Truscreen Cervical Screening System

Truscreen Pty Limited.
Ref.no: 0000110-01
Truscreen cervical screening system

Author: Catherine Stringer
Checked: Stewart Montano
KEYWORDS: Clinical trial, Accuracy, Evaluation, and General Screening Project

Abstract:
DOCUMENT HISTORY
Rev No.:
Change Note:
Date Prepared:
Date Released:
Rev No.:
Change Note:
Date Prepared:
Date Released:
General Screening Project K000110 01
Page 1 of 39
General Screening Project

Table of Contents
Page
1.
General Information
1.1 Schedule
1.2 Sponsor and Monitor
1.3 Authorised Protocol Signatories
1.4 Medical Adviser4
1.5 Abbreviations
1.6 Definitions
1.7 Participating Sites
10
1.8 Clinical Laboratories
10
Background Information
10
2.1 Technical description the device

2.2 Risk benefit analysis
11
2.3 Benefits/justifications 12
2.4 Compliance with the protocol 12
2.5 Population to be studied.
12
2.6 Supporting Documents 13

3
Trial Objectives and Purpose 13
Trial Design
14
4.1 Description of the Trial 14

4.2 Patient Withdrawal
14
4.3 Accountability Procedures

4.3.1 SUS Units 14
4.3.2 Patient ID 15
4.4 Source Data.
5.
15
Selection Criteria
16
5.1 Inclusion criteria
16
5.2 Exclusion criteria
16

Page 2 of 39
14
10
6 Treatment of Patients
17
6.1 TruScreen Examination 17

6.2 Colposcopic procedure 18
6.3 Biopsy Procedure
19
7 Assessment of Efficacy
19
8 Assessment of safety
20
8.1 Adverse Events. 20

8.2 Serious Adverse Events 20
9 Statistics
21
10 Direct access to source data/documents 21

11 Quality control and quality assurance 21
12 Ethics
21
13 Data handling and record keeping
22
14 Financing and insurance 23

15 Publication policy23
16 Attachments
24
ATTACHMENT A - CASE REPORT FORM
25
ATTACHMENT B - PATIENT INFORMATION SHEET AND CONSENT FORM

ATTACHMENT C - TRUSCREEN PRINT OUT 35
ATTACHMENT D - SUS PACKAGE LABELLING (EXAMPLE)
ATTACHMENT E - PROBING PATTERN
37
ATTACHMENT F - SITE SPECIFIC DETAILS 39

Page 3 of 39
36
33
General Screeningl Project
1.
GENERAL INFORMATION
Truscreen Clinical Implementation Team will be responsible for the overall coordination of
the General Screening Project (General Screening Population Project).
1.1
SCHEDULE
See ATTACHMENT F - SITE SPECIFIC DETAILS
1.2
SPONSOR AND MONITOR:
The sponsor and monitor of this trial is:
1.3
AUTHORISED PROTOCOL SIGNATORIES.
The Trial Chairman authorised to sign the protocol and amendments is:
1.4
MEDICAL ADVISER
The Medical Adviser for this trial is:
1.5
ABBREVIATIONS
AE
Adverse Event
ADE
Adverse Device Event
AIS
Adenocarcinoma in Situ
ARTG
Australian Register of Therapeutic Goods
ASCUS
Atypical Squamous Cells of Undetermined Significance
AWE
Aceto White Epithelium
CIS
Carcinoma in Situ
CIN
Cervical Intraepithelial Neoplasia
CRF
Case Report Form
GCP
Good Clinical Practice
DF
Documentation Folder
DNA
Deoxyribonucleic acid
HGEA High Grade Epithelial Abnormality
HSIL
High-Grade Squamous Intraepithelial Lesion
HREC
Human Research Ethics Committee
HRT
Hormone Replacement Therapy
HPV
Human Papillomavirus
ID
Identification
LSIL
Low-grade squamous intraepithelial
NCI
National Cancer Institute
OSE
Original squamous epithelium
PCR
Polymerise chain reaction
DF
Documentation Folder
Page 4 of 39

pNorm
Probability of normal
pmol/L
picomol per Litre
pg/mL
picograms per millilitre
PRN
When required
RCI
Reid Colposcopic Index
ROC
Receiver operator characteristic
SAE
Serious Adverse Event
STD
Sexually Transmitted Disease
SIL
Squamous Intraepithelial lesion
SCJ
Squamocolumnar Junction
SUS
Single Use Sensor
TGA
Therapeutic Goods Administration
TZ
Transformation Zone
VIA
Visual inspection with acetic acid
1.6
DEFINITIONS
ATYPIA
An abnormality of a cell, which may or may not be associated with later malignancy.
ADENOCARCINOMA OF THE CERVIX
A type of cervical cancer originating in the mucus-producing cells of the endocervix.
ADVERSE EVENT
Any undesirable clinical occurrence in a Patient whether it is considered to be device related
or not, that includes a clinical sign, symptom or condition and/or an observation of an
unintended technical performance or performance outcome of the device.
ADVERSE DEVICE EVENT (ADE)
A clinical sign, symptom or condition that is causally related to the device implantation
procedure, the presence of the device, or the performance of the device system.
ASCUS
The acronym in the Bethesda system terminology for atypical/abnormal squamous cells of
undetermined significance (ASCUS). It is used for reporting cervical/vaginal cytologic
diagnosis describing cellular abnormalities that are more marked than those attributable to
reactive changes but that quantitatively or qualitatively fall short of a definitive diagnosis of
squamous intraepithelial lesion (LSIL); may reflect a benign or a potentially serious lesion.
BETHESDA SYSTEM
Method of classifying Pap tests developed by the United States National Cancer Institute
(NCI) to provide more detailed information about Pap test results.
CARCINOMA IN SITU (CIS)
A lesion characterised by cytologic changes of the type associated with invasive carcinoma,
but with the pathologic process limited to the lining epithelium and without histologic
evidence of extension. The lesion is presumed to be the histologically recognisable precursor
of invasive carcinoma.
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CERVICAL INTRAEPITHELIAL NEOPLASIA (CIN)
Dysplastic changes beginning at the squamocolumnar junction in the uterine cervix that may
be precursors of squamous cell carcinoma: grade 1, mild dysplasia involving the lower onethird or less of the epithelial thickness; grade 2, moderate dysplasia with one-third to twothirds involvement; grade 3, severe dysplasia or carcinoma in situ, with two-thirds to fullthickness involvement.
CERVICAL SCREENING
Screening tests that are performed to detect the presence of pre-cancerous or cancerous
cervical cells in women who do not present with any symptoms of cervical cancer. Cervical
screening tests include TruScreen, Pap tests and direct visual inspection.
CONVENTIONAL PAP (PAPANICOLAOU) SMEAR/TEST
The Conventional Pap Smear test involves the visual examination of fixed, magnified and
stained cells and is the currently accepted screening test for cervical cancer and pre-cancer,
where ectocervical and endocervical samples are taken. A wooden spatula or a cytobrush are
used. A fixation agent is applied to preserve morphological cell structure. The Papanicolaou
stain utilises haematoxylin, orange-G-6 and EA preparations.
COLPOSCOPY
Visual examination of the cervix using a specially designed instrument, called a colposcope,
to view the cervix using magnification to detect abnormal cell changes that may be precancerous (dysplasia or CIN).
CONSENT FORM
A document explaining all relevant trial information to assist the trial volunteers in
understanding the expectations and requirements of participation in a clinical trial. This
document is presented to and signed by the trial subject.
DIRECT VISUAL INSPECTION
A cervical screening technique where the cervix is observed directly.
DYSPLASIA
Abnormal cell development. Cervical dysplasia is the abnormal growth of cells on the surface
of the cervix. These abnormal cells may disappear without treatment (regress) or they may
become cancerous.
ECTOCERVIX
The part of the cervix that extends into the vagina. It has a convex surface lined with
stratified squamous epithelium.
ENDOCERVIX
The cervical canal. This is lined with columnar epithelial cells.
GOOD CLINICAL PRACTICE (GCP)
International ethical and scientific quality standard for designing, conducting, monitoring,
recording, auditing, analysing and reporting studies. Insures that the data reported is credible
and accurate, and that subject's rights and confidentiality are protected.
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INFORMED CONSENT
Informed consent is a process where the voluntary verification of a patients willingness to
participate in a clinical trial, along with the documentation thereof is obtained. This
verification is requested only after complete, objective information has been given about the
trial, including an explanation of the trial's objectives, potential benefits, risks and
inconveniences, alternative therapies available, and of the subject's rights and responsibilities
in accordance with the current revision of the Declaration of Helsinki.
IMAGE CAPTURE
Digital imaging colposcopy allows image capture, processing and objective analysis.
HPV DNA TEST
The HPV DNA Test includes a range of techniques used to test for the presence of numerous
high and low risk HPV types in the cervical tissue. These techniques may include PCR and
Hybrid Capture.
HPV ATYPIA
A type of cellular abnormality typical caused by HPV infection.
TRUSCREEN
The TruScreen includes the console, handpiece and Single Use Sensor (SUS) unit.
TRUSCREEN HANDPIECE
The TruScreen handpiece is a device, which is intended to be fitted with a new disposable
Single Use Sensor (SUS) for each patient to prevent cross-infection. The handpiece with SUS
fitted allows the electrical and optical stimulation of cervical tissue. The data collected by the
biosensors is compared to an algorithm developed using histologically confirmed tissue
signatures.
HUMAN PAPILLOMAVIRUS (HPV)
Human Papilloma Virus (HPV) is a common DNA virus. Different types of the virus are
associated with warts on the hands, feet and mucous membranes of the oral, anal and genital
areas. Over 90 types of HPV have been identified and several are associated with cancerous
conditions, including pre-cancerous lesions of the cervix.
METAPLASIA
Specifically relating to the cervix, metaplasia is the normal transformation of columnar tissue
to squamous tissue.
ONCOGENIC
Causing, inducing, or being suitable for the formation and development of a neoplasm.
pNORM
The probability that the cervical epithelium is normal. The TruScreen uses a level of
pNORM=0.5 as a reference level for its reports. Values above this are reported as normal,
while levels below were reported as abnormal. This is the level that was used for all of the
clinical projects, and the reference used for calculation of sensitivity and specificity.
pNORM=0.5 is a suitable level for these determinations, however, the clinician is able to
interpret a borderline reading in light of the clinical presentation and patients history.
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SENSITIVITY
The ability to detect true-positive matches. In the context of cervical screening it refers to how
effective a test is at correctly detecting disease.
SINGLE USE SENSOR (SUS)
The Single Use Sensor (SUS) is a sleeve with electrodes and an optical window, designed to
be fitted over the TruScreen handpiece and used on a one-time basis only. The SUS is
discarded after each patient examination.
SERIOUS ADVERSE EVENT (SAE)
See section 8.2
SPECIFICITY
The ability to reject 'false-positive' matches. In the context of cervical screening, it is a
measure of how accurate a test is in correctly identifying women who do not have disease
SOURCE DATA
All information contained in original records and certified copies of results, observations or
other facets required for the reconstruction and evaluation of the trial that is contained in
source documents.
SQUAMOUS CELL CARCINOMA
This is the most common type of cervical cancer. It originates in the squamous cells on the
surface of the ectocervix.
SQUAMOUS INTRAEPITHELIAL LESION (SIL)
Abnormal growth of squamous cells on the surface of the cervix. SILs may be classified as
low-grade squamous intraepithelial lesions (LSILs) or high-grade, squamous intraepithelial
lesions (HSILs) depending on how abnormal the cells are and how much of the cervix is
affected. High-grade, squamous intraepithelial lesions correspond with CIN 2-3.
TRANSFORMATION ZONE (TZ)
The area of the cervix where the squamous epithelium of the vagina joins the columnar
epithelium lining the cervical canal. In this area, columnar cells are constantly being
transformed into flat squamous cells (metaplasia). It is in this transformation zone that
abnormal growth or dysplasia is most likely to develop.
VISUAL INSPECTION WITH ACETIC ACID (VIA)
A cervical screening technique where a solution of 3-5% acetic acid is applied to the cervix,
which is then observed with the naked eye or under magnification.
THINPREP TEST
The ThinPrep Test is a modified Pap Smear test. A sampling device similar to that used for a
conventional Pap smear is used to collect a sample. Instead of smearing the cells onto a glass
slide, the sampling device is immersed into a cell suspension vial. At the laboratory, an
automated slide preparation unit prepares the slide. The result is a slide with a uniform thinlayer of cells, free of obscuring artefacts.
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1.7
SITES
Sites will be chosen on the basis of their suitability to undertake the "General Screening
Project " in their practices' patient population, the patient throughput numbers, and the interest
in the technology on behalf of the clinician. The principal clinician at each site will be
responsible for the coordination of their site. The sites participating in this multi-centre trial
are listed in ATTACHMENT F - SITE SPECIFIC DETAILS
1.8
CLINICAL LABORATORIES
To enable any procedural differences between sites to be taken into account in the trial
analysis the medical adviser will review the local procedures reporting ranges used for
cytology and histology prior to the commencement of the trial at each site. The sites involved
in the trial will provide the Name(s) and address(es) of the clinical laboratory(ies) and other
medical and/or technical department(s) and/or institutions involved in the review of results.
2.
BACKGROUND INFORMATION
2.1
TECHNICAL DESCRIPTION OF THE DEVICE
TruScreen is a novel optoelectronic device, which uses low-level electrical and optical signals
to scan the cervix. The response is measured, and computer-based expert system software is
then used to classify the tissue response, by comparing the signals with those stored in a
computer database representative of the range of cervical tissue types.1,2
If the tissue is abnormal, the TruScreen technology will allow the clinician to immediately
make management decisions and communicate these decisions to the patient. Therefore it
may minimise the labour intensive follow-up and lessen the chance of a patient being lost to
recall.
The TruScreen is composed of a handpiece connected to a compact processing and
interpretation console with disposable single use only sensor. The tip of the probe, which is in
contact with the cervix, scans the tissue by repetitively pulsing it with low levels of optical
and electrical energy. Real-time interpretation of the cervix tissue response is achieved by
automatic comparison with a digitally stored catalogue of tissue signatures.
The TruScreen is mains powered with approved patient isolation, delivers several electrical
pulses for a duration of approximately one third of a second. Fifteen pulses are delivered per
observation, and fourteen observations are made per second. These very low energy pulses
are below normal sensation thresholds.
The TruScreen optical measurements operate within the visible and near infrared spectrum.
The light emitting diodes (LEDs) have a power output range of 7-130 microwatts. The light
intensity is far below that of the colposcope. Four LEDs are used to emit light at three
discrete wavelengths. The LEDs operate for approximately one hundredth of a second, once
per observation, and approximately 14 observations are made per second.
Quek SC, Mould T, Canfell K, Singer A, Skladnev V and Coppleson M, The Polarprobe - Emerging technology
for cervical cancer screening. Ann Acad Med Singapore 1998: 27; 717-721.
2
Coppleson M, Canfell K and Skladnev V, The Polarprobe - An instantaneous optoelectronic approach to
cervical screening. CME Journal Gynecol Oncol 2000: 5(1); 31-38.
Page 9 of 39

The handpiece of the TruScreen is a long, thin, pen-shaped instrument approximately 310 mm
in length, which is hand-held by the operator. The section of the probe that enters the vagina is
less than 150 mm in length with a tip diameter less than 7mm. The tip is used by the operator
to scan the cervix during the TruScreen examination.
A disposable sheath or Single Use Sensor (SUS) covers the handpiece, and this sheath is
discarded after use. This handpiece is part of the TruScreen device. For diagrams and
technical specifications please refer to the TruScreen Cervical Cancer Screening System user
training manual and the TruScreen cervical screening system, operators manual.
TruScreen was granted regulatory approval (CE Marking) by the European regulatory
authorities in 2014, as a screening instrument for the detection of cervical pre-cancer and
cancer.
2.2
RISK BENEFIT ANALYSIS
The risks and benefits of the TruScreen test procedure have been assessed. The investigators
participating in this trial will be fully trained in the use and interpretation of the TruScreen
system prior to being involved in this trial.
Investigators will be required to fully explain the procedure, potential risk, discomfort and
potential benefits prior to witnessing the patient sign informed consent. The safety data
associated with the TruScreen System is outlined below:
Testing has been performed to minimise the risk associated with the use of the system.
Foreseeable risks associated with the use of the system are cervical abrasion and minor
bleeding, and infection. Clinical evaluation of the TruScreen has involved testing of several
thousand patients in the UK, Australia, Singapore, The Philippines, Russia, South Korea,
China and Brazil. No major patient complications were noted in this population. The
following effects were noted in a small number of patients: minor abrasion and bleeding,
patient anxiety and discomfort (consistent with the level associated with the Pap Smear test).
A survey of 152 women was conducted to examine their reaction to being tested with the Pap
smear and with the TruScreen.3 The TruScreen was associated with less anxiety and fewer
after effects such as bleeding and discomfort. Of the tested population, 82% preferred the
TruScreen to the Pap Smear, 16% did not care, and 2% preferred the Pap smear.
Within this trial, all patients will receive TruScreen followed by +/- Pap smear, ThinPrep,
HPV DNA sampling, VIA, colposcopy and biopsy, pelvic examination and appropriate
investigations according to best local clinical practice. Patient care will not be based solely
on the results of the TruScreen test performed in the trial as in Figure 1.
The risks associated with the TruScreen Single Use Sensor (SUS), have also been discussed
and addressed. These are covered in the technical report Risk Analysis Cervix Digital
System Frontview and Single Use Sensor (SUS). Truscreen Document P00000724. Use of
the SUS introduces no additional risks than those associated with the TruScreen, discussed
previously.
3
Mould TAJ, Quek SC, Lovegrove J, Gallivan S, Singer A, The acceptability of cytological screening for
cervical cancer compared to a new electronic screening device - the Cervix Digital System. Proceedings of the
EUROGIN Third International Congress, March 1997.
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In view of the above factors, patient risk is considered to be of a low level when compared to
routine colposcopic examinations.
2.3
BENEFITS/JUSTIFICATIONS
The major potential benefits resulting from the use of the TruScreen include its use
as a primary screening tool,
as an adjunct to the Pap Smear, incorporated as part of the screening triage,
as an adjunct to HPV testing, incorporated as part of the screening triage.
The TruScreen can provide patients with an instantaneous result eliminating the waiting time
and consequent patient anxiety associated with the current Pap smear screening system.
TruScreen can also improve cervical screening practices in developing countries, where Pap
smear is not readily available. The benefits of using the TruScreen includes reduced cost, no
need for supporting infrastructure and most importantly an instantaneous result that will
enable patient management and treatment options to be discussed and possibly completed
within the same visit.
The Single Use Sensor (SUS) provides the convenience of a disposable sleeve, eliminating
any risk of cross contamination between patients. One SUS is used per patient.
2.4
COMPLIANCE WITH THE PROTOCOL
The sites undertake that the trial will be conducted in compliance with the protocol, GCP and
applicable local and international regulatory requirement(s) as outlined in their Memorandum
of Understanding. If the site does not comply with the protocol or signed agreements,
Truscreen reserves the right to terminate the agreement with the Principal Clinician and/site.
Appropriately trained Truscreen personnel may perform the trial monitoring, e.g., Clinical
Implementation Team particularly during the first stages of the trial and during the trial. They
will check for the accuracy and completeness of data collected during the trial.
2.5
DESCRIPTION OF THE POPULATION TO BE STUDIED
The women studied will be over the age of 18 and under the age of 65 who meet all of the
inclusion and none of the exclusion criteria who attend the clinic for general routine cervical
screening.
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2.6
SUPPORTING DOCUMENTS
Canfell K, Clinical Investigation Plan: Cervix Digital System Performance Evaluation and
Development Studies. Truscreen Document K0000044.
Canfell K, Evans J, Nassar N, Clinical Protocol: Frontview Reusable Cervix Digital System
Evaluation and Development Study. Truscreen Document K0000001.
Coppleson M, Reid BL, Skladnev VN and Dalrymple JC, An Electronic Approach to the
Detection of Pre-Cancer and Cancer of the Uterine Cervix: A Preliminary Evaluation of
Polarprobe. Int J Gynecol Cancer 1994: 4; 79-83.
Jeronimo J, Schiffman M, Colposcopy at the Crossroads. American Journal of Obstetrics and
Gynaecology. 2006 Volume 195 Edition 2 pages 349 - 53
International Standard IEC 60601-1. Medical Electrical Equipment - General Requirements
for Safety.
Mould TAJ, Quek SC, Lovegrove J, Gallivan S, Singer A, The acceptability of cytological
screening for cervical cancer compared to a new electronic screening device - the Cervix
Digital System. Proceedings of the EUROGIN Third International Congress, March 1997.
Ling B & Heikkinen S, Work Instruction: Cleaning and Handling Procedures for Cervical
Handpieces and SUS Units Returned from a Clinical Environment. Truscreen Document
K0000049.
Wunderman I, Coppleson M, Skladnev V and Reid BL, Polarprobe: A Precancer Detection
Instrument. J Gynaecol Tech 1995: 1; 105-10.
TruScreen cervical screening system Operator's Manual P0001689.
3.
TRIAL OBJECTIVES AND PURPOSE
The objectives of the trial are:
1. To allow clinicians to gain real world experience in the use of the TruScreen system as a
general routine screening tool in their health care environment.
2. To collect additional information and evaluate the results of the TruScreen system in
expanded patient populations.
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4.
TRIAL DESIGN
4.1
DESCRIPTION OF THE TRIAL
TruScreen will be used to assess women who attend the clinic (listed attachment F section
1.7) for routine general cervical screening. The trial will give clinicians 'real world'
experience using the device in the their hospital and healthcare environment. This trial also
enables the sponsor to collect additional information to evaluate the results of the TruScreen
system in expanded patient population.
Examination of all the enrolled women will follow best local clinical practice for general
routine cervical screening. All patients will receive TruScreen examination immediately after
vaginal speculum insertion, then +/- Pap smear, ThinPrep, HPV DNA sampling, VIA,
colposcopy and biopsy, pelvic examination and appropriate investigations according to best
local clinical practice. The TruScreen examination may add 1 - 2 minutes to the total
procedure time (Figure 1).
The clinical management and treatment of the patient will proceed based on the patients
general and gynaecological history, presenting signs and symptoms, physical and
gynaecological examination, and results of investigations, as the clinician deems appropriate.
4.2
PATIENT WITHDRAWAL
The clinician may terminate a patients participation in the trial if he/she determines that it is
not in the best interest of the patient or the patient is non-compliant with the trial
requirements. Participation is entirely voluntary and a patient can withdraw at any time. This
will not affect the patients medical treatment or their relationship with practice or the
hospital. If a patient chooses to withdraw from the trial, all data collected will be analysed up
into the point that the patient withdrew their consent.
4.3
ACCOUNTABILITY PROCEDURES
4.3.1 SUS UNITS

During normal clinical practice, each SUS unit must be discarded immediately after use and
disposed of as biohazard waste. Each site is to follow their standard infection control
procedures. The materials used in the manufacture of the SUS are pliable, which ensures that
sharp edges are not formed as a result of routine handling. Thus, disposal in a 'sharps'
container is not required. While it is not intended that the used SUS should be returned to
Truscreen for ongoing research and development, if this is becomes necessary, Truscreen will
advise how decontamination according to infection control guidelines (Truscreen document
K0000049) shall undertake prior to any SUS being returned.
Each SUS unit is packaged in a pouch. The manufacture date is stamped on the pouch and the
expiry date is to be checked prior to use (Attachment D). As an additional measure, the body
and cord of the handpiece shall be cleaned using a neutral cleaner/hospital grade disinfectant
(such as Viraclean) and lint-free cloth at the beginning and end of each clinic session. For
correct fitting and removal instructions for the SUS, refer to the TruScreen Cervical Cancer
Screening System operator's manual (P0001689).
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4.3.2 PATIENT ID
A unique identification (ID) code is allocated for each consented patient at each site. This ID
code will be based on the site number (two digit code allocated by Truscreen Clinical
Implementation Team) and a three digit sequential number from the Master Subject Log.
There will be no duplication of numbers, once a number has been allocated (even if the
patient withdraws), this number is not reused. The ID number will always be five digits. The
clinician will maintain the Master Subject Log, a list linking the names and addresses of
participating women to the patient ID code and the SUS serial number. Truscreen will not
collect copies of the Master Subject Log. . The clinician will file the Master Subject Log in
the Investigators DF which can be reviewed by authorised persons and the Clinical
Implementation Team. The clinician will refer to the Master Subject Log, to link the
histology and cytology results with the correct patient ID.
If available at the time, the results will be entered in a web based data entry form available to
participating sites. This software will be accessible using password protection and will be
encrypted for security. No patients names will be included, only the ID numbers.
The TruScreen report may be encrypted (see Attachment F for site-specific details). If
encrypted the principle investigator will be given the tools to decrypt. In addition, the result
can automatically be decrypted in the web-based data entry form or by submission to
Truscreen.
4.4
SOURCE DATA.
The source data (paper or electronic) includes and is not limited to the information contained
in original records and certified copies of results, observations or other facets required for the
reconstruction and evaluation of the trial. There is no direct data capture into the CRF.
Recruitment can commence when Green Light" has been obtained. Green Light is a
document issued from the Clinical Implementation Team at Truscreen to confirm that all the
training, documents, equipment and approvals have been obtained from the relevant
institutions. Once "Green Light" been obtained all patients whom cervical screening is
indicated should be included in the trial until the site has achieved the number as agreed in the
Memorandum of Understanding or as negotiated with the Clinical Implementation Team at
Truscreen.
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5.
SELECTION CRITERIA
The TruScreen is designed as a primary cervical screening device, and therefore the entry
criteria for this trial specify a broad cross-section of woman in the general screening
population. Clinicians are requested to include women to whom they would normally
perform general cervical screening. Once the site has started the trial all women to whom
general cervical screening is indicated should be included, until the site has completed the
target number. The site will perform the assessment, diagnosis and management of the
women according to best local clinical practice for management of their patient.
5.1
INCLUSION CRITERIA
The patient must meet the following criteria to enter the trial:
1. Able to understand the conditions of the trial.
2. Willing and able to sign the patient information sheet and consent form.
5.2
EXCLUSION CRITERIA.
The clinician is asked to confirm that the woman does not have any of the following exclusion
criteria:
1. Under the age of 18 and over the age of 65 years,
2. Recent (<6 weeks) Pap smear;
3. Current menstrual period with heavy flow (days 1-3);
4. Known to be pregnant or less than 4 months post-delivery;
5. Received surgical treatment to the cervix in previous 3 months (including punch biopsies);
6. Previous hysterectomy (corpus and cervix);
7. Receiving experimental photodynamic therapy or otherwise exposed to photosensitive
drugs, or suffering from a photosensitising disease (eg, porphyria, lupus erythematous);
8. Has received radiotherapy treatment in the pelvic region at any time previously;
9. Receiving chemotherapy, or has received chemotherapy within the last 5 weeks.
10. In the past three months and currently participating in any other clinical trial or trials other
than epidemiology studies.
6.
TREATMENT OF PATIENTS
Women will generally be attending for a general routine gynaecological screening and/or
pelvic examination. The patient will be given the patient information sheet and the consent
form. If they agree to participate in the trial, the informed consent process will be performed
by the clinician according to GCP guidelines. The patient will be given a copy of the patient
information sheet and consent form to take home with them. Patients will then receive a
TruScreen examination immediately after vaginal speculum insertion, then +/- Pap smear,
ThinPrep, HPV DNA sampling, VIA, colposcopy and biopsy, pelvic examination and
appropriate investigations according to best local clinical practice (Figure 1).
All tests and examinations (cytology and histology) may be performed according to routine
procedures and best local clinical practice. Practices with a colposcope available (or ready
access to referral colposcopy) may be preferred for the trial. If a patient undergoes a
colposcopy examination, biopsy should be performed as clinically indicated (with image
capture if available) and in accordance with the routine optimal management of the patient.
The clinical procedures for participating general screening institutions are summarised in
Figure 1.
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The patient management procedures may follow the following sequence:
Description of the trial and invitation to participate.
Inclusion/exclusion checklist.
Explanation and collection of the patient's written informed consent. Documentation of
the consent process in the patients clinical records or hospital notes.
Medical history and review of coexistent diseases and concomitant medications.
TruScreen examination.
Pap smear, ThinPrep, and/or HPV DNA sampling (according to best practice).
Colposcopy and acetic acid/iodine staining.
Image capture pre biopsy (if available)
Colposcopically directed punch biopsy, if clinically indicated. Document procedure.
Record colposcopic impression.
Image capture post biopsy (if available).
Record any adverse events or complications.
6.1
TRUSCREEN EXAMINATION
The TruScreen examination will be generally performed using the documented spot probing
technique (Attachment E).
1. Excessive discharge or mucus may be removed prior to the commencement of probing.
However, the technique used should ensure that the tissue of the cervix is not traumatised.
Suitable techniques may include dry swabbing with gauze or cotton, removal of mucus
with ring forceps, or a gentle saline wash.
2. The cervix should be probed in two areas - the posterior and the anterior.
3. A "spotting" technique should be used. The handpiece should be placed on a spot on the
surface of the cervix at an appropriate angle and with sufficient pressure so that good
tissue contact is achieved. The handpiece should be held in place for approximately 2
seconds (30-40 observations). The prompts given on the handpiece monitor should be
used by the operator as a guide to moving the handpiece to the next spot.
4. The probing method (attachment E) should be performed with the operator progressing
from one side of the cervix to the other, and moving by one probe diameter from one spot
to the next. This method should be repeated until the first half of the cervix is tested, then
be repeated on the remaining half of the cervix.
5. It is important that spot measurements are not overlapped.
6. It is important that the entire cervix is covered not just areas that look abnormal to the
naked eye
If the TruScreen result is abnormal ie pNorm <0.5 (attachment D) the patient will have a
Colposcopy examination following the collection of the cytology sample. If clinically
indicated a biopsy may be taken at that time.
If the TruScreen result is normal ie pNorm >0.5, the participating site will follow normal
clinical practice and wait for the cytology result.
Page 16 of 39

Following the receipt of the cytology result, if the result is ASCUS (Atypical Squamous
Cells of Undetermined Significance) or above, the patient will need to be recalled and the
patient will have a Colposcopy examination. If clinically indicated a biopsy will be taken
at that time also. Any additional testing normally done in this situation by the
participating institution should continue to be followed.
If the cytology result is normal normal clinical procedure should be followed this
likely to be no further treatment.
The clinician performing the TruScreen examination will write the ID code on the Master
Subject Log. In addition, the clinician will peel off the unique SUS serial number stickers
from the SUS packet (Appendix D) and affix label B to the CRF in the allocated space and
label C to the TruScreen print out. The TruScreen print out becomes source data.
Once all information and reports have been collated each CRF will be checked for
completeness, signed by the clinician and returned to the Sponsor. The CRF may be emailed
or faxed back, as arranged with each site.
If according to local best practice, the following tests (including and not limited to) may be
performed:
PAP SMEAR
A Pap smear may be collected following the TruScreen examination. A conventional and/or
ThinPrep (liquid cytology) Pap Smear/s may be obtained. Cytological sampling will follow
standard hospital clinical procedures. The results of the Pap smear may be recorded on the
CRF pages.
HPV DNA TESTING
HPV DNA testing may be performed following the TruScreen examination. The sites are to
follow standard hospital clinical procedures; the HPV DNA test may be performed in
conjunction with the ThinPrep test.
The use of HPV DNA testing for patients with an abnormal Pap smear diagnosis may provide
clinicians with added information as to the individual patient's risk of developing invasive
disease. This result can also aid in the determination of follow-up protocols. Written
information and a verbal discussion regarding the HPV testing will be provided to each
patient before informed consent is obtained. The significance of the result to clinical
management will be at the decision of the clinician. The HPV DNA test result may be
recorded on the CRF.
6.2
COLPOSCOPIC PROCEDURE
At the end of the probing session and after the Pap Smear has been performed (if required), a
colposcopy may be performed (at this visit) or depending on the results the patient may attend
for a follow up visit. For sites where image capture is available, an image of the cervix may
be taken prior to a biopsy.
Page 17 of 39

6.3
BIOPSY PROCEDURE
The clinician will determine how many biopsies are appropriate. In most cases in which an
abnormality is observed colposcopically, multiple punch biopsies may be appropriate. In
cases where biopsies have been taken from suspected abnormal areas, the biopsy findings
may be used to confirm the colposcopic assessment for comparison of the TruScreen results.
If separate analysis is to be done for each biopsy, each sample will be clearly numbered and
the location of each numbered biopsy site will be entered onto the CRF. Each biopsy may be
reported separately by the histologist and recorded in the relevant fields of the CRF. This will
allow direct correlation between the histology and colposcopy results. Following a biopsy of
the cervix, the clinician is asked to stop the bleeding by holding a swab on the biopsy site for
10 seconds. Then take a post biopsy image before the bleeding starts again. The images
should be made available to the sponsor/third party independent review upon request.
Multiple biopsies should be encouraged.4
Several separate analyses of the histopathology samples may be performed. This may vary
between sites depending on the individual requirements of each. The histopathologist at the
local laboratory will receive the clinical information recorded on the accompanying pathology
request form (however, the histopathologist will not be provided with the results of the
TruScreen examination).
Following analysis at the local laboratory, the slide/s may be transferred to an independent
laboratory and identified with an indexing number only. The independent histopathologist
may not be given any clinical information about the patient. In each case, the overall patient
histology result for each patient will be considered to be the highest-grade diagnosis from any
of the biopsies taken from the same patient.
Clinicians will be asked to complete and return to Truscreen the CRF for each patient, with
the results of the investigations performed including and not limited to TruScreen, Pap smear,
Colposcopy and histology (Attachment A). The CRF may be emailed or faxed back, as
arranged with each participating site.
7.
ASSESSMENT OF EFFICACY
Examination of all the enrolled women will follow standard clinical protocol for a pelvic
examination, with the inclusion of a TruScreen examination immediately after vaginal
speculum insertion and prior to colposcopic assessment. The TruScreen examination will add
1 2 minutes to the total procedure time. The suggested technique is described in the
TruScreen Cervical Cancer Screening manual.
The image (attachment D) shows the location of the pNorm value on the verbose report
printed following completion of the TruScreen examination. This result may be a number
between 0 and 1 (4 significant figures) or a 3-letter code if encryption is being used (see
Attachment F Site specific details). If encrypted, the letters are case sensitive and must be
transcribed or entered on data forms exactly as it is printed on the report. This result will be
recorded on the CRF and will be analysed for reporting in the final study report.
Jeronimo J, Schiffman M, Colposcopy at the Crossroads. American Journal of Obstetrics and Gynaecology.
2006 Volume 195 Edition 2 pages 349 - 53
Page 18 of 39

8.
ASSESSMENT OF SAFETY
Cytology and histology will be carried out according to established procedures at the sites.
The Bethesda system of classification will be used for the reporting of cytology results on the
CRF (Attachment A). Once a patient undergoes a TruScreen and colposcopy examination, a
biopsy should be performed as clinically indicated and in accordance with the routine optimal
management of the patient.
The sites will send the completed CRFs to the sponsor within 7 days of the patient's visit. The
Cytology and histology results should also be sent to the sponsor and within 7 days as agreed
in the Memorandum of Understanding. The sponsor will provide updates on a regular basis to
the TruScreen Medical Advisory Committee.
The CRFs are to remain on site until all the data queries have been resolved and the database
is locked. Archiving can be completed when the final study report has been released.
8.1
ADVERSE EVENTS
All complications or adverse event (AE) will be recorded and documented in the patient's
clinic or hospital notes and then recorded on the CRF, whether or not they are related to the
use of the TruScreen. The patient's clinic or hospital notes will include the event
name/diagnosis, start and stop date, the medical intervention prescribed, and relationship to
investigational device. AE reporting will follow the normal post-marketing surveillance
channels as customary in the country involved according to the Memorandum of
Understanding.
8.2
SERIOUS ADVERSE EVENT
A Serious Adverse Event (SAE) is:
Any untoward medical occurrence that:
Results in death,
Is life-threatening, (NOTE: The term "life-threatening" in the definition of "serious" refers
to an event/reaction in which the patient was at risk of death at the time of the
event/reaction; it does not refer to an event/reaction which hypothetically might have
caused death if it were more severe)
Requires in patient hospitalisation or prolongation of existing hospitalisation,
Results in persistent or significant disability/incapacity,
Is a congenital anomaly/birth defect, or;
Is a medically important event or reaction.
Medical and scientific judgment should be exercised in deciding whether other situations
should be considered serious, such as important medical events that might not be immediately
life-threatening or result in death or hospitalisation but might jeopardise the patient or might
require intervention to prevent one of the other outcomes listed in the definition above.
Examples of such events are intensive treatment in an emergency room or at home for allergic
bronchospasm, blood dyscrasias or convulsions that do not result in hospitalisation.
Page 19 of 39

The follow up of the SAE will be according to Australian Medical Devices Guidelines
http://www.tga.gov.au/docs/pdf/devguid1.pdf (a copy is located in the Investigator DF). In
the case of any serious adverse effects (SAE) or complications reported by patients or noted
by the attending clinician attributable to the use of the TruScreen, or in the unlikely event that
a patient dies, the event must be reported to the Clinical Implementation Team within 48
hours, and reported to the HREC if applicable.
9.
STATISTICS
All patients will have a TruScreen examination followed by +/- Pap smear, ThinPrep, HPV
DNA sampling, VIA, colposcopy and biopsy, pelvic examination and appropriate
investigations.
The analysis will include sensitivity calculation of the TruScreen, which may be compared to
abnormal Pap smear. Each patient will have the pNorm recorded from the TruScreen
examination this is made possible through the use of the verbose report and/or encryption.
The TruScreen Medical Advisory Committee can ask for the trial to be put on hold or
terminated for safety reasons. Truscreen as the sponsor has the right to terminate the study at
any time. Notice of termination and an explanation will be provided in writing to the
Principal Clinician and the HREC, or equivalent at participating sites.
10.
DIRECT ACCESS TO SOURCE DATA/DOCUMENTS
The sponsor will be responsible for monitoring the trial and maintaining contact with the site
during the course of the trial to monitor progress, review the clinical data, and help with any
queries or problems.
The investigator will permit the sponsor and/or agent from the relevant regulatory authority or
appointed member from the HREC, or equivalent, if requested, to inspect all case record
forms and corresponding portions of the study patients' original office and/or hospital records.
The Clinical Implementation Team responsible for the on-site surveillance may check the
CRF pages for accuracy and completeness and corresponding portions of the study patients'
original office and/or hospital records. All CRF pages will be collected and accounted for in
the analysis of the trial. The site will assist in ongoing data analysis by sending a copy of the
full verbose report to the sponsor.
11.
QUALITY CONTROL AND QUALITY ASSURANCE
This trial has been reviewed and approved by the Quality Assurance Officer and the
TruScreen Medical Advisory Committee at Truscreen.
12.
ETHICS
HREC approval for the trial should be obtained as required at each site. It is the responsibility
of Participating Project Partner in the Memorandum of Understanding to obtain HREC
approval, if required. The advice of the principal clinician will be sought in each case even if
the HREC does not feel entitled to deal with the trial; documentation of this decision is
needed.
Page 20 of 39

The following documents are filed in the investigator DF. The trial will be conducted in
accordance with the guidelines as set down in the:
Declaration of Helsinki (http://www.fda.gov/oc/health/helsinki89.html.)
National statement on Ethical conduct in Research involving Humans
(http://www.nhmrc.gov.au/publications/synopses/_files/e35.doc)
Note for Guidance on Good Clinical Practice
(http://www.tga.gov.au/docs/pdf/euguide/ich/ich13595.pdf)
The patient information sheet and consent form must be printed on the participating site
letterhead. Each page of this document should be numbered and the original signed and dated
document be filed in the Investigator DF supplied at the beginning of the trial by Truscreen. A
sample patient information sheet and consent form is available in Attachment B.
Women will be recruited within the gynaecology outpatients clinic. TruScreen technology
and the familiarisation trial will be explained by the clinician to the potential participant. The
potential patient will be given the patient information sheet and consent form to read. If the
woman agrees to participate, she will be asked to sign and date the patient information sheet
and consent form, the original will be filed in the Investigator DF and a copy will be given to
the patient to keep. Patient confidentiality will be preserved, all personal data will be deidentified and no patient names will be included on the CRF.
13.
DATA HANDLING AND RECORD KEEPING
For each patient the following data will be accessed from the source documents for recording
onto the CRF.
Demographic data Patient ID, age.
Assessment of signs and symptoms at visit.
Any concurrent therapy given.
+/- Pap Results (Bethesda classification).
TruScreen data including serial number of SUS used (SUS label B), pNorm value and
number of spots collected.
Colposcopy findings +/- biopsy results.
Adverse Events, outcome and resolution.

Once all information and reports have been included, each CRF will be checked for
completeness, signed by the clinician and returned to the Sponsor.
The sponsor may send data queries to the site. The site should answer the query within 7
working days. The site will fax the resolved data query to the sponsor, then file the original
signed data query in the patients CRF. The resolved data query becomes a CRF page. The
resolved data queries together with the original CRF will be collected/sent to the sponsor at
archiving.
All patient files and other trial records will be retained by the investigating institution and the
sponsor for a minimum period of fifteen years.
Page 21 of 39

14.
FINANCING AND INSURANCE
The participating site will not charge the patients for the TruScreen screening. The cost of the
test will include the use of the TruScreen Single Use Sheath (SUS). The SUS is a hightechnology sheath provided for one time use to protect against patient cross-infection.
Participating sites in the Trial described in this document will be offered the SUS and supplied
equipment free of charge by agreement between the local Distributor and Truscreen Ltd. The
agreement includes with the return of the completed CRF, as contracted in the Memorandum
of Understanding for each site. Operator training and customer support will be agreed by the
local distributor and Truscreen prior to trial start up.
15.
PUBLICATION
Within three months of the last patient out of the trial, the Trial Chairman will make available
a draft of the trial analysis. Within four months of the last patient out, the Trial Chairman or
appointed representative will present the final trial report to the Truscreen TruScreen Medical
Advisory Committee. The report would also include all reported SAEs as laid down in the
SAE forms.
Since the trial may provide information on the use of the product in day-to-day medical
practice in a large population of patients, publication of the results will be of interest to other
members of the medical profession as agreed in the Memorandum of Understanding.
Patient results in the trial may be reported/disclosed (in a manner that will not identify
individual patients) to Truscreen authorised personnel, regulatory agencies worldwide and in
medical literature and scientific papers.
Page 22 of 39
Figure 1. - Clinical Procedure

Perform TruScreen
Examination
TS pNorm
<=0.5
Abnormal
1
TS
pNorm>0.5
"Normal"
Conduct +/-Pap,
ThinPrep and/or HPV
DNA sampling, VIA(if
to be performed).
Colposcopy, +/- biopsy as
clinically indicated,
Perform pre and post biopsy
images (prn),
Record findings.
Wait for cytology

results to be
returned
If cytology result is
ASCUS or above
Wait for cytology

results
If cytology is
within normal
limits,
Colposcopy +/- biopsy

if clinically indicated
Perform pre and post
biopsy images (prn),
Record findings.
Complete CRF and
send to PLT.
Within 7 days
Page 23 of 39
ATTACHMENTS
ATTACHMENT A- CASE REPORT FORM
General Screening Project K000110
Page 24 of 39
Patient ID
Case Report Form
The evaluation of Truscreen in Cervical Cancer Screening.
(Please complete in blue or black pen)
Date:
OFFICE USE ONLY
day
month
year
Date Received:
Patient ID:
Date Entered:
Hospital Name:
Investigators Name:
Protocol No:
Entered By:
Checked
By:
Folder No.:
Tape No:
K0000110
PART 1: PATIENT ENTRY CRITERIA

Please confirm by ticking ALL boxes:
Pt has been informed of the study, has signed the patient information sheet & consent form.
Copy of the information sheet and consent form given to the patient.
Aged Between 18 and 65 years of age
Has not had a Pap Smear within 6 weeks of this visit.
Not currently menstruating with heavy flow (day 13)
Not known to be pregnant OR less than 4 months post-delivery
No previous hysterectomy (corpus and cervix)
No surgical treatment to cervix in last three months (including punch biopsies)
Not receiving photodynamic therapy; or exposed to photosensitising drugs; or suffering a
disease causing photosensitivity.
Not received radiotherapy treatment in the pelvic region at any time previously
Not receiving chemotherapy, or has not received chemotherapy within the last 5 weeks
In the past three months and currently not participating in any other clinical trial or projects
other than epidemiology studies.
PART 2: PATIENT HISTORY

2.1 Date of Birth:
/
day
/
month
2.2 Race:
Caucasian
African Descent
Asian Oriental
2.3 Post Menopausal:
no
yes
2.4 Any post-coital

bleeding?
no
yes
year
Asian Indian
Hispanic
Polynesian
Other
(specify)
Page 25 of 39
Patient ID
2.5 Any Vaginal Discharge
that bothers you?
no
yes
PART 2: PATIENT HISTORY (cont)

Has Patient ever had a previous abnormal
Pap smear (prior to this trial)?
2.6 Presenting Pap Smear
no
yes
uncertain
If Yes, Specify most recent Pap smear result: (Bethesda)
Result.................................
Month
(tick ONE box most recent treatment only)

none/unknown
punch biopsy
loop excision
cone biopsy
ablation - cryosurgery, electrocautery, laser
other
2.7 Tick previous biopsy /

treatment to uterus or
cervix?
Conventional Pap Smear

ThinPrep Pap Smear
Split Sampling (sampling for more than one test)
2.8 Which test was used for

cytological analysis?:
PART 3: TruScreen EXAMINATION

3.1 Is the TRUSCREEN
operator the Clinician?
yes
no specify TRUSCREEN Operator Name:
yes
3.2 Mucus/Discharge
present prior to
probing:
not removed
with swab
with ring forceps
no
3.3 Was there any blood

present prior to
probing:
none
minor bleeding
major bleeding
Attach label or write down Lot & Serial No of the SUS used
3.4 Details of handpiece

used:
Lot No:
Serial No:.
Confirm the SUS was discarded following use.
Page 26 of 39
Year
Patient ID
PART 3: TruScreen EXAMINATION (cont)
pNorm Result_____________________
Encrypted Result__________________
3.5 Results
Number of spots
Algorithm Version Number__________
3.6 Were there any

complications or
observations related to
the use of TRUSCREEN?
no complications
(tick ALL applicable boxes)
minor bleeding
major bleeding
minor discomfort
major discomfort
other
PART 4: COLPOSCOPIC EXAMINATION

4.1 Was a colposcopy performed at this session?
no
yes
4.2 Colposcopy Results Original Colposcopic Impression:

Normal (absence of CIN)
Low Grade
HPV
Condyloma
CIN 1
4.2.1 Tissue Type:

(tick ALL cervical
tissue types seen
on cervix )
High Grade - CIN 2-3

Invasive
Additional
Comments
4.2.2 Transformation
Zone:
Polyps
Nabothian Cysts
Inflammation/cervicitis/contact bleeding
Atrophy
TZ fully Seen (satisfactory for diagnosis)

TZ not fully visible (Unsatisfactory for diagnosis)
Page 27 of 39
Patient ID
4.2.3 Final
colposcopy
diagnosis:
Normal
Low Grade
High Grade
Cancer
Unsatisfactory. Colposcopy examination could not be performed due to
Images captured.
PART 4: COLPOSCOPIC EXAMINATION

4.3 Was a punch biopsy performed?
4.4 Was any treatment performed?
no
yes number taken:
none
loop excision
cone biopsy
ablation (cryosurgery, electrocautery, laser)
hysterectomy
4.5 Comments (related to Colposcopic examination
Page 28 of 39
Patient ID
PART 5:BIOPSY EXAMINATION RESULTS.
5.1 Centre Name:
(centre where Histology performed)
5.2 Histology Reviewer:

5.3 Were clinical notes/patient
history supplied with this sample?
yes
no
Histology Slide/Accession Numbers:

Note: Biopsies are labelled numerically
as 1,2,3, etc. by the colposcopy clinic.
Ensure that the clinic labels correspond
with the slide numbers on this CRF.
Biopsy 1:
Biopsy 2:
Biopsy 3:
Biopsy 4:
LEEP
Cone
Biopsy
Punch Biopsy/s
(Numbered)
Histology Results:
1
OClock position
(if available)
Unsatisfactory for
analysis
Acute cervicitis
Normal squamous
Normal columnar
Immature metaplasia
Mature metaplasia
Chronic inflammation
Other.
HPV
Atypia
Other
CIN I
Low grade glandular
Other
CIN II
CIN III
Microinvasive
Invasive squamous
High grade glandular
Subsequent
histology
following
treatment
Final Patient
Histology
Diagnosis
(consider all biopsies)
Date
/ /
Note: Tick ONE box only
Unsatisfactory
for Analysis
Acute
Cervicitis
Normal
HPV/Atypia
Low Grade
High Grade/
Invasive adenocarcinoma
Other
5.4
Comments (related to Diagnosis)
Page 29 of 39
Patient ID
Page 30 of 39
Patient ID
PART 6 ADVERSE EVENTS
Onset Date
Event
Intensity
Outcome
Stop date
Related to IP
Mild
Moderate
Severe
Recovered
Recovered
with sequelae
Still Present
Died
Not known
None
Unlikely
Possible
Probable
Definite
Mild
Moderate
Severe
Recovered
Recovered
with sequelae
Still Present
Died
Not known
None
Unlikely
Possible
Probable
Definite
Mild
Moderate
Severe
Recovered
Recovered
with sequelae
Still Present
Died
Not known
None
Unlikely
Possible
Probable
Definite
Onset date:
The date the adverse event began
Event:
Description of the event
Intensity:
Mild: No interference with functioning

Moderate: No significant interference with functioning
Severe: Significant interference with functioning
Outcome:
Recovered: Patient has made a full recovery.

Recovered with sequelae: Patient has recovered but there are some ongoing
problems that will never resolve
Still Present: Ongoing
Died: (SAE report required)
Not known: Patient has been lost to follow up and the outcome of the event is
not known
Relationship
to IP
None: There is no relationship to the investigational product (IP).

Unlikely: The relationship to the IP can not be excluded.
Possible: There is a plausible relationship to the IP.
Probable: There is reasonable sequence of events related to the IP.
Definite: There is no doubt the event is in relation to the IP
Page 31 of 39
Patient ID
PART 7 EQUIPMENT ISSUES AND OTHER OBSERVATIONS:
no
yes describe:
7.1 Any difficulties with data

collection equipment
7.2 Other observations or

comments:
I confirm that all the above data is correct.
Investigators Signature:
Date:
Day
/
Month
Year
Page 32 of 39
PATIENT INFORMATION SHEET

THE EVALUATION OF TRUSCREEN IN CERVICAL CANCER SCREENING IN
THE GENERAL SCREENING POPULATION
You have been asked to participate in this trial because we consider that you can help us in
our research to investigate TruScreen, a new device developed to screen pre-cancerous and
cancerous changes on the cervix (neck of the womb). It is anticipated that the TruScreen
screening may add one to two minutes of time to the normal gynaecology visit. TruScreen has
marketing approval in Europe and Australia.
TruScreen is composed of a probe-like handpiece with disposable single use sensor
connected to a small processing and interpretation unit. The handpiece, which comes into
contact with the cervix, uses very low levels of light and electricity to determine if the cells on
the cervix are normal or abnormal. The sponsor pays for the costs of your participation in the
TruScreen examination.
If you agree to participate in this trial, the examination will be carried out as follows. The
doctor who is carrying out the research will insert a speculum. A TruScreen handpiece with a
disposable tip will then be guided into your vagina and carefully moved over the surface of
your cervix to ensure the whole cervix is screened. This procedure takes 1 - 2 minutes and
you should have no discomfort from this. The TruScreen screening has been tested on more
than 10,000 women and no significant effects have been reported with the use of this
instrument. There has been some minor abrasion and bleeding in a few cases.
The TruScreen test plays no role in your diagnosis or treatment and you may not be given the
results of the test. Depending on the results of your routine examinations such as Pap smear
you may be recalled to the clinic for further investigations such as a colposcopy according to
established hospital guidelines.
As part of your routine examination, images of your cervix may be captured digitally and kept
on record. These images will not identify you in any way and may be made available to the
sponsor upon request. If your doctor recommends a biopsy of the cervix, you may feel some
discomfort when the biopsy is being taken and some pain similar to period pain. There may
be some spotting following the biopsy.
While we intend that this research trial furthers medical knowledge and may improve
detection of cervical abnormalities in the future, it may not be of direct benefit to you. It is
also a future prospect of the TruScreen to possibly improve cervical screening practices in
developing countries, where the Pap smear is not readily available.
Your data will be confidential and anonymous, and you will not be identified in any
presentation or publication that results from this trial. Your clinical data and results will be
held in a secure storage facility for at least fifteen years.
Participation in this trial is entirely voluntary, you are in no way obliged to participate if you
do participate you can withdraw at any time. Whatever your decision, please be assured that
it will not affect your medical treatment or your relationship with the medical staff. Only
your doctor will be aware of your participation or non-participation.
When you have read this information sheet, your doctor will discuss this with you further and
answer any questions you may have. This information sheet is for you to keep.
If you feel you have suffered by participating in this TruScreen trial, please contact Dr
____________ on telephone number __________.
Page 33 of 39
CONSENT FORM
THE EVALUATION OF TRUSCREEN IN CERVICAL CANCER SCREENING IN
THE GENERAL SCREENING POPULATION
1. I_______________________________________________________________agree
to participate as Patient in the trial described in the Patient Information Sheet.
2. I acknowledge that I have read and understood the Patient Information Sheet, which
explains why I have been selected, the aims of the trial and the nature and the possible
risk of the investigation. The statement has been explained to me to my satisfaction.
3. Before signing this Consent Form, I have been given the opportunity to ask any
questions relating to any possible physical and mental harm I might suffer as a result
of my participation. I have received satisfactory answers to my questions that I have
asked.
4. I understand that my decision whether or not to participate will not prejudice my
present or future treatment, or my relationship with the hospital, or any institution cooperating in this trial, or any person treating me. If I decide to participate, I am free to
withdraw my consent and to discontinue my participation at any time without
prejudice.
5. I agree that research data gathered from the results of the trial may be published,
provided that I cannot be identified.
6. I understand that if I have any questions relating to my participation in this research, I
may contact the trial doctor, Dr ____________ on telephone number __________,
who will be happy to answer my questions.
7. I acknowledge receipt of a copy of this Consent Form and the Patient Information
Sheet.
Patients Signature
_______________________ Date________________________
Please PRINT name _______________________

Investigators Signature_______________________ Date________________________
Page 34 of 39

ATTACHMENT C TRUSCREEN PRINT OUT
See over
page for
pNorn
location
Page 35 of 39
ATTACHMENT C TRUSCREEN PRINT OUT
Location of pNorm.
Alternatively, the result may
be encrypted to a case
sensitive 3 letter code
Page 36 of 39
ATTACHMENT D - SUS PACKAGE LABELLING (EXAMPLE)
Peal and stick onto

TruScreen print out
Peal and stick onto

CRF page
Page 37 of 39
ATTACHMENT E - PROBING PATTERN

During TruScreen examination, the following coverage patterns on the cervix, as shown
below, is recommended:
Follow the above pattern to probe the cervix, starting from the 9 o'clock position, on the
outer area ectocervix. Ensure full coverage of the anterior part of ectocervix.
Follow the pattern below to probe the posterior part of ectocervix.
Precautions
Do not overlap the spots too much
Probe to cover the entire cervix
Do not over-probe any ectropion (erosion) area
Page 38 of 39
ATTACHMENT F - SITE SPECIFIC DETAILS

1.1
SCHEDULE
MAR/2015:
APR/2015:
APR/2015:
MAY/2015:
JUN/2015:
NOV/2015:
DEC/2015:
Site selection.
Signing of Memorandum of Understanding
Registration of participating centres
TruScreen Training
Project Commences
Project Completion
Data analysis and final report.
1.3
AUTHORISED PROTOCOL SIGNATORIES.
The Project Chairman authorised to sign the protocol and amendments is:
1.4
MEDICAL ADVISER
The Medical Adviser for this project is:
1.7
SITE/S
It is anticipated that the project will involve a total of xxx patients the site as documented
below.
The participating site will be as follows:
7 ASSESSMENT OF EFFICACY
The console provided will give a VERBOSE report.
9 STATISTICS
Recruitment is anticipated at approximately XX patients per month from each site. This
sample size is expected to yield histologically acceptable for a primary outcome.
The analysis will include sensitivity calculation of the TruScreen compared to abnormal Pap
smear. The primary endpoint is the colposcopy and biopsy outcome. Each patient will have
the pNorm recorded from the TruScreen examination this is made possible through the use
of the verbose report.
Page 39 of 39

Truscreen Cervical Screening System

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Truscreen Cervical Screening System

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Truscreen Pty Limited.

Truscreen cervical screening system

KEYWORDS: Clinical trial, Accuracy, Evaluation, and General Screening Project

General Screening Project K000110 01

General Screening Project

1.2 Sponsor and Monitor

1.3 Authorised Protocol Signatories

1.4 Medical Adviser4

1.7 Participating Sites

1.8 Clinical Laboratories

2.1 Technical description the device

2.6 Supporting Documents 13

Trial Objectives and Purpose 13

4.1 Description of the Trial 14

4.3 Accountability Procedures

5.1 Inclusion criteria

5.2 Exclusion criteria

General Screening Project K000110 01

General Screening Project

6.1 TruScreen Examination 17

8.1 Adverse Events. 20

10 Direct access to source data/documents 21

13 Data handling and record keeping

14 Financing and insurance 23

ATTACHMENT A - CASE REPORT FORM

ATTACHMENT B - PATIENT INFORMATION SHEET AND CONSENT FORM

ATTACHMENT F - SITE SPECIFIC DETAILS 39

General Screening Project K000110 01

General Screeningl Project

General Screening Project K000110 01

General Screening Project

General Screening Project K000110 01

General Screening Project

General Screening Project K000110 01

General Screening Project

General Screening Project

General Screening Project K000110 01

General Screening Project

General Screening Project

General Screening Project

General Screening Project K000110 01

General Screening Project

General Screening Project K000110 01

General Screening Project

4.3.1 SUS UNITS

General Screening Project K000110 01

General Screening Project

General Screening Project K000110 01

General Screening Project

General Screening Project K000110 01

General Screening Project

General Screening Project K000110 01

General Screening Project

General Screening Project K000110 01

General Screening Project

General Screening Project

General Screening Project K000110 01

General Screening Project

General Screening Project K000110 01

General Screening Project

Demographic data Patient ID, age.

Assessment of signs and symptoms at visit.

Any concurrent therapy given.

+/- Pap Results (Bethesda classification).