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
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
Senator Verner: I am
Senator Verner, from Quebec.
Senator Enverga: Tobias Enverga, a senator from Toronto,
Senator Seth: My name is Asha Seth. I am from Toronto,
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
Dr. Beaudet: Not to my knowledge.
Senator Dyck: Would that be part of the research that DSEN
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
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
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
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
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: Two of my questions are quick and the
witnesses might be able to answer them, but the third will require a written
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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 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.)