Economic evaluations for intensive care unit randomised clinical trials in Australia and New Zealand: Practical recommendations for researchers.

OBJECTIVES: Economic evaluations of intensive care unit (ICU) interventions have specific considerations, including how to cost ICU stays and accurately measure quality of life in survivors. The aim of this article was to develop best practice recommendations for economic evaluations alongside future ICU randomised controlled trials (RCTs). REVIEW METHODS: We collated our experience based on expert consensus across several recent economic evaluations to provide best-practice, practical recommendations for researchers conducting economic evaluations alongside RCTs in the ICU. Recommendations were structured according to the International Society for Pharmacoeconomics and Outcomes Research (ISPOR) Consolidated Health Economic Evaluation Reporting Standards (CHEERS) Task Force Report. RESULTS: We discuss recommendations across the components of economic evaluations, including: types of economic evaluation, the population and sample size, study perspective, comparators, time horizon, choice of health outcomes, measurement of effectiveness, measurement and valuation of quality of life, estimating resources and costs, analytical methods, and the increment cost-effectiveness ratio. We also provide future directions for research with regard to developing more robust economic evaluations for the ICU. CONCLUSION: Economic evaluations should be built alongside ICU RCTs and should be designed a priori using appropriate follow-up and data collection to capture patient-relevant outcomes. Further work is needed to improve the quality of data available for linkage in Australia as well as developing costing methods for the ICU and appropriate quality of life measurements.

A New Strategy for Linking U.S. Historical Censuses: A Case Study for the IPUMS Multigenerational Longitudinal Panel.

This paper presents a probabilistic method of record linkage, developed using the U.S. full count censuses of 1900 and 1910 but applicable to many sources of digitized historical records. The method links records using a two-step approach, first establishing high confidence matches among men by exploiting a comprehensive set of individual and contextual characteristics. The method then proceeds to link both men and women by leveraging links between households established in the first step. While only the first stage links can be directly comparable to other popular methods in research on the U.S., our method yields both considerably higher linkage rates and greater accuracy while only performing negligibly worse than other algorithms in resembling the target population.

Sex differences in sepsis hospitalisations and outcomes in older women and men: A prospective cohort study.

PURPOSE: To examine the association of sex with hospitalisation due to sepsis and related outcomes. METHODS: Prospective cohort study of 264,678 adults, average age 62.7 years at recruitment (2006-2009) in Australia. Participants were followed for sepsis hospitalisation identified using the International Classification of Diseases coding. Outcomes included sex differences in the risk of an incident sepsis hospitalisation, mortality, length of ICU and hospital stay and readmissions during the following year. RESULTS: Over 2,070,343 years of follow-up there were 12,912 sepsis hospitalisations, 59.6% in men. Age-standardised risk of hospitalisation was higher in men versus women (10.37 vs 6.77 per 1,000 person years; age-adjusted HR 1.58; 95% CI 1.53-1.59) and did not attenuate after adjusting for sociodemographics, health behaviours and co-morbidities. Relative risks were similar for sepsis-related ICU admissions (adjusted HR 1.72; 95% CI 1.57-1.88). Death at one year was more common in men than women (39.3% vs 33.7% p<0.001). After adjusting for age, men had a longer hospital (12.0 vs 11.2 days; p<0.001) and ICU (6.5 vs 5.8 days; p<0.001) stays and were more likely to be readmitted to hospital for sepsis (22.3 vs 19.4%; p<0.001) or any reason (73.0% vs 70.7%; p<0.001) at one year. CONCLUSION: In older adults, compared to women, men are at an increased risk of sepsis hospitalisation, sepsis-related ICU admission, death and readmission to hospital within one year after a sepsis hospitalisation. Understanding these sex differences and their mechanisms may offer opportunities for better prevention and management and improved patient outcomes.

Long-term costs and cost-effectiveness of adjunctive corticosteroids for patients with septic shock in New Zealand.

OBJECTIVE: The aim of the study was to determine whether adjunctive hydrocortisone reduced healthcare expenditure and was cost-effective compared with placebo in New Zealand patients in the Adjunctive Glucocorticoid Therapy in Patients with Septic Shock (ADRENAL) trial. DESIGN: This is a health economic analysis using data linkage to New Zealand Ministry of Health databases to determine resource use, costs, and cost-effectiveness for a 24-month period. SETTING: The study was conducted in New Zealand. PARTICIPANTS AND INTERVENTION: Patients with septic shock were randomised to receive a 7-day continuous infusion of 200 mg of hydrocortisone or placebo in the ADRENAL trial. MAIN OUTCOME MEASURES: Healthcare expenditure was associated with all hospital admissions, emergency department presentations, outpatient visits, and pharmacy expenditure. Effectiveness outcomes included mortality at 6 months and 24 months and quality of life at 6 months. Cost-effectiveness outcomes were assessed with reference to quality-adjusted life years gained at 6 months and life years gained at 24 months. RESULTS: Of 3800 patients in the ADRENAL trial, 419 (11.0%) were eligible, and 405 (96.7% of those eligible) were included. The mean total costs per patient over 24 months were $143,627 ± 100,890 and $143,772 ± 97,117 for the hydrocortisone and placebo groups, respectively (p = 0.99). Intensive care unit costs for the index admission were $50,492 and $62,288 per patient for the hydrocortisone and placebo groups, respectively (p = 0.09). The mean number of quality-adjusted life years gained at 6 months and mean number of life years gained at 24 months was not significantly different by treatment group, and the probability of hydrocortisone being cost-effective was 55% at 24 months. CONCLUSIONS: In New Zealand, adjunctive hydrocortisone did not reduce total healthcare expenditure or improve outcomes compared with placebo in patients with septic shock.

Incidence and outcomes of sepsis in Aboriginal and Torres Strait Islander and non-Indigenous residents of New South Wales: population-based cohort study.

Objective: To estimate the incidence and outcomes of sepsis hospitalisations in Aboriginal and Torres Strait Islander and non-Indigenous residents of New South Wales. Design and participants: Prospective cohort study of residents aged 45 years and older, recruited between 2006 and 2009, and followed for hospitalisation for sepsis. Main outcome measures: Incidence and hazard ratio (HR) of sepsis hospitalisation and intensive care unit (ICU) admission identified using International Classification of Diseases (10th revision) coding on discharge data. Length of stay, readmission and mortality in those admitted for sepsis. Results: Of 264 678 participants, 1928 (0.7%) identified as Aboriginal and/or Torres Strait Islander. Sepsis hospitalisation was higher in Aboriginal and Torres Strait Islander participants (8.67 v 6.12 per 1000 person-years; age- and sex-adjusted HR, 2.35; 95% CI, 1.98-2.80) but was attenuated after adjusting for sociodemographic factors, health behaviour and comorbidities (adjusted HR, 1.56; 95% CI, 1.31-1.86). Among those hospitalised for sepsis, after adjusting for age and sex, there were no differences between the proportions of Aboriginal and Torres Strait Islander and non-Indigenous participants admitted to an ICU (18.0% v 16.1%; P = 0.42) or deceased at 1 year (36.1% v 36.8%; P = 0.92). Aboriginal and Torres Strait Islander participants had shorter lengths of hospital stay (9.98 v 11.72 days; P < 0.001) and ICU stay (4.38 v 6.35 days; P < 0.001) than non-Indigenous participants. Overall, more than 70% of participants were readmitted to hospital within 1 year. Conclusion: We found that the rate of sepsis hospitalisation in NSW was higher for Aboriginal and Torres Strait Islander adults. Culturally appropriate, community-led strategies targeting chronic disease prevention and the social determinants of health may reduce this gap. Preventing readmission following sepsis is a priority for all Australians.

The cost-effectiveness of adjunctive corticosteroids for patients with septic shock.

OBJECTIVE: To determine whether hydrocortisone is a cost-effective treatment for patients with septic shock. DESIGN: Data linkage-based cost-effectiveness analysis. SETTING: New South Wales and Queensland intensive care units. PARTICIPANTS AND INTERVENTION: Patients with septic shock randomly assigned to treatment with hydrocortisone or placebo in the Adjunctive Glucocorticoid Therapy in Patients with Septic Shock (ADRENAL) trial. MAIN OUTCOME MEASURES: Health-related quality of life at 6 months using the EuroQoL 5-dimension 5-level questionnaire. Data on hospital resource use and costs were obtained by linking the ADRENAL dataset to government administrative health databases. Clinical outcomes included mortality, health-related quality of life, and quality-adjusted life-years gained; economic outcomes included hospital resource use, costs and cost-effectiveness from the health care payer perspective. We also assessed cost-effectiveness by sex. To increase the precision of cost-effectiveness estimates, we conducted unrestricted bootstrapping. RESULTS: Of 3800 patients in the ADRENAL trial, 1772 (46.6%) were eligible and 1513 (85.4% of those eligible) were included. There was no difference between hydrocortisone or placebo groups in regards to mortality (218/742 [29.4%] v 227/759 [29.9%]; HR, 0.93; 95% CI, 0.78-1.12; P = 0.47), mean number of QALYs gained (0.10 ± 0.09 v 0.10 ± 0.09; P = 0.52), or total hospital costs (A$73 515 ± 61 376 v A$69 748 ± 61 793; mean difference, A$3767; 95% CI, -A$2891 to A$10 425; P = 0.27). The incremental cost of hydrocortisone was A$1 254 078 per quality-adjusted life-year gained. In females, hydrocortisone was cost-effective in 46.2% of bootstrapped replications and in males it was cost-effective in 2.7% of bootstrapped replications. CONCLUSIONS: Adjunctive hydrocortisone did not significantly affect longer term mortality, health-related quality of life, health care resource use or costs, and is unlikely to be cost-effective.