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.