Results for each trial are presented in a format similar to the figure below. Supplementary Appendix B Figure 1. Format for trial level results Outcome Difference in risk between control and treatment Number of patients affected if implemented at 65% Health service cost per person or day Economic Impact on health service costs QALY impact per person Economic impact on QALYS Total Economic Impact Primary Outcome 1 +/-x% A V A * V = C Y A * Y = D C + D Secondary Outcome 2 +/-x% B X B * X = E Z B * Z = F E + F Change in intervention costs Total INT C + D E + F C + D + E + F +/- INT
statistically significant, due to a lack of power. death, or haemorrhagic stroke. warfarin. ARCH provides the impetus for further hypothesis formation and additional trials. Stroke survivors expected to have moderate impairment (Rankin scale 2) at baseline. Proportion with an atherosclerotic plaque in the thoracic aorta = 14% N= 4,116 Outcome Difference in risk between control and treatment N if implemented at 65% Health service cost per person or day Economic Impact on health service costs if implemented QALY impact per person Economic impact on QALYS if implemented Total Economic Impact Primary Composite outcome -33% -100 - $37,130 -$4m -$0.3m -$26m -$29m Change in intervention costs Totals -$2m -$4m -$26m -$32m Columns may not sum due to rounding. Negative values are savings in the calculations. Health Service or Outcome Health service/outcome cost per person or day Explanation and costing assumptions Reference
The guidelines for use of paracetamol in NSW were adjusted to allow its use in stroke patients with a temperature of >37.5°C (updated from >38°C). Furthermore, the QASC Implementation Project found that participating trial sites were more likely to adhere to the hyperglycemia protocol (the protocol requiring the most amount of multidisciplinary teamwork) than sites that had not participated in the trial. Outcome Eligible participants if implemented Primary outcomes Secondary outcomes Clinical context Main clinical assumptions Treatment delivers better patient outcomes after discharge. Adults with stroke = 49,067 90 days after hospitalisation: death or dependency; functional dependency; mean mental & physical components. Processes of care: mean temperature; mean finger-prick blood glucose; proportion with swallowing screening undertaken; discharge diagnosis of aspiration pneumonia; LOS in hospital. The Fever, Sugar, Swallowing (FeSS) intervention has since been successfully implemented into 36 stroke services in NSW. The NSF clinical audit was also changed, and the NSW guidelines for paracetamol updated. Expect functional outcomes as based on Rankin score will capture the QALY impact of Barthel and SF-36 indices. Costing is based on Rankin score. Life expectancy based on Harald Hannerz et al. (2001). Proportion of patients excluded = 69% N= 15,211 Outcome Difference in risk between control and treatment N if implemented at 65% Health service cost per person or day Economic Impact on health service costs if implemented QALY impact per person Economic impact on QALYS if implemented Total Economic Impact Primary Functional outcomes at 3 months (Rankin scale score). Based on $ difference for treatment and QALY between treatment and control groups. -9,887 -$1,865 -$18m -$26,580 -$263m -$281m Change in intervention costs Totals +$0.6m -$18m -$263m -$281m Columns may not sum due to rounding. Negative values are savings in the calculations. LOS = length of stay. NSF = National Stroke Foundation. Health Service or Outcome Health service/ outcome cost per person or day Explanation and costing assumptions Reference
major sensorineural disability at 2 years of age. Adverse effects of hypothermia are negligible. sensorineural impairment at 2 years. sensorineural impairment at 2 years. method of therapeutic hypothermia is effective and safe. therefore not included. Benefit is primarily due to decreased mortality. No impairment in survivors, standard life expectancy. Proportion of infants with indicators of peripartum and moderate to severe clinical encephalopathy (1.2 per 1000) N= 369 Outcome Difference in risk between control and treatment N if implemented at 65% Health service cost per person or day Economic Impact on health service costs if implemented QALY impact per person Economic impact on QALYS if implemented Total Economic Impact Primary Composite outcome – individually costed below. - - - - - - - Secondary Mortality -35% -32 - - -$4.2m -$136m -$136m Sensorineural impairment No statistically significant difference. - - - - - - Change in intervention costs Totals +<$0.1m - -$136m -$136m Columns may not sum due to rounding. Negative values are savings in the calculations. Health Service or Outcome Health service/ outcome cost per person or day Explanation and costing assumptions Reference Mortality QALY: -$4,200,000 Incremental gain is extra survivors, who are not impaired or disabled. Survivors have full life expectancy. Confirmed through interview. Office of Best Practice Regulation, value of statistical life year.
Outcome Eligible participants if implemented Primary outcomes Secondary outcomes Clinical context Main clinical assumptions Preventive care at home leads to Improved behavioural outcomes for infants, and reduces anxiety and depression for primary caregivers. Infants born at <30 weeks' gestation with no major congenital brain anomalies associated with poor neurodevelopmental outcomes = 1.7% Infants: Cognitive, language and motor development at age 2. Mothers: and mental health of primary care-giver at same Infants: Child behaviour and emotional regulation at age 2. Prior to the trial, there was little existing evidence for the effectiveness for preventive care at home for newborns. It is unlikely the trial results will be implemented due to the cost of intervention. Main impact is through maternal outcomes rather than those for infants. Dysregulation will not be treated in clinical practice at this stage. Dysregulation may be predictive of longer term neurodevelopmental outcomes (e.g. autism), however, it is not costed here as the predictive association is not part of this study. Impairment for maternal anxiety and depression is for two years in parents of very preterm infants. Live births = 307277, mothers = 304777 Infants, N = 5224, Mothers, N = 5181 Outcome Difference in risk between control and treatment N if implemented at 65% Health service cost per person or day Economic Impact on health service costs if implemented QALY impact per person Economic impact on QALYS if implemented Total Economic Impact Primary Cognitive, language and motor development No statistically significant difference. - - - - - - Secondary Anxiety (maternal) -43% -326 -$2,000 -$0.7m -$60,979 -$20m -$21m Depression (maternal) -35% -1027 -$2,000 -$2m -$57,033 -$59m -$60m Change in intervention costs Totals +$6m -$3m -$78m -$75m Columns may not sum due to rounding. Negative values are savings in the calculations.
Outcome Difference in risk between control and treatment N if implemented at 65% Health service cost per person or day Economic Impact on health service costs if implemented QALY impact per person Economic impact on QALYS if implemented Total Economic Impact Primary Unplanned doctors visit (mean) -0.3 -6,347 -$130 -$0.8m - - -$0.8m Oral corticosteroid use (mean) -0.09 -2,327 -$9 <-$0.1m - - <-$0.1m Secondary Neonatal hospitalisation -53% -1,920 -$11,884 -$23m - - -$23m Change in intervention costs Totals +$2m -$24m - -$22m Columns may not sum due to rounding. Negative values are savings in the calculations. ED = emergency department. Health Service or Outcome Health service/outcome cost per person or day Explanation and costing assumptions Reference Unplanned doctor visits Service cost: -$130 Unscheduled doctor visits were in primary care. Confirmed through interview. The cost is based on MBS 597, out of hours cost, to offset some of the missed savings in additional nursing and ancillary support. Oral corticosteroid use Service cost: -$9 Costs of B2 agonists balance out due to overall different treatment profile, and are not thought to be economically salient. Cost of oral corticosteroids included as a primary outcome (raw material cost $9, PBS). No additional clinical costs (beyond GP visits). No QALY impairment for moderate asthma exacerbations resolved with oral corticosteroids. http://www.aafp.org/afp/2011/0701/p40.html http://www.pbs.gov.au/medicine/item/1916W-1917X-3152X
Outcome Difference in risk between control and treatment N if implemented at 65% Health service cost per person or day Economic Impact on health service costs if implemented QALY impact per person Economic impact on QALYS if implemented Total Economic Impact Primary Severe lung disease -40% -236 (included elsewhere) - -$5,460 -$1m -$1m Mechanical ventilation (hours) -24 -70,944 -$104 -$7m - - -$7m Secondary Surfactant use -25% -236 -$500 -$0.1m - - -$0.1m Patent ductus arteriosus -42% -148 -$4,182 -$0.6m -$5,460 -$0.8m -$1m Caesarean sections +16% +151 +$5,014 +$0.8m - - +$0.8m Change in intervention costs Totals +$0.5m -$7m -$2m -$9m Columns may not sum due to rounding. Negative values are savings in the calculations. Health Service or Outcome Health service/outcome cost per person or day Explanation and costing assumptions Reference Severe lung disease QALY: -$5,460 Cost is captured in mechanical ventilation and surfactant use (no difference in average length of stay or NICU admission rates). Confirmed through interview with senior trial investigators. AIHW disability weight 0.03 equivalent to surgically treated congenital atrial or ventricular septal defect. Impairment is for one year. Mathers et al.1999. The burden of disease and injury in Australia. AIHW cat. no. PHE 17. Canberra: AIHW.
Caesarean delivery Service cost: -$7,532 Incremental difference between vaginal delivery (baseline) and caesarean delivery. Casemix funding. ARDRG IHPA Version 7 Round 18. Intervention costs Captured in trial outcomes No incremental increase in intervention costs of expectant management as this will be absorbed in the average length of stay increase. -
QALY: stroke in Tan Tanny et al. (2013). Average disability weight (0.20) based on WHO. Impairment is for one year. Hours of Acute Ischemic Stroke. Stroke. 44:2269-2274. WHO (2013). WHO methods and data sources for global burden of disease estimates 2000-2011. Intervention costs Service cost: -$42,294 Average cost of intervention based on casemix funding for 2 cranial procedures (first procedure is the craniectomy to remove part of the skull and the second procedure is the cranioplasty to repair the skull 2-3 months later). Average of B02A, B02B, B02C = $42,294 per patient. Comparable to Western Australian study by Ho et al. 2011, ~USD $28,000. IHPA NWAU calculator for acute activity 2016-17. Ho et al. (2011). Cost-Effectiveness of Decompressive Craniectomy as a Lifesaving Rescue Procedure for Patients With Severe Traumatic Brain Injury. SAFE Trial (2004) – The SAFE study: saline vs. albumin for fluid resuscitation in the critically ill Context Fluid resuscitation, (the administration of intravenous fluids to maintain or increase intravascular volume), is a common intervention, used for around 35% of patients in the ICU. There has been enduring controversy as to the impact of the choice of resuscitation fluid on patients’ outcomes. The SAFE study compared patient outcomes when 4% albumin or 0.9% sodium chloride (normal saline) is used for intravascular fluid resuscitation in ICU. The SAFE study found that using 4% albumin and normal saline results in equivalent 28-day all-cause mortality, as well as similar use of mechanical ventilation and renal therapy, and similar length of stays.
While the cost of production for albumin is higher than saline ($133/L compared to $2/L), the actual use of albumin in Australia has not fallen drastically since the SAFE study (36.6% of patients receiving fluid resuscitation received albumin in 2007 compared to 31.6% in 2013). This may be because albumin is provided free-of-charge to public hospitals in Australia. The study has however likely prevented an increase in use of albumin. Outcome Eligible participants if implemented Primary outcomes Secondary outcomes Clinical context Main clinical assumptions Albumin and saline results in equivalent mortality, and mechanical ventilation use, renal replacement therapy, length of stay in ICU and hospital. There is some evidence that trauma patients benefit more from resuscitation with saline than non-trauma patients, but this requires further study. Total adult ICU admissions per year 123,564 Death from all causes at 28 days after randomisation. Survival time during the first 28 days, new organ failures, mechanical ventilation use, renal replacement therapy and length of ICU and hospital stay. Enduring controversy on the impact of resuscitation fluid on patient outcomes. No statistically significant difference shown. Use of albumin has remained consistent since the trial, possibly indicating a preference for albumin, which is provided free-of charge at the point of use, to Australian public hospitals., Cost based on study fluid administered (saline and albumin) and packed red blood cells. No cost differences required for process measures (net fluid balance, heart rate on day 1, central venous pressure and serum albumin). Proportion of ICU patients receiving albumin for fluid resuscitation = 35% N= 42,415 Outcome Difference in risk between control and treatment N if implemented at 65% Health service cost per person or day Economic Impact on health service costs if implemented QALY impact per person Economic impact on QALYS if implemented Total Economic Impact Primary & Secondary No statistically significant difference - - - - - Change in intervention costs Totals -$16m - - -$16m Columns may not sum due to rounding. Negative values are savings in the calculations. Health Service or Outcome Health service/outcome cost per person or day Explanation and costing assumptions Reference
Outcome Eligible participants if implemented Primary outcomes Secondary outcomes Clinical context Main clinical assumptions There is no significant difference in mortality between treatment and control groups.More patients in the treatment group however are treated with renal replacement therapy, and there are also more adverse events in the treatment group. Renal injury is more likely in the control group. Patients receiving fluid resuscitation in ICU 35%. Proportion excluded = 32% Death within 90 days Incidence of acute kidney injury, use of RRT, new organ failures, duration of mechanical ventilation and RRT; and mortality. The trial was undertaken in a society (starch not licensed until 2008 in Australia). There is now no use of starch in Australian ICUs. Without the trial, starch would have become standard practice in Australia. Renal failure indicated by use of RRT. Pruritus not clinically significant (resolves and has other causes). Adult ICU admissions = 123,564 N= 29,566 Outcome Difference in risk between control and treatment N if implemented at 65% Health service cost per person or day Economic Impact on health service costs if implemented QALY impact per person Economic impact on QALYS if implemented Total Economic Impact Primary No statistically significant differences - - - - - - - Secondary Included as intervention cost - - - - - - - Change in intervention costs Totals -$38m - - -$38m Columns may not sum due to rounding. Negative values are savings in the calculations. RRT = renal replacement therapy. ICU = intensive care unit. **If the unrestricted commercial funding amount described above is included, total funding to the CHEST trial will amount to approx. $10m, and the Net Profit will be $27m. The overall consolidated Benefit to Cost ratio will be 4.6:1 (if commercial funding from the PROGRESS trial within the ASTN is also included). Health Service or Outcome Health service/ outcome cost per person or day Explanation and costing assumptions Reference specific
The trial provided evidence to shift away from implementation of EGDT, which carried additional costs, in Australia. Outcome Eligible participants if implemented Primary outcomes Secondary outcomes Clinical context Main clinical assumptions There are no significant differences for mortality at 90 days, nor survival time, in-hospital mortality, duration of organ support, and length of hospital stay. There is a marginal reduction in time spent in the Emergency Department (ED), which is not considered to be sufficient to justify intervention with EGDT. Patients admitted to ICU = 123,564 All-cause mortality within 90 days after randomisation. Survival time to 90 days; mortality; LOS in the ED, ICU, or hospital; mechanical ventilation, vasopressor support, or RRT; adverse events. The trial has resulted in a shift away from using Early Goal Directed Therapy for patients with early septic shock. Trial confirms control as approach of choice. Increased treatment costs for EGDT driven by transfusions, dobutamine and intravenous fluids, time and materials. ED time is costed separately to the intervention as it was a statistically significant finding. Change in ED time however, may be an artefact of patients from both groups being part of the trial (and therefore experiencing more efficient care coordination). Proportion diagnosed with severe sepsis = 3% N= 3,648 Outcome Difference in risk between control and treatment N if implemented at 65% Health service cost per person or day Economic Impact on health service costs if implemented QALY impact per person Economic impact on QALYS if implemented Total Economic Impact Primary No statistically significant difference - - - - - - Secondary Duration in ED (hours) +0.6 +1,423 +$200 +$0.3m - - +$0.3m Change in intervention costs Totals -$1.5m +$0.3m - -$1.2m Columns may not sum due to rounding. Negative values are savings in the calculations. EGDT = early goal therapy. ED = emergency department. LOS = length of stay. ICU = intensive care unit. RRT = renal replacement therapy.