Adverse Drug Events

The 1999 IOM report To Err is Human: Building a Safer Health Care System has generated a great deal of discussion in the medical community and legislature because of the impact of ADEs on patient health and well-being, and because of economic implications. IOM analysts estimate that prescription medications are responsible for up to 7000 American deaths per year, with the cost of drug-related morbidity and mortality being nearly U.S. $77 billion per year. Their definition of ADEs includes both medication errors and adverse drug reactions (ADRs). Accurate statistics of the frequency of ADRs are difficult to assess for a particular drug since phase I–III of clinical research includes too small a sample size and frequently medications are taken for a short duration. For instance, rofecoxib (Vioxx) was a drug approved in 1999 as a safer alternative to first-generation nonsteroidal anti-inflammatory agents for elderly patients with pain. The drug was recalled on October 1, 2004 in the largest prescription drug withdrawal in history. The withdrawal was prompted after a new study examining the drug's impact on bowel cancer found that the drug caused an almost twofold increase in heart attacks and strokes. Although the Adenomatous Polyp Prevention on Vioxx® (APPROVe) trial began enrollment in 2000 and was being monitored by an independent data safety monitoring board, it was not stopped earlier because the results for the first 18 months of the trial did not show any increased risk of confirmed cardiovascular events with Vioxx®. The actual number of ADRs nationally reported is probably underestimated because the full range of patients likely to use the medications postmarketing are not included in premarketing studies. Frequently, these studies include patients with only one disease and exclude children, pregnant women, and the elderly. If a report is identified by a health professional or consumer, the Food and Drug Administration (FDA) has a voluntary reporting program to help identify and address these issues once the medication has become commercially available. However, it is estimated that the spontaneous reporting system captures only 1 to 10% of all adverse events., Therefore, this can be used only as a flag to stimulate further research in postmarketing surveillance studies. Communication and coordination among patients, physicians, pharmacists, and other health care professionals can help avoid these dangerous incidents., Pharmacists should cautiously recommend newly approved therapy by weighing the risk versus benefit, with an understanding that all information regarding adverse effects may not be available yet on a newly approved product. When a product is newly approved with claims of decreased frequency of side effects, these claims need to be tempered with the understanding that the depth of information that is available regarding these products is not as good as products that have been available for many years.

There may also be ADR implications when selecting medications for a formulary. When a new medication becomes commercially available, clinicians supporting a proactive formulary system will review and decide if that medication will be available for routine use for patients immediately. Because information regarding new medications is frequently limited, it may be wise to collect data on patients in a clinical setting and compare this use against a standard of how the drug should be used once the product becomes available in an institution. This can be accomplished through a medication use evaluation (MUE) program. Because the product is new, physicians and other health professionals need to know how to prescribe (select appropriate patient population and dose), administer, and monitor the drug to avoid ADEs and provide effective therapy. Many times, adverse effects of newly approved medications do not appear until a medication is used in a group of patients with multiple medical problems who are taking several other medications. Data acquired from this MUE will verify that the medication is indeed being used as recommended, and that it has been used safely.

Adverse events associated with dietary supplements provide an additional concern, because the manufacturers do not need to submit safety or efficacy data to the FDA prior to availability. Consumers and health practitioners have limited information to help them make decisions on safety. Large-scale studies that frequently include several thousand patients are required for a drug to be approved, but are not available with these products. Therefore, it is necessary to rely on reporting to the FDA after the supplement has become available to determine if there are safety concerns. In addition to having limited information on adverse effects, information is also limited in other areas such as appropriate dose, efficacy, and pharmacokinetics. Adverse effects that are reported to the FDA may be evaluated, and action may be taken. For instance, in 2004, the FDA prohibited sale of dietary supplements containing ephedrine alkaloids (ephedra) because of the limited data available on efficacy, and because of the risk of adverse health outcomes including myocardial infarction and stroke. In other cases, a communication to health care professionals may alert them to a particular side effect. For instance, recently the FDA issued a warning citing 25 reports of hepatotoxicity worldwide with kava, a dietary supplement used for several indications including insomnia. This product is still available in the United States. Because of these and other issues, most hospitals have policies regarding herbal product use.

Information on ADRs in patients receiving either medications or dietary supplements is frequently coordinated through an ADR program in a hospital. The ADR program for an institution has many components including identification of suspected side effects, assessment of probability, dissemination of information (documentation in the medical record and submission to a larger database of information), and monitoring of outcomes. In health care systems (e.g., hospitals), this initiative is performed by pharmacists, physicians, and other health professionals in a coordinated fashion. The ADR program is most often coordinated by the pharmacy department, and specifically, the drug information center, if available. Both medications as well as dietary supplements used for medicinal purposes are submitted to the coordinating group and evaluated in an ADR program. More information on ADEs can be found in .

Despite efforts to decrease the frequency of medical errors after the 1999 IOM report To Err is Human: Building a Safer Health System, many consumers are still dissatisfied with the quality of health care in the United States. In a recent survey, 40% of respondents believed that the quality of health care has gotten worse in the past 5 years, while only 17% said that it has improved. Thirty-four percent of respondents said that they or a family member had experienced a medical error at some point in their life. Efforts are ongoing to lobby for additional funding for initiatives to decrease the risk of medical errors in the United States. Because of the pharmacists' role in helping to identify and prevent ADEs in patients, this could have future implications.