Proceedings of the Standing Senate Committee on
Social Affairs, Science and Technology
Issue 14 - Evidence - April 25, 2012
OTTAWA, Wednesday, April 25, 2012
The Standing Senate Committee on Social Affairs, Science and Technology met this day at 4:14 p.m. to study prescription pharmaceuticals in Canada. (topic: Clinical Trials)
Senator Kelvin Kenneth Ogilvie (Chair) in the chair.
[Translation]
The Chair: Welcome to the Standing Senate Committee on Social Affairs, Science and Technology.
[English]
My name is Kelvin Ogilvie, a senator from Nova Scotia. I will ask my colleagues to introduce themselves. Senator Eggleton, deputy chair of the committee, please say hello.
Senator Eggleton: Hello, I am Senator Art Eggleton from Toronto.
Senator Merchant: Senator Pana Merchant from Regina, Saskatchewan.
Senator Callbeck: Senator Catherine Callbeck from Prince Edward Island.
Senator Dyck: I am Senator Lillian Dyck from Saskatchewan.
The Chair: Senator Demers, would you introduce yourself?
Senator Demers: Senator Demers from Quebec. Excuse me. We just left the Senate, you know.
Senator Martin: Senator Yonah Martin from Vancouver, British Columbia. Welcome.
The Chair: Thank you very much. We are continuing our study with regard to prescription pharmaceuticals in Canada. Our topic is that of clinical trials. We have four presentations today. We have agreed that the order will be the order that they are listed in the agenda. I will introduce them as I call them to present.
The first presenter will be Peter Brenders, President and Chief Executive of BIOTECanada.
Peter Brenders, President and Chief Executive Officer, BIOTECanada: Thank you for the opportunity to appear before you today.
BIOTECanada is a broad-based membership organization with over 250 companies, research institutes and universities working for the sustainable commercial development of biotechnology in Canada.
As you know, clinical trials are the last critical stages of development for health technologies. In Canada, we are proud to say we have 66 early stage Canadian companies with roughly 152 products in clinical trials today. Many of our biotech firms are focused on the discovery and manufacture of new drugs impacting rare diseases or relatively small populations with high, unmet needs which are also a key priority for our companies. Moreover, the work of our companies is proving to be a support for our broader global industry.
Professor Robert Kneller at the University of Tokyo published an analysis of the origins of a decade of new drugs in Nature Reviews Drug Discovery back in the fall of 2010. He noted that:
Biotechs, and universities that partner with biotechs, are responsible for the discovery of a disproportionately high number of innovative drugs.
He noted that scientific innovation in biotechs took more risks, with 70 per cent of the early development and 62 per cent of the priority review drugs.
There is it no question that the biotech development is extremely risky. I will highlight some stats in a moment. However, considering this and the fact that one can raise and make money much more simply elsewhere in other businesses results in the added challenge that our companies face to develop these products. Please make no mistake: It is companies that invest to develop these products. The fact that any development occurs is a testament to the commitment and stamina of these innovators.
As you have likely heard, not all products starting clinical trials successfully reach market approval. In fact, a recent analysis by our sister organization BIO in the United States, along with the BioMedTracker group, studied data from all companies — pharma and biotech, public and private — and looked at 4,275 drugs for roughly 7,350 indications in clinical trials from October 2003 to December 2010. They found a success rate of only 9 per cent. That means that out of 100 drugs that began the clinical trial, only 9 made it to market.
Success rates varied by phase and indication. You have heard of different phases of development of a clinical trial. For phase 1, 63 per cent of the products move successfully to phase 2. Only 33 per cent of products move out of phase 2 and into 3; 55 per cent move from phase 3 to regulatory filing; and of those that go into the filing only 80 per cent actually make it to market. There is your 9 per cent overall.
They also found that there are differences in success rates by diseases that were being studied. These can range from 5.6 per cent success rate for oncology products to as high as 13.4 per cent for infectious diseases. We see that not all clinical trials or diseases are equal.
We hear of many of the ups and downs that products face, but in Canada we are always reminded that we have been fortunate to see many successes of companies like QLT, Biovail, Anormed, Enobia, Theratechnologies, Aspreva, IDB, Biomedical, Angiotech and Cardiome, to name a few, that achieve deals and bring products to patients. These are just a few examples.
We have seen many products and companies also fail through these years through difficult times. We prefer to focus on the positive and remind Canadians of the durability of our industry and how much the industry has accomplished and how much more we can do.
Due to the sizeable cost of a full series of clinical trials that they may incur from small- to mid-sized biotechs, they look to other sources of capital. Considering the paucity of risk capital, the lead approach is to partner or license with mature global pharmaceutical companies for cash, marketing muscle, distribution channels and regulatory expertise. These collaborations are now key to combining existing expertise that we have in Canada in creating novel therapeutics with the scientific development and commercialization capability of a larger entity. If the recent success is any indication we have seen in the early part of 2012, this will be a year of deal making. The industry has seen over $2 billion in deals in the first quarter alone.
Enobia of Montreal worked a deal with Alexion of Connecticut for over $1 billion. These two companies are sharing a focus on transforming the lives of patients with severe and ultra rare disorders.
We saw Vancouver-based Zymeworks work a deal for $187 million with Merck continuing their effort in identifying new oncology and auto immune disorder therapies.
Xenon in Vancouver entered into a strategic alliance with Genentech, a Roche company, of over $600 million to discover compounds and a companion diagnostic for the potential treatment of pain.
Most recently, Montreal's Angiochem entered into a $300 million deal with GSK to collaborate, discover and commercialize treatments for lysosomal storage disorders.
Biotechnology matters. Our health-related firms generate over $1 billion a year in R & D activity in Canada, and they help Canadians access early promising treatments. However, even with the increasing knowledge and competition in our industry globally, Canadian companies remain focused on growth and executing strategies for success in spite of a terrible capital market and an incredibly difficult operating market.
I will close with a call that Canada must adapt long-term policy commitments which leverage investments, continue to grow the national capacity for discovery and development and provide an enabling environment for emerging companies and global partners to find a home in Canada.
The Chair: I will now turn to Hoffmann-La Roche Ltd. and the Genentech consortium. I invite Nita Arora, Regional Head Affiliate Management, North America, to please proceed.
Nita Arora, Regional Head Affiliate Management, North America, Hoffmann-La Roche Ltd.: Mr. Chair and honourable senators, on behalf of Hoffmann-La Roche Ltd., also known as Genentech in the United States, I am pleased to have the opportunity to speak with you today.
Located in Switzerland, Roche is one of the world's largest biotechnology companies and a leader in personalized health care. I would like to thank you for taking the time to study the issues impacting clinical trials in Canada. This is a timely study because the clinical trial world is rapidly changing.
My role as the regional head of clinical operations for North America for Hoffmann-La Roche Ltd. allows me to have a unique vantage point regarding clinical trial placements. I am part of a five-member regional head group that represents the interest and potential of 65 countries. The discussions and decisions that take place within this group allow me to have a great perspective on the strengths and weaknesses of the different regions of the world.
During the last five years, there has been a great excitement and push toward placing clinical trials in Brazil, Russia, India and China. These countries, with what appears to be a limitless patient population and lower operating costs, were seen as the solution to meeting the increasing demand for clinical trial data, while at the same time allowing pharmaceutical companies to maintain or lower their research cost. The situation in these countries has been more complex than anticipated, but you may be interested to note that the issues have not been of poor quality or the ethical conduct in a country as was anticipated.
Where does Canada fall into the spectrum of countries as it relates to clinical trials? Canada has many strengths and has been a strong contributor of clinical trial patients to research. It offers a stable landscape with a highly educated labour force and world class investigators. Canada's highly heterogeneous population and good standard of medical care is also very attractive to researchers.
Our experience at Roche has been generally positive in conducting clinical trials in Canada. However, there is also a perception amongst us that the research community in Canada has been quite passive in its approach to clinical trials and has not made much effort to draw on or to increase the Canadian participation rates in trials. Despite the fact that Canadian institutions charge pharma companies anywhere from 30 to 45 per cent overhead on every dollar spent in their institution on clinical trials, there has been relatively little reinvestment of those funds in creating structures or processes that strengthen their ability to compete for future trials.
Canadian investigators have relied heavily on their reputation for delivering good quality data and have come to expect that their historical performance will continue to make them the site of choice for clinical trials. What have not been fully realized are the extraordinary efforts and measures that other countries have put in place in order to be able to deliver high quality data at a lower cost within faster timelines.
The placement of clinical trials is based on three basic and simple principles: time, cost and quality.
The first and foremost criterion is the country's ability to deliver accurate, unbiased quality data. The fact that Canadian researchers consistently produce high-quality data is clearly a strength of Canada and one that we should all be very proud of.
The second factor that is used to assess the attractiveness for placing clinical trials is the cost of conducting a clinical trial in that country. Phase 2 and phase 3 clinical trials are the largest component of overall cost of drug development and, therefore, are scrutinized heavily, and every measure is put in place in order to preserve the integrity of the data but decrease cost.
The cost to conduct clinical trials in Canada is high relative to most countries. This is primarily due to the expensive infrastructure required to recruit small number of patients.
Currently, a gap in Canada is that institutions and physicians work in silos and are only able to tap into their own patient populations and are unable to predict the number of patients that they will ultimately be able to recruit. In order to draw from a larger pool of eligible patients, there needs to be better development of networks and referral patterns that funnel patients into appropriate clinical trials.
Utilizing the technology of electronic records to create a provincial or national database that could identify and inform patients of clinical trials that they could benefit from would catapult Canada as a leader.
The third and final factor in country selection is speed. We recognize the urgency of bringing these innovative products to patients. At Roche, we are in a privileged position to bring needed treatments to patients at a speed we have never seen before. A perfect example is our new personalized health care drug to treat metastatic melanoma, which received regulatory approval in the fastest time in Roche history.
The area of speed offers Canada the greatest opportunity to make some advancement. We very much welcome the pilot program launched by the Canadian Institutes of Health Research to create a national clinical trial agreement. This will hopefully decrease the four to six months that it currently takes to negotiate a clinical trial. Many countries around the world already utilize a national agreement, and we certainly hope that Canada will join the ranks soon.
The creation of a national ethics committee to review and approve clinical trial projects would also eliminate the delays and substantial administrative burden that is currently placed on investigators. This national model is used in most European countries and gives them an advantage of anywhere from three to five months in terms of getting studies up and running.
In conclusion, the conduct of clinical trials is a critical step in bringing important drugs to patients. The landscape is changing rapidly, and unless Canada works actively to create the right conditions for placement of clinical trials in the future, there is a danger of losing the investment and the access to innovative medicines that patients count on.
At Roche, we have a pipeline that offers hope to many patients. We hear from patients every day that they are counting on us to deliver these life sustaining therapies. Other countries are moving quickly to respond to the challenges that I have discussed here today. It is our hope as a company and my hope as a researcher that Canada can urgently address them as well.
Russell Williams, President, Rx&D: As I think many of you know, Rx&D is a national association that represents the innovative research-based pharmaceutical industry.
[Translation]
Our members research, discover, develop and deliver life-saving and life-changing medicines and vaccines for the benefit of Canadians. And our membership ranges from international pharmaceutical companies to innovative Canadian biotech start-ups.
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Rx&D members are the largest private sector investors in health research in Canada. Our industry is the most research intensive on the global scale. Over the past 20 years, we have invested well over $20 billion in the Canadian research enterprise. In 2010 alone, we invested $1.3 billion into R & D activities across Canada, and a little over 75 per cent of that $1.3 billion was in clinical trials.
Today, Rx&D members are conducting hundreds of clinical trials at over 2,000 Canadian sites, involving several thousand clinicians and scientists, which offer direct care to tens of thousands of Canadians. These trials offer real hope to Canadians and real services to our health care system. They allow clinicians and scientists to further science by learning what works and what does not work when treating illnesses.
[Translation]
And these clinical trials save the health care system valuable resources, now and into the future.
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Due to demographic shifts, chronic conditions along with the incidence of age-related illness are becoming more prevalent in Canadian society. At the same time, federal and provincial efforts are focused on disease prevention and treatment through education and vaccination campaigns. In these campaigns, our industry is working on the front lines of public health in partnerships with governments and health care providers. These factors, combined with primary care reform and other reform efforts, are resulting, and will condition to result, in the increased use of pharmaceutical therapy as a preferred and front-line intervention for keeping Canadians healthy and productive.
Contrary to some concerns of certain policy makers, this situation should be seen as an opportunity. In fact, with the proper use of pharmaceuticals, that is, getting the right medicine to the right patient at the right time, our sector can play a positive role in addressing health care sustainability. Effective use of medicines reduces the need for costly interventions such as invasive surgery, lengthy hospital stays and unnecessary ER or physician visits.
In previous testimony before this committee, you received a detailed overview of the clinical trials process from Health Canada officials. As well, Dr. Beaudet from the CIHR put the importance of clinical trials to Canada's scientific and health agenda into striking context. CIHR also spoke of Canada's standing in attracting clinical trials in an increasingly complex, competitive and challenging environment, as we have just heard from Roche.
[Translation]
As you have already heard, the global business model of our industry is undergoing unprecedented transformation. Canada is not immune to this change.
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However, what is emerging in Canada is the opportunity to capitalize on this business model that is relentlessly driven by innovation and partnerships to deliver historic, sustained and profoundly better health outcomes for Canadians. Across the world our members are consolidating their manufacturing facilities and globalizing their supply chains. In the midst of this change, our business model is driving an unprecedented number of partnerships with universities, hospitals and leading health sciences research institutes.
However, Canada must make rapid and enlightened policy choices if we are to compete to attract more clinical trials to our shores. If I can give you one message today, it would be that it is urgent to act on this now. I cannot overstate how fierce the competition is. We spend a little over $110 billion a year in research around the world. Canada, as I mentioned, gets about $1.3 billion, and most of that is in clinical trials. If we want to seize a greater part of that investment, now is the time to act.
This past Monday we provided your committee with a tripartite clinical trials action plan jointly developed by Rx&D, CIHR and ACAHO. This plan, which I am sure you read in great detail, and to which I hope to refer later, stems from the first ever national clinical trials summit held in Ottawa last September. It is a great action plan. To implement this action plan we need an unwavering and sustained commitment from government, industry, universities and health science centres; in fact, all relevant stakeholders.
[Translation]
When the pharmaceutical industry looks to invest in countries, it does so based on the relative strength of three critical factors: the capacity for quality science, the stability of the intellectual property regime and a policy environment that fosters, rewards and sustains innovation.
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To be fair, Canadian clinicians and researchers are world renowned for their capacity to push the frontiers of biomedical knowledge. From the co-discovery of insulin by Sir Frederick Banting in 1921 to sequencing the SARS virus in 2003 in British Columbia, our talent is world class. We can also boast of modern and globally competitive universities and hospitals with the capacity to conduct leading-edge research as a result of ongoing government and private sector investment.
However, over the last half decade the number of clinical trials conducted in Canada and the number of patients enrolled has steadily declined. The world is surpassing us at a steady pace. Part of this decline is directly related to our intellectual property regime. As a country we have fallen behind other countries in protection for discovery and innovation. We currently have an opportunity in the negotiations with the European Union to correct some of that. There are three areas we could be working on: establishing an effective right of appeal as a simple matter of fairness; implementing patent term restoration; and, finally, increasing data protection from 8 to 10 years along the European lines.
The last part brings us to the third axis that drives pharmaceutical investment; a policy environment that is, quite simply, more pro-innovation. Elements of this environment must include a health technology investment paradigm that understands and values innovation versus just driving costs; a reimbursement environment that provides citizens and residents with leading access to new and innovative medicines and vaccines; a tax policy framework that reflects and incents the international and multi-partner endeavours which require clinical research.
Unfortunately, notwithstanding some very interesting initiatives in the latest budget, there are some changes to the SR&ED rules that will not encourage or help the advancement of clinical trials in this country. That is inconsistent with some of the other messages we heard in the budget. Finally, a national clinical trials strategy is needed that measures and markets performance and excellence, streamlines administration while protecting patient safety, and standardizes site training and accreditation.
[Translation]
We are committed to doing our part to improve the environment for clinical trial excellence. This is why we recently renewed our partnership with the Canadian Institutes of Health Research over a five-year period with an objective to match CIHR's $150-million commitment, for a total of $300 million.
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To conclude, we leave you with three ideas. First, the raison d'être for clinical trials is clear: to bring new drugs, devices and vaccines that our industry creates to market through rigorous processes so we can save, improve and extend human lives.
Second, clinical trials allow us to invest in our greatest natural resource, which is Canadians. The resources are scientists, doctors, nurses and many others, with their unlimited capacity to build better conditions for science and innovation.
Finally, as I mentioned before and as was mentioned in other presentations, clinical trial investments are highly mobile and can help transform human health. Complacency and half measures are crippling our capacity to compete. The time for concerted action and concrete change is now, and we need an articulate action plan. We urge you to reflect on this sense of urgency in your first report when it is published in June.
If we can move forward on this, Mr. Chair and members of the committee, you will see that the industry will be able to respond as it has done in the past, and we can bring more clinical trials to Canada and build on the great science we have here.
The Chair: Now I will turn to Dr. Ward-Able from Amgen Canada Inc.
Dr. Clive Ward-Able, Executive Director, Research and Development, Amgen Canada Inc.: Thank you for allowing me to be here today. The fact that you do not have any notes is the result of the fact that I did not get notice of this meeting until yesterday morning.
Amgen is the world's largest biotech company. It has been around for about 30 years and is focused on grievous illness, such as cancer, rheumatoid arthritis, chronic kidney disease, and post-menopausal osteoporosis, for example. It has two values that I think are pertinent for today — two of a number of them. One is "being science-based" and the other being "putting patients first." I think that is everything we live by.
I am the Executive Director for Research and Development for Amgen Canada Inc., the affiliate in Canada, from Mississauga. Within the clinical trials arena, one thing we are particularly proud of is the fact that we are the second- largest recruiter for clinical trials for Amgen in the world. You might wonder how that happens with Canada to do that. We recruit approximately around 6 to 7 per cent of the global patients. If you want to compare that to sales, for instance, Canada generally contributes about 3 per cent. We double that amount. That should help explain why I am sitting here and talking to you today.
First, I think our success has primarily been because of our consistent performance in the fact that we have high quality and a very good environment in which to do clinical trials.
We support around about 200 jobs in Canada within the R & D department. We have a department dedicated to research in Burnaby, B.C., which is dedicated to preclinical, but I have about 130 people related to clinical trials. That is just within the company. The amount of investment that we do also helps to support a number of the researchers in the centres and the peripheral staff, as well.
It is quite pertinent that I am sitting here today because, just this morning, we had our first global teleconference call from our Development Operations Department, indicating that they will be really looking at how they divide up clinical trials globally. This will largely be due to cost and efficiencies. As my colleague from Roche has mentioned, speed, cost and quality are vitally important for any company in being able to recruit patients.
Out of those three components of speed, cost and quality, Canada has generally done well on speed up until now but there are still a number of improvements that can be made. On quality we have always been good, and that is why they always come back to Canada all the time. However, that is not a competitive advantage any longer because all the other countries are tending to catch up with us. Ms. Arora mentioned all the BRIC countries, but other competition is other developed countries. They have all realized that attracting clinical trials is important for the economy and important for the health of citizens.
On the cost aspect, Canada is now one of the most expensive, if not the most expensive, country to do clinical trials in. This is something that must be addressed because we cannot continue to increase our costs; it will tend to drive out investment in our areas.
There are a couple of areas I want to talk about. A lot has been mentioned before. This one might seem like a tangent, but I think it is vitally important. The question is about clinical trials and showing the value of your medicines to the public; how do you show value of medicine? This is an extremely important question because this is something related to the sustainable health care. How do we continue to maintain the level of health care provision now and particularly in the future? Value means different things to different people. Depending on whether you ask the payers, the patients or the providers, they might all give you a different answer.
When you think about whether it will be preventive medicine, curative medicine or palliative, they all have different values. The most critical thing we need to do is to be able to show the value of medicines within the systems in which they are being used, and we have not been able to do that up until now. This is where the appeal comes in.
What we need desperately, and where Canada is behind other countries, is the ability to have electronic patient records and accessible databases that can be interrogated to be able to show that, when you have an intervention, you actually get a result out of it that you are looking for.
On another point, though, Canada is blessed with having a very good environment for this. We have some of the best global experts within pharma economics, health economics and evidence-based medicine, concepts that have largely been developed here in Canada. We also have a health care system that, should we have a very good data record, will really be able to provide that data to be able to show this value. I wanted to talk about that because I think it is very important for the future.
The other thing I wanted to speak about is about quickly is the value of the clinical trials. As I mentioned, I have about 170 people, but that is not everything. Within the other centres, it has been shown that if you invest in those centres, they are able to have more resources to do their own clinical trials and their own research. It has also been shown by clinical trials that actually raise the level of health care provision to that area in which they are doing clinical trials.
I mentioned cost of clinical trials, as well. The overhead costs are increasing, as Ms. Arora mentioned. However, the costs are not transparent and we need to have a better idea of why they are becoming much more expensive.
The second item is the tax incentives. Canada used to be the best, or at least in the top three, for tax incentives for doing research in this country. That has gotten relatively worse over the years because other countries have gotten much better at it, and the changes in SR&ED now I do not necessarily talk about because it might not be so attractive to my headquarters.
Understanding that a lot of these initiatives to improve the clinical trial environment are provincial in nature, there are a couple of things I think the federal government can have an impact on. I have three things to request: Any support you can do to foster the environment to get electronic records and databases that are accessible; support improving tax incentives for research that is done here in Canada, including phase 2 and phase 3 research, because that is vitally important in translating from bench research to the actual clinic; and also anything you can do to help keep costs down to keep Canada competitive. These will allow me to attract more research, and more research investment into Canada, and thereby applying and providing more employment. Thank you.
The Chair: Thank you all very much. They were excellent presentations. I am sure my colleagues have a lot of questions. With that, I will open the floor to questions starting with the deputy chair, Senator Eggleton.
Senator Eggleton: I will start by picking up on Dr. Ward-Able's presentation where you say we are okay in speed and quality — you give a lot of things we seem to be doing quite well at — but said we are not competitive in costs. You have suggested three possible solutions: electronic health records. I agree with that. In fact, in our last report on the health accord, we recommended expediting electronic medical and electronic health records.
Are tax incentives for research over and above the SR&ED? Is it some variation of the SR&ED or would you suggest something new? The third thing you recommend is to keep the costs down. That is a very general statement. Can you tell us specifically where government can play a role in keeping the costs down?
Dr. Ward-Able: I will start with your last question first. I do not think the government itself has much to do with it, but I think you can foster the environment. These costs are put in by institutions. As a bit of a background, I have been very much involved in Ontario and Clinical Trials Ontario on work streams where we have actually advocated for the potential for either giving — I am not a financier by any means — some measure where the institution is providing them with money, a tax incentive or anything for them to be able to reduce their costs.
You can also ask for transparency of these costs because we do not know necessarily what they all are. They will be put as a percentage, as Mr. Williams mentioned, of what the patient's costs would be, whether that be 35 per cent or 40 per cent. Some have gone really way up.
I do not have anything specific you can do other than to keep that in mind, and being able to bring that up to the institutions. Perhaps we need someone else to do that.
The other one was the SR&ED. First, I think the way that the criteria have been interpreted lately have been very strict and not what they used to be. There have been suggested changes — which I think Mr. Williams will be able to talk to in more detail — recently about the SR&ED. It is making it less attractive for multinational investment. One of the things people have pointed out is that maybe it should not be for phase II and phase III studies. To me, that is critical. How do you translate anything from the bench to the bedside? You have to go through phase 2 and phase 3. It is a translational research. You have to have that done.
Senator Eggleton: Let me ask a question of Mr. Williams of Rx&D. You started out by talking about the investments, the degree of investments being made, including about 75 per cent of this amount dedicated to clinical trials. Then you went on to say if we really want to seize the moment, there are a lot of other things we have to do. I see your report, your action plan here. You laid them out and you laid some of them out for us today. It even includes some things that one might argue would require some big government change, including increasing protection from eight to 10 years in line with European standards and things like that, which of course are subject of some controversy. Number 8 in your document says optimize intellectual property protection as well.
There are those who would argue that the Rx&D companies never lived up to the original agreement that goes back to 1987 to get up to research at the 10 per cent level. In fact, last year the annual report from the Patent Medicine Prices Review Board, the PMPRB, says that less is being invested in applied research than the year before, and that also goes to all phases of clinical trials.
What is the explanation for this? Why would government want to help facilitate some of these suggested changes when the perception seems to be that you have not lived up to the ones you originally said you were going to do?
Mr. Williams: I appreciate the question, particularly the way you just phrased it when you called it perception. The facts are quite clear. In the same report last year, there is a mention of a supplementary report.
Back in the mid 1980s when this entente was made between the industry and governments when they moved towards the current IP regime, they basically said we will catch up to international standards from 20 years ago, but invest 10 per cent of sales into R & D. It also said as long as market conditions stayed the same; market conditions since then have not stayed the same.
Notwithstanding that, we have had restrictive formularies in the country and prize freezes for 15 of those 20 years. When you look the numbers — we did it with the PMPRB, with CIHR and Industry Canada with a proper definition of research, not just our definition — it showed the way the regulation was set up was we underreported 20 per cent of our research. When our PMPRB said we were investing a billion, it was 1.3 billion. That does not count other commitments. The study shows that each and every year we met our commitment and in many years we surpassed it.
I thank you for the question because you are right, there are critics out there — I will not name them — that have made it their business to try to say it has not.
For instance, given the debate about the budget right now, if we are going to count sales in SR&ED, there are all kinds of ways. Why are we evaluating based on all sales? Perhaps it should be a percentage of patented sales. What is the legitimate definition of "research?" By SR&ED rules back then — and it was just changed — you could claim 50 per cent of certain parts of the research. By definition, there is another 50 per cent not counted in that report.
Clearing it up, we have, continue to, and will continue to honour that commitment to the best of our ability.
The second thing is, when you look at it, there is no rule if we have 3 per cent of the market we should have 3 per cent of the R & D, but why not aim for that? Why not try and stand up and compete with other jurisdictions? I would argue we should have better IP than Europe, but I am not here to plead in front of the Senate committee to change those rules. We are trying to get IP that is equal to Europe. I think Canada and the health care system can grow. It is much more likely because of all the good things — our scientists, our health care system, our databases and our expertise — to bring in those clinical trials, and those funds can grow. The Roche announcement of $200 million will not be the exception; it could become the rule.
We have honoured it and business will follow where the environment supports innovation. That is why I mentioned the budget. The budget did a lot towards innovation and research this year. There was a problem when it comes to the changes of the SR&ED rules. Unfortunately, that passes a different message. We will work with that and we are still committed. That is why with CIHR we have said we will double our commitment over the next five years. Why? It makes sense for health care, economic development and Canada will win through that.
Senator Callbeck: Thank you for coming today and for your presentations. Ms. Arora, you talked about clinical trials in other countries, Brazil, Russia, India and China. You talked about the lower costs, and then you go on to say the situation in these countries has been more complex than anticipated. I would like to hear your comment on that.
Ms. Arora: Thank you for the question. In each country, the situation slightly differs. In Brazil, one of the problems that we have encountered is that there is no consistent standard of care. Part of the participation in clinical trials is that the pharmaceutical company covers anything over and beyond the standard of care and continues to cover that for as long as the patient is on drug. Many times, it is for many years after clinical trial.
In Brazil, when there is no standard of care, the pharmaceutical company has been asked to cover the entire cost of patient care related to that specific disease area that you are targeting, as well as any other disease area. Essentially, you have a patient that you have taken on for life.
Brazil is still a very fast-growing country with a very large middle income population, so it will still be a very important patient population for us. That is situation there.
In India, the problem is simply patent protection. India has made a decision that they are going to go the generic route at all cost and have broken patent, so there is a high level of discomfort in going to India.
I would say that China has done a remarkable job in terms of focusing on what it needs. However, everyone is now going to China, and it is very difficult to get the labour pool that speaks English, that is knowledgeable of the global environment, and they find it difficult to participate in some of the global trials.
Senator Callbeck: What about Russia?
Ms. Arora: Russia is actually doing quite well. I would say that, again, they have been very disciplined. They understand and they want to win in this game, so they have done extremely well.
Senator Callbeck: Thank you very much for that.
Mr. Brenders, you talked about costs. In your third paragraph you say, "Make no mistake. It is companies that invest to develop products."
The pharmaceutical companies invest, but also there is some government money in here, right through the Canadian Institutes of Health Research, and I am not sure if there are other government funds or not; maybe you can answer that. Plus, my understanding is that there are foundations such as the cancer foundation that invests a fair amount of money in pharmaceuticals. Do you have any idea how much?
Mr. Brenders: Sure I can give you a perspective on that. There is no question that governments invest heavily in early-stage discovery research, basic curiosity-based research. However that is not development. That is "come up with an idea of something that may work," but when you go from that early idea, then you have to validate the target and find lead candidates. You have to test those through. You have to go through your preclinical work, let alone even getting into your clinical trial phase. You are looking at millions of dollars.
I look at it from our pre-commercial companies here, the 66 I referred to. They are out seeking money from private capital, angel investment. What is great is that we have programs in Canada — things like IRAP, $50,000 here or $100,000 there — that help us take an idea that was in a university and test it to see if there is a proof of concept. That is great. Their next round is they need $2 million to $5 million ventured to test it further, and they spend that money in our institutions, in our hospitals and our universities. They outsource it. A lot of our money that is spent is outsourced out of these companies. They are virtual in their early days. After that, they go for their series A round, and they are looking between $5 to $10 million. Series B, they will run and get to $20 to $50 million, and then get to their C or D round. You look at a company like Enobia, who was in phase 2 trial earned $150 million. Before they could go any further and finish their phase 2, they had to work a deal with Alexion with $1 billion and finish it. That product is still in phase 2.
Those are good examples of the real costs of development and what it takes to develop. Make no mistake. Even in Enobia, they were recipients of some early grant money that came from research, which is helpful because especially in this those early stages when you are a company with six months' cash on hand and trying to pay the mortgage and keep the lights on, $10 or $20 grand keeps it there. A lot of these senior executives are working for equity and not for cash.
Senator Callbeck: The money from the government and foundations is just for the early stages?
Mr. Brenders: Yes.
Senator Callbeck: I have heard it said that for the pharmaceutical industry it costs over $1 billion to get a drug on the market. However, critics say a lot of things are added into that $1 billion that should not be there. It says here that the profits it would have made had the company invested the money elsewhere included revenues spent on successful products and so on.
When you talk about the cost, exactly what cost are you talking about?
Mr. Brenders: That is a great question because the studies that are referred to are often the DiMasi study from Tufts University back in 2003, I believe, and they did a second one in 2007. They looked at the full weighted costs. There are many studies on what it costs to develop a drug. You can take a look at a product like a company like Enobia that raised $140 million and then had to raise another 600 and then do 400, and then they do not even have a product to market. How much did their product cost? There is a billion dollars in on that one, and they are quite done yet.
Is everything spent there? Money goes to many different investors. When I see 91 out of 100 drugs not make it to market, the question is who pays for those 91 failures? That gets rolled in. At some point, for our little companies that are pre-commercial stage that are looking for investment communities, it is not the big pharma source. They want to be Genentech, but they need to find investors, and, typically investors, whether they be angels, VCs or otherwise, have an expectation that they make actually make a return on it, so it is more than charity. The problem with that is when they are investing in a lot of things, they know a lot will fail. When they do have that big win, they hope it balances out and that they make their 9 or 10 per cent profit.
What does it cost? If you guessed it right from the very beginning and did all through, could you do it for $500 million? Maybe. No one has ever done it, so it is there.
The goal of every company is to get that cost down. I know a couple of companies just closed another $30 million round, so they are good for 18 months. They want to make sure that $30 million, as there is no other pool and it is very hard to find it again, so they spend it efficiently. They will look where they will do those trials. They will look at Canada and say, "Okay, how many patient do you have, and what do you cost," and they look at us like, "You want a 40 per cent overhead on that?" No, I do not think so, and they will spend it elsewhere. They are astute cost managers. They love the quality and they love the opportunity for speed. Although there are some, I would argue, not probably as quickly as they want. You have to be efficient in terms of getting it because on the other side that one you take too much time, your patent runs out and you have no product.
Senator Merchant: I think it was Ms. Arora who spoke about speed. Perhaps you were talking about a different process, but I am sure every company that develops a drug wants to get it to market as quickly as possible.
I often wondered — and I am not sure if this exists — do we give any priority to speeding up drugs which are life- saving drugs? For instance, if, today, we were to come up with penicillin, and at the same time another company goes through all the steps and develops Accutane, which is a pharmaceutical for complexions, do we give any efforts to bring forward life-saving drugs more quickly? Are we prepared, perhaps, to take more of a chance on a drug that has greater benefits to humanity? I am not sure whether there are countries that do that.
Ms. Arora: Absolutely, that is done around the world. Again, when I speak about the metastatic melanoma, these patients have a poor life span and are at a critical stage where they have no other options.
In fact, there are several ways of decreasing the timelines. What Genentech Roche did was first combined the phases. In a general process, you tend to go through the phase 2 and 3 and then out to market. However, Roche recognized that this was so critical that they collapsed it. In conjunction with the FDA, the European Union and Health Canada, the conversations need to happen before. Absolutely, the data still needs to be there and it has to be of high quality. Just because this is the last option for patients does not mean that you can put out an unsafe drug. That conversation has to happen between the regulators and with the pharmaceutical industry. The regulators help us understand what the minimum requirement is before they are comfortable assessing the data and putting that information out there and then moving forward with the approval process.
Yes, there is a fast track, both in the conduct of clinical trials as well as in the regulatory approval process.
Senator Merchant: There is a perception in the public, and perhaps it is the reality, that when things do not go well in clinical trials the numbers are manipulated. There has been litigation, for instance with Vioxx, which has revealed that some of the negative things were hidden. What do your companies do to inform the public and instill more confidence in the public that these clinical trials are run on an ethical basis?
I know that some of this is interpretive, because different experts have different interpretations. However, how do you handle that? When one talks to people about clinical trials, some of them are skeptical.
Ms. Arora: People would be shocked to know how regulated our industry is. In practically every aspect of what we do there is a rule and international guidelines. It does not vary from country to country; it does not vary from study to study or patient population to patient population. In order to participate in these global trials you must meet the highest global standards that exist.
In terms of protecting and ensuring good quality data, several things happen. First, all these drugs are blinded, and not only to the patient or the investigator, but to us as well and to several levels within the organization. I have been in situations where, for some unfortunate reason, the blind has been broken. In such cases you are immediately either off that study or that patient can no longer be part of the data protection.
I do understand that perception. We have much still to do in terms of education. That is an area that the government and the pharmaceutical industry could develop together by educating people about their rights and how they are protected, be it through ethics committees, legislation or regulators.
I can assure you that every aspect of clinical trials has rules around it and that we follow the highest level of standards when it comes to that.
Ken Hughes, Vice-President, Scientific and Regulatory Affairs, Rx&D: I agree that we perhaps do not do the best job of getting the message out about how well regulated and ethical the clinical trial system is. There are multiple levels of control of all clinical trials, even in the Canadian system. Before any patient sees anything in a clinical trial, there is a scientific review at all the centres that are involved. A research contract also reviews the scientific realities. You have to go through research ethics boards in every jurisdiction you are involved in, declare conflict of interest, and set up a data and safety monitoring plan. That is before you even submit to Health Canada, who will then do their review. You have to get a "no objection" letter from Health Canada to go back to the research ethics board and the data and safety monitoring board before you can introduce anything to a patient.
There are multiple levels, all at the highest levels, involved here, and that is even before you consider the fact that the studies are blinded so that the physicians do not know what is being administered to patients, the patients do not know what is being administered to them, and the people who handle the data have never seen the patients. There are multiple levels at which these controls occur.
The problem is not the quality of the control in the sense of protecting patient safety; the problem is the operationalizing of these systems.
I will disagree a bit with Dr. Ward-Able. I completely agree with quality, but the timelines are not good within Canada because ethics are not coordinated and clinical trials agreements are not coordinated, and there is time associated with that. There is no problem with the quality of the ethics; it is the implementation of the ethics that makes us uncompetitive.
[Translation]
Senator Verner: Thank you very much, everyone, for being here this afternoon. You have just talked about coordination. My question is for Mr. Williams, concerning the action plan prepared in late March. Are we to understand that the provinces and territories were also consulted when you developed your plan?
Mr. Williams: Yes, they must be part of the solution. Dr. Hughes mentioned the example of the ethical review boards, and every province is working to reduce the number of boards, but even if we can correct that in every province, that will be 10 provinces plus the territories. When world-class companies look for the best place to make investments —and this is not to call ethical reviews into question — but we try to determine how many are really needed. The provinces play a very important role.
Senator Verner: In your plan, have you defined the various responsibilities of the different levels of government, or have you not gone that far?
Mr. Williams: It is quite clear. The real role is at the provincial level, but the role at the federal level may be to provide leadership and coordinate measures that should be put in place. At head offices — once again, I have never been invited to a head office at the decision-making level, but from what I have heard — they do not draw a distinction between Montreal, Quebec City, Toronto or Calgary. Instead, they look at whether they have invested in Canada. Can Canada present a simpler, more direct system? Even then, it is not just the review boards, but also the contracts. A contract is used in several other jurisdictions. That can help speed up a decision, and some provinces, such as Newfoundland and Labrador, have even adopted legislation setting a time limit for making a decision. I believe the message is quite clear: Canada wants these investments.
Senator Verner: That would be a good discussion to have at the conference of federal-provincial ministers of health. I imagine that is what you would like?
Mr. Williams: Yes, and even higher than that, because clinical trials are entering the life sciences ecosystem in Canada, and this is such an important part. A strategy will be necessary. As Ms. Arora mentioned, Russia is doing well because it is disciplined and is starting to work on speed, quality and administration. If Canada puts the same system in place, with the quality of science that we have in every university in Canada, we can really win. In addition, our health system gives us an information base. I do not know whether I can say it is the best system for data, but almost. With this combination, we can win.
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Senator Martin: Thank you so much. This is a topic has personally affected me recently with people who are very close to me going through a trial and error with drugs.
Mental health is one area where there seems to be quite a need for more drug choice for patients. I use the example of Abilify, which is one drug that was recently prescribed. The information that I heard as a supporter to the patient was quite limited compared to the advertisement I saw after the fact on the television of all of the side effects.
My question connects to my colleague's regarding clinical trials and the regulation around disclosure or transparency, all of those kinds of risks, how much patients should know and how complex the whole system must be. This is just a personal experience with a drug and how surprised I was to find out on an advertisement about Abilify that listed a whole slew of potential risks and adverse affects versus what I actually received.
Would you talk a bit about the regulations governing the kind of transparency that there needs to be once the drug goes through all the trials and what happens to that information from the trials themselves? Please comment on this specific statement: "There is no requirement under the Food and Drugs Act under its regulations to register drugs in Canada, although CIHR requires that all clinical trials that it funds be registered."
I guess I am questioning the level of transparency in Canada around registries and clinical trials.
The Chair: I will ask you to answer only with regard to the clinical trials. We will get into the post-approval regulations and all of those kinds of issues, so please focus on the part of the question that relates directly to the transparency of information from the clinical trial and the specific question with regard to the clinical trial.
Mr. Williams: I can start the answer. The members of Rx&D made a commitment as members of IFPMA, which is our international group, to post all clinical trials on one website. It is international and you can link it through our website. I will double check that, but it has been there; we keep changing it. My understanding is that it is available in five languages and is disease specific.
That is a movement forward. I understand your question. This is relatively recent — within the last three or four years. The information is out there.
I also want to comment about the other aspect, though you just told me not to, so we will save that.
The Chair: We will get into that and you will either be back or you will have the opportunity then.
Mr. Williams: I have one other point and then perhaps Dr. Ward-Able would like to point out something. You talked about choice. Canadians do not know what we do not know. We do not have as good a choice in this country as a lot of Canadians think. We did an international study, which I will gladly table with the committee. I do not have enough examples but we will send it over following the presentation.
We fall short on first-class medicines and in most disease areas, including mental health — it is here in this. Our medicines are not available. It takes longer to review; we do not have the clinical trial environment that we want. Then, later on, the listing decision takes longer than everywhere else. Therefore, people do not have the same choice. I will reserve the other comments for the next time I am here.
Senator Martin: In terms of Canada in comparison to other jurisdictions, would you say it is at par?
Mr. Williams: It is at par. I think we are all moving as an industry to do that better. That is what I am saying to you. When you post it on the Internet, it is available to everyone. That has changed recently for the better.
Dr. Ward-Able: May I take a stab at that as well? This is specific to clinical trials in the early development, so the early stages of that. That is one of the reasons why we do the research. That is what phase 1 and phase 2 basically are: You are looking for adverse events all the way through that.
I would like to reemphasize the point that Mr. Hughes made about the drug safety monitoring boards. On virtually everything single trial, they have a regular review of the adverse events that are reported by patients during their clinical trial. They would be able to see that data and be able to see whether anything is happening.
As you go through your phase, you learn more and more about the side-effects or adverse events profile. If you start a new study, you will inform that patient before going into the next trial. You then get into your market application and your approval and then that gets into the other part which we will not talk about now.
Senator Martin: There is disclosure all the way through and it is transparent, then.
Dr. Ward-Able: Yes. It is important to think about the data and safety monitoring board because that is what they are specifically looking for.
Ms. Arora: I wish to add a comment to that. One aspect of all of our trials is what we call monitoring. That is where the company actually funds monitors to go and to look at medical records on a regular basis and compare the information that needs to be put into the clinical research forms.
I am bringing this to your attention because their job is to ensure that, if by chance a physician has forgotten to input adverse event information on the case report form, which is the document that goes to the company, they are supposed to note that and have the physician input that complete information. That also adds up to hundreds of millions of dollars of cost in terms of overall clinical trial, but it is to ensure that the investigator is fulfilling the criteria that were set by the protocol, which is meeting the highest GCP, or good clinical practice, guidelines and those are at a global level.
Again, there is a real commitment to ensuring that we do not leave it to overworked physicians and nurses to ensure that all the data matches exactly; there is a huge staff of people hired by pharmaceutical companies to ensure that all happens.
Senator Cordy: Certainly the improvement in pharmaceuticals over the years or the last number of years has made a major difference in the lives of Canadians, most of it positive. Thank you for the work that you are doing.
To go back to Senator Martin's question, in February of this year the Canadian Medical Association Journal contained an article that said that the registration of clinical trials should be mandatory. I assume by that comment that it is not mandatory and that the disclosures you are making are strictly voluntary. Is it sufficient that it is voluntary, or am I wrong in that it is not voluntary and that it is mandatory?
Mr. Hughes: That is a good question that I would like to respond to directly. It is functionally mandatory. Rx&D has a code and all members are required to use that code, which is completely aligned with the Tri-Council Policy Statement on Transparency for Clinical Trials. To participate in clinical trials, we have to put it on a public database and we also have to publish the results. All clinical trials that exist at all and the results of them are all available out there.
The reality is that a lot of the cosponsoring agencies already require the publication of the results to be involved at all. The functional reality from multiple levels is that, for all trials that are being conducted, the results are available to anyone who wants them.
Senator Cordy: For Health Canada to do it is redundant because it is already being done.
Mr. Hughes: Yes.
Senator Cordy: Ms. Arora, you talked in your presentation about the creation of an ethics committee. Could you expand on that? I believe others, such as Mr. Williams, touched on that earlier. We talked about the quality, the time, and the cost. How would having a national ethics committee make things more efficient? I think you told us that it is happening in Europe; did you not?
Ms. Arora: That is right. I believe there would be great benefit to Canada by having a national ethics committee. The current status is that you have to go to the institution, and every institution that you interact with has its own ethics committee. They have their own processes, administration timelines. Many of them take the summer off, even though clinical trials do not stop in the summer.
There is a variation in the types of things that they want more information on and the types of things that they are concerned about. Therefore, we are finding that there is a huge amount of time that goes to responding to one ethics committee at a time.
There is no greater protection for any one site or one patient than any other. They are all protected, of course, through the ethics committee. However, the administration of the process, as well as the questions that are asked, vary to such a degree that it is very time consuming. If you have 25 or 30 sites, you may go to 30 different sites. Generally, there are some centralized. At least on a regional level there is some of that starting to happen, which makes it easier.
You also have to actually pay to have your ethics review happen, which is not a problem because this is in the best interests of the pharmaceutical companies to ensure we are meeting the highest standard from an ethics perspective. However, I would like to get something back for that dollar I spend. At a minimum, it would be that we get a response back in a timely manner.
I think sometimes ethics committees, even in their desire to protect the patient, forget that there is a patient desperate to participate in a clinical trial. It should not be administrative aspects of the ethics committee that delay the process.
Mr. Hughes: To add a little to that, very simplistically, it is the time to have a conversation. If there is one, you have one conversation. If there are 25, then you have 25 conversations. They are different, but even if they are the same, it has an effect on the time and cost associated with the trial.
Likewise, research contracts are negotiated at each trial site and each one is slightly different. You are having 25 conversations in that area as well, instead of one conversation which would get to the same place. The one conversation would deal with the ethical and contractual aspects, exactly the same as those 50 that you have to do.
Mr. Williams: If we can move away from this I think it would be hugely helpful; not away from the ethical review boards, everyone agrees with it. However, if we have 15 people in the room and basically all agree we have too many, there should be one, and they say it should be mine. If there is one thing the leadership can do here, now is the time to resolve both to have one main review board and one template contract. That could facilitate great deals, and all the criteria involved in those as well. No one is asking for shortcuts here, but just one.
Senator Cordy: It seems like a cumbersome process that will slow down what is happening with the patient.
Mr. Williams: Absolutely.
Senator Cordy: As someone said earlier, we forget the patient.
Mr. Brenders: These trials done in Canada are part of global trials. We are doing nothing different here. It is the same that is happening in major markets. From a competitive point of view, if you have an organized streamlined process with large populations in the U.S. or in Europe at some point — a pre-commercial company that has limited time and cash — they do not have time to wait for the summer to be over to enroll patients because they have 12 months of cash, and it is two months less than they have. The only people that get hurt in this are Canadian patients.
Senator Dyck: Thank you for your presentations this afternoon. Ms. Arora, I was intrigued by your statement that there is a perception that the research community in Canada has been passive in its approach to clinical trials. Is the research community passivity is a factor that has perhaps put Canada behind in terms of its participation? Does that have anything to do with the interaction at different institutions between their clinical scientists and their basic research scientists? Are there ways of optimizing the interaction or in some way rewarding the clinical people in a different way? Perhaps you need to have an incentive to attract some clinicians because maybe for some clinicians there is not that same motivation as there might be for a basic researcher?
Ms. Arora: The passivity is for multiple reasons. One is that our physicians are overworked and tired. Clinical trials almost become a secondary, volunteer part-time job. Although they may have started in it with a real love for clinical research, they find that the administrative burden and demands on them — in terms of participation in these complex clinical trials — has become so great that they are unable to manage both.
The other part for some of them is that the work has continued to come and whether they were key opinion leaders, or because they are well known globally in the world, that they have been able to call the shots. They have not really understood the impact of what is going on around the world. There are multiple reasons.
In terms of basic science, there is still a great deal of interest and that tends to move quite a bit faster than clinical trials. I think that it is a part of the clinical trial burden — the administrative burden — on these physicians. Again, if the institutions were geared towards supporting these investigators with the use of their overhead dollars, they would not have to go through the hoops they do, through their contract process, ethics process, documentation or trying to find these patients. It is really all left to them and it is quite a bit of work.
Senator Dyck: If I could ask a related question, Mr. Williams said that we need a policy environment that fosters rewards and sustains innovation. You are saying it is administrative and related somewhat to getting ethics approval and so on. This policy environment you talk about, would that be part of that? Can you expand what you meant by that?
Mr. Williams: There are a number of components. Those would certainly be two of them. Another example I talked about is access to medicines in this country. Can you imagine if Canada had a policy that — once we dealt with the issues of bringing clinical trials here, some of those barriers we have been talking about — if you have it on top with the industry and the government, if the value of the medicine is proven through the clinical trials, that medicine would be made available through provincial formularies? You have to first prove it. If you go through the clinical trial — and that is the reason for clinical trials — it falls short of that. Other jurisdictions are starting to say if you do clinical trials in our country and can prove the value of it, we will start using this medicine. Canada does not do that. That would be another element of an action plan that would incentivize the research. There are a number of other things we could be doing.
Mr. Brenders: An example of a good policy piece is orphan products. We are the last developed nation in the world that has no platform for treatment for rare disorders, orphan diseases, which have been neglected. Half of the products approved in the EU and the U.S. have not come to Canada. We have no framework to deal with these products. It is a product that might treat three or four debilitating conditions. Companies want to make them available and bring them here, but our process is 30 years out of date.
We have been chatting with Health Canada to develop regulations and are very optimistic that we can see them come forward. However, that is a simple policy piece. If you truly want to encourage new treatments and opportunities to come to Canada, you can recognize this like other nations; just use the formats that have already been done and make it easier to be able to bring these treatments and trials to Canada.
Senator Seidman: I would like to ask for your comments on the following: Drugs are only approved for populations in which clinical trial data is available. Often this means that drugs are not approved for use by children and pregnant women. Nevertheless, once approved, these drugs may be prescribed to these groups, and the costs associated with conducting further trials in these groups, in addition to the ethical difficulty involved as well as the added cost of a new drug submission to expand on the populations for whom the drug is approved, are impediments to the industry. Will you comment on that, please?
Mr. Hughes: I will make an introductory comment and invite Dr. Ward-Able to speak to specifics on that.
You are quite right; the difficulty with clinical trials is the requirement for a certain population. It is understandable why it would start in adults and then look down the line. There are post-approval programs and related programs associated with that recognizing these difficulties.
I know that Dr. Ward-Able has some specific understanding of these realities that he might like to share.
Dr. Ward-Able: These are very specific and highly sensitive populations. You do not want to give an untested drug to a pregnant woman or to a child that is still developing when you do not know what the impact of that would be.
You would ultimately have to get a good safety profile on the adult population and then carefully go back into those populations. It is very difficult. Recruitment is extremely difficult for clinical trials on pregnant women, and similarly with children.
Going back to Mr. Brenders' point, if you have an extremely rare disease and you have no other alternative, you may do something like that, but that often puts it into an orphan drug kind of situation, which needs special dispensation. It is a whole different ball game.
Senator Seidman: In June of 2011, the Canadian Medical Association Journal published an editorial about this. Among other things that I will not go into now because much of it deals with off-label use and things that are not pertinent to what we are discussing at the moment, they said that some clinical trials used to generate evidence for FDA approval for drugs enrolled Canadian children, yet the beneficiaries of such studies are only American children. For some reason, the results of U.S. studies are not applied in Canada.
Dr. Ward-Able: I can only imagine that is due to the fact that the indication was not approved in Canada, because the information goes across all borders; it is international.
Senator Seidman: I will leave it at that for the moment.
Supplementary to what has already been discussed about transparency issues, a Canadian Medical Association Journal article of February of this year suggested that there is no legal hurdle to making the disclosures we discussed here that have to do with clinical trial registration and date of reporting but that the barriers were institutional. In fact, they said that every Health Canada proposal for increasing transparency of clinical trials has been rejected by the pharmaceutical industry claiming they would breach proprietary interests.
Can you comment on what the proprietary barriers might be to clinical trial registration and access to clinical trial results?
Mr. Williams: As I mentioned, we are moving toward listing all clinical trials globally. As a preface, I do not always agree with everything I read in that journal, and we do comment back to them.
There are proprietary issues. We should undertake this race to transparency carefully. We should ensure that people get the right information at the right time in a usable way. However, there are some parts of the discovery process that are proprietary, but we do make the results public.
I do not see it as the issue as some of those critics do. We have made that public.
Senator Seidman: Do the U.S. and Europe not already have compulsory registration and reporting of clinical trial data as well as a lot of public hearings? I am trying to understand what the issues would be here.
Mr. Williams: Some of that information is public. As I mentioned, we are now on a website that does a no-borders listing.
Mr. Hughes: You are right; Europe and the U.S. do have requirements mandating the publishing of results. We do it as a matter of our ethical accord which is aligned with the tri-council and with our colleagues at IFPMA. You can mandate it, but it is already there. If you want to find the trials, go and find them.
The Chair: I would like to tie into the absolute aspect of Senator Seidman's question. You are referring to data that would be developed in a European trial, for example, where there is required publication, and you put that on your website.
What if there is a Canadian clinical trial related to the same drug which leads to data collection and observation? It might be possible that a subset of the population is struck here that is different than the others. To follow up on Senator Seidman's question, are you required to post that?
Mr. Williams: My understanding is, and if I am incorrect I will get back to the committee, that the answer the yes.
Senator Seidman: Thank you, chair.
Mr. Williams: I will make sure that I am on solid ground.
Ms. Arora: When we do global trials, we really do not differentiate between different countries in terms of the levels of their standards. It is easiest for us to create processes that match one standard, and that has to be the highest standard. If there are very specific additional requirements for a country, we will also follow those. From a global trial perspective, we do put it on a global website and that information is available.
Senator Seidman: Thank you.
The Chair: I would like to refer back to a question that was touched on with regard to the orphan drug situation. I want to be clear on the response that we received.
Does Canada adequately recognize the data developed in clinical trials done in other countries with regard to the approval of that drug for use in Canada?
While you are thinking about that, in the answer to the orphan drug question there was an implication that if it was well tested through trial process in another country that might not lead to approval for the use of that drug in Canada.
Can you help me with this overall issue?
Mr. Brenders: In terms of recognizing the data, when an application comes in for an orphan product, the biologics directorate of Health Canada is very good at understanding and working through the data for registration purposes. I do not think you will run into issues there. They work well and they understand what is going on in other jurisdictions.
As to whether they take advantage of or support the introduction of these orphan files more quickly than anything else or have automatic priority reviews and other designations like you see in other jurisdictions, Canada does not.
Especially with orphan diseases, you have to do a global trial. There is only a handful of patients around the world that are available for that. They are limited trials. That will get filed, but there is no incentive, encouragement or creative process to get those files into Canada. Canada, therefore, becomes a last and late market for the filings, per se. That does not mean a company would not make it available through a special access program.
They do recognize the data. It is a competent group and they do understand that. We do have orphan products approved in Canada.
I do not think there are any complaints on that side of it. It is just that when you have a product that might treat three patients in Canada, say, would you do a half-a-million-dollar filing to go through the process when it is just easier to make it available through an SAP?
The bigger question comes down is not through the trials or registration; it comes after the fact into the market. Since orphan products have not been recognized as unique in their nature and are treated like any other common drugs, your market access success in Canada is abysmal, to say the best.
Mr. Williams: To build on what Mr. Brenders has said, it is unrealistic to expect Health Canada to be able to match the same level of output as the FDA. They are 10 times the size, yet we are studying the same science and molecules.
There has been an effort to start to coordinate some of that work. Ultimately, the decision must be sovereign. I think what Ms. Arora said is important: Let us not forget about the patients. We have had in this country in the last couple decades almost a feeling of "last is best" in terms of the approval process. At risk of making a hockey analogy with experts in the room, it has been said in the past that if Health Canada was drafting a hockey team, they would pick all goalies. This is in the past. That may be a cheap comment about them because they are actually trying to work and coordinate this. It makes no sense to continually to repeat around the world the same analysis.
The Chair: You left us with quite an image, but I will ask both of you if you would follow up after this and give us a succinct summary of the issues. Mr. Brenders, you articulated it very well, but please follow up and provide that to us. This is an important issue for us and we would like to have those aspects down very clearly.
Mr. Brenders: Let me put one other context piece on that one as it relates back to clinical trials. I think Ms. Arora mentioned it well. Companies are very committed to their patients that they enroll in clinical trials and want to look after them. However, there is often an expectation that at the end of the day, after the trial is done and the product is approved and is available, that patients will move into the natural system. In orphan diseases, that does not happen because the market access world beyond that is very difficult.
Therefore, any company that wants to do a clinical trial on an orphan disease here really needs to think about it. They could be carrying that patient in Canada for life on a chronic disease basis. That does not help our competitiveness.
What would it take to help Canada? Come up with a process that encourages and supports clinical trials and the research in orphan diseases —
The Chair: We are spending a lot of time on this and there are other questions. You gave us a good outline of that and you are adding to it. What I am asking you to do is to put that in writing and get it to us so it is very clear. If Mr. Williams would complement that, that would be great. This is an important issue for us, Mr. Brenders. We would welcome that detailed summary, including the additional information that you were getting to.
Mr. Brenders: Okay, I am happy to do so.
The Chair: I want to go back to Mr. Williams with regard to the document you sent us in advance and that we have looked at. Early on, you have a number of recommendations for your action plan. Lessons of life teach us if an action plan is to be implemented, there must be some leadership or someone in charge of moving an action plan to action from the plan. I did not detect you assigning that role. I could interpret it that there was an implication that government might play a role in this in some way. If that is the case, is there a ministry that should take a lead in this regard?
I may have misinterpreted it entirely. Could you indicate to me what you were thinking in terms of putting this document forward, and who will move the action plan forward?
Mr. Williams: I was hoping you were volunteering. I will ask Dr. Hughes to comment in more detail.
You are absolutely right: It is a multidisciplinary approach. Maybe one of our problems is that we have not had a clear leadership on this. We have a responsibility, governments have a responsibility, academics have a responsibility and we are turning around.
I believe in the role of the federal government as a convener of these things and as a coordinator and instigator. Ultimately, people have to take their responsibilities.
We tried in the document to articulate which areas are doing it. You are right: We do not have a clear champion on that.
Mr. Hughes: The clinical trials action plan comes clearly under the SPOR initiative that Dr. Beaudet talked about in his testimony. CIHR, Rx&D and ACAHO are working together on the nuts-and-bolts implementation of this plan. There is a SPOR steering committee under which this falls and we are all engaged with, and it is driving it forward. It is very much a multidisciplinary, tripartite team driving this forward.
Where the federal government can help is to create the environment to help us push it forward when we need that help. There is a very good alignment of industry, hospitals and academia to push this forward, as beautifully articulated by Dr. Beaudet.
The Chair: You do have that concept of "who is on first" with regard to this issue, then?
Mr. Hughes: Absolutely. There is a management group and steering committee associated with this from the three groups.
The Chair: Thank you very much. There is a lot in this and, as I said, I did not detect that in the document.
On page 24, the issues you are dealing with there are the ideas of moving toward a clinical trial agreement model, and that has come up in other areas here. You indicated that by March 31 of this year, you hope that the review and study would be complete. Obviously it is not published yet or whatever. Are there any observations emerging that you could share with us at this time?
Mr. Hughes: The data is being collected and analyzed right now. I can share with you that it is indeed, as we expected, complex and that there are difficulties that we need to deal with. This is one of the big issues we need to get together.
One of the issues we have is that everyone has a lawyer and every lawyer likes to change things, so we are moving forward to finalize what will be the common clinical trial agreement along those lines.
Yes, the data has been collected and is being analyzed right now.
Mr. Williams: On that, I do not know if anybody can give us a deadline in which somehow we have to decide because this could keep going around and around.
The Chair: I was not asking for a deadline. I wanted to know if there were any observations. The issue of a standardized agreement and standardized ethics board requirements has come up in many ways — and you have articulated here — all the way from a single national ethics board, in the case of ethics, or at the very least a standardized approach so that the data you develop in applying for the ethics board approval is the same document you would provide, even if there are half a dozen or a dozen different ethics boards because they will require the same information as opposed to each one coming up with its own set of data requirement.
Mr. Williams: Absolutely. We will not be able to oblige the utilization of a single agreement, but we can set it up based on good consultation so that it makes sense to use it. Then common practice will bring it to be used more and more and that will facilitate it. If it has worked in other jurisdictions, it can work here.
The Chair: Thank you. Another issue that has arisen today and that is arising virtually every meeting is the issue of what I will call the under-represented groups at the clinical trial level. We have heard today about children and pregnant women. There is also the issue of the elderly because the aging body responds differently than the "middle eras" do.
I will not ask you to give us further expression on this today. I will ask you, however, to think about this challenge that you and the medical health systems have in dealing with how to identify the response of these groups to drugs that are approved for general use.
We are not getting into the actual aspect today but we are well aware that once a drug is approved, it is approved. Then it does get used in groups for which it was not tried at trial. I am sure this is an issue with which your industries have been seized in many ways over time.
If you have any suggestions for us as to how these drugs can be tested with regard to these specific groups — children, pregnant women and the elderly — we would welcome them subsequent to this meeting.
Ms. Arora has the answer right now, so we will get that on the record, but I still ask you all to follow up on this one.
Ms. Arora: I would like to pitch once more for a national registry or a national database. If we were able to collect appropriate information on there, we would have real life data. We already have a very difficult time attracting patients to clinical trials, for a variety of reasons, but in these very specific patient populations it is even more difficult.
If we could collect that information, it would be available to everyone, to physicians and to government, to be able to say that we thought this is what would happen and it did not, or the children are not responding to it in a certain way.
The Chair: That is important in two aspects. We are going to deal with what you are talking about deliberately in a subsequent study here, but I am speaking now with regard to getting that information before it is out there.
You will find a convinced audience here with regard to the electronic health data record. We are already on record in our recent report on how important that is, and pharmaceutical data and other issues came up during that study.
I have a general question about where things are going in terms of helping to identify early on the subsets of the population that are likely to be adversely affected by a drug that may be enormously beneficial to the larger population.
Over the last 40 years, history has given us a number of examples. More recently we have seen the famous Vioxx class of drugs, where we have not only a subset of a population but a subset of a subset of a population, which caused perhaps one of the most beneficial drugs to a set of the population to have been withdrawn from the market and no longer available to the population and so on.
Do you see in the future the concept of personalized medicine and the genetic analysis capabilities being able to enter early on in the trials for pharmaceuticals to give greater potential benefit to the population?
Mr. Brenders: We are seeing it today. You see orphan products, for example, that come out there. There are pre- commercial companies in Canada that are looking at things like Alzheimer's disease, but instead of looking at the huge part of it, they have been able to identify subsets of that population that are uniquely different. We are starting to find that broad diseases are not all so common. As we do genetic tests, we find the marker for that area and we start to build in companion diagnostics. We have companies in Canada that are working on companion diagnostics. It is the direction. It is to the company's advantage to do this research, because if you can identify high responders or eliminate non-responders, it makes it a more cost-effective trial.
The investment today is in the pre-commercial stage. The venture capital is going to companies that are much more targeted in their therapies. How can you isolate and identify high responders and those that do not respond or have adverse reactions? Much of that research is happening and it will be part and parcel of where treatment is going. We already see on the market here various examples of that. It is very much the front end.
Ms. Arora: I would like to echo that it is here. Several of our products at Roche are personalized health care. The melanoma drug that I was telling you about is personalized health care where the diagnostic and the treatment were approved at the same time.
Roche has made a commitment that by 2020, 50 per cent of all its drugs will have a personalized health care component to them. In areas such as mental disease, where patients need to be on a drug for a long period of time before you know whether it is working, it is absolutely critical that we know up front whether the patient will benefit from that type of drug.
Dr. Ward-Able: The development of biomarkers that might be able to tell us which are the better populations is something like the development of a drug. It is translational research. You have to identify the marker as a possible marker and then test that out. In that way you will fragment diseases into multiple diseases, and it will become extremely complex. That is my opinion.
Similar to what Roche has done, we serendipitously discovered one with one of our colorectal cancer products that can tell patients that they will not benefit and in fact might be harmed, and tell others that they have a good chance of a positive response. It is wonderful; clear-cut and simple.
Unfortunately, not all diseases behave like that. Unfortunately you get tens and hundreds of different genes. That is where the electronic database could help. The more data you have, the better you can analyze it and analyze the outcomes.
The Chair: Two senators have further questions. I will ask them to ask their questions and, if there is time, I will come back to Senator Seth's question. I want the questions on the record so that if there is not time for you to answer here you can follow up subsequently.
Senator Seth: Thank you very much for being here. I apologize for arriving late and having missed much of your discussion.
You have been talking about electronic biodata. I am a physician and I know that every year we hear that EMR will be coming out, but it is always delayed further. When will it be implemented?
I know there is an action plan and you have been saying that we have been very slow in Canada. Yes, in my practice I see medicine being used in other countries that we do not yet have in Canada. Perhaps the work that you have been doing globally will facilitate it coming here more quickly.
I am puzzled with regard to drug trials. In your trials do you test for long-term adverse affects? It is important that we get that. If a drug is already on the market but we do not know the long-term adverse effects, it is important for us to follow up with the patients. We do have problems with that.
Senator Eggleton: I have two follow-up questions. One is on the issue of transparency. You have answered a few questions on that already. The European Union and the United States makes provision of the information mandatory. There has been the suggestion now that Canada make it mandatory.
Your response is that we do not need to do that as you already provide all that information. However, sometimes a degree of public confidence can be achieved by making it mandatory. Do you have any objection to doing the same thing as the European Union and the United States have done?
Mr. Brenders: Are you suggesting that we create a Canadian database, or are you saying that making it public is sufficient? Are you asking for duplication of the work or for an acknowledgement or reflection of the work?
Senator Eggleton: Are they duplicating the work? The European Union has one regime and the United States has another. Are they different or is there duplication?
The Chair: Mr. Brenders, I did not understand your answer and I want you to follow-up. I believe that you were trying to figure out the question.
Mr. Brenders: I am trying to understand the question.
The Chair: I interpret it by the way the questions have been going on this. If there is a clinical trial in Canada, is there a requirement to register it publicly somewhere? That is the issue, I think. You have already made it clear with regard to Europe, and so on. Senator Eggleton, do you have another question?
Senator Eggleton: Do I understand the answer to be that there is no problem?
The Chair: No, I will have them follow up in writing because we are running out of time.
Senator Eggleton: Okay.
The Chair: I want us to have a clear summary. Obviously, this has been complicated by the way the questions have been asked and answered.
What we want to know is: Is there a requirement to register the data from clinical trials that are conducted in Canada and to make them available publicly? We have heard clearly what you are doing globally. What we want to know is with regard to clinical trials carried out in Canada.
Senator Eggleton: The other question is on personalized medicine. The current clinical trial regulatory framework operates under Health Canada. What changes are needed to facilitate personalized medicine? How adaptable is the present system to that? Have you made any representations to them with respect to that?
The Chair: You have these questions. The clerk will follow up. If you can understand all of the questions, we would appreciate answers to them. In particular, we would like clarification of the issue of data collected in Canadian trials with regard to the registration of the trial and the dissemination of it either by requirement or by your automatic process in your global websites.
With that, I thank you for your approach to this meeting. Your presentations were on the mark to a very high degree and we appreciate that as well as your frank answers. We would like you to follow up on specific things because your knowledge in these areas is enormously beneficial. You are wrestling with these questions, I have to instinctively assume, in particular with regard to those underrepresented presentations.
On behalf of the committee, I thank you for being here today.
(The committee adjourned.)