Health Committee on May 2nd, 2013

[David Lee]

Thank you, Madam Chair.

Orphanet aggregates a lot of information about rare diseases. So it will list disease states, patient organizations associated with them, and trials going on. Medical professionals can use it; patients can use it. It's typical that, if you are starting up a study, for example, on a particular rare disease or you've identified something new genetically, then you would enter that information into that world database.

It started off in France, and more and more countries have joined into it, so it's becoming a very global effort. Now that Canada has stepped in, we too will be contributing great primary research that's being conducted here.

On the innovation side, I would also point out that one of the exciting parts of the new framework being proposed is the regulation of orphan drugs. After you have identified that an orphan drug is maybe effective for the treatment of a rare disease, one of the next steps is to go to the regulators such as the USFDA and the European authorities and talk to them about how to design your trial. How you research and investigate the drug is an important discussion because it's a very hard thing to design when you have such small numbers. Our statistical models are often different, and how we have to approach it is different. It's one of the common areas where more and more often those two agencies are trying to give aligned advice because, if you can pool together that international look at this small population of data, that's just better.

They've been inviting Canada to join in those discussions, which I think from a participation point of view is quite an opportunity. So we would be involved in these discussions about innovative design and trying to get Canadian study arms up and running here in conjunction with our regulatory colleagues. So I think it's an important moment in the proposed framework to recognize.

[Colin Carrie, Conservative, Oshawa, ON]

While we're talking about the framework, I was wondering if you could explain a little bit some of the challenges from a federal standpoint when you're doing these frameworks. We've heard a lot of different witnesses say that in Canada the provinces are responsible for delivering health care, and the hospitals track different data, and they get it agreed to that they'll share information with the federal government, and the privacy issues, and all that stuff. Could you explain to us some of the challenges with these regulatory frameworks and how you're designing this to get through that little minefield—or big minefield maybe?

[David Lee]

Yes, I've certainly learned that making regulatory frameworks is not for the faint of heart.

For a framework like this, at the federal level you really have to go out and first listen and understand the needs across country, because it is quite true that there is a lot going on in the hospitals. There's a lot of research going on. Often patients are appearing and they're very hard to diagnose. You have to do some international collaboration to even understand if the disease is there, and then all of a sudden you're looking for a treatment.

That will start to involve us at the federal level, but there are many levels in play. There are funding levels. Getting a small research project off the ground is very important. At early stages you're not thinking about regulations when you're in your lab, trying to innovate and identify whether a therapy will work. But it's very important to approach the regulatory aspects early so that when you're doing your studies, you don't misfire. You can start to innovate, but if you don't start to build a case to get on the market, your research is not going to translate out.

I've been doing more work with Genome Canada and CIHR to go out and talk to researchers about what they're going to be expected to do as they work up their innovations. So that's one level of federal participation where we have to look at and talk with a lot of colleagues. That's both primary care physicians, research physicians, and academic physicians.

But really, there is an international discussion as well. One of the really interesting things about rare disease is that it does attract a lot of international cooperation. So part of what we need to do is look at the needs of our patients, our researchers, our provinces, and also see what we can draw from the international context and bring together. That's a good federal role because, as I mentioned, with things like trial advice, if we're setting up a global trial, that affects all those levels, but we're giving the advice. So we're trying to find ways to do that and build a framework so that people can have a voice at those early discussions.

It's not easy to design because we don't have a lot of good precedence in Canada. But we do get help from our international colleagues who have designed frameworks such as these, and they have been giving us very important advice on it. Putting it together is quite involved.

[Colin Carrie, Conservative, Oshawa, ON]

Thank you for that.

Do I have a little more time?

[The Chair, Conservative, Joy Smith]

You're just about out of time. You have about 45 seconds.

[Colin Carrie, Conservative, Oshawa, ON]

Off-label use and the challenges here in Canada were mentioned, because you can have a physician giving a patient something that maybe it wasn't originally intended for but they're finding that it does have an effect.

What would be the regulatory challenges to allowing more of this off-label use of product to be recognized on the formularies for certain purposes, and as was brought up, perhaps for reimbursement for patients in that situation?

[David Lee]

Off-label is a very important concept in our realm. Label indications mean that you've come to Health Canada and you have demonstrated, as a company, that the product works and it's safe for that indication or that claim. So we put that on the label.

It then goes out into the prescribing environment, and we don't, as Health Canada, tell physicians how to prescribe. They need to—

[The Chair, Conservative, Joy Smith]

Thank you, Dr. Lee.

Thank you. You're way over your time.

We'll now go to Dr. Fry. Perhaps she'd like to continue this line of questioning.

[Hedy Fry, Liberal, Vancouver Centre, BC]

Thank you very much, Madam Chair.

I am going to move into a different line of questioning. I want to talk about clinical trials. Given that the cohort group in clinical trials is so small because it's about rare diseases, there is a problem that I have heard about. People have come to me with this problem many times.

As you're looking at clinical trials, access to the clinical trial group is usually a very difficult thing. If you have two people in New Brunswick, for instance, they may need to come to Ottawa because there's a larger group in Ottawa, etc., and the problem they face is having somebody pay for them so that they are able to come to Ottawa and spend time here. There are costs for staying in a hotel, etc.

These costs of the clinical trials are often a burden for a lot of people, and I wondered if you would talk about how much greater that would be in regard to a rare disease, because we're really talking about small amounts going into one big place. That's the first thing.

Ms. Davies talked about drug safety. It is becoming a major problem for us here in Canada. What I like about your concept is that if, because of new communications technologies, we're suddenly going to work with places such as the United States and Europe now, and if it turns out that the FDA is doing a far better job of drug safety than we are, I would be prepared for the FDA to tell me that “this is a good drug to use in this kind of environment”. I think that's a great piece. I think it's good because we don't have to reinvent wheels and do that kind of stuff.

However, there is the problem of diversity, given that many rare diseases have a genetic component. Given that Canada has such a diverse population—very much unlike Europe in terms of ethnicity, race, and those kinds of diversities, which as we know do have certain DNA components and genetic components to them—and given that the United States also has, but has a difficult time breaking down that information because of their multiple insurance agents and privacy issues, how do you see us getting around that?

The final piece of the question may be more directed to the European Union. Dr. Carrie asked about how difficult it would be here in a federation where there are other jurisdictions, but I see the European Union mandating things for probably 50 countries that are all autonomous nations with their own things going on. They manage to do that relatively well, so maybe we could also learn about how to look at multiple jurisdictions and then come up with a good idea and some innovative ways of dealing with that. I'd like the presenter from Europe to answer that.

For the other questions on cohort size and trials and so on, could you please answer?

[David Lee]

Thank you.

Clinical trials are a key aspect of the new framework. This actually is a very international discussion as well.

A number of features will be uniquely Canadian. One is our geography. I think it's quite right to say that the disparity of where patients live and whether they have access to a trial site will be a uniquely Canadian factor. That's one of the reasons why we need good patient input and physician input at that front end when we're designing the trial site. We are reviewing the clinical trial regulations as well, to make sure that the definition of the trial site, for example, is not prohibiting being able to do some virtual work and reporting.

There's another important discussion that we're having, largely through our oncology researchers, our cancer researchers. They've talked about really being able to focus in the trial on the main things and really understanding the burden of paperwork and the innovation cycle, not dropping any of the safety, but really understanding what the basics of the trial need to be. We're having meetings to discuss our way through that. That, too, is also an international discussion. If you have multiple research ethics boards, and you have to file and file and file in each place that you're doing a study, that can be hard when you only have a few numbers.

In terms of that, we're really looking. Some of it's formative. Some of it is well defined internationally, but there are some new sciences gathering around trial size and being able to deal with small populations in regard to how you put that together pre-market and then how you follow it out into the market, in order to make sure that some of the assumptions you're making before you market are real in terms of both the benefit and the safety.

On the safety point, as regulators, it's more and more common that the moment we see a signal it's very important to make sure that globally we understand that. Within the framework, we're proposing to have fairly immediate updates, obligated in regulation, to tell us if there's anything is happening in any other jurisdictions. If you're running a trial or if you have a licence to sell in Canada, it would be a feature of the system to make sure that the constant flow of reporting on safety is really there. If in Canada we start to see safety signals when we get case reports, though, we need to feed that rapidly into the global understanding as well. We're all working together commonly.

Again, this is one area where there's a lot of cooperation among regulators. At least for the designation, it's the only place I'm aware of where the U.S. and the Europeans have a common application form. That's a really important thing from an innovation point of view.

[The Chair, Conservative, Joy Smith]

Perhaps we could also let Dr. Wong-Rieger make a comment because we're just about out of time.

Dr. Wong-Rieger.

[Dr. Durhane Wong-Rieger]

I would very much agree. From a clinical trial point of view, I think the importance of having this regulatory framework is that until now many of our patients didn't get early access to clinical trials because we didn't have a designation for an orphan drug so we weren't talking with Canadians at the same time. It meant that patients and clinicians didn't benefit from it.

The other thing I think, as Mr. Lee is saying, is that it's very important that lots of new flexible frameworks are being designed internationally, specifically for rare diseases. Quite frankly we are also part of developing and designing those clinical trials so that we can take advantage of small patient populations but also ensure that we've got the right balance of benefits and risks.

Right now, where we sit, I think we're going to be able to make sure that we have more patients involved and certainly better access to early treatments.

[Hedy Fry, Liberal, Vancouver Centre, BC]

How much time do I have left?

[The Chair, Conservative, Joy Smith]

You don't have any more time.

Thank you, Dr. Fry.

[Hedy Fry, Liberal, Vancouver Centre, BC]

Because of that, I didn't get the answer about how they deal with jurisdictional problems.

[The Chair, Conservative, Joy Smith]

Perhaps you'll have a chance later on, Doctor.

Mr. Wilks.

[David Wilks, Conservative, Kootenay—Columbia, BC]

That's about two days in a row you've done that, Chair, calling her doctor.

[The Chair, Conservative, Joy Smith]

It's just a suggestion, maybe you could become a doctor. You've done everything else.

[David Wilks, Conservative, Kootenay—Columbia, BC]

I'll consider it if I find an extra 10 years in my life to do so.

Anyway, thank you very much, Madam Chair, and the witnesses today.

Dr. Wong-Rieger, according to Orphanet, those affected by rare diseases are psychologically, socially, economically, and culturally vulnerable, in part because they face challenges with access to quality health care, overall social and medical support, effective liaison between hospitals and general practices, as well as professional and social integration and independence.

Could you tell me what role the federal government could play in addressing some of the additional challenges that people living with rare diseases face?

[Dr. Durhane Wong-Rieger]

Certainly. The proposal Europe-wide, and certainly what we would love to see in Canada, is the notion of a national strategy. What I didn't mention is that part of a national strategy would include, for instance, the recognition, as you say, of some of the social and psychological challenges and specific supports for that. Also one of the big challenges is with people getting appropriately diagnosed. Sometimes it may take 10, 20, 30 years to get an accurate diagnosis of a rare disease, even though there may be experts in Canada who could. So part of it is educating GPs and pediatricians so that they're more aware of what these rare diseases are, recognizing the possibilities, and having specialists they can refer them to.

So again from a federal point of view, being able to support an overall framework that looks beyond just the drugs, as you're saying quite appropriately, is extremely important. We think that only the federal government can play that kind of a leadership role.

[David Wilks, Conservative, Kootenay—Columbia, BC]

Thank you very much for that.

Dr. Lee, on March 5 of this year, Dr. Edwards of the Structural Genomics Consortium was before this committee, and he noted that the vast majority of biomedical research focuses on a very small number of well-understood proteins, often ones where there are tools readily available for their study.

He suggested that researchers and funding agencies should be less risk averse. In your view, is risk aversion, in the sense of uncertainty of financial benefits, a factor in the challenge to encourage research in the area of rare diseases, and is Health Canada able to help offset risk aversion by supporting research on rare diseases? Could you share some of the initiatives that might be of assistance to that end?

[David Lee]

Thank you for that question.

In terms of uncertainties, there are some uncertainties that Health Canada is able to address. I think others would be in the hands of entities like Genome Canada and CIHR, which are on the ground working with those who have proposed to conduct research.

We are keeping a very close eye on what's going on in the research community. One of the things we're doing is outreach for this new framework. With those involved in diagnosing and trying to find drugs to treat these diseases—and a lot of it is genetically based work—we're meeting with them early to try to understand what they're doing. We're doing that to try to take away uncertainties about what they need to look at for a potential regulatory filing in the future. You don't want the research to stall in the clinic. Eventually you want to achieve a market presence to make sure that you're translating your research into the most benefit for Canadian patients.

One of the uncertainties we can reduce and that can cause risk aversion is asking what the regulator needs. What is the pathway to taking this research into what the market will require? We're working on that part.

From a risk aversion point of view, I think that the costs of some failures, given the costs of development, are recognized by regulators. We do try to understand why we require data in the way that we do, because some of the expensive work is what you need to do to present the regulatory filing to the USFDA and Europe.

We do have some working groups and some initiatives worldwide. They are not only trained on rare diseases, but we're also trying to understand how to focus our data requirements better. We're on a group with the USFDA and Europe, trying to come to ground on that discussion. We have participants such as industry—a lot of very excellent scientists—trying to think that through.

It doesn't displace risk entirely, but it tries to bring more innovation to that research climate and how it might translate into the development of drugs.

[David Wilks, Conservative, Kootenay—Columbia, BC]

How much time do I have left?

[The Chair, Conservative, Joy Smith]

You have about one minute.

[David Wilks, Conservative, Kootenay—Columbia, BC]

Thank you.

I wonder if you could expand a little further on what Dr. Fry was speaking of or alluding to in her question. Could you go back to that for a second?