[Recorded by Electronic Apparatus]
Wednesday, May 1, 1996
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[English]
The Chairman: Ladies and gentlemen, we're going to start, if you don't mind.
This is the Subcommittee on HIV/AIDS of the Standing Committee on Health. You have already received the notice of the meeting. The order of the day is the National Roundtable on Compassionate Access to Experimental Drugs.
As you're all aware, the bells are ringing right now. We're going to have a vote about twenty minutes from now, so we will start right away.
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I would like to have our witnesses make a presentation for about five minutes, and after all the witnesses have presented we'll have questions from the members. We'll start with the Canadian Cancer Society and Mr. Neil Iscoe, the president of the Ontario chapter.
Mr. Iscoe, please.
[Translation]
Mr. Volpe (Eglinton - Lawrence): Mr. Iscoe, will you be coming back after the vote?
Mr. Neil Iscoe (President, Ontario Chapter, Canadian Cancer Society): Yes.
[English]
Thank you, Mr. Chairman.
I appreciate the opportunity to come before the committee once again and respond to the draft report following the initial series of round-table meetings.
I regret I have to leave shortly after my remarks and will miss the further deliberations of this committee, as the matters before it are much at the heart of concerns of cancer patients and the Canadian Cancer Society.
Again, I must inform the committee that because of the nature of the society, the views I will express are really mine and mine alone. They're in concert with the general position of the society, but they're really mine. They don't represent the other organizations I'm affiliated with: the University of Toronto, the Sunnybrook Health Science Centre or the Ontario Cancer Treatment and Research Foundation.
First let me say I think the report represents a fair summary of the content of the round table I attended, and I applaud the people who wrote it. I'd like to respond to the committee's concerns by identifying issues that arise in or as a consequence of the report.
There's no doubt in my mind that for the foreseeable future there will always be people suffering from immediately life-threatening conditions. Therefore, although it may not be the issue before this committee, I think it's appropriate to ask what problems the proposed program is meant to solve.
Is it a matter of a slow drug approval process? Is it a need for conditional approval, as was highlighted in the report? Is it poor access of affected individuals to the drugs being assessed? Is it a clinical trials process that is just too restrictive? This committee may want to consider those things as it looks towards altering the compassionate access program.
It's unclear to me from the report what the content of any compassionate release program would be. In general terms there might be two types: unlimited access and limited access. It is my view that in the present context it would be most likely that any such program would be limited in some fashion. If that is the case, how does one establish issues of fairness within this?
There are issues of fairness at a number of levels. There are issues of fairness in the context related to fairness of access within the illness and the treatment in question. There are issues of fairness within the limitations of the compassionate access programs, across illnesses and across treatments. There are issues of fairness between support for compassionate access and medical care for both present and future generations. The report speaks of intergenerational equity. I would submit to you that there are also questions of intra-generational equity that have to be dealt with here.
The society has no firm answer on any of these difficult questions, but I would like to restate what I stated at the first round table where I was present: the society believes in the right to self-determination, but does not believe that right permits one person or group to exercise that right to the disadvantage or detriment of another individual or group.
In the context of declining health care resources, which in the province of Ontario over the next two or three years will dramatically alter if not revolutionize the health care scene as we know it, the society believes we must first maintain our commitment to doing the things we know make a difference in patients' lives before we extend it beyond that.
In the report much is made of a standardized consent form. The society has no position on such a form, but supports a consent process that is open, informed and non-coercive; is respectful of the values of individuals, families and the society; and, importantly, is ongoing. Like the NCBHR, I would have to question whether or not a "standard form" is up to this challenge.
Moreover, it seems somewhat artificial to believe people in life-threatening situations will deal with a consent process in the same way as you would deal with the consent in an elective situation. So we have to be clear on what we expect from this process.
Within the process of consent is the issue of accountability. If accountability for consent processes lies with the practitioner and local REBs, then it is my belief they should have final say on whatever shape or matter this form has.
Mention is also made or implied of local REBs assuming an oversight function for consent processes in their institutions, or perhaps for their community of physicians. Are local REBs mandated or constituted to take on this task? Do they have the resources to do this? The volunteer members - and I emphasize the word "volunteer" - of the REB at my institution review between 200 and 300 research projects a year.
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The issue of the mandatory reporting vote comes from people not on clinical trials, and the paperwork involved appears repeatedly. I mentioned at the first round table that this society has had an investment of research through the National Cancer Institute of Canada for more than half a century now. As a result, the society values information where there is none. However, I can offer you no thoughts as to who is responsible for this activity.
Having said that, it is my belief that irrespective of whether the support comes from government or industry, ultimately the public or patients will bear the cost of this in terms of higher drug costs or alteration in support of existing drug programs. One has to bear that in mind.
Reports note that there was a limited discussion of conditional approval. I believe the society would support a conditional approval but has a number of questions.
What constitutes a life-threatening condition of an immediate nature? Would someone with Parkinson's disease or advanced multiple sclerosis qualify? Would an asymptomatic person with HIV or advanced breast cancer qualify? Would conditional approval be contingent upon the performance of a phase III trial or some other activity, such as mandatory post-marketing surveillance? Would there be a timeframe for these activities to be completed and assessed and reported upon? These things are not clarified in the initial report, but I think they have to be considered.
The report asks the question of who should receive compassionate access. I've already mentioned some of my thoughts on that. However, I must note that I found a statement towards the bottom of page 16 to be particularly troublesome.
While the idea of supplying drugs free to patients in clinical trials is not new, the idea of charging patients choosing not to enter the trial for the same agent raises the spectre of two classes of patients: those with the means to buy the drug and those who do not. In the context of people made vulnerable by life-threatening illness, this distinction is particularly odious and, at a minimum, highly coercive to those less affluent, forcing them to consider participating in a trial, a less than truly voluntary process.
The society is aware that the collection of information about patients enrolled in clinical trials is often on a per-case funding basis. Would a parallel group of patients on compassionate access have a similar cost-recovery function built in? As a member of the REB, at our institution I have seen post-marketing surveillance studies conducted with per-case funding identified. If this is done - and I think the motives behind it are irrelevant - is this any different from a company supporting the collection of information about activity and toxicity from patients receiving treatment through a compassionate access program?
It is my understanding that post-marketing surveillance of some fashion has been done as a matter of course in Great Britain for many years now. Perhaps we can learn how they do this and whether or not it provides them with satisfactory information.
Mr. Chairman, I thank you for the opportunity to bring my comments to the committee.
The Chairman: Thank you very much, Mr. Iscoe.
Now we have Dr. Michael O'Shaughnessy from the Canadian HIV Trials Network.
Mr. Michael O'Shaughnessy (Director, Canadian HIV Trials Network): Thank you. The Canadian Trials Network appreciates the opportunity to appear today and make these comments about the report.
As you know, the Trials Network has been actively involved in facilitating the establishment of national protocols for the compassionate release of new drugs. Under these initiatives thousands of Canadians have received drugs prior to licensing, and we believe the role the Canadian Trials Network has played has been pivotal. The CTN has provided a full range of services, including enrolment, data assembly and analysis, and in some circumstances a lottery system.
As you know, the latter activity occurred several times when the amount of drug available for compassionate release did not meet demand. The lottery was established according to guidelines set following extensive community consultation and direction. The CTN, however, believes that lotteries are a less desirable alternative to providing drugs to everyone enrolled in a program, but occasionally the CTN realizes that drug availability does not meet demand. We also believe that the final version of the process of supplying drug in times of drug shortage has yet to be developed.
After reading the report, one must ask whether the compassionate release of drugs is likely to continue. We believe the answer must be yes, since the review process for new drug submissions takes time.
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We still believe the process could be more efficient if approvals in North America were more synchronized. Recently, two important drugs received approval first in the United States. This asynchronous availability and the concomitant public relations activity that surrounds the approval of drugs in the United States did result in dramatic increases in the number of HIV positive Canadians seeking access to these drugs under compassionate release.
In other words, there's a flooding of demands of compassionate release and one only need think of 3TC and some of the other new drugs where you see the demand go from 500 to 3,500 within a matter of one or two months. We suggest there ought to be more sharing of resources and information between North American regulatory agencies.
Could the system that we have work better? We believe it could, since at present the compassionate release program has no grounding in the provinces. The program as it exists allows individuals to access treatments prior to the pharmaceutical company receiving approval to sell drug. Thousands of HIV positive persons access these new drugs, but once the compassionate release program terminates there is considerable uncertainty surrounding whether or not the drug will be covered by relevant provincial drug programs.
The mandate for the provision of drug then falls to the provinces when the compassionate release terminates. How and when the demands for the new agents are met are highly variable since the provincial economic environments in the country are so different. Hence, the provinces are left out of the loop and holding the bag since up to that point, all the previous discussions have been the federal government and the manufacturer.
We must remember that the compassionate release program itself does involve significant provincial resources and one just has to think about who pays for the patient visits, the laboratory tests and the institutional care that are all inherent to a compassionate release program. So these programs go on. They elicit thousands of individuals and no one speaks to the provinces and we think that is a weakness of the current system that needs more dialogue between the two layers of government.
Finally, after reading the report, we did believe that there was another overriding issue that we had to raise. The commitment of the federal government to AIDS reminds problematic for us. Today, before this subcommittee, we are speaking about the compassionate release of drugs to HIV positive persons, and this is an important issue. But we believe that the same federal government that arranges for this meeting while we are talking about compassionate release waffles about the future of its support for an AIDS strategy or program.
Frankly, the country cares little about whether the support resides in a strategy or is vested in the various departmental programs. The issue for all of us is that the support exists. We have heard the federal government does not endorse the continuation of this strategy in its present form and we have also heard the government is considering a draconian reduction to a level of 25% of its present allocation. This is clearly unacceptable. Federal estimates from the government of Canada put the total number of infected persons at nearly 50,000. The logic of reducing services and commitments as the epidemic continues to expand is incomprehensible. We don't believe that one can address the issue of the compassionate drugs - the release of drugs on a compassionate basis - in isolation from all of the other things that must go on at the same time.
We understand that HIV-AIDS can be a rather unpopular subject here in Ottawa, but the true measure of a government is in its ability to provide leadership and support. It is very easy to cave in to the fallacious arguments pitting one disease against another, but history will judge us all on what we do. We are also equally as accountable for what we do not do, for whatever reason.
I think I'd like to end there. Thank you.
The Chairman: Thank you very much, Dr. O'Shaughnessy. What we are going to do is, having about four of five minutes left, we are going to go back to the House of Commons and we're going to come back right after the vote. It will be about twenty minutes from now and we're going to start back with Mr. Benjamin Freedman right away when we return about twenty minutes from now. Thank you.
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The Chairman: Order, please. As was mentioned when we left for the vote, we're going to start with Mr. Benjamin Freedman, chair of the NCBHR Committee on the Ethics of Research Design.
The floor is yours, Mr. Freedman.
Dr. Benjamin Freedman (Chair, Committee on the Ethics of the Research Design, National Council on Bioethics in Human Research): Thank you very much, Monsieur le président. Mr. Chairperson, on behalf of the president and members of the National Council on Bioethics in Human Research, thank you for inviting us to participate in your final session on reforming the compassionate access to experimental therapies program of Health Canada.
We are pleased that some of the issues raised in our December 1995 brief to the subcommittee were explored in the Library of Parliament discussion document. That document and the discussion it generates should provide a sound basis for a final committee report.
We would like to confine our remarks to three points that were outlined in the ethical discussion section of the document, namely, national ethical standards and the role of research ethics boards or REBs, the definitional interface between research and treatment, and CBHR's role in compassionate access.
On the first point, national ethical standards, the report expresses the concern raised by some interveners that autonomous REBs are functioning at the expense of national standards.
The concern raises deeper questions about the role and functions of REBs or research ethics boards in a national system of research ethics review. Canada has adopted the model of research ethics review that consists of three general components: first, a requirement that research studies involving human participants pass before a local research ethics committee; second, national research ethics criteria that are applied to the evaluation of individual proposals; third, broadly articulated goals and purposes to guide the function of local research ethics committees. This basic model is shared with such countries as France, the United States, Australia, and Britain.
In some countries the obligations and procedures that are applied are governed by law. In other countries they are governed by guidelines, as has been the case in Canada. In either instance the centrepiece of the model is a national research ethics process that is expressed through local review. As NCBHR had previously noted, "by intentionally decentralizing the administration of research ethics review, the model incorporates an inherent tension between national guidelines or criteria and the local application of them".
One model that has tried to reconcile the opposing poles is that adopted in the United States for certain multi-centre studies. In that case a central group, the Office of Protection from Research Risks, prepares a model consent form that is forwarded to local committees who are permitted to adopt the model form or to modify it according to local needs. If the local committee wishes to alter some risk-benefit information provided, it would in that case need to forward its justification to the Office of Protection from Research Risks.
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The efforts to define minimum national norms in the function of research ethics committees constitute a necessary attempt to perfect this international model.
We would draw the attention of the subcommittee to the fact that on April 15 the Medical Research Council of Canada, the Social Sciences and Humanities Research Council, and the Natural Sciences and Engineering Research Council jointly released a draft code of conduct for research involving humans. This draft tri-council code contains many specifics regarding the composition and function of REBs, and it is intended to be more prescriptive than what we had previously had as guidelines.
The second point is definitional interface, and here I'll be brief.
In terms of the definitional interface between research and treatment, we want to re-emphasize the need for clarity in understanding the role of research ethics boards and compassionate access programs. This difficulty arises in part because REBs are generally responsible for reviewing the ethics of research protocols. Other institutional or hospital ethics committees - clinical bioethics committees, for example - have more typically been involved in the ethics of clinical treatment decisions.
The possibility of confusion of roles arises when a therapeutic undertaking, such as compassionate access to experimental therapies, contains elements of both research and treatment.
Whether the older categories of research versus established treatment are sufficient or whether new ones, such as innovative practice, are needed requires close study, some rethinking, and perhaps novel structures and responsibilities.
The third point has to do with the NCBHR role in compassionate access. The discussion document suggests that NCBHR may play a leadership role in, and asks whether NCBHR should manage, compassionate access. From our perspective, NCBHR currently plays at least two important roles in this area. The first is to advise and consult with local REBs on difficult or ambiguous ethical issues arising from compassionate access. The second is to serve as an independent national advisory body on research ethics norms for governments, research funders, investigators, the universities, industry, and the public.
Our current advisory and educative responsibilities are clearly distinct from regulatory or management roles. We recognize that we cannot in fairness call on others to reimagine how Canadian national resources might be mobilized into a coherent policy on compassionate access without reimagining our own world of potential contributions. Certainly it is true that NCBHR is open to exploring new roles and responsibilities that, with a proper mandate, authority, resources, and independence, would better allow its interdisciplinary expertise to benefit the public.
With your agreement, we will reserve comments on the technical facets of compassionate release for the discussion section.
Thank you for the opportunity to share with the committee some of our reflections on these matters. We look forward to fruitful cooperation with you and other federal players on this.
The Chairman: Thank you very much, Mr. Freedman.
Mr. Jones, you're next. Oh, you're going together? That's fine.
I'll now go back to Mr. Armstrong.
Mr. Russell Armstrong (Executive Director, Canadian AIDS Society): Thank you,Mr. Chairman, for the opportunity to speak today. I have some general comments on the report. Like my colleague Mr. Freedman, we thought we'd bring up the specific comments of the society on some of the technical aspects during the discussion process.
My general comments have to do with some concerns about words used in the transcript and their value implications. It's important for me to bring out some of these concerns and to stress that if we're going to get anywhere in this discussion we need to be sure that we share some underlying values.
I have three examples of what I'm talking about.
In a couple of sections in the transcript there's a discussion of what's called ``cheating". This is referred to where people who are participating in clinical protocols don't respect their protocol and share medications or try to discover which of the medications under study they're actually on. I don't like the use of the word "cheating", and I'm not sure it actually respects what actually is going on. Cheating is a question of perspective and it's really a judgment.
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For me, it's important to remember that when we're speaking of HIV-AIDS we're dealing with a disease where at first there was widespread refusal to treat and now we have widespread reluctance. It's clear that in the face of both those things becoming empowered and aware as a person living with the disease was, and is, the only way to receive adequate treatment.
Instead of cheating, I think what's going on here is that we're talking about young people dealing with a terminal illness, for the most part. We're also talking about people who can to some extent exercise rights of choice, can understand the processes they're participating in, and can choose to do certain things within that process to try to preserve their lives, basically, or at least try to make choices that will improve their chances against the disease.
If changes are made to the report, we might look at changing the word. What we're talking about is people not abiding by the terms of the protocol and reasons for their not doing that.
The second example is there's a reference in the transcript that says a significant proportion of people living with HIV-AIDS make emotional decisions around treatment. Certainly from the perspective of the Canadian AIDS Society and the perspective of the people living with HIV-AIDS who participate in this society this is for the most part not true. Again, the word implies a judgment statement and it's framed very negatively. I think it disrespects the evolution of treatment activism, the kind of activism that can bring an issue such as this to the table at the national level and get a committee such as this to deal with it. It doesn't suggest people living with HIV-AIDS can be informed about the disease and make rational choices in the face of alternatives.
The third example I'll dwell on is a paragraph discussing drug development. It has a statement that with the exception of the critically ill and their advocates, everybody else around the table thinks nothing should interfere with drug development. Again, I find this misleading. Finding effective therapy is at least as important for people living with HIV-AIDS as for anybody else. I'm troubled by the way the report is worded. It puts these people over here, against everyone else over here.
We're talking about a really difficult question of balance. Phrasing paragraphs in that way, positioning people against each other in that way, I don't think gets at some of the real issues.
Those three examples have led me to question some of the underlying assumptions in this discussion that's gone on now over the three sessions. Unfortunately I haven't been able to be here for all of them, but I have kept close track of the discussions and I've been reading the transcripts as they become available.
I just want to stress that to a large extent where this issue comes from is people who are living with HIV-AIDS and who are knowledgeable about their disease and motivated enough to question the status quo. Despite the examples I gave you from the transcript, these are not desperate people with mental pathologies. They are not selfish individuals after their own needs at the expense of all others. They are people who are really well informed about these issues, who can grapple with them and bring them to the table. I don't see the transcript really reflecting that very well.
Unfortunately, what I do see in the transcript is that the loudest voice at times comes from the representatives who spoke to the committee, who are physicians trying to treat people living with HIV-AIDS. I think sadly they're representative of the number of physicians who are stretched to their limit right now, dealing with the overwhelming needs to treat this disease. To some extent they appear to be at breaking point, so naturally they're going to say ``don't put anything else in front of me", etc. I don't want to disrespect the heroic work of these physicians. I'm just drawing your attention to that point because it underlies for me the question of balance in the issue and balance in the transcript.
It's clear to me we have conflicts of values and interests in this discussion, and it's certainly not an easy issue, but I'm not sure we're going to be able to move forward to a conclusion on the discussion unless we are very clear and very forceful about the fact that the concerns of people living with HIV-AIDS and others who are catastrophically ill need to be considered as at least equal with the others. When I read the report I don't get that sense. I really get the sense of a small, radical group of people with some problems being over here, and then the status quo, the institutional players, being over here and being able to be much more reasonable about this issue.
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I think one of the problems with the way in which it has been framed in the report is that there are too many either/ors in the discussion. There is too much of what appears to be the pitting of one interest against the other - and the examples I gave hopefully underline that. I think there seems to be a need for a bit more elucidation about what the values underlying this discussion are. I'm not sure there's enough treatment in the report about what the values are that take precedence over others when a balance is not possible.
Just to conclude my opening remarks, in terms of the Canadian AIDS Society, we certainly don't believe this discussion is either/or, nor is it the institutional interest versus the people living with HIV-AIDS. I think there are many ways in which everybody's needs can be met. What we need to create, as part of this discussion, is an environment in which we consider that rational choices can be made and respected, and that we can build a system that supports these options. The big example that's given is that if we open access too widely to experimental therapies, we'll never have good clinical research. My experience, in having worked in the field for over ten years now, has been that we're talking about a group of people - specifically, people living with HIV-AIDS - who I think clearly understand the need for clinical research and have the ability to ensure that in having needs met, the possibility of doing good clinical research is not jeopardized.
That's all I'd like to say as my opening statement. Thank you very much.
The Chairman: Thank you, Mr. Armstrong.
Now we'll hear from Mr. James Kreppner of the Canadian Hemophilia Society.
Mr. James Kreppner (Board of Directors, Canadian Hemophilia Society): Let me start by saying that I concur with everything Mr. Armstrong has said. He has pointed out some of the things I would have pointed out in terms of the tone of the report and how consumers seem to be lumped into one group. The impression seems to be left that perhaps they were too emotional and weren't understanding the full ramifications of all the issues. Certainly, based upon my experience, that simply isn't true.
A lot of thought has been given to this issue in the broader AIDS community, and a lot of discussion has gone on around this issue. We've looked at the pros and the cons, and we're aware of the pros and the cons. Ultimately, I think what it comes down to is the issue of compassionate access and what compassionate access is. I don't think we should lose sight of the fact that we are talking about compassion. We are talking about giving drug treatments to people who otherwise wouldn't be able to access those treatments, and we're doing this out of a sense of compassion for the difficult straits that these people find themselves in.
In the discussion paper we see a number of issues canvassed. We look at what the impact would be on some of the other actors; what the impact would be on the drug companies; whether or not it creates more paperwork for Health Canada; whether or not drug companies in the future would want to bring trials to Canada if in fact there were any types of onerous provisions put on drug companies with respect to compassionate arms. These are all important issues and, as I said, they're not new issues for our community. They are issues we have talked about. Like anyone else, we certainly don't want to take action that would stop clinical trials from occurring in this country.
We think, however, that a middle ground can be found where there is an incentive for these companies to have clinical trials within Canada with compassionate arms as well, and in such a way as to be positive for both the people living in the country and the pharmaceuticals participating in those trials. I think a good example of that is the Clinical Trials Network.
The fact that when people make submissions to the Clinical Trials Network for support, or when pharmaceuticals make submissions to the CTN for support, there is a question on the document that they have to fill out that asks what their plans are for a compassionate arm. Just having that question there I think is very helpful in terms of a moral-suasion perspective. The fact that the question is there brings to the attention of the drug company that this is something people are aware of and are thinking about and would like to know an answer on, and it provides an incentive to the drug company perhaps to take it seriously and do something about it.
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Looking at what has happened in terms of CTN-sponsored trials and at what's happened in terms of some of those same companies then putting forward compassionate arms, I would suggest that to a large extent it has worked. It has been helpful to have an agency ask that question and also make it quite clear that from that agency's perspective this is the preferred option.
It's one thing for the clinical trials network to do it, but I think much more importantly it would be better if we saw the Health Protection Branch do it. I think it would increase the amount of moral suasion there and you would start seeing the same types of results as you see now in terms of drugs that are submitted to the Clinical Trials Network for their assistance.
I know that COCQ-CIDA suggested - and I'm reading the report - the licensing of another drug in a company stable if they refused to give a satisfactory reply as to why they were not providing compassionate access, if they were in fact deciding not to provide compassionate access. That was one of the suggestions put forward.
I noticed that the report quickly shot that down and said, ``Well, what if the drug chosen was 3TC?" I submit to you that this is a little bit of a red herring. Certainly I think the proposal envisions a drug being chosen that perhaps has many competitors in the market and perhaps even has nothing whatsoever to do with AIDS and whose lack is not likely to have a significant impact on people's health.
So I don't think people were thinking about 3TC, for example, and I found that example to be a little bit strange.
Obviously, in the cases where maybe there just was no such drug.... Maybe every single drug that this drug company put out really did have important, efficacious results for people and there were no substitutes. In a situation like that, certainly you could have a fall-back position, which would be a monetary fine for the drug company not satisfactorily explaining why it isn't participating in a compassionate arm.
As for the above sorts of procedures being challenged through GATT or NAFTA, I find that hard to believe. First, anything can be challenged by anyone at any time. I'm a lawyer. I know that. People go to court whenever they want to go to court, whether they have a case or not. So, yes, it could be challenged through NAFTA or GATT. I don't think there would be much of a real case there. Countries can license and de-license drugs at will, and they do so all the time.
It would be a case only if you could prove that the drug was being delicensed in order to give an unfair trade advantage to a Canadian drug or in some way to affect the market in that respect, but clearly that's not what's being proposed here. So I think, again, that is a much overrated potential difficulty.
Finally, on the special access program, I can tell you that, having talked it over with some others and having read what this program entails, I have some problems with it. I think the EDRP has a fine record. The EDRP is actually known outside of Canada. I browse on the Internet all the time and I read messages on news groups, etc., and the EDRP has an excellent reputation. I've heard envious comments from other jurisdictions as to why they don't have an EDRP or its equivalent. I'm not sure that the SAP, as proposed, is really a satisfactory replacement for that.
It's one thing to have government go to a drug company and say "Will you make this drug available, because we have someone asking for it", and another thing to have a patient go to a drug company and say ``Will you make this drug available because I like it".
I have participated in both processes. I've been through EDRP. I've also gone straight to drug companies on occasion. It may or may not surprise you to learn that usually it's the EDRP requests that get more serious consideration on the parts of drug companies. That shouldn't be surprising, because they know very well that if they refuse it, at least that's something that's noticed by somebody.
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If the drug company tells you.... With the SAP their easiest response is to say no. If they say no, they don't have to do any further work. If they say yes, then they have to go to Health Canada and provide the information on the drug and everything else. They have to notify the drugs director within 48 hours.
From my standpoint, that seems to be setting up a system that makes it more difficult rather than less difficult to access these types of drugs on an emergency basis. I know they're saying you're taking out a middleman and that will speed things up. Well, trust me, drug companies can sometimes waste just as much time as, if not more time than, government, especially when government is not there to remind them they should be moving quicker.
There's another complaint, that EDR is overburdened by people requesting experimental AIDS therapies. I would just say, well, if that really is a problem for EDR, then if you put into effect a program or a set of policies that encourages companies when they do file protocols for approval of their drugs - I'm thinking of phase two, phase three protocols - if a compassionate arm is there, almost as a matter of course that will remove a lot of the incentive for people to call in and then try to get the drug through EDR, because they won't have to do that any more; there will now be this other arm, which will provide the drug. That would take a lot of the weight off EDR and it would solve the problem we're hearing about EDR from Health Canada.
Trials can be conducted in a manner that ensures recruitment and at the same time provides a compassionate arm. Some people don't qualify for the initial trial, and those people without a compassionate arm are left high and dry, without any type of recourse. We also know that just being able to get on a drug can have an immense psychological effect. We recently found the protease inhibitors have more than just a psychological effect. For sick people it actually made a difference.
Again, maybe I'm speaking anecdotally, but I'm speaking to you as somebody who had a CD-4 count of four and went on a combination of drugs, two of them through compassionate access protocols. My weight went from 105 to 140, my CD-4 count went from four to fifty, and I felt much better, to the extent that I'm here, whereas I couldn't make previous hearings. I know that is only anecdotal, but the point I'm making is that compassionate access can have a real effect on people's lives, and we should be doing everything we can to make compassionate access available.
The Chairman: Thank you very much.
Now we're going to pass on to Mrs. Atkinson, from AIDS Action Now.
Ms Maggie Atkinson (Co-Chair, AIDS Action Now): Thank you.
As you know, AIDS Action Now is a Toronto-based activist organization, fighting for improved research, treatment, and support services for people with AIDS.
Last year around this time my colleague Brian Farlinger, who was co-chair of AIDS Action Now at the time, spoke to this committee. At that time he asked me to come and speak to this committee as well, but unfortunately I was too ill to attend.
Like James, I am someone who has benefited from compassionate access personally. Last March I started taking 3TC through compassionate access. At that time I had been bedridden for about seven months. I was seriously ill. I wasn't expected to live. As a result of going on AZT and 3TC concurrently, my T-cell count went from 60 to 200 within a month. I had more energy and my prognosis is certainly a lot better than it was a year ago. So from a personal perspective I would speak strongly in favour of compassionate access. I have many acquaintances who have similarly benefited.
Unfortunately, delayed access to treatment is really access denied. Many people like Brian Farlinger, who didn't live to see saquinavir, for example, available on a compassionate basis, and who had exhausted all other options, have died before they were able to get access to these drugs.
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The environment has certainly changed significantly in Canada. Even in the last few months we've seen a real change in the way companies are approaching compassionate access. I think the Canadian HIV Trials Network has had an influence on this. Both James Kreppner and I are on the Canadian Advisory Committee of the Canadian HIV Trials Network, and in that capacity we have reviewed numerous protocols for drugs. I think we've seen a gradual change, not only with companies but also in the attitude of researchers towards the use of compassionate access programs.
Initially it was quite difficult to get companies to even talk about compassionate access. I think that having the Trials Network put this kind of question in their protocol application form has helped. The network has also followed up by having the national director write a letter to the companies inquiring as to their plans for compassionate access. This has sort of started moving things along.
Initially we saw the Glaxo 3TC compassionate access program. A lot of people enrolled in it and it was successful. After that there was the class of drugs called protease inhibitors, which are very powerful and also very difficult to manufacture. It's a much longer and more expensive process, so the drugs were limited. This led to some restricted compassionate access, which is something else the community has been grappling with. How do you ration compassion?
This led to the saquinavir or Roche compassionate access program in Canada. Since December, we've seen compassionate access to two new protease inhibitors, Crixivan and ritonavir, the drugs produced by Merck Frosst and Abbott. Again, those had restricted compassionate access but it's been gradually increasing.
As a matter of fact, we were just able to negotiate increased compassionate access to ritonavir with Abbott. They initially told us they wouldn't give any compassionate access whatsoever, then they said they would give some. A month ago they came to us and offered 160 spots across Canada, and just about a week ago they informed us that they've agreed to increase it to 500 spots immediately. So there is a gradual movement towards more compassionate access.
With each new drug that's coming close to being on the market, groups like AIDS Action Now are approaching the companies and encouraging them to start compassionate access programs. I think we're changing the environment in Canada so that it's the expectation that there will be compassionate access of some kind.
For example, in the fall we met with Boehringer Ingelheim and we were able to get the company to agree to compassionate access. Then at the beginning of the year we were actually approached by Pharmacia & Upjohn because they wanted to create a compassionate access program and they wanted community input. We just met with Janssen and we're having talks with them about setting up a compassionate access program.
The point I want to make is that I think there is an encouraging trend towards more compassionate access. I think something else that's changing in Canada is that there are more drugs available. Previously there really were very few options for people with AIDS. You're talking about three drugs: AZT, ddI, and ddC. There is also d4T, which is not licensed yet in Canada, and there was 3TC, which again is not licensed.
It's now licensed? I guess these things change pretty rapidly.
One point I want to make is that there are more options, so I think this may have an effect on the issue of whether compassionate access will compromise clinical trials. In the past people had so few options, they'd exhausted their options. Drugs like ddI and ddC have certain toxicities, like pancreatitis and peripheral neuropathy, so people weren't able to continue to take the drugs. Now that we have more options on the market, I think people will be less likely to want to jump out of a trial in order to access a new drug.
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In terms of what we want, I think the bottom line is that we all want quicker access to drugs. I think that comes in a variety of ways. First, there's compassionate access to the drugs. I think we'd like to see compassionate access as a requirement of phase two and phase three trials. That was brought out earlier, I understand, by COCQ-SIDA, based on some guidelines that had been developed by AIDS Action Now about a year ago.
With respect to compassionate access, I think there needs to be an improvement of the EDRP or the SAP system in order to expedite access. I would agree with James's comments in that there are some problems with the SAP. I think it's important to have the government have some kind of role in there in making the request. Even with EDRP, the companies still like to ignore individuals. We find that it's only when an organization like AIDS Action Now calls the company that they sit up and listen.
We'd like to see the drugs directorate drop the requirement for protocols. What we're finding is that we negotiate with the company to get compassionate access to the drug. The company agrees to provide immediate access to the drug through the EDRP to any individuals who request it. What we hear from the company is that the drugs directorate tells them that they need a protocol from them in order to supply this drug to the number of individuals who are applying.
The requirement of the protocol holds things up for months. The problem is that people are dying everyday from this. In Ontario alone, we're seeing one more person dying of AIDS every day. So holding this up for four months or six months is really intolerable when we think of the costs in human lives.
I think that it's also questionable whether we need approval for compassionate access. I would suggest that compassionate access is really treatment. It's not a trial, and I don't think it should be treated as such. For that reason, I don't think it's necessary for us to have a protocol, and I don't think it's necessary for us to have ethics approval.
If there is some requirement for ethics approval, perhaps you could have one central ethics approval. For example, the National Ethics Review Committee of the Canadian HIV Trials Network has performed this function in the past.
I would just like to make a statement. I'll be prepared to provide some written comments. I have a lot of problems with the disadvantages that are set out in the report. I would say that I would have to disagree with many of the statements, premises and various disadvantages as set out.
Now I'll be happy to contribute to the broader discussion. Thanks.
The Chairman: Thank you.
Mr. Milligan, from the Pharmaceutical Manufacturers' Association of Canada.
Mr. William D. Milligan (Vice-President, Pharmaceutical Manufacturers' Association of Canada): Thank you, Mr Chairman, for the opportunity to comment today on behalf of PMAC. In line with the intent of this final round table, I'm here to provide the subcommittee and the other participants with additional information and clarification of the PMAC position on the issues we've discussed, and offer some recommendations for addressing some of these issues related to the compassionate access to experimental drugs.
Due to a total reorganization of PMAC over the last few months and the resignation ofDr. Fourie as the chair of the PMAC HIV subcommittee, there has been no opportunity to fully debate the proposed mechanisms that came to us in the report to establish an official PMAC position on each.
My comments, however, will address PMAC positions on the four general areas we discussed during the round tables, including the issue of compassionate access, regulatory issues, ethical issues, legal issues, and the responsibilities of each of the stakeholders.
Also unfortunately, Dr. Levy wasn't able to attend today. He's our clinical and regulatory expert. He's away today due to illness.
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On the first point of the issue of compassionate access, in the last four months - Maggie alluded to this in her discussion - as we've been debating this issue, there has been new information relating to the availability of anti-HIV drugs.
In November 1995, just prior to the session's beginning, catastrophically ill AIDS patients has widespread access to only three nucleoside analogues or reverse transcriptase inhibitors: AZT, ddC and ddI, which Maggie Atkinson mentioned. Their only additional therapeutic option was to add d4T, 3TC or saquinavir through compassionate access programs for these drugs or through EDRP. We already mentioned the limited availability of the protease inhibitor at that point.
With the exception of saquinavir, the options were limited to combinations of nucleoside analogues, offering only one avenue of assault on the HIV and the disease. The protease inhibitors were in short supply as companies struggled to gear up production capabilities and meet the growing global demand.
In December, 3TC was approved by HPB and became widely available for use. Access was only hampered by the issue of who would pay for the drug. Then in March 1996, both d4T and saquinavir were approved by HPB for widespread use. Again, access was only hampered by the issue of who would pay for the drug.
By July 1996, two additional protease inhibitors, indinavir and ritonavir, will likely be approved by HPB for widespread use. Again, these will only be hampered by the issue of who will pay for the drugs.
By the end of 1996, twenty years after the pandemic arrived in North America, another class of drug, the first non-nucleoside reverse transcriptase inhibitor, nevirapine, will likely be approved by HPB for widespread use. Again, it will only be hampered by the issue of who will pay.
In 1996, therefore, physicians will have nine anti-HIV drugs with three different mechanisms of action that will be fully approved by HPB to use in combination against HIV. The critical issues may now become the cost of combination therapies and who will pay.
Both Dr. Cameron and Dr. Tsoukas reinforced the need to work together in resolving the issues related to the best use of the available combinations and of the cost of care.
PMAC companies in a recent survey predict that by 1999, there will be more than 17 anti-HIV therapies approved for use in Canada, representing four different mechanisms of action against the virus. Although there's no cure in sight, there is hope that with combination therapies and early intervention, HIV disease progression can be significantly suppressed.
All PMAC companies that have developed anti-HIV medications for use in Canada to date have provided compassionate access to the medications as logistical circumstances have permitted. PMAC does not expect that this intent to provide compassionate access will change as additional products are developed. PMAC continues to share with patients and physicians the desire to have life-saving and life-extending drugs available in the hands of physicians as soon as possible to treat their patients. We realize that, over the next few years, we will also see a great increase in options for other life-threatening illnesses.
As for the regulatory issues, PMAC, in the summary that was created following the round tables, does not see legislated, mandatory mechanisms as an acceptable solution to compassionate access. PMAC continues to believe that the best system of access to new drugs is through the Health Protection Branch.
The HPB has made significant progress in their review processes, and there will be additional measures that can be implemented to further streamline this. Some of the options that we have discussed, such as joint review with the U.S., conditional approvals and the use of external reviewers, are possible tactics for accelerating review and approval.
PMAC supports HPB's continued efforts to find creative solutions to making life-saving and life-extending drugs available to Canadians faster. The example of the 47-day conditional review of ritonavir in the U.S. versus an anticipated 180-day review in Canada indicates that there's still room for improvement.
PMAC agrees with the streamlined access process of the Health Protection Branch, the SAP, to better enable access to experimental drugs, and that the system needs careful design.
Dr. Logue and Dr. Tsoukas also referred to the burden of administration related to compassionate access programs and to the EDRP. We see the physician as the primary interface with the patient in the delivery of care with compassionate release drugs. Therefore, we do not see that the administrative burden can be reduced. However, we feel that there could be recognition and remuneration within the physicians' fee structure for these activities.
Other points regarding the SAP need to be more clearly resolved and further debated. A couple of those points are clear responsibilities for all stakeholders and the inclusion of the manufacturer's right to refuse availability on appropriate grounds.
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The process for this is open to debate, and we're happy to see that there are some mechanisms mentioned to get to that. Another point is to clarify definitions, like definitions of suspected serious side effects or events and emergencies. These types of terms need to be clarified in order to go forward.
On time lines for reporting, patient numbers, treatment periods, and the regulatory process expectations, are there going to be audits involved? What do the audit procedures look like? What information package demands are there? What are the terms of reference the pharmaceutical industry will need to meet in order to bring this new system into effect?
Also, the issue of preventing impact on the required clinical trials process is critical to avoid delays in the approval process. This needs much more debate. We believe that with further elaboration and clarification, the new process will lead to a more effective compassionate access system for all stakeholders without the need for legislated controls.
As for ethical and legal concerns, the ethical issues are very challenging because they involve societal values. We feel that the government has a significant role in providing guidance in keeping with societal values. We feel there is a role for both the NCBHR and the regional ethical boards in providing guidance, in keeping with societal values, to physicians and manufacturers making judgments on compassionate release of experimental drugs.
The government must clearly define the composition and mandate of the REBs and establish a mandate for the NCBHR in this role, prior to pursuing this action. This option provides a fair, societally correct position on a case-by-case approach in an existing medical and ethical experts' structure.
The legal issues we have discussed hinge on the ability or inability to achieve true informed consent. On drugs where very little data is established and/or proven, the risk-benefit assessment is not possible. If the drug is at an early stage of development, decisions in releasing the drug for use in individuals would default to ethical decisions. There, research on human subject guidelines and decisions relating to the physician's commitment to do no harm also impact.
PMAC feels that the proposed SAP system, the underlying legal framework and liability, must be addressed by the government before responsibility is delegated to physicians and manufacturers.
The moral, legal and fiduciary responsibilities of manufacturers have been covered in great detail. We must not overlook the manufacturer's responsibility to shareholders, the responsibility to manage risk and make sound business decisions.
The Pharmaceutical Research Manufacturers of America New Medicines Report, in its 1995 survey, has reported that there are currently over 110 medicines being developed for use in HIV and AIDS, and over 200 cancer medications being developed. Many of these investigational drugs will eventually be approved for treatment, and a great many will not be approved for treatment for a variety of safety and ethical reasons. This raises additional concerns and risks about providing products that may never be approved to physicians and patients, whether under a mandatory or voluntary control. If you provide a product through a compassionate release program, there are no guarantees that you're ever going to see the product approved or reimbursed in Canada.
The PMAC is committed to continue to work with the other stakeholders to find solutions to these complex issues and to achieve a compassionate access system that is more streamlined, efficient and fair.
At this point I would just like to reinforce the fact that we feel there has been insufficient debate within PMAC and between PMAC and Health Canada about the proposed mechanisms for access to experimental drugs. We request an opportunity for further discussion and debate of these mechanisms with Health Canada.
Thank you.
The Chairman: Thank you, Mr. Milligan.
Now from Health Canada we have Mr. Jacques Bouchard,
[Translation]
interim chief of the AIDS and Viral Diseases Division,
[English]
and Mrs. Beth Pietersen, associate director, Bureau of Biologics.
Mrs. Pietersen.
Ms Beth Pietersen (Associate Director, Bureau of Biologics, Health Canada): I don't think we have many comments that we want to make at this time. I have prepared some written comments that I will table.
The Chairman: Thank you very much.
Now, the second bell didn't start yet. When it rings we're going to have ten minutes and we need five minutes to go back to the House of Commons. It's a fifteen-minute bell. Are there any comments?
[Translation]
Mr. Ménard.
Mr. Ménard (Hochelaga - Maisonneuve): I would like to confirm that the Minister of Justice will appear in this room at 6 p.m. I will also have to be here.
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All of this is quite interesting. I will wait until Mrs. Atkinson is here, because I would like to talk to her.
I remember that when I first raised this issue in committee and suggested setting up a roundtable, it was after I had met AIDS Action Now! and Mr. Farlinger. I would like to have additional information. My questions are not necessarily for Mrs. Atkinson. I would like to remind the committee of what Mr. Farlinger said, because it seems obvious to me that this committee will have to make a recommendation on the implementation of compassionate access arrangements for pharmaceutical companies.
I think the isue is whether we should make the approval of protocols conditional... Are we having technical problems?
[English]
A voice: [Inaudible].
The Chairman: You need to switch from one to two.
Mr. Ménard: French is a good language.
As you know, Mr. Goldbloom tabled his report yesterday and is saying that there are two official languages here.
A voice: I beg your pardon.
The Chairman: That's fine.
Mr. Ménard: Alors, is everything all right?
[Translation]
I would like us to start from the principle that all committees and all members around this table agree that, concerning catastrophically ill people... I agree that we need to have clear definitions as some of you have recommended. Should we make it mandatory, through a government bill or a private member's bill I could introduce, that the government and pharmaceutical companies give compassionate access to experimental drugs? Health Canada or the Canadian HIV Trials Network could withhold approval of research protocols in Canada if pharmaceutical companies do not grant compassionate access.
Some witnesses, more particularly Mr. Armstrong, whose sensitivity to this issue I am well aware of, said that they had trouble with the content of remarks that have be reported. I would like to point out that we have not reached the report writing stage yet. We have simply reported remarks made by some of our witnesses. We will have to write a report and make recommendations to the government.
Do you think we should take a more coercive approach in this bill and make the approval of drug trial protocols dependent on the granting of compassionate access?
I can imagine what the response of the Pharmaceutical Manufacturers' Association of Canada will be, although it is quite important that you give us assurances or at least very clear ideas on this issue, since some witnesses have stated that it would cost a pharmaceutical company $30 to$40 million to make trials and give compassionate access to an experimental drug.
What should our approach be? Should we take a more coercive approach? Should we do it through a bill? What are the means this committee should take in your opinion?
[English]
The Chairman: Anyone who would like to may answer. Could we have short answers, please?
Mr. Milligan.
Mr. Milligan: I think one of the points of interest in Mr. Ménard's question is that when you look at compassionate access programs from the industry perspective - and logistics have been a big problem in providing a drug early or quickly - once the logistics are straightened out, there is an advantage for pharmaceutical companies in providing drugs for compassionate access programs. It allows patients and physicians to get experience. It puts an immense amount of pressure on provincial agencies to come up with reimbursement for these drugs when the period of that compassionate access provision runs out. There are a lot of advantages and benefits to pharmaceutical companies providing compassionate access products when they expect they're going to go to market.
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The issues arise when you're so early in the trial process that you don't know if you have a drug that's going to make it through the efficacy or safety standards you're going to need to go to market or to use this drug effectively in a therapeutic area. That's when, if you had a mandated or a legislated situation, you could run into extreme problems.
I'll get back to the earlier example of 3TC, which is an excellent example. It's made by a Canadian company, Biochem Pharma. They only have one drug, so if their second drug weren't offered on a compassionate basis and you had legislation that took away 3TC, that would be the destruction of a Canadian pharmaceutical company. Is that really what this group of witnesses and participants and the government want to build in Canada?
[Translation]
Mr. Ménard: I want to make sure I get it right. Let us take the case of Biochem, a Canadian and Quebec company. This is the perfect example, because I was put in a position to negotiate directly with this company on behalf of the committee. This is one of the few instances in my life where I got involved in something that is none of my business. I contacted the company directly and asked officials of the Canadian government whether we could all get together to discuss about a wider compassionate access.
We ended up in two very disturbing situations with affected people in Canada. First, we were not convinced that the drug would be made available in Canada before it would be in the United States. And then we had difficulties with the limited number of people who could have access. Access is being denied to people who want to participate.
You said that it is interesting for pharmaceutical companies to offer this kind of drug, but only when there is a very promising marketing potential.
I remember participating in a meeting where it was said that the Abbott company had originally eight spots for compassionate access to drugs on the verge of being marketed. I know that, in Montreal, the CPAVIH, not far from my riding, made very strong representations. You talked a while ago of 500 spots, and that is very good.
Do you agree with me that in a few instances compassionate access has been improved because activists and citizens' groups got organized? The 3TC case is a good example of difficulties that can arise, is it not?
The Chairman: Mr. Ménard, the members should not speak more than two and a half minutes, so that Mr. Milligan and Mr. Armstrong can answer our questions.
Mr. Ménard: Just cut me off if I talk too long, Mr. Chairman.
[English]
The Chairman: Mr. Milligan, do you want to finish?
Mr. Milligan: Mr. Ménard, again, as usual, you've brought up an excellent point, which is that there have been issues. You'll recall that earlier I mentioned all companies creating anti-HIV products, at least currently, plan to provide compassionate access based on logistical availability.
The issue with the protease inhibitors - and I know Maggie Atkinson referred to it, particularly ritonavir and saquinavir - is a production issue, not locally but globally. When a group like AIDS Action Now goes to bat and takes on a pharmaceutical company, they do in fact compete with other countries.
In the case of saquinavir, we had the same opportunity in December to debate increasing the saquinavir compassionate access program from 415 patients to 1,000 patients. The original number was set based on production limitations from our head office in Switzerland, because they're dealing with 132 countries.
We were able to actually negotiate with the United States and convince them to free up enough drug for more Canadians, even though their forecasts said they were going to have fully that demand in the United States. They took the risk of giving us additional drug based on the debate we got into with some of the....
So as far as negotiating, pushing or making noise on increasing the numbers goes, you can do that, but you have to understand it's a global competition with other countries. It's not a decision made locally that we're only going to do this many patients. It's done on a global basis.
The Chairman: Mr. Armstrong, you have one minute.
Mr. Ménard: I suggest we go to vote, and then we can come back after.
The Chairman: No, we cannot come back after; that's the problem. We're going to close it, and when we close it, if some of the witnesses would like to remain for a little bit, Mr. Murray will probably have a few questions to ask. He is our researcher.
Mr. Armstrong, a small comment, please.
Mr. Armstrong: I'd rather have James or Maggie speak last, then.
The Chairman: Either one, but one comment.
Ms Atkinson: I would say probably a coercive approach would be best - that there be a requirement to offer compassionate access in order to do phase two and phase three trials.
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I would suggest to Mr. Milligan that once a company is embarking on a phase three trial, they are offering the drug to thousands of people worldwide, so they do have a certain amount of safety and efficacy data upon which they're making these decisions. They're investing millions of dollars.
I would suggest it is a reasonable thing to offer compassionate access.
The Chairman: I would like to thank all our witnesses. We're very sorry, but we need to go back to the House of Commons for a vote. It's one of the few free votes, and we all want to be there. Thank you very much for being here this afternoon.
Thank you. The meeting is adjourned.