Reducing and Preventing Adverse Drug Events To Decrease Hospital Costs
Research in Action, Issue 1
Adverse drug events (ADEs) result in more than 770,000 injuries and deaths each year and cost up to $5.6 million per hospital, depending on size. Many ADE injuries and resulting hospital costs can be reduced if hospitals make changes to their systems for preventing and detecting ADEs. Some approaches found to be successful are summarized below.
ADEs Increase Costs
ADEs Cannot Be Predicted by Patient Characteristics or Drug Type
Medication Errors Are a Frequent Cause of ADEs
ADEs Can Be Prevented and Detected
Other Systems Can Prevent and Reduce ADEs
More Research Is Required To Fill the Gaps
Over 770,000 people are injured or die each year in hospitals from adverse drug events (ADEs),1-3 which may cost up to $5.6 million each year per hospital4,5 depending on hospital size. This estimate does not include ADEs causing admissions, malpractice and litigation costs, or the costs of injuries to patients. National hospital expenses to treat patients who suffer ADEs during hospitalization are estimated at between $1.56 and $5.6 billion annually.4-7.
Even though research on the cost and causes of ADEs has been reported for years in the medical literature, the problem was brought to the attention of a larger audience in late 1999 by a report by the Institute of Medicine (IOM), To Err Is Human: Building a Safer Health System. This report explores the events surrounding medical errors and the injuries that patients suffer as a result. The IOM concluded that the solution to preventing medical errors is "building a safer health system" that leads health care providers down the appropriate paths of treatment and limits their ability to make mistakes.8
Research in this area and the IOM report were based, in part, on studies sponsored by the Agency for Healthcare Research and Quality (AHRQ), the Federal agency charged with sponsoring research to improve the quality, appropriateness, and effectiveness of health care services.
Adverse Drug Events Increase Costs
Patient injuries resulting from drug therapy are among the most common types of adverse events that occur in hospitals.9 Although the incidence of ADEs and their effect on costs have been investigated in only a few hospitals in the United States, the implications are clear from published results that ADEs constitute a widespread problem that causes injuries to patients and disproportionately increases expenses.
Incidence rates of ADEs vary from 2 per 100 admissions to 7 per 100 admissions among the hospitals that have conducted ADE studies.1,5,10,11 A precise national incidence rate is difficult to calculate because various researchers use different criteria to detect and identify ADEs.12
ADEs can result in a number of different physical consequences, ranging from allergic reactions to death.1,4,5,9,10,12,13 One study estimated that 9.7 percent of ADEs caused permanent disability.14 Another study estimated that the increased risk of death for a patient who experiences an ADE is nearly twice that of a patient who does not.1
Figure 1 illustrates the distribution of several types of injuries among patients who suffered ADEs.
ADEs and their subsequent injuries lead to increased hospital costs. Depending on facility size, hospital costs annually for all ADEs are estimated to be as much as $5.6 million per hospital.4,5,7 Before the advent of managed care, hospitals would have shifted these costs to the patient or the insurance company. Today, however, hospitals are likely to absorb the extra expense.15 Patients who experience ADEs have longer, more expensive hospitalizations than patients who do not suffer ADEs. For example, at LDS Hospital in Salt Lake City, researchers found that patients who experienced ADEs were hospitalized an average of 1 to 5 days longer than patients who did not suffer ADEs, with additional costs of up to $9,000.1
Researchers conducting an AHRQ-funded study at Brigham and Women's Hospital and Massachusetts General Hospital found that, on average, ADEs increased the length of stay by as much as 4.6 days and increased costs up to $4,685.4
These research studies also found that the type of ADE affects length of stay and costs. For example, the costs attributable to ADEs at LDS Hospital ranged from $677 and almost 18 additional hours of hospitalization for itching to $9,022 and 5 1/2 additional days for a drug-induced fever.1
A prior study funded by AHRQ at LDS Hospital showed that patients with more severe ADEs (arrhythmia, bone-marrow depression, depression of the central nervous system, seizures, or bleeding) had an average length of stay of 20 days, patients suffering from less severe ADEs (those that required a change in therapy or a longer hospital stay) had an average stay of 13 days, and patients who did not suffer an ADE had an average stay of 5 days. Hospital costs for these patients were $38,007, $22,474, and $6,320, respectively.13
Adverse Drug Events Cannot Be Predicted by Patient Characteristics or Drug Type
Anticipating who will suffer an ADE, when, and from what medication is difficult. Research has not yet identified any valid predictors of the event. Patient characteristics currently are not useful predictors of an ADE because patients who have suffered ADEs are not a homogeneous group. Although older age, severity of illness, intensity of treatment, and polypharmacy have been associated with ADEs, no cause and effect relationship is known to exist between patients who suffer ADEs and age, comorbidity, or number of drugs received.2,12,13,16 However, ADEs are more likely to result in life-threatening consequences in intensive care unit (ICU) patients than in others.2
Medication type is not currently a predictor, either. All drugs have side effects, which are usually discovered during clinical trials required by the Food and Drug Administration (FDA).17 Because clinical trials are conducted on limited numbers of people under controlled conditions, additional problems are often discovered only after the medication has been prescribed for patients on a routine basis.17
For example, in studies funded by AHRQ at LDS Hospital, Brigham and Women's Hospital, and Massachusetts General Hospital, numerous classes of medications were found to be involved in ADEs, including antibiotics (19-30 percent of ADEs), analgesics or pain medications (7-30 percent), electrolyte concentrates (1-10 percent), cardiovascular drugs (8-18 percent), sedatives (4-8 percent), antineoplastic drugs (7-8 percent), and anticoagulants or blood-thinning drugs (1.3-3 percent).4,5,11,13,14,18 Other classes of medications, such as gastrointestinal drugs, antipsychotics, diabetic medications, antihypertensives, antidepressants, diuretics, hormonal agents, antihistamines, and antiemetics, also account for a small percentage of ADEs.4,5,12,18
AHRQ-Funded Research on Medication Errors and Adverse Drug Events
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Medication errors occur at any point in the medication administration process—during ordering, transcription (the process of manually transferring the physician order onto medication sheets), dispensing, and administering medications.11,12,19 However, as shown in Table 1, the majority of errors occur during the ordering and administration stages.5,19
Figure 2 shows the percent for selected types of errors that were commonly associated with ADEs. Other specific errors not shown in Figure 2 that have also been associated with ADEs include:
- Missed dose (7 percent).
- Wrong technique (6 percent).
- Illegible order (6 percent).
- Duplicate therapy (5 percent).
- Drug-drug interaction (3-5 percent).
- Equipment failure (1 percent).
- Inadequate monitoring (1 percent).
- Preparation error (1 percent).18,19,20
Adverse Drug Events Can Be Prevented and Detected
Hospital systems can be changed so that ADEs are more readily prevented and detected. Research funded by AHRQ shows that computerized systems can reduce medication errors and prevent ADEs. These studies indicate that anywhere from 28 to 95 percent of ADEs can be prevented.3-5,16,20
For example, at least two studies attribute 42-60 percent of ADEs to excessive drug dosage for the patient's age, weight, underlying condition, and renal function.1,13 Yet systems are available that prompt doctors to take these factors into consideration when ordering medications.
Even if an ADE is not preventable, computerized systems can detect ADEs early so that health care providers can initiate interventions to mitigate the effects and lessen the severity of the reaction.20 Hospitals usually rely on hospital staff to complete manual, written incident reports in order to track adverse events, improve quality, and assess risk. However, only a very few (6 percent) of ADEs are reported by this method.3 Automatic systems can improve detection considerably.
Computer monitoring systems prevent and detect ADEs
Computerized systems currently in use at hospitals perform many different functions. AHRQ has funded research on at least two functions essential to preventing and identifying ADEs—prevention and identification of ADEs and prescription order entry—to determine their effectiveness.
The following discussion of systems at LDS Hospital, Brigham and Women's Hospital, and Wishard Memorial Hospital gives examples of AHRQ-funded research that has focused on how automated systems can improve quality and decrease costs.
The HELP (Health Evaluation through Logical Processing) system at LDS Hospital in Salt Lake City identifies patients who may have an ADE through 24-hour monitoring of patient "signals."13 These signals, routinely recorded in a medical record, are clinical identifiers that indicate an ADE might have occurred:
- Change in respiratory rate, heart rate, hearing, or mental state.
The computer system alerts hospital staff if any of these signals appear or if other signals of possible ADEs occur, such as certain lab test results, high or low blood levels of certain medications, inappropriate medication dosage for the patient's age or weight, and pharmacy orders for medications generally used to treat allergic reactions.20
Other findings resulting from an AHRQ-funded grant showed that computer surveillance increased the identification of ADEs. At LDS hospital during 1988-89, ADEs were identified by hospital staff who voluntarily reported ADEs or medication errors. Beginning in 1989, computer monitoring was used to identify ADEs. As a result, significantly more ADEs were identified. LDS was able to isolate the medication errors that were occurring and implement practices that reduced the incidence of ADEs caused by known drug allergies and inappropriate administration.13,20 Because new signals were added to the computerized system to recognize ADEs during 1989-90, more ADEs were identified during 1990-91.20 Composite results from both studies are shown in Table 2.
Following AHRQ funding, LDS Hospital also developed a computer-assisted antibiotic-dose monitor that tracks renal function in patients on a daily basis and identifies patients who may be receiving excessive doses of antibiotics.21 The intervention study conducted with the antibiotic-dose monitor resulted in a reduction of the number, amount, and length of time patients received antibiotics, as well as a reduction in cost, number of days hospitalized, and ADEs, when compared to patients receiving antibiotics before the intervention (Table 3).21
By integrating the computer system to link pharmacy, lab, and other hospital information about the patient, pharmacists at LDS Hospital were able to identify and notify physicians of drug allergies and drug-drug interactions, as well as drug-food and drug-condition contraindications.13
Pharmacists also can monitor the amounts and levels of medication a patient is receiving to prevent ADEs that occur as the result of incorrect or excessive dosages. Notifying physicians immediately of a possible ADE gives them the chance to stop mild drug reactions before they escalate into severe ADEs. At LDS Hospital, when pharmacists notified physicians of an allergic reaction to a drug, 99 percent of the time the physician prescribed a different medication. As a result, during 1990-91, only eight ADEs resulted from allergic reactions.13
Brigham and Women's Hospital
The Brigham Integrated Computer System manages all administrative, financial, and clinical information as well as providing clinical-results reporting and computer-based physician order entry (POE). It also incorporates a detection system that identifies different combinations of orders and laboratory results that signal a possible ADE. For example, the system might alert hospital staff to clinical events such as orders for drug antidotes that, along with abnormal laboratory values, indicate a possible ADE. This alert would prompt the staff to further investigate the situation.10
Computer monitoring. To test the effectiveness of computer monitoring with regard to identifying ADEs, AHRQ sponsored a study that examined patient records of adult admissions to Brigham and Women's Hospital using three detection methods (computer monitoring, chart review, and voluntary reporting). A total of 617 ADEs were identified, some by more than one method. Although chart review found more ADEs (398) than computer monitoring (275) or voluntary reporting (23), computer monitoring was considered more efficient because it found more ADEs than voluntary reporting and took less time than chart review.10
Physician order entry (POE). According to another AHRQ-funded study at Brigham and Women's Hospital, computerized medication order entry has the potential to prevent an estimated 84 percent of dose, frequency, and route errors. Such a system eliminates illegible orders that lead to medication errors. Also, because the system requires the name of the medication, dosage, route, and frequency of administration to be entered, errors that arise from omission of critical information are eliminated. Programmed within the system are algorithms that check dosage frequency, medication interactions, and patient allergies. Once an order is entered, this computerized system also provides physicians with information about the consequences of therapy, benefits, risks, and contraindications.12
At Brigham and Women's Hospital, medication error rates and ADE rates were measured before and after implementation of a physician order entry computerized system.22 The system significantly reduced medication errors and the incidence of ADEs (Table 4). Other studies of the POE system at Brigham and Women's Hospital have shown that the computerized system decreased the incidence of preventable ADEs by at least 17 percent.23
Wishard Memorial Hospital
AHRQ has funded a number of studies at Wishard Memorial Hospital to support development of the Regenstrief Medical Record System (RMRS). The RMRS computer database contains a patient's entire medical record, including inpatient and outpatient data for Wishard's patients.24
One AHRQ-sponsored study examined whether or not automatically providing suggested "corollary" orders when physicians prescribe certain drugs electronically would reduce certain errors. For example, if a patient is receiving heparin (a blood thinner), a corollary order would be to order an initial platelet count and then another after 24 hours to determine if the patient is receiving too much or not enough medication. Another example of a corollary order is for tests that monitor electrolytes in a patient receiving a potassium supplement. The investigators predicted the incidence of ADEs would be reduced if these corollary orders were prompted.24
Results from this study showed that physicians who were offered corollary orders had the suggested tests done at twice the rate of physicians who were not offered the corollary orders (46.3 percent compared to 21.9 percent). As predicted, the incidence of ADEs was also reduced.24 The study also found that drug-related hospital incident reports were one-third lower for patients whose physicians wrote orders using computerized order-writing workstations than for patients whose doctors used paper forms.
Other research substantiates that computer systems can help reduce and prevent ADEs. A computer alert system at Good Samaritan Regional Medical Center was designed to detect and alert health care providers to prescription errors and ADEs. The computer database contained patient information such as demographics, pharmacy orders, drug allergies, radiology orders, and lab results.6
A series of primary prevention alerts identified possible prescription errors and recommendations for correction. For example, if lab tests revealed a low potassium or magnesium level or a high digoxin level for a patient prescribed digoxin, the computer recommended electrolyte replacement or reduction of digoxin dose. Secondary prevention alerts were programmed to indicate a potential ADE. For example, if a patient were suffering from delirium, the computer would prompt the pharmacist to review all medications to see if the delirium was drug induced.6
Improved systems can save direct costs
In 1992, 567 ADEs cost LDS Hospital $1.1 million in direct expenses (not including liability costs or the cost of injuries to patients). If 50 percent of these ADEs had been prevented, LDS Hospital would have saved $500,000 a year.1 Brigham and Women's Hospital would have saved $480,000 annually if the 17 percent decrease in ADEs had been applied hospital-wide; this figure does not include the costs to patients of injuries, malpractice costs, or the expense of additional work required to correct medication errors and treat patients who suffer from ADEs.23 Doctors at Wishard Memorial Hospital who used computer order-writing workstations had 13 percent lower inpatient charges (about $900 per hospitalization) than those who used paper forms.25
Tracking ADE occurrences to discover trends can save money also. At LDS Hospital, ADE trending identified 25 ADEs related to a new brand of vancomycin. This brand was being used because it cost $5,000 a year less than a brand they had previously used. However, treating the patients who suffered these ADEs cost $50,000 in extra care expenses. Thus, without tracking, the hospital would have assumed it was saving $5,000 a year, whereas switching brands actually cost the hospital $45,000.1
Other Systems Can Prevent and Reduce Adverse Drug Events
Computer systems are only part of the solution in preventing and reducing ADEs. Research studies (some funded in part by AHRQ) on medication errors support other methods that improve the medication delivery system. These include:
- Using the FDA's MedWatch program to report serious adverse drug reactions. Reporting would allow the FDA to pass safety information on to other providers, require labeling changes, or even withdraw a drug from the market. MedWatch reports can be submitted through the FDA's Web site at http://www.fda.gov/medwatch/ or by calling MedWatch at 1-800-332-1088 to obtain the necessary forms.17
- Improving incident reporting systems. The process of incident reporting can be streamlined to accommodate the health care provider's busy schedule and can offer feedback indicating that reported information is being used. Health care workers sometimes do not recognize that a change in a patient's condition is due to pharmaceutical treatment. Therefore, workers should be educated to identify signs and symptoms that might indicate an ADE and thus increase reporting of ADEs.3
- Creating a better atmosphere for health care providers to report ADEs where the person reporting the error does not fear repercussions or punishment.19 As the aviation industry has discovered, punishment is a deterrent to reporting an error; if an error is not reported, nothing can be done to correct the situation that created the potential for error.8 Health care personnel can find it difficult to acknowledge that they make mistakes.26
- Relying more on pharmacists to advise physicians in prescribing medications, and promoting health care provider education on medications.12,27 Brigham and Women's Hospital reduced the ADE rate in its Intensive Care Unit (ICU) from 33.0 per 1,000 patient days to 11.6 per 1,000 patient days by having a pharmacist participate in patient rounds with the ICU team. As a result, the hospital estimated it could reduce its costs by $270,000 per year simply by using the pharmacist's time in a different manner.27
- Improving the nursing medication administration and monitoring systems.12,28 These changes might include bar coding medications, along with additional warnings on medications with higher potential for harm, such as insulin, opiates, narcotics, potassium chloride, and anticoagulants.12
More Research Is Required To Fill the Gaps
AHRQ is the lead agency in the U.S. Department of Health and Human Services for supporting research designed to improve the quality of health care, reduce its cost, and broaden access to essential health services. AHRQ also is assuming responsibility for developing a major report to the Nation on health quality that will serve as a benchmark for all further efforts to improve patient safety.28
In 2000, AHRQ funded a number of research projects to improve quality and prevent medical errors. AHRQ awarded two grants to Brigham and Women's Hospital:
- "Improving Quality with Outpatient Decision Support."
- "Improving Safety by Computerizing Outpatient Prescribing."
Both of these research studies will focus on improving patient care and safety through the use of computerized systems.
AHRQ has funded a study at Stanford University, "Developing Best Practices for Patient Safety," which will develop strategies to improve patient safety in hospitals.
A grant awarded to the New England Medical Center, "TIPI Systems To Reduce Errors in Emergency Cardiac Care," will explore the effectiveness of using a time-sensitive predictive instrument to improve emergency care for patients suffering from acute cardiac ischemia.
A study at the University of Texas Health Science Center in Houston, Texas, "Teamwork and Error in Neonatal Intensive Care," will create a model of teamwork to reduce medical errors in preterm infants based on aviation models.
Funds also have been awarded to the Children's Research Institute for its study "Hospital-Reported Medical Injury in Children," which will examine the incidence of medical errors in pediatrics.
A study funded at the Virginia Commonwealth University will investigate the types of medical errors occurring in primary care from the patient's point of view and factors that contribute to their occurrence.
To improve patient care in nursing homes, AHRQ funded a study by the University of Massachusetts Medical Center, "Reducing Adverse Drug Events in the Nursing Home," which will test whether or not a computer-based monitoring system will lower the incidence of ADEs.
Over a 3-year period, AHRQ is funding Centers for Education and Research in Therapeutics (CERTs), an initiative to help reduce adverse drug events30 by increasing awareness of the benefits and risks of new uses or combinations of medical products and by improving the effectiveness of existing uses.31 The CERTs are located at:
- Duke University: Approved drugs and therapeutic devices in cardiovascular medicine.
- Georgetown University: Reduction of drug interactions, particularly in women.
- University of North Carolina: Rational use of therapeutics in the pediatric population.
- Vanderbilt University: Prescription medication use in the Medicaid managed care population.
- Harvard Pilgrim Health Care: Using large managed care databases to study prescribing patterns, dosing outcomes, and policy impact.
- University of Pennsylvania: Antibiotic drug resistance, drug utilization, and intervention studies.
- University of Alabama: Therapeutics for musculoskeletal disorders.32
During 2001, AHRQ will be funding a series of grants designed to reduce medical errors based on the integration of best practices, provider education, and advances in information technology. Requests for Applications (RFAs) will solicit research in the following areas:
- Health system error reporting, analysis, and safety improvement demonstrations.
- Clinical informatics to promote patient safety.
- Centers of Excellence for Patient Safety Research and Practice.
- Developmental Centers for Evaluation and Research in Patient Safety.
- Effect of working conditions on patient safety.
- Patient safety research dissemination and education.
Medication errors and ADEs are often the result of unique combinations of interactions among health care providers, patients, and medications. Costs of ADEs are very high and patients can suffer irreversible injuries that can result in permanent disability or death. Although ADEs cannot be predicted, they often can be prevented using computerized systems that:
- Monitor patients.
- Provide physician order entry.
- Integrate patient, pharmacy, and lab data.
- Track the incidence of ADEs.
By detecting and preventing ADEs, a hospital can reduce expenses while providing better quality care to its patients.
*2. Cullen DJ, Sweitzer BJ, Bates DW, et al. Preventable adverse drug events in hospitalized patients: A comparative study of intensive care and general care units. Crit Care Med 1997;25(8):1289-97.
*3. Cullen DJ, Bates DW, Small SD, et al. The incident reporting system does not detect adverse drug events: A problem for quality improvement. Journal on Quality Improvement 1995;21(10):541-8.
*4. Bates DW, Spell N, Cullen DJ, et al. The costs of adverse drug events in hospitalized patients. JAMA 1997;277(4):307-11.
*5. Bates DW, Cullen DJ, Laird N, et al. Incidence of adverse drug events and potential adverse drug events. JAMA 1995;274(1):29-34.
*10. Jha AK, Kuperman GJ, Teich JM, et al. Identifying adverse drug events: Development of a computer-based monitor and comparison with chart review and stimulated voluntary report. J Am Med Inform Assoc 1998;5(3):305-14.
*11. Bates DW, Boyle DL, Vander Vliet MB, et al. Relationship between medication errors and adverse drug events. J Gen Intern Med 1995;10(4):199-205.
*13. Evans RS, Pestotnik SL, Classen DC, et al. Prevention of adverse drug events through computerized surveillance. Proc Annu Symp Comput Appl Med Care 1992:437-41.
*16. Bates DW, Miller EB, Cullen DJ, et al. Patient risk factors for adverse drug events in hospitalized patients. Arch Intern Med 1999;159(21):2553-60.
*19. Leape LL, Bates DW, Cullen DJ, et al. Systems analysis of adverse drug events. JAMA 1995;274(1):35-43.
*20. Evans RS, Pestotnik SL, Classen DC, et al. Preventing adverse drug events in hospitalized patients. Ann Pharmacother 1994;28(4):523-7.
*24. Overhage JM, Tierney WM, Zhou X, et al. A randomized trial of "corollary orders" to prevent errors of omission. J Am Med Inform Assoc 1997;4(5):364-75.
*25. Tierney WM. Adverse drug events synthesis review—AHRQ. Personal correspondence with Christine Williams; 2001.
29. Eisenberg JM. The best offense is a good defense against medical errors: Putting the full-court press on medical errors. Speech given by Director, Agency for Healthcare Research and Quality, at the Duke University Clinical Research Institute; 2000 Jan 2.
30. Eisenberg JM. Statement on medical errors given by Director, Agency for Healthcare Research and Quality, before the Senate Appropriations Subcommittee on Labor, Health and Human Services, and Education; 1999 Dec 13.
32. Centers for Education and Research on Therapeutics: Overview. October 2000. Agency for Healthcare Research and Quality, Rockville, MD. URL: http://www.certs.hhs.gov/about/certsovr.htm