Pivotal Study of a Single-Use, Point-of-Care Molecular Diagnostic Device for the Detection of Neisseria Gonorrhoeae (NG), Trichomonas Vaginalis (TV), and Chlamydia Trachomatis (CT) in Women
Phase: NA
Conditions: Chlamydial Infection, Gonococcal Infection, Trichomoniasis
Sponsor: National Institute of Allergy and Infectious Diseases (NIAID)

REDACTED VERSION 19 NOVEMBER 2021 
 
Pivotal Study of a Single-Use, Point-of-Care Molecular 
Diagnostic Device for the Detection of Neisseria gonorrhoeae 
(NG), Trichomonas vaginalis (TV), and Chlamydia 
trachomatis (CT) in Women 
 
 
DMID Protocol Number: 18-0024 
 
 
Sponsored by: 
Division of Microbiology and Infectious Diseases 
National Institute of Allergy and Infectious Diseases 
National Institutes of Health 
 
 
DMID Funding Mechanism: 
Contract Number: HHSN272201300014I 
 
 
Principal Investigator: Sheldon Morris, MD, MPH 
 
 
Co-Principal Investigator: Jeffrey D. Klausner, MD, MPH 
 
 
DMID Clinical Project Manager: Peter Wolff, MHA 
 
 
Version Number: 1.0 
 
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Statement of Compliance 
 
The study will be carried out in accordance with Good Clinical Practice (GCP) as required by the 
following: 
• 
United States Code of Federal Regulations (CFR) 45 CFR Part 46: Protection of Human 
Subjects 
• 
Food and Drug Administration (FDA) Regulations, as applicable: 21 CFR Part 50 (Protection 
of Human Subjects), 21 CFR Part 54 (Financial Disclosure by Clinical Investigators), 21 
CFR Part 56 (Institutional Review Boards), 21 CFR Part 11  
• 
International Conference on Harmonisation: Good Clinical Practice (ICH E6); 62 Federal 
Register 25691 (1997); and future revisions 
• 
Belmont Report: Ethical Principles and Guidelines for the Protection of Human Subjects of 
Research, Report of the National Commission for the Protection of Human Subjects of 
Biomedical and Behavioral Research 
• 
National Institutes of Health (NIH) Office of Extramural Research, Research Involving 
Human Subjects, as applicable 
• 
National Institute of Allergy and Infectious Diseases (NIAID) Clinical Terms of Award, as 
applicable 
• 
Applicable Federal, State, and Local Regulations and Guidance 
 
The study is a nonsignificant risk device study and must comply with the Exempted 
Investigational Device Exemption (IDE) requirements under 21 CFR §812.2 (c). 
All key personnel (all individuals responsible for the design and conduct of this study) have 
completed Human Subjects Protections Training. 

 
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Signature Page 
 
The signature below constitutes the approval of this protocol and the attachments, and provides 
the necessary assurances that this trial will be conducted according to all stipulations of the 
protocol, including all statements regarding confidentiality, and according to local legal and 
regulatory requirements and applicable US federal regulations and ICH guidelines. 
 
Site Investigator:_______________________________________ 
 
 
Signed: 
 
Date: 
 
 
Name/Title 
 
 
 
 

 
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Table of Contents 
 
 
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1 
Key Roles ........................................................................................................................... 10 
2 
Background Information and Scientific Rationale .............................................................. 11 
2.1 
Background Information ......................................................................................... 11 
2.1.1 
Description of the Click Diagnostics Sexual Health Test System ............... 12 
2.1.2 
Reference Method ...................................................................................... 13 
2.2 
Scientific Rationale ................................................................................................. 15 
3 
Hypothesis, Objectives, and Outcome Measures .............................................................. 16 
3.1 
Hypothesis .............................................................................................................. 16 
3.2 
Study Objectives .................................................................................................... 16 
3.2.1 
Primary Objective ....................................................................................... 16 
3.2.2 
Secondary Objectives ................................................................................. 16 
3.3 
Study Endpoints and Outcome Measures .............................................................. 16 
3.3.1 
Primary Endpoint ........................................................................................ 16 
3.3.2 
Secondary Endpoints ................................................................................. 17 
3.3.3 
Exploratory Endpoints ................................................................................ 17 
3.3.4 
Primary Outcome Measures ....................................................................... 17 
3.3.5 
Secondary Outcome Measures .................................................................. 17 
3.3.6 
Exploratory Outcome Measures ................................................................. 18 
4 
Study Design ...................................................................................................................... 19 
5 
Study Population, Enrollment, and Discontinuation ........................................................... 20 
5.1 
Selection of the Study Population .......................................................................... 20 
5.1.1 
Minimum information required for each subject .......................................... 20 
5.1.2 
Symptomatic and asymptomatic subject status .......................................... 20 
5.2 
Inclusion Criteria ..................................................................................................... 20 
5.3 
Exclusion Criteria ................................................................................................... 21 
5.4 
Eligibility Criteria for Banked Specimens Obtained from Known Positive NG 
Subjects .................................................................................................................. 21 
5.5 
Subject Recruitment, Screening, and Enrollment ................................................... 21 
5.6 
Randomization ....................................................................................................... 22 
5.7 
Subject Discontinuation .......................................................................................... 22 
6 
Study Procedures/Evaluations ........................................................................................... 23 
6.1 
Site Selection and IRB Approval ............................................................................ 23 
6.2 
Training .................................................................................................................. 23 
6.3 
Visit 1: Eligibility, Enrollment, and Vaginal Swab Collection and Testing ............... 23 
6.3.1 
Study Procedures for Symptomatic and Asymptomatic Subjects ............... 24 
6.4 
Controls .................................................................................................................. 25 
6.5 
Selection of Study Operators at CLIA-Waived Sites .............................................. 25 
6.6 
Click Diagnostics Sexual Health Test ..................................................................... 26 
6.7 
Click Device Testing ............................................................................................... 26 

 
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6.7.1 
Device Accountability ................................................................................. 26 
6.8 
Study Procedures for Click Device Testing of Banked Specimens Collected From 
Known NG Positive Subjects .................................................................................. 27 
6.9 
Duplicate Subject Enrollment ................................................................................. 27 
6.10 
Laboratory Evaluations for Comparator Methods ................................................... 27 
6.10.1 Laboratory Evaluations/Assays .................................................................. 27 
6.10.2 Specimen Collection, Preparation, Handling .............................................. 27 
6.10.3 Instructions for Specimen Storage and Shipping........................................ 27 
6.10.4 Instructions for Comparator Testing ........................................................... 27 
7 
Statistical Considerations ................................................................................................... 28 
7.1 
Study Hypothesis ................................................................................................... 28 
7.2 
Sample Size Considerations .................................................................................. 28 
7.3 
Planned Interim Reports ......................................................................................... 31 
7.3.1 
Ongoing Investigative Product Performance Tracking ............................... 32 
7.4 
Analysis Plan .......................................................................................................... 33 
7.4.1 
Analysis Populations .................................................................................. 33 
7.4.2 
Baseline Characteristics and Subject Disposition ...................................... 33 
7.4.3 
Primary and Secondary Analyses .............................................................. 34 
7.4.4 
Exploratory, Ancillary, and Other Analyses ................................................ 34 
8 
Assessment of Safety ........................................................................................................ 36 
8.1 
Risks/Benefits and Adverse Events Reporting ....................................................... 36 
8.2 
Reporting for Studies .............................................................................................. 37 
9 
Clinical Monitoring .............................................................................................................. 38 
9.1 
Site Monitoring Plan ............................................................................................... 38 
10 
Data Handling and Record Keeping ................................................................................... 39 
10.1 
Data Management Responsibilities ........................................................................ 39 
10.2 
Types of Data ......................................................................................................... 39 
10.3 
Timing/Reports ....................................................................................................... 40 
10.4 
Study Records Retention ....................................................................................... 40 
10.5 
Protocol Deviations ................................................................................................ 40 
11 
Subject Confidentiality ........................................................................................................ 41 
11.1 
Future Use of Stored Specimens ........................................................................... 42 
12 
Quality Control and Quality Assurance .............................................................................. 43 
13 
Ethics/protection of human subjects .................................................................................. 44 
13.1 
Ethical Standard ..................................................................................................... 44 
13.2 
Institutional Review Board ...................................................................................... 44 
13.3 
Informed Consent Process ..................................................................................... 44 
13.3.1 Informed Consent/Assent Process (in Case of a Minor or Others Unable to 
Consent for Themselves) ........................................................................... 45 

 
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13.4 
Exclusion of Women, Minorities, and Children ....................................................... 46 
14 
Publication Policy ............................................................................................................... 47 
15 
Literature References ......................................................................................................... 48 
APPENDIX A: SCHEDULE OF EVENTS ................................................................................... 50 

 
 
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List of Abbreviations 
 
AE 
Adverse Event 
CDC 
CFR 
Centers for Disease Control and Prevention 
Code of Federal Regulations 
CIOMS 
Council for International Organizations of Medical Sciences 
CLIA 
CRF 
Clinical Laboratory Improvement Amendments 
Case Report Form 
CT 
DHHS 
DMID 
 
Chlamydia trachomatis 
U.S. Department of Health and Human Services  
Division of Microbiology and Infectious Diseases, NIAID, NIH, 
DHHS 
FDA 
FWA 
U.S. Food and Drug Administration 
Federalwide Assurance 
GCP 
Good Clinical Practice 
HCP 
ICF 
Health Care Provider 
Informed Consent Form 
ICH 
International Conference on Harmonisation 
IDE 
IEC 
Investigational Device Exemption 
Independent or Institutional Ethics Committee 
IRB 
Institutional Review Board 
MOP 
N 
Manual of Procedures 
Number (typically refers to subjects) 
NAAT 
NG 
NIAID 
Nucleic Acid Amplification Test 
Neisseria gonorrhoeae 
National Institute of Allergy and Infectious Diseases, NIH, 
DHHS 
NIH 
National Institutes of Health 
OCRA 
Office of Clinical Research Affairs, DMID, NIAID, NIH, DHHS 
OHRP 
Office for Human Research Protections 
ORA 
Office of Regulatory Affairs, DMID, NIAID, NIH, DHHS 
PCR 
PHI 
PI 
Polymerase Chain Reaction 
Personally Identifiable Information 
Principal Investigator 
PIS 
Patient Infected Status 
POC 
Point-of-care 
PRN 
“As Needed” (Latin: pro re nata) 
SAE 
Serious Adverse Event 
SDCC 
SOC 
SOP 
Statistical and Data Coordinating Center 
Standard of Care 
Standard Operating Procedure 
STI 
TV 
UADE 
Sexually Transmitted Infection 
Trichomonas vaginalis 
Unanticipated Adverse Device Effect 
 
 

 
 
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Protocol Summary 
 
Title: 
Pivotal Study of a Single-Use, Point-of-Care Molecular Diagnostic 
Device for the Detection of Neisseria gonorrhoeae (NG), 
Trichomonas vaginalis (TV), and Chlamydia trachomatis (CT) in 
Women 
 
Population: 
Approximately 1750 female subjects ≥14 years of age in the 
United States.  
 
Number of Sites: 
At least three clinical sites across diverse geographic areas in the 
United States; approximately one-third of sites will have a patient 
population with low prevalence. 
 
Study Duration: 
Approximately 9 months after enrollment of the first subject. 
 
Subject Duration: 
One visit, approximately 60 minutes. 
 
Primary Objective: 
To assess the performance of the Click Diagnostics point-of-care, 
single-use device for the detection of Chlamydia trachomatis (CT), 
Neisseria gonorrhoeae (NG), and Trichomonas vaginalis (TV) in 
self-collected vaginal specimens as compared to Patient Infected 
Status (PIS) determined by three approved comparator assays 
using vaginal specimens collected by a qualified health care 
provider (HCP) as defined by state/local regulatory authorities, in 
support of obtaining FDA clearance and a Clinical Laboratory 
Improvement Amendments (CLIA) waiver. 
 
Estimated Time to  
Complete Enrollment: 
Approximately 9 months or until evaluable sample size targets are 
met. 
 
 
 

 
 
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Schematic of Study Design for Symptomatic and Asymptomatic Subjects 
 
Study Visit 1 
 
 
 
 
 
 
Collect Vaginal Specimens  
1.
Obtain Informed Consent  
2.
Verify Eligibility  
3.
Enroll Subject 
Standard of Care Vaginal Swab, 
if applicable, Treatment per 
Standard of Care 
1 Self-Collected 
Vaginal Swab 
3 HCP-Collected 
Vaginal Swabs* 
Test with  
Click Device ŧ 
Ship remnant vaginal specimen 
to Click ŧ  
Ship vaginal specimens to 
Reference Laboratory for 
Comparator Testing ʈ 
First  
Second 
* Order of HCP-collected vaginal swabs will be randomized according 
to a provided randomization list.  
ʈ All study leftover comparator vaginal liquid media will be kept frozen at 
the Reference Laboratory and may be shipped per DMID instructions. 
 ŧ Used Click devices and leftover Click specimens will be returned to 
Click Diagnostics at intervals defined in the MOP. 
 
Pre-Screen 
Subject 
High- and Low-Prevalence Sites  

 
 
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1 
KEY ROLES 
 
Principal Investigator 
Sheldon Morris, MD, MPH 
Antiviral Research Center  
University of California, San Diego  
220 Dickinson Street, Suite A 
San Diego, CA 92103 
Phone: XXXXX 
Email: XXXXX 
Co-Principal Investigator 
Jeffrey D. Klausner, MD, MPH 
Principal Investigator, STAR STI CTG 
Professor of Medicine and Public Health 
Division of Infectious Diseases  
David Geffen School of Medicine and Jonathan 
and Karin Fielding School of Public Health 
University of California, Los Angeles 
Los Angeles, CA 90095-1772 
Phone: XXXXX 
Email: XXXXX 
DMID Clinical Project Manager 
Peter A. Wolff, MHA 
Division of Microbiology and Infectious 
Diseases/NIAID/NIH 
5601 Fishers Lane 
Bethesda, MD 20892-9825 
Phone: XXXXX 
Email: XXXXX 
 
 

 
 
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2 
BACKGROUND INFORMATION AND SCIENTIFIC RATIONALE 
 
2.1 
Background Information 
 
Sexually transmitted infections (STIs) are persistent and expanding problems. The US 
Centers for Disease Control and Prevention (CDC) estimates that nearly 20 million new 
STIs occur every year and account for almost $16 billion in health care costs. STIs affect 
men and women alike, and are especially common among young people ages 15-24 
years [1]. 
 
Chlamydia (Chlamydia trachomatis, [CT]) and gonorrhea (Neisseria gonorrhoeae, [NG]) 
are the most frequently reported bacterial STIs in the United States. These infections are 
called “silent infections,” as most infected people are asymptomatic and lack abnormal 
physical examination findings. The CDC estimates 2.86 million infections of chlamydia 
and 800,000 gonorrheal infections occur annually in the United States but not more than 
half are reported because most people are asymptomatic and do not seek testing [2,3]. 
Figures from 2015 support this assumption with only 1.5 million cases of chlamydia and 
400,000 cases of gonorrhea reported to the CDC. Almost two-thirds of new chlamydia 
infections occur among people aged 15-24 years, and about 1 in 20 sexually active 
women aged 14-24 years has chlamydia [3]. More than half of new gonorrhea infections 
per year are estimated to occur among people 15-24 years of age. Many cases of 
chlamydia and gonorrhea often co-exist, and continue to go undiagnosed and 
unreported [1,4]. CT can cause urethritis, epididymitis, proctitis, cervicitis, acute 
salpingitis, and pelvic inflammatory disease. CT infections are often asymptomatic in 
both males and females. Children born to CT-infected mothers are at higher risk for 
conjunctivitis and chlamydial pneumonia [5]. Gonococcal infections are more likely to be 
symptomatic and may cause lower and upper genital tract infections, and occasionally 
disseminated infections with gonococcemia with a characteristic rash, tenosynovitis, and 
arthritis [6]. The immunologic response triggered by lower genital tract infections with CT 
and NG leads to significant inflammation of the cervico-endometrial tissue [3]. Due to 
infection and the associated chronic inflammatory response, several important sequelae 
may result from these infections, including pelvic inflammatory disease, ectopic 
pregnancy, and infertility [7-10]. 
 
A third STI, trichomoniasis (Trichomonas vaginalis [TV]), is considered the most 
common curable STI but is not a notifiable disease. In the United States, an estimated 
3.7 million people have the infection, but only about 30% develop symptoms of 
trichomoniasis [11]. Infection is more common in women than in men, and older women 
are more likely than younger women to be infected. Further, trichomoniasis can increase 
the risk of contracting or spreading other STIs [5]. Infection of TV is often asymptomatic 
[12-14]. However, even asymptomatic infections are of public health concern. TV has 
been associated with a more than a 2.7-fold increase in the risk of HIV acquisition [15-
17], a 1.3-fold increase in preterm labor, and a 4.7-fold increase in pelvic inflammatory 
disease [18-19]. The U.S. CDC Sexually Transmitted Disease treatment guidelines 
recommend TV screening for all HIV-infected women when care is initiated, then at least 
annually, as well as diagnostic testing in symptomatic women presenting with vaginal 
discharge [10]. 

 
 
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If left untreated and undiagnosed, CT, NG, and TV can result in serious, permanent 
damage to the reproductive system, pelvic inflammatory disease, ectopic pregnancy, 
and infertility [20].  
 
Diagnostic testing for pathogens of CT, NG, and TV is currently performed at a variety of 
sites: public health, private, and hospital laboratories, physician’s offices/physician office 
laboratories, and some pharmacies. Sample collection is performed at the physician’s 
office. The sample is then transported and processed in a qualified laboratory. After 
testing, the results are transferred by a laboratory information system, or manually 
entered into patient records. Competition in these sectors ranges from very high quality 
testing and large test menus in the laboratories to a very limited menu of low quality 
rapid tests at the physician’s office. While laboratory-based tests for chlamydia and 
gonorrhea have high accuracy, they are far removed from patients and performed on an 
average sample-to-result-to-patient timeline of 3 to 5 days. Trichomoniasis testing is 
conducted using wet mount microscopy in the physician’s office, but has a poor 
sensitivity of 50-70% [21]. Nucleic acid amplification tests (NAATs) for TV have provided 
highly sensitive and specific diagnoses, but require laboratory infrastructure [22-25]. 
 
Agencies such as the CDC understand that NAATs are the most sensitive tests and can 
be performed on easily obtainable specimens such as vaginal swabs (either health care 
provider [HCP]- or patient-collected) or urine [3]. However, at this time, no simple, rapid 
NAAT test exists for physicians to test male and female samples for these three 
pathogens at the same time at the physician’s office. 
 
The amount of time until diagnosis, the lack of symptoms in most people, and the 
subsequent lack of treatment result in preventable disease spread. Thus, there is an 
urgent need for point-of-care STI diagnostic devices that provide rapid and highly 
accurate results. The performance of such diagnostics should be similar to the gold 
standard of NAATs [26,27]. 
 
The hypothesis of this clinical study is that the Click Diagnostics Sexual Health Test 
performs substantially equivalent to the NAAT predicate system. 
 
2.1.1 Description of the Click Diagnostics Sexual Health Test System 
 
The Click device is a single-use, disposable, fully integrated, rapid, compact 
device containing a polymerase chain reaction (PCR)-based NAAT for accurate, 
qualitative detection and differentiation of deoxyribonucleic acid (DNA) from CT, 
NG, and TV organisms. The device is intended to provide a highly accurate, 
simultaneous diagnosis of chlamydia, gonococcal, and trichomonas infections 
that can be used in a variety of environments without the need of a complex 
instrument. The Click device is intended for use with specimens from females 14 
years of age and older. 
 
The Click device integrates sample preparation, PCR amplification, DNA 
detection, and visible result indication into a single disposable test unit. The 
device uses 650 μL of sample, which is introduced into the device using a 
transfer pastette. The Sample Preparation module heat inactivates the sample. 

 
 
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PCR amplification is achieved by combining the inactivated sample with 
lyophilized PCR reagents, and then thermocycling. PCR primers are designed to 
target CT, NG, and TV. The output from PCR flows to the detection module 
where enzymatic processes provide a visually apparent colorimetric signal for 
multiplexed detection of the target pathogens. Amplified pathogenic target (if 
present) is hybridized to specific locations along a flow channel. This flow 
channel is configured to facilitate an enzymatic reaction that utilizes horseradish 
peroxidase (HRP) and a color-producing substrate. This will result in an 
observable color change for a positive reaction. The basic controls strategy relies 
on a positive control spot on the flow cell. If all elements in the Click device are 
functioning properly, the positive control spot will produce color. The positive 
control monitors effective sample prep, PCR amplification, and detection.  
 
The presence of any targeted pathogen in the sample leads to a purple color 
change in the corresponding viewing window of the device. This allows for easy 
visual discrimination of positive and negative test results as well as verification of 
a successful positive control, as directed by the Quick Start Instructions. 
 
2.1.2 Reference Method 
 
The Patient Infected Status (PIS) provides the reference for this study. This 
algorithm incorporates results from three recognized FDA-cleared methods for 
the CT and NG pathogens and from three recognized FDA-cleared methods for 
TV (Table 1). NAAT 1, NAAT 2, and NAAT 3 refer to BD Probetec, Hologic 
Aptima, and BD MAX, respectively. 
 
BD ProbeTec™ CT/GC Qx Amplified DNA Assays – BD Molecular Diagnostics 
BD ProbeTec™ Trichomonas vaginalis Qx Assay – BD Molecular Diagnostics 
APTIMA COMBO 2 Assay – Hologic, Inc. 
APTIMA Trichomonas Vaginalis Assay – Hologic, Inc. 
BD MAX™ CT/GC/TV – BD Molecular Diagnostics 

 
 
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Table 1: PIS Algorithm 
 
 
NAAT1 
Positive 
Negative 
Equivocal (EQ)* 
 
NAAT2 
POS 
EQ 
NEG 
INVALID 
POS 
EQ 
NEG  INVALID 
POS  EQ  
NEG 
INVALID 
NAAT3 
 
 
 
 
 
 
 
 
 
 
 
 
 
POS 
 
NAa 
POS 
POS 
POS 
POS 
IND 
NA 
IND 
POS  IND 
IND 
NA 
NEG 
 
NA 
INDb 
NEG 
IND 
NEG 
NEG 
NA 
NEG 
IND 
IND 
NEG  NA  
UNRc 
 
NA 
IND 
IND 
IND 
IND 
IND 
NA 
IND 
IND 
IND 
IND 
NA 
INVALIDd 
 
NA 
IND 
IND 
IND 
IND 
IND 
NA 
IND 
IND 
IND 
IND 
NA 
 
 
aNA = not applicable and indicates that no tie-breaker test is required because the first 
two reference tests were in agreement. 
bIND = indeterminate and indicates that the true patient status cannot be determined 
based on the results obtained from the three reference tests. 
cUNR = unresolved. 
dFor the BD MAX CT/GC/TV assay (NAAT 3), indeterminate and incomplete test results 
as reported by the instrument should be interpreted as INVALID using this composite 
comparator algorithm.  
 
The diagnostic variable of interest for this study is the binary infected/not infected 
findings for CT, NG, and TV on the Click Diagnostics Sexual Health Test as compared to 
PIS determined by existing comparator tests. The designation of a subject as being 
positive, negative, or indeterminate will be based on the combined results of the 
reference assay tests. A subject will be considered “Positive” where two reference 
assays are positive. A subject will be considered “Negative” where two reference assays 
are negative. If the results of the first two assays are discordant, the PIS will be 
determined by the third assay (tie-breaker). Any other potential combination of results 
will be considered an “Indeterminate” result. The testing methods utilized in the study are 
summarized in Table 2. 

 
 
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Table 2: Organism Type Testing Methods 
 
Organism 
Self-Collected/ 
Click Device 
HCP-Collected/Comparator Methods 
Vaginal Swab 
Vaginal Swab/ 
NAAT 1 
Vaginal Swab/ 
NAAT 2 
Vaginal Swab/ 
NAAT 3 (Tie-
breaker) 
CT 
X 
X 
X 
X 
NG 
X 
X 
X 
X 
TV 
X 
X 
X 
X 
 
2.2 
Scientific Rationale  
 
Click Diagnostics has developed a small, single-use, fully disposable point-of-care 
(POC) diagnostic device that is capable of being used to rapidly and accurately detect 
any form of infectious disease. Through dramatic miniaturization, optimization, and cost 
reductions, Click has reinvented PCR technology. Commercialization of this technology 
would dramatically expand the reach of molecular diagnostic testing, moving it from 
centralized test laboratories and large healthcare facilities to small clinics and outreach 
settings. The device in this clinical study focuses on detecting three of the most common 
sexually transmitted infections in women that cause significant morbidity. 
 
Current laboratory-based STI tests have an average sample-to-result-to-patient timeline 
of 3 to 5 days. This is a significant problem as many patients are lost to follow up before 
the test result is available, and without treatment, patients may continue to spread the 
infections and risk complications such as pelvic inflammatory disease, infertility, and 
perinatal complications. Women could benefit from the Click device because they suffer 
the most serious consequences of STIs, which could be curtailed with single visit POC 
diagnosis and treatment.  
 
The intended use of the Click device is for the qualitative detection and differentiation of 
DNA from CT, NG, and TV to aid in the diagnosis of chlamydial, gonorrheal, and 
trichomonas infections, respectively. The assay is to be used with vaginal swabs 
obtained by self-collection from asymptomatic and symptomatic females age 14 or older.  
 
Note that females younger than 14 years will not be included in the study, as they may 
not be able to follow directions to provide a self-collected vaginal specimen. 
 
 

 
 
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3 
HYPOTHESIS, OBJECTIVES, AND OUTCOME MEASURES 
 
3.1 
Hypothesis 
 
The identification of each organism (Chlamydia trachomatis [CT], Neisseria gonorrhoeae 
[NG], and Trichomonas vaginalis [TV]) in self-collected vaginal swabs by women using 
the Click device will agree with the PIS with a high sensitivity and specificity. 
 
3.2 
Study Objectives 
 
3.2.1 Primary Objective 
 
To assess the performance of the Click device for detection of CT, NG, and TV in 
self-collected vaginal specimens as compared to PIS determined by three 
approved comparator assays using vaginal specimens collected by a qualified 
HCP in support of obtaining FDA clearance and a Clinical Laboratory 
Improvement Amendments (CLIA) Waiver. 
 
3.2.2 Secondary Objectives 
 
3.2.2.1 To assess the performance of the Click device for detection of CT, NG, 
and TV in self-collected vaginal specimens among symptomatic 
subjects as compared to PIS determined by three approved comparator 
assays using vaginal specimens collected by a qualified HCP. 
 
3.2.2.2 To assess the performance of the Click device for detection of CT, NG, 
and TV in self-collected vaginal specimens among asymptomatic 
subjects as compared to PIS determined by three approved comparator 
assays using vaginal specimens collected by a qualified HCP. 
 
3.2.3 Exploratory Objective 
 
To assess the usability by non-laboratorian operators of the Click device for 
detection of CT, NG, and TV with subject self-collected vaginal specimens. 
 
3.3 
Study Endpoints and Outcome Measures 
 
3.3.1 Primary Endpoint 
 
The primary endpoint is the diagnostic accuracy reported as calculated point 
estimates for percent sensitivity and percent specificity along with their 
associated two-sided Wilson Score 95% Confidence Intervals (CIs) of the Click 
device as compared to PIS. 
 

 
 
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3.3.2 Secondary Endpoints 
 
Secondary endpoints include calculated point estimates for percent sensitivity 
and percent specificity along with their associated two-sided Wilson Score 95% 
CIs of the Click device as compared to PIS reported separately for the 
symptomatic and asymptomatic sub-populations within the study cohort. 
 
 
3.3.3 Exploratory Endpoints 
 
3.3.3.1    Ease-of-Use questionnaire results from study operators at CLIA-waived 
sites will be summarized to assess the usability (ease of understanding 
of instructions, operations, and visual interpretation) of the Click device. 
In this guidance, intended study operator (user) refers to a test operator 
with limited or no training or hands-on experience in conducting 
laboratory testing (e.g., medical assistant, nurse, doctor, or an individual 
with no medical training). 
 
3.3.3.2     Prevalence (reported as a percentage) of each infection will be 
reported across the entire study cohort and individually within the 
symptomatic and asymptomatic sub-populations. Sensitivity, 
specificity, and prevalence will be reported for each individual testing 
site. 
 
 
3.3.4 Primary Outcome Measures 
 
3.3.4.1 The i) percent sensitivity and ii) percent specificity of Click device for 
detection of Chlamydia trachomatis in self-collected vaginal specimens 
as compared to PIS using vaginal specimens collected by a qualified 
HCP. 
 
3.3.4.2 The i) percent sensitivity and ii) percent specificity of Click device for 
detection of Neisseria gonorrhoeae in self-collected vaginal specimens 
as compared to PIS using vaginal specimens collected by a qualified 
HCP. 
 
3.3.4.3 The i) percent sensitivity and ii) percent specificity of Click device for 
detection of Trichomonas vaginalis in self-collected vaginal specimens 
as compared to PIS using vaginal specimens collected by a qualified 
HCP. 
 
3.3.5 Secondary Outcome Measures 
 
3.3.5.1 The i) percent sensitivity and ii) percent specificity of Click device using 
self-collected vaginal swabs for detection of Chlamydia 
trachomatis from self-collected vaginal specimens as compared to PIS 

 
 
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using vaginal specimens collected by a qualified HCP among 
symptomatic subjects. 
 
3.3.5.2 The i) percent sensitivity and ii) percent specificity of Click device for 
detection of Neisseria gonorrhoeae in self-collected vaginal specimens 
as compared to PIS using vaginal specimens collected by a qualified 
HCP among symptomatic subjects. 
  
3.3.5.3 The i) percent sensitivity and ii) percent specificity of Click device for 
detection of Trichomonas vaginalis in self-collected vaginal specimens 
as compared to PIS using vaginal specimens collected by a qualified 
HCP among symptomatic subjects. 
 
3.3.5.4 The i) percent sensitivity and ii) percent specificity of Click device for 
detection of Chlamydia trachomatis in self-collected vaginal specimens 
as compared to PIS using vaginal specimens collected by a qualified 
HCP among asymptomatic subjects. 
 
3.3.5.5 The i) percent sensitivity and ii) percent specificity of Click device for 
detection of Neisseria gonorrhoeae in self-collected vaginal specimens 
as compared to PIS using vaginal specimens collected by a qualified 
HCP among asymptomatic subjects. 
  
3.3.5.6 The i) percent sensitivity and ii) percent specificity of Click device for 
detection of Trichomonas vaginalis in self-collected vaginal specimens 
as compared to PIS using vaginal specimens collected by a qualified 
HCP among asymptomatic subjects. 
 
3.3.6 Exploratory Outcome Measures 
3.3.6.1   Usability will be measured by 5-point Likert scale responses, yes/no 
questions, and open-text questions from study operators on questions 
around three domains of interest: i) instructions, ii) operations, and iii) 
visual interpretation for the Click device for detection of Chlamydia 
trachomatis, Neisseria gonorrhoeae, and Trichomonas vaginalis with 
patient self-collected vaginal specimens. 
3.3.6.2   The percentage of subjects with Chlamydia trachomatis, Neisseria 
gonorrhoeae, and Trichomonas vaginalis overall and within the 
symptomatic and asymptomatic sub-populations. 
 

 
 
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4 
STUDY DESIGN 
 
This study is a multi-center study with a minimum of three CLIA-waived intended 
operator sites in the United States; approximately one-third of the total number of sites 
will have a patient population of low NG, CT, or TV prevalence. Low-prevalence sites are 
defined as sites with a prevalence ≤2% for any of the three targets. Sites with a 
prevalence higher than 2% for all of the three targets will be defined as high prevalence 
sites. The study will enroll approximately 1750 female subjects. The study will continue 
enrolling subjects until the targets for positive specimens are met (as outlined below). 
Approximately one-third of the total subjects shall be recruited from low-prevalence sites 
for the infections of interest.  
 
Female subjects seen at the participating sites for any reason will be evaluated for 
enrollment in this study. All subjects will be managed per standard of care as applicable. 
Subjects who meet the inclusion/exclusion criteria will be offered enrollment into the 
study. Subjects who are enrolled in the study will provide clinical and demographic 
information, perform self-collection with a vaginal swab for the Click device, and allow 
the HCP to collect three additional vaginal swabs for the comparator methods. Subjects 
will complete the study in a single visit. The order of the swabs for comparator methods 
will be randomized per subject to account for the possibility that the yield of the swab is 
affected by previous swabs at the same anatomic site. The study specimens shall be 
collected according to institutional procedures as well as the manufacturer’s instructions. 
The self-collected specimen shall be collected according to the Click self-collection 
instructions.  
 
The study will include typical CLIA-waived collection and testing sites. At least nine 
different study operators among the study sites will perform the Click device testing, with 
each study operator testing a minimum of five positive and five negative specimens to 
support CLIA-waived status for CLIA categorization. Selected study operators should 
have non-laboratory background education and must not have certification for moderate 
or high-complexity testing to ensure representation of intended study operators to 
evaluate the use of the Click device.  
 
Recruitment goals for the 510(k) phase of the study are at least 100 specimens positive 
for CT, 100 specimens positive for TV, and 45 specimens positive for NG as determined 
by PIS. Recruitment goals for the CLIA waiver phase of the study are 120 positive 
specimens for CT and TV (prospective), and 45 positive specimens for NG. In order to 
achieve the required precision for sensitivity of NG detection, additional specimens may 
be required. Banked NG positive specimens may also be used and will be provided to 
the testing sites for Click device testing. Thus, the maximum target for the number of 
PIS-positive NG samples is 85. At specified enrollment targets, the sensitivity of the 
Click device with respect to NG will be estimated. If the NG estimate meets the 
requirements for the 510(k) and CLIA waiver phases at any of the interim points and the 
enrollment targets for CT and TV have been met, collection of samples will stop. 
Otherwise, collection of samples will continue. See section 7 for details on the interim 
reviews. At least 30% of total samples must be from sites considered low prevalence. All 
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5 
STUDY POPULATION, ENROLLMENT, AND DISCONTINUATION 
5.1 
Selection of the Study Population 
 
The study population comprises female subjects ≥14 years of age visiting any of the 
participating clinics for any reason, who may be symptomatic or asymptomatic for STIs 
at locations including but not limited to: OB/GYN and primary care offices, as well as 
sexually transmitted disease, teen, public health, and family planning clinics. Any subject 
who meets the inclusion/exclusion criteria is eligible to participate in this study. No 
exemptions are granted on Subject Inclusion and Exclusion Criteria in Division of 
Microbiology and Infectious Diseases (DMID)-sponsored studies. Subject Inclusion and 
Exclusion Criteria must be assessed by a study clinician licensed to make medical 
diagnoses and designated by the Investigator of Record. 
5.1.1 Minimum information required for each subject 
• 
Date of birth 
• 
Sex at birth 
• 
Sexual health and reproductive history within 7 days prior to enrollment 
• 
Recent (within 7 days prior to enrollment) genital tract infections or vaginal 
discharge 
• 
Pregnancy status (self-report or results), if available 
• 
Use of concomitant medications or genital products within 7 days prior to 
enrollment  
5.1.2 Symptomatic and asymptomatic subject status 
• 
Subjects will be classified as symptomatic if they report any of the following 
symptoms within 7 days prior to enrollment:  change in vaginal discharge, 
abnormal bleeding/spotting, lower abdominal pain/pelvic pain, painful 
urination, increased urinary frequency, vaginal irritation such as itching, 
burning and/or soreness, pain or bleeding with sex/intercourse. 
• 
Subjects will be classified as asymptomatic if they do not report any of the 
above symptoms.  
 
5.2 
Inclusion Criteria  
 
Subjects must meet all of the following inclusion criteria in order to be eligible to 
participate in this study: 
 
1. Willing and able to give voluntary written informed consent (or the parent/legal 
guardian will provide parental permission) before any study-related procedure is 
performed. 
2. Female at birth. (Pregnant and breastfeeding women are eligible.) 
3. Age ≥14 years at the time of enrollment. 
4. Able to read and understand the procedural information provided for the study. 

 
 
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5. Able and willing to follow all study procedures, including performing self-collection of 
one vaginal swab and permitting a licensed HCP to collect three additional vaginal 
swabs. 
 
5.3 
Exclusion Criteria 
 
Subjects meeting any of the following criteria at enrollment will be excluded from this 
study: 
 
1. Have a medical condition, serious intercurrent illness, or other circumstance that, in 
the Investigator’s judgment, could jeopardize the subject’s safety, or could interfere 
with study procedures. 
2. Enrollment in this study previously. 
3. Use of antiperspirants and deodorants or the following vaginal products: douches, 
washes, lubricants, vaginal wipes, vaginal moisturizers, or feminine hygiene spray in 
the genital area, within 48 hours prior to enrollment. 
 
5.4 
Eligibility Criteria for Banked Specimens Obtained from Known Positive NG 
Subjects  
Frozen NG banked specimens may be used and will be provided to the testing sites for 
Click testing as per the criteria in section 4. Positive NG-known subjects providing banked 
vaginal specimens should meet the following inclusion and exclusion criteria:  
5.4.1 Inclusion Criteria 
1. Vaginal specimen is from a female age ≥14 years at the time of specimen 
collection. 
2. A minimum of 2.0 mL of frozen sample taken from well-characterized 
specimens collected from known NG subjects not being treated since testing 
positive within the past 4 months. 
3. NG comparator results available. 
4. Vaginal specimen is obtained from a collection wherein the subject 
consented/assented to future unspecified research use of her specimen. 
5.4.2 Exclusion Criteria 
1. Previously enrolled in this study.  
 
5.5 
Subject Recruitment, Screening, and Enrollment 
 
Subjects arriving at the study sites for any reason who may meet the study 
inclusion/exclusion criteria will be evaluated for enrollment in this study. It is each site’s 
responsibility to enroll only subjects who satisfy the inclusion/exclusion criteria and to 
obtain parental/legal guardian permission when required. Sites must adhere to local 

 
 
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policies and regulations that govern enrollment of either minors or pregnant women. 
 
Sites may use any system for recruitment and enrollment that meets the study objectives 
and is IRB-approved. Recruitment can be by word-of-mouth, flyers, advertisement 
online, or any other means, subject to approval by the associated IRB. Each 
participating institution must provide for the review and approval of this protocol and the 
associated informed consent documents and recruitment materials by the IRB. 
 
5.6 
Randomization 
 
Each subject will be randomized to a particular order of HCP swab collection, allocating 
subjects equally to each of the possible swab orders. The list of randomized 
assignments will be prepared by statisticians at the Statistical and Data Coordinating 
Center (SDCC). Each subject’s randomization assignment for the order of swab 
collection will be documented. Details of the randomization process is further specified in 
the Manual of Procedures (MOP). 
 
5.7 
Subject Discontinuation 
 
Subjects are considered enrolled in this study once they meet all inclusion/exclusion 
criteria and sign an informed consent and assent form, as applicable. It is recommended 
that every subject remain in the study until completion of all study procedures; however, 
a subject's participation in the study may be discontinued. Should this occur, the reason 
for discontinuation must be documented in the source documentation. Reasons for 
discontinuation may include, but are not limited to, the following: 
• 
Subject withdrawal: Subject participation in this clinical study is voluntary and the 
subject may discontinue participation at any time without loss of benefit or penalty. 
• 
Investigator termination: Investigator may terminate the subject's participation 
without the subject's consent if the Investigator believes it is medically in the 
subject's best interest. 
• 
Adverse events (AEs): Investigator may terminate the subject's participation for 
reasons of adverse events associated with study procedures. 
• 
Termination of study: Although the study Sponsor has every intention of completing 
the study, the Sponsor reserves the right to terminate the study at any time for 
clinical or administrative reasons. Reasons for termination include, but are not limited 
to, study closure at the discretion of DMID. 
• 
Other: Subject may be terminated without the subject's consent for various other 
reasons including, for example, Sponsor's decision. 
 
 

 
 
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6 
STUDY PROCEDURES/EVALUATIONS 
 
6.1 
Site Selection and IRB Approval 
 
At least three geographically diverse clinical sites will collect vaginal swab specimens for 
the study and perform testing using the Click device. At least one reference laboratory 
will test the specimens obtained by the collection sites with the comparator methods. 
Each clinical site shall be assessed by the Sponsor, or a representative designated by 
the Sponsor prior to the start of the study, to ensure that the proper procedures, 
equipment, and personnel are in place to conduct the clinical study in accordance with 
the approved protocol, and that the site abides by the principles of good clinical practice 
(GCP) and in compliance with the principles enunciated in the Belmont Report. 
 
All study procedures must be performed at an investigational site, under the direction of 
a principal investigator (PI) or designee, and at which this protocol has been approved 
by an IRB or IEC. Any amendments to the protocol or consent materials must also be 
approved before they are placed into use. No subject’s personally identifiable 
information (PII) will be provided to the Sponsor. Additional sites may be included to 
meet sample size and testing requirements. 
 
6.2 
Training  
 
Site personnel will be trained prior to performing any study procedures. All investigators, 
co-investigators, and site personnel involved in the study will be required to attend a 
training session, which may be conducted at a site initiation visit (SIV) by Sponsor 
personnel or by an agent of the Sponsor. 
 
Training includes the protocol, case report form (CRF) completion, study personnel 
responsibilities, specimen documentation, data recording, and reporting. All investigators 
or study personnel who are trained will sign a training log. No investigator or study 
personnel will perform any study-related procedures prior to completion and 
documentation of required training. 
 
Study operators of typical CLIA-waived testing sites will receive no additional instructions 
(e.g., written or verbal training, coaching, or prompting) beyond providing them with the 
Click Quick Start Instructions. Operators will not know the SOC results of the subject’s 
specimens. Operators will be instructed not to discuss the test with other operators or 
otherwise coach or observe each other. Study operators will also be instructed not to 
discuss the test with clinic staff. 
 
6.3 
Visit 1: Eligibility, Enrollment, and Vaginal Swab Collection and Testing  
 
The investigator or designee will assess potential subjects and ascertain suitability to 
qualify for the study based on the inclusion and exclusion criteria. The potential subject 
will be fully informed of the study design and procedures. If the subject is interested in 
participating, written informed consent from the adult subject or from the parent/legal 
guardian as well as assent from a minor will be obtained as applicable. After the 

 
 
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inclusion and exclusion criteria are satisfied and informed consent (or assent) has been 
provided, subjects will be considered to be enrolled into the study. All subjects meeting 
the eligibility criteria shall be included, without further selection, until the required sample 
sizes are achieved. A subject can be enrolled only once in the study. Each clinical site is 
required to keep track of potential subject screening and enrollment using a Screening 
and Enrollment Log. All subjects who complete the informed consent process will be 
assigned a unique subject ID number from the Screening and Enrollment Log that will be 
used to identify the specimens during the study. The duration of the study for each 
eligible and enrolled subject will be one visit, which will last about 60 minutes. Study 
enrollment is expected to be completed in approximately 9 months or until evaluable 
sample size targets are met. The following will be performed for subjects who give 
informed consent: 
 
6.3.1 Study Procedures for Symptomatic and Asymptomatic Subjects  
 
1. Following informed consent, collect subject demographic and complete 
relevant sections of the CRF. 
2. Determine eligibility and subject enrollment.  
3. Collect sexual health and reproductive history.  
4. Collect subject-reported symptoms that occurred within 7 days prior to 
enrollment. 
5. Collect and review any medications or supplements taken within 7 days prior 
to enrollment. 
6. Collect all genital products (including deodorant or antiperspirant) used within 
the last 7 days. 
7. If the clinic has a rule regarding SOC specimen collection, then the site may 
abide by that rule. 
8. Provide subject with the Click Self-Collection Instruction Sheet, self-collection 
materials, and answer any questions the subject may have. 
9. Subject will perform one (1) self-collection of a single vaginal swab. The 
specimen will be tested on the Click device. The self-collection will be 
performed first in a private setting; the subject will collect the vaginal swabs 
according to the Click Self-Collection Instructions. The subject will place the 
self-collected vaginal swab in its own swab transport tube following collection. 
a. NOTE: The self-collected vaginal swab will be tested by study operators. 
b. NOTE: All used Click devices will be shipped to Click Diagnostics at 
intervals defined in the MOP. 
10. HCP will perform three (3) vaginal swab collections for comparator devices 
according to the order generated from the randomization assignment. 
a.  NOTE: Specimens should be taken without the use of a speculum. Using 
a speculum to collect specimens will not be considered a protocol 
deviation; however, it must be recorded on the CRF, along with the name 
of the lubricant, if applicable.  
11. Record any adverse events on the CRF. 

 
 
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12. Study operators and HCPs will process collected swabs in the collection 
media as appropriate. Click specimen must be tested on the Click device 
within two (2) hours of collection. The three (3) vaginal specimens for 
comparator tests will be processed and prepared for shipment/transport to a 
reference laboratory. 
13. Study operators will test the specimens according to the Quick Start 
Instructions. The study operator will take a photograph of the Click device 
upon completion of test (camera or equivalent) and record results on the 
appropriate CRF.  
14. Click specimens shall be stored frozen at -20⁰C or below after testing is 
complete. Leftover self-collected specimens will be shipped to Click 
Diagnostics at intervals defined in the MOP. 
15. HCP-collected vaginal swabs will be collected, transported, and tested 
according to the manufacturer’s instructions at a reference laboratory 
designated by the Sponsor. All vaginal swab specimens shall be stored 
according to the MOP. 
16. The remaining HCP-collected vaginal liquid media will be stored according to 
the MOP at the reference laboratory once all testing is performed. The 
disposition of those remaining HCP-collected vaginal liquid media samples 
may be shipped per DMID instructions. 
 
6.4 
Controls 
 
One external positive control (positive for all infections) and one negative control 
(negative for all infections) will be run at each investigational site each month of testing 
and with each new shipment or lot of the Click device to monitor the performance of the 
Click device, or to qualify a new study operator. The external controls for the comparator 
testing will be assayed in accordance with the laboratories’ standard operating 
procedures.  
 
The study operator should follow the Click Quick Start Instructions to prepare and test 
the controls, and ensure the controls give a valid result prior to testing subject 
specimens. If any of the controls gives an “ERROR”, “INVALID”, or “INCORRECT” 
(negative control gives a positive result or positive control gives a negative result), as 
defined in the Quick Start Instructions, the failed control shall be retested using a new 
device and a new external control vial. Retests will be labeled according to the MOP. All 
specimens and retest results will be provided to the Sponsor according to the MOP. 
 
If both control results are valid, the study operator shall proceed with testing subject 
specimens. If the retest does not give a valid result, call the Click representative (see 
contact information in the MOP). 
 
6.5 
Selection of Study Operators at CLIA-Waived Sites 
 
Prior to study start, the following information will be collected for each study operator 
participating in the study:  
• 
Education level 
• 
Certification status, if applicable  

 
 
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• 
Employment status at location (full-time, part-time, PRN, etc.) 
• 
Title at location 
• 
Years of employment at location at current title and previous titles, if applicable 
• 
Summary of daily duties at location 
 
All study operators (chosen and not chosen) identified by the PI will be documented on a 
List of Potential Study Operators form. A reason for the study operators not chosen shall 
be provided. 
 
Any new chosen study operators will run a set of controls and document the results on a 
self-training record form. The study operators will receive no help other than using the 
Quick Start Instructions as part of the test system. 
 
At the conclusion of the study, each study operator will complete the Click Ease-of-Use 
Questionnaire containing 5-point Likert Scale questions and yes/no questions designed 
to assess usability of the Click device. 
 
6.6 
Click Diagnostics Sexual Health Test 
 
The Click devices utilized in this study represent R&D manufactured devices. The 
devices will carry the label “For Investigational Use Only. The performance 
characteristics of this product have not been established.”  
 
6.7 
Click Device Testing 
 
The Click device testing will be performed by study operators according to the Quick 
Start Instructions. If the initial Click test result is “INVALID” or “ERROR”, a single retest 
will be performed according to the Quick Start Instructions, provided enough specimen is 
available for retesting. Retest will be labeled according to the MOP. All specimen test 
results and retest results will be provided to DMID according to the MOP. 
 
A valid result (e.g., positive for chlamydia) obtained upon retesting will be compared to 
the PIS result and classified as a true or false result. Specimens that remain unresolved 
after one retest will be recorded as such.  
 
The number and percentage of the Click device test that produce an “INVALID” or 
“ERROR” result will be tallied by the site per Click device overall and reported.  
 
6.7.1 Device Accountability 
 
Click Diagnostics will provide the Click devices. 
 
Each clinical site will be responsible for documenting the receipt, storage, use, 
and disposition of Investigational Use Only devices throughout the study. 
Records must be available for inspection by the DMID monitoring contractors. 
Used devices will be returned to Click per the MOP. The Monitors will not 
physically check the used Click devices. They may be returned prior to 

 
 
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monitoring of the device accountability logs, but must be logged according to the 
MOP. At the discretion of Click, remaining unused study supplies provided by 
Click may be returned at the conclusion of the study. 
6.8 
Study Procedures for Click Device Testing of Banked Specimens Collected 
from Known NG-Positive Subjects  
If additional NG+ samples are needed, Click will provide banked specimens to the 
clinical sites according to the MOP. 
 
6.9 
Duplicate Subject Enrollment 
 
If a subject is accidentally enrolled twice, the first result will be used in the analysis. The 
result from the second enrollment will be excluded from analysis.  
 
6.10 Laboratory Evaluations for Comparator Methods 
 
6.10.1 Laboratory Evaluations/Assays 
 
Specific instructions for specimen preparation, handling, and storage are 
described in the MOP. 
 
6.10.2 Specimen Collection, Preparation, and Handling  
 
Specimens will be collected and handled for comparator testing by HCPs 
according to manufacturer’s instructions/package insert. Handling of all 
specimens will be described in the MOP. 
 
6.10.3 Instructions for Specimen Storage and Shipping 
 
Shipping of clinical vaginal swab specimens for comparator testing will be 
performed according to the manufacturer’s instructions. Shipping and storage of 
all specimens will be described in the MOP.  
 
6.10.4 Instructions for Comparator Testing 
 
Comparator testing will be performed according to the manufacturer’s 
instructions. If the initial comparator test result for any of the three target 
organisms is “INVALID”, “ERROR”, “EQUIVOCAL”, “INDETERMINATE”, or 
“UNRESOLVED”, a single retest will be performed according to the 
manufacturer’s instructions, provided enough specimen is available for retesting. 
Retest will be labeled according to the MOP. All comparator test results and 
retest results will be provided to DMID according to the MOP. 
 
A valid result (e.g., positive for chlamydia) obtained upon retesting will be used to 
determine the PIS result and classified as a true or false result. Specimens that 
remain unresolved after one retest will be recorded as such.  

 
 
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7 
STATISTICAL CONSIDERATIONS 
 
7.1 
Study Hypothesis 
 
This study will assess the ability of the Click device to identify each of the CT, NG, and 
TV organisms. The device’s ability to identify each organism will be measured by its 
sensitivity and specificity compared to the PIS. The use of sensitivity and specificity 
assumes that PIS is the “true” status of each subject and indicates whether each 
organism is truly present or absent. Thus, the primary measures of interest are the 
device’s true positive (correctly identifying the presence of the organism) and true 
negative rates (correctly identifying the absence of the organism). Formal hypothesis 
testing will not be performed; instead, the study is designed to estimate the device’s 
sensitivity and specificity with a certain amount of precision (see next section). 
 
7.2 
Sample Size Considerations 
 
Recruitment goals for the 510(k) phase of the study are at least 100 specimens positive 
for each of CT and TV, and at least 45 specimens positive for NG, as determined by 
PIS. Recruitment goals for the CLIA waiver phase of the study are 120 positive 
specimens for each of CT, TV, and 45 NG. Approximately 585 subjects will be recruited 
from low-prevalence sites (one third of the 1,750) and approximately 1165 subjects will 
be recruited from high prevalence sites. The average expected proportion of samples 
positive via PIS for CT, TV, and NG among subjects enrolled at the high prevalence 
sites are, respectively, 12.4%, 19.5%, and 8.1%. The corresponding estimates for the 
low-prevalence sites are 1.7%, 1.0%, and 1.4%. Based on these prevalence estimates, it 
is expected that the enrollment targets will be met for the three organisms. Thus, the 
study as designed is expected to meet the 510(k) and CLIA waiver recruitment goals for 
all three organisms. If NG prevalence is lower than expected, banked NG+ samples may 
need to be leveraged to meet the recruitment goals for NG. As indeterminate PIS results 
or invalid or failed Click device results are expected for a small number of cases, 
enrollment may extend beyond 1750 to replace these results. The duration of enrollment 
may be extended if the actual prevalence of any of the organisms is lower than 
predicted. 
 
For the estimation of the sensitivity and specificity of the Click device, we assume both 
the sensitivity and specificity is at least 95%. For 510(k) clearance, the study aims to 
demonstrate that sensitivity to each of CT and NG is at least 95%, with a lower bound of 
the two-sided 95% Wilson Score confidence intervals at least 90%, and to demonstrate 
that sensitivity to TV is at least 95%, with a lower bound of the two-sided 95% Wilson 
Score confidence intervals at least 85%. Regarding specificity, the study aims to 
demonstrate specificity to each of CT, TV, and NG is at least 95%, with a lower bound of 
the two-sided 95% Wilson Score confidence intervals at least 90%. For the CLIA waiver, 
the study aims to demonstrate that both the sensitivity and specificity to each of CT, TV, 
and NG is at least 95%, with a lower bound of the two-sided 95% Wilson Score 
confidence intervals at least 89%. 
 

 
 
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To demonstrate this for CT and TV, 95% Wilson Score confidence intervals were 
calculated for a range of sample sizes, number of PIS-positive samples, and 
sensitivity/specificity estimates. Given the uncertainty in the exact number of subjects 
enrolled or PIS-positive samples, the following parameter ranges were explored: total 
sample sizes of 1500 to 2000, 100 to 200 PIS-positive samples, and 
sensitivity/specificity estimates of 95% to 99%. Wilson Score confidence intervals were 
calculated for each combination of sample size, number of PIS-positive samples, and 
sensitivity/specificity. As an example, Table 3 below displays the lower confidence 
bound using a sample size of 1750 and a select subset of the number of PIS-positive 
samples. 
 
Table 3: Lower 95% Wilson Score Confidence Bounds (%) for Various Number of PIS-
Positive Samples and Sensitivity and Specificity Values 
Number 
of PIS-
Positive 
Samples 
Sensitivity (%) 
Specificity (%) 
95 
96 
97 
98 
99 
95 
96 
97 
98 
99 
100 
88.8 
90.2 
91.5 
93.0 
94.6 
93.9 
94.9 
96.1 
97.2 
98.4 
101 
88.9 
90.3 
91.6 
93.1 
94.6 
93.9 
95.0 
96.1 
97.3 
98.4 
102 
89.0 
90.3 
91.7 
93.1 
94.7 
93.9 
95.0 
96.1 
97.3 
98.4 
103 
89.1 
90.4 
91.8 
93.2 
94.7 
93.9 
95.0 
96.1 
97.3 
98.4 
104 
89.2 
90.5 
91.9 
93.3 
94.8 
93.9 
95.0 
96.1 
97.3 
98.4 
105 
89.3 
90.6 
91.9 
93.3 
94.8 
93.9 
95.0 
96.1 
97.3 
98.4 
106 
89.4 
90.7 
92.0 
93.4 
94.8 
93.9 
95.0 
96.1 
97.3 
98.4 
120 
89.5 
91.7 
92.9 
94.1 
95.4 
93.9 
94.9 
96.1 
97.2 
98.4 
121 
89.6 
91.8 
93.0 
94.2 
95.5 
93.9 
94.9 
96.1 
97.2 
98.4 
122 
89.7 
91.9 
93.0 
94.2 
95.5 
93.9 
94.9 
96.1 
97.2 
98.4 
123 
89.8 
91.9 
93.1 
94.3 
95.5 
93.9 
94.9 
96.1 
97.2 
98.4 
124 
89.8 
92.0 
93.1 
94.3 
95.6 
93.9 
94.9 
96.1 
97.2 
98.4 
125 
89.9 
91.0 
93.2 
94.4 
95.6 
93.8 
94.9 
96.1 
97.2 
98.4 
126 
90.0 
91.0 
93.2 
94.4 
95.6 
93.8 
95.0 
96.1 
97.2 
98.4 
 

 
 
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Over the entire ranges of parameter values explored, the lower bound of the specificity 
confidence interval never fell below 93.6%. The lower bound of the sensitivity confidence 
intervals never fell below 88.8% and was greater than or equal to 89% for all 
combinations of parameter values except for the following scenario: 
• 
Sample Size = Any, Number of PIS-positive samples = 100 or 101, Sensitivity = 95% 
 
The lower bound of the sensitivity confidence intervals was greater than or equal to 90% 
for all combinations of parameter values except for the following scenarios: 
• 
Sample Size = Any, Number of PIS-positive samples = 100 to 112, Sensitivity = 95% 
• 
Sample Size = Any, Number of PIS-positive samples = 120 to 126, Sensitivity = 95% 
 
Thus, apart from a few scenarios, assuming the sensitivity/specificity of the Click device 
is at least 95%, the study as planned should be able to meet the confidence interval 
estimate requirements for 510(k) clearance and CLIA waiver for CT and TV. 
 
For NG, the minimum number of PIS-positive samples required for the 510(k) and CLIA 
Waiver reports is 45. The planned maximum sample size for NG-positive samples is 85.  
Due to the small 510(k) and CLIA Waiver enrollment targets for NG and the difficulty in 
recruiting NG-positive subjects, reviews of the sensitivity of the Click device with regard 
to NG detection will occur at specified enrollment targets to ensure adequate precision of 
the estimate is achieved while allowing for the collection of samples to stop early if 
further NG sample collection is not necessary and the enrollment targets for CT and TV 
have already been met.   
 
The first enrollment target at which sensitivity will be estimated is 45 PIS-positive NG 
samples. If the 510(k) and CLIA Waiver estimate requirements are met and the 
enrollment targets for CT and TV have already been met, then collection of NG samples 
will stop. If the estimate requirements are not met, then collection of samples may 
proceed to the next enrollment target, as described in Table 4. 
 
Note that, per Table 5 in section 7.3, an interim report will be provided to the FDA after 
the collection of 50 PIS-positive CT samples, 50 PIS-positive TV samples, and 20 PIS-
positive prospectively collected NG samples. The results presented in this interim report 
will not impact the operations of the study.  
 
 
 
 
 
 
 

 
 
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Table 4: NG Sensitivity Estimates for Various Interim Sample Sizes 
Enrollment Target 
(Number of PIS-
positive NG samples) 
Number of 
False 
Negatives 
Sensitivity Estimate 
(Lower 95% confidence 
bound) 
45 
0 
100% (92.1%) 
1 
97.8% (88.4%) 
2 
95.6% (85.2%) 
3 
93.3% (82.1%) 
>3 
≤91.1% (≤79.3%) 
55 
1 
98.2% (90.4%) 
2 
96.4% (87.7%) 
3 
94.5% (85.2%) 
>3 
≤92.7% (≤82.7%) 
70 
 
 
2 
97.1% (90.2%) 
3 
95.7% (88.1%) 
>3 
≤94.3% (≤86.2%) 
85 
3 
96.5% (90.1%) 
4 
95.3% (88.5%) 
>4 
≤94.1% (≤87.0%) 
 
Assessment of the specificity requirement for NG follows similarly to our investigation of 
specificity for CT and TV above; the study as planned should be able to meet the 
confidence interval estimate requirements for 510(k) clearance and CLIA waiver for NG.   
 
7.3 
Planned Interim Reports 
 
Interim reports may be generated during the course of the study. The reports will only be 
made available to the Sponsor team and Click Diagnostics for the purpose of submission 
to the FDA. The study operators and laboratory staff that run the assays will not have 
access to the reports. The study statistician will provide the reports, which will contain 
summaries from analyses outlined in section 7.4 and detailed in the separate Statistical 
Analysis Plan. 
 
The reports will be generated after the data are entered in the database; the 
approximate milestones for the generation of each report are provided in Table 5 below:

 
 
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Table 5. Types of Study Reports and Schedule 
Report Type 
Milestone 
Interim Report1 
After the collection of 50 PIS-positive 
CT samples, 50 PIS-positive TV 
samples, 20 PIS-positive 
prospectively collected NG samples 
510(k) Report 
After the collection of 100 PIS-positive 
CT samples, 100 PIS-positive TV 
samples, ≥45 PIS-positive 
prospectively collected NG samples 
CLIA Waiver Report 
After the collection of 120 PIS-positive 
CT samples, 120 PIS-positive TV 
samples, ≥45 PIS-positive 
prospectively collected NG samples 
1The need for this interim report depends on the rate of enrollment of subjects with PIS-
positive NG samples. The report will be generated if it is possible to do so without 
halting enrollment and/or losing momentum in accrual or if the rate of enrollment of 
subjects who are PIS-positive NG is such it is expected that multiple NG milestones will 
not be met in a short period of time. 
It is not anticipated that the study or its operations will be impacted by the analyses 
performed for the interim report (e.g., early termination of the study), but instead the 
report fulfills a regulatory requirement and provides the FDA an update on the progress 
of the trial. As such, adjustments for the multiple interim calculations of interval estimates 
are not planned.  
The 510(k) and CLIA Waiver reports will be generated once the NG enrollment has 
finished per the enrollment procedure outlined in section 7.2. Though it is possible that 
NG sensitivity will be estimated multiple times, no adjustments for the multiple 
calculations are planned.      
7.3.1 Ongoing Investigative Product Performance Tracking       
The primary analysis of agreement of Click Sexual Health Test results compared to 
PIS will be performed as described in section 7.4.3 and as shown in the example 2 
x 2 contingency table depicted in Figure 6 of this protocol on an ongoing basis 
during the course of the study.  These analyses will track performance of the 
investigative device and thereby serve to inform the Sponsor team and Click 
Diagnostics as to the likelihood of successful completion of the study with 
performance conforming to acceptance criteria, or conversely, to eventual futility of 
the study for failure to achieve acceptable performance.  In no case shall the 
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benefit, i.e. based upon early achievement of acceptable performance. 
In accord with DMID Policy, analysis results shall be distributed only to the 
Sponsor team and to Click Diagnostics and the receiving personnel shall not 
further distribute the results.  No results shall be supplied to study site personnel or 
to study monitors, and neither the raw data nor the analysis of these ongoing 
analyses shall be submitted to FDA. Study updates will only be provided to the 
FDA at timepoints listed in Table 5 above.  The results of these ongoing analyses 
shall not translate into study design changes, protocol amendments, or 
investigative device design changes.  As such, no adjustments for the multiple 
analysis will be made.   
 
7.4 
Analysis Plan 
 
A separate statistical analysis plan document will be generated that will contain the 
details of all interim and final analyses. This section outlines the major components of all 
analyses. 
 
7.4.1 Analysis Populations 
 
The following analysis populations will be defined separately for each report 
(Interim, 510(k), CLIA Waiver). The statistical analysis plan will include the further 
details on the definitions of the report-specific analysis populations.  
 
Enrolled Population: This population includes all participants enrolled at the 
time of the data cut-off for the report. 
 
Evaluable Population: This population includes all samples available at the time 
of the data cut-off for the report, which provide an evaluable Click Diagnostics 
Sexual Health Test result and an evaluable PIS result for each tested pathogen 
(CT, NG, TV). There will be a separate Evaluable population for each organism. 
 
A sample provides an evaluable result if both the Click device and the PIS 
provide a valid positive or negative result. 
 
The primary outcome measure of sensitivity and specificity of the Click 
Diagnostics Sexual Health Test will be evaluated in the evaluable population. 
 
7.4.2 Baseline Characteristics and Subject Disposition 
 
Baseline and demographic characteristics and subject disposition, including but 
not limited to the number of subjects who contributed vaginal swabs and reasons 
for withdrawn samples, will be summarized overall and by clinical site. For both 
continuous and categorical variables, appropriate summary statistics will be 
applied. For continuous variables, descriptive statistics will include the number of 
non-missing values, mean, standard deviation, median, minimum, and maximum. 
For categorical variables, descriptive statistics will include counts and 
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7.4.3 Primary and Secondary Analyses 
 
Sample proportions of subjects who are PIS-positive for each of the three 
organisms among all enrolled subjects and by symptomatic status will be 
estimated overall and by clinical site. Point estimates and 95% Wilson Score 
confidence intervals will be generated. 
 
Table 6 below presents a 2 x 2 contingency table displaying the potential 
performance outcomes for the Click device in comparison to PIS, Where TP = 
Number of True Positives, TN = Number of True Negatives, FP = Number of 
False Positives, and FN = Number of False Negatives. 
 
Table 6: 2 x 2 Contingency Table for Click Diagnostics versus PIS 
 
 
 
Sensitivity, specificity, positive predicted value (PPV), and negative predicted 
value (NPV) will be estimated along with their 95% Wilson Score confidence 
interval. The following formulae will be used to estimate the performance 
characteristics: 
• 
Sensitivity (%) = TP/(TP + FN) * 100 
• 
Specificity (%) = TN/(TN + FP) * 100 
• 
PPV (%) = TP/(TP + FP) * 100 
• 
NPV (%) = TN/(TN + FN) * 100 
 
The above estimates, along with the number of true/false positives/negatives, will 
be calculated overall, by clinical site, and by symptomatic status. Subject listings 
of test results will be generated. 
 
7.4.4 Exploratory, Ancillary, and Other Analyses 

 
 
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Responses to individual items on the Ease-of-use questionnaire will be 
summarized. For each item on the questionnaire, the proportion of study 
operators who select each level of the response will be summarized. In addition, 
the distribution of each item’s responses (e.g., mean, standard deviation, 
median, range) will be calculated. 
 
Multiple ancillary analyses, which support the primary and secondary analyses, 
will be performed and included in the interim and final reports. The statistical 
analysis plan will include full details of the planned analyses; below are high-level 
summaries of the analyses. 
 
The number of invalid or missing results from and failed tests of the Click device 
will be summarized overall and by clinical site. The different combinations of 
results among the PIS assays will be tabulated overall, by organism, and by 
symptomatic status. 
 
Using the observed sensitivity and specificity of the Click device, hypothetical 
PPV and NPV values will be calculated across a range of hypothetical 
prevalence rates given the following formulae: 
• 
PPV = sens * p / [Sens * p – (1 – spec)*(1 - p)] * 100 
• 
NPV = spec * (1 – p) / [(1 – sens) * p – spec*(1 - p)] * 100 
 
Where Sens = Sensitivity, Spec = Specificity, and p = prevalence. 
 
Additional supplemental and exploratory analyses, including sensitivity analyses, 
which assess the impact of indeterminate/invalid/failed/missing results on the 
analyses, may be performed and will be specified in the statistical analysis plan. 
 
 

 
 
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8 
ASSESSMENT OF SAFETY 
 
8.1 
Risks/Benefits and Adverse Events Reporting 
 
No adverse reactions are anticipated in this study, and the study procedures present no 
anticipated risks beyond the low risks of vaginal swab collection, i.e., risk of pain, 
discomfort, and/or vaginal bleeding. It is anticipated that the participants may experience 
discomfort when vaginal swab specimens are being collected; however, the risks and 
discomfort in this study are not greater than those ordinarily encountered during the 
routine collection of the vaginal swabs at a clinician’s office. There are no known risks to 
operators while handling the device. All adverse events (AEs) should be recorded by the 
investigator. An AE is any untoward medical occurrence in a patient or clinical 
investigation subject using an investigational device and that does not necessarily have 
a causal relationship with this device. An AE can therefore be any unfavorable and 
unintended sign (including an abnormal laboratory finding), symptom, or disease 
temporally associated with the use of an investigational device, whether or not related to 
the investigational device. The Sponsor will collect AE information via the CRF for the 
clinic visits. AEs will be collected from the time of swab collection to the time that the 
subject leaves the clinic. Such data collection will include the start and stop dates of the 
event, causality with the investigational device (not related, related), outcome (ongoing, 
recovered, recovered with sequelae, not recovered, fatal), code for seriousness (SAE, 
UADE, not serious), and intensity (mild, moderate, or severe). The definitions of mild, 
moderate, or severe are as follows: 
 
1 = Mild (awareness of a symptom but the symptom is easily tolerated) 
2 = Moderate (discomfort enough to cause interference with usual activity) 
3 = Severe (incapacitating; unable to perform usual activities; requires 
absenteeism or bed rest) 
 
Unanticipated adverse device effects (UADEs) means “any serious adverse effect on 
health or safety or any life-threatening problem or death caused by, or associated with, a 
device, if that effect, problem, or death was not previously identified in nature, severity, 
or degree of incidence in the investigational plan or application (including a 
supplementary plan or application), or any other unanticipated serious problem 
associated with a device that relates to the rights, safety, or welfare of subjects” (21 CFR 
§ 812.3). Adverse events of sufficient intensity and causality to the investigational device 
to meet the definition of a UADE will be investigated by the Sponsor as outlined in 21 
CFR § 812.46(b) and reported as outlined in 21 CFR § 812.150. The Sponsor shall 
report the results of the UADE investigation to FDA and to all reviewing IRBs and 
participating investigators within 10 working days after the Sponsor first receives notice 
of the effect. Thereafter, the Sponsor shall submit such additional reports concerning the 
effect as FDA requests. 
 

 
 
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A serious adverse event (SAE; experience) or reaction is any untoward medical 
occurrence that: results in death, is life-threatening, requires inpatient hospitalization or 
prolongation of existing hospitalization, results in persistent or significant 
disability/incapacity, or is a congenital anomaly/birth defect. SAEs must be recorded by 
the investigator. 
 
This study is performed entirely in vitro, and the result of the Click device and the study 
reference tests will not be used for patient management and will not be provided to 
health care providers or subjects. Therefore, there are no direct benefits to subjects who 
participate in this study. There may be benefits to future patients in the application of the 
Click Diagnostics Sexual Health Test in clinical care. 
 
8.2 
Reporting for Studies 
 
Any AEs will be collected from the first study enrollment through study completion. The 
site investigator is responsible for documenting and reporting all AEs that are reported 
during the study, regardless of their relationship to study procedures. 
 
All SAEs will be followed to adequate resolution or stabilization. Resolution of an SAE is 
defined as the return to pre-enrollment status or stabilization of the condition with the 
expectation that it will remain chronic. Time of resolution/stabilization of the event will be 
collected for device procedure-related SAEs. 
 
The Sponsor will notify all participating site PIs (i.e., all PIs to whom the Sponsor is 
providing study device) in a safety report of serious risks from clinical trials or any other 
source, as soon as possible, but in no case later than 10 working days after the Sponsor 
is notified of the UADE or SAE determines that the information suggests a causal 
relationship or association with the study device. Relevant follow-up information to a 
safety report will be provided as soon as the information is available. 
 
The investigator must report SAEs to the Sponsor, the reviewing IRB, and FDA within 24 
hours after the investigator first learns of the event. 
 
 

 
 
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9 
CLINICAL MONITORING 
 
9.1 
Site Monitoring Plan 
 
Site monitoring is conducted to ensure that the human subject protections, study and 
laboratory procedures, study intervention administration, and data collection processes 
are of high quality and meet Sponsor requirements, ICH/GCP guidelines, and applicable 
regulations, and that the study is conducted in accordance with the protocol, protocol-
specific MOP, and applicable Sponsor standard operating procedures. DMID, the 
sponsoring agency, or its designee, will conduct site-monitoring visits as detailed in the 
clinical monitoring plan.  
Site visits will be made at standard intervals as defined by DMID and may be made more 
frequently as directed by DMID. Monitoring visits will include, but are not limited to, 
review of regulatory files, accountability records, electronic case report forms (eCRFs), 
informed consent forms, source documents necessary to support the documentation 
entered into the CRFs, and protocol and GCP compliance. Site monitors will have 
access to the study site, study personnel, and all study documentation according to the 
DMID-approved site monitoring plan. Study monitors will meet with site PIs to discuss 
any problems and actions to be taken and will document visit findings and discussions. 
 
 

 
 
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10 
DATA HANDLING AND RECORD KEEPING 
 
The site PI is responsible to ensure the accuracy, completeness, legibility, and 
timeliness of the data reported. Data collection forms will be derived from the eCRFs and 
provided by the SDCC to the site to record and maintain data for each subject enrolled in 
the study as a source document. All source documents should be completed in a neat, 
legible manner to ensure accurate interpretation of data. Permanent ink is required to 
ensure clarity of reproduced copies. When making a change or correction, the original 
entry should be crossed out with a single line, and the change should be initialed and 
dated. Do not erase, overwrite, or use correction fluid or tape on the original. 
 
The DMID and/or its designee will provide guidance to investigators on making 
corrections to the source documents and eCRF. 
 
10.1 Data Management Responsibilities 
 
It is the responsibility of the PI to ensure that all team members handle data and related 
documentation appropriately. All non-operator completed data collection forms must be 
reviewed by the clinical team and data entry staff, who will ensure that they are accurate 
and complete. The Click study operator’s interpretation of Click test results should not be 
discussed with the operators nor should the operator’s interpretation of Click test results 
be changed after the assessment has been completed (see MOP). Data collection is the 
responsibility of the study staff at the site under the supervision of the site PI. During the 
study, the site PI must maintain complete and accurate documentation for the study. 
 
The SDCC for this study will be responsible for data management, quality review, 
analysis, and reporting of the study data. The SDCC will implement quality control (QC) 
procedures beginning with the data entry system and generate data QC checks that will 
be run on the database. Any missing data or data anomalies will be communicated to 
the site(s) for prompt clarification and resolution. 
 
Data Capture Methods 
 
All clinical (including, but not limited to, medical and sexual history, symptom status) and 
endpoint data will be entered into a 21 CFR 11-compliant Internet data entry system 
provided by the SDCC. The data system includes password protection and internal 
quality checks, such as automatic range checks, to identify data that appear 
inconsistent, incomplete, or inaccurate. Clinical data will be entered directly from the 
data collection forms/source documents completed by the study personnel. 
 
10.2 Types of Data 
 
Data for this study will include clinical, laboratory, demographic, behavioral variables, 
and outcome measures, including the operator questionnaire. 
 

 
 
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10.3 Timing/Reports 
 
A final report will be prepared following the availability of all the clinical and laboratory 
data. During the course of the study, interim statistical reports may be generated and 
made available to DMID and Click Diagnostics to submit to the FDA. 
 
10.4 Study Records Retention 
 
Study records and reports, including, but not limited to, CRFs, source documents, 
informed consent forms (except for future use informed consent forms), laboratory test 
results, and device inventory records, shall be retained for 2 years after the last 
marketing application is approved for the device and until there are no pending or 
contemplated marketing applications. If an application is not approved for the device, 
study documents should be retained at least 2 years after clinical development of the 
device for investigational use is discontinued and the FDA has been so notified. The site 
must contact DMID for authorization prior to the destruction of any study records. No 
records will be destroyed without the written consent of the Sponsor. It is the 
responsibility of the Sponsor to inform the investigator when these documents no longer 
need to be retained. Informed consent forms for future use will be maintained as long as 
the sample exists. 
 
10.5 Protocol Deviations 
 
A protocol deviation is any noncompliance with the clinical trial protocol, GCP, or MOP 
requirements. The noncompliance may be on the part of the subject, the investigator, or 
the study personnel. As a result of deviations, corrective actions are to be developed by 
the site and implemented promptly. These practices are consistent with ICH E6: 4.5 
Compliance with Protocol, sections 4.5.1, 4.5.2, and 4.5.3 as well as 5.1, Quality 
Assurance and Quality Control, section 5.1.1 and Noncompliance, sections 5.20.1, and 
5.20.2. It is the responsibility of the site PI and other study personnel to use continuous 
vigilance to identify and report deviations within 5 working days of identification of the 
protocol deviation, or within 5 working days of the scheduled protocol-required activity. 
All deviations must be promptly reported to DMID, via The Emmes Corporation’s 
Advantage eClinicalSM. 
 
All deviations from the protocol must be addressed in study subject case report forms. A 
completed copy of the DMID Protocol Deviation (PD) Form must be maintained in the 
regulatory file, as well as in the subject’s CRF. Protocol deviations must be sent to the 
local IRB/IEC per their guidelines. The site PI and other study personnel are responsible 
for knowing and adhering to their IRB/IEC requirements. 
 
 

 
 
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11 
SUBJECT CONFIDENTIALITY 
 
Subject confidentiality is strictly held in trust by the participating investigators, their staff, 
and the Sponsor(s) and their agents. This confidentiality is extended to cover testing of 
biological samples in addition to the clinical information relating to participating subjects, 
and all study subject information will be kept confidential and managed according to the 
requirements of the Health Insurance Portability and Accountability Act of 1996 (HIPAA). 
 
The study protocol, documentation, data, and all other information generated will be held 
in strict confidence. No information concerning the study or the data will be released to 
any unauthorized third party without prior written approval of the Sponsor. 
 
Applicable regulatory authorities, such as the FDA, or other authorized representatives 
of the Sponsor may inspect all documents and records required to be maintained by the 
investigator. The clinical study site will permit access to such records. 
 
Results from this study will be de-identified prior to transfer to the Sponsor in order to 
protect subject confidentiality. Subjects will have code numbers and will not be identified 
by name. No subject’s PII will be provided to the Sponsor. 
 
In the event that a subject revokes authorization to collect or use PII, the investigator, by 
regulation, retains the ability to use all information collected prior to the revocation of 
subject authorization. For subjects that have revoked authorization to collect or use PII, 
attempts should be made to obtain permission to collect at least vital status (i.e., that the 
subject is alive) at the end of their scheduled study period. 
 
Certificate of Confidentiality 
 
To further protect the privacy of study subjects, we have a Certificate of Confidentiality 
from the National Institutes of Health (NIH). This certificate protects identifiable research 
information from forced disclosure. It allows the investigator and others who have access 
to research records to refuse to disclose identifying information on research participation 
in any civil, criminal, administrative, legislative, or other proceeding, whether at the 
federal, state, or local level. By protecting researchers and institutions from being  
compelled to disclose information that would identify research subjects, Certificates of 
Confidentiality help achieve the research objectives and promote participation in studies 
by helping to ensure confidentiality and privacy to subjects.   
 
 

 
 
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A Certificate of Confidentiality does not prevent the subject from voluntarily releasing 
information about themselves or their involvement in this research. If any person or 
agency obtains a written consent to receive research information, then the researchers 
may not use the Certificate to withhold that information.   
The Certificate of Confidentiality does not prevent the researchers from reporting, 
without the subject’s consent, information that would identify the subject as a participant 
in the research project regarding matters that must be legally reported including: child 
and elder abuse, sexual abuse, or wanting to harm themselves or others.   
 
11.1 Future Use of Stored Specimens 
 
Click Diagnostics may store excess vaginal liquid media collected from this study 
indefinitely for the purposes of future testing and medical research related to CT/NG, TV, 
or other diseases or conditions. Each sample will be encoded (labeled) only with a 
barcode and a unique tracking number to protect the subject’s confidentiality. Reports 
about future research done with the subject’s samples will NOT be kept in the subject’s 
health records. Results will not be provided to subjects. At the time of informed consent, 
subjects may choose to withhold permission for storage of their specimens and may 
continue in the study if they decline permission. Specimens from subjects not consenting 
to storage and future research will be destroyed at the end of the study. 
 
 

 
 
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12 
QUALITY CONTROL AND QUALITY ASSURANCE 
Following a written DMID-accepted site quality management plan, each participating 
site(s) and its subcontractors are responsible for conducting routine quality assurance 
and QC activities to internally monitor study progress and protocol compliance. The site 
PI will provide direct access to all study-related sites, source data/data collection forms, 
and reports for the purpose of monitoring and auditing by the Sponsor, and inspection by 
local and regulatory authorities. The site PI will ensure all study personnel are 
appropriately trained and applicable documentations are maintained on site. 
The SDCC will implement QC procedures beginning with the data entry system and 
generate data QC checks that will be run on the database.  Any missing data or data 
anomalies will be communicated to the participating site(s) for clarification and 
resolution. 
 
 

 
 
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13 
ETHICS/PROTECTION OF HUMAN SUBJECTS 
 
13.1 Ethical Standard 
 
The site PI will ensure that this trial is conducted in full conformity with principles of the 
Belmont Report: Ethical Principles and Guidelines for the Protection of Human Subjects 
of Research (National Commission for the Protection of Human Subjects of Biomedical 
and Behavioral Research [April 18, 1979]), and codified in 45 CFR 46, 21 CFR 50, and 
21 CFR 56, as applicable. The PI will also ensure conformity with ICH E6 GCP, and 
applicable federal regulations, guidance, and guidelines for GCP and clinical trials with 
humans. 
 
13.2 Institutional Review Board 
 
Each site PI will obtain IRB approval for this protocol to be conducted at his/her research 
site(s), and send supporting documentation to the DMID before initiating recruitment of 
subjects. The investigator will submit applicable information to the IRB/IEC on which it 
relies for the review, to conduct the review in accordance with 45 CFR 46, ICH E6 GCP, 
and, as applicable, 21 CFR 56 (Institutional Review Boards) and 21 CFR 50 (Protection 
of Human Subjects), other federal, state, and local regulations. The IRB/IEC must be 
registered with Office of Human Research Protection (OHRP) [OHRP-only or 
OHRP/FDA] as applicable to the research. DMID must receive the documentation that 
verifies IRB/IEC approval for this protocol, associated informed consent documents, and 
upon request any recruitment material and handouts or surveys intended for the 
subjects, prior to the recruitment and enrollment of subjects. 
 
Any amendments to the protocol or consent materials will be approved by the IRB/IEC 
before they are implemented. IRB/IEC review and approval will occur at least annually 
throughout the enrollment and follow-up of subjects, and may cease if annual review is 
no longer required by applicable regulations. The investigator will notify the IRB/IEC of 
deviations from the protocol and reportable SAEs, as applicable to the IRB/IEC policy. 
 
Each institution engaged in this research will hold a current Federalwide Assurance 
(FWA) issued by the OHRP for federally funded research. 
 
The IRB/IEC will determine that adequate provisions are made for soliciting the 
permission of each child's parent(s) or legal guardian, including whether permission of 
one parent is sufficient for research or whether permission is to be obtained from both 
parents. 
 
13.3 Informed Consent Process 
 
Informed consent is a process that is initiated prior to the individual’s agreeing to 
participate in the study and continuing throughout the individual’s study participation. 
Extensive discussion of risks and possible benefits of participation in this study will be 
provided to the subjects and their families. Consent forms describing in detail the study 
procedures and risks are given to the subject, and written documentation of informed 

 
 
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consent is required prior to enrolling in the study. Subjects will be informed of the NIH 
Certificate of Confidentiality and the extent of confidentiality of subjects’ records the 
certificate covers. For enrollment of non-English speakers, a translated consent 
document will be available, and an appropriate person will conduct the consent process. 
Consent forms will be IRB approved and the subject will be asked to read and review the 
document. Upon reviewing the document, the investigator will explain the research study 
to the subject and answer any questions that may arise. The subjects will sign the 
informed consent document prior to being enrolled in the study. The subjects should 
have the opportunity to discuss the study with their surrogates or think about it prior to 
agreeing to participate. The subjects may withdraw consent orally or in writing at any 
time and for any reason throughout the course of the study. A copy of the informed 
consent document will be given to the subjects for their records. The rights and welfare 
of the subjects will be protected by emphasizing to them that the quality of their medical 
care will not be adversely affected if they decline to participate in this study. The consent 
process will be documented in the research record. 
 
The written informed consent form and any other written information to be provided to 
subjects should be revised whenever important new information becomes available that 
may be relevant to the subject’s consent. Any revised written informed consent form and 
written information should receive the IRB/IEC's approval/favorable opinion in advance 
of use. The subject should be informed in a timely manner if new information becomes 
available that may be relevant to the subject’s willingness to continue participation in the 
trial. The communication of this information should be documented. 
 
13.3.1 Informed Consent/Assent Process (in Case of a Minor or Others Unable to 
Consent for Themselves) 
 
In the cases of minors or others unable to consent for themselves, subjects may 
only be enrolled in the study with the consent of the subject’s parent(s) and/or 
legal guardian. The subject should be informed about the study to the extent 
compatible with the subject’s understanding. If capable, the subject should 
assent by signing and personally dating the written consent form. A separate 
IRB-approved assent form, describing (in simplified terms) the details of the 
study, study procedures, and risks may be used. Assent forms do not substitute 
for the consent form signed by the subject’s parent(s), legal guardian, and/or 
legally authorized representative. The IRB may have specific institutional policies 
regarding enrollment of subjects who are unable to provide informed consent for 
themselves. 
 
Where parental permission is to be obtained, the IRB may find that the 
permission of one parent is sufficient for research to be conducted. The IRB may 
also determine that both parents must give their permission unless one parent is 
deceased, unknown, incompetent, or not reasonably available, or when only one 
parent has legal responsibility for the care and custody of the child. 
 
If non-English speakers will be enrolled, a translated consent document will be 
available and an appropriate person will conduct the consent process. The study 
will include women, minorities, and adolescents 14-17 years old, per site 

 
 
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demographics. Females under 14 will not be enrolled, as is done similarly for 
pregnancy test studies. 
 
13.4 Exclusion of Women, Minorities, and Children 
 
The study will include women, minorities, and adolescents 14 years of age or older who 
meet the subject inclusion/exclusion criteria, regardless of religion, sex, or ethnic 
background. The demographic and ethnic distribution of the study population will be 
generally reflective of the distribution of subjects within the facilities in the US geographic 
locations of the study sites. The NIH has mandated that children (defined as anyone 
under the age of 21) be included in research trials when appropriate. This study will 
enroll children aged 14 to 20 who are able to give informed consent or parental/guardian 
permission granted as deemed by the IRB. Females under 14 will be excluded, as is 
done similarly for pregnancy test studies. 
 
 
 

 
 
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14 
PUBLICATION POLICY 
 
All investigators funded by the NIH must submit or have submitted for them to the 
National Library of Medicine’s PubMed Central (http://www.ncbi.nlm.nih.gov/pmc/) an 
electronic version of their final, peer-reviewed manuscripts upon acceptance for 
publication, to be made publicly available no later than 12 months after the official date 
of publication. The NIH Public Access Policy ensures the public has access to the 
published results of NIH-funded research. It requires investigators to submit final peer-
reviewed journal manuscripts that arise from NIH funds to the digital archive PubMed 
Central upon acceptance for publication. Further, the policy stipulates that these papers 
must be accessible to the public on PubMed Central no later than 12 months after 
publication. 
Refer to: 
• 
NIH Public Access Policy, http://publicaccess.nih.gov/ 
• 
NIH Office of Extramural Research (OER) Grants and Funding, 
http://grants.nih.gov/grants/oer.htm 
 
As of January 2018, all clinical trials supported by the NIH must be registered on 
ClinicalTrials.gov, no later than 21 days after the enrollment of the first subject. Results 
of all clinical trials supported by the NIH, generally, need to be submitted no later than 12 
months following the primary completion date. A delay of up to 2 years is available for 
trials that meet certain criteria and have applied for certification of delayed posting. 
 
As part of the result posting, a copy of this protocol (and its amendments) and a copy of 
the Statistical Analysis Plan will be posted on ClinicalTrials.gov. 
 
For this trial, the responsible party is DMID, which will register the trial and post results. 
 
 

 
 
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15 
LITERATURE REFERENCES 
 
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and Syphilis factsheet [Internet]. Centers for Disease Control and Prevention; 2015 
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2. Gonorrhea detailed factsheet [Internet]. Centers for Disease Control and Prevention; 
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https://www.cdc.gov/std/gonorrhea/stdfact-gonorrhea-detailed.htm. 
3. Chlamydia detailed factsheet [Internet]. Centers for Disease Control and Prevention; 
updated 2016 October 17. Available from: https://www.cdc.gov/std/chlamydia/stdfact-
chlamydia-detailed.htm. 
4. Chlamydia and Gonorrhea handout [Internet]. McKinley Health Center, University of 
Illinois at Urbana-Champaign; 23 January 2009. Available from: 
http://www.mckinley.illinois.edu/sites/default/files/docs/chlamydia_gonorrhea.pdf. 
5. Frommell GT, Rothenberg R, Wang S, McIntosh K. Chlamydial infection of mothers 
and their infants. J Pediatr 1979; 95(1): 28-32. 
6. Holmes KK, Counts GW, Beaty HN. Disseminated gonococcal infection. Ann Intern 
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7. Reighard SD, Sweet RL, Vicetti Miguel C, et al. Endometrial leukocyte 
subpopulations associated with Chlamydia trachomatis, Neisseria gonorrhoeae, and 
Trichomonas vaginalis genital tract infection. Am J Obstet Gynecol 2011; 205(4): 324 
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8. Peipert JF. Clinical practice. Genital chlamydial infections. N Engl J Med 2003; 
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9. Workowski KA, Berman S; Centers for Disease Control and Prevention. Sexually 
transmitted diseases treatment guidelines, 2010. MMWR Morb Mortal Wkly Rep 
2010; 59(RR-12): 1-110. 
10. Trichomoniasis factsheet [Internet]. Centers for Disease Control and Prevention; 
updated 2017 July 14. Available from: https://www.cdc.gov/std/trichomonas/stdfact-
trichomoniasis.htm. 
11. Holmes KK. Sexually transmitted diseases. 4th ed. New York: McGraw-Hill Medical; 
2008. 
12. Allsworth JE, Ratner JA, Peipert JF. Trichomoniasis and other sexually transmitted 
infections: results from the 2001-2004 National Health and Nutrition Examination 
Surveys. Sex Transm Dis 2009; 36(12): 738-44. 
13. Poole DN, McClelland RS. Global epidemiology of Trichomonas vaginalis. Sex 
Transm Infect 2013; 89(6): 418-22. 
14. Sutton M, Sternberg M, Koumans EH, McQuillan G, Berman S, Markowitz L. The 
prevalence of Trichomonas vaginalis infection among reproductive-age women in the 
United States, 2001-2004. Clin Infect Dis 2007; 45(10): 1319-26. 
15. Kissinger P, Adamski A. Trichomoniasis and HIV interactions: a review. Sex Transm 
Infect 2013; 89(6): 426-33. 
16. Laga M, Manoka A, Kivuvu M, et al. Non-ulcerative sexually transmitted diseases as 
risk factors for HIV-1 transmission in women: results from a cohort study. AIDS 1993; 
7(1): 95-102. 
17. McClelland RS, Sangare L, Hassan WM, et al. Infection with Trichomonas vaginalis 
increases the risk of HIV-1 acquisition. J Infect Dis 2007; 195(5): 698-702. 

 
 
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18. Cotch MF, Pastorek JG, 2nd, Nugent RP, et al. Trichomonas vaginalis associated 
with low birth weight and preterm delivery. The Vaginal Infections and Prematurity 
Study Group. Sex Transm Dis 1997; 24(6): 353-60. 
19. Paisarntantiwong R, Brockmann S, Clarke L, Landesman S, Feldman J, Minkoff H. 
The relationship of vaginal trichomoniasis and pelvic inflammatory disease among 
women colonized with Chlamydia trachomatis. Sex Transm Dis 1995; 22(6): 344-7. 
20. Centers for Disease Control and Prevention. STDs and Infertility [Internet]. USA: 
Centers for Disease Control and Prevention; updated 2016 October 18. Available 
from: https://www.cdc.gov/std/infertility/. 
21. Patil MJ, Nagamoti JM, Metgud SC. Diagnosis of Trichomonas Vaginalis from 
Vaginal Specimens by Wet Mount Microscopy, In Pouch TV Culture System, and 
PCR. J Global Infect Dis 2012; 4(1): 22-5 
22. Andrea SB, Chapin KC. Comparison of Aptima Trichomonas vaginalis transcription-
mediated amplification assay and BD affirm VPIII for detection of T. vaginalis in 
symptomatic women: performance parameters and epidemiological implications. J 
Clin Microbiol 2011; 49(3): 866-9. 
23. Huppert JS, Mortensen JE, Reed JL, et al. Rapid antigen testing compares favorably 
with transcription-mediated amplification assay for the detection of Trichomonas 
vaginalis in young women. Clin Infect Dis 2007; 45(2): 194-8. 
24. Nye MB, Schwebke JR, Body BA. Comparison of APTIMA Trichomonas vaginalis 
transcription-mediated amplification to wet mount microscopy, culture, and 
polymerase chain reaction for diagnosis of trichomoniasis in men and women. Am J 
Obstet Gynecol 2009; 200(2): 188 e1-7. 
25. Schwebke JR, Hobbs MM, Taylor SN, et al. Molecular testing for Trichomonas 
vaginalis in women: results from a prospective U.S. clinical trial. J Clin Microbiol 
2011; 49(12): 4106-11. 
26. U.S. Department of Health and Human Services. Food and Drug Administration. 
Brief Summary of the Microbiology Devices Panel Meeting – August 16, 2016. 
27. U.S. Department of Health and Human Services. Food and Drug Administration. 
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Biostatistics. Office of Surveillance and Biometrics. Guidance for Industry and FDA 
Staff. Statistical Guidance on Reporting Results from Studies Evaluating Diagnostics 
Tests. March 13, 2017. 
 
 

 
 
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APPENDIX A: SCHEDULE OF EVENTS 
Evaluation 
Screening/Enrollment 
Visit 1 
Signed consent/assent form 
X 
Confirmation of eligibility and enrollment 
X 
Demographics 
X 
Sexual health and reproductive history 
X 
Self-reported symptoms 
X 
Concomitant medications and supplements 
X 
Genital products 
X 
Self-collected vaginal swab 
X 
HCP-collected vaginal swabs 
X 
Adverse event during/post-vaginal swab 
collection 
X