Kidney disease: peritoneal dialysis in the treatment of stage 5 chronic kidney disease

Transcription

1 Kidney disease: peritoneal dialysis in the treatment of stage 5 chronic kidney disease Draft after consultation, April 2011 Appendix B Cost effectiveness of peritoneal dialysis provision The National Institute for Health and Clinical Excellence (NICE) has been asked to produce a guideline on decision making around the choice of dialysis options: that is, between peritoneal dialysis and haemodialysis. This is the cost effectiveness analysis developed to support the guideline development group (GDG) in making recommendations. The analysis was conducted according to NICE methods outlined in the Guide to the methods of technology appraisals, 2008 and the Guidelines Manual Therefore, it follows the NICE reference case (the framework NICE requests all costeffectiveness analysis to follow) in the method used. Contents Kidney disease: peritoneal dialysis in the treatment of stage 5 chronic kidney disease... 1 Draft after consultation, April Appendix B... 1 Cost effectiveness of peritoneal dialysis provision... 1 Decision problem... 2 Literature... 3 Model structure... 6 Assumptions... 7 Transition probabilities Quality of life Costs and resource use Analyses Results Limitations Discussion References Section 2 Cost effectiveness study checklists Section 3 WinBUGS code Section 4 Mapping Section5 Quality of life data Section 6 Cost effectiveness scatter plots Kidney disease peritoneal dialysis: appendix B cost effectiveness 1 of 74

2 Decision problem Scope Population Adults with a diagnosis of stage 5 chronic kidney disease who need or who are receiving renal replacement therapy Children and infants with a diagnosis of stage 5 chronic kidney disease who need or who are receiving renal replacement therapy Within this population, the following groups have been identified as needing special consideration: people older than 75 years people who are socially disadvantaged Interventions Continuous ambulatory peritoneal dialysis, Automated peritoneal dialysis assisted automated peritoneal dialysis Comparators Hospital haemodialysis Satellite haemodialysis Home haemodialysis Outcome(s) Hospitalisation rate Technique, peritoneal or venous access failure Anaemia, including erythropoietin use Adverse effects of dialysis, for example infections Mortality Health-related quality of life Patient involvement and satisfaction in decision making Resource use and costs Approach taken Adults with a diagnosis of stage 5 chronic kidney disease who need or who are receiving renal replacement therapy Continuous ambulatory peritoneal dialysis, Automated peritoneal dialysis assisted automated peritoneal dialysis Hospital haemodialysis Satellite haemodialysis Home haemodialysis Hospitalisation rate Technique, peritoneal or venous access failure Anaemia, including erythropoietin use Adverse effects of dialysis, for example infections Mortality Health-related quality of life. Patient involvement and satisfaction in decision making Resource use and costs Population The population of this analysis will be all adults (over 18) who require dialysis. The reason for the exclusion of children is that very few data have been identified for this population and there is insufficient evidence to conduct an economic analysis. In addition, people who are opting for immediate transplants are not considered because their pathway is different from that for people who require dialysis until a transplant becomes available. The population is an average of all adult patients. Kidney disease peritoneal dialysis: appendix B cost effectiveness 2 of 74

3 Interventions The modalities of dialysis that will be examined are continuous ambulatory peritoneal dialysis (CAPD), automated peritoneal dialysis (APD), assisted APD, haemodialysis delivered in a hospital or satellite setting, and home haemodialysis. Comparators Given the issue this guideline is addressing, instead of a comparison between peritoneal dialysis and haemodialysis, a comparison between different provision make-ups will be explored. This will allow the use of specific peritoneal dialysis and haemodialysis data without concerns over differences in populations. In addition, it addresses the key issue of this guideline, which is to determine how improved decision making could affect the provision of dialysis. Outcomes Costs, life years gained (LYG), quality adjusted life years (QALYs), cost per QALY, incremental cost effectiveness ratios (ICERS) and cost effectiveness acceptability. Literature A search for existing health economic analyses was undertaken and identified 14 cost effectiveness studies that included dialysis. Of these 14, 7 compared a form of haemodialysis with a form of peritoneal dialysis. A paper by Hooi et al. (2005) was not included in the final analysis because it does not examine the use of CAPD at home (the main form of CAPD used in the UK) and therefore was not considered applicable. A paper by Salonen et al. (2007) was not included because no consideration of quality of life was made and it had limited comparability to the UK. Kirby et al. (2001) was considered even though it did not include utilities, because it was the only UK based study recovered. A GRADE table summarising the remaining five papers is presented in Table 1. Quality checklists for these studies are presented in appendix 1. Kidney disease peritoneal dialysis: appendix B cost effectiveness 3 of 74

4 Table 1 GRADE table of cost effectiveness studies Study Population Comparators Costs LYG QALYS Kirby and Vale 2001 Scottish ESRD patients on initial modality CAPD 65,061-76, Hospital HD 63,370-79, Incremental LYG QALYS Costs ICER (incremental) Uncertainty Limitations Applicability NS Discount rate HD remains NS dominant strategy after changing effectiveness and costs Potentially serious limitations Partially applicable Comments: Model does not include transplantations or APD, home HD, satellite HD. Lack of quality of life potentially serious limitations since main difference between modalities is quality of life. De Wit et al Dutch population ESRD from 1998 Baseline ƒ3,240,312,000 41,149 32,955 Changes to Tx to 34 ƒ3,214,780,200 41,192 33, ƒ25,531,800 Dominates Tx to 44 ƒ3,181,044,100 41,249 33, ƒ59,267,900 Dominates 10% CHD to LCHD 20% CHD to LCHD 10% CHD to CAPD 20% CHD to CAPD 10% CHD to CCPD 20% CHD to CCPD ƒ3,253,006,500 41,289 33, ƒ12,694,500 +ƒ ƒ3,265,714,900 41,430 33, ƒ25,402,900 +ƒ ƒ3,230,890,900 41,234 33, ƒ9,421,100 Dominates ƒ3,221,425,800 41,319 33, ƒ18,886,200 Dominates ƒ3,240,392,000 41,221 33, ƒ80,000 +ƒ ƒ3,240,440,000 41,293 33, ƒ128,000 +ƒ 584 Comments: 1 euro = NLG The analysis is of good structure, but due to its age and changes in technology has limited applicability to the UK quality of life estimation from standard gamble to time trade off increase QALYs and reduces ICER Very serious limitations Partially applicable Sennfalt 2002 Sweden for 20 to 60 year old kidney failure patients CAPD $35,120 NR NR ICER varied between HD $36,780 NR NR NR NR 1660 $96,770.1 $90,766 to 100,070 when using high or low estimates for costs Potentially serious limitations Partially applicable Kidney disease peritoneal dialysis: appendix B cost effectiveness 4 of 74

5 Study Population Comparators Costs LYG QALYS Comments: Very short time horizon (5 years), limited reporting of results Incremental LYG QALYS Costs ICER (incremental) Uncertainty Limitations Applicability Teerawattanon et al to 70 year old Thai patients (Baht) Haemodialysis CAPD Same same Comments: Good structure and approach, however limited transferability due to country of origin CAPD dominates HD CEAF 0 to 650,000 Palliative care optimum 650,000 plus CAPD optimum Main areas for further research are maintenance costs of HD and PD according to EVPPI Minor limitations Partially applicable Howard et al ESRD population, Australia Hosp HD Sat HD PD Transplant (Tx) Baseline - AUD2,595,326,368 39,656 22,526 Discount rate 10% increase in AUD2,589,491,524 39,759 22, $5,834,844 Dominates no effect Tx - 50% increase in Tx - AUD2,569,147,811 40,164 23, $26,178,557 Dominates PD increase AUD2,473,264,905 39,656 22, $122,061,463 Dominates HHD increase AUD2,548,742,213 39,656 22, $46,584,155 Dominates Comments: Approach to question appropriate to guideline, but transferability affected by country setting and missing comparators Potentially serious limitations Partially applicable Kidney disease peritoneal dialysis: appendix B cost effectiveness 5 of 74

6 Kirby and Vale (2001) is the only paper identified that is based in the UK. However, it examines only life years gained and does not consider quality of life. This study used hospital costing data and systematic reviews to inform the model parameters. The authors conclude that haemodialysis is more effective and cheaper than CAPD. The main issue with this paper is that is now 10 years old so there may have been significant changes in the evidence base, costs and in the technology. The other studies are split into two types of analyses; Teerawattanon et al. (2007) and Sennfalt (2002) compare haemodialysis with CAPD. Both these studies conclude that CAPD is less expensive and more effective than haemodialysis. De Witt et al. (1998) and Howard et al. (2009) examine renal replacement therapies services and changing the proportion of people starting different modalities of dialysis and renal replacement therapies. These papers conclude that to increase transplantation and peritoneal dialysis would be the most cost effective options. The majority of these studies conclude that increasing the use of peritoneal dialysis is a cost effective approach. Of these studies none are entirely applicable to the current NHS and also none include APD and aapd. Therefore, a new analysis is required. The approach that examined what would happen if the proportion of peritoneal dialysis was increased appears to be appropriate for use in this guideline, which is principally examining improved decision making between choices of dialysis modalities and enabling patients to choose treatments that are appropriate. Model structure Figure 1 presents a simplified model structure. This is based on the previous models identified and Guideline Development Group input. Patients start in one of the six dialysis states. While on dialysis a number of different pathways are possible. Patients can stay on their first dialysis modality; or they can have a complication that can result in the patient returning to their first modality, switching to an alternative modality, or dying from the complication. Alternatively someone can switch modality at any time. Patients can have a transplant, although evidence from Kidney UK suggests that only 50% on Kidney disease peritoneal dialysis: appendix B cost effectiveness 6 of 74

7 dialysis will be suitable for a transplant. Finally, all patients can enter the absorbing dead state from any of the other states. Figure 1: Schematic of model Given the lack of information on the proportion of people on assisted APD, this is not a discrete health state. Instead, a proportion of people in the APD state are assumed to require assistance. The model is constructed in winbugs and the code is presented in appendix 2. Costs and benefits are discounted at 3.5% each. Time horizon Ideally a lifetime time horizon would be adopted to measure all the potential benefits of a treatment, in line with the NICE methods guide. However, given computational restrictions the probabilistic model is run over 10 years, different time horizons are examined in sensitivity analysis. Assumptions This model assumes that the actual dialysis determines the outcomes rather than the person s eligibility criteria. Therefore, someone eligible for APD, but receiving satellite haemodialysis will have the quality of life and survival associated with satellite haemodialysis. This could be considered erroneous because people eligible for APD would generally be healthier and therefore Kidney disease peritoneal dialysis: appendix B cost effectiveness 7 of 74

8 expected to have better outcomes. To explore the effect of this, a sensitivity analysis is conducted in which the survival estimates are the same but the costs associated with dialysis modality change. People don t change from one haemodialysis to another haemodialysis There were no data identified on people switching between different modalities of haemodialysis. Therefore, it is assumed that people can only stay on one form of haemodialysis and not switch to another. This could mean that people are being switched from haemodialysis to peritoneal earlier than they would in practice, because in reality people may try a number of different haemodialysis modalities. No differentiation of complications Complications are grouped into one state rather than individually specified. This may lead to under or overestimation of the cost of adverse events. Sensitivity analysis is undertaken to examine whether the cost of adverse events were increased and decreased around the mean value. Switching or restarting transplantation The model assumes that people who switch or restart dialysis after transplantation will do so according to the same proportion as people start dialysis. So if people are allocated to the modalities as follows: Hospital Satellite Home HD CAPD APD HD HD 20% 30% 10% 20% 20% then someone on haemodialysis who switches to peritoneal dialysis has a probability of 50% of transiting to CAPD (20 %/[20%+20%] = 50%), and if someone on peritoneal dialysis switches to haemodialysis then the probability of transiting to satellite haemodialysis is 50% (30/[ ] = 50%). Initial staring cohort For this economic analysis, instead of comparing haemodialysis with peritoneal dialysis, different combinations of the various modalities are compared to examine whether health services should offer the option of the various modalities and whether the proportion of peritoneal dialysis should be Kidney disease peritoneal dialysis: appendix B cost effectiveness 8 of 74

9 increased. The renal registry report 2009 gave proportions of patients in England and Wales on the various modalities (see Table 2). The proportion of people who require assistance was estimated to be 40% from GDG consensus and the clinical review. Table 2 Baseline scenario of RRT patients initial modality Dialysis modalities Proportion Hospital haemodialysis 47% Satellite haemodialysis 33% Home haemodialysis 2% Continuous ambulatory peritoneal dialysis 14% Automated peritoneal dialysis 4% The renal association suggests that the proportion of people who start on peritoneal dialysis could be increased to about 25% and possibly higher. Therefore, various proportions are examined as various scenarios, with Table 2 as the baseline. The proportions examined are split into three analyses. Analysis 1 (presented in Table 3) is based on data from the UK renal registry report 2009 with CAPD defined as discount peritoneal dialysis and APD/aAPD as cycling peritoneal dialysis for more than 6 nights, and using combinations from primary care trusts to represent a haemodialysis centric service and a peritoneal dialysis centric service. Table 3 Analysis 1 proportions Hosp HD Sat HD Home HD CAPD APD Baseline 47% 33% 2% 14% 4% 1 HD cen 28.5% 67.5% 0.5% 2% 1.5% 2 PD cen 8.5% 49% 9.5% 20% 13% Scenario 1 represents a health service that is centred on providing mainly haemodialysis in health care provision. Scenario 2 is a health service based on maximising the provision of home care. Analysis 2 scenarios look at varying the percentage increase in CAPD and APD over the baseline, under these assumptions equal numbers of people from hospital and satellite will be transferred to CAPD and APD. So a 10% Kidney disease peritoneal dialysis: appendix B cost effectiveness 9 of 74

10 increase in CAPD would result in 5% coming from hospital haemodialysis and 5% from satellite haemodialysis. The proportions are presented in Table 4. Table 4 Analysis 2 increases over baseline Hosp HD Sat HD Home HD CAPD APD Baseline 47% 33% 2% 14% 4% 25% Increase 45.25% 31.25% 2% 17.5% 4% in CAPD 50% increase 43.5% 29.5% 2% 21% 4% in CAPD 25% Increase 46.5% 32.5% 2% 14% 5% in APD 50% Increase 46% 32% 2% 14% 6% in APD 25% Increase 44.8% 30.8% 2% 17.5% 5% in PD 50% Increase 42.5% 28.5% 2% 21% 6% in PD 80% Increase in PD 39.8% 25.8% 2% 25.2% 7.2% Analysis 3 scenarios examine absolute proportions starting on various modalities of peritoneal dialysis. These are presented in Table 5. The proportion on haemodialysis is calculated as before. Table 5 Analysis 3 proportion starting on peritoneal dialysis Hosp HD Sat HD Home HD CAPD APD Baseline 47% 33% 2% 14% 4% 30% PD 40% 28.1% 2% 23.3% 6.7% 40% increase 34.1% 23.9% 2% 31.1% 8.9% in PD 50% increase 28.2% 19.8% 2% 38.9% 11.1% in PD 60% increase 22.3% 15.7% 2% 46.7% 13.3% in PD 70% increase 16.5% 11.6% 2% 54.4% 15.6% in PD 80% increase 10.6% 7.4% 2% 62.2% 17.8% in PD 90% increase in PD 4.7% 3.3% 2% 70% 20% Transition probabilities The following data were needed to populate the model: survival (haemodialysis/peritoneal dialysis) Kidney disease peritoneal dialysis: appendix B cost effectiveness 10 of 74

11 switching (haemodialysis/peritoneal dialysis) complications (haemodialysis/peritoneal dialysis) transplantation. The same approach was adopted for obtaining estimates for all these values. For the clinical review a review of registry data was conducted to obtain data to compare peritoneal dialysis and haemodialysis. Of these registry data where possible the most up-to-date and longest follow up were used. This is because there have been significant developments in technology and therefore the most recently published data should incorporate these developments. Ideally data from the UK were used because there may be issues with the transferability of clinical data. Survival on haemodialysis and peritoneal dialysis The conclusion of the clinical review was that there is little if any difference between haemodialysis and peritoneal dialysis in terms of survival, and it was not possible to split into the different modalities. Of the papers identified during the review of Taiwanese registry data Huanag et al. (2008) reported 10-year survival data for haemodialysis and peritoneal dialysis. There is 1-year survival data from the UK for peritoneal dialysis and haemodialysis from the UK renal registry report Therefore, data from the renal registry is used for the first year and data from Huanag et al for subsequent years. This is to incorporate where possible the most up-to-date UK relevant data into the model while also using the study that reported outcomes over the longest time period. The data used is presented in Table 6. Table 6 Survival data for peritoneal and haemodialysis Study Peritoneal dialysis Haemodialysis Renal registry report 2009: 94.5% 87.3% 1-year survival Huanag et al. 2008: 10-year survival 35% 33.8% These survival estimates are used for all modalities. Sensitivity analysis assumes that there is no survival difference between modalities. Kidney disease peritoneal dialysis: appendix B cost effectiveness 11 of 74

12 Switching from haemodialysis to peritoneal dialysis and peritoneal dialysis to haemodialysis From the clinical review and GDG opinion, the switching rate between modalities is time dependant. Data from Johnson et al. (2009) is summarised in Table 7. These values are used in the model for the corresponding time periods. Johnson et al. (2009) was chosen because it was the most recent publication that quoted switching rates between modalities and also accounted for the differences in the time. This is of particular interest over different time horizons. Table 7 Complication rates First modality Haemodialysis Peritoneal dialysis Second modality Peritoneal dialysis Haemodialysis 0 to 6 months 21.1% 8.59% 7 months to 6 years 5.89% 55.01% The second modality is dependent on the available modalities and on the initial proportions in which people are allocated to each. So if initially 10% are allocated to both CAPD and APD, people from haemodialysis have a 50:50 chance of transiting to CAPD or APD. It is assumed that this switching transition accounts for both clinical and patient choice. This may therefore be underestimated; however, it is collected from registry data so probably accounts for this. Complication rates for peritoneal dialysis and haemodialysis Peritoneal dialysis complications The clinical review identified a number of papers that gave details about complication rates. Data from Evans et al. (2010) stated that 70% of people on peritoneal dialysis had a complication by 5 years, calculated using Kaplan Meier methods. The GDG considered that this was an appropriate value and the value quoted best matched the structure of the model. Mortality The data quoted in the review of registry data were often difficult to interpret because the review gave absolute figures of mortality rather than the percentage of people with an adverse event who then subsequently died. Kidney disease peritoneal dialysis: appendix B cost effectiveness 12 of 74

13 Data from Johnson et al. (2009) stated that 2.8% of people with a complication by 10 years had died. Evidence from Jarvis et al. (2010) suggests that over a three year period 6% of people with peritonitis had died. Given that the Jarvis paper is more recent it is used in the base case. Switching due to complications Data from Barraclough et al stated that out of 4675 people, 635 with adverse events (13.6%) by 3 years switched to haemodialysis. GDG opinion was that 10% of people every year switch from APD to CAPD. The effect of this on the cost effectiveness analysis is examined in the sensitivity analysis. Haemodialysis complications Mortality Data from Johnson et al. (2009) stated that 1.7% of people with a complication at 10 years had died. Switching because of complications Data from Kirby et al. (2001) reported that switching to CAPD from haemodialysis was 1.6% per year. This value is used because it was based on systematic searches for evidence specifically on haemodialysis. Transplantation Waiting time Data from the NHS Blood and Transplant report 2009 states that the median waiting time is 3.04 years for a kidney transplant, both heart beating and nonheart beating. Survival and failure rates Estimates of 5-year survival from NHSBT 2009 report are presented in Table 8 Table 8: 5-year survival for transplantation Donor type Survival Graft failure Heart beating Non heart beating Kidney disease peritoneal dialysis: appendix B cost effectiveness 13 of 74

14 These estimates are used in the model. People with graft failure are assumed to restart dialysis. Restarting dialysis The GDG stated people whose graft fails restart dialysis according to the same percentage as they began in the initial cohort. Therefore, the initial starting cohort is used to calculate probabilities. Summary of selected values and model inputs Table 9 summarises the data selected, the monthly transitions are incorporated into the model and sources. Table 9: Parameter - transition probabilities summary table Parameter Value Monthly Source transition 1 st year survival Haemodialysis 87.3% at one year Renal Registry report 2009 Peritoneal dialysis 94.5% at one year Renal Registry Subsequent year survival report 2009 Haemodialysis 33.8% at 10 years Huanag et al Peritoneal dialysis 35% at 10 years Huanag et al Complications Haemodialysis 6% per year Kirby et al Peritoneal dialysis 70% over 5 years Barraclough 2010 PD AE HD 20% over 3 years Barraclough 2010 Dead 2.8% Johnson et al HD AE PD 1.6% Kirby et al Dead 1.7% Johnson et al Switching 0-6 months Switching 7 months + Haemodialysis to peritoneal dialysis 21.1 % at 6 months Johnson et al Peritoneal dialysis to haemodialysis 8.59% at 6 months Johnson et al Haemodialysis to 5.89% at 6 years Johnson et al. peritoneal dialysis 2009 Peritoneal dialysis to 55.01% at 6 years Johnson et al. haemodialysis 2009 APD to CAPD 10% per year GDG opinion Dialysis to transplant 50% receive NHSBT 2009 transplant at 3.04 report years Transplant graft survival HB 83% at 5 years NHSBT 2009 report Transplant survival HB 87% at 5 years NHSBT 2009 Kidney disease peritoneal dialysis: appendix B cost effectiveness 14 of 74

15 report Transplant graft survival NHB 80% at 5 years NHSBT 2009 report Transplant survival NHB 76% at 5 years NHSBT 2009 report Quality of life A search was undertaken for appropriate quality of life data: 23 papers were identified along with the 14 cost effectiveness papers identified earlier. NICE s methods state a preference for the EQ-5D or other generic quality of life instruments to allow comparisons across a number of conditions. Of these papers four included EQ-5D values. These papers were De Witt et al. (1998), Sennfalt et al. (2002), Teerawattananon et al. (2007) and Liem et al. (2008). Liem et al. (2008) and Teerawattananon et al. (2007) were based on metaanalyses. In addition, three papers were identified that collected SF-36 and EORTC data that could be converted to EQ-5D using mapping techniques. A further paper by Frimat et al. (2006) was identified during consultation on the guideline. It includes SF-36 values for people with a contraindication to transplantation. It was decided to exclude this paper because the population represented a subgroup to the population of interest. To convert SF-36 to EQ- 5D two methods were used based on the reported data: Ara and Brazier (2008) and Franks et al. (2004). To convert EORTC to EQ-5D methods by McKenzie et al. (2009) were used. The authors of this paper concluded that their algorithm is valid, but that more evidence is required before it can be the recommended method for conversion. This method was developed from patients with oesophageal cancer and therefore may not be appropriate for use in this population. This conversion was used in a previous NICE technology appraisal and was considered appropriate ( Azacitidine for the treatment of myelodysplastic syndromes, chronic myelomonocytic leukaemia and acute myeloid leukaemia, NICE technology appraisal guidance 218, 2011). All the relevant values are summarised in Section 5. Section 4 outlines the data extracted from the papers and mapping calculations. The other quality of life studies used instruments that were not appropriate to calculate QALYs because they were not fixed scales with 0 corresponding to Kidney disease peritoneal dialysis: appendix B cost effectiveness 15 of 74

16 dead and 1 to perfect health, for example KQOL, unfortunately no mapping tool was identified. Liem et al. (2008), which is a meta-analysis of EQ-5D values, would appear to be the most robust. However, to use all the data collected a mean could be taken across all the values, which could be biased because this is effectively a naive combination. The studies also all used different methodologies. This is done as a sensitivity analysis to explore its effect. The main issue is the quality of life to associate with different types of peritoneal dialysis and haemodialysis. There is only one value for satellite haemodialysis, from De Witt et al. (1998). The GDG commented that since the paper was published the type of satellite haemodialysis has changed significantly, and in the UK the difference in quality of life between satellite and hospital-based haemodialysis has probably reduced. The difference between CAPD and APD is also uncertain with only data from mapping and De Witt et al. (1998) being available. Given these issues, the same quality of life will be used for both haemodialysis modalities and all peritoneal dialysis modalities. As a sensitivity analysis satellite haemodialysis will be increased to be the same as peritoneal dialysis. Home haemodialysis is delivered in the home environment and is generally considered close to a normal quality of life, so it will be associated with utility equivalent to transplantation. Chosen utilities Table 10 outlines the quality of life values chosen and the source. Table 10: Base case quality of life values State Value Standard deviation Source Hospital HD Liem et al Satellite HD Home HD CAPD APD aapd Transplant Complication HD % reduction from baseline Complication PD based on Sennfalt et al Kidney disease peritoneal dialysis: appendix B cost effectiveness 16 of 74

17 Alternative values from averaging values across the EQ-5D values different studies are presented in Table 11. In this analysis the different modalities of haemodialysis and peritoneal dialysis are merged together. The assumptions made in the base case hold for this analysis as well (for example, assuming that home haemodialysis has the same utility as transplantation). Table 11: Averaged quality of life values State Value Range Hospital HD Satellite HD Home HD CAPD APD aapd Transplant Complication HD Complication PD Costs and resource use Dialysis haemodialysis and peritoneal dialysis A search for resource data applicable to the UK setting and relevant to current practice identified one paper. Baboolal et al. (2008) conducted a top down costing study of the provision of CAPD, APD, hospital haemodialysis and satellite haemodialysis in a number of UK hospitals. A breakdown of the costs is provided in Table 12. Table 12: Cost breakdown from Baboolal et al Haemodialysis (main unit) Haemodialysis (satellite unit) APD CAPD Direct nursing Other nursing activities Disposables 10,952 10,952 14, Medical supervision Dialysis machines Machine maintenance Anaemia therapy Hospital transport Overheads Total 35,023 32,669 21,655 15,570 Kidney disease peritoneal dialysis: appendix B cost effectiveness 17 of 74

18 This paper does not directly give data on the resource use and unit costs used to calculate these values. There were also several assumptions used to help account for evidence gaps. In addition, one of the co-authors on the paper has links to a peritoneal dialysis manufacturer. However, the data comes from hospital finance departments and probably represents the true cost to the provider for the service. An alternative source of cost information is the NHS kidney care report 2009, which collected data from 16 NHS trusts. This data was used to derive the NHS reference costs and the indicative tariff. A summary of the data from this report is provided in Table 13. Table 13: Breakdown of costs from NHS kidney report 2009 Cost per Session ( ) Annual sessions Annual cost ( ) Monthly cost ( ) All Haemodialysis LC02A , Hospital Haemodialysis , Satellite Unit Haemodialysis , Home Haemodialysis , Cost per therapy day ( ) Annual days Annual cost ( ) All Peritoneal Dialysis LC04A , Continuous Ambulatory PD , Automatic PD , The NHS reference costs were not used because they do not differentiate between hospital and satellite haemodialysis. The main difference is that Baboolal et al. (2008) includes overheads, transport costs and the cost of anaemia therapy. These additional costs are important considerations to the NHS and therefore this will be used in the base case. However, the Kidney care report 2009 will be used in the sensitivity analysis. For Baboolal et al. (2008) standard deviations were calculated from the data in the paper based on the variation around the various centres included in the study. The cost of assistance for aapd was assumed to be seven visits by a nurse, costing 30 per visit based on the cost of a home visit from the PSSRU. Kidney disease peritoneal dialysis: appendix B cost effectiveness 18 of 74

19 Evidence from the GDG suggested that this could be overestimated and the true cost of closer to 15. Therefore, the monthly cost of 915 for assistance is the subject of sensitivity analysis. The cost of home haemodialysis was estimated from the kidney report 2009 because it was not included in Baboolal et al. (2008). These costs may be an underestimate, but are included in the base case. Complications Peritoneal dialysis The main complication from peritoneal dialysis is peritonitis. The Kidney care report 2009 suggests that this complication is costed in reference cost code LA05A and LA05B Renal Replacement Peritoneal Dialysis Associated Procedures with CC and no CC with an average cost of 3103 (IQR: 1836 to 3761). Haemodialysis The main complications from haemodialysis are infections and possibly MRSA. The cost of these complications was taken from the EURODICE study (reported in Kirby et al. 2001), which estimated that dialysis complications cost When uplifted to present prices this came to Transplantation The cost of transplantation was obtained from the NHS reference cost code for cadaveric kidney transplant. In the model both heart beating and non-heart beating donors are included. Therefore the costs used are LA01A Kidney Transplant from Cadaver non-heart beating donor 19 years and over 10,250 and LA02A Kidney Transplant from Cadaver Heart beating donor 19 years and over 13,627. This code was chosen because people opting for a living transplant follow a different treatment pathway and are not included in this model. The cost of maintenance treatment for transplantation was obtained from Wight et al. (2003) which gave a cost of 4851 per year, which when uplifted to current prices is Kidney disease peritoneal dialysis: appendix B cost effectiveness 19 of 74

20 Cost summary Table 14 outlines the monthly costs used in the model: Table 14: Summary of costs used in model Parameter Monthly cost ( ) (range/sd) Hospital haemodialysis Satellite haemodialysis Home haemodialysis CAPD APD aapd Peritoneal dialysis complications (per event) Haemodialysis complications (per event) Cost of transplantation HB 13, Cost of transplantation NHB 10, Cost of maintenance on transplantation HD = Haemodialysis; PD = Peritoneal dialysis; Hosp HD = Hospital haemodialysis; Sat HD = Satellite haemodialysis; Home HD = Home haemodialysis; CAPD = Continuous ambulatory peritoneal dialysis; APD = Automated peritoneal dialysis; aapd = Assisted automated peritoneal dialysis; HB = Heart beating donor; NHB = Non-heart beating donor Analyses Deterministic sensitivity analysis Several sensitivity analyses were done to explore variation in the data sources. These include: time horizon, alternative costs, varying quality of life values and exploring uncertainty in survival analysis. Probabilistic sensitivity analysis All variables in the model have a distribution attached to them. Given that a number of estimates did not include a measure of variance (such as confidence intervals and standard deviations), it was necessary to make some assumptions around the distribution used. For transition probabilities the sample size the data was obtained from was used to calculate alphas and betas. Table 15 summarises the distributions used in the probabilistic sensitivity analysis. Kidney disease peritoneal dialysis: appendix B cost effectiveness 20 of 74

21 Table 15: Distributions used in probabilistic sensitivity analysis Parameter Distribution Alpha Beta Comment 1 st year survival HD Beta n = 6634 Subsequent years survival PD n = 6634 HD n = PD n = Complications HD Switching 0-6 months Switching 7 months plus PD n = 8559 HD n = PD n = HD n = PD n = Dialysis to transplant n = 6980 Transplant graft survival HB n = 2860 Transplant survival HB n = 2860 Transplant graft survival NHB n = 169 Transplant survival NHB n = 169 Quality of life Hospital HD Beta Satellite HD Home HD CAPD APD aapd Transplant Complication HD Complication PD Cost Hospital haemodialysis Gamma Satellite haemodialysis Home haemodialysis Uniform CAPD Gamma APD aapd Uniform Peritoneal dialysis complications (per event) Haemodialysis complications (per event) Gamma Cost of transplantation HB Cost of transplantation NHB Cost of maintenance on transplantation Kidney disease peritoneal dialysis: appendix B cost effectiveness 21 of 74

22 Results Base case Table 16 presents the deterministic base case results of the analysis and Table 17 presents the probabilistic results. The time horizon in both cases is 10 years. Table 16 Base case deterministic results Cost ( ) LYGs QALYs Incremental ICER NMB ( ) Cost ( ) QALY ( ) 20,000 30,000 Base line HD centred Dominated PD centred Dominates % Increase in CAPD Dominates % increase in CAPD Dominates % Increase in APD Dominates % Increase in APD Dominates % Increase in PD Dominates % Increase in PD Dominates % Increase in PD Dominates % start PD Dominates % start PD Dominates % start PD Dominates % start PD Dominates % start PD Dominates % start PD Dominates % start PD Dominates Abbreviations: APD, automated peritoneal dialysis; CAPD, continuous ambulatory peritoneal dialysis; HD, haemodialysis; ICER, incremental cost effectiveness ratio; LYG, life years gained ; NMB, net monetary benefit; PD, peritoneal dialysis; QALY, quality-adjusted life year; Sat HD, satellite haemodialysis. Dominates: less expensive and more effective, Dominated: more expensive and less effective Kidney disease peritoneal dialysis: appendix B cost effectiveness 22 of 74

23 Table 17: Base case probabilistic results Cost ( ) LYGs QALYs Incremental ICER NMB ( ) Cost QALY ( ) 20,000 30,000 Base line HD centred Dominated PD centred Dominates % Increase in CAPD Dominates % increase in CAPD Dominates % Increase in APD % Increase in APD Dominates % Increase in PD Dominates % Increase in PD Dominates % Increase in PD Dominates % start PD Dominates % start PD Dominates % start PD Dominates % start PD Dominates % start PD Dominates % start PD Dominates % start PD Dominates HD = Haemodialysis; PD = Peritoneal dialysis; Hosp HD = Hospital haemodialysis; Sat HD = Satellite haemodialysis; Home HD = Home haemodialysis; CAPD = Continuous ambulatory peritoneal dialysis; APD = Automated peritoneal dialysis These results indicate that a policy of increasing the use of home dialysis is the most cost effective option. Cost effectiveness plane Section 6 presents the cost effectiveness planes for the various cohorts compared to the baseline. These plots show that the simulations are spread over all four quadrants of the cost effectiveness plane. However, the majority of the scenarios indicate greater variation in effectiveness rather than in costs. Generally the costs are below the x-axis, suggesting that increasing peritoneal dialysis is likely to lead to cost savings. However, the effectiveness varies across the y-axis, suggesting that the cost effectiveness estimate for increasing peritoneal dialysis could be less clinically effective and cost saving. Kidney disease peritoneal dialysis: appendix B cost effectiveness 23 of 74

24 Cost effectiveness acceptability curve Figure 2, Figure 3 and Figure 4 present the results for the three sets of analyses. Figure 2: Cost effectiveness acceptability curve analysis set 1 Kidney disease peritoneal dialysis: appendix B cost effectiveness 24 of 74

25 Figure 3: Cost effectiveness acceptability curve analysis set 2 Kidney disease peritoneal dialysis: appendix B cost effectiveness 25 of 74

26 Figure 4: Cost effectiveness acceptability curve analysis set 3 These sets of figures suggest that all the analyses that increase the proportion on peritoneal dialysis are assoicated with probablities over 50% of this increase in peritoneal dialysis being cost effective at all cost per QALY thresholds. Table 18 outlines the probability, for each of the analyses, of the treatment being cost effective at 20,000 and 30,000 per QALY threshold. Kidney disease peritoneal dialysis: appendix B cost effectiveness 26 of 74

27 Table 18: Probability of analyses being cost effective at cost per QALY thresholds Probability of analysis being cost effective at cost per QALY thresholds Analysis 20,000 per QALY 30,000 per QALY Baseline - - HD centred PD centred % increase in CAPD % increase in CAPD % increase in APD % increase in APD % increase in PD % increase in PD % increase in PD % start PD % start PD % start PD % start PD % start PD % start PD % start PD These analyses show that increasing the proportion on peritoneal dialysis is likely to be cost effective. To increase certainty in the decision the variation in the clinical effectiveness would have to be reduced. Sensitivity analysis Time horizon Table 19 presents deterministic results at different time horizons. These results suggest that as the time horizon is increased, increasing the use of peritoneal dialysis becomes more cost effective. This is from the greater QALY gains from people staying on peritoneal dialysis and the slight survival benefit. Kidney disease peritoneal dialysis: appendix B cost effectiveness 27 of 74

28 Table 19: Results of altering time horizon Years Baseline HD centred PD centred % increase in CAPD % increase in CAPD % increase in APD % increase in APD % increase in PD % increase in PD % increase in PD % start PD % start PD % start PD % start PD % start PD % start PD % start PD Quality of life alternatives Average values Table 20 presents deterministic sensitivity analysis for the average utilities presented in Table 11. This results in the incremental QALYs increasing and reinforcing the conclusions from the base case analysis. Therefore, if peritoneal dialysis is associated with a larger incremental difference in quality of life than haemodialysis then the cost effectiveness will improve. Kidney disease peritoneal dialysis: appendix B cost effectiveness 28 of 74

29 Table 20: Cost effectiveness results using averaged utilities Cost ( ) LYGs QALYs Incremental ICER NMB ( ) Cost ( ) QALY ( ) 20,000 30,000 Baseline HD centred Dominated PD centred Dominates % increase in CAPD Dominates % increase in CAPD Dominates % increase in APD Dominates % increase in APD Dominates % increase in PD Dominates % increase in PD Dominates % increase in PD Dominates % start PD Dominates % start PD Dominates % start PD Dominates % start PD Dominates % start PD Dominates % start PD Dominates % start PD Dominates HD = Haemodialysis; PD = Peritoneal dialysis; Hosp HD = Hospital haemodialysis; Sat HD = Satellite haemodialysis; Home HD = Home haemodialysis; CAPD = Continuous ambulatory peritoneal dialysis; APD = Automated peritoneal dialysis Satellite haemodialysis has same quality of life as home based haemodialysis Table 21 presents deterministic results over 10 years, assuming that satellite haemodialysis has the same quality of life as home dialysis. This results in negative QALY gains in a number of scenarios. This is unsurprising because this results in a QALY loss from moving from satellite haemodialysis to peritoneal dialysis. The reason the peritoneal dialysis-centric scenario is associated with high QALY gains is that people have been switched from hospital haemodialysis to either satellite haemodialysis or one of the peritoneal dialysis modalities. However, the majority of scenarios appear cost effective, but these results need to be treated with caution because ICERs in the south west quadrant are difficult to interpret. For example, it is uncertain what the appropriate threshold should be. The GDG considered that the QALY gain associated with satellite haemodialysis is unlikely to be as high as home haemodialysis but may be higher than hospital haemodialysis. Kidney disease peritoneal dialysis: appendix B cost effectiveness 29 of 74

30 Therefore, it is likely that there is a benefit for peritoneal dialysis over satellite haemodialysis in certain people, leading to QALY gains. Table 21: Cost effectiveness results with satellite haemodialysis quality of life being equivalent of home haemodialysis Cost ( ) LYGs QALYs Incremental ICER NMB ( ) Cost ( ) QALY ( ) 20,000 30,000 Baseline HD centred PD centred Dominates % increase in CAPD % increase in CAPD % increase in APD Less costly 50% increase and less in APD effective 25% increase in PD % increase in PD % increase in PD % start PD % start PD % start PD Less costly % start PD and less % start PD effective % start PD % start PD HD = Haemodialysis; PD = Peritoneal dialysis; Hosp HD = Hospital haemodialysis; Sat HD = Satellite haemodialysis; Home HD = Home haemodialysis; CAPD = Continuous ambulatory peritoneal dialysis; APD = Automated peritoneal dialysis No quality of life difference Table 22 presents results when peritoneal dialysis and haemodialysis are assumed to be associated with equivalent quality of life values (n this case the haemodialysis value has been used). This results in a smaller QALY gain (wholly on the basis of the slight survival gain associated with peritoneal dialysis). This results in lower net monetary benefits, but increasing peritoneal dialysis is still a cost effective option. Kidney disease peritoneal dialysis: appendix B cost effectiveness 30 of 74

31 Table 22: Cost effectiveness results assuming no quality of life difference between peritoneal dialysis and haemodialysis Cost ( ) LYGs QALYs Incremental ICER NMB ( ) Cost ( ) QALY ( ) 20,000 30,000 Baseline HD centred Dominated PD centred Dominates % increase in CAPD Dominates % increase in CAPD Dominates % increase in APD % increase in APD Dominates % increase in PD Dominates % increase in PD Dominates % increase in PD Dominates % start PD Dominates % start PD Dominates % start PD Dominates % start PD Dominates % start PD Dominates % start PD Dominates % start PD Dominates HD = Haemodialysis; PD = Peritoneal dialysis; Hosp HD = Hospital haemodialysis; Sat HD = Satellite haemodialysis; Home HD = Home haemodialysis; CAPD = Continuous ambulatory peritoneal dialysis; APD = Automated peritoneal dialysis Alternative costs Table 23 presents deterministic results using costs from the NHS kidney report This results in the incremental costs reducing, and in the case of APD becoming cost ineffective. However, by increasing the number on peritoneal dialysis a greater number switch from hospital haemodialysis to peritoneal dialysis. This results in a significant cost saving, because hospital haemodialysis is the most expensive form. Kidney disease peritoneal dialysis: appendix B cost effectiveness 31 of 74