In research, prospective review is needed, both by a research sponsor and by an REB, that brings to bear independent medical, scientific, and ethical expertise to ensure that the rights of subjects are protected.
When a catastrophic right is defined as the right of a catastrophically ill adult to elect, in consultation with a physician, any therapy whatsoever that does not cause direct harm to others, the ethical procedure appropriate to treatment rather than research is chosen. The same would be true of the emergency release program described in the drug directorate's discussion paper.
The treatment model relies upon a doctor supplying a patient with a well-grounded treatment recommendation based on the sole interest of the patient, who may then choose to accept that after being informed. The safeguards of expertise in informed consent are less available in the context of non-validated treatments. If the manufacturer of the drug in question can impose conditions upon access, such as special follow-up tests and examinations, then an incipient conflict of interest may be present.
The role the drug manufacturers play is influenced, or ought to be, by their ethical and legal duties. The notion of partnership further suggests that the role they play matters most because they do so in a relational context, for both ethics and law recognize that duties connect to corresponding rights.
If we were to recognize, for instance, that one has catastrophic rights to drugs, such recognition would impose corresponding duties on those who have drugs or those who manufacture them. The content of any such rights and duties and valid limitations placed on them are explored in the query response set out in appendix A. That discussion articulates some of the ethical and practical considerations that inform why Canadian public policy and law to date have opted to facilitate access to new experimental drugs rather than to impose full duties.
Without attempting to settle the validity or content of such rights and duties, I would add two related points.
First, an unstated but implicit assumption of the analysis in our letter is the tendency of both ethics and law to grant fuller recognition of negative rights than positive rights. A positive right means a right to be provided with some good. A negative right means a right to be free from interference.
Secondly, even if the modern social contract between citizens includes rights to treatment, it is clear that such rights are not absolute. A patient's right to health care does not imply that he or she has the right to be supplied with all treatments.
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Justice requires that any reform of policy be conceived and accomplished in an equitable manner. Justice has been violated in the past when some patient populations and diseases have received inordinately low or inordinately great infusions of research. Issues of justice are particularly important when considering diseases that disadvantage certain sections of the population that have been historically the objects of prejudice or are currently under-served. These points apply to HIV/AIDS.
Reforms need to consider as well, though, the heterogeneity of the patient population. Persons with AIDS contracted by intravenous drug use, for example, are doubly disadvantaged and do not have the same access to up-to-date information and medical attention that others with AIDS possess, including those most active in speaking out for AIDS patients. To be equitable, reforms must not be designed for the sole satisfaction of that segment of the population that is highly motivated and educated.
These lead us to some policy conclusions. Let me direct your attention to two of them.
The Chairman: Would it be possible to speed up a little bit, Mr. Jones? I'm very sorry, but we have other witnesses.
Mr. Jones: Drug research in Canada involves a partnership between companies and research participants. Many research ethics boards have taken the position that to satisfy this partnership, companies must agree to supply those research subjects who have been assigned the placebo with the test drug if the trial's results are positive.
Drug research involves a further partnership with the Canadian government and public. Drug companies take advantage of the favourable tax and financial climate paid for by the taxpayer.
Reciprocity and equity suggest that companies be made to understand that open label supply of experimental drugs in conformity with the policy and ethics is part of doing business in Canada.
Finally, the committee is concerned with such questions as: When should persons on placebo be switched to an active agent? Is it ethical to extend access to asymptomatic persons whose lives may be shortened? These and other questions are currently considered by Canadian research ethics boards, yet these groups are given no formal consideration in the background documents. This is a mistake that should be rectified.
We have outlined reasons why it may be dangerous to leave the question of access to non-validated treatments strictly within the bounds of the doctor-patient relationship. We have in place across the country, in the form of research ethics boards, bodies with the appropriate expertise and sensitivity to provide objective, reasonable, prospective evaluation of such interactions.
Imagination is needed to explore how these Canadian resources may be mobilized towards the end of safe and early access to experimental treatments. Thank you.
The Chairman: Thank you, Mr. Jones. Now we'll go to the Canadian Cancer Society and its president, Dr. Neill Iscoe.
Dr. Neill Iscoe (Member, National Board; President, Ontario Division, Canadian Cancer Society): Thank you, Mr. Chairman. I'm not the president of the Canadian Cancer Society. I'm a president of one of the divisions and a member of the national board. I'm sure Mr. Potter wouldn't mind from time to time.
Mr. Chairman, I would like to thank you and your committee for giving the Canadian Cancer Society the opportunity to make a presentation on this very important matter and for recognizing that the issues before it involve patients with more than just HIV and AIDS, but involve a good number of patients.
You will have noted in the brief forwarded you late last week the values held by the society - I should note that the brief was shared with a number of senior volunteers but is not general policy in the society - and the role the society has played and continues to play in cancer control in Canada. In the interest of time I will restrict my remarks to answering the seven questions posed by the committee.
The first question is, are pharmaceutical companies ethically obligated to extend compassionate access to the catastrophically ill?
Within the context of the principle of ensuring known effective therapies are available to patients who wish them, and within the principles that acknowledge the importance of ethically and scientifically approved clinical trials as a priority in the improvement of patient care and the development of knowledge, the society believes companies should make drugs available to those who could benefit outside the clinical trial setting. However, in order to advance knowledge so that future generations of patients will not be faced with the same uncertainty, the society believes that such use not undermine important trials seeking to determine the role of drugs in that same situation, and that regardless of the context in which the released drug is used, this use be accompanied by sufficient documentation so that the activity of the treatment in question will be clarified.
The second question is, what criteria should drug companies use in determining whether they should or should not charge for an unproven therapy?
First and foremost, the society does not believe an individual's ability to pay should ever enter into a decision surrounding these criteria. As a principle, the society does not believe people should be charged for therapies that have not received notice of compliance. The difficult situation arises in which a drug has received an NOC for a particular indication and in which compassionate use has been sought for another indication. As the drug is on the market, there is no compelling reason for the company to supply the drug free of charge. The society, however, does not believe companies should be able to charge for a drug in which there is no consensus that the drug has a role to play in the treatment of that condition when compared to routine therapies.
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Do catastrophic rights have defined limits? I have chosen to rephrase this question as asking, do the rights of those with catastrophic illness have defined limits?
The answer to this question is yes. The society believes in the right to self-determination but does not believe this right permits one person to exercise that right to the disadvantage or detriment of another individual. As there can be no doubt any more that resources are not infinite, there is the need to ensure that we do the greatest good for the greatest number. Most importantly, the manner and process by which decisions now and in the future are reached is open and transparent to the public and involves the participation of those directly and indirectly affected by those decisions.
Fourth, what are the rights of the catastrophically ill enrolled in double-blind controlled trials? That is, in the event of a positive result, when should patients receiving the placebo be switched to the test agent?
Patients on clinical trials have many rights spelled out to them in the consent process. In my experience, generally speaking, a patient is given a copy of the consent form to keep as their own record.
The committee is correctly concerned about how patients in trials are cared for as new information becomes available. For many clinical trials, a monitoring committee is in place. This committee is responsible for deciding whether to stop or unblind a trial if differences in the treatment, outcomes, or adverse events exceed predetermined criteria.
Problems can occur when no such rules for the predetermined definition of benefit or harm have been developed, when the results are at odds with other information, or when the benefits are felt to be clinically very small. The society believes these questions should be resolved by consensus process among the professionals, with input from those affected by the decision.
The society believes if a trial demonstrates a new therapy as effective or, conversely, ineffective, the first people to be apprised of this should be those people who volunteered to participate in the study. The society believes the sponsoring company or agency should be obliged to offer, if appropriate, the new treatment to those patients in the trial who did not receive it, before making the therapy available, even on a compassionate basis, to those outside the trial.
The fifth question is, is it ethical to extend compassionate access to asymptomatic HIV-positive people when the unproven drug could diminish the quality of life and hasten death?
I would like to respond to this question by changing its focus to the cancer patient who may or may not have symptoms, although this could just as readily be someone with relatively asymptomatic multiple sclerosis, ALS, or someone found to have a genetic marker for a catastrophic disease that may take many years to develop. The society believes it is always ethical to consider therapy if there is a very real possibility that the therapy could do more good than harm.
Let me consider a not uncommon situation: the cure of an asymptomatic person with progressive and incurable cancer who either has an abnormal x-ray or an abnormal blood test. People in this situation, rightly or wrongly, but certainly most understandably, are often preoccupied with the results of their tests.
For the purpose of this discussion, let me also state that therapy in this situation has some side effects that are not life threatening, but the treatment will result in some diminished physical performance in one sphere or another, and finally, the treatment in advance of symptoms does not prolong life. Patients in this situation are aware that they have no physical symptoms of the disease, but emotionally many could benefit from therapy if they would prefer an active approach to a passive stance in face of what many could view as a ticking time bomb. For these people, the benefits of early therapy may offset any side effects. Therefore, for a number of patients with catastrophic illness, any treatment may in itself provide mental comfort, even if the physical costs of the therapy are real.
The sixth question is, at what point in clinical trials should a promising agent be considered a candidate for compassionate access?
There are at least two possible situations that come to mind: first, the situation in which access is sought for the condition being examined in the trial; and secondly, the situation in which the access is sought for a similar condition to that examined in the trial.
In the first situation, this is a matter for the trial committee to decide when it examines the data. There have been a number of circumstances in recent years in the cancer field in which clinical alerts have been issued. These took place in the context of marketed therapies. I do not, however, see any reason why similar activities accompanied by rapid review of the data by regulatory agencies could not occur. In advance of rapid regulatory review, I would hope and expect that the sponsoring company would make the agent available on a compassionate basis.
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In the second case, any promising agent involved in clinical trials could be considered for compassionate release if the condition for which release was sought was similar to the condition for which the trial had received scientific and ethical approval.
The society believes that companies should make the agent in question available to appropriate patients until such time as it has been demonstrated to be of benefit in that situation, or demonstrated to be of no benefit. At the same time, the society believes that compassionate access should not be so free as to undermine the ability to answer critical clinical questions in approved clinical trials.
The seventh question: at what point can research clinicians and/or the news media ethically call an experimental drug ``promising''?
Mr. Chairman, the society is very mindful of the criticism about the war on cancer and the view in some quarters that there is a cancer conspiracy within the medical establishment. It can be easily asked then, if there are so many breakthroughs, why do we hear that there is so little progress in the treatment of common malignancies, which means breast cancer in women, lung and colorectal cancer in men and women, and prostate cancer in men?
The society believes that much of the unhappiness with this situation relates to miscommunication about what these advances truly mean, and that the words ``promising'' and ``breakthrough'', as generally reported in the news media, imply something that many clinicians and researchers would argue is an overstatement of their work.
In most circumstances, I suspect clinicians and researchers mean that the study provided information that merits further investigation, and that at some point in the future there may be a role for this approach in cancer care, provided the benefit-to-risk ratio for the therapy exceeds that of standard treatment.
Mr. Chairman, there have been too many ``promising'' treatments in the past. These are promises that have not been kept. Both the news media and the medical and scientific communities must accept their share of responsibility in raising expectations unduly.
Here's a final thought to bear in mind. Perhaps these communities will be able to restrain themselves and not build up expectations beyond what can be delivered, but how do we make people aware that promises on the so-called information highway may not be the same as promises in other venues? These and other questions will continue to occupy information services and health care providers in the years ahead.
Thank you, Mr. Chairman, on behalf of the Canadian Cancer Society, for providing us with this opportunity.
The Chairman: Thank you, Dr. Iscoe.
From the Faculty of Medicine of Dalhousie University, Dr. John Ruedy, please.
Dr. John Ruedy (Individual Presentation): I am dean of the faculty of medicine at Dalhousie University, but I'm speaking as an individual.
My credentials are that I've been involved in clinical trials for thirty years in Canada. For a decade, I was involved in clinical trials in HIV disease when I was based at UBC.
I would just like to limit my remarks to some ethical questions around access to investigational drugs and who should bear the cost. I have provided my answers to the other questions in my brief.
Traditionally, access to investigational drugs has been restricted. The ethical dilemma, in my mind, is whether it's acceptable to restrict access to investigational drugs to individuals who have a severe form of the disease, or even a more severe form of the disease, who are not enrolled in a clinical trial.
The question of compassionate access gets very complicated. I can identify for you immediately five different categories of individuals suffering the disease who have a restriction to the early availability to that investigational drug.
First, in clinical trials in AIDS, they are often placebo-controlled or they are a comparison with an existing therapy. They are not crossovers. So usually half the patients are placed on a placebo. Therefore, even within the clinical trial, there is a restriction of access to the exciting, new investigational drugs to individuals with disease of equal severity.
There are individuals who are unable to participate in a clinical trial, although willing, because of distance or travel costs. So that appears inequitable.
There is a group that's unwilling to volunteer for the clinical trial because they don't want the chance of receiving the placebo or traditional drug; they want the availability of the investigational drug.
There are individuals who have just as severe a form of the disease but they have criteria that exclude them from a trial. They may have kidney disease or some coexistent disease. Therefore, they aren't included in the trial because their inclusion might confuse the interpretation of the results.
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There are others who might not meet inclusion criteria. They may have a more severe form of the disease than those in the group chosen for the clinical trial.
Why have these restrictions been placed on an investigational drug? I think there are two reasons. One is to protect the individual. Quite clearly these are unproven therapies, which may be harmful to the individual. The other is that they may be ineffective. Hopefully, they're not.
We have decided in Canada, as in many western countries, to choose a certain point in drug development at which efficacy and safety is proved to a satisfactory level to give a notice of compliance. Then the drug becomes available by prescription from physicians.
Let me point out that this point in the development of drugs is an arbitrary point. It's a practical level, but it's not the end of drug development. Efficacy means you've shown the drug has some relevant biological activity to the condition that's going to be treated. Safety means that, for that period of time, it's been safe in the individuals who are being tried.
Those don't address the question of effectiveness, which is only done at another phase. Perhaps I can give you an example. In mild hypertension, it's not difficult to show we have many drugs that lower blood pressure. That's a relevant biological activity of a drug, but it's taken two decades for us to show that those drugs are effective in mild hypertension for preventing stroke.
The point I'm making is that this timing of the notice of compliance is arbitrary and artificial in the whole history of drug development.
So one purpose is to protect the individual; the other purpose is public good. Clinical trials are an ethical imperative. They are necessary to establish the potential benefit and the potential risks of unproven therapies. The more efficiently that clinical trials are done, the greater the public good, because the answer is provided at the earliest possible time.
That raises the issue of the diversion of volunteers from a clinical trial if compassionate release is wide open. We've had some evidence of the effective diversion of patients from clinical trials when access to the drug was available without enrolling in the clinical trial.
In Canada, we also may suffer from not having the drug available at all to Canadians if we have access that is so out of context with what is practised in the United States or the United Kingdom or other countries with a much larger pharmaceutical market and a much larger stake in drug development.
The dilemma is that the individual with a severe disease that may result in death or severe disability without compassionate release may not have the opportunity to take advantage of potential beneficial therapy. This raises the issue of autonomy and self-determination and the right of the individual to choose to take an unproven drug.
In my opinion, I think compassionate access is an ethical imperative, but there have to be limitations. I think compassionate access should be available to individuals with a more severe form of the disease than those involved in the clinical trial, particularly if that's going to lead to disability or death before the results of the trial are known.
I think compassionate access should be provided to those willing to volunteer for the trial but are unable to do that because of distance or other constraints. I think that would fit in with the principle in the Canada Health Act of equivalent access to medically necessary services.
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I think those unwilling to enrol in the clinical trial have to be respected, but there have to be some controls to prevent such a great diversion that the public good is not met because the clinical trial cannot be completed. I think one can devise a quota of compassionate release related to enrolment so that there is a limit to the number of compassionate releases until enrolment is full in the trial. I think that's the way we can seek a balance.
Briefly, what about cost? It's important to realize that the cost of an investigational drug isn't just the drug cost. There is the cost of surveillance of the use of that drug by the individual taking that drug. That may mean special laboratory tests for that individual's protection. There is also the cost of the consequences of an unfortunate adverse affect.
I think the latter is not an issue. We don't discriminate against smokers or drinkers who continue to take poison in spite of informed consent of the risks, but the drug costs and the surveillance costs are at issue.
Most provincial health programs don't include prescription drugs as a benefit, so it's hard to make a case that compassionate release drugs should be borne by the provincial health plan. The industry has nothing to gain, but perhaps something to lose, in compassionate release, because there may be a false alarm of an adverse reaction that leads to significant complications. It seems to me the public, if it's compassionate, has to bear the costs of compassionate release. That's both the cost of the drug and the cost of the surveillance of the use of the drug.
The answers to the other questions are in my brief.
The Chairman: Thank you very much, Doctor.
From the Canadian HIV Trials Network, Dr. Don Zarowny.
Dr. Donald Zarowny (Program Head, Scientific and Industrial Liaison, Canadian HIV Trials Network): Mr. Chairman, committee members, I am pleased to have the opportunity to address the House of Commons subcommittee on HIV/AIDS this afternoon.
My comments are not only from the perspective of the Network, but from my personal perspective, my experience. This experience has been collected in three areas: first, as a family physician in a small city; second, as a medical director in the Canadian pharmaceutical industry; and third, in my present role as a research administrator in the Canadian HIV Trials Network.
I can't think of a more controversial subject than compassionate access to experimental medications by persons who are catastrophically ill. The subject is complex and often confusing. I believe that part of the confusion is due to the use of terminology that has different meanings in the minds of various parties. Therefore, it is important that I provide you with my definitions for some of the terms before we start discussing them.
First, ethical issues in medicines specifically regarding human experimentation include three things: one, respecting the rights of individuals and recognizing when they are capable of making decisions for themselves; two, trying to be fair to the individuals while appreciating that we have a responsibility to society as a whole; and three, recognizing our duty to do no harm.
Next is catastrophic illness. The illness is one of a relatively unexpected occurrence, is severely debilitating, may even be fatal, and traditional medicine seems unable to offer effective treatment. In the case of a disease like HIV/AIDS, it occurs in the age span usually identified with maximum physical and intellectual energy. Thus, the diagnosis seems even more unbelievable for the individual, with consequent feelings of anger, urgency and frustration.
The next definition that I want you to understand is ``experimental medication''. To me, this is any form of therapy that has not been validated by appropriate experiments. Part of the validation is the assessment of the benefit of the new therapy versus its attendant risks. In this context, the risk is two-edged. It may be a desired effect accompanied by toxicity, or it may have no therapeutic benefit accompanied by worsening of the disease.
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I will deal with three of the issues you identified in your covering letter.
Promising agent. I have a problem with the use of this term. A non-validated drug treatment can be described in terms of what we know about it, that is, its chemistry and pharmacology, how it has behaved in pre-clinical animal studies and what human experience we have. Thus, we can chart its course at any time along the pathway of drug development in fairly precise terms. The use of the descriptor ``promising'' is unscientific and, I suggest, unethical. It is open to many interpretations and is likely to exploit the sense of urgency associated with a life-threatening, catastrophic illness that I referred to previously.
Access to non-validated therapy. I believe it is possible to define conditions under which it is ethical to provide a non-validated therapy to a patient with a catastrophic illness. If we acknowledge that we are offering supportive care in a situation where there is little else to offer and that science tells us the risk of harm is small or at least acceptable, then we can define the circumstances of distribution.
In the event the drug is undergoing full development, it will be available to certain members of the affected population by participation in clinical trials. Ethically, we have a duty to ensure that the proper tests are conducted to provide the evaluation. Clinical trials must be assigned a priority so that we can conduct this evaluation.
However, availability in the context of a clinical trial does not seem to satisfy the ethical principle of the individual's autonomy to decide for themselves. Therefore, we have begun to recognize that it is feasible to distribute a non-validated therapy during the development stage. Our experience with defining the conditions for distribution is increasing, and we are learning that the conditions are not uniform but vary with the disease and the agent.
To date, for example, the Canadian HIV Trials Network has participated in the distribution of five non-validated agents. Despite the fact that the Network is not mandated to distribute drugs, the pharmaceutical industry, the health protection branch and the community all recognize that we have a unique and valuable role to play in compassionate access. The CTN's national ethics review committee provides ethical review of the so-called compassionate release protocols when we are requested to by the industry.
Important ethical issues about access remain unresolved. Who should receive an agent in a compassionate access program? Patients who might gain some benefit if the agent proves effective, or those who could have what could be described as end-stage disease? How should we decide and who should decide? For example, the selection of individuals by means of a lottery, an ethical method?
The obligations of the pharmaceutical industry. The pharmaceutical industry is an essential partner in the health care process. Its role is to develop new drugs and distribute them. Companies make money doing this and return some of it to the drug discovery and development process. We acknowledge their role in our society by providing the inventor of the drug with a period of protection by issuing patents. Since we accord them a defined role and specific benefits, I believe it is ethical to expect them to participate in the resolution of the issues around compassionate access.
Consequently, in my view of things, companies are obligated to provide non-validated treatments under certain circumstances. These circumstances include implementation of a development program adequate to provide the data necessary to evaluate the agent and sufficient supplies to complete the development and information about toxicity. Since the therapeutic agents' risk benefit is undefined, they should neither charge for the product nor should they be held liable for its lack of beneficial results or occurrence of toxicity.
I'll stop there.
[Translation]
The Chairman: Thank you very much, doctor. We will now suspend the meeting until the end of the vote. As I mentioned at the beginning, we have a vote at 5:15 and we must leave. We will come back afterwards. Thank you.
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.1800
The Vice-Chairman (Mr. Ménard): Since we have a quorum, we will resume. Our chairman, Bernard Patry, had to leave and, as vice-chairman, I will chair the remainder of this meeting. We have two more witnesses to hear as well as the PMAC who asked to appear. It will be a pleasure to give them the opportunity, after which we will have an exchange with the members of the political parties represented here.
With your permission, I will give the floor to Dr. Sharon Walmsley, for five minutes.
[English]
Dr. Sharon Walmsley (Individual Presentation): Thank you, Mr. Vice-Chairman. I appreciate the opportunity to come and speak to your committee today.
I will be speaking from my experience. I am an HIV practising physician. I'm a specialist in infectious diseases and microbiology. I have had many of my patients involved in the compassionate access programs over the years.
Most of these compassionate access programs have been made available for anti-retroviral drugs. But we also have to think about this in the context of drugs used for the treatment of some of the complications these patients experience.
Like many of the members of the panel, I do find some conflicts in my roles. First of all, I am a physician and so I have a duty to my patient to do the optimum to maintain the health of this patient.
It is very difficult, as a physician, to say the words and to have a patient hear the words ``There's nothing more that can be done''. This is especially the case if there is a drug being used in another country or if there are some preliminary data to suggest this drug may in fact be helpful to that patient.
On the other hand, if a drug is not completely evaluated, then I'm in conflict in terms of giving that drug to a patient when there is a potential risk I could do harm to this patient. The ethics of compassionate use then become intertwined with the legal liability.
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My other role in my practice is as a clinician researcher. Again, this comes into the other conflicts in terms of my role in making sure we understand how best to use these drugs for our future patients as opposed to the individual in my office.
I believe compassionate access should be considered an arm or branch of the controlled clinical trial. As has been raised in these discussions, for HIV patients most of the clinical trials are done in patients fairly early on in the disease. We monitor the effects of these compounds on certain virulogic and immunological markers. This is usually the basis upon which these drugs are released and marketed. Then we wait for the clinical trial to suggest whether or not these drugs actually improve the quantity and quality of life for these individuals.
Even if those clinical trials do show a benefit for a drug, we cannot necessarily extrapolate to the patient with very advanced disease. In fact, very few clinical trials are done on patients in the terminal stages of HIV disease. First of all, it is very risky for pharmaceutical companies to do trials in these patients as the chances of success are much smaller. I think because of the other drugs and the other problems these patients have, there is a bigger opportunity for failure or adverse reactions. It could be these patients have reached a threshold of immunological failure where even the optimal antiviral drug will not be useful for them.
When we look at these drugs in the compassionate release programs, it is very difficult for us to evaluate success. We often don't see changes in patients' immunological markers. We often don't see changes in their quality of life. But we do give hope, and it's very difficult for us to measure either quantitatively or qualitatively the effect of this hope.
I think if we're going to develop compassionate access programs to a greater extent, we need some clear guidelines on how we use these drugs, how we can evaluate if they're doing some good, and how to be sure we're not just doing harm.
Another point I would like to bring to the committee's attention is that patients living with HIV are a heterogeneous group of individuals. They come from different educational backgrounds. They come from different cultures. They speak different languages.
Many of these patients take a very active role in their own therapy and in helping make the decisions, but I have as many patients who want to do what the doctor thinks is best. So are these patients really able to understand the risks and benefits they may be taking when faced with the decision about a new compassionate drug?
In the same context, they are often under a lot of pressure. They're under pressure from advocates who say they should take these drugs. They're under pressure from the lay reports and the literature, which talks about how good these drugs are but may not emphasize some of the potential adverse events. They're under pressure from their family and their friends who don't want to lose their loved one and want them to have everything that might help. Lastly, they may also be under the influence of the medical professional. People who work extensively in HIV have a hard time understanding how best to use these drugs, and many physicians out there don't know any more than the lay public.
The timing of these compassionate release programs also has to be considered. I think it's crucial we do have adequate safety data to ensure we're not doing serious harm to these patients. We need some degree of efficacy.
I would like to emphasize, as many people said earlier today, that we don't want these compassionate access programs to interfere with our ability to do the controlled clinical trials that will really help us understand the place of these drugs in the management of patients.
There certainly have been precedents that if patients have a choice, they would rather take the drug than go into a clinical trial. Although we may help today's patients, we may not understand how best to use these drugs in the future.
I think I will end my comments there and just state that I do believe there is a role for compassionate access. I think we can learn a lot, but we certainly need guidelines on how best to use drugs in this context.
[Translation]
The Vice-Chairman (Mr. Ménard): Thank you, Doctor. We will now go to Mr. John Dixon.
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[English]
Mr. John Dixon (Individual Presentation): Thank you. I am a past president of the B.C. Civil Liberties Association, author of the book Catastrophic Rights, Experimental Drugs and AIDS, and, to put my experience in some context, I served for two years here in Ottawa as senior policy adviser to the deputy minister of justice, in his office.
By the way, I didn't get the questions in time. I'm here, like Arn, at the last second. I'll speak very programatically and I hope quite briefly.
My first experience of this issue was when the civil liberties association in British Columbia was approached by Kevin Brown and Greig Layne, who were two of our original activists. They alleged to our board that they were unable to get reasonable flexibility treatment, release of drugs, from the health protection branch.
I must say that our original view of this was most skeptical. There are many scientists who serve on our board; we understood the very great importance of conserving our country's ability to make scientific advances. If you anarchically let everybody take whatever they want, you can never figure out what works. We understood all of that, and we expected to go to work with government and discover that in fact they were blameless and there was nothing to complain about.
We had had experience before working with federal officials, and we discovered that officials at the health protection branch were mindlessly obstructionist, pompous, impossible to work with - not just for AIDS activists, not just people with this disease, but for the civil liberties association. The problem seemed to be that in distinction to the FDA in the United States, Canada had, to its shame, let thalidomide into the country.
A deep, almost pathological, conservatism gripped the bureaucracy, to the extent that even when people were near death and their physician concurred with them that they had absolutely nothing to lose in trying a drug, the government exerted its regulatory authority to forbid release of the drug.
The ``catastrophic right'' spoken of in my book was the right of patients - catastrophically ill patients - to be free of the regulatory obstructions of government when it was clear that no other alternative remained to them and the scientific needs of our country were preserved. That is in answer to one of the questions: is there a limit to catastrophic rights?
The civil liberties association and certainly activist groups such as Persons with AIDS Society of British Columbia in Vancouver concurred there are going to be other generations of people with this disease; we can't simply let anybody take whatever they want. But there was an important area in which, if I can put it this way, science may be wasteful of many things while it achieves its objects. It may be wasteful of money; it may be wasteful of talent; it may also be wasteful of patients' autonomy rights.
In the case of AIDS in the early days - 1989, 1990, 1991 - I would work with Greig Layne and Kevin Brown late at night, working with people at Health and other government departments, until they fainted, arguing about this issue. Finally it was understood that government ought not, out of purely paternalistic considerations, prevent catastrophically ill patients from having access to drugs.
In a way that's the easy question. I sometimes have the sense, though, that it's like cutting the grass. You have to go back to it over and over and over again. There is a deep conservatism - and appropriate conservativism in some sense - in the regulatory agencies and in the medical profession itself.
As we knew back then, the difficult issue in a funny way, at least intellectually and legally, isn't the civil rights issue; the difficult issue is the practical and moral issue of who pays.
Before I came here I was in San Francisco Bay, where there's much talk in the press about the new drugs. If you held them this far away, you'd swear they were from the business page. It was all figures, numbers: Can the state governments pay? Can the insurers pay? Can Medicaid pay?
This question is very, very difficult because people who in our culture are developing drugs, industries, are not doing it out of compassion; they're doing it to make money.
We're in a situation in which Canada has a generally socialized medicare program in which float these icebergs of free enterprise, and there's a lot of friction.
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About the question of whether government has a moral obligation to pay when very promising drugs come out.... I'm going to set to one side all the niceties of how far along the trial is and so on. About whether government has a moral as opposed to legal - I do not believe it has a legal - obligation to support compassionate treatments, the answer is yes, but it depends.
I would offer this case as one that ought to engage our moral intuitions. Imagine that a small university group has developed a very promising drug. The medical findings look dynamite, and the initial clinical findings, over the first four to six months of human experimentation, are wonderful; it looks as if this may be the AIDS insulin. If that group doesn't have sufficient resources to provide the drug free of charge, compassionately, to everybody who wants it, and it costs $5,000 a year per patient in Canada, in those circumstances should the Government of Canada feel it has an obligation to perform...? Given that we not only want to keep the state out of the bedroom but we want to keep the invisible hand of the market out of the sick room, I would say yes.
If we are looking at a more problematical and clouded circumstance, in which a drug may, it seems, used in combination with others, add 5, 10, 15 years - we're not sure yet - to the life expectancy of persons with AIDS, and it costs $50,000 to $75,000, does the Government of Canada or the provincial governments rest under an obligation? I wouldn't think so. I think once we get out of the area of rights and we start talking about the moral responsibility of Canadians, given the convictions we have and the commitments we've made to medicare and keeping the invisible hand of the market out of the sick room, it really does depend.
I want to make one last comment about drug companies. A CEO of one of Canada's largest drug companies once said to me, when I was working on catastrophic rights, ``when interests get as large as ours, they become rights''. One of the very difficult things for governments to grapple with when it faces an issue like this is do we make new laws or do we spend more money?
There's a very great temptation to think this is a problem that may yield to more laws. If the drug companies are going to experiment here, they're going to have to offer the drugs compassionately.
Drug companies have options. Canada isn't the biggest country in the world dealing with this problem. They can experiment in the United States, where the real action is. They can experiment in Brazil. We can chase badly needed money out of this country with laws that won't work for industry.
That's something, it seems to me, you hear echoed from the McGill people and so on. I think it's important for government to face up to the fact that this isn't a problem that will easily be handled by making new law. It may be one of those issues in which you have to face the fact that at a certain level you have to spend more money.
I do believe government has a moral, as distinct from a legal, obligation to support persons living with AIDS in connection with very promising compassionate drugs, but I don't think there's any way of creating some sort of moral algorithm or decision machine that will just tell you at what point that has to kick in.
[Translation]
The Vice-Chairman (Mr. Ménard): Thank you, Mr. Dixon. We will now give the floor to the representative of the PMAC. I believe Dr. Levy would like to start.
[English]
Dr. Levy: Thank you, Mr. Vice-Chairman, for the opportunity to comment today on behalf of the Pharmaceutical Manufacturers' Association of Canada on the ethical considerations of compassionate access. The PMAC did not receive advance notice of the seven questions that are of special interest to the committee either. My remarks will be of a more general nature.
Let me begin by stating that the PMAC does support the need for Canadian patients to have access to new therapies. For example, most of the manufacturers involved in HIV/AIDS do have compassionate access programs in place. My own company, Glaxo Wellcome, has made 3TC available to nearly 2,900 people living with HIV/AIDS in Canada prior to its approval. This is quite a significant number when you consider that there are only 7,500 people receiving treatment for HIV/AIDS in Canada today.
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To answer the question that Mrs. Hayes asked a little earlier, the company made the drug available at its own expense. The distribution costs alone ran into several millions of dollars.
The ethical conduct of clinical research in Canada is guided by the investigator's conscience and by the judgment of the research ethics board. Of course, we assume that the investigator is always acting in good faith, but really it is the research ethics boards that provide the checks and balances in the system.
There are two fundamental principles that guide these boards. The first is an assessment of the risk-benefit ratio. There must be the possibility of some benefit to the patient, either directly through therapy or indirectly through the hope of future therapy, or to society as a whole through the advancement of knowledge. These risks must be commensurate with the potential benefits, although there are some risks, such as the death of a patient, that are clearly unacceptable and must come before the advancement of knowledge.
The second principle is the need for true informed consent. We've already heard earlier from Dr. Fourie and from others about the difficulties in providing informed consent at an early stage of drug development when key information may not yet be available.
The system I have just described and the principles I have just enunciated are in place for the conduct of clinical research in Canada. However, the system for compassionate access is much less well-established. For example, research ethics boards are often loath to adjudicate on the ethics of open label trials or compassionate access and they typically consider straightforward emergency drug release to be completely outside the scope of their mandate. Any new system put in place to handle special access must take these deficiencies into account.
Let me highlight a number of existing issues with respect to research ethics boards reviewing compassionate access programs.
First, I've already mentioned that it's often difficult to assess risks at an early stage and that it's incumbent upon the researchers and upon the boards to err on the side of safety by overestimating any and all possible risks.
Second, I think it's well worth noting that the make-up of ethics boards in the United States, for example, is dictated by federal law and monitored by the FDA. For example, there must be local community representation, there must be laypersons on the board, etc. In Canada, the composition is not mandated by law, although there are MRC guidelines in place. But the result is that the structure of the research boards varies considerably across the country.
Third, research ethics boards typically govern the practice of physicians affiliated with teaching hospitals. It's often difficult to find boards to govern general practitioners who also can have real needs to compassionate access for their patients.
An additional point to consider that is of specific interest to this committee is the ethical consideration of compassionate access for patients with catastrophic illness. In particular, how does one assess the risk-benefit ratio for patients in this situation?
We heard arguments from the community last week that persons with serious life-threatening illnesses should have access to any drug, since even a remote chance of benefit outweighs any potential risks, even though these risks may include death. But it would be inappropriate to leave the responsibility for this judgment with the manufacturers and physicians alone, without any guidance. We think there's a real role here for the government to provide guidance to us in keeping with societal values.
Finally, we're left with the question of the relative ethical merits of open access programs versus random clinical trials, which we discussed a great deal last week. Last week, we heard argumentation that open access programs are essentially more ethical than random trials. I'm not sure that all ethicists would support this point of view. There a number of factors to consider.
Open label programs by their very nature make available unproven therapy to a wide target population in an uncontrolled situation. We typically assume this is a good thing, but we may, at times, be exposing patients to more risks. There are real examples of this. For example, trials in 1989 in Canada showed a deterioration of the health status of people living with HIV/AIDS who were receiving certain therapies.
Open label programs do lead to delays in the conduct of clinical trials. This in turn means that important medical questions are answered later than otherwise, which can be detrimental to the health of the larger population. In support of this, I can quote a trial conducted by Montaner and his colleagues in Canada that showed that when patients were given the choice, 18% chose to enter clinical trials and 72% chose to enter open label studies.
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In summary, the Pharmaceutical Manufacturers' Association supports the need to ensure access to new therapy for patients in Canada. However, a number of questions and issues need to be answered about any new program before we can support such a new program; for example, the HPB's proposed special access program.
Thank you.
[Translation]
The Vice-Chairman (Mr. Ménard): Thank you, Dr. Levy.
I personally have two questions and you may answer them directly or indirectly. In my view, the question we will need to answer in a very clear way in our recommendations to the government is one that has been somewhat avoided, maybe because it is so complex or sensitive. Should we compel manufacturers, under very clear conditions set out in a legislation, to make accessible a product which is not yet a therapy but a research substance? This seems to me to be the central issue.
I believe I already know the answer of the PMAC but I would be interested to hear the views of the other panellists.
My second question is addressed more specifically to Dr. Levy who indicated that in the United States the composition of the ethics research boards is prescribed by legislation. So there is a prescription and a number of parameters are set out in a legislation. I think it is extremely important that we should get the maximum amount of information on this. Maybe we should ask our researchers to look into the pros and cons of this formula.
Dr. Levy, I would like to know what you think about the pros and cons of this system, since we may well adopt it here in Canada.
Those are my two questions. I don't know if somebody else would like to speak on whether access should be made voluntary or compulsory for the manufacturers. I will first give the floor to Dr. Levy and then to the Reform Party. Go ahead, sir.
[English]
Dr. Ruedy: Again, the difficulty is the answer is not yes or no.
The risk in making it mandatory to have compassionate release of all investigational drugs is it may not be to the public good. It may reduce the rate of recruitment into the clinical trial. If the company chooses, because of that hurdle, not to investigate the drug in Canada, the drug would be available to no Canadian. Third, quite clearly the public good isn't met if the supply of the drug is so limited that it is insufficient to meet both compassionate needs and clinical trial needs.
I can't give you a categorical yes or no answer. Yes, the pharmaceutical industry should be obliged to provide compassionate release provided the public good, in a variety of ways, doesn't suffer.
[Translation]
The Vice-Chairman (Mr. Ménard): You are dean of the Faculty of Medicine but earlier in your career you have also been a clinical researcher.
AIDS Action Now stated categorically that no linkage should be made between giving patients compassionate access and the success of clinical trials conducted by the Network or others.
Based on your knowledge in this area, is there a relationship?
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[English]
Dr. Ruedy: I'm not aware of that having occurred in Canada. Dr. Zarowny, perhaps, could answer that question better than I because he's more in touch with all the clinical trials that have been undertaken.
[Translation]
The Vice-Chairman (Mr. Ménard): We will give Dr. Zarowny a chance to speak.
Dr. Zarowny: Thank you, Mr. Chairman.
[English]
I think that's called a forward pass.
The perspective I have is that in the instances where there have been major demands for compassionate access to drugs, it has been possible to have the individuals concerned - that is, the community persons and the companies - sit in some fashion, discuss it, and generally resolve the problem.
I'm not sure if the comments you heard earlier from some section of the community - and I look at Arn on this to refute or agree with me - go back to another time in our experience with provision of treatments and differentiating between treatment versus research in Canada. Maybe we've progressed now to something that is a little different from what appeared to be happening five years ago.
[Translation]
The Vice-Chairman (Mr. Ménard): Thank you.
Dr. Levy, before giving the floor to the Reform Party, would you like to speak about the situation in the United States regarding the research ethics boards?
[English]
Dr. Levy: Right. I think if we rely on the research ethics boards to provide a check and a balance in the system, it is important to ensure there is some consistency across the country. For example, it would rarely make sense for a review board in one part of the country to think that a particular trial or a particular open label program was acceptable and for a similar body in another part of the country to think it wasn't acceptable. In order to achieve consistency and make sure we are fully representing the viewpoint of society, it could be helpful for the government to regulate the composition of the ethics research boards.
This is especially true if the government, and I'm thinking of the health protection branch, delegates its responsibilities to such boards as is proposed in a new HPB proposal. I think this is in the best interest of the patients, other stakeholders such as physicians who are involved in the programs, and the industry, which is relying on the boards to make these decisions.
[Translation]
The Vice-Chairman (Mr. Ménard): Thank you, Dr. Levy. Sharon, the floor is yours.
[English]
Mrs. Hayes: Thank you Mr. Chairman. I have several questions, but I'll ask the first one first. Do I have five minutes?
[Translation]
The Vice-Chairman (Mr. Ménard): I will be flexible with you.
[English]
Mrs. Hayes: The title of this forum is the National Round Table on Compassionate Access to Experimental Drugs. I see that as a very broad and quite inclusive topic - or it should be, shall I say.
I'm concerned, in some of the discussion we've been hearing, how much of the universe of the need for compassionate access for catastrophic illness or anything else is addressed and prioritized in our present compassionate access program. Several people have said needs are evaluated. Risk versus the benefit to the public good or whatever are the guidelines for granting compassionate access. This is used in the selection of candidates, programs and so on.
I was looking at some statistics relating to different diseases, and we have representatives from both of these areas of HIV and cancer. So far my understanding is there have been 16,000 cases cumulative of HIV, since it has begun to be reported, with 2,000 to 3,000 per year anticipated to the year 2000. Comparing that to the numbers we have for cancer, there have been 125,000 new cases in 1995 alone. There have been 61,000 deaths due to cancer in 1995. This is projected to grow because of an aging population, and cancer does affect older people or seems to have an incidence as people get older. So we can only expect that to become much greater in time.
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I have a couple of questions - and you can probably see where I'm going. Specifically, I would like to ask the Medical Research Council what percentage of its funds in research go to HIV/AIDS research-directed projects.
Dr. Denis: At the present time, out of our base budget of $240 million, approximately$2.5 million is spent on AIDS-related research. It's approximately 1%.
Having said that, I think it's important to point out that it's difficult to categorize some of the research that's being done. Some of the research we fund is very basic fundamental research, which may impact on AIDS, although it's not specifically labelled as being AIDS-related research.
By the same token, if one makes the same divisions as to what is being spent on cancer and arthritis, one sees the same type of difficulty. Essentially we are spending $2.5 million this fiscal year on AIDS-related research.
Mrs. Hayes: Is there a corresponding number for cancer?
Dr. Denis: I do not know the exact data for cancer-related research. Certainly, as you know, we have a special initiative dealing with breast cancer, which is co-administered with NHRDP and the National Cancer Institute. The amount of money from the base budget from MRC is $2 million per year. But there are certainly more expenditures on cancer research in general in our base budget. I just don't know what that number is exactly.
Mrs. Hayes: Taking this back specifically to compassionate access, my understanding is that the clinical trials program, specifically the Canadian HIV clinical trials, is specifically for HIV. It is funded through government funds, albeit to the administrative part of that. I can't remember the budget, but there are several million dollars at least involved in that.
Maybe I could ask somebody related to ethics...I won't specify the target of this question, but comparing the two diseases, we have clinical trials for HIV funded by the Department of Health and clinical trials for cancer funded by public donation, with no government input, as far as I know. Maybe someone can compare the funding of HIV and cancer trials, and also perhaps the general funding from Health Canada for the two diseases in compassionate care.
Mr. Dixon: I'd like to suggest several differences between cancer and AIDS. First of all, cancer didn't just sneak up on us. It is a disease with which Canadians have lived, and we have fought it for years and years. There is a very developed network of private agencies outside of the public realm that support cancer research.
AIDS burst upon us and it has not, as yet, attracted a similar support network in the private area. So it seems to me most necessary for government to step in.
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I noticed in a news report yesterday that there was a relationship drawn between the prevalence of AIDS compared to that of cancer and other life-threatening diseases.
AIDS is almost unique - I suppose ``almost unique'' is an oxymoron - in the age group that it strikes and in the numbers of productive years it cheats Canadians of. Those are differences. I think the most striking is that cancer didn't spring on us the way AIDS did. AIDS has not yet developed a private network.
Mrs. Hayes: Could I just comment on that?
[Translation]
The Vice-Chairman (Mr. Ménard): Since we have gone eight minutes, we could give a chance to Mrs. Fry and allow a quick answer by Dr. Zorowny before going back to the general exchange. Do you agree, Mrs. Fry?
You indicated you wanted to briefly answer the question from...
[English]
Dr. Zarowny: On the question about the funding for the Canadian HIV Trials Network, it is part of the national AIDS strategy. It receives $2.9 million for three years, running out in March 1998. There is only one agency in Canada that I'm aware of that tries to raise money for research, and that is CANFAR, the Canadian Foundation for AIDS Research. They raise modest amounts of money.
If you begin to play this game, which is a game that I, most of the investigators, and most of the community that we're regularly in touch with don't play - that is, comparing one disease to another in terms of incidence and dollars available - it is totally inappropriate. One of the characteristics that we have with respect to HIV disease and cancer is a disturbance of an immune system. In many ways, any money you put in one area versus the other will develop basic scientific knowledge that will be transferred in part or in total to other areas.
Mrs. Hayes: Can I just comment on that? I'll do it just briefly for both of these comments.
A dear friend of ours is 48 years old and has been diagnosed with cancer. To tell him the money that might have helped him has been spent otherwise, or that we're depending on the private enterprise to help him while government is focusing on something else, doesn't make sense to me. I think government has a duty to the public good to look at the needs that are there for the population.
In terms of cost, I guess when we talk about compassionate access, we should be talking about compassionate access to the total population and should be deeming it according to the need that's there, not just to one particular group, either within the HIV group or within the total population. The issue within the HIV group has been brought out in this discussion. If that's true within that group, then it should be true in the universe of who needs that compassionate access.
That's the point I wanted to make.
[Translation]
The Vice-Chairman (Mr. Ménard): Could we quickly give the floor to the people from British Columbia, to Mr. Schilder, to be followed by Mr. Iscoe?
[English]
Mr. Schilder: I'll do this very quickly. I'd like to point out to the Reform.... That sounds like a Reform comment. It's Hayes, isn't it?
I find it rather repulsive to make disease comparisons. Unfortunately, doing so has been a tactic of your party. If you're thinking about the public good, you should be reminded that this is an infectious agent as well as a chronic disease.
Dr. Iscoe: This shouldn't be a mud-slinging match between various groups at all. I agree with Dr. Zarowny on that.
These issues are far too complex. In fact, we're not going to be able to do everything we would like for everybody. My personal perspective, as somebody who sits here and sees genetic research, is that the next ten years are going to be even more difficult. You're going to be looking at genetic issues and how to control those with pharmacological agents. Those are going to be even more compelling, and that's going to affect a broader swath of the population.
The comments made by the colleague from the Medical Research Council are entirely correct. Research can't be pigeon-holed very easily. The research that was done on genetic make-up for cancer is the research that helped find a cystic fibrosis gene. You can't know where you're going to go, so to try to put things into nice little compartments doesn't do anybody any good.
If I can Mr. Chairman, I'd like to make a couple of comments about things that were said.
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I have served on a research ethics board at my institution. I have some misgivings about asking research ethics boards to review compassionate access, but not because it can't be done. I would hope research ethics boards are in fact good at doing the thing they do, which is dealing with general issues, but when we're talking about compassionate access, we're talking about a case-by-case review. That's what compassionate access is all about.
Compassionate access is looking at the individual request that comes before you. Is it appropriate? Does the balance of risk and benefit favour release of this agent for this individual? Are they sure they understand what's going on? I would submit that you can't do that within the context of the framework in which research ethics boards now work. One will have to try to find another mechanism, and I think that's the challenge.
Secondly, I unfortunately didn't see any of the hearings, but there were comments about randomized clinical trials being unethical. I would vehemently oppose that viewpoint as both a clinician and as somebody who sat on an ethics board. There are legions of examples in which the new therapy does more harm than good. It is delusional for people to think they are benefiting by going off a placebo and onto an active therapy.
The last component of that relates to the issue that this working group, this committee, is dealing with: drugs. The issue extends far beyond that to other sorts of health technologies. Bone marrow transplantation is a classic case in point in this situation. People there could claim compassionate access to a technology that they see as life saving. Now there's no way that's going to take place because resources are finite, but where does one draw the line? Hopefully, randomized trials will in fact resolve that issue, but if it resolves it in favour of bone marrow transplantation, there will be real problems.
[Translation]
The Vice-Chairman (Mr. Ménard): You have the floor, Mrs. Fry. Thank you for your patience.
[English]
Ms Fry (Vancouver Centre): Thank you very much.
I just want to respond to a couple of things that Ms Hayes asked, and they have to do with government funding.
Government doesn't only fund through Health Canada. As you know, Health Canada has about $42.5 million a year dedicated towards the national AIDS strategy. Some of that goes into research and the rest goes into various components like support, etc. When the research councils do their work, they're funded through government funds. So the funding doesn't come from just one little spot; there is a multitude of funding.
I am disappointed because there's such a slippery-slope tendency here. When you talk about one disease and start comparing it to others, it becomes trying and you get fighting amongst the groups. I think it was well said by the last speaker that when you in fact do work on one disease, it often branches off into assisting, helping and setting up a snowball effect towards others diseases.
Health Canada does in fact give money to research for breast cancer and for lots of other diseases. This question has been asked before not only by you, but by other members from your party at this particular health committee. I think maybe one should answer the question, which is, ``Why?'' This has always been the question, and it is one that has been specifically directed at HIV funding: Why is the government spending this kind of money on HIV funding? I think the answer is clear.
It was said earlier on that between the ages of 25 and 44 this is the number one cause of death among men in every single metropolitan area of this country. Secondly, it is an infectious disease with a high rate of transmission. We have an epidemic with this disease, and it is not only restricted to men. The increase in HIV in heterosexual persons and in women is escalating far more rapidly than it is in the gay population and among intravenous drug users. It is a preventable disease. That is the third reason why one has to spend a lot of time and funding on it.
The fourth thing is that obviously the cost is exorbitant when it comes to taking care of persons who are ill, of those who are HIV positive, who begin to get AIDS and eventually spend a few years being ill. We're spending billions of dollars, so it is therefore imperative and important that we get into research and look for funding and ways to curtail this particular disease.
I want it to be very clear that I really feel we shouldn't spend time comparing diseases. Doing so sets up sort of a mean-spirited kind of attitude amongst people when we don't want to particularly do that.
Thank you very much.
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[Translation]
The Vice-Chairman (Mr. Ménard): You have been very clear, Dr. Fry, and we thank you.
We will now have a free exchange between all the panellists. So, feel free to express yourself at will. If you have questions, we are listening.
[English]
Mr. Lemmens: I also think it's regrettable that we're all in fact involved in a discussion about where money is spent, because I thought what we were really discussing here was a drug release program that would apply not only to people with HIV and AIDS, but to all kinds of situations. I really did not want to limit my comments to the drug release program for people with HIV and AIDS.
Secondly, Dr. Iscoe referred to the proposal to use research ethics boards and an emergency drug release program. I understood from his comments in the pause that his main objection was a question of time and of using research ethics boards for what they were really constituted for. It might be true that as they are actually functioning they would not be able to efficiently deal with this issue, but maybe the research ethics board was used as a paradigm to raise an example of how things could be dealt with in an efficient way, where there would be cooperation of medical people with community people and with bioethicists and lawyers, and that was the main aim.
The Vice-Chairman (Mr. Ménard): Merci, monsieur Lemmens.
Dr. Ruedy.
Dr. Ruedy: I too would like my remarks to be taken in a wider context. I think the principles of catastrophic release and compassionate release are generally applicable and I don't think we should accept different principles for different disorders. For any disorder that is fatal or rapidly disabling I think we should fulfil the same principles.
I don't think we have the luxury to remove monetary costs from other costs in any ethical issue. I think the monetary costs are of fundamental importance in our decisions - in our ethical decisions. So I don't think we have the luxury of separating off monetary costs, which are only part of the costs, from our discussion.
[Translation]
The Vice-Chairman (Mr. Ménard): Mr. Iscoe, you are next.
[English]
Dr. Iscoe: Thank you, Mr. Chairman.
I agree with Dr. Ruedy that monetary costs cannot be ignored. One of the issues that I don't think has surfaced altogether clearly at this table has been the indirect monetary cost. We've been talking about the monetary costs related to the actual agent itself. Dr. Levy spoke about the distribution costs exceeding $1 million, if my memory is correct. Even if the drug is provided free, there are monetary costs within the health care system that can't be ignored.
There are pharmacists who will have to be involved. There is time, there's paperwork, and all that type of material. Anybody who's been involved in clinical trials knows that the basic cost of running a clinical trial is the infrastructure support, and if one is going to ask that compassionate release drugs have the same sort of information retrieval so that one will gather information, then there's that cost that has to be understood as present. The question is whether the system can actually support that sort of cost.
There are other issues involved as well, and those are issues of just physical resources besides the paperwork. Thank you.
The Vice-Chairman (Mr. Ménard): Merci.
Mr. Schilder.
Mr. Schilder: This discussion is somewhat lofty in terms of the face of the reality of what I see in my communities across this country. Working at the national level, I do spend a great deal of time travelling from city to city working in consultation. The escalating scale of poverty and marginalization of the vast majority of people with HIV, no matter what their background is, is becoming very, very serious, especially since the HIV antibody test has excluded many people from acquiring disability in any form.
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What this has done is it has put people with HIV into a reality where they must on a daily basis seek out shelter, food, and care and support. The actual issue of being able to consider a new HIV compound or catastrophic rights or compassionate access is not a probability in that this is very low on their priority. You do not consider these things when you're dealing at this level.
One of the problems is that even if you do get to that point, you'll never have the resources available, and the majority of the people with HIV in this country simply will not have the resources to pay for any of these drugs should you make them available in one form or another. With other disease groups, such as cancer, many of the patients will have some resources or some disability, but the vast majority of people with HIV now and in the future will be living on something like $771 a month in downtown Vancouver and trying to survive.
So the issue of the availability of a new compound is not a reality, even if they have the understanding that the drug exists or how to access it through the current clinical trials process.
[Translation]
The Vice-Chairman (Mr. Ménard): We now go to Mr. Derek Jones.
[English]
Mr. Jones: Thank you, Mr. Vice-Chairman. I wanted to make a few comments about the function and mandate of research ethics committees, since this has been addressed by a few interveners and yourself in your response to Dr. Levy's suggestions.
First, on the latter issue about the role of law and guidelines in Canada regarding the function of research ethics boards or REBs, I would point out a couple of things. Dr. Levy is correct about the federally mandated composition and function of REBs in the United States. That is one model. I would also draw the committee's attention to an ongoing initiative in which the Medical Research Council and many of the funding councils in Canada are involved, and that is essentially to rewrite the third edition of the guidelines involving human research in Canada.
Two weeks ago at the Canadian Bioethics Society, a draft discussion paper on the functioning composition of REBs was tabled. There will be a six-month comment period, etc. This is all to suggest that the composition, function, and mandate of REBs is very much alive in Canada and is under thorough discussion.
That is not to say that the suggestion about the federally mandated composition is out of order. In fact, I think as we look across the country we would conclude that the law is beginning to play an increasing role in this. An example I would give is Quebec, which mandates certain prospective research ethics reviews for research protocols.
I would conclude by returning to this distinction between treatment and research, and again this goes to the mandate of REBs, which is to review prospectively research ethics protocols. The HPB proposal tends to treat most of compassionate access as treatment, which would seem to suggest that REBs perhaps would not be involved.
I would suggest to the committee and to Health Canada that we be absolutely clear in terms of our definition, because it may well be that we have a conflict of mandates and definitions. In that respect, I would point out that the Medical Research Council's definition of research is extremely broad and that the research ethics committees work under that broad definition. Correspondingly, therefore, the definition of treatment or of compassionate access and the particular branches that HPB is proposing have to be clear and explicit so these committees can function and know what they're doing.
[Translation]
The Vice-Chairman (Mr. Ménard): We have gone through all the speakers on my list. Unless any others wish to speak, this consultation session is over.
I would like to make two requests. Mr. Denis, would you provide the members of the sub-committee, through our clerk, the guidelines for trials on humans that your colleague mentioned, so that we have them on record.
Dr. Denis: I have a copy right here.
The Vice-Chairman (Mr. Ménard): You have a copy. Maybe the clerk could gather all the relevant documents. We could also ask our researchers to get some more information on the role of research ethics boards in the United States. We can also undertake to provide to you the results of the research done by our staff.
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As for us, we will resume our hearings tomorrow morning, at 9 o'clock, in room 237C in the Centre Block. We will look into the financial aspects of compassionate access to research drugs.
I would like to thank you all for your efforts and energy in coming here. Rest assured that we will make good use of your input. It will help us to develop the recommendations we have to make to the government. Again, thank you to all.
The meeting is adjourned.