Research Protocol
Prospective Collection of Normal Female Serum Specimens Used For In Vitro Diagnostic
Normal Female Research Study
Sponsor:
BD Diagnostics
Diagnostic Systems, TriPath Inc.
4025 Stirrup Creek Drive, Suite 400
Durham, NC 27703
Phone (919) 206-7132
Fax: (919) 572-6214
BD TriPath Protocol #: 2007-12
Authors:
Ananda Lal, Clinical and Research Trials Manager
Hema Doobay, Manager, Product Development
Date of Protocol:
December 27, 2007
The study will be conducted according to the protocol and in compliance with Good Clinical
Practice (GCP), with the Declaration of Helsinki, and with other applicable regulatory
requirements.
This document contains confidential information of BD Diagnostics, Diagnostics Systems TriPath
Inc. Do not copy or distribute without written permission from the Sponsor.
CONFIDENTIAL
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BD Diagnostics TriPath Inc.
PROTOCOL SIGNATURE SHEET
Prospective Collection of Normal Female Serum Specimens Used For In Vitro Diagnostic
Normal Female Research Study
(Protocol# 2007-12)
Principal Investigator Agreement
I confirm that I have read this protocol, I understand it, and I will follow the protocol as outlined. I
will conduct the study according to all applicable regulations, guidelines, and operational
procedures.
_______________________________________
Principal Investigator Name (printed)
_______________________________________
_________________
Principal Investigator Signature
Date
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I.
Introduction
BD Diagnostics, TriPath is conducting research to develop new screening assays for breast
and ovarian cancer. Serum from females ≥ 30 years of age is required for the development of
such assays.
The only risks to subjects participating in this protocol are those associated with a routine
blood draw. The information obtained from these studies may benefit others by providing a
better understanding of diagnostic assays and their potential to aid physicians in the
diagnosis and/or treatment of disease.
This study will be conducted in compliance with this protocol, Good Clinical Practices (GCP),
International Conference on Harmonization Guidelines (ICH), and the applicable regulatory
requirements.
II.
Objective
The objective of this study is to collect serum specimens from females≥ 30 years of age for
the use in research and development of new screening assays for ovarian and breast cancer.
III.
Eligibility Criteria
Inclusion Criteria

Non pregnant female donors ≥ 30 years of age with the following criteria:
-A total of 80 donors’ 30-50 years (should be evenly distributed across the range)
-A total of 170 donors’ ≥ 50 years of age

Female donors must be in good health and should not have received any kind of
cancer treatment (except skin cancer) in the past five years at the time of
enrollment.

Female donors must be HIV negative

Female donors must be Hepatitis B negative

Patient must read and complete Full-Length Donor History Questionnaire
(Attachment 2)
Exclusion Criteria

Donors with a history of heart, lung, or liver disease or who are pregnant will be
excluded.

Donors will be excluded if they are known to have engaged in behavior that put
them at risk of infection
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
Donors will be excluded if they received any kind of cancer treatment except skin
cancer in the past 5 years at the time of enrollment.
IV.

Donors will be excluded if they are on hormone replacement therapy.

Donors who are HIV and Hepatitis B positive will be excluded.
Expected Enrollment
Overall study goal: 500 normal blood donors
Total sites: at least 2
Individual site goal: 250.
The duration of the study will depend on the rate of enrollment. Accountability must be
maintained for all specimens collected and individuals enrolled into this study by the
designated sites.
V.
Study Design
Blood samples will be obtained from individual healthy donors at a specific location site. Four
to six blood samples (a total of 40 mls.) will be taken from each donor to yield approximately
20 to 30 mls. of serum according to the site’s standard phlebotomy procedures. Samples will
be processed according to instructions in Attachment 1.
VI.
Collection and Processing of Blood Specimens
Blood will be collected from healthy donors into BD Vacutainer® Serum Glass Tubes. The
tube type is listed in Table 1. Two different lot numbers of BD Vacutainer® Serum Glass
Tubes will be used for blood collection from 250 normal blood donors.
The BD Vacutainer® Serum Glass Tubes will be processed as described in Attachment 1.
Table 1: Blood Collection Tubes
Tube Type
Catalog Number
BD Vacutainer® Serum Glass
Tube
VII.
366430
16x100mm
Clinical Information Requested with each Serum sample
The healthy donors will read and complete Full-Length Donor History Questionnaire
(Attachment 2). Four to six tubes of blood (10mL each) will be collected in BD Vacutainer
Glass Collection Tubes from each healthy donor. Healthy donor serum samples will be
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provided to BD Diagnostics, Diagnostic Systems, TriPath with all the information listed in the
attached case report form (Attachment 3). CRFs will be reviewed for completeness,
legibility, and acceptability by BD Diagnostics, TriPath.
VIII.
Specimen Shipping
All collected serum specimens should be shipped on dry ice as needed to BD Diagnostics,
TriPath. When shipping, specimen must be packaged and labeled in compliance with
applicable state, federal, and international regulations governing the transport of clinical
specimens and infectious substances.
IX.
Patient Confidentiality
Participant identification will be strictly protected. Each specimen will be assigned a unique
identification number at Clinical Research Center for Cape Cod Inc. and only Clinical
Research Center for Cape Cod Inc. will be able to connect the identification number to the
study participant. No person from BD Diagnostics, TriPath Inc. will have any knowledge of
participant identity and BD Diagnostics, TriPath Inc. will not contact the study participants at
any time.
Samples and documentation with be labeled so that all samples and documentation are
clearly identified. The samples and clinical annotation will be provided without any patient
identifiers or any patient information. Samples and clinical information will be examined and
verified and Clinical Research Center for Cape Cod Inc. and BD Diagnostics, TriPath to
ensure that no patient identifiers remain.
The study participant can withdraw her sample from the study at anytime by notifying the
study doctor. If the sample has not been shipped to BD Diagnostics, TriPath, the sample will
be destroyed on site. If the sample has been shipped to BD Diagnostics, TriPath for testing, it
is the responsibility of the site staff to notify the sponsor to destroy the sample as per the
study participant wishes.
X.
Shipping
All collected serum specimens should be shipped on dry ice as needed to BD Diagnostics,
TriPath. When shipping, specimen must be packaged and labeled in compliance with
applicable state, federal, and international regulations governing the transport of clinical
specimens and infectious substances.
BD Diagnostics, Diagnostic Systems, TriPath will cover all costs associated with the shipping
of the samples and related information. Use FedEx Account (2646 2867 9) for shipping.
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Samples should be sent by overnight delivery to BD Diagnostics, Diagnostic Systems,
TriPath on dry ice. Shipments should be made when samples have been accrued.
Ship Attn. Ananda Lal
BD Diagnostics, Diagnostic Systems, TriPath
4025 Stirrup Creek Drive
Suite 400
Durham, NC 27703
XI.
Compensation
Please refer to Attachment 4.
XII.
Regulatory Requirements
IRB Approval
Prior to beginning the collection of any samples, the assigned Institutional Review Board
(IRB) will review and approve the protocol. A copy of the approval letter will be filed at the
site/medical center and BD Diagnostics, Diagnostic Systems, TriPath.
Protocol Changes
Changes to the study protocol may be made (i) in accordance with procedures outlined in the
study protocol, or (ii) by written agreement of the site investigators, site/medical center and
BD Diagnostics, Diagnostic Systems, TriPath. Changes to the study protocol are subject to
prior review and approval of the IRB.
Principal Investigator
Clinical Research Center for Cape Cod Inc. will supervise the portions of the study to be
conducted by the site/ medical center.
Regulations
Clinical Research Center for Cape Cod Inc., BD Diagnostics, Diagnostic Systems, TriPath
and the site/medical center shall comply with the study protocol and with all applicable laws,
rules, regulations and all other governmental requirements in the performance and
documentation of the study.
Informed Consent
Clinical Research Center for Cape Cod Inc. shall use the informed consent form approved by
the site/medical Center IRB to obtain informed consent from all subjects who participate in
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the study prior to their participation. Clinical Research Center for Cape Cod Inc. will not
request consent from any patient nor allow any patient to participate in the study prior to
receiving IRB approval and the IRB approved Informed Consent Form.
Use of Specimens in Clinical Trial Study
Since all specimens will be collected under an IRB approved protocol and informed consent,
it will be possible to include these specimens in a clinical trial study.
Reporting Requirements
Clinical Research Center for Cape Cod Inc. shall furnish all data resulting from this study to
BD Diagnostics, Diagnostic Systems, TriPath. Clinical Research Center for Cape Cod Inc.
shall keep BD Diagnostics, Diagnostic Systems, TriPath advised of the status of the study via
periodic reports. The frequency of reports shall be as agreed upon by the Principal
Investigator and BD Diagnostics, Diagnostic Systems, TriPath.
Conflict of Interest
Representatives at Clinical Research Center for Cape Cod Inc. represents and warrants that
neither they nor any member of his immediate family (defined as spouse and children) have
any real or perceived conflict of interest in the execution of the study (e.g. stock or other
equity in the BD Diagnostics, Diagnostic Systems, TriPath) and that participation herein does
not conflict with any other obligation to third parties.
Compliance with Legal Requirements and Medical Center Policies
Clinical Research Center for Cape Cod Inc. shall comply at all times with all applicable legal
requirements and all applicable site/medical center policies in performing the study.
Safety Rules, Programs or Services
Clinical Research Center for Cape Cod Inc. agree to comply and cooperate with the
implementation of any reasonable safety rules, programs or services that may be required by
site/medical center with respect to the conduct of clinical trials by site/medical center with
respect to the conduct of clinical trials at the medical center.
HIPPA
BD Diagnostics, Diagnostic Systems, TriPath and Clinical Research Center for Cape Cod Inc.
agree to comply with Site/medical center’s policies and procedures for complying with the
requirements of the Health Insurance Portability and Accountability Act of 1996 (“HIPPA”).
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Record Keeping
Clinical Research Center for Cape Cod Inc. will prepare and maintain complete and accurate
records in connection with this study. Clinical Research Center for Cape Cod Inc. will retain
such study documentation until notified by Company that the study documentation is no
longer required. Company will have the right to visit Clinical Research Center for Cape Cod
Inc. site to inspect records and review all study documentation upon reasonable notice.
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Attachment 1
Detailed Blood collection and Processing Procedure in BD Vacutainer® Glass and
Plastic Tubes
1. Blood Collection
1.1 Use BD Vacutainer no additive, red-topped glass collection tubes, catalog number
366430 or BD Vacutainer no additive, red-topped plastic collection tubes, catalog number
367820 for blood collection. Record the lot number of the blood collection tube on the case
report form
1.2
Draw a sufficient amount of blood to yield the required serum volume (two samples,
10ml each).
1.3 Do not refrigerate or freeze whole blood. Processing of whole blood to serum (section
2 below) should begin immediately after collection of blood.
2. Serum Preparation Procedure
2.1.
Place collection tube(s) upright in a rack and store at room temperature. Allow blood
to clot for a minimum of 60 minutes and not exceeding 90 minutes from time of
collection. Blood should be thoroughly clotted before centrifugation. Blood from
patients receiving anti-coagulant therapy (such as heparin or coumadin) may take
longer to clot. Record time allowed to clot on checklist.
2.2.
After blood is thoroughly clotted, balance collection tubes and centrifuge for 10
minutes at the rpm necessary to attain a force of 1300 g using either a swing-head
or fixed-angle centrifuge rotor.
To calculate the number of rpm necessary to attain 1300g, use the following
formula:
rpm = 10774/ √r
Where r, expressed in cm, is the radial distance from the center of the centrifuge
head to the bottom of the tube. For example if r = 15cm, rpm is approximately 2780.
Caution: prolonged centrifugation may cause hemolysis.
2.3.
Allow the centrifuge to come to complete stop before removing tubes. Remove
tubes carefully without disturbing the red cells at the bottom. Record centrifugation
parameters on case report form.
2.4.
Holding the collection tube(s) upright, carefully remove the stopper without
disturbing the cell pellet (s). Combine all sera for each donor into a labeled tube
using a disposable transfer pipette. Do not disturb the cell layer or allow any cells
into the pipette. If cells are disturbed, re-centrifuge specimen as described in 2.2 2.3. Do not pour the serum or invert the tube.
2.5.
Once sera for each specific donor is combined into one tube, mix by inverting tube
gently 5 times. Pipet 2 mL aliquot into labeled tubes and freeze at -70C –or colder.
Serum should not be stored at room temperature for more than 2 hours or at 2-8C for
more than 8 hours prior to freezing at -70C or colder. Frozen serum can be kept for
up to 3 months prior to shipping to Sponsor. Record storage conditions on case
report form.
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Attachment 2
Questionnaire for Healthy Donors
Yes
No
Are you
1. Feeling healthy and well today?
2. Currently taking an antibiotic?
3. Currently taking any other medication for an infection
Medications
1. Are you currently taking any medications?
If yes, list the medications:
In the past 6 weeks
1. Female donors: Have you been pregnant or are you pregnant now?
In the past 12 months have you
1. Had a blood transfusion?
2. Had a transplant such as organ, tissue, or bone marrow?
3. Had a graft such as bone or skin?
4. Come into contact with someone else’s blood?
5. Had an accidental needle-stick?
6. Had sexual contact with anyone who has HIV/AIDS or has had a positive
test for the HIV/AIDS virus?
7. Had sexual contact with a prostitute or anyone else who takes money or
drugs or other payment for sex?
8. Had sexual contact with anyone who has ever used needles to take drugs
or steroids, or anything not prescribed by their doctor?
9. Had sexual contact with anyone who has hemophilia or has used clotting
factor concentrates?
10. Female donors: Had sexual contact with a male who has ever had sexual
contact with another male?
11. Had sexual contact with a person who has hepatitis?
12. Lived with a person who has hepatitis?
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13. Had a tattoo?
14. Had ear or body piercing?
15. Had or been treated for syphilis or gonorrhea?
16. Been in juvenile detention, lockup, jail, or prison for more than 72 hours?
From 1977 to the present, have you
1. Received money, drugs, or other payment for sex?
Have you ever
1. Had a positive test for the HIV/AIDS virus?
2. Used needles to take drugs, steroids, or anything not prescribed by your
doctor?
3. Used clotting factor concentrates?
4. Had hepatitis?
5. Had malaria?
6. Had Chagas’ disease?
7. Had babesiosis?
8. Received a dura mater (or brain covering) graft?
9. Had any type of cancer, including leukemia?
10. Had any problems with your heart or lungs?
11. Had a bleeding condition or a blood disease?
12. Had sexual contact with anyone who was born in or lived in Africa?
Use this area for additional questions/concerns
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Attachment 3
Case Report Form for Normal Donors
(Clinical Research Center for Cape Cod Inc.)
Subject Number: _ _ _ _ _ _
Date: _ _/_ _ _/ 20_ _
(dd/mon/yyyy)
I. Inclusion /Exclusion Criteria
Inclusion Criteria
1. The subject is of 30 years of age and has signed and dated an
informed consent form on _ _/ _ _ _ / 20 _ _.
(dd/mon/yyyy)
2. The subject is in good health (see medical history) and is a nonpregnant female ≥ 30 years of age
3. The subject has not been diagnosed with any kind of cancer except
skin cancer in the past 5 years
II. Exclusion Criteria
4. The subject has a history of heart, lung, or liver disease (see medical
history).
5. The subject has engaged in that behavior that has put them at risk for
infectious disease (see medical history).
6. The subject is on oral contraceptives or hormone replacement
therapy.
□YES
□NO
□YES
□NO
□YES
□NO
□YES
□NO
□YES
□NO
□YES
□NO
Enroll subject if ALL items in the Inclusion Criteria section are checked “YES” and if ALL
items in Exclusion Criteria section are checked “NO”.
III. Subject Profile
1. Date of Birth
4. Gender
5. Race (check all that apply)
_ _/ _ _ _/ _ _ _ _
(dd/mon/yyyy)
□Female
□Caucasian
□African American
□Asian
□American Indian/Alaska Native
□Hispanic
□Other:_________________
□Unknown
IV. List of medications at the time of blood draw
1.____________________________________
2.____________________________________
3.____________________________________
4.____________________________________
5.____________________________________
6.____________________________________
7.____________________________________
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V. Medical History
Yes
No
Yes
No
Yes
No
1. Are you of good health and do you feel well today?
2. Are you currently pregnant?
3. Are you now taking oral contraceptives or hormone replacements?
In the past 12 months have you
4. Are you currently taking any other medication for an infection?
5. Have you had a blood transfusion; an organ, tissue, or bone marrow
transplant; or a bone or skin graft?
6. Come into contact with someone else’s blood or had and accidental
needle stick?
7. Had sexual contact with anyone with Hepatitis or who has HIV/AIDS or
has had a positive test for the HIV/AIDS virus?
8. Had sexual contact with a prostitute or anyone else who takes money or
drugs or other payment for sex?
9. Had sexual contact with anyone who has ever used needles to take
drugs or steroids, or anything not prescribed by their doctor?
10. Had sexual contact with anyone who has hemophilia or has used
clotting factor concentrates?
11. Had sexual contact with a male who has ever had sexual contact with
another male?
12. Lived with a person who has hepatitis?
13. Had a tattoo or had ear or body piercing?
14. Had or been treated for syphilis or gonorrhea?
15. Been in juvenile detention, lockup, jail, or prison for more than 72 hours?
Have you EVER
16. Received money, drugs, or other payment for sex?
17. Had a positive test for the HIV/AIDS virus or have hepatitis?
18. Used needles to take drugs, steroids, or anything not prescribed by your
doctor?
19. Used clotting factor concentrates or received a dura mater graft?
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20. Had any type of cancer, including leukemia?
21. Had any problems with your heart or lungs?
22. Had a bleeding condition or a blood disease?
23. Had sexual contact with anyone who was born in or lived in Africa?
VI. Specimen Processing
1. Date and Time Specimen collected
_ _/_ _ _/ 20 _ _ at
(dd/mon/yyyy)
_ _: _ _
(24hour clock)
_ _/_ _ _/ 20 _ _ at
(dd/mon/yyyy)
_ _: _ _
(24hour clock)
_ _/_ _ _/ 20 _ _ at
(dd/mon/yyyy)
_ _: _ _
(24hour clock)
2. Lot Number of BD Red Top Glass Collection
Tube (Ref 366430)
3. Length of Time Blood Allowed to Clot at
Room Temperature (minutes)
4. Length of Cenrifugation (minutes)
Horizon Premier Laboratory Centrifuge
Model 755VES – Fixed Angle
2700 rpm
5. Date and Time Serum Stored at 2-8 C
OR □ N/A
6. Date and Time Serum Stored at ≤-70 C
(Time from draw must be <5 hrs)
7. Number of aliquots
8. Barcode assigned to sample collected in
glass tube
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Attachment 4
Budget and Proposal
(Healthy Donors)
Study Procedure
Cost per sample
Informed Consent
Phlebotomy
Data Management
Packaging Specimens
Subtotal
Overhead
Total per sample
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