THE STANDING SENATE COMMITTEE ON SOCIAL AFFAIRS, SCIENCE AND TECHNOLOGY
OTTAWA, Wednesday, October 17, 2012
The Standing Senate Committee on Social Affairs, Science and Technology met this day at 4:15 p.m. to study prescription pharmaceuticals in Canada (topic: post approval monitoring).
Senator Kelvin Kenneth Ogilvie (Chair) in the chair.
The Chair: Honourable senators, I call the meeting to order.
Welcome to this meeting of the Standing Senate Committee on Social Affairs, Science and Technology.
My name is Kelvin Ogilvie. I am chair of the committee and am a senator from Nova Scotia. I will ask my colleagues to introduce themselves, starting on my left.
Senator Eggleton: Art Eggleton, a senator from Toronto. I am deputy chair.
Senator Cordy: I am Jane Cordy, a senator from Nova Scotia. Welcome.
Senator Verner: I am Senator Verner, from Quebec.
Senator Enverga: Tobias Enverga, a senator from Toronto, Ontario.
Senator Seth: My name is Asha Seth. I am from Toronto, Ontario.
Senator Seidman: Judith Seidman, from Montreal, Quebec.
Senator Dyck: Lillian Dyck.
The Chair: I want to remind colleagues that we have two sessions today. The first one will end at 5:15 and the second one will end at 6:15.
I want to also remind us that we are dealing with post-approval monitoring in our studies on prescription pharmaceuticals. In this first panel, we have two witnesses. From the Canadian Institutes of Health Research is Dr. Alain Beaudet, President. From the Drug Safety and Effectiveness Network, we have Dr. Robert Peterson, who is Executive Director. Welcome to you both.
At this point, I will turn the meeting over to Dr. Beaudet. Please begin when ready.
Dr. Alain Beaudet, President, Canadian Institutes of Health Research: Thank you, Mr. Chair.
Honourable senators, thank you for providing me with the opportunity to appear before you today to discuss post-market surveillance of pharmaceutical products. I will be sharing my time, as you heard, with Dr. Bob Peterson, who is the Executive Director of the Drug Safety and Effectiveness Network of the Canadian Institutes of Health Research, or CIHR.
Senators, Canadians want to know that they get the right diagnosis, the right treatment and the right prescription to meet their health care needs. To ensure that they do, multiple research projects are undertaken every year across Canada for the evaluation of new drugs, as well as to determine how Canadians use and respond to already-approved drugs.
While we have had great success in the area of post-market surveillance, we need to acknowledge the fact that we could do more and that we have to do more.
As you know, drugs may sometimes have, differentially among patients, unpredictable and unintended side effects and adverse reactions. In addition to the harm these cause, these represent a significant financial burden on our health care system. To give you an example, a recent study by the U.S. Institute of Medicine estimated that $750 billion were wasted in the U.S. health care system. This includes $55 billion related to addressing unintended effects and adverse drug reactions.
In addition, there is the issue of the misuse of drugs. A concrete example is reflected in recent events related to Oxycontin. As many of you know, Oxycontin is a narcotic used as a pain reliever for the treatment of moderate to severe short-term and long-term pain, and produces an opiate-like effect similar to morphine. Media reports have shed light on how various communities in Canada are struggling with Oxycontin prescription practices and abuse issues.
CIHR is committed to supporting research that will not only determine drug efficacy and efficiency but that will also maximize patient and public safety by providing relevant, timely and accessible evidence of risk. This is why we have created the Drug Safety and Effectiveness Network, to which Dr. Peterson will speak momentarily.
This is why we have committed to better support through our Patient-oriented Research Strategy, comparative effectiveness research that evaluates not only new drugs and therapies but also assesses the effectiveness — and cost-effectiveness — of drugs that are currently in use. This is why we support work on the misuse of drugs and drug addiction; for instance, the work of Dr. Benedikt Fischer from Simon Fraser University, who is examining the associations between non-medical prescription opioid use and mental health and pain.
Our aim is not only to generate new knowledge, but also — by working closely with decision makers and representatives from key government sectors and affected professional fields and agencies — to ensure that research results are systematically disseminated and integrated into relevant areas of policy, programming and practice.
Throughout this process, CIHR is deeply committed to ensuring the ethical conduct of research involving humans. Indeed, to be eligible to receive and administer research funds from one of the three federal funding agencies, recipients must agree to comply with the exacting Tri-Council Policy Statement on Ethical Conduct for Research Involving Humans.
Mr. Chairman, CIHR is committed to collaborating with the provinces, our partners at universities and teaching hospitals, health professionals, and decision makers in the health system and industry. The objective is to develop a common vision and joint processes to both build knowledge and move it into improved patient care, while making the Canadian health-care system more efficient.
I believe that with initiatives such as the Drug Safety and Effectiveness Network, combined with rigorous safeguards like our Tri-Council Policy Statement and related research policies, we are doing just that.
I will now ask Dr. Peterson to speak to you on activities related to the DSEN.
Dr. Robert Peterson, Executive Director, Drug Safety and Effectiveness Network, Canadian Institutes of Health Research: Honourable senators, many of you will already be familiar with the mandate of CIHR's Drug Safety and Effectiveness Network, but please allow me to reiterate its key objectives. DSEN was announced in 2009 with the objective of providing evidence to support drug policy decisions in Canada at both the federal and provincial levels. Specifically, DSEN responds to queries from public drug plan managers, policy-makers, health technology assessors and regulators in order to increase evidence on the post-market safety and effectiveness of drugs in Canada.
DSEN fills important gaps that include the paucity of assessments on the comparative benefits and harms of drug products that are approved for the Canadian health care market. The CIHR/DSEN strategic initiative recognizes the limitations of the international regulatory environments that allow for these gaps to occur and provide the basis for the DSEN program.
Many drug clinical trials, while fulfilling regulatory requirements, are simply not able to be generalized to the Canadian population where they will be prescribed. In this regard, both benefits as well as harms require further evidence development in the real world. Risk is a concept that applies not only to the potential for harm of a new drug product, but also applies in regard to the potential that a new drug will not provide a benefit to a patient population that has never been evaluated in a pre-market clinical trial.
DSEN funds and coordinates the efforts of Canada's top research experts to provide authoritative responses to queries that originate with decision-makers, and it does this through a peer-reviewed and independent research program. This initiative, therefore, complements Health Canada's requirements for rigorous pre-market testing of new drugs, and we do so by studying how Canadians respond over time to already-approved drugs outside of the restrictions that are often imposed by randomized clinical trials and in the “real world” of Canadian health care.
I would like to stress that this process is entirely independent of the pharmaceutical industry. I also should point out that neither CIHR nor DSEN has regulatory responsibility or authority; rather, the new evidence that is developed within the DSEN is conveyed to the federal regulators in a timely fashion in order for decisions to be taken on their part.
DSEN further fulfills its mandate by supporting research to build the needed evidence for better decisions on the part of both federal and provincial drug plan managers. Often, CIHR/DSEN-supported research becomes an important input into pharmacoeconomic analyses that contribute to the assessment of a marketed drug product's value proposition, thereby leading to payment decisions on the part of federal and provincial drug plans.
DSEN currently funds seven research teams in three broad collaborating centres. The network of national and international researchers encompasses more than 150 researchers distributed geographically across Canada. They form the research capacity upon which DSEN relies.
Current funding commitments for DSEN research projects, guided by a national steering committee that advises on priorities, are currently approximately $25 million.
Since its official announcement just three years ago, the Drug Safety and Effectiveness Network has made good progress. All organizational components are in place and operational; research is well under way on prioritized topics; strong ties have been established with Health Canada and new ones are being forged with provincial and territorial decision makers.
DSEN has established relationships with its counterparts both in the United States and Europe, and we are exploring opportunities to further international expansion in order to increase the impact of DSEN-supported studies.
Honourable senators, DSEN evaluates both the potential for benefit as well as the potential for harm, and thus goes well beyond the more focused concept of pharmacovigilance that you have heard so much about from others. The CIHR/DSEN program provides the basis for a balanced assessment of the comparative value of a marketed drug, not only in terms of the risks associated with its use in the real world but also in producing evidence in determining economic value — a factor that is so essential to a sustainable health care system.
Senator Eggleton: Thank you, gentlemen. I am trying to sort out what you do versus what the regulator, Health Canada, is doing. In the post-approval process Health Canada has this MedEffect Canada, and it has the Canada Vigilance Program within MedEffect. You have this DSEN and I believe you have a sub-entity within that as well, called the Canadian Network for Observational Drug Effect Studies. This collection of entities is confusing as to how they all might work together in the post-approval process.
I understand Health Canada is the regulator and you are not, but you are obviously trying to make drugs safer for people and have more efficacies in the drugs. You are both monitoring. Do you use the same adverse reaction report information? What do you do differently and how do you blend it?
Dr. Peterson: I will try to be succinct, Senator Eggleton. The regulator, as you point out, has authority in respect of drugs that are marketed in Canada as to whether they come on to the market, whether they stay on the market and whether there would be any amendment to the licence they would have in order to be on the Canadian market.
We are not engaged in operating an adverse drug reaction reporting system. The federal regulator does that. Oftentimes, they are based upon the information that comes to them in that environment and are able to identify signals. These are issues that cause them concern but for which, because this is a voluntary reporting system and it is often anecdotal in response to a given patient, it is very difficult and very problematic for the regulator to produce evidence-based decisions on adverse report events.
What they will do, therefore, is turn to a number of different sources internationally, but in Canada specifically it is to the Drug Safety and Effectiveness Network, with a specific question that has arisen from that signal. They will ask us whether we can identify, based on the use of a product in Canada over a specified time period, evidence of that signal that would be derived from the observational studies that you have pointed out. CNODES is one of the seven teams we are funding now. We have six different teams that rely on different methodologies that we can recruit in order to be able to address these questions. They do not recruit randomized clinical trials, however. We are not engaged in that at this point in time.
We will, however, focus our attention on the experience of the drug that has occurred within the provinces in Canada in a research designed question, if it in fact is a query of the linked administrative health records. We will take that question that has arisen from the regulators. We will with interface the researchers with the regulators in order to refine that question, so that it can be addressed in a research environment.
We then allow for that question to be translated into an application that is peer-reviewed in a standard fashion by CIHR, so that the authority behind the research that occurs in response to these questions is garnered through the CIHR process.
If it is an observational study, we would then develop a centrally defined question for the distributed database. We will define a centrally created statistical query package. It then gets sent out to the provinces and to the other holders of those data. The query is addressed to that. The results come back. They are seen by the provinces before they are pooled centrally. We then take them all together at this point in time. We are looking at data from eight provinces in Canada, plus a large database in the United Kingdom, plus several managed care databases from the United States. We will query them independently and then bring all that information back together and form the basis for rather an authoritative answer to that signal that occurred within the domain of the regulator.
Senator Eggleton: Does all of this work within what the regulator, Health Canada, is attempting to find out? If they get adverse reaction reports, do they come to you at that point in time and say, “Okay, we have this; can you do further research”? How does it work? Do you work on their request?
Dr. Peterson: We do.
Senator Eggleton: Do you report back to them later?
Dr. Peterson: That is exactly correct. We have formed the basis for this funding of this program to be highly responsive to decision makers. The federal regulator often is asking questions in the realm and domain of drug safety. We are seeing questions regarding safety as well as comparative effectiveness coming from provincial sources. However, this is not independent researcher-initiated grant projects. This is entirely in response to questions that have been posed by the regulator about what is on their mind, depending upon the method that we can recruit. In some instances there is a large body of literature that we can address. We use some rather sophisticated statistical methods in order to be able to bring the individual studies together, comparing drugs directly and comparing drugs indirectly, in order to answer these questions.
There is a different timeline associated with the different methods we use; therefore we are responsive to the regulator in terms of their timelines. If they need a fast answer, it will be developed probably within six months.
Senator Eaton: Picking up on where Senator Eggleton left off, Dr. Peterson, you talked about the experience of the drug and queries. In your queries, do you take into account the person's psychotic state or psychological state, their weight, age, and certain characteristics? I would imagine that a drug might work differently on different people. We are not talking about misuse; we are just talking about age, weight and what other drugs a patient may be taking at the time. Are these all part of your queries?
Dr. Peterson: Essentially, yes. That is part of this interface between the source of the query, the decision maker and the researcher. In order to actually define that question in research terms, we do exactly what you have suggested. We will come up with the definition of the type of patient that we are proposing to ask this question on. There may be age ranges that will create categories, and weight ranges if that is appropriate for the question that is being asked, yes. However, they are translated into terms that allow for that question to be asked against the data.
We do have some limitations in the data in terms of health outcomes, for example. Not all of the databases that we have access to have the results of the laboratory investigation recorded in that database. We may know that an individual was tested for an important factor as they were receiving the drug, but we may not know the answer if we simply use the observational studies on the databases. As a consequence of that, we may be able to provide a preliminary answer and then they will we will recruit a second method in order to be able to take it to the next step.
Senator Eaton: From my own personal experience this summer, I have a herniated disk and I was put on a drug called Lyrica. My doctor gave it to me because I asked to be put on it. I heard about it from a neighbour. No one else seemed to be able to give me a drug. After four or five days, I was falling down. I will renew my prescription because I am going away. I said to the pharmacist — and this question is leading somewhere — I think I will cut back on the dosage. She said, “No. How long have you been on it?” She then went on to explain, first, the side effects and, second, that it was a neurotransmitter and had to build up in my body and I had to take it for three weeks for it to have a real effect.
In your research do you have good relationships with the pharmacists? It seems to me that a pharmacist is the person at the forefront. They are giving out the drugs and they can determine, by what drug other someone is taking, what their age is, if it is appropriate far more than a doctor. Do you ever use them in your queries and your research? These are your front-line people, even more than doctors in some respects.
Dr. Peterson: You are very astute in observing the fact that many of the adverse drug reactions are filed by pharmacists at that level of front-line interaction with the patients, and the fact that you conveyed that information to them perhaps in preference to your physician because your opportunity was greater.
Senator Eaton: She is accessible. You walk in and see her.
Dr. Peterson: That translates into the level of activity that pharmacists have in adverse drug reaction reporting. That is probably closer to the front end of signal generation than where we are at this point in time.
I can tell you that in order to answer one of the questions that we have now, looking at the effects and the comparative benefits and harms of smoking cessation therapies has been to let a grant that looks at community-based pharmacy programs that are collecting exactly the type of information that you are looking at. We found we could not get it in any other fashion and are therefore using that as a means to recruit that.
The Chair: Dr. Beaudet, do you want to add something?
Dr. Beaudet: First, your question about the various levels of receptivity to drugs depending on age, sex and genetic build-up is absolutely fundamental. This is why we are investing so much money right now into what is called personalized medicine.
One of the objectives of personalized medicine is to be able to determine, through the genetic build-up of the patient, first, whether they will respond to the drug or not. If they do not have a receptor for a drug, what is the point of giving this patient this drug? They will have only the side effects.
They will also, through the same mechanisms, allow us to determine whether certain patients would be more prone to have certain side effects, in which case we would know not to give the drug.
The advantage in the future, as we see it, of personalized medicine is that we will be able to target treatments to those patients who will respond with minimal side effects and we will not be treating patients that either will not respond or would be prone to have side effects. This is really important in the design of drugs and the design of trials also, because it means that when we put people in a clinical trial, we will be able to regroup them into groups of patients that will be more likely to respond to the treatment, thus being able to do it on not quite as large a sample of patients. We would then avoid subjecting patients who would not respond to the drug to the side effects.
The Chair: We are getting back into clinical trials and we want to stick to the post-market surveillance here. I will move to Senator Cordy and will put you on the second round. We will run out of time.
I will say to the witnesses that at the point where it is clear that we will run out of time I will get the remaining questions on the record and ask you to be so kind as to follow up with us with a written response. The clerk will provide you with a detailed summary of the question that was put.
Senator Cordy: I want to know how this whole process works.
The approval has been done and now we want to do post-approval monitoring. Do you just research every drug that has been approved, or how do you find out which drugs you will monitor and which ones you will not monitor? Do you work with pharmaceutical companies? If there is a concern as a result of the research that you do, do you then just turn that over to CIHR or do you have a process that you follow? What exactly can you do if you have a concern?
Dr. Beaudet: He is CIHR, by the way.
Senator Cordy: Yes, but it is an arm of that. Thank you. That is a good point to raise.
Dr. Peterson: Thank you for the opportunity to clarify a number of points.
First, the DSEN program does not monitor drugs, per se. There is no comprehensive nature associated with that. That is the domain of the regulator who has a responsibility, in order to track safety through its pharmacovigilance programs and other requirements of the manufacturers, for every drug that has been granted market authorization in Canada.
What we will do is listen to the questions and the issues that are currently on their minds and focus down on those specifically. This is not a comprehensive look at all drugs that are on the market. We are responding to questions that have been generated.
I do not wish to suggest that this is a small number of drugs. Presently, we have more than 50 active research programs that respond to questions that have arisen, either at the federal or at the provincial decision-makers' level. Often they are picked up on as a safety issue for a specific drug. More frequently in our research environment we are looking at the comparative harms that could occur between a class of drugs, whether it is Lyrica or another of the drugs that might be used in that environment, and look at their comparative benefits and harms, and attempting to do so simultaneously.
There probably is no safe drug that is a prescription medicine on the Canadian or other market at this point in time. The reason why there must be both a prescriber and a dispenser between the patient and the drug is associated with these issues of safety and the harms that can occur.
Picking up on what Dr. Beaudet has pointed out, not all drugs are going to provide a benefit to everyone. In fact, we see a large range of the numbers of patients that needed to be treated with a drug in order to derive one health outcome as a consequence of that drug. Under the pharmacogenomic, the personalized medicine program, we would like the number needed to treat with a drug to be one: with a drug given to a single patient we can rely upon the fact that there will be a benefit. That is the outcome of what our personalized medicines program will hopefully provide to us.
We are seeing drugs today that are approved on the market where the number needed to treat in order to get the health outcome may be more than 50. That means that 49 times out of 50 you may not derive the benefit of that drug. That will not be seen necessarily in the pre-market trials. You will not be able to define who those patients are. To the extent that we are able to go into health records and to look at the experience of that drug within our general population, we are able to now begin to focus in a bit more on that measure.
Senator Cordy: When you were speaking earlier you talked about the limitations of the international regulatory environment. I assume that you work with international agencies.
Dr. Peterson: Yes. We have a working relationship with the international agencies. You will find that, just as we have been funded to be highly responsive to the Canadian post-market surveillance both to the federal regulator and to the Canadian provinces, our counterparts in other countries are also responsible to their own either national or local authorities. Therefore, we are able to share information. We certainly are able to share access to information as it becomes available to us.
Senator Cordy: We heard concerns from some witnesses who appeared that if a drug is under review they have no information about it. We look at international information — I will use a drug name, as Senator Eaton did — and Tysabri was fast-tracked. We know that it causes a fatal brain infection. As of September of this year there were 285 cases of PML worldwide and 62 people have died, yet it is given frequently to MS patients.
It is under review and MS patients are wondering if they should or should not take it. Sometimes you look at a medication and look at the side effects and think I am not sure if I really want to take it. That is a choice you have to make, you look at the risk/benefits.
If it has been fast-tracked you sort of think it must be okay. What information can you get if a drug is under review? If you hear that a drug is under review and you are nervous about it, do you keep taking it? That certainly would add to the risk side of the balance scale.
Dr. Peterson: Yes. Once again, to distinguish, “under review by the federal regulator” is outside of the domain we are talking about today. The business transacted between the federal regulator and the drug manufacturer in determining what the label will be, what the warnings will be, whether it continues on the market, and whether or not it is suspended, is outside of the area in which we work. If the regulator has a question regarding the occurrence of PML from that particular drug, the application of the virus responsible for that, then we would be responsive to that.
In looking at the experience in Canada, as you have pointed out, it is rather rare. Therefore, in our population base we will not have a lot of cases. By the way, that happens to be a known risk of the drug. Without wishing to overstep my position at CIHR, the regulator would wish to ensure that the product label, the information available to prescribers and to patients who had received that, is as up-to-date as possible. However, should a question be asked to DSEN, then we will bring this through our prioritization process without speaking publicly about that. At the time that we launch the actual research on that, we will, on our website, provide information to the extent that this is the question that we are being asked and that we are addressing under a research grant. This is the timeline; this is the methodology that we will be using. When the results are made available for that, there is an obligation author that to be published.
Senator Seidman: I want to ask you about the Drug Safety and Effectiveness Network framework that was the April 2012 version. In this, you clearly — and you have referred to it in your presentation — identified parties who are eligible to submit a DSEN query.
I would like to ask you about that. You say here that federal regulator FPT drug plans, organizations mandated to support FPT decision-making with respect to drugs are all parties who are eligible to submit a DSEN query, which is the primary signal right at the outset. However, you say “parties who are not eligible to submit directly a DSEN query at the moment” — and I will ask you to explain that — “are voluntary health organizations, for-profit enterprises, individual practitioners, community pharmacies and the public,” meaning patients and consumer organizations.
Those are the groups who are not eligible to present a query at the moment. Could you speak to that?
Dr. Peterson: Yes. I am disappointed that we are not able to take queries from any broad spectre of those individuals who need to have evidence in order to make decisions. We have, for both economic reasons and capacity restraints, at this point in time, at the initiation of this program, targeted relatively high-level decision makers, recognizing that at some point in time I will undoubtedly be sitting adjacent to the Auditor General of Canada explaining why $32 million-worth of value was derived to the Canadian public from this program. As a consequence, we have wanted to be certain that in the early days we are looking at issues that are very much on the mind of high level decision makers.
Having said that, the intake into Health Canada’s adverse drug reaction program comes from the public as well. There is a portal that allows for that to happen. Pharmacies are influential through the Canadian Pharmaceutical Association. In a previous study that you had done, I sat here next to their executive director. We are interfacing with them, so that there is a strong desire not to lose sight of any question that has sufficient importance and relevance to a spectre of the population that would allow for us to answer that. We are stretched at this point in time, given the number of questions that are coming to us.
We have developed a national steering committee that involves ADM level representation from the federal government, from Health Canada, as well as ADM level representation from at least three of the provinces in Canada — ADMs who are responsible for their pharmacare programs, as well as a patient advocate, and others, to allow us to prioritize. Their job is not easy because we are receiving a relatively large number of questions and we are somewhat capacity constrained at this point in time.
Having said that, I am elated to respond to the number of questions that we have been able to at this point in time and I think that, with good attention to efficiencies, we will be able to broaden that, but not at this point in time. I would think it will be sometime before we are able to broaden it out that far. What we do have, however, is clear guidance documents.
There is a template for what the query must look like. It involves issues such as not only what is the question and what is the relevance of the question but it also challenges the decision makers. It asks them: What will you do with the results that we will be able to provide with you in order to be able to target this to. Exactly how much influence will this have in a given area? There is a guidance document that accompanies that. That is publicly available. For example, if you had a question, while we would not be able to take that directly at this point in time, we have a nice working relationship with the drug plan in Quebec at this point in time in order to ensure that questions that come up through a more local environment are able to see the light of day.
Senator Seidman: That is good because you answered the second part of my question which was exactly that: What kind of working relationship do you have with the regional provincial governments and the regulators.
Senator Dyck: Thank you for your presentations. My question is related to pharmacoeconomics. Dr. Beaudet, in your presentation you talked about the fact that in the U.S. it is estimated that $750 billion were wasted in the Health Canada system and 55 of those were related to unintended side effects and at-risk drug reactions. Do we have the corresponding data for Canada?
Dr. Beaudet: Not to my knowledge.
Senator Dyck: Would that be part of the research that DSEN would undertake?
Dr. Beaudet: No.
Dr. Peterson: No. That would live more in the policy environment at that level. We are much more focused on a drug product or a class of products: What are their benefits, their harms, and how can you compare them? They become inputs into the types of decisions that would be followed up on that.
I live close to this environment and I am not aware of authoritative information regarding this in Canada. Do keep in mind the fact that adverse reactions will accompany benefits. Harms and benefits are present for virtually all drugs, so that while there is a cost associated with that, you have to be careful of just focusing on safety exclusively or just on the harms because undoubtedly there have been benefits that have been derived as well that are not necessarily reported at the same time.
Senator Dyck: Right. In your presentation you said that the DSEN research can become an input into pharmacoeconomic analyses, which contribute to the assessment of a marketed drugs products value proposition, thereby leading to payment decisions. Could you explain what that means?
Dr. Peterson: From the provincial perspective, a large number of questions that we have received have been of a comparative nature. The basis of those questions are for drug plan managers who exist within a fixed budget in order to make a decision as to whether or not they should put on to their provincial formulary for public payment a new drug. What is the value of that drug in comparison to those that exist on the market and that are currently being paid for?
A good example of that are the new oral anticoagulants that have been developed in order to be able to overcome a number of the challenges in using Coumadin or Warfarin as an anticoagulant. These drugs do cost more than the old established Warfarin. Questions asked of us are to look at three new oral anticoagulants that have come on to the market and provide information on a comparative fashion as to what are the relative benefits and harms of that class of drugs versus the existing drug on the market and costs, perhaps, 25 cents a day in order to prescribe and perhaps $1.50 a day when you look at the monitoring and things as compared to the products that are coming in at a higher price.
We will address, in this comparative fashion, all those issues. Keep in mind that the pharmacoeconomic analysis looks at the issues associated with the harms that are created: What are the adverse events, what are the costs associated with those, what are the benefits, and how can you now make a decision based upon what the actual value of that product is on the Canadian market?
This, by the way, has become the second hurdle for pharmaceutical manufacturers to bring their product effectively to any market in the established world. The regulatory hurdle is the first one. You get licence or authority to market your product. The second hurdle is to develop this value proposition with the comparative benefits that allow for you to convince a payer that it is worthwhile paying for.
The Chair: This is interesting, but we are getting away from the monitoring issue, which is the focus of the study.
Dr. Beaudet, does your intervention deal with monitoring?
Dr. Beaudet: Just to say that we are not looking at monitoring exclusively through DSEN. We focus on DSEN enormously. As Dr. Peterson says, DSEN does not fund clinical trials. However, we do fund clinical trials, and some of these trials are comparative effectiveness research, doing exactly what Dr. Peterson referred to, looking at your blockbuster that costs a fortune, to the good old drug that costs 5 cents a pill, and looking at the advantages and inconvenience through a rigorously controlled trial between the two drugs.
Senator Dyck: If I could make a comment, they are saying that risk is also if there is not a benefit to the drug, so that you would pick that up in your monitoring. That becomes part of the risk analysis.
The Chair: That becomes another analysis of the issue, and it is a very important one, Senator Dyck; you are absolutely right. We have that now on the record. However, in order to get there, we have to do the monitoring. That is the aspect I want to pick up on now, and then I will get the other questions on the record.
I want to come back to the issue of monitoring and getting the information that actually allows a regulator to make changes in the label or whatever, the approval of a drug. I appreciate that you do not have the authority to make that, and so the question I will put to you is as follows: Does the following sound like a good idea? If so, what body should be the one that deals with it?
I will preface it a bit more by noting, Dr. Peterson, as you indicated, that once a drug is approved, it gets into the general population, and therefore it gets into the subsets of the population, which were not identified in the original clinical trial, and that observation is enormously important; women, children, pregnant women, for example.
Another comment you made that concerned me a little bit, and perhaps you can clarify in your answer, was when you said that pharmacists are part of it. However, I did not get the idea that their observations go to someplace directly that collects that information and leads to the regulator having data that would be useful for them.
I appreciate that you both referred to personalized medicine, but that only occurs after you have sufficient information to know what the subsets are and which drug applies there. Unless you have done a specific clinical trial on a subset, the larger amount of evidence can come from the population, once a drug is approved, if we get the information back as to how those patients broadly respond to it.
From what we have heard and read, the issue comes down to the fact that clearly it is not an efficient process to get the reaction of individual patients (a) identified relative to it perhaps being associated with the drug and (b) to get that information back somewhere where it can be collected and used.
My question to you is which is the best organization to lead to the collection of this data, and would the following be useful ways of getting that information to whatever that body is: that pharmacists have to report directly to that body with what they observe from their experience, which we have heard in the H1N1 pandemic can be a good experience, very useful, if that information is made available to someone who is in a decision-making capability. There was this week a story about social media being used by patients, and one situation where patients can use social media, get that information back to a central area, which will collect it and sort out, obviously, the information that is useful.
My questions are the following: What bodies should collect information from, say, pharmacists, from social media? Should there be a requirement on doctors who prescribe medication to patients who are not included in the original trial — children, pregnant women, et cetera — to pay attention to the behaviour of their patients more than they normally would when they are prescribing it off-label, as they will? Because that would provide an enormously important body of data to come back quickly to whatever body you are going to suggest should collect it, in order to make decisions with regard to how the drug label perhaps should be changed.
There is not time for you to answer all of that. I will leave those questions on the table for you. I want to get the questions on the record from a couple more of my colleagues, and we will be out of time. I will get the next questions on the record, but I would ask you to please follow up on that.
Senator Enverga: You mentioned that you were providing evidence to support drug policy decisions. I am wondering if you could give us some examples in your research and how it affected the decisions of the federal and provincial government.
The Chair: If you would give a brief response and then follow up in writing, if it is appropriate.
Dr. Peterson: I would be happy to. It is relative early days, so the number of examples that take it all the way through to the end outcome of what the decision maker did with the research is relatively limited, but I will provide for you what I can.
In the realm of health policy, we are really addressing issues associated with whether a decision would be taken to list a new drug on a drug plan formulary for a public payment of that drug, and what would be the basis for that decision or lack of decision. We do not make the decision. We provide an evidence base that allows for a decision maker to objectively look at the benefits, the harms and what the economic value is if they were to do that.
At the level of the federal regulator, usually when questions are asked of us, it is because they are not black and white. The easy questions they will deal with directly. These are ones that exist in somewhat of an aura of uncertainty.
The Chair: I asked you to give a quick summary, and then you will follow up with this nice detail.
I will get the questions on the record, starting with Senator Eggleton.
Senator Eggleton: Two of my questions are quick and the witnesses might be able to answer them, but the third will require a written response.
The Chair: Please put your questions on the record, because there are other senators.
Senator Eggleton: The government introduced Bill C-51 back in 2008, but then it died on the Order Paper at the end of the Thirty-ninth Parliament, in September. Is what you are doing the replacement of that bill?
The Chair: If there is a quick yes or no; otherwise, go on to your second question.
Dr. Peterson: No.
Senator Eggleton: So there still might be a bill.
Dr. Peterson: Bill C-51 —
The Chair: Continue. I want the questions on the record. I want all our questions to be answered. Your next question, please.
Senator Eggleton: The next question they may want to answer quickly.
It is important to have public confidence in these processes, and there is public funding involved here. You are separate from the regulators and from the government. One of the criticisms we have heard here is the pushing of the pharmaceutical industry, and is the pharmaceutical industry not on the governing board of the CIHR?
Dr. Beaudet: I would not say there is the pharmaceutical industry on the board of CIHR. There is a representative of the pharmaceutical sector on our board, as there is a representative of the biotech sector, as there is a representative of the health providers, as there is a representative of —
The Chair: You can provide us with a list of your board.
Gentlemen, we want the questions on the record. All the questions and answers are important, but we will not get answers if the questions do not get asked.
Senator Eggleton: I have one more. How will you measure the success of your operation, the value added into the system for this and how it will benefit the public? How will this be communicated to the public, either directly or through Parliament?
Senator Cordy: We have spoken a lot about drugs with adverse effects, but do you also do research on prescription practices? It brings to mind what one of you mentioned. Oxycontin was an example. I have heard stories where people have gotten prescriptions for 30 Oxycontin tablets at a time, which seems to me to be a large number of Oxycontin tablets to be giving to someone at one time.
The Chair: Take that into the issue of monitoring the numbers of prescriptions per patients, per whatever, as appropriate.
Dr. Beaudet: It is more an issue of practice than research.
The Chair: It is, but the issue of just your views.
Senator Cordy: We deal with prescription practices. We have spoken today about adverse effects. What else do you look at, and would prescription practices be part of that?
Dr. Peterson: We will provide an answer.
Senator Eaton: Is there a special category for post-market evaluation of people with a known history of mental health problems?
Dr. Peterson: I am happy to provide you with examples of what we are doing in that area.
The Chair: Thank you all very much. With some encouragement, we got all the questions on the record. It is important to us to have detailed responses. I am appreciative of the fact that you have agreed to follow up and provide those answers to us. The clerk will make sure the questions come to you, hopefully in a manner that allows you to respond to us in a very helpful way.
I will invite the next witnesses to present in the order I have them on my list here, since we did not get a discussion among you to arm wrestle out who would decide to go first.
Mr. Young, you will go first, please.
Terence Young, Member of Parliament for Oakville and founder of Drug Safety Canada: I thank you for inviting me here today. This subject is close to my heart. I have worked on these issues for 12 years, long before I got here. I think you will be interested in a number of things I have to say.
I will be reading the first two pages, and then I will jump to the numbered items just to read the titles. I will stick to about seven minutes, which is your agenda.
The post-market monitoring of prescription drugs in Canada essentially relies on the major pharmaceutical companies marketing the drugs, known as big pharma, to monitor their own safety. These companies are treated by society at large with the utmost deference and respect because of their carefully crafted corporate images as great corporate citizens, creating jobs and investing their massive revenues in a struggle to save lives. These claims and their actions go largely unchallenged.
The reality is much different. The big pharma companies are, in fact, the most sophisticated marketing machines in history, selling billions of dollars in products that often do not work to tens of millions of people who do not need them, leading to millions of hospitalizations in North America every year and the fourth leading cause of death in North America.
The companies that call themselves research-based companies in truth spend more on administration and marketing than they do on R&D. This includes billions of dollars every year in gifts to our doctors, the gatekeepers of medicine, to influence their prescription-buying decisions, a practice that is illegal in virtually every other business in the civilized world.
Ironically, with regard to the post-market monitoring of prescription drugs, what is thought to be the most important way we protect patients who take prescription drugs and make sure they are taking them only when they are safe has been completely perverted by big pharma and instead does the exact opposite, making sure doctors and patients have no way to know when a drug is safe and when it is not. This is because post-market monitoring has been left primarily in the hands of the big pharma companies themselves, whose primary goal is to market blockbuster drugs — lifestyle drugs and those that treat chronic conditions that sell over a billion dollars a year — and keep them on the market even as a growing number of injuries and deaths are reported related to their use. This is how Merck's Vioxx was allowed to kill 55,000 to 65,000 patients due to heart attacks.
How did we get so far off track? In the late 1990s, under former Minister of Health Alan Rock, Health Canada was directed to close their testing labs, relying on drug companies to test their own drugs and partner with the pharmaceutical industry. How have patients fared since that time? Since 1997, 27 drugs that the big pharma companies told us were safe for our families have been yanked off the market in Canada for killing and injuring patients. Hundreds more have had to have their labels changed repeatedly, ostensibly to reduce the serious adverse drug reactions that injured and killed patients, while their sales continued to grow.
What is the scope of the problem? All drugs cause adverse reactions — not some, all. It is only a matter of how serious and frequent the adverse reactions are. All drugs are poisons. The only difference between a drug and a poison is dosage. Many drugs have what is called a narrow therapeutic index, which means the difference between the dosage that can help the patient and the dosage that can hurt the patient is small.
Prescription drugs are the fourth leading cause of death in North America today, 70 per cent of which are preventable. Since Vanessa Young died on March 19, 2000, the situation has not improved; it has become worse.
Since all drugs cause adverse reactions, every decision to prescribe a drug should be based on the answer to one question: Will the benefits of this drug outweigh the potential risks for me?
The big pharma companies do everything they can to make sure doctors and patients have no way to answer that question properly, or even recognize its importance. They do this by making sure doctors hear only positive things about their drugs and by covering up the true number and severity of adverse drug reactions, which are both corrupt practices.
How does post-approval monitoring in Canada fail patients and help big pharma companies cover up adverse reactions? I will just do the top lines.
Safety warnings are designed to fail. Drug labels are rarely read by doctors, and everyone involved knows this. They are written to ensure doctors have no way of knowing if a drug is safe enough. They are written by lawyers, for lawyers. If they end up in court, they can go to page 19 and say, “You see, Your Honour? Here it is, right here. There is the safety warning.” The labels are up to 60 pages long. The print is only eight points. They are full of language that even doctors sometimes cannot understand. It is called label clutter.
Health Canada-approved “Dear Doctor” letters are also rarely read by doctors. In fact, many doctors get up to 100 pages a day faxed to them. At the end, after seeing many patients in their office, at 7:00 in the evening they do not go to their machine and read all these faxes. The problem is this: Doctors believe that if a drug is dangerous, Health Canada would order it off the market. The reality is Health Canada's position is that the doctors must judge for themselves.
Health Canada has no effective process for public notice when drugs are given new contraindications or pulled off the market.
Patient information leaflets, the ones you get in a drug store, create a false sense of security and, as a result, are dangerous for patients. They talk about the common side effects, like headache or diarrhea, but not the most important ones, the rare and dangerous ones.
Adverse drug reaction reporting has been a facade. Adverse drug reactions reported to Health Canada by doctors and health care professionals are about 1 per cent of the true number. That means that if you go to Health Canada's website and look at the number for any drug, you can usually multiply it by a hundred to get the true safety picture.
Health Canada officials do not analyze adverse drug reaction reports or do anything useful with them.
Recently, The Toronto Star did a series on ADHD drugs. This is a report from David Bruser, the author of the article:
While the reports accumulate, the Canadian regulator says on its website it does not have the expertise to analyze the information for trends and is relying on the U.S. Food and Drug Administration . . . .
Adverse drug reactions are reported by the big pharma companies only after months and months of analysis. That delays regulatory action and delays early warnings for drugs that are harming patients. Inevitably, the drug company reports blame the patient in some way. The patient must have taken too much. The patient must have mixed it with some other drug.
Incredibly, big pharma companies often only report the deaths and injuries that occur in the jurisdiction. They might report the deaths in Canada and the injuries, but they do not report the ones happening in a hundred other countries. This gives regulators a skewed safety picture.
Gag orders are placed on researchers and also patients who are offered out-of-court settlements for their injuries or loss of life. That covers up the harm drugs cause and keeps blockbusters on the market.
Corrupt practices by big pharma companies go unchallenged. They never ever admit their drug harmed or hurt a patient, even after they paid billions of dollars in damages. That is because they buy insurance against their drug crashing off the market, and if they ever admit their drug caused harm, their insurance is no good. They might have a settlement, like what Merck did with Vioxx and then could not collect their insurance.
We are in dire need of transparency. Independent researchers are unable to properly study the safety record of drugs because Health Canada will not release what their big pharma partners claim is proprietary competitive information from clinical trials. Information on adverse drug reactions that patients have in clinical trials is not commercial information. It is life-saving information that is often hidden from researchers and the public.
The Chair: Thank you.
From the Psychiatric Medication Awareness Group, we will now hear from Ms. Currie.
Janet Currie, Representative, Psychiatric Medication Awareness Group: Thank you and I appreciate the invitation. I am with the Psychiatric Medication Awareness Group. I coordinate the group. This small, consumer-led, voluntary and independent organization provides information to consumers about psychiatric drugs and their risks and effectiveness. We do a lot of public education as well. We get about 12,000 hits on our website every month. As far as I know, we are the only organization in Canada that is an independent source of information.
We deal with psychiatric drugs. I want to make that point because psychiatric drugs, which include sleeping pills, sedatives, antidepressants, antipsychotics, are the second-most prescribed group of drugs in Canada and in most jurisdictions, and have been so for many years. They cover all kinds of issues, mainly emotional problems that people have, lifestyle types of issues, so many thousands, millions of Canadians are taking them, and primarily women. Two thirds of psychiatric drugs are prescribed to women, so women correspondingly suffer more from post-approval adverse drug reactions.
I would like to talk a bit about the importance of post-approval monitoring, which I will call pharmacovigilance. First, so many more people are exposed to prescription drugs today than were previously, and psychiatric drugs are a very good example. Approximately 20 to 25 per cent of women in the 50 age range are taking antidepressants. Add on to that maybe sleeping pills, benzodiazepines, perhaps antipsychotics and you may have some populations where 40 to 60 per cent of the population are taking a psychiatric medication. The scope of adverse drug reactions is much broader.
We know that adverse drug reactions constitute one of the most serious public health problems we have. There are at least 10,000 deaths in Canada due to adverse drug reactions and 150,000 injuries. Many of these costs are hidden: the contribution of psychiatric drugs to automobile accidents, to falls and hip fractures, which cost British Columbia, for example, $75 million a year, the costs in disability payments, emergency visits, hospitalizations, diagnostic tests. One time I was tapering about seven to ten women off of psychiatric drugs. Every single one of them was on a disability pension of some type, and all of those women were professionals. Some of them never were able to go back to work, although all withdrew successfully.
Adverse drug reactions surface over months, years, decades or generations. This is why post-approval monitoring is so important. We need large databases. We need to analyze them carefully because sometimes rare effects only surface in large databases, but we could have effects that affect the children of our children, and that has happened in some cases.
Finally, there are two examples where post-approval monitoring is so important. One is where drugs are fast-tracked. Drugs that are fast-tracked are not completely tested at the pre-approval stage. Companies are obliged to do safety tests after the drug has gone to market. The compliance with this demand is often very poor so that we have an issue where the regulator must insist that the company follow through on the safety studies and often it does not. Health Canada does not insist on compliance.
The other issue is off-label prescribing. Few Canadians would realize that a doctor can prescribe any drug he or she wishes for any reason at all. It does not have to be tested or approved. Off-label prescribing is very common, particularly with psychiatric drugs. Over 50 per cent of antipsychotics are prescribed off-label with no testing at all.
What are our current problems? In my view, the current problem is Health Canada has an inherent conflict of interest. It is mandated to deal with drug safety; on the other hand, it is expected to fast-track drug approval. In answer to one of your questions, when a drug is fast-tracked, can we assume it is safer? No, we cannot, because it has not been tested adequately.
Health Canada as an agency, as a ministry, has an inherent conflict of interest, which is why we feel there needs to be an independent safety agency that supports safety of prescription drugs and is very focused on post-approval monitoring.
We are concerned about the imbalance of resources that go towards drug safety and protection of the public as opposed to drug approval and fast-track approval. We are concerned about the conflict of interest that exists at every level of Health Canada and the over-influence of the pharmaceutical industry in decision making.
We are very concerned about the passive system of collecting adverse drug reactions that now exists. Senator Eaton described a serious drug reaction. Few Canadians know that we should be reporting those reactions to Health Canada. We have a pathetic adverse drug reaction database of only 13,000 public reports a year.
As well as creating an independent safety agency, we should focus on buoying up, supporting, building capacity around producing better adverse drug reaction reports. We should develop creative methods of gathering adverse drug reactions. For example, in the U.K., every new drug is marked with an upside down triangle, which notifies the pharmacist, the doctor and the patient that adverse drug reactions should be reported. We should also use methods such as sampling institutions and specific sets of doctors to get much more in-depth adverse drug reaction reports. We should engage the public in understanding that all drugs are toxic, as Mr. Young said. It depends on the dose, the purpose and the need. Canadians need to elevate their level of drug literacy and become more critical and responsible consumers. We feel that an independent safety agency would carry out this role in a much better way.
The Chair: Thank you very much. I will now turn to my colleagues, starting with Senator Eggleton.
Senator Eggleton: I do not know where to start. What a contrast from what we have heard prior to this.
Let me explore, Ms. Currie, your suggestion of an independent safety agency. You are saying that Health Canada cannot do this; they do not have a culture of safety; they do not go through the procedure properly.
Are you suggesting that an independent agency replace their involvement in both clinical trials and post approval monitoring?
Ms. Currie: I am just dealing with post-approval monitoring at this time. I do not want to write off all of Health Canada. The Marketed Health Products Directorate has a safety mandate but it is under resourced and has limited capacity in comparison to the post approval component of Health Canada. There is an inherent conflict of interest. It would be like the Transportation Safety Board overseeing safety in the aviation industry while marketing for WestJet and Air Canada at the same time. It is an inherent conflict of interest. Separating the two functions would be a very good start in terms of refocusing on protecting the health of Canadians.
Senator Eggleton: In previous submissions, there has been suggestion that we are not getting as much of the clinical trial process. We talked about the fast-track process. Do you think that creates a culture of wanting to have more of these clinical trials, which also can affect the post-approval process and to be able to move them along so that these things can get to market? Is that where you see a conflict in terms of safety?
Ms. Currie: There is a conflict. Progressive licensing, which is the intent of Health Canada, can be a fast-track approval process. Drugs are currently approved on a fast-track process called “notice of compliance with conditions.” The preapproval stage of those drugs is telescoped and part of the clinical trial phase is dropped off with the supposed guarantee that the industry will conduct safety studies after the drug is in the general population; but compliance is very poor.
There are problems at the clinical trial stage, as you probably know, because drugs are not fully tested until they get into the general population. They are tested for approval, but they are not tested fully for adverse drug reactions until they are in the general population, which is the real world where we all have different health problems, may be taking other drugs, and are different ages and genders. In one sense, the Canadian population is one big clinical trial because that is where the real adverse drug reactions will occur.
Senator Eggleton: Can you name other places that have this independent safety board, I believe you called it?
Ms. Currie: That is a very good question. Certainly, other countries have independent safety agencies, but they are usually under the rubric of other ministries. I cannot completely answer that.
Senator Eggleton: Maybe you can find out if there are any and let us know.
Ms. Currie: Yes.
Senator Eggleton: I have a question for Mr. Young, who has authored a book on the subject. I know of his passion on this subject and the personal tragedy that he has experienced.
Mr. Young, you have given a damning indictment of this process and Health Canada. One of the things that you have at the top on practices is that they spend over $3 billion a year giving our doctors free samples. I understood that had been curtailed.
Mr. Young: There are rumours that a lot of things are curtailed in the pharmaceutical industry. As far as I know, free samples are still going around. I know of a young man who was given an SSRI antidepressant free sample last year with no safety warning or prescription, and he did not get a chance to talk to a pharmacist. He went out and hanged himself from a tree in a public park. The coroner's office will not even give the family the forensic evidence so they can check how much of the drug was in his body. As far as I know, free samples are still happening. It is a dangerous practice that promotes the most expensive drugs and only new drugs, which present new adverse drug reactions. What Ms. Currie is saying is perfectly right: When you get a new drug, it is phase 4 of testing. Does your doctor ever say that they are testing the drug and ask if you would like to try it? They do not tell you; there is no disclosure.
In the fast-track drug approval process, under pressure from the pharmaceutical industry, Health Canada agreed a few years back to take it from 300 days down to 180 days to say yes or no to a drug approval. On October 8, Dr. Joel Lexchin, a leading Canadian expert, had gone through all the drugs that needed to be taken off the market and those that needed new safety warnings added to their labels because they were harming patients. He looked at the fast-track drugs, which are primarily for cancer and serious illnesses, versus the regular population of drugs. It was found that 35 per cent of the fast-tracked drugs had to be either taken off the market or have new safety warnings issued.
I spoke before the House of Commons Standing Committee on Health in 2005 and said, “Do not go down this road.” If you are in an airplane, you do not want someone standing over the air traffic controller saying, “Hurry up; get those planes in.” That is not safe practice. They should be taking the time needed to ensure that the drug is safe, not hurrying to rush the drug through because the drug company is in a hurry to make money and they have only 20 years on their drug patents.
Senator Eggleton: We heard in the previous panel from CIHR about the Drug Safety and Effectiveness Network. How does that fit into this? How does that help or not help?
Ms. Currie: I think it is a good move. Most post-approval safety studies have been done by industry. Any attempt to have a more independent research agency carry on more of those studies is a good idea. There are some caveats, as long as industry does not decide to be too direct in determining what research takes place and as long as there is some freedom on the part of the network. Certainly, any movement toward more independent research on safety issues post approval is a good move.
Mr. Young: It is a really good step in the right direction. I wish there was more of it, but it is reactionary. They are doing it sporadically because resources are limited. The government put $30 million into this. When I first heard about it, I was very pleased. However, as both gentlemen here previously said: They are not the regulator; they can provide results and get answers. Did you notice he said that a fast answer to them is six months? A good answer on a complete study might be two years. In the meantime, there could be a body count with a risky drug.
Ms. Currie: “Signals” is a term used when Health Canada looks at its databases on adverse reactions, which are supplied primarily by industry and consumer reports. The job of Health Canada is to determine when a signal indicates something serious and when it should be acted upon. I was surprised to hear DSEN say that Health Canada is giving them data to interpret signals. I have been in consultation with Health Canada over many years around many issues. We have never been able to get an answer from Health Canada on how they interpret signals, what process they use, when an alert goes on in their heads, or when they decide to issue an advisory or a warning on MedEffect. I was surprised to hear that they are asking DSEN to do it because that will mean a delay, which in turn will mean that more people will be harmed by an adverse drug reaction in the interim.
Senator Cordy: The questions that I had planned originally have gone out the window after hearing your presentations. It is a good thing. We heard from Dr. Alain Beaudet earlier who said that while they have had great success in the area of post-market surveillance, they need to acknowledge that they can do more. I would suggest to you that there has not been success in the area of post-market surveillance.
Mr. Young, I read your book a few years ago. It should be recommended reading for everyone on the committee. It certainly was excellent. Thank you very much for doing that and for the work that both of you are doing.
You talked about the marketing of the pharmaceutical companies. We all know that there are golf trips and dinners and that kind of thing. Should we have a sunshine law here in Canada, as they have in the U.S. so that people are aware of the fact that perhaps a pharmaceutical company took the doctor and his family on a golf trip the previous week. Should we have that or something like that?
Mr. Young: We need more than that. We should ban all gifts to doctors. Why should doctors be taking gifts from drug representatives? It starts with mouse pads, coffee cups, lunch and a golf game. If you are a thought leader who influences the decisions of other doctors or decides what drugs get into the hospitals, it might be a trip to Egypt or the Bahamas. The problem is that doctors are so naive. They are wonderful people; and I love them. However, they think that they are not being influenced, which is a drug rep's dream. They say, “Well, that would never influence my clinical judgement.” What about their colleagues? They say, “Well, it could influence theirs.” The reps shower them with gifts. They spend $3 billion a year on free samples and $4 billion on gifts, and they create powerful debts of gratitude. They should just ban them all.
In the States, they have the sunshine laws. The doctors on the advisory councils of the FDA that get the drugs approved and that make the pharmaceutical companies billions of dollars say, “Yes, I have done work for the company.” It is an open secret, and they go ahead and do it anyway. They should not be on those boards if they are taking money from the pharmaceutical companies. Shining a light is helpful, but why not just ban it and say, “No, your loyalty is to your patient. You are sworn to do no harm. You have no right taking any money from a third party.” The only way a doctor can pay a debt to a drug rep is by putting their drugs into your blood stream. If it is a brand new drug, you have no idea what the outcome is going to be.
Senator Cordy: If the gifts did not work, they would not continue to do it.
Mr. Young: That is right.
Ms. Currie: Relating to that — and probably, in my mind, a more important issue — is that doctors receive almost 100 per cent of the information that they have about drugs from drug company representatives called detailers. There are some pilot projects under way in Canada using objective academic detailers to educate doctors, in their offices, about prescription drugs. I think those pilot projects are very worthy. When you consider that there are not only debts of gratitude but also that the primary information that doctors are getting is from drug company representatives, that is a concern to me.
Mr. Young: It has been proven in studies that they tell them all the good things about their drug, which are often exaggerated. They do not tell them the bad stuff. They skip over that. As part of post-market surveillance, doctors, to maintain their licenses, have to attend continuing medical education meetings. In Canada, 70 per cent of those are funded by drug companies. They do not send their sales guy to the front; they have a doctor on their payroll who is a thought leader. He goes up and does it for them. It is all highly credible. He tells them all the good stuff, and the bad stuff just sort of gets sloughed off. It is funny; the language of drug safety is euphemisms.
The Chair: We are looking at post-approval monitoring. You have made the point that this is an issue to deal with; I do not think that we need anything additional.
Senator Cordy: I would like to talk about the fast-tracked drugs that you both mentioned earlier because I think that Canadians think that when a drug is fast-tracked there is not much wrong with it. I gave the example to the previous panel about Tysabri. Genelia would fall under into same category as it has been fast-tracked. It really makes me nervous when you say that we should multiply the numbers given by 100 because 62 people have died from Tysabri. There have also been 285 cases worldwide of brain infection because of a disease. To multiply that by 100 is a lot.
I would like to know about the process for the fast-tracked drugs because 35 per cent have been taken off the market. There have been new warnings for doctors, but doctors are not necessarily reading the new warnings. At the end of the day, you are right; I doubt that they go to their computers to read them. You have given documentation, in your research, of the fact that people tend not to look at all of the pamphlets that are inside when you get your prescription. What should we do about fast-tracking, monitoring and getting the information?
Ms. Currie: I see a doctor writing a prescription as almost requiring a consent process between the patient and the doctor. I think the patient should be aware that a drug was fast-tracked and that there were aspects of the clinical trial phase that were skipped. You asked a question in the previous session about how one would find out what is going on between Health Canada and the manufacturer in terms of that drug and whether there are any safety issues. The answer is that you cannot. Health Canada will not release that information and neither will the drug companies, so we do not know what the record of that drug is.
If Health Canada fast-tracks a drug, it is with the agreement that certain safety studies will be done by the manufacturer. There is only 50 per cent compliance with those safety studies. There needs to be much more compliance. If that manufacturer has been given an easier road, then there are obligations that that manufacturer must live up to and is not being asked to live up to right now.
Mr. Young: It is a much broader issue. It is how patients get information and how they do not. The pharmacist could be more part of the solution if they were more empowered. Doctors sometimes get angry at pharmacists if they start to question prescriptions.
To give you an example, I said that people do not read drug labels. They are too long, and the print is too small. I have two drug labels here, one from the U.S. and one from Canada, for the exact same drug — Oxycontin, apparently the most addictive drug on the planet right now. If you look at the Canadian warning and go through it — and I have done this — you will not get anything on the safety of this drug until page 10, which lists warnings that it must be swallowed whole not chewed or dissolved or anything, and then it talks about what could be fatal respiratory depression. Then you look at the U.S. warning. Right on the front page is what is called a black box warning. Two hundred of the riskiest drugs in the United States have a black box warning. The very first thing that you read is that it is similar to morphine and can be used in a manner similar to other opioid anagenis. It gives you the warning right on the front page. This is a corrupt practice. They have been doing this for years. The same companies, with the same drugs, give Americans a black box warning and a handout in the pharmacy with the same information. Canadians get no black box warning and no handout or only one that talks about diarrhea and headaches. Purdue paid $600 million, out of court, for illegally marketing Oxycontin. You think that illegal marketing does not sound that serious, but when they market drugs illegally, a lot of people die.
Senator Seth: It was interesting to hear all that I have just heard. My question to you — and I am not asking because I am a doctor — is: Why has it taken so long to realize that these pharmaceutical representatives come to the doctors' office and give such wrong information? Why have we been sleeping for so long? So much has happened for many years, and we did not realize. Everything was happening in the United States, and Canada let it go.
I never got that kind of gift or offer. That was interesting to find out about.
With regard to Oxycontin, as you know, according to new regulations, we cannot write to any patient. We have to write our CPSO number so that it can be tracked, and we have to record fully, on the prescription pad, that this is the patient and that their health number is this to make the record. That is already happening. What have we been doing so far? Why did we not realize that this was incorrect information given to us?
Those are all my questions.
Mr. Young: Shall I go ahead, senator?
The Chair: Please, one of you start; we are running out of time.
Ms. Currie: I honestly think it is because the industry carries a huge amount of weight in Health Canada. Consumer representatives who are independent of industry do not really carry the same weight as the pharmaceutical companies that are involved in every process and every decision-making process. Consumers actually have been sounding the alarm for many years. I myself have been involved in this issue for over 12 years. I think the capacity of consumer groups to bring this to the attention of the Canadian public is limited. Most of our groups are voluntary; we do not accept money from pharmaceutical companies, so we do not get any funding at all. Health Canada has just eliminated all of the funding for the Centres of Excellence for Women's Health across Canada at the end of this fiscal year. These research centres were often on the front line in discussing health and safety in relation to prescription drugs, and they will be gone. I think a few hearty consumers have been trying to drumbeat the message, and I think that it is a tough road.
Mr. Young: I agree with everything that Ms. Currie has said so far.
The fourth leading cause of death; how could that be? People think that I am exaggerating. They think this poor guy lost his daughter; now he lost his mind.
Let me tell you some of the ways they cover up the deaths. The first is the Coroner's Act in Ontario. When someone dies, a jury or a coroner has to answer the cause of death. If it is a drug death with a prescription drug used as prescribed — not an accident — it is a natural death under law in Ontario. We tried to get them to change it. That is a natural death in Ontario. That is one of the ways they cover it up.
Adverse drug reactions are not reported, generally. I have never met a doctor outside of the doctors I work with in drug safety who has ever even reported one. The regulators have had great issues; they need more power.
There is no death registry in Canada. A lot of countries have a death registry where you can research these things. Statistics Canada has no category for prescription drug deaths, so they are not even close to where they should be. Also, the drug companies influence everywhere; they put their money everywhere. They have unlimited money to create good will, such as in universities — every institution we rely on for creative thought.
The special interest groups — disease groups — are sometimes even created and financed by them. They are parent companies. So they have a special interest group out there talking about needing this drug approved. They are all paid for. They give them what is called “unrestricted educational grants,” otherwise known as free money. Their influence is absolutely everywhere. They talk about saving lives and they create this image with their money.
I visited Bart Stupak, a 20-year congressman in Washington, a year and a half ago. His son died three months after my Vanessa did, from Accutane, which is an acne drug that causes suicide and birth defects. Before they can take it, young women have to sign that they will use two forms of birth control. His son died from suicide.
He fought 10 years in court and could not prove that his son should have had a proper warning. I said, “Look, I have been working on this for 10 years. You have been working on this for 10 years in Congress. Why have we not been able to get the message through?” He said, “People do not want to believe it. It is human nature. It is too hard to believe that they could walk into their doctor's office and be given something that could hurt or kill them. It is hard for people to believe.”
Senator Ataullahjan: How do we educate consumers about the risks of the drugs that they take? I did not know that if you had an adverse reaction to a drug, you should be reporting it, and I consider myself to be a reasonably well-educated person who realizes what is happening. How do we get the word out?
Ms. Currie: We need independent agencies that are free from pharma influence to do that. Someone asked a question about using social media. Yes, we could do that.
We need to elevate the literacy of Canadians with regard to the drugs they take. We need to help them become more critical consumers. For example, most Canadians do not realize that when they go to get a prescription drug and they read the insert on the package — like you did when you took your drug — that this is created by the drug store from their own software. There is no regulation in Canada that requires manufacturers to list all the adverse drug reactions that are possible for that drug. Therefore, the inserts are very minimal. If you were to get the same drug in Europe, you would be given a complete list of adverse drug reactions, or a more complete list, because that is the law.
Consumers do not know that many drugs are not fully tested. You are absolutely right; we have to engage with and educate the public. I see an independent safety agency with outreach offices. Marketed Health Products Directorate has seven regional offices that do a good job, although they are under-resourced and understaffed. Those kinds of systems could do a public outreach strategy, and independent consumer groups could also do an outreach strategy.
Drug safety is, in a sense, in its infancy. Let us compare deaths from aviation accidents. I put a chart in my submission comparing deaths from aviation accidents, which also is a safety-dependent industry. Last year, there were under 100 deaths. From prescription drugs? Over 10,000. Why are we not more concerned? This is the most serious public health problem we have.
I agree with you that education of and engagement with the public has to be a priority. We have to do it outside of the pharmaceutical companies. We need organizations and agencies with credibility to do it. We need to use methods that reach young people, so social media is the answer.
Mr. Young: I want to make one point that I have not made before and it is really important. The drug company representatives will say, “We are concerned about adverse drug reactions.” They put on this big front, because they want to talk about when someone did take the wrong drug, which is a serious problem, or when someone takes too much of a drug, which is also a serious problem. The deaths that I and Ms. Currie are talking about are deaths caused by prescription drugs taken the right way, as prescribed. There are over 10,000 or more a year in Canada.
Senator, I have had a private member’s motion on the Order Paper for a year and half. Due to the election and stuff, it has not come up. It will come up next year. It is to create an independent drug agency similar to the Canadian Transportation Safety Board and Canadian Nuclear Commission. It would be responsible for keeping Canadians safe when using prescription and over-the-counter drugs, and for reducing injuries and deaths.
I have worked for 12 years to get plainly-worded information leaflets into a patient's hands in the pharmacy. It would list the real risks of a drug. It would list the contraindications. The most important word in drug safety is “contraindication,” which means you never mix these two drugs; you never mix this drug, for example, with grapefruit juice. There are 50 drugs that if you take them with grapefruit juice could stop your heart. Who knew?
It would also have plain language and would list a whole range of things related to the safety of the drug. That would be a great start. They are doing that in the States, but I found out recently that even that good black box warning I told you about is done only 17 per cent of the time in the States, so they have a problem, too.
Senator Seth: We are all —
The Chair: We will not get into that.
Mr. Young: Empowering patients is what we are working on. An independent agency could look at all these issues and coordinate with the provinces. We have no federal authority over doctors. Doctors can prescribe any drug, at any time, for any patient, for any condition. It is the Wild West. It is provincial authority, so we have to work with provinces. An independent drug agency could take the time to do that, I think.
The Chair: Those are excellent suggestions for us.
Senator Seidman: You both started to touch on my questions, so I will put it straightforwardly out there. I would like to know what changes you would propose to adverse drug reaction reporting. For example, if you had two or three clear, crisp proposals to make to change our reporting system now, what would they be?
Also, going back to the consumer question that Ms. Currie started to answer, what suggestions do you have — maybe two or three clear, crisp suggestions — on how to get more objective and impartial information to Canadian consumers?
Ms. Currie: In terms of expanding adverse drug reaction reporting, we have a pitiful number of drug reactions that are reported. Consumer reports are very useful. In fact, sometimes consumers have discovered very common reactions, for example, to psychiatric drugs through reporting systems like that.
First, I would build capacity at the regional offices. Staff have the skills. They should be implementing much more of a public education outreach strategy.
Health Canada should be promoting the reporting of adverse drug reactions so that consumers and health professionals do it. I would like to see some piloting of mandatory health provider reporting — physician reporting — in certain sectors. I do not think “across the board,” mandatory reporting for physicians will work, but I think if certain groups of doctors were, for a short period of time, mandated to report — or from certain institutions — I think that could work.
I would like to see all new drugs labelled as they are in the U.K., with an upside down triangle, with education at the pharmacy saying, “This is a new drug. If you notice anything of concern, here is the process of reporting.”
Reporting should be made much simpler. I have encouraged many people to report and it is quite difficult, even though staff are receptive. Elderly people find it hard to report and they are the ones who have the most drug reactions because they take the most drugs.
Therefore, I would like to see the process made simpler; I would like to see a very simple online reporting system for physicians and for patients; and I have one other suggestion. I would like to see what they call a signal method. For example, you would choose certain institutions across Canada — pediatric hospitals, general hospitals, geriatric hospitals and clinics — and you would for a period of two to three years have a champion at each of these settings who would support, encourage and kind of push people to make reports and you would give enough support to those institutions so that they would make those reports. Again, a smaller sample, but if you put the effort into it, you can get good reports from that kind of system. That has been used by Health Canada for the assessment of medical products, so they have some experience with it. I think, again, that is a good method to use, a much more targeted and creative approach, and Health Canada or a new regulatory agency should be encouraged to use these approaches.
Mr. Young: I totally agree. I think that adverse drug reaction has to be compulsory. This is information that saves lives. I call this a conspiracy of silence. Doctors do not report adverse drug reactions because they are in a hurry, they have a room full of patients, they feel bad because they injured a patient, they are not sure, they do not want to be sued, or a whole range of reasons, but they should be asked to do it by law.
How long does it take to log on to a website and fill out a one-page form that says “suspected adverse drug reaction”? You do not put the name of the patient, as there is no private information, but you put their age, et cetera. Get that in as an early warning system to our regulator. For instance, a drug like Vioxx, which killed 55,000 to 65,000 people over four years, if they started getting those reports in the first few months, they could have taken the drug off the market sooner.
Dr. David Healy has written 17 books. He is a leading expert on psychiatry and SSRI antidepressants. He is building a worldwide database where consumers, ordinary patients, will be able to put information on drugs they are taking into this database. You will get some helpful information very quickly because you have it in all 100 countries where the pharmaceutical companies are selling the drug.
This also has to include dentists. In my community and others, teenagers are getting their wisdom teeth out and dentists are using oxycodone — another version of OxyContin — to stop the pain in the wisdom teeth. A number of them have become addicted. They are driving to a methadone clinic in Burlington twice a week with their parents. Dentists have got them addicted to OxyContin. It is ridiculous what is going on.
Senator Eaton: In your post-monitoring market idea, I really think you are undervaluing the role of a very accessible pharmacist. They are very knowledgeable. They are there when they give you the drug. They can say to you, “Please come back, Senator Cordy, if you have any of these adverse effects” and “Do not take Advil,” like one of them told me, “because it will eat out your stomach,” because I was taking something. They are right there. You know them. You deal with them. The doctor should be doing other things. I really believe pharmacies could play a huge role.
Mr. Young: In pharmacy school, they study pharmacology. They understand how drugs work in the body. In most medical schools, doctors do not study pharmacology. They might just take one short course. Doctors learn how to write prescriptions. That is called therapeutics. I think the pharmacists can play a much greater role. You are absolutely right.
The Chair: I will make an observation on that, because I think that is an important point. We raised this in earlier meetings, and it is an important issue.
Senator Enverga: Your reply about the worldwide database answered my question, so I am fine for now.
Senator Seth: I heard you saying there has been new law implemented to the pharmacists. If I write any prescription of medicine given by a pharmacist, they give you all information of side effects, with water, all information. They bring those back to us again because they are nervous when they read all those side effects. They bring it back to us and wonder whether they should take it or not, because there is an interaction between medications. They are on a few medications.
We have been seeing this. It is not true that we do not have this in Canada. Yes, it has been for a long time, all side effects, full pages. Sometimes there are 10 pages given to each patient when they buy the medicine from the pharmacy. I just wanted to correct you, because I am still in practice, so I know what the rules are. They are already there.
Mr. Young: Perhaps after the meeting I can show you the difference between the Canadian and American documents, and you will see the superior documents the American patients and doctors get.
Senator Seth: I cannot comment on that.
The Chair: We can discuss the point that there are these pages. The issue the witnesses raised was the value of them, the quality and nature of the information that is in them. We have that on the record and that can be pursued.
Senator Cordy: Ms. Currie, you spoke about prescription cascading. Someone gets a prescription. They have side effects, so they are given another prescription for the side effects, which creates more side effects. We certainly hear about this, particularly for seniors, who are on 10 different medications. How common is prescription cascading?
Ms. Currie: It is a serious problem. It is a serious problem for all drugs, but particularly psychiatric drugs. I tried to give you an example of Effexor. It has a list of dozens and dozens of side effects. I am talking about the real world here. This is not theoretical. I work with people. I help people who have these side effects.
One young woman, a professional in her late twenties, approached me once. She had started taking a sleeping pill. She was being told by her doctor that she now had severe arthritis. She had severe pain. We tracked back all the drugs she had been given. She started with a sleeping pill. Then she got anxious as she got addicted to the sleeping pill. I use “addicted.” It is exactly what happens. The drug companies prefer to call it having “withdrawal effects,” but it is addiction.
She started having anxiety and panic during the day. She got an antidepressant. Then I think she got an antipsychotic because she started getting more and more agitated during the day, what we call agitated depression. She was on two drugs, getting side effects. Then she started getting muscle pain, which is a common side effect of psychiatric drugs, and now her doctor was telling her she was depressed, anxious and had arthritis.
People have gastric problems, so they get a proton pump inhibitor. They have sexual dysfunction problems, so they get Viagra.
Not to speak of diagnostic tests. Many of the people I work with to help taper off drugs have had diagnostic testing and seen specialists extensively. I would love to see a study of the contribution that adverse drug reactions make to the cost of our health care system simply in through diagnostic procedures. I have heard of people having surgical interventions. For example, jaw pain is a common side effect of taking benzodiazepines. I have heard of people having multiple teeth pulled. I have had people being diagnosed with dementia when they did not have it. I have heard of people being diagnosed with multiple sclerosis when they did not have it.
Those are rare situations, but it is very common for people to have a problem resulting from a prescription drug, such as depression. If one takes a benzodiazepine, like Ativan or clonazepam, for a certain length of time, they will become depressed, because benzodiazepines are central nervous system depressants. They will be prescribed an antidepressant, and so it goes, and that is a prescription cascade.
Mr. Young: Could I describe one other one?
The Chair: Just go to the conclusion, not the example, if it makes a point with regard to monitoring. What I would like to come back to is the issue of monitoring, because both of you have raised a number of issues.
Ms. Currie, in your report that Senator Seidman picked up on, you had a number of recommendations of what should be done with information once you have it. The real, critical issue we are dealing with is the collection of the information. You do not get to any of these marvellous things you can do if we do not get the information.
The issue in terms of the collection is what I want to focus in on. We have a lot of other aspects of the post-marketing issues.
I want to come back to the issue of the pharmacist. In our study on the H1N1 pandemic, the Canadian Pharmacists Association told us that they knew two weeks in advance. I will not go into who made the announcement, but the country, knowing there was an epidemic of the flu, although they could not know what species of flu it would be, they knew from the number of prescriptions of Tamiflu that there was a substantial outbreak of the flu occurring. Even in that report, there was the recommendation that pharmacists can play a much bigger role in the surveillance of the drugs.
You referred to my question in the earlier meeting about the mechanism to get this information forward. Mr. Young has used numbers about how much more there is than is reported. My reading is that one of the most difficult issues is actually getting a report that there has been an adverse drug reaction, so this concept of using social media as a way that people are interfacing with the world to get this information forward.
You have indicated a possible organization that might be created to deal with this; and Mr. Young, you made recommendations along these lines. What I would like to ask both of you to do is to reflect more on this particular aspect. You both have reflected a great deal on it, but if something occurs to you after you leave here with regard to the issue of using some new modern communication — like social media, which people are really taking up — and what kind of vehicle to get that posted and a mechanism that absorbs that and then is able to distribute to an appropriate organization to deal with it, we would really appreciate that. Furthermore, we would welcome any further thoughts you have after you leave here, based on the questions my colleagues have asked you, that stimulates an idea that occurs to you after you leave here. We would welcome your giving us a written submission on that.
With that, I want to thank you both for having been here, a well as my colleagues for their questions.
(The committee adjourned.)