Evaluating the clinical and financial impact of severe sepsis with Medicare or other administrative hospital data.
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Critical Pathways↗
Biomedical subjects
Walter T Linde-Zwirble
Publications and source records attributed to Walter T Linde-Zwirble.
Methods to adjust for bias and confounding in critical care health services research involving observational data.
Observational data are often used for research in critical care. Unlike randomized controlled trials, where randomization theoretically balances confounding factors, studies involving observational data pose the challenge of how to adjust appropriately for the bias and confounding that are inherent when comparing two or more groups of patients. This paper first highlights the potential sources of bias and confounding in critical care research and then reviews the statistical techniques available (matching, stratification, multivariable adjustment, propensity scores, and instrumental variables) to adjust for confounders. Finally, issues that need to be addressed when interpreting the results of observational studies, such as residual confounding, causality, and missing data, are discussed.
Bias↗
How does lack of insurance affect use of intensive care? A population-based study.
OBJECTIVE: One in six Americans aged <65 yrs are without health insurance. Although lack of insurance is associated with reduced access to many health services, the relationship between lack of insurance and use of intensive care services is unclear. We sought to compare the use of intensive care by insured and uninsured populations. DESIGN: Retrospective population-based cross-sectional study of five U.S. states (Florida, Massachusetts, New Jersey, New York, and Virginia), analyzing use of hospital and intensive care unit (ICU) services by all residents of these states <65 yrs of age. Data sources included the five 1999 state hospital discharge databases and the 2000 U.S. Census Bureau Current Population Survey. SETTING: Nonfederal hospitals in the five states (all hospitalizations in these during 1999). INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: There were 39.3 million and 7.8 million individuals aged 0-64 yrs with and without insurance, respectively, in the five-state sample. The uninsured population was far less likely to be hospitalized (odds ratio [OR], 0.458; 95% confidence interval [CI], 0.456-0.460; p < .001) and to be admitted to the ICU (OR, 0.581, 95% CI: 0.576-0.587, p < .001). Differences persisted irrespective of age, gender, ethnicity, or reason for admission. Among those hospitalized, the uninsured were more likely to receive intensive care (OR, 1.24; 95% CI, 1.22-1.25; p < .01). Hospital mortality rates for patients admitted to the ICU ranged by age from 4.0% to 6.9% for the uninsured and from 2.7% to 5.5% for the insured (OR, 1.12-1.54; p < .01). CONCLUSIONS: Americans without insurance use ICU services less often than those with insurance, primarily because of decreased likelihood of hospital admission in the first place. Outcome is worse for those who are admitted to the ICU, possibly because they are sicker when they seek care.
Adolescent↗
Healthcare costs and long-term outcomes after acute respiratory distress syndrome: A phase III trial of inhaled nitric oxide.
OBJECTIVE: To determine the costs and long-term outcomes of acute respiratory distress syndrome (ARDS) in previously healthy adults. To determine whether treatment with inhaled nitric oxide affects these costs and outcomes. DESIGN: One-year follow-up of a randomized trial of inhaled nitric oxide. Hospital bills were collected, and follow-up was performed at hospital discharge, 6 months, and 1 year. SETTING: Forty-six U.S. centers. PATIENTS: Three hundred and eighty-five previously healthy adults with ARDS. INTERVENTIONS: Subjects were randomized to 5 ppm inhaled nitric oxide or placebo gas. MEASUREMENTS AND MAIN RESULTS: One-year survival was 67.8%, with no difference by treatment arm (67.3% vs. 68.3% for inhaled nitric oxide vs. placebo, p = .71). Hospital costs from enrollment to discharge were high and similar in the inhaled nitric oxide and placebo arms ($48,500 vs. $47,800, p = 0.8). There were also no differences in length of stay or Therapeutic Intervention Scoring System points. Almost half (43.4%) of subjects were discharged to another healthcare facility or to home with professional help, and 24.1% were readmitted in 6 months, with no differences between groups. At 1 year, survivors reported low quality of life with no differences by treatment arm (Quality of Well-Being score [range 0-1], 0.61 vs. 0.64 for inhaled nitric oxide vs. placebo, p = .11) and poor function with no differences by treatment arm (32.5% returned to </=5 points of baseline Activities of Daily Living [range 0-100], 63.3% returned to </=10 points, and the remaining 36.7% suffered a mean decrement of 27 points). CONCLUSIONS: ARDS, even in previously healthy adults, not only is followed by poor survival, quality of life, and function but also is associated with high costs of care and postdischarge resource use. Inhaled nitric oxide at 5 ppm had no effect on these outcomes.
Administration, Inhalation↗
Racial variation in end-of-life intensive care use: a race or hospital effect?
OBJECTIVE: To determine if racial and ethnic variations exist in intensive care (ICU) use during terminal hospitalizations, and, if variations do exist, to determine whether they can be explained by systematic differences in hospital utilization by race/ethnicity. DATA SOURCE: 1999 hospital discharge data from all nonfederal hospitals in Florida, Massachusetts, New Jersey, New York, and Virginia. DESIGN: We identified all terminal admissions (N = 192,705) among adults. We calculated crude rates of ICU use among non-Hispanic whites, blacks, Hispanics, and those with "other" race/ethnicity. We performed multivariable logistic regression on ICU use, with and without adjustment for clustering of patients within hospitals, to calculate adjusted differences in ICU use and by race/ethnicity. We explored both a random-effects (RE) and fixed-effect (FE) specification to adjust for hospital-level clustering. DATA COLLECTION: The data were collected by each state. PRINCIPAL FINDINGS: ICU use during the terminal hospitalization was highest among nonwhites, varying from 64.4 percent among Hispanics to 57.5 percent among whites. Compared to white women, the risk-adjusted odds of ICU use was higher for white men and for nonwhites of both sexes (odds ratios [ORs] and 95 percent confidence intervals: white men = 1.16 (1.14-1.19), black men = 1.35 (1.17-1.56), Hispanic men = 1.52 (1.27-1.82), black women = 1.31 (1.25-1.37), Hispanic women =1.53 (1.43-1.63)). Additional adjustment for within-hospital clustering of patients using the RE model did not change the estimate for white men, but markedly attenuated observed differences for blacks (OR for men =1.12 (0.96-1.31), women = 1.10 (1.03-1.17)) and Hispanics (OR for men =1.19 (1.00-1.42), women = 1.18 (1.09-1.27)). Results from the FE model were similar to the RE model (OR for black men = 1.10 (0.95-1.28), black women = 1.07 (1.02-1.13) Hispanic men = 1.17 (0.96-1.42), and Hispanic women = 1.14 (1.06-1.24)) CONCLUSIONS: The majority of observed differences in terminal ICU use among blacks and Hispanics were attributable to their use of hospitals with higher ICU use rather than to racial differences in ICU use within the same hospital.
Adult↗
Cost-effectiveness of fixed-dose combination of isosorbide dinitrate and hydralazine therapy for blacks with heart failure.
BACKGROUND: Fixed-dose combination of isosorbide dinitrate/hydralazine (ISDN/HYD) improved clinical outcomes in the African-American Heart Failure Trial (A-HeFT). We assessed the resource use, costs of care, and cost-effectiveness of ISDN/HYD therapy in the A-HeFT trial population. METHODS AND RESULTS: We obtained resource use data from A-HeFT, assigning costs through the use of US federal sources. Excluding indirect costs, we summarized the within-trial experience and modeled cost-effectiveness over extended time horizons, including a US societal lifetime reference case. During the mean trial follow-up of 12.8 months, the ISDN/HYD group incurred fewer heart failure-related hospitalizations (0.33 versus 0.47 per subject; P=0.002) and shorter mean hospital stays (6.7 versus 7.9 days; P=0.006). When study drug costs were excluded, both heart failure-related and total healthcare costs were lower in the ISDN/HYD group (mean per-subject heart failure-related costs, 5997 dollars versus 9144 dollars; P=0.04; mean per-subject total healthcare costs, 15,384 dollars versus 19,728 dollars; P=0.03). With an average daily drug cost of 6.38 dollars, ISDN/HYD therapy was dominant (reduced costs and improved outcomes) over the trial duration. Assuming that no additional benefits accrue beyond the trial, we project the cost-effectiveness of ISDN/HYD therapy using heart failure-related costs to be 16,600 dollars/life-year at 2 years after enrollment, 37,100 dollars/life-year at 5 years, and 41,800 dollars/life-year over lifetime (reference case). CONCLUSIONS: ISDN/HYD therapy, previously shown to improve clinical outcomes, also reduced resource use and costs in A-HeFT, primarily because of a large reduction in hospitalizations. Long-term use of ISDN/HYD therapy should be associated with a favorable cost-effectiveness profile in this population.
Black People↗
Impact of HIV/AIDS on care and outcomes of severe sepsis.
INTRODUCTION: There has been dramatic improvement in survival for patients with HIV/AIDS; however, some studies on patients with HIV/AIDS and serious illness have reported continued low rates of intensive care. The purpose of this study was to examine patterns of care and outcomes for patients with severe sepsis and HIV/AIDS and compare them with those of patients with severe sepsis without HIV/AIDS. METHODS: We assessed data from all 1999 discharge abstracts from all non-federal hospitals in six US states. Patient demographic characteristics, discharge diagnoses, resource use, and outcomes were extracted. Analyses were performed using chi-square, Wilcoxon rank sum, or regression techniques, as appropriate. RESULTS: We identified 74,020 patients with severe sepsis (7,638 (10.3%) had HIV/AIDS) using ICD-9-CM codes. Patients with severe sepsis and HIV/AIDS had a similar mean length of stay (16.9 days versus 17.7 days; p = 0.0669), had lower mean hospitalization cost (24,382 dollars versus 30,537 dollars; p < 0.0001), were less likely to be admitted to the intensive care unit (37% versus 56%; p < 0.0001), and had a greater mortality (29% versus 20%; p < 0.0001) than those without HIV/AIDS. After adjustment for cohort differences, patients with severe sepsis and HIV/AIDS had increased likelihood of death (OR (95% CI) = 2.41 (2.23-2.61)) and were substantially less likely to be admitted to the intensive care unit (OR (95% CI) = 0.54 (0.51-0.59)). When compared with those with severe sepsis and HIV/AIDS, patients with severe sepsis without HIV/AIDS were universally more likely to be admitted to the intensive care unit, even when they had comorbid illnesses with equal or worse expected in-hospital mortality (e.g., metastatic cancer). CONCLUSION: For patients with severe sepsis, there are differences in care and outcomes for those with HIV/AIDS. Further research is needed to examine the delivery of care for patients with severe sepsis and HIV/AIDS.
Adult↗
Incidence, cost, and mortality of neutropenia hospitalization associated with chemotherapy.
BACKGROUND: Neutropenia is a common side effect of chemotherapy, often requiring hospitalization for treatment of severe cases. Neutropenia hospitalization (NH) rates have been reported in individual studies, but national estimates are needed. METHODS: Chemotherapy-induced NHs were identified in the 1999 hospital discharge data bases from 7 states. Cancer and chemotherapy prevalence data from the National Cancer Institute's Surveillance, Epidemiology, and End Results Program and the National Cancer Data Base were used to calculate national NH rates for 13 cancer types. NH cost was estimated by multiplying charges by institution-specific, cost-to-charge ratios from the 1999 Centers for Medicare and Medicaid Services Hospital Cost Report. NH incidence was projected to national levels using population data from the United States Census and the Centers for Disease Control and Prevention. RESULTS: There were 20,780 discharges with documentation of cancer, chemotherapy, and neutropenia identified. Projecting to national levels, NH incidence was estimated at 60,294 cases (7.83 cases per 1000 cancer patients). The mean NH cost was 13,372 dollars. The mortality rate among patients with NH was estimated at 6.8% or 1 death for every 14 hospitalized patients. Among 13 selected cancer types, the NH rate was 34.20 cases per 1000 patients receiving chemotherapy (1 in 29 patients). NH was particularly common in patients with hematologic tumors, with an incidence of 43.3 cases per 1000 patients with such tumors (1 in 23 patients). The average NH cost for hematologic malignancies was 20,400 dollars, more than double the cost of NH for solid tumors. CONCLUSIONS: According to the current study, NH affects > 60,000 patients with cancer each year in the United States, with an average cost of 13,372 dollars per hospitalization and an associated inpatient mortality rate of 6.8%.
Adolescent↗
Dynamic microsimulation to model multiple outcomes in cohorts of critically ill patients.
BACKGROUND: Existing intensive care unit (ICU) prediction tools forecast single outcomes, (e.g., risk of death) and do not provide information on timing. OBJECTIVE: To build a model that predicts the temporal patterns of multiple outcomes, such as survival, organ dysfunction, and ICU length of stay, from the profile of organ dysfunction observed on admission. DESIGN: Dynamic microsimulation of a cohort of ICU patients. SETTING: 49Forty-nine ICUs in 11 countries. PATIENTS: One thousand four hundred and forty-nine patients admitted to the ICU in May 1995. INTERVENTIONS: None. MODEL CONSTRUCTION: We developed the model on all patients (n=989) from 37 randomly-selected ICUs using daily Sequential Organ Function Assessment (SOFA) scores. We validated the model on all patients (n=460) from the remaining 12 ICUs, comparing predicted-to-actual ICU mortality, SOFA scores, and ICU length of stay (LOS). MAIN RESULTS: In the validation cohort, the predicted and actual mortality were 20.1% (95%CI: 16.2%-24.0%) and 19.9% at 30 days. The predicted and actual mean ICU LOS were 7.7 (7.0-8.3) and 8.1 (7.4-8.8) days, leading to a 5.5% underestimation of total ICU bed-days. The predicted and actual cumulative SOFA scores per patient were 45.2 (39.8-50.6) and 48.2 (41.6-54.8). Predicted and actual mean daily SOFA scores were close (5.1 vs 5.5, P=0.32). Several organ-organ interactions were significant. Cardiovascular dysfunction was most, and neurological dysfunction was least, linked to scores in other organ systems. CONCLUSIONS: Dynamic microsimulation can predict the time course of multiple short-term outcomes in cohorts of critical illness from the profile of organ dysfunction observed on admission. Such a technique may prove practical as a prediction tool that evaluates ICU performance on additional dimensions besides the risk of death.
Cohort Studies↗
Severe sepsis epidemiology: sampling, selection, and society.
Three new articles in Critical Care add to an expanding body of information on the epidemiology of severe sepsis. Although there have been a range of approaches to estimate the incidence of severe sepsis, most studies report severe sepsis in about 10 +/- 4% of ICU patients with a population incidence of 1 +/- 0.5 cases per 1000. Importantly, the availability of ICU services may well determine the number of treated cases of severe sepsis, and it seems clear that these studies are reporting the treated incidence, not the incidence, of severe sepsis. In the future, we must focus on whether all severe sepsis should be treated, and, consequently, what level of ICU services is optimal.
Consensus↗
Use of intensive care at the end of life in the United States: an epidemiologic study.
OBJECTIVE: Despite concern over the appropriateness and quality of care provided in an intensive care unit (ICU) at the end of life, the number of Americans who receive ICU care at the end of life is unknown. We sought to describe the use of ICU care at the end of life in the United States using hospital discharge data from 1999 for six states and the National Death Index. DESIGN: Retrospective analysis of administrative data to calculate age-specific rates of hospitalization with and without ICU use at the end of life, to generate national estimates of end-of-life hospital and ICU use, and to characterize age-specific case mix of ICU decedents. SETTING: All nonfederal hospitals in the states of Florida, Massachusetts, New Jersey, New York, Virginia, and Washington. PATIENTS: All inpatients in nonfederal hospitals in the six states in 1999. INTERVENTION: None. MEASUREMENTS AND MAIN RESULTS: We found that there were 552,157 deaths in the six states in 1999, of which 38.3% occurred in hospital and 22.4% occurred after ICU admission. Using these data to project nationwide estimates, 540,000 people die after ICU admission each year. The age-specific rate of ICU use at the end of life was highest for infants (43%), ranged from 18% to 26% among older children and adults, and fell to 14% for those >85 yrs. Average length of stay and costs were 12.9 days and $24,541 for terminal ICU hospitalizations and 8.9 days and $8,548 for non-ICU terminal hospitalizations. CONCLUSIONS: One in five Americans die using ICU services. The doubling of persons over the age of 65 yrs by 2030 will require a system-wide expansion in ICU care for dying patients unless the healthcare system pursues rationing, more effective advanced care planning, and augmented capacity to care for dying patients in other settings.
Adolescent↗
No longer the "expensive scare unit"?
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Cost-Benefit Analysis↗
Medicare intensive care unit use: analysis of incidence, cost, and payment.
OBJECTIVE: To determine the incidence, cost, and payment for intensive care unit services among Medicare beneficiaries. DESIGN: Retrospective observational database cohort study. SETTING: All nonfederal hospitals with intensive care unit beds (n = 5003) paid through the inpatient prospective payment system (IPPS). PATIENTS: We used all fiscal year 2000 Medicare IPPS hospitalizations with consistent payment information (n = 10,657,587). INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: We examined the distribution of cost and payments overall, by hospital type, and by diagnosis related group. Intensive care was used in 2,353,208 cases (21.1%). The overall incidence was 59.8 cases per thousand beneficiaries in the aged (65+) population, increasing with age from 36.2 (65-69) to 91.6 (85+). Intensive care unit patients cost nearly three times floor patients (4,135 dollars vs. 5,571 dollars), with two thirds of costs associated with the intensive care unit portion of the stay, 2,278 dollars per intensive care unit day. However, intensive care unit cases were paid at a rate only twice floor cases (11,704 dollars vs. 5,835 dollars). Only 83% of costs were paid for intensive care unit patients, compared with 105% for floor patients, generating a 5.8 billion dollars loss to hospitals when intensive care unit care is required. There was a linear association between the percent intensive care unit in a diagnosis related group and the percent paid, with payment >90% of cost only in diagnosis related groups with >/=60% intensive care unit cases. We found that teaching hospitals were better paid than nonteaching hospitals (87% vs. 78% of costs, respectively), but this was only due to indirect medical education payments. CONCLUSIONS: Intensive care is common, expensive, and poorly paid in the Medicare population. Few diagnosis related groups have a large enough intensive care unit population to ensure adequate payment. Additional diagnosis related groups for conditions common to the intensive care unit would improve payment and enable incentives for efficiency.
Adult↗
Estimated frequency of nursing facility-acquired pneumonia?
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Aged↗
Pneumonia: still the old man's friend?
BACKGROUND: Hospital mortality of patients admitted with community-acquired pneumonia (CAP) has been well described. However, the long-term survival of those discharged alive is less clear. We sought to determine long-term survival of patients hospitalized with CAP and compare the outcome with controls hospitalized for reasons other than CAP. METHODS: We performed a matched case-control analysis using the Medicare hospital discharge database from the first quarter of 1997. We compared all Medicare recipients 65 years or older hospitalized with CAP and controls matched for age, sex, and race hospitalized for reasons other than CAP. We measured 1-year mortality determined from the Medicare Beneficiary Entitlement file and the Social Security Administration. RESULTS: We identified 158 960 CAP patients and 794 333 hospitalized controls. Hospital mortality rates for the CAP cohort and hospitalized controls were 11.0% and 5.5%, respectively (P<.001). One-year mortality rates for the CAP cohort and hospitalized controls were 40.9% and 29.1%, respectively (P<.001). One-year mortality rates in hospital survivors of the CAP and control cohorts were 33.6% and 24.9%, respectively (P<.001). The difference in mortality between the CAP and control cohorts was not explained by underlying disease. Standardized against the general population, the risk of death for both cohorts decreased monthly but was still elevated 1 year after hospital discharge. The standardized mortality ratio was 2.69 (95% confidence interval, 2.47-2.93) for CAP patients and 1.93 (95% confidence interval, 1.79-2.08) for hospital controls. CONCLUSIONS: Almost half of all elderly patients admitted for CAP die in the subsequent year, with most deaths occurring after hospital discharge. The mortality is considerably higher than that of either the general population or a control population hospitalized for reasons other than CAP.
Aged↗
Cost-effectiveness of drotrecogin alfa (activated) in the treatment of severe sepsis.
OBJECTIVE: To assess the cost-effectiveness of drotrecogin alfa (activated) therapy, which was recently shown to reduce mortality in severe sepsis. DESIGN: Estimates of effectiveness and resource use were based on data collected prospectively as part of a multicenter international trial. Estimates of hospital costs were based on a subset of the patients treated in the United States (33% of all enrolled patients). Lifetime projections were modeled from published sources and tested in sensitivity analyses. Analyses were conducted from the United States societal perspective, limited to healthcare costs, and using a 3% annual discount rate. SETTING: A total of 164 medical institutions in 11 countries. PATIENTS: Adults > or = 18 yrs of age with severe sepsis INTERVENTIONS: Eligible patients were randomly assigned to receive a 96-hr intravenous infusion of drotrecogin alfa (activated) at 24 microg/kg/hr (n = 850) or placebo (n = 840). MEASUREMENTS AND MAIN RESULTS: Base Case: incremental short-term (days 1-28) healthcare costs per day-28 survivor; Panel on Cost-Effectiveness in Health and Medicine Reference Case: incremental lifetime healthcare costs per quality-adjusted life-year. Over the first 28 days (short-term Base Case), drotrecogin alfa (activated) increased the costs of care by $9,800 and survival by 0.061 lives saved per treated patient. Thus, drotrecogin alfa (activated) cost $160,000 per life saved (with 84.7% probability that ratio is <$250,000 per life saved). Projected to lifetime (lifetime Reference Case), drotrecogin alfa (activated) increased the costs of care by $16,000 and quality-adjusted survival by 0.33 quality-adjusted life-years per treated patient. Thus, drotrecogin alfa (activated) cost $48,800 per quality-adjusted life-year (with 82% probability that ratio is <$100,000 per quality-adjusted life-year). Estimates were generally robust to sensitivity analyses, although cost-effectiveness deteriorated to >$100,000 per quality-adjusted life-year if survivors lived <4.6 yrs on average. Drotrecogin alfa (activated) cost $27,400 per quality-adjusted life-year when limited to patients with an Acute Physiology and Chronic Health Evaluation II score > or = 25 and was cost-ineffective when limited to patients with a score <25. CONCLUSIONS: Drotrecogin alfa has a cost-effectiveness profile similar to that of many well-accepted healthcare strategies and below commonly quoted thresholds.
Adult↗
Reassessing the value of short-term mortality in sepsis: comparing conventional approaches to modeling.
OBJECTIVE: Clinical trials of therapies for sepsis have been mostly unsuccessful in impacting mortality. This may be partly due to the use of insensitive mortality end points. We explored whether modeling survival was more sensitive than traditional end points in detecting mortality differences in cohorts of patients with sepsis. DESIGN: Patients were stratified into seven a priori defined paired subgroups that reflected high and low mortality risk according to known clinical risk factors. We fitted an exponential survival model to the high- and low-risk cohort of each subgroup, providing estimates of the rate of dying, long-term survival, and excess day 1 mortality. Mortality in the high- and low-risk cohorts in each subgroup was compared using model parameters, fixed-point mortality, and Kaplan-Meier survival analysis. SETTING: Eight intensive care units within a university teaching institution. PATIENTS: One hundred thirty patients with severe sepsis or suspected Gram-negative bacteremia. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Overall mortality of the cohort was 58.5% at 28 days. The survival of the entire cohort was well described by an exponential model (r2 =.99). Modeling identified differences in high- and low-risk cohorts in five of the seven paired subgroups, while conventional end-points only detected differences in 2. CONCLUSIONS: Modeling survival was more sensitive than conventional end-points in identifying survival differences between high- and low-risk subgroups. We encourage further evaluation of modeling in the search for more sensitive mortality end points.
APACHE↗
Cost-effectiveness of inhaled nitric oxide in the treatment of neonatal respiratory failure in the United States.
OBJECTIVE: Two recent randomized controlled trials (RCTs) reported that inhaled nitric oxide (iNO) decreased the incidence of extracorporeal membrane oxygenation (ECMO) or death in term and near-term newborns with hypoxic respiratory failure. Our objective was to estimate the cost-effectiveness ratio of iNO in this population. METHODS: We studied 1000 simulation cohorts (n = 483 for each cohort) of term/near-term newborns with hypoxemic respiratory failure. We conducted our study following US Public Health Service Panel on Cost-Effectiveness in Health and Medicine guidelines, adopting the US societal perspective. We constructed a decision tree reflecting iNO use, subsequent ECMO use, death, and long-term neurologic and respiratory morbidity in survivors, as determined from the combined outcomes of the 2 RCTs (n = 483). We estimated costs on the basis of length-of-stay data for the initial episode of care from 1 of the RCTs, unit costs from administrative data sets, and current pricing for iNO. We ran a Monte Carlo simulation to generate estimates of differences in costs and effects at 1 year, along with the stochastic uncertainty around these estimates. We expressed effects as quality-adjusted survival, assuming quality of life = 1 with no comorbidity, 0.7 with 1 comorbidity, and 0.49 (0.7 x 0.7) with 2 comorbidities. We constructed a base case, in which iNO was initiated at tertiary care ECMO centers (mimicking the RCTs) and a Public Health Service Panel on Cost-effectiveness in Health and Medicine reference case, in which iNO was initiated at the local hospital before transfer (mimicking real-world practice). We exposed our assumptions to a sensitivity analysis. RESULTS: Direct application of the trial results (base case) suggested that iNO was both more effective and cheaper (cost savings of 1880 dollars per case despite acquisition costs of 5150 dollars, predominantly as a result of decreased need for ECMO), with 84.6% probability that the cost-effectiveness ratio was better than 100,000 dollars per quality-adjusted life-year. Under the reference case, iNO was also more effective (though slightly less so) and was even cheaper (cost savings of 4400 dollars per case), with 71.6% probability that iNO was cheaper and more effective and 91.6% probability that the cost effectiveness ratio was better than 100,000 dollars per quality-adjusted life-year. Sensitivity analyses showed these estimates to be sensitive to patient selection and the price of iNO but insensitive to assumptions regarding quality of life. CONCLUSIONS: From a US societal perspective, iNO has a favorable cost-effectiveness profile when initiated either at ECMO centers or at local hospitals in term/near-term neonates with hypoxemic respiratory failure.
Cost-Benefit Analysis↗