The cost-effectiveness of early goal-directed therapy: an economic evaluation alongside the ARISE trial.

Objective: To determine the cost-effectiveness of early goal-directed therapy (EGDT) for patients with early septic shock. Design: Within-trial cost-effectiveness evaluation. Setting: Nineteen hospitals in Australia and New Zealand. Participants and interventions: Patients with early septic shock enrolled in the Australasian Resuscitation in Sepsis Evaluation (ARISE) trial were randomly assigned to EGDT versus usual care. A subgroup of patients participated in a nested economic evaluation study in which detailed resource use data were collected until 12 months after randomisation. Outcome measures: Clinical outcomes included lives saved, life-years gained and quality-adjusted life-years (QALYs), with mortality collected until 12 months and health-related quality of life assessed at baseline, 6 and 12 months using the 3-level EuroQol five dimensions questionnaire (EQ-5D-3L). Economic outcomes included health care resource use, costs and cost-effectiveness from the Australian health care payer perspective. Results: A total of 205 patients (100 EGDT, 105 usual care) participated in the nested economic evaluation study, of which 203 had complete resource use data. Unadjusted mean health care costs to 12 months were $67 223 (standard deviation [SD], $72 397) in the EGDT group and $54 179 (SD, $61 980) in the usual care group, with a mean difference of $13 044 (95% CI, -$5791 to $31 878). There was no difference between groups with regards to lives saved (EGDT, 69.4% v usual care, 68.6%; P = 1.0), life-years gained (mean EGDT, 0.746 [SD, 0.406] v usual care, 0.725 [SD, 0.417]; P = 0.72) or QALYs (mean EGDT, 0.318 [SD, 0.291] v usual care, 0.367 [SD, 0.295]; P = 0.24). EGDT was dominated (higher costs, lower effectiveness) by usual care in 80.4% of bootstrap replications. For a willingness-to-pay threshold of $50 000 per QALY, the probability of EGDT being cost-effective was only 6.4%. Conclusions: In patients presenting to the emergency department with early septic shock, EGDT compared with usual care was not cost-effective. Clinical trial registration:ClinicalTrials.gov number NCT00975793.

Health economic evaluations of sepsis interventions in critically ill adult patients: a systematic review.

BACKGROUND: Sepsis is a global health priority. Interventions to reduce the burden of sepsis need to be both effective and cost-effective. We performed a systematic review of the literature on health economic evaluations of sepsis treatments in critically ill adult patients and summarised the evidence for cost-effectiveness. METHODS: We systematically searched MEDLINE, Embase, and the Cochrane Library using thesaurus (e.g. MeSH) and free-text terms related to sepsis and economic evaluations. We included all articles that reported, in any language, an economic evaluation of an intervention for the management of sepsis in critically ill adult patients. Data extracted included study details, intervention details, economic evaluation methodology, and outcomes. Included studies were appraised for reporting quality using the Consolidated Health Economic Evaluation Reporting Standards (CHEERS) checklist. RESULTS: We identified 50 records representing 46 economic evaluations for a variety of interventions including antibiotics (n = 5), fluid therapy (n = 2), early goal-directed therapy and other resuscitation protocols (n = 8), immunoglobulins (n = 2), and interventions no longer in clinical use such as monoclonal antibodies (n = 7) and drotrecogin alfa (n = 13). Twelve (26%) evaluations were of excellent reporting quality. Incremental cost-effectiveness ratios (ICERs) ranged from dominant (lower costs and higher effectiveness) for early goal-directed therapy, albumin, and a multifaceted sepsis education program to dominated (higher costs and lower effectiveness) for polymerase chain reaction assays (LightCycler SeptiFast testing MGRADE®, SepsiTest™, and IRIDICA BAC BSI assay). ICERs varied widely across evaluations, particularly in subgroup analyses. CONCLUSIONS: There is wide variation in the cost-effectiveness of sepsis interventions. There remain important gaps in the literature, with no economic evaluations identified for several interventions routinely used in sepsis. Given the high economic and social burden of sepsis, high-quality economic evaluations are needed to increase our understanding of the cost-effectiveness of these interventions in routine clinical practice and to inform decision makers. TRIAL REGISTRATION: PROSPERO CRD42018095980.

Quality of Life and 1-Year Survival in Patients With Early Septic Shock: Long-Term Follow-Up of the Australasian Resuscitation in Sepsis Evaluation Trial.

OBJECTIVES: To examine long-term survival and quality of life of patients with early septic shock. DESIGN: Prospective, randomized, parallel-group trial. SETTING: Fifty-one hospitals in Australia, New Zealand, Finland, Hong Kong, and the Republic of Ireland. PATIENTS: One-thousand five-hundred ninety-one patients who presented to the emergency department with early septic shock between October 2008 and April 2014, and were enrolled in the Australasian Resuscitation in Sepsis Evaluation trial. INTERVENTIONS: Early goal-directed therapy versus usual care. MEASUREMENTS AND MAIN RESULTS: Long-term survival was measured up to 12 months postrandomization. Health-related quality of life was measured using the EuroQoL-5D-3L, Short Form 36 and Assessment of Quality of Life 4D at baseline, and at 6 and 12 months following randomization. Mortality data were available for 1,548 patients (97.3%) and 1,515 patients (95.2%) at 6 and 12 months, respectively. Health-related quality of life data were available for 85.1% of survivors at 12 months. There were no significant differences in mortality between groups at either 6 months (early goal-directed therapy 21.8% vs usual care 22.6%; p = 0.70) or 12 months (early goal-directed therapy 26.4% vs usual care 27.9%; p = 0.50). There were no group differences in health-related quality of life at either 6 or 12 months (EuroQoL-5D-3L utility scores at 12 mo early goal-directed therapy 0.65 ± 0.33 vs usual care 0.64 ± 0.34; p = 0.50), with the health-related quality of life of both groups being significantly lower than population norms. CONCLUSIONS: In patients presenting to the emergency department with early septic shock, early goal-directed therapy compared with usual care did not reduce mortality nor improve health-related quality of life at either 6 or 12 months.

Stated and Revealed Preferences for Funding New High-Cost Cancer Drugs: A Critical Review of the Evidence from Patients, the Public and Payers.

BACKGROUND: The growing focus on patient-centred care has encouraged the inclusion of patient and public input into payer drug reimbursement decisions. Yet, little is known about patient/public priorities for funding high-cost medicines, and how they compare to payer priorities applied in public funding decisions for new cancer drugs. OBJECTIVES: The aim was to identify and compare the funding preferences of cancer patients and the general public against the criteria used by payers making cancer drug funding decisions. METHODS: A thorough review of the empirical, peer-reviewed English literature was conducted. Information sources were PubMed, EMBASE, MEDLINE, Web of Science, Business Source Complete, and EconLit. Eligible studies (1) assessed the cancer drug funding preferences of patients, the general public or payers, (2) had pre-defined measures of funding preference, and (3) had outcomes with attributes or measures of 'value'. The quality of included studies was evaluated using a health technology assessment-based assessment tool, followed by extraction of general study characteristics and funding preferences, which were categorized using an established WHO-based framework. RESULTS: Twenty-five preference studies were retrieved (11 quantitative, seven qualitative, seven mixed-methods). Most studies were published from 2005 onward, with the oldest dating back to 1997. Two studies evaluated both patient and public perspectives, giving 27 total funding perspectives (41 % payer, 33 % public, 26 % patients). Of 41 identified funding criteria, payers consider the most (35), the general public considers fewer (23), and patients consider the fewest (12). We identify four unique patient criteria: financial protection, access to medical information, autonomy in treatment decision making, and the 'value of hope'. Sixteen countries/jurisdictions were represented. CONCLUSIONS: Our results suggest that (1) payers prioritize efficiency (health gains per dollar), while citizens (patients and the general public) prioritize equity (equal access to cancer medicines independent of cost or effectiveness), (2) citizens prioritize few criteria relevant to payers, and (3) citizens prioritize several criteria not considered by payers. This can explain why payer and citizen priorities clash when new cancer medicines are denied public funding.

A comparison of directly elicited and pre-scored preference-based measures of quality of life: the case of adhesive capsulitis.

PURPOSE: To assess the convergent validity and comparative responsiveness in measuring the health-related quality of life associated with adhesive capsulitis of a disease-specific measure (Shoulder Pain and Disability Index), a generic quality of life measure (SF-36), a preference-based multi-attribute utility scale (assessment of quality of life), and two direct patient preference elicitation methods (willingness to pay and time trade-off). METHOD: Instruments administered to all 156 participants in both arms of a randomized placebo-controlled trial of physiotherapy following arthrographic joint distension at baseline were reported at 6, 12, and 26 weeks. Convergent validity was measured using both pooled correlation between instruments and within subjects over time. Responsiveness was measured using the effect size for those with no improvement, moderate improvement, and marked improvement. RESULTS: With the exception of the monetary measure, all of the instruments showed a low quality of life at baseline with adhesive capsulitis (66- 87 % of perfect health) and a substantial improvement in quality of life to week 26 on recovery. The time trade-off and willingness to pay measures of patient preferences were not responsive to changes in health, but all of the other instruments were at least moderately sensitive to change and moderately correlated with one another. CONCLUSIONS: These findings verify the significant adverse impact of adhesive capsulitis upon quality of life found in larger studies. There was a fair degree of convergence, as measured by the correlation between the instruments but while the time trade-off mean values were quite plausible, at a mean of 87 % of full health before treatment, there was a low correlation with health profile and disease-specific measures. It may be that the time trade-off measured wider aspects of quality of life and that individuals were not prepared to trade survival for potential gains in a self-limiting condition.

Health economic methods: cost-minimization, cost-effectiveness, cost-utility, and cost-benefit evaluations.

Health care resources are limited, and health care providers must strive to maximize health benefits to patients within available resources. This is becoming increasingly important in critical care as demand for services grows and costs associated with treatment increase. Economic evaluations enable comparisons of both the costs and effects of an intervention. There are four main types: cost-minimization, cost effectiveness,cost-utility, and cost-benefit. The costs associated with the intervention are measured in monetary units (dollars); the evaluation types differ with respect to how outcomes are measured. This article introduces the methodology for performing these economic evaluations,highlighting important aspects regarding critical care.

Expensive care - a rationale for economic evaluations in intensive care.

The demand for intensive care services is growing, and the cost of these services is increasing, with newer technologies consuming larger portions of the health care budget. We contend that both the costs and benefits of interventions must be considered to truly understand their value in critical care. Economic evaluations provide an explicit framework to compare the costs and benefits of an intervention. If these factors are not considered together, decisions may be made that do not result in the most efficient use of constrained resources. Despite limitations arising from variations in economic evaluation methodology, logistical complexity and problems of generalisability, the Australian trial environment provides an ideal opportunity to obtain robust economic data to help decision-making. Here, we outline the rationale for conducting economic evaluations in the critical care setting and argue that these evaluations need to be routinely incorporated into all large-scale clinical trials.

The role of value for money in public insurance coverage decisions for drugs in Australia: a retrospective analysis 1994-2004.

OBJECTIVE: To analyze the relative influence of factors in decisions for public insurance coverage of new drugs in Australia. DATA SOURCES: Evidence presented at meetings of the Australian Pharmaceutical Benefits Advisory Committee (PBAC) that makes recommendations on coverage of drugs under Pharmaceutical Benefits Scheme. STUDY SELECTION: All major submissions to the PBAC between February 1994 and December 2004 (n = 858) if one of the outcomes measured was life year gained (n=138) or quality-adjusted life years (QALYs) gained (n=116). RESULTS: Clinical significance, cost-effectiveness, cost to government, and severity of disease were significant influences on decisions. Compared to the average submission, clinical significance increased the probability of recommending coverage by 0.21 (95% confidence interval [CI] 0.02 to 0.40), whereas a drug in a life-threatening condition had an increased probability of being recommended for coverage of 0.38 (0.06 to 0.69). An increase in $A10,000 from a mean incremental cost per QALY of $A46,400 reduced the probability of listing by 0.06 (95% CI 0.04 to 0.1). CONCLUSIONS: The PBAC provides an example of the long-term stability and coherence of evidence-based coverage and pricing decisions for drugs that weighs up the evidence on clinical effectiveness, clinical need, and value for money. There is no evidence of a fixed public threshold value of life years or QALYs, but willingness to pay is clearly related to the characteristics of the clinical condition, perceived confidence in the evidence of effectiveness and its relevance, as well as total cost to government.

Economic evaluation of a clinical protocol for diagnosing emergency patients with suspected pulmonary embolism.

BACKGROUND: The objective of this paper is to estimate the amount of cost-savings to the Australian health care system from implementing an evidence-based clinical protocol for diagnosing emergency patients with suspected pulmonary embolism (PE) at the Emergency department of a Victorian public hospital with 50,000 presentations in 2001-2002. METHODS: A cost-minimisation study used the data collected in a controlled clinical trial of a clinical protocol for diagnosing patients with suspected PE. The number and type of diagnostic tests in a historic cohort of 185 randomly selected patients, who presented to the emergency department with suspected PE during an eight month period prior to the clinical trial (January 2002-August 2002) were compared with the number and type of diagnostic tests in 745 patients, who presented to the emergency department with suspected PE from November 2002 to August 2003. Current Medicare fees per test were used as unit costs to calculate the mean aggregated cost of diagnostic investigation per patient in both study groups. A t-test was used to estimate the statistical significance of the difference in the cost of resources used for diagnosing PE in the control and in the intervention group. RESULTS: The trial demonstrated that diagnosing PE using an evidence-based clinical protocol was as effective as the existing clinical practice. The clinical protocol offers the advantage of reducing the use of diagnostic imaging, resulting in an average cost savings of at least $59.30 per patient. CONCLUSION: Extrapolating the observed cost-savings of $59.30 per patient to the whole of Australia could potentially result in annual savings between $3.1 million to $3.7 million.

How are solar keratoses treated by general practitioners in Australia?

BACKGROUND: This study aimed to obtain clinical and economic information about patterns of treatment of solar keratoses (SKs) by general practitioners in Australia. The study design was a retrospective survey relating to the treatment of patients presenting to their doctor with previously untreated SKs. METHODS: Data were collected between May and June 2000, from a sample of doctors who were asked to randomly select two SK patients from their medical records and complete a self-administered postal questionnaire. Information about treatment types, number of visits, treatment complications, and specialist referrals were directly extracted from the patient records. RESULTS: A total of 156 patients were recruited to the study (61% male) who had been treated for a total of 251 SKs (average 1.6 lesions/patient). The most common treatment employed was cryotherapy (63%). Excision was also commonly used (18%). Five per cent of patients were treated with a mixture of excision and cryotherapy. Topical agents were not commonly employed. Of those patients who consulted a doctor, 9% were referred to a specialist for diagnosis or treatment, of which 57% were referred to a dermatologist. CONCLUSION: The typical number of doctor visits varied from 1.9 to 4.6 with a range of cost per patient of 55.13-249.70 Australian dollars depending on complexity of the case and the need for referral.

A randomised trial of the cost effectiveness of buprenorphine as an alternative to methadone maintenance treatment for heroin dependence in a primary care setting.

BACKGROUND AND AIM: Buprenorphine offers an alternative to methadone in the treatment of heroin dependence, and has the advantage of allowing alternate-day dosing. This study is the first to examine the cost effectiveness of buprenorphine as maintenance treatment for heroin dependence in a primary care setting using economic and clinical data collected within a randomised trial. STUDY DESIGN AND METHODS: The study was a randomised, open-label, 12-month trial of 139 heroin-dependent patients in a community setting receiving individualised treatment regimens of buprenorphine or methadone. Those who were currently on a methadone program (n = 57; continuing therapy subgroup) were analysed separately from new treatment recipients (n = 82; initial therapy subgroup). The study took a broad societal perspective and included health, crime and personal costs. Data on resource use and outcomes were a combination of clinical records and self report at interview. The main outcomes were incremental cost per additional day free of heroin use and per QALY. An analysis of uncertainty calculated the likelihood of net benefits for a range of acceptable money values of outcomes. All costs were in 1999 Australian dollars (DollarA). RESULTS: The estimated mean number of heroin-free days did not differ significantly between those randomised to methadone (225 [95% CI 91, 266]), or buprenorphine (222 [95% CI 194, 250]) over the year of the trial. Buprenorphine was associated with an average 0.03 greater QALYs over 52 weeks (not significant). The total cost was DollarA 17,736 (95% CI -DollarA 2981, DollarA 38,364) with methadone and DollarA 11,916 (95% CI DollarA 7697, DollarA 16,135) with buprenorphine; costs excluding crime were DollarA 4513 (95% CI DollarA 3495, DollarA 5531) and DollarA 5651 (95% CI DollarA 4202, DollarA 7100). With additional heroin-free days as the outcome, and crime costs included buprenorphine has a lower cost but less heroin-free days. If crime costs are excluded buprenorphine has a higher cost and worse outcome than methadone. With additional QALYs as the outcome, the cost effectiveness of buprenorphine is DollarA 39,404 if crime is excluded, but buprenorphine is dominant if crime is included. CONCLUSIONS: The trial found no significant differences in costs or outcomes between methadone and buprenorphine maintenance in this particular setting. Although some of the results suggest that methadone may have a cost advantage, it is difficult to infer from the trial data that offering buprenorphine as an alternative would have a significant effect on total costs or outcomes. The point estimates of costs and outcomes suggest that buprenorphine may have an advantage in those initiating therapy. The confidence intervals were wide, however, and the likelihood of net benefits from substituting one treatment for another was close to 50%.

The cost effectiveness of prenatal ultrasound screening for trisomy 21.

OBJECTIVES: The cost-effectiveness of opportunistic nuchal translucency ultrasound screening in pregnancy was compared with alternative screening strategies for trisomy 21 in Australia. METHODS: A decision analytic model was used of various pregnancy screening strategies based on a systematic review of the literature on the effectiveness of nuchal translucency ultrasound and serum screening and costs based on current reimbursement fees. The model included the likelihood and cost of terminations after diagnostic testing and the associated risk of fetal loss. All prices are in 2001 Australian dollars. RESULTS: With a twenty percentage point difference in detection rate, the incremental cost for a combination of nuchal translucency and serum screening with age in the first trimester compared with maternal serum screening in the second trimester was 105,484 dollars per extra case detected and 374,779 dollars per live trisomy 21 birth avoided. Serum screening in the second trimester had an incremental cost per extra case detected of between 61,700 dollars and 117,100 dollars per extra live birth avoided when compared with no screening. CONCLUSIONS: The cost-effectiveness of ultrasound screening for trisomy 21 would appear to be more attractive if it were done at the same time as current dating ultrasound. Any funding mechanism for screening should take this strategy into account by incorporating, as far as possible, provision of nuchal translucency screening into existing services provided in early pregnancy.

Cost of community gastroenteritis.

BACKGROUND AND AIM: Gastroenteritis is a common illness that causes considerable morbidity in developed countries. Endemic gastroenteritis that is not associated with outbreaks causes the greatest number of cases, but information is limited about the burden of this disease, and the resources required to manage its impact on society. In the present study, we estimated the rate of endemic gastroenteritis, the number of visits to the local doctor, use of medication, and the cost of gastroenteritis in Australia. METHODS: Data from a community-based study of gastroenteritis, a general practice surveillance network, the Australian Bureau of Statistics and the Health Insurance Commission were used to measure endemic gastroenteritis and other study outcomes. The results were then extrapolated to the Australian Community. RESULTS: There were an estimated 0.8 cases of gastroenteritis per person per year in Australia. This equated to 15,173,430 cases of gastroenteritis in Australia annually. The age-standardized estimate of the total number of visits to the general practitioner (GP) for gastroenteritis was 1024,214 at a cost of 26,722,691 Australian dollars. The average cost of prescribed medication per visit was 6.83 Australia dollars; the estimated total cost of prescribed medication was 6995,381 Australian dollars. The estimated cost of over-the-counter medication was 14,587,477 Australia dollars. It was estimated that people working full or part-time had 0.13 days-off per person per year because of gastroenteritis, at a cost of 137,924,170 Australian dollars. The estimated total cost of endemic gastroenteritis in Australia was 342,855,616 Australian dollars of which 75,908,274 Australian dollars was direct medical costs and 266,947,342 Australian dollars was time costs and the costs for time off work to care for a sick family member. CONCLUSIONS: Endemic gastroenteritis is an important illness in both developed and developing countries. Although in developed countries, the majority of individual cases are mild to moderate in their severity; the overall costs are significant. The results highlight the need for ongoing research to identify the main causes of endemic gastroenteritis.

Quality of life and Kaposi sarcoma: using preference techniques to value the health gains from treatment.

The goal of this work was to investigate preference techniques to value potential health gains from treatments of Kaposi sarcoma (KS). The study was designed to take the form of face-to-face interviews with a sample of men with a history of HIV/AIDS ( n=15) or HIV/AIDS and KS ( n=17). The main outcome measure was quality of life (QoL) associated with various KS disease states expressed on a scale from 0 (death) to 1 (perfect health), obtained though time trade-off (TTO) and rating scale techniques. For cutaneous lesions only, the mean TTO preference score value was 0.27. In other words, the men were willing to trade a life expectancy of 5 years for a shorter period (1.4 years) in perfect health. More severe KS health states were rated lower (0.07-0.09). The mean rating scale value for cutaneous lesions only was 0.11 and ranged from -0.10 to -0.04 for the more severe conditions; these values were systematically lower than the TTO ( P=0.014). A large overall potential gain in QoL from treatment (partial response minus stable disease) was found for each condition to be reflected in both the TTO (from 0.31 to 0.55) and the rating scale (from 0.38 to 0.44). Respondents associate KS health states with extremely poor QoL and indicate that large gains are possible through modest treatment effects. While TTO returns higher values than the rating scale, potential gains from treatments were similar. The techniques appear to be suitable for application to QoL and economic evaluation of treatments of KS.