INSTRUCTION MANUAL FOR LABORATORY AND SPECIMEN PROCEDURES

Transcription

1 INSTRUCTION MANUAL FOR LABORATORY AND SPECIMEN PROCEDURES CARDIOVASCULAR INFLAMMATION REDUCTION TRIAL (CIRT) Sponsor: Brigham and Women s Hospital All individuals connected with the clinical phase of this study should carefully review all instructions. If there are any questions concerning the procedure for filling out the LabCorp requisition forms, sample requirements, results or specimen shipping, please contact your LabCorp Project Monitor, Angela Murphy at or Project Manager, Jennifer Loichle at GCP12032 Cardiovascular Inflammation Reduction Trial (CIRT) Laboratory Manual draft

2 TABLE OF CONTENTS 1.0 General Information 1.1 Primary Contacts Site Registration Overview of CIRT Blood Collection Schedule of Assessments Initial Study Supplies Central Lab Blood Collection Overview 2.1 General Reminders Weekend and Holiday Considerations On-Site Blood Collection Procedures 3.1 Instructions for Completion of Requisition Forms Instructions for Sample Collection Instructions for Use of Sample Labels Packaging Instructions for Courier Pick-Up Patient Service Center Collection 4.1 General Information Instructions for Requisition Form Use and Labeling Results Reporting for On-Site/PSC Collections 5.1 Expected Turnaround Critical Alert Values BWH Biorepository Blood Collection 6.1 Schedule of Assessments Weekend and Holiday Considerations Kits and Materials Instructions for Sample Collection, Packaging and Shipment Quick Reference Guide for BWH Collections Appendices Appendix A Investigator Information Confirmation Form 20 Appendix B Supply Re-Order Form 21 Appendix C BWH Blood Kit Form 22 GCP12032 Cardiovascular Inflammation Reduction Trial (CIRT) Laboratory Manual draft 2

3 1.0 General Information 1.1 Primary Contacts Your site is participating in the Cardiovascular Inflammation Reduction Trial (CIRT), a randomized, double-blind, placebo-controlled trial evaluating low dose methotrexate in the secondary prevention of cardiovascular events among stable post-myocardial infarction patients with type 2 diabetes and/or the metabolic syndrome. Laboratory Corporation of America (LabCorp) provides full medical laboratory services for US sites and is please to have the opportunity to cooperate closely with you in order to ensure the successful undertaking of this project. In order to assist you in carrying out the study, we have prepared this detailed Instruction Manual describing the material, forms, and procedures to follow to support CIRT blood specimen collection. Please place the manual within easy access during the trial. LabCorp representatives will be pleased to answer all your questions regarding sample requirements, procedures for filling out requisition forms, specimen shipping or other issues you may have. Site Support Please feel free to call if you have any questions or if we can be of assistance in any way! Project Monitor: Angela Murphy Project Manager: Jennifer Loichle hr Emergency Line CIRT Coordinating Center GCP12032 Cardiovascular Inflammation Reduction Trial (CIRT) Laboratory Manual draft 3

4 1.3 Site Registration Completion of the Investigator Information Confirmation Form (Appendix A) is required for account set up. If not already submitted upon site initiation with the trial, please complet and this form to your LabCorp Project Manager, Jennfier Loichle, at You will receive confirmation of registration within 1 business day and the account will be created and account information (including account number) will be returned via within 2 business days. 1.4 Overview of CIRT Blood Collection Blood and urine samples will be acquired by the central lab (LabCorp for US sites) using one of two methods: 1) On-site collection by an on-site phlebotomist and transport to LabCorp laboratory facility by courier service (as described in Section 3.0) 2) LabCorp Patient Service Center (PSC) collection is an alternative which requires that the subject be sent to a center with the visit specific lab requisition (described in Section 4.0) BWH Biorepository blood specimens will also be collected at 4 timepoints for shipment to Boston (described in Section 6.0) GCP12032 Cardiovascular Inflammation Reduction Trial (CIRT) Laboratory Manual draft 4

5 1.5 Schedule of Assessments Visits V1 V2 Tests Screening Wk-6 V3, V6, V10, V13 Wk-1, M8, M24, M36 V4.5, V4.6, V4.7, V5.5, V5.6, V6.5, V7.5, V8, V9, V9.5, V10.5, V11, V12, V12.5, V13.5, V14, V15, V15.5 M1,M2,M3,M5, M6, M10, M14, M16 M20 M22 M26, M28 M32 M34, M38 M40 M44, M46 V5 M4 V7, V8.5, V11.5, V14.5 M12, M18, M30 M42 V16FV WV M48 M51-52 Tube Chemistry Panel X X X X X 8.5ml SST hscrp X X X X Lipids X X X X 8.5ml SST CBC with Differential X X X X X 4.0ml EDTA HbA1C X X X X X X 4.0ml EDTA Hepatitis B sag X Hepatitis C Ab X Microalbumin: Creatinine Ratio BWH Kit X X X X X V3, V6, V10 8.5ml SST 10ml urine transfer tube BWH Kit Unscheduled visits: Please use requisition provided for unscheduled visits and select required testing. GCP12032 Cardiovascular Inflammation Reduction Trial (CIRT) Laboratory Manual draft 5

6 1.6 Initial Study Supplies Once sites are registered with LabCorp, they will be sent an initial supply of collection and shipping materials. The initial shipment will include: 1. Bulk supplies: a. 8.5 ml SST (serum separator, tiger top black and red) tubes b. 4.0 EDTA (lavender top) tubes c. Tube labels d. 30 ml Urine collection cups e. 10 ml Urine transfer tubes f. Pipettes g. Small biohazard bags (with absorbent material) h. 21 G x 1 ¼ needles i. Needle holders j. Alcohol pads k. Band Aids l. Tourniquets m. Requisition Slips 2. BWH Kits, including in each kit: a. Small kit box (shipping kit with styrofoam liner) b ml EDTA lavender top tubes (V1 and V3 require 2 6 ml tubes) c. 1 absorbent pad d. 1 small biohazard bag e. 2 refrigerated packs f. 1 FedEx diagnostic bag g. 1 standard safety collection kit (needle tourniquet, needle holder) GCP12032 Cardiovascular Inflammation Reduction Trial (CIRT) Laboratory Manual draft 6

7 Note: Each site will receive, in a separate shipment from the BWH CIRT Coordinating Center, the following items: 1. BWH blood collection forms 2. Blood collection instructions 3. Bar-Coded tube labels 4. Pre-addressed/Pre-paid FedEx airbill 2.0 Central Lab Blood Collection Overview 2.1 General Reminder SUPPLIES Both initial supply and re-supply for this study will be provided by the LabCorp branch. A Supply Re-Order Form (Appendix B) is included in this manual and may be photocopied as needed. Supplies will be shipped to your site via commercial courier. PLEASE MONITOR SUPPLIES AT YOUR SITE AND ORDER NEW SUPPLIES IF YOU ARE RUNNING LOW OR CLOSE TO EXPIRATION DATES FOR THE TUBES. Visit-specific requisition forms will be supplied by LabCorp Clinical Trials, Cranford, NJ. TRANSPORT Specimens will be picked up by a LabCorp courier at the predetermined pickup time (see Section 3.4). SPECIMEN COLLECTION Universal Precautions such as blood collection gloves, protective eyewear and lab coats should be worn throughout the collection and specimen handling procedure. Particular caution should be observed during the needle sticking procedure. The specimen requirements for testing have been carefully reviewed with respect to the type of specimen, specimen volume, and the state of the specimen (non-frozen or frozen). It is imperative that the instructions in this manual and on the LabCorp Request Forms be followed exactly. Subject information on the tube (subject initials, study ID, date, visit) must match the information on the requisition form. Reporting of results may be delayed if a discrepancy occurs. Requisition Forms consist of one original copy and two carbon copies. The bottom copy should be retained at your site for your records. The first two copies are to be sent to the lab with samples. FINAL REPORTS GCP12032 Cardiovascular Inflammation Reduction Trial (CIRT) Laboratory Manual draft 7

8 When contacting the Clinical Trials Department, please have available site information, protocol number, subject identification number, date of sample, and the 11-digit accession 11-digit acc number on the report in question. 2.2 Weekend and Holiday Considerations Saturday and Sunday samples must be prearranged with your Project Manager. In addition, LabCorp observes the holidays listed below. Advanced notification is required for samples to be submitted on these dates. Coverage cannot be absolutely guaranteed in all situations. Support options will be explored once pre-notification occurs. HOLIDAY New Year s Day January 1 January 1 January 1 Memorial Day May 27 May 26 May 25 Independence Day July 4 July 4 July 4 Labor Day September 2 September 1 September 7 Thanksgiving Day November 28 November 27 November 26 Christmas Day December 25 December 25 December 25 IMPORTANT! There is NO COURIER SERVICE available on the holidays listed above and LabCorp will be closed on these dates. 3.0 On-Site Blood Collection Procedures 3.1 Instructions for Completion of Requisition Forms Specimens submitted for testing must have an accompanying test requisition form. Your account has been supplied with LabCorp requisition forms specific for the study. All information listed below must be entered on the forms to ensure proper processing in the laboratory. Each requisition is a carbonless triplicate form. Send copies 1 & 2 of the completed requisition form with specimens; retain copy 3 for your records. Please print clearly in block letters using a BLACK or BLUE ballpoint pen. It is imperative that the subject demographics are CORRECT and are used consistently throughout the study and that the information on the requisition forms MATCHES the information on the specimen labels. GCP12032 Cardiovascular Inflammation Reduction Trial (CIRT) Laboratory Manual draft 8

9 FIELD Account#: Fasting / Nonfasting: INSTRUCTIONS FOR COMPLETION To be assigned Indicate Fasting or Non-fasting with an x, fasting is defined as 8 or more hours since last ate (except water and medications) Specimen Date: Date of collection as mm/dd/yy (e.g. 01/13/14) Specimen Time: Time of collection as hh:mm (24 hour clock; e.g. 14:30) Patient Initials: Patient Number: Sex: ABC or A-C LEAVE BLANK. Use OTHER as noted below. M (male) or F (female) Date of Birth mm/dd/yy (e.g. 01/03/1960) Patient Visit Number: LEAVE BLANK at the top of the requisition, but mark the blank space next to the appropriate visit in the body of the form. Other: Hours since last ate: Enter 10-digit STUDY ID number. Hours since last ate need to be entered in the following space. Should be time since last ate, including snacks. HOURS SINCE LAST ATE HR GCP12032 Cardiovascular Inflammation Reduction Trial (CIRT) Laboratory Manual draft 9

10 Sample Requisition Form Check fasting status Collection Date (mm/dd/yy) Leave blank Collection Time (hh:mm 24 hour clock; e.g. 14:30) Date of Birth (mm/dd/yy) Gender (M or F) Subject Initials (ABC or A-C) 10-digit Study ID LEAVE BLANK Check Visit Complete number of hours since subject last ate Tubes to be drawn GCP12032 Cardiovascular Inflammation Reduction Trial (CIRT) Laboratory Manual draft 10

11 3.2 Instructions for Sample Collection GENERAL SPECIMEN HANDLING Blood should be drawn using routine venipuncture procedures. Please reference the draw order chart contained in this section. Specimens must be packed one patient per bag, along with the corresponding requisition. All samples are to be submitted to LabCorp on the day of collection. Since samples will be submitted to LabCorp on the day of collection, all specimens may be kept at room temperature until courier pick-up. GUIDELINE A: COLLECTION AND PREPARATION OF SST TUBES 1. Collect blood into SST red and black tiger top tubes. Please reference schedule of assessments chart (Section 1.5) for visit-specific tube requirements. 2. Mix blood by gently inverting the tube(s) 5 times. 3. Affix completed ID labels to the tubes. Be sure labels correspond to the requisition form. 4. Allow blood to clot upright at room temperature for 30 minutes. 5. Centrifuge at g for 15 minutes at room temperature. 6. Do not remove top of SST. Tube is to be sent in as is after centrifugation. 7. Do not send uncentrifuged specimens. Do not submit hemolyzed serum (occurrence of pinkage tinge to serum component). 8. Maintain specimens at room temperature after collection and while awaiting courier pick-up. UNSPUN SPECIMENS MAY NOT SIT LONGER THAN 45 MINUTES. GCP12032 Cardiovascular Inflammation Reduction Trial (CIRT) Laboratory Manual draft 11

12 GUIDELINE B: COLLECTION AND PREPARATION OF EDTA TUBES 1. Collect blood into EDTA lavender top tube. Be sure to fill tube until vacuum is exhausted for the correct mixture of blood an anticoagulant. A clotted sample cannot be tested. Please reference schedule of assessments chart (Section 1.5) for visit-specific tube requirements. 2. Mix blood by gently inverting the tube(s) 8-10 times. 3. Affix completed ID label to the tube, making sure that it corresponds to the request form. 4. DO NOT CENTRIFUGE. 5. Maintain specimens for CBC at room temperature after collection and while awaiting courier pick-up. GUIDELINE C: COLLECTION AND PREPARATION OF URINE SAMPLES 1. Instruct subject to use the collection cup to collect a mid-stream void, i.e. to start voiding and then use the cup to collect the sample. The following instructions may be provided to the participant as a guide: It is best to collect what is called a mid-stream urine. Pass a small amount of urine into the toilet bowl, then pass a sample into the container. Do not allow the container to touch your body and keep fingers away from the rim and inner surface of the container. Fill the container three-quarters full. 2. Men should be advised to retract foreskin while voiding. 3. Using a pipette, transfer 10 ml to urine transfer tubes (at required visits, see Section 1.5). 4. Be sure to affix completed ID labels to all containers and make sure they match the requisition form. 5. Maintain urine specimens at room temperature after collection and while awaiting courier pick-up. 3.3 Instructions for Use of Sample Labels Write the Subject Initials (ABC or A-C), Visit (e.g. V2), 10-digit Study ID, Colleciton Date (eg. 01/13/14), and Collection Time (e.g. 14:30) on the label. Peel and attach the label to each tube (blood and urine). Account: TBD Protocol: CIRT Initials: Visit: Study ID: Collec.Date: Time: GCP12032 Cardiovascular Inflammation Reduction Trial (CIRT) Laboratory Manual draft 12

13 3.4 Packaging Instructions for Courier Pick-Up Packaging Instructions Place labeled tubes inside the biohazard bag container absorbent material. Place copies 1 and 2 of the completed requisition form in rear pouch of biohazard bag. Place the biohazard bag in the transport container. Transport of Non-Frozen Non-Infectious Specimens Via LabCorp Courier Specimens may be picked up Monday through Sunday; weekends must be prearranged; contact your project manager. Samples collected at the site for processing at the Central Lab must be ready for courier pick-up according to the courier pick-up schedules the same day. LabCorp courier pick-ups may already be well-established for many sites. However, if the site is new to these vendors, courier pick-up will be arranged during the site registration process. Your local LabCorp laboratory contact information will be sent to you by your project manager (Jennifer Loichle, telephone: , loichlj@labcorp.com). Upon receipt, please contact the labs distribution team to set up a pickup schedule. Please contact you project manager or monitor, with any questions. As samples will be transported the same day, all samples may remain at room temperature until courier pick-up. 4.0 Patient Service Center (PSC) Collection GCP12032 Cardiovascular Inflammation Reduction Trial (CIRT) Laboratory Manual draft 13

14 4.1 General Information For local Patient Service Centers (PSC), please go to and enter the subject s address. Appointments can be made on line or by calling the local Patient Service Center. However, no appointment is needed. 4.2 Instructions for Requisition Form Use and Labeling Please send subjects to the LabCorp PSC with their completed LabCorp requisition. If the subject loses or forgets the requisition, you can fax a copy of the requisition to the Patient Service Center directly. Please call the PSC to obtain the fax number. Please affix the label below to the top copy of the requisition form, prior to providing it to the subject. PSC Staff Please do not accession in TOUCH. Please send samples to local lab for accessioning. If you are faxing a request form to the PSC, fax the top copy only. Do not send tube labels to the PSC, the PSC will provide tube labels. 5.0 Results Reporting for On-Site/PSC Collections 5.1 Expected Turnaround This study is blinded, therefore there will be no reports provided unless alert levels are exceeded (see section 5.2 for values). The following list indicates the tests and test numbers specific to Protocol CARDIOVASCULAR INFLAMMATION REDUCTION TRIAL (CIRT). Turnaround time (TAT) is the time that elapses between the specimen s arrival at LabCorp and result availability to the CIRT Coordinating Center; TAT may be extended if repeat testing is required. Sources of reporting delays include: 1) repeat analysis is required, 2) incomplete or conflicting subject information, 3) unidentifiable samples, 4) improper specimen shipping, or 5) in the case of critical alerts, communication difficulty with the site (fax, telephone or electrical service interruption). GCP12032 Cardiovascular Inflammation Reduction Trial (CIRT) Laboratory Manual draft 14

15 EXPECTED TURNAROUND TIMES (TAT) Test Name Test Number TAT Chemistry Panel hrs hscrp hrs Lipids hrs CBC w/differential hrs HbA1c hrs HBsAg hrs Hepatitis C Ab hrs Microalbumin:Creatinine Ratio hrs 5.2 Critical Alert Values Test Units Reference Interval Low Limit High Limit Bilirubin, Total mg/dl Calcium mg/dl Age Specific Glucose mg/dl Potassium mmol/l Sodium mmol/l Hematocrit % F : M : Hemoglobin g/dl F : M : Platelets x10e3/ul WBC x10e3/ul Neutrophils, Abs x10e3/ul You will be contacted by telephone within 24 hours should an alert level be reached. GCP12032 Cardiovascular Inflammation Reduction Trial (CIRT) Laboratory Manual draft 15

16 6.0 BWH Biorepository Blood Collection 6.1 Schedule of Assessments In addition to the Central Lab collections described above, there will be 4 blood collections which must be done on-site and shipped via overnight FedEx to the BWH Biorepository in Boston. These kits will NOT be sent to the LabCorp and will be stored at the BWH lab and utilized after trial follow-up ends. No assays will be run during the trial and no results will be reported to sites or subjects during or after the trial. The 4 visits are: Visit 2: Enrollment Visit 3: Pre-Rand/Post Run-In Visit 6: 8 Month Visit 10: 24 Month (two 6 ml EDTA tubes) (two 6 ml EDTA tubes) (one 6 ml EDTA tube) (one 6 ml EDTA tube) 6.2 Weekend and Holiday Considerations Arrange for blood draw on Monday through Thursday ONLY and NOT the day before a holiday. The following is a list of holidays observed by the hospital. HOLIDAY New Year s Day January 1 January 1 January 1 Martin Luther King Day January 21 January 20 January 19 Presidents Day February 18 February 17 February 16 Memorial Day May 27 May 26 May 25 Independence Day July 4 July 4 July 4 Labor Day September 2 September 1 September 7 Thanksgiving Day November 28 November 27 November 26 Columbus Day October 14 October 13 October 12 Christmas Day December 25 December 25 December 25 The Lab Address is as follows. You will be provided with a pre-addressed pre-paid FedEx airbill in your shipment from the CIRT Coordinating Center (Toll free: for questions or re-supply). 6.3 Kits and Phlebotomy Materials Kits and phlebotomy supplies will be provided by LabCorp. Please use the Supply Re- Order Form to obtain additional kits as needed. After an order is placed, note that it takes 5 TO 7 BUSINESS DAYS FOR SUPPLIES TO ARRIVE. Therefore, be sure to order in advance of the scheduled BWH collections if supplies are low. GCP12032 Cardiovascular Inflammation Reduction Trial (CIRT) Laboratory Manual draft 16

17 6.4 Instructions for Sample Collection, Packaging and Shipment 1. Arrange for blood draw on Monday, Tuesday, Wednesday or Thursday ONLY and NOT the day before a holiday. The lab in Boston cannot receive shipments on weekends or holidays. Schedule collections early enough to allow for > 8 hour fast (nothing but water/meds), and to allow FedEx pick-up early enough to guarantee overnight delivery to Boston. 2. Take one BWH blood kit, 6mL EDTA (purple top) collection tubes and a solidly frozen gel pack. 3. Collect a BWH Blood Kit Form, a sheet of barcode labels specific to the current visit (Visit 2, 3, 6 or 10) and the pre-paid, pre-addressed FedEx label from the site supplies. 4. Complete Sender information on the FedEx label 5. Using one sheet of barcode labels for the current visit, all with the same barcode number, add a label to each collection tube and the collection form where indicated. Add the 4- digit Site ID and 3-digit Subject ID to each label. Discard any unused labels from the sheet. 6. Complete the BWH Blood Kit Form as far as possible before sending the subject/kit/instructions/form to the phlebotomist. The phlebotomist must add date and time of collection and hours since last ate to the form. The Site Coordinator must indicate on the form whether the subject agreed to use of a part of the blood collected for future genetic testing. This is found in the Main Consent Form where the subject answers Yes or No and initials their answer. 7. Place the BWH Blood Kit Form inside the ship box, but outside the Styrofoam liner with tube(s) being shipped. Keep a copy at the site (this form is not sent electronically to the EDC). 8. One BWH Kit and one sheet of bar code labels is to be used for one study subject/one visit only. Do not re-use labels and do not combine more than one subject s blood tubes in one kit as the FedEx pre-paid label assumes the weight based on one subject s tubes only. 9. All tubes are sent chilled, on a frozen gel pack inside the kit. Do not freeze the tubes, do not centrifuge. Fill completely and invert times gently to mix. 10. Place tubes inside a biohazard Ziploc containing absorbent material in case of breakage. Place the Ziploc directly on the frozen gel pack which should be in the bottom of the Styrofoam box liner. Place the Styrofoam lid on top, then fold and place the collection form on top of the Styrofoam lid but under the cardboard box lid. Seal and call GO- FEDEX to arrange pick-up. 11. Complete Sender address and telephone on the FedEx label and place on the box. 12. If Instructions, Collection Forms, Label Sheets or Pre-addressed FedEx labels are needed (paperwork) order from the CIRT Data Coordinating Center. GCP12032 Cardiovascular Inflammation Reduction Trial (CIRT) Laboratory Manual draft 17

18 BWH Blood Kit Sample Collection - US Visit Sample Aliquot Participant Preparation Scheduling of Blood Draw Collection Materials Required Labels & Forms Shipping V2: Enrollment V3: Pre- Randomization / Post Run-In Two 6mL EDTA tubes Fasting (8 hours) Water / Medication(s) Only Call FedEX GO-FEDEX to schedule pick-up early enough to guarantee overnight delivery to Boston. Kit supplied by LabCorp Write 4 digit Site number and 4 digit Subject number on the visit specific bar code label for tubes and visit specific BWH Blood Kit Form. Place tube(s) in bubble bag. Place bubble bag and absorbent material inside Ziploc biohazard bag. V6: 8 months post randomization V10: 24 months post randomization One 6mL EDTA tube Fill completely and invert times gently to mix. Do not freeze tubes. Do not centrifuge. Arrange for blood draw on Monday, Tuesday, Wednesday or Thursday ONLY and NOT the day before a holiday 1. Make sure gel pack is frozen. Note: Gloves not provided 6mL EDTA (lavender top) tube(s) Frozen gel pack Discard any unused labels from sheet. Affix label to tube and BWH Blood Kit Form. Complete the BWH Blood Kit Form with 10 digit Study ID, date, time of collection and hrs since last ate. Place Ziploc biohazard bag on frozen gel pack in bottom of Styrofoam box. Close Styrofoam lid and place BWH Blood Kit Form on top within box and seal box. Place box in FedEx diagnostic bag. Compete Sender address on air bill, place in pouch, remove adhesive flaps and affix to diagnostic bag. Call FedEx for pick up. 1. BWH Holidays: New Year s Day, Martin Luther King Day, Presidents Day, Memorial Day, Independence Day, Labor Day, Columbus Day, Thanksgiving Day & Christmas Day GCP12032 Cardiovascular Inflammation Reduction Trial (CIRT) Laboratory Manual draft 18

19 7.0 Appendices Appendix A Investigator Information Confirmation Form Appendix B Supply Re-Order Form Appendix C BWH Blood Kit Form GCP12032 Cardiovascular Inflammation Reduction Trial (CIRT) Laboratory Manual draft 19

20 Investigator Information Confirmation Form PROTOCOL CIRT LabCorp Clinical Trials has been chosen to be your laboratory for the CIRT study. We need your help to perform the set-up requirements for your Investigator site. Please review the information below and correct or add the requested/required information. We look forward to working with you on this study. Please note that we cannot begin the set-up process without return of this document. Approximately 10 business days is required to ship supplies primarily due to the time required for receipt of your study-specific shipment waybills. Principal Investigator: Site Number: Study Coordinator: (OPTIONAL- please complete if Main Contact for Data Clarifications) Address: Phone Number: ( ) - Fax Number: ( ) - Investigator (if you wish to communicate via ) Coordinator Samples will be collected (please check all that apply): At Investigator site (by site staff) LabCorp Patient Service Center Do you have a current LabCorp account?: Yes No If Yes, are you currently scheduled for daily pickups? Yes No Do you have a centrifuge? Yes No Comments: Information is accurate and complete. Signed by: (Approved PI, Co-I, or SC Signature) (Date) (Print Name) PLEASE FAX COMPLETED FORM TO: LabCorp Clinical Trials Attn Jennifer Loichle GCP12032 Cardiovascular Inflammation Reduction Trial (CIRT) Laboratory Manual draft 20

21 SUPPLY REORDER FORM Protocol CIRT Project GCP12032 Complete this form and fax to: (908) Attn: Jennifer Loichle Site Investigator: Account: TBD Bulk supplies must be ordered with the supply form included in this section. The form may be photocopied. If you need items that are not listed on the form, please fax list to (908) Item Description 8.5 ml SST (Tiger top) Tubes, Box of XXX 4.0 ml EDTA (Lavender top) Tubes, Box of XXX 10 ml transfer tubes (for urine collection), Box of XXX 30ml Urine Collection Cups, Bag of XXX Pipettes, Pkg of XXX 21 G 1.1/4 Needles, Box of XXX Needle Holder, Each Tourniquet, Each Alcohol Pads Pkg of XXX Quantity Ordered Small Biohazard Bag with Absorbent Pak, Bag of XXX Band-Aids, Box of XXX Tube Labels, Pkg of XXX Requisition Labels for PSC, Pkg of XXX Requisitions for VISIT: BWH Shipping Kits for V2 (Enrollment) and V3 (Pre-Rand/Post Run-In), Each BWH Shipping Kits for V6 (8M) and V10 (24M), Each Date Supplies Needed: Ordered by: For Additional Supplies or Assistance Contact Jennifer Loichle at WHEN ORDERING, PLEASE ALLOW 5 TO 7 WORKING DAYS FOR YOUR ORDER TO ARRIVE *** For LabCorp Use Only *** Date of Fax Receipt: Initials: Date Order Forwarded to Kit Prep: Initials: GCP12032 Cardiovascular Inflammation Reduction Trial (CIRT) Laboratory Manual draft 21

22 BWH Blood Kit Form STUDY ID: - - Country Code Site # Subject # Place Site # and Subject # on sample label Subject Initials: Visit (check one) Visit 2: Enrollment Visit 3: Pre-Randomization/Post Run-In Visit 6: Mo 8 Visit 10: Mo 24 All BWH blood collections require >= 8 hours fasting. Meds with water is okay. All BWH blood collections MUST be done Monday through Thursday and NOT the day before a holiday to guarantee overnight FedEx delivery to the Boston BWH lab (the lab is not open weekends or holidays). Visit 2 and Visit 3 require 2-6ml EDTA tubes of whole blood Visit 6 and Visit 10 require 1-6ml EDTA tube of whole blood Ship chilled tube(s) same day as collected using solidly frozen gel pack and kit provided including pre-paid FedEx label addressed to BWH lab, 961 Commonwealth Ave, Boston, MA Site must fill in Sender info on FedEx label. Do not centrifuge tubes, do not freeze tubes. Mix gently but do not shake tubes. Place label on each tube and one on this form with same barcode. Add Site # and Subject # to each label. Complete rest of this form, fold and place original inside BWH Kit. Did subject consent to use of a portion of their blood sample for genetics? (See Main CIRT Consent form) Yes No Date of collection: / / M M D D Y Y Y Y Time: : am pm Hours since last meal (water with meds ok): hrs Add one of the barcode labels from the visit-specific sheet of labels here: Put label here with Site # and Subject # filled in Be sure to put this form inside the blood kit. Keep a copy at the site. Form completed by: Telephone (in case of questions): - - GCP12032 Cardiovascular Inflammation Reduction Trial (CIRT) Laboratory Manual draft 22

23 BWH Blood Kit Form STUDY ID: - - Country Code Site # Subject # Place Site # and Subject # on sample label Visit (check one) Visit 2: Enrollment Visit 3: Pre-Randomization/Post Run-In Visit 6: Mo 8 Visit 10: Mo 24 All BWH blood collections require >= 8 hours fasting. Meds with water is okay. All BWH blood collections MUST be done Monday through Thursday and NOT the day before a holiday to guarantee overnight FedEx delivery to the Boston BWH lab (the lab is not open weekends or holidays). Visit 2 and Visit 3 require 2-6ml EDTA tubes of whole blood Visit 6 and Visit 10 require 1-6ml EDTA tube of whole blood Ship chilled tube(s) same day as collected using solidly frozen gel pack and kit provided including pre-paid FedEx label addressed to BWH lab, 961 Commonwealth Ave, Boston, MA Site must fill in Sender info on FedEx label. Do not centrifuge tubes, do not freeze tubes. Mix gently but do not shake tubes. Place label on each tube and one on this form with same barcode. Add Site # and Subject # to each label. Complete rest of this form, fold and place original inside BWH Kit. Did subject consent to use of a portion of their blood sample for genetics? (See Main CIRT Consent form) Yes No Date of collection: / / M M D D Y Y Y Y Time: : am pm Hours since last meal (water with meds ok): hrs Add one of the barcode labels from the visit-specific sheet of labels here: Put label here with Site # and Subject # filled in Be sure to put this form inside the blood kit. Keep a copy at the site. Form completed by: Telephone (in case of questions): - -

24 CIRT: BWH Blood Kit Collection Instructions Upon receipt of blood kits/supplies 1. Sites will be sent a supply of BWH blood kits including gel packs and 6mL EDTA (purple top) blood collection tubes. The gel packs should be placed in a regular freezer and frozen solid before packing a blood kit for overnight shipment to BWH. Expiration dates on tubes must be checked and tubes replaced as needed. 2. LabCorp/GDML will provide the following: alcohol pad gauze/cotton balls needle needle holder tourniquet bandaid absorbent pouch to hold the tube(s) during shipment biohazard ziploc to hold the absorbent pouch with the tube(s) NOTE: gloves are not provided 3. To be added from CIRT study supplies sent by DCC to each site: BWH Blood Kit Form Copy of this BWH Blood Kit Collection Instructions One sheet with barcode labels, specific to each visit, for collection tubes and for form sent with tubes Site # and Subject # to be added to all labels used FedEx pre-paid label which is pre-addressed to the BWH Lab in Boston (sites must add Sender address and telephone number Call FedEX (1-800-GO-FEDEX) to determine whether there are any special local pick-up requirements in your area, including a cut-off time for pick-up, to guarantee overnight delivery to BWH Lab in Boston. FedEx usually provides a 3-4 hour window for pick-up. Be sure the blood kit is accessible during window provided. Day of Collection 1. Arrange for blood draw on Monday, Tuesday, Wednesday or Thursday ONLY and NOT the day before a holiday. The lab in Boston can not receive shipments on weekends or holidays. 2. Schedule collections early enough to allow for >= 8 hour fast (nothing but water/meds), and to allow FedEx pick-up early enough to guarantee overnight delivery to Boston. 3. Take one BWH blood kit, 6mL EDTA (purple top) collection tubes and a solidly frozen gel pack. 4. Add the BWH Blood Kit Form, a sheet of barcode labels specific to the current visit (Visit 2, 3, 6 or 10) and the pre-paid, pre-addressed FedEx label from the site supplies.

25 5. Complete Sender information on the FedEx label 6. Using one sheet of barcode labels for the current visit, all with the same barcode number, add a label to each collection tube and the collection form where indicated. Add the subject s Site # and Subject # to each label. Discard any unused labels from the sheet. 7. Complete the BWH Blood Kit Form as far as possible before sending the subject/kit/instructions/form to the phlebotomist, including adding the bar code labels with Site # (4 digits) and Subject # (4 digits). The phlebotomist must add date and time of collection and hours since last ate to the form. The Site Coordinator must indicate on the form whether the subject agreed to use of a part of the blood collected for future genetic testing. This is found in the Main Consent Form where the subject answers Yes or No and initials their answer. The same tubes are still collected but the portion of the blood that could be used for genetics is only saved at the BWH Lab if the subject says Yes. 8. Place the BWH Blood Kit Form inside the ship box, but outside the Styrofoam liner with tube(s) being shipped. Keep a copy at the site (this form is not sent electronically to the EDC). 9. One BWH Kit and one sheet of bar code labels is to be used for one study subject/one visit only. Do not re-use labels and do not combine more than one subject s blood tubes in one kit as the FedEx pre-paid label assumes the weight based on one subject s tubes only. 10. Visit 2:Enrollment and Visit 3: Pre-Randomization/Post-Run-In require two 6mL EDTA tubes. Visit 6: 8 Month Follow-Up and Visit 10: 24 Month Follow-Up require one 6mL EDTA tube. All tubes are sent chilled, on a frozen gel pack inside the kit. Do not freeze the tubes, do not centrifuge. Fill completely and invert times gently to mix. 11. Place tubes inside a biohazard Ziploc containing absorbent material in case of breakage.. Place the Ziploc directly on the frozen gel pack which should be in the bottom of the Styrofoam box liner. Place the Styrofoam lid on top, then fold and place the collection form on top of the Styrofoam lid but under the cardboard box lid. Seal and call GO-FEDEX to arrange pick-up. 12. Complete Sender address and telephone on the FedEx label and place on the box. 13. CIRT: BWH Lab Brigham and Women s Hospital 961 Commonwealth Ave Boston, MA Toll free:

26 14. NOTE: if tubes are needed, order from the Central Lab (LabCorps in US or GDML in Canada) or use any EDTA (purple top) 6mL tube equivalent if necessary. Extra 6mL EDTA tubes and gel packs may also be ordered from LabCorp or GDML if needed. 15. If Instructions, Collection Forms, Label Sheets or Pre-addressed FedEx labels are needed (paperwork) order from the CIRT Data Coordinating Center.