Good morning, honourable members.
The Office of Surveillance and Epidemiology focuses on monitoring post-marketing safety of human drugs and therapeutic biologics, on the development and evaluation of risk management programs, and on the prevention of medication errors. The monitoring of post-approval safety of the blood supply, vaccines, tissues and other biologic products, medical devices, and dietary supplements is located in other FDA units.
I am pleased and honoured to appear before you today to describe our post-marketing drug safety surveillance system and to answer any questions you may have.
FDA's mission is to ensure that safe and effective new drugs are available as quickly as possible and that drugs already marketed remain safe and of the highest quality. The monitoring and understanding of the safety of drug and therapeutic biologic products is a process that proceeds throughout the product's life cycle, spanning the period prior to first administration to humans, through the entire marketing life of the product.
In each stage of drug development, important drug safety information is obtained. At the time a drug is approved, there is a substantial amount of data regarding its safety profile. In the pre-approval review process, FDA reviews these data, along with data on the product's efficacy, to determine if the potential benefits of the drug exceed the potential risks for its intended use. The risks of a product are presented in a product's approved labelling, a document that can be updated throughout the product's post-marketing life.
Although the pre-approval testing of a drug is very rigorous--and the review of the data is very thorough--there are still some uncertainties about the complete safety profile of a drug when it is brought to market. Even the most extensive pre-market testing cannot anticipate all the potential adverse reactions that might occur. This is because clinical trials include a limited number of patients, a relatively short duration of treatment, relatively narrow patient populations, and often do not include special groups such as the elderly, children, pregnant women, or different ethnicities.
The goal of the post-marketing safety program is to identify adverse events that were not identified prior to approval and to understand better the spectrum of adverse events associated with a drug, including adverse events recognized prior to approval.
A core aspect of the post-marketing drug safety system in the United States is the reporting of adverse events to FDA. In the U.S., suspected adverse events in individual patients are generally identified at the point of care. Patients, physicians, nurses, pharmacists, or anyone else at the point of care who suspects there may be an association between an adverse event and a drug or a therapeutic biologic product can, but is not generally required to, report the adverse event to either the manufacturer or to the FDA.
The public can send reports directly to FDA via the MedWatch program, which was established in 1993 to allow health care providers and consumers to send a report about serious problems that they suspect or associate with any medical product--be it a drug, biologic, or medical device--directly to FDA. Members of the public can also voluntarily report suspected adverse events to a product's manufacturer, which is then subject to regulations regarding the submission of these reports to FDA.
For certain serious adverse events, manufacturers must report them to FDA in an expedited fashion, within 15 days. These requirements vary according to the marketing authorization status of the drug. For other adverse events, manufacturers report on a periodic basis, either quarterly or annually, depending on how long the drug has been on the market.
The adverse event reports that FDA receives from the public and from manufacturers are entered into a database known as the Adverse Event Reporting System, or AERS for short. FDA receives more than 450,000 reports a year. About 94% of them are from manufacturers. The remaining 6% are directly from the public via the MedWatch program. This database currently contains over four million reports of adverse events.
FDA safety evaluators review these individual case safety reports to determine if new safety information needs to be added to the products label. The review of adverse event reports is a complex process and cannot be covered here in detail. The analysis of these reports has been a cornerstone of our post-marketing safety system for over four decades, and will continue to be an important part of our drug safety system. However, the science of drug safety has evolved over the past two decades. New sources of data and other methodological approaches are being developed and implemented to complement the information we obtain from the reports we receive from patients and practitioners.
Today there are available to us certain large databases containing administrative medical data as well as electronic medical records. With increasing staffing and access, we anticipate much greater availability of these resources in the future. These are rich sources of information on the potential side effects of medications. Observational epidemiological studies, which include case control studies and cohort studies, are approaches that can confirm an association between a drug and an adverse event and can also provide a quantitative measure of that association. Observational epidemiological studies are time-consuming and costly. FDA uses them to examine important drug safety questions that cannot be answered with data from spontaneous report systems.
Clinical trials also provide another approach to examining drug safety questions. Many clinical trials are designed primarily to examine a drug's efficacy; nonetheless, they collect important safety information. Clinical trials for new doses and new uses of drugs often continue after a drug is approved. In some cases, clinical trials are designed primarily to examine a specific safety question. I would like to emphasize that many recent important drug safety actions in the U.S. have been on the basis of observational studies or clinical trials, and not on the basis of individual case safety reports.
Active surveillance systems are also being explored to identify and examine drug safety issues. Active drug safety surveillance systems, which take advantage of large repositories of automated health data, are now being developed and tested by multiple organizations. The commonality of these systems is that they do not rely on individual health care providers or patients to recognize and report adverse events that may be related to medication use. Rather, these systems often use sophisticated statistical methods to actively search for patterns in databases that link prescription use, outpatient medical care, and in-patient medical care in a way that might suggest the occurrence of an adverse event related to drug therapy.
While there is much interest in developing these systems, there is also much work to be done in the validation of these systems. In any case, one system is unlikely to address all drug safety problems for all patient populations. Thus, while the spontaneous reporting system has been the cornerstone of post-approval drug safety in the United States for several decades, new approaches based on large population-based databases are being used and are being explored, and will likely play an increasingly important role in this system.
In addition to our activities related to the monitoring of drug safety, we are interested in the safe use of drugs. Toward that end, we have implemented risk management plans for certain drugs whose benefits exceed their risks only when there is careful adherence to certain conditions of use. Many of our current efforts are directed at assessing the public health benefits of these plans, which involve all sectors of the health care system.
New legislation passed in the United States in September of 2007, the Food and Drug Administration Amendments Act, recognizes the importance of post-marketing drug safety by explicitly granting FDA the authority to require companies, under certain conditions, to make post-marketing safety-related labelling changes; to perform post-marketing studies and clinical trials to answer drug safety questions; and to implement risk evaluation and mitigation strategies for prescription products.
In addition, this legislation directs FDA to evaluate formally the safety of new drugs 18 months after they have been on the market, or after 10,000 patients have been treated. We are currently in the process of implementing these and other drug-safety-related provisions of this law.
To ensure that the public is aware of our safety findings, we have embarked on many efforts to enhance our public communications of safety-related findings. These include labelling information specifically directed toward patients, communication of new safety findings before the product label has been changed, and the publication of a quarterly drug safety newsletter. The Food and Drug Administration Amendments Act also includes provisions for providing information to the public.
Finally, but not least importantly, drug safety is a global activity. At FDA, our relations with our international counterparts are very important to us. We have especially close and productive relations with our colleagues at Health Canada in a multitude of settings, including at World Health Organization meetings, other international meetings, bilateral meetings, and routine information exchanges.
I'm happy to answer any questions you may have. Thank you.
We face all these challenges. I think our challenges are very similar.
In terms of reporting adverse events, we do not have a requirement in the United States for physicians, nurses, pharmacists, patients, or anyone else at the point of care to report an adverse event related to a drug to either the manufacturer or to the FDA. We understand that only a fraction of the adverse events that are really happening are reported. It's often quoted to be 1% to 10%. The real percentage is probably not known, but probably varies from drug to drug.
What's most important about these systems, though, isn't the number of reports you get, but the quality of reports you get. We get over 450,000 reports a year, but a lot of them are lacking the kind of critical information we'd need or want to make an accurate determination of what role, if any, the drug played in the adverse event. We can go back and get follow-up information. We can do that. That's very time-consuming and resource-intensive, and we don't have the resources for that.
With regard to other kinds of surveillance systems--these systems that rely on large databases of health care information and electronic medical records--FDA doesn't own them. The drug companies don't own them. These are owned by independent parties. In the United States, with a private health insurance system, they're often owned by health insurers or health plans. One of the challenges we're going to have is how to get everybody together: the FDA, other government agencies, the companies, the people who hold the data--health systems, hospital systems, practitioners, and academics who have the skill to look into these data. How do we bring all these people together--and handle important issues of patient privacy and confidentiality and things like that—to look at this data to see what's happening?
So FDA is just starting some initiatives.
Good afternoon. I will be giving my presentation in French.
I will begin by introducing myself. I am a lawyer specializing in health law. I am first and foremost a practitioner. My practice is a bit special because it deals with approximately half of all health care-related legal cases in Quebec. We basically defend the rights of users and patients in all areas of the health care system. Today I will be presenting from the point of view of patients and patients' rights, since this is a very important factor when we are talking about oversight of drugs after they come on the market. It is an important issue for patient safety.
I would first say that my practice is not an ordinary one; it is not an American-style approach either. We promote certain values such as quality, safety and accessibility, in particular. My comments today will focus primarily on our commitment to safety.
I am very pleased to be here and I thank the committee for giving us this opportunity to express our views. It is important that the whole process be reviewed because, if we look at the current regulations, it is clear that they are extremely weak and limited from the standpoint of the public, consumers, and those taking these drugs. The regulations are based mainly on self-regulation by the pharmaceutical companies as to the undesirable effects of drugs put on the market. The only control is the obligation that companies have under section 16 of the regulations to indicate to Health Canada any cases where the drug is found to have had an undesirable effect.
Under the act, Health Canada can ask for analyses, etc., but the public has no concept of how the companies interpret the rules. In other words, are they using a restrictive interpretation, which would result in too few cases being reported? Moreover, the public has no idea whether Health Canada checks or validates how the companies interpret the information. And people do not really know what Health Canada does with all the reports. The department is empowered to do additional analysis and testing, but I personally have not seen any reports or documentation or anything else to show that those rules are actually implemented.
There is also the possibility of clinical trials being carried out in phase 4 as well. There are a lot of rules governing clinical testing in phases 1, 2 and 3, but practically none for phase 4 testing. So there is a problem. That aspect should be looked at in the legislation.
There is also a system of voluntary reporting by health professionals and the general public. This is a voluntary, administrative system that does not have any process set out for it. Likewise, there is no follow-up mechanism for these reports. So an ordinary citizen or a professional might report a problem, but what happens to that report? Nothing is known about what the process might be. I think that this is an important precaution, since it is a major issue for health safety, as I have said.
As one possible approach, I would mention the Quebec Health Safety Act passed in 2002. In Quebec, the legislation did get changed. It resulted from a case that was dealt with by my office. Steps were taken to amend the legislation, to change the rules governing the safety of care. The premise was that a certain number of health care accidents occur in our health system. Similarly, there are certain undesirable effects of drugs as well. Up to that point, they were often considered to be anecdotal incidents that were talked about and reported but there was never any follow-up. In 2002, the legislation was changed to make the reporting of health care incidents and accidents mandatory.
Under the Quebec act, drug side-effects are considered to be health care accidents. The legislation requires that they be reported within each health care institution. Incidents must be reported to an internal body called the Risk Management and Health Care Quality Committee, which the law requires to be set up. So disclosure must be made to patients whenever they suffer complications, and they must be given support or told what action will be taken if such a thing happens. The committee is required to investigate all incidents to determine what occurred, prepare reports and recommendations, and keep a registry.
So Quebec's health system already has a very structured legal framework. This legal framework would be extremely useful in this case for reporting the adverse effects of drugs, or for reporting any unexpected results linked to taking prescription medication.
If we generally consider what might be more useful for Health Canada, it might be a good idea to take into account Quebec's system without creating any overlap. I believe that the legislation in Quebec and Manitoba is fairly similar. These two provinces are ahead of the others in this regard. Whatever the case may be, what is important is that we now have an organized and accountable system that allows people to report accidents. These cases are handled by an organization that investigates and makes recommendations to improve the situation.
Today, the voluntary disclosure system is purely administrative. There has been a significant increase in the number of disclosures made. This system, which is not very well known by the public, involves a lot of red tape. Despite this fact, it received thousands of disclosures. It's unbelievable. Further, I believe this is only the tip of the iceberg. My impression is that in reality, if the system were better known, more user-friendly, tighter and more accountable, we would receive many more complaints. And if that was the case, we would certainly be in a better position to improve the safety of the public.
As I said, these statements are often perceived by doctors as being nothing more than more bloody paperwork. Even if they see things which should be reported, most of the time doctors don't do so because they can choose between making a report to the federal government, which is a lengthy process, or to treat the patient. That's often their dilemma. Further, people have no idea what happens after they send in their statement. Under a post-market surveillance system of pharmaceutical products, perhaps disclosure should be mandatory for health care professionals. But even under a mandatory system, people usually under-report any incidents. If they are not forced to do so, the under-reporting will be even greater.
I know that this information is not relevant to the committee's mandate, but it is estimated that only between 4% and 5% of post-vaccination accidents or complications are reported, despite the fact that there is a mandatory reporting process in place for post-vaccination incidents. So just imagine the very low number of cases which would be reported under a system where that is not mandatory. However, I think this is one solution that we should consider.
Perhaps we should also force manufacturers to do a bit more. The packaging of drugs provides information and medical terms. It also contains a package insert describing the risks and effects of the medication, and so on. Why should we not force manufacturers to also include a telephone number or an Internet address which people could access to report any adverse reaction or complication? That way, manufacturers would be more accountable to the people who take their drugs. They also could indicate what to do in case of an adverse effect. I think this would be the very least that should be done.
I also believe that the regulations, or even the act, should outline the disclosure process, so that people realize it is important. For now, it's a purely administrative issue. People might think that the information ends up somewhere, but they don't really know where. There should be some kind of organization within Health Canada to conduct follow-ups and people should know what the process involves, rather than hearing that there were 30, 40 or 50 other complaints without being able to in any way appreciate the significance of what has happened.
Regarding the management of risks and the safety of these medications, we should benefit from provincial experience. It's clear that from a marketing point of view, we can benefit from provincial health care systems, at least in the case of Quebec, where there is a system for managing health care accidents which is structured, regulated and organized. In order to avoid overlap and wasting time, it would be important to benefit from that experience.
It is all the more imperative to do this because there is growing pressure to shorten the time it takes to licence drugs. The same applies to the access to medication under the Special Access Programme, for example. There is the risk that we will see more drugs ending up on the market for which the trials during phases 1, 2 and 3 will not have been extensive enough. It therefore becomes all the more important to strengthen monitoring during phase 4, to implement a legal framework, and to create ethics oversight committees under phase 4.
At present, ethics committees get almost no legal supervision. Their makeup and operation varies. With regard to the object of the research, we know that these practices are not very reassuring. Clearly, this needs thinking about. Unfortunately, a number of these aspects also fall under provincial jurisdiction.
Thank you very much. I'm honoured to be able to present to this committee, and I thank you for inviting us.
l was employed by the federal government between 1974 and 1989, and l was the chief policy analyst on the 1987 Patent Act amendments. Those created the Patented Medicine Prices Review Board and curtailed the use of compulsory licensing. l was acting director at the Patented Medicine Prices Review Board between 1987 and mid-1989, when I left to create a private company, Brogan Incorporated. The idea was to bridge the gap between government and the private sector. I saw when I was in government that there was not a lot of communication of much substance. So we've tried to create an empirical base on which both parties could communicate on equal grounds.
It was not planned at that time, but we now have the largest prescription database in the country. We have somewhere around 1.5 billion prescriptions in our database, coming from a very large number of sources. We have140 dedicated professionals analysing and reporting on these data. These data obviously permit very extensive and complete analysis on a large range of issues, and they do so without jeopardizing patient privacy, since we don't have a patient ID. There's a scrambled code put in place of any direct patient identifier. These are the kinds of data that Dr. Dal Pan was talking about...owned by the private sector in the U.S.
Over this period of time, we've pioneered the analysis of administrative drug data, including beating the Americans to the punch, which I'm proud to say. We've already done many of the current and proposed new proposals that you heard about from previous witnesses. These analyses have been used by government, academia, and industry to inform decisions about drug coverage and utilization. We've conducted a number of studies measuring drug cost by age groups, regional variations, and a detailed analysis of high-cost claimants. By the way, some of that is provided in a briefing document I provided earlier.
Recently we completed an analysis of the Alberta seniors drug plan, a project we worked on in conjunction with the Alberta Ministry of Health. Another study looked at drug use by 1.2 million Canadian children. This is the largest study on pediatrics ever done anywhere from an administrative database. You've probably heard about NPDUIS. That's a simple re-creation of what we have already created. It's been under way at an exorbitant cost. The government could have bought something right off the shelf.
l think the committee will see there is a direct relevance to our activities and the questions it quite astutely has put forward for examination. Specifically, l would like to speak to just a few points: capacity for monitoring; surveillance and research; public access to information; and adverse reaction reporting.
We've developed a significant database and expertise in handling these complicated and large data sets. There is no risk to patient privacy. However, the government does not make adequate use of this capacity for monitoring, for surveillance, or for research. I think too much effort is put into replicating what already exists.
While the knowledge derived from our existing database is powerful and can be used for the better management of health systems, we're hampered by limited access to data. While we have the largest prescription database, we don't have data from every provincial government. Some government officials have been resistant to making these kinds of data available, and there's no clear reason for their position. This means valuable information for the management and improvement of the health care system is not being used.
I will give you a specific example to explain. We've discussed a data-sharing arrangement with all the cancer agencies in the country, and the participants are very interested in creating a central repository. However, it's not an unwillingness but a lot of effort is required for them to extract the data to send to us. While we have one province on board now, and we're looking for several others, it's a very slow and tedious project. This means that there is no comparative information on the use of cancer therapies across the country, little data on the effectiveness of treatments, and of course little data on adverse events rates in real life.
I don't want to dismiss the value of clinical trials; this is an add-on to clinical trial information.
The most powerful information will come from an integrated database where you're putting together all aspects of a patient's health resource use—again, without knowing who the patient is—and that would be lab tests, doctor visits, hospital visits, drug use. This is not difficult to do, but it is a very large project. Everything is there to have it done, but there has to be a willing spirit to make it happen.
We hope this committee would encourage Health Canada, for one, to make more use of the private sector in monitoring surveillance and research in all areas of health care. There is a capacity among private sector participants to dramatically expand what government agencies are trying to accomplish.
We would also suggest that this committee encourage governments that hold data to share this with the private sector. A more broadly based data set would allow us to extend our analysis significantly, and the more eyes examining the data, the more insights that will be developed. Of course, this will be done under the privacy and confidentiality rules that prevail now. I believe that all of this information can play a pivotal role in managing many aspects of the health care system.
Thank you, Madam Chairman.