Performance and Usability Evaluation of Cardiometabolic Point-of-care Devices in a Target Use Setting
Phase: NA
Conditions: Diabetes Mellitus, Chronic Kidney Diseases, Hyperlipidemias
Sponsor: Foundation for Innovative New Diagnostics, Switzerland

 
Cardiometabolic devices study 
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CLINICAL STUDY PROTOCOL 
Protocol Title   
Performance and usability evaluation of cardiometabolic  
point-of-care devices in a target use setting 
 
Short title 
Cardiometabolic devices study 
 
Protocol Version Number: 
NC001 v2.0 
Date:  
30-March-2022 
 
Disease Programme:  
Non-communicable diseases (NCDs) 
 
Regulatory Agency Identifying Number(s):  
NHRC Proposal ID: 654/2021 
 
Clinicalstudys.gov Registration Number: 
NCT05257564 
 
 
 
 
 
 
 
 
 
FIND 
Campus Biotech 
Chemin des Mines 9 
1202 Geneva, Switzerland 
T: +41 (0)22 710 05 90 
 
 
 

 
Cardiometabolic devices study 
NC001 Protocol v2.0 
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Confidentiality Statement:  
The information contained in this document, especially unpublished data, is the property of FIND 
(or under its control) and may not be reproduced, published or disclosed to others without prior 
written authorization from FIND.  
 
 
 

 
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Table of Contents 
Institutions/Organizations/Partners Involved in the Study ...................................................... 6 
Signature Page (Sponsor) .......................................................................................................... 7 
Statement of Principal Investigator ........................................................................................... 8 
Protocol History/Amendment Summary* .................................................................................. 9 
List of Abbreviations and Acronyms ....................................................................................... 10 
Protocol Synopsis .................................................................................................................... 11 
Schedule of Activities ............................................................................................................... 12 
1 
Introduction ....................................................................................................................... 13 
1.1 
Study Rationale ........................................................................................................... 13 
1.2 
Background ................................................................................................................. 14 
1.3 
Benefit/Risk Assessment ............................................................................................. 14 
2 
Study Objectives and Endpoints ...................................................................................... 14 
3 
Study Design ..................................................................................................................... 15 
3.1 
General Design ........................................................................................................... 15 
3.2 
Scientific Rationale for Study Design ........................................................................... 16 
3.3 
End of Study Definition ................................................................................................ 16 
3.4 
Study Population and Eligibility .................................................................................... 16 
3.5 
Inclusion Criteria .......................................................................................................... 17 
3.6 
Exclusion Criteria ......................................................................................................... 17 
3.7 
Lifestyle Considerations ............................................................................................... 17 
3.8 
Screen Failures ........................................................................................................... 17 
4 
Study Intervention ............................................................................................................. 17 
4.1 
Investigational Product (or Study Intervention) ............................................................ 18 
4.2 
Preparation/Handling/Storage/Accountability ............................................................... 20 
4.3 
Minimisation of Error and Bias ..................................................................................... 21 
4.3.1 
Blinding Procedure .................................................................................................. 21 
5 
Participant Discontinuation/Withdrawal .......................................................................... 21 
5.1 
Participant Discontinuation/Withdrawal from the Study ................................................ 21 
6 
Study Procedures ............................................................................................................. 22 
6.1 
Participant enrolment ................................................................................................... 24 
6.2 
Specimen Collection, Handling, Transport and Storage ............................................... 24 
6.2.1 
Capillary blood sample collection ............................................................................. 25 
6.2.2 
Venous blood sample collection ............................................................................... 25 

 
Cardiometabolic devices study 
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6.3 
Index Test and Reference Test Procedures ................................................................. 25 
6.3.1 
Index tests procedure summary ............................................................................... 25 
6.3.2 
Reference tests ....................................................................................................... 26 
6.4 
Training ....................................................................................................................... 26 
6.5 
Genetic Analysis .......................................................................................................... 26 
6.6 
Experimental Biomarkers ............................................................................................. 26 
6.7 
Other Tests (Specify) ................................................................................................... 27 
6.8 
Safety Assessments .................................................................................................... 27 
6.9 
Other Study Procedures .............................................................................................. 27 
7 
Safety and Incident Reporting .......................................................................................... 27 
7.1 
Medical Device Incidents (including Malfunctions) ....................................................... 27 
7.2 
Time Period for Detecting Medical Device Incidents .................................................... 28 
7.3 
Follow-up of Medical Device Incidents ......................................................................... 28 
7.4 
Reporting of Medical Device Incidents to FIND ............................................................ 28 
7.5 
Regulatory Reporting Requirements for Medical Device Incidents ............................... 28 
8 
Statistical Considerations ................................................................................................ 29 
8.1 
Populations for Analyses ............................................................................................. 29 
8.2 
Statistical Analyses ...................................................................................................... 29 
8.2.1 
Analysis of primary and secondary outcomes .......................................................... 29 
8.2.2 
Safety Analysis ........................................................................................................ 30 
8.2.3 
Other Analyses ........................................................................................................ 30 
8.3 
Planned Interim Analyses ............................................................................................ 30 
8.3.1 
Data Monitoring Committee (DMC) .......................................................................... 30 
8.4 
Sample Size Determination ......................................................................................... 31 
8.5 
Statistical software ....................................................................................................... 31 
9 
Regulatory and Ethical Considerations ........................................................................... 32 
9.1 
Regulatory and Ethics Approvals ................................................................................. 32 
9.2 
Financial Disclosure .................................................................................................... 33 
9.3 
Informed Consent Process .......................................................................................... 33 
9.4 
Data Protection ............................................................................................................ 33 
10 
Data Handling and Record Keeping ................................................................................. 34 
10.1 
Source Data and Source Documents ........................................................................... 34 
10.2 
Data Management ....................................................................................................... 35 
11 
Quality Management ......................................................................................................... 35 

 
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11.1 
Quality Control (monitoring) ......................................................................................... 36 
11.2 
Quality Assurance (auditing) ........................................................................................ 36 
11.3 
Study and Site Closure ................................................................................................ 36 
12 
Publication Policy ............................................................................................................. 36 
13 
References ......................................................................................................................... 37 
14 
Appendices ........................................................................................................................ 37 
Appendix 1:  Safety Definitions and Reporting ........................................................................ 37 
Appendix 2:  Incident Definition and Reporting ........................................................................ 39 
Appendix 3: Protocol Amendment Summary Table ................................................................. 40 
 
 
 

 
Cardiometabolic devices study 
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Institutions/Organizations/Partners Involved in the Study 
Organization/Institution/Company/Partner 
Role in the Study 
FIND, Geneva, Switzerland 
Sponsor 
BP Koirala Institute of Health Science, Dharan, 
Nepal 
Local institution for study implementation; principal 
investigator site 
Hôpitaux Universitaires de Genève, Switzerland 
Study manager and Sub-principal investigator site 
Kakarvitta Health Post, Nepal  
Investigational Site 1 
Dhulabari Primary Healthcare Centre, Nepal  
Investigational Site 2 
B.P Koirala Institute of Health Sciences,  
Postal Code 56700,  
Ghopa Camp, Dharan, Province No.1, Nepal 
Reference testing site 
Tascom Ltd, South Korea 
Device manufacturer 
Jana Care, India/Boston 
Device manufacturer 
FIND (Sponsor) 
Contact person:  
Dr. Beatrice Vetter 
Address: 
 
Campus Biotech 
 
 
Chemin des Mines 9 
 
 
1202 Geneva, Switzerland 
Nepal 
Principal investigator: Dr. Sanjib Kumar Sharma 
Sub-Principal investigator: Dr. Vijay Kumar Khanal 
 
 
       Dr. Sagar Poudel 
Address:  
 
B.P. Koirala Institute of Health Sciences 
 
 
Buddha Road, Dharan 56700, Nepal 
Hôpitaux Universitaires de Genève (HUG) 
Study Manager:  
Mrs. Marina Giachino 
Sub-Principal Investigators: Dr. Jorge César Correia, Prof. Dr. med. Zoltan Pataky, Dr. Sigiriya 
Aebischer Perone, Mr. Bruno Lab, Mrs. Olivia Heller 
Address:   
 
Unit of Therapeutic Patient Education; WHO Collaborating Centre  
 
 
Division of Endocrinology, Diabetology, Nutrition and Therapeutic Patient  
 
 
Education; Department of Medicine 
 
 
Geneva University Hospitals 
 
 
Villa Soleillane; 7, Chemin Venel 
 
 
1206 Geneva, Switzerland 
 
 
Division of Tropical and Humanitarian Medicine 
 
 
Geneva University Hospitals 
 
 
Rue Gabrielle-Perret-Gentil 4 
 
 
1205 Geneva, Switzerland 
Terms of references and nature of agreements are available from FIND on request. 

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25/APR/2022
Pamela Nabeta
 pp. Rita Szekely
28/APR/2022
Stefano Ongarello
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Marina Giachino
25/APR/2022
SIGN

 
Cardiometabolic devices study 
NC001 Protocol v2.0 
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Protocol History/Amendment Summary* 
Version number 
Release date 
Comments 
1.0 
 
Initial version 
2.0 
30-MAR-2022 
After Site Initiation Visit, Technical Amendments 
 
 
 
 
 
*Refer to Appendices for Protocol Amendment History 
 

 
Cardiometabolic devices study 
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List of Abbreviations and Acronyms  
Abbreviation/acronym 
Meaning 
CRF 
Case Report Form 
CVD 
Cardiovascular Disease 
EDL 
Essential Diagnostic List 
GCLP 
Good Clinical Laboratory Practice 
GCP 
Good Clinical Practice 
HbA1c 
Glycated Haemoglobin 
Hb 
Haemoglobin 
HUG 
Hôpitaux Universitaires de Genève 
ICF 
Informed Consent Form 
ICH 
International Council on Harmonisation 
IEC 
Independent Ethics Committee 
IFU 
Instructions for Use 
IRB 
Institutional Review Board 
ISF 
Investigator Site File 
KHDC 
Chronic Kidney Diseases, Hypertension, Diabetes and 
Cardiovascular disease in Community 
LMIC 
Low and Middle Income Country 
NCD 
Non-communicable Disease 
PEN 
Package of Essential Non-communicable Diseases 
POC 
Point-of-Care 
QA 
Quality Assurance 
QC 
Quality Control 
QMS 
Quality Management System 
PHC 
Primary Healthcare 
RA 
Regulatory Authority 
SAE 
Serious Adverse Event 
SAP 
Statistical Analysis Plan 
SUS 
System Usability Score 
TPP 
Target Product Profile 
WHO 
World Health Organisation 
 
 

 
Cardiometabolic devices study 
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Protocol Synopsis 
Title 
Performance and usability evaluation of cardiometabolic point-of-care devices in a target 
use setting 
Short title  
Cardiometabolic devices study 
Version and date 
V2.0 30-March-2022 
Background and 
rationale 
With the rise of cardiovascular diseases (CVD) and diabetes, the global disease burden 
is shifting towards non-communicable diseases (NCDs). An increasing number of low- and 
middle-income countries (LMICs) are currently experiencing the double burden of 
infectious and non-communicable diseases. In order to facilitate a patient-centred 
approach to healthcare, there is an urgent need to ensure that primary healthcare (PHC) 
facilities in LMICs are capable of addressing diagnosis and monitoring of non-
communicable diseases at the point-of-care (POC). Important minimum parameters for 
PHC POC diagnosis and monitoring of cardiometabolic diseases are lipids/lipoproteins, 
glucose, glycated haemoglobin (HbA1c) and serum creatinine, to address cardiovascular 
disease, diabetes and chronic kidney disease.  
While several technologies of multi-parameter POC devices capable of supporting 
diagnosis and monitoring of cardiometabolic diseases exist, their quantitative accuracy is 
often not well evaluated outside of the manufacturer’s laboratories and published 
independent evaluations can be rare, particularly in the settings of intended use. These 
settings are PHC facilities in varying climatic environments and with staff without specialist 
laboratory training. Our study aims to evaluate the quantitative accuracy of 2 
cardiometabolic POC devices (the SimplexTAS 101 from Tascom and the Aina Station 
from JanaCare) in a setting of intended use and performed by the intended user.   
Primary 
objective(s) 
1.1. To determine the accuracy of quantitative measurements of glucose, HbA1c, total 
cholesterol and creatinine as measured in a healthcare setting with point-of-care 
multiparameter devices compared to a laboratory reference method 
Secondary 
objective(s) 
2.1 To evaluate the operational characteristics and system usability of each 
cardiometabolic device when used in a PHC setting 
Primary endpoints 
(outcomes) 
1.1. Estimates of correlation and linear dependence between quantitative measurements 
of glucose, HbA1c, total cholesterol and creatinine evaluated in a healthcare setting 
with point-of-care multiparameter devices and in a laboratory reference assay. 
1.2. Estimates of accuracy and limits of agreement for quantitative measurements of 
glucose, HbA1c, total cholesterol and creatinine evaluated in a healthcare setting with 
point-of-care multiparameter devices (compared to a laboratory reference assay). 
Secondary 
endpoints 
(outcomes) 
2.1 Operational characteristics and usability of study devices: 
- 
Rate of invalid test results and error types 
- 
System usability score 
Study design 
Prospective quantitative accuracy study  
Study sites/setting 
Multi-centre: Dhulabari Primary Healthcare Centre, Kakarvitta Health Post, Nepal 
Study population  
Members of the local community attending the facility under the KHDC program 
Sample Size 
400 
Eligibility criteria  
Age: ≥20 years; KHDC clinic attendees; Hb ≥8 g/dL; Consenting 
Study duration  
4 months 
Time schedule 
Anticipated start Q1 2022 
 

 
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Schedule of Activities  
Procedure 
Daily 
(working 
days) 
Weekly 
Notes 
Eligibility assessment  
X 
 
excluding haemoglobin testing 
Informed consent 
X 
 
- 
Haemoglobin testing 
X 
 
- 
Demographic information 
X 
 
- 
Fingerstick testing 
X 
 
- 
Venous sample collection 
X 
 
- 
Venous sample transport to reference lab 
X 
 
- 
Reference lab testing 
X 
 
- 
Data entry 
 
X 
- 

 
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1 Introduction 
With the rise of cardiovascular diseases (CVD) and diabetes, the global disease burden is shifting 
towards non-communicable diseases (NCDs). An increasing number of low- and middle-income 
countries (LMICs) are currently experiencing the double burden of infectious and non-
communicable diseases [1]. CVD and diabetes alone make up more than two thirds of the global 
burden of the four most common NCDs, including chronic respiratory diseases and cancer [2]. In 
order to facilitate a patient-centred approach to healthcare, there is an urgent need to ensure that 
primary healthcare (PHC) facilities in LMICs are capable of addressing diagnosis and monitoring 
of both infectious and non-communicable diseases at the point-of-care.  
In 2020 the Foundation for Innovative New Diagnostics (FIND), together with technical inputs from 
the World Health Organization (WHO), developed a landscape of multi-parameter point-of-care 
(POC) devices capable of supporting diagnosis and monitoring of cardiometabolic diseases at PHC 
facilities [3]. Cardiometabolic risk factors include raised blood pressure, raised blood glucose, 
raised blood lipids, excess weight and obesity. The WHO Package of Essential Noncommunicable 
Disease Interventions for primary health care in low resource settings (WHO PEN package, [4], as 
well as the WHO Model List of Essential In Vitro Diagnostics (EDL, [5]), include several parameters 
for the use at POC that should be used to detect and manage cardiometabolic risk. These include 
lipids/lipoproteins, glucose, glycated haemoglobin (HbA1c) and serum creatinine, to address 
cardiovascular disease, diabetes and chronic kidney disease. 
Together with a range of clinical and laboratory experts, FIND developed a target product profile 
(TPP) for cardiometabolic POC devices, with the aim to define the minimal and optimal 
requirements for such devices in PHC settings in LMICs [6]. Beyond the test menu available, 
requirements considered related to device design, usability, storage and operating temperature, 
data management and affordability.  
The diagnostic devices identified in the landscape were evaluated against the TPP requirements 
and in discussion with experts, to evaluate which of the devices meet minimal and optimal 
requirements, with the aim to select two devices for a quantitative accuracy and system usability 
evaluation.  
1.1 Study Rationale 
While several technologies of multi-parameter POC devices capable of supporting diagnosis and 
monitoring of cardiometabolic diseases exist, their diagnostic accuracy is often not well evaluated 
outside of the manufacturer’s laboratories and published independent evaluations can be rare, 
particularly in the settings of intended use. These settings are PHC facilities in varying climatic 
environments and with staff without specialist laboratory training.  
Our study aims to evaluate the diagnostic accuracy of two cardiometabolic POC devices in a setting 
of intended use and performed by the intended user. The results will generate evidence on the 
expected accuracy of these POC devices and their performance in comparison to a standard 
laboratory method.  

 
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1.2 Background 
Independent performance evaluation of POC devices have shown that many devices, regardless 
of their intended use, do not perform as well as the manufacturers’ claims may suggest [7, 8]. There 
are a variety of reasons for this, including difference in skills levels of personnel who were involved 
in generating the data for the manufacturer’s claims and who actually perform the test in a clinic, 
limited evaluation of samples from different geographical locations and thus potential interfering 
substances or less controlled environmental conditions (e.g. dust, heat and humidity).  
Independent performance evaluations to assess clinical accuracy, as well as system usability are 
important to drive adoption of any technology, and even more so, if the technology is intended to 
move testing outside of the traditional setting, i.e. away from the central laboratory to the point-of-
care. Many devices appear ideally suited for certain settings, however when it comes to actual 
implementation, the users often discover that the device and workflow do not meet their needs. 
The choice of a suboptimal device means badly invested resources and may lead to inappropriate 
use, resulting in fewer reliable tests for patients in the absence of alternatives. Data from real-world 
evaluations in settings of the intended use can support decision makers to select the right device.   
The setting for this study will be a primary healthcare facility and a health post in Nepal, where 
study participants attend the facility in the context of the “Early detection and management of 
Chronic Kidney Diseases, Hypertension, Diabetes and Cardiovascular disease in Community in 
Nepal (KHDC-Nepal) program”, conducted by the University Hospital of Geneva and the B.P. 
Koirala Institute of Health Science in Nepal.   
1.3 Benefit/Risk Assessment 
The risks for study participants are minimal as the study procedures only include collection of 
fingerstick blood and venous blood. Participants are facility attendees in the context of the above 
mentioned KHDC-Nepal early detection program, under which they have access to the relevant 
healthcare related to any clinical findings from this diagnostic accuracy study.   
2 Study Objectives and Endpoints 
TABLE 1: STUDY OBJECTIVE AND ENDPOINTS 
Objectives 
Endpoints 
Primary 
 
1.1 To determine the accuracy of quantitative 
measurements of glucose, HbA1c, total cholesterol 
and creatinine* as measured in a healthcare setting 
with 
point-of-care 
multiparameter 
devices 
compared to a laboratory reference method. 
1.1. Estimates of correlation and linear dependence 
between 
quantitative 
measurements 
of 
glucose, HbA1c, total cholesterol and creatinine 
evaluated in a healthcare setting with point-of-
care multiparameter devices and in a laboratory 
reference assay. 
 
1.2. Estimates of accuracy and limits of agreement 
for quantitative measurements of glucose, 
HbA1c, 
total 
cholesterol 
and 
creatinine 

 
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evaluated in a healthcare setting with point-of-
care multiparameter devices (compared to a 
laboratory reference assay). 
Secondary 
 
2.1 To evaluate the operational characteristics and 
system usability of each cardiometabolic device 
when used in a PHC setting 
2.1 Operational characteristics and usability of 
study devices: 
- 
Rate of invalid test results and error types 
- 
System usability score 
*note: Creatinine is only available for one of the two 
investigational products 
 
3 Study Design 
3.1 General Design 
This is a prospective quantitative accuracy study to assess the performance of clinical chemistry 
POC devices in comparison to a standard state of the art laboratory reference method available in 
the study country.  
The general study concept is shown in Figure 1. For more information on the investigational product 
see section 4.1. Note that creatinine on the Aina Jana Care cardiometabolic platform is still in 
development and not available for evaluation.  
FIGURE 1: STUDY CONCEPT, PARAMETERS EVALUATED AND REFERENCE TESTS  
 

 
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3.2 Scientific Rationale for Study Design 
The study design was chosen with the objective in mind to evaluate the performance of POC 
devices compared to standard laboratory methods. In most countries, standard of care testing of 
the assessed parameters is done in centralized laboratories using venous whole blood. POC 
methods have several advantages over centralized methods, in that they use simpler sampling 
collection methods, i.e. fingerstick whole blood, do not require sample transport networks and can 
deliver results while the patient is at the healthcare facility. However, their adoption is often 
hampered by the perception that POC devices are less accurate, compared to centralized 
laboratory methods and the only comparison data available are generated by the manufacturers.  
3.3 End of Study Definition 
A participant is considered to have completed the study if he/she has completed the visit and all 
procedures as shown in the Schedule of Activities. The end of the study is defined as the date 
when all data entry is completed in the clinical study data base.  
3.4 Study Population and Eligibility  
The study will be conducted in two sites, at the Dhulabari primary healthcare centre (PHC) and at 
the Kakarvitta Health post in the rural area of Jhapa in Eastern Nepal. The study will be embedded 
in the KHDC-Nepal program, which has the objective to improve the health of the Nepalese 
population in Eastern Nepal through early detection and management of chronic non-
communicable diseases. The program runs community awareness sessions and door-to-door visits 
to encourage members of the community to attend a screening visit at selected primary health 
facilities, health posts or at a pre-designated location. During this visit, people are screened for 
hypertension, diabetes, chronic kidney and cardiovascular disease, including (but not limited to) 
testing for glucose, lipids, HbA1c and creatinine.  
Focus of the program are individuals ≥40 years of age based on the WHO risk prediction chart [9] 
and anyone ≥20 years is eligible for screening. In the program region, 50% of the population above 
40 is expected to be screened, in which 25% may have at least one non-communicable disease 
(e.g. diabetes or elevated blood pressure) [10]. Anyone who screens positive for the NCDs in focus 
of the program is linked or referred to care at their local healthcare facility. 
Community members who attend the Dhulabari PHC facility and the health post Kakarvitta in the 
context of the KHDC program will be invited to participate in the present study until the daily 
recruitment target across both sites is reached (5 participants per site/per day, or more if the site 
has capacity to test more participants per day). The Dhulabari PHC facility and the Kakarvitta health 
post run screening activities for the KHDC program during three hours in the morning. If interested 
and eligible study participants cannot be tested during these hours, they will be given appointments 
on a first-come-first-served basis for study participation. Additionally, KHDC program participants 
can be enrolled if they visit the Dhulabari PHC facility or Kakarvitta health post for a follow up 
appointment. 
Results generated with the investigational products, or the reference assay will not be used for 
clinical decision making as the participants will have received these screening tests in the context 
of the KHDC program.  

 
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During the eligibility procedure, potential study participants will also be tested for haemoglobin to 
investigate if they suffer from abnormal haemoglobin values, which may have an impact on their 
HbA1c levels [11]. If potential participants are found to have haemoglobin levels of <8 g/dL, they 
will not be eligible for the study and will be referred by the local physician for follow up care.   
Prospective approval of protocol deviations to recruitment and enrolment criteria, also known as 
protocol waivers or exemptions, is not permitted. 
3.5 Inclusion Criteria 
Participants are eligible to be included in the study only if all of the following inclusion criteria apply:  
x 
20 years or older (in line with KHDC eligibility age) 
x 
Attending the Dhulabari PHC facility or Kakarvitta health post in the context of the KHDC 
program  
x 
Haemoglobin levels ≥8 g/dL 
x 
Able and willing to provide informed consent 
3.6 Exclusion Criteria  
Participants are excluded from the study if any of the following exclusion criteria apply:  
x 
Inability to provide sufficient capillary or venous whole blood sample for all tests 
x 
Haemoglobin levels < 8g/dL 
x 
Anyone attending the Dhulabari PHC facility or Kakarvitta health post for other reasons than 
the KHDC program 
3.7 Lifestyle Considerations  
None 
3.8 Screen Failures  
Screen failures are defined as participants who consent to participate in the clinical study but do 
not subsequently undergo any of the study procedures. A minimal set of screen failure information 
is required to ensure transparent reporting of screen failure participants to meet the Consolidated 
Standards of Reporting Studies (CONSORT) publishing requirements and to respond to queries 
from regulatory authorities. Minimal information includes demography, screen failure details, 
eligibility criteria, and any serious adverse event (SAE). 
4 Study Intervention 
Study intervention is defined as any investigational intervention(s), marketed product(s), or medical 
device(s) intended to be used with a study participant according to the study protocol.   

 
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4.1 Investigational Product (or Study Intervention) 
Table 2 shows test principle, sample types, sample volume and testing time for each of the 
parameters and investigational product, as well as the reference method.  
 

 
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TABLE 2: KEY CHARACTERISTICS OF THE INVESTIGATIONAL PRODUCT METHODS AND REFERENCE METHODS 
 

 
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Medical device incidents, including those resulting from malfunctions of the device (or IVD), must 
be detected, documented and reported by the investigator at each site throughout the study (see 
Appendices). 
4.2 Preparation/Handling/Storage/Accountability 
Acquisition 
Procurement of the investigational products will be done through FIND, who will coordinate 
shipments from the manufacturer. It is the responsibility of the study site to maintain an updated 
inventory of the study materials and to inform FIND immediately if additional materials are required. 
The investigator or designee must confirm appropriate temperature conditions have been 
maintained during transit for the investigational product received and any discrepancies are 
reported and resolved before its use. 
Storage 
Procedures for product storage and disposal will be described in the Study Manual.  
The investigational product must be stored in a secured, environmentally controlled, and monitored 
(manual or automated) area in accordance with the labelled storage conditions with access limited 
to the investigator and authorized site staff. 
Test Handling and Performance 
Testing using the investigational products will be performed according to the manufacturer’s 
instructions for use and as outlined in the study manual.  
Only blood samples from participants enrolled in the study will be processed with the investigational 
product and only authorized site staff will be responsible for processing. 
Accountability 
The investigator is responsible for study intervention accountability, reconciliation, and record 
maintenance (i.e., receipt, reconciliation, and final disposition records). Investigational Product 
Accountability logs filled at each site will ensure the proper follow-up of the used, failed and 
remaining investigational products. 
Further guidance and information for the final disposition of unused investigational product are 
provided in the study manual.  
Export and Import Permits 
Local sites are responsible for making import permit applications in a timely manner.   
Quality Control Check for Incoming Shipments 
Upon arrival of each new shipment of assays, the sites will conduct and document an incoming 
quality check following the Study Manual. New lots may only be used after this quality check is 
successfully passed. 
Local procurement 
Sites are responsible for assessing their needs and procuring any supplies, reagents and kits 
needed for the study that are locally available in order to include these costs in the study budget.  

 
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4.3 Minimisation of Error and Bias 
To avoid the risk of sample and participant information mix ups, participants will be assigned a 
unique study ID and this number will be used in all study-related materials with participant 
information or sample material (either with specific labels or hand-written on e.g. cartridges without 
sufficient space for labels).   
The risk of procedural errors for fingerstick blood collection and running of the assay on the 
investigational device will be reduced through the provision of training and competency assessment 
on the sample collection procedure and device operation. Training will be provided either by the 
manufacturers or by a manufacturer-trained FIND member of staff from the clinical trials unit. 
Training will be provided in person or remotely via live-video, in case of COVID-related travel 
restrictions.   
The risk of procedural errors regarding the venous blood collection and the centrifugation are 
minimized since these procedures are undertaken by study personnel who perform phlebotomy 
and centrifugation as part of their daily routine. Further to this, they receive dedicated training on 
any study-specific procedures such as preparation of aliquots. With respect to mitigating of any 
sample mix-up the unique study ID label is used on all tubes (as well aliquots tubes). There is little 
risk for contamination as appropriate equipment is used, such as single-use pipette tips for aliquot 
preparation. All waste is discarded in biohazard waste bags. 
There is little risk of bias in result interpretation, as the investigational devices produce alpha 
numeric results, which do not require interpretation by the user. Up to three members of staff, per 
site,will be trained to operate both investigational devices. For an individual participant, the same 
member of staff will collect samples for both devices for maximum comparability of results and to 
remove the risk of user-induced factors when comparing results from the same participant. 
Participants will be split approximately 50:50 between the two users and they will process 
participant samples interchangeably during the course of the study. 
Participants ≥20 years of age are eligible for this study. The KHDC program focuses on members 
of the community who are 40 years or older, yet anyone ≥20 years can also be screened. However, 
this is not anticipated to introduce any bias, as the study purely focuses on the quantitative accuracy 
of the investigated parameters, which is unrelated to a participant’s age.  
4.3.1 Blinding Procedure 
Blinding of operators to any health status or result is not necessary in this study, as all results will 
be generated automatically by the investigational device and do not require operator interpretation.  
5 Participant Discontinuation/Withdrawal  
5.1 Participant Discontinuation/Withdrawal from the Study  
A participant may be withdrawn at any time at the discretion of the investigator for safety, 
behavioural, compliance, or administrative reasons. 
If the participant withdraws consent for disclosure of future information, FIND may retain and 
continue to use any data collected before such a withdrawal of consent. 

 
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If a participant withdraws from the study, he/she may request destruction of any samples taken and 
not tested, and the investigator must document this in the site study records. 
See Schedule of Activities for data and/or samples to be collected at the time of study 
discontinuation and follow-up and for any further evaluations that need to be completed. 
6 Study Procedures 
Study procedures and their timing are summarized in the Schedule of Activities and outlined in 
Figure 2. Protocol waivers or exemptions are not allowed. Adherence to the study design 
requirements, including those specified in the Schedule of Activities, is essential and required for 
study conduct. 
All screening evaluations must be completed and reviewed to confirm that potential participants 
meet all eligibility criteria. The investigator will maintain a screening log to record details of all 
participants screened and to confirm eligibility or record reasons for screening failure, as applicable.  
Procedures conducted as part of the participant’s routine clinical management and obtained before 
signing of the Informed Consent Form (ICF) may be utilized for screening or baseline purposes 
provided the procedures met the protocol-specified criteria (see 6.1) and were performed within the 
time frame defined in the Schedule of Activities. 
 
 

 
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FIGURE 2: STUDY FLOW 
 

 
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6.1 Participant enrolment 
Eligibility assessment and enrolment through signing of the informed consent form will be done at 
the PHC facility and the health post by trained staff. All individuals attending these facilities in the 
context of the KHDC program will be invited to participate in the study until the daily recruitment 
target of 10 participants (5 participants per site/per day, or more if the site has capacity to test more 
participants per day) is reached.  
Individuals will be screened for eligibility and must provide their written consent to participate. After 
obtaining the signed consent, a participant screening ID is assigned to him/her for Haemoglobin 
testing and if eligible, a participant study ID is assigned to him/her and the participant is recorded 
in the enrolment log.   
At enrolment, the following information will be collected for each participant, based on verbal 
information provided by the individual:  
x 
Age 
x 
Gender 
x 
Pre-existing conditions (including but not limited to diabetes, hypertension, 
haemoglobinopathy, heart failure, dyslipidaemia, chronic kidney diseases, liver disease) 
x 
Medications taken (including but not limited any glucose, lipid and blood pressure 
lowering medication in particular beta blockers and diuretics, traditional local medication 
(such as Hoodia, Gymnema, Aloe) 
x 
Fasting status 
 
Results of the following procedures as performed in the context of the KHDC program will also be 
collected from the medical records of each participant: 
x 
BMI 
x 
Smoking status, alcohol intake 
x 
Diagnosis made of KHDC screening for chronic kidney diseases, hypertension, diabetes 
and cardiovascular disease 
 
After recording the participant’s demographic and clinical data in the dedicated Participant 
Worksheet, blood samples can be collected to perform all necessary study testing. 
6.2 Specimen Collection, Handling, Transport and Storage 
The maximum amount of blood collected from each participant over the duration of the study will 
not exceed 7 drops of fingerstick capillary blood (approximately 0.35 ml) for the study procedure, 1 
drop of fingerstick capillary blood for the haemoglobin eligibility test and 9 ml of venous whole blood 
for the reference tests. Repeat or unscheduled samples may be taken for safety reasons or for 
technical issues with the samples. 

 
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6.2.1 Capillary blood sample collection 
Fingerstick capillary blood will be collected according to each manufacturer’s IFU, e.g. with a 
provided capillary or sample collection device. The fingerstick capillary blood samples will be used 
immediately on the point-of-care assays. 
6.2.2 Venous blood sample collection 
The 9ml venous blood will be collected in NaF/K-Oxalate tubes for plasma (GLU), K2-EDTA tubes 
for whole blood (HbA1c) and in a plain vial for serum (CRE, CHOL). All tubes will be pre-labelled 
with a study specific identification label. Plasma will be separated by centrifugation within a 
maximum of 30 minutes from blood collection at the PHC facility and health post and aliquots will 
be prepared. Serum will be left to clot for a maximum of 60 min prior to centrifugation and serum 
aliquots will be prepared at the PHC facility and health post. The samples will be stored at 2-8°C 
until transfer to the BPKIHS reference lab. Once reference testing is completed, the left-over 
samples will be stored at 2-8°C until the results are validated according to the reference laboratories 
validation procedure. All left-over samples will be destroyed according to the laboratory’s bio-safety 
procedures and sample destruction will be recorded. 
6.3 Index Test and Reference Test Procedures 
Test procedures for the reference tests and the POC index tests will be performed according to the 
manufacturer’s IFUs, which are provided separately from this protocol. 
6.3.1 Index tests procedure summary 
SimplexTAS 101 
The Tascom TAS101 sample cartridges contain an integrated sample collection device with a 
capillary tube. This tube is used to collect the required amount of fingerstick capillary whole blood 
by removing the collection device from the cartridge and holding it to the drop of blood on the finger. 
The filled collection device is subsequently re-inserted into the cartridge and loaded into the 
analyzer.  
More information on appropriate sample collection techniques, loading of the cartridges and 
running of the test will be provided in the study manual and the manufacturer’s analyzer handbook. 
Sample volumes needed for each test do not exceed 20 µl per test and the exact volumes, as well 
as testing time and method are provided in Table 2.  
JanaCare 
The Aina JanaCare Monitoring System is intended to be used for quantitative measurement using 
a dry strip, a universal reader and a connected device. The required amount of fingerstick capillary 
whole blood are either collected directly on the test strip or via a small sample capillary before 
loading on the test strip. The test strip is subsequently inserted in the Aina universal reader device. 
The collected sample is then analyzed through the connected device.  
More information on appropriate sample collection techniques and running of the test will be 
provided in the study manual and the manufacturer’s analyzer handbook. 

 
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Even though a higher volume of blood collection is needed for performing Total Cholesterol 
parameter, the sample volumes needed for each test do not exceed 15 µl per test and the exact 
volumes, as well as testing time and method are provided in Table 2. 
 
6.3.2 Reference tests 
Reference testing will be done at the B.P. Koirala Institute of Health Sciences. The reference test 
for HbA1c will be the HbA1c Immunoassay (A1C) on the Roche cobas analyzer, which requires 3 
ml of whole blood using K2-EDTA as anticoagulant. This is a validated sample type for this analyzer 
as per the manufacturer’s instruction for use.   
The reference tests for glucose, for total cholesterol and creatinine will be based on Enzymatic test 
principles, on the Roche cobas analyzer. Creatinine (CRE) and total Cholesterol (CHOL) are 
requiring 4 ml of whole blood (for 2ml of Serum) for analysis in total, and Glucose (GLU) 2 ml of 
whole blood (1.5 ml of Plasma). All sample types are validated by the manufacturers for use with 
the respective tests.  
All reference tests will be performed according to the manufacturer’s instruction for use and quality 
controls and calibrations for the tests are performed by the laboratory according to the 
manufacturers’ recommendations (or based on the laboratories standard operating procedures for 
quality assurance of tests).  
6.4 Training 
All healthcare workers at the enrolment sites involved in participant testing will be trained in the 
procedures of the POC investigational devices, including instrument maintenance and control, 
sample collection and testing workflow. On-site Training or Online Training will be performed by 
the manufacturers or by the FIND study manager after having received training from the 
manufacturer.  
Healthcare workers involved in participant eligibility assessment, participant information and 
informed consent as well as data management will be trained on the procedures specifically by the 
FIND study manager. 
Proficiency will be documented in a training log.   
6.5 Genetic Analysis 
Genetic data will not be evaluated in this study. 
6.6 Experimental Biomarkers 
Experimental biomarkers are not evaluated in this study. 

 
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6.7 Other Tests (Specify) 
Participants will have been tested for haemoglobin levels during the eligibility assessment. The 
results will be used in the statistical analysis to correlate haemoglobin levels with HbA1c results. 
The test will be performed with the Hemocue Hb301+ point-of-care hemoglobin analyzer requiring 
a fingerstick blood sample. 
6.8 Safety Assessments 
There will be no planned safety assessments as the risks for the participants are considered 
minimal (see section 1.3). 
6.9 Other Study Procedures 
No other study procedures are planned. 
7 Safety and Incident Reporting 
Given that this is a quantitative accuracy study of clinical biochemistry point-of-care assays, the 
probability of an adverse event (AE) or a serious adverse event (SAE) occurring to a study 
participant to be associated with the investigational products is extremely low (see Appendix 1 for 
definitions of AE or SAE). Considering this, only deaths occurring between the start of the 
fingerstick blood collection and until the participant leaves the study will be recorded on a 
standardized form and reported to FIND by the investigator within 24 hours of becoming aware. 
7.1 Medical Device Incidents (including Malfunctions) 
Medical devices are being provided for use in this study for the purpose of assessing their 
diagnostic accuracies. In order to fulfil regulatory reporting obligations worldwide, the investigator 
is responsible for the detection and documentation of events meeting the definitions of incident or 
malfunction that occur during the study with such devices.  
The definition of a Medical Device Incident can be found in Appendix 2. 
Examples of a medical device incident for this study could be: 
x 
A broken sample collection device (if provided) 
x 
A broken or malfunctioning capillary tube or pipette provided  
NOTE: Incidents fulfilling the definition of an SAE will also follow the processes outlined above and 
in Appendix 2 of the protocol. 

 
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7.2 Time Period for Detecting Medical Device Incidents 
Medical device incidents or malfunctions of the device that result in an incident will be detected, 
documented, and reported during all periods of the study in which the medical device is used.  
If the investigator learns of any incident at any time after a participant has been discharged from 
the study, and such incident is considered reasonably related to a medical device provided for the 
study, the investigator will promptly notify FIND. 
The method of documenting Medical Device Incidents is provided in Appendix 2. 
7.3 Follow-up of Medical Device Incidents 
All medical device incidents involving an SAE will be followed and reported in the same manner as 
other SAEs (see Section 7.1.2). This applies to all participants, including those who discontinue 
study intervention. 
The investigator is responsible for ensuring that follow-up includes any supplemental investigations 
as indicated to elucidate the nature and/or causality of the incident. 
New or updated information will be recorded on the originally completed form with all changes 
signed and dated by the investigator. 
7.4 Reporting of Medical Device Incidents to FIND 
Medical device incidents will be reported to FIND within 24 hours after the investigator determines 
that the event meets the protocol definition of a medical device incident. 
The Medical Device Incident Report Form will be sent to FIND by email. If email is unavailable, 
then a mobile phone photo and text messaging should be utilised. 
The same individual(s) will be the contact for the receipt of medical device incident reports and 
SAE reports.  
7.5 Regulatory Reporting Requirements for Medical Device Incidents 
The investigator will promptly report all incidents occurring with any medical device provided for 
use in the Study in order for FIND to fulfil the legal responsibility to notify appropriate regulatory 
authorities and other entities about certain safety information relating to medical devices being used 
in clinical studies. 
The investigator, or responsible person according to local requirements (e.g., the head of the 
medical institution), will comply with the applicable local regulatory requirements relating to the 
reporting of incidents to the IRB/IEC. 

 
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8 Statistical Considerations  
This section provides summary of the planned statistical analyses of the primary and secondary 
endpoints, as well as details on the sample size calculation. A Statistical Analysis Plan (SAP) will 
be written before the start of recruitment and will describe the analysis strategy in detail. Analysis 
of the exploratory objectives will be described in the SAP.  
8.1 Populations for Analyses 
For purposes of analysis, the following populations will be defined as per Table 3. 
TABLE 3: POPULATION FOR ANALYSIS 
Population 
Description 
Enrolled  
All participants who sign the informed consent 
Evaluable/Per Protocol 
Population (PP) 
All participants who fully complied with the protocol and for whom index 
test results and reference test results are available for all tests. 
Partially Compliant Population 
(PCP) 
All participants who complied partially with the protocol, i.e. those for 
whom index test results and reference test results are available but not in 
a complete form (e.g. missing one POC result) 
8.2 Statistical Analyses 
8.2.1 Analysis of primary and secondary outcomes 
The primary and secondary outcomes of the study are presented in the Table 4. 
TABLE 4: ENDPOINTS AND ANALYSIS METHOD 
Endpoints 
 
Analysis method 
Primary 
 
1.1 Estimates of correlation and linear dependence 
between 
quantitative 
measurements 
of 
glucose, 
HbA1c, 
total 
cholesterol 
and 
creatinine evaluated in a healthcare setting with 
point-of-care multiparameter devices and in a 
laboratory reference assay. 
 
1.2 Estimates of accuracy and limits of agreement 
for quantitative measurements of glucose, 
HbA1c, 
total 
cholesterol 
and 
creatinine 
evaluated in a healthcare setting with point-of-
care multiparameter devices (compared to a 
laboratory reference assay). 
1.1 Point 
estimates 
of 
Pearson 
correlation 
coefficient, coefficient of determination (R2), 
intercept and slope coefficient of linear 
regression (with 95% confidence intervals), will 
be computed for all biomarkers and devices 
compared to the reference assay. 
 
1.2 Point estimates of fixed and proportional bias 
(with 95% confidence interval), coefficient of 
variation and limits of agreement, calculated via 
Bland-Altman analysis in absolute and relative 
units, will be computed for all biomarkers and 
devices compared to the reference assay. 
Secondary 
 

 
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2.1 Operational characteristics and usability of 
study devices: 
- 
Rate of invalid test results and error types 
- 
System usability score 
2.1 Proportion of invalid tests per parameter (with 
95% confidence interval based on Wilson’s 
score method) will be computed for each 
device. System usability score will be analyzed 
with descriptive statistics.  
Point estimates of correlation between concentrations of biomarkers, measured with the POC 
devices and reference assay, will be calculated based on Pearson’s method separately for each 
device and marker type. The dependence between the measurements of POC devices and the 
reference method will be visualized with the use of scatter plots and analyzed using linear 
regression. Point estimates of intercept and slope coefficient, with 95% confidence intervals, and 
coefficient of determination (R2) will be computed separately for each device and marker type. 
To evaluate the systemic deviation of POC device measurements from the established reference 
assay, Bland-Altmann analysis will be performed for each marker type and device. The deviation 
will be visualized with the Bland-Altman plot in absolute and relative units. Point estimates of fixed 
bias (mean difference between measurements) and proportional bias (dependence of the 
difference on concentration level), with 95% confidence intervals, will be computed. Standard 
deviation of the difference between the measurements of POC device and reference assay will be 
evaluated, along with the coefficient of variation and 95% prediction interval (limits of agreement) 
of the error. All calculations will be performed in absolute and relative units. 
Secondary endpoints include the evaluation of system usability score and proportion of invalid tests 
for POC devices. The mean and 95% confidence interval will be estimated for these characteristics 
separately for each device. Confidence interval for the proportion of invalid tests will be calculated 
based on Wilson’s score method. 
8.2.2 Safety Analysis 
No safety analysis will be performed as the risks for the participants are considered minimal (see 
section 1.3). 
8.2.3 Other Analyses 
Descriptive statistics tables will be generated to summarize the characteristics of the samples in 
the different populations. The number of samples included and excluded will be reported, and 
among the included samples, information will be broken down by gender, age group, medication 
taken, disease status (pre-existing condition and new diagnosis in KHDC program), BMI, 
smoking/alcohol. Results will be reported either in absolute numbers (e.g. number of subjects in a 
group) or summarized by mean, standard deviation, minimum, median, maximum and quartiles.  
The information may be used for interpretation of the POC test performance. 
8.3 Planned Interim Analyses  
No interim analyses are planned for this study. 
8.3.1 Data Monitoring Committee (DMC) 
There will be no data monitoring committee. Interim data monitoring will be conducted by FIND. 

 
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8.4 Sample Size Determination 
Available data from an external evaluation study of the performance of the Tascom and Jana Care 
assays, showed Pearson correlation coefficients greater than 0.98 for all markers compared to the 
reference laboratory standard [xxx = reference corresponding to Excel table]. The precision 
estimated as the standard deviation of difference of measurements compared to reference divided 
by the mean concentration (%CV) was in range of 1.8-4.1% for SimplexTas 101 and 1.9-3.9% for 
Jana Care, depending on the marker and its concentration. 
 
TABLE 5: INVESTIGATIONAL PRODUCTS PERFORMANCE CLAIMS AS PER IFU 
Assay 
ρ, Pearson correlation 
Precision (%CV) 
at low and high concentrations 
SimplexTAS 101 Glucose 
0.998 
Low = 2.5% 
High = 1.8% 
SimplexTAS 101 HbA1c 
0.995 
Low = 3.6% 
High = 2.4% 
SimplexTAS 101 Total 
cholesterol 
0.996 
Low = 4.1% 
High = 2.5% 
SimplexTAS 101 Creatinine 
0.997 
Low = 4.1% 
High = 2.4% 
Jana Care Glucose 
0.995 
Low = 2.7% 
High = 2.4% 
Jana Care HbA1C 
0.99 
Low = 1.9% 
High = 2.5% 
Jana Care cholesterol 
0.981 
Low = 3.9% 
High = 3.7% 
Considering the possibility of a lower performance of POC device outside of the manufacturer’s 
laboratories, the Pearson’s correlation coefficient and precision were conservatively assumed to 
be 0.9 and 5%, respectively. Based on this assumption, at least 337 samples (for each marker and 
device) will be needed to detect statistically significant r1.5% fixed bias of POC measurements 
compared to the reference (using two-tailed t-test with 80% power and 5% significance level). 
To improve the precision of the test, the number of samples per marker analyzed in this study was 
increased to 400 per device, recruited at two trial sites. Assuming that the expected Pearson’s 
correlation coefficient (ρ) between POC and reference measurements is 90%, 95% or 99%, the 
proposed sample size will allow to estimate ρ with the 95% confidence interval of 88–91.7%, 93.9–
95.9% and 98.8–99.2%, respectively. 
8.5 Statistical software 
The analysis will be performed using the R statistical language, version 3.6 or higher, and Microsoft 
Excel (for the initial inspection of the data) version 16.16 or higher. 

 
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9 Regulatory and Ethical Considerations   
Ethical conduct of the study; i.e. that the study will be conducted in accordance with the Protocol, 
all ICH and GCP regulations governing clinical study conduct; ethical principles that have their 
origin in the Declaration of Helsinki, and all applicable local laws and regulations. 
Informed Consent; i.e. that the Investigator or his/her representative will explain the nature of the 
study to the subject, and answer all questions regarding this study, prior to obtaining Informed 
Consent 
Participant confidentiality; i.e. that the Investigators must ensure that the subject’s anonymity will 
be maintained. 
FIND should ensure that the Investigator(s)/institution(s) will permit study-related monitoring, 
audits, IEC/IRB review, and regulatory inspection(s), providing direct access to source 
data/documents. This is mentioned in the Statement of Investigator above.  
9.1 Regulatory and Ethics Approvals 
This study will be conducted in accordance with the protocol and with the following: 
x 
Consensus ethical principles derived from international guidelines including the Declaration 
of Helsinki  
x 
Applicable Good Clinical Practice Guidelines: ICH GCP E6 (R2) 
x 
Applicable laws and regulations 
The protocol, protocol amendments, ICF and other relevant documents (e.g. advertisements) must 
be submitted to an IRB/IEC by the investigator and reviewed and approved by the IRB/IEC before 
the study is initiated. A copy of the IRB/IEC approval letter will be filed in the investigator site file.  
FIND-approved versions of an amended study protocol must be signed by the Investigator(s). Any 
substantial amendments to the protocol will require IRB/IEC approval before implementation of 
changes made to the study design, except for changes necessary to eliminate an immediate hazard 
to study participants. Protocol amendments restricted to clerical edits only will be provided to the 
study sites and submitted to the IRB/IEC for informational purposes.    
The investigator will be responsible for the following: 
x 
Providing written summaries of the status of the study to the IRB/IEC annually or more 
frequently in accordance with the requirements, policies, and procedures established by the 
IRB/IEC 
x 
Notifying the IRB/IEC of SAEs or other significant safety findings as required by IRB/IEC 
procedures 
x 
Providing oversight of the conduct of the Study at the site and adherence to requirements 
of ICH guidelines, the IRB/IEC, the WHO Good Clinical Laboratory Practice (GCLP), and 
with applicable national regulations. 

 
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9.2 Financial Disclosure 
Investigators and sub-investigators will provide FIND with sufficient, accurate financial information 
as requested to allow FIND to submit complete and accurate financial certification or disclosure 
statements to the appropriate regulatory authorities.  
9.3 Informed Consent Process 
The investigator or his/her representative will explain the nature of the study to the participant or 
his/her legally authorized representative in a language understandable to him/her and answer all 
questions about the study.  
Participants must be informed that their participation is voluntary. Participants or their legally 
authorized representative will be required to sign and date a statement of informed consent that 
meets the requirements of local regulations, ICH guidelines and the IRB/IEC or study centre.  
There must be evidence that written informed consent was obtained before the participant was 
enrolled in the study, and ample time was given to participant to consent. The date the written 
consent was obtained (as well as the time, ideally) must be recorded. The authorised person 
obtaining the informed consent must also sign and date the ICF. 
Illiterate participants must provide a thumbprint on the ICF and the ICF signed and dated by an 
impartial witness. 
Participants must be re-consented to the most current version of the ICF(s) during their participation 
in the study. A copy of the ICF(s) will be given to the participant or the participant’s legally 
authorized representative.  
A participant who is rescreened is not required to sign another ICF if the rescreening occurs within 
(3) days from the previous ICF signature date. 
9.4 Data Protection 
Participants will be assigned a unique study identifier generated by FIND once enrolled in the study 
(see example in Figure 3). During the screening process, a separate unique screening identifier 
will be assigned to each participant. The purpose of the screening identifier is to link participants 
who did not pass the screening process to entries in the enrolment log. Only participants who pass 
the screening process (including meeting haemoglobin enrolment criteria) will be assigned a unique 
study identifier.  
Any participant records or datasets that are transferred to FIND will contain the identifier only; 
participant names or any information, which would make the participant identifiable, will not be 
transferred.  
The participant will be informed that his/her personal study-related data will be used by FIND in 
accordance with local data protection law. The level of disclosure must also be explained to the 
participant.  
The participant will be informed that his/her medical records may be examined by quality assurance 
(QA) auditors or other authorized personnel appointed by FIND, by appropriate IRB/IEC members, 
and by inspectors from regulatory authorities. 

 
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FIGURE 3: PARTICIPANT ID EXAMPLE 
10 Data Handling and Record Keeping 
FIND is responsible for the data management of this study including quality control (QC) checks of 
the data and assessment of overall protocol compliance. All participant data relating to the study 
will be recorded in source documents and transcribed on to a paper Case Report Form (CRF) by 
study site staff. Data will then be entered from the paper CRF into FIND’s online clinical study 
platform (OpenClinica Enterprise Edition version 4.0). The investigator is responsible for verifying 
that data entries are accurate and correct.  
Records and documents, including signed ICFs, pertaining to the conduct of this study must be 
retained by the investigator for 10 years after study completion unless local regulations or 
institutional policies require a longer retention period. No records may be destroyed during the 
retention period without the written approval of FIND. No records may be transferred to another 
location or party without written notification to FIND.  
10.1 Source Data and Source Documents 
Source documents provide evidence for the existence of the participant and substantiate the 
integrity of the data collected. The investigator/institution should maintain adequate and accurate 
source documents and study records that include all pertinent observations on each of the site’s 
study participants (source data). Source documents are filed at the investigator’s site. 
Source data should be attributable, legible, contemporaneous, original, accurate and complete. 
Changes to source data should be traceable, should not obscure the original entry and should be 
explained if necessary.   
The definition of what constitutes source data can be found in Table 3. 
The investigator must permit study-related monitoring, audits, IRB/IEC review, and regulatory 
agency inspections and provide direct access to participant medical records and source documents 
used for this study. 
Participant data will consist of participant demographics, clinical examination and laboratory test 
results. Information on demographics will be recorded directly into the CRF (source data). Results 
of the clinical examination under the KHDC program will be transcribed from the program or medical 
records (source data) into a study-specific paper CRF. Results from the POC devices and the 
reference analyzers will also be transcribed into study-specific paper CRFs from the 
device/analzyer print-outs/electronical files (source data).   

 
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Any source data directly entered into the paper CRF must be signed and dated by the person who 
generated the data.  
TABLE 3: TYPES OF SOURCE DATA AND CRFS. 
Type of data 
Source data  
(original place of data) 
CRF 
Demographics 
Paper CRF 
Study-specific paper CRF: 
Clinical 
Medical information 
Paper CRF 
Study-specific paper CRF: 
Clinical (same as above) 
Specimen collecting 
time and date 
Paper CRF 
Study-specific paper CRF: 
Specimen collection 
POC test result  
Device print-out or electronic file 
Study-specific paper CRF: 
POC results 
Reference test result 
Device print-out or electronic file 
Study-specific paper CRF: 
Reference results 
System usability score 
Paper CRF 
Study-specific paper CRF: 
SUS 
10.2 Data Management 
Data Management procedures at FIND, including the setup of the database, programming edit and 
range checks and querying, are described in the Data Management Plan.  
Site staff will be responsible for entering their data from a paper CRF into OpenClinica. Detailed 
timelines for data transfer will be provided in the Study Manual. Data will be cleaned of errors by 
FIND throughout the study as it is captured electronically. 
The investigator is responsible for verifying that data entries are accurate and correct. Data entered 
in the OpenClinica database must be consistent with the source documents or the discrepancies 
must be explained.  
The site will be provided with individual password-protected accounts to access OpenClinica, 
following a training session given by FIND. 
OpenClinica provides an audit trail system recording all data entries/changes and queries between 
FIND and the site. Data entry training will be provided by FIND, either on site or remotely sharing 
screen through Skype or any other similar system.  
No information concerning the study or the data generated from the study will be released to any 
unauthorized third party without prior written approval of FIND.  
11 Quality Management  
Quality Management for this study consists of Quality Control activities, training and capacity 
building provided by FIND (or designee) to the investigational sites, as well as the use of Standard 
Operating Procedures, Work Instructions, Tools and Templates. Prior to study start FIND will verify 
that the reference laboratory has adequate quality management procedures in place to ensure 

 
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reliability of test results. This will be verified by reviewing relevant quality management system 
(QMS) documents of the laboratory and verifying evidence of adherence through e.g. availability 
of analyser calibration and control results.  
Training on the protocol, GCP and the use of the POC tests will be provided by FIND. A study 
Manual, which describes all of the sample testing procedures, will be provided by FIND prior to the 
commencement of the study. Training on the EDC system will be provided by FIND Data 
Management prior to first participant enrolment.  
11.1 Quality Control (monitoring) 
Quality control should be applied to each stage of data handling to ensure that all data are reliable 
and have been processed correctly. The investigational site is responsible for performing regular 
quality control checks on the data they generate.  
FIND will perform risk-based monitoring of this study, and associated quality control checks, as 
described in the monitoring plan. Study monitors will perform source data review and source data 
verification to confirm that data entered into the CRF by authorized site personnel are accurate, 
complete, and verifiable from source documents; that the safety and rights of participants are being 
protected; and that the study is being conducted in accordance with the currently approved protocol 
and any other study agreements, ICH GCP, and all applicable regulatory requirements.  
11.2 Quality Assurance (auditing) 
As part of routine quality assurance, FIND or designee may conduct an audit of the investigational 
site.  
11.3 Study and Site Closure 
FIND reserves the right to close the study site or terminate the study at any time for any reason at 
its sole discretion. Investigational sites will be closed upon study completion. A study site is 
considered closed when all required documents and study supplies have been collected or 
destroyed.  
The investigator may initiate study-site closure at any time, provided there is reasonable cause and 
sufficient notice is given in advance of the intended termination. 
Reasons for early closure of a study site by FIND are described in the contractual agreement. 
12 Publication Policy  
Data obtained from participation in this study are considered confidential and may be used to 
support market approval. The investigators must adhere to the non-disclosure requirements set 
forth in the FIND agreement. 
The investigator is obligated to provide FIND or its designee with complete test results and all data 
obtained in this study. Only FIND may make information obtained during this study available to 
other investigators and third parties, including regulatory agencies. 

 
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Authorship for scientific publication of the study results will be determined by mutual agreement 
and in line with International Committee of Medical Journal Editors authorship requirements, as 
described in the publication policy section of the contractual agreement.  
13 References 
1. 
Jamison, D.T., Disease Control Priorities, 3rd edition: improving health and reducing 
poverty. Lancet, 2018. 391(10125): p. e11-e14. 
2. 
IHME. Institute for Health Metrics, Global Burden of Disease Compare Viz Hub. 2019  [cited 
2021; Available from: https://vizhub.healthdata.org/gbd-compare/. 
3. 
FIND. Landscape of Point-of-Care Devices for Testing of Cardiometabolic Diseases. 2020  
[cited 
2021 
17-Mar]; 
Available 
from: 
https://www.finddx.org/wp-
content/uploads/2020/02/Landscape-of-poc-devices-for-cardiometabolic-diseases-
28FEB2020.pdf. 
4. 
WHO. Package of Essential Noncommunicable (PEN) Disease Interventions for Primary 
Health Care in Low Resource Settings. 2020  [cited 2021 17-Mar]; Available from: 
https://www.who.int/publications/i/item/who-package-of-essential-noncommunicable-
(pen)-disease-interventions-for-primary-health-care. 
5. 
WHO. The selection and use of essential in vitro diagnostics - TRS 1031. 2021  [cited 2021 
17-Mar]; Available from: https://www.who.int/publications/i/item/9789240019102. 
6. 
Vetter, B., Beran, D., Boulle, P., Chua, A., delaTour, R., Hattingh, L., Perel, P., Roglic, G., 
Sampath, R., Woodman, M., Aebischer-Perone, S., Development of a target product profile 
for a point-of-care cardiometabolic device. BMC Cardiovascular Disorders, 2021. 
Manuscript submitted. 
7. 
Drain, P.K., et al., Diagnostic point-of-care tests in resource-limited settings. Lancet Infect 
Dis, 2014. 14(3): p. 239-49. 
8. 
Hirst, J.A., et al., Performance of point-of-care HbA1c test devices: implications for use in 
clinical practice – a systematic review and meta-analysis. Clin Chem Lab Med, 2017. 1(2): 
p. 167-180. 
9. 
Group, W.C.R.C.W., World Health Organization cardiovascular disease risk charts: revised 
models to estimate risk in 21 global regions. Lancet Glob Health, 2019. 7(10): p. e1332-
e1345. 
10. 
WHO. Non Communicable Disease Factors: STEPS Survey Nepal 2013. 2013  [cited 2021 
17-Mar]; 
Available 
from: 
https://www.who.int/ncds/surveillance/steps/2012-
13_Nepal_STEPS_Report.pdf. 
11. 
WHO, Use of Glycated Haemoglobin (HbA1c) in the Diagnosis of Diabetes Mellitus 2011, 
World Health Organization: Geneva. 
14 Appendices 
Appendix 1:  Safety Definitions and Reporting 
Adverse Event (AE) Definition 
x 
An AE is any unfavourable and unintended sign (including abnormal laboratory finding), 
symptom or disease temporally associated with the use of an investigational product, whether 
or not related to the investigational product.   

 
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The Protocol Author is responsible for verifying safety reporting requirements. SAE Reporting to FIND may 
differ than described below. If that is the case, describe the procedure in detail. 
SAE Reporting to FIND  
x 
The SAE Report must be sent to the FIND Head of Program and Study Manager via e-mail, 
marked High Priority, with a follow up call to ensure receipt.  
x 
Initial notification via telephone does not replace the need for the investigator to complete 
and sign the SAE Report within the designated reporting time frames. 
x 
Contacts for SAE reporting can be found on the front of the protocol. 
Serious Adverse Event (SAE) Definition: 
a. Results in death 
b. Is life-threatening 
The term 'life-threatening' in the definition of 'serious' refers to an event in which the participant was 
at risk of death at the time of the event. It does not refer to an event, which hypothetically might have 
caused death, if it were more severe. 
c. Requires inpatient hospitalization or prolongation of existing hospitalization 
In general, hospitalization signifies that the participant has been detained (usually involving at least 
an overnight stay) at the hospital or emergency ward for observation and/or treatment that would not 
have been appropriate in the physician’s office or outpatient setting. Complications that occur during 
hospitalization are AEs. If a complication prolongs hospitalization or fulfils any other serious criteria, 
the event is serious. When in doubt as to whether “hospitalization” occurred or was necessary, the 
AE should be considered serious. 
Hospitalization for elective treatment of a pre-existing condition that did not worsen from baseline is 
not considered an AE. 
d. Results in persistent disability/incapacity 
x 
The term disability means a substantial disruption of a person’s ability to conduct normal life 
functions. 
x 
This definition is not intended to include experiences of relatively minor medical significance 
such as uncomplicated headache, nausea, vomiting, diarrhoea, influenza, and accidental 
trauma (e.g., sprained ankle) which may interfere with or prevent everyday life functions but 
do not constitute a substantial disruption. 
e. Is a congenital anomaly/birth defect 
f. 
Other situations: 
x 
Medical or scientific judgment should be exercised in deciding whether SAE reporting is 
appropriate in other situations such as important medical events that may not be immediately 
life-threatening or result in death or hospitalization but may jeopardize the participant or may 
require medical or surgical intervention to prevent one of the other outcomes listed in the 
above definition. These events should usually be considered serious. 
Examples of such events include intensive treatment in an emergency room or at home for 
allergic bronchospasm or convulsions that do not result in hospitalization, or development of 
drug dependency or drug abuse. 

 
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Appendix 2:  Incident Definition and Reporting 
Verify with the IVD manufacturer what the procedure will be for reporting incidents to them and describe 
below.  
Medical Device/IVD Incident Definition  
x 
A medical device incident is any malfunction or deterioration in the characteristics and/or 
performance of a device or IVD as well as any inadequacy in the labelling or the instructions 
for use which, directly or indirectly, might lead to or might have led to the death of a 
participant/user/other person or to a serious deterioration in his/her state of health. 
x 
Not all incidents lead to death or serious deterioration in health. The non-occurrence of such 
a result might have been due to other fortunate circumstances or to the intervention of health 
care personnel. 
 
It is sufficient that: 
x 
An incident associated with a device happened. 
 
AND 
 
x 
The incident was such that, if it occurred again, might lead to death or a serious deterioration 
in health. 
A serious deterioration in state of health can include any of the following: 
x 
Life-threatening illness 
x 
Permanent impairment of body function or permanent damage to body structure 
x 
Condition necessitating medical or surgical intervention to prevent one of the above  
x 
Foetal distress, foetal death, or any congenital abnormality or birth defects 
 
Medical Device Incident Documenting  
x 
Any medical device incident occurring during the study will be documented in the participant’s 
medical records, in accordance with the investigator’s normal clinical practice, and on the 
appropriate form of the CRF. 
x 
For medical device incidents fulfilling the definition above, complete the SAE Report Form. 
x 
It is very important that the investigator provides his/her assessment of causality (relationship 
to the medical device provided by FIND) and describes any corrective or remedial actions 
taken to prevent recurrence of the incident. 
x 
A remedial action is any action other than routine maintenance or servicing of a medical 
device where such action is necessary to prevent recurrence of an incident. This includes 
any amendment to the device design to prevent recurrence. 
 

 
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Appendix 3: Protocol Amendment Summary Table 
The Protocol Amendment Summary of Changes Table for the current amendment is located directly 
before the Abbreviations section.   
Amendment [v2.0]: 30-MAR-2022 
Overall Rationale for the Amendment 
After the Site Initiation Visit, several technical points had to be revised.  
Section # and 
Name 
Original 
description (V1.0) 
Description of Change (V2.0) 
Brief Rationale 
Institutions/Or
ganizations/Pa
rtners Involved 
in the Study 
Sub PI: Dr Anup 
Ghimire 
Name of Sub-Principal 
Investigator in Nepal Changed.  
Dr. Anup Ghimire was not 
available anymore to follow this 
study and is replaced by Dr. 
Vijay Khanal & Dr. Sagar 
Poudel.  
4.3 
Minimization of 
Error and Bias 
No mention about 
risk mitigation on 
venous blood 
collection and 
centrifugation 
The sentence “The risk of 
procedural errors regarding the 
venous blood collection and the 
centrifugation are minimized 
since these procedures are 
undertaken by study personnel 
who perform phlebotomy and 
centrifugation as part of their 
daily routine. Further to this, 
they receive dedicated training 
on any study-specific 
procedures such as preparation 
of aliquots. With respect to 
mitigating of any sample mix-up 
the unique study ID label is used 
on all tubes (as well aliquots 
tubes). There is little risk for 
contamination as appropriate 
equipment is used, such as 
single-use pipette tips for aliquot 
preparation. All waste is 
discarded in biohazard waste 
bags.” Was added 
Additional information for risk 
mitigation on this procedure was 
required.  
6. Study 
Procedure; 
Study Flow 
On the Study flow, 
the Glucose was 
mentioned as 3ml of 
venous Whole Blood 
to be collected.  
The study flow graph was 
changed according to the new 
volumes collected 
2ml instead of 3ml venous blood 
collection for Glucose and the 
vials names had to be changed 
on the graph as well.  
6.1 Participant 
enrolment 
“Ethnicity” was 
mentioned as an 
information 
requested to our 
participants.  
“Ethnicity” was deleted 
This is not an information we 
request from our participants, 
since all of them are Nepali.  

 
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6.2 Specimen 
Collection, 
Handling, 
Transport and 
Storage 
7 drops of blood 
(was mentioned as of 
0.2 ml), and 10 ml in 
total.  
7 drops of blood is not 0.2ml, but 
0.35 ml (counting 1 drop as 
0.05ml).  
9ml of venous whole blood 
instead of 10ml 
Due to a miscalculation, 7 drops 
of blood is not 0.2ml, but 0.35 ml 
(counting 1 drop as 0.05ml). And 
9ml of venous whole blood 
instead of 10ml, even if initially 
we were concerned that we 
would not have enough plasma 
for making aliquots, we saw that 
2ml is sufficient volume.   
6.2.1 Capillary 
blood sample 
collection 
The sentence “All 
sample cartridges 
will be pre-labelled 
manually with the 
study-specific 
participant number.” 
Was mentioned 
The sentence “All sample 
cartridges will be pre-labelled 
manually with the study-specific 
participant number. “ was 
deleted 
Refer to Protocol Deviation.  
The sample cartridges are not 
pre-labelled manually with the 
study-specific participant 
number, since there is no need 
to (participant come one after 
the other) and it is already 
entered electronically into the 
POC machine. 
6.2.1 Venous 
blood sample 
collection 
Before the 
temperature rate was 
written as “4°C” 
Instead of 4°C we added “2-8°C” 
This is the usual range of a 
fridge to operate.  
6.2.2 Venous 
blood sample 
collection 
Before the vacutainer 
mentioned on the 
protocol for Glucose 
collection was 
NaF/Na2EDTA and 
for HbA1c K3EDTA. 
The vacutainers to be used for 
venous blood collection of 
Glucose are NaF/K-Oxalate and 
not NaF/Na2EDTA. And for 
HbA1c, it is K2EDTA and not 
K3EDTA. 
This applies to all samples in the 
trial, the change was made prior 
the start of recruitment. 
According to the package inserts 
these vacutainer are compatible 
for Roche Cobas.  
Refer to protocol deviation. 
6.2.2 Venous 
blood sample 
collection 
The volume of blood 
collection for 
Glucose was 
mentioned as 3ml.  
The volume of blood collection 
for Glucose in NaF/K-Oxalate is 
not 3ml but 2ml instead.  
Initially we were concerned that 
we would not have enough 
plasma for making aliquots, we 
saw that 2ml is sufficient 
volume. This change was made 
prior the start of recruitment.  
Refer to protocol deviation. 
6.2.2 Venous 
blood sample 
collection 
The clotting time was 
initially stated as for 
a maximum of 30 
minutes.  
Change of the clotting time for 
the Serum Total Cholesterol & 
Creatinine Venous blood 
collection. It is not 30 min but 60 
min. 
This is the recommended time 
on BD package inserts.  
6.7 Other 
Tests (Specify) 
Initially it was 
mentioned Hb201+ 
Hb201+ was changed into 
Hb301+ 
Correction of a mistake: The 
HemoCue machine is the 
Hb301+ and not as initially 
written Hb201+ 
Other sections 
Minor formulation 
issues on v1.0 
Minor formulation and re-
phrasing  
Administrative changes for 
clarification purposes