Proceedings of the Standing Senate Committee on
Social Affairs, Science and Technology
Issue 16 - Evidence - May 9, 2012
OTTAWA, Wednesday, May 9, 2012
The Standing Senate Committee on Social Affairs, Science and Technology met this day, at 4:16 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, and I am a senator from Nova Scotia and chair of the committee. I will ask my colleagues to introduce themselves starting on my left with the deputy chair.
Senator Eggleton: Senator Art Eggleton, from Toronto and deputy chair.
Senator Cordy: Senator Jane Cordy from Nova Scotia.
[Translation]
Senator Verner: My name is Josée Verner, and I am a senator from Quebec.
Senator Demers: Jacques Demers, senator from Quebec.
Senator Rivard: Michel Rivard, from the Laurentians, in Quebec.
[English]
Senator Wallace: John Wallace from New Brunswick.
Senator Seidman: Good afternoon. I am Judith Seidman from Montreal, Quebec.
The Chair: I would like to welcome our distinguished witnesses to the committee. I will introduce you by association as I call you to present. By earlier agreement we will start from my left across the table. Without any further ado, I will start with the Association of Canadian Academic Healthcare Organizations. We have both Dr. David Hill and Dr. Tina Saryeddine. Dr. Hill is Co-chair of the Vice-Presidents of Health Research Group, and Dr. Tina Saryeddine is Assistant Vice-President of Research and Policy Analysis. It is my understanding that Dr. Hill will make the presentation.
David Hill, Co-chair, Vice-Presidents of Health Research Group, Association of Canadian Academic Healthcare Organizations: Good afternoon. Thank you for inviting us to contribute to this important session. This afternoon ACAHO would like to focus its brief remarks on the National Clinical Trial Summit hosted by ACAHO, Canada's researched-based pharmaceutical companies, which is Rx&D; and the Canadian Institutes of Health Research, CIHR, in September 2011.
During my remarks I would like to tell you about what motivated this initiative, what is recommended from it and what government could do to help.
For those of you unfamiliar with the Association of Canadian Academic Healthcare Organizations, ACAHO is the national voice of Canada's 40-some academic health care organizations. That is our country's research hospitals our academic regional health authorities and their research institutes. It is spread across the country. You have all likely been inside one of these organizations at some point. You will know them for leading-edge patient care services provided to you, your families, friends, neighbours and communities. However, these organizations are also national resources and economic engines. They attract acclaim internationally and play a significant role in the health system as well as in our economy.
Clinical trials are a practical example of how academic health care organizations help to achieve human, social and economic benefit. Clinical trials enable us to provide leading edge care to patients and families, and in so doing they attract leading clinicians who want to explore the full possibilities of their professions. Studies have shown that organizations that participate in clinical trials also have better patient outcomes. At the same time they allow us to generate products, services, jobs and revenues.
For instance, in 2008-09 new clinical trial contracts across the ACAHO membership were estimated to have a potential revenue earning ability of $340 million. However, Canada's capacity to continue its tradition of excellence in clinical trials is not a given. Increasingly global competition, especially coming from Asia is limiting our ability to get the sort of trials we want. Combined with our own idiosyncrasies in our own business environments, that is costing us substantially in terms of lost opportunity. For example, when a company is interested in conducting a clinical trial here in Canada it faces multiple jurisdictions, multiple forms, multiple processes and multiple standards before it can start a trial. Individual ethics board reviews for the same protocol may have many different requirements, results and inconsistent turnaround times. Eligible patients may be difficult to find, recruit and retain in trials. After all, we have a relatively small population. Contracts might differ from centre to centre. All of this results in costs and delays and can discourage clinical trials investments in Canada.
Pockets of excellence and innovation exist across the country, but what can Canada do at a national level to help address this issue? This is the question posed by 130 representatives from academia, health care organizations, governments and industry at the National Clinical Trial Summit. If we begin with the premise that if we start by improving cost, quality, speed and relationships as they pertain to clinical trial start-up, then we can more attractively become the business partner of choice for the international clinical trials market.
The document Starting the Conversation is in your packages and provides you with much more background information as to the motivation for the initiative.
The conclusion of the Clinical Trial Summit conversation is called: To Your Health and Prosperity. It is a draft action plan that resulted from the summit consultations. It was only intended to be a starting point, but the aim of the action plan is to help clinical trial companies succeed and stay in Canada. The goals are threefold: First, to halt and reverse the downward trend in investments — we have calculated that clinical trials investments are declining about 12 per cent per year in this country; second, to improve business practices as they pertain to clinical trials operations; and third, to create a stable, forward-looking opportunity for clinical trials in the future.
Most of the nine recommendations that were in the action plan need to be led by us, the field. We have to break down jurisdictions, domains, sectors and organizations, but what can the federal government do to give this plan a better chance of success? We believe that the government should assume three roles. The first is leadership. The federal government can signal a nation-wide interest in reclaiming Canada's leadership position in global trials, and this will really energize the sector. The second is incentives. It can incentivize collaboration instead of competition and regulation. This will help to achieve efficiency by balancing flexibility with standardization. The third is resources. It can provide coordination-type resources that allow the field to implement the individual recommendations in this action plan.
We believe that through focused attention and collaboration, Canada can succeed in its effort to reinvigorate our tradition of excellence in clinical trials. That will result in health and prosperity for all.
The Chair: I will now go to Dr. Robin Walker, Integrated Vice-President, Medical Affairs and Education, London Health Sciences Centre and St Joseph's Health Care.
Dr. Robin Walker, Integrated Vice-President, Medical Affairs and Education, London Health Sciences Centre and St. Joseph's Health Care, as an individual: I have the honour of being the chair of the Paediatric Expert Advisory Committee of the Health Products and Food Branch of Health Canada. Dr. MacLeod is also a member of that committee. I will be talking about our work and recommendations to improve the prescribing of medications for children and youth in Canada.
Increasingly health products and food regulatory bodies around the world are turning attention towards the safety of children. Health Canada, in keeping with this trend, formed the Paediatric Expert Advisory Committee. It provides the department with expert advice on how to better protect the health and safety of children, and of pregnant and nursing women, in keeping with the work of the branch.
The committee, which I will now refer to as PEAC, has 15 members, including pediatric specialists, university professors, pharmacists, researchers, representatives from both industry and patient groups, not-for-profit organizations and parents. The committee has been meeting since February 2009.
Among the complex questions the assistant deputy minister of the Health Products and Food Branch has tasked PEAC to examine most focus on the current challenges with health products, drugs, medical devices, biologics, including vaccines; and natural health products. There is a need to develop, test, evaluate and label these with appropriate information for safe use in children, issues that need input from industry, clinicians, parents and regulators.
Let me tell you a bit about myself. I came to Canada in the 1970s after completing my medical degree and my first two years of specialty training in Manchester, England. My subsequent training in pediatrics in neonatology was at Dal — I am glad to see the senators from the Maritimes here. From there I have worked in Moncton, New Brunswick; Kingston, Ontario; Ottawa, Ontario; Halifax again until a year ago; and now in London, Ontario. In addition to the official title you heard, I am also a professor of pediatrics at the Schulich School of Medicine and Dentistry at Western University and, in my voluntary capacity, chair of the board of the Canadian Institute of Child Health.
The real reason why I was chosen to chair the PEAC was because I practised as a neonatologist, a specialist in the intensive care of newborn infants, for 30 years and now practice in the field of developmental follow-up of newborns. I am well aware of the challenge of prescribing treatment to children, particularly the smallest children at the start of life. Children react differently to health products and to foods and their ingredients.
Assumptions of efficacy, safety and drug interactions cannot be made from adult data. Many health and food products are not designed or formulated specifically for use in children. Although regulatory authorities around the world are focusing more on pediatric needs, clinical research is not undertaken systematically with a few exceptions in pediatric age groups. As a result there are challenges to developing precise information on the label to guide use in children. Most medications used in children are in fact used off label. Even where there is research to guide use in children, that information is often missing from the label, making it difficult for pediatric practitioners to use the product appropriately.
In my field of neonatology, for example, I have been part of extensive clinical trials on the gas nitric oxide, which is a gas that occurs naturally in the body and is used for newborns with respiratory failure. It opens up the blood vessels and the lungs when they fail to open spontaneously after birth. When nitric oxide is not enough, we have to turn to drugs that are better known in adult medicine. It may surprise the committee to know that one such drug, Sildenafil, is better known to you as Viagra, a drug which also opens up blood vessels. When we use this drug to help newborn lungs, we still have relatively little information on safety and efficacy of the drug in newborns, which makes using it a challenge. If that information on use in children does eventually become available for it a particular product, manufacturers are often reluctant to make it available on the label, so a valuable drug may not be used in children because the information still is not known to prescribers. I would add that as a neonatologist that I am aware that similar issues affect care for pregnant and nursing women.
On labelling, we have provided for you an excellent article by Dr. Robert Peterson, former director general of the therapeutic products directorate; and coauthored by the vice-chair of the PEAC, Dr. Noni MacDonald. This is called "Industry's Neglect of Prescribing Information for Children." We have also provided another excellent resource to you, namely, a 2011 statement by the Canadian Paediatric Society of which I am a former president. The principal author of that statement is Dr. Michael Rieder, a pediatric pharmacologist from Children's Hospital in London, Ontario.
In the meantime, I will also bring your attention to a PEAC-sponsored initiative during which the Minister of Health has asked the Council for Canadian Academies to provide an evidence-based and authoritative assessment on the state of therapeutic products for children in Canada and abroad. The assessment will attempt to answer the question: What is the state of clinical pharmacology in Canada and abroad that can be applied to the ethical development of safe and effective pharmaceuticals and biologics labeled as therapies for infants, children and youth?
This assessment will be highly relevant to the ethical development of safe and effective pharmaceuticals and biologics labelled as therapies for infants, children and youth.
Finally, I wish to thank Health Canada's Office of Paediatric Initiatives for their support of the needs of children and youth, as well as pregnant and nursing women, in terms of their therapeutic needs. The work of this office is essential to the safety and care of these vulnerable populations, and our committee could not have been as effective in bringing these concerns forward without their continuing support.
Thank you for inviting us to appear today.
Dr. Stuart MacLeod, Professor, Child and Family Institute, University of British Columbia, as an individual: I started down this road of studying drugs and children in 1969 at McGill University as a graduate student in pharmacology. I am really delighted to have a chance to reinforce with this committee what I think is the tremendous potential for Canada to make a contribution in our pursuit of better drug treatments for children.
I will give just a bit of background. There are now 7 billion people in the world, and while you might not recognize this in Canada, about 35 per cent of them are children under the age of 18. In some African countries, the proportion is even much greater than that. I go to Uganda frequently, and 50 percent of the population in that country is under the age of 15.
There is a huge population of children who need appropriate drug therapy and the kind of research we are supporting here today in order that appropriate labelling will come forward for drugs for use in children in the way that Dr. Walker has described.
Canada has a particular chance to contribute here. We have had 30 years of world leadership in pediatric pharmacology, coming from many of our major pediatric institutions. During that time, we have developed effective networks. We have strong international linkages to our counterparts in the United States, in Europe, in the World Health Organization, and in many low- and middle-income countries. We have a range of expertise that is quite broad: Everything from epidemiology and population health sciences through to very basic pharmacology and genetic aspects of pharmacology.
In 2006 the 17 Canadian Academic Health Science Centres got together and created what is called MICYRN, the Mother-Infant-Child-Youth Research Network. We actually have a network already created that is dedicated to the study of drugs in children and to the promotion of pan-Canadian clinical trials.
As you have heard from Dr. Hill, there is concern now about diminishing clinical research activity in Canada and the point is well taken. However, in the domain of child and youth health, we are actually punching well above our weight. Canada is a world leader in clinical trials. We are second only to the United States in the number of pediatric clinical trials under way here. We are well beyond what one might expect on the basis of our numbers of children.
We have a competitive advantage, and we need to capitalize on it.
I think there are some key deliverables that could be recognized in the short term. We could develop a major network that would focus on clinical trials in obstetrical patients and in the perinatal time period, in infants, children and adolescents. We have shown we can bring together all the various disciplines needed for this, and we are already a world leader in training the kinds of highly-qualified personnel you need to do this, particularly at the Hospital for Sick Children in Toronto.
I believe that we can become leaders in the kinds of implementation science that is needed to go from the things we know in pediatrics, pediatric therapeutics and toxicology to better drug treatments. We can develop better models for evaluating innovations in therapy and can provide the kind of evidence necessary to support decision making.
I have come this morning from Winnipeg, although that is not where I live, where there has been a meeting for the last two days of what is called StaR Child Health, Standards on Research in Child Health. People from 20 different countries are talking about how to design better trials for children. Canada is leading in this effort.
I believe if we play our role appropriately, we can make a major impact on child survival in the developing world and do much to improve child health in low- and middle-income countries.
I think we have something to export. This expertise which, as I am describing, is in great demand in other parts of the world, both in developed and developing countries. We have real strengths in a number of the key disciplines: neonatology, infectious disease, vaccine development, nutrition and the use of micronutrients, clinical epidemiology, and clinical pharmacology. Maybe most importantly we have quite a bit of expertise in Canada in telecommunications, and that is very important in the knowledge transfer process for the developing world.
What would we like this committee to recommend? We need a stronger regulatory framework that has been modernized to encourage a greater degree of investigation of drug efficacy and safety in obstetrics and neonatology, and pediatrics generally. We need specific funding to strengthen the Canadian training capacity in the various disciplines that enter into therapeutic evaluation for pediatrics and obstetrical drugs. We need to export that expertise to developing countries, particularly in South Asia and sub-Saharan Africa.
As you have heard from Dr. Walker, the Paediatric Expert Advisory Committee is a good beginning. We feel that committee should be mandated to promote further enhancement of knowledge mobilization strategies to ensure that the kinds of information we now possess get out to practitioners across the country in order to promote better prescribing based on the best possible evidence.
Thank you very much.
The Chair: Thank you.
Now, from the Canadian Medical Association we have Dr. Maura Ricketts. With her is Millicent Toombs, Senior Policy Analyst, Health Policy and Research.
[Translation]
Dr. Maura Ricketts, Director, Health Policy and Research, Canadian Medical Association: The CMA appreciates the opportunity to appear before this committee today as part of your study of clinical trials and drug approvals.
[English]
The CMA represents about 76,000 physicians in Canada, and our mission is to serve and unite the physicians of Canada and to be a national advocate in partnership with all Canadians for the highest standards of health and health care. Prescription drugs are an essential component of health care, so we have developed an extensive body of policy in the area of pharmaceutical issues.
However, there is one fundamental principle that we can extract from the policy, and that is that the CMA believes our country requires a National Pharmaceuticals Strategy in order to ensure that every individual has timely access to safe, effective and affordable prescription drugs. Despite the commitment in the 2004 Health Accord to the creation of such a strategy, Canadians continue to wait for government leadership on this issue. Drugs replace more costly and invasive medical interventions and they are an essential tool in a physician's tool box.
To ensure safety and effectiveness, the CMA also believes in the need for a strong, unbiased, evidence-based system for research and approval. This is at the heart of our commitment to patient-centred care. In evaluating whether to prescribe a new drug to a patient, a physician will weigh several factors. Does this product offer any benefits over that which I am prescribing now? Will it be more effective? Will this drug be safer? Will it solve any tricky clinical problems, such as drug interactions; or reduce side effects that prevent a medication from being used properly? The physician might also ask: What is the evidence that this new drug is an improvement? Can I trust the evidence? Where can I get access to accurate, reliable information and data on the drug? Pre-approval drug research must provide the answers to all these fundamental questions.
Clinical trials: I will now focus on two particular issues of concern to practicing physicians with regard to clinical trials. First, what is being compared with what? Clinical trials may be sufficient for Health Canada's regulatory purposes but may provide only part of the information that a physician actually needs. For example, is a new cholesterol drug effective in all patients or only some of them? Would other patients derive equal benefit from an existing drug or from a lifestyle change, such as diet or exercise instead of medication? The CMA recommends that researchers compare new products to other drugs on the market and to other interventions as well.
Second, is timely, reliable objective information available on all clinical trial results, not just the positive ones? Canadians need to be informed when a drug has performed disappointingly in trials if they are to make informed decisions about their health care. The CMA, therefore, recommends that the results of all clinical trials, not just those with positive results, be made public and available to health professionals.
I would like to add that the current documentation is not really very user-friendly. We recommend that Health Canada prepare summaries of the most essential data not only for physicians but also for Canadians so that they can have access to the information they need.
With respect to the drug approval process: The Canadian Medical Association believes the following principles apply: Primary criteria for approval should be whether the drug improves health outcomes and offers an improvement over products that are currently on the market. The review process needs to be as timely as possible to ensure optimal health outcomes and the safety of the drug supply. The review process should be impartial and founded on the best scientific evidence. The review process should be open and transparent.
Finally, approval of a drug is not an endpoint but rather one step in the drug's life cycle. It is not uncommon to identify serious safety hazards after a drug has been approved because that is when it first goes into wide use into the larger population. It is important that the approval process be complemented by a rigorous and vigilant post-market surveillance process. We look forward to presenting our recommendations on this subject to the committee at a future session.
[Translation]
Before closing, I would like to briefly address two other matters.
[English]
First is the issue of drugs for rare disorders. We are aware that the current clinical trial and approval processes that place a high value on studies with large population samples may be unable to adequately capture the value of drugs prescribed to only a handful of people. Some patient groups are active in this area, such as the Canadian MPS Society and Alpha-1 Canada, and have shared their concerns about this with us; and I imagine with this committee to some point. These groups, along with the Canadian Organization for Rare Disorders, have been advocating for years for a fair process for evaluating drugs for rare diseases. However, Canada does not have a rare disorder strategy, so Canadian patients have access to fewer therapies than patients in other developed countries. The issue of how to approve drugs for rare disorders merits closer attention. The CMA recommends that the federal government develop a policy on drugs for rare disorders that would encourage their development, call for ongoing evaluation of their effectiveness and ensure fairness so that all patients who might benefit could have reasonable access to them.
Second is that Health Canada's review process provides little guidance on another question that physicians are increasingly asking: Can my patient afford this drug? It is not sufficient that the Common Drug Review conducts reviews of the cost-effectiveness of drugs and that provincial and territorial formularies undertake similar studies, as the fact remains that the cost is one of the factors physicians need to consider when deciding whether to prescribe a drug.
This is especially true in the case of new biologics, which are very expensive. Canadian doctors believe that the difficulty of making effective prescribing decisions without information about cost needs to be overcome. This only underscores the necessity for a national pharmaceutical strategy.
[Translation]
Thank you. We would be happy to answer your questions.
[English]
The Chair: I thank the witnesses for covering a range of aspects. Before I open to questions, I should remind all that we are doing a four-part study on the pharmaceutical process, so we will be doing a separate study of off-label and post-approval surveillance and so on. I will confine the questions today to phase I and phase II clinical trial process to a very high degree. We will move to questions.
Senator Eggleton: I primarily would like to focus on children. As a general comment about clinical trials, we started off with Dr. Hill telling us that we are losing ground and that we need to halt and reverse that, improve business practices and overcome costs and delays. Dr. MacLeod spoke from a pediatric perspective. He said that we are punching above our weight and that we are leading in many respects. Maybe it is a misunderstanding as to what he specifically referenced versus what Dr. Hill referenced.
The CMA came out with an editorial in its journal on June 14, 2011. It is pretty strong editorial. It starts by saying:
The pharmaceutical industry generally has not submitted evidence in its possession supporting safe pediatric doses and dosing intervals to Health Canada.
Even when pediatric data exist they will only be provided to help professionals in jurisdictions where manufacturers choose to apply for pediatric indication. Canadian children and youth may fall victim to medication errors and mistreatments simply because of limited access to information.
The article continued:
In fact, a recent query of the US Food and Drug Administration (FDA) website showed that many drugs that have obtained pediatric-specific labelling in the US are described as having "insufficient evidence" in Canada.
It said that trials used to generate evidence for FDA approval of drugs enrol Canadian children, yet the beneficiaries of such studies, are only American children. Such opportunistic behaviour and permissive rules allow Canadian children to be put at risk in regulated trials but denied the benefits of that same research.
The final conclusion states that it is utterly unacceptable for pharmaceutical manufacturers to profit from risky off-label use of medications in children because they have failed to conduct the studies and have chosen to withhold this important drug safety information from a country's drug regulators, especially given that it is little more trouble than cutting and pasting an FDA submission on a Health Canada form. Unfortunately, laws seem to be the only way to control such unethical behaviour.
Pretty strong. We should ask our politicians to protect Canadian children by enacting strict legislation similar to the U.S. Pediatric Research Equity Act.
Dr. MacLeod, there is an article in here by you. You were a little bit critical and concerned about similar kinds of issues, as far as I can gather.
Dr. Ricketts, does the CMA stand by the editorial in the journal? I would like to hear the reaction of everyone else to what I have just said.
Dr. Ricketts: The Canadian Medical Association Journal is independent from the Canadian Medical Association. However, it is hard to argue with a reasonable statement. I believe the reason we call for a national pharmaceutical strategy is to see questions like this addressed as quickly as possible and in a rational manner. Part of the issue that Dr. Bob Peterson is referring to in the Canadian Medical Association Journal is also another issue we have mentioned in our brief to you: The results of all clinical trials should be posted and available for people. They should not be concealed by the drug companies. Certainly on two matters within that we have provided some information. Without any doubt, I defer to my colleagues in pediatrics who have far more experience in this area than I have.
Dr. MacLeod: The chair pointed out that you really want to talk about clinical trials. However, in pediatrics it is all about your third question, which is the off-label use of prescription pharmaceuticals.
The Chair: We will go into that in real detail. That is part of the reason we have a separate —
Dr. MacLeod: I understand, but allow me to say that in pediatrics three quarters of drug therapy is off-label because the clinical trials have not been done. You point out some inconsistencies and I think they have to do with proportions. Canada does quite well in pediatric trials, but those trials are not sponsored by industry for the most part. The pharmaceutical industry is not particularly interested in children because they consider it to be a small market and not highly profitable. With a few exceptions — things like antibiotics — they are not eager to get into major clinical trials. In Canada, while we do a lot of trial work in children and neonates, most of it is investigator sponsored, government sponsored or institution sponsored. Our hospitals may have a question about how to use nitric oxide in the newborn nursery so they may initiate a trial. We are very good at that, but we are not doing well because there are a lot of industry trials lined up looking for qualified researchers to conduct them.
The glass is half full. We actually have the expertise to do trials. The demand is nothing compared to what it is in adult medicine or geriatrics where there is a greater range of diseases and conditions that need drug treatment.
On the editorial, Dr. Peterson is absolutely right, of course. We have been looking at drugs in children for a good many years and many of the international trials involved Canadian children. However, there is no legislation that requires a pharmaceutical company to bring back that data once a trial is completed and apply for a labelling change at Health Canada.
Senator Eggleton: Would you suggest we do that? Would you go along with that?
Dr. MacLeod: Certainly Health Canada could force them to do so.
Dr. Walker: In addition to the need for changes in regulations to bring the information to label, and the need to support research in clinical trials across the board, but certainly in pediatrics through groups like MICYRN. I would also argue that we need to emulate the United States and the European Union which have passed specific legislation. The editorial references the U.S. legislation, the Pediatric Research Equity Act, which helps ensure that industry will also do trials in the pediatric population on drugs that might be valuable in that population. There are specific incentives to encourage companies to do that.
That is the other piece of this particular puzzle, in addition to those that the other speakers have mentioned.
Dr. Hill: I do have a lot to add except purely my own experience trying to do intervention studies for childhood diabetes, where we are looking at adult off-label drugs for use in pre-diabetic adolescents. It has been incredibly difficult to do innovative research because Health Canada has come back and said: Show us the pediatric data. We have literally had to wait until two or three publications come out of Europe — where they have much better regulation — to show that this is a safe approach and by then, where is the innovation? It has already been published.
Senator Seidman: If I could just pursue this a little more, I do have another question. However, this issue of inclusion of children and pregnant women — and even women in clinical trials — has been one of the most challenging we have confronted over the weeks we have heard witnesses here. I am very interested because you are saying there are incentives and regulatory issues here; things that you see the federal government can do to help encourage private industry, pharmaceutical companies, and perhaps even facilitate academic institutions and researchers coming out of that venue in this area.
Could you please be more specific about these incentives and regulations that you are referring to?
Dr. Walker: There are many approaches that are used in the different jurisdictions, which can sometimes be extending the length of a patent if one does research in pediatrics, for example. The advantage to the company doing the research is longer and therefore the investment is recouped. One has to be honest here. We have a relatively small population; only about 20 per cent of our population is under 19 in Canada. We are an older society, so no incentive will ensure that drug companies do huge trials in Canada across the board. That is not realistic.
What we are missing here is anything that helps support incentivized companies to at least look at the pediatric population and more importantly — as Dr. MacLeod has said — where the studies have been done elsewhere to ensure that information will be brought through the regulatory process to our label so our prescribers have that information. That is a fundamental gap at the moment in how we approach drugs for any population that is unrepresented and that is not just children; it is certainly pregnant women and women across the board.
That is one piece of this that is a specific need.
Senator Seidman: You are saying quite clearly that if a drug has been approved for market in the U.S., for example, there is no reason that it should not then be approved in Canada without clinical trials here?
Dr. Walker: It should go through our regulatory process, but if the information from elsewhere is done in a comparable population — it is hard to argue that the U.S. and Europe at least are not comparable — it should be brought into the regulatory process and then that information brought to label. That really does not happen right now.
Senator Seidman: I asked pharmaceutical people when they were here and that was, in fact, their response to this very question. They did not understand the reason that pediatric drugs were not approved in Canada and were not available for Canadian children as they were in the U.S., because of this very big issue.
Dr. MacLeod: Be careful in your choice of words. It is not so much that the drugs are not available. Clinical trials, whatever side of the border they are done on, can be used for regulatory purposes. That is not an issue, and most of the drugs available in the United States are available in Canada within a fairly short period of time. The same is true for Europe. The issue we are touching on is the labelling, which you will come to later. The companies have information that would improve prescribing and outcomes that they are not sharing with the practice community.
Could I comment on your first question? What has worked in Europe and in the United States has been a mixture of carrot and stick, so both of them have a pretty big stick. You cannot really register a drug in the United States or in Europe nowadays without being directed to do studies in children if that is appropriate. In the United States the PREA and in Europe the EMA requires you to file what is called a PIP — a pediatric investigation plan — and you have to file that early in the development of the drug. That is the stick. The carrot, which is mostly employed in the United States, is that you get six months of patent extension, which can be worth a lot of money for an important drug.
Dr. Ricketts: In terms of what you might get out of the national pharmaceutical strategy in relating specifically to the issue of research, one specific item comes up when we talk about pediatrics and rare disorders and even international and cross-border studies: how we choose to support networks. As you heard from the pediatricians, they are actually particularly brilliant at forming networks. I think the amount of volunteerism among pediatrics is very impressive. A collaborative atmosphere is very impressive, so you see an ideal opportunity. Infrastructure costs for maintaining networks can be extremely high, and the infrastructure costs have to cover items like informatics and maintaining trained staff so they are not hired for nine months on a clinical trial, let go for three months and then where have they gone? You have lost all of these essential people. Even ensuring that you have PhD candidates in the program and that you are bringing in new researchers — all the needs — and infrastructure, et cetera is something that I hope can be considered as part of the strategy and in your considerations as well.
Senator Seidman: That is wonderful because you have led me into the second part of my question, which had to do about infrastructure. I thank you, Dr. Ricketts, for that.
Dr. Hill, you talked about fragmentation in the clinical trial infrastructure in Canada. You said there is multiple everything; that is, multiple players, jurisdictions, standards, ethics boards, et cetera. We have just heard from Dr. Ricketts a louder emphasis on this fragmentation and the whole infrastructure issue.
When you talked about what the federal government can do, you talked about leadership and about incentives for collaboration and resources for coordination. Were you referring there to something that we could do about this infrastructure fragmentation?
Dr. Hill: Yes, exactly. If we approach it from how we can get to the most competitive position, we need to cut the time it takes to negotiate clinical trial contracts and to get the research ethics board approval to commence on a study. Time to recruitment of first patient is a crucial metric for sponsoring pharmaceutical companies. The smaller the company, and often the more innovative the drug, the more crucial it is that they get their patients through trials quickly because they are burning their investment money.
Some practical things we could do are move to a national reciprocated system of research ethics board approvals. If a multi-centre study has 12 centres across Canada, at the moment it has to go through 12 research ethics boards. At sub-sites, it then has to go through even more. If we were to have a reciprocated system, such that it went through the lead REB but then all of the other centres were able to accept the recommendations of that research ethics board, we would cut the time frame dramatically. For that to happen we have to have an accreditation system, we have to have some standards, and we have to have a common submission process for research ethics boards. That is, one that uses the same sort of forms so that we are able to combine that data through electronic registries, et cetera. We could cut the time and therefore increase our competitiveness enormously if we had these basic tools. For a relatively small amount of money invested by the federal government specifically at this project, we could get that in place. It is a limited term project; probably in three years, we could get the basic building blocks done.
The same applies to clinical trials contracts. At the moment there is a pilot standardized clinical trials contract which has been co-sponsored by CIHR, ACAHO and Rx&D. That is being trialled at a number of places, London being just one of them. Based on the findings of that pilot, we will then try to move this out as a national standard. Obviously each individual hospital may have some particular clauses that are relevant to that hospital, but we should be able to get the main framework of the contract standardized. Again, that can shave weeks off the time to recruitment of first patients.
Putting a small amount of money in place to enable us to create these common templates and registries would really give us a head start in achieving this sort of team Canada approach to clinical trials. Imagine having one coordinated registry of available patients for a particular type of trial on a national basis. That would be incredible and it would give us a global lead that no other country would be able to do. We are not talking about a huge amount of money here; we are talking about targeted investment.
Senator Cordy: I want you to know that this committee did recommend that we have a National Pharmaceuticals Strategy, so we certainly agree with you.
I am interested in clinical trials and, Dr. Ricketts, your comment about what is being compared to what, which was interesting; and that trials may provide only part of the information.
How much of that information is given out when a clinical trial takes place in terms of what is being compared to what? I think you recommended that researchers compare a new product to other products on the market. We hear often about patients for whom the drug that they have been using for years is suddenly no longer available because there is a new drug on the market. However, the new drug is too expensive for this patient, who may or may not have a medical plan. If it is a drug that is extremely expensive, your medical plan often has an upper limit.
How much information are we given — doctors particularly, but patients as well — in terms of what is being compared to what? Is the new drug really necessary? I think you talked about the effect that it would have, perhaps, on older people or on people with certain conditions. What is happening now in terms of that information? Is it available?
Dr. Ricketts: Actually, I almost feel that you answered the question by asking it. To that point, I am thinking that people who have more experience with the results of clinical trials outcomes maybe would use their time. Would one of you prefer to respond? I know we are short of time.
Dr. MacLeod: I would say that it is not a problem with access to the information by the research community. Nowadays we are at the tail end of a movement which has seen clinical trials all over the world being registered. An important clinical trial is almost certainly in the public domain even before it begins. The results of the trial will also be in the public domain, but it is clearly not accessible to patients or to primary care practitioners in the way that you would probably like. We need to improve the knowledge transfer capacity. The trials themselves are conducted in a pretty open and transparent way.
Senator Cordy: Sort of like political speak, is not it, or medical speak?
Dr. MacLeod: The experts know, but they do not necessarily communicate it to everyone else.
Senator Cordy: My next question was about the documentation. Dr. Ricketts, you said that it was not user friendly for doctors. If it is not user friendly for doctors or for medical people, it is sure not user friendly for someone who has the illness and who has a background in something totally not related to medicine. Is it changing so that documentation is becoming more user friendly or is that an area where we have to work on it, where the department of health has to make it more user friendly?
Millicent Toombs, Senior Policy Analyst, Health Policy and Research, Canadian Medical Association: I think there has been some improvement. The people in CMA's knowledge transfer department hear frequently from the practising physician as opposed to the research physician that they want the information in bullet form as brief and as user friendly as possible. Somewhere in the research community and the practise community, there is another process of distilling the information to ensure that the essential information is available. That includes not only the physician but to the patient as well.
There has been slow progress on that, but we hope to see more.
Senator Cordy: Many countries do ask that the clinical trials are registered. We have a global market and we have international pharmaceutical companies. If a clinical trial is held in the U.S. or the U.K. or China, or whatever country, what happens if we want to use that drug in Canada? Do we have to start at step one or can we start at step three?
Dr. MacLeod: It depends on the circumstances. In order for a drug to become licensed in Canada, there must be a sponsor; someone has to request the licensing. In the normal course of events, that is a private company. If a private company chooses to bring in a drug that has been developed in China, up to a point at least they could use the clinical trial evidence from China. It probably would not be up to North American standards or to European standards, but it might be. Certainly someone bringing in a drug from the United States would have no trouble at all.
Senator Cordy: The company could just bring it in and put it in pharmacies and it could be accessible?
Dr. MacLeod: No; they have to go through the regulatory process with Health Canada.
Senator Cordy: But not the clinical trials?
Dr. MacLeod: They do not have to repeat the clinical trials, no.
Senator Cordy: Dr. Hill, you talked about having to halt the downturn in clinical trial investment. We have heard before that clinical trials in Canada are significantly reduced from what they were a number of years ago. You talked about leadership and I assume you mean federal leadership —
Dr. Hill: That is right.
Senator Cordy: — from Health Canada.
You talked about leadership incentive and resources, and you talked about all three. I wonder if you could expand on that a little bit.
Dr. Hill: To add to the question previously from the senator, leadership is important because what we really need is a national coordinating centre to get these various pieces of work done to enable us to become an integrated clinical research community. That could be done through Health Canada or it could be done through the Canadian Institutes of Health Research, which already has a patient-orientated research strategy.
Again, it does not require a huge amount of resources to establish a national coordinating office but it does require a very visible leadership by the federal government to say that clinical trials are not just essential for bringing the best medicines to the Canadian population, but an important part of our economic sector.
That statement alone is valuable. Then taking the lead in helping to establish a coordinating apparatus would be a very important first move.
Senator Martin: I think you have answered some of the questions that I had, and I feel like there are so many other areas we could go into because they are all interconnected.
I will follow-up on something from your last response, Dr. Hill, when you talked about the national coordinating centre. I imagine there are challenges in looking at standardizing a system, such as creating common templates and registers. However, given the different sectors that would have to come to agreement, we also hear that one size does not fit all, so I would imagine that there are challenges there as well.
This is potentially off-topic, but it is what we have been discussing during the session. I am curious what the challenges would be, and has it been tried in the past, because this is not a new problem, but it is one that we face in Canada.
Dr. Hill: We already have a pilot template for a national clinical trials contract. If we can do it for that, we can do it for research ethics boards.
Individual provinces are also moving in the same direction. Alberta and Ontario are already making enormous progress, for instance, in figuring out how to get to a reciprocated research ethics board system. It may not be as complicated as stitching together 50 or 60 different health hospitals or regional health systems. We may be able to do it by simply bringing provinces and territories together.
However, again, we need the federal leadership there to really kick-start this, as well as a small amount of incentivizing money to give us the opportunity to create the systems.
Dr. Ricketts: To reinforce that, the Canadian HIV Trials Network is a classic example. It is over 20 years old. Clinical trial 001 was AZT for HIV/AIDS. It was initiated by the federal government. I have a lot of familiarity with it; it was my first job in the federal government. It was very successful, so I think you have every right to think it would be possible to do.
Dr. MacLeod: What you are asking about has been established because of the legislation in the United States and in Europe related to drugs for children. We now have national pediatric trials networks in the United States, the United Kingdom, France, Germany, the Netherlands — in several countries. They really are designed very much the way Dr. Hill has described it, only with a focus on pediatrics.
Therefore, you create a shared infrastructure, and then you have some common templates for ethics and other contractual elements. Then you hope that you can initiate a study with a minimum of background discussion.
Senator Martin: In terms of the subgroups that are either under-represented or perhaps not even tested due to various reasons in the clinical trials, are there specific challenges to specific subgroups, or are they similar challenges in terms of getting the clinical trials done for the subgroups? They are small groups, but are there specific challenges related to, say, the elderly? I would think that there are, but would you elaborate on whether there are some common challenges and some specific ones?
Dr. Walker: I want to remind the committee that when we talk about subgroups, children are only 19 per cent of our population, but they can hardly be considered as a subgroup because we were all children. We have to be children before we are adults. You could make exactly the same argument for the elderly, of course. Most of us will hopefully get there.
Having legislation and regulations that essentially remove them from the information stream for prescribers is inherently foolish and clearly inequitable. I think that is where the language in the editorial came from; that there is a fundamental lack of justice here. That is the first thing I would say.
It clearly depends on the subgroup. There are subgroups, if one wishes to call them that, where the issue is compounded, however, by the nature of the group and the fact that they respond differently to medications. That is the fundamental issue here — children are different and newborns are even different from children. The elderly are significantly different. There are other divides, as well. We have an Aboriginal population with shockingly poor health. There are certain situations where they may respond differently from middle-class Caucasian males who form the bulk of many clinical trials.
It depends on the particular subgroup.
I wanted to make the point that these subgroups are still part of us and, for large groups who are part of our total population, I think one just has to recognize the inequity of our present system. It is not a medical issue; I guess I am making a social advocacy point here.
Senator Martin: I am interested in looking at emerging technologies and how that is changing the nature of clinical trials. In Canada, are we keeping up with these changes? I heard you say that we are doing well in certain respects, but I am wondering how we are doing with the emerging technologies available.
Dr. MacLeod: There are many different technologies that may have an impact on clinical trials, certainly, but the one that is probably the most exciting nowadays is the chance to capitalize on what we have learned about the human genome, or the full genetic make-up of individuals. We probably are moving toward a new kind of clinical trial that will be much more tailored to individuals who have a particular genetic predisposition to respond to a therapy.
In that particular area — and the chair knows probably as much as I do about this — Canada is very well positioned. We have real strength through Genome Canada, through the provincial genomic organizations in Ontario, Quebec, and B.C. I think we can do very well in this coming era of personalized medicine. However, make no mistake: It will require a completely different approach to clinical trials.
Senator Callbeck: I want to ask about participants for clinical trials. We have heard that it is often difficult to get people for clinical trials. There has been concern expressed about incentives to recruit a specific number of people, and about payment to patients — that is becoming more common. In fact, I saw an ad in the paper last weekend.
I would like to get you to comment on what you are advocating in this whole area. Maybe Dr. Ricketts, we could start with you. Does the CMA have a policy regarding industry compensation in clinical trials?
Dr. Ricketts: I am not sure what you mean by a policy on industry compensation for clinical trials.
Senator Callbeck: I was reading an article in the Canadian Medical Association Journal, and it suggested that although numerous documents address the ethical dilemma of payment to participants, the restrictions are only guidelines. Do you have guidelines?
Dr. Ricketts: Definitely, yes.
Senator Callbeck: Do you think that there should be anything stronger than that?
Dr. Ricketts: I do not, no. I think that properly worded guidelines, that are well understood, have been extremely effective. For many situations, going to regulations or to law is not necessarily a good route. It can remove the flexibility that is essential to creativity in clinical trial design. The guidelines for physicians in interactions with the industry were developed over 20 years ago and it is an excellent document, a good approach to things. I do not think we need more than guidelines, no.
Dr. MacLeod: I would say it is very unusual in Canada for patients to be paid for participation in trials. Usually patients are eager to participate in trials because they get an innovative, and potentially better, treatment. There are payments usually in normal volunteer studies, some sorts of phase I studies, but rarely beyond that. As I said before, in pediatrics 75 per cent of the trials are investigator initiated. The investigators do not have any money to pay the patients to participate in their trial. We all agree with the principle that there should be no coercion, implied or otherwise. I do not think it is a big issue.
Guidelines are probably sufficient, and they are looked at very closely by the research ethics boards at individual institutions. No reputable institution in Canada would allow you to do a trial if they thought you were coercing patients by offering them money.
Dr. Hill: All of the ACAHO academic centres would not take on a clinical trial that paid the clinical trial subjects. What is acceptable is parking, if an individual has to travel a long distance to participate in a trial then travel costs could be reimbursed, but certainly not payment. It would be unheard of.
Dr. Ricketts: I think it would be very hard to imagine that a person was actually giving full, informed consent in a situation where they were being paid. Perhaps that is something important to consider. How can you give informed consent when you are being paid? It does not make sense to me.
Senator Callbeck: None of you are really advocating any changes in this area?
Dr. Hill: I do not think the system is broken. Quite honestly, I think it is working well at the moment in that respect.
The Chair: I think we should clarify what you have been saying here. There is a distinction between phase I/II and phase III and subsequent. You made the point that in seeking volunteers to simply test the safety of the drug in phase I, there may be an incentive package that is there but it is also highly proscribed and not the kind of thing where people will get wealthy by doing that particular issue. With that clarification, are you okay with that?
Dr. MacLeod: You are absolutely correct.
Senator Wallace: Thank you for your presentations. I am a new member to this committee, so all of this is new to me. One thing that strikes me when I hear the comments you have made is that in Canada, of all countries, you would think we would be leaders in creating a focused collaboration. We are leaders in medical technology and know-how and yet my sense is we are trailing as compared to what is happening in the U.S. and in Europe. I am wondering why that is. Why is it that we are not leading the pack?
Obviously I get the sense you feel there is a stronger regulatory regime required in Canada, and that is a role for the federal government to play, but what of the private sector associations, the CMA, the associations that regulate the pharmaceutical companies? What has their role been in this? Have they not taken as strong a lead as they should to create this collaboration?
When I say that, I think of a number of other professions, such as engineering or others, where the associations that regulate them take a strong lead in ensuring that there is a collaborative effort and common standards and not simply left to government to knit all of this together.
Is there anything unique about the Canadian experience? Are there other buttons that would have to be pushed in all of this to bring together this collaborative effort that go beyond looking to the federal government to take a lead and put it all together?
Dr. Hill: One problem is that international pharmaceutical companies tend not to spend a lot of R & D in Canada, as you know. Their most innovative pipelines are often not brought first to Canada. Typically there is a feeling that if the important phase I and II studies are done in the U.S., somehow that will help their regulatory situation. I would dispute that but, at the end of the day, Canadian subsidiaries to international companies do not tend to have a loud voice in their global headquarters.
There is a way to counter that, which is through helping Canadian subsidiaries, if you like, speak with one voice, and giving them the evidence that we do have a well-integrated, performing machine that can overcome the fact that we are a relatively small market down the road for future sales.
Other countries have realized how to market themselves. There are now clinical trials hospitals, literally hospitals that do nothing but clinical trials, in India, Pakistan, other emerging countries, which not only compete exceptionally well on cost compared to Canada, but also now provide exceptional quality as well. There was a time when we could say our cost structure is higher but you will get a level of quality in Canada that you will not get anywhere else in the world. I do not think that is true anymore. Other parts of the world have caught up.
The next obvious way to make ourselves competitive is to integrate more so that, in fact, our population becomes the potential test bed for international pharmaceutical companies. In that way, they are not simply looking at a centre in Toronto or Vancouver or whatever, they are actually looking at an integrated nation that can provide their needs for them.
Dr. Walker: Dr. Hill has spoken very eloquently to the role of industry. What I want to point out is that in many sectors Canadian investigators have not just sat back and waited for someone to come and subsidize them, they have created the collaborations. You have heard of the HIV/AIDS network, and you have heard of the pediatric networks.
Let me give you a front-line perspective. As an investigator who helped create the nitric oxide studies that I referenced in my comments, we created the Canadian inhaled nitric oxide study group. We were so successful in that group, which was about 10 members coast to coast across Canada, that the two nitric oxide trials in the States, which were struggling, ended up rolling themselves into our Canadian trial and we ended up producing the major work in this field.
It was not easy. It was not easy because, although we had done all that work to create the collaboration and it was that successful, it was not easy, for the exact reasons that Dr. Hill has referenced. We had to deal with not 10 research ethics boards but more like 20, because every hospital at that time had its own. In London then there would have been two or three and in Halifax, until recently, there were three.
These really rather small investments can make a huge difference in removing barriers where the investigating community has already done the work to create the collaboration, but we are still struggling because of this un-integrated infrastructure that gets in our way.
Dr. MacLeod: Just going back, you suggested that it was not simply about government supporting it. That is true, but you cannot do leading clinical research without infrastructure. The reality is that in Canada we lack the infrastructure and we lack the mechanism to obtain the infrastructure. In the United States, the National Institutes of Health in almost every major hospital in the U.S. supports a clinical research unit. They had a big competition in the last five years for what they call clinical and translational science awards, large annual grants to individual major academic centres to work on clinical research and the translation of that research.
We just do not have anything like that. What we have, we have cobbled together within our existing hospitals. We have some outstanding hospitals and we have some facilities, but we do not have any dedicated funding. We hoped this would come a few years ago with the Research Hospital Fund. Unfortunately, that is not what the money got used for.
Senator Wallace: Dr. MacLeod, just comparing our situation to clinical research facilities in the U.S., would most of those facilities be privately owned rather than publicly owned?
Dr. MacLeod: In the United States the major academic hospitals generally belong to the universities. It is not exactly clear whether they are private or public. They are more private than ours are. The provincial governments, of course, could equally step in and fund this but they see their remit as delivering services to patients, which is correct, and they do not necessarily see an investment in clinical research infrastructure as being a critical element. I think in the pediatric world the jurisdictions that have taken an interest in this have all received national funding for clinical trials infrastructure.
The Chair: I will pursue this a little bit because the senator asked a really specific question about the role of the professional associations in this. In actual fact, in all the organizations you are talking about, the people involved in the actual conduct and organization of clinical trials are physicians; within the professional society; I would guess they are all members of the CMA, or at least overwhelmingly members of the CMA. I think the question directly is, as the senator indicated, the engineering society, the chemical societies and so on often organize their members with regard to these very kinds of issues: approval standards, et cetera. I want to tie that in, because you have given two or three examples where you said groups came together, the HIV, the nitrous oxide, but as Dr. Walker pointed out, you still had to deal with a myriad of different approvals for the ethics boards and I would guess to some degree the contracts within each of them, which, if we come back to it, are two of the major barriers for the conduct of trials in Canada.
I want to broaden his question just a bit. I want to come back to why does CMA not have a role in helping its own members have more access to clinical trials by helping drive the standardization. Second, the federal government already has a number of agencies that deal with these matters; the CIHR, for example, is an agency funded by the federal government which has a direct role in this area.
I want to take the senator's question and come back and ask specifically, is there a role for the CMA in helping move this forward? Is there a role for the CIHR in helping move this forward, as examples?
Dr. Ricketts: The fact that the CMA is at this table is one of the ways we are trying to multiply the impact of what our members are actually asking to have happen. You see in front of you an investment from the organization and from the members to try to convince you that we need a national pharmaceutical strategy, we need more research, et cetera.
During 2009, H1N1, we realized there was insufficient clinical information for physicians about the use of antiviral agents, for example, in children and in pregnant women. Canadian Paediatric Society and the Society of Obstetricians and Gynaecologists stepped up to the bat and actually did produce many of these things that were needed. What did they need in order to do that? They had the expertise.
The Chair: Can I get you to focus purely on the question of standardized ethics board requirements and standardized contracts, not into these other areas?
Dr. Ricketts: What I would have to say to you is the CMA has neither the expertise nor the resources to undertake the work you are describing. That is it: We have neither the expertise nor the resources.
The Chair: What about the CIHR?
Dr. Ricketts: That is a completely different question.
The Chair: It is, but I am asking it.
Dr. Ricketts: I have seen CIHR undertake wonderful work in the area of pulling groups together, clinical trials; areas in imaging technology come to mind. CIHR is a completely different kettle of fish. It is federally funded. The point I would like to get across here is the need for something national. It does not have to be done in the federal government but you need to have a national centre that is willing to take on these things that has the resources and the expertise.
The Chair: Dr. Hill, you raised these things initially.
Dr. Hill: I wholeheartedly agree with you that CIHR should take a leadership role in those particular issues of harmonizing our research ethics board and moving along the project of a standardized clinical trials contract, not simply to facilitate parties coming together, but to actually lead the project. That will need the dedication of resources.
In defence of CIHR, this has been in their strategic plan for at least three years, with the Strategy for Patient-Oriented Research, or SPOR, as it is known. There are two wings to that. The first is expanding the creation of networks of the type that Dr. MacLeod and Dr. Walker have talked about. The second prong of the strategy is to create core support units. Once the core support units are there to enable and help the investigators do standardized research, pulling those together then into a national platform would be the next logical step. This has to be, I think, backed up by new resources.
Tina Saryeddine, Assistant Vice-President, Research and Policy Analysis, Association of Canadian Academic Healthcare Organizations: Just responding to that question and the points Dr. Hill raised about leadership, incentives and resources, and the role of the federal government, in the clinical trial action plan from the summit, which you have in your packages, what you are really seeing is the effort of the industry to come together. You have academic health care organizations, companies that do industry-led trials, and CIHR are all coming together to ask how can we organize, because it is incumbent on the field to organize itself. The recommendations you are seeing in the action plan, and there are nine summarized on one page in your package, would require, on top of that, the support and leadership to market this strategically and to bring the country together to create some excitement and movement because there are many operational things that have to be done.
The other piece I would add is that some of the issues around ethics reviews are not just physician-based, so we look at the role of organizations and the role of research ethics boards. A great example of the role of organizations is the Network of Networks, which is a grassroots organization of individuals involved in the organization of clinical trials who got together to try to standardize. They are referenced in the action plan because so much of their work has been grassroots; can we really pull them up to the surface and leverage their capacity nationally and formally?
The Chair: I will go back to some of the questions and answers that have come up. I want to go to Dr. MacLeod with regard to the issue of the involvement of youth in trials and the availability of the results. Through documents that have come to us, we have learned that in a number of cases, Canadian youth are involved in international clinical trials. Ultimately, as you pointed out, the drug may be approved, for example in the United States, but the producer does not make an effort to apply for licensing of the drug in Canada. While Canadian youth have been involved in the trial, the evidence from it does not do Canadian youth any good in terms of their health.
I do not want to lead you in this so I will stop right there.
Dr. MacLeod: I understand your point. There is a distinction again between licensing and labelling.
The Chair: I will come to that.
Dr. MacLeod: Most of the drugs that are studied in the pediatric age group, I assume you are using youth to mean 0 to 18 years, have been licensed already in the United States or Canada or other jurisdictions, for adult use. Licensing is not normally the issue. The question arises when you have approval for a new indication, let us say neonates.
The Chair: In the U.S.
Dr. MacLeod: In the U.S. The company is under no obligation. Even though they may have studied 100 children in Montreal and 100 in Toronto as part of their study, they are under no obligation to come to Health Canada to say they want to change the labelling so Canadians can legally use the product in their neonatal intensive care units. They are, however, probably using it anyway because they read the literature.
The Chair: We are going to get into that. On that particular point, Dr. Walker, I will add one bit. I will violate my own rule briefly because I want to get the answer now since it has come up. When you were referring to adding information on the label, I assume you were referring to both positive and negative indications.
Dr. Walker: Certainly, it should be, although you have already heard that there is publication bias that impacts clinical trials and so on. The answer is, yes.
The Chair: We will get into the depth of that in the next phase, but I wanted that part there.
Dr. Ricketts, you made very good points with regard to knowledge of the pharmacopeia in Canada and the value of a new drug versus existing drugs, et cetera. You did not say this specifically so I will ask you the question: Even though it might have been implied in your answer, would you like to see an emphasis on clinical trials in areas where there are drugs on the markets to deal with the indication? Would you like to see the clinical trial in those cases always include, as part of the trial group, patients who are given clearly identified doses of existing drugs, not just the historic gold standard of the new drug versus the placebo?
Dr. Ricketts: Ms. Toombs, do you want to answer this? I can detect a certain amount of interest on the part of my colleague to do this.
Ms. Toombs: The short answer is that if there is new information to be gained by conducting such a trial, yes. The more information that the practicing physician could know about the drug, the more helpful it would be. It would be the case if a researcher has acknowledged there is an information vacuum there.
The Chair: Surely one of the issues is that when drugs reach the limit of patent coverage, there is enormous incentive for the companies to have a modification of that drug tested as a new indicator. When tested against the placebo, it shows positive activity. The question to society is: If an approved drug nearing the end of its patent life is in there and has had positive benefit to society, is there not, from society's point of view, a clear value to know whether the new drug compares favourably or unfavourably with the existing drug?
Dr. Ricketts: Very definitely.
The Chair: You would see that as a possibility?
Dr. Ricketts: There is probably a clarification on the issue of new drug versus placebo and new drug versus existing drug.
Dr. MacLeod: All of us who prescribe drugs would favour comparative effectiveness data, which is what you are describing. How does the new drug compare with the current standard therapy? There are, however, many situations where is there is no standard therapy or the evidence is rather weak for the usual drug.
The Chair: I want to stick to the case because you are right: I do not want to get it clouded. I want to ask the case where there is an existing prescription drug.
Dr. MacLeod: There are existing prescription drugs for which the evidence is not very good, honestly.
The Chair: That may be another reason to do this.
Dr. MacLeod: We do not want you to come out and say: Thou shalt never do a placebo trial. That would not be a good outcome for Canada.
Dr. Hill: I would point out that a lot of investigator-led research is actually comparing a new drug with the gold standard drug so that research does occur. It does not tend to be sponsored by the drug companies. There is not a vacuum there, because it is being done.
The Chair: I will go back to Senator Seidman for additional questions.
Senator Seidman: You pointed out this package that you brought to us, and I just opened it to the action plan recommendation. I notice that number 5 is to develop a database of registries and consider a national patient recruitment strategy. In fact, Dr. Ricketts and Dr. Hill touched on that. Dr. Ricketts talked about the transition issue and a registry of clinical trials. That has been a subject that we have considered a lot here. There has been a good deal of confusion about the registry issue, who is responsible to create and maintain such a registry and what kind of information should be collected in this registry of clinical trials.
Dr. Hill, you went beyond that and said what an enormous innovation it would be and how fantastic for this country to have a patient registry of clinical trials. If we could combine those two things and if you could tell us the answers to these questions, that would be very good.
Dr. Hill: They are two separate goals. The idea of registering a trial is that health professionals will know the outcome of that study, positive or negative; and any reputable journal will not publish a clinical trial that has not been registered. The trouble is that many pharmaceutical companies do not actually see the need to publish and is not a major priority for them anyway. I am a proponent that all trials should be registered, including those that are going on in pharmaceutical companies.
The patient registry would be a way of enabling us to put together cohorts of patients rapidly, such that we could be competitive in getting the type of clinical trial we would like to do in Canada. It may be difficult to get the recruitment numbers together quickly from a small number of centres, but if we had a central registry for particular types of trials, perhaps initially; we could have a consensus on the suitable patients in Canada. Obviously, that data would have to be very securely handled. There are models of how that can be done in Canada and we could then put together large cohorts very quickly. That would be a real competitive advantage.
Senator Seidman: Who would be responsible for it?
Dr. Hill: I would suggest the CIHR would be the organizing body.
Senator Seidman: There is no question that a patient registry is totally different from the clinical trial registry. The clinical trial registry is has been a subject that has come up here often: the whole issue of transparency and why we in Canada are pretty much alone as far as the U.S. and Europe are concerned in actually having a clinical trial registry that provides the kind of fully transparent information that people feel is necessary. I think Dr. Ricketts talked about this.
Dr. Ricketts: It is simply to say it is essential that you have these. Several things can happen from it. Number one, if you publish the methods for your clinical trial far enough in advance, you may find out that other people are already undertaking the trial so you can avoid duplication. You can make opportunities for skilled researchers to comment on the methods you are using so you can be sure the outcomes will be valid in the long run. Sometimes the methods are wrong. It is tricky doing these things.
Finally, you will know that there actually was a clinical trial and if it had a negative result. You would be able to get the information about those negative results without having to be a top-notch expert attending the most arcane of meetings, the most unusual of sites and having a corridor conversation with someone. This is not appropriate. In the interest of transparency, we should know that all of these things are happening.
Beyond that, I do not really have a comment. We want to see the registry, but we have not talked internally about what that would actually look like.
Senator Seidman: You have not talked about what kind of data you would like to see collected in the registry and who would be responsible for maintaining and collecting the data?
Dr. Ricketts: Not as such. I feel very confident that there are others who know how to answer those questions.
Dr. MacLeod: I am not sure if you are implying that Canada is better or worse?
Senator Seidman: Our understanding is we are worse, but you are saying they are not.
Dr. MacLeod: I do not think so. There is an international registry. There are trials and there are trials. If we are talking about the upper layer of trials — important trials, internationally significant trials — they are almost universally registered now from Europe, North America, Japan and Australia. They are not so universally registered from China and India, but there is a developed world standard right now and WHO maintains a registry. It has a huge number of trials and Canada is one of the better performers in registering trials.
There is also a website called clinicaltrials.gov where you can go to see most major trials. What is missing is this large number of trials that are initiated by investigators or institutions. They have no intention of publishing them in the New England Journal of Medicine or the CMAJ so they do not have to register them.
Senator Seidman: Are they contract companies?
Dr. MacLeod: No, mostly individual practitioners working in hospitals who just have a question they want to answer. Quite often it is a project for a trainee — as part of their training — to conduct a trial in a neonatal intensive care unit or a pediatric emergency room. Those trials do not necessarily get registered, but the ones that are looking at new therapies, comparative therapies and placebo controlled comparisons are being registered in all developed countries now.
Senator Seidman: The information that is kept is, from your point of view, complete?
Dr. MacLeod: I could not speak to that. I think they want you to register the protocol. I am not sure how well people comply with that, but they certainly register the trial, the number of patients that are being entered and the kind of institution it is being done in.
Senator Seidman: Do they register trials if they stop or the dropout rate?
Dr. MacLeod: Yes, absolutely. Once they register they have to report on what happens.
Senator Seidman: There is standardized information that is collected?
Dr. MacLeod: There is. However, the main incentive is you have to do that if you want to publish in a high ranking journal. If you have not registered your trial, it will not be published. The private sector is actually more determined to do this than anyone else because they want their results to be published.
Senator Eggleton: I have a quick comment on that: It keeps coming up, though. There is something that is not coming out of all of this. Perhaps a lot of it is getting registered and maybe there is a fair bit of transparency, but every now and then we hear something that is not, and you even suggested some things that are not there. Some have advocated we make it mandatory, similar to what the Europeans or Americans do.
I want to ask you about comments that came from Health Canada in an earlier session that when it comes to clinical trials, there are few breakthrough drugs that come through very often. What you are usually getting are things that maybe have some value-added to them. They are a little bit better and the sponsor takes them into the process and thinks that it is of some value to have them. However, the value-added component of it does not seem to get evaluated by Health Canada.
I take it that is goes through the full clinical trials process, even if it is marginally better than something that already is on the market. Is there some room for some streamlining of these kinds of what you might call copycat drugs? Perhaps they are. What would you suggest in that? Should we be taking something different from the traditional clinical trials infrastructure for those?
Dr. MacLeod: If you knew in advance that it would turn out to be a copycat drug it would be easy to say, "Do not waste your time." The problem is that until you do the trial you do not know whether it is significantly better or worse than other available treatments, so it is hard to prejudge the situation, I would say.
Dr. Hill: ACAHO academic centres would select to spend their resources on innovations or perceived innovations that they consider could really make an impact, and not the minor enhancements. I think that is happening. Choosing the pediatric field — if you look at the trials being done in Canada at the moment, there is a once-a-day, long-acting insulin trial, and insulin pumps linked to automatic glucose sensors to see if this reduces the rate of diabetic complications. Should it be added at the time of diagnosis or a few months later? These are important questions that will have impacts on health for many future years. I would dispute that we are not selecting the high impact innovations to test.
Dr. MacLeod: At the meeting I was at in Winnipeg on standards for research in child health, there was a lot of discussion about what people nowadays are calling "waste" in clinical research. Again, with the benefit of hindsight, it is easy to see there are many studies and trials being done that were not worth doing. The problem is judging that in advance.
The Chair: To the frustration of their investors and the company who sponsored.
Dr. MacLeod: We were told in Winnipeg that there are 1.5 million publications a year on clinical issues around the world. That is a lot of publications and clearly we could be fine with many less, including fewer trials.
The Chair: Thank you very much. We have had a lot of questions about why Canada is not better organized in these areas. In fact, it came up here today in different areas early on. I thought I would give you an anecdotal experience that I had a number of years ago. There was a premier of Nova Scotia who was a medical doctor and was very interested in trying to get this kind of activity going in Atlantic Canada, and trying to pull together the Atlantic Canadian opportunity with regard to clinical trials. Dr. John Savage was the premier. He managed to get a group of hospitals and leading practitioners from across Atlantic Canada to come to Nova Scotia for a weekend meeting, and he asked me to chair.
My observation was that there was incredible friction among the different hospitals in Atlantic Canada at that time with regard to any possible cooperation on anything that might lead to another dollar coming in to someone's coffers. I did not see a lot more cooperation expressed among a number of the participants with regard to their enthusiasm for getting together, even though Dr. Savage had some advisers. Of course he was very knowledgeable in a lot of these areas and there are subsets of the population with particular genetic characteristics in Atlantic Canada for which there might have been particular opportunities with regard to clinical trials.
I have been encouraged by the evidence we are hearing here before us that we have moved a little bit forward, but in terms of organizing this balkanized country, even in an area of such obvious potential benefit to us, both economically and to the benefit of our citizens, we still have a ways to go.
Honourable senators, before I thank our witnesses on your behalf, there is a piece of information that I have to read into the record according to the Rules of the Senate, and so I will now so do.
Honourable senators, this morning Senator Merchant made a written declaration of private interest regarding the special study on prescription pharmaceuticals in Canada. In accordance with rule 32.1, the declaration shall be recorded in the minutes of proceedings of the committee.
That is the end of my required intervention according to the Rules of the Senate.
Having done that, I want to thank all of you. This has been a very good session. I appreciate your frankness and the depth of knowledge that you have brought to us. Even though you have a lot of similar interests, you have brought us a breadth of experience today. I hope you recognize from my colleagues their appreciation of your testimony today. On their behalf, I want to thank you for appearing before us today. I encourage you that if something occurs to you after leaving here, one of those unique examples, the kind of thing where you say, "I wish I thought of that particular example;" or if there are additional points that you want to get to us that we would benefit from, unless the evidence is before us we are not allowed to use it. I would appeal to you to think about that and to contact us through the clerk.
With that, I declare the meeting adjourned.
(The committee adjourned.)