About CERTs
Annual Report Year 3
CERTs Progress
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University of Arizona Health Services Center—
Drug Safety Begins in School
The focus of the Arizona CERTs is to improve therapeutic outcomes and reduce adverse events caused by drug interactions, especially those affecting women. The CERTs is also focused on identifying and understanding mechanisms for drug-induced arrhythmias. These goals are accomplished by basic and clinical research programs and a variety of educational efforts.
Key Projects:
- Identifying gaps in education on therapeutics for women and developing responsive curricula
- Establishing and maintaining an international registry of cases of torsades de pointes
- Developing an online educational model on drug interactions, especially in women
A 1999 Institute of Medicine report estimated that as many as 98,000 Americans die each year from medical mistakes. Other studies have put the number at 44,000, but even with this more conservative estimate, medical errors would be one of the 10 worst killers in the United States, ahead of motor vehicle accidents, breast cancer, or AIDS.
One of the chief contributors to medical errors is adverse drug reactions (ADRs), resulting in more than 770,000 injuries or deaths each year. ADRs are responsible for $136 billion in additional healthcare costs each year, more than the total costs for cardiovascular disease or diabetes. With approximately 2.8 billion outpatient prescriptions filled each year, an amount equal to 10 prescriptions for every person in the nation, the potential for ADRs is high.
Despite recent innovations in healthcare organization, including electronic prescription entry and bar-coding of drugs, adverse drug reactions remain prevalent. Physicians cannot rely on technology alone to prevent them.
Dr. Raymond Woosley, director of the University of Arizona CERTs, and his colleagues are homing in on the root causes of these potentially disastrous interactions.
The major finding from the Arizona CERTs in the last year was the result of the Web-based International Registry for Drug-Induced Arrhythmia. A medication prescribed for over 45 years was discovered as a potential cause of a lethal arrhythmia. Arizona CERTs investigators performed basic laboratory research to prove that methadone, long used to treat narcotic addiction, could block potassium channels in the heart in ways similar to the prescription antihistamine terfenadine (Seldane®), a drug removed from the market for this very complication.
Arizona CERTs investigators then began a series of collaborative clinical research projects with government agencies and addiction treatment specialists to further define the nature of methadone's cardiac risk to women. They not only discovered the avenue by which methadone increases a woman's chance for arrhythmia, but also found that a component of a common methadone solution contributed as well.
These results stimulated a group of clinicians prescribing methadone to review their experience with the drug. As a result, they identified 17 cases, 10 of which were in women, and published their findings in the Annals of Internal Medicine.
The Arizona CERTs has recently begun a series of clinical research projects designed to identify risk factors for the development of life-threatening arrhythmias in patients treated with methadone. As with Seldane and other drugs that induce this form of arrhythmia, the available data from spontaneous cases reported to the U.S. Food and Drug Administration and the Arizona CERTs suggest that women are at higher risk than would be expected.
The Arizona CERTs clinical projects will examine gender in relationship to drug interactions and also evaluate the potential importance of drug interactions, heart rate, electrolytes and other factors that could predispose a patient to this form of lethal toxicity. While the whole story is being worked out through more research, drug treatment centers are now actively monitoring patients on methadone to assure its safety as a result of this new finding. The research has also guided the revision of treatment guidelines from the Substance Abuse and Mental Health Services Administration.
Like all CERTs, the Arizona CERTs knows its research findings, no matter how insightful, help no one if they are not properly disseminated. Their educational efforts on ADRs include a significant look at the fundamental medical education on this understudied topic, as well as a pioneering use of the Internet to spread their groundbreaking results.
In 2001, Dr. Woosley and his team surveyed medical schools and training programs across the country, including every director of a third-year internal medicine clerkship. The results were revealing.
Only 16% of internal medicine clerkships had formal lectures on adverse drug reactions/interactions. This medical specialty training was particularly important to the survey and the most telling on the state of education about adverse drug reactions.
“We chose internal medicine clerkship programs because, based on national averages, medical students spend an average of 12 weeks in this rotation, the most of any required clinical experience,” notes Dr. Woosley. “Also, the discipline of internal medicine trains future physicians to care for patients with complex medical problems that frequently require multiple medications, which may place patients at an increased risk of experiencing an adverse drug reaction.”
The results were published in the September 5, 2001 issue of the Journal of the American Medical Association. Clerkship and residency directors overwhelmingly agreed that a significant educational gap existed. In an era of increasingly complicated and time-consuming medical school curricula, how could this be addressed most efficiently?
Demonstrating the synergy across sectors that makes CERTs such a dynamic network, the Arizona CERTs and the Center for Drug Evaluation and Research at the FDA collaborated on a multimedia educational module. The program consists of a computer presentation, accompanying note set, and a pocket reference card. Every third-year clerkship director and residency training director in the U.S. received one.
The module covers the gamut of ADR topics, from the latest incidence and impact figures to the pharmacology behind drug interactions. In addition to the clinical nuts and bolts, the program also teaches young doctors how to develop a systematic approach to and a “tool box” for predicting and preventing adverse drug interactions.
Knowing that information is useless if it is not accessible, the Arizona CERTs and the FDA provide the educational module for download on their respective Websites.
This openness and interactivity are mainstays of the success of CERTs. The Arizona Center is already responsible for two Web sites devoted to gathering information on drug-induced arrhythmias: www.qtdrugs.org and www.torsades.org.
“Your list has been an invaluable resource…a real life saver! Thanks so much for your work in this area. I check your updated list every time my 14-year old son's meds are changed, along with checking with his electrophysiologist/cardiologist.”
—Maggie H., mother of a child with long QT syndrome.
Torsades.org is a list of drugs that produce a prolongation of the QT interval on an electrocardiogram (ECG). This can result in a dangerous arrhythmia called torsades de pointes. QTdrugs.org is a registry of cases of torsades de pointes. Physicians from across the country can access the registry and submit data on patients suffering from this arrhythmia. The doctors send in ECG readings, as well as a mouth swab or blood sample for genetic information.
From this wealth of data, Arizona CERTs seeks to identify not only the drugs responsible for these QT-interval abnormalities, but also the associated genetic risk factors. Armed with this information, the researchers hope to develop a test to identify those patients most at risk.
Further demonstrating their commitment to education and patient safety, Dr. Woosley and his group have lectured on ADRs at a number of grand rounds this year and Dr. Woosley presented their findings at the Arizona Health Sciences Center's 27th Annual Primary Care Update.