Sources of cost inputs; base case and summary of sensitivity analyses
In our economic evaluation, resource use and costs were estimated from the perspective of the NHS. All costs reported in this chapter are based on 2010/11 prices unless otherwise specified.
Base case
Our main source of information on cost and resource use was from a previous HTA report undertaken by Sharples et al.30 In the Sharples et al.30 study, patient-specific resource-use data were collected for VAD implant, HT, and patients on MM while awaiting transplant. For all three patient groups, costs were collected as monthly costs from the date of VAD implantation, or the date the patients were accepted on to the transplant WL, until the study cut–off date. Post-transplantation and VAD monthly cost were assumed to be constant from month 7 onwards in all groups. Importantly, the study recorded actual costs incurred by patients and, hence, provides a more accurate representation of costs. For our model, these costs were inflated to current levels by applying the projected health services costs.120 VAD costs were obtained from five UK centres operating under the auspices of the National Specialist Commissioning Team (NSCT), which commissions the VAD programme. We did not include the cost of the VAD supplied by GJNH which was based on a single VAD used at this centre; however, this was used in scenario analysis. The base-case cost inputs for the three health states are summarised in . It is worth mentioning that Sharples et al.30 estimated resource use from the perspective of the NHS and centre. In such settings, the cost does not include setting-up costs for a new centre and we would emphasise that setting up a new service would incur additional set-up costs.
Base-case costs for each health state. Summary of cost inputs for the base-case economic analysis – 2010/11 prices
State 1: Support on bridge to transplant with a ventricular assist device until heart transplant
This health state consists of an early short-term phase associated with the VAD implant procedure cost which includes the cost of the device, theatre cost and cost of immediate post-operative hospital stay, and a second long-term follow-up phase that includes the costs of outpatient visits, adverse events and rehospitalisation.
We obtained costs of VADs from five centres (listed below) providing long-term VAD support:
The base-case cost per VAD (£80,569) was a weighted value according to the number of devices used by BTDB BTT patients and costs of different devices. Details of unit cost of VADs used in this study are given in .
Device maintenance cost
The costs of maintaining the VAD per patient and associated costs of replacing batteries, cables and other hardware are not incorporated in any of the published cost-effectiveness models. We contacted two long-standing VAD manufacturers, who suggested that the yearly VAD maintenance and other hardware costs were trivial. Although we obtained costs of VADs from six centres, only two centres provided an annual maintenance cost (of £4000/year from year 2 onwards). All other centres reported that the purchase price of the device included a maintenance element and that they did not incur any additional cost on maintenance. We again contacted the device manufactures to verify the maintenance element, but no response was forthcoming. We therefore did not adjust the Sharples et al.30 estimate for the cost of device maintenance.
We estimated the VAD implant procedure cost based on a GJNH finance department costings (£3728.20) supplied to us on request. Detailed information on this is given in .
Pre-VAD implant preparation and theatre costs (GJNH finance department)
State 2: Support on medical management until heart transplant
The input required is an estimate of the average monthly cost while patients are medically managed. This includes medication, such as inotropes, and follow-up assessment as inpatient or out-patient visits.
An inotrope-dependent patient subgroup of BTDB MM patients was selected for the base-case analysis. We consulted our clinical advisors and they advised that medications and inotropes used will have remained similar as the previous analysis.30 The intravenous inotropes used were enoximone 5 μg/kg/minute and dopamine 5 μg/kg/minute. We inflated the cost of inotrope-dependent patients' medications to 2011 prices by applying the projected Health Services Cost Index.120 The resulting monthly costs with distribution parameters where appropriate are shown in .
State 3: Support on heart transplant
The cost inputs include average presurgery preparatory cost, procedural cost and short-term post-surgery cost. The transplantation procedure cost was considered to be different between groups to address the increase in theatre time for VAD explant. Post-transplant monthly costs were assumed to be the same for both groups from month 2 onwards. Post-HT support costs include follow-up outpatient visits, investigation, blood test and drugs (see ).
Clinical experts advised that the costs of the transplant donor procedure were trivial and we therefore did not include this cost in our model.
Sources of cost inputs: summary of sensitivity analyses
Sensitivity analyses around cost inputs
A sensitivity analysis (I A1] in Table 54) was conducted around the TP for MM to death which assumed the MM group was constituted of all BTDB MM patients (both 307 inotrope patients and 1189 non-inotrope patients). The monthly cost for these is shown in .
Cost inputs for patients on MM (both inotrope and non-inotrope)
The monthly cost of all MM was a weighted value according to the number of both inotrope and non-inotrope patients from the BTDB. We used previously reported costs30 for inotrope- and non-inotrope-supported MM patients, inflated to 2010/11 prices for the sensitivity analysis .
Cost inputs for patients medically managed with inotropes and without inotropes
Sensitivity analyses II A and II B around cost inputs
In univariate sensitivity analyses, the cost of the VAD was varied from that in the base case as shown in . This analysis is designated II A in the results section.
Summary of costs used in univariate sensitivity analyses
In a further sensitivity analysis (designated II B) the cost of patient maintenance on a VAD was decreased from base case by 30%.
This was undertaken because clinical experts advised that patients on second- and third-generation VADs experience relatively fewer adverse events than those supported with earlier VAD designs. To address the potential cost savings of reduced adverse events, we lowered the monthly post-VAD implantation cost by 30% in sensitivity analysis.
Sensitivity analyses (II C and II D) around costs for both arm using Golden Jubilee National Hospital and national schedule of reference costs data
Further sensitivity analyses used a detailed list of resource use and associated costs which were supplied from Glasgow the Glasgow centre, the GJNH, one of the UK centres operating with the NSCT (analysis II C). The GJNH cost data and definitions used are all presented exactly as provided by GJNH. This provided information on all three health states. In addition, we also sourced the mean cost for three health states from the national schedule of reference costs (NSRC) 2010/11 (analysis II D).122 These alternative sources are described in further detail below.
Support on medical management until heart transplant
Resource-use data from the Glasgow GJNH finance department were collected on hospital stay, drugs, investigations and outpatient visits for patients with advanced HF. The GJNH finance department reported a total cost of £10,111.66 per hospital stay per patient with advanced HF for the year 2009/10, based on a total of 92 patients costing £842.63 (£10,111.66/12) per patient in month 1. Further detailed information on the resource use and costs supplied by GJNH involved in managing patients in hospital with advanced HF is shown in .
Cost of hospital stay for advanced HF (GJNH finance department)
From the cost provided by the GJNH finance department, it was not possible to identify the drugs and inotropes used in hospital at the time of admission. We assumed that patients admitted to hospital for advanced HF were inotrope-dependent and patients at home on the WL were non-inotrope-dependent (Dr Mark Petrie, GJNH, 2012, personal communication).
Patients at home and on the WL were seen in the HF clinic every third month. The cost per initial visit was £437.79, and after 3 months patients are reassessed by a multidisciplinary team consisting of a cardiologist, a cardiac surgeon and a specialist nurse. The cost for every other consecutive follow-up was £160.11 per visit.
We also sourced the mean cost of MM (from the NSRC) 2010/11 and these were explored in the sensitivity analysis (see ).
Summary of cost inputs for sensitivity (analyses II C and IID) based on the GJNH finance department and NSRC– 2010/11 prices
Support on bridge to transplant with a ventricular assist device until heart transplant
A detailed description of resource-use data and unit cost estimates were collected for VAD implant from the GJNH finance department. Resource-use data were collected on VAD assessment cost, implant procedure cost, cost associated with ward and ICU stay, follow-up outpatient visits, investigation, blood test and drugs. The cost was based on one long-term VAD (HMII) patient for 2009/10. We recommend caution in interpreting this result partly because of this and partly as we believe that the cost from the GJNH might be overestimated (as throughput for this intervention is at present insufficient for economies of scale to be in evidence). However, the GJNH data give us details of the cost component for immediate post-operative hospital stay following VAD implant, and are shown in .
Cost of immediate post-operative hospital stay following VAD implant (GJNH finance department)
Following a VAD implant, patients were requested to attend fortnightly for a follow-up visit for 1 month, then to visit monthly for 3–4 months and then to visit 3-monthly for 6 months. Outpatient follow-up visit was estimated at £894.06 per visit (an outpatient visit post VAD is resource intensive with several invasive tests and non-invasive test undertaken during a follow-up visit).
We also sourced the mean cost of VAD implantation from the NSRC 2010/11 and this was explored in the sensitivity analysis (see ).
Support on heart transplant
We determined the transplantation procedure cost for both VAD and MM patients from the GJNH finance department. The theatre cost of retrieving a donor heart was reported as £16,811.66. This includes the cost of surgical support for organ retrieval and does not include the cost of investigations; and summarise HT theatre cost and immediate post-operative hospital stay cost following four HTs. We recommend caution in interpreting this result partly because of these small numbers and partly as we believe that the cost from the GJNH might be overestimated owing to lack of economies of scale.
Pre-HT preparation and theatre cost (GJNH finance department)
Costs of immediate post-operative hospital stay following HT (GJNH finance department)
Following a HT, the follow-up management for both VAD and MM patients was assumed to be the same. The transplant management guidelines from the GJNH detailing follow-up outpatient visits, blood tests, chest radiograph and the biopsy regimen are provided in .
Scottish National advanced HF service transplant management guidelines recommendations for post-transplantation patients
We also sourced the mean cost of HT from the NSRC 2010/11 and this was explored in the sensitivity analysis. These are summarised in .
Model assumptions for transition probabilities, utilities and cost inputs
A summary of the transition probabilities, utilities and cost inputs to the cost–utility model is detailed in . We also include here a list of model assumptions.
Summary of transition probabilities, utilities and cost inputs to the cost–utility model
Model assumptions – transition probabilities
The model was simplified by assuming all patients have the same survival post HT despite receiving a donor heart at different times (up to maximum of 42 months) and despite different treatment (VAD or MM) prior to transplant. The assumption is supported by data published by Russo
et al.100 and Nativi
et al.89 The same assumption has been made in previous economic analyses.
30,98In our base-case analysis < 1% of patients are alive supported by a VAD beyond 70 months.
In the base case, the model assumes that for an equitable comparison of the compared therapies the same probability of receiving a donor heart should be applied for both treatment and comparator groups.
In the base case, survival of BTDB MM and VAD-supported patients who were censored on receipt of a HT was assumed to represent survival of patients eligible for HT who never received one; the impact of this was examined in extensive sensitivity analysis. Furthermore, constant hazard extrapolations were assumed to be reasonable estimates for extension of survival beyond the observed data. The same assumption has been made in previous economic analyses.
30,98It is assumed that the MM patients in the BTDB who were classified as baseline users of ‘inotropes’ represent a distinct subpopulation of all MM patients in the database.
The model assumes that post-HT survival remains the same irrespective of previous therapy (BTT with VAD or MM) and can be estimated from observed survival of UK BTDB patients who receive a donor heart.
Model assumptions – costs
The model assumes that, other than for VAD cost, resource use associated with MM and VAD support have remained essentially the same as the previous analysis
30 so that relative costs merely require inflating to current prices. Expert clinical advice supported this assumption.
We simplified assumptions on adverse event costs occurring in the long term (due to lack of reliable data).
For costing we assumed that patients on second- and third-generation VADs rarely require a VAD replacement within a 7-year period; this was based on personal communication with HW manufacturers (Mr Timothy Homer, Global Market Access, 2012, personal communication).
Model assumptions – utilities
The base-case model assumptions were explored in sensitivity analyses. In the next section we describe results from the cost-effectiveness model.
Assessment of quality of cost inputs
The Sharples et al.30 study was a good-quality study estimating cost inputs by combining two methods: direct observation of patients cost and cost estimated from NHS finance departments. The estimated unit costs were specific to the intervention and events of interest, and were generalisable to the study population. The resource use was measured for all three patient groups from the perspective of the NHS until the study cut-off date. Quality and validity of the cost data are good in relation to criteria suggested by Drummond et al.97 The study by Sharples et al.30 was the only study to report patient-specific resource-use data for the VAD procedure and subsequent stay in ICU and cardiac ward. The unit cost reflected the level of resource aggregation for procedure and itemised subsequent costs appropriately (e.g. stay in ICU and cardiac ward; device cost; HT procedure and associated ICU and ward stay; transplant assessment; follow-up readmission to ICU or ward; outpatient visits; investigation and drugs). A weakness of the study for the purposes of the current report is that it describes the results of a mixture of first- and second-generation VADs; however, it is the only available comparable study with the most recent resource-use data and unit cost estimates published in the UK setting.
