This is the first U.S. study to utilize nationally representative data to examine annual rates of ADEs in the ambulatory setting. We estimate that approximately 4.5 million ambulatory ADE visits occur each year, and that these visits are associated with approximately 400,000 hospitalizations annually. Among outpatient (non-ED) ADE visits, the factor most strongly associated with ADE visits was the number of medications recorded for the visit.
Although this study cannot elucidate the mechanism by which medication burden leads to ADE visits, we suspect there are multiple contributing causes, as prior regional studies have suggested (Woods et al. 2007
). First, at the physiologic level, the use of multiple prescription and over-the-counter medications (NCHS 2010
) increases the potential for drug–drug interactions and difficulties with self-administration (Budnitz et al. 2007
; Leendertse et al. 2008
). Second, multiple studies have documented the inadequacy of medication counseling in ambulatory medical visits and in pharmacy settings (Svarstad 1974
; Scherwitz et al. 1985
; Cockburn, Reid, and Sanson-Fisher 1987
; Makoul, Arntson, and Schofield 1995
; Stevenson et al. 2000
; Richard and Lussier 2006
; Tarn et al. 2006
), Future research explicitly examining medication counseling and ADE risk are needed. Third, prior studies clearly demonstrate that patients often cannot accurately interpret or carry out medication instructions, clearly increasing potential for ADEs (Davis et al. 2006
; Schillinger et al. 2006
; Persell et al. 2007
; Wolf et al. 2007
). In-depth, real-time investigation of ambulatory ADEs would shed light on the relative contributions of these possible mechanisms.
Clearly, not all ADEs are preventable. Indeed, a baseline number of ADEs are an expected, and presumably acceptable, aspect of the risk–benefit equation in prescribing medications. However, given the substantial number of ADEs recorded in this nationally representative sample of ambulatory health care visits, further work to determine the proportion of preventable and ameliorable events must be a priority. This will require not only systematic surveillance for ambulatory ADEs but also investigation into underlying causes and preventability. As health information technology becomes more widespread in ambulatory health care delivery (Blumenthal et al. 2010
), automated surveillance for ADEs (Gandhi et al. 2010
) will become more feasible, and it should be a focus of future research and quality improvement.
Because prior studies have used different ADE detection methods, it is difficult to compare their ADE rates to this visit-based data. However, Gurwitz's study of older adults (Gurwitz et al. 2000
) used multiple detection methods, including patient survey and chart review, and uncovered a rate of 5 percent per year in those 65 and older, compared with our estimate of 3.8 per 10,000 persons per year. A similar study of adults receiving primary care found a rate of 27 per 100 patients (Gandhi et al. 2003
), using a combination of patient survey and chart review. The lower rates seen in this study are expected, because all ADEs would not be expected to lead to visits. Moreover, it suggests that providers are not aware of all ambulatory ADEs, as we have found in prior work (Sarkar et al. 2008
In these data, the relationship of older age with ADE risk is complex. In consonance with prior ED data (Budnitz et al. 2006
), older adults experience the highest rates of ADE visits per population. However, the largest absolute number of ADE visits occurred among 45–64-year-olds, suggesting that ADEs are a clinical and public health concern across the larger age spectrum. Moreover, our multivariate analysis of outpatient ADE visits demonstrates that after adjustment for race/ethnicity, gender, and insurance status, older age is no longer significantly associated with ADE visits. Our sequential adjustment strategy further revealed that after adjustment for comorbidities and number of medications, the effect of increasing age on ADE visits was further attenuated. While we may lack statistical power to capture an age effect, it is clear from this data that ADE prevention strategies must extend beyond geriatric populations to include a focus on medications and comorbidities.
Surprisingly, ADEs were more likely to be reported in primary care visits, although we expected that patients with multiple medications would be seeing subspecialists and have multiple prescribers. It is possible that ADEs were more likely to be uncovered and reported by primary care providers than at subspecialty visits with a narrower focus. An alternative explanation would be that relative ease of access to primary care means that patients experiencing ADEs are more likely to present acutely to their primary care providers than subspecialists.
Among those of “other” ethnicity, ADE visits were less likely. This finding is difficult to interpret in this very small and likely heterogenous group. More detailed race/ethnicity information within these national data sources, as well as more patient safety research among diverse populations, could illuminate this issue. Similarly, the lower odds of ADE visits among those lacking health insurance and those with “other” insurance persisted even after adjustment for all patient and visit characteristics. Although the “other” insurance category is no doubt heterogenous, it is likely to represent under-insurance, including catastrophic health insurance, as most public and private insurance types were separately categorized. As such, we can infer that uninsured and under-insured patients, even when chronically ill and taking multiple medications, may be less likely to seek medical care when they experience ADEs because of costs and access constraints, particularly in non-ED settings (McWilliams et al. 2007
Several limitations of the study should be noted. First, we have only captured ADEs that led to health care utilization; prior studies that surveyed patients would suggest that this under-estimates ambulatory ADEs (Gandhi et al. 2000
; Gurwitz et al. 2003
; Sarkar et al. 2008
). Second, use of a large national survey, which has the strength of allowing for reliable national estimates, contains limited data for each visit. From the NAMCS/NHAMCS questionnaire, we cannot determine whether the ADE was the primary reason for the visit, and they do not permit attribution of the ADE to a specific medication or treatment. Moreover, the survey has limited medication information. A maximum of eight medications can be included, and this likely underestimates the influence of polypharmacy on ADE visits. Medications discontinued at the visits are also not captured. We recommend that national surveys consider collecting more comprehensive ADE and medication information to help to fully illuminate the factors involved. Third, in using these estimates to calculate population rates for ADE visits, we cannot account for multiple ADE visits by the same individuals. Finally, our multivariate model does not elucidate underlying causes of ADE visits. Instead, we aimed to identify factors associated with ADE visits in order to characterize those at increased risk, with the goal of devising and testing strategies to prevent and ameliorate ambulatory ADEs. Despite these limitations, these are the first available national estimates for the burden of ADEs in ambulatory health care settings.
In this analysis, nearly one-third of ADE visits were associated with subsequent health care utilization (compared with 15 percent of visits overall), with 9 percent associated with hospitalization. In addition to the harm to patients, ambulatory ADEs are costly to the health care system. A prior study used data from a single academic health care system to estimate that charges for individuals experiencing ambulatory ADEs were U.S.$926 more than individual receiving ambulatory care with no ADEs (Burton et al. 2007
). The current data should better inform national cost estimates, and it certainly underscores the importance of preventing and ameliorating ambulatory ADEs.
We found that ADEs confer a significant burden on ambulatory health systems, and we suggest that the consequences and costs of ADEs in ambulatory settings may be comparable to or even greater than those in the inpatient and acute care setting, making ambulatory research and safety promotion all the more pressing.