The economic burden of patient safety targets in acute care: a systematic review.

We developed a list of patient safety targets based on prior systematic reviews, 8 and existing national and international safety initiatives. 9 , 10 Patient safety targets were based on three characteristics: (1) a clinical outcome (eg, hospital-acquired methicillin-resistant Staphylococcus aureus [MRSA] infection) or a surrogate with an established link to a clinical outcome (eg, MRSA colonization); (2) high specificity as a measure of patient safety, as opposed to being a naturally occurring condition; and (3) a sufficiently long history of measuring this outcome in the literature, such that some studies on the economic burden could be expected. Patient safety targets included: adverse events, adverse drug events, ventilator-associated pneumonia, nosocomial urinary tract infection, antibiotic-resistant organism colonization, antibiotic-resistant organism infection, catheter-associated bloodstream infection, nosocomial Clostridium difficile -associated disease, surgical site infection, nosocomial pressure ulcers, wrong site surgery, retained surgical foreign bodies, contrast-induced nephropathy, nosocomial venous thromboembolism, and nosocomial fall-related injuries. We also included six improvement strategies (hand hygiene, rapid response teams, bundles, check-lists, automatic stop orders and bar coding) to ensure that we obtained all relevant economic literature that may not be captured through searches based solely on patient safety targets. We sought burden-of-illness or cost-of-illness studies. A search was performed using the MEDLINE database for articles published between 2000 and 2010 using the following search terms for costs: “costs and cost analysis” (Medical Subject Headings [MeSH]), “cost-effectiveness” (text word), “cost” (text word), and “financial management, hospital” (MeSH). We also searched the Agency for Healthcare Research and Quality Patient Safety Network (see http://psnet.ahrq.gov ) using the term “cost.” Reviews, editorials, and articles with no costing information in the abstract were excluded. One member of the study team (MK) excluded reviews, editorials, and articles with no costing information in the abstract. Two independent members of the study team (MK and EE) reviewed the remaining abstracts and obtained the full publication of any abstract considered potentially relevant by either member. Full publications of any abstracts considered potentially relevant were retrieved. Two investigators (EE and NM) independently evaluated each publication, using adapted relevant methodologic features (n = 21) as described by Drummond and Jefferson. 6 Each feature was arbitrarily scored one point, for a maximum score of 21. Features from the original list were excluded if they were not applicable to economic burden studies. If the two reviewer scores were within five points of one another, the higher score was taken. Otherwise, reviewers met to discuss and resolve discrepancies. We report all cost data in 2010 United States dollars for comparative purposes between patient safety targets. The original year and currency is stated in the summary data. Each cost was first converted to US dollars of the same year as indicated in the publication using the Bank of Canada currency converter. 11 Then, each converted cost was inflated to 2010 US dollars using the United States Department of Labor Bureau of Labor Statistics inflation calculator. 12

Our initial search yielded 1948 citations. We screened out 1749 abstracts that were review articles, editorials, or lacking in any costing information or results. We obtained and reviewed the remaining 199 publications. We excluded 41 publications for the following reasons: no evaluation of the economic burden of a patient safety target (n = 5), no primary data on economic burden (n = 23), not conducted in an acute care setting (n = 7) or were review papers with no primary data or analysis (n = 6). This left 158 potentially eligible publications. Ninety-seven (61%) of the 158 potentially eligible publications described no economic methodology despite reporting an estimate of economic burden and were excluded from further review ( Figure 1 ).

We found eight studies of the economic burden of surgical site infections. Study designs included prospective cohort (n = 1), retrospective cohorts (n = 3), retrospective case control (n = 2), and two nested case control designs. The average cost per case of surgical site infection in a general patient population was reported to be $1105, 22 $2604, 31 and $14,422 32 in three studies. In orthopedic patients, the median attributable cost of surgical site infection was $24,058. 33 Surgical site infection in patients after colorectal procedures was $14,868, 34 head-and-neck cancer-related surgery was $22,234, 35 coronary artery bypass graft procedures were $10,245, 36 and low transverse cesarean delivery were $2888 to $3574 37 per case. The latter study found similar attributable costs for surgical site infections using two different statistical methods for attributing costs (attributable cost for surgical site infection was $3529 by regression and $2852 by propensity score). 37 We found ten studies of the economic burden of nosocomial blood stream infections (one prospective, three retrospective cohorts, five retrospective case controls, and one case series). In general European patient populations, nosocomial bloodstream infection was associated with costs ranging from $2604 to $22,414. 22 , 31 , 38 – 41 One American study reported average incremental costs of $21,013. 42 In a pediatric intensive care unit (ICU), nosocomial bloodstream infection was estimated to cost $49,663. 43 Very-low-birth-weight infants with nosocomial bloodstream infection incurred average total costs $71,384 higher than those without the infection. 44 S. aureus bacteremia in patients with prosthetic implants was associated with $81,743 in costs per nosocomial case in one prospective case series. 45 We found two studies of the economic burden of nosocomial sepsis. In one retrospective cohort study, nosocomial sepsis was associated with mean additional costs of $33,872 46 per case. In one prospective cohort, ICU-acquired sepsis was associated with a mean increase of $44,178 in total costs per case. 47 We reviewed three studies of nosocomial rotavirus infection. One prospective cohort study estimated the costs associated with nosocomial rotavirus infection in children under 30 months of age, but did not provide a per-case result; this study estimated that the national cost of all cases in 1 year in Italy is $11,952,319. 48 Rotavirus in children under 48 months of age was associated with $3591 in costs per case in one prospective case series. 49 One prospective study with a nested case control reported $2210 in mean excess costs per case. 50 We found four studies of the economic burden of nosocomial urinary tract infections. These included one prospective, two retrospective cohorts, and one retrospective case control study. The average costs attributable to urinary tract infection ranged from $788 to $18,717. 22 , 31 , 51 , 52 We found four studies of the economic burden of nosocomial pneumonia. Two studies were prospective cohort studies and found that nosocomial pneumonia was associated with average additional costs of $856 53 and $23,624. 35 One German article detailed both a prospective case control and a retrospective case control, reporting average excess costs of $10,387 and $21,057, respectively. 54 In one study, the average cost attributable to ventilator-associated pneumonia in a pediatric ICU was $55,333. 55 We included three studies on the economic burden of nosocomial respiratory tract infections: one retrospective cohort, one retrospective case control, and one case control study. Respiratory tract infections were associated with additional mean costs of $3476 31 and $4509 22 in two studies, respectively. In one additional study, a case was defined as an infection of nosocomial respiratory syncytial virus; this infection was associated with mean costs of $13,083 per case. 56 We included 12 studies that described the economic burden of miscellaneous nosocomial infections. During a Pseudomonas aeruginosa outbreak, it was retrospectively estimated that infected patients who had been on mechanical ventilation incurred excess costs of $26,522. 57 Another retrospective case series investigated the economic impact of a norovirus outbreak that affected patients and staff, and did not provide a per-case cost estimate; dividing the total outbreak costs by the given number of case infections yielded a crude estimate of $1282 per case; 58 another similar study yielded an estimate of $2972 per case of outbreak-related norovirus. 59 In one drug-resistant Salmonella typhimurium outbreak in a Turkish neonatal ICU, cases incurred charges $1208 higher than controls. 60 A pertussis outbreak incurred total hospital costs of $34,956 and $50,668 in two hospitals. 61 The attributable costs during a Salmonella outbreak in one Australian tertiary care complex were reported in total costs rather than per case, and dividing by the number of cases yields an estimate of $2552 per case. 62 One retrospective case control study defined a case as a multidrug-resistant infection of Acinetobacter baumannii in burn patients, and reported a mean additional cost per case of $121,371. 63 In one Irish hospital, postoperative MRSA infection incurred additional costs of $13,651. 64 Another retrospective case series reported the attributable cost of MRSA to be $123,367 and vancomycin-resistant Enterococcus (VRE) to be $128,690. 65 One prospective study with a nested case control reported a median incremental cost of $9708 per case of Clostridium difficile -associated disease (CDAD). 66 One case control study reported the attributable costs of VRE in the medical ICU and in hospital to be $9543 and $14,532, respectively. 67 One retrospective cohort study examined the cost associated with potentially preventable complications and found it to be $634,432,559. 68 We identified two burden studies published since 2000. One study focused on nosocomial deep vein thrombosis after hip replacement surgery. 69 The cost of deep vein thrombosis was modeled in patients undergoing total hip replacement surgery, with Markov decision and univariate analyses. The article reported the annual per-patient cost of deep vein thrombosis to be $4676. Also provided are the discounted lifetime costs of $3779, as well as costs specific to deep vein thrombosis-related complications, namely post-thrombotic syndrome with ulcer ($4700) and pulmonary embolism ($8131). A retrospective US study of deep vein thrombosis (n = 15,679), pulmonary embolism (n = 7653) and post-thrombotic syndrome (n = 624) found annual attributable direct medical costs of $19,430 for deep vein thrombosis, $21,033 for pulmonary embolism, $28,713 for combined deep vein thrombosis, and pulmonary embolism, and $5455 for patient safety target. This study did not explicitly distinguish cases of nosocomial deep vein thrombosis, but 78% of the study cohort had abdominal or orthopedic surgery prior to the index venous thrombosis event. 70 We reviewed three burden-of-illness studies related to nosocomial falls. Two studies were case series. 71 , 72 The third study had a prospective cohort design. 73 One study 73 identified cases only in patients aged over 60 years. One study focused on legal compensation rather than hospital-related costs, 72 and neither of the other two articles 71 , 73 clearly stated what methods were used for determining attributable costs. There was one additional case control study reported attributable length of stay, but not costs. 74 Oliver found that 60.5% of legal claims related to in-hospital falls resulted in payment of costs or damages, with mean payment of $25,793. 72 Nurmi provided the cost per treating an in-hospital fall, estimated at $1359. 73 The third study did not describe costs per case or per fall, but did provide the total estimated attributable cost of all cases included in the study; dividing by the provided number of cases yields a crude estimate of $3230 per case. 71 We did not find any eligible studies for the following target conditions: nosocomial pressure ulcers, wrong site surgery, retained surgical foreign bodies, contrast inducted nephropathy.

We found that 61% of published studies on the economic burden of patient safety targets in acute care describe or report no clear costing methodology. Among the remaining 61 studies (39%), which did report costing methodology, there were wide variations in methodologic features and methods for attributing costs. These studies report wide estimates of the economic burden of patient safety in acute care. For example, the attributable costs of patient safety targets ranged from $2000 to $200,000. In general hospital populations, the cost per case of hospital-acquired infection ranged from $2132 to $15,018. Nosocomial bloodstream infections were associated with costs ranging from $2604 to $22,414. We also found no adequate economic burden data for important patient safety, such as wrong site surgery, retained surgical foreign bodies, contrast-induced nephropathy, and acute care-acquired pressure ulcers. Our results are consistent with the few prior reviews of the economic burden of patient safety in the acute care setting. A 2005 review identified 165 articles that included an economic analysis as an objective, but 35% of these articles provided no economic analysis, and 25% provided no primary economic data. The remaining studies had significant gaps in their costing methodology, and only 16% conducted sensitivity analyses that could address these limitations. 75 Another review of comparative economic evaluations of patient safety programs identified 40 studies published between 2001 and 2004, none of which provided sufficient information about both the cost of the prevention program and the cost of the patient safety being targeted. 76 A 1999 study estimated the economic burden of patient safety in Utah and Colorado at $1,442,024 per event (1996 US dollars). This early estimate is much higher than estimates in our systematic review, because the 1999 study evaluated not just direct acute care costs, but also outpatient direct health care costs after the event, as well as indirect (societal) costs such as lost workforce productivity up to age 75 years. None of the adverse event studies in our review considered this broad range of costs for a prolonged time horizon. 77 Our findings, in conjunction with these prior reviews, indicate that greater attention is needed to the methodologic standards for evaluating the economic burden of patient safety in the acute care setting. Better knowledge of the economic burden of patient safety will inform decisions about health policy, patient safety research programs, and improvement priorities. High quality economic burden studies are an essential component of comparative economic analyses, such as cost effectiveness studies. Most of the studies we identified considered only the acute care hospital economic perspective, but the economic perspective should extend beyond the acute care hospital, as it has been estimated that 22%–66% of the economic burden of patient safety in acute care are borne by the hospital. 78 , 79 Economic burden studies for patient safety should explicitly consider cost categories, legal, marketing and operational perspectives (direct or indirect), and time frames (including short- and long-term effects). There are also important methodologic considerations when attributing costs to patient safety, rather than the patient’s underlying condition. These considerations include the reliability of data sources used to identify patient safety, the adequacy of methods to control for confounding factors such as comorbidity and severity of illness, and the appropriateness of estimation methods including the incorporation of adverse event timing, matching methods, and regression modeling. 80 Differential timing of the occurrence of patient safety can lead to wide estimates of attributable costs. 81 – 83 Our review has several important limitations. First, we focused on studies published between 2000 and 2010 and indexed in MEDLINE. Studies outside of our search strategy may contain potentially useful data. For example, we did not include a 2010 study by the Society of American Actuaries because it was not indexed in MEDLINE. 84 However, our finding that 61% of studies provide no or limited costing methodology would be unchanged by the inclusion of a few additional studies. Second, we focused only on patient safety targets in the acute care setting. We did not include studies of patient safety targets from other settings, such as community or chronic care. Third, we did not evaluate the interrater reliability of our methodologic reviews. Our review method was designed to yield higher methodologic ratings, as we always took the higher rating of the two reviewers, yet we still identified a significant lack of methodologic features. Fourth, we arbitrarily assigned one point for each methodologic feature, so that we could report a simple summary measure of methodologic features. However, we recognize that methodologic features are not necessarily equally weighted. Finally, there was heterogeneity in study methods. Variability in costing and methodologic features made it impossible to generate summary estimates of economic burden for all patient safety targets. In summary, the burden of patient safety targets ranged from as little as $2000 to $200,000 in hospitalized individuals to $600 million at a population level. These results are dependent on the resources and costs included in the analysis. We found that the majority of published studies on the economic burden of patient safety targets in acute care described no costing methodology. The methodologic quality of the remaining studies was moderate, but there were wide variations in methodologic quality and methods for attributing costs. Greater attention is needed to the methodologic standards for evaluation of economic burden. This study highlights the limitations in the methods required to conduct economic evaluations in patient safety. Such limitations make decision-making regarding the adoption of patient safety initiatives difficult. The identification of limitations will allow for focused work on their improvement and will allow for the development of guidelines for future economic evaluation in patient safety.

Patient safety has received considerable public, professional, political, and scientific attention over the past decade. Although the human burden associated with adverse events is well established, the economic cost of patient safety has received less attention. Despite the substantial effort that has been expended to develop and implement safety improvements, there is uncertainty about both the economic impact of unsafe care and the improvement strategies that offer the best value. Significant resources have been expended across the world to reduce patient safety events through interventions, without clear improvements. 1 , 2 A fuller understanding of the economic burden of patient safety may inform health policy, health services research priorities, safety improvement priorities, and patient safety priorities. High quality data on economic burden of a condition are an essential component of comparative economic analyses such as cost-effectiveness analyses. The objective of an economic burden study is to describe the economic impact of a patient safety target. These types of studies generally examine the overall cost of the condition to an environment (eg, acute care setting, society). Economic burden studies should be based on rigorous analytical methods, be impartial and credible in the use of data, and be transparent for and accessible by the reader. 3 Economic burden studies are conducted using recognized frameworks which can be modified for specific target conditions. 4 , 5 Drummond and Jefferson and Drummond et al constructed a checklist of economic parameters used worldwide. 6 , 7 Economic burden studies should clearly outline the resource studies, the method for attributing costs to these resources, the method for measuring the resources used, the time frame for measuring the resources, and the economic perspective (hospital, third-party payer, or society) from which the resources were measured. Our objective was to determine the quality of literature in costing of the economic burden of patient safety targets in the acute care environment.

For the remaining 61 studies, the median methodologic feature score was 15/21 (mean 14.6 ± 21, range 9–20). All studies had essential methodologic features such as a statement of the research question, a statement of the economic importance of the research question, and a justification of the economic viewpoint. Fewer than 50% of these 61 studies reported productivity changes, discussed the relevance of productivity changes, provided details of inflation adjustments or currency conversions, or described any sensitivity analyses. Studies used different methods for identifying attributable cost, including propensity scores, case–controls, and regression analysis ( Tables 1 and 2 ). There was heterogeneity in study populations, resources incorporated, methods and results, so economic burden summary for all patient safety targets could not be calculated. We summarize the methodologic feature scores and range of results for each type of adverse event in Table 1 . The maximum score was 21. We provide detailed summaries of each study organized by patient safety target ( Table 3 ). We identified eight studies of the economic burden of adverse events and adverse drug events published since 2000. Five of these studies used a retrospective cohort study design, and relied on regression analyses to determine the attributable costs. Of these, two articles broadly focused on any adverse event or hospital-acquired complication. 13 , 14 An additional article evaluated the economic burden of a broad range of adverse events in patients with spinal cord injuries. 15 One article included five specific adverse events: medication errors, patient falls, urinary tract infection, pneumonia, and pressure ulcers. 16 Another article evaluated costs related only to surgical adverse events, but did not further define them. 17 The three remaining studies related to adverse events were either case series 18 or prospective cohorts with nested cases and controls. 19 , 20 Two of these studies defined a case as any adverse events 19 or a case leading to a medical dispute. 18 One study specifically evaluated adverse drug events. 20 Costs attributable to adverse events were $4571 19 and $10,074 14 in two studies. In patients with spinal cord injury, the cost attributable to adverse events was $6258, but were significantly higher for specific complications; for example, procedural complications in these patients were associated with additional costs of $20,183. 15 The cost attributable to adverse drug events was $2830. 20 In another study, medication error in medical and surgical cases were associated with costs of $361 and $568, respectively. 16 Attributable length of stay related to adverse events ranged from 0.77 days to 32 days. 15 , 19 , 20 Three of the eight articles did not record length-of-stay data. 16 – 18 We identified ten studies of the economic burden of general nosocomial infections not otherwise specified by type of infection. These included one prospective design, five retrospective cohort designs, three retrospective case control designs, and one decision model. Analytic methods included regression analysis, such as linear regression, multivariate regression, and ordinary least-squares regression analysis. In general hospital populations, the cost per case of hospital-acquired infection ranged from $2132 to $15,018. 21 – 27 Hospital-acquired infections cost $2910 in gastrectomy patients 28 and $21,856 29 in neonates. The estimated costs of hospital-acquired infections over one fiscal year in New Zealand in medical patients were US$5,626,640 and surgical patients were US$4,803,046. 30