PRIMA Investigator‘s Meeting Protocol MO18264 ASH 2006 Bio-Imaging Technologies, Inc. December 9 th, 2006

Agenda Bio-Imaging Overview Role of Bio-Imaging Imaging Requirements Bio-Imaging Responsibilities Site Responsibilities

Bio-Imaging Overview Imaging Core Lab –Standardization of Imaging –Collection and QC of Image Data –Independent Review of Image Data State-of-the-Art, FDA Compliant Centralized Core Labs –Newtown, PA –Leiden, The Netherlands 269 Employees –201 USA –68 Leiden

Obtain High Quality Standardized Image Data –Standardized Imaging Protocol ›Ensures Consistent Acquisition Across All Clinical Sites and Imaging Timepoints Standardized Procedure to Submit Image Data Provides Image Data in Standard Format Perform Independent Blinded Review Maximize Power of Image Data Role of Bio-Imaging

Study MO18264 (PRIMA) Imaging Endpoints –Progression Free Survival from maintenance randomization (PFS) defined as the time from randomization to progression, relapse, or death from any cause.

Imaging Requirements Timepoints –Baseline –Induction –Maintenance –End of Treatment –Follow-up Anatomical Region –Chest, Abdomen, Pelvis

Imaging Requirements Scans Must be Performed Consistently Between All Timepoints to Assess Endpoints Same Scanner & Technique Must be Used Throughout the Trial

Retrospective Study Kit –Instructional Letter –Contains basic instructions –Retrospective Data Transmittal Forms (rDTF) –Film Labels –Pre-addressed Waybills –Supply Reorder Forms –Envelopes/Padded Mailers –Paint pens –Used for blinding films Retrospective Data Collection

Retrospective Data Transmittal Forms (rDTF) rDTF can be completed by Monitors, CRA’s or site Multiple patients (3) can be listed on one rDTF Each retrospective timepoint must be accompanied with an rDTF.

Provide Complete Image Data Set –Film or Digital Data Must be Submitted –Include Retrospective Data Transmittal Form –Ship all data to Bio-Imaging using the provided envelopes/padded mailers and pre-addressed Waybills All Retrospective data should be sent to our Newtown Office Image Submission Procedure (Retrospective)

Imaging Study Kit (for prospective data) –Imaging Guidelines –Includes blinding instructions –Image Data/Archival Transmittal Instructions –Data Transmittal Forms –Pre-addressed Waybills –Supply Reorder Forms –Paint Pens –Image Archival Media  Optical Disks, Tapes, CDs Imaging Study Kit

Imaging Guidelines Provide Detailed Imaging Requirements –Sets Standards for Proper Image Acquisition –Defines Timepoints for Imaging –Sample Images, Both Correct and Incorrect –Blinding –Shipment of Images –Bio-Imaging Contact Information Important for Radiology Technologists to Read and Understand Guidelines

Provide Complete Image Data Set –After Each Timepoint –Submit Within Days of Scan –Digital Data Must be Submitted –Include Data Transmittal Form Image Submission Procedure (Prospective)

Blinding Film Data –Black paint pen are provided to blind/mask sensitive data –Do not place tapes or stickers on the films. ›Only use labels provided by Bio-Imaging ›Do not place labels over the imaging parameters on the film. Blinding Digital Data –Digital data should be anonymized (masked) prior to archiving, by utilizing the study specific Investigator Number, Patient Number and Patient Initials. Blinding/Masking Procedures Film and Digital

Bio-Imaging will strictly maintain patient confidentiality at all times. In the event that unmasked data is unintentionally submitted, Bio-Imaging will remove patient identifiers. –A Quality Notification Form (QNF) will be forwarded to the site Blinding/Masking Procedures (continued)

Image Data Flow Initial QC Digitize or Translate Transmit Log/Track Site Image QC & Archival Independent Review Site Preparation & Standardization

Provides Bio-Imaging with Vital Information to QC and Track Image Data –Site and Patient Identification –Imaging Timepoint Information –Imaging Parameter Information Must be Completed for Each Timepoint Submit with Image Data Three (3) Part NCR Form Site Retains Pink Copy Data Transmittal Form

Media A Media Label Must be Present on All Image Data Submitted to Bio-Imaging Digital Media will be Supplied with an Attached Pre-Printed Label but Needs to be Completed by Site

Provided With Pre-printed Courier Waybills Pre-addressed With Bio-Imaging as Recipient Sites Must Complete Sender Information Contains a Unique Project Code –Bio-Imaging specific Courier Waybills

Central Image Collection Data Collection –Coordinate –Log and Track Initial QC of Image Data –Preliminary Check –Image Data Clarifications Image Data Tracking

Image QA/QC Review Performed by Radiology Technologist Protocol Compliance Technical Adequacy Rapid Review Process –Detect Problems Early –Prevent Backend Delays

Communication To Sites On Quality Data Clarification Form (DCF) –Query Regarding ›Imaging Data Received ›Data Transmittal Form (DTF) Quality Notification Form (QNF) –Notice on Quality of Imaging ›Identify Improvements Needed for Future Imaging

Generated by Bio-Imaging Requires a Site Response Must be Returned within 1 Week of Issuance of Original DCF Form Image Data Clarification Form

Reasons For Queries Missing Demographic Information on DTF –Patient registration #, Patient initials, etc… Mismatch Between DTF and Digital Media/Films Site Not Consistent with Imaging Parameters Between Timepoints Clarification of Information Missing Image Data Missing Forms (DTF) Repeat Scans (Quality Issues)

How To Ensure Quality At Your Site Establish Communication with Radiology Department Communicate Regularly With Radiology Department Schedule Patients in a Timely Manner Ensure CT Scan Consistency Timely Submission of Images to Bio-Imaging

Site Responsibilities Notify Radiology Dep. of Imaging Requirements Perform Protocol Compliant Imaging Proper Labeling of Image Data Completion of Data Transmittal Form Timely Submission of Image Data Prompt Response to Data Clarification Form

Bio-Imaging Responsibilities Send Imaging Study Kit Collect Image Data Quality Control of Image Data Follow-up on Image Data Clarifications Analyzing/Reviewing Imaging Data Export Analysis to Roche

Bio-Imaging Technologies, Inc. 826 Newtown-Yardley Road Newtown, PA Tel: Tel: Fax: Bio-Imaging Supplies Tel: Fax: Web Address: Contact Information