About CERTs
Annual Report Year 1
Year 1 Progress
Developing Knowledge | Managing Risk | Improving Practice | Informing Policies | Program-wide Activities
Managing Risk
People must have an accurate picture of the benefits and risks associated with therapies as used in practice. Our focus is on improving the ability to detect beneficial and harmful effects of therapies, then maximizing the benefits and minimizing the risks. The systems that we are developing will provide the information needed to stimulate basic research into mechanisms of disease and the effects of therapies.
Children and Adolescents
We know much more about the safety of drugs for adults than we do for children. We have begun a pilot study of a new reporting system for adverse drug events in children. For the larger issue of how many drug errors occur in children, we are studying another reporting system, MedMARx.
More than 20,000 children and teens in this country may be infected with HIV. How they respond to given doses of anti-HIV drugs such as protease inhibitors may differ from how adults respond. We are assessing the relation between the dose of protease inhibitors, the amount of drug in the bloodstream, measures of drug safety and effectiveness, and what may cause variations in the response to treatment.
Few tools exist to measure a child's health status and quality of life, which are an important part of the assessment of therapeutic effects. Existing tools typically are variations of those used in adults. We are grading and evaluating these tools, to tailor them to the needs of children. We also have proposed establishing a common definition or set of definitions for adverse medical events, to allow them to be measured consistently across studies.
Adults
Many drugs used to correct an irregular heartbeat carry an increased risk of death, especially many of the older drugs, but they continue to be prescribed in large numbers despite this risk. A newer agent for treatment of atrial fibrillation or flutter, dofetilide, appears not to increase mortality, but its use can carry an increased risk of other abnormal heart rhythms. The FDA therefore requires that doctors complete a risk-management program before using the drug.
Many prescribers may be unaware of the evidence or how to monitor therapy properly. We are now tracking the use of dofetilide at one center, before examining compliance with the FDA's rigorous requirements for education and monitoring with dofetilide use.
"To believe with certainty we must begin by doubting."
—King Stanislas I of Poland
For our drug-interactions project, we will be testing potential interactions in the laboratory. When this is complete, we will begin verifying their relevance with studies in humans.
We are harnessing the power of the Internet to aid in our efforts to manage risk. For example, we have been working with MedWatch scientists at the FDA to analyze cases of a potentially fatal, irregular heart rhythm (torsades de pointes). People can develop torsades de pointes because of an inherited gene, but they also can develop it after taking certain drugs, and women are more susceptible than men.
We have created a Web-based registry (http://www.qtdrugs.org) for physicians to report cases of torsades de pointes that are caused by drugs. The program will help identify individual drugs, drug interactions, and genetic mutations associated with this disorder.
Devices used in the treatment of heart disease generally undergo even less study than drugs, especially after the devices have been approved for use. We are working with the FDA, device manufacturers, and professional societies to develop models for learning more about cardiovascular devices. One model is to use existing databases.
We are working on a program to monitor outcomes of transmyocardial laser revascularization (TMR), a new device used to bring more blood to the heart muscle. In this case, the Society for Thoracic Surgeons (STS) holds the database. This project is partly funded by the Women's Health Initiative and includes partners from the FDA's Center for Devices and Radiological Health (CDRH) and the STS.
The elderly take an average of 16 prescription drugs each year and three to four of them at any given time. The likelihood that one is a drug that combats an inflammatory condition, such as arthritis, is high. Traditional anti-inflammatory drugs (but not steroids) carry increased risks of bleeding and ulcers in the gut, especially in older people. Newer agents, such as the cyclo-oxygenase (COX)-2 inhibitors, are presumed to cause less bleeding and fewer ulcers than the older drugs while being just as effective, but they also are much more expensive than over-the-counter drugs such as ibuprofen.
We are comparing the rates of ulcers among elderly men and women taking these new agents, those taking another anti-inflammatory drug, and people taking no such drug. We also are measuring the costs associated with disorders of the gut in these same three groups.