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RESEARCH ARTICLE Open Access
Cost-effectiveness analysis of a low-cost bubble
CPAP device in providing ventilatory support for
neonates in Malawi – a preliminary report
Ariel Chen1
, Ashish A Deshmukh2,3
, Rebecca Richards-Kortum1,4
, Elizabeth Molyneux5
, Kondwani Kawaza5
and Scott B Cantor2*
Abstract
Background: A low-cost bubble continuous positive airway pressure (bCPAP) device has been shown to be an excellent
clinical alternative to nasal oxygen for the care of neonates with respiratory difficulty. However, the delivery of bCPAP
requires more resources than the current routine care using nasal oxygen. We performed an economic evaluation to
determine the cost-effectiveness of a low-cost bCPAP device in providing ventilatory support for neonates in Malawi.
Methods: We used patient-level clinical data from a previously published non-randomized controlled study. Economic
data were based on the purchase price of supplies and equipment, adjusted for shelf life, as well as hospital cost data
from the World Health Organization. Costs and benefits were discounted at 3%. The outcomes were measured in terms
of cost, discounted life expectancy, cost/life year gained and net benefits of using bCPAP or nasal oxygen. The
incremental cost-effectiveness ratio and incremental net benefits determined the value of one intervention
compared to the other. Subgroup analysis on several parameters (birth weight categories, diagnosis of respiratory
distress syndrome, and comorbidity of sepsis) was conducted to evaluate the effect of these parameters on the
cost-effectiveness.
Results: Nasal oxygen therapy was less costly (US$29.29) than the low-cost bCPAP device ($57.78). Incremental
effectiveness associated with bCPAP was 6.78 life years (LYs). In the base case analysis, the incremental
cost-effectiveness ratio for bCPAP relative to nasal oxygen therapy was determined to be $4.20 (95% confidence
interval, US$2.29–US$16.67) per LY gained. The results were highly sensitive for all tested subgroups, particularly
for neonates with birth weight 1– < 1.5 kg, respiratory distress syndrome, or comorbidity of sepsis; these subgroups
had a higher probability that bCPAP would be cost effective.
Conclusion: The bCPAP is a highly cost-effective strategy in providing ventilatory support for neonates in Malawi.
Keywords: Cost-effectiveness analysis, Neonate, Malawi, Prematurity, Respiratory distress syndrome, Sepsis,
Ventilatory support, Bubble continuous positive airway pressure
Background
Forty-one percent of all deaths of children under the age
of five years occur during the neonatal period, i.e., within
the first 28 days of life [1]. Conditions that compromise
respiratory function, including prematurity, birth as-
phyxia, and pneumonia, are responsible for more than half
of the 3.6 million neonatal deaths that occur around the
world each year [2]. In developed countries, mechanical
ventilation, surfactant therapy, and bubble continuous
positive airway pressure (bCPAP) are the major technolo-
gies used to reduce neonatal mortality from respiratory
distress [3]. Due to inaccessibility of equipment and cost
constraints, the developing world is in need of appropriate
treatments for providing ventilatory support for neonates.
Malawi, a small landlocked country in the southeast-
ern area of the African continent, has the highest rate of
preterm births in the world: 18.1% of all newborns in
Malawi are born prematurely [4]. In addition, Malawi
* Correspondence: sbcantor@mdanderson.org
2
Department of Health Services Research, The University of Texas MD
Anderson Cancer Center, Houston, Texas, USA
Full list of author information is available at the end of the article
© 2014 Chen et al.; licensee BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative
Commons Attribution License (http://creativecommons.org/licenses/by/4.0), which permits unrestricted use, distribution, and
reproduction in any medium, provided the original work is properly credited. The Creative Commons Public Domain
Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article,
unless otherwise stated.
Chen et al. BMC Pediatrics 2014, 14:288
http://www.biomedcentral.com/1471-2431/14/288
has a neonatal mortality rate of 30 per 1000 live births
[5]. The current standard of care in Malawi for babies
with any type of respiratory difficulty is nasal oxygen
therapy. Although bCPAP devices have been successfully
implemented in low-resource settings, these life-saving
machines are commercially available for approximately
US$6000, and are prohibitively expensive [6,7].
In the early 2010s, a team of Rice University bioengi-
neers and Texas Children’s Hospital physicians and re-
spiratory therapists developed a low-cost bCPAP device
that can be assembled at a cost of $350. This device de-
livers pressure and air flow equivalent to the bCPAP
systems used in the developed world [6]. The low-cost
bCPAP device has been determined to be highly effica-
cious compared to nasal oxygen therapy (from this point
forward, bCPAP refers to this specific low-cost bCPAP).
Absolute improvement in survival among neonates re-
ceiving bCPAP in one study was 27% [8]; however, the
resource consumption in the delivery of bCPAP and its
cost-effectiveness relative to nasal oxygen therapy was
undetermined.
Using the healthcare system perspective, we sought to
determine the cost-effectiveness of low-cost bCPAP in
providing ventilator support for neonates in Malawi.
The purpose of this study is to inform decision makers
such as Malawi’s government and the World Health
Organization (WHO) of the relative clinical and economic
value of bCPAP compared to nasal oxygen therapy.
Methods
We used the net benefit regression approach to perform
a cost-effectiveness analysis comparing two interven-
tions—nasal oxygen and bCPAP—targeted to treat neo-
nates with respiratory difficulty. The overall outcomes
are reported using incremental cost-effectiveness ratio
(ICER) and incremental net benefit (INB).
The net benefit regression approach was deemed suit-
able for this study, as it accounts for individual-level
variation and addresses the important issues associated
with negative ICER when conducting an economic
evaluation using data from a clinical trial [9,10]. The is-
sues with negative ICER are of particular importance, as
the original study outcomes were reported in terms of
life and death (i.e., 1 if a patient survived and 0 if a pa-
tient died).
Clinical study and data
To perform the economic evaluation, we used the
individual-level clinical and cost data available from a
non-randomized controlled study [8]. The trial was con-
ducted over a 10-month period (from January 2012 to
October 2012) in the neonatal ward of Queen Elizabeth
Central Hospital in Blantyre, Malawi, in 2012. The inclu-
sion criteria for the study were neonates with: (1) severe
respiratory distress from any cause, (2) spontaneous
breathing, (3) a minimum weight of 1 kg, and (4) neuro-
logical viability. Patient diagnoses included RDS, transi-
ent tachypnea of the newborn, birth asphyxia, and
meconium aspiration. Clinical signs and symptoms were
used to determine if comorbidity of sepsis was also
present. Based on machine and staff availability, the eli-
gible patients were given bCPAP treatment. If the bCPAP
machine or appropriate staff were unavailable, the patients
received standard nasal oxygen therapy and became the
controls for the study. Babies who began treatment with
standard nasal oxygen therapy were switched to the
bCPAP machine if it became available. In the study nine
infants who initially received nasal oxygen were transi-
tioned from oxygen to bCPAP when a bCPAP device be-
came available. The outcomes of these nine children were
analyzed with the bCPAP group. 60-day survival rates and
sample sizes for all patients and subgroups identified in
the previous study as having an impact on survival are
shown in Table 1 [8].
Clinical outcome and effectiveness
Neonates enrolled in the study had a clinical outcome of
“died” or “discharged”. If a patient was discharged, the
baby was assumed to have remained alive by day 60. All
neonates were hospitalized for less than 60 days. For the
lifetime analysis, if the patient died, then the discounted
life expectancy of the patient was assumed to be zero
years. If the assumed 60-day outcome was alive, then we
assumed that the patient then had the standard life ex-
pectancy for a Malawian person of the same sex using
the standard Malawian life tables for men and women
in 2011 from the World Health Organization Global
Health Observatory Data Repository [11].
The effectiveness used for the lifetime analysis was the
standard life expectancy discounted at a rate of 3% per
year for men and women [12]. The standard life expectan-
cies of Malawian men and women are 56.80 and
58.50 years, respectively. The discounted life expectancy
was estimated using a Markov model that used age-specific
annual mortality probabilities from the WHO life table for
Malawi for the year 2011 and a discount rate of 3%. As-
suming that a newborn survives the first 60 days of life, the
Markov model extrapolated the life expectancy (DLE) dis-
counted for the period after the first 60 days and up to the
expected time of death using the equation DLE ≈
X110
i¼0
1−m0
ð Þ 1−m1
ð Þ… 1−mi−1
ð Þ  mi
½  i þ 1
2
 
1 þ r
ð Þi , where mi
is the mortality probability in the ith
year and r is the
discount rate. The calculated discounted life expectan-
cies of men and women were calculated to be 25.06 and
25.34 years, respectively.
Chen et al. BMC Pediatrics 2014, 14:288 Page 2 of 8
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During the clinical study, only mild and temporary com-
plications from bCPAP treatment were observed, includ-
ing nasal irritation, facial irritation, and epistaxis. Since no
major morbidity was observed from bCPAP, outcomes
were reported in life years (LYs) rather than the standard
unit of cost-effectiveness analysis, disability-adjusted life
years (DALYs) [11]. Our estimations were based on the
assumption that nasal oxygen and bCPAP treatment do
not decrease subsequent quality of life and survival time
of infants.
Costs
The total number of days in the neonatal ward and the
level of care the infant received each day of hospitalization
(i.e. nasal oxygen, bCPAP, or no respiratory support) was
recorded in the clinical study. With the provided data,
individual-level costs were calculated based on the level of
care each day
The costs associated with spending a day with respira-
tory support were divided into general hospital costs and
costs associated with the treatment of bCPAP or nasal
oxygen. The costs associated with spending a day without
respiratory support only included general hospitalization
costs. For the general hospitalization cost, we applied the
WHO “choosing interventions that are cost-effective” pro-
ject (WHO-CHOICE) Malawi cost estimates for inpatient
unit costs of a tertiary-level hospital bed-day for a day
with respiratory support and a secondary-level hospital
bed-day for a day without respiratory support [13]. The
cost per bed-day estimates include “hotel” components of
hospitalization, such as personnel, capital, and food, but
not the cost of drugs [13]. The general hospitalization
costs were converted to 2012 US dollars using the
Consumer Price Index for All Urban Consumers: Medical
Care Services as shown in Table 2 [14]. Costs associated
with the treatment of bCPAP or nasal oxygen were cate-
gorized either as per-day or per-patient costs. Per-patient
costs were costs that were constant for each patient
regardless of the duration of hospitalization. The equip-
ment per-day costs were calculated using a formula that
annualized the costs of capital investments:
E ¼ K
1− 1 þ r
ð Þ−n
r
 −1
;
where E is the equivalent cost per period, K is the pur-
chase price, r is the period interest or discount rate, and
n is the useful life of the equipment [12]. The equipment
prices were obtained from the purchase price as given
by the equipment vendor or hospital supplier, adjusted
for shelf life. These costs were already valued at 2012 US
dollars. For all equipment, an annual discount rate of 3%
was applied according to WHO guidelines [12]. The per-
day costs of each piece of equipment were calculated on
the basis of the annualized cost of each piece of equip-
ment, the number of patients it served in one day, and
an assumed 80% usage rate of capacity [12].
Although we recognized that providing bCPAP is more
time-intensive for the nurses than providing nasal oxy-
gen therapy, the difference in labor cost between bCPAP
and nasal oxygen therapy was not included for two rea-
sons. First, we assumed that, due to the constraints of
Malawi’s healthcare system, Malawi would not hire more
nurses to accommodate this extra labor requirement for
bCPAP. Second, personnel costs were already accounted
for in the WHO-CHOICE estimates and we did not want
to count any costs twice. We also did not include training
costs in our analysis. Based on the guidelines for economic
evaluation, we conducted the analysis assuming that the
clinicians already possessed the skills to administer bCPAP
therapy and would not require further training [12]. In
addition, the fixed costs associated with training would be
distributed over a large number of patients, thus, render-
ing such costs to be negligible.
Analysis
The results of the economic evaluation for overall out-
comes were expressed in the form of ICER and INB.
The outcomes for the subgroups—birth weight categor-
ies, diagnosis of respiratory distress syndrome (RDS),
and comorbidity of sepsis—were reported using INB. The
INB measures the value of extra patient outcome with re-
spect to extra cost [9]. The ICER is computed as the ratio
of the difference in costs and difference in effectiveness
(in this study, life years).
The net benefit approach is based on the principle that
a decision-maker will consider an intervention worth-
while if its cost-effectiveness ratio is less than the max-
imum willingness to pay per life year gained (λ). The net
monetary benefit (NMB) was calculated for each patient
based on λ and the incremental cost and incremental ef-
fectiveness. To conduct the analysis the data were fitted
Table 1 60-day survival rates and sizes of subgroups of
neonates receiving nasal oxygen or bCPAP [8]
Group/subgroup 60-day survival
Nasal oxygen bCPAP
n (%) n (%)
All 11/25 (44 · 0) 44/62 (71 · 0)
Birth weight
1.0–  1 · 5 kg 2/13 (15 · 4) 19/29 (65 · 5)
1 · 5–  2 · 5 kg 5/7 (71 · 4) 16/24 (66 · 7)
≥2 · 5 kg 4/5 (80 · 0) 9/9 (100 · 0)
RDS 4/17 (23 · 5) 31/48 (64 · 6)
Sepsis 0/7 (0 · 0) 16/26 (61 · 5)
bCPAP = bubble continuous positive airway pressure. RDS = respiratory
distress syndrome.
Chen et al. BMC Pediatrics 2014, 14:288 Page 3 of 8
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in a linear regression model using an indicator variable
based on the treatment received (bCPAP versus nasal
oxygen) [15].
The joint uncertainty in cost and effectiveness of bCPAP
compared to nasal oxygen therapy is presented in the
form of a cost-effectiveness acceptability curve [16-18].
The x-axis of the curve gives λ and the y-axis gives the
proportion of estimated joint uncertainty that falls in the
cost-effective half of the plane, i.e., the probability that the
intervention is cost-effective.
Protection of human subjects
The clinical component of the study was approved by
the Malawi College of Medicine research and ethics
committee and the institutional review boards at Rice
University and Baylor College of Medicine. The economic
component of the study was approved by the institutional
review board at The University of Texas MD Anderson
Cancer Center.
Results
As in the original clinical trial, 87 patients were used for
this study: 62 were bCPAP patients, and 25 were nasal
oxygen patients. The mean number of days in the hos-
pital of a nasal oxygen patient and a bCPAP patient were
9.1 and 15.3, respectively. From the number of days in
the hospital and the level of care received each day, the
average cost per patient was US$29.29 (standard devi-
ation [SD] =26.52) for a patient on nasal oxygen and
$57.78 (SD = US$40.92) for a patient on bCPAP. The ef-
fectiveness of nasal oxygen and bCPAP was 11.08 LYs
(SD =12.76) and 17.86 LYs (SD =11.51), respectively.
Thus, the ICER for the bCPAP intervention in comparison
to the usual treatment of nasal oxygen is US$4.20 (95%
confidence interval, US$2.29–US$16.67) per LY gained.
Table 3 summarizes the overall INB as well as the INB
for the subgroups at a λ ranging from US$0 to US$20.
At the λ = US$5, the intervention was cost-effective over-
all. It also was cost-effective for the subgroups of birth
weight of 1–  1.5 kg, birth weight of ≥2.5 kg, diagnosis of
RDS, and comorbidity of sepsis. At λ = $20, the interven-
tion was highly cost-effective overall and for all subgroups,
except the subgroup of birth weight of 1.5–  2.5 kg (for
which the INB was negative).
The cost-effectiveness acceptability curves determine
the probability that an intervention is cost-effective at a
number of λ values. Overall, the probability that bCPAP
was cost-effective was almost 100% at λ = US$20 (Figure 1).
The probability of cost-effectiveness of bCPAP for patients
with weight 1–  1.5 kg (Figure 2a), a diagnosis of RDS
(Figure 2b), or comorbidity of sepsis (Figure 2c) was
higher than the probability of cost-effectiveness for
patients with birth weight 2.5 kg or who had no diag-
nosis of RDS or no comorbidity of sepsis. Given the
relatively small hospital bed-day cost, the incremental
cost-effectiveness ratio for bCPAP compared to nasal
oxygen did not significantly change (results not shown).
Discussion
Using bCPAP is a highly cost-effective strategy in provid-
ing ventilatory support for neonates in Malawi. In our
subgroup analysis, we determined that a patient’s birth
weight, a diagnosis of RDS, and comorbidity of sepsis had
a high impact on the cost-effectiveness of bCPAP. Accord-
ing to WHO international guidelines, interventions are
considered highly cost-effective when the ICER in terms
of cost per DALY is less than a country’s per-capita gross
domestic product (GDP), cost-effective when the ICER is
between one and three times the per-capita GDP, and not
cost-effective when the ICER is above three times the
GDP [19]. The national per-capita GDP of Malawi in 2012
was approximately US$268 [20]. Given that the ICER for
bCPAP versus nasal oxygen is US$4.20 per LY gained,
the bCPAP would be considered highly cost-effective by
Table 2 Cost estimates per patient in 2012 US$
Item assessed Cost (US$) Treatment Calculation Source
Equipment
bCPAP 350 · 00 bCPAP Per day Equipment vendor
Oxygen concentrator 1,248 · 00 Both Per day Equipment vendor
Suction machine 282 · 00 Both Per day Equipment vendor
Nasal prongs 8 · 43 bCPAP Per patient Hospital supplier
Stockinette hat 0 · 15 bCPAP Per patient Hospital supplier
Suction tube 0 · 56 Both Per day Hospital supplier
Hospital bed-day
With respiratory support 2 · 55* Both Per day WHO-CHOICE
Without respiratory support 1 · 98* Both Per day WHO-CHOICE
bCPAP = bubble continuous positive airway pressure. WHO-CHOICE = World Health Organization “choosing interventions that are cost-effective” project.
*Prices were inflated from 2008 to 2012 US$ using the Consumer Price Index for All Urban Consumers: Medical Care Services for the relevant years.
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Table 3 INB from net benefit regression models at selected levels of willingness to pay per LY gained (λ) in 2012 US$
Group/subgroup Incremental net benefit
λ =0 λ =5 λ =10 λ =15 λ =20
(CI 95%) (CI 95%) (CI 95%) (CI 95%) (CI 95%)
All patients −28 · 49 5 · 38 39 · 26 73 · 13 107 · 00
(−46 · 1–10 · 86) (−18 · 64–29 · 41) (−9 · 83–88 · 34) (−3 · 08–149 · 33) (3 · 21–210 · 79)
Birth weight
1–  1 · 5 kg −39 · 71 23 · 48 86 · 67 149 · 86 213 · 05
(−70 · 02–9 · 40) (−2 · 91–49 · 87) (27 · 90–145 · 44) (53 · 99–245 · 73) (79 · 23–346 · 88)
1 · 5–  2 · 5 kg −27 · 25 −33 · 58 −39 · 91 −46 · 25 −52 · 58
(−51 · 79–2 · 70) (−72 · 15–5 · 00) (−129 · 72–49 · 90) (−188 · 85–96 · 36) (−248 · 28–143 · 13)
≥ 2 · 5 kg −3 · 71 21 · 38 46 · 48 71 · 57 96 · 66
(−33 · 68–26 · 27) (−42 · 88–85 · 64) (−55 · 85–148 · 80) (−69 · 58–212 · 71) (−83 · 57–276 · 89)
Diagnosis of RDS
Yes −33 · 70 17 · 88 69 · 45 121 · 02 172 · 59
(−56 · 61–10 · 78) (−6 · 08–41 · 84) (15 · 84–123 · 05) (34 · 86–207 · 18) (53 · 33–291 · 86)
No −13 · 46 −6 · 80 −0 · 14 6 · 53 13 · 19
(−36 · 87–9 · 95) (−54 · 04–40 · 44) (−79 · 82–79 · 55) (−107 · 06–120 · 12) (−134 · 76–161 · 14)
Comorbidity of sepsis
Yes −26 · 64 52 · 52 131 · 67 210 · 82 289 · 97
(−69 · 43–16 · 15) (12 · 52–92 · 51) (54 · 14–209 · 19) (88 · 08–333 · 56) (120 · 38–459 · 56)
No −27 · 95 −7 · 81 12 · 33 32 · 47 52 · 61
(−44 · 20–11 · 69) (−34 · 63–19 · 01) (−45 · 78–70 · 44) (−58 · 29–123 · 23) (−71 · 08–176 · 30)
INB = incremental net benefit. CI, confidence interval. LY, life year. RDS, respiratory distress syndrome.
Figure 1 Overall cost-effectiveness acceptability curve for bCPAP compared to nasal oxygen.
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the international standards (assuming that the cost-
effectiveness thresholds can be extended from DALYs
to LYs).
There are several limitations to our study. First, the
baseline efficacy data were obtained from a very small
non-randomized population, with only 62 bCPAP and
25 nasal oxygen patients. The results of this study, in-
cluding the subgroup analysis, should be considered pre-
liminary and should be reexamined with data from a
larger clinical trial. For ethical reasons, it is challenging
to carry out a randomized controlled trial of potentially
life-saving appropriate technologies when the benefits of
counterpart technologies designed for high-resource set-
tings are significant and well-documented. On the other
hand, it is critical to assess technology performance in
low-resource settings because performance is dependent
on many aspects of infrastructure, including low staffing
levels, potential interruptions in electrical power, uncon-
trolled climate, etc.
Currently, a prospective study evaluating the effective-
ness of bCPAP compared to nasal oxygen therapy is be-
ing conducted at four central and 27 district hospitals in
Malawi. Results of that study are expected after 2015.
Second, we used life tables for Malawi to extrapolate
long-term effectiveness by translating clinical outcome
in terms of 60-day survival to reflect discounted life ex-
pectancy. We assumed that once patients were discharged,
they completed their lives following the standard life ex-
pectancy patterns. Although other exogenous factors can
affect life expectancy, our analysis did not account for
such factors.
Third, the overall calculated costs of treatment were
largely based on the WHO-CHOICE estimates. These
calculated costs were determined using an econometric
model that used variables like GDP per capita and occu-
pancy rate to predict country-specific hospital costs.
However, these costs may not be a true representation of
the actual bed-day costs in Malawi.
Fourth, we recognize that treatment with nasal oxygen
at high concentration can reduce quality of life. There
are limited data that address this issue that can be incor-
porated in an economic evaluation [21-23]. However, if
we were able to include quality of life into the analysis
then our conclusion would be strengthened because
quality of life after nasal oxygen would likely be no
better than quality of life after bCPAP making the
Figure 2 Cost-effectiveness acceptability curve by the subgroups: a. birth weight, b. diagnosis of respiratory distress syndrome, and c.
comorbidity of sepsis.
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incremental cost-effectiveness ratio for the bCPAP strat-
egy even lower.
Despite the limitations, our calculations show that
low-cost bCPAP is substantially below the international
thresholds for being highly cost-effective. Even if the
ICER was ten times its current value, bCPAP intervention
would still be considered cost-effective. The increase in
60-day survival rates from nasal oxygen to bCPAP, the low
cost of the bCPAP machine and accompanying equip-
ment, the lack of noticeable complications from bCPAP,
and the fact that this intervention takes place so early
in life contribute to the extreme cost-effectiveness of
bCPAP therapy.
Although from an economic standpoint, bCPAP is
clearly cost-effective, we must recognize the infrastruc-
tural and cultural barriers to implementing the device
on a national scale. While we chose not to include dif-
ferences in labor demand, the administration of bCPAP
therapy is an additional burden on the nurses who are
already dealing with understaffed wards and high patient
volumes. In addition, most clinicians are not trained to
recognize the clinical indication for bCPAP, nor are they
trained to administer it. Efforts are being made to train
clinicians and incorporate bCPAP into the nursing cur-
riculum in Malawi; however, transitioning bCPAP treat-
ment to be a part of routine care has more obstacles
than just cost. It requires the availability of a constant
supply of equipment, trained clinicians, and a medical
system that supports the administration of bCPAP. Cul-
tural barriers also exist; for example, many Malawians
associate nasal prongs with dying patients [24]. It takes
extra time and effort to build the mothers’ trust that the
nasal prongs used with bCPAP, or with nasal oxygen, will
increase their children’s likelihood of survival.
Conclusion
Our analysis indicates that this low-cost bCPAP is a highly
cost-effective use of healthcare resources in Malawi. This
intervention provides life-saving treatment at the earliest
stages of life for a minimal cost, and offers an important
strategy for the treatment of neonates with respiratory dif-
ficulty in other developing countries. We look forward to
the results of the larger multicenter trial, which we expect
will reinforce our conclusions of the effectiveness and
cost-effectiveness of this intervention for neonates.
Abbreviations
bCPAP: Bubble continuous positive airway pressure; RDS: Respiratory distress
syndrome; INB: Incremental net benefit; LY: Life year; CI: Confidence interval;
SD: Standard deviation; ICER: Incremental cost-effectiveness ratio;
WHO: World Health Organization; GDP: Gross domestic product; NMB: Net
monetary benefit.
Competing interests
The authors declare that they have no competing interests.
Authors’ contributions
AC, ADD, and SBC made substantial contributions to the conception or
design of the work; RRK, EM, and KK made substantial contributions to the
acquisition and interpretation of data. AC and ADD wrote the initial draft.
SBC, RRK, EM, and KK revised the manuscript and contributed important
intellectual content. All authors agree to be accountable for all aspects of
the work in ensuring that questions related to the accuracy or integrity of
any part of the work are appropriately investigated and resolved. All authors
read and approved the final manuscript.
Acknowledgments
This project was supported in part by a grant to Rice University from the
Howard Hughes Medical Institute through the Precollege and
Undergraduate Science Education Program. This research also is made
possible through the generous support of the Saving Lives at Birth Partners:
the United States Agency for International Development, the government of
Norway, the Bill  Melinda Gates Foundation, Grand Challenges Canada, and
the United Kingdom government. This paper was prepared by employees of
The University of Texas MD Anderson Cancer Center and Rice University. It
does not necessarily reflect the view of the Saving Lives at Birth Partners. We
appreciate the helpful suggestions of Jeffrey S. Hoch, Ph.D., and Joshua A.
Salomon, Ph.D. The authors wish to thank Maria Oden, Ph.D., for data
management, Mary Kate Quinn, B.S., for research assistance, and Luanne
Jorewicz, B.A., for editorial contributions.
Author details
1
Institute for Global Health Technologies, Rice University, Houston, Texas,
USA. 2
Department of Health Services Research, The University of Texas MD
Anderson Cancer Center, Houston, Texas, USA. 3
Cancer Prevention Training
Research Program, The University of Texas MD Anderson Cancer Center,
Houston, Texas, USA. 4
Department of Bioengineering, Rice University,
Houston, Texas, USA. 5
Department of Pediatrics, College of Medicine, Queen
Elizabeth Central Hospital, Blantyre, Malawi.
Received: 10 June 2014 Accepted: 6 November 2014
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paradigm. Neonatology 2014, 105(4):323–331.
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epidemics, population of babies at risk and implications for control.
Early Hum Dev 2008, 84(2):77–82.
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Camarena-Garcia E, Diaz-Alatorre C, Gutierrez-Padilla JA, Gilbert C: Retinopathy
of prematurity as a major cause of severe visual impairment and blindness
in children in schools for the blind in Guadalajara city. Mexico. Br J
Ophthalmol 2011, 95(11):1502–1505.
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an oxygen concentrator system in district hospital paediatric wards
throughout Malawi. Bull World Health Organ 2008, 86(5):344–348.
doi:10.1186/s12887-014-0288-1
Cite this article as: Chen et al.: Cost-effectiveness analysis of a low-cost
bubble CPAP device in providing ventilatory support for neonates in
Malawi – a preliminary report. BMC Pediatrics 2014 14:288.
Submit your next manuscript to BioMed Central
and take full advantage of:
• Convenient online submission
• Thorough peer review
• No space constraints or color figure charges
• Immediate publication on acceptance
• Inclusion in PubMed, CAS, Scopus and Google Scholar
• Research which is freely available for redistribution
Submit your manuscript at
www.biomedcentral.com/submit
Chen et al. BMC Pediatrics 2014, 14:288 Page 8 of 8
http://www.biomedcentral.com/1471-2431/14/288

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Cpap fer

  • 1. RESEARCH ARTICLE Open Access Cost-effectiveness analysis of a low-cost bubble CPAP device in providing ventilatory support for neonates in Malawi – a preliminary report Ariel Chen1 , Ashish A Deshmukh2,3 , Rebecca Richards-Kortum1,4 , Elizabeth Molyneux5 , Kondwani Kawaza5 and Scott B Cantor2* Abstract Background: A low-cost bubble continuous positive airway pressure (bCPAP) device has been shown to be an excellent clinical alternative to nasal oxygen for the care of neonates with respiratory difficulty. However, the delivery of bCPAP requires more resources than the current routine care using nasal oxygen. We performed an economic evaluation to determine the cost-effectiveness of a low-cost bCPAP device in providing ventilatory support for neonates in Malawi. Methods: We used patient-level clinical data from a previously published non-randomized controlled study. Economic data were based on the purchase price of supplies and equipment, adjusted for shelf life, as well as hospital cost data from the World Health Organization. Costs and benefits were discounted at 3%. The outcomes were measured in terms of cost, discounted life expectancy, cost/life year gained and net benefits of using bCPAP or nasal oxygen. The incremental cost-effectiveness ratio and incremental net benefits determined the value of one intervention compared to the other. Subgroup analysis on several parameters (birth weight categories, diagnosis of respiratory distress syndrome, and comorbidity of sepsis) was conducted to evaluate the effect of these parameters on the cost-effectiveness. Results: Nasal oxygen therapy was less costly (US$29.29) than the low-cost bCPAP device ($57.78). Incremental effectiveness associated with bCPAP was 6.78 life years (LYs). In the base case analysis, the incremental cost-effectiveness ratio for bCPAP relative to nasal oxygen therapy was determined to be $4.20 (95% confidence interval, US$2.29–US$16.67) per LY gained. The results were highly sensitive for all tested subgroups, particularly for neonates with birth weight 1– < 1.5 kg, respiratory distress syndrome, or comorbidity of sepsis; these subgroups had a higher probability that bCPAP would be cost effective. Conclusion: The bCPAP is a highly cost-effective strategy in providing ventilatory support for neonates in Malawi. Keywords: Cost-effectiveness analysis, Neonate, Malawi, Prematurity, Respiratory distress syndrome, Sepsis, Ventilatory support, Bubble continuous positive airway pressure Background Forty-one percent of all deaths of children under the age of five years occur during the neonatal period, i.e., within the first 28 days of life [1]. Conditions that compromise respiratory function, including prematurity, birth as- phyxia, and pneumonia, are responsible for more than half of the 3.6 million neonatal deaths that occur around the world each year [2]. In developed countries, mechanical ventilation, surfactant therapy, and bubble continuous positive airway pressure (bCPAP) are the major technolo- gies used to reduce neonatal mortality from respiratory distress [3]. Due to inaccessibility of equipment and cost constraints, the developing world is in need of appropriate treatments for providing ventilatory support for neonates. Malawi, a small landlocked country in the southeast- ern area of the African continent, has the highest rate of preterm births in the world: 18.1% of all newborns in Malawi are born prematurely [4]. In addition, Malawi * Correspondence: sbcantor@mdanderson.org 2 Department of Health Services Research, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA Full list of author information is available at the end of the article © 2014 Chen et al.; licensee BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly credited. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated. Chen et al. BMC Pediatrics 2014, 14:288 http://www.biomedcentral.com/1471-2431/14/288
  • 2. has a neonatal mortality rate of 30 per 1000 live births [5]. The current standard of care in Malawi for babies with any type of respiratory difficulty is nasal oxygen therapy. Although bCPAP devices have been successfully implemented in low-resource settings, these life-saving machines are commercially available for approximately US$6000, and are prohibitively expensive [6,7]. In the early 2010s, a team of Rice University bioengi- neers and Texas Children’s Hospital physicians and re- spiratory therapists developed a low-cost bCPAP device that can be assembled at a cost of $350. This device de- livers pressure and air flow equivalent to the bCPAP systems used in the developed world [6]. The low-cost bCPAP device has been determined to be highly effica- cious compared to nasal oxygen therapy (from this point forward, bCPAP refers to this specific low-cost bCPAP). Absolute improvement in survival among neonates re- ceiving bCPAP in one study was 27% [8]; however, the resource consumption in the delivery of bCPAP and its cost-effectiveness relative to nasal oxygen therapy was undetermined. Using the healthcare system perspective, we sought to determine the cost-effectiveness of low-cost bCPAP in providing ventilator support for neonates in Malawi. The purpose of this study is to inform decision makers such as Malawi’s government and the World Health Organization (WHO) of the relative clinical and economic value of bCPAP compared to nasal oxygen therapy. Methods We used the net benefit regression approach to perform a cost-effectiveness analysis comparing two interven- tions—nasal oxygen and bCPAP—targeted to treat neo- nates with respiratory difficulty. The overall outcomes are reported using incremental cost-effectiveness ratio (ICER) and incremental net benefit (INB). The net benefit regression approach was deemed suit- able for this study, as it accounts for individual-level variation and addresses the important issues associated with negative ICER when conducting an economic evaluation using data from a clinical trial [9,10]. The is- sues with negative ICER are of particular importance, as the original study outcomes were reported in terms of life and death (i.e., 1 if a patient survived and 0 if a pa- tient died). Clinical study and data To perform the economic evaluation, we used the individual-level clinical and cost data available from a non-randomized controlled study [8]. The trial was con- ducted over a 10-month period (from January 2012 to October 2012) in the neonatal ward of Queen Elizabeth Central Hospital in Blantyre, Malawi, in 2012. The inclu- sion criteria for the study were neonates with: (1) severe respiratory distress from any cause, (2) spontaneous breathing, (3) a minimum weight of 1 kg, and (4) neuro- logical viability. Patient diagnoses included RDS, transi- ent tachypnea of the newborn, birth asphyxia, and meconium aspiration. Clinical signs and symptoms were used to determine if comorbidity of sepsis was also present. Based on machine and staff availability, the eli- gible patients were given bCPAP treatment. If the bCPAP machine or appropriate staff were unavailable, the patients received standard nasal oxygen therapy and became the controls for the study. Babies who began treatment with standard nasal oxygen therapy were switched to the bCPAP machine if it became available. In the study nine infants who initially received nasal oxygen were transi- tioned from oxygen to bCPAP when a bCPAP device be- came available. The outcomes of these nine children were analyzed with the bCPAP group. 60-day survival rates and sample sizes for all patients and subgroups identified in the previous study as having an impact on survival are shown in Table 1 [8]. Clinical outcome and effectiveness Neonates enrolled in the study had a clinical outcome of “died” or “discharged”. If a patient was discharged, the baby was assumed to have remained alive by day 60. All neonates were hospitalized for less than 60 days. For the lifetime analysis, if the patient died, then the discounted life expectancy of the patient was assumed to be zero years. If the assumed 60-day outcome was alive, then we assumed that the patient then had the standard life ex- pectancy for a Malawian person of the same sex using the standard Malawian life tables for men and women in 2011 from the World Health Organization Global Health Observatory Data Repository [11]. The effectiveness used for the lifetime analysis was the standard life expectancy discounted at a rate of 3% per year for men and women [12]. The standard life expectan- cies of Malawian men and women are 56.80 and 58.50 years, respectively. The discounted life expectancy was estimated using a Markov model that used age-specific annual mortality probabilities from the WHO life table for Malawi for the year 2011 and a discount rate of 3%. As- suming that a newborn survives the first 60 days of life, the Markov model extrapolated the life expectancy (DLE) dis- counted for the period after the first 60 days and up to the expected time of death using the equation DLE ≈ X110 i¼0 1−m0 ð Þ 1−m1 ð Þ… 1−mi−1 ð Þ mi ½ i þ 1 2 1 þ r ð Þi , where mi is the mortality probability in the ith year and r is the discount rate. The calculated discounted life expectan- cies of men and women were calculated to be 25.06 and 25.34 years, respectively. Chen et al. BMC Pediatrics 2014, 14:288 Page 2 of 8 http://www.biomedcentral.com/1471-2431/14/288
  • 3. During the clinical study, only mild and temporary com- plications from bCPAP treatment were observed, includ- ing nasal irritation, facial irritation, and epistaxis. Since no major morbidity was observed from bCPAP, outcomes were reported in life years (LYs) rather than the standard unit of cost-effectiveness analysis, disability-adjusted life years (DALYs) [11]. Our estimations were based on the assumption that nasal oxygen and bCPAP treatment do not decrease subsequent quality of life and survival time of infants. Costs The total number of days in the neonatal ward and the level of care the infant received each day of hospitalization (i.e. nasal oxygen, bCPAP, or no respiratory support) was recorded in the clinical study. With the provided data, individual-level costs were calculated based on the level of care each day The costs associated with spending a day with respira- tory support were divided into general hospital costs and costs associated with the treatment of bCPAP or nasal oxygen. The costs associated with spending a day without respiratory support only included general hospitalization costs. For the general hospitalization cost, we applied the WHO “choosing interventions that are cost-effective” pro- ject (WHO-CHOICE) Malawi cost estimates for inpatient unit costs of a tertiary-level hospital bed-day for a day with respiratory support and a secondary-level hospital bed-day for a day without respiratory support [13]. The cost per bed-day estimates include “hotel” components of hospitalization, such as personnel, capital, and food, but not the cost of drugs [13]. The general hospitalization costs were converted to 2012 US dollars using the Consumer Price Index for All Urban Consumers: Medical Care Services as shown in Table 2 [14]. Costs associated with the treatment of bCPAP or nasal oxygen were cate- gorized either as per-day or per-patient costs. Per-patient costs were costs that were constant for each patient regardless of the duration of hospitalization. The equip- ment per-day costs were calculated using a formula that annualized the costs of capital investments: E ¼ K 1− 1 þ r ð Þ−n r −1 ; where E is the equivalent cost per period, K is the pur- chase price, r is the period interest or discount rate, and n is the useful life of the equipment [12]. The equipment prices were obtained from the purchase price as given by the equipment vendor or hospital supplier, adjusted for shelf life. These costs were already valued at 2012 US dollars. For all equipment, an annual discount rate of 3% was applied according to WHO guidelines [12]. The per- day costs of each piece of equipment were calculated on the basis of the annualized cost of each piece of equip- ment, the number of patients it served in one day, and an assumed 80% usage rate of capacity [12]. Although we recognized that providing bCPAP is more time-intensive for the nurses than providing nasal oxy- gen therapy, the difference in labor cost between bCPAP and nasal oxygen therapy was not included for two rea- sons. First, we assumed that, due to the constraints of Malawi’s healthcare system, Malawi would not hire more nurses to accommodate this extra labor requirement for bCPAP. Second, personnel costs were already accounted for in the WHO-CHOICE estimates and we did not want to count any costs twice. We also did not include training costs in our analysis. Based on the guidelines for economic evaluation, we conducted the analysis assuming that the clinicians already possessed the skills to administer bCPAP therapy and would not require further training [12]. In addition, the fixed costs associated with training would be distributed over a large number of patients, thus, render- ing such costs to be negligible. Analysis The results of the economic evaluation for overall out- comes were expressed in the form of ICER and INB. The outcomes for the subgroups—birth weight categor- ies, diagnosis of respiratory distress syndrome (RDS), and comorbidity of sepsis—were reported using INB. The INB measures the value of extra patient outcome with re- spect to extra cost [9]. The ICER is computed as the ratio of the difference in costs and difference in effectiveness (in this study, life years). The net benefit approach is based on the principle that a decision-maker will consider an intervention worth- while if its cost-effectiveness ratio is less than the max- imum willingness to pay per life year gained (λ). The net monetary benefit (NMB) was calculated for each patient based on λ and the incremental cost and incremental ef- fectiveness. To conduct the analysis the data were fitted Table 1 60-day survival rates and sizes of subgroups of neonates receiving nasal oxygen or bCPAP [8] Group/subgroup 60-day survival Nasal oxygen bCPAP n (%) n (%) All 11/25 (44 · 0) 44/62 (71 · 0) Birth weight 1.0– 1 · 5 kg 2/13 (15 · 4) 19/29 (65 · 5) 1 · 5– 2 · 5 kg 5/7 (71 · 4) 16/24 (66 · 7) ≥2 · 5 kg 4/5 (80 · 0) 9/9 (100 · 0) RDS 4/17 (23 · 5) 31/48 (64 · 6) Sepsis 0/7 (0 · 0) 16/26 (61 · 5) bCPAP = bubble continuous positive airway pressure. RDS = respiratory distress syndrome. Chen et al. BMC Pediatrics 2014, 14:288 Page 3 of 8 http://www.biomedcentral.com/1471-2431/14/288
  • 4. in a linear regression model using an indicator variable based on the treatment received (bCPAP versus nasal oxygen) [15]. The joint uncertainty in cost and effectiveness of bCPAP compared to nasal oxygen therapy is presented in the form of a cost-effectiveness acceptability curve [16-18]. The x-axis of the curve gives λ and the y-axis gives the proportion of estimated joint uncertainty that falls in the cost-effective half of the plane, i.e., the probability that the intervention is cost-effective. Protection of human subjects The clinical component of the study was approved by the Malawi College of Medicine research and ethics committee and the institutional review boards at Rice University and Baylor College of Medicine. The economic component of the study was approved by the institutional review board at The University of Texas MD Anderson Cancer Center. Results As in the original clinical trial, 87 patients were used for this study: 62 were bCPAP patients, and 25 were nasal oxygen patients. The mean number of days in the hos- pital of a nasal oxygen patient and a bCPAP patient were 9.1 and 15.3, respectively. From the number of days in the hospital and the level of care received each day, the average cost per patient was US$29.29 (standard devi- ation [SD] =26.52) for a patient on nasal oxygen and $57.78 (SD = US$40.92) for a patient on bCPAP. The ef- fectiveness of nasal oxygen and bCPAP was 11.08 LYs (SD =12.76) and 17.86 LYs (SD =11.51), respectively. Thus, the ICER for the bCPAP intervention in comparison to the usual treatment of nasal oxygen is US$4.20 (95% confidence interval, US$2.29–US$16.67) per LY gained. Table 3 summarizes the overall INB as well as the INB for the subgroups at a λ ranging from US$0 to US$20. At the λ = US$5, the intervention was cost-effective over- all. It also was cost-effective for the subgroups of birth weight of 1– 1.5 kg, birth weight of ≥2.5 kg, diagnosis of RDS, and comorbidity of sepsis. At λ = $20, the interven- tion was highly cost-effective overall and for all subgroups, except the subgroup of birth weight of 1.5– 2.5 kg (for which the INB was negative). The cost-effectiveness acceptability curves determine the probability that an intervention is cost-effective at a number of λ values. Overall, the probability that bCPAP was cost-effective was almost 100% at λ = US$20 (Figure 1). The probability of cost-effectiveness of bCPAP for patients with weight 1– 1.5 kg (Figure 2a), a diagnosis of RDS (Figure 2b), or comorbidity of sepsis (Figure 2c) was higher than the probability of cost-effectiveness for patients with birth weight 2.5 kg or who had no diag- nosis of RDS or no comorbidity of sepsis. Given the relatively small hospital bed-day cost, the incremental cost-effectiveness ratio for bCPAP compared to nasal oxygen did not significantly change (results not shown). Discussion Using bCPAP is a highly cost-effective strategy in provid- ing ventilatory support for neonates in Malawi. In our subgroup analysis, we determined that a patient’s birth weight, a diagnosis of RDS, and comorbidity of sepsis had a high impact on the cost-effectiveness of bCPAP. Accord- ing to WHO international guidelines, interventions are considered highly cost-effective when the ICER in terms of cost per DALY is less than a country’s per-capita gross domestic product (GDP), cost-effective when the ICER is between one and three times the per-capita GDP, and not cost-effective when the ICER is above three times the GDP [19]. The national per-capita GDP of Malawi in 2012 was approximately US$268 [20]. Given that the ICER for bCPAP versus nasal oxygen is US$4.20 per LY gained, the bCPAP would be considered highly cost-effective by Table 2 Cost estimates per patient in 2012 US$ Item assessed Cost (US$) Treatment Calculation Source Equipment bCPAP 350 · 00 bCPAP Per day Equipment vendor Oxygen concentrator 1,248 · 00 Both Per day Equipment vendor Suction machine 282 · 00 Both Per day Equipment vendor Nasal prongs 8 · 43 bCPAP Per patient Hospital supplier Stockinette hat 0 · 15 bCPAP Per patient Hospital supplier Suction tube 0 · 56 Both Per day Hospital supplier Hospital bed-day With respiratory support 2 · 55* Both Per day WHO-CHOICE Without respiratory support 1 · 98* Both Per day WHO-CHOICE bCPAP = bubble continuous positive airway pressure. WHO-CHOICE = World Health Organization “choosing interventions that are cost-effective” project. *Prices were inflated from 2008 to 2012 US$ using the Consumer Price Index for All Urban Consumers: Medical Care Services for the relevant years. Chen et al. BMC Pediatrics 2014, 14:288 Page 4 of 8 http://www.biomedcentral.com/1471-2431/14/288
  • 5. Table 3 INB from net benefit regression models at selected levels of willingness to pay per LY gained (λ) in 2012 US$ Group/subgroup Incremental net benefit λ =0 λ =5 λ =10 λ =15 λ =20 (CI 95%) (CI 95%) (CI 95%) (CI 95%) (CI 95%) All patients −28 · 49 5 · 38 39 · 26 73 · 13 107 · 00 (−46 · 1–10 · 86) (−18 · 64–29 · 41) (−9 · 83–88 · 34) (−3 · 08–149 · 33) (3 · 21–210 · 79) Birth weight 1– 1 · 5 kg −39 · 71 23 · 48 86 · 67 149 · 86 213 · 05 (−70 · 02–9 · 40) (−2 · 91–49 · 87) (27 · 90–145 · 44) (53 · 99–245 · 73) (79 · 23–346 · 88) 1 · 5– 2 · 5 kg −27 · 25 −33 · 58 −39 · 91 −46 · 25 −52 · 58 (−51 · 79–2 · 70) (−72 · 15–5 · 00) (−129 · 72–49 · 90) (−188 · 85–96 · 36) (−248 · 28–143 · 13) ≥ 2 · 5 kg −3 · 71 21 · 38 46 · 48 71 · 57 96 · 66 (−33 · 68–26 · 27) (−42 · 88–85 · 64) (−55 · 85–148 · 80) (−69 · 58–212 · 71) (−83 · 57–276 · 89) Diagnosis of RDS Yes −33 · 70 17 · 88 69 · 45 121 · 02 172 · 59 (−56 · 61–10 · 78) (−6 · 08–41 · 84) (15 · 84–123 · 05) (34 · 86–207 · 18) (53 · 33–291 · 86) No −13 · 46 −6 · 80 −0 · 14 6 · 53 13 · 19 (−36 · 87–9 · 95) (−54 · 04–40 · 44) (−79 · 82–79 · 55) (−107 · 06–120 · 12) (−134 · 76–161 · 14) Comorbidity of sepsis Yes −26 · 64 52 · 52 131 · 67 210 · 82 289 · 97 (−69 · 43–16 · 15) (12 · 52–92 · 51) (54 · 14–209 · 19) (88 · 08–333 · 56) (120 · 38–459 · 56) No −27 · 95 −7 · 81 12 · 33 32 · 47 52 · 61 (−44 · 20–11 · 69) (−34 · 63–19 · 01) (−45 · 78–70 · 44) (−58 · 29–123 · 23) (−71 · 08–176 · 30) INB = incremental net benefit. CI, confidence interval. LY, life year. RDS, respiratory distress syndrome. Figure 1 Overall cost-effectiveness acceptability curve for bCPAP compared to nasal oxygen. Chen et al. BMC Pediatrics 2014, 14:288 Page 5 of 8 http://www.biomedcentral.com/1471-2431/14/288
  • 6. the international standards (assuming that the cost- effectiveness thresholds can be extended from DALYs to LYs). There are several limitations to our study. First, the baseline efficacy data were obtained from a very small non-randomized population, with only 62 bCPAP and 25 nasal oxygen patients. The results of this study, in- cluding the subgroup analysis, should be considered pre- liminary and should be reexamined with data from a larger clinical trial. For ethical reasons, it is challenging to carry out a randomized controlled trial of potentially life-saving appropriate technologies when the benefits of counterpart technologies designed for high-resource set- tings are significant and well-documented. On the other hand, it is critical to assess technology performance in low-resource settings because performance is dependent on many aspects of infrastructure, including low staffing levels, potential interruptions in electrical power, uncon- trolled climate, etc. Currently, a prospective study evaluating the effective- ness of bCPAP compared to nasal oxygen therapy is be- ing conducted at four central and 27 district hospitals in Malawi. Results of that study are expected after 2015. Second, we used life tables for Malawi to extrapolate long-term effectiveness by translating clinical outcome in terms of 60-day survival to reflect discounted life ex- pectancy. We assumed that once patients were discharged, they completed their lives following the standard life ex- pectancy patterns. Although other exogenous factors can affect life expectancy, our analysis did not account for such factors. Third, the overall calculated costs of treatment were largely based on the WHO-CHOICE estimates. These calculated costs were determined using an econometric model that used variables like GDP per capita and occu- pancy rate to predict country-specific hospital costs. However, these costs may not be a true representation of the actual bed-day costs in Malawi. Fourth, we recognize that treatment with nasal oxygen at high concentration can reduce quality of life. There are limited data that address this issue that can be incor- porated in an economic evaluation [21-23]. However, if we were able to include quality of life into the analysis then our conclusion would be strengthened because quality of life after nasal oxygen would likely be no better than quality of life after bCPAP making the Figure 2 Cost-effectiveness acceptability curve by the subgroups: a. birth weight, b. diagnosis of respiratory distress syndrome, and c. comorbidity of sepsis. Chen et al. BMC Pediatrics 2014, 14:288 Page 6 of 8 http://www.biomedcentral.com/1471-2431/14/288
  • 7. incremental cost-effectiveness ratio for the bCPAP strat- egy even lower. Despite the limitations, our calculations show that low-cost bCPAP is substantially below the international thresholds for being highly cost-effective. Even if the ICER was ten times its current value, bCPAP intervention would still be considered cost-effective. The increase in 60-day survival rates from nasal oxygen to bCPAP, the low cost of the bCPAP machine and accompanying equip- ment, the lack of noticeable complications from bCPAP, and the fact that this intervention takes place so early in life contribute to the extreme cost-effectiveness of bCPAP therapy. Although from an economic standpoint, bCPAP is clearly cost-effective, we must recognize the infrastruc- tural and cultural barriers to implementing the device on a national scale. While we chose not to include dif- ferences in labor demand, the administration of bCPAP therapy is an additional burden on the nurses who are already dealing with understaffed wards and high patient volumes. In addition, most clinicians are not trained to recognize the clinical indication for bCPAP, nor are they trained to administer it. Efforts are being made to train clinicians and incorporate bCPAP into the nursing cur- riculum in Malawi; however, transitioning bCPAP treat- ment to be a part of routine care has more obstacles than just cost. It requires the availability of a constant supply of equipment, trained clinicians, and a medical system that supports the administration of bCPAP. Cul- tural barriers also exist; for example, many Malawians associate nasal prongs with dying patients [24]. It takes extra time and effort to build the mothers’ trust that the nasal prongs used with bCPAP, or with nasal oxygen, will increase their children’s likelihood of survival. Conclusion Our analysis indicates that this low-cost bCPAP is a highly cost-effective use of healthcare resources in Malawi. This intervention provides life-saving treatment at the earliest stages of life for a minimal cost, and offers an important strategy for the treatment of neonates with respiratory dif- ficulty in other developing countries. We look forward to the results of the larger multicenter trial, which we expect will reinforce our conclusions of the effectiveness and cost-effectiveness of this intervention for neonates. Abbreviations bCPAP: Bubble continuous positive airway pressure; RDS: Respiratory distress syndrome; INB: Incremental net benefit; LY: Life year; CI: Confidence interval; SD: Standard deviation; ICER: Incremental cost-effectiveness ratio; WHO: World Health Organization; GDP: Gross domestic product; NMB: Net monetary benefit. Competing interests The authors declare that they have no competing interests. Authors’ contributions AC, ADD, and SBC made substantial contributions to the conception or design of the work; RRK, EM, and KK made substantial contributions to the acquisition and interpretation of data. AC and ADD wrote the initial draft. SBC, RRK, EM, and KK revised the manuscript and contributed important intellectual content. All authors agree to be accountable for all aspects of the work in ensuring that questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolved. All authors read and approved the final manuscript. Acknowledgments This project was supported in part by a grant to Rice University from the Howard Hughes Medical Institute through the Precollege and Undergraduate Science Education Program. This research also is made possible through the generous support of the Saving Lives at Birth Partners: the United States Agency for International Development, the government of Norway, the Bill Melinda Gates Foundation, Grand Challenges Canada, and the United Kingdom government. This paper was prepared by employees of The University of Texas MD Anderson Cancer Center and Rice University. It does not necessarily reflect the view of the Saving Lives at Birth Partners. We appreciate the helpful suggestions of Jeffrey S. Hoch, Ph.D., and Joshua A. Salomon, Ph.D. The authors wish to thank Maria Oden, Ph.D., for data management, Mary Kate Quinn, B.S., for research assistance, and Luanne Jorewicz, B.A., for editorial contributions. Author details 1 Institute for Global Health Technologies, Rice University, Houston, Texas, USA. 2 Department of Health Services Research, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA. 3 Cancer Prevention Training Research Program, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA. 4 Department of Bioengineering, Rice University, Houston, Texas, USA. 5 Department of Pediatrics, College of Medicine, Queen Elizabeth Central Hospital, Blantyre, Malawi. Received: 10 June 2014 Accepted: 6 November 2014 References 1. Oestergaard MZ, Inoue M, Yoshida S, Mahanani WR, Gore FM, Cousens S, Lawn JE, Mathers CD, United Nations Inter-Agency Group for Child Mortality E, the Child Health Epidemiology Reference G: Neonatal mortality levels for 193 countries in 2009 with trends since 1990: a systematic analysis of progress, projections, and priorities. PLoS Med 2011, 8(8):e1001080. 2. 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