Proceedings of the Standing Senate Committee on
Social Affairs, Science and Technology
Issue 14 - Evidence - April 4, 2012
OTTAWA, Wednesday, April 4, 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.
Senator Kelvin Kenneth Ogilvie (Chair) in the chair.
[Translation]
The Chair: Good afternoon. I want to welcome you to the Standing Senate Committee on Social Affairs, Science and Technology.
[English]
I am Kelvin Ogilvie, a senator from Nova Scotia, chair of the committee. I will ask my colleagues to introduce themselves starting on my left with the deputy chair.
Senator Eggleton: Art Eggleton, senator from Toronto.
Senator Cordy: I am Jane Cordy, a senator from Nova Scotia. Welcome.
Senator Dyck: Lillian Dyck from Saskatchewan.
[Translation]
Senator Demers: Jacques Demers from the province of Quebec.
[English]
Senator Seidman: Judith Seidman from Montreal, Quebec.
The Chair: Before I introduce our witnesses today, I remind the committee and the witnesses that we will need to adjourn the meeting at about 5:10 because of votes in the Senate.
We will begin by getting your presentations on the record followed by questions from committee members. You can then begin answering the questions, and if more questions arise, we will get them on the record. The clerk will follow up with you with these questions in writing, and we would hope that you would be willing to respond subsequently to these questions in writing to us because we certainly have two groups that are extremely important to our study here with us today, and we value your input.
Our witnesses are from the Office of the Auditor General of Canada Neil Maxwell, Assistant Auditor General; and we have Louise Dubé, Principal; and from Health Canada we have the permanent members of our committee, Mr. Glover, Barbara Sabourin and Dr. Stewart. Welcome to you all.
We pre-determined that Mr. Maxwell will begin.
[Translation]
Neil Maxwell, Assistant Auditor General, Office of the Auditor General of Canada: Honourable senators, thank you for the opportunity to present the results of our audit on the regulation of pharmaceutical drugs at Health Canada. With me today is Louise Dubé, the Principal responsible for audits in the health sector.
The audit covered a number of aspects of pharmaceutical drug regulation. We found that the department had not adequately fulfilled most of its key responsibilities related to clinical trials, medication submission reviews and post- market activities. Today, we are focusing on our findings on clinical trials and the drug approval process.
Our two main concerns in those areas are timeline and transparency issues within Health Canada's activities.
[English]
Each year about 700 drugs are tested in clinical trials in Canada. Health Canada estimates that there are 4,000 active clinical trial sites in the country with many sites testing the same drug. In 2009 and 2010, the department reviewed about 2,600 applications and about 1,800 amendments to clinical trials to assess whether the proposed trial or amendment posed undue risks to trial participants. We found the department had reviewed clinical trial applications and amendments in a timely manner.
Health Canada also plays a key role in overseeing clinical trials. Under the Food and Drug Regulations, clinical trial sponsors, such as drug companies and hospitals, must inform the department of all serious unexpected adverse drug reactions for drugs being tested in Canadian clinical trials, regardless of whether the adverse drug reaction occurred at a trial site in Canada or in another country. The department received 115,000 reports in 2010, which is up from 43,000 in 2007.
At the time of our audit, there were no standard operating procedures for Health Canada's monitoring activities to ensure that it consistently focused on the trials that posed the greatest risk. Hundreds of potential safety issues were waiting to be assessed, and the department did not have documented criteria for prioritizing these assessments based on the risk posed to clinical trial participants.
Health Canada also inspects clinical trial sites to verify that authorized trials comply with the Food and Drug Regulations so the rights and safety of clinical trial subjects are respected. The department verifies that the data generated by the trial site is of high quality. Its strategy is to inspect 2 per cent of Canadian clinical trial sites which is about 80 sites in any given year.
In 2010 Health Canada inspected only 50 sites. According to the department, this was because it lacked resources. Furthermore, because the department does not regularly collect up-to-date information from all clinical trials, such as the number of participants enrolled, it is not able to make comparative risk-based decisions about which sites to inspect.
[Translation]
We examined steps taken by Health Canada to support the transparency of authorized clinical trials. In 2004, the House of Commons Standing Committee on Health recommended that the department create a public database that would provide information on trials in progress, trials abandoned and trials completed. Health Canada committed to enhancing public access to information about clinical trials.
In the fall 2011 audit, we found that, despite this commitment, Health Canada has not taken action. This lack of information increases the risk of Canadians being unaware of the new treatment options or unknowingly participating in an unauthorized trial.
In 1999 and 2004, parliamentary committees requested that Health Canada report annually on the findings of clinical trial centre inspections. However, the department reported publicly on its inspection activities only in 2003 and 2004.
With your indulgence, I will now present our findings on the drug approval process. Health Canada received about 4,400 drug submissions in 2009 and 2010. The department is not meeting its service standards for the timely review of most of the drug submissions it receives, thus delaying Canadians' access to the health benefits of new drugs. In addition, access to more affordable treatments is limited.
We recommended that Health Canada consider streamlining its review processes and using information from foreign regulators. We found that the drug approval process needed to be more transparent. Unlike some regulators in other countries, Health Canada does not disclose information on drugs that it rejects, drugs that the manufacturer withdraws from the review process, or drugs that are approved with conditions.
Health care professionals have the discretion to prescribe a drug for a condition that the drug has not been authorized to treat. Therefore, it is important that health care professionals be informed when Health Canada rejects a drug for new use, so they can understand the department's concerns.
[English]
Mr. Chair, the regulation of pharmaceutical drugs is important to Canadians. With an aging population, the role of pharmaceuticals is expected to grow as researchers come up with new therapies to replace previous treatments or provide new options where no treatment existed before. The committee may wish to obtain assurance and commitment from Health Canada to implement our recommendations in a timely manner.
Mr. Chair, this concludes my opening statement. We would be pleased to answer the committee's questions.
[Translation]
Paul Glover, Assistant Deputy Minister, Health Products and Food Branch (HPFB), Health Canada: Thank you and good morning, Mr. Chair. I am pleased to have the opportunity to discuss the recommendations set out in the 2011 Fall Report of the Auditor General of Canada.
[English]
It is important to note at the outset that the Auditor General did not question the safety or effectiveness of drugs authorized by Health Canada but rather identified ways to strengthen and improve processes that are already in place.
Health Canada agrees with the Auditor General's 10 recommendations and is already taking action to address them. Indeed, thanks to the work done by the department before and during the audit period, we are well on our way to meeting many of the recommendations and commitments in terms of responding to those recommendations. Clear and specific timelines for action have been adopted that will be used to measure and report our progress.
Rather than going into each of the 10 recommendations in detail, Mr. Chairman, I want to highlight a few of the key findings that may be of special interest to the committee and which are fundamental to the department's performance and reputation as a pharmaceutical regulator.
First, Mr. Chair, there is the issue of timeliness of our review of drug submissions. Health Canada's scientists carefully review thousands of drug submissions annually. As was mentioned, 4,400 were submitted in 2009 and 2010. We eliminated backlogs for brand name drug submissions as of December 2011. We do note, however, that as of December 2011 about 60 per cent of the generic drug submissions remain in backlog.
Given this volume of work, we were not surprised by the Auditor General's findings in respect to timeliness. We have simply not had the financial and human resources we needed to do the rigorous safety-focused reviews that Canadians deserve in a timely manner. It is very important for the committee to note that in the time since the audit was concluded we have taken important steps to rectify the underlying resource constraints that are at the root of many of the Auditor General's negative findings.
In April 2011, with strong support of Parliament, increased industry user fees came into effect. User fees are charged to companies for regulatory services and activities, such as evaluating drug submissions, performing inspections, issuing licences and monitoring drug safety. Unlike other comparable regulators, Health Canada had not updated these fees since the 1990s. Without updated fees, Health Canada faced growing financial challenges resulting in increased backlogs in product reviews and inspections which resulted in delays in access to therapies, compromised opportunities for industry and Canadian investment.
We had, frankly, fallen behind. We had fallen behind in technology. We had fallen behind in keeping up with our work. It is not at all surprising to find that we were not meeting many of these measures of timeliness.
To date, the revenues generated from the revised user fees have enabled the hiring of approximately 160 scientific experts, professionals and support staff. Health Canada increased its clinical review staff and nearly doubled its chemistry review capacity for generic drugs.
Mr. Chair, the Auditor General also found that Health Canada does not always take timely action and is slow to assess potential safety issues. Canada had one of the safest and most rigorous drug safety systems in the world. Our standards and methods are frequently used as benchmarks against which regulators the world over measure themselves.
We have been active in protecting Canadians through our post-market surveillance. In 2010 and 2011, Health Canada identified over 1,500 potential safety issues with varying degrees of urgency and severity. One hundred fifty of these underwent more in-depth safety assessments to determine appropriate action. So far in 2011-12 there have been approximately 130 safety issues that were analyzed via more complex safety assessment. Approximately 60 risk communications and or labelling changes related to Health Canada's post-market surveillance have been issued.
Mr. Chairman, as a result of the new revenues being generated by user fees, we have and will continue to improve performance in key areas identified by the Auditor General.
Finally, Mr. Chair, the Auditor General found that we were not meeting commitments to be transparent with Canadians on clinical trials, nor in respect to drug submissions we rejected.
Health Canada has long been committed to providing better, more easily understandable information to Canadians so that they may make informed choices on health products.
Health Canada web posts adverse reaction reports and all authorized labels on the Health Canada website. The department is also working with stakeholders so that labels have plain language and are simpler to read for Canadians.
Through our Summary Basis of Decision project we are already consulting on expanding public access to drug review decisions including, as the Auditor General suggested, information on approval with conditions, rejections and withdrawals from marketed drugs. A report on this project will be published in June 2012.
Mr. Chair, Health Canada recognizes the value of making clinical trial information available to Canadians. In respect of clinical trial transparency, Health Canada is exploring options to make registration of clinical trials mandatory.
Health Canada's approach right now is to encourage sponsors to register their clinical trials within 21 days of the trial's onset, using publicly available registries recognized by the World Health Organization.
Following the audit, Health Canada also committed to publish annual clinical trial inspection summary reports. I am pleased to report that the first of these reports was published on March 26 of this year, ahead of the schedule that we had committed to with the Office of the Auditor General of Canada.
Given the growing number of drug products available, the rapid pace of innovation and the worldwide nature of production and supply, Health Canada is constantly looking for ways to strengthen its drug authorization and safety systems.
Health Canada has embarked on a far-reaching agenda to change the way we regulate pharmaceuticals. Our goal is a modern system that delivers more timely approval of needed medications, strengthens drug safety and is more transparent and understandable to Canadians.
The findings of the Auditor General identify specific issues that support and give focus to our agenda for change.
[Translation]
This concludes my presentation. I look forward to taking the committee's questions.
[English]
The Chair: Thank you very much, Mr. Glover, and for specifically addressing the issues raised in the Auditor General's report.
I want to remind all my colleagues again that we will be terminating at 5:10. I have three people on the question list at this point. The points that I wanted to make sure I got on from the report Mr. Glover were largely addressed.
What I will do, given that I now have four on the questioner list, I will start with the questions and at some point, probably about ten to five, for those who remain on the question list I will ask you to put your questions to ensure we get them recorded, and then we will go back to seeing how many we can get answered now. We will have them on the record and will invite our witnesses to follow up.
Senator Eggleton: Thank you for your presentations. There are many areas I would like to cover. I hope my colleagues get to cover them all. I will focus on two: enhanced transparencies and the new cost-recovery framework.
The auditor says in his statement:
The department promised to:
. . . enhancing public access to information about clinical trials in the fall of 2011 audit, we found that despite this commitment Health Canada has not taken action.
Mr. Glover said the other day they were encouraging sponsors to register, but that does not go as far as, it seems to me, what some other countries are already doing.
In putting this question, I want to also quote a couple of small passages here from a document that I read, written by Elizabeth Wright, Why Canada's drug-approval process isn't as safe as you think. There are three people quoted here, and one is Terence Young, a Conservative member of Parliament for Oakville. Another is Dr. Barbara Mintzes from British Columbia, and the third one is Dr. Joel Lexchin, who is a professor at York University. All of these people have quite a number of opinions.
On the understanding of transparency, they say that part of the problem of understanding Canada's drug approval process is so much takes place behind closed doors. They point out that the FDA in the United States and the European countries all have to submit this as a matter of it being mandatory, but we do not do that. We are not required to do that. We just encourage, as we have heard.
They also say in this article:
. . . like at the federal level, technical details are still bound by confidentiality agreements. "Which is crazy," says Mintzes, "if you think that this is evidence of potential for benefit or harm of a pill or medicine that a person is actually going to take. Those people, and the doctor who is recommending it, and the whole community, should have access to the full body of scientific evidence."
They agree that the provinces generally have more transparency and are better informed about the drug approval process.
I would like to get your comments about that. Why are we not going the whole distance of making it a requirement and doing what they do in the European Union or in the United States? Why are we so reluctant? Why are we holding back here?
The second issue is a question of new cost recovery, which I think most of us would think is a reasonable idea. It is interesting; in this same article they think there are some issues. They suggest:
Many critics say that money exerts too big an influence on approvals. The biggest culprit is user fees, in which pharmaceutical companies pay the government to fund the approval process.
They then go on and talk about why they think this is rather undue influence. I think the MP, Terence Young, suggested it should be a levy as opposed to the way it is calculated now.
I would like to know why they would think that this is an undue influence. I do not know whether the auditor looked at this at all, but is there something about the way this is paid by these companies that exerts some influence, as opposed to it being a fee, levy or tax procedure? I thought those were interesting comments out of this article, so I would like to get reactions to that.
The Chair: The list is growing, so I will ask you not to respond. He took the full five minutes. Those are on the record. If we do not get back, especially with answering the first question on transparency, we will come back to his question after we move on. I will allow five minutes and then I will get the remaining questions.
Senator Callbeck: Thank you all for coming today.
Mr. Glover, in your brief you say you agree with the 10 recommendations of the Auditor General and that you simply did not have the financial and human resources that you needed to do all these things.
You say here:
We have taken important steps to rectify the underlying resource constraints.
You talk about user fees. Are there other ways that you will get money? The money you are talking about to rectify all these problems, is that all coming from the user fees? How much do you anticipate in a year, or let us say over the next five years, that you will be getting in user fees?
We are putting these on the table.
The Chair: Would you put them on, and if there is time within the five minutes I will have them come back to your first question.
Senator Callbeck: The other question is the adverse reactions during clinical trials. The literature here says that 95 per cent of those adverse reactions come from foreign trials, so that means 5 per cent come from Canadian ones.
Has that 5 per cent changed in the last 10 years or has it been pretty well that figure all the way along? The 95 per cent that come from foreign trials, why is that figure so high? Why is there 95 per cent for foreign trials and only 5 per cent for Canadian?
The adverse reaction certainly has gone up tremendously. The figure that was used here was 43,000 in 2007 and 115, 000 in 2010. I would like to know why there has been such a tremendous increase. Has the auditor assessed whether Health Canada advises the trial sets in Canada when foreign trials report adverse reactions to the same drug? I think it was in here somewhere that you were looking into that, and I am wondering if it happened and what the findings were.
I would like to know about the clinical trials also. In the Auditor General's report, it said that Health Canada should strengthen its risk-based approach for inspecting clinical trial sites. Health Canada indicated that they were looking at this and reviewing them, and that was supposed to be completed in 2011. I am wondering, was it completed? What were the findings, and have those findings been implemented?
The Chair: Again, given the time, I will move on to get the other questions, and we will come back to you.
Senator Seidman: I will quickly go through some of the comments by the Auditor General's Office. The Auditor General specified that there were 115,000 reports, in 2010, of adverse drug reactions during clinical trials. That is a substantial increase in a three-year period. It is almost triple the number of adverse drug reactions. I would like to know if you have some way of understanding that and if you could provide us with some information about that.
As far as your inspections are concerned, you take from 56 to 142 days before Health Canada notifies sites of deficiencies found during inspections. As far as I understand, that is what the report notes. I would like to know why it takes so long.
The transparency issue comes up over and over again. You have been here before, and you have told us that you understand and agree that Health Canada ought to be more transparent in publishing all kinds of things about ongoing trials, trials that are completed, trials that are stopped midstream, and various things. My question to you is: What is the barrier to greater transparency?
The Chair: Are those your questions?
Senator Seidman: That is it for now. Thank you.
The Chair: We will get those on the record and go to Senator Cordy.
Senator Cordy: We all seem to be on the same theme. I am greatly concerned about the transparency access aspect of this also.
The Chair: Do you have a number of questions?
Senator Cordy: Yes, I do.
The Chair: Could you list them?
Senator Cordy: First of all, it has been a problem according to the Auditor General's office, yet we hear that Health Canada is exploring regulatory options. I would think, after the Auditor General came out with this report, that you would do a little bit more than explore the options. You would actually have options in place so that it would be more transparent.
I am also concerned about drug approval. It has to be more transparent. There is no knowledge of "approved with conditions." Like Senator Eggleton, I have read a number of articles about it and a book by Terrence Young, a Conservative MP, that was troubling to read because the lack of conditions. This drug had been approved with conditions, one of which was not to give it to younger teenagers or young people. In fact, his doctor did not know anything about that.
I would also like to know a little bit about clinical trials. Who does the clinical trials. When I was listening to Mr. Glover, he said that Health Canada oversees the clinical trials. I am wondering, going back to what Senator Eggleton said, if you are overseeing, I am concerned about a potential conflict of interest. If you are overseeing people who are doing the clinical trials, do they have to sign a conflict of interest form, and, if they do, is that made public?
The Chair: Thank you very much.
Senator Dyck: We are on a roll here. I am also interested in the adverse drug reactions and the large increase that you have reported. I would also like you to elaborate on why there has been such an increase. I am wondering if it has anything to do with which countries were involved. You said 95 per cent of them were from other countries. Which countries are involved, and is this in any way related to genetic differences in drug metabolizing enzymes, for example, as a kind of obvious factor that might be looked at? What control, regulations, or regulatory effect would Health Canada have with respect to clinical trials held in other countries that are being led by someone within Canada, and what percentage of clinical trials are held in Canada versus in other countries?
I think I said this already. Are such clinical trials in other countries available for inspection by Health Canada? My last question would be a little different. You talked about the off-label use of drugs, but I am wondering about regulations with respect to adjuvant use where there are two drugs that are put together and, for some reason, supposed to act synergistically. Is there any way that we keep track of that or of adverse drug reactions?
The Chair: That completes the list. I will go back to pick out a question from each of them to get started on the answers. Before I do that, one thing I would like you to follow up, if you could, is the issue of the authority that you have and the areas identified either by the Auditor General or in questions where you feel that Health Canada may not have adequate authority to deal with gaining sufficient information or the right to make public with regard to other jurisdictions. Could you give us a comment in that regard? It may be affecting some of the issues that are before us
Of the questions that came up, I think, Mr. Glover, that you can probably fairly quickly answer this one from Senator Dyck on the issue of the synergy among proven drugs and whether or not that requires additional clinical trials. What is required with regard to potential new trials of existing drugs and the idea of combining them in some way for some new application? Dr. Stewart, would you be about to answer that?
Dr. John Patrick Stewart, A/Director General, Clinical Trials Office, TPD, HPFB, Health Canada: I want to clarify. The question is: What are the regulatory requirements, or what does Health Canada do?
The Chair: Yes, do you need to bring them back into the clinical trial process and, if so, at what stage?
Mr. Stewart: It depends who is doing the research. A drug gets developed for a particular indication. It approaches the regulator. If the evidence supports the risk-benefit profile, it will get market approval. Once the drug enters the Canadian market, it is used under the label indication, but there is also off-label use. If that drug is put back into clinical trials in Canada for a use that is different than the indicated label use, then the regulations require that the sponsor of that trial has to come back to Health Canada, submit a clinical trial application, and have that evaluated as to whether it is appropriate or not. Depending on the merits of the trial, there will be no objection for it to proceed or not.
On the other hand, if physicians learn about the use of a drug in some other jurisdiction, hear that it is of benefit, combined with another drug, as an adjuvant therapy, and start to use it in that manner, that would be considered off- label use. That is a practice-of-medicine issue.
The Chair: We will come back to that aspect, then, in that phase of that study.
Mr. Stewart: I will add one more thing. If the manufacturer of that drug wanted to advertise that drug for that kind of use, they would have to come back to Health Canada with a submission to demonstrate that the new use has a positive therapeutic benefit and a reasonable risk-benefit profile in order to go out and publicly advertise that it has now been approved for this use, in addition to the original indication.
The Chair: I would like to come back to Senator Eggleton. His question with regard to transparency was picked up in a number of ways. Do you wish to elaborate further? I will go directly to Mr. Glover with regard to that. Perhaps you can handle the aspects of transparency that came up from my colleagues.
Mr. Glover: Clearly, that was a theme that ran throughout. We certainly appreciate the seriousness of the observations that were raised by the Auditor General. We take those very seriously. We understand the concerns and frustrations about the time it has taken us to move forward on this. We, too, support the need for increased transparency.
Let us talk about the barriers, as we see them. Quite frankly, you talked about comparison to other jurisdictions. We do not currently have a legislative or regulatory authority to compel that transparency. We spend a lot of time working through access to information requests and confidential business information claims of the different organizations as they move forward.
I will not make excuses for what we have done in the past. We need to do better. We will do better. However, we certainly do not have the authority at this point in time to compel transparency.
Senator Eggleton: But you would not object to getting legislative authority if this committee recommended it to the government, would you?
Mr. Glover: That authority was part of a previous bill that was put forward and not successful. It would certainly help us.
However, I would like to underscore that, given that we have not had that legislative authority in the past, I am looking at other options that I can do that would allow us to move forward with transparency anyway. I am trying to do that before we receive submissions from a company. We are trying to see, before we look at them, see if there are ways to be more transparent.
Senator Eggleton: What is your time frame to come back and tell us what you are doing on that?
Mr. Glover: We would be happy to come back on a regular basis to report progress.
Senator Eggleton: You are practically a member of the committee now.
The Chair: It would be helpful if you could follow up with us and give us some clear outline of where your authority is limited with regard to a number of these key areas.
Mr. Glover: They are the areas I have identified. We cannot compel. We have to deal with confidential business information, privacy constraints, access to information laws, and those sorts of things as we move forward.
The Chair: Senator Callbeck asked a question about user fees. Could you answer her?
Mr. Glover: The user fees are critically important to us. There are a number of aspects, not just with Senator Callbeck's questions but a number of other senators, that create a conflict here. Regarding cost recoveries right now, the fees we charge to industry, as I have said, were way out of line before; they had not been updated for many years, so our fees were too low. They were not in line with what we saw with other jurisdictions where sometimes they are 100 per cent or sometimes they are 70 per cent cost recovered.
The new fees we have restore the balance of 50 per cent cost recovered and 50 per cent A-based budget through appropriations from Parliament, which is thought to represent both the public and private good. Restoring that balance is critically important. It also means if the fee is significantly high enough, there is an incentive for industry to not just throw anything at us because it is cheap. They have to think carefully when a fee is several hundred thousand dollars to approve a new drug before they do that. If the fees are too low, why not give it a try? We have had to look at that.
The fees will have gone from about $33 million to about $75 million in the area of pharmaceuticals for the last year. There has been a significant increase.
The Auditor General did raise potential conflicts in his report. We were following standard Treasury Board guidelines. We have committed to do a risk assessment to acknowledge that perhaps what we do may need additional steps beyond the Treasury Board policy. That study was just completed. It has been delivered to my office. We will be carefully considering that, and plan to have a new place for dealing with potential conflict of interests by September. However, in the interim, I asked all of our employees to proactively declare if they had or did not have any conflicts before continuing to undertake their responsibilities.
Those fees have allowed us to staff up significantly and to regularize staff who were on contract and other things. In answer to one of the other senator's questions, I am pleased to report that is why it would take us so long. We did not have the resources. We are now meeting performance commitments and have been able to develop performance standards in all of our lines, with the exception of generic drugs. Therefore, it will not take that long anymore.
The Chair: Would you like to respond to a question that Senator Cordy initiated with regard to adverse drug reactions, which came up from the other senators dealing both in the Canadian situation and the international situation within the clinical trial phase? They were asking questions with regard to the identification of adverse reactions, their availability and so on in the clinical trial phase of drugs that may ultimately be approved in Canada, even though some of those trials may be occurring in another country. Would you like to comment on that?
Mr. Glover: I will turn to some of my colleagues to help in this. I do recognize the time.
First and foremost, while we have introduced user fees, we have not introduced user fees for clinical trials. We think that is important. We did not want to create barriers around new therapies. We wanted to ensure there was an appropriate market in Canada that welcomed this type of research, so there are not fees for clinical trials. I think that is important.
The other thing that came up in a number of the comments by members of the committee is the increase in adverse event reporting. It is important to note that it is mandatory for adverse events to be reported to us, through the clinical trials that we approve. That is part of the oversight that we perform.
Why has it increased? We have done a significant push to ensure everyone understands that obligation and are taking it seriously. We have increased our inspection activities in those areas. We have broadly tried to increase the profile of adverse event reporting, broadly, and ensure that all sponsors of clinical trials know their obligations to report any adverse events to us.
I will turn to Dr. Stewart to answer further.
Mr. Stewart: To build on what Mr. Glover said, the regulations require sponsors to submit not only adverse events that are serious and that happen in the context of a clinical trial, it is also for marketed use. A number of the drugs that are in clinical trials in Canada are in multinational trials. There may be sites in Canada, but there may be other sites in many other countries. That alone will feed in a lot of reports. Also, many of the drugs may not be marketed in Canada but may already be marketed in the EMA or FDA, so there is already a much larger population exposure. That will generate a lot of reports.
There was a question about the 5 per cent versus 95 per cent. I think that reflects the amount of research happening worldwide and that 80 per cent of our trials that we get are multinational trials that have a foreign sponsor. The amount of exposure or access happening in Canada is a small part of the larger global research happening. Drug development these days is very much a global activity.
As Mr. Glover said, we believe that sponsors now better understand the requirements to report, so they are reporting a lot. I do not think the increase in number means there are a lot more events happening. It is just that we are finding out about them.
The Chair: Senator Cordy touched on the issue of potential conflict of interest. She did not mention this specific aspect but it ties to her question: Do you monitor the fees paid to those who manage the actual trials and/or the fees that are paid to the volunteers who participate in a clinical trial? Does Health Canada have any role in that area?
Mr. Glover: I will start and then turn to my colleagues to elaborate. The one thing we do with all clinical trials is ensure they are subject to reviews of the various ethics boards of the institutions for these types of issues. There is the question of ethics, for the patient, the sponsors, and workers involved, and we do ensure that they have gone through an ethics review.
Mr. Stewart: The division 5 regulations that oversee clinical trials have no text around funding. There is no requirement for a sponsor to declare where the funding is coming from or how much funding there is.
The only caveat in the regulations is that the clinical trial is designed such that the results have to be achievable. The sponsor has to put in place the infrastructure to carry out the trial, and to carry it to its end. We never ask about funding; we never receive information about funding.
The Chair: That is dealt with, as Mr. Glover indicated, through the requirements of the individual centre.
Mr. Stewart: Yes.
Barbara Sabourin, Director General, Therapeutic Products Directorate (TPD), HPFB, Health Canada: I will just add a small piece of clarification. We often use scientific experts in our expert advisory committees, and they are always required at every meeting to look at conflict of interest because the community is very active in clinical research, and we want to ensure that we capture any of those conflicts and deal with them at the beginning of meetings, so we are very active on the conflicts of interest side.
Senator Cordy: Is that information made available to the public?
Ms. Sabourin: The names of the experts that we use and short biographies are on our website. The agendas for the meetings are put up most of the time in advance, that is our goal, and also the records of proceedings are put up on our website.
Senator Cordy: Are the conflicts made public?
Ms. Sabourin: I am not positive on that. I believe so. We can check into that for you.
Senator Cordy: Thanks.
The Chair: Mr. Maxwell, before I go to Senator Seidman would you like to make any comments with regard to the responses to this point? You are not required to, but would you like to intervene?
Mr. Maxwell: No, I do not think I have anything to add but thank you for the request.
The Chair: Senator Seidman, some of your questions have been touched on, but would you like to pick one specifically?
Senator Seidman: The big question had to do with the barriers, and that was very much responded to, thank you.
Now you have me on the spot. Go ahead, thank you.
The Chair: We do not have a lot of time. I will come back to Senator Callbeck.
Senator Callbeck: I asked about inspecting clinical trial sites, and the Auditor General's report said that Health Canada should strengthen the risk-based approach for inspecting clinical trial sites. Health Canada said that they were doing a review that would be completed in the fall of 2011. Has that been completed? If so, what were the findings and have they been implemented?
Mr. Glover: Mr. Chairman, absolutely, we have developed a set of standard operating procedures that strengthens how we do the risk-based selection of the sites that we would inspect. We have begun to implement that. We would not declare that successful yet. We are evaluating to determine how well that is working.
As the Auditor General pointed out, there are some information gaps around whether the trials have to report if they are active or not, how many participants they have registered, so we are trying to look at the information we have, we do not have, how well we are able to develop a risk profile and assess the effectiveness.
We have introduced a number of other criteria, the type of clinical trial, the history of the site, potentially the sponsors, if the population is particularly at risk, if it is global, other adverse events. We are assessing how well that risk-based approach is working.
Overall, we have reported as part of the report that I said was just published on March 26 our findings of all of our inspections of clinical trials over the last year. Generally, we are finding that the trials struggle with some of the more basic issues, like record keeper standard operating procedures and ensuring that they are aware of some of those issues, but we do have a full report that we would be happy to table with the committee if there was interest, and it is also available publicly on our website.
The Chair: Senator Eggleton needs to get in another quick question.
Senator Eggleton: Very quick one here. You said, Mr. Glover, that you simply do not have the financial and human resources needed to do the rigorous safety-focused reviews that Canadians deserve in a timely manner. You then go on to say Health Canada has taken important steps to rectify the underlying resource constraints at the root of many of the Auditor General's negative findings.
Last week we had a budget that said we are cutting 19,000 people out. It said we are cutting all the departments by one percentage or another. How do you swim upstream on this?
Mr. Glover: Thank you for the question. We have ensured that our activities that are subject to user fees have, by and large, been untouched by those reductions. In my area of responsibility, reductions will be in those areas that are not subject to user fees. As the Assistant Deputy Minister for Health Products and Food Branch, we have a range of activities, not all of which are cost recovered, not all of which are solely the focus of this committee's activities.
For the areas the Auditor General focused on, we were simply not able to keep up with the volume of work. We now have the resources. I fully admit that we were struggling to keep up with just reviewing the inspections, but we were busy reviewing inspections, not developing standard operating procedures and checking how well we were doing against those things, so some of the good business practices you would expect we simply were not doing. Now we have the resources, we will be able to do that.
Senator Eggleton: Unless you raise the fees, are you robbing Peter to pay Paul?
Mr. Glover: The fees have been significantly increased, yes.
The other part of that underlying issue that the senator mentions, Mr. Chair, is the fees were introduced and they never escalated. We have now ensured with the new fees we have introduced there is a built-in escalator so we do not have to go through this large process a few years from now to say it is time to update the fees again because they are out of date. We want to ensure they do continue to escalate.
Mr. Maxwell: Mr. Chair, I am belatedly taking you up on the offer.
One thing I would add about resourcing, from our audit, we talked about it as some aspects, resources, were constrained. We highlighted several other things, so I think our sense and recommendation was that Health Canada should look at the resourcing side but equally well about streamlining existing operations to look at the process to see where efficiencies could be gained.
We drew particular attention to opportunities that may lie in using information that other foreign regulators have. As the Health Canada officials have said, quite often these products are already on the market in other places. Other scientists, just like Canadian scientists, have already been through those files, so we thought there was quite an important opportunity there.
The Chair: Thank you. I can see that the time moves on without our ability to affect it. I know if we introduce a new question that will take up more than the time before we have to leave.
Mr. Glover, is there a quick final comment you would like to make?
Mr. Glover: Only to the respond to the Auditor General's last intervention. He is absolutely correct, and if I go back to the testimony that I provided, we fully acknowledge that we have to move from being a domestic regulator to an international regulator. As Dr. Stewart pointed out, these are multi-national companies, the clinical trials and drugs they are introducing, so we have been moving aggressively to things like the Regulatory Cooperation Council and others to try to improve the exchanges we have with other jurisdictions so we can, just as the AG pointed out, share our science with other jurisdictions and benefit from the science they have already done.
The Chair: Thank you, and if I recall correctly, you appeared before this committee with regard to that business of fees and the new structure and how they were going to keep pace, so I am pleased to see that they actually are making a difference.
On behalf of the committee, thank you very much. We will follow up with the written questions that did not get covered. Once again, as always, if any additional thoughts occur to either group after you leave, we would welcome your input, and we will see a lot of, over the phases, both groups as we move forward.
(The committee adjourned.)