Validation of a Low-Cost, Point-of-Care Bilirubin Measurement to Diagnose Neonatal Jaundice and Monitor Phototherapy in Hospitals in Sub-Saharan Africa
Conditions: Hyperbilirubinemia, Neonatal, Jaundice, Neonatal
Sponsor: William Marsh Rice University

 
 
 Validation of a Low-Cost, Point-of-Care Bilirubin Measurement to Diagnose Neonatal Jaundice and Monitor Phototherapy in 
Hospitals in sub-Saharan Africa Version 4 
October 31, 2018 
 
 
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A. Title 
Validation of a Low-Cost, Point-of-Care Bilirubin Measurement to Diagnose Neonatal Jaundice 
and Monitor Phototherapy in Hospitals in sub-Saharan Africa 
 
B. Investigators  
 
Principal Investigator:  
Dr. Queen Dube, College of Medicine, Blantyre, Malawi 
Dr. Msandeni Chiume, Head of Department, Department of 
Paediatrics, Kamuzu Central Hospital, Lilongwe, Malawi 
 
Co-Investigators: 
Rebecca Richards-Kortum, PhD, Dept. of Bioengineering, Rice 
University, Houston, TX USA 
 
Maria Oden, PhD, Dept. of Bioengineering, Rice University, 
Houston, TX USA 
 
Other Investigators: 
Jessica Anderson 
 
Rice 360o: Institute for Global Health, Rice University, Houston TX 
 
 
Alyssa Shapiro 
 
PhD Student in Bioengineering, Rice University, Houston TX 
 
 
Prince Mtenthaonga 
 
Rice 360o: Institute for Global Health 
 
 
Meaghan Bond 
 
PhD, Dept. of Bioengineering, Rice University, Houston, TX, USA 
 
 
Investigators’ CVs: 
 
(see Appendix 4) 
 
 
 
 

 
 
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C. Institutions under whose umbrella the research project will be conducted 
 
[i] University of Malawi College of Medicine, Blantyre, Malawi 
[ii] Rice University, Houston, TX, USA 
 
D. Executive summary 
 
Type of Study: 
This is a prospective study, the goal of which is to validate the accuracy of the BiliSpec device in 
measuring bilirubin levels in neonates relative to the laboratory spectrophotometric 
bilirubinometer and transcutaneous bilirubinometer measurements. 
 
Problem: 
Neonatal jaundice affects approximately 24 million newborns each year. If left untreated, severe 
jaundice can result in brain damage (kernicterus); while kernicterus is preventable, it is not 
treatable (1). Severe jaundice may not present until several days after birth, thus early monitoring 
of serum bilirubin levels is critical, particularly in premature babies who are more likely to suffer 
from jaundice and who are at greater risk of death and disability due to jaundice.  In high-resource 
settings, tools to measure serum bilirubin levels are readily available and have made neurological 
damage from jaundice exceedingly rare; these tools have proven too expensive and complex to 
implement widely in under-resourced settings (2, 3). As a result, jaundice is diagnosed clinically 
in most low-resource settings using visual inspection of scleral yellowing; results are subjective 
and poor accuracy has been reported.   
 
Recently, a team of researchers at Rice University in partnership with clinicians at Queen 
Elizabeth Central Hospital created BiliSpec, a low-cost battery-powered reader designed to 
immediately quantify serum bilirubin levels from a small drop of whole blood applied to a lateral 
flow strip.  The simple and affordable BiliSpec system offers a faster and more cost-effective 
means to detect neonatal jaundice in under-resourced clinics and determine when phototherapy 
is needed.  In 2017, a small 100 patient pilot study was performed at Queen Elizabeth Central 
Hospital in Blantyre, Malawi (Appendix 3).  Results showed BiliSpec has comparable accuracy to 
laboratory standard and outperforms transcutaneous measurement of bilirubin (4). 
 
Objectives: 
The purpose of this study is to validate the accuracy of BiliSpec in comparison to laboratory 
standard spectrophotometric and transcutaneous measurement of bilirubin levels in neonates at 
two central hospitals: Queen Elizabeth Central Hospital in Blantyre, Malawi and Kamuzu Central 
Hospital in Lilongwe, Malawi.  
 
Methodology: 
We will recruit up to 500 neonates at QECH and KCH each, for a total of up to 1000 neonates, at 
risk for jaundice based on clinical signs and symptoms or undergoing phototherapy for treatment 

 
 
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of 
jaundice. 
BiliSpec, 
laboratory 
standard 
spectrophotometric 
measurement, 
and 
transcutaneous measurement will be used to analyze bilirubin levels in both male and female 
babies with no preference towards a specific gender. Informed consent will be requested from 
the parents of all eligible babies on the ward for this study (Consent Forms in Appendix 1). If the 
guardian does not consent, the patient's bilirubin levels will be assessed using the standard of 
care on the ward.   All eligible participants with consenting guardians will have their blood drawn 
via heel stick and measured with the three methods: BiliSpec, a commercially available 
spectrophotometric bilirubinometer according to standard laboratory practices, and a 
commercially 
available 
transcutaneous 
bilirubinometer. 
BiliSpec, 
the 
laboratory 
spectrophotometric bilirubinometer (Reichert UNISTAT® Bilirubinometer), the transcutaneous 
bilirubinometer, and accompanying equipment will be provided by the Rice study team. The Data 
Collection Form is found in the Appendix 2.) 
 
Expected Findings: 
We expect to find BiliSpec accurate and easy to use. 
 
Dissemination: 
The results of this study will be made available to the Ministry of Health, COMREC, the College of 
Medicine Library, the Department of Paediatrics at QECH and KCH, and other partners working 
in neonatal and child health. A copy of the final report and any published papers or abstracts will 
be submitted to The Health Sciences Research Committee and the University Research and 
Publication Committee (URPC) through the COMREC Secretariat. Findings will be published in 
academic journals and conference proceedings in an effort to disseminate results to potential 
end-users. The research findings of this study will be critical in the evaluation of future 
interventions. 
 
 
 

 
 
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E. Literature Review and Background Information 
Neonatal jaundice accounts for 114,000 infant deaths globally, with 85,500 of those deaths 
occurring in sub-Saharan Africa or South Asia.  A further 180,000 neonates suffer permanent 
neurological damage every year from jaundice.  Jaundice occurs when excess bilirubin builds up 
in the blood, and it is an especially common condition in premature babies, who lack sufficient 
liver function to excrete the excess bilirubin produced when fetal hemoglobin is broken down. 
Preterm babies also have a more permeable blood-brain barrier, which increases their risk of 
kernicterus by allowing unconjugated bilirubin 
easier access to brain tissue. Neonatal sepsis and 
Rhesus incompatibility also increase the risk of 
jaundice.  Fortunately, the complications of 
neonatal jaundice can be prevented through the 
use of phototherapy which has been highly 
successful in well-resourced hospitals (5). Bilirubin 
absorbs blue light, and phototherapy using blue 
light can be used to photodecompose bilirubin to 
a form that can be excreted. Laboratory 
determination of serum bilirubin concentration is 
vital in managing babies who are jaundiced. 
However, current methods of measuring total 
bilirubin are not feasible for district and health 
center laboratories.  The standard for many 
hospitals is the diazo method for determining 
bilirubin levels in the patients.  The diazo method 
requires many reagents, highly trained personnel, 
and a fully equipped laboratory to perform; all of 
which make implementation at the district level 
infeasible.  Spectrophotometric determination of bilirubin requires no reagents, but requires 
both a centrifuge and a calibrated spectrophotometer, tools that cost thousands of dollars and 
are often not available in district hospital or health center laboratories. Transcutaneous 
measurement of bilirubin requires hardware and calibration consumables that are not 
affordable in many low-resource settings; accuracy of these devices is worse for neonates with 
dark skin and decreases during phototherapy (3, 6, 7). 
 
In response to this need for early bilirubin monitoring, researchers at Rice University created 
BiliSpec, a low-cost battery-powered reader designed to immediately quantify serum bilirubin 
levels from a small drop of whole blood applied to a lateral flow strip. BiliSpec has two 
components: (1) an inexpensive, disposable lateral-flow strip on which the clinician spots a drop 
of whole blood from a heel prick and (2) a battery powered reader which measures the light 
transmitted through the serum on the detection strip and displays a digital report of the bilirubin 
concentration (Figure 1).  
 
 
Figure 1. (a) Photograph of disposable lateral 
flow cards for blood collection. (b) BiliSpec 
Reader for measuring bilirubin 

 
 
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BiliSpec has been evaluated in the laboratory and in a small pilot study (Appendix 3) at QECH to 
test efficacy and usability (4).  The BiliSpec lateral flow strip is capable of handling a range of 
blood volume to account for variations in volume from heel sticks.  Full separation of plasma on 
the lateral flow strip takes approximately 1-2 minutes.  In this time, the lateral flow device is 
sealed by the user after application of blood to prevent contamination or leaking. Measurement 
of bilirubin using BiliSpec during the pilot study yielded an average absolute difference of 0.8 
mg/dL (95% CI of −1.7–2.2 mg/dL) as compared to the laboratory spectrophotometric 
measurement. The lateral flow strip costs less than $0.05 and we estimate the reader can be built 
for less $200 at low volume. We are optimizing BiliSpec to achieve a target accuracy of ±20% or 
0.4mg/dL, whichever is greater (United States CLIA Standard) with a dynamic range up to 35 
mg/dL, consistent with performance of bilirubin measurement techniques used in high-resource 
settings (3).  During the pilot study, 95% of samples were within CLIA guidelines, and simple 
changes are expected to improve performance. One limitation of the pilot study was the limited 
range of bilirubin concentrations tested; during the validation study, we will increase the number 
of neonates tested to increase the number of samples at high bilirubin concentrations. We 
believe that rapid adoption of this technology is possible since BiliSpec is affordable and simple 
to use at the bedside. 
 
BiliSpec provides an important tool to monitor the efficacy and progress of phototherapy, 
ensuring appropriate treatment dosage and duration.  Used together, BiliSpec and blue light 
phototherapy have the potential to reduce the morbidity and mortality associated with neonatal 
jaundice.   
 
F. Rationale/Justification for the research project 
 
Neonatal jaundice affects approximately 24 million newborns each year. Unfortunately, bilirubin 
monitoring systems used in the developed world are too expensive for low-resource settings; 
instead, nurses and doctors often must visually monitor babies to watch for possible 
development of jaundice based on yellowing of the sclera.  This method has been shown to lack 
sufficient accuracy. Also, in this geographical setting, there are few pediatricians, and nurses 
often staff many babies at a time. The poor predictive ability of visual diagnosis and the high ratio 
of babies to nurses and doctors means that cases of jaundice are often not identified early 
enough, resulting in brain damage or death. This challenge is prevalent in district hospitals 
throughout Malawi.  A more consistent, low-cost method of jaundice diagnosis and monitoring 
is needed. Based on the results of the pilot study, BiliSpec may meet this goal. It is now necessary 
to validate performance of the improved BiliSpec device in a larger population of neonates with 
a larger range of bilirubin concentrations. 
 
G. Objectives of the study 
 
[i] Broad  

 
 
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The objective of this work is to validate the accuracy and usability of a new point-of-care device 
called BiliSpec to measure bilirubin concentration in neonates in low-resource settings. 
 
[ii] Specific 
The specific aim of this study is to determine the accuracy of the BiliSpec device relative to a 
laboratory spectrophotometric bilirubinometer and transcutaneous bilirubinometer in the 
neonatal wards of Queen Elizabeth Central Hospital (QECH) and Kamuzu Central Hospital (KCH). 
 
H. Methodology  
 
[i] Study Type 
 
This is a prospective study, the goal of which is to validate the accuracy of the BiliSpec device in 
measuring bilirubin levels in neonates relative to the laboratory spectrophotometric 
bilirubinometer and transcutaneous bilirubinometer measurements. 
 
[ii] Place of Study  
The clinical study will take place at QECH in Blantyre, Malawi and KCH in Lilongwe, Malawi. 
Patients will be recruited from the neonatal wards at QECH and KCH who are deemed to be at 
risk for jaundice or are undergoing blue light phototherapy to treat jaundice.  
 
[iii] Study Population  
 
Participants will be identified using the eligibility criteria stipulated below.  
 
Inclusion Criteria: 
1. The patient is currently being treated at QECH or KCH in the neonatal ward. 
2. The patient is less than 28 days old (neonate). 
3. The patient is deemed to be at risk for jaundice or the patient is undergoing blue light 
phototherapy for treatment of jaundice. 
4. The patient’s parent or guardian has provided informed consent for their child to participate. 
 
Exclusion Criteria: 
1. Parent or guardian is unable or unwilling to provide informed consent. 
2. The patient is unable to receive a blood draw/heel stick as determined by their clinician.  
 
Families of neonates meeting eligibility criteria will be approached for consent to participate in 
the study by the investigator.  If consent is not granted the patient will be treated with standard 
of care and will not participate in the study.  
 
[iv] Study Period 
 

 
 
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See the below graphical representation and table of our anticipated timeline. 
 
 
 
Task 
Start Date (month) 
Duration (Months) 
End Date (month) 
Setup in QECH 
0 
0.5 
0.5 
Acquire up to 500 Samples from QECH 
0.5 
6 
6.5 
Setup in KCH 
2 
0.5 
2.5 
Acquire up to 500 Samples from KCH 
2.5 
6 
8.5 
Data Analysis 
6.5 
2.75 
9.25 
Compilation of Results 
9.25 
0.75 
10 
 
 
[v] Sample Size 
 
We will recruit a total of up to 1000 neonates at risk for jaundice based on clinical signs and 
symptoms.  
 
During our pilot study, we evaluated 100 participants and collected 147 samples total.  However 
only 7 samples collected were over 20 mg/dL.  In addition to confirming the accuracy of BiliSpec 
in this validation study, we also want to ensure we have enough samples of clinically high bilirubin 
concentrations (>20mg/dL) to ensure our device functions properly over our intended dynamic 
range (0-35 mg/dL).  To accomplish this, we will collect data from up to 500 participants at each 
location. Previous data have determined that the standard deviation of the difference between 
the Bilirubinometer and our device is 1.0 mg/dL.  In order to detect a statistical difference 
between the Bilirubinometer and our device of 0.8 mg/dL, our target accuracy, at a statistical 
power of 90% and α of 0.05 using a paired test, we need 34 samples (8).  Since only 7 samples 
out of 100 participants during our pilot study were over 20 mg/dL, we will need up to 500 
0
1
2
3
4
5
6
7
8
9
10
Setup in QECH
Acquire up to 500 Samples from QECH
Setup in KCH
Acquire up to 500 Samples from KCH
Data Analysis
Compilation of Results
Duration (Months)
BiliSpec Validation Timeline

 
 
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participants at each location to acquire the statistically significant number of samples over 20 
mg/dL.  The larger sample sizes will also us to conclusively validate the accuracy of the BiliSpec 
system over the full dynamic range of clinically relevant bilirubin concentrations. 
 
In summary, 300 samples at each location are needed to show that the accuracy of BiliSpec is 
within 0.2 mg/dL of the laboratory standard spectrophotometric measurement (95% power, 
assuming 0.98 standard deviation of difference based on the pilot study); we have increased the 
number to up to 500 patients per location (1000 total) to increase the chances of recruiting 
patients over the full clinically encountered range of bilirubin concentrations, particularly at high 
concentrations. 
 
This study will enroll up to 500 neonates at Queen Elizabeth Central Hospital and 500 neonates 
at Kamuzu Central Hospital who are deemed to be at risk for jaundice or who are receiving blue 
light phototherapy treatment for jaundice. We will compare the detection of bilirubin levels by 
BiliSpec to bilirubin monitoring with laboratory spectrophotometric bilirubinometry and 
transcutaneous bilirubinometry, the standard of care in developed settings.   
 
[vi] Data Collection 
 
Training 
1. Prior to the start of the study, all study nurses/clinicians will receive training from a trained 
study engineer on BiliSpec and transcutaneous bilirubinometer use. Each member will pass a 
standard evaluation in order to operate the devices.  
2. The local researchers will be available on site or by phone, email, and site visits to respond to 
any questions and/or concerns. The US based researchers will be in frequent contact with the 
local team. 
 
Informed Consent 
 
The investigator will provide details of the study to the guardians of all eligible subjects and will 
answer any questions. Guardians who consent to participation will be asked to sign a form 
documenting their consent (Consent Forms in Appendix 1) prior to the start of any study 
procedures. 
 
Documentation of the consent process includes the following elements: 
 
• Date of consent; 
 
• Topics discussed with the subject’s guardian (e.g. risk, benefits, etc.); and 
 
• Confirmation that the consent was reviewed, that the guardian’s questions were answered, 
and that a signed copy of the consent was provided to the subject’s guardian. 

 
 
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The consent form will be updated or revised whenever important new safety information is 
available, whenever the protocol is amended, or whenever any new information becomes 
available that may affect participation in the study. 
 
Enrollment  
 
Enrollment will be after fully informed and written consent from the parent or guardian. 
Guardians will not be required in any way to have their child participate. If they choose not to 
participate, the care of their child will not be jeopardized.  A parent will be free to withdraw 
their child from participating at any time, without explanation and such a decision will not 
affect standard of care.  Each participant will be compensated 10USD (in local currency) per 
visit.  
 
A participant identification number will be assigned. This number will be used for identification 
purposes throughout the study. 
 
Bilirubin Testing of Neonates 
 
The trained study nurse will assess the subject for clinical complications before performing the 
necessary heel prick blood draw.  
 
 A transcutaneous measurement of bilirubin and a heel stick will be performed on the neonate 
by a trained study nurse or clinician.  
 One drop of blood will be collected on the sample card and immediately used for analysis. 
BiliSpec will be operated by a trained nurse or trained research assistant. 
 Another drop of blood, collected in a capillary tube, will be centrifuged and then measured 
using the laboratory spectrophotometric bilirubinometer (Reichert UNISTAT® 
Bilirubinometer 1310310C).  The spectrophotometric bilirubinometer will be operated by 
trained research assistants from the Rice department of bioengineering and the University 
of Malawi.  Bilirubin concentration values measured by the gold standard laboratory 
bilirubinometer will be used to guide diagnosis. 
 
Measurements will be made at multiple time points as indicated clinically.  
 
Data will be collected on paper forms (Appendix 2) as is consistent with current clinical practice. 
Clinical and/or research personnel will record information, excluding personal identifiers, on a 
standardized patient monitoring form. After the patient’s participation is completed, a research 
assistant will collect and scan the form. 
 
The following section details the variables that will be measured or calculated in the pilot study. 
 

 
 
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Variables/Time Points of Interest:  
 
1. Baseline demographic and relevant medical information 
a. Date of Study 
b. Time of test 
c. Date of Birth 
d. Sex 
e. Weight 
f. Other comorbidities 
g. Start time of phototherapy (if applicable) 
h. Duration of phototherapy at time of measurement (if applicable) 
 
2. Accuracy 
a. Bilirubin levels as measured by BiliSpec using blood drawn from a heel stick. 
b. Bilirubin levels as measured by laboratory spectrophotometric determination 
which will be used as the gold standard for determining bilirubin concentration 
and validating the BiliSpec system. 
c. Bilirubin levels as determined by transcutaneous measurement. 
 
[vii] Data Analysis 
 
We will determine the neonatal bilirubin concentration in mg/dL using the BiliSpec device, the 
gold standard laboratory spectrophotometric bilirubinometer, and the transcutaneous 
bilirubinometer described in the testing procedure.  Measurements of bilirubin levels will be 
compared.  All data will be recorded using the data collection form (Appendix 2).  We will also 
analyze the usability and robustness of BiliSpec with regards to usability and device function by 
maintaining a log of any user error in using the device and a log of any observed device 
malfunctions. Data will also be collected on the effectiveness of BiliSpec to monitor neonates 
undergoing phototherapy.  
 
Personal identifiers will be removed and confidentiality of the subjects will be strictly preserved. 
The data will be kept on a secure server accessible only to the study personnel.  
 
The research team from Rice University, QECH, and KCH will be responsible for all data analysis. 
Data will be entered and stored in a database that will export to a CSV file.  We plan to analyze 
data using Excel and Matlab and associated statistics packages.  
 
[viii] Results Presentation 
 
We will validate the accuracy and usability of Bilispec in comparison to laboratory 
spectrophotometric measurement and transcutaneous measurement during use in a low-
resource hospital. A research manuscript will be prepared describing the device in detail and the 

 
 
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results of the study.  
 
[ix] Dissemination of Results 
 
The results of this study will be made available to the Ministry of Health, COMREC, the College of 
Medicine Library, the Department of Paediatrics at QECH and KCH, and other partners working 
in neonatal and child health. A copy of the final report and any published papers or abstracts will 
be submitted to The Health Sciences Research Committee and the University Research and 
Publication Committee (URPC) through the COMREC Secretariat. Findings will be published in 
academic journals and conference proceedings in an effort to disseminate results to potential 
end-users. The research findings of this study will be critical in the evaluation of future 
interventions. 
 
I. Ethical considerations 
 
The study protocol will be approved by COMREC and the Institutional Review Board at Rice 
University prior to initiation of the study. All investigators will be required to take the online 
Protecting Human Research Participants course provided by the NIH Office of Extramural 
Research.  Any loss of patient data will be reported to the University of Malawi COMREC through 
the PI and to the Institutional Review Board at Rice University. Information will be de-identified 
to ensure patient confidentiality and data integrity.   
 
All studies involving human subjects will be conducted in a manner that will minimize the risk to 
the individual, utilize all patient materials for scientifically meaningful purposes, and protect 
individual rights to confidentiality. The associated clinical protocols will be approved by COMREC 
in Malawi and by the Institutional Review Board of Rice University, Houston, TX. All researchers 
will conform to the standards set forth by the National Institutes of Health regarding experiments 
involving human subjects.  
 
The co-investigators will take the following steps to protect the participant's identities during this 
study: (1) Each participant will be assigned a number; (2) The co-investigators will record any data 
collected during the study with this number and not by name; (3) Any original data files, as well 
as the informed consent forms, will be stored in a locked cabinet in the PI’s office space. All data 
will be recorded in a password-protected database. Only the investigators listed in this study will 
have access to the data, and if the data is published at any time in the future, it will be reported 
collectively with no reference to the subjects' identities. 
 
 
J. Possible Constraints 
 
The risks and discomfort associated with participation in this study are no greater than those 
ordinarily encountered in daily life or during a routine pediatric checkup. The BiliSpec device is 

 
 
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exempt from the US Investigational Device Exemption (IDE) requirements as it meets the 
exemptions outlined in 21 CFR §812.2(c)(3).  
 
Potential Benefits and Compensation of the Proposed Research to Human Subjects and Others:   
Neonates and infants at risk for jaundice may benefit from participating in this study as 
alternative forms of accurate monitoring may not be readily available. This study may benefit 
neonates in the future as BiliSpec may enable cost-effective, accurate detection bilirubin levels 
in neonates at risk for jaundice. In addition, each participant will be compensated 10USD (in local 
currency) per visit. 
 
K. Study Requirements 
 
The study will require the following:  
 
Personnel: 
Dr. Queen Dube, College of Medicine, Blantyre, Malawi: Principal Investigator 
Dr. Msandeni Chiume, Head of Department, Department of Paediatrics, Kamuzu Central Hospital, 
Lilongwe, Malawi: Principal Investigator 
Technical Engineer: An engineer from Rice University will travel to Blantyre (supported by Rice 
University). 
Study Nurse: Malawian nurse supported by Rice University to obtain consent and operate 
BiliSpec. 
 
Training: Prior to the start of the study, all study nurses/clinicians will receive training on BiliSpec 
and the transcutaneous bilirubinometer use by the Rice research team. Each member will pass a 
standard evaluation in order to operate the device. The Rice researcher and Dr. Dube at QECH or 
Dr. Chiume at KCH will be available on site or by phone, email, and site visits to respond to any 
questions and/or concerns. The US based Investigators will be in frequent contact with the local 
team. 
 
Paper: The Rice researcher will bring all forms from Houston, Texas to Blantyre, Malawi and 
Lilongwe, Malawi.  
 
No transport, reagents, drugs or additional space will be required for the study.  
 
L. Budget and budget justification 
 
Salary Description 
Cost (MK) 
Cost (USD) 
Quantity 
Cost (MK) 
Cost (USD) 
Paediatrician Salary, QECH 
7,200,000 
$10,000 
1 
7,200,000 
$10,000 
Paediatrician Salary, KCH 
7,200,000 
$10,000 
1 
7,200,000 
$10,000 
Clinician Salary 
4,320,000 
$6,000 
1 
4,320,000 
$6,000 
Nurse Technician Salary 
3,024,000 
$4,200 
1 
3,024,000 
$4,200 

 
 
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Supplies 
 
 
 
 
 
Gloves 
 
3,500 
$4.86 
10 
35,000 
$30 
Cotton Roll 
9,500 
$13.19 
5 
47,500 
$80 
Lancets 
3,800 
$5.28 
20 
76,000 
$32 
Spirit Swabs 
2,200 
$3.06 
20 
44,000 
$20 
Plaster 
1,900 
$2.64 
50 
95,000 
$16 
Participant Compensation 
 
 
 
 
 
Participant Compensation 
7,200 
$10 
1000 
7,200,000 
$10,000 
Direct Costs Subtotal  
 
 
 
29,241,500 
$40,378  
10% F&A Costs 
 
 
 
2,924,150 
$4,038 
COMREC Fee 
 
 
 
108,000 
$150 
Total 
 
 
 
32,273,650 
$44,566 
 
The BiliSpec devices, laboratory spectrophotometric bilirubinometry devices, transcutaneous 
bilirubinometery devices, and paper forms (consents and monitoring forms) will be provided by 
Rice University. We have received funding from USAID’s Saving Lives at Birth program to support 
this study which provides for a subcontract to COM that includes the 10% F&A costs. 
 
 
N. References 
 
1. V. K. Bhutani, A. Zipursky, H. Blencowe, R. Khanna, M. Sgro, F. Ebbesen, J. Bell, R. Mori, T. M. 
Slusher, N. Fahmy, V. K. Paul, L. Du, A. a. Okolo, M.-F. de Almeida, B. O. Olusanya, P. Kumar, S. 
Cousens, J. E. Lawn, Neonatal hyperbilirubinemia and Rhesus disease of the newborn: incidence 
and impairment estimates for 2010 at regional and global levels, Pediatr. Res. 74, 86–100 
(2013). 
2. W. H. O. March of Dimes, The Partnership for Maternal Newborn & Child Health, Save the 
Children, Born Too Soon: The Global Action Report on Preterm Birth., World Heal. Organ. , 1–
126 (2012). 
3. K. Grohmann, M. Roser, B. Rolinski, I. Kadow, C. Müller, A. Goerlach-Graw, M. Nauck, H. 
Küster, Bilirubin measurement for neonates: comparison of 9 frequently used methods., 
Pediatrics 117, 1174–1183 (2006). 
4. P. A. Keahey, M. L. Simeral, K. J. Schroder, M. M. Bond, P. J. Mtenthaonnga, R. H. Miros, Q. 
Dube, R. R. Richards-Kortum, Point-of-care device to diagnose and monitor neonatal jaundice in 
low-resource settings, Proc. Natl. Acad. Sci. , 201714020 (2017). 
5. J. V. Colindres, C. Rountree, M. A. Destarac, Y. Cui, M. P. Valdez, M. H. Castellanos, Y. Mirabal, 
G. Spiegel, R. Richards-kortum, M. Oden, Prospective randomized controlled study comparing 
low-cost LED and conventional phototherapy for treatment of neonatal hyperbilirubinemia, J. 
Trop. Pediatr. 58, 178–183 (2012). 
6. K. L. Tan, F. Dong, Transcutaneous bilirubinometry during and after phototherapy., Acta 
Paediatr. 92, 327–331 (2003). 

 
 
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7. M. J. Maisels, Treatment of jaundice in low birthweight infants, Arch. Dis. Child. - Fetal 
Neonatal Ed. 88, 459F–463 (2003). 
8. R. B. Dell, S. Holleran, R. Ramakrishnan, Sample Size Determination, ILAR J. 43, 207–213 
(2002). 
 
 
 
 

 
 
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Appendix 2 – Data Collection Form 
 
Protocol Title: Validation of a Low-Cost, Point-of-Care Bilirubin Measurement to Diagnose 
Neonatal Jaundice and Monitor Phototherapy in Hospitals in sub-Saharan Africa. 
 
**Record subject # on consent** 
 
Subject #_____________________   
Date___________________ 
COMREC Protocol #____________                         Rice Protocol # ______________ 
Protocol Expiration   
__ 
              
Protocol Expiration  ________ _ 
Patient #                 of 1000 Max Accrual       
Patient # 
       of 1000 Max Accrual 
 
NO CLINICAL WORK SHOULD PROCEED WITHOUT FIRST COMPLETING THE 
ENTIRE SECTION ABOVE!!! 
 
DOB: ______ Gender:   M    F 
Consent signed:  
YES          NO         
Birth Weight (kg): _________   
 
Phototherapy Start date (dd/mm/yy): __________________ 
 
Bilirubin results: 
Date 
(d/m/y) 
Time 
(24hr) 
BiliSpec 
(mg/dL) 
Transcu-
taneous 
(mg/dL) 
Bilirubin-
ometer 
(mg/dL) 
Phthrpy 
(y/n) 
Notes 
1 
 
 
 
 
 
 
 
2 
 
 
 
 
 
 
 
3 
 
 
 
 
 
 
 
4 
 
 
 
 
 
 
 
5 
 
 
 
 
 
 
 
6 
 
 
 
 
 
 
 
7 
 
 
 
 
 
 
 
8 
 
 
 
 
 
 
 
9 
 
 
 
 
 
 
 
10 
 
 
 
 
 
 
 
 
Comorbidities: _________________________________________________________________ 
 
Codes for notes (indicate in notes above if occurs): 
1. Difficult blood collection 
2. Collection pad not visibly filled 
3. Visible lysis on strip 
4. Visible lysis in laboratory standard sample 
5. Device Error: ___________________________ Sample#(s):______________ 

 
 
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Other Patient Notes: ____________________________________________________