Implementing a Combination of Clinical Parameters (Rapid Diagnostic Tests (RDTs), Biomarkers, and Standard of Care Procedures (SoCs) for the Etiology Diagnoses of Pneumonia in Pediatric Patients to Improve Clinical Management in Indonesia.
Conditions: Pneumonia
Sponsor: INA-RESPOND Secretariat

 
 
PROTOCOL 
 
Protocol Number: INA-201 
 
 
RESEARCH TITLE: 
Implementing a Combination of Clinical Parameters 
(Rapid Diagnostic Tests, Biomarkers, and Standard of Care Procedures) for 
The Etiology Diagnoses of Pneumonia in Pediatric Patients to Improve Clinical 
Management in Indonesia 
 
(PEER-PePPes) 
 
 
 
Sponsored by: 
Partnerships for Enhanced Engagement in Research (PEER Health) 
Indonesia Research Partnership on Infectious Disease (INA-RESPOND) 
 
Confidentiality Statement: 
This document is confidential and is to be distributed for review only to investigators, potential investigators, 
consultants, study staff, and applicable independent ethics committees or institutional review boards. The 
contents of this document shall not be disclosed to others without written authorization from PEER Health or 
INA-RESPOND. 
 
 
Final Version 8.0 
Dated Mar 13, 2019

INA201 
Final Version 8.0 
13 Mar 19 
i 
 
TABLE OF CONTENTS 
TABLE OF CONTENTS................................................................................................................... i 
GLOSSARY ................................................................................................................................... 1 
RESEARCH SUMMARY ................................................................................................................ 2 
1. 
BACKGROUND .................................................................................................................... 4 
2. 
RESEARCH BENEFITS .......................................................................................................... 5 
3. 
OBJECTIVE .......................................................................................................................... 6 
3.1. 
Primary Objective ........................................................................................................ 6 
3.2. 
Secondary Objectives .................................................................................................. 6 
4. 
METHODS ........................................................................................................................... 7 
4.1. 
Study Plan .................................................................................................................... 7 
4.2. 
Study Sites and Duration ............................................................................................. 8 
4.3. 
Type and Design of Study ............................................................................................ 8 
4.4. 
Population and Sample Size ........................................................................................ 9 
4.5. 
Eligibility Criteria ......................................................................................................... 9 
4.5.1. 
Inclusion criteria................................................................................................... 9 
4.5.2. 
Exclusion criteria ................................................................................................ 10 
4.6. 
Study Procedures and Evaluations ............................................................................ 10 
4.6.1. 
Screening and enrollment .................................................................................. 10 
4.6.2. 
Baseline (study visit day 0 = day 1 hospitalization) ........................................... 10 
4.6.3. 
Follow up during hospitalization (Daily study visit day 1 up to day 12 = day .... 11 
2nd up to day 13th hospitalization) ................................................................................... 11 
4.6.4.   During discharge .................................................................................................. 12 
3.6.5. 
Follow up (Study Visit Day 14th after hospitalization) ....................................... 12 
3.6.6. 
Follow up (day 30th after hospitalization) .......................................................... 12 
3.6.7. 
Laboratory procedures for Molecular and Serological Testing ......................... 12 

INA201 
Final Version 8.0 
13 Mar 19 
ii 
 
4.7.  Study Withdrawal ......................................................................................................... 14 
4.8.  Study disposition status ............................................................................................... 14 
4.9.  Study Instruments ........................................................................................................ 15 
5. 
LABORATORY SPECIMENS AND BIOHAZARD CONTAINMENT ......................................... 15 
5.1. 
Universal Precaution and Biohazard Containment ................................................... 15 
5.2. 
Specimen Repository and Destruction ...................................................................... 16 
6. 
DATA MANAGEMENT AND ANALYSIS .............................................................................. 17 
6.1. 
Data Management .................................................................................................... 17 
6.2. 
Analysis ...................................................................................................................... 18 
6.3.  Operational Definitions ................................................................................................ 18 
7. 
REPORTING THE LOSS OR UNANTICIPATED DESTRUCTION OF SPECIMENS/ DATA TO THE 
IRB 19 
8. 
RESEARCH MONITORING ................................................................................................. 19 
9. 
SAFETY MONITORING AND REPORTING .......................................................................... 20 
9.1. Definition of an Adverse Event ..................................................................................... 20 
9.2. Definition of a Serious Adverse Event ........................................................................... 20 
9.3. Definition of Reportable Event ..................................................................................... 21 
9.4. Definition of an Unanticipated Problem ....................................................................... 21 
10. 
ETHICAL CONSIDERATION ............................................................................................. 21 
10.1.  
Informed consent process ..................................................................................... 21 
10.2.    Illiterate Subject’s parent or legal guardian .......................................................... 22 
10.3    
Parental Consent ................................................................................................... 22 
10.4.  
IRB Review ............................................................................................................. 22 
10.5. 
Participant Confidentiality ..................................................................................... 23 
10.6. 
Rationale for Subject Selection ............................................................................. 23 
10.7. 
Benefits .................................................................................................................. 23 

INA201 
Final Version 8.0 
13 Mar 19 
iii 
 
10.8.  
Risks and Discomforts ............................................................................................ 23 
10.9.  
Plan for Maintaining Privacy and Confidentiality of Subject Records ................... 24 
10.10  
Recording/Documentation .................................................................................... 24 
11. 
PROTECTION OF INTELLECTUAL PROPERTY (IPR), MATERIAL TRANSFER AGREEMENT 
(MTA), AND GENETIC RESOURCES AND TRADITIONAL KNOWLEDGE (GRTK) ......................... 25 
11.1. Publication and Dissemination Policy ......................................................................... 25 
11.2. Material Transfer Agreement ..................................................................................... 25 
11.3. Genetic Resources and Traditional Knowledge .......................................................... 26 
12. 
RESEARCH TEAM ........................................................................................................... 27 
13. 
APPROXIMATE TIMELINE OF PLANNED RESEARCH ACTIVITIES .................................... 30 
14. 
PRINCIPAL INVESTIGATOR’S CURICULUM VITAE .......................................................... 31 
15. 
REFERENCES .................................................................................................................. 33 
APPENDICES ............................................................................................................................. 35 
Appendix A. Laboratory Work Flow ..................................................................................... 35 
Appendix B. Science and Technology agreement between the Government of the Republic 
of Indonesia and the Government of the United States of America. .................................. 36 
Appendix C. SOP INA-RESPOND, Specimen Ownership, Access, and Use ........................... 48 
Appendix D: Guidelines for maximum blood draw for pediatric patients ........................... 50 
 
 

INA201 
Final Version 8.0 
13 Mar 19 
iv 
 
TABLE AND FIGURES 
Figure 1. The Study Plan............................................................................................................. 7 
Table 1. Laboratory Procedures for Molecular and Serological Testing ................................. 13 
Table 2. PCR Panel for Bacterial & Viral Pathogens ................................................................. 14 

INA201 
Final Version 8.0 
13 Mar 19 
1 
 
GLOSSARY 
AE 
Adverse Event 
AFB 
Acid Fast Bacilli 
CBC 
Complete Blood Count 
CRF 
Case Report Form 
CRP 
C-reactive protein 
EC 
Ethics Committee 
EDMS 
Electronic Data Management System 
FU 
Follow-Up 
GRTK 
Genetic Resources And Traditional Knowledge 
GCP 
Good Clinical Practice 
Hib 
Human Influenza Virus B 
HIV 
Human Immunodeficiency Virus 
ICF 
Informed Consent Form 
ICH 
International Conference on Harmonisation 
ICU 
Intensive Care Unit 
IgG 
Immunoglobulin G 
IgM 
Immunoglobulin M 
INA-RESPOND 
Indonesia Research Partnership on Infectious Diseases 
IPR 
Intellectual Property Rights 
IRB 
Institutional Review Board 
MoP 
Manual of Procedure 
MTA 
Material Transfer Agreement 
NPS 
Nasopharyngeal Swab 
NPV 
Negative Predictive Value 
PCR 
Polymerase Chain Reaction 
PCT 
Procalcitonin 
PPV 
Positive Predictive Value 
RA 
Research Assistant 
RDT 
Rapid Diagnostic Tests 
ROC 
Receiver Operating Characteristic 
RR 
Respiratory Rate 
RSV 
Respiratory Syncytial Virus 
SDW 
Source Document Worksheet 
SAE 
Serious Adverse Event 
SoC 
Standard of Care 
 
 

INA201 
Final Version 8.0 
13 Mar 19 
2 
 
RESEARCH SUMMARY 
Full title 
Implementing a Combination of Clinical Parameters (Rapid Diagnostic Tests (RDTs), 
Biomarkers, and Standard of Care Procedures (SoCs)) for the Etiology Diagnoses of 
Pneumonia in Pediatric Patients to Improve Clinical Management in Indonesia. 
Short title 
PEER PePPes (INA-201) 
Study type 
Prospective observational study 
Principal investigator 
Dr. Herman Kosasih, PhD  
Co-Principal investigator 
RSU Kabupaten Tangerang 
 
Dr. Dewi Lokida, SpPK 
 
Dr. Arif Budiman, SpA 
RS An Nisa  
Dr. Arif Budiman, SpA 
Dr. Chakrawati, SpPK 
RSUP Dr. Kariadi 
 
Dr. Helmia Farida, M.Kes, SpA, PhD 
 
Dr. M.S. Anam, MSi.Med, SpA 
     Dr. Dwi Wastoro, SpA (K) 
     Dr. Mujahidah, SpMK 
RSUD Dr. Adhyatma, MPH / RSUD Tugurejo 
     Dr. Helmia Farida, M.Kes, SpA, PhD      
     Dr. Setya Dipayana, SpA 
RS Bhakti Wira Tamtama 
     Dr. Helmia Farida, M.Kes, SpA, PhD      
     Dr. Setya Dipayana, SpA 
RSUP dr Sardjito 
     Dr. Rina Triasih, SpA(K) 
     Dr. Amalia Setyati, SpA(K) 
     Dr. Abu Tholib Aman, M.Sc., Ph.D, Sp.MK(K) 
RSA UGM 
    Dr. Rina Triasih, SpA(K) 
    Dr. Ade Febriana Lestari, M.Sc, Sp.A(K) 
Study objectives 
Primary objective 
 
To develop an algorithm for the diagnosis of viral and bacterial pathogens in pediatric 
 
patients with pneumonia.  
 

INA201 
Final Version 8.0 
13 Mar 19 
3 
 
Secondary objectives 
• To identify the etiologies of pneumonia in children in Indonesia, which are 
currently unavailable. 
• To document outcomes in pediatric patients with pneumonia in Indonesia.  
• To evaluate the performance of each rapid point of care test (to detect influenza 
and viral syncytial viruses, legionella urinary antigen, biomarkers of bacterial 
infections (C-Reactive Protein (CRP) and Procalcitonin (PCT)), and standard of care 
procedures (Chest X-ray) compared to the gold standard molecular assays in 
differentiating virus and bacterial infections. 
• To analyze the performance of combined tests in differentiating virus and bacterial 
infections. 
• To provide information regarding updated strains of circulating respiratory viruses 
and pathogens in children. 
Study Population 
Hospitalized patients with pneumonia whose ages range from 2 months to 5 years. 
Sample size 
The total sample is 275 participants. 
Study duration 
Study will accrue participants up to September 2019. Each participant will have follow up 
visits in a period of 30 days from the enrollment day.  
Eligibility criteria 
Inclusion criteria 
• Pediatric inpatients whose ages range from 2 months to 5 years 
• Meet the case definition for pneumonia which is cough or fever with at 
least one other following symptoms: 
 Shortness of breath  
 Tachypnea  
 Grunting 
 Crackles/rhonchi 
 Decreased vesicular breath sound 
 Bronchial breath sound 
 Chest x-ray consistent with pneumonia 
• Comply with all study procedures including to store required specimens 
for diagnostic testing and archiving. 
Exclusion criteria 
• Being Hospitalized for more than 24 hours at enrollment 
• Having a cancer or history of cancer 
• Having a history of long term exposed of steroid (at the minimum of 2 
months) 
• Having any condition that might interfere with study procedure and 
compliance (based on clinicians’ judgement) 

INA201 
Final Version 8.0 
13 Mar 19 
4 
 
Study Procedures 
Participants who meet the inclusion and exclusion criteria will be enrolled and then having 
a daily follow up for maximum of 13 days’ hospitalization. Next follow up will be taken time 
at day 14th after hospitalization date, either on ward or policlinic. The participations will be 
ended by day 30th after hospitalization date when the called follow up is done by the 
Research Assistant (RA).   
This study will collect demographic data, medical history, clinical data, treatment, and risk 
factors of pneumonia. The study also recorded the supporting examination results include 
but not limited to Complete Blood Count (CBC) results, blood gas analyses result, CRP, PCT, 
culture result, rapid test for influenza, Respiratory Syncytial Virus (RSV), legionella, and 
chest X-ray. In order to produce a robust data, this study will conduct the serological and 
molecular tests at the reference laboratory. 
Whole blood, serum, urine, Nasal Pharyngeal Swab (NPS), sputum/induced sputum, and 
other respiratory specimens (if available) will be collected for storage and testing at 
enrollment. Any left-over respiratory specimens and/ or plasma on day 2 and 3 of 
hospitalization will also be collected to be stored. For additional, at day 14th after 
hospitalization serum will be processed from 4 mL of blood for archiving and testing at the 
reference laboratory. 
1. BACKGROUND 
Pneumonia accounts for an estimated 920,136 fatalities or 16% of all deaths in children under 
five years of age.(1) Based on Indonesia National Basic Health Survey, period prevalence of 
pneumonia in children under 5 years is 18.5 per mil.(2) The high rate of morbidity in children 
with pneumonia may be prevented by promoting exclusive breastfeeding, vaccination, and 
an improved environment, whereas the mortality can be reduced by providing appropriate 
management including appropriate antibiotic treatment for bacterial infection which is now 
still very low (30%).(1) 
Diagnosing pneumonia using current WHO pneumonia diagnostic criteria is challenging as no 
one clinical feature is sufficient to diagnose pneumonia definitively. To improve diagnostic 
performance, a combination of clinical features has to be used. (3) Chest X-rays are neither 
sensitive nor specific. Radiological findings lag behind clinical findings and are unable to 
differentiate between viral and bacterial etiologies of pneumonia. Differentiation between 
viral and bacterial pathogens is becoming more important since the introduction of Hib and 
pneumococcal vaccines that may shift the substantial causes of pneumonia to viruses. (3) This 
distinction is also important for guiding appropriate antibiotic treatment. (4) The gold-standard 
for microbiological pathogen assays require specimens that are difficult to collect such as 

INA201 
Final Version 8.0 
13 Mar 19 
5 
 
nasopharyngeal wash or bronchoalveolar lavage and may need several days for the results to 
be available. 
Considering all the factors above, a combination of rapid diagnostic and biomarker tests, using 
non-invasive or relatively easily collected specimens, and standard of care procedures may 
help to differentiate between viral and bacterial pneumonia to better guide management 
(antiviral vs antibacterial treatment). 
2. RESEARCH BENEFITS 
This study will provide the data and algorithm to differentiating bacterial and viral 
pneumonia. This algorithm will be useful to transform the management of pneumonia cases 
and to determine the prevention strategies as well. Other benefit from this study is to obtain 
a better understanding of pathogen caused by pneumonia to provide the evidence that might 
change a clinical pathway, for example, for example, the identification of influenza or other 
viruses as the causes of pneumonia may have an impact on the perceptions of clinicians and 
health policy makers that these viruses may also cause severe illness and therefore antiviral 
should be provided. The importance of viral pathogens as the cause of pneumonia will also 
have an impact on the risk of nosocomial infection and the need of vaccination to health care 
workers and children. Thus, better understanding of identified pathogens, particularly the 
newly reported may bring us to new strains invention. Those benefits hopefully will give us 
the evidence to advice the policy maker, hospital management, and to increase the clinician 
awareness.  
 
 
 
 
 

INA201 
Final Version 8.0 
13 Mar 19 
6 
 
3. OBJECTIVE 
3.1. Primary Objective 
To develop an algorithm for the diagnosis of viral and bacterial pathogens in pediatric 
patients with pneumonia. 
3.2. Secondary Objectives 
• To identify the etiologies of pneumonia in children in Indonesia, which are currently 
unavailable. 
• To document outcomes in pediatric patients with pneumonia in Indonesia. 
• To evaluate the performance of each rapid point of care test (to detect influenza and 
viral syncytial viruses, legionella urinary antigen, biomarkers of bacterial infections 
(CRP and PCT), and standard of care procedures (Chest X-ray, O2 saturation, CBC, 
blood Gas Analyses (if available) compared to the gold standard molecular assays in 
differentiating virus and bacterial infections. 
• To analyze the performance of combined tests in differentiating virus and bacterial 
infections. 
• To provide information regarding updated strains of circulating respiratory viruses 
and pathogens in children. 
 
 
 
 
 
 
 
 
 

INA201 
Final Version 8.0 
13 Mar 19 
7 
 
4. METHODS 
4.1. Study Plan 
For brief explanation of the study plan please go to Figure 1, the study plan. 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Figure 1. The Study Plan 
Potential participants who meet these following criteria: 
Inclusion criteria 
•
Pediatric inpatients whose ages range from 2 months to 5 years. 
•
Meet the case definition for pneumonia which is cough or fever with at least one 
other following symptoms: 
Shortness of breath, marked by at least one of the following signs: head 
bobbing; nasal flaring; chest indrawing or intercostal retracting. 
Tachypnea (RR ≥40 /minute, for children 1 to 5 y.o, and RR ≥50 /minute, for 
children 2 to 12 m.o) 
Grunting 
Crackles/rhonchi 
Decreased vesicular breath sound 
Bronchial breath sound 
Chest x-ray consistent with pneumonia 
•
Comply with all study procedures including to store required specimens for 
diagnostic testing and archiving. 
Exclusion criteria 
•
Being Hospitalized for more than 24 hours at enrollment 
•
Having a cancer or history of cancer 
•
Having a history of long term exposed of steroid (at the minimum of 2 months) 
•
Having any condition that might interfere with study procedure and compliance 
Informed consent signed 
Baseline & Enrollment Procedures  
Daily Study Visit during hospitalization 
Procedures 
For maximum of 13 days’ hospitalization 
Study Visit Day 14th after 
hospitalization Procedures 
Follow-up Day 30th after hospitalization 
(End of study Procedures) 
Laboratory testing in the references 
lab. 

INA201 
Final Version 8.0 
13 Mar 19 
8 
 
4.2. Study Sites and Duration 
This study will be conducted at following INA-RESPOND sites:  
• RSU Kabupaten Tangerang, Tangerang 
• RSUP Dr. Kariadi, Semarang 
• RSUP Dr. Sardjito, Yogyakarta 
• RS An Nisa, Tangerang 
• RSUD Dr. Adhyatma, MPH / RSUD Tugurejo, Semarang 
• RS Bhakti Wira Tamtama, Semarang 
• RSA UGM, Yogyakarta 
Maximum duration for participants’ accrual will be up to September 2019. However, the 
study laboratory testing may take up to 6 months to be completed.  
4.3. Type and Design of Study 
This study is an observational study, conducted at the pediatric department at three 
hospitals in Indonesia. It will recruit hospitalized children aged between 2 months to 5 
years who meet the inclusion and exclusion criteria. Participants will be followed up for 
maximum 13 days’ hospitalization. At day 14th after hospitalization date each participant 
will be assessed for his/her symptoms, clinical data, clinical outcome, and serum specimen 
collection. The end of their participation will be ended on day 30th after hospitalization 
date, after followed up phone from RA.   
Laboratory test procedures will be conducted during the study and/or after study 
completion. Chest X-Ray, CBC, blood and respiratory specimen cultures including antibiotic 
resistance test will be performed either as part of standard of care or study addition. Rapid 
tests for Influenza A and B; Respiratory Syncytial Virus (RSV); and Legionella will be 
performed as study requirement. C-reactive protein (CRP) and Procalcitonin (PCT) will also 
be measured for study interest. Molecular assays to identify bacterial and viral pathogens 
and serological assays to detect infections of several viruses and bacteria will be conducted 
at the reference laboratory. Any left-over respiratory specimens and/or plasma from day 
2 and 3 hospitalization will be stored for archiving.  
Specimen that will be stored for archiving, will be maintained for further laboratory testing 
for up to 5 years after the study is completed. After 5 years, with the decision of Steering 

INA201 
Final Version 8.0 
13 Mar 19 
9 
 
Committee and Governing Board, specimens in the INA-RESPOND specimen repository in 
NIHRD Jakarta, will either be destroyed, or after IRB approval, transferred to another 
existing protocol or a repository. 
4.4. Population and Sample Size 
This is a preliminary study to characterize the pathogens present in this cohort. The 
number of participants’ that will be enrolled is based on the number of pneumonia cases 
in 5 years old children or less. This study plan to enroll with total of 275 participants.  
With 275 participants, the 95% confidence interval for the prevalence of each pathogen 
will be no greater than ± 7%. The study is not powered to test the diagnostic accuracy of 
the algorithm. The algorithm developed from this study will be evaluated in a larger study, 
powered to estimate sensitivity and specificity. As a result, no formal power calculations 
have been provided.  
4.5. Eligibility Criteria 
4.5.1. Inclusion criteria 
• Pediatric inpatients whose ages range from 2 months to 5 years. 
• Meet the case definition for pneumonia which is cough or fever with at 
least one other following symptoms: 
 Shortness of breath, marked by at least one of the following signs: 
head bobbing; nasal flaring; chest indrawing or intercostal 
retracting. 
 Tachypnea (RR ≥40 /minute, for children 1 to 5 years old, and RR 
≥50 /minute, for children 2 to 12 months old) 
 Grunting 
 Crackles/rhonchi 
 Decreased vesicular breath sound 
 Bronchial breath sound 
 Chest x-ray consistent with pneumonia 
• Comply with all study procedures including to store required specimens for 
diagnostic testing and archiving. 

INA201 
Final Version 8.0 
13 Mar 19 
10 
 
4.5.2. Exclusion criteria 
• Being hospitalized for more than 24 hours at enrollment 
• Having a cancer or history of cancer 
• Having a history of long term exposed of steroid (at the minimum of 2 
months) 
• Having any condition that might interfere with study procedure and 
compliance (based on clinicians’ judgement).  
4.6. Study Procedures and Evaluations 
4.6.1. Screening and enrollment 
Potential pediatric participants who come to the emergency room or 
outpatient clinic and have been admitted to the hospital will be referred by 
physicians at participating hospitals to be observed and screened according to 
the study eligibility criteria. If the patients meet the criteria, the parent/legal 
guardian will be offered information about the study. If agree, he/she must 
provide a documented informed consent form (ICF) and will undergo the 
enrollment procedures. Participants who have finished or completed the study 
can’t be re-screened and re-enrolled into the study. 
4.6.2. Baseline (study visit day 0 = day 1 hospitalization) 
Following baseline procedures will be collected on all participants, these 
include:  
1. Demographic data including age, sex, birth order, parent’s education, 
parent’s occupation, and family income. 
2. Medical history including history of mother’s pregnancy and breastfeeding, 
vaccination, vitamin A supplementation, growth and development, history 
of past and presence illness including congenital disease, and allergic. 
3. Clinical data including chief complaint, sign and symptoms, vital signs, 
anthropometric, initial diagnosed, comorbidities, chest X-Ray (if available).  
4. Treatment including antibiotic, steroid, and oxygen therapy. 
5. Risk factors including smoking exposure, TB contact, poultry contact 
(contact with sick and/or dead poultry and contact with poultry’s faeces 

INA201 
Final Version 8.0 
13 Mar 19 
11 
 
and/or derivative), contact with someone who has cold, air pollution 
exposure, going to daycare, living in a densely populated area.  
6. Laboratory examinations including CBC test, CRP, PCT, Blood gas analysis, 
blood culture, respiratory culture (if available), antimicrobial sensitivity 
test, HIV test, influenza rapid test, legionella Ag, Gram negative test, AFB, 
Xpert MTB/RIF (according to SoC). 
7. Laboratory examinations at the reference laboratory including molecular 
and serological tests. 
8. Specimen archiving including left over specimens (whole blood, serum, 
urine, NPS, sputum/induced sputum) and isolate from culture (if available) 
Whole blood and serum must be collected and processed during 24 hours after 
the enrollment. Other specimens’ collection can be postponed up to 48 hours 
after the enrollment.  
Blood culture should be performed on all participants prior to antibiotic 
administration in the study site, however any condition where blood culture is 
done after the antibiotic administer is still allowed. Blood culture worked prior 
to the enrollment will be recorded in the CRF and no repetition needed.  
For the detail of study procedures, please check out the Manual of Procedures 
(MoP). 
4.6.3. Follow up during hospitalization (Daily study visit day 1 up to day 12 = day  
    2nd up to day 13th hospitalization)  
This follow up schedule will be conducted daily during hospitalization of 
participants, but limited up to daily study visit day 12 (day 13th hospitalization). 
The following procedures will be collected from each participant, if available:  
1. Clinical data including sign and symptoms, vital signs, and chest X-Ray. 
2. On-going treatment 
3. Specimen archiving. Any respiratory left-over specimen and/or plasma 
from daily study visit day 1 & 2 (day 2 & 3 of hospitalization) will also be 
collected to be stored.   

INA201 
Final Version 8.0 
13 Mar 19 
12 
 
4.6.4.   During discharge 
Hospitalization and discharge information including complication, discharge 
diagnoses, and clinical outcome. Procedure will be collected at discharge day.  
3.6.5.  Follow up (Study Visit Day 14th after hospitalization) 
This study follow up will be conducted at day 14th after hospitalization. There 
will be ± 4-days window period for this follow up schedule. The following 
procedures will be collected from each participant, if available: 
1. Clinical data including sign and symptoms, vital signs, anthropometric, 
clinical outcome. 
2. Laboratory examinations at the reference laboratory including serological 
tests. 
3. Specimen archiving. Serum will be collected and stored.  
3.6.6. Follow up (day 30th after hospitalization) 
In this follow up schedule, the RA will conduct follow up by phone and the 
participants will be assessed for their self-reported health condition. If needed, 
home visit can be conducted for this visit. There will be ± 4-days window period 
for this follow up schedule. No specimen will be collected in this follow up. 
3.6.7. Laboratory procedures for Molecular and Serological Testing 
This study will carry out molecular and serological testing that will be done at 
the reference laboratory. The study will cover all the costs of those tests. 
Table 1 and Table 2 will furtherly explain the required specimen volume and 
tests needed. Also see appendix A for the work flow. 
 
 
 
 
 
 

INA201 
Final Version 8.0 
13 Mar 19 
13 
 
Table 1. The research specimen and laboratory testing 
 
Visit 
/Time 
Collected Specimen 
Amount 
Laboratory Testing at 
Hospital 
Reference Lab 
Enrollment (up to 
24 hours after 
enrollment) 
Whole Blood  
2 x 1 ml – 2 ml blood  
 
1 x 3 ml blood 
Blood culture (2 sides) 
CBC 
PCR (Streptococcus 
pneumonia, 
Staphylococcus aureus, 
Haemophilus influenza) 
Serum 
1 x 4 ml blood 
CRP, Procalcitonin, 
HIV (can be done up 
to 5 days after 
enrollment) 
Serology IgM and IgG 
(Influenza A, B, RSV, 
Parainfluenza virus, 
Adenovirus, Mycoplasma 
pneumonia, Chlamydia 
pneumonia, Bordetella 
pertussis, Legionella 
pneumonia) 
Enrollment 
(up to 48 
hours after 
enrollment) 
Urine 
1 ml – 3 ml urine 
Rapid test 
Legionella 
antigen 
PCR (Legionella 
pneumoniae, 
Leptospira) 
 
Nasopharyngeal 
swab 
2 VTM (1.5 ml) 
Rapid test 
Influenza 
Rapid test RSV 
 
PCR (18- Viral Panel) 
Sputum/induced 
sputum 
2 ml  
Culture, MTB 
(genexpert, if AFB 
positive) 
 
PCR (11 Bacterial and 
18 viral panel) 
Other resp specimen  (leftover – 
efusi pleura, BAL) 
If available 
Culture, MTB 
(genexpert, if AFB 
positive) 
 
PCR (11 Bacterial and 
18 viral panel) 
Daily study visit 
during 
hospitalization  
Left-over respiratory 
specimen and/or plasma 
(Daily study visit day 1 & 2 
(day 2 & 3 of hospitalization) 
 
If available 
None 
 
TBD 
Study Visit Day 
14th after 
hospitalization 
Serum 
4 ml blood 
None 
Serology IgM and IgG 
(Influenza A, B, RSV, 
Parainfluenza virus, 
Adenovirus, 
Mycoplasma 
pneumonia, Chlamydia 
pneumonia, Bordetella 
pertussis, Legionella 
pneumonia) 
Follow-up Day 
30th after 
hospitalization 
 
None 
None 
None 
None 
 
NOTE:  Maximum amount of blood drawn in pediatric patients weight 7.3 – 45.5 kgs is 10 
ml - 30 ml at any one time or 60 ml – 350 ml cumulative during hospitalization or maximum 
1 month (Garza D, Becan-McBride K).   
 
 
 

INA201 
Final Version 8.0 
13 Mar 19 
14 
 
 
Table 2. PCR Panel for Bacterial & Viral Pathogens 
 
 
 
 
 
 
 
 
 
 
 
4.7.  Study Withdrawal 
Participants may voluntarily withdraw from the study for any reason at any time. The 
Investigator also may withdraw participants from the study in order to protect their safety 
and/or if they are unwilling or unable to comply with required study procedures after 
consultation with the Research Team. 
Participants also may be withdrawn if the study sponsor, government or regulatory 
authorities, or Institutional Review Board (IRB) terminate the study prior to its planned end 
date. Every reasonable effort will be made to complete a final evaluation of participants 
who terminate from the study prior to the planned termination time period, and study site 
team will record the reason(s) for all withdrawals from the study in participants’ study 
records. 
4.8.  Study disposition status  
Study disposition status will be completed by the Research Assistant when the participants 
considered as end of study. Participants followed until 30 days after hospitalization will be 
considered as completing the study procedure and end of study. 
PCR Viral Panel 
PCR Bacterial Panel 
Human Influenza A virus 
Haemophilus influenza 
Human Influenza B virus 
Streptococcus  pneumoniae 
Adenovirus 
Legionella pneumoniae 
Enterovirus 
Mycoplasma  pneumoniae 
Respiratory Syncytial Virus A 
Chlamydia  pneumoniae 
Respiratory Syncytial Virus B 
Chlamydia psittaci 
Human Metapneumo virus 
Bordetella pertussis 
Rhinovirus 
Moraxela catharalis 
Human Parainfluenza Virus 1 
Staphylococcus aureus 
Human Parainfluenza Virus 2 
Klebsiella pneumoniae 
Human Parainfluenza Virus 3 
Burkholderia pseudomallei 
Human Parainfluenza Virus 4 
  
Corona Virus 22E 
Corona Virus OC43 
Corona Virus SARS 
Corona Virus NL63 
Parechovirus 
Bocavirus 

INA201 
Final Version 8.0 
13 Mar 19 
15 
 
 
The rest of the Participants will be considered as end of study at the following time point: 
• Participant is dead 
• Participant withdraws consent 
• Participant who can’t be reached for follow-up visit (lost to follow-up) 
• Based on investigator discretion 
• Termination of study 
4.9.  Study Instruments 
The following instruments will be used in this study. Further information will be found in 
the study MOP.  
a. Forms 
• Informed consent 
• Source Document Worksheet (SDW) 
• Case Report Form (CRF) 
b. Log 
• Screening log 
• Enrollment log 
• Specimen log 
 
c. Electronic Database 
• OpenClinica 
• Manual Specimen Repository Database 
• INA-RESPOND Electronic Data Management System (EDMS) 
 
5. LABORATORY SPECIMENS AND BIOHAZARD CONTAINMENT 
5.1. Universal Precaution and Biohazard Containment 
As the transmission of blood-borne pathogens and air-borne pathogens can occur 
through contact with contaminated needles, blood, respiratory specimens and its 
products, appropriate blood and secretion precautions will be employed by all personnel 

INA201 
Final Version 8.0 
13 Mar 19 
16 
 
in the drawing of blood, collecting respiratory specimen, shipping and handling of all 
specimens for this study. These will be further described in the study MoP.5.2 Specimen 
Collection and Aliquots 
Each study site will adhere to standards of good clinical laboratory practice and the study 
SOPs for specimen management including proper collection, processing, alliquoting, 
labeling, transport, and storage of specimens. In general, all laboratory procedures will be 
done locally in the study sites and in the reference laboratory for molecular and serological 
testing. These will be further described in the study MoP.  
Samples will be collected at baseline and some follow-up visits according to the study 
procedures. If available, specimens will be tested either on hospital laboratory or reference 
laboratory. Samples will be coded with a unique identifier that does not contain any 
information capable of linking the sample to the participant. A code that links the unique 
identifier with the study volunteer will be kept in a locked file cabinet in a secure room or 
on a password-protected computer. Only authorized personnel will have access to the 
code. 
Specimens from blood approximately will be divided into aliquot of 3. One will be stored 
at the site and two will be sent to the reference laboratory.  
5.2. Specimen Repository and Destruction 
Some of the specimens collect under this protocol would be stored for repository. Based 
on the clinical presentation and laboratory data, the researchers will determine further 
testing to be done on specimens from participants who are willing to allow storage of 
specimens for use in future studies of infectious disease. Upon this evaluation, researchers 
will develop a new protocol. Specimen will be maintained for further laboratory testing for 
up to 5 years after the study is completed. After 5 years, with the decision of Steering 
Committee and Governing Board, specimens in the INA-RESPOND specimen repository in 
NIHRD Jakarta, will either be destroyed, or after IRB approval, transferred to another 
existing protocol or a repository. The used and destruction of the archived specimens in 
the future, will be determined per INA-RESPOND SOP of Specimen Ownership, Access, and 
Use (see appendix C).   

INA201 
Final Version 8.0 
13 Mar 19 
17 
 
6. DATA MANAGEMENT AND ANALYSIS 
6.1. Data Management 
Participants’ data will be coded with a unique identifier that does not contain any 
information capable of linking the data to the study participants. A code that links the 
unique identifier with the study participants will be kept in a locked file cabinet in a secure 
room. Only authorized study personnel will have access to the code and the data. Data will 
be keyed and tracked using the OpenClinica.  
Data will be periodically sent to the INA-RESPOND Central Data Management Center. Site 
and national data will be analyzed by all investigators. The investigator is responsible for 
ensuring that the data collected is complete, accurate and recorded in a timely manner. 
Following each study visit, the investigator or designated site staff member will upload the 
completed Case Report Form (CRF) to INA-RESPOND EDMS. The data will then be entered 
into the database and reviewed for completeness and accuracy. The study team will be 
notified of any discrepancies for clarification. 
The study team should also complete accurate source documentation to support the data 
collected on the CRF. Source documents include all recordings of observations or notations 
of clinical activities and all reports and records necessary for the evaluation and 
reconstruction of the clinical study. Source documents include, but are not limited to, the 
participant’s medical records, laboratory reports, X-ray(s), radiologist reports, participant 
progress notes, pharmacy records and any other similar reports or records of procedures 
performed in accordance with the protocol. 
It is not acceptable for the CRF to be the only record of the participant’s participation in 
the study and participant progress should also be recorded in the participant medical 
records. This is to ensure that anyone who would access the participant’s medical records 
has adequate knowledge that the participant is participating in a clinical study. 
Any document that acts as a source document (the point of the initial recording of a piece 
of data) should be signed and dated by the person recording or reviewing the data for 
issues of medical significance (for example the review of laboratory reports). Persons 
signing the source documents should be listed as a site staff member. 

INA201 
Final Version 8.0 
13 Mar 19 
18 
 
6.2. Analysis 
An interim analysis will be conducted every 3-6 months to discuss the operation and 
challenges of the screening and enrollment process, the collection of data and specimens, 
and to analyze the results of bacterial culture, biomarkers, rapid diagnostic tests, 
molecular and serogical assays. 
It is expected that the gold standard measurements will fall into three categories: 
confirmed viral (33%), confirmed bacterial (20%), and mixed/unconfirmed (47%). For 
purposes of algorithm development and assessment, we will combine the latter two 
groups (confirmed bacterial and mixed/unconfirmed) into a single group. The justification 
for the grouping is that clinically, a patient who receives a mixed/unconfirmed diagnosis 
will likely be treated in the same manner as a patient with a confirmed bacterial diagnosis. 
As this is a preliminary study, we will fit the data using a variety of different approaches 
for combining diagnostic tests, including classification and regression trees, random 
forests, and multivariate logistic regression. For models with binary outputs, we will 
calculate the sensitivity and specificity (defined using confirmed bacterial as "cases" and 
confirmed viral as "controls"). For models with continuous outputs, we will calculate the 
receiver operating characteristic (ROC) curve. The relative performance of the models will 
primarily be evaluated based on sensitivity and specificity. 10-fold cross- validation or 
similar methods will be used to account for potential over optimism from fitting multiple 
models. 
While clinical relevance is of primary importance, we may also consider algorithms that 
perform three-category classifications (with the categories as originally defined), as such 
results may be of etiologic interest. Furthermore, for all analyses, we may consider 
calculating the positive predictive value (PPV) and negative predictive value (NPV); while 
sensitivity and specificity are of primary importance, PPV and NPV may provide further 
useful descriptive information. 
6.3.  Operational Definitions 
• Fever : temperature recorded ≥ 37.5°C during the first 24 hours period of 
hospitalization or at home. 
• Study specimens: specimens collected from study subjects. 

INA201 
Final Version 8.0 
13 Mar 19 
19 
 
• Respiratory samples: leftover respiratory samples (BAL, pleural fluid, etc) that are 
collected by the attending physician based on clinical presentation. 
• Study clinical data: clinical data collected from study subjects.  
• Study completion: Subjects followed until 30- days (± 4-days window period) after 
hospitalization or die. 
• Subject withdrawal: if the subject’s parents or legal guardians  decides to voluntarily 
discontinue participation or the study physician decides to terminate subject 
participation at any time during the study.  
• Missed visit: a scheduled study visit which a study subject fails to attend or a home 
visit does not occur. 
7. REPORTING THE LOSS OR UNANTICIPATED DESTRUCTION OF SPECIMENS/ 
DATA TO THE IRB 
Any loss or unanticipated destruction of data or samples (for example, due to freezer 
malfunction) that compromises the scientific integrity of the data collected for the study will 
be reported to the IRB. Additionally, participants may decide at any point not to have their 
samples stored. In this case, the principal investigator will destroy all known remaining 
samples and report what was done to both the participant and to the IRB. 
8. RESEARCH MONITORING 
The study will be conducted in compliance with this protocol, the International Conference 
on Harmonization (ICH) Guideline for Good Clinical Practice (GCP), and any applicable 
regulatory and ethical requirement(s). Independent monitors, under contract by the Sponsor, 
will visit the study sites to monitor all aspects of the study in accordance with the monitoring 
plan. The objective of a monitoring visit is to oversee the progress of the study, and of 
ensuring that it is conducted, recorded, and reported in accordance with the protocol, 
Standard Operating Procedures (SOPs), Good Clinical Practice (GCP), and the applicable 
regulatory requirement(s).   
Site investigators will allow study monitors to inspect study facilities and documentation (e.g., 
ICF, clinic and laboratory records, other source documents, CRFs), as well as observe the 
performance of study procedures. Investigators also will allow inspection of all study-related 

INA201 
Final Version 8.0 
13 Mar 19 
20 
 
documentation by authorized representatives of the local IRB or ethic committee (EC), the 
local and national regulatory authorities, and the sponsor representatives. A site visit log will 
be maintained at the study site to document all study monitoring and auditing visits. 
9. SAFETY MONITORING AND REPORTING 
All reportable adverse events (events that occur within 48 hours of the study specimen 
collection and are possibly, probably, or definitely related to the study specimen collection) 
that result in a serious outcome (Serious Adverse Event (SAE)) will be evaluated by Site PI 
within 24 hours of the investigator’s awareness.  The SAE will also be reported to the IRB 
within 10 working days, or follows on local ethic requirement, of the investigator’s 
awareness. 
All reportable adverse events (events that occur within 48 hours of the research blood draw 
and are possibly, probably, or definitely related to the research blood draw) will be reported 
in the summary form to the IRB at the time of Continuing Review.  
All reportable event (RE) and unanticipated problem (UP) will be reported by the site PI to 
the IRB within 10 working days, or follows on local ethic requirement, of the investigator’s 
awareness as required for US federally funded trials. 
9.1. Definition of an Adverse Event 
An adverse event (AE) is any untoward or unfavorable medical occurrence in a human 
subject that occurs within 48 hours of a study-related study blood specimen collection 
that is possibly, probably, or definitely related to the study specimen collection. Any event 
outside of this 48 hours’ window period will not be considered an AE for this study. 
But for induce sputum collection, if the subject’s conditions worsening from the original 
condition prior to the enrollmentis observed such as, but not limited to, increase in 
coughing or wheezing, it will be considered as AE for this study if  occurred within 2 hours 
after sputum induction procedure. For every AE that occurs based on the subject’s 
conditions, the RA needs to consult with the site PI or site Co-PI to determine AE or not. 
9.2. Definition of a Serious Adverse Event 
A serious adverse event (SAE) is defined as any AE related to study specimen collection 
that meet one / more of the seriousness criteria below: 

INA201 
Final Version 8.0 
13 Mar 19 
21 
 
 Death 
 Life-threatening (places the subject at immediate risk of death from the event as 
it occurred); 
 Requires in inpatient hospitalization (unplanned hospitalization) or prolongation 
of existing hospitalization; 
 Persistent or significant disability / incapacity; 
 Congenital anomaly/birth defect or fetal/neonatal death; or 
 Important Medical Event: Based on appropriate medical judgment, may 
jeopardize the subject’s health and may require medical or surgical intervention 
to prevent one of the other outcomes listed in this definition. 
9.3. Definition of Reportable Event 
A Reportable Event (RE) is defined as any event outside of an AE definition that meet 
one / more seriousness criteria as stated in the section 9.2. 
9.4. Definition of an Unanticipated Problem 
An unanticipated problem is defined as any incident, experience, or outcome that is 
defined as: 
1. Unexpected in terms of nature, severity, or frequency in relation to: 
 the research risks that are described in the research protocol and informed 
consent document or other study documents; and 
 the characteristics of the subject population being studied; and  
2. Related or possibly related to the participation in the research; and 
3. Places subjects or others at a greater risk of harm (including physical, psychological, 
economic, or social harm) than was previously known or recognized or is an SAE. 
10. ETHICAL CONSIDERATION 
10.1.  Informed consent process 
Informed consent is a process in which information is presented to enable persons to 
voluntarily decide whether or not to participate as a research subject. It is an ongoing 
conversation between the human research subject and the researchers covering the essential 

INA201 
Final Version 8.0 
13 Mar 19 
22 
 
information about the study which begins before consent is given and continues until the end 
of the subject’s involvement in the research.  
Their parents or legal guardians  will sign an ICF after discussion of essential information about 
the research by the study staff. This will include the purpose of the study, duration, 
procedures, alternatives, risks, and benefits. Subjects and/or their parents or legal guardians 
will have the opportunity to ask questions about the study and have their questions 
answered. 
Legal guardian is a person who has rights and responsibilities to look after / take care the 
child. They are usually related by blood, members of the family, or legal parents of an adopted 
child.  Neighbor, friends, or maid of the family cannot serve as the child’s legal guardian. 
Subject’s parent or legal guardian will sign/thumb print an appropriate informed consent 
document prior to any procedures being done specifically for the study. The subjects may 
withdraw consent at any time throughout the course of the trial. A copy of the informed 
consent document will be given to the subjects for their records. The researcher will 
document the signing of the consent form in each subject’s study record.  
10.2.    Illiterate Subject’s parent or legal guardian 
If the subject’s parent or legal guardian is illiterate, oral consent will be obtained. The 
administrator of the oral consent will sign and date the form. The subject’s parent or legal 
guardian will thumbprint the consent form. An impartial witness should be present during the 
entire informed consent discussion and should sign and date the consent form. 
10.3    Parental Consent  
Parental/legal guardian consent will be obtained for all study subjects. For further 
information, please refer to IRB checklist: studies involving children. 
10.4.  IRB Review 
Prior to the implementation of the protocol, the protocol and ICF for this study will be 
submitted for approval to the appropriate IRB. Any change to the protocol, ICF, or a change 
of the site investigator, will only be made after approval from the IRB. Records of the IRB 
review and approval of all the documents pertaining to the study will be kept on file by the 
site investigator and are subject to inspection at any time during the study. Continuing 

INA201 
Final Version 8.0 
13 Mar 19 
23 
 
reviews or study progress report will be submitted according to the requirement of the 
appropriate IRB, but once a year at a minimum. 
10.5. Participant Confidentiality 
All records will be kept confidential to the extent provided by the law. The study monitors and 
other authorized representatives may inspect all documents and records required to be 
maintained by the site investigator, including, but not limited to, medical records. Records 
will be kept in a locked cabinet, and all computer entry and networking programs will be done 
with coded numbers only. Clinical information, attributable to the subject, will not be released 
without written permission of the subject, except as necessary for monitoring by INA-
RESPOND and  the EC/IRB.  
10.6. Rationale for Subject Selection 
Children under age 2 month are excluded from participating in the study due to concerns 
regarding blood volume.  
10.7. Benefits 
This study is meant as a pilot study to provide knowledge on the etiology of pneumonia 
among hospitalized pediatric patients in study hospitals and to identify areas of potential 
research in the future. It may not provide direct benefit to participants. All test may help the 
physician to establish diagnose.  
The study will provide two blood cultures, sputum culture, CBC, CRP, Procalcitonin and rapid 
diagnostic test for Influenza, RSV, and Legionella as listed in section 4.6.6 and 4.6.7. 
Transportation costs and time compensation will be reimbursable up to Rp.150,000 for  study 
Visit Day 14th  after hospitalization. The study will not provide costs for routine care or 
hospitalization. 
10.8.  Risks and Discomforts 
This is a minimal-risk, observational study and does not involve experimental interventions. 
The only study intervention is a blood draw and all other procedures are considered as part 
of standard care for hospitalized pneumonia patients. 

INA201 
Final Version 8.0 
13 Mar 19 
24 
 
The hazards of blood drawing are minimal and consist of mild discomfort and or bleeding at 
the venipuncture site, bruising and rarely fainting and local infection. In case of any immediate 
serious side effect like fainting the patient will be stabilized by the study team if needed.  
The hazards of sputum collection are minimal and consist of mild discomfort when subjects 
tried to produce sputum to be collected. 
10.9.  Plan for Maintaining Privacy and Confidentiality of Subject Records 
The information obtained during the conduct of this clinical study is confidential. The results 
of the research study may be published according to the INA-RESPOND policy, but subject 
names or identities will not be revealed. To maintain confidentiality, study documents, 
including case report forms will be kept in locked filing cabinets, in a secure room at each 
clinical research site. 
10.10  Recording/Documentation 
At each contact with the subject, assessment information will be elicited by appropriate 
questioning and examination, and they will be recorded on source documents. Source 
documents may include worksheets, progress notes, laboratory reports, consult notes, and 
data collection tools. Data is to be transcribed onto CRFs from source documents on an 
ongoing basis during the study. The study monitor may review and audit all documents and 
records required to be maintained by the site investigator.   
Any type of corrections to study documents should be initialed and dated by the person who 
is making the correction. The site investigator is responsible for ensuring that the data 
collected are complete, accurate, and recorded in a timely manner. All CRFs should be 
reviewed by the site investigator and signed as required with written signature. CRFs will be 
maintained and kept in locked cabinets at the site for at least 5 years after study completion. 
Each subject’s name will be paired with a numeric code in the enrollment log. Access to data 
identifying subjects will be kept in a locked file, accessible only by study staff. Finally, the 
importance of subject confidentiality will be impressed upon all research staff. The site 
investigator is responsible for the accuracy and completeness of the data reported.  

INA201 
Final Version 8.0 
13 Mar 19 
25 
 
11. 
PROTECTION OF INTELLECTUAL PROPERTY (IPR), MATERIAL TRANSFER 
AGREEMENT (MTA), AND GENETIC RESOURCES AND TRADITIONAL 
KNOWLEDGE (GRTK) 
11.1. Publication and Dissemination Policy 
Publication of the results of this study will be governed by the INA-RESPOND publication 
policy. Any presentation, abstract, or manuscript will be made available for review by the 
supporters prior to submission. 
Publication and dissemination will be guided by the IPR terms as outlined in Article X and 
Annex I of the Science and Technology agreement between the Government of the 
Republic of Indonesia and the Government of the United States of America. Article X 
(Protection of Intellectual Property) states: 
1. Provisions for the protection and distribution of intellectual property created or 
furnished in the course of cooperative activities under this Agreement are set forth in 
Annex I, which shall form an integral part of this Agreement.  
2. Scientific and technological information of a non-proprietary nature resulting from 
cooperation under this Agreement (other than information which is not disclosed for 
commercial or industrial reasons) shall be made available, unless otherwise agreed, to 
the world scientific community through customary channels and in accordance with 
normal procedures of the participating agencies and entities.  
and under Paragraphs III.A and III.B(1), (2)(a), (2)(b), (2)(c) of Annex I, Intellectual 
Protection Rights, of the Science and Technology agreement between the Government of 
the Republic of Indonesia and the Government of the United States of America. 
11.2. Material Transfer Agreement 
Research materials used in the collaborations under this protocol may, on agreement of 
the participants, be transferred using Material Transfer Agreements (MTAs) as appropriate 
in the particular collaborations, as outlines in Article VIII of the Science and Technology 
Agreement. 

INA201 
Final Version 8.0 
13 Mar 19 
26 
 
11.3. Genetic Resources and Traditional Knowledge 
The collection, conservation and exchange of genetic resources and associated traditional 
knowledge under this protocol shall be subject to Article VI of the S and T Agreement and 
will be based on the following considerations: 
• Obtaining informed consent from appropriate authority/institutional review board 
prior to accessing genetic resources collected during the conduct of this protocol.  
• Equitably sharing the benefits arising from the use of traditional knowledge and genetic 
resources.  
The complete Science and Technology agreement between the Government of the 
Republic of Indonesia and the Government of the United States of America is in Appendix 
B. 
 

INA201 
Final Version 8.0 
13 Mar 19 
27 
 
12. RESEARCH TEAM 
ROLE 
NAME, INSTITUTION 
& LOCATION 
EXPERTISE 
CONTACT INFORMATION 
Principal 
Investigator 
dr Herman Kosasih, PhD 
INA-RESPOND, Jakarta 
Infectious 
Disease 
Phone: 0816 1182 072 
Email: 
hermaninarespond@gmail.com 
US 
Collaborator 
Dr Cliff Lane, M.D. 
NIH, Bethesda, Maryland, 
USA 
NIAID Deputy 
Director for 
Clinical 
Research & 
Special Projects
Phone: +1301 4967 196 
Email: clane@niaid.nih.gov 
US 
Collaborator 
Dr Sophia Siddiqui, MPH 
NIAID, Bethesda, 
Maryland, USA 
Public Health 
Phone: +1301 496 7196 
Email: 
Sophia.siddiqui@nih.hhs.gov 
Co-Principal 
Investigator  
dr. Dewi Lokida, SpPK 
RSU Kab. Tangerang, 
Tangerang 
Pathology Clinic 
Phone: 0816 620 605 
Email: lokidadewi@yahoo.com 
Co-Principal 
Investigator 
dr. Arif Budiman, SpA 
RSU Kab. Tangerang, 
Tangerang 
Pediatrician 
Phone: 0817 0871 080 
Email : abud_817@yahoo.com 
Co-Principal 
Investigator 
dr. Chakrawati 
Hayuningsih, Sp.PK, 
MARS 
RS An Nisa, Tangerang 
Pathology Clinic 
Phone: 08128343367 
Email : chakrawati_h@yahoo.com 
 
Co-Principal 
Investigator 
dr. Helmia Farida, MKes, 
SpA, PhD 
RSUP Dr Kariadi, 
Semarang 
RSUD Dr. Adhyatma, 
MPH / RSUD Tugurejo, 
Semarang 
RS Bhakti Wira Tamtama, 
Semarang 
Pediatrician 
Phone: 0812 2521 7878 
Email: 
helmia_farida@yahoo.com 
Co-Principal 
Investigator 
dr. M.S. Anam, MSi.Med, 
SpA 
RSUP Dr Kariadi, 
Semarang 
Pediatrician 
Phone: 0815 654 3014 
Email: 
msanamped2010@gmail.com 
Co-Principal 
Investigator 
Dr. Dwi Wastoro, SpA (K) 
RSUP Dr Kariadi, 
Semarang 
Pediatrician 
Phone: 0812 2908 023 
Email: dwiwastoro@gmail.com 

INA201 
Final Version 8.0 
13 Mar 19 
28 
 
ROLE 
NAME, INSTITUTION 
& LOCATION 
EXPERTISE 
CONTACT INFORMATION 
Co-Principal 
Investigator 
Dr. Mujahidah, SpMK 
RSUP Dr Kariadi, 
Semarang 
Microbiologist 
Phone: 081325882184 
Email: ida_khamidi@yahoo.com  
Co-Principal 
Investigator 
Dr. Setya Dipayana, SpA 
RSUD Dr. Adhyatma, 
MPH / RSUD Tugurejo, 
Semarang 
RS Bhakti Wira 
Tamtama, Semarang 
 
Pediatrician 
Phone: 081325388788 
Email: doktersetya@gmail.com 
Co-Principal 
Investigator 
dr. Rina Triasih, SpA(K) 
RSUP dr Sardjito, 
Yogyakarta 
RSA UGM, Yogyakarta 
Pediatrician 
Phone: 0813 9276 4269 
Email: rina_triasih@yahoo.com 
Co-Principal 
Investigator 
Dr. Amalia Setyati, 
SpA(K) 
RSUP dr Sardjito, 
Yogyakarta 
Pediatrician 
Phone: 0816 685 510 
Email: amaliasetyati@gmail.com 
Co-Principal 
Investigator 
Dr. Abu Tholib Aman, 
M.Sc., Ph.D, Sp.MK(K) 
RSUP dr Sardjito, 
Yogyakarta 
Microbiologist 
Phone: 0815 7880 0042 
Email: abutholibaman@ugm.ac.id 
Co-Principal 
Investigator 
Dr. Ade Febriana Lestari, 
M.Sc, Sp.A(K) 
RSA UGM, Yogyakarta 
Pediatrician 
Phone: 0811 256 147 
Email: adefebrina@gmail.com 
 
INA- 
RESPOND 
Investigator 
Dr M Karyana, MKes 
NIHRD, Jakarta 
Public Health 
Phone: 0816 789 817 
Email: mkaryana@gmail.com 
 

INA201 
Final Version 8.0 
13 Mar 19 
29 
 
ROLE 
NAME, INSTITUTION & 
LOCATION 
EXPERTISE 
CONTACT INFORMATION 
Laboratory 
Team 
Specialist 
dr Srilaning Driyah, MSi.Med, 
SpPK 
NIHRD, Jakarta 
 
Ungke Antonjaya, SSi,  
M Biomed 
INA-RESPOND, Jakarta 
 
Wahyu Nawang Wulan, 
MAppSc 
INA-RESPOND, Jakarta 
 
 
Deni Pepy Butarbutar, SSi 
INA-RESPOND, Jakarta 
 
 
 
Rizki Amalia, AMAK 
INA-RESPOND, Jakarta 
 
 
dr Nurhayati, MEpid 
INA-RESPOND, Jakarta 
 
 Pathology Clinic 
 
 
 
Molecular 
Biology 
 
 
Molecular 
Biology 
 
 
 
Biology 
 
 
 
 
Biology 
 
 
 
Public Health 
Phone: 0813 3006 7086 
Email: laninglitbang@gmail.com 
 
 
Phone: 0818 400 021 
Email: ungkeajy@gmail.com 
 
 
Phone: 0858 8100 1497 
Email: 
wwahyunawang@gmail.com 
 
Phone: 0857 7109 9282 
Email: 
denipepy_rentina@yahoo.com 
Phone: 0812 8720 6603 
Email: amalia17.sari@gmail.com 
Phone: 0811 972 1903 
Email:  
unurhayati@ina-respond.net 
Data 
Manager/ 
Statistician 
Kanti Laras, SSi, MKes 
INA-RESPOND, Jakarta 
 
Lori E Dodd, PhD 
NIAID, Bethesda, Maryland, 
USA 
 
Jason Liang, PhD 
NIAID, Bethesda, 
Maryland, USA 
Public Health 
 
Statistician 
 
 
 
Statistician 
Phone : 0812 8030 425 
Email : klaras@ina-respond.net 
 
 
Email: doddl@niaid.nih.gov  
 
Email: Jason.liang@nih.gov 
 

INA201 
Final Version 8.0 
13 Mar 19 
30 
 
13. APPROXIMATE TIMELINE OF PLANNED RESEARCH ACTIVITIES 
 
2017 
2018 
2019 
J 
F 
M 
A 
M 
J 
J 
A 
S 
O 
N 
D 
J 
F 
M 
A 
M 
J 
J 
A 
S 
O 
N 
D 
Protocol & ICF 
development 
X 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
IRB submission & 
approval 
 
X 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Site feasibility, 
assessment 
X 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Study Preparation 
X 
X 
X 
X 
X 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Study duration 
 
 
 
 
 
 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Patient recruitment 
 
 
 
 
 
 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
 
 
 
 
 
 
Specimen and Data 
collection 
 
 
 
 
 
 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
 
 
 
 
 
 
Interim Analysis 
 
 
 
 
 
 
 
 
 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
 
 
 
 
 
 
Data Analysis 
 
 
 
 
 
 
 
 
 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Data Dissemination 
& Publication 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
X 
X 
X 
X 
X 
X 
X 
X 
X 
 

INA201 
Final Version 8.0 
13 Mar 19 
31 
 
 
14. PRINCIPAL INVESTIGATOR’S CURICULUM VITAE 
 
Herman Kosasih 
Jl Percetakan Negara VB no 8, Jakarta Pusat 
Indonesia 
 62-8161182072  
HKosasih@ina-respond.net 
 
 
Experience 
 
Scientific Lead, Indonesia Research Partnership on Infectious Diseases (INA-
RESPOND)  
October 2010-now, INA RESPOND, Jakarta, Indonesia 
 
Secretary for the “WHO CC for influenza at the human and animal interface” 
establishment team 
October 2010-September 2011, NIHRD, Ministry of Health, Indonesia 
 
 
Medical Research Scientist, Head of Clinical Studies, Viral Diseases Program 
August 1998-May 2010,  NAMRU#2, Jakarta, Indonesia 
 
 
Medical Advisor 
January 1998-August 1998,  PT Darya Varia Laboratoria, (Pharmaceutical 
Company) Jakarta, Indonesia 
 
 
Head of Primary Health Center 
July 1996-December 1997,  Puskesmas Dieng Kulon, Banjarnegara, Central 
Java, Indonesia 
 
Head of Primary Health Center 
February 1992-August 1993,  Puskesmas Wawo Utara, Bima, NTB, Indonesia 
 

INA201 
Final Version 8.0 
13 Mar 19 
32 
 
Education 
2014: PhD, Radboud University, Nijmegen, The Netherlands 
2009: Emerging Infectious Disease Certificate, Iowa University 
2008: Post Graduate Certificate  in Medical Virology, Liverpool University, UK (by 
distance) 
2002: Summer Training in Epidemiology, Erasmus University, Rotterdam, The 
Netherlands 
1990: Medical Doctor, Padjadjaran University, Bandung, Indonesia 
 
 
Organization 
Indonesia Medical Association 
 
 
References 
Dr Kevin R Porter, NMRC, Silver Spring, US 
Patrick J Blair, PhD, NHRC, San Diego, US 
Prof Dr. David M Muljono, PhD, Eijkman Institute, Jakarta, Indonesia 
Dr. Bachti Alisjahbana, PhD, Medical Research Center, Padjadjaran 
University, Bandung, Indonesia 
 
Peer-review 
publication 
Detection and identification of coxsackievirus B3 from sera of an Indonesian patient with 
undifferentiated febrile illness. Wiyatno A, Antonjaya U, Ma'roef CN, et al. J Infect Dev Ctries. 
2016 Aug 31;10(8):880-3 
 
Case report: Weil's disease with multiple organ failure in a child living in dengue endemic 
area. Lokida D, Budiman A, Pawitro UE,et al.BMC Res Notes. 2016 Aug 15;9(1):407. 
 
Comparison of the Hemagglutination Inhibition Test and IgG ELISA in Categorizing Primary 
and Secondary Dengue Infections Based on the Plaque Reduction Neutralization Test. 
Lukman N, Salim G, Kosasih H, et al.  Biomed Res Int. 2016;2016:5253842 
 
Global Influenza B Study. Temporal Patterns of Influenza A and B in Tropical and Temperate 
Countries: What Are the Lessons for Influenza Vaccination? PLoS One. 2016 Mar 31;11(3) 
Caini S, Andrade W, Badur S, et al. 
 
The Epidemiology, Virology and Clinical Findings of Dengue Virus Infections in a Cohort of 
Indonesian Adults in Western Java. PLoS Negl Trop Dis. 2016 Feb 12;10(2) Kosasih H, 
Alisjahbana B, Nurhayati, et al. 
 
Study of viremic profile in febrile specimens of chikungunya in Bandung, Indonesia. J Clin 
Virol. 2016 Jan;74:61-5. Riswari SF, Ma'roef CN, Djauhari H, et al. 
 
Epidemiological and virological characteristics of Influenza B: results of the global influenza 
B study. Influenza Other Respir Viruses. 2015 Aug;9 Suppl 1:3-12. Caini S, Huang QS, Ciblak MA, 
et al; Global Influenza B Study. 
 
INA-RESPOND: a multi-centre clinical research network in Indonesia. Health Res Policy Syst. 
2015 Jul 29;13:34. 
 
Karyana M, Kosasih H, Samaan G, Tjitra E, Aman AT, Alisjahbana B, Fatmawati, Gasem MH, 
Arif M, Sudarmono P, Suharto, Merati TP, Lane C, Siswanto, Siddiqui S. 

INA201 
Final Version 8.0 
13 Mar 19 
33 
 
15. REFERENCES 
1. WHO. http://www.who.int/mediacentre/factsheets/fs331/en/. 2016. 
2. Rambaud-Althaus C, Althaus F, Genton B, D'Acremont V. Clinical features for 
diagnosis of pneumonia in children younger than 5 years: a systematic review and meta-
analysis. The Lancet infectious diseases. 2015;15(4):439-50. 
3. Qazi S, Were W. Improving diagnosis of childhood pneumonia. The Lancet Infectious 
Diseases. 2015;15(4):372-3. 
4. WHO. Technical bases for the WHO recommendation on the management of 
pneumonia in children at first-level health facilities. 1991. 
5. Corless CE, Guiver M, Borrow R, Edwards-Jones V, Fox A, Kaczmarski E. Simultaneous 
detection of Neisseria meningitidis, Haemophilus influenzae, and Streptococcus 
pneumoniae in suspected cases of meningitis and septicemia using real-time PCR. 
Journal of clinical microbiology. 2001;39(4):1553-8. 
6. Heddema ER, Beld MG, De Wever B, Langerak A, Pannekoek Y, Duim B. Development 
of an internally controlled real‐time PCR assay for detection of Chlamydophila psittaci 
in the LightCycler 2.0 system. Clinical microbiology and infection. 2006;12(6):571-5. 
7. Reischl U, Lehn N, Sanden GN, Loeffelholz MJ. Real-Time PCR Assay Targeting IS481of 
Bordetella pertussis and Molecular Basis for Detecting Bordetella holmesii. Journal of 
clinical microbiology. 2001;39(5):1963-6. 
8. Pitcher D, Chalker VJ, Sheppard C, George RC, Harrison TG. Real-time detection of 
Mycoplasma pneumoniae in respiratory samples with an internal processing control. 
Journal of medical microbiology. 2006;55(2):149-55. 
9. Gadsby N, McHugh M, Russell C, Mark H, Morris AC, Laurenson I, et al. Development 
of two real-time multiplex PCR assays for the detection and quantification of eight key 
bacterial pathogens in lower respiratory tract infections. Clinical Microbiology and 
Infection. 2015;21(8):788. e1-. e13. 
10. Novak RT, Glass MB, Gee JE, Gal D, Mayo MJ, Currie BJ, et al. Development and 
evaluation of a real-time PCR assay targeting the type III secretion system of 
Burkholderia pseudomallei. Journal of clinical microbiology. 2006;44(1):85-90. 
11. Jansen RR, Schinkel J, Koekkoek S, Pajkrt D, Beld M, de Jong MD, et al. Development 
and evaluation of a four-tube real time multiplex PCR assay covering fourteen 

INA201 
Final Version 8.0 
13 Mar 19 
34 
 
respiratory viruses, and comparison to its corresponding single target counterparts. 
Journal of Clinical Virology. 2011;51(3):179-85. 
12. Beld M, Minnaar R, Weel J, Sol C, Damen M, van der Avoort H, et al. Highly sensitive 
assay for detection of enterovirus in clinical specimens by reverse transcription-PCR with 
an armored RNA internal control. Journal of clinical microbiology. 2004;42(7):3059-64. 
13. Garza D, Becan-McBride K, Phlebotomy Handbook: Blood collection Essentials, 
Seventh Edition  
14. Heather J Zar, David Hanslo, Patricia Apolles, et.al. Induced sputumversus gastric 
lavage for microbiological confirmation of pulmonary tuberculosis in infants and young 
children: a prospective study. Lancet. 2005; 365: 130-34. 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

INA201 
Final Version 8.0 
13 Mar 19 
35 
 
APPENDICES 
Appendix A. Laboratory Work Flow  
Enrollment Visit 
Clinical Data collection (Demography, vital 
sign, initial information, oxygen therapy, signs 
and symptoms, pregnancy, vaccination and  
breast-feeding history, history of antibiotic 
and steroid administration, medical history, 
risk factors history, Chest X-ray, hematology, 
chemistry result, culture result, microscopic 
and Rapid test result, antibiotic sensitivity, 
collected and stored specimen) 
 
Specimen collection for study: whole blood, Serum, 
Nasopharyngeal swab, Sputum/induced sputum, Urine, and 
isolate from culture (if available). 
 
Lab testing: 
a. SOC: Blood culture and culture from respiratory specimen 
b. Study required:  
- At the hospital: CBC, CRP, Procalcitonin, HIV, Rapid 
Diagnostic Test (Influenza A&B, RSV, Legionella) 
- At reference lab:  
• 
PCR (Streptococcus pneumonia, Staphylococcus 
aureus, Haemophilus  influenzae, Legionella 
pneumoniae, Leptospira, 18- Viral panel, 11 
bacterial panel) 
• 
Serology IgM and IgG (Influenza A,B, RSV,  
Parainfluenza virus, Adenovirus, Mycoplasma 
pneumoniae, Chlamydia pneumoniae, Bordetella 
pertussis, Legionella pneumoniae ) 
 
 
 
Daily Study Visit during hospitalization  
for maximum of 13 days’ hospitalization 
Clinical data collection:  
-Daily: vital signs, signs and symptoms, chest x-ray, oxygen 
therapy, hematology, blood gas analysis, hematology, stored 
leftover specimen 
-At discharge: Hospitalization information, clinical outcome at 
discharge 
Specimen collection: If available store 
left-over respiratory specimens from 
daily study visit day 1 & 2 (day 2 & 3 of 
hospitalization) 
 
 
 
Study Visit Day 14th after hospitalization  
Clinical data collection (vital sign, signs and 
symptoms, clinical outcome during day 14, 
collected specimen) 
Specimen collection: serum 
Lab testing at reference lab : 
• 
Serology IgM and IgG (Influenza A, B, RSV,  
Parainfluenza virus, Adenovirus, Mycoplasma 
pneumoniae, Chlamydia pneumoniae, Bordetella 
pertussis, Legionella pneumoniae ) 
 
 
 
Follow-up Day 30th after hospitalization 
Clinical Data collection (Outcomes)  
 
 
 
 
Study Outcome Analysis 

INA201 
Final Version 8.0 
13 Mar 19 
36 
 
Appendix B. Science and Technology agreement between the Government of the Republic 
of Indonesia and the Government of the United States of America. 
 
 

INA201 
Final Version 8.0 
13 Mar 19 
37 
 
 

INA201 
Final Version 8.0 
13 Mar 19 
38 
 
 

INA201 
Final Version 8.0 
13 Mar 19 
39 
 
 

INA201 
Final Version 8.0 
13 Mar 19 
40 
 
 

INA201 
Final Version 8.0 
13 Mar 19 
41 
 
 

INA201 
Final Version 8.0 
13 Mar 19 
42 
 
 

INA201 
Final Version 8.0 
13 Mar 19 
43 
 
 

INA201 
Final Version 8.0 
13 Mar 19 
44 
 
 

INA201 
Final Version 8.0 
13 Mar 19 
45 
 
 

INA201 
Final Version 8.0 
13 Mar 19 
46 
 
 

INA201 
Final Version 8.0 
13 Mar 19 
47 
 
 

INA201 
Final Version 8.0 
13 Mar 19 
48 
 
Appendix C. SOP INA-RESPOND, Specimen Ownership, Access, and Use 
 

INA201 
Final Version 8.0 
13 Mar 19 
49 
 
 
 
 

INA201 
Final Version 8.0 
13 Mar 19 
50 
 
Appendix D: Guidelines for maximum blood draw for pediatric patients 
 
Patient’s Weight 
Pounds 
Patient’s Weight 
Kilograms (approx.) 
Maximum Amount 
to be drawn at any 
one time (mL) 
Maximum Amount of 
blood–cumulative to be 
drawn during a given 
hospital stay (1 month or 
less-mL) 
6-8 
2.7-3.6 
2.5 
23 
8-10 
3.6-4.5 
3.5 
30 
10-15 
4.5-6.8 
5 
40 
16-20 
7.3-9.1 
10 
60 
21-25 
9.5-11.4 
10 
70 
26-30 
11.8-13.6 
10 
80 
31-35 
14.1-15.9 
10 
100 
36-40 
16.4-18.2 
10 
130 
41-45 
18.6-20.5 
20 
140 
46-50 
20.9-22.7 
20 
160 
51-55 
23.2-25.0 
20 
180 
56-60 
25.5-27.3 
20 
200 
61-65 
27.7-29.5 
25 
220 
66-70 
30.0-31.8 
30 
240 
71-75 
32.3-34.1 
30 
250 
76-80 
34.5-36.4 
30 
270 
81-85 
36.8-38.6 
30 
290 
86-90 
39.1-40.9 
30 
310 
91-95 
41.4-43.2 
30 
330 
96-100 
43.6-45.5 
30 
350 
 
Reference: Becan-McBride, K., Phlebotomy Handbook - Blood Collection Essentials, 
Seventh Edition 
 

Page 1 of 7 
 
Implementing a Combination of Clinical Parameters 
(Rapid Diagnostic Tests, Biomarkers, and Standard of Care Procedures) 
for the Etiology Diagnoses of Pneumonia in Pediatric Patients to Improve Clinical 
Management in Indonesia 
 
Protocol Number: 
INA201 
Site Number: 
[insert site number] 
Protocol Title: 
Implementing a Combination of Clinical Parameters 
(Rapid Diagnostic Tests, Biomarkers, and Standard of 
Care Procedures) 
for the Etiology Diagnoses of Pneumonia in Pediatric 
Patients to Improve Clinical Management in Indonesia 
Subject Name 
 
 
 
(Subject’s full name in CAPITAL LETTER 
Protocol Principal 
Investigator: 
Site PI Name: 
Name: [insert Site PI's name]  
Address:   [insert site address] 
Telephone number: [insert Site PI's contactable phone 
number(s)]  
 
INTRODUCTION 
 
We invite your child to take part in a pneumonia study. The doctor in charge of this study 
at this site is (<<insert name of Site Investigator>>). Before you decide if you want your 
child to be a part of this study, we want you and your child to know about the study.  
 
This is an information sheet. It gives you and your child information about the study. The 
study staff will inform you and your child about the study. You and your child are free to 
ask questions about this study at any time. If you agree that your child may take part in 
this study, you will be asked to sign the consent form. You will get a copy of the information 
sheet and informed consent of this study.  
 
 
 
 
 
 
WHY IS THIS STUDY BEING DONE? 

Page 2 of 7 
 
The purposes of this study are: to develop a procedure for diagnosing pneumonia, to 
identify the causes of pneumonia in children in Indonesia and to evaluate the performance 
of each rapid diagnostic test. Results of this study will be beneficial because until now the 
causes of pneumonia in children are currently unavailable in Indonesia. This study may 
help better diagnosing pneumonia to better guide management.  
 
WHAT WILL HAPPEN TO MY CHILD IN THIS STUDY? 
 
1. Screening 
This evaluation will be conducted to see whether your child is eligible to take part in   
this study. The screening evaluation will take about 15 minutes. 
 
Your child may be enrolled into this study if he/she has meet the following criteria: 
• He/she is between 2 months of age to 5 years old  
• He/she has cough OR fever and at least one sign of lung infection 
• Willing to follow all study procedure including allowing researcher to store and use 
his/her biological specimen for testing 
 
However your child may not be enrolled into this study if: 
• He/she has been hospitalized for more than 24 hours 
• He/she has received intravenous antibiotic 
• He/she has history of cancer or long term (at the minimum of 2 months) use of 
steroid 
• Based on clinicians’ judgement, the minimum required specimens are not 
possible to be collected 
• They have any condition which might interfere with the compliance of the study.  
 
 
If you agree to your child joining this study, you will be asked to sign this informed consent.  
 
2. Entry (This evaluation may be combined with the Screening evaluation) 
This evaluation may take about 30 minutes. At this evaluation, your child will have the 
following done:  
• We will check your child’s blood pressure, pulse, respiratory rate, temperature, 
signs and symptoms and your child will have a physical exam, unless these are 
already done by the doctor treating your child.  
• About 8-10 mL (approximately two to three teaspoon) of your child’s blood will be 
drawn for culture testing, CRP, Procalcitonin and Complete Blood Count (CBC). 
You and your child will be told the results of this test as soon as this information 
becomes available. The remaining specimen will be drawn for future research 
tests. All of these samples will be taken to the hospital laboratories or specimen 
repository for storage and analysis. We cannot ensure that you will be told the 
results of the research done on these samples.  
• Besides blood, respiratory specimens and urine are also required for this study. 
These will be collected by trained laboratory technician for culture tests, rapid 

Page 3 of 7 
diagnostic tests for some pathogens.  You and your child will be told the results of 
this test as soon as this information becomes available. The remaining respiratory 
specimens will be stored for future research tests. 
• Nasopharyngeal swab will be performed this way: Your child will be asked to cough 
before the test begins and then tilt your head back. A sterile cotton-tipped swab is 
gently passed into your nose. The swab is quickly rotated and removed. The 
sample is sent to a laboratory for rapid diagnostic test. You and your child will be 
told the results of this test as soon as this information becomes available. The 
remaining specimen will be stored for future research tests. 
 
• Sputum induction will be performed if your child unable to produce sputum 
spontaneously. Your child will inhale fluid for around 30 minutes. Then the sputum 
will be collected while your child cough or by mucus extractor. This procedure can 
be repeated once again to reach sufficient amount of sputum. 
• The doctor treating your child may decide to collect other biological samples 
(sputum, induced sputum, urine, pleural fluid, others) to determine why your child 
is sick. If some of the samples are left after the necessary testing, we will store for 
our study. These samples may be tested to look for infection caused by viruses 
and bacteria or parasites. We cannot ensure that you will be told the results of the 
research done on these samples.  
 
3. Daily Follow-Up Visit 
During daily follow-up at the hospital, daily clinical data will be collected until discharged 
from the hospital or up to maximum 14 days of hospitalization. Left over blood will be 
stored for the study from day 3 hospitalization.  
4. Next Study Follow-Up Visits (These evaluations may be performed at this hospital 
site or your home): 
 
a. Day 14 Visit (One Visit) Post Enrollment  
This visit may take about 30 minutes. At this visit, your child will have the following 
done:  
• We will check your child’s blood pressure, pulse, respiratory rate, 
temperature, signs and symptoms. 
• About 4 mL (approximately two teaspoons) of blood will be drawn for future 
research tests.    
 
b. At 30 days Post Enrollment 
We will contact or visit you to ask about your child condition. No specimen is taken 
at this visit. 
 
4. Stored Samples and Future Research  
At entry and Day 14 visits, respiratory specimens and blood will be collected for this 
research. The remaining specimens may be used for future research. 
 
 
 

Page 4 of 7 
HOW MANY PEOPLE WILL TAKE PART IN THIS STUDY? 
 
About 200 children will take part in this study. 
 
HOW LONG WILL MY CHILD BE IN THIS STUDY?  
 
Your child will be in this study for one month.  
 
WHY WOULD THE DOCTOR TAKE MY CHILD OFF THIS STUDY EARLY? 
 
You may withdraw your child from the study at any time. Your child will not be asked for 
further information or blood samples.  
 
The study doctor may need to take your child off the study early without your permission 
if: 
• The study is cancelled or terminated by the sponsors or the site’s Institutional 
Review Board (IRB)/Ethics Committee (EC).  
• You and your child are not able to attend the study visits as required by the study. 
• Continuing the study may be harmful to your child. 
 
 
WHAT ARE THE RISKS OF THE STUDY? 
 
The researchers believe that the risks or discomforts to your child are minimal and 
includes the risks associated with obtaining blood, nasopharyngeal swab and induced 
sputum.  Blood drawing will cause slight pain and redness or bruising at the site where 
the blood is drawn and in rare cases, fainting.  Bruising may be alleviated by a warm 
compress.  There is a very small chance the site where the blood is drawn may become 
infected.  This is unlikely since the person drawing the blood will clean the site with alcohol 
before blood is taken and use a sterile blood drawing material. In Nasopharyngeal swab 
procedure your child may gag a little or feel some pressure or discomfort. Your child’s 
nose may feel irritated or bleed a little bit after the procedure. A humidifier may ease these 
symptoms. In sputum induction procedure your child may produce excessive sputum and 
gag a little. But these events are rare.    
 
 
 
WHAT OTHER CHOICES DOES MY CHILD HAVE BESIDES THIS STUDY? 
 
The alternative is not having your child participate in this study. If you decide not to have 
your child participate in this study, your physician will still provide similar treatment for 
your child’s pneumonia. 
 
 
 
 

Page 5 of 7 
ARE THERE BENEFITS FOR MY CHILD TO TAKE PART IN THIS STUDY? 
 
The study will pay for the blood and sputum culture testing and other important diagnostic 
testings described in the protocol. You and your child’s transportation costs and time 
compensation will be reimbursed for up to Rp 150,000 per visit (at enrollment and follow-
up visit day 14), The study will not provide costs for routine care or hospitalization. The 
results of this study may help your child’s clinician to provide better treatments and 
improve the management of pneumonia.  
WILL WE RECEIVE ANY PAYMENT? 
You and your child will not receive any payments for taking part in this study.   
 
WHAT ABOUT CONFIDENTIALITY? 
 
All information about your child will be kept confidential and will not be shared with anyone 
who is not responsible for their care. Your child’s medical record will only be reviewed by 
those who are working on this study.   
 
All the research documents and samples will be labeled using your child’s study number. 
Your child’s name will not be used for labeling samples and your child’s name will not 
appear in study related reports or scientific publications.  
 
WHAT HAPPENS IF MY CHILD IS INJURED? 
 
We will provide immediate medical care for study related injuries e.g. an infection where 
blood has been taken. The study cannot pay for long term disability that may have 
resulted from the subject’s illness.   
 
 
WHAT ARE MY CHILD’S RIGHTS AS A RESEARCH PARTICIPANT? 
 
Your child’s participation in this study is completely voluntary.  If you do not want your 
child to participate, your child will still get standard treatment.  You may discontinue your 
child’s participation in this study at any time you choose.  
 
We will tell you and your child about new information from this or other studies that may 
affect your child’s health, welfare, or willingness to stay in this study.  If you want the 
results of the study, let the study staff know. 
 
 
 
 

Page 6 of 7 
WHAT DO I DO IF I OR MY CHILD HAS QUESTIONS OR PROBLEMS? 
 
If you or your child has questions regarding this study, you may contact:  
 
[Site PI’s name & Phone number] 
[Site Co-PI’s name & phone number] 
[Research assistant’s name & phone number]  
 

Page 7 of 7 
 
Implementing a Combination of Clinical Parameters (Rapid Diagnostic Tests, 
Biomarkers, and Standard of Care Procedures) for the Etiology Diagnoses of 
Pneumonia in Pediatric Patients to Improve Clinical Management in Indonesia 
 
I have read the study information sheet or this information sheet has been read to me. I 
have had the opportunity to ask questions about it and any questions I have asked have 
been answered to my satisfaction. I have been explained that I have the right to withdraw 
my child from the study at any time. 
 
I freely and voluntarily choose my child to participate in this study. I will be given a copy 
of this information sheet and signed consent form to keep for my reference.  
 
 
Child’s Name: __________________________________     Age: __________ 
 
 
 
Parental relationship or legal custodianship with the child: ____________________ 
 
Name of Parent/Legal Guardian: _________________ 
 
Signature*: __________________________                Date: ____/____/____                                        
 
                                                                   (dd/mm/yy)       
   
 
 
 
 
 
            Time of Consent: ____________                     
 
*A thumb print can be used if the person cannot write. 
 
 
Name of the Investigator: _________________   Signature: ______________________    
 
Date: ____/____/____                             
   Time of Consent: ________________                  
             (dd/mm/yy) 
 
 
Name of Witness: _______________________      Signature*:__________________    
 
Date: ____/____/____                    
Time of Consent: _________________                        
             (dd/mm/yy)