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.

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.

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.

Drivers of choice of resuscitation fluid in the intensive care unit: a discrete choice experiment.

OBJECTIVE: To understand the fundamental drivers, and their relative importance, of doctors' and nurses' choice of resuscitation fluid in critically ill patients in Australia and New Zealand. DESIGN: A discrete choice experiment (DCE) administered via an online survey. Respondents were presented with one of four randomly selected DCE choice sets, each including five patient scenarios. The respondent chose between two types of hypothetical resuscitation fluid. The fluid type was characterised by several attributes and each attribute had pre-specified levels. PARTICIPANTS: Convenience sample of 367 Australian and New Zealand intensive care unit doctors and nurses. MAIN OUTCOME MEASURES: The dependent variable was fluid choice, and a regression equation was used to estimate the effect of each fluid attribute on the probability of observing the sequence of choices made over the five patient scenarios. The relative importance of each of the respective fluid attributes was calculated based on the percentage contribution to overall utility (ie, fluid preference). RESULTS: For doctors, safety concerns, patient type and fluid type were collectively responsible for almost three-quarters of decision-making utility (71%). The volume of intravenous fluid administered was the only clinical parameter not reaching statistical significance as a driver of fluid choice (P = 0.06). For nurses, decision making was influenced to a greater extent by the same three attributes (90%), although other unmeasured attributes may have been driving choice. CONCLUSIONS: Doctors and nurses rely on different information when choosing resuscitation fluids, although both cohorts are heavily influenced by safety concerns, patient type and fluid type. This information can be used to modify prescribing behaviour.

Temperature management in patients with acute neurological lesions: an Australian and New Zealand point prevalence study.

BACKGROUND: Given the scientific uncertainty of the efficacy and safety of normothermia (36.0°C to 37.5°C) on disability and death after acute neurological lesions, we sought to understand how temperature is managed in usual clinical care for this patient population in Australia and New Zealand. OBJECTIVE: To describe temperature management in patients with acute neurological lesions. DESIGN: Prospective, observational, multicentre, single-day point-prevalence study. PARTICIPANTS, SETTING AND METHODS: Observational data of usual practice were recorded for all patients with an intensive care admission diagnosis of acute neurological lesions and who were present in 33 intensive care units at 10:00 on the study day. Data were collected prospectively for the ensuing 24-hour period. MAIN OUTCOME MEASURES: Achieved temperature, interventions used to modify temperature and target temperature. RESULTS: There were 106 patients with acute neurological lesions (61% with either stroke or traumatic brain injury) with a mean APACHE (Acute Physiology and Chronic Health Evaluation) II score of 19.3 ± 7.4, age of 53.5 ± 19.0 years and median time from intensive care admission to data capture of 3 days (interquartile range, 1-9). A target temperature was specified in 24% of patients. Although paracetamol was commonly used (56%), it was infrequently used at the maximum licensed dose and there was no use recorded of non-steroidal anti-inflammatory drugs and cyclooxygenase-2 inhibitors. Physical cooling was used in 25% of patients and core temperature was measured in 32%. Measured temperature often exceeded 37.0°C (62% of readings), 37.5°C (43%) and 38.0°C (22%). CONCLUSIONS: Temperature readings above 37.5°C are common. Further cohort studies are required to validate these preliminary, exploratory findings.

Helicopter emergency medical services (HEMS) over-triage and the financial implications for major trauma centres in NSW, Australia.

BACKGROUND: In NSW Australia, a formal trauma system including the use of helicopter emergency medical services (HEMS) has existed for over 20 years. Despite providing many advantages in NSW, HEMS patients are frequently over-triaged; leading to financial implications for major trauma centres that receive HEMS patients. The aim of this study was to investigate the financial implications of HEMS over-triage from the perspective of major trauma centres in NSW. METHODS: The study sample included all trauma patients transported via HEMS to 12 major trauma centres in NSW during the period: 1 July 2008 to 30 June 2009. Clinical data were gathered from individual hospital trauma registries and merged with financial information obtained from casemix units at respective hospitals. HEMS over-triage was estimated based on the local definition of minor to moderate trauma (ISS≤12) and hospital length of stay of less than 24 hrs. The actual treatment costs were determined and compared to state-wide peer group averages to obtain estimates of potential funding discrepancies. RESULTS: A total of 707 patients transported by HEMS were identified, including 72% pre-hospital (PH; n=507) and 28% inter-hospital (IH; n=200) transports. Over-triage was estimated at 51% for PH patients and 29% for IH patients. Compared to PH patients, IH patients were more costly to treat on average (IH: $42,604; PH: $25,162), however PH patients were more costly overall ($12,329,618 [PH]; $8,265,152 [IH]). When comparing actual treatment costs to peer group averages we found potential funding discrepancies ranging between 4% and 32% across patient groups. Using a sensitivity analysis, the potential funding discrepancy increased with increasing levels of over-triage. CONCLUSIONS: HEMS patients are frequently over-triaged in NSW, leading to funding implications for major trauma centres. In general, HEMS patient treatment costs are higher than the peer group average and the potential funding discrepancy varies by injury severity and the type of transport performed. Although severely injured HEMS patients are more costly to treat, HEMS patients with minor injuries make up the majority of HEMS transports and have larger relative potential funding discrepancies. Future episode funding models need to account for the variability of trauma patients and the proportion of patients transported via HEMS.

Primary scene responses by Helicopter Emergency Medical Services in New South Wales Australia 2008-2009.

BACKGROUND: Despite numerous studies evaluating the benefits of Helicopter Emergency Medical Services (HEMS) in primary scene responses, little information exists on the scope of HEMS activities in Australia. We describe HEMS primary scene responses with respect to the time taken, the distances travelled relative to the closest designated trauma hospital and the receiving hospital; as well as the clinical characteristics of patients attended. METHODS: Clinical service data were retrospectively obtained from three HEMS in New South Wales between July 2008 and June 2009. All available primary scene response data were extracted and examined. Geographic Information System (GIS) based network analysis was used to estimate hypothetical ground transport distances from the locality of each primary scene response to firstly the closest designated trauma hospital and secondly the receiving hospital. Predictors of bypassing the closest designated trauma hospital were analysed using logistic regression. RESULTS: Analyses included 596 primary missions. Overall the HEMS had a median return trip time of 94min including a median of 9min for activation, 34min travelling to the scene, 30min on-scene and 25min transporting patients to the receiving hospital. 72% of missions were within 100km of the receiving hospital and 87% of missions were in areas classified as 'major cities' or 'inner regional'. The majority of incidents attended by HEMS were trauma-related, with road trauma the predominant cause (44%). The majority of trauma patients (81%) had normal physiology at HEMS arrival (RTS = 7.84). We found 62% of missions bypassed the closest designated trauma hospital. Multivariate predictors of bypass included: age; presence of spinal or burns trauma; the level of the closest designated trauma hospital; the transporting HEMS. CONCLUSION: Our results document the large distances travelled by HEMS in NSW, especially in rural areas. The high proportion of HEMS missions that bypass the closest designated trauma hospital is a seldom mentioned benefit of HEMS transport. These results along with the characteristics of patients attended and the time HEMS take to complete primary scene responses are useful in understanding the benefit HEMS provides and the services it replaces.

Hydroxyethyl starch or saline for fluid resuscitation in intensive care.

BACKGROUND: The safety and efficacy of hydroxyethyl starch (HES) for fluid resuscitation have not been fully evaluated, and adverse effects of HES on survival and renal function have been reported. METHODS: We randomly assigned 7000 patients who had been admitted to an intensive care unit (ICU) in a 1:1 ratio to receive either 6% HES with a molecular weight of 130 kD and a molar substitution ratio of 0.4 (130/0.4, Voluven) in 0.9% sodium chloride or 0.9% sodium chloride (saline) for all fluid resuscitation until ICU discharge, death, or 90 days after randomization. The primary outcome was death within 90 days. Secondary outcomes included acute kidney injury and failure and treatment with renal-replacement therapy. RESULTS: A total of 597 of 3315 patients (18.0%) in the HES group and 566 of 3336 (17.0%) in the saline group died (relative risk in the HES group, 1.06; 95% confidence interval [CI], 0.96 to 1.18; P=0.26). There was no significant difference in mortality in six predefined subgroups. Renal-replacement therapy was used in 235 of 3352 patients (7.0%) in the HES group and 196 of 3375 (5.8%) in the saline group (relative risk, 1.21; 95% CI, 1.00 to 1.45; P=0.04). In the HES and saline groups, renal injury occurred in 34.6% and 38.0% of patients, respectively (P=0.005), and renal failure occurred in 10.4% and 9.2% of patients, respectively (P=0.12). HES was associated with significantly more adverse events (5.3% vs. 2.8%, P<0.001). CONCLUSIONS: In patients in the ICU, there was no significant difference in 90-day mortality between patients resuscitated with 6% HES (130/0.4) or saline. However, more patients who received resuscitation with HES were treated with renal-replacement therapy. (Funded by the National Health and Medical Research Council of Australia and others; CHEST ClinicalTrials.gov number, NCT00935168.).

Injury trends and mortality in adult patients with major trauma in New South Wales.

OBJECTIVE: To examine trends in mechanism and outcome of major traumatic injury in adults since the implementation of the New South Wales trauma monitoring program, and to identify factors associated with mortality. DESIGN AND SETTING: Retrospective review of NSW Trauma Registry data from 1 January 2003 to 31 December 2007, including patient demographics, year of injury, and level of trauma centre where definitive treatment was provided. PARTICIPANTS: 9769 people aged ≥ 15 years hospitalised for trauma, with an injury severity score (ISS) > 15. MAIN OUTCOME MEASURES: The NSW Trauma Registry outcome measures included were overall hospital length of stay, length of stay in an intensive care unit and in ospital mortality. RESULTS: There was a decreasing trend in severe trauma presentations in the age group 16-34 years, and an increasing trend in presentations of older people, particularly those aged ≥ 75 years. Road trauma and falls were consistently the commonest injury mechanisms. There were 1328 inhospital deaths (13.6%). Year of injury, level of trauma centre, ISS, head/neck injury and age were all independent predictors of mortality. The odds of mortality was significantly higher among patients receiving definitive care at regional trauma centres compared with Level I centres (odds ratio, 1.34; 95% CI, 1.10-1.63). CONCLUSIONS: Deaths from major trauma in NSW trauma centres have declined since 2003, and definitive care at a Level 1 trauma centre was associated with a survival benefit. More comprehensive trauma data collection with timely analysis will improve injury surveillance and better inform health policy in NSW.

An investigation into the cost, coverage and activities of Helicopter Emergency Medical Services in the state of New South Wales, Australia.

BACKGROUND AND CONTEXT: Helicopter Emergency Medical Services (HEMS) have been incorporated into modern health systems for their speed and coverage. In the state of New South Wales (NSW), nine HEMS operate from various locations around the state and currently there is no clear picture of their resource implications. The aim of this study was to assess the cost of HEMS in NSW and investigate the factors linked with the variation in the costs, coverage and activities of HEMS. METHODS: We undertook a survey of HEMS costs, structures and operations in NSW for the 2008/2009 financial year. Costs were estimated from annual reports and contractual agreements. Data related to the structure and operation of services was obtained by face-to-face interviews, from operational data extracted from individual HEMS, from the NSW Ambulance Computer Aided Despatch system and from the Aeromedical Operations Centre database. In order to estimate population coverage for each HEMS, we used GIS mapping techniques with Australian Bureau of Statistics census information. RESULTS: Across HEMS, cost per mission estimates ranged between $9300 and $19,000 and cost per engine hour estimates ranged between $5343 and $15,743. Regarding structural aspects, six HEMS were run by charities or not-for-profit companies (with partial government funding) and three HEMS were run (and fully funded) by the state government through NSW Ambulance. Two HEMS operated as 'hub' services in conjunction with three associated 'satellite' services and in contrast, four services operated independently. Variation also existed between the HEMS in the type of helicopter used, the clinical staffing and the hours of operation. The majority of services undertook both primary scene responses and secondary inter-facility transfers, although the proportion of each type of transport contributing to total operations varied across the services. INTERPRETATION: This investigation highlighted the cost of HEMS operations in NSW which in total equated to over $50 million per annum. Across services, we found large variation in the cost estimates which was underscored by variation in the structure and operations of HEMS.

A systematic review of the costs and benefits of helicopter emergency medical services.

INTRODUCTION: Helicopter emergency medical services (HEMS) are popular in first world health systems despite inconsistent evidence in the scientific literature to support their use. The aim of the current study was to perform a systematic review of economic evaluations of HEMS, in order to determine the economic cost of HEMS and the associated patient-centered benefits. METHOD: A systematic review was performed of studies that provided a cost estimate of HEMS. The inclusion criteria consisted of English language articles that estimated both the costs and outcomes of a HEMS and fulfilled pre-specified criteria in relation to a cost analysis, cost-minimisation, cost-effectiveness or cost-benefit evaluation. Identified studies were synthesised according to the patient diagnosis (trauma, non-trauma or non-specific) and the type of HEMS transport under review (primary scene retrieval or secondary inter-facility transport). All costs were converted to US dollars and indexed for inflation. RESULTS: Fifteen studies met the inclusion criteria. Among all studies the annual cost of HEMS ranged from $115,777 to $5,571,578. Five studies showed HEMS to be a more expensive transport alternative without an associated benefit while eight studies provided cost-effectiveness ratios of $3292 and $2227 per life year saved for trauma, $3258 per life saved and $7138 and $12,022 per quality adjusted life year for non-trauma and $30,365 and $91,478 per beneficial mission for non-specific patient populations. One study also evaluated the cost of HEMS to societal benefit, producing a ratio of 1:6. INTERPRETATION: The cost and effectiveness of HEMS varied considerably between studies. Despite generally being more expensive than ground transport, a number of studies found HEMS to be cost-effective. However, given the variation in the intervention design, context and study methods between studies it was not possible to assess the cost-effectiveness of HEMS in general. Given the variation inherent in the health systems in which HEMS operate, synthesis and extrapolation of study findings across differing health environments is difficult. To address economic and clinical evidence in relation to HEMS, future research that is tailored to account for local system factors is required.

Incidence, risk, and protective factors of mild traumatic brain injury in a cohort of Australian nonprofessional male rugby players.

BACKGROUND: Mild traumatic brain injury (mTBI) is an emerging public health issue in high-contact sports. Understanding the incidence along with the risk and protective factors of mTBI in high-contact sports such as rugby is paramount if appropriate preventive strategies are to be developed. PURPOSE: To estimate the incidence and identify the risk and protective factors of mTBI in Australian nonprofessional rugby players. STUDY DESIGN: Cohort study; Level of evidence, 2. METHODS: A cohort of 3207 male nonprofessional rugby players from Sydney, Australia, was recruited and followed over 1 or more playing seasons. Demographic information, history of recent concussion, and information on risk and protective factors were collected. The incidence of mTBI was estimated and the putative risk and protective factors were modeled in relation to mTBI. RESULTS: The incidence of mTBI was 7.97 per 1000 player game hours, with 313 players (9.8%) sustaining 1 or more mTBIs during the study. Players who reported always wearing protective headgear during games were at a reduced risk (incident rate ratio [IRR], 0.57; 95% confidence interval [CI], 0.40-0.82) of sustaining an mTBI. In contrast, the likelihood of mTBI was almost 2 times higher among players who reported having sustained either 1 (IRR, 1.75; 95% CI, 1.11-2.76) or more mTBIs (IRR, 1.65; 95% CI, 1.11-2.45) within the 12 months before recruitment. CONCLUSION: Nonprofessional rugby has a high incidence of mTBI, with the absence of headgear and a recent history of mTBI associated with an increased risk of subsequent mTBI. These findings highlight that both use of headgear and the management of prior concussion would likely be beneficial in reducing the likelihood of mTBI among nonprofessional rugby players, who compose more than 99% of rugby union players in Australia.