DR. CHAN: Well, what can I say? I promise I won't speak as fast as Dr. Nightingale. Probably not as clearly.

I'd like to thank you first. And I probably -- although this was the meeting that I was asked to speak about held by the National Blood Safety Council on variants of CJD and issues for the blood system, I think I need to talk a little bit about our process and the background that brought us to these meetings before I go into a description of the meeting.

So, if I could have -- what I'd like to talk about is a little bit about what the council is, what the issue was, the process, and the background around which this meeting was set.

I'll go through just the agenda, very briefly mention a few things about the actual meeting, then the recommendations, and, although the meeting was held less than a month ago, what has happened since then.

So very briefly, the National Blood Safety Council is probably the Canadian equivalent to the Advisory Committee on Blood Safety and Availability that Dr. Nightingale was talking about. There are a few differences, some of which I may highlight.

It has 16 members. Three are consumers. Two are from industry. I should stress that none of the members are representatives of an organization. They were invited for their experience and their expertise, but not as representatives.

And when I say industry, both the members that come from industry come because of fractionation, experience and perspective. And we don't actually have any people from the current operators of the blood system -- that is, the collection blood services.

However, within the group that I've listed under treating physicians, we have an ethicist, we have a hemophilia treater, we have several people with the experience in apheresis. We also have a couple that have been involved in the blood services previously.

We've got a couple of people, public health officials. And this is significant not only because of their expertise, but because of the regional and more local basis for public health. So it gives us sort of a broader dimension to the discussions.

We've got a hospital laboratory technologist, a lawyer and an anesthetist. Our mandate is to advise the federal Minister of Health directly. We are -- independent staff, I guess, is me, which means that I don't work actually for the federal government.

I'm not within the actual Department of Health. My job is to support the council entirely, so that is a slight difference. And this, I'll get into a little later, means that the council determines its own agenda, the issues that it will deal with.

The history, just very, very briefly. I'm sure you're all fully aware of the Commission of Inquiry that took about four years and focused a tremendous amount of attention on blood safety, on decision making, and, as I'll describe a little bit later, set the background very strongly.

At that time that the report was released, the Minister of Health announced the formation of this council. And it was seen as a means of overseeing blood safety, of helping to prevent such disasters occurring, opening a dialogue, etc.

He named initially just seven members. And there has been a period of probably a year where we've expanded the membership, determined the mandate and all of that.

So, the functions have sort of been broken down into three. These are the functions of the council. One is more or less a watchdog over the blood system.

Now, as we advise the federal minister, it's largely the structural organization and performance of the federal departments, which are the regulator equivalent to your FDA, and the LCDC, which is equivalent to your CDC.

So we have a mandate to watch the actions, the organizational structure, is this the best for maintaining the safety of the blood system. We also have the role of helping to identify any risks to blood safety that the council may consider are not being dealt with.

And we have a very strong role in communication, and this means putting the parties together, having consumers being totally open to the public in information exchange, education, and certainly provide a forum for open debate on any issues.

We have two types of meetings. There are planning meetings which, as I mentioned before, we set out own agenda. It is not set by the government, therefore it takes a time to work out how and what the issues are. And we do have fairly frequent meetings with the Minister of Health.

And then we have open forums. And it's going to be the third of the open forums that I'm going to be describing. The outcomes are not necessary that we have to come out with recommendations. We're not given questions to answer.

If we think there's a recommendation that needs being made, then council will make it. If the process has been sufficient, the people have got there and talked about things and courses of action become fairly obvious, then hopefully we can facilitate that process.

So the issue that we dealt with in early May was "do variants of CJD pose a risk to blood safety?" And we sort of divided it into the classic variant and others. The others came out of, I'm sure you're all aware, of the scare that we all had over the Utah donor was this a possible chronic wasting disease, etc.

So we just put that issue on the table and let's see where it went. Our process -- we circulated a notice widely to all associations, consumer groups. We've sort of got a mailing list that's growing.

The day before the meeting, there was a flurry of activity. The two blood service organizations in Canada both issued a press release. And I think it was either that day or the day before the regulator had also issued a letter to the blood services regarding donor deferral and variant CJD.

So I have to tell you that obviously it wasn't council that put this issue on the table. There was a tremendous background that we set our meeting on. And I did already mention the climate that has been set from the Krever report and some significant impact on the way we're dealing with things.

The first, and probably most significant, is there's been a total reorganization of the blood system such that the Red Cross is no longer running the services. We now have two blood service organizations. Héma Québec is in the providence of Québec, and Canadian Blood Services over the other provinces and territories.

And there were some principles -- I've called them principles. You can talk about them as standards, but sort of moral standards that came out very strongly out of the report. And I think there's very heightened awareness of these issues still in Canada.

And these I've labeled the precautionary principle or perhaps safety is paramount. And there were two things that Justice Krever laid out fairly clearly that you should not await scientific certainty to act, and you should also consider the likelihood and the severity when you're considering risk.

And I'll go into a couple of quotes from the report because I think they're fairly important for a background here. He also talked about "the importance of national standards, but that they should be local variation if it was deemed important for protecting safety and independent decision making."

So that's sort of the general background or environment. And then specifically, on the area of new variant CJD and the possibility of deferring donors who had resided in Britain, at the end of 1998, there was a report released by the Bayer Advisory Council on bioethics in Canada.

And it had 20-odd recommendations, one of which was that donors who had resided in a BSE country should be deferred from donation. And then, subsequently, I think it was in January of this year the LCDC had asked for a risk assessment to be performed on new variant, and that report contained a recommendation also for the deferral of donors from UK.

And then we do have what is called the Expert Advisory Committee on Blood Regulation, which, like your plethora of committees, is equivalent to your BPAC. It's a more technical advisory committee to the regulator.

Their meetings are not open to the public. And they had also considered this issue and made a recommendation to the regulator on the issue of donor deferral. However, they had asked to await the data on -- now, if you want to know whether that's a spelling mistake, yes, it is, but it could be considered as a -- the implications or the impact so that you have a new word for it -- that's the donor survey.

Now, I've just copied a few -- and I've really cherry picked excerpts from Krever Report, those that were discussed in the meeting that set a sort of a standard here.

And the first excerpt I've chosen was "the operator of the blood supply system and the health protection branch must not wait for scientific certainty about the spread of a transfusion or infusion associated disease and the effectiveness of particular risk reduction measures before they actually reduce risks."

Now, that second part means that just because you cannot totally eradicate the risk doesn't mean that you shouldn't consider taking actions to reduce the risk if there are actions that are possible.

And the balancing of risks and benefits of taking action should be dependent not only on the likelihood of the risk materializing, but also the severity of the effect if the risk does materialize on the number of persons who should be affected and the ease of implementing protective or preventive measures.

And clearly, the more severe the potential effect, the lower the threshold should be for taking action. So you can see we're setting standards here.

It recommended that Canada "have a national system for the collection and delivery of blood components and blood products." That clearly was not implemented. We have two systems.

However, a national blood supply system will have national standards to ensure that all persons in Canada needing blood components or blood products have access to products of uniform quality.

Now, this poses a little bit of an interesting dilemma. And even within the report, like most things that some people refer to as the Bible there, you can find a quote that says something that's a little bit different.

And so another excerpt says that "the National Office of the Operator must create an enforced national standards, but it should permit its local centers to exceed them."

So, as long as you've got a minimal standard, then regions can take actions or should take actions to exceed those standards if it's necessary.

It's recommended that the "Bureau of Biologics and Radiopharmaceuticals" -- that's our regulator -- "make decisions with respect to the safety of blood components and blood products independently of those made by manufacturers and distributors."

Now this one has a lot of historic significance, and perhaps I've only used it here to say that really the manufacturers and the regulator need to make independent decisions: "Obviously the manufacturers have to meet the regulatory standards; however, they can exceed them."

And that's what the next part is, that "the regulator accept manufacturers' or distributors' decisions to take actions that exceed the standards of safety set by the Bureau." And I think this is the final quote.

"The regulator should never interfere with the decisions of a manufacturer or the operator to take a risk reduction measure that exceeds its regulatory standards."

I realize that I've spent rather a lot of time on that, and I apologize. But I think the context for the meeting is fairly important. I very briefly, on the next two, outlined the agenda. I've taken off some of the details.

And, as you will notice, your Chair here today was also the person who started our meeting off, and I might say he started it off by saying two things. One is, "I intend to be controversial." And secondly, he also said, "If you're looking for answers, you're not going to get them."

So that having been said about our meeting, the first section was really the overview. It was an information session, but we also tried to capture the experimental data that was available. And following strictly the experimental data, we went into a panel discussion where we asked what's the likelihood of transmission by blood and blood products.

Unfortunately, in the discussion, the distinction was not kept perhaps as clearly as it should have been between the components and the products. And is it likely to be the same for classic and new variant?

And thirdly, the question was: What is the biological plausibility, from our experimental data, that there will be other variants of CJD? I won't go into the attempts of answering these.

We had a discussion by Dr. Will about the situation in the United Kingdom with respect to new variant and the actions they had taken. We had descriptions of what's going on in Canada, particularly on the surveillance system that we have for CJD in Canada; the current prion research; the precautions; and, for blood safety, our regulatory policy and our policy development.

Then we had time for submissions and discussion, and a panel discussion again.

If we can go to the next slide.

The second day we figured that we would change gears because we were not just looking at the science, but we were looking at the area that Dr. Brown had said: When we don't have the answers from the science, but we still have to develop policies, what are the things we need to consider?

And Dr. Hoots, who is also a member of the Blood Safety and Availability Committee here in the U.S., did kind of a nice overview of some of the factors that are important.

And Mr. David Page, who is a hemophiliac, and he talked about some of the factors that are very important in the decision making from the perspective of consumers. And one of the critical things, and perhaps why I've gone into the Krever setting the standards, is the tremendous loss of faith in the blood system and the implications for scientists, physicians and people who have to make decisions and why this has to be a factor to be considered when you are making decisions. Then we had the recommendations that I've already described, one from the Bayer Bioethics Report, and one from the Risk Assessment Report that was given to the LCDC. And then we had the impact of deferring donors.

And Dr. Marc Germain and Dr. JoAnne Chiavetta presented the data from surveys that were not unlike those that Dr. Williams just presented. In fact, I believe there was collaboration in the establishment of the types of questions that were asked.

I'm not going into the data here. Dr. Germain and Dr. Chiavetta are both here and any questions about that should really be addressed to them. I will make just two points. One is that the data vary between the two organizations and, like Dr. Williams said, within regions for each of the organizations, particularly for the Canadian Blood Services.

And perhaps the Canadian Blood Services data are more analogous to those of the -- the one that was conducted here in U.S. I really won't say anymore about that. As I say, the raw data, I think hopefully, will be circulated to you all.

Then we had submissions and discussion on the impact. And the last part of the second day we devoted to look back notification of recipients. And we had a description of a process that had gone on that started from the actual notification, the follow up after the notification, and, I might say, the lawsuits that are still pending over it.

We debated some of the ethical issues, and then we had a very interesting consumer panel which consisted of people who -- we had David Page, who is a hemophiliac, from his perspective. We had a thalassemic who is a constant user of components.

And we had a couple of parents of children who had been notified that their children had received products that were CJD implicated when that was the policy in Canada.

So that was our meeting. And then I think I would just -- oh, yeah, there you go. That's the data from the survey. It will be circulated, I promise, and we can discuss those.

Finally, the recommendations that council came up with. And the first is a little long winded, but what it's trying to say here is, consistent with the letter from the regulator that went out, as I said, the day before the meeting, that members of Héma Québec and the Canadian Blood Services should get together, and we were prepared to serve as the independent third party, to make decisions about deferral of donors who have resided in the UK such that there is a single, high standard.

Donor deferral policies must be coupled with strategies to increase donor recruitment. So that's really not giving a time, but saying that the two organizations have to work out a single standard and that council would facilitate that process.

The rest of the recommendations I'll go through very briefly. Health Canada had not standardized its -- not finalized its policy on classic CJD, and we advised that they do so.

The blood services should provide clear statements about the reasons for believing that there are no longer concerns regarding the classic sporadic CJD; that Health Canada and the blood services provide communication regarding all aspects of product quarantine.

And that was because there's considerable confusion over the Utah donor case. Health Canada identify and provide information that all products that contain trace amounts of blood products -- this was interesting.

Many of the physicians did not even know which products that were being distributed contained blood products. We thought this was an important issue. All products can be tracked in the event of an infected donor. And that they take steps to discourage manufacturers from using blood products in the production or formulation of other products.

That mechanisms are developed to ensure that -- oh, this is the surveillance for CJD. That criteria have to be established to determine between classic and variant forms, which I know is the topic that you are going to be discussing this afternoon.

And that these criteria should be very clearly put out to people and it's clear what they do when they get a case.

There was concern about the partitioning of the experimental data regarding the partitioning of the prion with the cryoprecipitate. And this recommendation says that the use of cryoprecipitate should be reviewed.

Finally, I think -- I keep saying finally. I think I'm getting to the end. That the information -- oh, that our equivalent to the BPAC, their recommendations be made more public so that people know when these things are going to occur; that Health Canada take the steps to ensure that notification policies are consistent.

And this was felt very strongly, the next one, from the consumers because notification without education and follow up is worse than no notification at all. All notification programs must include appropriate education and follow up components.

That Health Canada then ensure that the recipients notified in the past are informed of the facts and the policy changes. And that Health Canada ensure the simple, clear education of the public and physicians on CJD as it relates to blood transfusion.

Since May 7, 1999, lots of things have happened. However, the decisions have not been made. There is a deadline of June 10th which the regulator has asked the operators to decide how long and what deferral criteria will be put in place.

And there are several meetings. The CBS has convened yesterday, I think it was, a meeting of their advisory committee to help them look at all the implications of donor deferral.

And the meeting that's scheduled to have the operators together to make a decision will occur, we hope, next week. There have been lots of other things. But I hope that gives you a little bit of an understanding of our process and perhaps the environment in which we're dealing with many of the same issues that you are.

(Applause.)

CHAIRMAN BROWN: Thank you very much, Dr. Chan.

Do we have a question for Dr. Chan? We could probably work any comparative discussion into this afternoon's open public hearing or committee discussion.

Yes, Jay.

DR. EPSTEIN: The issue of elasticity of the blood supply arises any time you contemplate deferring donors. And, you know, there was loose talk about UK exposure related deferral reckoned by, you know, even just weeks to months of exposure.

And I just wonder, is there any figure that you can provide that represents what you think the Canadians believe can be recovered by new recruitment or increased frequency of donation?

In other words, what percent donor loss through deferral do you think your system tolerates?

DR. CHAN: I will not -- I cannot answer that question, but I can say that the types of -- the two services will have quite different elasticity. There's absolutely no doubt about that. For one, the inventory levels are different between the two organizations, plus the number of donors that would have to be deferred if you drew the line at one month or six months.

These are two numbers that have been bandied around, but I really would much prefer either or both of the operators to speak to that if you want a specific answer. Different is the issue. Maybe 5 percent was the number that was bandied around.

Is that sufficient, or can we -- okay.

CHAIRMAN BROWN: Larry.

DR. SCHONBERGER: When we had the problem with the human growth hormone, the solution turned out to be to switch to molecularly engineered hormone. Is there any such solution to our blood problem in the near future?

Does anybody have any information on that; that is, using some substitute that would not require the human donator?

CHAIRMAN BROWN: Well, Factor VIII is available as a recombinant. I don't know of any other derivatives are yet available.

DR. EWENSTEIN: Let me comment on that. I mean, you're right, Factor VIII is available. There's still albumin in many of the preparations, although there are movements afoot to slowly release products that don't have any albumin as stabilizers.

There is a Factor IX product that's available without any human component. But there's still a group of patients even in the coagulation area that are dependent on the plasma derived products. There's a recombinant, von Willebrand's product, that's under development, but I would predict would be years away.

And so just licensed, for example, was a product to treat von Willebrand's disease with an intermediate purity, Factor VIII. So I think the answer to your question is we're getting there, but that there are still large segments of the bleeding disorders community that rely on plasma derived products.

And then, of course, I can't see, at least as a hematologist, any time soon having a recombinant IV Ig preparation.

CHAIRMAN BROWN: This -- yes, Peter.

DR. LURIE: Just back to the question of elasticity of the blood supply. And I apologize. This being raised now raises questions for me about the particularly central slide that Dr. Nightingale presented.

Can you put that one up again? Criss crossing lines. I guess I have first a question for you and then, depending on your response, two or three comments on it.

My question is: Are the extrapolations that you present in that slide extrapolations from just the '94 to '97 period, just those two data points, or are we really looking back further in time?

DR. NIGHTINGALE: The slide is what it is; it's a '94 survey and a '97 survey. It comes with confidence intervals that you can see. It is our current best estimate, and it is understood that this is not a prediction within those confidence intervals.

But I think the message in the slide is that there's not a lot of slack in the blood supply right now.

DR. LURIE: I think the message in the slide is overstated for several reasons. The first is that the Y axis begins at about 11 million units of transfused blood, and so it makes the -- in a section, look rather sharper than, in fact, it is if you extended it all the way down to zero.

The second point is that you've made an extrapolation based just on two points, as you say; and which, in effect, makes it seem as if the two lines are independent of one another. I like to think that the blood transfusion industry, aware of the change between '94 and '97, is, in fact, reacting in some way, presumably by increased recruitment.

So there is a kind of inevitability applied to all of this that doesn't really quite seem right to me.

DR. NIGHTINGALE: Sure. And the -- what doesn't seem right is that past experience will predict future experience, and that is not the implication. I think the implication of the slide is that there are -- there is a bit of concerning information raised at the meeting.

For example, Dr. Williams' survey finding -- again, preliminary -- that in 1995, 26 percent of donors reported receiving some incentive; in 1997, that 62 percent reported receiving some incentive.

The conclusion that the speakers in the public comment section brought to our advisory committee was, as I stated at the outset, was that there's not a lot of slack in our current blood supply, and attempts to quantitate that, you make your best effort and that's what I think this slide represents.

CHAIRMAN BROWN: Yes, Peter, that's fine.

Thank you, Dr. Nightingale.

This is certainly going to be heatedly discussed in the discussion period this afternoon. And so I'm going to call time for lunch now, but we're going to come back to that and particularly since there are present on this committee now two or three people who were present there.

And clearly this is an important issue. And we'd like to thrash it out as thoroughly and satisfactorily as possible, and we will.

I'm going to reconvene at 1:30 rather than 1:45. That's 45 minutes. 1:30.

(Whereupon, the proceedings recessed for lunch at 12:45 p.m.)

 

A-F-T-E-R-N-O-O-N S-E-S-S-I-O-N

(1:42 p.m.)

CHAIRMAN BROWN: This afternoon's program will begin with several presentations as a part of the open public hearing.

And Bill, did you have anything that you wanted to say about the public hearing part?

DR. FREAS: Nothing other than the fact that we do welcome comments from the audience. And this your opportunity, if you're not on the agenda, to come forth and express your views to this committee.

CHAIRMAN BROWN: Yes, there have been several speakers who have given the FDA notice that they wanted to make a short presentation. And in general, as I recall from past meetings, these presentations should be limited to five minutes.

DR. FREAS: That is correct.

CHAIRMAN BROWN: The first speaker from the Armed Services Blood Program, who you've already heard from earlier this morning, is the Director of this blood program, and it's Captain Bruce Rutherford.