Designs of two randomized, community-based trials to assess the impact of alternative cookstove installation on respiratory illness among young children and reproductive outcomes in rural Nepal
BMC Public Health
Designs of two randomized, community-based trials to assess the impact of alternative cookstove installation on respiratory illness among young children and reproductive outcomes in rural Nepal
James M Tielsch 0
Joanne Katz 2
Scott L Zeger 1
Subarna K Khatry 6
Laxman Shrestha 5
Patrick Breysse 4
William Checkley 3
Luke C Mullany 2
Steven C LeClerq 2 6
0 Department of Global Health, Milken Institute School of Public Health, George Washington University , Washington, DC , USA
1 Department of Biostatistics, Johns Hopkins Bloomberg School of Public Health , Baltimore, MD , USA
2 Department of International Health, Johns Hopkins Bloomberg School of Public Health , Baltimore, MD , USA
3 Department of Medicine, Johns Hopkins School of Medicine , Baltimore, MD , USA
4 Department of Environmental Health Sciences, Johns Hopkins Bloomberg School of Public Health , Baltimore, MD , USA
5 Department of Pediatrics and Child Health, Institute of Medicine, Tribhuvan University , Kathmandu , Nepal
6 Nepal Nutrition Intervention Project - Sarlahi , Kathmandu , Nepal
Background: Acute lower respiratory infections (ALRI) are a leading cause of death among children. Low birthweight is prevalent in South Asia and associated with increased risks of mortality, and morbidity, high levels of indoor household air pollution caused by open burning of biomass fuels are common and associated with high rates of ALRI and low birthweight. Alternative stove designs that burn biomass fuel more efficiently have been proposed as one method for reducing these high exposures and lowering rates of these disorders. We designed two randomized trials to test this hypothesis. Methods/design: We conducted a pair of community-based, randomized trials of alternative cookstove installation in a rural district in southern Nepal. Phase one was a cluster randomized, modified step-wedge design using an alternative biomass stove with a chimney. A pre-installation period of morbidity assessment and household environmental assessment was conducted for six months in all households. This was followed by a one year step-wedge phase with 12 monthly steps for clusters of households to receive the alternative stove. The timing of alternative stove introduction was randomized. This step-wedge phase was followed in all households by another six month follow-up phase. Eligibility criteria for phase one included household informed consent, the presence of a married woman of reproductive age (15-30 yrs) or a child < 36 months. Children were followed until 36 months of age or the end of the trial. Pregnancies were identified and followed until completion or end of the trial. Phase two was an individually randomized trial of the same alternative biomass stove versus liquid propane gas stove in a subset of households that participated in phase one. Follow-up for phase two was 12 months following stove installation. Eligibility criteria included the same components as phase one except children were only enrolled for morbidity follow-up if they were less than 24 months. The primary outcomes included: incidence of ALRI in children and birthweight. Discussion: We presented the design and methods of two randomized trials of alternative cookstoves on rates of ALRI and birthweight. Trial registration: Clinicaltrials.gov (NCT00786877, Nov. 5, 2008).
Pneumonia; ALRI; Birthweight; Biomass fuel; Household air pollution; Improved cookstoves; Randomized trials
Acute lower respiratory infections (ALRI) remain a
leading cause of death among children in the developing
world with the highest risk among the youngest children
. Small size at birth, including low birthweight (LBW)
is also common and an important risk factor for early
infant death with 28% of all neonatal deaths attributable
directly to this condition . Over the past few decades,
there has been an increasing focus on the role of
environmental exposures in the etiology or exacerbation of
ALRI. In the mid-1950s in London, thousands of excess
deaths, especially among young children and the elderly,
were associated with extensive outdoor particulate air
pollution due to smoke from coal burning household
stoves . More recent studies of outdoor air pollution
have confirmed that respirable particulate exposure,
even at the relatively low levels now seen in
highincome settings, can increase respiratory mortality and
morbidity [4-6]. While outdoor exposures in low- and
middle-income countries play a role in the incidence
and severity of respiratory disease , outdoor exposures
are most extreme in urban environments and the vast
majority of the studies on outdoor air pollution from
developing countries have been done in these settings. Of
more concern in rural areas is indoor air pollution
where particulate matter concentrations can be many
times those found outdoors . Such high levels are
particularly frequent in south Asia where biomass materials
(dung, wood, and crop residue) are the predominant
sources of fuel used for cooking and heating and where
typical houses have limited ventilation and use open
stoves without flues. It is not uncommon to observe
concentrations between 2,000 and 15,000 ?g/m3 during
cooking [8-10], but very high exposures can continue
throughout the day if the stove is also used for heat or the
family prepares food items for sale. The observational
epidemiological literature on the association of indoor smoke
exposure and ALRI in young children demonstrates that
exposure to incomplete combustion of biomass fuels
increases by 2?12 fold the risk of respiratory symptoms or
disease in preschool age children .
It is well known that certain particulate matter and
other chemical respiratory exposures can cause reduced
birthweight, intra-uterine growth restriction (IUGR), and
preterm birth; the best examples being active and
passive tobacco smoke exposure during pregnancy .
The observational evidence on the association between
indoor air pollution and infant birth outcomes suggests
that exposure to biomass fuel smoke is associated with a
97 g reduction in birthweight but the depth and quality
of this literature varies substantially .
Other chronic disease outcomes are also associated
with poor indoor air quality and the global burden of
illness due to indoor burning of biomass fuels in 2010 has
been recently estimated at 4.3% of all disability adjusted
life years (DALYs) . Use of cookstoves that utilize
alternate fuels or incorporate a chimney for ventilation
may reduce exposure and thus improve outcomes, but
neither the exposure reduction nor the concomitant
health gains have been adequately studied at the
population level. We have implemented trials in rural Nepal to
examine these questions, and present here the design of
The Nepal Cookstove Intervention Project is a pair of
randomized trials to evaluate the impact of using
alternative cookstoves to improve indoor air quality,
respiratory morbidity in young children, and reproductive
outcomes in a population where indoor open burning
of biomass fuels sources are the norm. The study was
initially designed as a single trial with two identical
cohorts, but after examining the exposure reduction
performance of the alternative stove used in the first trial,
it was decided to alter the second phase to a separate,
but complementary randomized trial.
Phase One: This was a cluster-randomized, modified
step-wedge trial (Figure 1). The study area was initially
divided into 51 sectors of 20?30 households that were
each estimated to provide between 25 and 40 children <
36 months of age. These sectors served as units for
concurrent installation by a single stove installation team of
the alternate biomass stove over a one month period.
Sectors were then combined into 12 groups that served
as the unit of randomization and corresponded to the
12 months of the step-wedge portion of the design.
Within a group, sectors were geographically spread
across the study area using a stratified systematic
sampling procedure in order to prevent an additional level
of clustering and within group correlation of the primary
This standard step-wedge design was modified by
adding a six month period of outcome assessment in all
groups prior to the start of the step-wedge and a similar
six month period of outcome assessment following
completion of the 12 month step wedge. This provided
additional person-time and balance on season both before
and after new stove installation. All three primary
outcomes show marked seasonality in this population [15,16].
Phase Two: The design of phase two was an
individually randomized trial at the household level (Figure 1).
Eligible households that participated in phase one and
newly eligible households that did not participate in
phase one were randomized to either an alternate
biomass stove with chimney or a LPG stove with gas tank
and 12 month supply. Follow-up of phase two was for
12 months following stove installation.
6 S S S S S E S S S S S I S S S S S E S S S S S S Randomize I S S S S S E S S S S S S
7 S S S S S S E S S S S S I S S S S S E S S S S S Eligible Households I S S S S S S E S S S S S
S = Surveillance for ALRI & reproductive outcomes
E = Environmental Assessment and Surveillance for outcomes
I = Cookstove replacement for this group of sectors.
I= LPG stove installation for households randomized to this intervention.
Figure 1 Trials design scheme.
The study population for Phase 1 consists of residents of
all households in four Village Development Committees
(VDCs) in Sarlahi District in the terai region of southern
Nepal. The study population for Phase 2 included only
households in 2 of these VDCs. The terai lies along the
border with north India and is part of the flood plain of
the Ganges River and its tributaries that drain from the
Himalayas to the Bay of Bengal. This is not a high
mountain area, but one characterized as low and flat
(approximately 600 ft. elevation) with high population
density. It is typical of most of northern India and large
parts of western Bangladesh and northern and central
Pakistan with a population of over one billion. It is
predominately an area of traditional, rural, Hindu culture.
The population is mostly peasant farmers (58%) or
laborers (26%) and their families, and is considered a poor
area, even in Nepal. It is an extremely poor environment
with a per capita income of $146 .
Did not currently have an improved, ventilated
biomass cookstove, LPG cookstove or electric
cookstove in the household.
Used their traditional open burning biomass
cookstove indoors or in an area contained by at least
Had household walls of mud, brick, cement, or
wood. Thatch or bamboo walled houses that were
not plastered with mud were not eligible for fire
Were willing to have us install an alternative,
ventilated biomass cookstove and be willing to use it
for at least 12 months.
Have a married woman 15?30 years of age or at
least one child <36 months of age residing in the
household at the time of trial initiation.
Resided in two of the original four VDCs from the
Phase 1 trial.
Participated in the first trial and continued to have a
married woman age 15?30 years of age or at least
one child <24 months of age residing in the
household at the initiation of Phase 2.
Were a new household in the study VDCs that had
at least one married woman age 15?30 years of age
or at least one child <24 months of age residing in
the household at the initiation of Phase 2.
Were willing to be randomized to either continuing
with their alternative, ventilated biomass stove from
Phase 1 or to an LPG stove and to use it for
Phase 1: The cookstove intervention in the first phase
consisted of replacing the household?s traditional open
burning stove with a commercially available two burner
biomass stove with a chimney outlet and a chimney
constructed from sheet metal. The stove used was model
G-3300 with the G-3355 two pot attachment
manufactured by Envirofit International (Colorado Springs, CO,
USA) (Figure 2). Chimney pieces were manufactured by a
local sheet metal firm and installed on-site by project
stove installation teams. In addition to the provision of a
new stove, extensive training and demonstration in the
use and maintenance of the stoves was conducted and
Figure 2 Alternative biomass cookstove used in both trials.
reinforced regularly throughout the follow-up period by a
special team of stove monitors.
Phase Two: The cookstove intervention in phase two
consisted of either, the continued placement and support
for use of the alternate biomass stove (Envirofit model
G-3300 + G-3355 with chimney), or the installation of an
LPG two-burner stove with gas tank and adequate LPG
supply for 12 months. The LPG stoves were
manufactured in India and the LPG was sourced from one of
three suppliers in Nepal and distributed monthly. All
households who were randomized to the improved
biomass stove arm were provided with a LPG stove, gas tank,
and one month of LPG fuel at the end of the study.
Primary and secondary outcomes
Primary outcomes for both trials included:
1. Incidence of ALRI among children < 36 months of
age. An episode of ALRI was defined as two or more
consecutive days with maternal report of fever and
fast/difficult breathing with both symptoms reported
on at least one day during the episode and during
which at least one symptom occurred each day.
Consecutive episodes had to be separated by a
minimum of 7 symptom free days. An episode of
severe ALRI was defined as an episode of ALRI plus
one or more of the following:
respiratory rate >50 if the child was 12 months or
older; >60 if the child was younger than
chest auscultation finding of crackles in at least
Respiratory morbidity was assessed during
weekly household visits where mothers or other
caregivers were asked about signs and
symptoms on each day in the preceding week.
Maternal report of signs and symptoms
included high fever, persistent cough, fast or
difficult breathing, wheezing, watery stool, ear
discharge, and burn injury. We also asked
whether the child had been taken for care and
where the child was taken. If a child had an
episode of fast/difficult breathing in the past
week, a separate visit was scheduled for
examination as soon as possible by a more
senior staff member to assess the child for
danger signs, measure respiratory rate, oxygen
saturation and conduct digital chest auscultation.
2. Birthweight as measured by study staff using digital
infant scales (Tanita Corp., Tokyo, Japan).
3. Gestational age as measured by the start of last menstrual period. Secondary outcomes for both trials included:
1. Forced expiratory volumes among married women
15?30 years of age and one other randomly selected
adult (15 yrs or older) member of the household.
Forced expiratory volume in one second (FEV1) and
forced expiratory volume in six seconds (FEV6) were
measured using the Piko-6 pocket spirometer
(nSpire Health, Longmont, CO, USA) and a
disposable mouthpiece under a standardized
2. Respiratory symptoms as assessed using a modified
version of a standardized questionnaire  among
married women 15?30 years of age and one other
randomly selected adult (15 yrs or older) member of
3. Blood pressure and pulse among married women
15?30 years of age and one other randomly selected
adult (15 yrs or older) member of the household.
Blood pressure was measured using an automated
osscilometric device (BpTrue 300, VSM MedTech
Ltd, Coquitlam, Canada).
4. Oxygen saturation, carboxyhemoglobin level, and
heart rate during pregnancy using a pulse oximeter
(Rad-57. Masimo Corp., Irvine, CA).
5. Indoor air concentrations of respirable particulates
(PM2.5) and carbon monoxide (CO).
Phase One: Randomization of the 12 groups to the
timing of new stove installation was conducted in the
project office in Kathmandu and was a transparent process
with participation of senior field representatives. The
numbers 1 through 12 were written on separate slips of
paper and senior Nepal-based project staff drew slips
one at a time out of a hat with the first group selected
being the group that would have their stoves replaced in
the first month, the second group selected having stoves
replaced in the second month, etc.
Phase Two: Eligible households in phase two were
individually randomized stratified by VDC and Ward using
the sample procedure in STATA (StataCorp LP, College
Station, TX). Households that had participated in phase
one were randomized separately from newly eligible
A census of all households in the study area was
conducted as a part of phase 1 in order to identify all
eligible households for recruitment, obtain informed
consent for participation, address eligible households for
ease of identification during the data collection phase,
and to collect basic information about residents of
eligible households. A full household roster was collected
and included identifying information, age, date of birth,
sex, marital status, literacy, years of education, occupation,
tobacco use, weight, height (length for children < 2 yrs),
and individual consent status for all household residents.
For married women 15?30 yrs and one randomly selected
other adult (?15 yrs), the following additional
measurements were collected: FEV1, FEV6, blood pressure, and
heart rate. These people also completed a respiratory
Assessment of household characteristics was collected for
all eligible consented households. Variables collected
included measures of household socioeconomic status using
an asset index, ethnicity, number and types of cookstoves,
house construction materials and size, source of drinking
water, household sanitation practices, and whether there
were members of the household working outside the local
area or country (as a measure of additional cash income).
Pregnancy identification and data collection
Initial identification of pregnant women occurred at the
baseline enrollment visit. Subsequently, all married
women between 15 and 30 years of age were visited
every 5 weeks and asked about their menstrual period in
the preceding 5 weeks. If the woman had her period, the
week of the period was recorded and she was visited
again 5 weeks later. If she reported no menstrual period,
she was offered a urine-based pregnancy test at her
home. If the test was positive, she received a pregnancy
enrollment interview that included her reproductive
Monthly during Day of
6 End of Monthly follow-up X X
Table 1 Data collection schedule
Pregnancy history &
Maternal Blood Pressure
Maternal carboxyHb, O2
saturation & pulse
Respiratory rate & O2
*For children receiving ALRI case examination.
history, morbidity in the previous month, date of her last
menstrual period, tobacco and alcohol use, and plans for
where and by whom she would deliver her baby. We also
measured her weight, height, blood pressure, pulse,
oxygen saturation, and carboxyhemoglobin level. Pregnant
women were encouraged to attend antenatal care clinics
in the public or private sector and to deliver at a
certified birthing facility. The study provided education on
nutrition, clean delivery, and danger signs at this visit.
We also provided pregnant women with 90 days of
ironfolic acid supplements, a clean birthing kit (included a
clean blade, string, plastic tarp, and small plastic disc on
which to cut the cord), chlorhexidine ointment for
umbilical cord antisepsis, and a single dose of albendazole.
We visited all women monthly throughout their
pregnancy to collect pregnancy-related morbidity in the
previous month, to ask about tobacco and alcohol use, and
to measure weight, blood pressure, pulse, oxygen
saturation, and carboxyhemoglobin levels.
Pregnancy outcome assessment
When a baby was born, the family contacted a local staff
member as soon as possible, often during labor. Project
staff then visited the home to collect extensive information
Table 2 Power to compare ALRI incidence before and after alternative biomass cookstove installed for varying
relative odds and degrees of trend in ALRI rates over time
on the birth process and the health of the mother and
newborn infant(s). Birthweight, length, head circumference,
and temperature of the infant(s) were measured and
recorded. One week following delivery, a visit was made to
record information on infant and maternal post-partum
Respiratory morbidity assessment
All eligible children (0 through 35 months of age) were
visited weekly for morbidity assessment as described
previously. Once a child reached 36 months of age he/she
was discharged from the study.
Cause of death assessment
All women and children who died were identified and a
verbal autopsy was conducted with members of the
family after a culturally appropriate mourning period.
Each household received a measurement of indoor air
quality once prior to new stove installation and once
afterwards. This assessment consisted of measurements
of PM2.5, CO, and temperature and humidity over an
18 hour period that included all the cooking events
during the day. All measurements were taken using logging
devices set to record every 10 seconds. The instrument
used for airborne particulate concentration was the
DataRAM pDR 1000AN (Thermo Fisher Scientific Inc.,
Waltham, MA). This instrument provides particle mass
concentration in units of ?g/m3 and was used in passive
mode as a nephelometer. As nephelometric readings
vary according to relative humidity, values were
corrected based on calibrations with gravimetric
measurements as previously described . The instrument for
measuring CO concentration data (in units of ppm) was
the EL-USB-CO300 (Lascar Electronics Ltd, Salisbury,
UK). Temperature and humidity were measured using a
HOBO data logger (Onset Computer Corp., Bourne, MA,
Data management and statistical analysis plans
Interview-based data were collected on paper forms and
checked for errors and missing values before being sent
from the field site to Kathmandu for data entry. Data
entry programs checked for inconsistencies and out of
range values. Errors were corrected by data supervisors
based on all relevant forms or sent back to the field for
clarification if necessary.
The first step in the statistical analysis is calculation of
descriptive statistics for exposure, demographic and health
outcome data to elucidate basic features in the data, to
identify gross outliers and to examine bivariate relationships
between pairs of variables. We then proceeded with
exposure modeling and health effects analysis at both the
individual and village levels for ALRI and birthweight.
Throughout, standard software packages such as SAS and
R were used, as appropriate.
The raw exposure PM2.5 and CO data were pre-processed
as follows. First, 10 minute average values were calculated
from the 10 second data using 3% trimmed means to
avoid undue influence of outliers. The 10 minute averages
were then filtered using running medians of length 5 to
eliminate short-term excursions caused by larger particle
contamination. A base-line value was estimated using the
10th percentile of all measurements for a day. We then
defined Stove Influenced Time (SIT) to be any 10-minute
interval for which it?s filtered value exceeded the baseline
by a multiple of more than 1.2. We defined the Stove
Influenced Particulate (SIP) or CO (SIC) as the total
difference between the 10-minute average value and the
baseline, over the SIT times for a 24 hour period.
For each exposure measure, we used a linear mixed
effects regression model as defined below to estimate the
average difference between households with an improved
stove as compared to control households without one,
while controlling for season and secular trend. Because
the effect of the stove on indoor air quality can vary by
season, we considered two measures: (1) the average
household exposure for the year after stove installation
as compared to the annual average before; and (2) the
average change in exposure immediately after stove
installation was done as compared to immediately before.
The former captures the season-specific effects of stoves
but can be biased by secular trends. The latter is less
biased, but more variable and more dependent on the
adjustment for seasonal and secular trends.
Health effects modeling
To estimate the effect on ALRI of having a new cook stove
installed in the home, while fully accounting for the salient
features of the stepped wedge trial design  and for
sources of variation at both the individual and village levels,
we used a generalized mixed effects model as summarized
in Hussey and Hughes . Let Yijt denote a positive ALRI
response for individual j = 1,?,N from village i = 1,?,I at
time point t = 1,?,T. Let pijt denote the risk of ALRI, that is
the expected value for Yijt. We assume pijt satisfies the
logistic random effects model:
where: ?0 is the overall baseline log odds of having
ALRI; ?i1eN 0; ?21 is the random effect for cluster i to
account for correlation among children from the same
village; ?2ijeN 0; ?22 is the random effect for child j in
cluster i to account for possible within-child-level
correlation; s(t, v) is a fixed, smooth function of time to
control for secular and seasonal trends; and ? is the fixed
cook stove intervention effect that is of primary
scientific interest. In this model, we will represent s(t, v) by
natural cubic splines with v degrees of freedom. A priori,
with two years of data, we chose v = 8 (4 degrees of
freedom per year) but will conduct sensitivity analyses to
determine whether the major findings are sensitive to this
choice over a range of reasonable choices v = 4 to 12 for
this smoothness constraint. The generalized linear mixed
model above will be estimated using the method of
maximum likelihood as implemented in the R package glmer
Robust variance estimates of the stove effect coefficient
will be calculated and compared to the model based values
as a sensitivity analysis to check on the assumed
correlation model within children and among children within
villages. If the robust variances are significantly larger than
their model-based counterparts, the former will be used
for testing and confidence interval calculations.
A similar approach will be used to estimate the
treatment effect on birthweight. While seasonality of
birthweight and other reproductive outcomes is present
in this population, it is not as dramatic as seen for
ALRI, nor is the clustering by sector as high .
Birthweight will be treated as both a continuous
variable and as dichotomous with low birthweight defined
as weights <2500 g.
The power of the study to test the null hypothesis that
the stove installment effect is zero (? = 0) for the ALRI
outcomes was done as follows. We adopted the design
represented in Figure 1 with 12 groups of sectors and
explain the sample size calculation using the notation
from the statistical plan in the previous section. We set
the true value the stove effect to take values between
? = ?0.1 to ?0.3 corresponding to 10 to 30% reductions in
the odds of ALRI attributable to installation of the clean
cook stove. To estimate the power, we specify the
parameters of the design and study population as via the following
(1) The number of eligible children per sector follows a
Poisson distribution with mean 35.
(2) The ALRI rate will be approximately 1.0 episodes
per child per year, conservatively lower than the
value 1.3 observed in previous studies in the same
(3) There will be 4 sectors in each of the 12 groups.
(4) Seasonality is represented by a sinusoid with
relative amplitude of 1.05 so that the peaks and
troughs have ALRI rates that are 1.05 times higher
or lower than the long-term average.
(5) There are two cases for secular trend: (5a) no
secular trend; (5b) a large trend that starts at time 1
with a 50% increase in the odds of ALRI and
decreases to 0 over 10 months.
(6) The random effects variances for village and child
are 0.025 and 0.10 respectively. These values imply
that villages can have ALRI rates that vary by ?30%
(2*?.025) across the population while individuals
within a village have rates that vary by ?60% (2*?.1).
To estimate power, we conducted a simulation study
in which we first generated a random data set given the
parameters described above, then estimated cook-stove
affect parameter using the generalized linear mixed
effects model specified in Equation (1) above. The
simulation was run 100 times for each situation and the
estimated power is reported in the table below with
standard error of the power less than 5%.
The degrees of freedom v used in specifying the time
function s(t; v) was allowed to vary between 0 (no secular
trend) to 8 (4 per year). When the data are generated
without a secular trend, all three values for v produce
consistent estimates of the cook stove effect. However, when in
the case where there is a sizeable trend, the v = 2,8 models
give consistent estimates, but the model that ignores the
trend produces strongly biases estimates. The simulation
study shows that the design has adequate poser to detect a
decrease of 20% or greater relative to baseline (Table 2).
Based on previous research in this study area, we
originally expected approximately 6000 live births in the
study area for these trials over 4 years. However fertility
declined significantly since that previous research was
conducted and a modified expectation was in the range
of 3000 live births. Approximately 1% died prior to our
being able to weigh them leaving approximately 2350
live births in phase one and 600 in phase two. The mean
birthweight in our last trial was 2700 grams with a
standard deviation of 437 grams . The intra-sector
correlation for birthweight was estimated to be 0.03357.
Assuming 80% power and a Type I error of 5% (2- sided),
the minimum detectable mean difference in birthweight
was approximately 57 g in phase 1 and 83 g in phase two.
These detectable differences in mean birthweight are in the
range of those reported for infants whose non-smoking
mothers are exposed to second hand tobacco smoke during
pregnancy and well below the mean differences between
women who do and do not smoke during pregnancy.
The rate of low birthweight (<2500 grams) was 29% in
our most recent trial in this area and the cluster related
design effect for the proportion born low birthweight
was 2.36. Assuming a Type I error of 5% (2-sided), a
20% treatment effect, and sample size of 1175 enrolled
live births before stove installation and an equivalent
number after installation, the power was >80% for phase
one but only 47% for phase two.
These trials were reviewed and approved by the
Institutional Review Boards at the Johns Hopkins Bloomberg
School of Public Health (USA) and the Institute of
Medicine at Tribhuvan University (Nepal) and registered at
Clinicaltrials.gov (NCT 00786877, Nov. 5, 2008). An
independent Data and Safety Monitoring Board (DSMB) was
formed and met once prior to the start of the study, once
approximately mid-way through the first trial, and is
scheduled to meet again in early 2015 to review the results
of both trials. The DSMB did not adopt any formal
stopping rules or guidelines for efficacy, safety, or futility.
These trials were designed to address an important public
health risk that is especially prevalent in low- and
middleincome countries where large proportions of the population
use open burning of biomass as their primary household
fuel. Phase two was redesigned during phase one when it
was clear that reductions in PM concentrations were not as
large as anticipated and to provide another point on the
dose response curve that was not estimable using
commercially available low-cost, biomass stoves. The results of
these trials will provide important new information on
whether such interventions can impact the most important
health outcomes associated with high PM exposure in
households and whether scaling programs using currently
available technologies is likely to impact health status in
these high risk populations. We anticipate results from both
phases will be reported in late 2014 or early 2015.
JT, JK, SZ, and LM contributed to the design of the study and helped to draft
the manuscript. SK, SL, LS, LM, JT, PB WC and JK supervised the conduct of
the study in the field. JK and SZ served as study statisticians. PB supervised
the environmental sampling protocols. WC developed and supervised the
pulmonary function testing protocols. JT conceived of the study and secured
funding for the project. All authors read and offered revisions to initial drafts
of the manuscript and approved the final version.
Financial support was received from the National Institute of Environmental
Health Sciences, United States National Institutes of Health (ES015558), the
Thrasher Research Fund (02830?4), and the Global Alliance for Clean
Cookstoves of the United Nations Foundation (UNF-12-380).
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