Community Based Safety Study of 2-drug (Diethylcarbamazine and Albendazole) Versus 3-drug (Ivermectin, Diethylcarbamazine and Albendazole) Therapy for Lymphatic Filariasis
Phase: NA
Conditions: Lymphatic Filariasis
Sponsor: Washington University School of Medicine

“Community Based Safety and Efficacy Study of 2-drug (Diethylcarbamazine and 
Albendazole) versus 3-drug (Ivermectin, Diethylcarbamazine and Albendazole) 
Therapy for Lymphatic Filariasis in Indonesia” 
Protocol Identifier: DOLF_IDA_Indonesia 
Type: Community Based Mass Drug Administration 
Project Principal Investigator(s): Gary Weil, MD, Washington University, USA 
Christopher King, MD, PhD, MPH, Case Western Reserve University, USA 
Study Principal Investigators: Peter U. Fischer1, PhD (USA) and Taniawati Supali2, PhD 
(Indonesia) 
Study Co-Investigators: Yenny Djuardi, MD, PhD2 (Indonesia), Gary J. Weil, MD1 (USA), Philip 
Budge, MD, PhD1 (USA) 
1 Infectious Diseases Division, Department of Medicine, Washington University School of 
Medicine, St. Louis, MO, USA 
2 Department of Parasitology, Faculty of Medicine, Universitas Indonesia, Jakarta 
Initial Protocol:  v1.0   5 April 2016 
Amendment 1:   v2.0   22 May 2016 
Amendment 2: v3.0 27 July 2016 
Amendment 3: v4.0 30 Aug 2016 
Amendment 4: v5.0 24 May 2017 
 
 

 
 
DOLF_IDA_Indonesia_Protocol v5.0_24May17 
 
Page 1 of 39 
 
INVESTIGATOR AGREEMENT 
“Community Based Safety Study of 2-drug (Diethylcarbamazine and Albendazole) 
versus 3-drug (Ivermectin, Diethylcarbamazine and Albendazole) Therapy for 
Lymphatic Filariasis in Indonesia” 
DOLF_IDA_Indonesia: v5.0   24 May 2017 
I have read the protocol, including the appendices, and I agree that it contains all necessary 
details for me and my staff to conduct this study as described.  I will conduct this study as 
outlined and make a reasonable effort to complete the study within the time designated. 
I will provide all study personnel, participating in the study under my supervision copies of the 
protocol and access to all study related information provided by the DOLF project. I will discuss 
with them to ensure they are full informed about the study drug(s) and the study procedures. 
Project Principle Investigator: ___________________________________________    
 
                        Name/Title  (Print/Type) 
 
Signed:  
Date: 
 
NOTE:  Both the Project PI and local PI should have signed investigator agreements on file.   
 
 

 
DOLF_IDA_Indonesia_Protocol v5.0_24May17 
 
Page 2 of 39 
INVESTIGATOR AGREEMENT 
“Community Based Safety Study of 2-drug (Diethylcarbamazine and Albendazole) 
versus 3-drug (Ivermectin, Diethylcarbamazine and Albendazole) Therapy for 
Lymphatic Filariasis in Indonesia” 
DOLF_IDA_Indonesia: v5.0   24 May 2017 
I have read the protocol, including the appendices, and I agree that it contains all necessary 
details for me and my staff to conduct this study as described.  I will conduct this study as 
outlined and make a reasonable effort to complete the study within the time designated. 
I will provide all study personnel, participating in the study under my supervision copies of the 
protocol and access to all study related information provided by the DOLF project. I will discuss 
with them to ensure they are full informed about the study drug(s) and the study procedures. 
Local Principle Investigator: ___________________________________________    
 
                         
 
Signed:  
Date: 
 
NOTE:  Both the Project PI and local PI should have signed investigator agreements on file.   
 
 

 
DOLF_IDA_Indonesia_Protocol v5.0_24May17 
 
Page 3 of 39 
 
TABLE OF CONTENTS 
 
TABLE OF CONTENTS ..................................................................................................... 3 
LIST OF ABBREVIATIONS ................................................................................................ 6 
1 
PROTOCOL SUMMARY ......................................................................................... 8 
2 
BACKGROUND INFORMATION AND RATIONALE ............................................. 11 
2.1 
Country Specific Background ................................................................................ 12 
3 
POTENTIAL RISKS AND BENEFITS.................................................................... 13 
3.1 
Risks of Blood Draw ............................................................................................. 13 
3.2 
Risks of Study Drugs ............................................................................................ 13 
3.3 
Potential Participant and Community Benefit ........................................................ 13 
3.4 
Participant Participation and Cost ......................................................................... 14 
3.5 
Compensation for Injury ........................................................................................ 14 
4 
STUDY DESIGN AND OBJECTIVES.................................................................... 15 
4.1 
Study Objectives ................................................................................................... 15 
4.1.1 
Secondary Objectives ............................................................................... 15 
4.2 
Study Design ........................................................................................................ 15 
4.3 
Study Screening and Enrollment ........................................................................... 15 
4.4 
Preparatory Activities ............................................................................................ 16 
4.5 
Hospital-Based Treatment .................................................................................... 16 
4.6 
Community-Based Treatment ............................................................................... 17 
4.7 
Social Mobilization ................................................................................................ 17 
4.8 
Household Enumeration, Census and Geo-Referencing ....................................... 17 
4.9 
Pre-Treatment Assessment Team ........................................................................ 17 
4.10 
Inclusion and Exclusion Criteria ............................................................................ 17 
4.11 
Pregnant Females ................................................................................................ 18 
4.12 
Informed Consent ................................................................................................. 18 
4.13 
Plan for Inclusion of Non-Bahasa Indonesia Speaking Individuals ........................ 18 
4.14 
Baseline Survey .................................................................................................... 19 
4.15 
Screening for Filarial Antigenemia, Antibodies and Microfilaria ............................. 19 
4.16 
Assessment of Efficacy of IDA vs DA on STH (including Strongyloides by 
qPCR) 20 
4.17 
Randomization ...................................................................................................... 20 
4.18 
Withdrawal ............................................................................................................ 21 
4.19 
Efficacy and Effectiveness of IDA vs DA ............................................................... 21 
4.20 
Retreatment .......................................................................................................... 21 
4.21 
Guidelines for Stopping the Trial ........................................................................... 22 
4.22 
Triple Drug Regimen Acceptability ........................................................................ 22 
5 
INVESTIGATIONAL PRODUCT ........................................................................... 23 
5.1 
Study Drug Background ........................................................................................ 23 
5.2 
Product Supply and Storage ................................................................................. 24 

 
DOLF_IDA_Indonesia_Protocol v5.0_24May17 
 
Page 4 of 39 
6 
STUDY PROCEDURES/EVALUATIONS/SCHEDULE ......................................... 25 
6.1 
Triple Drug Therapy (IDA) and Two-Drug Therapy (DA) ....................................... 25 
6.2 
Overall Study Schedule and Timeline ................................................................... 25 
7 
SAFETY REPORTING AND SAFETY MONITORING .......................................... 26 
7.1 
Definitions ............................................................................................................. 26 
7.2 
Assessment of Adverse Events ............................................................................ 27 
7.3 
Serious Adverse Event (SAE) Assessment and Management .............................. 27 
7.4 
Country Specific SAE Reporting Requirements .................................................... 28 
7.5 
Reporting of Pregnancy ........................................................................................ 28 
7.6 
Safety Monitoring by the Oversight Committee ..................................................... 28 
8 
CLINICAL MANAGEMENT OF EVENTS .............................................................. 29 
8.1 
Adverse Event Monitoring and Management ........................................................ 29 
8.1.1 
Mild Localized Symptoms .......................................................................... 29 
8.1.2 
Moderate to Severe Localized Adverse Events ......................................... 29 
8.1.3 
Moderate to Severe Systemic Adverse Events .......................................... 30 
8.2 
Rapid Response Teams for Management of Adverse Events ............................... 30 
9 
STATISTICAL CONSIDERATIONS ...................................................................... 31 
9.1 
Safety 31 
9.2 
Efficacy 31 
9.3 
Enrolling Additional Participants ............................................................................ 31 
10 
DATA HANDLING/RECORD KEEPING/SOURCE DOCUMENTS ....................... 32 
10.1 
Types of Data Collected ........................................................................................ 32 
10.2 
Study Records Retention ...................................................................................... 33 
10.3 
Source Documents ............................................................................................... 33 
11 
RESPONSIBILITIES ............................................................................................. 34 
11.1 
Investigator Responsibilities.................................................................................. 34 
11.1.1 Good Clinical Practice ............................................................................... 34 
11.2 
Institutional Review Board (IRB)/Ethics Committee (EC) ...................................... 34 
11.3 
Informed Consent ................................................................................................. 34 
11.3.1 Informed Consent Training ........................................................................ 34 
11.3.2 Country Specific ICF Information ............................................................... 35 
11.4 
Participant Privacy ................................................................................................ 35 
11.5 
Data Ownership .................................................................................................... 35 
12 
PUBLICATION POLICY ........................................................................................ 36 
13 
LITERATURE REFERENCES .............................................................................. 37 
14 
LIST OF APPENDICES......................................................................................... 39 
APPENDIX 1: Study Flow Diagram (Country Specific) ..................................................... 1 
APPENDIX 2: Participant Enrollment Form ...................................................................... 1 
APPENDIX 3: Participant Monitoring Form [Example] ...................................................... 1 
APPENDIX 4: Guide to Assigning Adverse Event Severity .............................................. 1 
APPENDIX 5: Adverse Event Evaluation and Report Form (AEERF) [Example] .............. 1 
APPENDIX 5a: Required Reporting & Guidelines for SAE(s) ............................................. 1 
APPENDIX 6A: Informed Consent Form (V.3, 30 August 2016) ......................................... 1 
APPENDIX 6B: Informed re-Consent Form (V.1, 24 may 2017) ......................................... 1 

 
DOLF_IDA_Indonesia_Protocol v5.0_24May17 
 
Page 5 of 39 
APPENDIX 7: Protocol for a treatment ACCEPTABILITY STUDY FOLLOWING THE 
TRIPLE DRUG COMMUNITY SsAFETY tRIALS .................................................... 1 
APPENDIX 8: Acceptability Survey for community respondents [example] .............. Error! 
Bookmark not defined. 
APPENDIX 9: Topic guide – focus group discussion on the acceptability of ida 
[example] ................................................................................................................ 1 
APPENDIX 10: Topic guide – In depth interviews with key informants for acceptability 
of ida [example] ...................................................................................................... 1 
Appendix 11: Visitation Matrix ............................................................................................ 1 
 
 
 
 
 

 
DOLF_IDA_Indonesia_Protocol v5.0_24May17 
 
Page 6 of 39 
 
LIST OF ABBREVIATIONS 
 
GENERAL PROJECT ABBREVIATIONS 
AE 
Adverse Event/Adverse Experience 
AEERF 
Adverse Event Evaluation and Report Form 
AFC 
Anti-Filariasis Campaign 
Ag 
antigenemia 
ALB 
Albendazole 
CDD 
Community Drug Distributor 
CRF/eCRF 
Case Report Form also referred to as eCRF (electronic case report form) 
CRO 
Contract Research Organization 
DA 
Two Drug Therapy (dyethilcarbamzine and albendazole)  
DEC 
Diethylcarbamazine 
DOLF 
Death for Onchocerciasis and Lymphatic Filariasis 
DOT 
Directly Observed Treatment 
DSMB, DSRB or DMC 
Data and Safety Monitoring Board also called Data Safety Review Board or  
Data Monitoring Committee 
EC 
Ethics Committee (may also be called IRB or Institutional Review Board) 
EDC 
Electronic Data Capture 
FTS 
Filariasis Test Strip 
GCP 
Good Clinical Practice 
GPELF 
Global Programme to Eliminate Lymphatic Filariasis 
GPS 
Global Positioning System 
ICF 
Informed Consent Form 
ICH 
International Conference on Harmonization 

 
DOLF_IDA_Indonesia_Protocol v5.0_24May17 
 
Page 7 of 39 
IDA 
Triple Drug Therapy (Ivermectin, Diethylcarbamazine,and Albendazole) 
IMA 
IMA World Health 
IRB 
Institutional Review Board (may also be called EC) 
IVM 
Ivermectin 
KAP 
Knowledge, Attitude and Practices 
LF 
Lymphatic Filariasis 
MDA 
Mass Drug Administration 
MF 
Microfilaria(e) 
Mg 
Milligram 
NTD 
Neglected Tropical Diseases 
NLM 
National Library of Medicine 
PHM 
Public Health Midwife 
PI 
Principal Investigator 
SAE 
Serious Adverse Event/Serious Adverse Experience 
SOP 
Standard Operating Procedure 
STH 
Soil transmitted helminthes 
TAS 
Transmission Assessment Surveys 
UNID 
Unique Study Identification Numbers 
UR 
University of Ruhuna 
USAID 
United States Agency for International Development 
WHO 
World Health Organization 
 
COUNTRY SPECIFIC ABBREVIATIONS 
 
UI 
 
Universitas Indonesia 

 
DOLF_IDA_Indonesia_Protocol v5.0_24May17 
 
Page 8 of 39 
1 
PROTOCOL SUMMARY 
Study Title: 
Community Based Safety Study of 2-drug (Diethylcarbamazine 
and Albendazole) versus 3-drug (Ivermectin, Diethylcarbamazine 
and Albendazole) Therapy for Lymphatic Filariasis in Indonesia 
Type of Study: 
Mass Drug Administration 
Population: 
IDA/ Triple Drug Arm: participants more than or equal to 5 years 
of age 
DA/ Dual Drug Arm (DA): participants more than or equal to 5 
years of age 
Number of Treated 
Areas: 
Treated areas include Flores (Flores Timur District, Ojandetun 
village, B. timori MF prevalence 8.6%) and Sumba (Sumba Barat 
Daya District, Karang Inda, Kahale, and Rada Malando villages, 
B. timori MF prevalence 6.5%) islands that are mainly endemic 
for B. timori. 
Duration of Participant 
Participation 
Single treatment with daily adverse event follow-up thru Day 7, 
then a long-term follow-up visit at 1 year. Hospital-based 
participants will be observed in hospital for the first 48 hours. 
Some participants may also be selected for follow-up at 1 month 
for stool collection, or follow-up at 2-4 months for an acceptability 
survey.  
 
 
Study Drugs 
Ivermectin (3 mg tablets)  *not included in two drug arm 
treatment 
Diethylcarbamazine (100 mg tablets) 
Albendazole (400 mg tablets) 
Primary Objectives: 
Determine the safety profile of triple-drug therapy by measuring 
frequency, type, and severity of adverse events following triple 
drug therapy (IVM+DEC+ALB) compared to the standard two 
drug treatment (DEC+ALB) in infected and uninfected individuals 
in a community  
Compare the efficacy of IDA (3 drug therapy) to DA (2 drug 
therapy) administered in communities for clearance of MF and  
filarial antibody for Brugia timori. 
Secondary Objectives: 
 
Assess the effect of intensity of filarial infection on the frequency 
and severity of adverse events 

 
DOLF_IDA_Indonesia_Protocol v5.0_24May17 
 
Page 9 of 39 
Compare community acceptance of Mass Drug Administration 
with three drug vs two drug therapy 
To compare the efficacy of DA vs IDA on soil-transmitted 
helminthes (STH) 
DOLF Project 
This protocol is specific to Indonesia, but results will also be 
included in the larger DOLF project.  Data will be 
available/reviewed at a country level and at the project level.  

 
DOLF_IDA_Indonesia_Protocol v5.0_24May17 
 
Page 10 of 39 
STUDY DESIGN 
General Flow Diagram: 
 
DOLF_IDA_Indonesia Study 
ARM 1 
Sample Size: 2000 
Triple Drug 
ARM 2 
Sample Size: 2000 
Two Drug 
NOTE: A Study Flow Diagram specific for Indonesia is provided in Appendix 1.  
Community Teams: 
Consent and Screen 
 
 
Review 
Eligibility 
Triple Drug 
(IDA) 
Two Drug 
(DA) 
Clinical and AE Assessment 
Data Entered into 
EDC 
Demography/Physical Exam 
  
BR, FTS, MF Survey, Study Drug Administration 
  

 
DOLF_IDA_Indonesia_Protocol v5.0_24May17 
 
Page 11 of 39 
2 
BACKGROUND INFORMATION AND RATIONALE 
In 2000, the World Health Organization (WHO) launched the Global Programme to Eliminate 
Lymphatic Filariasis (GPELF) to eliminate lymphatic filariasis as a public health problem by 
2020. To interrupt transmission, WHO recommends therapy using combinations of two 
medicines delivered to entire at-risk populations through a strategy known as mass drug 
administration (MDA). Ivermectin and albendazole are administered in areas where 
onchocerciasis is co-endemic; diethylcarbamazine and albendazole are administered in areas 
where onchocerciasis is not co-endemic. 
Lymphatic filariasis (LF) is a parasitic worm infection caused by the filarial nematodes 
Wuchereria bancrofti, Brugia malayi and Brugia timori. Adult worms reside in the human 
lymphatic system and release immature forms (microfilariae) into the blood stream. These are 
taken up by mosquitoes that continue the cycle when they bite another person. Dying adult 
worms provoke disabling and disfiguring obstruction of the lymphatic vessels and can cause 
lymphedema leading to elephantiasis (known as “Kaki Gajah” in Indonesia). In addition, the 
species W. bancrofti causes hydrocele in men and breast/ vulva enlargement in women. In 
2000, WHO launched the Global Programme to Eliminate Lymphatic Filariasis (GPELF) to 
eliminate LF as a public health problem by 2020. For Asia, WHO recommended the co-
administration of diethylcarbamazine (DEC) and albendazole. The programme’s current strategy 
to interrupt transmission relies on the annual single dose mass drug administration (MDA) of 
these 2 drugs (DA) given to the entire eligible population in endemic districts. The program has 
made significant progress driving microfilaria (MF) prevalence (a measure of the distribution of 
infection) below 1% in many areas of the world as of 2015 [1]. Despite this success in some 
endemic countries, MF prevalence has remained >1% in a many areas within a number of 
countries, including Indonesia. Therefore, additional treatment strategies are needed to help 
interrupt transmission in these areas and ensure that the GPELF meets its goal by 2020 [2]. 
Results of a pilot study [3] in Papua New Guinea (PNG) showed that a single dose of three 
drugs [ivermectin, DEC, albendazole (IDA)] completely cleared W. bancrofti MF for at least 1 
year in all participants, which was superior to the currently recommended two-drug regimen 
(DA). This observation was confirmed with results from a larger clinical trial in PNG where IDA 
completely cleared MF in 57 of 58 people with heavy LF infections while DA cleared only 33 of 
112 participants (King et al. unpublished data). These results suggest that IDA effectively kills or 
permanently sterilizes adult filarial worms. Many people treated in these studies experienced 
transient systemic adverse events (AE) commonly associated with DEC or ivermectin treatment 
of filariasis, and AEs were more frequent after IDA than after DA. However, no serious adverse 
events (SAEs) were observed in these trials or in a trial that is currently in progress in the West 
African country of Côte d’Ivoire (King et al. personal communication). No information is available 
on the frequency or type of AEs following IDA treatment of uninfected persons, but this is 
expected to be low since most symptoms appear to be the response to dying or damaged 
worms. The dramatic reduction and sustained decrease of MF along with the safety profile seen 
in the PNG studies suggest that the triple drug therapy may be a useful tool for eliminating LF in 

 
DOLF_IDA_Indonesia_Protocol v5.0_24May17 
 
Page 12 of 39 
areas where MF rates have remained > 1% following MDA with the standard DA regimen. The 
addition of ivermectin in an MDA regimen would also provide additional public health benefits, 
since it complements the deworming effect of albendazole (a global initiative) and eliminates lice 
and scabies mites [4].  
2.1 
Country Specific Background 
Indonesia is the only country in the world that is endemic for all three filarial species that cause 
LF, with Brugia causing the majority of infections. The country has one of the highest burdens of 
LF, and it is a key member of GPELF. Our team has shown that an MDA strategy can eliminate 
brugian LF [5]. But since achieving high MDA compliance for 5-6 years is a challenge in some 
areas in Indonesia [6], the country could benefit from the more rapid IDA MDA approach. 
Comparative trials between Wuchereria and Brugia using DEC with albendazole indicate a 
similar efficacy for both species, but adverse events may be more common in Brugia infection 
because of a more rapid killing of MF [7, 8]. IDA has not been previously studied for the 
treatment of brugian filariasis.   
Although the studies mentioned above have clearly demonstrated the superiority of the triple 
drug therapy for clearing W. bancrofti microfilariae from the blood, more safety and efficacy data 
are needed before triple therapy can be rolled out on a large scale as a mass drug 
administration regimen in lymphatic filariasis endemic countries. WHO recommends a best 
practice called “cohort event monitoring” for demonstrating safety of new drug regimens for 
public health program use. Establishing safety through such methodology requires pre and post 
treatment assessments from at least 10,000 people treated with the triple therapy across 
multiple settings. 
A consortium consisting of Washington University, Case Western Reserve University, the 
Universitas Indonesia, Jakarta, the Indonesian Ministry of Health, the Papua New Guinea 
Institute for Medical Research (PNG), the Papua New Guinea Department of Health (PNG), the 
National Vector-Borne Disease Control Programme (India), and The Centers for Disease 
Control (Haiti) was formed to test efficacy for brugian LF and to comparatively evaluate the AE 
and SAE profiles of DA and IDA. This IRB-approved protocol is being submitted specifically for 
WUSM and UI teams who will be in charge of the Indonesia study and actively coordinate with 
the other consortium members and sponsors to conduct this study. 

 
DOLF_IDA_Indonesia_Protocol v5.0_24May17 
 
Page 13 of 39 
3 
POTENTIAL RISKS AND BENEFITS 
3.1 
Risks of Blood Draw 
Blood collection via finger prick is considered to be minimal risk and little or no discomfort is 
anticipated.  The risk of infection is minimized by the use of standard sterile techniques.  On 
occasion a participant may faint during or after the finger prick.  Study personnel will be alert to 
participant reactions after the blood collection and will provide aid as needed 
3.2 
Risks of Study Drugs 
The combinations of ivermectin plus albendazole or DEC plus albendazole are widely used for 
MDA. There also have been clinical trials of DEC plus Ivermectin and for triple drug therapy that 
show no significant drug interactions [3]. Risks of each drug is summarized below:  
Diethylcarbamazine (DEC): The most common side effects reported are itching and swelling of 
face, headache, joint pain, unusual tiredness or weakness. These are transient. Less common 
are dizziness, nausea or vomiting. Fever, painful and tender glands in groin, neck and armpits 
or skin rash can occur, and are usually associated with high burdens of infection as judged by 
the level of blood microfilaremia.  
Albendazole (ALB): The most common side effects reported are headache, nausea, stomach 
pain and vomiting and are usually associated with heavy soil-transmitted helminths infections. 
Severe allergic reactions occur rarely, and include rash, hives, itching, difficulty breathing, 
tightness in the chest, swelling of the mouth, face, lips, or tongue, dark urine. Mild elevation in 
liver transaminases can occur, but normalize with cessation of treatment. These AEs are usually 
associated with prolonged ALB therapy.  
Ivermectin (IVM):  The most common side effects reported are diarrhea, dizziness and nausea. 
Rare side effects include rash, hives, itching, difficulty breathing, chest tightness, swelling of the 
mouth, face, lips, or tongue, eye pain, fainting, and fast heartbeat. Mild decrease in leukocyte 
counts, elevated liver function tests, and cardiovascular effects that included tachycardia and 
orthostatic hypotension have been described. Infrequently, treatment can exacerbate bronchial 
asthma. These AEs are usually also associated with prolonged therapy. 
3.3 
Potential Participant and Community Benefit 
Infected individuals, who sign an informed consent, will be treated for the LF infection. LF 
transmission to the community will be reduced by participation in either treatment arm.  A 
broader community benefit may be facilitated by the triple drug regimen as it is believed the 
triple drug regimen has the potential to markedly reduce the number of MDA treatments needed 
to achieve transmission interruption and elimination of LF.  
Both regimens provide treatment for intestinal worms, and the triple drug treatment has the 
added benefit of providing an effective treatment for scabies.  

 
DOLF_IDA_Indonesia_Protocol v5.0_24May17 
 
Page 14 of 39 
If the triple drug intervention proves successful, the triple therapy is likely to be adopted in many 
LF endemic areas globally. In order to facilitate such an uptake of triple therapy into national 
treatment policies, the study will be performed by Dr. Taniawati Supali and Dr. Yenny Djuardi 
from Universitas Indonesia and local health districts. Results from this study will be combined 
and shared with the World Health Organization. 
3.4 
Participant Participation and Cost  
Participation is voluntary and participants may decline participation without consequences.  
There will be no cost to the participant to participate in the study. Participants in the community-
based study activities will not be paid for their participation. Participants in the hospital-based 
study will be compensated (Rp 300.000,00) to replace their lost income while staying in the 
hospital.  The study will cover cost associated with laboratory test, study drugs, and clinical 
monitoring. 
3.5 
Compensation for Injury 
The study drugs have been widely used for treatment of lymphatic filariasis and it is anticipated 
that injury resulting from treatment will be rare.  In the event that a participant experiences a 
serious adverse event (SAE) attributable to study treatment, the project will help in supporting 
the medical treatment and/or hospitalization required.  

 
DOLF_IDA_Indonesia_Protocol v5.0_24May17 
 
Page 15 of 39 
4 
STUDY DESIGN AND OBJECTIVES 
4.1 
Study Objectives 
1. To determine the safety profile of triple-drug therapy by measuring the frequency, type 
and severity of adverse events following triple-drug therapy (IVM+DEC+ALB, IDA) 
compared to the standard two-drug treatment (DEC+ALB, DA) in Brugia-infected and 
uninfected individuals in a community. 
2. To compare the efficacy of IDA vs. DA administered in communities for clearance of 
Brugia MF and filarial antibodies. 
4.1.1 Secondary Objectives 
1. To assess the effect of intensity of filarial infection on the frequency and severity of 
adverse events. 
2. To compare community acceptance of MDA with IDA vs. DA. 
3. To compare the efficacy of DA vs IDA on soil-transmitted helminthes (STH) 
4.2 
Study Design 
This trial will be an open labeled two-armed study.  The two arms are (1) MDA with IDA (triple 
drug therapy) and (2) MDA with the currently used combination of DA (two-drug regimen).  An 
overview of the study flow is provided in Appendix 1. 
 
The primary endpoint will be the rate of AE(s) and SAE(s) among participants.  The definitions 
of mild, moderate, severe, and serious AE are provided in Appendix 4.  
4.3 
Study Screening and Enrollment 
This study will provide treatment for 4000 people who are living in areas with Brugia MF 
prevalence rates >5%. Co-endemicity with bancroftian filariasis is not an exclusion criterion. 
Pilot surveys have identified suitable study villages in Flores (Flores Timur District, B. timori MF 
prevalence 8.6%) and Sumba (Sumba Barat Daya District, B. timori MF prevalence 6.5%) 
islands that are mainly endemic for B. timori. Anecdotal information from local doctors indicates 
relatively high scabies rates on Sumba, but low rates on Flores. Ojandetun village located in 
Flores Timur consist of 2 sub-villages with a total population of 600. Karang Inda, Kahale, and 
Rada Malando villages with a total of 4,000 people in Sumba Barat Daya district. Unfortunately, 
we were not able to find a suitable study population of sufficient size in a single area (island) 
In the first part of the study, 60 B. timori MF positive individuals will be treated in a hospital to 
observe AEs in a controlled environment. Thirty adult participants will receive IDA and 30 adult 
participants will receive the standard treatment (DA). This pilot treatment trial requires a suitable 
hospital/health centre in the vicinity of the endemic villages. It is planned that the rest of the 
study population will be treated and monitored as outpatients in their home villages. A total 

 
DOLF_IDA_Indonesia_Protocol v5.0_24May17 
 
Page 16 of 39 
population of 4,000 eligible individuals (MF positive or negative) will be selected with 2,000 
receiving IDA and 2,000 receiving DA.  
4.4 
Preparatory Activities 
This study will be performed in two phases (1) A smaller hospital-based trial comparing the 
safety and efficacy of DA and IDA in MF positive individuals and (2) a large community-based 
trial comparing the safety and efficacy of DA and IDA in a population at risk of infection. This 
part of the study will include both MF positive and MF negative individuals and will be performed 
after phase 1 shows acceptable adverse events.  
Nurses and community health workers will act as AE assessors, following standardized training, 
across both phases of the study. Individuals with basic medical training (nurses or community 
health workers) and who are able to complete and pass a training course will perform the AE 
evaluations and provide symptomatic relief as indicated by the protocol.  
Prior to community-based treatment, medical teams will be located at strategic locations in the 
community. Both study participants and the drug administrators will be informed about the 
availability of these medical teams including their mobile phone numbers so that they can report 
directly to these teams if necessary. These medical teams will be available during the entire 
enrollment/treatment period. Each team will have a vehicle for transporting participants for AE 
evaluation and management. Teams will be comprised of a medical officer, a staff nurse, and a 
pharmacist, and they will have access to essential lifesaving drugs.  
4.5 
Hospital-Based Treatment 
About 1,000 individuals who consent to participate in the study will be screened in the 
community for MF in peripheral blood by the examination of finger prick night blood (60 µL, 
collected between 8 PM and 11 PM). Dried blood spots and plasma will be preserved for later 
analysis. The total amount of capillary blood collected will not exceed 300µL. Sixty MF positive 
adult individuals eligible for treatment will be recruited for hospital-based treatment. Participants 
will be brought to the hospital for treatment. Venous blood will be collected for filtration at three 
time points: before IDA or DA treatment, 24 hours, and 48 hours after. Approximately 12 mL of 
blood will be collected at each time point.  6 mL for immunological tests and PCR, 2 mL for 
filarial filtration diagnosis, 2 mL for microscopic tests, and 2 mL for reserve. Participants will be 
monitored for adverse events during their stay. Any adverse events that occurs during the 
observation period will be recorded in a patient medical record. At 24 and 48 hours the adverse 
events will be entered into the electronic data capture system. If an adverse event changes in 
severity during the reporting period the highest grade reported will be entered into the electronic 
data capture system. Seven days after being treated the participant will be visited at home to 
record any adverse events that presented late.  Participants will be told to expect to be unable 
to work for 3 days to account for the hospitalization and travel to and from the hospital setting. 
Minors will not be selected for hospital based treatment, because they would require guardians 
during their stay.  

 
DOLF_IDA_Indonesia_Protocol v5.0_24May17 
 
Page 17 of 39 
 
4.6 
Community-Based Treatment 
The community-based study will follow the hospital-based study. The rest of the study 
population, including the participants screened and not included in the hospital-based study, will 
be treated and monitored as outpatients in their home villages. Monitoring teams will visit 
participants at 24 and 48 hours. Participants will be told to seek out designated passive 
monitors who will visit the communities through day 7 if they experience any adverse events. 
4.7 
Social Mobilization 
Prior to the administration of the drugs, intense social mobilization activities will be conducted to 
ensure maximum community participation. This will include development and distribution of key 
messages that will emphasize the acceptance and swallowing of the drugs along with their 
benefits and safety.  
4.8 
Household Enumeration, Census and Geo-Referencing 
Communities within areas known to be highly endemic for brugian filariasis will be selected on 
the basis of willingness to participate and ability to access the area.  Furthermore, the area 
should have had no LF MDA during the last 10 months, because MF (microfilaremia) rates are 
likely to be too low following MDA.  
Health workers with the research team and community drug distributors (CDD) will enumerate 
and record the GPS coordinates of each Kampung within the selected study areas (PHMs) 
(House Visit #1, Appendix 1). A census will be performed to collect name, age and sex of each 
household member greater than or equal to 5 years of age. Basic information on house 
structure that might affect mosquito exposure to lymphatic filariasis infection, e.g. type of 
structure, whether screened windows present, existence of a toilet, running water, electricity 
and/or insecticide treated bed nets will also be collected. 
4.9 
Pre-Treatment Assessment Team 
The pre-treatment assessment (House visit #2, Appendix 1) team will be composed of people 
with basic medical training able to perform a medical history and a basic physical examination 
(local health workers, physicians, and nursing or medical students), laboratory technicians, and 
community drug distributors involved in previous MDA for LF and known by the local 
community. 
4.10 Inclusion and Exclusion Criteria 
Inclusion Criteria 
1. Age ≥ 5 years, for IDA and DA arms (males and females).  

 
DOLF_IDA_Indonesia_Protocol v5.0_24May17 
 
Page 18 of 39 
2. Able to provide informed consent or give parental consent for minors to participate in the 
trial  
3. No evidence of severe or systemic co-morbidities except for features of filarial disease  
Exclusion Criteria 
1. Age < 5 years (ivermectin is not approved for use in children less than 5 years of age) 
2. Unable to provide informed consent or give parental consent for minors to participate in 
the trial 
3. Pregnant women (DEC, ivermectin and albendazole are not known to be safe for use 
during pregnancy) 
4. Severe chronic illness (chronic renal insufficiency, severe chronic liver disease, or any 
illness that is severe enough to interfere with activities of daily living) 
5. History of previous allergy to MDA drugs 
4.11 Pregnant Females 
Pregnant females will not be eligible to participate in this study because of the unknown effects 
of the drugs and drug combination used in this study.  Females will be asked about the timing of 
the first day of their last menstrual period. Females who report that their last menstrual period 
started 4 weeks or longer before the interview will be excluded from the study. Females who do 
not recall the timing of their last menstrual period will have their urine tested for pregnancy. 
4.12 Informed Consent 
All participants will provide written informed consent before any study procedures are done. 
Participation of minors (less than 18 years of age) will require their assent and the written 
consent of at least one parent. Participants will sign a written, informed consent before the 
inclusion process (Appendix 6).  In the event that a participant is unable to read or has 
insufficient level of knowledge to comprehend the consent form, another villager with sufficient 
reading and writing skills will act a witness to the consenting process. The witness should not be 
involved in the implementation of the study.  
A waiver of consent is being requested for the Census and Geo-referencing portion of the study 
prior to receiving formal consent.  The study team will be collecting information about the 
communities and residents.  This portion of the study is not greater than minimal risk and the 
members of the study team who are conducting the Census and Geo-referencing portion of the 
study will explain what they are collecting to village residents. 
4.13 Plan for Inclusion of Non-Bahasa Indonesia Speaking Individuals  
Participants who do not speak or read Bahasa Indonesia are neither specifically included nor 
excluded from this study. There are many local languages in eastern Indonesia and a native-

 
DOLF_IDA_Indonesia_Protocol v5.0_24May17 
 
Page 19 of 39 
speaking community worker who is knowledgeable about research and the study will translate 
the consent form from Bahasa into the local language. 
4.14 Baseline Survey 
B. timori is nocturnally periodic and MF are present in the blood stream only at night. A study 
team will visit each household or compound in the evening to interview each member for 
demography, treatment history and general health. Each study participant will be tested for MF 
in finger prick night blood. Dried blood spots and plasma will be preserved for later analysis. The 
total amount of capillary blood collected will not exceed 300µL. A subset of participants will be 
asked to provide a stool sample for assessment of STH. However, participants may choose not 
to provide a stool sample and will still be eligible for the rest of the study. Eligible individuals 
who were screened, but not selected for the hospital based trial, can be directly enrolled in the 
community-based treatment without repetition of the finger prick blood collection. Study 
participants will be given their assigned treatment (DA or IDA) under supervision of a study 
team member. No more than 50 participants will be enrolled and treated per team per night to 
ensure sufficient staff capacity for follow-up AE monitoring. 
After consenting, and prior to evaluation for LF infection and treatment, all individuals will be 
assigned a unique ID and be enrolled using a participant enrollment form (Appendix 2). They 
will also get an information card with emergency contact so they would know whom to call in 
case of emergency. Questions will be asked to each participant about their general health and 
last menstrual period (to establish pregnancy for women of childbearing age). Female 
participants who fail to recall their last menstrual period will have their urine tested for 
pregnancy. Each individual will be asked if they have signs of LF complications (hydrocele, 
lymphedema, lymphangitis, and lymphadenitis), if they took treatment during the previous MDA 
for LF and if they recently took albendazole, diethylcarbamazine, or ivermectin for other 
conditions. Participants reporting lymphedema will be examined to identify the location of the 
lymphedema. A photo of each participants will be captured electronically and stored in a secure 
folder. The photo will be helpful in identifying participants in the future, considering there are 
numbers of villagers who share the same name and who are unable to recall their exact date of 
birth.  
4.15 Screening for Filarial Antigenemia, Antibodies and Microfilaria 
Approximately 75µl of capillary blood from each eligible individual will be collected via finger 
prick to be deposited on the rapid diagnostic test Filariasis Test Strip (FTS, Alere™, WHO 
approved) for LF antigen (Wuchereria) detection in the field. The BrugiaRapid (Rezon™, WHO 
approved) diagnostic test will be used in parallel to detect infection with Brugia. The 
BrugiaRapid test requires 35µl of capillary blood. All participants will undergo microfilaria testing 
(60 μl measured volume blood smear- 3 lines, prepared according to the project SOP) collected 
by the finger prick method. 
Study participants will be informed that their blood samples may be stored in Department of 
Parasitology Universitas Indonesia. As many as 10% of the samples (approximately 300-400 

 
DOLF_IDA_Indonesia_Protocol v5.0_24May17 
 
Page 20 of 39 
samples) will be chosen randomly to be shipped to other laboratories for quality control of filarial 
diagnosis. 
Universal precautions for individuals collecting and working with blood samples to include 
proper disposal of contaminated materials (test strips, lancets, capillary tubes, blood film slides) 
will be in accordance with the guidelines prescribed by the local health authorities.  
4.16 Assessment of Efficacy of IDA vs DA on STH (including Strongyloides by 
qPCR) 
Expected number of positive individuals per treatment arm: We assume that per treatment 
arm we will collect stool samples from a community of about 300 individuals (a total of 600 
individuals for two arms). With a confidence level of 95% and a confidence interval of 5%, we 
would require testing at least 278 subjects. Assuming a sample size of 300 (~278) and a 
confidence level of 95% we expect to treat at a prevalence of 50% (ie any STH) between 133 
and 167 infected individuals and at a prevalence of 10% (i.e. one STH species only) between 
20-40 infected individuals. Based on previous data from eastern Indonesia and PNG we expect 
a minimum prevalence of any STH of 50%. 
Study sites: It is sufficient to select the 300 individuals per treatment arm from one study 
area/village, because a more homogeneous distribution of STH compared to LF can be 
expected. Susceptibility to the drug treatment should not vary within the same region.     
Collection of stool samples: We will follow the DOLF ‘SOP for Stool Collection’.  A 
convenience sampling method will be used without special regard to sex and age, because drug 
efficacy is unlikely to depend on these parameters.  A follow-up stool sample will be collected 2-
4 weeks and one year after treatment from the same individuals that provided the baseline 
sample. We expect a compliance of 90% because of pre-selection of compliant individuals.    
Assessment of STH eggs: We will use the Kato Katz method before and after treatment, 
because of its sufficient sensitivity in high prevalence areas, its simple performance in the field, 
and the standardized quantitative assessment.  We will follow the DOLF ‘SOP Kato Katz 
Procedure’.  Stool aliquots will be preserved for later examination by qPCR. This will enable us 
to archive STH DNA samples before and after IDA treatment and to test for efficacy of IDA for 
Strongyloides. We will follow the DOLF ‘SOP Stool Sample Management’ (version 2016). 
(Some samples may randomly be picked and shipped to other laboratories for quality control). 
These samples may be stored for a longer time after the intended testing. No HIV or human 
genetic testing will be performed. 
 
4.17 Randomization 
A randomization scheme will be prepared for the hospital-based study. Individuals will be 
assigned to one of two treatment arms using a random number generator; 50% will be assigned 
to DA therapy and 50% to IDA. The randomization scheme will be maintained in a locked file at 
all times with limited access.  However, should it be necessary to link participants to their 

 
DOLF_IDA_Indonesia_Protocol v5.0_24May17 
 
Page 21 of 39 
assigned treatment, the randomization will be available to the DSMB and a copy will be 
maintained in a locked cabinet at the coordinating site. 
Communities will be assigned treatment either by randomization in the level of dusun or by 
purposively matching communities based on population and prevalence of LF. If the prevalence 
is homogenous across the communities each site may be randomly assigned to one of the two 
treatment arms. If the prevalence is heterogeneous, communities will be selected into each arm 
so that the population and prevalence between the two treatment arms is similar. 
4.18 Withdrawal 
Participation in this project is completely voluntary, and participants may terminate participation 
at any time.  Also if the well-being of the participant is compromised in any way, based on the 
opinion of the investigator, the participant can also be withdrawn from the study. Even if the 
participant leaves the project early, we will encourage them to contact us at any time within the 
month after treatment to report any possible study-related AEs. 
All participants that sign the informed consent and receive study drug will be included in the 
analysis. 
4.19 Efficacy and Effectiveness of IDA vs DA 
One year post MDA all participants who were positive for microfilariae, filarial antigenemia 
(FTS),or antibody (Brugia Rapid) during the baseline visit will be tested for nocturnal 
microfilariae. Finger prick blood will be collected at night from the community participants to be 
tested for microfilaremia by thick blood smear. Venous blood will be collected from hospital-
based study participants for filtration membrane test.  Serological tests using FTS and Brugia 
Rapid, will also be used to assess their responses to treatment and compare the efficacy of the 
two treatment regimens. 
We will also collect stool samples from all treated individuals who were positive for helminth 
infections in order to describe the long term effect of both treatment regimens on STH. 
 
4.20 Retreatment 
Any individual who tests positive for lymphatic filariasis at 12 months (by microscopy or antigen 
test) will be re-treated with the standard MDA regimen (single dose of DEC with Albendazole). If 
triple drug therapy (IDA) is recommended by the WHO or by national regulatory agencies for 
lymphatic filariasis and if investigators have adequate supply of ivermectin, infected individuals 
may be offered IDA. This practice is meant to ensure that all participants who participated in the 
study may get the most beneficial treatment. 

 
DOLF_IDA_Indonesia_Protocol v5.0_24May17 
 
Page 22 of 39 
4.21 Guidelines for Stopping the Trial 
There are no pre-specified criteria for terminating the study early. 
Upon review of the data for the trial, the DSMB will make decisions regarding the continuation of 
the trial.  The final decision to stop the trial is left to the recommendation of the DSMB.  If the 
DSMB recommends discontinuation or modification of the study, the Chair of the DSMB will 
meet or talk with the DOLF Project Team at the earliest opportunity to review the basis for the 
recommendation. The study should be stopped if a treatment arm shows a significant increase 
in unacceptable side effects that would include, death, fever, and nausea that persist more than 
a day and would require hospitalization.   
4.22 Triple Drug Regimen Acceptability 
A survey to assess the treatment acceptability in the community is planned to follow the safety 
trial. The overall aim is to understand the community’s acceptance of the 3-drug regimen as well 
as gain insight into the feasibility of administering this new therapy in the future. Part of the 
investigation will include assessing community member’s perception of the possible side effects 
experienced as a result of the 3-drug therapy compared to the 2-drug therapy, and how that 
might affect future rounds of mass drug administration (MDA) at the community level. 
Community acceptance will be measured using a survey to community members receiving both 
the 2-drug and 3-drug treatments during the safety trial. The survey participants will be identified 
from the roster of individuals enrolled in the safety trial. To complement this survey, a series of 
focus group discussions in the community as well as key informant interviews are proposed with 
community leaders, health personnel and drug distributors in the same communities to assess 
perceptions about the 3-drug versus the 2-drug regimen. The community acceptability study will 
be carried out within one month of the completion of the safety trial. The protocol for the 
acceptability survey is included in Appendix 7 of this protocol. The community questionnaire and 
topic guides will be submitted to the EC for approval as an amendment prior to implementation 
of the survey. 

 
DOLF_IDA_Indonesia_Protocol v5.0_24May17 
 
Page 23 of 39 
5 
INVESTIGATIONAL PRODUCT 
Each of the drugs used in this study is approved for human use and has a prior history of use in 
the treatment of Lymphatic Filariasis.   
5.1 
Study Drug Background 
Albendazole (ALB) has been known to cause degenerative alterations in the tegument and 
intestinal cells of the worm by binding to the colchicine-sensitive site of tubulin, thus inhibiting its 
polymerization or assembly into microtubules [10]. The loss of cytoplasmic microtubules leads 
to impaired uptake of glucose by larval and adult stages of the parasite, and depletes glycogen 
stores. Degenerative changes in endoplasmic reticulum and mitochondria of the germinal layer, 
and the subsequent release of lysosomal enzymes result in decreased production of adenosine 
triphosphate, which is the source of energy required for survival of the helminth. Due to 
diminished energy production, the parasite is immobilized and eventually dies. Adverse events 
are uncommon in persons who are treated with a single dose of albendazole (apart from AEs 
that result from parasite death). Some patients report mild gastrointestinal AEs such as nausea 
after ingesting the tablet. 
Ivermectin (IVM) is an avermectin compound of macrocyclic lactones derived from the 
bacterium Streptomyces avermitilis [11]. The mechanism by which IVM kills LF microfilariae is 
not known with certainty, but the drug interferes with glutamate gated ion channels that can 
affect parasite contractility and release of immunomodulatory molecules by the parasite [12]. 
IVM also has a direct effect on the central nervous system and muscle function of worms as it 
enhances strength of inhibitory neurotransmission pathways.  The main concern with the use of 
IVM in animals and humans is neurotoxicity, which can be manifest as ataxia. Neurotoxicity has 
not been observed in humans given single dose IVM for LF or other parasitic infections [13]. 
IVM has been used to treat millions of people with LF and onchocerciasis. Peak IVM serum 
concentrations are reached approximately 4-5 hours after administration. The half-life of IVM in 
various populations ranges from 12 to 56 hours [14]. There is no evidence for pharmacokinetic 
drug to drug interaction between ALB and IVM [14]. IVM can cause nausea, dizziness and 
occasionally pruritus, but these are infrequent, transient and usually mild. Serious adverse 
events have occurred in patients with heavy Loa loa infections. 
DEC (diethylcarbamazine citrate) is an anthelminthic drug that is structurally distinct from ALB 
and IVM [15]. DEC inhibits arachidonic acid metabolism by LF, and inducible nitric oxide synthase 
and the cyclooxygenase pathway may be essential for activity in vivo [16]. DEC also has anti-
inflammatory properties. The mechanisms of action of DEC remain poorly understood. Its ability 
to kill MF and adult worm depends on the host immune responses since the drug has little direct 
activity on parasites in vitro. The drug has potent activity against LF microfilaria. DEC has about 
50-70% efficacy in killing or sterilization of adult worms [17]. The drug is rapidly absorbed from 
the gastrointestinal tract, has a serum half-life of 12 to 14 hours, and is excreted in the urine with 

 
DOLF_IDA_Indonesia_Protocol v5.0_24May17 
 
Page 24 of 39 
little modification by liver metabolism. Adverse events from DEC are unusual apart from those 
that result from killing filarial worms.  
5.2 
Product Supply and Storage 
Only WHO approved drugs will be used in this study. DEC and albendazole will be provided by 
the Indonesian Lymphatic Filariasis Elimination Program and the WHO. A request will be 
submitted to the manufacturer Merck to provide ivermectin for the present study. Alternatively 
WHO approved generic ivermectin may be purchased..  
Albendazole and DEC are approved for use and commonly used in Indonesia. Ivermectin 
(Mectizan) is registered in numerous countries around the world for use in humans, but not in 
Indonesia. Approval for its use in the present study will be sought from the government of 
Indonesia together with the Ethical Review of this proposal. 
All three study drugs are approved and distributed globally by WHO as part of GPELF. Detailed 
information for each drug is available from the pharmaceutical manufacturer. All products should 
be maintained at ambient temperature, and if possible <30 °C.  

 
DOLF_IDA_Indonesia_Protocol v5.0_24May17 
 
Page 25 of 39 
6 
STUDY PROCEDURES/EVALUATIONS/SCHEDULE 
6.1 
Triple Drug Therapy (IDA) and Two-Drug Therapy (DA)  
The triple-drug combination will consist of a single dose of ivermectin (200 µg /kg), DEC 
(6mg/kg) and albendazole (flat dose of 400 mg). The two-drug combination will consist of a 
single dose of DEC (6 mg/kg) and albendazole (flat dose of 400 mg). Study personnel will 
directly observe oral administration of drugs. Drugs will be given after the informed consent has 
been obtained. The study population will be encouraged to eat before swallowing the medicine 
(without chewing the tablets) with a glass of water. Vomited doses will be replaced. Drug 
administration will be supervised (directly observed treatment or DOT) to ensure that all enrolled 
individuals swallow the drugs. There will be one supervisor per study team. 
6.2 
Overall Study Schedule and Timeline 
A flow diagram illustrating the study events schedule is presented in Appendix 1.  

 
DOLF_IDA_Indonesia_Protocol v5.0_24May17 
 
Page 26 of 39 
7 
SAFETY REPORTING AND SAFETY MONITORING 
The post-treatment assessment team will be composed of individuals with basic medical training 
who are able to perform a medical history and a basic physical examination (Physicians, local 
health workers, nursing and/or medical students). Physicians from the area will be available to 
assist in the evaluation and management of adverse events. 
7.1 
Definitions 
Adverse Event (AE)  
Any untoward medical occurrence in a clinical investigation participant who has received a study 
product intervention and that does not necessarily have to have a causal relationship with the 
study product. An AE can, therefore, be any unfavorable and unintended sign (including an 
abnormal laboratory finding, for example), symptom, or disease temporally associated with the 
use of a study medicinal product, whether or not considered related to the study medicinal 
product. 
An AE does not include: 
 
Medical or surgical procedures (e.g. surgery, tooth extraction, transfusion). The 
condition that leads to the procedure is an adverse event 
 
Pre-existing diseases or conditions or laboratory abnormalities present or detected 
prior to the screening visit that do not worsen. 
 Serious Adverse Event (SAE)  
An SAE is any adverse event that results in any of the following outcomes: 
 
Death; 
 
Life-threatening (immediate risk of death); 
 
Inpatient hospitalization or prolongation of existing hospitalization; 
 
Persistent or significant disability or incapacity; 
 
Congenital anomaly/birth defect; 
 
Important medical events that may not result in death, be life threatening, or require 
hospitalization may be considered a serious adverse event when, based upon 
appropriate medical judgment, they may jeopardize the participant and may require 
medical or surgical intervention to prevent one of the outcomes listed in this 
definition. Examples of such medical events include allergic bronchospasm requiring 
intensive treatment in an emergency room or at home, blood dyscrasias or 
convulsions that do not result in inpatient hospitalization, or the development of drug 
dependency or drug abuse. 

 
DOLF_IDA_Indonesia_Protocol v5.0_24May17 
 
Page 27 of 39 
Unexpected 
An adverse reaction, the nature or severity of which is not consistent with the applicable product 
information (e.g., Package Insert). 
Expedited Safety Report  
Documentation in appropriate form and format summarizing an SAE that meets expedited 
safety reporting criteria, submitted within the required reporting time frame of applicable 
regulatory authorities and/or IRBs/IECs of participating countries. 
7.2 
Assessment of Adverse Events 
Adverse event monitoring will be performed approximately 24 and 48 hours following drug 
administration (late afternoon and evenings following treatment, house visit #3 and 4, Appendix 
1). All those participants will be followed for adverse events through Day 7. 
Evaluations will be documented on pre-printed Patient Monitoring forms (Appendix 3) using the 
scoring instructions for AEs (Appendix 4) or entered directly into an electronic form using tablet 
computers.  
Most adverse events after mass drug administration are associated with killing of MF and are 
seen in the first 12-24h following treatment. However, occasional adverse events related to 
adult worm death may be delayed by several days.  
To capture these adverse events and to assure that any systemic adverse events that occurred 
earlier have resolved, study personnel will also visit study villages daily on days 3 through 7 
after treatment (passive AE monitoring). Individuals with AEs that interfere with activities of daily 
living (grade 2 or higher) will have more detailed assessments that will include a brief physical 
examination (including measurement of temperature, blood pressure and pulse).  
7.3 
Serious Adverse Event (SAE) Assessment and Management 
Study participants with definite or suspected serious AEs (any event ≥ grade 3) will be referred 
to a physician or appropriate health care professional for evaluation. These evaluations will be 
documented with special adverse event evaluation forms (Appendix 5), following the instructions 
(Appendix 5a).  
An SAE may qualify for reporting to regulatory authorities if the SAE is possibly attributable to 
one or more of the study drugs, and is unexpected based on the Company Core Safety 
Information.   
A Data Safety Review Board will monitor the type and frequency of AEs and SAEs recorded by 
the teams and provide guidance to the PIs and the teams in the field. 

 
DOLF_IDA_Indonesia_Protocol v5.0_24May17 
 
Page 28 of 39 
The investigator should notify the Institutional Review Board (IRB) or Ethics Committee (EC) as 
soon as is practical, of serious events in writing where this is required by local regulatory 
authorities, and in accordance with the local institutional policy. 
7.4 
Country Specific SAE Reporting Requirements 
All local SAEs will be reported to the PI of the study and sponsor within 24 hours: 
 
Peter U Fischer PhD, Pufische@dom.wustl.edu 
 
Taniawati Supali PhD, taniawati@yahoo.com, phone +6221-310 2135 (office), +62 812 
8400 5628 
 
Yenny Djuardi MD PhD yenny_djuardi@yahoo.com, phone +62 812 8852 7832).  
In parallel, all SAEs will be reported to the ethics committee and District Health Authority via the 
head of the local Primary Health Center (Puskesmas) within three days. 
Serious Adverse Drug Reactions (SADRs) will be reported to the Badan Pengawas Obat dan 
Makanan (BPOM). All SADRs will be reported to BPOM within 15 days since the first day of 
discovery by sponsor or within 7 days if the SADR is life- threatening or results in death. If there 
is any subsequent event following the initial event, it will be reported as soon as possible. 
7.5 
Reporting of Pregnancy 
Pregnancy is an exclusion criteria for this study. Although not AEs, pregnancies are reportable 
events. In the event that a pregnant woman is inadvertently dosed efforts will be made to follow-
up and ascertain and report the pregnancy outcome (e.g., any premature terminations, elective 
or therapeutic, and any spontaneous abortions or stillbirths, as well as the health status of the 
mother and child including date of delivery and infant’s gender and weight). Any pregnant 
woman inadvertently dosed who has a miscarriage or spontaneous abortion within the week of 
follow-up will be reported as an SAE. 
7.6 
Safety Monitoring by the Oversight Committee 
A Data Safety Monitoring Board consisting of 4 experts (including 3 physicians) knowledgeable 
in neglected tropical diseases will be in place to monitor the safety data per country and across 
countries participating in the DOLF project. 

 
DOLF_IDA_Indonesia_Protocol v5.0_24May17 
 
Page 29 of 39 
8 
CLINICAL MANAGEMENT OF EVENTS 
Individuals who have basic medical training (physicians and/or nursing or medical students) who 
are able to complete and pass a training course will be responsible for the initial adverse event 
evaluations.  
In the case of mild symptomatic reactions local health workers/study personnel will provide 
antipyretics/analgesics and anti-allergic agents at the time of follow-up. It is anticipated that the 
majority of adverse events will resolve within a day or two and will not require treatment.  In the 
initial adverse event monitoring if any of the following are noted a physician will be notified to 
evaluate the participant for a potential serious adverse event: 
 
Participant reports they are unable to participate in their normal daily activities 
 
Participant has or reports a temperature >39ºC 
 
Participant has or reports a significant drop in blood pressure 
 
Participant has other significant objective findings that should be referred to a physician 
All grade 3, 4 or 5 events or overnight hospitalization will require completion of the Adverse 
Event Evaluation and Report Form (Appendix 5). The physician will provide any required 
immediate treatment and facilitate admission into the hospital or health center as deemed 
appropriate. 
8.1 
Adverse Event Monitoring and Management 
Adverse event monitoring and management will follow or exceed WHO guidelines.  Participants 
will be visited on the two days following treatment by study personnel with medical training.  
Formal assessment of adverse events (with a standard form) will take place on days 1 and 2 
and later if symptoms persist or start late.   
Study personnel will use the toxicity table (Appendix 4) to score adverse events for severity. 
Serious adverse events will be followed until resolution. Study personnel will visit each study 
area daily for 7 days following MDA treatment to manage any adverse events as follows:   
8.1.1 Mild Localized Symptoms 
Participants who develop painful lymphadenopathy, scrotal pain or painful swelling or nodules 
along lymphatic vessels will be treated with acetaminophen or ibuprofen. 
8.1.2 Moderate to Severe Localized Adverse Events 
Participants with more severe local adverse effects (Grade 3, Appendix 4) like acute swelling or 
severe scrotal pain that is not relieved by acetaminophen will be transported by study personnel 
to the medical facility identified for the study for evaluation by one of the physicians or other 
qualified medical personnel involved in the study. If necessary, participants will be transferred 
(after stabilization) to the Departmental Hospital or primary health center. 

 
DOLF_IDA_Indonesia_Protocol v5.0_24May17 
 
Page 30 of 39 
8.1.3 Moderate to Severe Systemic Adverse Events 
Participants with more severe systemic adverse effects (fever over 39 C > 72 hours, other 
adverse events ≥ Grade 3, syncope, jaundice, or any condition that might require 
hospitalization) will be transported by study personnel for physician or other qualified medical 
personnel for evaluation at the medical facility identified for the study. If necessary, participants 
will be transferred (after stabilization) to a local hospital. 
8.2 
Rapid Response Teams for Management of Adverse Events 
Medical teams will be located at strategic places close to the study sites. Participants, and 
persons involved in the study (inclusion process and AE monitoring) will be informed about the 
location and phone numbers of these teams so that they can report directly to these teams if 
necessary. These teams will be in position from the day of drug administration until the 
completion of operations. 

 
DOLF_IDA_Indonesia_Protocol v5.0_24May17 
 
Page 31 of 39 
9 STATISTICAL CONSIDERATIONS 
All participants receiving study drug will be included in both the safety and efficacy analysis 
9.1 
Safety  
The sample size of 2000 participants in each arm will contribute to the total sample size for the 
project. The WHO requires a total of 10,000 participants to detect an SAE rate of 0.1% for each 
of the treatment regimens and recruitment in other countries (e.g., Haiti, India, Papua New 
Guinea, and Sri Lanka) is planned to contribute to the overall sample size required. It is well 
known that systemic AEs are related to killing of MF and that the severity of AEs is related to MF 
counts.  
WHO recommends a best practice called “cohort event monitoring” for demonstrating safety of 
new drug regimens for public health program use. Establishing safety through such methodology 
requires pre and post treatment assessments from at least 10,000 people treated with the triple 
therapy across multiple settings. The Triple Drug Therapy for LF study is a multi-center study with 
5 sites that together will reach the 10,000 target. The Indonesia sites will contribute 2,000 
individuals treated with triple drug therapy to the overall 10,000. 
The primary endpoint for safety studies will be the rates of SAEs that occur in infected and in 
uninfected participants within the first 7 days post MDA. Total AEs will be a secondary endpoint 
for the study.  
9.2 
Efficacy 
Assuming an average MF-prevalence of 5% in the study population at baseline, the survey is 
expected to detect at least 100 MF positive participants in each arm. A minimum of 70 (70%) of 
all these MF-positive participants in each arm will be retested at 12 months post-treatment for 
microfilaraemia, antigenemia (for Wuchereria) and IgG 4 (Brugia Rapid for Brugia), assuming 
there will be participants lost to follow up due to urbanization or transmigration and those who 
choose to end their participation in the study. This sample size is adequate to demonstrate 
superiority of the IDA regimen (assumptions: 90% reduction in MF prevalence after IDA and 60% 
reduction after DA, 80% power for detecting an effect size of 30%). The primary endpoint for 
efficacy will be complete clearance of MF 12 months post MDA.  
9.3 Enrolling Additional Participants 
It is possible that recruitment in other countries may be less than anticipated. In this case the 
number of participants enrolled in this study may need to be increased to make up for the loss in 
another country. The number of additional people enrolled will be no more than is necessary to 
reach the total of 10,000 participants treated with IDA. In this situation the principal investigators 
will inform the ethics review committees of the expanded enrollment. 

 
DOLF_IDA_Indonesia_Protocol v5.0_24May17 
 
Page 32 of 39 
10 
DATA HANDLING/RECORD KEEPING/SOURCE DOCUMENTS 
Data will be collected using a tablet based system, pre-loaded with study templates.  Field 
teams will be trained in the use of the instruments and data will be uploaded as entries are 
completed. 
10.1 Types of Data Collected 
Enrollment Data will include (Appendix 2): 
 
Site Identification 
 
Participant Identifier 
 
Informed Consent Date 
 
Demographic Information 
 
Digital photo 
 
Pregnancy/last menstrual period 
 
Medical History 
 
Presence of hydrocele and lymphedema 
 
Bed Net and Window Screen Use 
 
History of prior MDA treatment 
 
Pre-treatment adverse event assessment 
 
Limited Physical Exam 
Laboratory Results   
 
FTS (filarial antigen test)  
 
FTS score 
 
BrugiaRapid (filarial antibody test) 
 
MF slide (including MF count) 
 
Soil Transmitted Helminthes egg counts and qPCR diagnostics 
Participant Monitoring Forms (24 & 48 hour post treatment): 
 
Adverse Event Assessment 
 
Physical Examination, as appropriate 
Adverse Event Evaluation and Report (Appendix 5) 
 
Participant Identification 
 
MDA Treatment 
 
Concomitant Medication taken at the time of the MDA 
 
AE Description,  
 
Start and Stop Date 
 
Outcome 
 
SAE Evaluation and causality to MDA (definite, probable, possible, or unrelated) 

 
DOLF_IDA_Indonesia_Protocol v5.0_24May17 
 
Page 33 of 39 
10.2 Study Records Retention  
Study documents will be retained for a minimum of three (3) years after the last participant has 
completed the study.  These documents will be retained for a longer period, however, if required 
by local regulations. No record will be destroyed without the written consent of DOLF. 
Each participating site will maintain appropriate medical and research records for this trial, in 
compliance with ICH E6, Section 4.9, regulatory and institutional requirements for the protection 
of confidentiality of participants. Each site participating in this study will permit authorized 
representatives of the sponsor and regulatory agencies to examine (and when required by 
applicable law, copy) clinical records for the purposes of clinical site monitoring, quality 
assurance reviews, audits, and evaluation of the study safety and progress.  
10.3 Source Documents 
This study will use both paper and electronic source and this may vary by location due to local 
availability.  All sites will be provided with hard copy data collection forms derived from the 
eCRFs. If data is first entered on paper the study staff will enter the data into the electronic 
capture system. 

 
DOLF_IDA_Indonesia_Protocol v5.0_24May17 
 
Page 34 of 39 
11 
RESPONSIBILITIES 
11.1 Investigator Responsibilities 
11.1.1 Good Clinical Practice 
The investigator will ensure that the basic principles of Good Clinical Practice are followed along 
with the appropriate laws and regulations of the country in which the research is conducted.  
11.2 Institutional Review Board (IRB)/Ethics Committee (EC) 
The protocol and any accompanying material to be provided to the participants such as the 
informed consent will be submitted to the EC for review and approval.  Approval from the 
committee must be obtained before starting the study and should be documented in 
correspondence to the investigator. 
Any modifications to the protocol after receipt of the IRB or EC approval must be submitted to 
the committee for approval prior to implementation. 
11.3 Informed Consent 
It is the responsibility of the investigator to obtain written informed consent from each individual 
participating in the study after adequate explanation of the aims, methods, objectives and 
potential risk of any study related procedures.  The investigator must use an IRB/EC approved 
informed consent.  The investigators will accept either signed (cursive) or printed signatures or a 
witnessed mark in the case of illiterate study participants on the consent form.   
Only the principal investigators or study staff authorized and certified to obtain consent will 
consent participants for this study.  Only individuals who have signed the consent form and meet 
eligibility criteria will be enrolled in the study.  
Entry into the study and participation will be strictly voluntary.  It will be made clear that refusal to 
participate or a decision to withdraw can occur at any time throughout the course of the study and 
will not influence their rights or the care they receive at local health facilities. Potential participants 
will be told that all of their health information will be confidential and that records will be coded 
without personal identifiers before they are shared with statisticians or project scientists outside 
of the village/region/country. They will also be told that no monetary or other gains are offered in 
exchange for participation apart from compensation for time and reimbursement of travel 
expenses as described above. 
11.3.1  Informed Consent Training 
Each step of the study will be explained in detail to the local study personnel. The basic 
principles of informed consent process, documentation of informed consent, protection of 
participants’ rights, confidentiality, and handling of data will be covered in these training 
sessions. Study personnel will be monitored by the on-site project coordinator on a regular basis 
to ensure compliance with the principles of informed consent. The investigators and study 

 
DOLF_IDA_Indonesia_Protocol v5.0_24May17 
 
Page 35 of 39 
personnel who will obtain consent from study participants will also receive training in the 
informed consent process and good clinical practices (GCP). 
11.3.2 Country Specific ICF Information 
The Informed Consent for the hospital based trial will include the collection of venous blood and 
additional testing. 
11.4 Participant Privacy  
Privacy of the study participants will be maintained by assigning study participants a unique study 
identification number (UNID). All data, blood samples and laboratory results will be recorded and 
analyzed by UNID with no personal identifiers.  All information collected, including demographic 
information about enrolled participants and their photos will be kept confidential and available only 
to the investigators and authorized study personnel such as the data manager. 
Though most data will be collected on tablets, all written forms (i.e., consent and any paper data 
collection forms) will be stored in a designated locked area with limited control. All forms will be 
labeled and filed in cabinets with the study protocol number, PI’s names and collection dates. 
These cabinets will be metal and have functioning locks. Keys will be kept with the Project 
Coordinator.  All electronic devices on which data are entered will be password protected. PIs 
and/or Project Coordinator will authorize access. The paper forms will be stored for the duration 
of the study plus three years per IRB protocol for primary data storage. 
11.5 Data Ownership 
The data are the property of UI. The Principal Investigators, Co-investigators and key personnel 
may use the results of this study for publications, presentations at scientific meetings or as 
preliminary data for subsequent grant applications. Confidentiality of study participants will be 
maintained by not using names or personal identifiers. UI will provide de-identified data from the 
study to DOLF for use in publications and presentations that present results across different study 
sites. At least one Indonesian researcher will be included as an author for any publications with 
data from Indonesia.  
The study site Project Coordinator will permit access to all documents and records that may 
require inspection by the funding agencies, governmental regulatory agencies, institutional 
review boards or its authorized representatives.  

 
DOLF_IDA_Indonesia_Protocol v5.0_24May17 
 
Page 36 of 39 
12 
PUBLICATION POLICY  
Manuscripts should be submitted for publication no later than one year following the date of the 
“last patient/last visit”. This study includes follow-up data collection past the primary end point, 
including acceptability and efficacy results. It is not necessary to wait for the follow-up studies to 
be completed in order to publish the primary safety data. 
Endemic country investigators have an obligation to publish the results of DOLF studies 
conducted in their country. These results benefit the national NTD programs and the citizens of 
the country where the study was completed. DOLF collaborating institutions are willing to help 
their endemic country partners with the data analysis, manuscript preparation, publication fees, 
etc. However, the lead author should be an investigator from the country where the study was 
performed. 
DOLF scientists will be responsible for publishing the results from the aggregated data that 
combines the results from multiple study sites. The purpose of these manuscripts is to consider 
the similarities and differences in results obtained in different countries. These publications will 
not include as much detailed data or analyses as the country specific publications. Publications 
that report multi-country results will have at least one co-author from each country included in the 
manuscript. 

 
DOLF_IDA_Indonesia_Protocol v5.0_24May17 
 
Page 37 of 39 
13 
LITERATURE REFERENCES 
1. 
Hooper, P.J., et al., Assessing progress in reducing the at-risk population after 13 
years of the global programme to eliminate lymphatic filariasis. PLoS Negl Trop 
Dis, 2014. 8(11): p. e3333. 
2. 
Ichimori, K., et al., Global programme to eliminate lymphatic filariasis: the 
processes underlying programme success. PLoS Negl Trop Dis, 2014. 8(12): p. 
e3328. 
3. 
Thomsen, E.K., et al., Efficacy, Safety, and Pharmacokinetics of Coadministered 
Diethylcarbamazine, Albendazole, and Ivermectin for Treatment of Bancroftian 
Filariasis. Clin Infect Dis, 2016. 62(3): p. 334-41. 
4. 
Romani, L., et al., Mass Drug Administration for Scabies Control in a Population 
with Endemic Disease. N Engl J Med, 2015. 373(24): p. 2305-13. 
5. 
Supali, T., et al., Impact of six rounds of mass drug administration on Brugian 
filariasis and soil-transmitted helminth infections in eastern Indonesia. PLoS Negl 
Trop Dis, 2013. 7(12): p. e2586. 
6. 
Dewi, R.M., et al., Brugia Rapid antibody responses in communities of Indonesia 
in relation to the results of 'transmission assessment surveys' (TAS) for the 
lymphatic filariasis elimination program. Parasit Vectors, 2015. 8: p. 499. 
7. 
Fischer, P., et al., Long-lasting reduction of Brugia timori microfilariae following a 
single dose of diethylcarbamazine combined with albendazole. Trans R Soc Trop 
Med Hyg, 2003. 97(4): p. 446-8. 
8. 
Supali, T., et al., Treatment of Brugia timori and Wuchereria bancrofti infections in 
Indonesia using DEC or a combination of DEC and albendazole: adverse reactions 
and short-term effects on microfilariae. Trop Med Int Health, 2002. 7(10): p. 894-
901. 
9. 
Bockarie, M.J., et al., Randomised community-based trial of annual single-dose 
diethylcarbamazine with or without ivermectin against Wuchereria bancrofti 
infection in human beings and mosquitoes. Lancet, 1998. 351(9097): p. 162-8. 
10. 
Horton, J., Albendazole: a review of anthelmintic efficacy and safety in humans. 
Parasitology, 2000. 121 Suppl: p. S113-32. 
11. 
Goa, K.L., D. McTavish, and S.P. Clissold, Ivermectin. A review of its antifilarial 
activity, pharmacokinetic properties and clinical efficacy in onchocerciasis. Drugs, 
1991. 42(4): p. 640-58. 
12. 
Edwards, G., Ivermectin: does P-glycoprotein play a role in neurotoxicity? Filaria 
J, 2003. 2 Suppl 1: p. S8. 
13. 
Ottesen, E.A. and W.C. Campbell, Ivermectin in human medicine. J Antimicrob 
Chemother, 1994. 34(2): p. 195-203. 
14. 
Awadzi, K., et al., The co-administration of ivermectin and albendazole--safety, 
pharmacokinetics and efficacy against Onchocerca volvulus. Ann Trop Med 
Parasitol, 2003. 97(2): p. 165-78. 
15. 
Ottesen, E.A., Efficacy of diethylcarbamazine in eradicating infection with 
lymphatic-dwelling filariae in humans. Rev Infect Dis, 1985. 7(3): p. 341-56. 
16. 
McGarry, H.F., L.D. Plant, and M.J. Taylor, Diethylcarbamazine activity against 
Brugia malayi microfilariae is dependent on inducible nitric-oxide synthase and the 
cyclooxygenase pathway. Filaria J, 2005. 4: p. 4. 

 
DOLF_IDA_Indonesia_Protocol v5.0_24May17 
 
Page 38 of 39 
17. 
Noroes, J., et al., Assessment of the efficacy of diethylcarbamazine on adult 
Wuchereria bancrofti in vivo. Trans R Soc Trop Med Hyg, 1997. 91(1): p. 78-81. 
18. 
Ottesen, E.A., et al., Strategies and tools for the control/elimination of lymphatic 
filariasis. Bull World Health Organ, 1997. 75(6): p. 491-503. 
19. 
World Health Organization (2006). Preventive chemotherapy in human 
helminthiasis: coordinated use of anthelminthic drugs in control interventions: a 
manual for health professionals and programme managers. 
 

 
DOLF_IDA_Indonesia_Protocol v5.0_24May17 
 
Page 39 of 39 
14 
LIST OF APPENDICES 
Appendix 1: Study Drug Flow Diagram (country specific) 
Appendix 2: Participant Enrollment Form Example 
Appendix 3: Participant Monitoring Form Example 
Appendix 4: Guide to Assigning Adverse Event Severity 
Appendix 5: Adverse Event Evaluation and Report Form (AEERF) Example 
Appendix 5a: Required Reporting & Guidelines for SAE(s) 
Appendix 6: ICF  
Appendix 7: Treatment Acceptability Study Protocol 
Appendix 8: Acceptability Survey for community respondents [Example] 
Appendix 9: Topic Guide – Focus Group Discussion on the Acceptability of IDA [Example] 
Appendix 10: Topic Guide – In Depth Interviews with Key Informants for Acceptability of IDA 
[Example] 
Appendix 11: Visitation Matri

 
 
DOLF_IDA_Indonesia_Protocol v5.0_24May17 
 
Page 1 of 2 
 
APPENDIX 1: 
STUDY FLOW DIAGRAM (COUNTRY SPECIFIC) 
Study Flow Diagram: Triple Drug 
 
 
 

 
DOLF_IDA_Indonesia_Protocol v5.0_24May17 
 
Page 2 of 2 
Study Flow Diagram: Two Drug 
 
 
 

 
 
DOLF_IDA_Indonesia_Protocol v5.0_24May17 
 
Page 1 of 6 
 
APPENDIX 2: 
PARTICIPANT ENROLLMENT FORM 
Participant ID (Barcode): 
 
1. DEMOGRAPHICS 
Team (required): 
 
Data Entry Clerk ID (required):  
Informed Consent Date (required) (DD-MM-YYYY):     ______-______-______ 
Site Location (required) 
☐  Site 1  
☐  Site  2  
☐  Site  3  
☐  Site  4  
☐  Site  5  
☐  Site  6  
☐  Site  7  
☐  Site  8  
☐  Site  9  
☐  Site 10  
☐  Site 11 
Gender: ☐M    ☐F 
               ☐ 
Unknown 
Note: if exact date is not known, birth year is sufficient 
Age (Years): 
Birth Day (DD): 
Birth Month 
(MM): 
Birth Year 
(YYYY): 
Weight (in kg):  
Height (in cm): 
BMI Calculation [(weight/height*0.01)^(2)] :  
 
2. PRE-TREATMENT MEDICAL HISTORY 
Do you feel well today? 
☐Yes  
☐No 
Symptoms/Signs  
• 
Grade 2 requires Vital Signs 
• 
Grade 3 and higher requires physical examination by medical personnel or refer out to 
            local health clinic.  Do not enroll. 
NOTES: If participant does not feel well today, please mark the symptoms they 
describe and identify the grade. 
Sign/Symptom 
1 - Mild   
2 -Moderate   3 - Severe 
4 - Life-
threatening 
Fever 
 
 
 
 
Dizziness, lightheaded 
 
 
 
 
Headache 
 
 
 
 
Fatigue 
 
 
 
 

APPENDIX 2: 
PARTICIPANT ENROLLMENT FORM [EXAMPLE] 
Participant ID (Barcode): 
 
 
DOLF_IDA_Indonesia_Protocol v5.0_24May17 
 
Page 2 of 6 
Difficulty breathing (wheezing or 
dyspnea 
 
 
 
 
Cough 
 
 
 
 
Joint pain 
 
 
 
 
Muscle pain 
 
 
 
 
Muscle Weakness 
 
 
 
 
Rash 
 
 
 
 
Itchy skin 
 
 
 
 
Swelling in armpit  
 
 
 
 
Swelling in groin 
 
 
 
 
Pain in armpit  
 
 
 
 
Pain in groin 
 
 
 
 
Men only: pain in your scrotum 
 
 
 
 
Nausea 
 
 
 
 
Vomiting 
 
 
 
 
Diarrhea 
 
 
 
 
Stomach Pain 
 
 
 
 
Other illness or symptoms (specify): 
Other Grade: 
 
 
 
 
Did the participant report any symptoms that are Grade 2 or greater?    
☐Yes  
      ☐No  
      ☐ Not Applicable 
 
If YES, you must notify a member of the medical team to conduct vital signs.  
 
Any Grade 3 symptom requires physical examination by medical personnel or refer out to 
local health clinic.  Do not enroll. 
Subject can be enrolled 
☐Yes  
      ☐No  
 
3. Special Interest Events - LF 
Do you have swelling in your arms or legs (lymphedema)?                         ☐Yes   ☐No 
If lymphedema: Confirm and indicate 
which limbs are affected  
☐Left Arm 
Severity of lymphedema: 
☐ Mild 
☐ Moderate 

APPENDIX 2: 
PARTICIPANT ENROLLMENT FORM [EXAMPLE] 
Participant ID (Barcode): 
 
 
DOLF_IDA_Indonesia_Protocol v5.0_24May17 
 
Page 3 of 6 
☐Right Arm 
☐Left Leg 
☐Right Arm 
☐Severe - Elephantiasis 
☐ Severe - Disabled 
Males only:  Are your testicles swollen? 
☐Yes   ☐No 
Males only:  Are your testicles swollen all the time or only when carrying heavy things?  
  ☐ All the time 
  ☐ Only when carrying heavy things 
 
5. Pre Treatment Vital Signs (Grade 2 and higher Pre-Tx Medical History only) 
 
Measurements 
Values / status 
Systolic blood pressure, sitting 
_________ (mm HG)     ☐Not done 
Diastolic blood pressure, sitting 
_________ (mm HG)     ☐Not done 
      Blood pressure: Systolic under 100  
      and/or Diastolic under 60? 
☐Yes     
☐No 
If Yes, send home to eat and 
return tomorrow 
 
Was individual orthostatic?  
Note: Systolic BP at least 20 points lower and diastolic 
BP at least 10 points lower when standing. 
☐Yes     ☐No 
Pulse rate 
_________ (bpm)            ☐Not done 
Temperature 
_________ (Celsius)        ☐Not done 
 
6.  Filarial Antigen test (FTS) results 
 
FTS Results: 
☐Positive 
☐Negative 
☐Undetermined  
 
FTS Score:   
 ☐Weak 
 ☐Medium 
       ☐Strong 
 ☐Not Done 
If FTS is Positive, Night Blood Collection is required.  MDA will be administered after night 
blood has been collected.  
If Negative, continue form and administer MDA 
If Undetermined, repeat the test – if 2nd test is undetermined, then treat this as positive 
Indonesia Only: 
BrugiaRapid date  (DD-MM-YYYY):       
 
           ______-______-______ 
BrugiaRapid Results: 
☐Positive 
☐Negative 

APPENDIX 2: 
PARTICIPANT ENROLLMENT FORM [EXAMPLE] 
Participant ID (Barcode): 
 
 
DOLF_IDA_Indonesia_Protocol v5.0_24May17 
 
Page 4 of 6 
      ☐Undetermined 
 
7. Pregnancy Test Results  
 
Indonesia Only: 
Pregnancy test date  (DD-MM-YYYY):       
       
            ______-______-______ 
      Pregnancy Test Results: 
☐Positive 
☐Negative 
☐Undetermined 
 
8. Inclusion/Exclusion Criteria 
 
Inclusion Criteria: 
 
Able to provide informed consent or parental consent to 
participate in the study (Forms to be attached) 
☐No  ☐Yes 
Exclusion Criteria: 
 
FEMALE ONLY:  Pregnant women (DEC, ivermectin and 
albendazole are contraindicated in pregnancy) 
☐No  ☐Yes 
FEMALE ONLY: Childbearing age (between age 12 -50) who has 
not had a menstrual period in the last 4 weeks 
☐No 
☐ Yes or Do not Recall 
☐Not Applicable 
FEMALE ONLY: Breastfeeding in first 7 days following delivery 
☐No  ☐Yes 
Severe acute or chronic illness (for example: chronic renal failure, 
inability to care for oneself with activities of daily living) except for 
features of filarial disease 
☐No  ☐Yes 
History of previous allergy to MDA drugs 
☐No  ☐Yes 
 
 
 
 
 
 

APPENDIX 2: 
PARTICIPANT ENROLLMENT FORM [EXAMPLE] 
Participant ID (Barcode): 
 
 
DOLF_IDA_Indonesia_Protocol v5.0_24May17 
 
Page 5 of 6 
 
9.  MDA Treatment  
 
Please calculate dose using Dosage according to Below Chart 
Weight (kg): ___________________ 
Drug Regimen: 
☐ Double drug therapy (ALB, DEC) 
☐ Triple drug therapy (ALB, DEC, IVM) 
MDA Treatment Date (DD-MM-YYYY):    
______-______-______    
Albendazole (ALB) dose (400 mg) 
☐ 1 tablet (400 mg) Not done 
Diethylcarbamazine citrate (DEC) dose 
(6mg/kg) 
☐ 1 tablet (100 mg)  
☐ 2 tablets (200 mg)  
☐ 3 tablets (300 mg) 
☐ 4 tablet (400 mg)  
☐ 5 tablets (500 mg)  
☐ 6 tablets (600 mg) 
Ivermectin (IVM) dose (200 ug /kg) 
☐ 1 tablet (3 mg) 
☐ 2 tablets (6 mg) 
☐ 3 tablets (9 mg) 
☐ 4 tablets (12 mg) 
☐ 5 tablet (15 mg)  
☐ 6 tablets (18 
mg)  
☐ 7 tablets (21 
mg) 
 
Did Patient vomit or spit out the pills? 
 
 
☐Yes       ☐No 
2nd MDA Treatment Date (DD-MM-
YYYY):    
______-______-______    
2nd Albendazole (ALB) dose (400 mg) 
☐ 1 tablet (400 mg) Not done 
2nd Diethylcarbamazine citrate (DEC) 
dose (6mg/kg) 
☐ 1 tablet (100 mg)  
☐ 2 tablets (200 mg)  
☐ 3 tablets (300 mg) 
☐ 4 tablet (400 mg)  
☐ 5 tablets (500 mg)  
☐ 6 tablets (600 mg) 

APPENDIX 2: 
PARTICIPANT ENROLLMENT FORM [EXAMPLE] 
Participant ID (Barcode): 
 
 
DOLF_IDA_Indonesia_Protocol v5.0_24May17 
 
Page 6 of 6 
2nd Ivermectin (IVM) dose (200 ug /kg) 
☐ 1 tablet (3 mg) 
☐ 2 tablets (6 mg) 
☐ 3 tablets (9 mg) 
☐ 4 tablets (12 mg) 
☐ 5 tablet (15 mg)  
☐ 6 tablets (18 mg)  
☐ 7 tablets (21 mg) 
 
 
 
DOLF IDA MDA DOSING CHART (by weight) 
Albendazole 
(ALB) 
dosing 
(400 mg) 
Diethylcarbamazine 
citrate (DEC) 
dosing 6mg/kg 
Ivermectin 
(IVM) 
(dosing 200 ug /kg) 
15 kg-120kg 
1 tablet 
(400 mg) 
15-25kg 
1 tablet (100 mg)  
15-23kg 
1 tablet (3 mg)  
 
 
26-41kg 
2 tablets (200 mg) 
24-38kg 
2 tablets (6 mg) 
 
 
42-58kg 
3 tablets (300 mg) 
39-53kg 
3 tablets (9 mg)  
 
 
59-75kg 
4 tablets (400 mg) 
54-68kg 
4 tablets (12 mg) 
 
 
76-92kg 
5 tablets (500 mg) 
69-83kg 
5 tablets (15 mg)  
 
 
93-100kg 
6 tablets (600 mg) 
84-98kg 
6 tablets (18 mg)  
 
 
 
 
99-100kg 
7 tablets (21 mg)  
 

 
 
DOLF_IDA_Indonesia_Protocol v5.0_24May17 
 
Page 1 of 14 
 
APPENDIX 3: 
PARTICIPANT MONITORING FORM [EXAMPLE] 
 
Team (required): 
Clinician (required): 
 
Data Entry Clerk ID (required): 
 
1. PARTICIPANT INFORMATION 
Site #: 
Treatment Date (DD-MM-YYYY):    ______-______-______        
Monitoring Start Date (DD-MM-YYYY):          ______-______-______    
Day 1 
Day 2 
Day 3 
Day 4 
Day 5 
Day 6 
Day 7 
☐ 
☐ 
☐ 
☐ 
☐ 
☐ 
☐ 
Was Participant found during Active 
Monitoring? 
Day 1 
☐  Yes    ☐  No  
Day 2 
☐  Yes    ☐  No 
 
Team (required): 
Clinician (required): 
 
Data Entry Clerk ID (required): 
 
1. PARTICIPANT INFORMATION 
Site #: 
Treatment Date (DD-MM-YYYY):    ______-______-______        
Monitoring Start Date (DD-MM-YYYY):          ______-______-______    
Day 1 
Day 2 
Day 3 
Day 4 
Day 5 
Day 6 
Day 7 
☐ 
☐ 
☐ 
☐ 
☐ 
☐ 
☐ 
Was Participant found during Active 
Monitoring? 
Day 1 
☐  Yes    ☐  No  
Day 2 
☐  Yes    ☐  No 
 
2. ASSESSMENT INFORMATION 
 
Were any adverse events 
experienced? 
 
☐Yes 
☐No 
AE Identifier 
Record unique identifier for each adverse event for this 
subject.   
 
Number sequence for all following forms should not 
duplicate existing numbers for the subject. 
Symptoms/Signs  
• 
Grade 2 requires Vital Signs 

APPENDIX 3: 
PARTICIPANT MONITORING FORM [EXAMPLE] 
Participant ID (Barcode): 
 
 
DOLF_IDA_Indonesia_Protocol v5.0_24May17 
 
Page 2 of 14 
• 
Grade 3 requires Vital Signs AND Physical Exam by Medical Personnel 
 
Day 1 and 2: All participants should be asked all the questions in Table 1. 
Days 3-7: Any participant who presents with a complaint should have their AEs graded below 
in Table 1.  
 
Table 1:  Reported Symptoms 
 
Record a symptom grade from 0-5 for each day on which the participant 
experienced symptoms.  
 Refer to the Guide for Assigning Adverse Event Severity for symptom-specific 
scoring criteria. 
 Report Start and Stop dates for each Adverse Events 
 If Participant has an Adverse Event and is lost to follow-up, please indicate  
 
Symptom Grading 
0 = No adverse event or within normal limits 
1 = Mild adverse event, does not interfere with work or school 
2 = Moderate adverse event, interferes with work or school at least 1 day 
3 = Severe and undesirable adverse event; interferes with ADL, requires medical assessment 
4 = Potentially life-threatening or disabling adverse event; requires transfer to medical facility 
5 = Death  
 
 
 
 

APPENDIX 3: 
PARTICIPANT MONITORING FORM [EXAMPLE] 
Participant ID (Barcode): 
 
 
DOLF_IDA_Indonesia_Protocol v5.0_24May17 
 
Page 3 of 14 
Symptoms
/Signs 
Were any 
adverse 
events 
experience
d by 
participant? 
___-___-
___ 
 
Day 1 
 
___-
___-___ 
 
Day 2 
___-
___-
___ 
 
Day 3 
___-
___-
___ 
 
Day 4 
___-
___-
___ 
 
Day 5 
___-
___-
___ 
 
Day 6 
___-
___-
___ 
 
Day 7 
 
Con
tin-
uin
g?  
Lost 
To 
Foll
ow-
up? 
Is 
the 
Adve
rse 
Even
t 
Serio
us? 
Neurologic-  
 
 
Fever - 
Grade 
 
 
 
 
 
 
 
☐ 
☐ 
☐ 
Dizziness, 
lightheaded 
- Grade 
 
 
 
 
 
 
 
☐ 
☐ 
☐ 
Headache - 
Grade 
 
 
 
 
 
 
 
☐ 
☐ 
☐ 
Fatigue - 
Grade 
 
 
 
 
 
 
 
☐ 
☐ 
☐ 
Respiratory 
 
 
Difficulty 
breathing 
(wheezing 
or dyspnea) 
- Grade 
 
 
 
 
 
 
 
☐ 
☐ 
☐ 
Cough - 
Grade 
 
 
 
 
 
 
 
☐ 
☐ 
☐ 
Musculoskel
etal 
 
 
Joint pain - 
Grade 
 
 
 
 
 
 
 
☐ 
☐ 
☐ 
Muscle pain 
- Grade 
 
 
 
 
 
 
 
☐ 
☐ 
☐ 
Muscle 
Weakness - 
Grade 
 
 
 
 
 
 
 
☐ 
☐ 
☐ 
Skin 
 
 
Rash - 
Grade 
 
 
 
 
 
 
 
☐ 
☐ 
☐ 
Itchy Skin - 
Grade 
 
 
 
 
 
 
 
☐ 
☐ 
☐ 
Lymphatic 
 
 
Swelling in 
armpit - 
Grade 
 
 
 
 
 
 
 
☐ 
☐ 
☐ 

APPENDIX 3: 
PARTICIPANT MONITORING FORM [EXAMPLE] 
Participant ID (Barcode): 
 
 
DOLF_IDA_Indonesia_Protocol v5.0_24May17 
 
Page 4 of 14 
Swelling in 
groin - 
Grade 
 
 
 
 
 
 
 
 
 
 
Pain in 
armpit - 
Grade 
 
 
 
 
 
 
 
☐ 
☐ 
☐ 
Pain in 
groin - 
Grade 
 
 
 
 
 
 
 
 
 
 
Genital 
 
 
Men only: 
pain in your 
scrotum - 
Grade 
 
 
 
 
 
 
 
☐ 
☐ 
☐ 
Gastrointest
inal 
 
 
Nausea - 
Grade 
 
 
 
 
 
 
 
☐ 
☐ 
☐ 
Vomiting - 
Grade 
 
 
 
 
 
 
 
☐ 
☐ 
☐ 
Diarrhea - 
Grade 
 
 
 
 
 
 
 
☐ 
☐ 
☐ 
Stomach 
Pain - 
Grade 
 
 
 
 
 
 
 
☐ 
☐ 
☐ 
New 
Swelling - 
Grade 
 
 
 
 
 
 
 
☐ 
☐ 
☐ 
Specify the 
location of 
the unusual 
swelling 
 
 
 
 
 
 
 
 
 
 
Other  
 
 
Other 
illness or 
symptoms - 
Grade 
 
 
 
 
 
 
 
☐ 
☐ 
☐ 
Other 
(please 
specify): 
 
 
 
 
 
 
 
 
 
 
 
If there are any symptoms Grade≥2, participant’s vital signs must be taken by a Health Worker. 
 
If there are any symptoms Grade ≥ 3, you must notify the supervising medical officer and the 
participant must be evaluated by the medical team.    
 
 
Table 2:  Special Interest Events – Lymphatic Filariasis 

APPENDIX 3: 
PARTICIPANT MONITORING FORM [EXAMPLE] 
Participant ID (Barcode): 
 
 
DOLF_IDA_Indonesia_Protocol v5.0_24May17 
 
Page 5 of 14 
 
Record the result under the column that corresponds to the day the 
assessment was taken.   
 
Results for individual questions are listed under question 
 
These questions only are answered if the corresponding AE above is 
recorded 
 
“Swelling in armpit or groin” and/or “New Swelling” 
 
“Men only: pain in your testicles or scrotum” 
Special Interest Events - LF 
Post-treatment day(s) 
Day 
1 
Day 
2 
Day 
3 
Day 
4 
Day 
5 
Day 
6 
Day 
7 
Lymphedema (Swelling in arms or 
legs 
Results: Yes, No 
 
 
 
 
 
 
 
Confirm and indicate which limbs are 
affected   
Results: 1- Left arm, 2- Right arm,  3 - Left 
leg, 4- Right arm 
 
 
 
 
 
 
 
Severity of lymphedema  
Results: 1- Mild, 2 – Moderate, 3 – Severe 
Elephantiasis, 4 – Severe Disabling 
 
 
 
 
 
 
 
Hydrocele (testicle swollen) 
Results: Yes, No 
 
 
 
 
 
 
 
Testicle swelling  
Results: 1 – all the time; 2- only when carrying 
large objects 
 
 
 
 
 
 
 
 
Table 3:  Vital Signs  
 
You must complete this table for any participant reporting any symptom 
Grade ≥2  
 
Record the result under the column that corresponds to the day the 
assessment was taken.   
Measurements 
Post-treatment day(s) 
Day 
1 
Day 
2 
Day 
3 
Day 
4 
Day 
5 
Day 
6 
Day 
7 
Systolic blood pressure, sitting (mm 
Hg) 
 
 
 
 
 
 
 
Diastolic blood pressure, sitting (mm 
Hg) 
 
 
 
 
 
 
 
Orthostatic? Results: Yes, No 
 
 
 
 
 
 
 
Pulse rate (beats per minute) 
 
 
 
 
 
 
 

APPENDIX 3: 
PARTICIPANT MONITORING FORM [EXAMPLE] 
Participant ID (Barcode): 
 
 
DOLF_IDA_Indonesia_Protocol v5.0_24May17 
 
Page 6 of 14 
Temperature (in Celsius) 
 
 
 
 
 
 
 
 
 
Table 4:  Abnormal Physical Findings 
 
You must complete this table for any participant reporting any symptom 
Grade ≥3  
 
Record the result under the column that corresponds to the day the 
assessment was taken.   
 
Post-treatment day(s) 
D
ay 
1 
D
a
y 
2 
D
a
y 
3 
D
a
y 
4 
D
a
y 
5 
D
a
y 
6 
Da
y 
7 
Was participant referred for further assessment?  
Results: Yes, No 
 
 
 
 
 
 
 
Tender Lymph node locations  
Results: 1 - Axilla, 2 - Inguinal, 3 - Scrotal 
 
 
 
 
 
 
 
For participants with GI symptoms, record the following  
Results: 1 - Abdominal tenderness, 2 - Enlarged spleen, 
3- Enlarged liver 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Post-Exam Adverse Event Grade (Assign grade of 0-5 for the adverse reactions 
below based on physical exam. See “post-exam assessment” for specific grading 
criteria) 
Allergic reaction 
 
 
 
 
 
 
 
Lung Wheezing 
 
 
 
 
 
 
 
Lymphangitis (streaks of redness, warmth, and 
swelling in arms or legs) 
 
 
 
 
 
 
 
Are there any abnormal physical findings?  
Results: Yes, No 
 
 
 
 
 
 
 
Additional notes or comments: 
 
 
 
 
 
 
 
 
 
 
 
 

APPENDIX 3: 
PARTICIPANT MONITORING FORM [EXAMPLE] 
Participant ID (Barcode): 
 
 
DOLF_IDA_Indonesia_Protocol v5.0_24May17 
 
Page 7 of 14 
Table 5:  Body Systems Physical Exam 
 
Everyone with Grade ≥3 AE will have a Physical Exam by a Medical Examiner. 
 
Not all body systems need to be examined as these are directed physical 
exams; review body systems related to reported AEs. 
Body Systems 
Post-treatment day(s) 
Da
y 1 
Da
y 2 
Da
y 3 
Da
y 4 
Da
y 5 
Da
y 6 
Da
y 7 
Has anything changed since the last physical 
exam?  Results: Yes, No 
 
 
 
 
 
 
 
Exam performed: 
Results: Yes, No 
 
 
 
 
 
 
 
Reason Not Performed: 
 
 
 
 
 
Review of Body Systems  
Record whether:  1 – Normal, 2- Abnormal, 3 – Not 
Done 
Post-treatment day(s) 
 
Da
y 1 
Da
y 2 
Da
y 3 
Da
y 4 
Da
y 5 
Da
y 6 
Da
y 7 
Cardiac 
 
 
 
 
 
 
 
Ear and Labyrinth 
 
 
 
 
 
 
 
Endocrine and Lymph  
 
 
 
 
 
 
 
Eye 
 
 
 
 
 
 
 
Hepatobiliary, Renal and Urinary 
 
 
 
 
 
 
 
Mouth, Throat and Gastrointestinal 
 
 
 
 
 
 
 
Musculoskeletal and Connective Tissue 
 
 
 
 
 
 
 
Nervous System 
 
 
 
 
 
 
 
Reproductive System and Breast 
 
 
 
 
 
 
 
Respiratory, Thoracic and Mediastinal 
 
 
 
 
 
 
 
Skin and Subcutaneous Tissue 
 
 
 
 
 
 
 
Vascular  
 
 
 
 
 
 
 
Other 
 
 
 
 
 
 
 

APPENDIX 3: 
PARTICIPANT MONITORING FORM [EXAMPLE] 
Participant ID (Barcode): 
 
 
DOLF_IDA_Indonesia_Protocol v5.0_24May17 
 
Page 8 of 14 
Abnormal Findings: 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
RESULTS 
 
D
a
y 
1 
D
a
y 
2 
D
a
y 
3 
D
a
y 
4 
D
a
y 
5 
D
a
y 
6 
D
a
y 
7 
PE 
Identi
fier 
Clinically significant 
Results:  Yes, No 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Reporting 
Clinician Name  
 
Day 4 
 
Day1 
 
Day 5 
 
Day 2 
 
Day 6 
 
Day 3 
 
Day 7 
 
 
 
Symptoms
/Signs 
Were any 
adverse 
events 
experience
d by 
participant? 
Post-treatment day(s) on which symptoms or signs were present 
 
___-___-
___ 
 
Day 1 
 
___-
___-___ 
 
Day 2 
___-
___-
___ 
 
Day 3 
___-
___-
___ 
 
Day 4 
___-
___-
___ 
 
Day 5 
___-
___-
___ 
 
Day 6 
___-
___-
___ 
 
Day 7 
 
Con
tin-
uin
g?  
Lost 
To 
Foll
ow-
up? 
Is 
the 
Adve
rse 
Even
t 
Serio
us? 

APPENDIX 3: 
PARTICIPANT MONITORING FORM [EXAMPLE] 
Participant ID (Barcode): 
 
 
DOLF_IDA_Indonesia_Protocol v5.0_24May17 
 
Page 9 of 14 
Neurologic-  
 
 
Fever - 
Grade 
 
 
 
 
 
 
 
☐ 
☐ 
☐ 
Dizziness, 
lightheaded 
- Grade 
 
 
 
 
 
 
 
☐ 
☐ 
☐ 
Headache - 
Grade 
 
 
 
 
 
 
 
☐ 
☐ 
☐ 
Fatigue - 
Grade 
 
 
 
 
 
 
 
☐ 
☐ 
☐ 
Respiratory 
 
 
Difficulty 
breathing 
(wheezing 
or dyspnea) 
- Grade 
 
 
 
 
 
 
 
☐ 
☐ 
☐ 
Cough - 
Grade 
 
 
 
 
 
 
 
☐ 
☐ 
☐ 
Musculoskel
etal 
 
 
Joint pain - 
Grade 
 
 
 
 
 
 
 
☐ 
☐ 
☐ 
Muscle pain 
- Grade 
 
 
 
 
 
 
 
☐ 
☐ 
☐ 
Muscle 
Weakness - 
Grade 
 
 
 
 
 
 
 
☐ 
☐ 
☐ 
Skin 
 
 
Rash - 
Grade 
 
 
 
 
 
 
 
☐ 
☐ 
☐ 
Itchy Skin - 
Grade 
 
 
 
 
 
 
 
☐ 
☐ 
☐ 
Lymphatic 
 
 
Swelling in 
armpit - 
Grade 
 
 
 
 
 
 
 
☐ 
☐ 
☐ 
Swelling in 
groin - 
Grade 
 
 
 
 
 
 
 
 
 
 
Pain in 
armpit - 
Grade 
 
 
 
 
 
 
 
☐ 
☐ 
☐ 
Pain in 
groin - 
Grade 
 
 
 
 
 
 
 
 
 
 
Genital 
 
 

APPENDIX 3: 
PARTICIPANT MONITORING FORM [EXAMPLE] 
Participant ID (Barcode): 
 
 
DOLF_IDA_Indonesia_Protocol v5.0_24May17 
 
Page 10 of 14 
Men only: 
pain in your 
scrotum - 
Grade 
 
 
 
 
 
 
 
☐ 
☐ 
☐ 
Gastrointest
inal 
 
 
Nausea - 
Grade 
 
 
 
 
 
 
 
☐ 
☐ 
☐ 
Vomiting - 
Grade 
 
 
 
 
 
 
 
☐ 
☐ 
☐ 
Diarrhea - 
Grade 
 
 
 
 
 
 
 
☐ 
☐ 
☐ 
Stomach 
Pain - 
Grade 
 
 
 
 
 
 
 
☐ 
☐ 
☐ 
New 
Swelling - 
Grade 
 
 
 
 
 
 
 
☐ 
☐ 
☐ 
Specify the 
location of 
the unusual 
swelling 
 
 
 
 
 
 
 
 
 
 
Other  
 
 
Other 
illness or 
symptoms - 
Grade 
 
 
 
 
 
 
 
☐ 
☐ 
☐ 
Other 
(please 
specify): 
 
 
 
 
 
 
 
 
 
 
 
If there are any symptoms Grade≥2, participant’s vital signs must be taken by a Health Worker. 
 
If there are any symptoms Grade ≥ 3, you must notify the supervising medical officer and the 
participant must be evaluated by the medical team.    
 
 
Table 2:  Special Interest Events – Lymphatic Filariasis 

APPENDIX 3: 
PARTICIPANT MONITORING FORM [EXAMPLE] 
Participant ID (Barcode): 
 
 
DOLF_IDA_Indonesia_Protocol v5.0_24May17 
 
Page 11 of 14 
 
Record the result under the column that corresponds to the day the 
assessment was taken.   
 
Results for individual questions are listed under question 
 
These questions only are answered if the corresponding AE above is 
recorded 
 
“Swelling in armpit or groin” and/or “New Swelling” 
 
“Men only: pain in your testicles or scrotum” 
Special Interest Events - LF 
Post-treatment day(s) 
Day 
1 
Day 
2 
Day 
3 
Day 
4 
Day 
5 
Day 
6 
Day 
7 
Lymphedema (Swelling in arms or 
legs 
Results: Yes, No 
 
 
 
 
 
 
 
Confirm and indicate which limbs are 
affected   
Results: 1- Left arm, 2- Right arm,  3 - Left 
leg, 4- Right arm 
 
 
 
 
 
 
 
Severity of lymphedema  
Results: 1- Mild, 2 – Moderate, 3 – Severe 
Elephantiasis, 4 – Severe Disabling 
 
 
 
 
 
 
 
Hydrocele (testicle swollen) 
Results: Yes, No 
 
 
 
 
 
 
 
Testicle swelling  
Results: 1 – all the time; 2- only when carrying 
large objects 
 
 
 
 
 
 
 
 
Table 3:  Vital Signs  
 
You must complete this table for any participant reporting any symptom 
Grade ≥2  
 
Record the result under the column that corresponds to the day the 
assessment was taken.   
Measurements 
Post-treatment day(s) 
Day 
1 
Day 
2 
Day 
3 
Day 
4 
Day 
5 
Day 
6 
Day 
7 
Systolic blood pressure, sitting (mm 
Hg) 
 
 
 
 
 
 
 
Diastolic blood pressure, sitting (mm 
Hg) 
 
 
 
 
 
 
 
Orthostatic? Results: Yes, No 
 
 
 
 
 
 
 
Pulse rate (beats per minute) 
 
 
 
 
 
 
 

APPENDIX 3: 
PARTICIPANT MONITORING FORM [EXAMPLE] 
Participant ID (Barcode): 
 
 
DOLF_IDA_Indonesia_Protocol v5.0_24May17 
 
Page 12 of 14 
Temperature (in Celsius) 
 
 
 
 
 
 
 
 
 
Table 4:  Abnormal Physical Findings 
 
You must complete this table for any participant reporting any symptom 
Grade ≥3  
 
Record the result under the column that corresponds to the day the 
assessment was taken.   
 
Post-treatment day(s) 
D
ay 
1 
D
a
y 
2 
D
a
y 
3 
D
a
y 
4 
D
a
y 
5 
D
a
y 
6 
Da
y 
7 
Was participant referred for further assessment?  
Results: Yes, No 
 
 
 
 
 
 
 
Tender Lymph node locations  
Results: 1 - Axilla, 2 - Inguinal, 3 - Scrotal 
 
 
 
 
 
 
 
For participants with GI symptoms, record the following  
Results: 1 - Abdominal tenderness, 2 - Enlarged spleen, 
3- Enlarged liver 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Post-Exam Adverse Event Grade (Assign grade of 0-5 for the adverse reactions 
below based on physical exam. See “post-exam assessment” for specific grading 
criteria) 
Allergic reaction 
 
 
 
 
 
 
 
Lung Wheezing 
 
 
 
 
 
 
 
Lymphangitis (streaks of redness, warmth, and 
swelling in arms or legs) 
 
 
 
 
 
 
 
Are there any abnormal physical findings?  
Results: Yes, No 
 
 
 
 
 
 
 
Additional notes or comments: 
 
 
 
 
 
 
 
 
 
 
 
 

APPENDIX 3: 
PARTICIPANT MONITORING FORM [EXAMPLE] 
Participant ID (Barcode): 
 
 
DOLF_IDA_Indonesia_Protocol v5.0_24May17 
 
Page 13 of 14 
Table 5:  Body Systems Physical Exam 
 
Everyone with Grade ≥3 AE will have a Physical Exam by a Medical Examiner. 
 
Not all body systems need to be examined as these are directed physical 
exams; review body systems related to reported AEs. 
Body Systems 
Post-treatment day(s) 
Da
y 1 
Da
y 2 
Da
y 3 
Da
y 4 
Da
y 5 
Da
y 6 
Da
y 7 
Has anything changed since the last physical 
exam?  Results: Yes, No 
 
 
 
 
 
 
 
Exam performed: 
Results: Yes, No 
 
 
 
 
 
 
 
Reason Not Performed: 
 
 
 
 
 
Review of Body Systems  
Record whether:  1 – Normal, 2- Abnormal, 3 – Not 
Done 
Post-treatment day(s) 
 
Da
y 1 
Da
y 2 
Da
y 3 
Da
y 4 
Da
y 5 
Da
y 6 
Da
y 7 
Cardiac 
 
 
 
 
 
 
 
Ear and Labyrinth 
 
 
 
 
 
 
 
Endocrine and Lymph  
 
 
 
 
 
 
 
Eye 
 
 
 
 
 
 
 
Hepatobiliary, Renal and Urinary 
 
 
 
 
 
 
 
Mouth, Throat and Gastrointestinal 
 
 
 
 
 
 
 
Musculoskeletal and Connective Tissue 
 
 
 
 
 
 
 
Nervous System 
 
 
 
 
 
 
 
Reproductive System and Breast 
 
 
 
 
 
 
 
Respiratory, Thoracic and Mediastinal 
 
 
 
 
 
 
 
Skin and Subcutaneous Tissue 
 
 
 
 
 
 
 
Vascular  
 
 
 
 
 
 
 
Other 
 
 
 
 
 
 
 

APPENDIX 3: 
PARTICIPANT MONITORING FORM [EXAMPLE] 
Participant ID (Barcode): 
 
 
DOLF_IDA_Indonesia_Protocol v5.0_24May17 
 
Page 14 of 14 
Abnormal Findings: 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
RESULTS 
 
D
a
y 
1 
D
a
y 
2 
D
a
y 
3 
D
a
y 
4 
D
a
y 
5 
D
a
y 
6 
D
a
y 
7 
PE 
Identi
fier 
Clinically significant 
Results:  Yes, No 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Reporting 
Clinician Name  
 
Day 4 
 
Day1 
 
Day 5 
 
Day 2 
 
Day 6 
 
Day 3 
 
Day 7 
 

 
 
DOLF_IDA_Indonesia_Protocol v5.0_24May17 
 
Page 1 of 4 
 
APPENDIX 4: 
GUIDE TO ASSIGNING ADVERSE EVENT SEVERITY 
 
(Grade 0 = no symptoms; grade 5 = death from adverse event) 
Symptoms/Signs 
Grades 
1. Mild 
2. Moderate 
3. Severe 
4. Life-threatening 
Fever (non-axillary 
temperatures only) 
38.0 – 39.0ºC 
39.1 – 40.0ºC 
> 40.0ºC 
> 40.0ºC for > 48 hrs 
Dizziness, 
giddiness, or 
fainting 
Mild, not 
interfering 
with work or 
school 
Moderate, 
unable to work 
or attend 
school for 1 
day, but no 
fainting 
Any loss of 
consciousness 
(fainting) 
- 
Confusion or 
excess 
drowsiness* 
Mild, not 
interfering 
with work or 
school 
Moderate; 
confusion or 
drowsiness 
interfering with 
ability to work 
Confusion, 
loss of 
memory, or 
sleepiness 
interfering with 
activities of 
daily living 
Delerium, inability 
rouse, or coma  
Fatigue 
Mild, not 
interfering 
with work or 
school 
Moderate, 
unable to work 
or attend 
school  at least 
1 day 
Unable to 
perform 
activities of 
daily living, > 
1day 
Required 
hospitalization 
Headache 
Mild pain not 
interfering 
with work or 
school 
Moderate pain; 
pain or 
analgesics 
interfering with 
ability to work 
or attend 
school 
Severe pain; 
pain or 
analgesics 
interfering with 
activities of 
daily living 
Disabling, duration > 
48 hr 
Cough 
Mild, relieved 
by non-
prescription 
medication 
Requiring 
narcotic 
antitussive 
Severe cough 
or coughing 
spasms, poorly 
controlled by 
treatment 
Hospitalization or 
respiratory failure 
requiring mechanical 
ventilation 

APPENDIX 4: 
GUIDE TO ASSIGNING ADVERSE EVENT SEVERITY 
(Grade 0 = no symptoms; grade 5 = death from adverse event) 
DOLF_IDA_Indonesia_Protocol v5.0_24May17 
 
Page 2 of 4 
Symptoms/Signs 
Grades 
1. Mild 
2. Moderate 
3. Severe 
4. Life-threatening 
Difficulty breathing 
(wheezing or 
dyspnea) 
Mild, not 
interfering 
with work or 
school 
Moderate, 
unable to work 
or attend 
school for 1 
day 
Severe, more 
than 1 day and 
required 
transfer to 
clinic or 
hospital 
Hospitalization or 
respiratory failure 
requiring mechanical 
ventilation 
Nausea 
Able to eat 
Oral intake 
significantly 
decreased 
No significant 
intake, 
requiring IV 
fluids 
- 
Vomiting 
1 episode in 
24 hours over 
pretreatment 
2-5 episodes 
in 24 hours 
over 
pretreatment 
≥ 6 episodes in 
24hours,  or 
need for IV 
fluids 
(0upatient) 
Hemodynamic 
collapse or overnight 
hospitalization 
Diarrhea 
Increase of < 
4 stools/day 
over pre-
treatment 
Increase of 4-6 
stools/ day, or 
nocturnal 
stools 
Increase of ≥ 7 
stools/ day or 
need for 
outpatient 
parenteral 
support for 
dehydration 
Physiologic 
consequences wth 
hemodynamic 
collapse or requiring 
hospitalization 
Abdominal pain 
Mild pain not 
interfering 
with work or 
school 
Moderate pain; 
pain or 
analgesics 
interfering with 
ability to work 
or attend 
school 
Severe pain; 
pain or 
analgesics 
interfering with 
activities of 
daily living 
Disabling, duration > 
48 hr 
Unusual swelling 
(beyond baseline 
lymphedema) 
Mild, not 
interfering 
with work or 
school 
Moderate, 
unable to work 
or attend 
school 1 day  
Severe, unable 
to work/school 
>1 day 
Severe, limiting 
activities of daily 
living (unable to 
walk) > 2 days 
Joint or muscle 
pain 
Mild pain not 
interfering 
with work or 
school 
Moderate pain; 
pain or 
analgesics 
interfering with 
ability to work 
or attend 
school 
Severe pain; 
pain or 
analgesics 
interfering with 
activities of 
daily living 
Disabling, duration > 
48 hr 

APPENDIX 4: 
GUIDE TO ASSIGNING ADVERSE EVENT SEVERITY 
(Grade 0 = no symptoms; grade 5 = death from adverse event) 
DOLF_IDA_Indonesia_Protocol v5.0_24May17 
 
Page 3 of 4 
Symptoms/Signs 
Grades 
1. Mild 
2. Moderate 
3. Severe 
4. Life-threatening 
Swelling or pain in 
your armpit or 
groin* 
Mild, not 
interfering 
with work or 
school 
Moderate, 
unable to work 
or attend 
school 1 day  
Severe, unable 
to work/school 
>1 day 
Severe, limiting 
activities of daily 
living (unable to 
walk) > 2 days 
Men only:  
testicular or scrotal 
pain 
Mild, not 
interfering 
with work or 
school 
Moderate, 
unable to work 
or attend 
school 1 day  
Severe, unable 
to work/school 
>1 day 
Severe, limiting 
activities of daily 
living (unable to 
walk) > 2 days 
Itching skin 
Mild, not 
interfering 
with work or 
school 
Moderate, 
unable to work 
or attend 
school 1 day  
Severe, unable 
to work/school 
>1 day 
 
Rash 
 
 
Localized 
rash (covers 
only one part 
of the body) 
Diffuse rash 
(covers 
multiple parts 
of the body)  
Diffuse rash 
(covers 
multiple parts 
of the body) 
AND has any 
blisters or 
ulcers or 
mouth sores 
Extensive areas with 
blisters or ulcers OR 
peeling or 
blackening of skin 
Other illness or 
symptoms  
 
 
Mild, not 
interfering 
with work or 
school 
Moderate, 
unable to work 
or attend 
school  at least 
1 day 
Unable to 
perform 
activities of 
daily living, > 
1day 
Required 
hospitalization 
 
 

APPENDIX 4: 
GUIDE TO ASSIGNING ADVERSE EVENT SEVERITY 
(Grade 0 = no symptoms; grade 5 = death from adverse event) 
DOLF_IDA_Indonesia_Protocol v5.0_24May17 
 
Page 4 of 4 
 
Post-Exam 
Assessment 
Grades 
1. Mild 
2. Moderate 
3. Severe 
4. Life-threatening 
Acute allergic 
reaction 
Transient 
rash, drug 
Fever <38ºC 
(<100.4ºF) 
Urticaria, drug 
fever ≥38ºC 
(≥100.4ºF) 
and/or 
asymptomatic 
bronchospasm 
Symptomatic 
bronchospasm, 
requiring 
parenteral 
medication(s) 
with or without 
urticaria 
Anaphylaxis with 
hypotension 
required 
hospitalization 
Hypotension (low 
blood pressure) 
Changes, but 
not requiring 
therapy 
(including 
transient 
orthostatic 
hypotension) 
Requiring brief 
fluid 
replacement 
(such as oral 
rehydration) 
but not 
hospitalization 
Requiring i.v. 
fluids without 
overnight 
hospitalization.  
No sequelae. 
Required overnight 
hospitalization for 
i.v. fluids, or Shock 
(acidemia and 
impaired vital organ 
function due to 
tissue 
hypoperfusion) 
Lymphangitis 
Mild, not 
interfering 
with work or 
school 
Moderate, 
unable to work 
or attend 
school 1 day  
Severe, unable 
to work/school 
>1 day 
Severe, limiting 
activities of daily 
living (unable to 
walk) > 2 days 
Note on general aspects of grading 
0 = No adverse event or within normal limits 
1 = Mild adverse event, does not interfere with work or school 
2 = Moderate adverse event, interferes with work or school at least 1 day 
3 = Severe and undesirable adverse event; interferes with ADL, requires medical assessment 
4 = Potentially life-threatening or disabling adverse event; requires transfer to medical facility 
5 = Death  
Note: Any event ≥ grade 2 requires a medical evaluation and notification of the medical 
officer. 

 
 
DOLF_IDA_Indonesia_Protocol v5.0_24May17 
 
Page 1 of 3 
 
APPENDIX 5: 
ADVERSE EVENT EVALUATION AND REPORT FORM 
(AEERF) [EXAMPLE] 
Instructions: Complete this form AFTER completing the Participant Monitoring Form for 
anyone with symptoms or signs of grade 3 or higher (unable to perform activities of daily 
living without assistance for at least one day) and determined by a physician or health care 
worker to be a potential Serious Adverse Event (SAE). The purpose of this form is to provide 
additional information on more severe adverse events and to assist the medical monitor in 
determining whether a Serious Adverse Event (SAE) has occurred.   
 
PROTOCOL:  DOLF IDA 
 
Country:          
Site#:          
 
Participant Barcode:   
 
SECTION 1: REPORT TYPE 
 Initial - Date:   -   -     
                              DD-MMM-YYYY 
 Follow-up #      - Date:   -   -     
                                                     DD-MMM-YYYY 
SECTION 2:  DEMOGRAPHICS 
Gender: 
 Female 
 Male 
 
Date of Birth:    -     
                          MMM-YYYY 
SECTION 3:  ADVERSE EVENT INFORMATION 
 
SAE Term (concise medical diagnosis):       
 
Start Date:   -   -     
                    DD-MMM-YYYY 
End Date:   -   -      
                       DD-MMM-YYYY 
Serious Criteria (check all that apply):   
Outcome (check one): 
 
 Inpatient or Prolonged Hospitalization - If yes,  Date of Admission:    -   -     
                                       DD-MMM-YYYY  
       Date of Discharge:    -   -     
            DD-MMM-YYYY  
 Life-threatening (immediate risk of death) 
 
 A persistent or significant disability/incapacity  
 
 Congenital Anomaly or Birth Defect 
 
 Other Serious or Important Medical Event 
 
 Death - If yes, Cause of Death:          Date of Death:   -   -     
                                                                                         DD-MMM-YYYY  
Was autopsy completed?        
 No    
 Yes - If yes, please forward report 
Is death certificate available?  
 No    
 Yes - If yes, please forward 
 
 Recovered/Resolved 
 
 Recovered/Resolved with 
sequelae (describe sequelae 
in narrative) 
 
 Recovering/Resolving   
 
 Not Recovered/Not Resolved  
 
 Fatal 
 
 Unknown 
 
CTCAE Grade Version 4.03 / Severity (check one):  
 Grade 1/Mild     
 Grade 2/Moderate     
 Grade 3/Severe     
 Grade 4/Life-threatening     
 Grade 5/Death 
 
 
 
 
 
 
 

APPENDIX 5: ADVERSE EVENT EVALUATION AND REPORT FORM (AEERF) 
[EXAMPLE] 
Participant ID (Barcode): 
 
 
DOLF_IDA_Indonesia_Protocol v5.0_24May17 
 
Page 2 of 3 
PROTOCOL:  DOLF IDA 
 
Country:          
Site#:          
 
Participant Barcode:   
 
 
 
SECTION 4:  STUDY DRUG INFORMATION  
MDA Treatment Date 
  
Albendazole 
(400 mg tablets) 
DEC  
(100 mg tablets)  
Ivermectin  
(3 mg tablets) 
Relationship of SAE to MDA 
 (check one) 
  -   -     
DD-MMM-YYYY 
# Tabs  
 
# Tabs  
 
# Tabs  
 
   NA     
 
   
 Not Related 
   
 Possibly Related 
   
 Probably Related 
   
 Related 
 
Possible alternate cause other than Study Drug (select all that apply): 
 
 Study Disease-related                                                                               
 Pre-existing condition - Specify:       
 
 Concomitant medication - Specify:                                                       
 Other - Specify:       
 
    SECTION 5:  RELEVANT LABORATORY/DIAGNOSTIC TESTS     
 None   
Test Name 
Date 
Result 
Unit 
Normal Range 
      
  -   -     
DD-MMM-YYYY 
      
      
      
      
  -   -     
DD-MMM-YYYY 
      
      
      
      
  -   -     
DD-MMM-YYYY 
      
      
      
      
  -   -     
DD-MMM-YYYY 
      
      
      
      
  -   -     
DD-MMM-YYYY 
      
      
      
SECTION 6:  RELEVANT CONCOMITANT MEDICATIONS     
 None   
Medication  
Start Date 
Stop Date or Ongoing 
Dose & 
Unit 
Frequency 
Route 
Indicatio
n 
      
  -   -     
 DD-MMM-YYYY 
  -   -     OR 
 Ongoing 
    DD-MMM-YYYY 
      
      
      
      
      
  -   -     
DD-MMM-YYYY 
  -   -     OR 
 Ongoing 
    DD-MMM-YYYY 
      
      
      
      
      
  -   -     
DD-MMM-YYYY 
  -   -     OR 
 Ongoing 
    DD-MMM-YYYY 
      
      
      
      
      
  -   -     
DD-MMM-YYYY 
  -   -     OR 
 Ongoing 
     DD-MMM-YYYY 
      
      
      
      
      
  -   -     
DD-MMM-YYYY 
  -   -     OR 
 Ongoing 
     DD-MMM-YYYY 
      
      
      
      
SECTION 7:  RELEVANT MEDICAL HISTORY     
 None   
Diagnosis 
Start Date 
Stop Date  or Ongoing 
      
  -   -     
DD-MMM-YYYY 
  -   -     OR 
 Ongoing 
      DD-MMM-YYYY 
      
  -   -     
DD-MMM-YYYY 
  -   -     OR 
 Ongoing  
      DD-MMM-YYYY 

APPENDIX 5: ADVERSE EVENT EVALUATION AND REPORT FORM (AEERF) 
[EXAMPLE] 
Participant ID (Barcode): 
 
 
DOLF_IDA_Indonesia_Protocol v5.0_24May17 
 
Page 3 of 3 
PROTOCOL:  DOLF IDA 
 
Country:          
Site#:          
 
Participant Barcode:   
 
      
  -   -     
DD-MMM-YYYY 
  -   -     OR 
 Ongoing 
      DD-MMM-YYYY 
      
  -   -     
DD-MMM-YYYY 
  -   -     OR 
 Ongoing 
      DD-MMM-YYYY 
      
  -   -     
DD-MMM-YYYY 
  -   -     OR 
 Ongoing 
       DD-MMM-YYYY 
SECTION 8:  NARRATIVE SUMMARY 
Describe the event in detail from onset through resolution.  Include rationale for causality and any interventions given. 
      
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
SECTION 9:  REPORTER INFORMATION 
 
Reporter Name (if not Investigator):       
 
Location:        
I, the undersigned investigator, attest that I have reviewed this SAE Report and agree with the content.  
 
Investigator Name: 
 
 
Investigator Signature: 
 
Date:   -   -     
         DD-MMM-YYYY 

 
 
DOLF_IDA_Indonesia_Protocol v5.0_24May17 
 
Page 1 of 4 
 
APPENDIX 5A: 
REQUIRED REPORTING & GUIDELINES FOR SAE(S) 
An Adverse Event Evaluation and Report Form (AEERF) should be completed for every severe 
adverse event (those scoring grade 3 or higher, see Appendix 4). However, a grade 3 or severe 
adverse event is NOT the same as a Serious Adverse Events (SAE) and the majority of grade 3 
adverse events will not be classified as SAE. The term "severe" is often used to describe the 
intensity (severity) of a specific event (as in mild, moderate, or severe myocardial infarction); the 
event itself, however, may be of relatively minor medical significance (such as severe 
headache). This is not the same as "serious," which is based on patient/event outcome or action 
criteria usually associated with events that pose a threat to a patient's life or functioning. 
Seriousness (not severity) serves as a guide for defining regulatory reporting obligations.  
The AEERF should guide the medical monitor or health care provider evaluating the patient 
experiencing a severe AE to determine whether a SAE has occurred.  All SAE must be reported 
promptly. (See Safety Reporting Plan for SAE Reporting Timeline) 
Required Reporting  
A written report or case report form (CRF—in this study, the AEERF) must be sent from the 
local physician and local medical monitor by email (scanned records) in the stated timeframes to 
the Country PI, Global Medical Monitor including the Project PI for the events listed below.  
Guidelines for Reporting - Standard Reporting Information   
The following information should be included in the initial report/CRF (additional 
information may be requested): 
Minimum Criteria for Reporting  
Information for final description and evaluation of a case report may not be 
available within the required time frames for reporting outlined below. Initial 
reports should be submitted within the prescribed time as long as the following 
minimum criteria are met: an identifiable patient; an identifiable reporting 
source; and an event or outcome that can be identified as serious. Follow-up 
information should be actively sought and submitted as it becomes available.  
Complete the following information if available on the initial report and complete a follow-up 
report as new or additional information becomes available as noted below: 
 
Description of the event 
Date, time of onset 
Clinical history 
Associated signs and symptoms 
Temporal association with study agent 
Medical management, including rationale 

APPENDIX 5A: REQUIRED REPORTING & GUIDELINES FOR SAE(S) 
 
 
DOLF_IDA_Indonesia_Protocol v5.0_24May17 
 
Page 2 of 4 
Pertinent laboratory tests 
Severity – see definitions or toxicity score 
Causal relationship to the study drug/vaccine 
 
Other information 
Relevant past medical history 
Concomitant medications 
Autopsy report or expectation of an autopsy in the case of death 
 
Outcome of event 
Date, time of resolution, if resolved 
 
Plans for study participant 
Follow-up 
Treatment of event 
Return to treatment/Contraindicate 
 
Location/Study Centre 
 
Reporting Physician 
 
Verification of notification to IRB and Safety Monitor or DSMB 
Definitions 
 
Adverse Event [Experience] (AE): 
Any untoward medical occurrence, including dosing errors, that may arise during 
administration of study agent, and which may or may not have a causal relationship with 
the study agent. 
 
Unexpected Adverse Event [Experience]: 
Any adverse experience that has not been previously observed (i.e., included in the 
labelling), whether or not the event is anticipated because of the pharmacologic 
properties of the study agent.  
 

APPENDIX 5A: REQUIRED REPORTING & GUIDELINES FOR SAE(S) 
 
 
DOLF_IDA_Indonesia_Protocol v5.0_24May17 
 
Page 3 of 4 
 
Serious Adverse Event (SAE): 
Any adverse event occurring at any dose that results in any of the following outcomes: 
a. Death 
b. Life threatening – defined as an experience that places the patient or participant, in 
the view of the Investigator, at immediate risk of death from the reaction as it 
occurred.  (Note; this does not include a reaction that, had it occurred in a more 
severe form, might have caused death.) 
c. Requires inpatient hospitalization or prolongation of existing hospitalization 
d. Results in a congenital anomaly or birth defect 
e. Results in a persistent or significant disability or incapacity 
f. 
Important medical events that may not result in death, be life-threatening, or require 
hospitalization may be considered a serious adverse experience when, based upon 
appropriate medical judgment, they may jeopardize the patient or participant and 
may require medical or surgical intervention to prevent one of the outcomes listed in 
this definition.  (The event might be defined as serious based on progression of 
grade if Toxicity Tables are being used.) 
Severity  
Adverse experience/events should be assessed by the on-site investigator as to their 
severity and/or intensity. 
a. Life threatening 
b. Severe: incapacitating with inability to work or do usual activity 
c. Moderate: enough discomfort to cause interference with usual activity 
d. Mild: awareness of sign or symptom, but easily tolerated 
Relationship or Association with Use of Study Agent or Participation in the Study 
Causal relationship with the investigational study treatment must be assessed by the on-site 
investigator using the following or similar terms: 
 
Definite – clear-cut temporal association, with a positive re-challenge test or laboratory 
confirmation. 

APPENDIX 5A: REQUIRED REPORTING & GUIDELINES FOR SAE(S) 
 
 
DOLF_IDA_Indonesia_Protocol v5.0_24May17 
 
Page 4 of 4 
 
Probable – clear-cut temporal association, with improvement upon drug withdrawal, and 
not reasonably explained by the participant’s known clinical state. 
 
Possible – less clear temporal association; other aetiologies are possible. 
 
None – no temporal association with the study drug; related to other aetiologies such as 
concomitant medications or conditions, or participant’s known clinical state. 
Other Reporting 
Investigators are reminded that they may have other reporting obligations: 
 
For all studies, there must be compliance with the clinical site Ethics/IRB’s policy for 
reporting adverse events. (As soon as possible for SAEs and as required for AEs.) 
 
 

 
 
DOLF_IDA_Indonesia_Protocol v5.0_24May17 
 
Page 1 of 6 
 
APPENDIX 6A: 
INFORMED CONSENT FORM (V.3, 30 AUGUST 2016) 
INFORMED CONSENT FORM (Version 3, 30 August 2016) 
Community Based Safety Study of 2-drug versus 3-drug Therapy for Lymphatic Filariasis in 
Indonesia 
Principal Investigators: Peter U. Fischer, Ph.D. (USA), Taniawati Supali, Ph.D. (Indonesia) 
Lymphatic filariasis, commonly called Elephant foot is a problem in this village. This disease is 
caused by infection of worms that live in the blood, left untreated for a long time. If this disease 
has gotten to a stage elephant foot which cause your limbs to swell, then the swollen parts cannot 
go back to normal. This disease might make it difficult for you to work and to perform daily 
activities. 
Elephant foot is commonly treated in Indonesia with two drugs. These two drugs need to be 
taken by most people in the community every year for five years in order to get rid of the disease.  
We, the team of Department of Parasitology Faculty of Medicine Universitas Indonesia together 
with Washington University and the local health district are doing a new MDA approach along 
with research study to see if there is a better and faster treatment for elephant foot. We will 
study the effect of two different drug combinations given to men, women, and children aged 5 
years or more in this village.  The study will look at the effects of the drugs in treating gut worms 
since each drug is known to kill gut worms. 
Aim of the study and the reason you are asked to participate 
Two drugs are currently used to treat elephant foot. They are called Diethylcarbamazine (DEC) 
and Albendazole. There is another drug called Ivermectin that has been used safely to treat 
elephant foot in Africa. The purpose of this research is to learn if three drugs (DEC, Albendazole 
and Ivermectin) work better than the two drugs (DEC and Albendazole). We will also look at the 
side effects of these drugs used together to get rid of elephant foot and to treat gut worms. This 
research will be done in four villages in two districts. The villages are Karang Inda,Kahale and 
Rada Malando in Southwest Sumba District and Ojandetun village in East Flores District. 
The reason why that we are asking you to be in this study is because your village is in an area 
with a high risk of elephant foot. In order to get rid of this disease your village like every village 
in Indonesia needs to get treatment. In addition to comparing how the treatment with two or 
three drugs work to get rid of elephant foot we also want to know if the drugs will be accepted 
by you and your community, so it is important that you participate in this study. 
 

APPENDIX 6A: 
INFORMED CONSENT FORM (V.3, 30 AUGUST 2016) 
DOLF_IDA_Indonesia_Protocol v5.0_24May17 
 
Page 2 of 6 
Drug administration and Drug Reaction 
In this study, you will take either two drugs (albendazole and DEC) or three drugs (albendazole, 
DEC, and ivermectin). The number of pills you take depend on how much you weigh. The pills 
must be swallowed in front of the study officer in charge. The first 60 adults in this study will take 
the drug at the hospital in the city (RSUD Waikabubak). Everyone else will take the drug in their 
villages where they live. 
You may have drug reaction after taking the drugs. The side effects that might include things like 
headache, nausea, vomiting, stomach pain, tiredness, difficulty in breathing, faint, itching, rash, 
or swelling in some parts of your body. However those drug reaction do not occur so often. There 
may be some side effects we do not know about yet. 
Hospital- Based Treatment (Procedure, Potential risk, and Compensation) 
We will come to your village to take blood from your finger at night. If we find the elephant foot 
worm in your blood you may be chosen to be one of the 60 people who will take the drug at the 
hospital. If you are selected, you will be asked to stay at the hospital for three nights and four 
days. The reason you have to be hospitalized is that we want to carefully see if you have any side 
effects and to make sure the drugs are working. The drug is supposed to kill the worms. The dead 
worms may cause reactions in your body, causing symptoms like fever, drowsiness, and 
weariness which generally happens in people who have elephant foot. There is a small chance 
that you are allergic to one or more of the drugs. We want to monitor all of these possible effects, 
either by  a doctor’s examination or laboratory test, to make sure you are safe and that the drug 
is working. You will be given the medicine to treat the effect, if you experience any reaction. 
The blood collection in the hospital will be done by drawing blood from your vein which may 
cause slightly more discomfort compared to finger prick blood collection. Infection, bruising and 
bleeding might also occur but this is very unlikely to happen. The amount of blood collected is 
approximately as much as two table spoons. The blood collected will be tested for worms. 
Four days after you leave the hospital, we will visit your home to ask if you have had any other 
side effects since leaving the hospital. You will not be charged any fee during the hospitalization. 
All transportation to and from your home to the hospital, as well as your treatment and meals 
will be free. To replace the lost income that you might get from working, we will give you 
compensation in amount of IDR 300,000. You are free to quit the study any time for any reason 
or no reason. If you leave the hospital early you will still receive partial payment for the time you 
stayed at the hospital. If you leave the study there will be no impact on your medical care. We 
will provide full insurance if you get sick, have an accident or get injured because of the study. 
Community- Based Treatment (Procedure, Potential Risk, and Compensation) 

APPENDIX 6A: 
INFORMED CONSENT FORM (V.3, 30 AUGUST 2016) 
DOLF_IDA_Indonesia_Protocol v5.0_24May17 
 
Page 3 of 6 
Everyone who was not chosen to be treated at the hospital will be treated in their community 
where they live. 
Basically, the same steps will be done. You will be given medication, then we will visit you to see 
how the medicine worked and look at any side effects caused by the medicine. If you have side 
effects we will record it and give you treatment to help you. We will visit you twice, once on the 
first day after you have taken the medicine and again on the second day. If you have any side 
effects during the next five days (7 days after you took the medicine) you should tell the head of 
your Dusun about it. Someone from our research team will visit the head of your Dusun to ask if 
anyone has a side effect and will find you. Health workers from the Faculty of Medicine, 
Department of Health, or the primary health care will accompany you during your treatment. In 
order to see if the medicines are working we will take blood samples from you finger. Blood 
collection might  cause some pain. Infection and bleeding might also occur but this is very unlikely 
to happen. 
In addition to taking blood, some of you will be asked to collect your poo in a special container 
which we have provided. We will ask for your poo before and after you take the drug. We will 
use your poo to see if you have gut worms and also to see if the drug works to kill gut worms. 
You will not be charged to participate in this study. You will also not be compensated in this 
community-based study. We will provide full insurance if you get sick, have an accident or get 
injured because of the study. You may quit the study at any time for any reason or no reason 
with no impact on your medical care. 
Acceptability Study 
After all treatment is over, we will do a survey to learn what the community thinks about the 
three drug treatment compared to the standard two drug therapy. In this survey you will be asked 
questions about how you felt about taking the drug, your opinion on the side effects, and your 
opinion about taking three drugs again in the future. 
Sample Size and Study Participants’ Criteria 
We expect 4,000 participants in total to take part in this study. This includes male and female 
adults, and children aged 5 years old or older. People will be picked from these villages: Karang 
Inda, Kahale, Rada Malando and Ojandetun. Sixty people with high infection of worms will be 
picked to take the drug at the hospital. We will ask for poo from 600 participants to see the effect 
on gut worms. 
To be in the study you must be 5 years old or older, you must not have severe disease at the 
moment (which may cause problems for the study or cause harm to yourself), you must not have 
an allergy or bad reaction to drugs used to treat elephant foot, if you are a woman you must not 

APPENDIX 6A: 
INFORMED CONSENT FORM (V.3, 30 AUGUST 2016) 
DOLF_IDA_Indonesia_Protocol v5.0_24May17 
 
Page 4 of 6 
be pregnant or be breastfeeding at the moment. If you are not sure if you are pregnant or forget 
when you had your last menstrual period, we will give you a pregnancy test to tell whether you 
are pregnant or not. 
If you meet this criteria, you can be in this study. To be in the study, you have to provide written 
consent for yourself or for your children (as a parent or legal guardian). 
Duration and Term and Condition of Participation 
If you decide to be in this study, you will be part of the study for one year. This starts from the 
day you are given treatment. You will be visited on the first and second day after taking the drug. 
If you tell the head of the dusun that you have side effects, you may be visited again. Within four 
months after you took the drug, you may be asked to participate in acceptability study. After 
that, one year later we may visit you again. You will be asked to give finger prick blood to see 
how the drug worked. 
Your participation in this study is voluntary. You are free to decide if you or your children want 
to be involved. You are also free to decide to quit the study at any time. If you move away outside 
of the study villages during the study you can be taken out of the study. If you are taken out of 
the study there will be no impact on your medical care. If you do not want to be part of this study, 
you will still be given medication for elephant foot  (DEC and ALB given once a year for five years). 
The two drugs are part of a mass treatment program for elephant foot given to people by the 
Health Ministry of Indonesia. 
Confidentiality 
For long term follow up purpose, we will take your photo and store it in our data. This data can 
be seen only by study team. We will keep your identity secret. A code using only numbers will be 
used to identify your blood and stool. You will be given an identification card which you might 
write your name on it. This card will be kept by yourself. There will be an emergency contact on 
the card which you can call if you have an emergency situation within 7 days after taking the 
drug. You name or any other information about you will not be put on your blood or stool. Your 
information will be kept secret even if you are taken out of the study or decide to quit the study. 
Sample Storage and Usage 
All blood and stool sample will be stored in Department of Parasitology Universitas Indonesia. 
The blood collected from you will only be used for the study described above related to elephant 
foot and gut worms. Some blood and stool may be picked at random (like rolling dice) to be sent 
to other laboratory to check that the tests for worms are done correctly. 
 

APPENDIX 6A: 
INFORMED CONSENT FORM (V.3, 30 AUGUST 2016) 
DOLF_IDA_Indonesia_Protocol v5.0_24May17 
 
Page 5 of 6 
WHOM TO CALL IF I HAVE QUESTIONS OR PROBLEM RELATED TO THE STUDY? 
If in the future you have a question or problem related to your participation in the study, you 
may call the field coordinator, dr. Michael Christian (081237587120) or study coordinator, Dr. 
Yenny Djuardi at this number: +62812 8852 7832. 
 
 
 
ASSESSMENT OF CONSENT  
Point to be confirmed 
Yes 
No 
Do you understand the explanation? 
 
 
Do you have any question? 
 
 
If yes: 
 
 
 
Are you voluntarily willing to be involved in this study? 
 
 
If yes, in which part of the study would you participate? 
☐ Hospital- based treatment 
☐ Community- based treatment 
Will we draw blood from you? 
 
 
Will we ask you to collect your stool in a container we provide? 
 
 
Are you free to decide to quit the study anytime? 
 
 
Are you charged for participating in this study? 
 
 
Are you going to receive a compensation by taking part in this study? 
 
 
Do you know whom to call if in future you have questions or problems 
related to your participation? 
 
 
 
By signing this document you agree that: 
1. ____________________________ has explained what we are going to do, the risk, and 
the benefit of participating in this study. 
2. You have understood the explanation given to you about your involvement and you 
have been given time to ask questions. 
3. We (the study team) have checked that you understand this study by asking you 
questions about the study. 
By signing this page, you confirm that you or your children whom you represent has agreed to 
participate in this study voluntarily.  

APPENDIX 6A: 
INFORMED CONSENT FORM (V.3, 30 AUGUST 2016) 
DOLF_IDA_Indonesia_Protocol v5.0_24May17 
 
Page 6 of 6 
 
Participant’s name: 
 
Consent date: 
 
(For participant aged < 18 years old, please fill out the assent form 
next page) 
Signature/thumbprint 
 
 
 
 
Explainer’s name: 
 
Date: 
 
Signature 
Investigator’s name: 
 
Date: 
 
Signature 
Witness’ name: 
 
Date: 
 
Signature 
 
ASSENT FORM 
, My name is ______________________________ and I am the child of my parent whose name 
is: ___________________________________. I confirm that I am voluntarily willing to be in this 
study and that my parents/legal guardian agree that I can participate. I understand that I will be 
given medication, have my blood drawn and tested, and might have side effects that were 
explained to me by the study researchers. I also understand that I may decide to quit the study 
at any time.  
Participant’s name: 
 
Consent giver’s name: 
 
Relation to participant: 
(Parent/ Legal guardian) 
 
Signature/thumbprint 
 

 
 
DOLF_IDA_Indonesia_Protocol v5.0_24May17 
 
Page 1 of 2 
 
APPENDIX 6B: 
INFORMED RE-CONSENT FORM (V.1, 24 MAY 2017) 
STUDY NAME:  
Community Based Safety and Efficacy Study of 2-drug versus 3-
drug Therapy for Lymphatic Filariasis in Indonesia 
 
PRINICIPLE INVESTIGATORS:  
Prof. Dr. Taniawati Supali 
 
Approximately one year ago, you volunteered to be a part of a research study about lymphatic filariasis, 
which is caused by worms that live in your blood. You may also hear people calling this disease filaria 
or Kapola. 
 
Researchers from Universitas Indonesia and Washington University in the United States talked to you 
about the study and when you agreed to be in the study they gave you the study medicine.  The study 
team came back to see you to see if you had any side effects from the medicine and we told you that 
we would come back in one year to see how well the medicine killed the worms.  We are now visiting 
you to see if the worms are still inside your blood. Beside collecting your blood, we will also 
collect your poo to see if there is any worm in your gut, since the study medicine also have 
effect on gut worm. 
 
Today you are being asked to continue participating in the study to see how well the medicine killed the 
worms. If you agree, you will be tested for the worms with the test listed in the table below. If we find 
worms we will give you medicine to treat the worms.  
Type of Test 
What Will Happen 
Filaria Test Strip, 
Brugia Rapid &  
Thick Blood Smear 
We will ask for a small amount of blood from your finger. It will only take 2 to 5 
minutes for us to collect this blood. The blood collection might cause some pain. 
Infection and bleeding may also occur, but this is VERY UNLIKELY to happen. If 
you have history of prolonged bleeding, please REPORT this to study team. We will 
test your blood to see if you have worms in your blood.  
 
This procedure will be done for COMMUNITY BASED STUDY participants, who 
were treated in the village in the previous study stage. 
Filarial Test Strip, 
Brugia Rapid, and 
Venous Blood Draw 
This procedure will be done for HOSPITAL BASED STUDY participants who were 
treated in the hospital in the previous study stage. 
 
We will draw blood from your vein in your arm. It will take about 5 to 10 minutes to 
collect this blood. This may cause pain. Infection, bruising and bleeding may occur, 
but this is VERY UNLIKELY. If you have history of prolonged bleeding, please 
REPORT this to study team. The amount of blood collected is approximately two 
tablespoons. We will test your blood to see if you have worms in your blood. 
Stool Sample 
We will ask for a small amount of your poo or po’e in a special container that we will 
give you. We will test your poo to see if you have worms in your gut. 
 
You will not be charged to be in the study. You will not be given any gifts to be in the study. If you are 
injured or get sick because of this study we will pay for your care.  
 
Your participation is voluntary. You will not be punished if you do not want to volunteer. Your worms can 
still be treated during the government’s regular community treatment program.  You may stop the study 
at any time and you do not have to give a reason. If you stop the study you will not be changed for any 
of the medicines you took. 
 

APPENDIX 6B: 
INFORMED RE-CONSENT FORM (V.1, 24 MAY 2017) 
DOLF_IDA_Indonesia_Protocol v5.0_24May17 
 
Page 2 of 2 
We will keep your identity secret. Your name and information about you will be kept in a safe place and 
can only be seen by the study team. A code using only numbers will be used to identify your blood and 
stool samples. Your information will be kept secret even if you stop the study. 
 
All blood and stool samples will be stored in Department of Parasitology Universitas Indonesia. Some 
samples may be sent to other laboratories to check that the tests for worms were done correctly. The 
blood and stool samples we collect from you will only be used in this study. 
 
If you have questions about your participation in this study you may call dr. Michael Christian on 
081237587120 
 
By signing this page, you confirm that you and/or your children have voluntarily agreed to be in this 
study. 
Participant’s name: 
 
Consent date: 
 
(For participant aged < 18 years old, please fill out the assent 
form) 
Signature/thumbprint 
 
 
 
 
Explainer’s name: 
 
Date: 
 
Signature 
Witness’ name (if necessary): 
 
Date: 
 
Signature 
 
 
ASSENT FORM (To Be Signed For All Children Less Than Age 18 yo) 
 
My name is ________________________________________________________ 
My parent’s/legal guardian name is: _____________________________________  
I agree that I am volunteering to be in this study and that my parents/legal guardian agree that I can 
participate. I understand that I will be given medication, have my blood drawn and tested, and might have 
side effects that were explained to me by the study researchers. I also understand that I may decide to 
quit the study at any time.  
Participant’s name: 
 
Consent giver’s name: 
 
Relation to participant: 
(Parent/ Legal guardian) 
 
Signature/thumbprint 

 
 
Protocol for Acceptability Study; version 29.06.2016 
 
Page 1 of 16 
 
APPENDIX 7: 
PROTOCOL FOR A TREATMENT ACCEPTABILITY STUDY 
FOLLOWING THE TRIPLE DRUG COMMUNITY SAFETY TRIALS 
 
Version 29 June 2016 
 
Research team 
Alison Krentel PhD, Investigator, Bruyère Research Institute, Ottawa Canada 
Joshua Bogus MPH, Global Health Project Manager for Operations, DOLF project, Washington 
University, USA 
 
Co-investigators in Fiji 
Myra Hardy, University of Melbourne 
Andrew Steer, University of Melbourne 
John Kaldor, Kirby Institute 
Lucia Romani, Kirby Institute 
Margot Whitfeld, St. Vincent’s Hospital 
 
Co-investigators in Haiti 
Dr. Jean Frantz Lemoine, Coordinator of National LF and Malaria Programmes, MoH 
Christine Dubray, CDC Atlanta 
Carl Fayette, IMA World Health 
Abdel Direny, RTI, consultant 
Valery Madsen De Rochars, University of Florida, consultant  
 
Co-investigators in Indonesia 
Taniawati Supali, Universitas Indonesia 
Adriani Lomi Ga, Government of Nusa Tenggara Timur, consultant 
Maddi Djara, consultant 
 
Co-investigators in Papua New Guinea 
Leanne Robinson, Papua New Guinea Institute of Medical Research 
Chris King, Case Western University 
Daniel Tisch, Case Western University 
James Kazura, Case Western University 
Krufinta Bun, Case Western University 
Cade Howard, Case Western University 
 
Statistical support 
Ken Schechtman, Washington University in St. Louis 
 
 
 

APPENDIX 7: 
PROTOCOL FOR A TREATMENT ACCEPTABILITY STUDY 
FOLLOWING THE TRIPLE DRUG COMMUNITY SAFETY TRIALS 
Protocol for Acceptability Study; version 29.06.2016 
 
Page 2 of 16 
 
A. Summary 
As part of the larger “Community Based Safety Study of 2-drug versus 3-drug Therapy for 
Lymphatic Filariasis” a study to assess treatment acceptability in the community is planned in 
each research site: Papua New Guinea, Indonesia, Haiti, Sri Lanka and India. The overall aim of 
this research is to understand the community’s acceptance of the 3-drug regimen as well as 
gain insight into the feasibility of administering this new therapy in the future. Part of the 
investigation will include assessing community member’s perception of the possible adverse 
events experienced as a result of the 3-drug therapy, and how that might affect future rounds of 
mass drug administration (MDA) at the community level. Community acceptance will be 
measured using a survey to community members receiving treatment during the trial. In 
addition, focus group discussions (FGD) will be carried out with community members and 
community health workers to further investigate acceptability of the new therapy. To 
complement the community survey and focus group discussions, a series of key informant 
interviews are proposed with community leaders and health personnel in the same communities 
to assess perceptions about the 3-drug versus the 2-drug regimen as well as gain insight into 
the feasibility of distributing the new regimen as well as perceptions about managing adverse 
events. 
 
 
B. Rationale for the study 
With the introduction of a new treatment regimen for the elimination of lymphatic filariasis (LF), 
understanding community perceptions about the treatment, its adverse events (AE) as well as 
its efficacy will be an important component of assessing the acceptability of the 3-drug therapy. 
In particular, perceptions about the severity of experienced or observed AE, the efficacy of the 
treatment in killing the worms and understanding the positive presence of AE will be important 
to investigate. 
 
Research has demonstrated the important impact that AE can have on individuals’ acceptance 
of LF treatment using the 2-drug regimen [1, 2]. In some areas where MDA has been ongoing 
for many years, we might expect these AE to be objectively of minimal clinical significance, yet 
subjectively community members continue to report “fear of AE” as a deterrent to comply with 
MDA. In recent research in a low prevalence area in Indonesia, 33% of individuals interviewed 
reported experiencing some form of side effect or AE as a result of taking the LF treatment (A. 
Krentel personal experience). Thomsen et al (2016) reported a higher rate of AE in those who 
were administered the 3-drug regimen versus those who received the 2-drug therapy [3]. As the 
wider application of this new therapy is considered, it will be important to understand if the 
perception of these AE is different in between the two treatment arms.  
 
Another important deterrent to compliance with MDA is a lack of understanding of the benefit of 
treatment [4, 5]. The 3-drug regimen has been shown to be highly effective in the reduction of 
microfilariae [3]; therefore communicating this message to participants will be of crucial 
importance. Measuring participants’ understanding of this message will be essential in 
determining their acceptance of AE associated with the treatment. In PNG and in neighboring 

APPENDIX 7: 
PROTOCOL FOR A TREATMENT ACCEPTABILITY STUDY 
FOLLOWING THE TRIPLE DRUG COMMUNITY SAFETY TRIALS 
Protocol for Acceptability Study; version 29.06.2016 
 
Page 3 of 16 
 
Indonesia when communities understand the reasons AE occur, they welcome them as a sign 
that the drugs are working [6, 7]. Knowing if this message also works with the 3-drug therapy 
where more AE are expected to occur is important in the future promotion of this treatment.  
 
For the purposes of this research, a mixed method approach is recommended, combining the 
use of a community survey, focus group discussions and in depth interviews with key 
informants. The community survey will allow a robust comparison of treatment acceptability 
between those receiving the 2-drug regimen and those receiving the 3-drug regimen. A 
composite score will measure acceptability, combining outcomes like the respondents’ intention 
to take the treatment again and willingness to recommend it to other family members. 
Acceptability will be analyzed by the impact of some of the known factors that impact 
compliance: perception of AE, knowledge about AE, perceptions about the drug characteristics 
(safe, number of pills, taste), knowledge of vector, belief that the treatment is associated with 
health, and others. In order to assess the difference between the two treatment arms, the 
sampling frame for the community survey will take into account which regimen the individual 
received.  
 
To complement the community surveys and provide further in depth analysis, focus group 
discussions (FGD) are planned with specific groups in the community, namely men, women, 
young people and community health workers. The FGDs will provide further insight and depth 
for some of the questions asked in the community survey. Specifically FGDs will investigate 
issues expected to relate to the 3-drug regimen: number of pills, perception of AE, how to 
ensure directly observed treatment and proposed messages to encourage compliance.  
 
These results will be further substantiated by interviews with key community leaders, as well as 
community and professional health workers working in LF elimination at the village level. These 
interviews will provide an understanding of the macro level issues that key informants perceive 
as critical to consider with the use of the 3-drug therapy. With this, interview respondents will be 
asked what advantages and concerns they have with regards to the 3-drug regimen based on 
their participation in and understanding of the safety trial. 
 
The outcome of this research will provide operational recommendations to accompany the 
safety study. These will inform additional acceptability research if the 3-drug regimen is adopted 
as global policy. An important outcome will be to determine if there are any real differences in 
community acceptance of the 3-drug regimen when compared to the standard treatment. If 
there are any differences, then further investigation may be recommended. In addition, the 
global programme will need to consider how to adjust the delivery protocols and recommended 
messages used by community drug distributors giving out the 3-drug regimen. The acceptability 
study will provide a preliminary understanding of these issues and will provide important insights 
into the use of this regimen on a wider scale.    
 
 
 

APPENDIX 7: 
PROTOCOL FOR A TREATMENT ACCEPTABILITY STUDY 
FOLLOWING THE TRIPLE DRUG COMMUNITY SAFETY TRIALS 
Protocol for Acceptability Study; version 29.06.2016 
 
Page 4 of 16 
 
C. Study objectives 
1) Measure the perception of AE reported by safety trial participants, comparing those in 
the 2-drug versus 3-drug arms 
2) Assess the overall acceptability in the community of the 3-drug regimen, as compared to 
the 2-drug regimen 
3) Assess the overall acceptability in the community of those individuals who are mf 
positive, as compared to those who are mf negative 
4) Investigate the acceptability and feasibility of delivering the 3-drug regimen   
 
 
D. Community survey 
Community surveys are often called Knowledge, Attitudes and Practice (KAP) surveys because 
they use a cross sectional survey design to understand what community members know about 
disease, treatment and prevention; how they perceive factors related to the disease and finally 
what they do about it (e.g. take a drug, hang a bednet, use a condom). For the purposes of this 
survey, it is recommended to use a cross sectional survey design.  However the terminology 
and format of the KAP may not be the most appropriate questionnaire design for the study 
proposed. Specific knowledge about LF disease is not a strong predictor for compliance in MDA 
for LF, with the exception of knowing that mosquitoes transmit LF [8, 9]. For the purposes of this 
research, focusing on knowledge of LF disease may not inform community acceptability of the 
3-drug regimen as compared to the 2-drug regimen. Furthermore research has shown that there 
are important intrinsic reasons that affect people’s decisions to take or not to take the LF 
treatment during MDA. Social norms of compliance, emotional cues, altruism and an individual’s 
personal situation have all been shown to be associated with taking the LF drug [5, 10-12]. 
Understanding some of these intrinsic factors associated with taking the 3-drug regimen as 
opposed to the 2-drug regimen will be important in building a picture of community acceptability. 
As a result, although there may be similarities in some of the questions asked, it is 
recommended to call the community survey a “treatment acceptability survey” as opposed to a 
“KAP survey.”  
 
1. Timing 
Coverage surveys are recommended to occur as soon as possible after MDA occurs in order to 
reduce recall bias in respondents [13]. In order to allow some space between the clinical 
assessment and monitoring of AE in the community trial as well as some time for the effects of 
ivermectin to become apparent, individuals approached for enrollment in the community survey 
will be approached at least two weeks after the completion of their drug administration and 
adverse events monitoring. 
 
2. Questionnaire development 
Questionnaire development is based on previous LF surveys carried out in Indonesia and in 
Papua New Guinea. In addition, known influences based on the most recent literature on 
compliance will be included in the acceptability survey, where appropriate. Validated questions 
from acceptability research as well as quality of life indicators for scabies will be included in the 
questionnaire.  

APPENDIX 7: 
PROTOCOL FOR A TREATMENT ACCEPTABILITY STUDY 
FOLLOWING THE TRIPLE DRUG COMMUNITY SAFETY TRIALS 
Protocol for Acceptability Study; version 29.06.2016 
 
Page 5 of 16 
 
 
Questionnaires will be written in English and translated into the local language. In order to test 
the understandability of the questionnaire with the local population, the enumerators will give 
advice on the vocabulary used during the training and a small sample of individuals will be 
administered the questionnaire prior to survey implementation. At the end of this testing, these 
respondents will be asked to comment on the questions themselves, whether they were clear 
and the language was appropriate. Changes will be made if needed. The questionnaire will then 
be translated back into English.  
 
3. Sampling frame 
In estimating the sample size for the acceptability survey, one of the challenges we have is that 
we do not know the estimated acceptability rates in people who have received the 3-drug 
regimen. From recent research in Indonesia (A. Krentel, personal experience) in low (mf 
rate=1%) and high prevalence (mf=8%) areas, we know that acceptability with DEC+ALB, as 
measured in the intent to take the LF drugs again, was measured as 79% and 82% respectively.  
 
Because we do not have a 3-drug acceptability rate, we cannot estimate the difference we might 
expect in between the regimen groups. As a result, this survey will create preliminary data, 
estimating the difference in acceptability rates between those individuals receiving the 2 and 3 
drug regimens as well as the difference in rates between those with positive mf rates at the start 
of the safety trial and those who are mf negative. This survey will provide insight into possible 
trends in acceptability and will inform if further investigation is needed.  
 
The range of mf prevalence is expected to be wide in between the study sites. As such, we will 
oversample those areas where it will be higher. The target samples for the acceptability survey 
are as follows:  
 
 
400 individuals in Papua New Guinea 
 
400 individuals in Indonesia 
 
400 individuals in Haiti 
 
400 individuals in Fiji 
 
Within each country, equal numbers of subjects will be enrolled in the two drug and the three 
drug intervention arms.  In PNG, we will oversample those villages were LF prevalence is 
expected to be higher. With a projected 50% infection rate, this is the only participating country 
that is expected to have an infection rate in excess of 10%.  It is therefore the only country that 
will provide a universe of infected subjects that is sufficiently large to provide accurate measures 
of the acceptability of study medications in subjects who are infected.  Specifically, if we add the 
50 subjects who are expected to be infected in Indonesia, Haiti, and Fiji combined to the 200 
anticipated infected subjects in PNG, we anticipate that this acceptability study will enroll 250 
infected subjects, or 125 in each intervention arm.  With a total of 125 infected subjects in each 
arm, a dichotomous measure (yes or no) of the acceptability of a particular drug combination 
will, with 95% certainty, differ by no more than 9% from the true acceptability rate. 
 

APPENDIX 7: 
PROTOCOL FOR A TREATMENT ACCEPTABILITY STUDY 
FOLLOWING THE TRIPLE DRUG COMMUNITY SAFETY TRIALS 
Protocol for Acceptability Study; version 29.06.2016 
 
Page 6 of 16 
 
Because we expect the acceptability of a particular drug combination to be highly correlated 
within families, our protocol permits the enrollment of precisely one subject from each 
participating family.  Eligible family members will have to be at least 14 years of age. As chronic 
manifestations of the disease begin to show at adolescence, so personal experience with LF 
may also begin at this age [14]. Both men and women will be included in the sample.  
 
Enrollment procedures are as follows.  Our goal will be to interview acceptability study 
participants beginning at least two weeks after the AE monitoring has been completed within a 
given village.  The reason for waiting at least two weeks is that we want to minimize the 
likelihood that we will interview individuals who are still experiencing the symptoms of any 
adverse events that may have occurred in the parent study.  If we were to conduct acceptability 
interviews while subjects were still experiencing adverse effect symptoms, the immediacy of 
those symptoms might bias subjects’ perceptions of acceptability. 
 
All families within a village that participated in the parent safety study will be eligible to 
participate in this acceptability study, with consent for such participation having been a part of 
the consent form of the parent study.  Within each country, we will enter villages sequentially in 
the order that they were entered in the parent study.  We will continue to interview subjects in a 
particular country until the target number within a given study arm has been reached.  When the 
target number has been reached in one study arm, we will stop enrolling subjects in that arm 
and will continue enrolling in the other study arm until the target has been reached. 
 
The family member to be interviewed for this study will be selected using the following 
procedures.  A list of family members over the age of 14 who have been enrolled in the parent 
study will be compiled as soon as possible after the parent study has been concluded in a 
village.  From this list, a random family member will be selected as the target participant in the 
acceptability study.  When we approach a household, we will seek to interview the randomly 
selected family member.  If that family member is not immediately available, we will discuss 
whether the logistics of conducting the interview with that family member at a different time are 
feasible.  If we conclude that waiting for that alternative time is not reasonable or if the selected 
family member does not wish to participate, we will conduct the interview in whatever family 
member is available, independent of which individual has been randomly selected. 
 
Enumerators will travel to the house to interview the identified individual. Data will be collected 
using the REDCap system.  
 
4. Outcome of interest: 
Acceptability of the 3-drug therapy will be measured in a composite score from the following 
questions1:  
- 
Intention to take LF drugs in the future measured on a 5-point scale ranging from “I will 
never take this drug again” to “I will definitely take this drug again.” (Adapted from Liau 
and Zimet 2001 ) 
                                               
1 Scoring concept amended from Treatment Acceptability Research (see Carter SL (2007) “Review of Recent 
Treatment Acceptability Research” Education and Training in Developmental Disabilities 42(3): 301-316. 

APPENDIX 7: 
PROTOCOL FOR A TREATMENT ACCEPTABILITY STUDY 
FOLLOWING THE TRIPLE DRUG COMMUNITY SAFETY TRIALS 
Protocol for Acceptability Study; version 29.06.2016 
 
Page 7 of 16 
 
- 
Willingness to encourage other family members to take the LF drug, if offered in the 
future measured as a 5-point scale ranging from “I will never encourage my family to 
take the LF drugs” to “I will definitely encourage my family to take the LF drugs.” 
- 
Overall feeling about the LF elimination program as a 5-point scale ranging from “Very 
negative” to “Very positive” 
- 
Perception of health since taking the LF drugs as a 5-point scale ranging from 
“Considerably worse” to “greatly improved” 
- 
In addition to the scoring, each outcome can be converted to a binary variable for 
multivariate modeling. 
4.  
5. Inputs / Exposure variables:  
- 
SES data 
- 
Data from safety trial (clinical presence of AE, mf rate, household information) 
- 
Treatment arm (2-drug versus 3-drug) 
- 
Informed about the treatment before receiving the drug (e.g. did they receive any 
information) 
- 
Belief in the efficacy of the treatment to eliminate / prevent LF (e.g. believe that the 
drugs work to prevent / treat LF) 
- 
Belief in the efficacy of the treatment to treat scabies (e.g. believe that the drugs work to 
treat scabies) 
- 
Belief in the efficacy of the treatment to treat other intestinal worms (e.g. believe that the 
drugs work to treat worms) 
- 
Knowledge of the ‘positive’ component of AE (e.g. occur because the medicine is 
working) 
- 
Perception of AE (e.g. none, mild, moderate, severe) 
- 
Understanding that taking LF medicine is good for promoting health 
- 
Knowledge that mosquitoes transmit LF 
- 
Perception that the rest of the family/ household would take the LF drugs, if offered in 
the future (yes/no) 
- 
Belief that the drug distributors are doing a good job (using a 10-point scale) 
- 
Perceptions of the drugs (e.g. safe, neutral, dangerous) 
- 
Components of the drugs (e.g. number, size, taste of pills) 
- 
Emotions surrounding LF treatment (e.g. how does taking LF treatment make you feel?) 
 
6. Analysis 
For the data cleaning and data reduction, the following steps will be performed: 
- 
Check response bias 
- 
Clean the raw data set (range check, consistency checks)  
- 
Transfer corrected data set to STATA statistical software (Stata Corporation, College 
Station, Texas). 
- 
Group continuous variables into categorical variables, namely age. Recode certain 
variables where needed. 
 
For the analysis, a descriptive analysis of the whole dataset will be prepared. The data from the 
community survey will be linked to the safety trial within the REDCap system.  
 
Likert scales will be analyzed as both dichotomous and as continuous variables.  

APPENDIX 7: 
PROTOCOL FOR A TREATMENT ACCEPTABILITY STUDY 
FOLLOWING THE TRIPLE DRUG COMMUNITY SAFETY TRIALS 
Protocol for Acceptability Study; version 29.06.2016 
 
Page 8 of 16 
 
 
For both of the predictors of acceptability (drug regimen and presence of mf) logistic regression 
models will be created. Presence of AE as measured in the clinical surveys will be considered in 
the analysis, as will subjective perceptions of AE.  
 
 
E. Focus Group Discussion 
 
H. Timing 
The focus group discussions will take place at the same time as the community survey, in the 
same communities. 
 
2. Sampling frame 
For the focus group discussions, we will identify persons from specific groups of people:  
women of reproductive age, young people, men and community health workers. The rationale 
behind the selection of each of these groups is related to the prevailing evidence of their 
participation in MDA in the literature. Women of reproductive age often do not comply with 
treatment because they are either pregnant or breastfeeding, however they are often the 
gatekeepers for health in the household and ensure members of their household takes the 
treatment when offered. Men and young people have been known to be less compliant with 
MDA and so understanding their perceptions about the 3-drug regimen, MDA in general and 
soliciting their advice about how best to promote and reach their communities will be 
informative. Finally, as community health workers are usually the persons responsible for 
distributing the drug at the community level, understanding their perspectives on DOT, AE and 
messaging for the 3-drug regimen is important.  
 
For the FGD, women, young men and men will be selected from the cohort of individuals 
receiving the 3-drug regimen.  
 
3. Range of issues to explore include:  
- 
How is LF elimination different / similar from the other health programs in their village? 
- 
What are the health benefits from taking the treatment? 
- 
What are the social benefits from taking the treatment? 
- 
Do people like to take the pills in front of the distributor? Why or why not?  
- 
How do you feel about the number of pills that you have to take? 
- 
Why don’t people want to take it? 
- 
Did you have any side effects after you took the drugs (positive or negative)? How did 
you feel about them? 
- 
What suggestions do you have to promote MDA to their community? Household? 
- 
Are there any specific messages you would recommend to us? 
 
4. Analysis 
Recorded focus group discussions will be transcribed word for word in the local language. They 
will be translated into English. A second researcher with knowledge of English and the local 

APPENDIX 7: 
PROTOCOL FOR A TREATMENT ACCEPTABILITY STUDY 
FOLLOWING THE TRIPLE DRUG COMMUNITY SAFETY TRIALS 
Protocol for Acceptability Study; version 29.06.2016 
 
Page 9 of 16 
 
language will check translation, sampling portions of each transcript and back translating them 
from English to the local language to check the reliability of the translation. The researchers will 
read through each transcript, recording emergent themes in an Excel matrix. NVivo will be used 
to assess trends and patterns in the interview transcripts.   
 
 
F. In depth interviews with key informants 
 
H. Timing 
The key informant interviews will take place at the same time as the community survey, in the 
same communities. 
 
2. Sampling frame 
A purposive sampling frame will be used, with individuals identified based on their leadership 
and cultural position with the village as well as their involvement with LF elimination and with the 
community trial. With this in mind, a range of 8-10 individuals will be included in the sample. In 
order to understand the acceptability of administering the 3-drug regimen, individuals to be 
interviewed would need to be those persons who are either directly involved with LF activities in 
the village or who would be involved in MDA in the future. Suggestions include community 
and/or religious leaders, community health workers, teachers.  
 
3. Range of issues to explore include:  
- 
What are the advantages of the 3-drug therapy in MDA? Disadvantages? 
- 
What opportunities do they see in the administration of the 3-drug therapy, versus the 2-
drug therapy? 
- 
What concerns or challenges do they see in the administration of the 3-drug therapy, 
versus the 2-drug therapy? 
- 
How do they feel about the number of pills that the community is asked to take?  
- 
How do they feel about the side effects people might have / have? 
- 
What suggestions do they have to promote MDA in this village? This province? The 
country? What messages would they recommend using? 
- 
Which groups of people do they think will be difficult to reach with future MDA? Why? 
Any advice to approach them? 
 
4. Analysis 
Recorded interviews will be transcribed word for word in the local language. They will be 
translated into English. A second researcher with knowledge of English and the local language 
will check translation, sampling portions of each transcript and back translating them from 
English to the local language to check the reliability of the translation. The researcher will read 
through each transcript, recording emergent themes in an Excel matrix. Nvivo will be used to 
assess trends and patterns in the interview transcripts.   
 
 
G. Ethical Considerations 

APPENDIX 7: 
PROTOCOL FOR A TREATMENT ACCEPTABILITY STUDY 
FOLLOWING THE TRIPLE DRUG COMMUNITY SAFETY TRIALS 
Protocol for Acceptability Study; version 29.06.2016 
 
Page 10 of 16 
 
 
H. Community survey 
Ethical approval will be obtained from the local national research institution in each country as 
well as Washington University in St. Louis, Case Western University and Bruyère Research 
Institute.  
 
Prior to giving consent to participate, the enumerator will read out the information sheet in the 
local language containing the aim of the survey, the length of time it is expected to take (15 
minutes) as well as the protection of confidentiality for each respondent. Following this, each 
respondent will be asked to sign the informed consent form and where respondents are illiterate, 
a mark can be made. The enumerator will indicate that informed consent has been given.  Age of 
eligible respondents is 14 years of age and older. For those aged 14 – 18 years, parental consent 
will be sought and provided on the informed consent form before the interview can begin. All forms 
will remain with the research team and will not contain any personal information other than the 
individual’s signature.  
 
At the end of the interview, each respondent will be given an information sheet with the principal 
investigator’s contact details, should there be any questions. With this sheet, the respondent will 
also receive a brief information sheet on lymphatic filariasis, the mass drug administration and 
who is eligible for treatment.  
 
The data will be stored on Washington University servers during the duration of the study. After 
the study ends, electronic copies of the de-identified datasets will be kept by the PI indefinitely. 
 
2. Focus Group discussions 
Ethical approval will be obtained from the local national research institution in each country as 
well as Washington University in St. Louis, Case Western University and Bruyère Research 
Institute.  
 
The interviewer will read the informed consent form to each person participating in the focus 
group discussion. The respondents will be asked to each sign an informed consent form for their 
participation. All interviews will be recorded with the permission of the respondent. Where 
permission is not granted, the interviewer will ask to take notes throughout the interview.  
 
Any identifying information (name, address) will not be recorded. Individuals will not be identified 
in the transcripts or in the recordings and their anonymity will be maintained in all reporting and 
in the manuscripts. Transcripts of the interviews will remain with the research team. 
 
The data will be stored with the PI, under password protection. After the study ends, electronic 
copies of the de-identified datasets will be kept by the PI indefinitely. 
 
 
3. In depth interviews with key informants 

APPENDIX 7: 
PROTOCOL FOR A TREATMENT ACCEPTABILITY STUDY 
FOLLOWING THE TRIPLE DRUG COMMUNITY SAFETY TRIALS 
Protocol for Acceptability Study; version 29.06.2016 
 
Page 11 of 16 
 
Ethical approval will be obtained from the local national research institution in each country as 
well as Washington University in St. Louis, Case Western University and Bruyère Research 
Institute.  
 
The interviewer will read the informed consent form to each person participating in the interview. 
The respondents will be asked to sign an informed consent form for their participation. All 
interviews will be recorded with the permission of the respondent. Where permission is not 
granted, the interviewer will ask to take notes throughout the interview.  
 
Any identifying information (name, address) will not be recorded and the identity of the 
respondent will be kept confidential in reporting. Transcripts of the interviews will remain with 
the research team. The data will be stored with the PI under password protection. After the 
study ends, electronic copies of the de-identified datasets will be kept by the PI indefinitely. 

APPENDIX 7: 
PROTOCOL FOR A TREATMENT ACCEPTABILITY STUDY 
FOLLOWING THE TRIPLE DRUG COMMUNITY SAFETY TRIALS 
Protocol for Acceptability Study; version 29.06.2016 
 
Page 12 of 16 
 
References: 
 
1. 
Krentel A, Fischer PU, Weil GJ. A Review of Factors That Influence Individual 
Compliance with Mass Drug Administration for Elimination of Lymphatic Filariasis. PLoS 
neglected 
tropical 
diseases. 
2013;7(11):e2447. 
Epub 
November 
21, 
2013. 
doi: 
doi:10.1371/journal.pntd.0002447. 
2. 
Babu BV, Babu GR. Coverage of, and compliance with, mass drug administration under 
the programme to eliminate lymphatic filariasis in India: a systematic review. Transactions of the 
Royal Society of Tropical Medicine and Hygiene. 2014;108(9):538-49. Epub 2014/04/15. doi: 
10.1093/trstmh/tru057. PubMed PMID: 24728444. 
3. 
Thomsen E, Sanuku N, Baea M, Satofan S, Maki E, Lombore B, et al. Efficacy, Safety, 
and Pharmacokinetics of Coadministered Diethylcarbamazine, Albendazole, and Ivermectin for 
Treatment of Bancroftian Filariasis. Clinical Infectious Diseases. 2016;62(3):334-41. doi: 
10.1093/cid/civ882. 
4. 
Ramaiah KD, Kumar KNV, Hosein E, Krishnamoorthy P, Augustin DJ, Snehalatha KS, et 
al. A campaign of 'communication for behavioural impact' to improve mass drug administrations 
against lymphatic filariasis: structure, implementation and impact on people's knowledge and 
treatment coverage. Annals of Tropical Medicine and Parasitology. 2006;100(4):345-61. doi: 
10.1179/136485906x105598. PubMed PMID: WOS:000238656500007. 
5. 
Babu BV, Suchismita M. Mass drug administration under the programme to eliminate 
lymphatic filariasis in Orissa, India: a mixed-methods study to identify factors associated with 
compliance and non-compliance. Transactions of the Royal Society of Tropical Medicine and 
Hygiene. 2008;102(12):1207-13. doi: http://dx.doi.org/10.1016/j.trstmh.2008.05.023. PubMed 
PMID: 20083317171. 
6. 
Bockarie MJ, Tisch DJ, Kastens W, Alexander NDE, Dimber Z, Bockarie F, et al. Mass 
treatment to eliminate filariasis in Papua New Guinea. New England Journal of Medicine. 
2002;347(23):1841-8. 
7. 
Krentel A, Fischer P, Manoempil P, Supali T, Servais G, Rückert P. Using knowledge, 
attitudes and practice [KAP] surveys on lymphatic filariasis to prepare a health promotion 
campaign for mass drug administration in Alor District, Indonesia. Tropical Medicine & 
International Health. 2006;11(11):1731-40. 
8. 
Cantey PT, Rao G, Rout J, Fox LM. Predictors of compliance with a mass drug 
administration programme for lymphatic filariasis in Orissa State, India 2008. Tropical Medicine 
and 
International 
Health. 
2010;15(2):224-31. 
doi: 
http://dx.doi.org/10.1111/j.1365-
3156.2009.02443.x. PubMed PMID: 2010046751. 
9. 
Mathieu E, Lammie PJ, Radday J, Beach MJ, Streit T, Wendt J, et al. Factors associated 
with participation in a campaign of mass treatment against lymphatic filariasis, in Leogane, Haiti. 
Annals 
of 
Tropical 
Medicine 
and 
Parasitology. 
2004;98(7):703-14. 
doi: 
10.1179/000349804x3135. PubMed PMID: WOS:000224651200006. 
10. 
Krentel A, Aunger R. Causal chain mapping: a novel method to analyse treatment 
compliance decisions relating to lymphatic filariasis elimination in Alor, Indonesia. Health Policy 
Plan. 2011. Epub 2011/06/30. doi: 10.1093/heapol/czr048. PubMed PMID: 21712348. 
11. 
Fraser M, Taleo G, Taleo F, Yaviong J, Amos M, Babu M, et al. Evaluation of the program 
to eliminate lymphatic filariasis in Vanuatu following two years of mass drug administration 

APPENDIX 7: 
PROTOCOL FOR A TREATMENT ACCEPTABILITY STUDY 
FOLLOWING THE TRIPLE DRUG COMMUNITY SAFETY TRIALS 
Protocol for Acceptability Study; version 29.06.2016 
 
Page 13 of 16 
 
implementation: results and methodologic approach. The American journal of tropical medicine 
and hygiene. 2005;73(4):753-8. 
12. 
Nandha B, Sadanandane C, Jambulingam P, Das P. Delivery strategy of mass annual single 
dose DEC administration to eliminate lymphatic filariasis in the urban areas of Pondicherry, South 
India: 5 years of experience. Filaria J. 2007;6:7. Epub 2007/08/28. doi: 10.1186/1475-2883-6-7. 
PubMed PMID: 17718908; PubMed Central PMCID: PMC2020462. 
13. 
Worrell C, Mathieu E. Drug Coverage Surveys for Neglected Tropical Diseases: 10 Years 
of Field Experience. American Journal of Tropical Medicine and Hygiene. 2012;87(2):216-22. 
14. 
Witt C, Ottesen EA. Lymphatic filariasis: an infection of childhood. Tropical Medicine & 
International Health. 2001;6(8):582-606. 
 
 
 

APPENDIX 7: 
PROTOCOL FOR A TREATMENT ACCEPTABILITY STUDY 
FOLLOWING THE TRIPLE DRUG COMMUNITY SAFETY TRIALS 
Protocol for Acceptability Study; version 29.06.2016 
 
Page 14 of 16 
 
Information sheet and informed consent for community survey 
As part of the “Community Based Safety Study of 2-drug versus 3-drug Therapy for Lymphatic 
Filariasis” that just happened in your area last month, we are asking some people who 
participated in that study to take part in a short survey so that we can understand more about 
lymphatic filariasis [or local name], the drugs used in the safety trial and health in general. Your 
name was selected randomly from the list of people who participated in that safety trial. 
 
It is important that you understand why we are doing this survey, so please read this information 
sheet carefully. If you have any more questions, ask the interviewer and they will try to answer 
them for you.  
 
We are interested in the experiences people had participating in the safety trial and what they 
understand about lymphatic filariasis [or local name]. We would like to talk to about 400 people in 
this area so that we can understand better how people felt about taking the LF drugs. Your 
participation is entirely voluntary and you are under no obligation to participate. Whether or not 
you choose to participate, your status and access to health care will not be affected in any way.  
 
If you do choose to help with this study, we will only need about 15 minutes of your time to ask 
you some questions. At any time during this discussion, you are free to stop and withdraw from 
the study. You do not have to give the interviewer a reason. 
 
The information that you provide during our discussion will be completely confidential.  We will 
record your answers on a tablet. All digital files will remain with the main investigator and will be 
password protected. 
--------------------------------------------------------------------------------------------------------------------- 
I have read the information sheet provided or it has been read to me concerning this study and I 
understand what will be required of me if I participate in this study, which will be a verbal interview 
and discussion. 
 
My questions regarding this study have been answered by: _________________. 
 
I understand that at any time I may withdraw from this study without giving a reason and without 
having any effect on my access to health care. 
 
I agree to take part in this study. 
 
 
Signature of the respondent: ______________________________________ 
 
Signature of a witness: __________________________________________ 
 
Signature of the enumerator to indicate that the informed consent has been read and the 
information sheet given to the respondent:  __________________________________ 

APPENDIX 7: 
PROTOCOL FOR A TREATMENT ACCEPTABILITY STUDY 
FOLLOWING THE TRIPLE DRUG COMMUNITY SAFETY TRIALS 
Protocol for Acceptability Study; version 29.06.2016 
 
Page 15 of 16 
 
Information sheet and informed consent for in depth interviews with key informant 
 
As part of the “Community Based Safety Study of 2-drug versus 3-drug Therapy for Lymphatic Filariasis” that 
just happened in your area last month, we are asking some people who participated in that study to take part 
in a verbal discussion so that we can understand more about lymphatic filariasis [or local name], the drugs 
used in the safety trial and health in general.  It is important that you understand why we are doing this survey, 
so please read this information sheet carefully. If you have any more questions, ask the interviewer and they 
will try to answer them for you.  
 
We are interested in the experiences people had participating in the safety trial and what they understand about 
lymphatic filariasis [or local name]. We would like to talk to about 8 people in this area so that we can understand 
better how people felt about taking the LF drugs. Your participation is entirely voluntary and you are under no 
obligation to participate. Whether or not you choose to participate, your status and access to health care will not 
be affected in any way.  
 
If you do choose to help with this study, we will only need about one hour of your time to ask you some questions 
and to discuss informally. At any time during this discussion, you are free to stop and withdraw from the study. 
You do not have to give the interviewer a reason. 
 
The information that you provide during our discussion will be completely confidential and we will not even write 
down your name or address.  We will take some written notes during our discussion and if you agree, we may 
also record the interview using a digital recorder so that it will be easier to remember what we discussed. All 
digital files will remain with the main investigator and your name and address will not be recorded. We will write 
down the conversation and store it safely, with a password. Other researchers may ask to look at our discussion 
together, and we may share it with them, provided that they respect the same rules of confidentiality.  
--------------------------------------------------------------------------------------------------------------------- 
I have read the information sheet provided or it has been read to me concerning this study and I understand 
what will be required of me if I participate in this study, which will be a verbal interview and discussion. 
 
My questions regarding this study have been answered by: _________________. 
 
I understand that at any time I may withdraw from this study without giving a reason and without 
having any effect on my access to health care. 
 
I agree to take part in this study. 
 
Signature of the respondent: ______________________________________ 
 
Signature of a witness: __________________________________________ 
 
Signature of the enumerator to indicate that the informed consent has been read and the 
information sheet given to the respondent:  __________________________________ 
Information sheet and informed consent for focus group discussion participants 

APPENDIX 7: 
PROTOCOL FOR A TREATMENT ACCEPTABILITY STUDY 
FOLLOWING THE TRIPLE DRUG COMMUNITY SAFETY TRIALS 
Protocol for Acceptability Study; version 29.06.2016 
 
Page 16 of 16 
 
 
As part of the “Community Based Safety Study of 2-drug versus 3-drug Therapy for Lymphatic Filariasis” that 
just happened in your area last month, we are asking some people who participated in that study to take part in 
a focus group discussion so that we can understand more about lymphatic filariasis [or local name], the drugs 
used in the safety trial and health in general.  It is important that you understand why we are doing this survey, 
so please read this information sheet carefully. If you have any more questions, ask the interviewer and they will 
try to answer them for you.  
 
We are interested in the experiences people had participating in the safety trial and what they understand about 
lymphatic filariasis [or local name]. We would like to talk to about 4 groups of people in this area so that we can 
understand better how people felt about taking the LF drugs. Your participation is entirely voluntary and you are 
under no obligation to participate. Whether or not you choose to participate, your status and access to health care 
will not be affected in any way.  
 
If you do choose to help with this study, we will only need about one hour of your time to ask you some questions 
and to discuss informally. At any time during this discussion, you are free to stop and withdraw from the study. 
You do not have to give the interviewer a reason. 
 
The information that you provide during our discussion will be completely confidential and we will not even write 
down your name or address.  We will take some written notes during our discussion and if you agree, we may 
also record the interview using a digital recorder so that it will be easier to remember what we discussed. All digital 
files will remain with the main investigator and your name and address will not be recorded. We will write down 
the conversation and store it safely, with a password. Other researchers may ask to look at our discussion 
together, and we may share it with them, provided that they respect the same rules of confidentiality.  
--------------------------------------------------------------------------------------------------------------------- 
I have read the information sheet provided or it has been read to me concerning this study and I 
understand what will be required of me if I participate in this study, which will be a verbal interview 
and group discussion. 
 
My questions regarding this study have been answered by: _________________. 
 
I understand that at any time I may withdraw from this study without giving a reason and without 
having any effect on my access to health care. 
 
I agree to take part in this study. 
 
Signature of the respondent: ______________________________________ 
 
Signature of a witness: __________________________________________ 
 
 
Signature of the enumerator to indicate that the informed consent has been read and the 
information sheet given to the respondent:  _________________________________

 
 
Protocol for Acceptability Study; version 29.06.2016 
 
Page 1 of 5 
 
 
APPENDIX 9: 
TOPIC GUIDE – FOCUS GROUP DISCUSSION ON THE 
ACCEPTABILITY OF IDA [EXAMPLE]  
MAIN RESEARCH QUESTION: UNDERSTANDING THE FEASIBILITY OF ADMINISTERING IDA: WHAT ARE 
THE FACTORS AND CONSIDERATIONS FOR THE INTRODUCTION OF TRIPLE DRUG THERAPY FOR LF 
ELIMINATION INTO THIS COMMUNITY? 
 
RATIONALE 
REFER TO THE INFORMATION SHEET 
 
CONFIDENTIALITY   
REFER TO THE INFORMED CONSENT SHEET 
 
WARM-UP QUESTIONS 
AS YOU’VE READ THE INFORMATION SHEET, YOU WILL REMEMBER THAT WE ARE HERE TO COLLECT SOME INFORMATION 
THAT WILL HELP THE GOVERNMENT TO MAKE YOUR HEALTH AND THE HEALTH OF PEOPLE IN YOUR VILLAGE BETTER.  SO 
MAYBE YOU COULD TELL ME A LITTLE BIT ABOUT THE HEALTH OF PEOPLE IN YOUR VILLAGE… 
 
 
 (IF NO RESPONSE… THEN PROMPT WITH: ARE THERE MANY SICK PEOPLE IN YOUR VILLAGE? WHAT DO PEOPLE GET 
SICK FROM IN YOUR VILLAGE?) 
 
LEAD IN TO DISCUSSION 
AS I MENTIONED IN THE BEGINNING OF THE INTERVIEW, WE ARE INTERESTED IN THE DISEASE FILARIA AND ITS TREATMENT. IS 
THAT SOMETHING THAT YOU’VE TAKEN MEDICINE FOR?  AND WHAT DID YOU TAKE?  
 
 
(INTERVIEWER: OH, THAT’S INTERESTING… MAYBE WE CAN TALK ABOUT THAT A BIT MORE LATER…) 
 
KNOWLEDGE ABOUT LF 
ASK THEM TO TELL YOU WHAT THEY KNOW ABOUT THE DISEASE LF: 
 
DEPENDING ON THE IDENTITY OF THE RESPONDENT (MEDICAL V NON-MEDICAL) PROMPT WITH THE FOLLOWING: 
- 
LOCAL NAMES 
- 
HOW DO YOU GET IT? 
o PROMPT: WOULD YOU LIKE TO DRAW HERE FOR ME HOW THE DISEASE ENTERS THE BODY? 
- 
TELL ME WHAT HAPPENS TO YOU WHEN YOU GET IT. 
- 
WHERE DID YOU HEAR ABOUT FILARIA? 
- 
WHO DO YOU THINK GETS IT MOST? (PROMPT: MEN? WOMEN? CHILDREN?) 
- 
DO YOU KNOW ANYONE WHO HAS FILARIA?  CAN YOU TELL ME ABOUT THEM?  

APPENDIX 9: 
TOPIC GUIDE – FOCUS GROUP DISCUSSION ON THE 
ACCEPTABILITY OF IDA [EXAMPLE] 
 
Protocol for Acceptability Study; version 29.06.2016 
 
Page 2 of 5 
 
 
PAST PARTICIPATION IN MDA ACTIVITIES 
 
RESPONDENTS’ COMMENTS ABOUT PAST PARTICPATION WITH MDA 
YOU’VE ALREADY TOLD ME ABOUT YOUR EXPERIENCE WITH THE DRUGS FOR FILARIA.  
 
 
[FOR FGD WITH CDDS] COULD YOU TELL ME ABOUT YOUR ROLE IN THE DISTRIBUTION FOR LF DRUGS IN YOUR AREA? 
 
IF NECESSARY PROMPT THE STORY WITH: 
- 
ANY PART YOU PLAYED IN THE PROMOTION AND/OR DISTRIBUTION OF THE DRUGS 
- 
HOW DID YOU TELL PEOPLE ABOUT THE TREATMENT DAY? 
- 
WHAT WAS THE ROLE OF COMMUNITY LEADERS: VILLAGE LEADER, SCHOOL TEACHERS, CHURCH OR MOSQUE 
LEADERS, NEIGHBOURS, HEALTH STAFF 
 
 
CAN WE TALK ABOUT THE PEOPLE AROUND YOU AND HOW THEY FELT ABOUT THE TREATMENT? 
 
IF NECESSARY PROMPT WITH: 
- 
FAMILY/HOUSEHOLD: ANY DISCUSSION? FEELINGS OR VIEWS ABOUT THE TREATMENT? DID THEY TAKE IT? 
- 
NEIGHBOURS? FEELINGS OR VIEWS ABOUT THE TREATMENT? DID THE NEIGHBOURS TAKE IT?  
- 
OTHER PARTS OF THE VILLAGE? DID THEY TAKE IT?  
- 
ANYONE WHO DIDN’T TAKE IT? WHAT HAPPENED TO THEM? 
- 
HOW DID YOU KNOW WHO TOOK IT AND WHO DIDN’T?  
 
LET’S TALK A LITTLE MORE ABOUT THE PEOPLE WHO DIDN’T TAKE THE LF PILLS IN THE PAST. WHAT CAN YOU TELL ME 
ABOUT THEM? 
 
IF NECESSARY PROMPT WITH: 
- 
WHY DO YOU THINK THEY DIDN’T TAKE THE LF PILLS? 
- 
WHAT SUGGESTIONS DO YOU HAVE TO BETTER REACH THIS GROUP OF PEOPLE? 
 
 
I’D LIKE US TO TALK A BIT MORE ABOUT THE GOOD AND BAD PARTS ABOUT TAKING THE LF PILLS?  
 
IF NECESSARY PROMPT WITH: 
- 
WHO DO THINK GAINS THE MOST FROM TAKING FILARIA TREATMENT? 
- 
WHO DO YOU THINK IS HURT BY THE TREATMENT / WHO LOSES MOST? 
 
 

APPENDIX 9: 
TOPIC GUIDE – FOCUS GROUP DISCUSSION ON THE 
ACCEPTABILITY OF IDA [EXAMPLE] 
 
Protocol for Acceptability Study; version 29.06.2016 
 
Page 3 of 5 
 
LET’S THINK ABOUT THE GOOD THINGS FIRST, AND FOR YOU,  
 
IF NECESSARY PROMPT WITH: 
- 
WHAT DO YOU THINK IS GOOD ABOUT THE TREATMENT?  
- 
HOW DID IT HELP YOU? 
- 
WHAT DID YOU GAIN FROM TAKING THE TREATMENT? 
 
 
STILL THINKING ABOUT THE GOOD THINGS, BUT NOW FOR OTHERS,  
 
IF NECESSARY PROMPT WITH: 
- 
WHAT IS GOOD ABOUT THE TREATMENT FOR OTHERS? 
 
 
LET’S DO THE SAME FOR THE BAD THINGS, STARTING WITH YOU,  
 
IF NECESSARY PROMPT WITH: 
- 
WHAT DO YOU THINK IS BAD ABOUT THE TREATMENT?  
- 
HOW DID IT HURT YOU? 
 
 
AND THEN FOR OTHERS? 
 
IF NECESSARY PROMPT WITH: 
- 
DO YOU KNOW ANYONE WHO SUFFERED IN SOME WAY AFTER TAKING THE TREATMENT?  
- 
HOW DID IT HURT THEM? 
 
IN ORDER TO MAKE SURE THAT PEOPLE ACTUALLY TAKE THE PILLS THAT ARE GIVEN TO THEM, IT IS RECOMMENDED THAT 
COMMUNITY MEMBERS TAKE THE PILLS IN FRONT OF THE DISTRIBUTOR. I’D LIKE TO TALK A BIT MORE ABOUT THAT. 
- 
CAN YOU TELL ME HOW THIS HAPPENED IN YOUR COMMUNITY? 
- 
HOW DO YOU THINK PEOPLE FEEL ABOUT TAKING PILLS IN FRONT OF THE DISTRIBUTOR? 
- 
WHAT RECOMMENDATIONS DO YOU HAVE TO IMPROVE THE FREQUENCY OF PEOPLE TAKING PILLS IN FRONT 
OF THE DISTRIBUTOR? 
 
 
HOW DO YOU THINK THE DISTRIBUTION OF LF PILLS DIFFERS FROM OTHER HEALTH ACTIVITIES IN YOUR COMMUNITY? 
 
 
RECENT SAFETY TRIAL FOR IDA 

APPENDIX 9: 
TOPIC GUIDE – FOCUS GROUP DISCUSSION ON THE 
ACCEPTABILITY OF IDA [EXAMPLE] 
 
Protocol for Acceptability Study; version 29.06.2016 
 
Page 4 of 5 
 
AS YOU KNOW, THERE WAS A SAFETY TRIAL IN YOUR COMMUNITY RECENTLY TO ASSESS THE SAFETY OF A NEW DRUG 
COMBINATION FOR LF TREATMENT THAT HAS BEEN SHOWN TO BE VERY GOOD AT KILLING THE LF WORMS. NOW, I WOULD 
LIKE TO TALK ABOUT THAT RECENT LF DRUG DISTRIBUTION A BIT MORE AND THE FUTURE PROSPECTS OF DELIVERING THE 
THREE DRUGS IN YOUR COMMUNITY.  
 
CAN YOU TELL ME ABOUT THE SPECIAL LF DRUG DISTRIBUTION THAT TOOK PLACE RECENTLY? 
 
IF NECESSARY PROMPT WITH: 
- 
HOW WAS IT DIFFERENT FROM PAST MDA ACTIVITIES? 
- 
WHAT WERE PEOPLE TALKING ABOUT IN THE COMMUNITY WHEN THE SAFETY TRIAL TOOK PLACE? 
 
LET’S TALK ABOUT THE PILLS THEMSELVES A BIT. ADULTS IN YOUR COMMUNITY RECEIVED # [FILL IN FOR THE SPECIFIC 
COUNTRY] OF PILLS. CAN YOU TELL ME ABOUT THAT? 
 
IF NECESSARY PROMPT WITH: 
- 
WHAT MESSAGES OR INFORMATION DID YOU TELL PEOPLE ABOUT TAKING THE PILLS? 
- 
HOW DID PEOPLE FEEL ABOUT TAKING # OF PILLS?  
- 
CAN YOU GIVE US ANY ADVICE ABOUT WHAT MESSAGES OR INFORMATION WE COULD USE IN THE FUTURE TO 
ENCOURAGE PEOPLE IN YOUR COMMUNITY TO TAKE ALL OF THESE PILLS? 
 
 
SOMETIMES PEOPLE HAVE SIDE EFFECTS AFTER THEY TAKE THE LF PILLS. I’D LIKE TO ASK YOU ABOUT ANY SIDE EFFECTS 
THAT OCCURRED HERE AFTER THE SPECIAL LF DISTRIBUTION.  
 
IF NECESSARY PROMPT WITH: 
- 
TELL ME ABOUT THE SIDE EFFECTS THAT YOU WITNESSED OR HEARD ABOUT IN YOUR COMMUNITY 
- 
TELL ME ABOUT THE REACTION IN THE COMMUNITY TO THESE SIDE EFFECTS 
- 
WERE THERE ANY MORE SIDE EFFECTS THAN IN PREVIOUS YEARS? 
- 
WHAT ADVICE DO YOU HAVE FOR THE PROGRAMME TO ENSURE PEOPLE UNDERSTAND WHY THESE SIDE 
EFFECTS OCCUR?  
- 
WHAT ADVICE DO YOU HAVE FOR THE PROGRAMME TO ENSURE PEOPLE FEEL REASSURED IF THERE ARE ANY 
SIDE EFFECTS? 
 
SOME OF THE SIDE EFFECTS FROM THE LF PILLS CAN BE ALSO CONSIDERED AS ‘GOOD’. PLEASE TELL ME ABOUT ANY 
‘GOOD’ SIDE EFFECTS THAT OCCURRED IN YOUR COMMUNITY? 
 
IF NECESSARY PROMPT WITH: 
- 
WHAT ADVICE DO YOU HAVE FOR THE PROGRAMME TO PROMOTE THESE ‘GOOD’ SIDE EFFECTS IN YOUR 
COMMUNITY? 
 

APPENDIX 9: 
TOPIC GUIDE – FOCUS GROUP DISCUSSION ON THE 
ACCEPTABILITY OF IDA [EXAMPLE] 
 
Protocol for Acceptability Study; version 29.06.2016 
 
Page 5 of 5 
 
WHAT SUGGESTIONS DO YOU HAVE FOR THE MESSAGES WE MIGHT USE TO PROMOTE THE 3-DRUGS IN THE COMMUNITY 
IN THE FUTURE? 
 
IF NECESSARY PROMPT WITH: 
- 
WHAT WOULD MOTIVATE / ENCOURAGE PEOPLE TO SWALLOW THE PILLS? 
- 
WHO SHOULD DELIVER THOSE MESSAGES? 
- 
IN YOUR OPINION, DO WE NEED TO MAKE A NEW MESSAGE? 
 
 
[FOR FGD WITH CDDS] IF THE NEW TREATMENT WERE INTRODUCED HERE, WHAT WOULD YOU NEED TO HELP YOU TO 
DISTRIBUTE IT? 
 
IF NECESSARY PROMPT WITH: 
- 
SPECIFIC TOOLS (MATERIALS)? 
- 
TRAINING? 
- 
CAN YOU TELL ME ABOUT ANY SPECIFIC CHALLENGES THAT WE NEED TO CONSIDER? 
- 
WHAT OPPORTUNITIES DOES THE 3-DRUG COMBINATION OFFER THE COMMUNITY? 
 
 
PLEASE PROBE CONTINUALLY THROUGHOUT WITH THINGS LIKE:  
- 
WHY DID YOU SAY THAT? 
- 
WHAT DO YOU MEAN BY THAT? 
- 
COULD YOU TELL ME A BIT MORE? 
- 
CAN YOU SAY WHAT YOU MEAN BY THAT? 
- 
SO THEN WHAT HAPPENED? 
- 
OH, THAT MAKES SENSE…  
- 
THAT’S INTERESTING…  
 
THANK YOU FOR YOUR TIME!   
MAKE SURE THEY KNOW WHERE TO GET FURTHER INFORMATION.  

 
 
Protocol for Acceptability Study; version 29.06.2016 
 
Page 1 of 5 
 
APPENDIX 10: 
TOPIC GUIDE – IN DEPTH INTERVIEWS WITH KEY 
INFORMANTS FOR ACCEPTABILITY OF IDA [EXAMPLE] 
 
MAIN RESEARCH QUESTION: UNDERSTANDING THE FEASIBILITY OF ADMINISTERING IDA: WHAT ARE 
THE FACTORS AND CONSIDERATIONS FOR THE INTRODUCTION OF TRIPLE DRUG THERAPY FOR LF 
ELIMINATION INTO THIS COMMUNITY? 
 
RATIONALE 
REFER TO THE INFORMATION SHEET 
 
CONFIDENTIALITY   
REFER TO THE INFORMED CONSENT SHEET 
 
WARM-UP QUESTIONS 
AS YOU’VE READ THE INFORMATION SHEET, YOU WILL REMEMBER THAT WE ARE HERE TO COLLECT SOME INFORMATION 
THAT WILL HELP THE GOVERNMENT TO MAKE YOUR HEALTH AND THE HEALTH OF PEOPLE IN YOUR VILLAGE BETTER.  SO 
MAYBE YOU COULD TELL ME A LITTLE BIT ABOUT THE HEALTH OF PEOPLE IN YOUR VILLAGE… 
 
 
 (IF NO RESPONSE… THEN PROMPT WITH: ARE THERE MANY SICK PEOPLE IN YOUR VILLAGE? WHAT DO PEOPLE GET 
SICK FROM IN YOUR VILLAGE?) 
 
LEAD IN TO INTERVIEW 
AS I MENTIONED IN THE BEGINNING OF THE INTERVIEW, WE ARE INTERESTED IN THE DISEASE FILARIA AND ITS TREATMENT. IS 
THAT SOMETHING THAT YOU’VE TAKEN MEDICINE FOR?  AND WHAT DID YOU TAKE?  
 
 
(INTERVIEWER: OH, THAT’S INTERESTING… MAYBE WE CAN TALK ABOUT THAT A BIT MORE LATER…) 
 
KNOWLEDGE ABOUT LF 
ASK THEM TO TELL YOU WHAT THEY KNOW ABOUT THE DISEASE LF: 
 
DEPENDING ON THE IDENTITY OF THE RESPONDENT (MEDICAL V NON-MEDICAL) PROMPT WITH THE FOLLOWING: 
- 
LOCAL NAMES 
- 
HOW DO YOU GET IT? 
o PROMPT: WOULD YOU LIKE TO DRAW HERE FOR ME HOW THE DISEASE ENTERS THE BODY? 
- 
TELL ME WHAT HAPPENS TO YOU WHEN YOU GET IT. 
- 
WHERE DID YOU HEAR ABOUT FILARIA? 
- 
WHO DO YOU THINK GETS IT MOST? (PROMPT: MEN? WOMEN? CHILDREN?) 
- 
DO YOU KNOW ANYONE WHO HAS FILARIA?  CAN YOU TELL ME ABOUT THEM?  

APPENDIX 10: 
TOPIC GUIDE – IN DEPTH INTERVIEWS WITH KEY 
INFORMANTS FOR ACCEPTABILITY OF IDA [EXAMPLE] 
Protocol for Acceptability Study; version 29.06.2016 
 
Page 2 of 5 
 
 
PAST PARTICIPATION IN MDA ACTIVITIES 
 
RESPONDENTS’ COMMENTS ABOUT PAST PARTICPATION WITH MDA 
YOU’VE ALREADY TOLD ME ABOUT YOUR EXPERIENCE WITH THE DRUGS FOR FILARIA. COULD YOU TELL ME ABOUT YOUR 
ROLE IN THE DISTRIBUTION FOR LF DRUGS IN YOUR AREA? 
 
IF NECESSARY PROMPT THE STORY WITH: 
- 
ANY PART YOU PLAYED IN THE PROMOTION AND/OR DISTRIBUTION OF THE DRUGS 
- 
HOW DID YOU TELL PEOPLE ABOUT THE TREATMENT DAY? 
- 
WHAT WAS THE ROLE OF OTHER LEADERS: VILLAGE LEADER, SCHOOL TEACHERS, CHURCH OR MOSQUE 
LEADERS, NEIGHBOURS, HEALTH STAFF 
 
 
CAN WE TALK ABOUT THE PEOPLE AROUND YOU AND HOW THEY FELT ABOUT THE TREATMENT? 
 
IF NECESSARY PROMPT WITH: 
- 
FAMILY/HOUSEHOLD: ANY DISCUSSION? FEELINGS OR VIEWS ABOUT THE TREATMENT? DID THEY TAKE IT? 
- 
NEIGHBOURS? FEELINGS OR VIEWS ABOUT THE TREATMENT? DID THE NEIGHBOURS TAKE IT?  
- 
OTHER PARTS OF THE VILLAGE? DID THEY TAKE IT?  
- 
ANYONE WHO DIDN’T TAKE IT? WHAT HAPPENED TO THEM? 
- 
HOW DID RESPONDENT KNOW WHO TOOK IT AND WHO DIDN’T?  
 
 
I’D LIKE US TO TALK A BIT MORE ABOUT THE GOOD AND BAD PARTS ABOUT TAKING THE LF PILLS?  
 
IF NECESSARY PROMPT WITH: 
- 
WHO DO THINK GAINS THE MOST FROM TAKING FILARIA TREATMENT? 
- 
WHO DO YOU THINK IS HURT BY THE TREATMENT / WHO LOSES MOST? 
 
 
LET’S THINK ABOUT THE GOOD THINGS FIRST, AND FOR YOU,  
 
IF NECESSARY PROMPT WITH: 
- 
WHAT DO YOU THINK IS GOOD ABOUT THE TREATMENT?  
- 
HOW DID IT HELP YOU? 
- 
WHAT DID YOU GAIN FROM TAKING THE TREATMENT? 
 
 
STILL THINKING ABOUT THE GOOD THINGS, BUT NOW FOR OTHERS,  
 

APPENDIX 10: 
TOPIC GUIDE – IN DEPTH INTERVIEWS WITH KEY 
INFORMANTS FOR ACCEPTABILITY OF IDA [EXAMPLE] 
Protocol for Acceptability Study; version 29.06.2016 
 
Page 3 of 5 
 
IF NECESSARY PROMPT WITH: 
- 
WHAT IS GOOD ABOUT THE TREATMENT FOR OTHERS? 
 
 
LET’S DO THE SAME FOR THE BAD THINGS, STARTING WITH YOU,  
 
IF NECESSARY PROMPT WITH: 
- 
WHAT DO YOU THINK IS BAD ABOUT THE TREATMENT?  
- 
HOW DID IT HURT YOU? 
 
 
AND THEN FOR OTHERS? 
 
IF NECESSARY PROMPT WITH: 
- 
DO YOU KNOW ANYONE WHO SUFFERED IN SOME WAY AFTER TAKING THE TREATMENT?  
- 
HOW DID IT HURT THEM? 
 
IN ORDER TO MAKE SURE THAT PEOPLE ACTUALLY TAKE THE PILLS THAT ARE GIVEN TO THEM, IT IS RECOMMENDED THAT 
COMMUNITY MEMBERS TAKE THE PILLS IN FRONT OF THE DISTRIBUTOR. I’D LIKE TO TALK A BIT MORE ABOUT THAT. 
- 
CAN YOU TELL ME HOW THIS HAPPENED IN YOUR COMMUNITY? 
- 
HOW DO YOU THINK PEOPLE FEEL ABOUT TAKING PILLS IN FRONT OF THE DISTRIBUTOR? 
- 
WHAT RECOMMENDATIONS DO YOU HAVE TO IMPROVE THE FREQUENCY OF PEOPLE TAKING PILLS IN FRONT 
OF THE DISTRIBUTOR? 
 
 
HOW DO YOU THINK THE DISTRIBUTION OF LF PILLS DIFFERS FROM OTHER HEALTH ACTIVITIES IN YOUR COMMUNITY? 
 
 
RECENT SAFETY TRIAL FOR IDA 
AS YOU KNOW, THERE WAS A SAFETY TRIAL IN YOUR COMMUNITY RECENTLY TO ASSESS THE SAFETY OF A NEW DRUG 
COMBINATION FOR LF TREATMENT THAT HAS BEEN SHOWN TO BE VERY EFFECTIVE AT KILLING THE LF WORMS. NOW, I 
WOULD LIKE TO TALK ABOUT THAT RECENT LF DRUG DISTRIBUTION A BIT MORE AND THE FUTURE PROSPECTS OF 
DELIVERING THE THREE DRUGS IN YOUR COMMUNITY.  
 
CAN YOU TELL ME ABOUT THE SPECIAL LF DRUG DISTRIBUTION THAT TOOK PLACE RECENTLY? 
 
IF NECESSARY PROMPT WITH: 
- 
HOW WAS IT DIFFERENT FROM PAST MDA ACTIVITIES? 
- 
WHAT WERE PEOPLE TALKING ABOUT IN THE COMMUNITY WHEN THE SAFETY TRIAL TOOK PLACE? 
 

APPENDIX 10: 
TOPIC GUIDE – IN DEPTH INTERVIEWS WITH KEY 
INFORMANTS FOR ACCEPTABILITY OF IDA [EXAMPLE] 
Protocol for Acceptability Study; version 29.06.2016 
 
Page 4 of 5 
 
LET’S TALK ABOUT THE PILLS THEMSELVES A BIT. ADULTS IN YOUR COMMUNITY RECEIVED # [FILL IN FOR THE SPECIFIC 
COUNTRY] OF PILLS. CAN YOU TELL ME ABOUT THAT? 
 
IF NECESSARY PROMPT WITH: 
- 
WHAT MESSAGES OR INFORMATION DID YOU TELL PEOPLE ABOUT TAKING THE PILLS? 
- 
HOW DID PEOPLE FEEL ABOUT TAKING # OF PILLS?  
- 
CAN YOU GIVE US ANY ADVICE ABOUT WHAT MESSAGES OR INFORMATION WE COULD USE IN THE FUTURE TO 
ENCOURAGE PEOPLE IN YOUR COMMUNITY TO TAKE ALL OF THESE PILLS? 
 
 
SOMETIMES PEOPLE HAVE SIDE EFFECTS AFTER THEY TAKE THE LF PILLS. I’D LIKE TO ASK YOU ABOUT ANY SIDE EFFECTS 
THAT OCCURRED HERE AFTER THE SPECIAL LF DISTRIBUTION.  
 
IF NECESSARY PROMPT WITH: 
- 
TELL ME ABOUT THE SIDE EFFECTS THAT YOU WITNESSED OR HEARD ABOUT IN YOUR COMMUNITY 
- 
TELL ME ABOUT THE REACTION IN THE COMMUNITY TO THESE SIDE EFFECTS 
- 
WERE THERE ANY MORE SIDE EFFECTS THAN IN PREVIOUS YEARS? 
- 
WHAT ADVICE DO YOU HAVE FOR THE PROGRAMME TO ENSURE PEOPLE UNDERSTAND WHY THESE SIDE 
EFFECTS OCCUR?  
- 
WHAT ADVICE DO YOU HAVE FOR THE PROGRAMME TO ENSURE PEOPLE FEEL REASSURED IF THERE ARE ANY 
SIDE EFFECTS? 
 
SOME OF THE SIDE EFFECTS FROM THE LF PILLS CAN BE ALSO CONSIDERED AS ‘GOOD’. PLEASE TELL ME ABOUT ANY 
‘GOOD’ SIDE EFFECTS THAT OCCURRED IN YOUR COMMUNITY? 
 
IF NECESSARY PROMPT WITH: 
- 
WHAT ADVICE DO YOU HAVE FOR THE PROGRAMME TO PROMOTE THESE ‘GOOD’ SIDE EFFECTS IN YOUR 
COMMUNITY? 
 
WHAT SUGGESTIONS DO YOU HAVE FOR THE MESSAGES WE MIGHT USE TO PROMOTE THE 3-DRUGS IN THE COMMUNITY 
IN THE FUTURE? 
 
IF NECESSARY PROMPT WITH: 
- 
WHAT WOULD MOTIVATE / ENCOURAGE PEOPLE TO SWALLOW THE PILLS? 
- 
WHO SHOULD DELIVER THOSE MESSAGES? 
- 
IN YOUR OPINION, DO WE NEED TO MAKE A NEW MESSAGE? 
- 
HOW SHOULD THIS NEW TREATMENT BE PROMOTED TO THE DISTRIBUTORS? THE LOCAL LEADERS? 
 
 
 
RESPONDENT ORDERS STATEMENTS: 
  

APPENDIX 10: 
TOPIC GUIDE – IN DEPTH INTERVIEWS WITH KEY 
INFORMANTS FOR ACCEPTABILITY OF IDA [EXAMPLE] 
Protocol for Acceptability Study; version 29.06.2016 
 
Page 5 of 5 
 
IN THIS LAST PART OF THE INTERVIEW, WE WILL BE LOOKING AT 5 STATEMENTS. LET’S READ THEM TOGETHER.  
 
1. TAKE THE PILLS SO YOU WON’T GET FILARIA. 
2. TAKE THE PILLS SO YOUR CHILDREN WON’T GET FILARIA. 
3. TAKE THE PILLS SO OUR COMMUNITY WILL NOT GET FILARIA. 
4. TAKE THE PILLS SO THE [DISTRICT / DEPARTMENT NAME] DOESN’T GET FILARIA. 
5. TAKE THE PILLS SO [COUNTRY NAME] DOESN’T GET FILARIA.  
 
CAN YOU PUT THEM IN ORDER OF IMPORTANCE? WHY DID YOU ARRANGE THEM THIS WAY? 
 
 
PLEASE PROBE CONTINUALLY THROUGHOUT WITH THINGS LIKE:  
- 
WHY DID YOU SAY THAT? 
- 
WHAT DO YOU MEAN BY THAT? 
- 
COULD YOU TELL ME A BIT MORE? 
- 
CAN YOU SAY WHAT YOU MEAN BY THAT? 
- 
SO THEN WHAT HAPPENED? 
- 
OH, THAT MAKES SENSE…  
- 
THAT’S INTERESTING…  
 
THANK YOU FOR YOUR TIME!   
MAKE SURE THEY KNOW WHERE TO GET FURTHER INFORMATION.  

 
 
Protocol for Acceptability Study; version 29.06.2016 
 
Page 1 of 1 
 
APPENDIX 11: VISITATION MATRIX 
* During passive follow-up participants reporting AEs grade 2 or higher will be followed until AE resolves. Participants with grade 1 
should be told to seek out passive monitors if symptoms persist or get worse  
 
 
Pre-
Treatment 
Active Adverse 
Event Monitoring 
Passive Adverse Event  
Monitoring 
STH 
Efficacy 
Acceptability 
Study 
FTS/MF on 
FTS (+) 
individuals 
before 
treatment 
Activity 
Before 
Dosing 
Day 
0 
Day 
1 
Day 
2 
Day 
3 
Day 
4 
Day 
5 
Day 
6 
Day 
7 
1 Month 
2-4 Months 
Day 365 (+ 
30 days) 
Census 
x 
 
Informed 
Consent 
x 
 
Demographics 
x 
 
Physical Exam 
 
x 
 
 
 
 
 
 
 
 
 
 
 
Baseline Stool 
 
x 
 
 
 
 
 
 
 
 
 
 
 
MDA 
Treatment 
x 
 
AE 
Assessment* 
 
 
 
x 
x 
x* 
x* 
x* 
x* 
x* 
 
 
 
Stool collection 
 
 
 
 
 
 
 
 
 
 
x 
 
 
Acceptability 
Survey  
 
x 
Efficacy 
Survey 
 
x