Original Investigation

Economic Evaluation of Neutral-pH, Low–Glucose Degradation

Product Peritoneal Dialysis Solutions Compared With Standard
Solutions: A Secondary Analysis of the balANZ Trial
Kirsten Howard, PhD,1 Alison Hayes, PhD,1 Yeoungjee Cho, MD,2,3 Alan Cass, PhD,4
Margaret Clarke, RN,5 and David W. Johnson, PhD2,3

Background: Biocompatible solutions may lower peritonitis rates, but are more costly than conventional
solutions. The aim of the present study was to assess the additional costs and health outcomes of biocom-
patible over conventional solutions in incident peritoneal dialysis patients to guide practice decisions.
Study Design: Secondary economic evaluation of a randomized controlled trial.
Setting & Population: 185 participants in the balANZ trial.
Model, Perspective, & Timeframe: Cost-effectiveness of biocompatible compared to standard solution
over the 2 years using an Australian health care funder perspective.
Intervention: Intervention group received biocompatible solutions and control group received standard
solutions over 2 years.
Outcomes: Costs included dialysis charges, costs of treating peritonitis, non2peritonitis-related hospital
stays, and medication. Peritonitis was the health outcome of interest; incremental cost-effectiveness ratios
were reported in terms of the additional cost per additional patient avoiding peritonitis at 2 years.
Results: Mean total per-patient costs were A$57,451 and A$53,930 for the biocompatible and standard-
solution groups, respectively. The base-case analysis indicated an incremental cost of A$17,804 per additional
patient avoiding peritonitis at 2 years for biocompatible compared to standard solution. In a sensitivity analysis
excluding extreme outliers for non2peritonitis-related hospitalizations, mean per-patient costs were A$49,159
and A$52,009 for the biocompatible and standard-solution groups, respectively. Consequently, the incremental
cost-effectiveness ratio also was reduced significantly: biocompatible solution became both less costly and
more effective than standard solution and, in economic terms, was dominant over standard solution.
Limitations: Peritonitis was a secondary outcome of the balANZ trial. Health outcomes measured only in
terms of patients avoiding peritonitis over 2 years may underestimate the longer term benefits (eg, prolonged
technique survival).
Conclusions: Biocompatible dialysis solutions may offer a cost-effective alternative to standard solutions
for peritoneal dialysis patients. Reductions in peritonitis-related hospital costs may offset the higher costs of
biocompatible solution.
Am J Kidney Dis. 65(5):773-779. Crown Copyright ª 2015 Published by Elsevier Inc. on behalf of the National
Kidney Foundation, Inc. All rights reserved.

INDEX WORDS: Biocompatible; neutral pH; low glucose degradation product; cost-effectiveness; economic
evaluation; peritonitis; hospitalisation; peritoneal dialysis (PD); peritoneal dialysis solutions; balANZ trial;
end-stage kidney disease (ESKD).

P eritoneal dialysis (PD) is a type of home-based

dialysis that is used to treat end-stage kidney
disease in more than 200,000 patients worldwide.1,2
It has various advantages over hemodialysis,
including better preservation of residual kidney
function, improved initial patient survival, reduced
erythropoiesis-stimulatory agent requirements, and
preservation of vascular access sites.3-5 Furthermore,
increasing use of PD has been estimated to lead to an
annual cost saving of up to 40% compared to in-
center hemodialysis.6 Despite these benefits, PD
uptake remains low, accounting for only 19% of all
dialysis in Australia7 and 11% of the global dialysis
population.1 Its wider implementation is compro-
mised by higher technique failure from infections
(eg, peritonitis); inadequate small-solute clearance,
and ultrafiltration failure7 and concerns about the
development of encapsulating peritoneal sclerosis
with longer PD vintage.8-10
These adverse clinical outcomes have been attrib-
uted to cumulative peritoneal injury in PD patients
from repeated exposures to conventional PD solutions,
characterized by their acidic pH and high–glucose
From the 1Sydney School of Public Health, University of Syd-
ney, NSW; 2Centre for Kidney Disease Research, Translational
Research Institute at University of Queensland; 3Department of
Nephrology, Princess Alexandra Hospital, Brisbane, QLD; 4The
Menzies School of Health Research, Darwin, NT, Australia; and
5
Fresenius Medical Care South Asia Pacific, Singapore.
Received July 15, 2014. Accepted in revised form December 26,
2014. Originally published online March 4, 2015.
Address correspondence to David W. Johnson, PhD, Depart-
ment of Nephrology, Level 2, ARTS Building, Princess Alexandra
Hospital, Ipswich Road, Woolloongabba, Brisbane, QLD 4102,
Australia. E-mail: david.johnson2@health.qld.gov.au
Crown Copyright  2015 Published by Elsevier Inc. on behalf
of the National Kidney Foundation, Inc. All rights reserved.
0272-6386
http://dx.doi.org/10.1053/j.ajkd.2014.12.017

Am J Kidney Dis. 2015;65(5):773-779 773


degradation product (GDP) content.11 Similarly, the
use of conventional PD solutions poses theoretical
concern; it could contribute to peritonitis through
impaired peritoneal mesothelial cell viability and func-
tion, resulting in compromised peritoneal immune
defenses.12-18 These undesirable sequelae may be pre-
vented by the administration of commercially available
“biocompatible” PD solutions, characterized by neutral
pH and low-GDP content. Preclinical studies have
shown significant improvement in peritoneal membrane
cellular function and integrity following exposure to
biocompatible solutions versus conventional solu-
tions,17,19-21 whereas observational cohort studies have
reported reduced inflammatory marker levels,22 perito-
nitis, and exit-site infection rates23 and improved tech-
nique and patient survival.24-26 Recently, the balANZ
randomized controlled trial demonstrated significant
patient benefits in terms of longer time to anuria and
first peritonitis episode (median, 492 vs 323 days;
P 5 0.01), as well as a significant reduction in the
number of patients developing peritonitis (P 5 0.01).27
The primary outcome measure of the balANZ trial,
slope of kidney function decline, was not statistically
significantly different between the biocompatible and
control groups,27 but because peritonitis is one of the
most serious complications of PD, resulting in consid-
erable morbidity (w20% PD technique failure)28 and
mortality (2%-6%),29,30 we considered this an appro-
priate outcome for this economic evaluation.
Nonetheless, these biocompatible solutions are more
costly compared with conventional solutions and the
cost difference between these 2 treatment options has
never been formally evaluated. The aim of the present
study therefore was to conduct an economic evaluation
to assess the relative costs and health outcomes of
biocompatible solutions over conventional solutions in
incident PD patients to guide practice decisions.
METHODS
Study Design and Setting
We conducted a trial-based economic evaluation of biocom-
patible and conventional PD solutions from the perspective of the
health care funder, using data from a multicenter, multicountry,
randomized, controlled trial, the balANZ trial. The methods and
results of this trial have been reported in detail elsewhere.27
Briefly, incident adult PD patients who had both a residual
measured glomerular filtration rate $ 5 mL/min/1.73 m2 and
measured urine volume $ 400 mL/d at enrollment were included
in the study. Patients were randomly assigned 1:1 to receive either
biocompatible, neutral-pH, lactate-buffered, low-GDP solutions
(Balance; Fresenius Medical Care) or conventional, standard,
lactate-buffered PD solutions (stay,safe; Fresenius Medical Care;
control group). Each patient was followed up for 24 months.
Health Outcome Measures
The health outcome measure for this economic evaluation was
peritonitis; specifically, the proportion of patients experiencing at
least one episode of peritonitis by trial end.27 Peritonitis was
defined as a dialysate white blood cell count . 100/mL with
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Howard et al
.50% polymorphonuclear leukocytes in a patient with a
compatible clinical picture (abdominal pain, fever, or cloudy
dialysate).31,32 Each episode was documented using a serious
adverse event form by a local clinician at the time of each peri-
tonitis episode. In keeping with the International Society of Peri-
toneal Dialysis recommendations,31,33 a peritonitis episode
complicated by relapse was counted as a single episode.
Costs
Overview
Costs were estimated from a health funder perspective and
included the costs of dialysis, costs of treating peritonitis
(including any inpatient hospital costs), costs of non2peritonitis-
related hospital stays, and medication costs. Dialysis type, vintage
and frequency, and health service and medication use for each
patient were collected routinely as part of the BalANZ trial.
Cost of Dialysis
PD costs were based on site-specific costing data collected
(from each state or individual hospital contracts) as part of the trial
and included solution charges and ancillaries. Hemodialysis costs
were based on the Australian refined diagnosis-related groups
(AR-DRG) 5.2 National Hospital Cost Data Collection (Round
14)34 item cost for renal dialysis and assuming an average of 3.5
dialysis sessions per week.
Health Service Use and Costs
All inpatient hospitalization episodes were costed using AR-
DRG 5.2 cost weights34 and adjusted for actual patient length of
stay. Adverse events were categorized as being related or unrelated
to peritonitis. Other outpatient health care use was not collected
routinely as part of the trial; therefore, outpatient physician costs
were estimated based on the trial visit schedule for each center.
Visits (including home visits) were costed using the Medicare
Benefits Schedule.35 Outpatient management of peritonitis also
was assumed to incur the cost of one physician visit.
Medication Costs
Costs of medications used over the 2-year trial period were
estimated using the Australian Pharmaceutical Benefits Scheme.36
For patients from New Zealand and Singapore receiving medica-
tion not available in Australia, the cost for an equivalent
Pharmaceutical Benefits Scheme–listed medication was used.
Medications were categorized as being related or unrelated to
peritonitis. When medications were related to an inpatient hospi-
talization for peritonitis, medication costs were not counted
separately because inpatient pharmaceutical costs were already
included in the AR-DRG costs; medications for outpatient man-
agement of peritonitis episodes were included under the cost
category “outpatient peritonitis” and other medication costs were
specified as “other concomitant medications.”
All costs were aggregated across participants in each arm of the
trial to obtain a mean cost per participant. All costs were valued in
2012 Australian dollars, and to account for the differential timing
of costs and outcomes, a discount rate of 5% per year was applied,
in line with current Australian reimbursement guidelines.37
Statistical Analysis
Cost-effectiveness analysis was undertaken from the funder
perspective and all analyses were carried out using Stata/SE12.0
(StataCorp LP). Total costs of the solution treatments were
compared between the biocompatible-solution and control groups.
Costs and effects were derived from patient-level data; therefore,
bootstrapping was used to estimate a distribution around costs and
health outcomes. Incremental cost-effectiveness ratios (ICERs) were
calculated, which represented the additional expenditure required to
deliver each additional unit of benefit. ICERs were expressed as the
Am J Kidney Dis. 2015;65(5):773-779
Economic Evaluation of Biocompatible PD Solutions

Table 1. Baseline Patient Characteristics by Peritoneal Dialysis solutions (n 5 93).27 Ninety-one patients in each
Solution Type group were available for the analysis of health care
Biocompatible Control costs and outcomes for the economic evaluation. The
Characteristic (n 5 91) (n 5 91) 2 groups were well matched for all baseline charac-
teristics (Table 1).27
Age (y) 59.3 6 14.2 57.9 6 14.7
Female sex 39 (43) 43 (47) Effectiveness
Ethnicity
As noted in a previous publication,27 the number of
White 77 (85) 69 (76)
Aboriginal and Torres Strait 0 (0) 2 (2) patients experiencing peritonitis in the biocompatible-
Islander solution group was significantly lower than that in the
Asian 10 (11) 13 (14) control group (27 of 91 [30%] vs 45 of 91 [49%],
Maori and Pacific Islander 4 (4) 7 (7) respectively), giving a risk difference of 219.8%
Diabetic nephropathy 30 (33) 31 (34) (95% confidence interval [CI], 25.5% to 234.0%;
Body mass index (kg/m2) 27.7 6 5.02 28.4 6 6.16 Table 2).
Note: Baseline patient characteristics from Johnson et al.27
Values for categorical variables are given as number (percent-
Costs
age); values for continuous variables are given as mean 6 Mean total costs per patient over the 2 years were
standard deviation. A$57,451 for patients in the biocompatible solution
group and A$53,930 in the control group. Six patients
cost per additional patient avoiding peritonitis at 2 years. To examine (3 biocompatible and 3 control) had missing medi-
their joint probability distribution, 1,000 cost and outcome pairs were cation costs. The major contributor to the mean cost
generated by bootstrap sampling with replacement and plotted on an per patient in each group was the cost of dialysis
incremental cost-effectiveness plane. A cost-effectiveness accept-
provision (A$28,612 and A$27,662 per patient for the
ability curve was derived to capture uncertainty around the proba-
bility that the biocompatible solution was cost-effective, given a biocompatible-solution and control groups, respec-
decision maker’s willingness to pay for an additional patient avoiding tively). Mean per-patient cost of hospitalizations un-
peritonitis.38 Sensitivity analysis of the main drivers of total cost related to peritonitis made up the next largest cost
was conducted, excluding patients in both arms of the trial if their category for both treatment groups. As would be
nonperitonitis hospital costs exceeded 3 standard deviations (SDs)
expected, the mean per-patient cost for treatment
from the mean nonperitonitis hospital cost across all participants.
of peritonitis (both inpatient and outpatient) was
RESULTS lower for the biocompatible-solution group, and this
partially offset the increased cost of biocompatible
Patient Characteristics solution. The mean per-patient cost of nonperitonitis
A total of 185 patients were randomly assigned to hospital admission was higher in the biocompatible-
receive biocompatible (n 5 92) or conventional PD solution than control group (A$21,773 compared to

Table 2. Discounted Mean Cost per Patient, Health Outcomes, and ICER

Biocompatible Control PD
PD Solutiona (n 5 91) Solution (n 5 91)a Increments (biocompatible 2 conventional)b,c

Costs
Dialysis 28,612 6 14,489 27,663 6 14,394 949 (23,237 to 5,249)
Concomitant medications 4,108 6 6,084 4,099 6 6,302 9 (21,774 to 1,751)
Home visits 675 6 474 644 6 464 31 (2113 to 164)
Clinic visits 800 6 562 752 6 509 47 (298 to 211)
Outpatient peritonitis 33 6 85 53 6 103 220 (245 to 9)
Hospital treatment
Peritonitis 1,450 6 4,094 4,436 6 9,428 22,986 (25,102 to 2990)
Other 21,773 6 37,256 16,282 6 27,303 5,491 (24,159 to 14,395)
Total costs 57,451 6 46,124 53,930 6 33,836 3,522 (27,608 to 13,750 )

Peritonitis health outcome 27 (0.296) 45 (0.494) 20.198 (20.055 to 20.340)

ICERd $17,804/pt avoiding peritonitis at 2 y (dominant to $114,783)
Note: Cost values are given in Australian dollars.
Abbreviations: CI, confidence interval; ICER, incremental cost-effectiveness ratio; PD, peritoneal dialysis; pt, patient; SD, standard
deviation.
a
Values given as mean 6 SD, except for peritonitis health outcome, which is given as number (proportion).
b
Except where indicated, values given as mean (95% CI 1,000 bootstraps).
c
Incremental costs have been calculated and then rounded to the nearest full dollar.
d
Incremental cost per additional patient avoiding peritonitis.

Am J Kidney Dis. 2015;65(5):773-779 775


A$16,282). This difference was driven by small dif-
ferences in the number of patients experiencing
extended lengths of stay in the hospital; for example,
2 patients in the control group with hospital stays
of 64 days (estimated cost, A$90,227) and 51 days
(A$59,617) compared with 3 patients in the
biocompatible-solution group with hospital stays of
51 (A$75,495), 68 (A$71,400), and 136 days
(A$160,551).
Cost-Effectiveness
The point estimate and bootstrapped estimates of
incremental cost and incremental benefit of the
biocompatible solution are presented in Table 2 and in a
cost-effectiveness plane (Fig 1); the associated cost-
effectiveness acceptability curve is presented in Fig 2.
The cost-effectiveness plane (Fig 1) represents the
additional cost (biocompatible compared with control)
on the y-axis to achieve incremental benefits (propor-
tion of patients avoiding peritonitis) on the x-axis. The
mean ICER was A$17,804 per additional extra patient
avoiding peritonitis at 2 years. The bootstrapped
95% CI ranged from biocompatible solution being both
more effective and less costly than conventional solu-
tion (dominant) to an ICER of wA$115,000 per
additional patient avoiding peritonitis. There was a 27%
probability that biocompatible solution was cost saving
(Fig 2). The probability that biocompatible solution is
cost-effective is dependent on a decision maker’s
willingness to pay (Fig 2). For example, if a decision
maker is willing to pay A$40,000 to avoid an extra
patient experiencing peritonitis over a 2-year time
frame, there is an w70% probability that biocompatible
solution is cost-effective.
Figure 1. Base-case analysis: incremental cost-effectiveness
scatter plot for biocompatible versus conventional dialysate; cost
per additional patient avoiding peritonitis (white circle, mean incre-
mental cost-effectiveness ratio; grey circles, 1,000 bootstrapped
replicates).
776
Howard et al
Sensitivity Analysis
In a sensitivity analysis, total costs were recalcu-
lated after the removal of extreme outliers (.3 SDs
from mean nonperitonitis hospital costs) in the
cost of other hospitalizations (5 participants from
the biocompatible solution group; 1 from control),
resulting in mean per-patient total costs of A$49,159
(biocompatible) and A$52,009 (control). Biocom-
patible solution on average was A$2,850 less costly
per patient than control solution. This has a large
impact on the ICER, making biocompatible solution
both less costly and more effective than control so-
lution; in economic terms, dominant over control
solution. The bootstrapped 95% CI ranged from
biocompatible solution being dominant over control
solution to an ICER of A$6,135 per additional pa-
tient avoiding peritonitis. The sensitivity analysis
suggests a 75% probability that the biocompatible
PD solution is cost saving (Fig 2).
DISCUSSION
Biocompatible PD solution recently has been
shown to have significant patient benefits compared to
standard solution in terms of longer time to anuria and
first peritonitis episode, as well as a significant
reduction in the number of patients developing peri-
tonitis.27 To our knowledge, this is the first cost-
effectiveness analysis of biocompatible compared
with conventional solution. Our base-case analysis
indicated that biocompatible solution is likely to be a
good value, with an incremental cost of A$17,804 per
extra patient avoiding peritonitis at 2 years and a 25%
probability that biocompatible solution would be cost
saving over this time frame. The additional cost of
biocompatible solution is offset by the reduction in
peritonitis episodes and in particular the associated
hospital costs in the biocompatible-solution group.
Figure 2. Cost-effectiveness acceptability curve (probability
cost-effective at different willingness-to-pay thresholds for each
extra patient avoiding peritonitis over 2 years) for biocompatible
versus conventional dialysate (solid line, base-case analysis;
dashed line, sensitivity analysis omitting outliers (.3 SDs from
mean; n 5 6) for nonperitonitis hospitalization costs.
Am J Kidney Dis. 2015;65(5):773-779
Economic Evaluation of Biocompatible PD Solutions
A sensitivity analysis excluding outliers for non–
peritonitis-related hospital costs found that biocom-
patible solution was less costly than standard solution.
This significantly reduced the ICER to the point that
biocompatible solution was dominant (both less
costly and more effective) over standard solution.
Under these circumstances, there was a 75% proba-
bility that biocompatible solution was cost-saving.
Although these results suggest that biocompatible
solutions offer good value, unfortunately there
currently is no established threshold value for an
acceptable willingness to pay for each extra patient
avoiding peritonitis. What is considered good value is
highly context specific and dependent on competing
calls on resources. We have some information for
what decision makers might be willing to pay for a
quality-adjusted life-year (QALY) gained across
different jurisdictions. The acceptable value in terms
of incremental cost per QALY gained ranges from US
$50,000 to $100,000 in the United States39 to
w£20,000 to £30,000 in the United Kingdom.40,41 In
Australia, ICERs less than wA$50,000 per QALY
were more likely to be acceptable.42 In this context
and given the considerable morbidity and mortality
implications of peritonitis, biocompatible PD solution
appears to offer good value, although additional an-
alyses should confirm and extend our results.
The current economic evaluation considered perito-
nitis as the health outcome measure of interest because
it is explicitly a patient-relevant outcome. Because
peritonitis is one of the most serious complications of
PD, resulting in considerable morbidity (w20% PD
technique failure)28 and mortality (2%-6%),29,30 we
considered this an appropriate outcome for the eco-
nomic evaluation. Although peritonitis was a second-
ary outcome measure of the balANZ trial, patients
receiving biocompatible solutions had significantly
longer times to first peritonitis episode and experienced
lower overall peritonitis rates.27 There are several
theoretical reasons that support biological plausibility
between the use of biocompatible solutions and a
decrease in the peritonitis risk.32 These relate to su-
perior physical protection from improved preservation
of peritoneal membrane integrity and from enhanced
local immune defense mechanisms by avoiding expo-
sure to solutions that are high in GDP content with
acidic pH (ie, conventional solutions) based on
experimental evidence.12-18 In the context of high
peritonitis burden imposed upon PD patients, espe-
cially in countries such as Australia,31,33 any inter-
vention that can effectively lower its occurrence can
lead to better patient outcomes by reducing associated
morbidity and mortality risks.
Our analysis has a number of significant strengths.
It is based on one of the largest and most method-
ologically robust randomized controlled trials of
Am J Kidney Dis. 2015;65(5):773-779
biocompatible solution versus standard solution. The
balANZ study was a multicenter, multinational,
parallel-design, randomized, controlled trial with
one of the longest follow-up periods (2 years) re-
ported in the literature. The outcomes (eg, patients
avoiding peritonitis) represent a directly patient-
relevant outcome rather than a surrogate outcome.
Moreover, the current evaluation included costs
associated with temporary hemodialysis due to
various medical reasons (eg, postperitonitis and
hernia repair) during the trial participation to provide
the cost comparison in “real terms.” However,
despite these strengths, our analysis has a number of
limitations that should be acknowledged. The bal-
ANZ trial was designed primarily to examine the
effect of biocompatible solutions on residual kidney
function decline and peritonitis was one of its sec-
ondary outcome measures. We used data collected
routinely as part of the trial on health care use,
adverse events, and hospitalizations to inform the
economic evaluation. Other outpatient health care
use (eg, specialist visits and emergency department
visits) was not collected as part of the trial. There-
fore, the total reported per-patient cost may be
slightly underestimated; however, because these
additional costs are incurred in both trial arms, they
are unlikely to substantially affect the ICER. We
have considered only health outcomes reported in
natural units (patients experiencing peritonitis) rather
than a multidimensional health outcome such as
QALYs. The QALYs would facilitate comparison to
other interventions in these patients and to other
decisions in different contexts. Despite balANZ be-
ing the longest trial of biocompatible solution re-
ported to date, it still is a relatively short-term
follow-up period for a chronic disease and ideally,
we would want to consider health outcomes and
costs over a longer time horizon. Although the
ICERs reported here suggest that biocompatible
solution offers good value (and possibly both cost-
savings and fewer patients experiencing perito-
nitis), the benefits may be underestimated. The study
did not capture the improvement in residual kidney
function with the use of biocompatible solution,27
which may prolong technique survival on PD ther-
apy in these patients. A modeled analysis extrapo-
lating health outcomes beyond the trial duration and
over a patient lifetime to capture these and other
longer term health outcomes, including the consid-
eration of consequences of technique failure and
resuming hemodialysis therapy, is likely to offer
favorable cost-effectiveness.
Moreover, the disease burden imposed by perito-
nitis extends beyond the cost of acute treatment (ie,
medications, hospital visits, or admission) because it
leads to peritoneal membrane injury11 and contributes
777

to technique failure28 and mortality.29 In contrast,
presently there is no evidence to suggest that the use
of biocompatible solutions leads to patient harm. Its
use is supported further by greater urine output and
higher residual kidney function from treatments using
biocompatible solutions, as reported by a recent meta-
analysis.43 Therefore, superior cost-effectiveness of
using these solutions based on conservative modeling
on acute peritonitis from the present investigation
encourages its use in PD patients until further evi-
dence is obtained.
In conclusion, biocompatible solution offers a
cost-effective alternative to standard solution for
PD patients. The relatively high cost of receiving
biocompatible solutions was offset by reductions in
peritonitis occurrence and subsequent peritonitis-
related hospital costs. Until further evidence eval-
uating the role of biocompatible solutions in
peritonitis is available, its use appears to lead to
a number of beneficial patient-relevant clinical
outcomes while also being cost-effective.
ACKNOWLEDGEMENTS
Collaborators (balANZ Investigators) are as follows: Australian
centers: G. Rangan, L. Liew, Blacktown Hospital, Sydney; H.
Kulkarni, U. Steinwandel, Fremantle Hospital, Fremantle; B.
Jones, L. Garvey, John Hunter Hospital, Newcastle; M. Surayni,
M. Gilbert, Liverpool Hospital, Sydney; F. Brown, I. Abraham, J.
Nandkumar Monash Medical Centre, Melbourne; A. Coburn, V.
Bali, Princess Alexandra Hospital, Brisbane; S. McDonald, S.
Frasca, M. Hockley, C. Russ, The Queen Elizabeth Hospital,
Adelaide; T. Elias, K. Bannister, M. Hockley, K. Pirone, Royal
Adelaide Hospital; D. Ranganathan, L. Williams, Royal Brisbane
Hospital, Brisbane; K. Warr, G. Smith, Perth; N. Boudville, S.
Pellicano, Sir Charles Gairdner Hospital, Perth; R. Langham, E.
O’Flaherty, St Vincents Hospital, Melbourne. New Zealand cen-
ters: J. Schollum, L. Reed, L. Anderson Dunedin Hospital, Dun-
edin; D. Voss, B. Jagannathan, P. Nicholls Middlemore Hospital,
Auckland. Singapore centers: M. Foo, C.K. Tam, Singapore
General Hospital, Singapore; R. Lee, Tang Tock Seng Hospital,
Singapore; S.H. Tan, Kidney and Medical Clinic, Mount Elizabeth
Medical Centre, Singapore.
Support: Dr Cho is a current recipient of an Australian Post-
graduate Award. De Johnson is a current recipient of a Queensland
Government Health Research Fellowship. Dr Hayes acknowledges
salary support from National Health and Medical Research
Council Capacity Building Grant in Health Economics #571372.
Financial Disclosure: Drs Cass and Johnson have been con-
sultants for Baxter Healthcare Pty Ltd and have received research
funds from this company. They have also received speakers’
honoraria (Drs Cass and Johnson) and research grants (Dr John-
son) from Fresenius Medical Care. Ms Clarke is an employee of
Fresenius Medical Care. The other authors declare that they have
no other relevant financial interests.
Contributions: Research idea and study design: DWJ, KH, AC;
data acquisition: YC, MC; data analysis/interpretation: AH, KH;
statistical analysis: AH, KH; supervision or mentorship: DWJ, AC,
KH. Each author contributed important intellectual content during
manuscript drafting or revision and accepts accountability for the
overall work by ensuring that questions pertaining to the accuracy
or integrity of any portion of the work are appropriately investi-
gated and resolved. DWJ takes responsibility that this study has
778
Howard et al
been reported honestly, accurately, transparently; that no important
aspects of the study have been omitted; and that any discrepancies
from the study as planned have been explained.
REFERENCES
1. Jain AK, Blake P, Cordy P, Garg AX. Global trends in rates
of peritoneal dialysis. J Am Soc Nephrol. 2012;23(3):533-544.
2. Fresenius Medical Care. ESRD patients in 2011—a global
perspective 2012. http://www.vision-fmc.com/files/download/
ESRD/ESRD_Patients_in_2011.pdf. Accessed November 20,
2013.
3. Davies SJ, Van Biesen W, Nicholas J, Lameire N. Integrated
care. Perit Dial Int. 2001;21(suppl 3):S269-S274.
4. McDonald SP, Marshall MR, Johnson DW,
Polkinghorne KR. Relationship between dialysis modality and
mortality. J Am Soc Nephrol. 2009;20(1):155-163.
5. Blake PG. Integrated end-stage renal disease care: the role of
peritoneal dialysis. Nephrol Dial Transplant. 2001;16(suppl 5):
61-66.
6. Lee H, Manns B, Taub K, et al. Cost analysis of ongoing
care of patients with end-stage renal disease: the impact of dialysis
modality and dialysis access. Am J Kidney Dis. 2002;40(3):
611-622.
7. Brown F, Fulyani A, Dent H, Hurst K, McDonald S. Chapter
6: peritoneal dialysis. Australia & New Zealand Dialysis &
Transplantation (ANZDATA) Registry 2011. http://www.anzdata.
org.au/anzdata/AnzdataReport/34thReport/2011c06_peritoneal_v1.
8.pdf. Accessed June 22, 2012.
8. Johnson DW, Cho Y, Livingston BE, et al. Encapsulating
peritoneal sclerosis: incidence, predictors, and outcomes. Kidney
Int. 2010;77(10):904-912.
9. Brown EA, Van Biesen W, Finkelstein FO, et al; ISPD
Working Party. Length of time on peritoneal dialysis and encap-
sulating peritoneal sclerosis: position paper for ISPD. Perit Dial
Int. 2009;29(6):595-600.
10. Kawaguchi Y, Kawanishi H, Mujais S, Topley N,
Oreopoulos DG. Encapsulating peritoneal sclerosis: definition,
etiology, diagnosis, and treatment. International Society for Peri-
toneal Dialysis Ad Hoc Committee on Ultrafiltration Management
in Peritoneal Dialysis. Perit Dial Int. 2000;20(suppl 4):S43-S55.
11. Williams JD, Craig KJ, Topley N, et al. Morphologic
changes in the peritoneal membrane of patients with renal disease.
J Am Soc Nephrol. 2002;13(2):470-479.
12. Catalan MP, Santamaria B, Reyero A, Ortiz A, Egido J.
3,4-Di-deoxyglucosone-3-ene promotes leukocyte apoptosis.
Kidney Int. 2005;68(3):1303-1311.
13. Topley N. In vitro biocompatibility of bicarbonate-based
peritoneal dialysis solutions. Perit Dial Int. 1997;17(1):42-47.
14. Topley N, Mackenzie R, Petersen MM, et al. In vitro
testing of a potentially biocompatible continuous ambulatory
peritoneal dialysis fluid. Nephrol Dial Transplant. 1991;6(8):
574-581.
15. Witowski J, Topley N, Jorres A, Liberek T, Coles GA,
Williams JD. Effect of lactate-buffered peritoneal dialysis fluids on
human peritoneal mesothelial cell interleukin-6 and prostaglandin
synthesis. Kidney Int. 1995;47(1):282-293.
16. Witowski J, Wisniewska J, Korybalska K, et al. Prolonged
exposure to glucose degradation products impairs viability and
function of human peritoneal mesothelial cells. J Am Soc Nephrol.
2001;12(11):2434-2441.
17. Mortier S, De Vriese AS, McLoughlin RM, et al. Effects of
conventional and new peritoneal dialysis fluids on leukocyte
recruitment in the rat peritoneal membrane. J Am Soc Nephrol.
2003;14(5):1296-1306.
Am J Kidney Dis. 2015;65(5):773-779
Economic Evaluation of Biocompatible PD Solutions
18. Schambye HT. Effect of different buffers on the biocom-
patibility of CAPD solutions. Perit Dial Int. 1996;16(suppl 1):
S130-S136.
19. Boulanger E, Wautier MP, Wautier JL, et al. AGEs bind to
mesothelial cells via RAGE and stimulate VCAM-1 expression.
Kidney Int. 2002;61(1):148-156.
20. Devuyst O, Topley N, Williams JD. Morphological and
functional changes in the dialysed peritoneal cavity: impact of
more biocompatible solutions. Nephrol Dial Transplant.
2002;17(suppl 3):12-15.
21. Mackenzie R, Holmes CJ, Jones S, Williams JD, Topley N.
Clinical indices of in vivo biocompatibility: the role of ex vivo cell
function studies and effluent markers in peritoneal dialysis pa-
tients. Kidney Int Suppl. 2003;88:S84-S93.
22. Stankovic-Popovic V, Nesic V, Popovic D, et al. Effects
of conventional versus biocompatible peritoneal dialysis solu-
tions on peritoneal and systemic inflammation, malnutrition and
atherosclerosis in CAPD patients. Clin Nephrol. 2011;76(4):
314-322.
23. Furkert J, Zeier M, Schwenger V. Effects of peritoneal
dialysis solutions low in GDPs on peritonitis and exit-site infection
rates. Perit Dial Int. 2008;28(6):637-640.
24. Han SH, Ahn SV, Yun JY, Tranaeus A, Han DS. Mortality
and technique failure in peritoneal dialysis patients using advanced
peritoneal dialysis solutions. Am J Kidney Dis. 2009;54(4):
711-720.
25. Lee HY, Choi HY, Park HC, et al. Changing prescribing
practice in CAPD patients in Korea: increased utilization of low
GDP solutions improves patient outcome. Nephrol Dial Trans-
plant. 2006;21(10):2893-2899.
26. Lee HY, Seo BJ, Do JY, et al. Superior patient survival for
continuous ambulatory peritoneal dialysis patients treated with a
peritoneal dialysis fluid with neutral pH and low glucose degra-
dation product concentration (Balance). Perit Dial Int. 2005;25(3):
248-255.
27. Johnson DW, Brown FG, Clarke M, et al. Effects of
biocompatible versus standard fluid on peritoneal dialysis out-
comes. J Am Soc Nephrol. 2012;23(6):1097-1107.
28. Brown F, Gulyani A, McDonald S, Hurst K. Chapter 6:
peritoneal dialysis. In: ANZDATA 2012 Annual Report —35th
edition 2012. http://www.anzdata.org.au/anzdata/AnzdataReport/
35thReport/2012c06_peritoneal_v3.pdf. Accessed November 21,
2013.
29. Boudville N, Kemp A, Clayton P, et al. Recent peritonitis
associates with mortality among patients treated with peritoneal
dialysis. J Am Soc Nephrol. 2012;23(8):1398-1405.
30. Troidle L, Finkelstein F. Treatment and outcome of CPD-
associated peritonitis. Ann Clin Microbiol Antimicrob. 2006;5:6.
Am J Kidney Dis. 2015;65(5):773-779
31. Li PK, Szeto CC, Piraino B, et al. Peritoneal dialysis-
related infections recommendations: 2010 update. Perit Dial Int.
2010;30(4):393-423.
32. Johnson DW, Brown FG, Clarke M, et al. The effects of
biocompatible compared with standard peritoneal dialysis solu-
tions on peritonitis microbiology, treatment, and outcomes: the
balANZ trial. Perit Dial Int. 2012;32(5):497-506.
33. Piraino B, Bernardini J, Brown E, et al. ISPD position
statement on reducing the risks of peritoneal dialysis-related in-
fections. Perit Dial Int. 2011;31(6):614-630.
34. Australian Department of Health. Round 14 (2009-10)
National Public Cost Weight Tables—version 6.0x and version
5.2. 2012. http://www.health.gov.au/internet/main/publishing.nsf/
Content/Round_14-cost-reports. Accessed April 28, 2013.
35. Australian Department of Health. Medicare Benefits
Schedule. www.mbsonline.gov.au. Accessed January 25, 2015.
36. Australian Department of Health. Australian Pharmaceu-
tical Benefits Scheme. www.pbs.gov.au. Accessed January 25,
2015.
37. PBAC Committee. Guidelines for preparing submissions to
the Pharmaceutical Benefits Advisory Committee (version 4.3).
Department of Health and Ageing, Australian Government, 2008.
http://www.pbac.pbs.gov.au/content/information/archived-versions/
pbac-guidelines-v4.3-2008.pdf. Accessed November 21, 2013.
38. Fenwick E, Marshall D, Levy A, Nichol G. Using and
interpreting cost-effectiveness acceptability curves: an example
using data from a trial of management strategies for atrial fibril-
lation. BMC Health Serv Res. 2006;6:52.
39. Neumann PJ, Cohen JT, Weinstein MC. Updating cost-
effectiveness—the curious resilience of the $50,000-per-QALY
threshold. N Engl J Med. 2014;371(9):796-797.
40. Dakin H, Devlin N, Feng Y, Rice N, O’Neill P, Parkin D.
The influence of cost-effectiveness and other factors on
NICE decisions. 2014. http://www.herc.ox.ac.uk/downloads/
NICE. Accessed October 14, 2014.
41. The National Institute for Health and Clinical Excellence.
Guide to methods of technology appraisal 2013. http://www.nice.
org.uk/article/pmg9/resources/non-guidance-guide-to-the-methods-
of-technology-appraisal-2013-pdf. Accessed October 14, 2014.
42. Harris AH, Hill SR, Chin G, Li JJ, Walkom E. The role of
value for money in public insurance coverage decisions for drugs
in Australia: a retrospective analysis 1994-2004. Med Decis
Making. 2008;28(5):713-722.
43. Cho Y, Johnson DW, Badve SV, Craig JC, Strippoli GF,
Wiggins K. Impact of neutral pH, low glucose degradation product
peritoneal dialysis solution on clinical outcomes in peritoneal
dialysis: a systematic review of randomized controlled trials.
Kidney Int. 2013;84(5):969-979.
779