Evaluation of the Catalyzing Pediatric TB Innovations Project: A Pre- and Post-Implementation Assessment Across Ten Countries
Conditions: Tuberculosis, Pediatric
Sponsor: Elizabeth Glaser Pediatric AIDS Foundation

 
 
 
       
 
 
 
Project title: Evaluation of the Catalyzing Pediatric TB Innovation Project: A Pre- and Post-
Implementation Assessment (TIPPI) across ten countries 
 
Protocol version 3. 3 dated 8th March 2021 
 
 
Principal Investigator(s):  
 
Martina Casenghi, PhD 
Technical Director 
Elizabeth Glaser Pediatric AIDS Foundation 
WCC Center, 150, Route de Ferney, 1 Route des Morillons 
PO Box 2100, Bureaux Jura 137 - 143, CH-1211 Geneva 2, Switzerland 
mcasenghi@pedaids.org 
+39 329 141 1374 
 
Jean-François Lemaire, MSc 
Diagnostics & Systems Lead 
Elizabeth Glaser Pediatric AIDS Foundation  
WCC Center, 150, Route de Ferney, 1 Route des Morillons 
PO Box 2100, Bureaux Jura 137-143, CH-1211 Geneva 2, 
Switzerland 
Jlemaire@pedaids.org 
+41 22 791 6457  
 
Co-investigators: 
 
 
Mikhael de Souza 
Project Director 
Elizabeth Glaser Pediatric AIDS Foundation  
WCC Center, 150, Route de Ferney, 1 Route des Morillons 
PO Box 2100, Bureaux Jura 137 - 143, CH-1211 Geneva 2, Switzerland 
mdesouza@pedaids.org 
+41 76 376 41 77  
 
Shirin Kakayeva, MPP 
Senior Strategic Information and Evaluation Officer 
Elizabeth Glaser Pediatric AIDS Foundation 
1140 Connecticut Ave., NW, Suite 200 
Washington, DC, USA 
skakayeva@pedaids.org  
+1 (202) 280-1640 

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Rhoderick Machekano, PhD, MPH 
Senior Biostatistician 
Elizabeth Glaser Pediatric AIDS Foundation  
1140 Connecticut Ave., NW, Suite 200 
Washington, DC, USA 
rmachekano@pedaids.org  
+1 (202) 470-6654 
 
Boris Tchounga, PhD 
Associate Director of Public Health Evaluation – Cameroon 
Elizabeth Glaser Pediatric AIDS Foundation  
 
Patricia Fassinou Ekouévi, MD 
Country Implementation Manager – Cote D’Ivoire 
Elizabeth Glaser Pediatric AIDS Foundation 
 
Vicky Ilunga, MD 
Country Implementation Manager – DRC 
Elizabeth Glaser Pediatric AIDS Foundation  
 
Phelix Mboya, MD 
Country Implementation Manager – Kenya 
Elizabeth Glaser Pediatric AIDS Foundation  
 
Samson Lanje, MD 
Country Implementation Manager – Lesotho 
Elizabeth Glaser Pediatric AIDS Foundation  
 
Sathish Kumar, MD 
Country Implementation Manager – India 
Solidarity and Action Against The HIV Infection in India  
 
Yusuf Bhamu, MD 
Country Implementation Manager – Malawi 
Elizabeth Glaser Pediatric AIDS Foundation  
 
Leo Haule, MD 
Country Technical Advisor for TB – Tanzania 
Elizabeth Glaser Pediatric AIDS Foundation  
 
Mary Namubiru, MDCountry Implementation Manager – Uganda 
Elizabeth Glaser Pediatric AIDS Foundation  
 
Tichaona Nyamundaya, MD 
Country Implementation Manager – Zimbabwe 

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Elizabeth Glaser Pediatric AIDS Foundation  
 
 
Project Locations:   
 
Cameroon, Cote d’Ivoire, Democratic Republic of the Congo, Kenya, Lesotho, India, Malawi, 
Tanzania, Uganda, Zimbabwe 
 
Proposed Project Dates:           
EGPAF Project: October 1, 2017-September 30, 2021 
Data collection activities: October 2017-September 2021  
 
 
 
 
 
 
 
 
 

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Table of Contents 
ACRONYMS .................................................................................................................................. 7 
I. 
Rationale & Background Information.................................................................................. 8 
II. 
Project Goals and Objectives ............................................................................................... 9 
A. 
Goal .................................................................................................................................. 9 
B. 
Objectives ....................................................................................................................... 10 
1. 
Primary Objective ....................................................................................................... 10 
2. Secondary Objectives........................................................................................................ 10 
III. 
Expected Outcomes of the Study ....................................................................................... 11 
IV. 
Study Design ...................................................................................................................... 11 
A. 
Methodology .................................................................................................................. 11 
1. 
Description of the CaP TB Project ............................................................................. 11 
2. 
Country-Level Activities ............................................................................................ 13 
3. 
Duration of the Project ............................................................................................... 14 
V. 
Description of Project Evaluation ...................................................................................... 14 
A. 
Pre-intervention Evaluation- Baseline assessment ......................................................... 15 
VI. 
Evaluation Design and Methods ........................................................................................ 16 
A. 
Table 1. Indicator Outcomes and Data Sources ............................................................. 18 
B. 
Table 2. Additional Indicator Outcomes and Data Sources ........................................... 20 
VII. 
Use of data generated through CaP TB program evaluation to perfom secondary analysis      
                                                                                                                                                        21 
A. 
Use of CaP TB Program evaluation data to inform cost-effectiveness analysis ............ 21 
B. 
Use of TIPPI data to assess the impact of COVID 19-related measures on accessibility 
and delivery of pediatric TB services ....................................................................................... 22 
VIII. Data Gathering Activities................................................................................................... 23 
A. 
Table 3. Study Data Gathering Activities During Pre-intervention and CaP TB 
Intervention Phases ................................................................................................................... 23 
IX. 
Data Management and Statistical Analysis........................................................................ 24 
A. 
Quality Assurance .......................................................................................................... 24 
X. 
Privacy and Confidentiality ............................................................................................... 25 
XI. 
Ethical Considerations ....................................................................................................... 27 
A. 
IRB Review .................................................................................................................... 27 
B. 
Ethics Training ............................................................................................................... 27 

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C. 
Conflict of Interest.......................................................................................................... 27 
D. 
Informed Consent ........................................................................................................... 27 
E. 
Risk and Benefits to Participants.................................................................................... 28 
F. Follow-Up .......................................................................................................................... 28 
XII. 
Dissemination of Results and Publication Policy .............................................................. 28 
XIII. Problems Anticipated ......................................................................................................... 29 
XIV. Project Management .......................................................................................................... 29 
XV. 
Annex A: CaP TB Information System ............................................................................. 30 
References ..................................................................................................................................... 31 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

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ACRONYMS  
WHO-AFRO WHO Africa Regional Office 
BMU  
Basic Management Unit 
CaP TB 
Catalyzing Pediatric TB Innovation 
DOB  
Date of Birth 
DRC  
Democratic Republic of the Congo 
DR-TB 
Drug-resistant Tuberculosis 
DS-TB  
Drug-sensitive Tuberculosis 
EGPAF 
Elizabeth Glaser Pediatric AIDS Foundation 
EPTB  
Extra pulmonary TB 
GF-ERP 
Global Fund Expert Review Panel 
HCW  
Health Care Worker 
HF 
 
Health Facility 
HIV 
 
Human Immunodeficiency Virus 
HQ 
 
Headquarters 
ICF 
 
Intensified Case Finding 
IPT 
 
Isoniazid Preventive Therapy 
IQR 
 
Interquartile Range 
IRB 
 
Institutional Review Board 
M&E  
Monitoring and Evaluation  
MDRTB 
Multidrug-resistant TB 
MNCH 
Maternal, Neonatal and Child Health 
MOH  
Ministry of Health 
MOU  
Memorandum of Understanding 
MTB  
Mycobacterium Tuberculosis 
MTB-Rif 
Mycobacterium Tuberculosis Rifampicin 
NNS                Number Needed to Screen 
NTP 
 
National Tuberculosis Programs 
PMTCT 
Prevention of Mother to Child Transmission 
PT 
 
Preventive therapy 
PTB 
 
Pulmonary TB 
QA 
 
Quality Assurance 
RIF 
 
Rifampicin 
SAATHII  
Solidarity and Action against the HIV Infection in India 
SEARO 
WHO Southeast Asia Regional Office 
SIE 
 
Strategic Information and Evaluation  
SOP   
Standard Operating Procedure 
TA 
 
Technical Advisor 
TAT 
 
Turn Around Time 
TB 
 
Tuberculosis 
Xpert  
GeneXpert 
WHO  
World Health Organization 
 
 
 
 

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I. Rationale & Background Information 
 
Tuberculosis (TB) in children is often missed or overlooked due to non-specific symptoms and 
difficulties in diagnosis. This has made it difficult to assess the actual magnitude of the childhood 
TB epidemic, which may be higher than currently estimated.I Due to this paucity of data, the extent 
of TB in children remains largely unknown.II In 2016, the World Health Organization (WHO) 
estimated that over one million children (<15 years) suffer from TB worldwide. With over 201,000 
child deaths globally in 2016, including 52,000 among HIV/TB co-infected children, TB is a top 
ten cause of death in children. HIV co-infected children and the general population of children 
under five years of age (irrespective of HIV infection) are also at higher risk of pediatric TB.III 
 
Significant gaps exist across the entire cascade of care for pediatric TB including prevention, 
screening, diagnosis and treatment for pediatric TB. Globally, only 39% of pediatric TB cases are 
notified to national TB programmes (NTPs), with the remaining children undiagnosed or 
unreported.IV. Those who are not diagnosed experience high case fatality rates of 50% or more. V 
VI A recent analysis of the cascade of care for pediatric TB in Kenya and Uganda demonstrated 
that only 20% of the estimated pediatric TB cases in the cohort completed TB treatment, with the 
largest shortfall being in diagnosing patients.VII  
 
The heaviest burden of pediatric TB is in sub-Saharan Africa and South Asia. Africa accounts for 
about one-third of all pediatric TB cases,VIII with an incidence of 29-34/100,000, which is double 
of the global average.IX In HIV-endemic African countries, 40-60% of pediatric TB patients are 
also infected with HIV.X,XI At 23% of pediatric TB cases, sub-Saharan Africa disproportionately 
contributes to the global pediatric TB burden. Further, at 46% of the global pediatric TB mortality, 
sub-Saharan Africa disproportionately contributes to pediatric TB mortality.XII Sub-Saharan Africa 
leads in the contribution to TB under-diagnosis and under-reporting. Weak case finding, lack of 
and underuse of diagnostic tools, inadequate linkage to care, and lack of appropriate pediatric TB 
formulations result in poor clinical outcomes.XIII,XIV  
 
With the estimated incidence of 2.8 million TB cases in 2017, India is the highest TB burden 
country in the world in terms of absolute numbers of incidence cases each year. Due to the heavy 
burden and large population, India accounts for the largest number of pediatric TB cases globally, 
with an estimated 255,000 incident pediatric TB cases in 2015.XV Pediatric TB makes up 6% 
(approx 0.1 million) of notified 1.8 million cases. However, the exact scope of the epidemic is 
unknown, due to inadequate data and surveillance systems. Additionally, nearly half of all TB 
patients are treated in the private sector, and many are not notified to the National TB Program.XVI  
 
Models of care that include service integration and decentralization may improve clinical 
outcomes for children living with TB. Recently, critical progress has been achieved after years of 
neglect and underfunding. At the global policy level, the WHO post-2015 End TB Strategy,XVII the 
Stop TB Partnership Global Plan to End TB 2016-2020,XVIII and the Roadmap for Childhood TB 
have raised global awareness, developed a global policy framework and guidance to support 
national pediatric TB programmes,XIX and set a global target of providing effective TB treatment 
to 90% of key populations living with TB, including children, by 2020. The Roadmap for 
Childhood TB highlights the key priorities of developing integrated strategies for screening, 
diagnosis, and care; developing training materials for health workers; and collecting and reporting 

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better data on pediatric TB. Improved diagnostics such as the GeneXpert MTB-Rif system have 
also entered the market and may help improve diagnosis of pediatric TB.XX  
 
Very recent data from several small single-country studies have demonstrated that integration of 
TB interventions into other healthcare entry points can improve outcomes for pediatric TB.XXI 
Growing evidence from other disease areas like HIV, including HIV and TB service integration, 
have shown that integration and decentralization results in good clinical outcomes.XXII, XXIII In the 
era of the Sustainable Development Goals, with a focus on universal health care, developing, 
documenting, and catalysing the scale-up of innovative models of care focused on integration is a 
timely and critical intervention. In addition, the HIV pediatric community recently released their 
research prioritization which included a call for evidence generation for “optimal prevention and 
clinical management of co-infections, particularly tuberculosis” which includes implementation 
strategies such as integration.XXIV  
 
While policies, such as those noted above and in-country policies to use improved diagnostics (e.g. 
Xpert) and provide TB preventive therapy, have been strengthened, the proposed strategies are 
still poorly implemented.  A recent analysis of pediatric TB programmes in 12 African countries 
shows that about 40% of countries still rely on sputum smear microscopy as the primary diagnostic 
tool despite the wide knowledge of challenges related to sputum production in children under-five 
and the WHO recommendation (issued in 2018) to use Xpert MTB/RIF as the initial diagnostic 
test for diagnosis of childhood TB.XXV In addition, 64% noted very limited use of Isoniazid 
preventive therapy (IPT) in HIV-infected children.XXVI Globally only 7% of eligible children were 
started on preventative therapy in 2015.XXVII 
 
General underfunding of TB programsXXVIII and lack of dedicated resources for pediatric TB XXIX 
has historically hindered effective implementation and led to the gap described above. Strategic 
allocation of resources towards most impactful intervention is critical in such context. Costing and 
cost-effectiveness data could help informing national programs planning and budgeting but 
evidence currently available for childhood TB remains limited. 
Given the critical and urgent need to improve models of care for pediatric TB that include 
strengthened case finding and use of innovative diagnostics and drugs that may offer improved 
outcomes for children with TB infection or disease, The Elizabeth Glaser Pediatric AIDS 
Foundation (EGPAF) is implementing the Unitaid-funded Catalyzing Pediatric TB Innovation 
(CaP TB) project. CaP TB will develop and implement innovative models of care and accelerate 
the broad introduction of WHO-recommended and quality-assured drugs and diagnostics that will 
help bring care closer to children living with and at risk for TB and close the pediatric TB gap.  
 
This protocol describes the program evaluation that will help to document the outcomes of the CaP 
TB project.  
II. Project Goals and Objectives  
A. 
Goal 
To evaluate the effectiveness of the CaP TB project across ten countries on key service delivery 
and clinical outcomes and compare these outcomes to those obtained at baseline.  
 

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B. 
Objectives 
1. 
Primary Objective 
1. To evaluate the below TB service indicators and clinical outcomes for children 0-14 in 
facilities implementing the CaP TB project: 
2. To evaluate the below TB service indicators and clinical outcomes for children 0-14 in 
facilities implementing the CaP TB project: 
a. Number and proportion of children screened for TB among clinic attendees 
b. Number and proportion of presumptive TB cases identified among children 
screened for TB 
c. Number and proportion of presumptive TB cases referred for lab-based TB 
diagnosis 
d. Number and proportion of pediatric presumptive TB cases who are tested with 
Xpert  
e. Number and proportion of pediatric TB cases diagnosed with active TB among 
presumptive pediatric TB cases.  
 
f. Number and proportion of presumptive TB cases identified among children 
screened for TB 
g. Time between when a child is identified as a presumptive TB case and when the 
child is diagnosed with TB 
h. Number and proportion of pediatric TB cases started on DS-TB treatment 
i. Time between when a child is identified as a presumptive TB case and when the 
child is initiated on TB treatment 
j. Number and proportion of pediatric DS-TB cases or cases treated with first-line 
TB treatment who achieve treatment success 
k. Number and proportion of all TB index cases for whom successful contact tracing 
has been done 
l. Number and proportion of pediatric household contacts who are negative to TB 
screening 
m. Number and proportion of screened negative pediatric contacts eligible for 
preventive therapy 
n. Number and proportion of pediatric patients started on preventive therapy of those 
who are eligible for preventive therapy 
o. Number and proportion of pediatric patients on preventive treatment who 
completed therapy 
 
2. Secondary Objectives 
 
a. To determine the effect of the CaP TB project on the above TB service indicators 
and clinical outcomes compared to baseline (standard of care) in a subset of 
project sites. 
 
b. Utilize the evidence generated from this program evaluation to support strategic 
recommendations to improve pediatric TB care.  
 

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c. Utilize clinical aggregated data generated by this study to inform cost-
effectiveness analysis of pediatric TB interventions implemented by CaP TB 
project that can contribute informing childhood TB planning and strategic  
allocation of financial resources  
 
d.  Utilize evidence generated from this program to assess the impact of measures 
enforced to control the COVID -19 pandemic on accessibility and availability of 
pediatric TB services 
 
III. Expected Outcomes of the Study 
The main expected outcome of CaP TB project is to reduce morbidity and mortality associated 
with pediatric TBXXX by reducing the pediatric TB diagnostic and treatment gap, increasing 
coverage of quality assured TB treatments, as well as scale up of TB preventive therapy through 
innovative models of care for pediatric TB that focus on integration and decentralization. We 
expect that this program evaluation will document a positive impact of the CaP TB model, with 
estimated two-fold increase in case detection and four-fold increase in pediatric patients started 
on TB preventive therapy based on project target estimates.  The evaluation of the CaP TB 
project will allow for dissemination of the results and further uptake of proven models by other 
countries.  
 
 
IV. Study Design  
We are planning a pre-/post-project (quasi experimental) intervention evaluation. The population 
will include all pediatric patients (0-14 years of age) who present to a CaP TB project site in any 
of the 10 countries and receive TB services (including screening, diagnosis and treatment for 
active TB, and provision of TB preventive therapy).  
 
 
A. 
Methodology 
1. 
Description of the CaP TB Project 
The CaP TB project is a 4-year (October 1, 2017-September 30, 2021) Unitaid-funded project 
implemented by EGPAF (in sub-Saharan Africa) and SAATHII (in India) to improve pediatric TB 
outcomes by introducing models of care and strengthening access to WHO-recommended drugs 
and diagnostics. EGPAF and SAATHII, through the CaP TB project will develop, implement, and 
document innovative models of pediatric TB care focusing on integration, decentralization, and 
community-based care. Integration refers to supporting TB activities, such as screening and TB 
sample collection for children, into non-TB health care services, such as general pediatric 
outpatient clinics. Decentralization refers to moving pediatric TB services from higher levels of 
health clinics to lower levels. Community-based care refers to care that is delivered outside the 
facility, often, but not exclusively, at household level.   We hypothesize that such models of care 
will increase case detection and care delivery, thus improving key pediatric TB outcomes. CaP TB 
focuses on the regions with the largest contributions to pediatric TB: AFRO and SEARO. The CaP 
TB countries where the project and project evaluation will be carried out are: Cameroon, Cote 

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d’Ivoire, DRC, Kenya, Lesotho, India, Malawi, Tanzania, Uganda and Zimbabwe.  
 
Innovative models of care will include integration of TB services into MNCH, HIV, nutrition, and 
other key pediatric health care entry points. CaP TB will also support improved intensified 
community case finding including through contact tracing of adult and pediatric index TB patients, 
optimized clinical-radiological diagnosis, increased uptake of molecular diagnostics, and where 
feasible, decentralized or community-based initiation of TB preventive therapy. CaP TB will not 
be altering treatment algorithms for TB preventive therapy or for those with active  infection, but 
will be following national guidelines or MOH guidance to the project as to the type and duration 
of treatment provided.  
 
a) 
Figure 1: Intensified Case Finding & Integration of Services 
 
 
 
 
While most of the CaP TB project will be implemented in public facilities, in some EGPAF-
supported countries, EGPAF has worked with the private sector, including faith-based clinics. 
EGPAF will also support select private health facilities that EGPAF currently supports to adopt 
CaP TB project interventions, including integration of care and improved models of care for case 
finding and uptake of TB preventive therapy. In India, SAATHII has focused much of its work 
supporting the private sector through public-private partnership models. These models have shown 
considerable promise to improve TB care in India and similar contexts and SAATHII has utilized 
this model to improve pediatric care in the private sector in India.XXXI  
 
Initially, CaP TB will be implemented in approximately 15-20 purposefully selected and diverse 
sites per country for the first 2 years of the project (October 2017-October 2019) to refine 
approaches, determine costs, and inform a second phase of expanded implementation to prove 
scale-ability, avoid interventions becoming stuck in the pilot phase, and bridge to scale up. Data 
gathered will be used to demonstrate the effectiveness and feasibility of innovative interventions.  
During the last six months of this intensive monitoring phase, EGPAF will analyze the results and 
lessons learned from early implementation of these innovative models of care.  Results will be 
discussed with key in-country and international stakeholders in order to help refine the models and 
plan for a period of expanded implementation.  
 
EGPAF will then enter into a period of expanded implementation that will help to prove and 
catalyze scalability and bridge to transition. The number of sites chosen for the expanded 
implementation phase was selected to ensure sufficient strength of evidence to induce catalytic 
change nationally, be generalizable and build a good basis for eventual transition and scale up. 
Thus, within each country, EGPAF’s site selection aimed to include: 1) Multiple types of sites 
including different health facility levels; 2) varying health entry points (e.g. nutrition centers, sites 

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with pediatric inpatient wards, etc.); 3) diverse geographic setting and ease of access to health 
facilities; and 4) different population types (including key populations such as refugee populations, 
fisher folk). Depending on the size of the country and the diversity of the contexts within each 
country, this resulted in a varying number of sites per country.  
 
2. 
Country-Level Activities 
EGPAF and SAATHII have strong expertise in implementing innovative service delivery models  
and will provide training, supportive supervision, job aids, and standard operating procedures 
(SOPs) to health care workers who are engaged in the care of pediatric patients at CaP TB facilities. 
The goal of these activities is to support the strengthened uptake of current recommendations on 
TB screening, diagnosis and treatment as well as allow for decentralization and integration of 
pediatric TB care. CaP TB will also provide training to strengthen completion of TB registers, and 
may develop other M&E tools to improve the documentation of pediatric TB. EGPAF and 
SAATHII will also assess and provide SOPs and infrastructure upgrades to improve infection 
control. EGPAF and SAATHII will support innovations to improve service delivery including 
creating facility-specific TB champions to monitor service quality, regular performance feedback 
to facilities, and work with civil society to identify areas to improve care.   
 
Specific packages of activities will vary by country and will be determined based on (1) national 
policies and guidelines; (2) planned and existing activities supported through other efforts; and (3) 
country-specific pediatric TB burden and barriers and bottlenecks. For Country Submission- refer 
to country specifics.  
 
In general, country-level activities will include: 
 Decentralizing and integrating delivery of pediatric TB care (diagnosis, treatment (where 
feasible), and prevention) into MNCH, HIV, nutrition and other key pediatric entry points 
at the facility level;  
 Supporting community-level contact tracing and screening of pediatric contacts for index 
patients with active TB and where feasible according to MOH guidance, initiation of 
preventative TB therapy at the community level; 
 Documenting and generating evidence for innovative models of care through M&E; 
 Strengthening data systems through support for improved use of current registers as well 
as introduction of new data tools where gaps exist (e.g. for tracking of TB preventive 
therapy completion in some countries); 
 Supporting rapid uptake through trainings, site monitoring and mentorship and 
strengthening sample transport and referral systems of new diagnostics and medicines that 
are included in WHO guidelines and are either included in country guidelines or are in the 
process of being incorporated into national guidance, such as:  
o GeneXpert diagnostic assays (i.e Xpert MTB/RIF Ultra)XXXII  
o Quality-assured pediatric dispersible formulations of fixed dose isoniazid-
rifampicin-pyrazinamide and rifampicin-isoniazid as well as ethambutol single 
formulation for the treatment of active TB disease;   

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o Quality-assured pediatric formulations of dispersible isoniazid single formulation 
and fixed dose rifampicin-isoniazid for preventive therapyXXXIII.  
 Supporting the introduction and use of e-/m-health technologies (i.e connectivity 
solutions, SMS-reminders) to strengthen performance of TB screening at household 
level, linkage to care and/or  patient’s treatment  adherence strategies 
 
Drugs and diagnostics used in CaP TB must have approval from a stringent regulatory agency or 
be recommended by the Global Fund ERP, the WHO prequalification program or WHO Global 
TB program and be registered by the country national regulatory authority or have an exemption 
for import and routine use in the country. Cepheid recommends that gastric aspirate (GA) samples 
tested on the Cepheid GeneXpert platform be centrifuged to improve yield. As some of our Xpert 
testing sites will not have access to the appropriate centrifuge and infection control equipment, we 
will use direct GA specimens without centrifugation for Xpert testing. Testing without a 
concentration step (achieved through centrifugation) may reduce the sensitivity of Xpert testing 
for this specific sample type. It will not affect specificity. As the sensitivity of GA even with a 
centrifugation step is estimated to be 83% according to a WHO meta-analysis, WHO 
guidelinesXXXIV recommend that a negative result from a GA sample tested on Xpert not be used 
to definitively rule out TB. As the sensitivity from testing without a centrifugation step may be 
lower, we will stress in our trainings that a negative result from an Xpert test on GA does not rule 
out TB. This practice will be reviewed with the National TB Program before implementation.  
 
 
3. 
Duration of the Project 
Data collection of pre-intervention retrospective baseline data collection will take place in the 
months prior to or immediately after the start of CaP TB project interventions. Post-intervention 
data collection will take place once the facility is enrolled in CaP TB and will be on-going over 
the course of the project (through September 30, 2021). It is expected that most countries will 
begin enrolling pilot facilities by September 2018.     
 
V. Description of Project Evaluation 
The CaP TB model represents one potential way of improving the care of pediatric TB. However, 
it will be important to measure this model’s effect on key service and clinical indicators related to 
pediatric TB in order to help guide future programming and resource prioritization. In order to 
describe the effect of the CaP TB model on these indicators, we plan a pre- and post-intervention 
evaluation in all project countries. We have chosen this pragmatic approach to allow us to compare 
the outcomes after we begin CaP TB implementation with the same indicators baseline (pre-
implementation). This can help us define the effect of our specific project on the project evaluation 
indicators. As this is an evaluation of program implementation a randomized approach would not 
be feasible for both programmatic and financial reasons. We do recognize that secular trends may 
affect our outcomes, but we feel that the duration of the evaluation (over several years) and the 
large size and multi-country nature will help to mitigate that risk.  

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A. 
Pre-intervention Evaluation- Baseline assessment 
In each country, a pre-intervention retrospective data collection will take place in a sub-set of 
project sites.  
 
This data collection activity will: 
1. Capture data that will answer the TB service indicators and clinical outcomes listed in the 
primary objectives.  
2. Capture key data points that will be needed to estimate project targets 
 
 
The main objectives of the CaP TB interventions are: 
- 
to increase the number of children diagnosed with TB 
- 
To increase the number of children who are started on  and complete DS-TB treatment  
- 
To increase the number of children who are started on and complete TB preventive 
therapy. 
 
Key indicators that will be used to monitor project interventions and assess impact will 
therefore be: 
- 
Number of pediatric cases diagnosed with active TB disease  
- 
Number and proportion of pediatric DS-TB cases who achieve treatment success 
- 
Number and proportion of pediatric patients started on preventive therapy of those who 
are eligible for preventive therapy 
- 
Number and proportion of pediatric patients on preventive treatment who completed 
therapy 
Data sources for these indicators during the pre-intervention phase are described in Table 1. 
 
In each site, trained data collectors will retrospectively extract data from appropriate registers, 
logs, and in some cases patient files, for a period of 12 months starting 6 or more months before 
the start date of data extraction. This time frame has been selected in order to allow to accurately 
measure indicators on treatment completion for both drug-sensitive TB treatment and preventive  
therapy (treatment lasts 6 months in both cases). In certain cases, the data sampling frame will 
start more than 6 months before the data extraction if CaP TB interventions had started during 
the sampling frame. Thus the sampling frame was chosen so that the end date of retrospective 
pre-intervention data abstraction would be before the start of any intervention to ensure that the 
baseline data was not affected by the early activities.  For some indicators, baseline data will not 
be available in existing registers or logbooks. Data collectors will extract data from all pediatric 
entry points within the facility, including MNCH, HIV, nutrition and other relevant pediatric 
health care entry points. Only required variables will be abstracted and entered into the 
password-protected computers. Data with the patient date of birth (DOB), patient ID (if any), TB 
treatment ID and preventive treatment ID will be collected.  The patient ID (if any), TB 
treatment ID and preventive treatment ID will all be encrypted before being uploaded into the 
CaP TB Database Entry Tool.   DOB will be abstracted in order to facilitate tracking across 
registers if needed, as well as for data quality assurance purposes. This information will only be 
used to link registers. Only de-identified patient data will be abstracted into our global project 

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database.  No other unique identifiers such as contact details of the children or their caregiver 
will be abstracted from the registers. Data from included pediatric patients will be extracted from 
the registers and recorded in the CapTB Baseline Data Abstraction form from where the data will 
be entered into a CaP TB Database Entry Tool (Excel-based and/or Web/mobile App-based) 
developed for pre-and post-intervention data , in a password protected computer and/or Android 
device (See Annex A: CapTB Information System).  
 
The target population for the pre-intervention assessment is the records of any pediatric patient 
(0-14 years of age) who attend one of the sub-set of pilot sites in any of the 10 CaP TB countries 
who receive TB services. TB services include: 
 Screening for TB (clinical symptoms or signs) 
 Receiving services (such as contact tracing) as a result of being a contact of a TB index 
case 
 Clinical diagnostic assessment for TB 
 Microbiologic diagnostic assessment for TB 
 Treatment for active TB 
 TB preventive therapy 
 
 
Data collection of pre-intervention baseline data will take place prior to the start of CapTB 
interventions or immediately after, ensuring that the calculated data abstraction period does not 
overlap with any of the early project interventions. Data collection in each site may last up to 4 
days and in some cases data collection may last several days longer.  
 
VI. Evaluation Design and Methods 
CaP TB implementation data will be collected by project-specific data collection tools and/or 
from existing registers. Whenever possible, the CaP TB data collection will use existing site 
level data collection tools to gather the data for the project. However, where such tools do not 
exist or the tools have gaps to capture all the necessary indicators, we will introduce project-
specific data collection tools, the Pediatric TB Intensified Case Finding Screening Tool (ICF 
tool), the CaP TB Pediatric TB Form and any other form that may evolve as we learn lessons 
from project implementation.  
 
Use of project-specific data collection tools 
As part of the CaP TB intervention, healthcare workers will fill out a Pediatric TB Intensified 
Case Finding Screening Tool (ICF tool). This tool has no identifying information and will 
provide information on 1) number of children screened for TB in each healthcare entry point 
(e.g. pediatric ward, outpatient department, MNCH clinic, and nutrition clinic); 2) sex of the 
child; 3) age of the child; 4) if the child has any signs of symptoms concerning for TB (according 
to WHO guidance); 5) if the child is a contact of a TB case; and 6) the date of screening. The 
forms are also color coded according to the healthcare entry points where children are seen 
(White= MCH/PMTCT; Blue= outpatient department; Pink= Nutrition; Yellow= Pediatric Ward, 
Other=to be decided). See Attachment: Pediatric TB Intensified Case Finding Screening Tool. 
 

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For children with presumptive TB: For all patients with a positive TB screen (children who have 
signs and symptoms concerning for TB according to the left side of the ICF tool), or for children 
who are a household contact of a TB case, the CaP TB Pediatric TB Form will be used to collect 
data on TB clinical and bacteriological investigations, as well as treatment initiation information 
at patient level. In addition, this form will be used directly to screen for TB symptoms in HIV 
clinics and during screening of contacts of TB index cases in the community, instead of the ICF 
tool for those 2 entry points, in effort to minimize unnecessary duplication of data entry. This 
CaP TB Pediatric TB Form will be adapted to country-specific requirements in collaboration 
with the MOH. This form will be printed on quadruplicate carbonated multi-colored papers (See 
Attachment C: CapTB Pediatric Form).  
 
After the child has a positive TB screen the appropriate healthcare worker, such as the treating 
clinician or TB nurse, will begin filling out their section designated for requesting health workers 
on the CaP TB Pediatric TB Form, pre-printed with sequential numbers in each country using the 
Form. For children screened at HIV clinics or during contact tracing, this section will be directly 
filled for all children screened, irrespective of the presence of signs or symptoms or TB.  This 
part of the form contains identifying information of the pediatric patient, contact information and 
identifies if the patient is exhibiting sign or symptoms concerning of TB, and if so which ones. If 
signs or symptoms of TB are identified, the facility TB nurse or focal point will then detach the 
last copy of the form (the pink form) and keep this form at the facility. The remaining three 
carbonated copies of the CaP TB Pediatric TB form will then be used as a referral form for 
sample collection and TB testing. The patient or patient’s caregiver will be sent with the 
remaining three copies of the carbonated form to have a specimen collected. The healthcare 
worker collecting the sample will then fill out the section “To be filled at specimen collection 
site.” This section contains information on the date of collection and type of specimen collected. 
The remaining three copies of the carbonated form, along with the specimen will be sent to the 
laboratory for specimen processing. The laboratory staff will fill out the section “To be filled by 
lab personnel.” This section will contain information about the type of testing performed, the 
date of testing and the results of testing. The laboratory staff will detach one copy (the blue form) 
and keep this at the laboratory. The remaining two copies of the CaP TB Pediatric TB form, 
which contains the patient’s results, will then be returned to the requesting facility. The 
requesting facility/treatment unit will then complete the section “To be filled by TB treatment 
unit.” This section will contain additional information, including results of chest X-ray and if the 
patient was diagnosed based on clinical symptoms with or without radiologic signs. This section 
will also contain information about treatment initiation or the facility to which the patient was 
referred for treatment initiation as well as the patient’s TB treatment register number. The first 
(white) page will be kept at the requesting facility for their records.  
 
The CaP TB Pediatric TB Form will also be used for referral for an initiation of TB preventive 
therapy, primarily during contact tracing or screening at HIV clinics. The relevant healthcare 
worker will fill the section “To be filled by requesting health worker” and the section “To be 
filled during contact tracing and in HIV clinic only.” These sections contain identifying 
information of the pediatric patient, contact information and information on eligibility for TB 
preventive therapy. If the child was identified at the HIV clinic, the healthcare worker keeps the 
last copy (pink) and the child/caregiver will bring with him/her the three remaining copies of the 
carbonated form and gives them to the unit initiating PT. If the child was identified through 

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contact tracing in the household, the community health worker (CHW) gives the last copy (pink) 
to the patient or patient’s caregiver and the CHW brings the remaining 3-copy form to the TB 
unit. When the patient presents to the facility for TB preventive therapy initiation, the healthcare 
worker initiating TB preventive therapy will complete the section “To be filled by HCW 
providing PT.” This section contains information on TB preventive therapy initiation, date of 
initiation and the patient’s preventative therapy register number. In the event that the initiation 
date is not recorded, an EGPAF data collector will be responsible for following up with the entry 
point or facility providing TB preventative therapy.  Upon completion of the form, one copy will 
remain at the facility (1st page) and the data entry copy (2nd page) will be transferred to the 
EGPAF office for entry into the project database.    
 
CaP-TB data collector will ensure timely data collection and reporting from all CaP-TB sites. 
This copy is the project’s data collection form. The form that data collectors will be collecting 
has all identifying information for the patient blocked out, except the child ID (if any), the TB 
treatment register number (or TB preventive therapy register number), the sex, and the date of 
birth to protect patient confidentiality.  
 
Data collectors will also collect the ICF tools from the various entry points and collate 
aggregated data using an ICF data abstraction tool (Attachment B: Pediatric TB Intensified Case 
Finding Screening Data Abstraction Tool) which will be entered directly into the electronic data 
entry form. Data collectors will also extract information, such as date of treatment completion, 
from the TB treatment and TB preventive therapy registers. In the pilot phase (years 1 and 2), 
data collectors will visit sites frequently for data extraction (approximately every 4-6 weeks). In 
the expansion phase (years 3 and 4), data collectors will visit sites less frequently for data 
extraction (approximately every 1-3 months).  
 
Data collection when the project-specific data collection tools are not used 
If the CaP TB Pediatric TB Form is not completed or the country does not support use of the ICF 
Tool and/or CaP TB Pediatric TB Form for all or part of the data collection, data collectors will 
extract data from relevant sources such as existing registers and logs as in the pre-intervention 
baseline data collection phase. An indicator mapping exercise will first be conducted to identify 
the location and source of all required data.  This indicator mapping exercise is expected to 
inform the data collection process which will take place on site, at the project facility.  Data will 
be extracted from the source register or log and, recorded in the baseline data abstraction tool 
and entered  into the CaP TB Database Entry Tool developed for pre-and post-intervention data.  
Only data required for the project M&E activities will be extracted and will be the same data 
collected through the CaP TB Pediatric TB Form.  EGPAF will closely monitor data collection 
activities of any country team that cannot use the CaP TB Pediatric TB Form to ensure high 
quality data is collected.  All data collection tools and processes will be approved by the in-
country IRB.   
 
 
A. 
Table 1. Indicator Outcomes and Data Sources 
 
This table presents an example of data sources. Specific data sources may vary from country to 
country. All country-specific data sources will be approved for data extraction by the local IRB.  

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Primary Outcomes 
Data Source Pre-Intervention  
Data Source Post-Intervention 
Number and proportion of 
children screened for TB among 
clinic attendees  
TB screening logbooks/registers 
Pediatric TB Intensified Case 
Finding Screening Tools and 
Clinic attendance registers 
 
And/or 
 
TB screening 
logbooks/registers 
 
Number and proportion of 
presumptive pediatric TB cases 
identified among children 
screened for TB 
 
TB screening logbooks/registers 
Presumptive TB registers 
CaP TB Pediatric TB Form 
 
And/or 
 
TB screening 
logbooks/registers 
Number and proportion of 
presumptive TB cases referred 
for lab-based TB diagnosis 
 
TB screening logbooks/registers or 
Presumptive TB registers 
CaP TB Pediatric TB Form 
 
And/or 
 
TB screening 
logbooks/registers, 
Presumptive TB registers 
Number and proportion of 
pediatric (0-14 years) 
presumptive TB cases who are 
tested with Xpert  
 
TB diagnostic logbooks/registers or 
Xpert logbooks/registers 
CaP TB Pediatric TB Form 
 
And/or 
 
TB diagnostic 
logbooks/registers or Xpert 
logbooks/registers 
Number and proportion of 
pediatric TB cases diagnosed 
with active TB disease among 
presumptive TB cases 
Presumptive TB registers and TB 
registers 
CaP TB Pediatric TB Form 
 
And/or 
 
TB registers/logbooks 
Time between when a child is 
identified as a presumptive TB 
case and when the child is 
diagnosed with TB 
 
Presumptive 
TB registers, 
TB 
registers/logbooks 
CaP TB Pediatric TB Form 
 
And/or 
 
Presumptive TB registers, TB 
registers/logbooks 
Number and proportion of 
pediatric TB cases started on 
DS-TB treatment 
 
TB registers/logbooks 
CaP TB Pediatric TB Form 
 
And/or 
 
TB registers/logbooks 
Time between when a child is 
identified as a presumptive TB 
case and when the child is 
initiated on TB treatment 
Presumptive 
TB registers, 
TB 
registers/logbooks 
CaP TB Pediatric TB Form 
 
And/or 
 

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B. 
Table 2. Additional Indicator Outcomes and Data Sources 
 
Additional data will be collected during the pre-intervention phase and will be used to estimate 
project targets. This table presents an example of data sources. Specific data sources may vary 
 
Presumptive TB registers, TB 
registers/logbooks 
Number and proportion of 
pediatric DS-TB cases who 
achieve treatment success 
 
TB treatment register 
 
TB treatment register 
 
Number and proportion of all 
TB index cases for whom 
successful contact tracing has 
been done 
 
TB registers/logbooks  
Contact tracing forms and registers 
if available 
 CaP TB Pediatric TB Form  
and TB register 
 
And/or 
 
TB registers/logbooks  
Contact tracing forms and 
registers if available 
Number and proportion of 
pediatric household contacts 
who are negative to TB 
screening 
 
TB registers/logbooks  
Contact tracing forms and registers 
if available 
CaP TB Pediatric TB Form   
 
And/or 
 
TB registers/logbooks  
Contact tracing forms and 
registers if available  
Number and proportion of 
screened negative pediatric 
contacts eligible for preventive 
therapy 
 
TB registers/logbooks  
Contact tracing forms and registers 
if available 
CaP TB Pediatric TB Form   
 
And/or 
 
TB registers/logbooks  
Contact tracing 
forms and 
registers if available  
Number and proportion of 
pediatric patients started on 
preventive therapy of those who 
are eligible for preventive 
therapy 
 
TB preventive therapy register  
CaP TB Pediatric TB Form   
 
And/or 
 
TB preventive therapy register  
Number and proportion of 
pediatric patients on preventive 
treatment who completed 
therapy 
 
TB preventive therapy register  
 
TB preventive therapy register 
 
And/or 
 
TB preventive therapy register 
 
 
 
 

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from country to country. All country-specific data sources will be approved for data extraction 
by the local IRB.  
 
 
 
 
VII. Use of data generated through CaP TB program evaluation to 
perfom secondary analysis 
 
A. 
Use of CaP TB Program evaluation data to inform cost-effectiveness analysis 
 
Data documenting the costs and cost-effectiveness of pediatric TB interventions remains 
limitedXXXV,XXXVI, and this represents one of the contributing factors to the under-funding of 
childhood TB programming XXXVII. The data generated through the TIPPI evaluation are well 
placed to inform the cost-effectiveness assessment of the package of pediatric TB interventions 
implemented under the CaP TB project.  
To this aim, EGPAF will sub-contract University of Sheffield, key leader in childhood TB health 
economic modelling, to perform a cost-effectiveness analysis (CEA).The resulting effects 
estimates will be based on routinely collected project intervention country-level aggregates from 
key indicators describing the cascade of care, as well facility-level data for the comparison of the 
pre- and post- project intervention phase.  All data to be used will have already been collected 
through TIPPI Pre-Intervention evaluation (described in section V, subsection A) and CaP-TB 
implementation evaluation (described in section V, subsection I). 
Only aggregated clinical data will be shared with University of Sheffield and thus considered for 
the CEA analysis, as described below: 
Primary Outcomes 
Data source 
Number of HIV positive children (0-14 years) in 
care  
HIV clinic register 
Number of adult TB cases notified 
(disaggregated by age, sex, type of TB [PTB 
smear positive, PTB smear negative; EPTB], 
new or previously treated case, DS or MDRTB 
case) 
TB treatment Register 
Number of pediatric household contacts 
recorded for each adult TB case (disaggregated 
by age, sex) 
TB register or TB contact tracing register 
In countries where information is not recorded in the 
above described register, there might be the need to 
extract this information from a sample of patient 
forms  
Number of HIV positive pregnant women in 
care (disaggregated by age) 
PMTCT register 
 
Number of HIV+/TB  pregnant women  
(disaggregated by age, type of TB [PTB smear 
positive, PTB smear negative; EPTB], new or 
previously treated case, DS or MDRTB case) 
PMTCT register 
 

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i. Averaged monthly rates per site (including absolute numerator and denominator) of 
pediatric (children aged 0-14 years) TB notifications, DS-TB initiations, and PT 
initiations for a subset of sites for which both baseline and prospective data have already 
been collected (restricting to sites where data on both periods are available).  
ii. Country-aggregated project intervention numbers of:  a) Children screened for TB , b) 
Children identified as presumptive TB, c) Children with presumptive TB tested with 
Xpert, d) Children diagnosed with TB, e) Children treated for DS- TB, f) All TB index 
cases for whom successful contact tracing has been done, g) Children started on TB 
Preventive Therapy (disaggregated by HIV and Contact investigation entry points), and 
h) Sites contributing to the country-level dataset.  
All patient-level indicators mentioned in points i and ii above are included in Table 1. The cost-
effectiveness analysis will use pre-intervention and project intervention data, with the potential 
for sub-analysis of shorter targeted period during the intervention phase.  
The final cost-effectiveness analysis outcomes are expected to be reported by country, and 
individual countries will be identified to allow to use context-specific results to inform decision-
making. 
 
The costs will be estimated as follows: 
 Core health services costs will be derived from published literature. 
 CaP TB intervention costs will be estimated based on EGPAF CaP TB budgets and 
expenditure data from EGPAF’s financial system. 
 EGPAF country team staff will assist in allocating cost items to specific activities within 
the CaPTB cascade of service delivery. 
 
 
B. 
 Use of TIPPI data to assess the impact of COVID 19-related measures on 
accessibility and delivery of pediatric TB services 
 
The COVID-19 pandemic and the measures enforced by governments to control it have affected 
health services in general, and the repercussions on TB services have been estimated to be 
significantXXXVIII. However, evidence on the impact on pediatric TB services is scarce.  CaP TB 
project data collection processes could continue throughout the crisis caused by the COVID-19 
pandemic. Therefore data collected under the TIPPI protocol could be utilized to analyze the 
impact that the measures enforced by governments to control the COVID-19 pandemic had on 
the accessibility and delivery of pediatric TB services. 
 
Below is a summary of the analyses that we would perform to assess this impact: 
 
- 
Measure the changes in number of pediatric patients seeking care at facility, through 
uninterrupted time series  of variations in the number of clinic attendees 
- 
Measure the changes in quality determinants of pediatric TB services offered before and 
during the COVID-19 pandemic throughout the cascade of care.  To measure such 
changes, we will run uninterrupted timeseries analysis comparing number and 
proportions of most of the TB services-related indicators described in this protocol 

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Only routine protocol data will be collected as per the description of indicators, data collection 
tools, data gathering and data management activities described elsewhere in this document. 
 
VIII. 
Data Gathering Activities 
 
A. 
Table 3. Study Data Gathering Activities During Pre-intervention and CaP TB 
Intervention Phases 
 
Data Gathering 
Activities  
Pre-intervention evaluation 
CaP TB evaluation  
Retrospective data collection in a sub-set 
of project sites (15-20 pilot sites per 
country) 
Periodic data collection in all 
project sites 
Study population  
Pediatric patients (0-14) who attend a CaP 
TB pilot site who receive TB services 
Pediatric patients (0-14) who 
attend a CaP TB site who receive 
TB services 
Sample size  
10-20 purposively selected pilot sites in 
each country, for a total of up to 200 sites 
across all ten countries. Sites will be 
selected based on geography (urban vs 
rural) and health facility level. We estimate 
that 12 months of data will be sufficient to 
appropriately assess the indicators from the 
primary objectives under standard of care 
conditions. The overall sample size in each 
country and per facility sample size will 
vary greatly by facility level, pediatric 
population density and indicator. However, 
we estimate that we will collect data for at 
least 5 children with presumptive TB in 
each clinic.  
Up to 70 sites in each country for 
a total of up to 700 sites across all 
ten countries.  
Location of activity 
15-20 CaP TB pilot sites in each country  
All CaP TB sites across 10 
countries (up to 700 sites) 
Timing 
Retrospective data collection will occur 
upon site selection. It is estimated that the 
retrospective data collection for all sample 
project sites in a given country will take 
six to ten weeks. 
Data collection will begin when 
each site begins implementation of 
CaP TB and will go on through 
the end of the project  
Method  
Data abstraction of TB registers, HIV 
registers, PMTCT registers and other 
relevant logbooks 
Data abstraction from clinic 
attendees registers, Pediatric TB 
Intensified Case Finding 
Screening Tool, CaP TB Pediatric 
TB Form, TB treatment register, 
TB preventive therapy register and 
other TB registers and logbooks as 
needed 

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Informed Consent 
documents   
Informed consent waiver to be requested  
Informed consent waiver to be 
requested 
Data collection tool    Baseline data abstraction tool 
Pediatric TB Intensified Case 
Finding Screening Data 
Abstraction Tool  and CaP TB 
Database Entry Tool 
 
IX. Data Management and Statistical Analysis 
Quantitative de-identifiable data extracted from the source documents will be coded and entered 
directly into a database that will be designed specifically for the project and stored on a secure 
cloud server. Data will be aggregated in the database and entered into an electronic dashboard that 
will demonstrate the data standardized to project indicators and data elements. Frequencies will be 
calculated for each response and descriptive statistics will be calculated.  
 
Project data sample size: As this is a project evaluation, no specific sample size has been 
calculated. However, we estimate that the project will increase case detection by 2-fold and 
result in an additional 16,471 pediatric TB cases being treated.XXXIX This is based on an 
assessment of the number of children we project to screen (both HIV positive and HIV negative) 
in our project sites throughout the project. From the literature, we estimate that approximate 
Number Needed to Screen (NNS) to identify 1 TB case is 41 children. Assume that Number 
Needed to Screen (NNS) to identify 1 TB case is 41 (estimated NNS when symptom based 
screening is the only primary screening done)XL,XLI 
Preventive treatment coverage is estimated to increase by four-fold, with an additional 52,317 
children to be initiated on preventive therapy. This is based on the estimated number of child TB 
contacts we will identify through contact tracing plus HIV-infected children who qualify for 
preventative treatment.  
 
To compare pre- and post-intervention outcomes, we will use either the ratio of the two 
proportions (relative risk) or the difference between the two proportions (risk difference). We 
will use Z-tests to assess the statistical significance of the estimated effect of CaP TB. 
 
For measuring turn-around-time (TAT) between when a child is identified as a presumptive TB 
case and when the child is diagnosed with TB and the TAT between when a child is diagnosed as 
a presumptive TB case and when the child initiates TB treatment, if the TATs are approximately 
normally distributed, we will use the paired t-test to assess for statistical significance, otherwise 
we will use the Wilcoxon rank sum non-parametric test.  
 
 
A. 
Quality Assurance 
All data collectors will be trained in quantitative data collection by EGPAF staff. Prior to training, 
all data sources, abstraction and collection tools and procedures will be reviewed and tested. The 
HQ EGPAF team will provide on-going support to in-country teams throughout program 
implementation and all data collection activities. 
 

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All data from project tools and registers will be entered into a database that will be designed 
specifically for the project and stored on a secure web-based server. The database will allow data 
quality checks on a routine basis throughout the data collection period to ensure that data are 
within a feasible range. For instance, data values related to dates must be inferior to the actual 
database upload dates, and superior to dates of birth, etc. in order to be coherent with the cascade 
of care. Any out of range values will be verified by tracing data through the source document 
during the data collection visits described below, and by contacting the facility for further 
discussion and resolution. 
 
Data quality will be ensured by training EGPAF staff in-country and comprehensive 
documentation of data collection processes and procedures prior to the collection of data.  In 
addition to training and documentation of data collection procedures, quality assurance rounds will 
be conducted by in-country EGPAF staff during data collection at randomly selected sites to ensure 
proper completion of the project forms (the ICF tool and the CaP TB Pediatric TB Form). Quality 
assurance rounds will assess for completeness and consistency to check for anomalous data 
recording, omission and extraction. Data will be reviewed by CaP TB project facility focal person 
and in-country EGPAF staff who will undergo data quality assurance training. In addition, the 
project Country Implementation Manager and M&E focal person will routinely review the data 
for completion and accuracy, comparing a randomly selected sample of CaP TB Pediatric TB 
forms with data entered into the database.   Corrections will be made as necessary and data 
collection and entry clerks re-trained if needed.  The Washington-based Senior Strategic 
Information and Evaluation (SIE) Officer and HQ SIE backstops will receive de-identified data on 
a regular basis for additional data validation, to ensure completeness of data.  The HQ Senior SIE 
Officer and project M&E team will be responsible for maintaining the integrity of the in-country 
project database.  The project will design and implement strict data quality and management SOPs 
and a tracking system for documentation of all entries, changes, or updates to the project database.   
 
As with pre-intervention aggregated data, post-intervention aggregated data will be subject to 
data quality verification processes. 
 
X. Privacy and Confidentiality 
Aggregated data will not contain any identifiable information about clients and there is minimal 
potential for a breach in confidentiality. Additionally, patient level data abstracted for pre and post-
intervention analysis will be aggregated for dissemination of findings to further protect 
confidentiality and will not contain any identifiable information about patients. The CaP TB 
Database Entry Tool will be located on a password-protected computer and/or Android device.  
The name of the patient and their caregiver, contact details and other identifiable information such 
addresses, phone numbers will not be entered into the CaP TB Database Entry Tool at any time.  
 
Only the health facility staff will have access to the identification number that links the ID to the 
patient’s name and other identifiable patient information such as caregiver’s name and address,   
TB Prevention therapy number, TB treatment number and patient identification numbers (if 
available) will be automatically encrypted before upload to the global database, so that upon 
review at headquarter level, an evaluation identification number is assigned to all children. 

CaP TB ME Protocol Version 3.3 8th March 2021  
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However, to protect the confidentiality of the patient, we will implement the following protective 
measures:  
 
a) At the country level, patient information, including the patient ID (if any) and treatment 
register numbers will be entered into the country CaP TB Database Entry Tool, and will be 
automatically encrypted, with the exception of DOB, before uploaded into the project 
database. 
b) The database with global data is housed in Microsoft cloud.  The database developers, the 
Diagnostics Advisor and the Senior Strategic Information and Evaluation Officer and other 
key relevant staff such as the Senior Biostatistician responsible for data analysis, have 
access to all the country files, globally.   These are the files that contain the patient IDs.  
Access to the database is password protected and access to this file can only be provided by 
the database developer.  
c) All calculations are done on the backend of the database system, including the count of 
unique number of patients; the dashboard which is the project’s data visualization tool, 
presents aggregated data without patient IDs or treatment register numbers.   
d)   The CaP TB Pediatric Form ID Number, generated by the project, will be made visible and 
will be used to track records with data quality errors. 
e) Permission must be given to access the global dashboard by either the database developer 
or the Senior Strategic Information and Evaluation Officer to the project.  Permission is 
granted to key EGPAF project staff only, such as country implementing managers, M&E 
staff and principal investigators.    
f) The dashboard is password protected and only EGPAF employee, with an EGPAF email 
can be granted access to the global dashboard.  
g) Patient and treatment register IDs will not be included in any analysis or dissemination of 
results. 
 
As new security measures become available to protect the data in the database and the dashboard, 
they will be implemented as possible.  Whenever feasible, an agreement on data sharing policy or 
practices will be established between EGPAF and participating country.  
All computers used for data entry and analysis will be password protected. Once at EGPAF offices, 
computers will be in a locked cabinet, in a locked office with limited access in each project country.  
Only relevant members of the project team in country will have access to these data for entry, 
quality audit, analysis and reporting purposes.   
 
Facility based data abstraction and any discussions about data quality, patient care and 
management will be conducted in private areas free from general view and out of hearing range as 
much as possible.   
 
Data presented as part of study findings in papers or at conferences will not include any 
participants’ names, IDs or any other identifiable information.  By virtue of their presence in the 
clinic and data abstraction and quality improvement activities from existing clinic registers and 
additional sources, project staff will view records of patients attending the various clinic units, 
including those not enrolled in the evaluation.  However, individual data from non-study 
participants will not be abstracted/collected for evaluation purposes.  All project staff will receive 
ethics training to ensure compliance with human subject research requirements.   

CaP TB ME Protocol Version 3.3 8th March 2021  
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Following the completion of the evaluation and all analyses, paper-based documents for all data 
collection activities, including the second yellow copy of the Cap TB form, will be stored for 
three years and then destroyed. The first white copy of the form will stay at requesting health 
facilities and will be kept according to local regulations.  Key patient information from the CaP 
TB form will also have to be recorded by the site personnel on NTP forms, registers, and patient 
files. 
 
 
XI. Ethical Considerations 
 
A. 
IRB Review 
This protocol will be reviewed by an Institutional Review Board (IRB) in the US and an ethical 
review committee in each of the ten project countries. The local ethics committees will also receive 
country-specific details about the evaluation. Participants will not be compensated.  
 
 
B. 
Ethics Training 
All EGPAF data collectors, monitoring and evaluation staff and management staff will be trained 
in research ethics prior to starting data abstraction and collection activities.   
 
 
C. 
Conflict of Interest 
The PIs and co-investigators listed on this protocol have no affiliations with or involvement in 
any organization or entity with any financial interest (such as honoraria, grants, employment, 
consultancies), or non-financial interest (such as personal or professional relationships, 
affiliations, knowledge or beliefs) in the subject matter or materials discussed in this protocol. 
  
D. 
Informed Consent  
The pre- and post- intervention, quantitative data abstraction is limited to data that are routinely 
documented as part of standard medical care and/or program services. The data will be abstracted 
from CaP TB project forms (Pediatric TB Intensified Case Finding Screening Tool or CaP TB 
Pediatric TB Form), registers, logbooks or rarely, patient files.  With the exception of the patient 
ID (if any), the TB treatment register number or the Preventative Therapy register number, no 
identifying information will be collected. This information will be encrypted before upload to the 
database. Only the health facility staff will have access to the identification number that links the 
ID or treatment register number to the child’s name and other identifiable patient information such 
as caregiver’s name and address.    
 
 
A waiver of informed consent is being requested for all patients whose data will be abstracted for 
the following reasons according to the U.S. Code of Federal Regulations (CFR 46.116(d)) XLII: 
1. “The research presents no more than minimal risk of harm to subjects;  

CaP TB ME Protocol Version 3.3 8th March 2021  
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2. The waiver or alteration will not adversely affect the rights and welfare of the subjects; 
and 
3. The research could not practically be carried out without the waiver or alteration”  
 
E. 
Risk and Benefits to Participants 
The pre- and post-intervention, quantitative data being abstracted for evaluation purpose are 
identifiable but it poses no more than minimal risk to pediatric patients receiving TB services and 
it is no greater than what they would experience during routine provision of these services. 
Potential, minimal risks include the unintended disclosure of TB status of children if the child is 
known to the data abstractor during data abstraction activities. The interventions the CaP TB 
project supports utilize quality-assured and WHO-recommended drugs and diagnostics that are in 
use in country and/or are part of country guidance and thus we view the risks of the CaP TB project 
itself to be of no greater risk to participants than that of receiving standard healthcare in the project 
countries.  
 
Potential benefits to participants include access to improved pediatric TB care, including improved 
access to WHO-recommended diagnostics and treatments. Potential benefits to society include 
identifying and resolving problems in the quality of pediatric TB care services sooner, providing 
information to MOH, other implementing partners and donors that may help to plan and prioritize 
more effective pediatric TB services. These improved services may lead to reduced morbidity and 
mortality associated with pediatric TB.   
 
F. 
Follow-Up  
Beyond standard care and treatment provided by CaP TB and the MOH, no additional follow up 
of patients is planned in this evaluation.  
 
XII. 
Dissemination of Results and Publication Policy 
Data abstracted or collected for this evaluation will be used to 1) Estimate project targets; 2) 
evaluate the effect of CaP TB as compared to standard of care pediatric TB services as well as to 
3) assess the effects of CaP TB during the continued scale up phase (years 3 and 4). Data will be 
abstracted/collected, analyzed and reviewed on a routine basis to inform program implementation 
and quality improvement activities, target setting and adjustments, internal and external reports, 
abstracts, presentations and international guidelines..  Findings will be shared across the project 
countries, with MOHs, with other implementing partners, with Unitaid and the WHO and the 
international community through semi-annual reports to the funder (Unitaid), grey literature, and 
publications in peer-reviewed journals, meetings and presentations. In order to perform cost-
effectiveness analysis, aggregated clinical data will be abstracted and shared with University of 
Sheffield. Unpublished data analysis and databases might be shared with WHO and with WHO’s 
collaborators that will be commissioned to compile and assess the evidence needed to support 
revisions of guidelines and policy formulation. Findings will also be shared through EGPAF data 
dashboards and website.  
 

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Data presented as part of study findings in papers or at conferences will not include any 
participants’ names, IDs or study identifiers. Only the names of project countries will remain 
identifiable if required.  
 
 
XIII. 
Problems Anticipated 
Implementation of the CaP TB project is dependent on the approval and continued support of the 
country MOHs and National TB Programs (NTPs). At the time of protocol drafting, the CaP TB 
project has been presented to the MOHs and National TB Programs in all ten countries and all 
country MOHs and NTPs are supportive. However, national MOHs and National TB Programs 
may withdraw support at any time which may affect the overall duration of the project.  The 
project is also dependent on the national procurement and supply chains to maintain an adequate 
supply of appropriate drugs and diagnostics. While the CaP TB project includes activities to 
strengthen procurement and supply chain systems, drug or diagnostic stock outs may occur. 
However, as this is an evaluation of a pragmatic program implemented in a “real-world” setting, 
documenting stock shortages or stock outs will be important to evaluating the feasibility of our 
project. Finally, political instability or other instability may interrupt project activities or data 
collection. At this point, project areas in all ten countries are sufficiently stable to allow for 
project activities and data collection, and the project and country team will continue to monitor 
the situation and plan accordingly.  
 
XIV. 
Project Management 
The Elizabeth Glaser Pediatric AIDS Foundation is responsible for protocol development and 
other study documents, overall conduct and management and the scientific integrity of the study. 
EGPAF will also serve as the liaison for communication and coordination with ethical review 
boards, the Ministry of Health in each project country, UNITAID and other stakeholders. The 
overall project management, including all aspects of the intervention, will be led by Dr. Jennifer 
Cohn, Senior Director of Innovations at EGPAF.  The day-to-day management of the project’s 
implementation will be managed by Mikhael de Souza, Project Director of CaP TB and Martina 
Casenghi, Technical Director of CaP TB. The data and program evaluation will be managed by 
Shirin Kakayeva, Strategic Information and Evaluation lead for the CaP TB project. Dr. Rhoderick 
Machekano is a Senior Biostatistician at EGPAF and will be responsible for developing of the 
statistical analysis plan, review and analysis of data, and contribute to the write up of study 
findings.  Each project country has a country implementation manager who will be responsible for 
the day-to-day management of activities, and a Senior Strategic Information and Evaluation officer 
who will manage day-to-day responsibilities for the project evaluation.  
 
 

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XV. 
Annex A: CaP TB Information System 
 
The CaP TB Database Entry Tool will abstract the information contained on, and matching the 
2nd page (blinded for patient personal details) of the CaP TB Pediatric TB Form.  We will use a 
combination of web/mobile App or Excel entry templates, both directly feeding into a unique 
database. Below are example of data flow in both models. A generic Excel based template of the 
CaP TB Database Entry Tool is provided as part of this protocol submission.  As the CaP TB 
Pediatric TB Form will be adapted by countries to align with country-specific requirements, the 
CaP TB Database Entry Tool will also be consequently adapted to a perfect match. 
 

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XLII US Code of Federal Regulations (46.116 (d); bolded by author): 
(d) An IRB may approve a consent procedure which does not include, or which alters, some or all of the elements of informed 
consent set forth in this section, or waive the requirements to obtain informed consent provided the IRB finds and documents that: 
 (1) The research involves no more than minimal risk to the subjects; 
 (2) The waiver or alteration will not adversely affect the rights and welfare of the subjects; 
 (3) The research could not practicably be carried out without the waiver or alteration; and 
 (4) Whenever appropriate, the subjects will be provided with additional pertinent information after participation. 
US Code of Federal Regulations (46.117; bolded by author): 
“(c) An IRB may waive the requirement for the investigator to obtain a signed consent form for some or all subjects if it 
finds either: 
 (1) That the only record linking the subject and the research would be the consent document and the principal risk 
would be potential harm resulting from a breach of confidentiality. Each subject will be asked whether the subject 
wants documentation linking the subject with the research, and the subject's wishes will govern; or 
 (2) That the research presents no more than minimal risk of harm to subjects and involves no procedures for which 
written consent is normally required outside of the research context.”