Proceedings of the Standing Senate Committee on
Social Affairs, Science and Technology
Issue 33 - Evidence - March 6, 2013
OTTAWA, Wednesday, March 6, 2013
The Standing Senate Committee on Social Affairs, Science and Technology met this day at 4:16 p.m. to study prescription pharmaceuticals in Canada (subject: Off-label use).
Senator Kelvin Kenneth Ogilvie (Chair) in the chair.
[Translation]
The Chair: Welcome to the Standing Senate Committee on Social Affairs, Science and Technology.
[English]
My name is Kelvin Ogilvie, and I am a senator from Nova Scotia. I will ask my colleagues to introduce themselves, starting on my left.
Senator Eggleton: I am Art Eggleton, a senator from Toronto and deputy chair of this committee.
Senator Munson: I am Senator Munson from Ottawa, a senator from Ontario.
Senator Enverga: I am Tobias Enverga from Ontario.
Senator Demers: I am Jacques Demers from Quebec.
[Translation]
Senator Verner: Hello, my name is Josée Verner, and I am a senator from Quebec.
[English]
Senator Seidman: I am Judith Seidman from Montreal, Quebec.
The Chair: We welcome our witnesses to this meeting, which is a continuation of the third phase of our study on prescription pharmaceuticals specifically dealing with off-label use. We have three guests today. By agreement we will start with Dr Joel Lexchin, Professor at the School of Health Policy and Management of York University.
Dr. Joel Lexchin, Professor, School of Health Policy and Management, York University, as an individual: Thank you for the opportunity to appear here. Besides teaching health policy, I still work in an emergency department as a doctor, so we have sometimes seen the results of off-label prescribing. I will go through my recommendations for how to deal with this issue and try to minimize the problems that result.
The first thing is to recognize that if Health Canada does not approve an application for an indication for either an existing drug or a new drug, that information never reaches anyone, such as public health care practitioners. That means that if it is an existing drug and doctors are prescribing it off-label, they will not know that Health Canada did not find evidence that this drug was effective. They will continue to prescribe it, basically not knowing that it does not work or that it is unsafe for that indication.
In the European Union, the European Medicines Agency has since 2005 been publicizing when it denies approval for new indications. We could do the same.
Second, there is no good source of information for doctors to consult about prescription medications. The Compendium of Pharmaceuticals and Specialties, or CPS, which is the blue book that you will find in every doctor's office, is out of date.
Drugs in the same class do not necessarily have the same information in their product monographs, and this could be changed. Australia has something called the Australian Medicines Handbook. The U.K. has the British National Formulary. A similar publication could be set up in Canada, either run by medical organizations, which is what happens in Australia, or run indirectly through government funding, which I believe is how the British National Formulary gets its money.
Third, in France, as a result of recent scandals around prescription drugs, the French have adopted a new system for drugs that are still on patent but are being prescribed off-label. Essentially the French regulatory authority is issuing what is called a Temporary Recommendation for Use. This is granted for three years. If you prescribe the drug for that indication for three years, then you are prescribing it on-label. This gives the manufacturer enough time to assemble information to submit to try to get that indication formally approved.
Fourth, when drugs go off-patent, no manufacturer will investigate off-label uses of those products, simply because you cannot know for sure whose version of the drug will be dispensed. You may spend all the money and someone else will get all the profits out of it. This means that the only way to gather conclusive evidence about whether off-label uses for off-patent drugs actually are beneficial is probably through public funding. Therefore, I believe that CIHR should be funding clinical trials to specifically look at common off-label uses for drugs whose patents have expired.
Fifth, when drugs are being used off-label, under our current system, it has to be the manufacturer who applies to add that indication to the product monograph; in other words, to put it on-label. Sometimes there is no incentive for manufacturers to do this, even if drugs are on-patent; the use would be relatively small, the drug is getting near to the end of its patent life, and for some other reasons. Therefore, I think Health Canada should have the authority on its own to examine the evidence around whether an off-label indication is appropriate and then be able to add that to the indications for the drug without having to wait for the manufacturer to apply.
Sixth, a number of drugs are approved on the basis of what are called either intermediate end points or surrogate end points. These are things like the drug lowers blood pressure, blood sugar or cholesterol, or that the drug improves bone density, but none of these things count for doctors or patients. What counts for doctors or patients is whether the drug reduces morbidity or mortality. However, because this is the indication for the drug — in other words, that it reduces blood sugar — that is what the manufacturers advertise it for and that is all they can legally do. At the same time, doctors will often translate ``this lowers blood sugar'' into meaning ``this will prevent kidney disease.'' Therefore, I would advocate that whenever Health Canada approves a drug on the basis of surrogate end points — in other words, biochemical or physiological changes — all promotional material for that drug should have to carry a statement such as, ``This product was approved on the basis of only surrogate end points and not on the grounds that it affects morbidity and mortality.'' This will send a message, possibly, to doctors that they should not expect that it will prevent kidney disease just because the drug lowers blood sugar.
Seventh, evidence has been gathered. This is based on a study done by myself and my colleague in British Columbia, Barbara Mintzes. It looks at interactions between drug company sales representatives and general practitioners in Montreal and Vancouver. Drug company reps only give doctors adequate safety information about one time in every twenty.
Therefore, as an ongoing measure, I think that we should be looking at what information sales reps give to doctors. This could be done by having a panel of doctors that rotates, say, every year. After these doctors see sales reps, they would fill out a short survey form that would then be sent to the body coordinating this to see what kind of information sales reps are giving to doctors. For instance, are they advocating off-label use? By the way, sales reps are the most effective form of promotion. That is why I think this particular measure is extremely important.
My final point is related to what happens at the provincial level, not with Health Canada. If doctors write a prescription for off-label use, on that prescription they should have to write that it is for off-label use so that the patients know that they are getting something for a use not approved by Health Canada.
The Chair: Thank you.
Now we have two guests from McGill University who I understand are quasi-sharing a presentation but who will each make a contribution. I will start with Dr. Eguale from the Clinical and Health Informatics Research Group at the McGill University Health Centre.
Dr. Tewodros Eguale, Clinical and Health Informatics Research Group, McGill University Health Centre, as an individual: Thank you for giving me this opportunity to present part of my PhD to this committee. My PhD is involved with the study of prescription drugs, specifically off-label prescribing and its outcomes, including adverse drug reactions.
The main problem with off-label prescribing is that physicians do not write the treatment indication on prescriptions or in any other way. There is a need to study off-label prescribing. We do not have the treatment indication to measure this problem. For example, there was a review done by Dr. Dal Pan, Director of the Office of Surveillance and Epidemiology at the United States' FDA. He identified that there is a lack of data; therefore, drug regulatory authorities are unable to measure the prevalence of off-label prescribing.
There is a need, for example, to assess and monitor adverse drug events, which occur in off-label prescribing settings, but we do not have a way of measuring this. One hurdle identified is the link between the drug and the treatment indication. In McGill, the Clinical and Health Informatics Research Group has an electronic health record. It is called the ``Medical Office of the 21st Century,'' and by using this electronic health record, we have managed to link the prescribed drug to its indication. By using this data, we were able to measure the off-label prescribing rate in primary care physicians, and this is done for the first time in Canada. This data on treatment indication was first validated in another publication.
To give you the highlights of this publication, one in nine drug prescriptions are off-label, and we also looked at the whether there is any evidence for prescribing off-label, and 79 per cent of the time, or 4 in 5, there is no strong scientific evidence to use the drug for that specific indication.
We also looked at different drug groups. For example, with central nervous system drugs, 26 per cent of the time, or 1 in 4, the drugs were prescribed off-label. In the case of anticonvulsant drugs, 67 per cent of the time these drugs are prescribed off-label. For antipsychotics it is 44 per cent, and for antidepressants it is 33 per cent, or 1 in 3.
For example, in our study we also identified quinine, a drug which was originally approved to treat severe malaria, and it was prescribed 99.5 per cent of the time for nocturnal leg pain. That same drug was identified to be a cause of adverse drug reactions, and, in 41 cases, resulted in a life-threatening adverse drug reaction. When you look at why this drug was prescribed in these adverse drug reactions, it was prescribed for malaria in only four cases.
In the United States, there were 665 serious adverse drug reaction reports, and there were 93 deaths. As a result of this spontaneous reporting of adverse drug reactions, both Health Canada and FDA had issued warnings for this dangerous off-label practice.
The other drug I cited, which we included in our study, was gabapentin. In our study, it was prescribed 99.2 per cent of the time for off-label indications. We identified that there was strong evidence to prescribe it off-label in 4 per cent of the uses. For this same drug, in the U.S.A., the drug company was fined close to half a billion dollars for illegal promotion of this drug, but in the same year, the sales of this drug were close to $2.7 billion.
The third drug I included in this discussion is quetiapine. In two out of three cases it was prescribed for off-label indications. For this drug, there is a black box warning not to prescribe it for elderly patients because it increases the risk of death, and for children it also increases the risk of suicide.
We also reported the association between off-label prescribing and adverse drug reactions in a pharmaco- epidemiology conference, and we reported a 43 per cent increase in adverse drug reactions compared to on-label prescribing.
I would also like to make the point that the comprehensive nature of our data allowed us to identify medical conditions with high prevalence of off-label drug use that would benefit from new drug development or from new randomized control trials.
We also identified that generic and older drugs and drugs that have one or two approved indications have a high rate of off-label prescribing. We also identified that physicians with more evidence-based orientation have a low rate of prescribing off-label.
In this publication, we identified a number of determinants of off-label prescribing as well.
I will pass the implications part to Dr. Tamblyn.
The Chair: I will now welcome Dr. Tamblyn to make her presentation.
Robyn Tamblyn, Scientific Director, Research Institute, McGill University Health Centre, as an individual: Thank you, senators, for allowing me to come back to speak to you about this particular topic.
To stand back a little, I want to put this in context of when drugs are approved because we have a rigorous approach to approving drugs in Canada, as in all Western countries. They are approved for certain indications and populations.
When a drug is prescribed for circumstances in which it has not shown scientific evidence of benefit, it is considered off-label. A drug can be approved for certain indications in Canada and for others in another country, so it does not mean there is not any scientific evidence. It means that the company, for whatever reason, has not chosen to apply for it.
The last time I was here, we talked about children and very old people who were typically on multiple drugs. Those people tend to be excluded, as are pregnant women, from drug trials, which is a rigorous approach to look at the safety and benefits of drugs. Therefore, by definition, we consider that drugs prescribed in those populations are off-label because they do not have scientific evidence. They were never included in the studies.
Extra care needs to be taken to set up a very proactive system of monitoring drugs in those populations, otherwise they would not have any drugs to use, and we do not want that, but we do not know what the effect will be because they have not been studied in those populations.
The much harder thing, which Dr. Eguale talked about, is when a drug is prescribed for a treatment indication for which it was never studied. We have some great examples of that happening where bad things happen. For example, an anticonvulsant that was supposed to be for seizures was used to treat chronic pain with very sad effects. In that particular piece — meaning the indication — why the drug was prescribed to begin with is not a required part of a legal prescription, so you do not know it. You do not know what it is, especially if it is off-label. If it is for some wild thing like night sweats for a drug that is supposed to be for lowering lipids, you would never know. One of the greatest difficulties and a worldwide challenge is to say: How do we figure out what the indication was or the reason the drug was prescribed so we can monitor off-label use?
That is a big challenge, and it is a little of what Dr. Eguale has tackled in his studies, namely, developing a new method altogether, the first in the world, of monitoring off-label use so it could be studied in a systematic way.
Why do we want to know that? It is for three or four reasons. First, these now become social experiments. You are prescribing a drug. You do not know what the risk will be in that population or for that indication, and you do not know what the benefit will be. You do need to follow how much of this is happening and conduct proper surveillance to determine the risk and the benefit of that drug in that population.
One of the most famous drugs we have ever had is Aspirin. Aspirin was for fever, but it has become a miracle drug for protecting against cardiovascular disease. It is not to say that drugs, when they are prescribed off-label, do bad things for a particular problem. It is wonderful to be able to both monitor the risk and the potential benefits that you may not know.
The second issue is that when they pay for a drug, the payer is expecting — and in Canada, about half of our population is covered by provincial taxes that are raised for our health insurance plan — that they will get this benefit. If the drug is prescribed 99 per cent of the time for things for which it has never been tested and you do not know what the benefit is, then you could say you are either getting some benefit you do not even know or you are completely wasting your money and you may be increasing your risk of something. A payer really wants to know. There have been examples of payers demanding reimbursement for drugs that were clearly promoted and prescribed off-label for what turned out to be later indications where the drug had no benefit whatsoever. I think the payer really wants to know.
The third area is really the research agencies or the funders, like the place I belong to part of my time. They want to know because you need to know two things. First, when a drug is prescribed where you do not have scientific evidence, you need to be able to identify the gaps and say we need to put scientific evidence into those gaps. That is a priority for research.
Second — and I think this was discovered in Dr. Eguale's study — there are conditions for which we have no treatment. People are attempting to treat to the best of their ability, but we have no means of saying, ``Is that working or not?'' I think that is very important.
For all of those reasons, it is probably very important for us to monitor off-label use.
I think that Canada could take the leadership internationally to provide that off-label monitoring and investigation for three reasons. First, we have spent a fair bit of money, about $2.5 billion, on putting in place complete repositories of all drugs that are dispensed and eventually all electronic prescriptions. That is through Canada Health Infoway's investment along with the provinces. We now have the capacity to add these additional features, which is to say that we want to know why it is prescribed, and then you have a perfect monitoring system. Nowhere else in the world do they have that complete suite of infrastructure that will allow you to do that; this is a huge plus for Canada.
Second, we have researchers who have shown that they can produce a very successful prototype to collect and monitor this information. We have a proof of concept.
Third, we have the Drug Safety and Effectiveness Network, which has the capacity, the people power, to do this kind of monitoring, and we have already set up the mechanism for that to happen. We are about to introduce the strategy for patient-oriented research, which will not only allow monitoring to occur but also set up intervention that could change how things are done on the ground today to improve outcomes for Canadians. That is what that strategy is about. It is a partnership with the provinces and the CIHR.
In terms of how to do it, we could make it a legal requirement, just like other things that are legal requirements for a prescription. Documenting the treatment indication could be a legal requirement and it could be one way of doing that.
Another way that may be less abrasive would be to put in place carrots and sticks. For example, a stick could be that if you do not put in a treatment indication, the drug cannot be monitored and it will be more expensive for the provider who is actually prescribing the medication. We could also ask patients why the drug was prescribed and empower them to be more involved and engaged in both why drugs are prescribed and then monitoring for adverse effects. I think we should be doing that anyway, but it is another avenue we can pursue.
I will end there. Thank you very much for asking me to be here today.
The Chair: Thank you very much.
I will now open the meeting up to questions from my colleagues. We will start with Senator Eggleton, to be followed by Senator Seidman and then Senator Munson.
Senator Eggleton: Let me start with Dr. Lexchin. You gave eight recommendations. In your second one, you talk about the sources of information. Doctors have these books. You talked about the CPS blue book in our context, and you also talked about Australia and the British.
I sensed that the problem with the blue book that doctors have is that it is not kept up to date. Is it quite adequate if it is kept up to date?
Dr. Lexchin: No, not really. Besides not being up to date, it has a number of other problems, such as different drugs in the same class. Let us take anti-inflammatories. Advil and the other drugs in that same group were all introduced at varying periods of time. The earlier ones will have one set of information about them. For drugs that come along later, the information will be different. Drugs that are more recent will again be different. Although these drugs all belong to the same class, they will have different levels of information about them.
The third thing is that the CPS is not a source of comparative information, so it does not tell you how drug X compares to drug Y in the treatment of a particular condition.
Finally, the CPS does not necessarily list all the drugs. It only lists the drugs that the manufacturers want to have included.
Senator Eggleton: Do you think the Australian or the British models are far better for us to follow?
Dr. Lexchin: I do. I have lived and worked as a doctor in Australia and used the Australian Medicines Handbook. As a source of information about medications, it is far superior. It is not just based on the product monograph. They take other information into account and they also provide comparative information.
Senator Eggleton: You mentioned that France has put in place a Temporary Recommendation for Use document, a TRU, for up to three years. I am trying to understand exactly how that works. That means for a drug that is approved for a certain indication, if it comes to the attention of the French authorities that in fact it is being used for off-label purposes, they will provide this TRU for up to three years. Is that it?
Dr. Lexchin: Yes.
Senator Eggleton: Who initiates that? Does the manufacturer?
Dr. Lexchin: No. I believe that is the regulatory authority that can issue it.
Senator Eggleton: Where do they get the information?
Dr. Lexchin: I do not know. This is all very new. This has all taken place within the past six to nine months, when this started, so no one has evaluated this system to know how well it will work.
Senator Eggleton: Let me ask you about recommendation 7. This is where you are concerned about sales representatives, as mentioned, from the drug companies.
Dr. Lexchin: Yes.
Senator Eggleton: You are saying there should be monitoring by doctors as to the kind of information these sales representatives provide, that is, a self-regulatory thing with doctors heading it up. Is that the idea, or who appoints the doctors?
Dr. Lexchin: The doctors would not be monitoring it. All the doctors would be doing is filling out a brief questionnaire. For example, ``What did the drug company tell you the drug was used for? Did the drug company representative mention side effects? Which ones?'' Things like that. This would then be fed into the agency regulating the activities of the sales representatives, which could be Health Canada or another independent agency. That agency would then review the data to see whether or not what the sales representatives were telling doctors was appropriate. The doctors would be randomly selected and asked if they would be willing to do it.
Senator Eggleton: Let me go to Dr. Eguale, if I might, and the statement you made today — and I saw it in this Maclean's article last year as well — about 79 per cent lacking scientific evidence, as you have said. I put your quote to a couple of other people who have been here at our previous sessions, and it seems to be greeted with some astonishment. How do you validate this 79 per cent figure? Are you saying that a lot of this lacks total evidence or just insufficient evidence?
Dr. Eguale: We are saying with this publication that it lacks strong scientific evidence to use them. There is a lack of strong scientific evidence to prescribe the particular drug for the particular indication. To take you back to the methods, we used a method that was developed in 2001 in the U.S. We used a compendium which divides these off- label uses into available strong evidence and lack of strong evidence.
For example, in the U.S., what they reported is 73 per cent, but their study included only 160 drugs. Our study included 684 drugs, and that is our report.
Senator Eggleton: Other studies seem to indicate that you are on the right track in terms of your numbers on this. Is that what you are saying?
Dr. Eguale: Yes, we are on the right track. If you compare the methods used in the U.S. study and the methods we used, it is completely different. We get the treatment indications directly from the physicians at the time of prescribing. This is the same medical language used by the physicians. However, if you look at the U.S. study, they used ICD-9 codes, which are really difficult to interpret as an indication.
Senator Eggleton: Dr. Tamblyn, you mentioned you were here before, and indeed you were, when we were doing the post-approval monitoring phase of this study. You talked about electronic prescribing at the time, as I recall.
In terms of electronic prescribing and off-label use, can it play a role here? Can it help enhance the monitoring or safety and effectiveness using electronic prescribing in terms of off-label use?
Ms. Tamblyn: Absolutely. We have an excellent database of all drugs that are approved in Canada over many years that are on the market, and we have vendors in Canada who compile that and keep it up to date. They also keep track of whether or not a drug is approved. Computerized prescribing is a worldwide phenomenon. It is a low-hanging fruit to try to reduce errors related to illegible prescriptions. Many nations are pushing down that pathway, ours being one.
If you ask for the treatment indication at the point of prescribing, you can actually clearly indicate which are on- label and which are off-label. If you attach it to the scientific evidence produced by the Centers for Medicare & Medicaid in the United States — they are the biggest insurer in the United States — they have made the effort to look at whether or not they want to insure a drug as a function of the likely indication. You can provide powerful evidence at the point of prescribing to the physician who is prescribing, the pharmacist who is dispensing and ultimately to the person who is using the drug so they can make their own decision. I think that would be great.
Senator Seidman: There is no question that what we have been hearing is how vital off-label use is, as you suggested, Dr. Tamblyn, especially to certain subgroups of the population who are never included in the original trials pre- approval. Therefore, in the name of trying to be pragmatic and trying to figure out how we can make recommendations that will be useful in this area, I will start with a question to Dr. Lexchin.
I will go back to a question that Senator Eggleton asked you at the outset that had to do with your recommendations about the TRU system, which is the French system that indeed was — you are right — just written up in the New England Journal of Medicine at the end of 2012, so it is really new.
Dr. Lexchin: It is.
Senator Seidman: If you look at this article about the system, one of the features of it is that before a TRU can be issued, the quality of the scientific evidence is critical. In other words, assessing the quality of the scientific evidence is critical to a TRU being issued. As we know, in the population subgroups, scientific evidence is lacking. I would like to understand some of the pieces here and how we can put them together in terms of trying to make a difference for these population subgroups and allow them to have the medications they need but also ensure there is a safety mechanism built in somehow in monitoring it.
Dr. Lexchin: Whether or not there is scientific evidence would at least partly depend on where in the life cycle the drug is. Early on, you are right; there would not be scientific evidence for elderly people or children. However, if we went along with what Dr. Tamblyn is suggesting in terms of linking the drug to the indication and having the ability to also look for side effects, you could get a reasonable idea after a number of years. These drugs will get used in old people or in children, and you could get an idea of whether or not there is significant off-label use and if it appears that the drug, at least, is safe in those indications. Then you could go ahead and issue this kind of Temporary Recommendation for Use document to allow the companies to get more information about what is going on so that they could then ask for a formal indication.
Senator Seidman: That is one piece of the puzzle we could look at in the French system and see exactly how it is operationalized.
Dr. Lexchin: I think you would probably have to get someone from the French regulatory system to talk about this. Aside from that New England Journal of Medicine article, I have seen nothing else about this.
Senator Seidman: Interesting.
Dr. Tamblyn, you talked about how vital off-label use is. The big question is: How do we operationalize the system? One of the issues that has come up is who would do this? Who would be responsible for a functional electronic system, for example, which is obviously one way to do it? Who would collect the information, and how would it be disseminated and shared, given jurisdictional issues, the provincial federal responsibilities and all that?
Ms. Tamblyn: That is why I mentioned the Drug Safety and Effectiveness Network. It is started by leveraging the fact that we have a health care system, so everyone gets a health number in each of the provinces. A variety of services are captured on what is done for individuals, what drugs they get, what services they have, what hospitalizations they have. We are data rich in Canada. It does not mean we have access to that data, but we have rich data.
A couple of provinces — British Columbia, Manitoba and Ontario — have provided enormous leadership in how you can use that data for the purpose of initially monitoring the safety of medications and then monitoring their effectiveness. The first databases to be used were in Saskatchewan and they are purchased by the United States all the time. In fact, the FDA purchases those databases, and they discovered the huge benefits of inhaled steroids for reducing asthma attacks and asthma deaths in kids. That was an incredible benefit. We just need to push that up.
We have international leadership capacity, but we do not have equitable access across the nation. We now have a mechanism of sharing those results through this Drug Safety and Effectiveness Network. We really have all the pieces. We just need to push it a little further over the edge. We should be monitoring systematically in children, older people, people on multiple medications, in pregnant women. We could do that. We are like Finland, Sweden and Denmark. We are like that.
Senator Seidman: What you are saying is we do have all the pieces; it is just a question of finding a way to put them all together?
Ms. Tamblyn: Exactly. Now we are bringing on board these other pieces, which are very rich clinical data — lab data, diagnostic imaging data, actual electronic prescribing data. Now we have this data. If we have the right envelope in terms of assuring the public that they are secure, that they can even monitor the trials and that they have access to all the results that come out of that, we have a win-win situation.
Senator Munson: Life is a journey and sometimes the journey, even in the Senate, takes you to a place where you do not completely understand all the issues at hand. While it may be simple to the three doctors and to some senators here, I think it is a complex issue for Canadians to understand.
Dr. Lexchin, you said that off-label prescribing also occurs because doctors prescribe on the basis of surrogate end points rather than hard clinical end points. I do not think a lot of us really understand that. Why should the general public be paying strong attention to off-label usage? We are trying to grab the attention of people who are being treated and we are trying to grab the attention of Health Canada, so if you could provide a better understanding, in a language that we can all understand, I would appreciate that.
Dr. Lexchin: I do not know if you have in front of you the report that I prepared, but if you go to page 6, there is a list of drugs that were approved on the basis of surrogate end points, meaning that they had an effect on some biochemical or physiological measure. For example, if they lowered blood pressure, that is a physiological measure; if they lowered cholesterol, that is a biochemical measure.
The drugs on this list were all approved not on the basis that they actually reduced disease or increased lifespan but simply that they affected some biochemical or physiological parameter. If you look at the far right column, you see what happened when they were actually tested to see whether or not they improved health. If you go down the list, you will see that virtually every one of those drugs killed more people than they helped. That is why people should be concerned about prescribing based on surrogate end points.
Sometimes surrogate end points are quite useful. We know that if a new drug for HIV/AIDS comes on the market and reduces the viral load or increases what is called the CD4 count — do not worry about what that means — those surrogate end points are valid. That means that the drug will actually help people. However, often we do not know that.
Senator Munson: It takes a long time around here to have new laws, new rules and new guidelines. You talked about your recommendations, but I would like to hear them again. What can change here? When you look at your list, the ``True outcome'' column reads ``Increased mortality.'' Increased mortality is scary stuff.
Dr. Lexchin: Yes.
Senator Munson: Why would I want to take any of these drugs if they were off-label?
Dr. Lexchin: Most of them are off the market because they killed too many people. However, there are some things that could be done, that Health Canada could do. For instance, first, if it approves drugs on the basis of surrogate end points and if those surrogate end points have not been validated, then Health Canada could mandate that the companies undertake long-term trials. The drug would still come on the market, but there would be ongoing studies to see whether or not the fact that it lowered cholesterol means that it actually helped people's health.
The second thing that Health Canada should do, in my view, is that when it approves drugs on the basis of surrogate end points, it should require manufacturers, in all their promotional material, to put a statement something like the one I mentioned, which is, ``This product was approved on the basis of only surrogate end points and not on the grounds that it affects morbidity or mortality.'' That simple statement, if doctors read it, would then send a message to them to say, ``Be careful; the drug may or may not actually be beneficial to patients.''
Senator Munson: You do not seem to be too happy with Health Canada. With regard to the letters you have written, they seem to have ignored you.
Dr. Lexchin: Yes, but that is all right. I do not think they have to listen to me to make changes, although I would be happy if they made them.
Senator Munson: To follow up on Senator Eggleton's chat with you about recommending stricter regulation of the activities of drug company reps, you talked about random monitoring. Are doctors under any guidelines right now to verify off-label usage?
Dr. Lexchin: No.
Senator Munson: Why not?
Dr. Lexchin: Because those guidelines would be virtually impossible to enforce. You are not going to have someone in a doctor's office saying, ``Did you look it up to see whether that is an approved indication?'' You have to rely on doctors to do the right thing. What I am asking is to provide help for doctors to be able to do that.
Senator Cordy: I would like to go back to the drug reps question also. You said that you believe that when they are meeting with medical personnel, the doctor mainly, they are only giving safety information about a drug one time in twenty; is that correct?
Dr. Lexchin: In the study we did, we recruited general practitioners in the Montreal and Vancouver areas. After they were recruited, for the next eight times that a sales rep visited them to talk about a prescription medication, we asked them to fill out a survey form. We then collected the survey form and analyzed it.
One of the things we defined beforehand was what we regarded as adequate safety information that the sales rep should give to the doctor. We had a number of things. If the drug had a serious adverse effect, you had to give that. If the drug had warnings attached to it, you had to give at least one warning. We had a list of things.
If you look at how often the sales reps provided that list of items, it was one time in twenty. Also, as I said here, if you look at how often they recommended an off-label use of the drug, it was about one time in eight.
Senator Cordy: That was my next question. Is it against the law for the drug companies to advertise off-label usage?
Dr. Lexchin: It is.
Senator Cordy: However, the drug reps can actually discuss that.
Dr. Lexchin: No.
Senator Cordy: That is what I would have guessed.
Dr. Lexchin: That would be violating the Food and Drugs Act, in addition. However, the point is that no one knows what goes on, because these visits between doctors and sales reps are in doctors' offices and there are only two parties.
Senator Cordy: Should we advocate having a sunshine law in Canada, as they do in the U.S.?
Dr. Lexchin: A sunshine law is where the companies have to disclose payment to the doctors. That still would not get around this issue of what the drug rep is saying to the doctor. That is why I think we need an ongoing surveillance mechanism.
The brand name companies have a code of marketing practices, but they rely strictly on a complaint basis for enforcing that. Someone has to complain.
Senator Cordy: We heard witnesses who told us that they use off-label drugs, and for groups as were mentioned earlier, like seniors, children and pregnant women. They get their knowledge of off-label usage by word of mouth from other doctors who tell them how to use it.
I am quite concerned that we do not have a record of off-label usage, and we do not have accurate information. We have heard today that 79 per cent of drugs used off-label do not have strong scientific evidence. All drugs have benefits and risks, and it is up to the patient, in coordination with the doctor, to determine whether the benefit outweighs the risk.
What should the federal government do? We are looking at this from that perspective. In Canada it is always tricky because we have provincial, territorial and federal jurisdictions. What should we be looking at from the federal perspective in order to ensure that people are aware that they are being given an off-label drug and to start accumulating the data?
Dr. Tamblyn said that we have a mechanism in place to record all the drugs that have been dispensed. However, should we not be saying why these drugs are being dispensed, whether it is for the clinical trial determination or for off- label use? Patients should be aware that it is off-label. What should we be doing from a federal perspective?
Dr. Lexchin: You say ``from a federal perspective.'' With that, you are in a bit of a bind because anything that doctors or pharmacists do is regarded by Health Canada as either the practice of pharmacy or the practice of medicine. If you want doctors to write on a prescription that a drug is an off-label use, that is the practice of medicine; and Health Canada will say, ``Not us.'' Similarly, if you want pharmacists to be required to give out a patient information leaflet, that is the practice of pharmacy; and Health Canada will say, ``Not us.''
Giving patients the information about what is on- or off-label would be very difficult to do, in my view, from a federal point of view. It would require action by the provincial colleges, either pharmacy or medicine.
Senator Cordy: When should Health Canada say, ``Maybe us''?
Ms. Tamblyn: Health Canada has an obligation to monitor the safety of drugs and to the extent that off-label use represents an unknown risk and maybe an unknown benefit. They have the regulatory framework to monitor and to be required to monitor because they are responsible for taking a drug off the market or issuing warnings should there be safety issues.
To the extent that the safety problems are arising because you are using a drug in situations where it was never tested, so you do not know, you have to monitor it. All regulatory agencies realize they have to monitor because it is within their purview to monitor it.
Senator Cordy: I agree with you.
Ms. Tamblyn: The mechanism by which they monitor it is to partner with the provinces and use provincial data. The provinces have a huge interest in doing that because they spend a combined $200 billion per year on health care, and about 18 per cent of that is for drugs. They want to know whether they are getting a bang for their buck. Are they paying for a drug that has no likelihood of ever doing any good and just throwing money down the drain?
Senator Cordy: How difficult would it be to use the mechanism already in place to look at drugs that have been dispensed? How difficult would it be to add the off-label use of drugs to that?
Ms. Tamblyn: You have set up an infrastructure that is, I would say, one of the premier infrastructures in the world. The FDA has set up a similar infrastructure, the FDA's Sentinel Initiative. Canada has leading stars in this area in terms of the capacity to use this information in an effective way to monitor the risk, so you have two things going for you.
The third thing that has to be addressed, which is now on the table for both CIHI and Canada Health Infoway, is to look at the health system's use of new electronic clinical data that did not exist before we started digitizing health care. The regulatory framework around that needs to be sorted out, which is in process, and integrated and linked with the administrative data; then you are good to go. However, you need to institute this requirement that indication be excluded in electronic prescription so that you can monitor it and give feedback back to people using the same mechanism.
Senator Enverga: Thank you for all the great comments and presentations. On page 6 are the drugs that are gone. Hopefully they never change the names and put them back on the market. We have you been talking to different doctors, and I have asked this of other presenters. Given that 79 per cent of drugs lack scientific evidence for use in the adult population, how comfortable are doctors in prescribing all of these off-label medicines?
Dr. Eguale: We do not measure whether physicians know whether a drug for a certain indication is on- or off-label. In one study in the United States in 2006, physicians were given a drug and indication, and 55 per cent of the time, they identified whether it was on-label or off-label. Even from the physician side, there is a clear lack of knowledge. That is something that could be addressed using an electronic prescribing system.
Senator Enverga: I heard that Australia has a better system. Is there a quick recommendation that you can say we should adopt to make this better for us?
Dr. Lexchin: We could develop better information systems for doctors to use to look at how effective and safe drugs are. The current Compendium of Pharmaceuticals and Specialties is grossly inadequate for this purpose.
It does not take that long to do. The Australian Medicines Handbook started out as an idea at a conference in 1995. Within four or five years, the first edition of the book was out. It is a commercial product for sale, which is how they generate revenue. There is a group of 25 to 30 medical and pharmacy associations or societies on the board of the organization. It is run independently of government so doctors do not have to worry that they are being told by some politician what or how to prescribe, and it is regarded as highly authoritative. If we got behind this and encouraged groups like the Canadian Medical Association, the Canadian Pharmacists Association and other organizations to develop a similar thing, it could be done.
Senator Enverga: Would you say that we should adopt the idea as soon as possible as a quick fix for our system?
Dr. Lexchin: Having objective, up-to-date information is essential to being able to practise proper medicine, whether a paper book or something to run on an iPad. This is something that we need to develop as quickly as we can.
Senator Seth: Dr. Eguale, you mentioned gabapentin off-label prevalence, which is 99.2 per cent used and 4 per cent scientific evidence that, yes, it will work for a particular indication. You say the company was fined half a billion dollars, but in the same year it had $2.5 billion in sales. Do you think it is because of the effectiveness and it measures also the off-label drug use? Why is it so?
Dr. Eguale: Concerning this drug, a number of studies clearly showed that the company advertised illegally for these off-label indications. That is why the company pleaded guilty and paid this money. Therefore, this drug is approved only to treat epilepsy, but it was pushed for at least 10 different off-label indications, and there is no evidence we need to use it for those indications.
Senator Seth: What is it about the off-label drug use? What is there? Are there more side effects than there should be compared to other drugs that are on-label?
Dr. Eguale: We did a study that tries to tie off-label prescribing to adverse drug reactions. We reported last year in Barcelona that there is 43 per cent increase in adverse drug reactions if a drug is used off-label compared to if a drug is used on-label. We clearly showed that.
Senator Seth: Why are we allowed to use it? Why do we get into that?
Ms. Tamblyn: You do not know why it is being prescribed, so you cannot police it.
The Chair: I think I will cut this off. This cannot go anywhere directly. This is what we are reviewing to try and get the background information on.
Dr. Lexchin: Can I say something quickly on that point?
The Chair: Yes.
Dr. Lexchin: If a drug does not work, or does not have any evidence that it works, it still can cause harm. Therefore, the less effective a drug is, the greater the harm-to-benefit ratio is. If you have no evidence that the drug works and someone takes it, they are still subject to the same side effects. It becomes more and more dangerous to take that drug; the less and less benefit you get.
The Chair: Again, I think we are going down an area here. You have to get into the issue of what it is being prescribed for off-label; it may well be it is being prescribed in a more vulnerable population, and on and on. It is a very complex area. I will pull this part back. Senator, do you have a further question?
Senator Seth: No.
The Chair: Dr. Lexchin, you clarified in your verbal presentation of your recommendations an issue that struck me. It was your first recommendation that Health Canada does not approve an indication for a drug; that information should be made public and placed on Health Canada's website. My first reaction is: How could they possibly say all the things it might possibly do? However, you clarified that by saying there has been a study that showed that there was an application presumably applied for or presented to Health Canada, and Health Canada rejected that specific request for approval. Is that correct?
Dr. Lexchin: That is correct. If Merck has a new drug on the market and they want to get it approved to raise people from the dead, and Health Canada does not find any evidence that it does that, the knowledge that Health Canada rejected that indication would never be made public.
The Chair: Thank you. That was a very important clarification. I wanted to get it clearly on the record, namely, that such a case is what you were referring to.
Dr. Tamblyn and Dr. Eguale made comments with regard to the issues and the business of information and how this is available. I do not want to get into jurisdictional issues. Our objective is to try to identify mechanisms that might really be effective in both the collection and dissemination of the evaluation of the evidence in the end.
Ms. Tamblyn: Yes.
The Chair: We can figure out where we can direct the recommendations later. Let us look at that information- gathering piece and information-use piece.
I want to start with the information-use piece first. One of the examples given to us in previous testimony as to what should be really easy today with the electronic capabilities is to use a drop-down menu. I will not get into this, because we want to do adverse reactions in the next phase. However, we know that one of the problems is that physicians often choose the wrong drug to prescribe for a given situation. There is even some evidence in the current electronic prescriptions that the number problems have not decreased in certain areas, but that is partly because of the way those are structured, it appears.
Why would it not be possible in terms of the prescription that is written to require — let us not worry about jurisdiction — that the particular drug is being prescribed for a specific disease characteristic? The physician pulls down the drug on the list, and then there is a separate drop-down list of what that drug has been prescribed for — its indications. Why would it not be really easy if it was an electronic prescription being written to have off-label appear on that script?
Second, as part of the evidence gathering we had in the earlier phase, we know of the off-label use of drugs for underrepresented populations, specifically children, pregnant women and the elderly. Why would it not be possible also for the prescribing physician to simply indicate the category of patient for whom this is being prescribed?
I do not want to go further. My point to you all here is — and I think in the example that Dr. Lexchin gave clarifying for me the answer he gave — that it would be equally possible to indicate in that drop-down list. If the physician sees that and it says, as Dr. Lexchin has recommended, that this is not allowed to be prescribed or Health Canada says it has not been approved this particular application, the physician would immediately see that.
You all represent academic areas and therefore you are using electronic capabilities probably at a much greater rate than the physician population in general. As a result of that, you also have a greater understanding of its potential. Do you think as we move in this direction that drop-down lists and electronic prescribing combined have the potential to move us forward, if at the other end we subsequently do follow-ups in some way with how the drug actually works? I will come to that as the second part of the question.
Give me another example of how the electronic world could speed up the transfer of knowledge between physician, patient and the pharmacist.
Ms. Tamblyn: I am glad you mentioned that, because that is exactly the successful prototype that has been in place in Quebec since 2003. The study Dr. Eguale did was based on the data generated through that exact model. You got it exactly in your mind what was there, which is a structured, electronic prescription with a drop-down menu with a mandatory field for why you prescribed it if it is not in the menu. You could easily at that point indicate it is on-label or off-label, with or without good scientific evidence. You know the age of the person and you know what other drugs they are on, so you will know at least two parts of the vulnerable population. You will not necessarily know if they are pregnant, but you can remove that possibility for men, so you are stuck with women potentially being pregnant. You really have a lot of pieces of information that you can actually make it mandatory at that point to complete.
The beauty of that successful prototype, and it is the first time in the world that has been done, is that it actually takes that indication, puts it on the person's problem list and starts adding all the drugs you have tried for that already and what happened as a result of that. Did they work; did they have adverse effects? You can keep track of the whole treatment history behind that. There are huge value-added clinical features for people who are prescribing to having that information and to taking the extra second for documenting the reason for prescribing that medication.
The Chair: Let us go to the other end. The drug is now in the hands of the patient. We know from previous testimony and from what we have read on these issues that, in actual fact, a number of problems arise post- prescription. Part of that is that patients simply do not take the drugs in the appropriate manner or they do not take them. However, that is another issue.
Let us take the issue of collecting data on how well it behaved. We had specific examples in our previous study, and so I will not go back to those. I want to introduce another thing on the record with regard to the collection of the data, because in the end it is really the collection of data that is critical to determining how these things work. We know that well under 5 per cent of adverse reactions are likely coming forward. We also know from our previous study that our witnesses have strongly recommended that those adverse reports that do come forward must be electronic and must be capable of being analyzed, as you have indicated, by a wider group of interested practitioners.
One thing that has appeared in some reports is about patient groups. Let us take Crohn's disease as an example, because that is one where I know this has occurred. Patients got frustrated with trying to find information to help understand the medications and what they are being told, so they formed kind of an online association. I understand all the risks of this. Nevertheless, out of some of these, it appears information has been collected strongly suggesting both positive benefits of off-label use and adverse kinds of things. Lithium is another example in which a patient group has collected together. They find one another online, and there is a spontaneous, patient-generated sort of thing.
Is there a possibility of using that more deliberately and having patient groups get involved themselves in putting in the information that they develop for some body, perhaps DSEN or some other organization or some collection centre, but centred around the disease symptoms? You have patients with a particular disease who tend to be interested in managing their own disease to some degree. I am not going to go on. Is there something in that aspect where we can stimulate the patient groups to be more proactive in collecting and providing data rather than filling out forms of any length?
Ms. Tamblyn: I think we are absolutely going down that pathway. We absolutely have to go down that pathway. I think it is necessary from the get-go. We have personal health records now. We do not have them well-linked to the provider. We could easily do that. Your medication list should be updated for you. We want to hear monitoring results from you. You could call them on their phone and get monitoring results. You know when they have been prescribed something, and you know when they have been dispensed something. You can call them on their phone, and they can enter it. They are starting creative ways of using mobile technologies or personal health records to try to collect that, even using social networking, people with Crohn's disease or asthma or whatever, so you are sharing information about that.
The capability is all there now. I think the technology is all there. Now it is just knitting it together in a way that you can systematically monitor it. It is very powerful. I think we could see a huge leap in terms of what will be possible. That is a very exciting thing.
Kaiser Permanente has started monitoring primary non-adherence because they have all electronic prescriptions, all dispensed prescriptions. They are starting to monitor the experience because they have a patient portal where they can actually monitor what has been going on. They have e-visits about your thing, and so on. It is all there.
The Chair: My final question is in regard to your opinion of how rapidly we are moving forward in the electronic area from a practical point of view. We know from one of our previous studies that one of the limiting factors has been that even though a computer apparently exists on the desks of most practitioners, the operating systems often do not communicate even within a given clinic, let alone within a given hospital floor, let us say, and obviously that is a limitation in terms of distribution. Again, you people are really at the front end of the use of electronic capability in academic settings. In your interface with the practice of medicine, are you getting a sense that the intercommunication capability of the practitioners is increasing? If so, is it increasing at a rate that you are pleased with, or are you still frustrated by it? I will not ask you if you are frustrated. Do you feel it could go faster?
Dr. Lexchin: I will talk about two things. Downtown Toronto has multiple teaching hospitals. Right now, Toronto General and Toronto Western can communicate with Mount Sinai but cannot communicate electronically with Women's College, Hospital for Sick Children, St. Michael's or Sunnybrook.
The Chair: The three largest off-label subsets.
Dr. Lexchin: The other observation I will make is based on what my wife has told me. She is a general practitioner in a community health centre in Toronto. They are now on their fifth electronic medical record in 20 years, which still does not work properly, and they cannot communicate with any hospital.
Ms. Tamblyn: Canada went a certain way. We focused on building big repositories of data. We got into a snag there because putting everyone's data in a big repository scared people, understandably so. I think we have not taken a strategy that says let us put some quick wins on the ground first. Let us put in some value-added features right from the get-go.
If you look at places that have been far more successful than we are, which is not to say that eventually we will not be successful, but more successful at rolling it out faster, one of the best examples was Group Health, which said, ``It is patients first.'' They get to have access first to all that digital data, and then suddenly the providers wanted to have access: ``If you have it in your mobile phone, I want to see it.''
We just had an experience at the McGill University Health Centre, which you may know for other reasons, where they put a little thing on your mobile phone, and you could have a view of that person's record no matter where you were. We have to bring in some quick wins such as value-added features. Everyone wants to book their appointments online to their health care providers. No one wants to get on the phone and try to do that. There are some quick wins we could do that would really take this faster down the pathway.
The Chair: I think you are absolutely right, and the evidence is overwhelming that you have to start it from the point of view of things that people use. I know of a particular physician who, when required by the clinic to use a computer, was fuming in colourful language but now dispenses prescriptions directly to pharmacies of the patients' choice. That is a quick win because there were examples that clearly showed the benefits in personal time, which is a big thing to practising physicians.
You referred to a certain facility. Do you think if the magnificent facility gets constructed, it will be fully electronically capable within the system? Is that one of the features that is being looked at as a requirement? You do not have to answer that.
Senator Eggleton: The eighth recommendation you make, Dr. Lexchin, is that provincial colleges of physicians should require doctors to write ``off-label'' on all prescriptions, obviously where they are off-label. Are you just saying the word ``off-label,'' or are you saying off-label with more detail? How much more detail would you put?
Dr. Lexchin: It is hard to put a lot of detail on a prescription. Theoretically you could put the indication and say that the indication is off-label, but you are limited, at least the way we currently do prescriptions, by space. If you transmitted prescriptions electronically, and most people now have smartphones, or at least many people do, you could give the patient their prescription on their smartphone, which they would then take to the pharmacy, and the amount of data you could transmit onto a smartphone is virtually unlimited.
Senator Eggleton: Dr. Eguale, you said at the end of your statement that physicians with more evidence-based orientation were less likely to prescribe off-label. This was in this study of the Evidence Practicality Conformity Scale. Do you have anything particular in mind as a mechanism for disseminating that more evidence-based orientation? Do you have any particular thoughts about how that might be done?
Dr. Eguale: Evidence-based is more of a characteristic of the physician. We administer a questionnaire when physicians enroll in the MOXXI system, when they start to use the system, and the evidence scale measures how evidence-based the physician is. We associate this particular measure with off-label prescribing, and found out that if they are more evidence-based, they tend to prescribe less off-label. It is more of the characteristic of the physician. However, at the same time, to be more evidence-based, for example, they need to look at randomized control trials as one measure of using to prescribe drugs. That makes them more evidence-based, if they tend to follow randomized control trials.
Dr. Lexchin: I would say, though, that if you want to make doctors more evidence-based, you have to make evidence easier to get. One way to do that, which would be to use an existing service, is to set up a system that allows all doctors in Canada to access the Cochrane database for free. The Cochrane database is a database of systematic reviews. It is housed more or less in Britain. However, if you do not go through an academic library, all you get is the abstract.
Senator Eggleton: There has been reference made in this meeting and previous meetings to fines that have been levelled against drug manufacturers. For example, I have a New York Times article here. It says the British drug maker GlaxoSmithKline agreed to pay $3 billion in fines in part for promoting antidepressants. Johnson & Johnson, on another matter, agreed to $181 million. One witness we had said that that is easy. It is a drop in the bucket. They make a lot more money than that, so they pay these fines. This is advertising when they are not supposed to, or promoting, I suppose.
What about Canada? Is this happening here as well? Do you know of any cases where this is happening? The Food and Drugs Act has a maximum fine of $5,000, which is pretty small compared to these ones I just mentioned, I am not sure whether for advertising or promoting or whether they are interchangeable. What is the situation in Canada? Is it similar or different?
Dr. Lexchin: It is completely different. I do not think there have been any cases taken by governments against drug companies for illegal promotion. It is possible that it could happen. For instance, if a company was illegally promoting a drug in Canada that was being paid for through a provincial drug plan, the province could take the company to court for that, but that kind of thing has not happened in Canada. One of the reasons for it, although not the only one, is that Canada does not have whistle-blower legislation. In the U.S., they have this, whereby if you blow the whistle on your company and then there is a subsequent court case and the court case is successful, you get a percentage of whatever the fine is.
Senator Eggleton: It is because we do not have a mechanism for dealing with these matters as opposed to whether they occur or not. These companies exist here. Could they not be doing the same kind of thing here that they do in the United States that they get fined for?
Dr. Lexchin: It would be reasonable to think that they are, but no one has shown they do.
Senator Eggleton: What do you suggest? I think you were starting on to some of that.
Dr. Lexchin: You have to encourage people who have inside knowledge to speak up, and that requires protecting them. You also have to be more aggressive about finding out what are the promotional practices of the companies, but we do not do that.
Senator Eggleton: If we did that, the $5,000 fine would seem rather inadequate.
Dr. Lexchin: That is under the Food and Drugs Act. For instance, if the provinces think they spent $500 million on a product that was being illegally promoted, they could go after the company for whatever amount of money they wanted. The Food and Drugs Act only affects how much Health Canada could fine a company. In fact, most of these fines were not as a result of anything that the Food and Drug Administration did. These were Department of Justice going after the companies.
Senator Cordy: I was looking at the New York Times and there is an article today, ironically enough, about finding hidden side effects with web search data. It is based on a study published in the Journal of the American Medical Informatics Association. It has been done by Microsoft, Stanford and Columbia together. They are collecting data from queries made to Google, Yahoo! and Microsoft about side effects and are actually in touch with over 6 million Internet users. The Internet does not have borders, so we are talking about people from around the world. Are we doing enough, particularly since we are talking about off-label usage, particularly for areas for people like children, pregnant women and seniors, where we do not have that big a population? Are we doing enough internationally in terms of off- label use of collecting data?
Ms. Tamblyn: We have now the digital age. We are in a different land now. We have a lot of countries that have invested heavily. Israel, for example, has 100 per cent electronic health records; the United Kingdom has almost 100 per cent electronic health records. There is a capacity now to create international cohorts of people who are, for example, diabetics and are prescribed new drugs and you could start monitoring the risks and benefits worldwide. That would be great because that means you have a small fraction of people who are over the age of 90 who have this complex array of drugs. However, worldwide it could be happening that one person every hour will get a drug like that. You could actually monitor it.
I think the potential is definitely there, and we are currently funding research to support the investigation and development of international prototypes for pharmaco-surveillance.
Senator Cordy: This study is pretty amazing. I have not seen the study, just the article about it. Do you think you could actually be in touch online with over 6 million people to determine the drugs that they are taking and also, from what I have read, interaction of drugs? If you take this drug with that drug, it does not work. I think sometimes we are missing out on a lot of information that we should be gathering, particularly when we are talking about off-label use here, but especially since this is an area where we do not have a lot of scientific evidence. There is a lot of word of mouth prescribing going on.
Ms. Tamblyn: You are absolutely right. One of our scientists that we lost to the United States, hopefully to return, actually used the same methodology, but now he is monitoring infectious disease outbreaks that way. We could do the same thing for drugs.
Senator Martin: I hope I can ask the right questions. You have given us so much to consider and add to the study.
Ms. Tamblyn, you said that we are actually data rich in Canada, but the question is regarding the access of that data.
Ms. Tamblyn: Exactly.
Senator Martin: Dr. Lexchin, you were talking about accessing such data as the Cochrane database. Even having the ability to access whatever data is available within their practice, is there time for doctors to decipher it? I guess depending on the drug they are using, if they had that access and it was readily available, that information will be there at the time of prescribing a drug. That is one key. Is there also an issue of organizing this data? You talked about our infrastructure. Is it about designing the mechanism and organizing this data in a way that is user-friendly, so to speak, or are there other issues you can point to?
It seems like we have the big pieces, but who will put it together and how can we connect these pieces? You have pointed to some key areas or gaps, and I am just trying to get at a few more points.
Ms. Tamblyn: I want to separate two chunks that you just talked about. One is information that you can use to monitor in real time how well a drug is working in the population that is receiving it. That is kind of pharmaco- monitoring information. That is one chunk of information where you need experts who actually can turn that into the comparative risk and benefit of those medications, now that they are being used in pregnant women and young children, for indications they were never tested.
We have access issues that can be cleared up with leadership. However, we are data rich and we could surely take the lead internationally in this area.
The second chunk is this: Given that we have that information, how do we return that and the information that Dr. Lexchin talked about — the Cochrane reviews and other such pertinent information — back to the point of care? There is a win-win situation because you have a digital platform. The person is using it to make clinical decisions. Instead of giving them a 100-page guideline on how to use narcotics — like the recent one out of Quebec — you could say, ``It is this narcotic, in this population, for this reason. I can give you the thing for it today.''
In fact, McMaster University is one of the pioneers in bringing the right evidence just at the right moment, at the right time, to the person at the point of care to make the best decision. They are international leaders in that area. There are many others as well, but I have to say we are rich with the huge capacity that we have in this country to get it right. That is why I think we should take the lead.
Senator Martin: To harness that capacity, to create that exchange, you say we need leadership, but is it also something that should be legislated? Is it that there is no mandate for, say, the physicians themselves? Would they buy into this on their own? I am going back to Dr. Eguale talking about a certain characteristic, an evidence-based orientation. How do we get the profession to engage and do this exchange? What is needed there? You talk about leadership, but how do we make that happen?
Ms. Tamblyn: Can I go back and say it will be a little bit like how we tackle smoking? Smoking is bad. You need to say that we want to have a monitoring system for actually monitoring the safety and effectiveness of drugs post- market. We want to be able to monitor off-label. We want to be able to provide information back to patients, prescribers and dispensing pharmacists at the point of care, at the time they are making decisions, on the safety and effectiveness of those medications that are happening.
If we set that out as our goal, we will be funding some programs, maybe framing policy framework. There may be some regulatory aspects to it that we want to add on, especially mandating timely access to data for the purposes of monitoring, just like we do for mandatory disease monitoring. We do that, but we do not do that in any other area. We could do that. We could. I would say it will be a basketful.
I would be pleased to summarize what I think are some of the basketful of things and provide back to you, with my colleagues, some of the key levers we think we should pull and put it in that basket. If that is our goal, we can do it.
Senator Martin: That is very helpful. I feel really satisfied because I felt, like you were saying, that we have the infrastructure, we are data rich and there are all these great models, so how do we make that happen? It would be great to have the list.
Ms. Tamblyn: I would be pleased to follow up.
Dr. Lexchin: The other thing I would say is if you show doctors that it will help with the care they deliver, that is likely to get the best lever for getting buy-in from physicians. You need to not just collect data from doctors, but you need to feed it back to them, and feed it back to them in a clinically relevant way to show them that by providing this data in aggregate, they are helping their patients in terms of better therapy.
The Chair: Thank you very much. As we have heard from the two of you before, you continue to be very clear and forthright with regard to your answers.
Dr. Eguale, we thank you for joining us here today and for your contributions to this discussion. I want to thank my colleagues again for focusing in on the important aspects of this issue.
I am formally, on behalf of the committee, asking that when you leave here and you think about the issues we have talked about, if there are succinct ways or suggestions you can make to us, we would most welcome those. If you could get those to us in a timely fashion, we would most appreciate it. You have certainly been extremely helpful to us today.
(The committee adjourned.)