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ADE Rate Uncertain, Reporting Systems Inadequate, GAO Tells Legislators

Nancy Tarleton Landis

Relatively little is known about the frequency of adverse drug events (ADEs), Janet Heinrich of the General Accounting Office (GAO) told congressional committee members in hearings on medical error. GAO's summary of available research on ADEs–adverse drug reactions and medication errors--was unveiled February 1 at a hearing held by the Senate Committee on Health, Education, Labor, and Pensions.

A spate of hearings on medical error and patient safety followed the release in late 1999 of the Institute of Medicine (IOM) report "To Err is Human: Building a Safer Health System." The GAO report on ADEs was requested by members of Congress more than a year ago; Heinrich presented the findings to health-related subcommittees of the House of Representatives as well as to the Senate committee. This article gives highlights of the report and of Heinrich's prepared testimony. 

How many ADEs? About one fifth of all adverse events caused by medical treatment are ADEs, Heinrich said, yet the full magnitude of the problem is elusive for several reasons. Clinical trials and postmarketing surveillance identify adverse reactions associated with specific drugs but do not focus on determining how often ADEs occur. ADE data from clinical trials are limited by the short duration of drug use and the relatively small number of patients involved. Patients in clinical trials are unlikely to reflect the full range of consumers who will use the drug. The first patients to receive newly marketed drugs are likely to be those who have not responded to older drugs and may be sicker than those in clinical trials. 

Once a drug is marketed, adverse event reporting to FDA is voluntary, and such reporting cannot determine the incidence of ADEs. The ADEs that are reported to FDA are unlikely to be representative (e.g., more reports are received during a drug's first few years on the market than later, and drug manufacturers with extensive postmarketing surveillance efforts gather more reports than other companies do). 

Attempts to quantify ADEs from all drugs have been limited. Only a few studies, conducted in specific hospitals or nursing homes, have provided insight into the overall incidence of ADEs. The occurrence of ADEs outside institutions is largely unexplored, so estimates of overall ADE incidence can be applied only to institutional settings, said the report. 

The best evidence. The most broadly based evidence, said GAO, comes from two studies using statewide samples of hospital inpatients with ADEs that resulted in disability, prolongation of hospital stay, or death. These studies found ADE rates per every 100 patients admitted of 0.56 (Colorado and Utah) and 0.72 (New York). Other studies with less restrictive definitions of ADE found rates of 2 to 30 ADEs per 100 patients. Two studies in individual nursing homes reported an incidence of 0.44 to 0.71 ADEs per patient month. 

Estimates questioned. Published estimates of costs and mortality associated with ADEs are "open to question because of the limited underlying data on overall incidence available to support them," the report states. Since even fewer data are available on fatalities from ADEs than on the overall rate of ADEs, "a stable estimate" of total fatalities is not possible. To illustrate the lack of solid data on mortality, the GAO report notes that one published projection of fatal adverse drug reactions in 1994 was based largely on data from 20 years earlier-when drug therapy was very different than it is today. 

Cost estimates that are based on studies at one or two hospitals have limited value on a national level, says the report. Estimates of adverse outcomes and associated costs depend on the specific setting or the experts used in the study. For example, the widely quoted estimates from studies by Johnson et al. (Archives of Internal Medicine, 1995, pages 1949-56) and Bootman et al. (Archives of Internal Medicine, 1997, pages 2089-96) were based on judgments of expert panelists about the probability of negative outcomes; the panelists' statements were "inherently subjective and would be likely to change if the composition of the panel changed," the GAO report states. 

Reporting systems limited. The deficiencies of reporting systems make it extremely difficult to gather useful information about adverse events, Heinrich testified. Systems for spontaneous reporting of adverse events by health care providers—both mandatory and voluntary systems–have serious limitations that result in "a high level of underreporting." FDA's adverse event reporting system is believed to capture only 1-10% of all ADEs and is used primarily to "signal" new ADEs for further investigation. Heinrich cited information collected by the IOM about mandatory reporting programs in 13 states; there was great variation in the annual numbers of adverse event reports, leading to the assumption that underreporting occurs even in mandatory programs. 

Valid information on the frequency of adverse events, Heinrich said, needs to come not from spontaneous reporting systems but from "proactive examination of a random sample of patient records," similar to the New York and the Colorado and Utah studies. Heinrich noted that the IOM report proposed a new Center for Patient Safety that would collect adverse event data through studies of that type. 

Other voices heard. Among those testifying at the February 1 hearing were Janet Woodcock, director of the FDA Center on Drug Evaluation and Research; Richard Platt, professor of ambulatory care and prevention at Harvard Medical School and director of research at Harvard Pilgrim Health Plan; and Michael R. Cohen of the Institute for Safe Medication Practices. Woodcock said FDA needs additional funding for postmarketing surveillance. 

Platt, according to a Philadelphia Inquirer report, said public concern about protecting the privacy of medical information could result in laws restricting access to patient information. This would make it difficult to conduct the type of ADE research that Heinrich advocates. Cohen supported voluntary reporting of adverse events, saying voluntary programs are more likely than mandatory programs to be effective. 

ASHP calls for mandatory reporting system. ASHP responded to the IOM report on medical error with a new position statement in support of a standardized, uniform nationwide system for mandatory reporting of adverse events that cause death or serious harm, as well as continued efforts to improve voluntary reporting. The policy is subject to approval by the 2000 House of Delegates. 

ASHP submitted its analysis of the IOM recommendations as written testimony to the Senate committee ( and has offered to act as a resource as Congress moves toward legislation on medical error. The Society also issued a legislative action alert urging members to ask their representatives in Congress to seek the advice of health-system pharmacists on ways to improve patient safety.