Centralized Imaging Services

H. LUNDBECK A/S

Stroke - Desmoteplase

DIAS-4

Investigators’ Meeting, Chicago , July, 2011

Presented by Thomas Truelsen, Lundbeck

DIAS-4 Study Imaging summary 1/2

Indication Stroke

Total number patients

400 randomized and completed patients (BL and 12-24h)

(Estimated 800 screened patients (BL only))

Imaging time point

- Baseline- 12-24hrs- Unscheduled (from BL to D90)

Imaging Modality

MRI: DWI + MRA + T2* + T2 FLAIR

(Perfusion Imaging (PI) as optional sequence, only for sites confirmed by Lundbeck to provide their PI source data)

CT: NCT + CTA

DIAS-4 Study Imaging summary 2/2

Image collection

On-going Image Collection and Quality Control

Central Reading and Assessments

Eligibility reading: inclusion/exclusion criteria at BL

Safety reading: Presence of ICH Hemorrhage or Ischemic Oedema at 12-24hrs and Unscheduled

Quantitative reading: Assessment of Infarction Volume at BL and 12-24hrs

Vessel status reading: Vessel status at BL and recanalization sub-study at 12-24hrs

DIAS-4 Study Imaging Worflow

Start up phase Running phase of the study

of the study

Site Imaging Evaluation

Studysupplies

ImageCollection &Initial Check

Image QualityControl

QueryManagement

CentralReadingOrganization

Data transfer to sponsor

Site Phone Training

Site Imaging Evaluation (1/6):Purpose

For Synarc:- Verify the ability of each site to acquire images according to the

requirements described in the Imaging Manual and the MR & CT Procedure Manual

- Verify the readibility of the images in Synarc Imaging software (DICOM format)

For the site:- Sites are encouraged to record the DIAS-4 study specific parameters in

the device(s) (according to settings pre-defined in the Imaging Manual).- These parameters are not mandatory any more, however, in order to standardize the

imaging procedure study sites are highly recommended to stick to them.

Site Imaging Evaluation (2/6):Workflow

InvestigatorSite

3 Qualification Notification

LUNDBECK

SYNARC

4 Imaging package shipment

1Initial site selection questionnaire

2Filled in questionnaires

new imaging survey

Site Imaging Evaluation (3/6):

• Before study start each study site should fill in an imaging survey with data on potential CT or MRI scanners to be used in this trial

– E.g. brand, software, availability of DICOM standard, availability of DICOM saving, etc..

• Phantom scans no longer needed

• Each survey can be filled in with information for 3 CT and 3 MRI scanners

• Already qualified scanners do not need to be entered in the survey

• The forms should be sent via email to Jamal Smyej JSYM@lundbeck.com

• After evaluation the study site will receive an email notification from the imaging lab Synarc

Site Imaging Evaluation (4/6):Site supplies

• Evaluation survey:– Provided to the site once site has been selected for the trial

• Complete supply package:– Provided to the sites once evaluation completed– to perform exam acquisitions all along the study:

• Imaging Binder containing Imaging Manual and Procedure Manual• triplicate Transmittal Forms and pre-labelled CD-ROMs• Courier shipping material (UPS)• One acknowledgement of receipt to be faxed back to Synarc upon package receipt

Site Imaging Evaluation (5/6):MR&CT Imaging Procedure Manual

• Document which summarizes imaging protocol and data handling

• All personnel involved in the imaging part of the trial (Neuroradiologist, Technologist, Study Coordinator) need to read and fully understand the Imaging Manual

• And to sign Page i of the Imaging Procedure Manual

• Please fax a copy of this completed page to Synarc San Francisco

• Keep original in the procedure manual

Site Imaging Evaluation (6/6):Remote Site Phone Training

• Purpose: Logistical Training provided by Synarc to site (by phone). It is organized once complete supply package has been received and has to be followed by the MRI and/or CT technologist and the study site Coordinator.

• Content:– Presentation of the study material and documents– Image acquisition details– Image and exam identification– Package preparation and shipment (FedEx)– Data Clarification Form

• For information: Additionally to the Synarc phone training, one web-based training will be coordinated and organized by Lundbeck to provide information regarding eligibility criteria .

Image acquisition and collection (1/6) :Image flow

Store images on the CD-ROM.Fill in the patient/visit information on the CD-ROM

Place the Transmittal Form (original) and the labeled CD-ROM in the

padded envelope

Images to be shipped to SYNARC via courier

Images should Images should be sent to be sent to SYNARC SYNARC

within 2 days within 2 days of acquisitionof acquisition

Fill in the Transmittal Form, Fax it to SYNARC San Francisco

Keep yellow and pink copies at site.

A copy of all images must be kept at site

Image acquisition and collection (2/6)electronical data transfer

• A new option has been agreed on with Synarc to replace shipment of physical films by an FTP transfer

• This change should not be forced on to sites as mandatory – but rather implemented where the sites think this could be an advantage

• A short feasibility questionnaire need to be sent to the sites to check for compatibility

• The CRAs will be asked to send the FQ to the sites and feedback the results of the discussions to Lundbeck and Synarc

Image acquisition and collection (3/6) : Expected exams/sequences

 

MRI CTPost-

Processed Images

Central Assessment Purpose

Baseline (BL)

ScoutDWIT2*T2 FLAIRMRAPI (optional)

ScoutNCTCTA

All Post-processed

Images to be sent to Synarc

(Trace/ADC for DWI, MIP/3D

Reconstruction for MRA and

CTA, Maps for optional PI)

Eligibility reading - check of the exclusion and inclusion criteria:- Exclude hemorrhage- Include occlusion in MCA M1, MCA M2, ACA or PCA

Quantitative Reading:- Assess the Initial Infarct Volume

Vessel Status Reading (TIMI):- Confirm vessel status (presence of occlusion)Perfusion: to be discussed between Lundbeck and Synarc

12-24 Hrs (12-24h)

ScoutDWIT2*T2 FLAIRMRA (substudy)PI (optional)

ScoutNCTCTA (substudy)

Safety Reading:- Assess the presence of hemorrhage or ischemic oedema

Quantitative Reading:- Assess the Final Infarct Volume

Vessel Status Reading (TIMI) (substudy):- Check vessel recanalization

Unscheduled (UNS)

All Unscheduled Scans performed within the study from BL to D90 to be

sent to Synarc

Safety Reading:- Assess the presence of hemorrhage or ischemic oedema

Image acquisition and collection (4/6) :Image Labeling

• Main information needed for images identification:

– Study patient number– Date of Birth– Acquisition date– Visit code

• Please be careful to anonymize/de-identify the images for legal reasons

• Make sure to enter the cerebral hemisphere side affected by the acute stroke in the image.

DICOM FIELD: To be entered at the time of acquisition:

PATIENTNAME

Make sure that subject name (or patient address, social securitynumber, phone number) is NOT entered or if entered, make sure

toanonymize/de-identify it before making the CD-Rom copy.

PATIENT I.D Enter Patient Screening number as reported on the CRF(S+4digits e.g :S0001)

PATIENT DATEOF BIRTH

Enter Patient’s date of birth as reported on the CRF

PATIENTCOMMENTS

Enter Site ID as reported on the CRF(2 letters+3 digits e.g :IN001)

PATIENTGENDER

Enter Patient gender as reported on the CRF.

ADDITIONNALPATIENTHISTORY

Cerebral Hemisphere side affected by the acute stroke:Enter “Right” for right hemisphere or “Left” for left hemisphere

STUDYDESCRIPTION

Visit code:Enter the visit code corresponding to the visit:BL (Baseline), 12-24h (12-24 Hours), UNS (Unscheduled)

Same information has to be present on transmittal form and within the images.

Image acquisition and collection (5/6) : Transmittal Forms

Image acquisition and collection (6/6):Transmittal Forms

Filling the Transmittal Forms Contains the description of the

images sent (to be filled-in according to the GCP guidelines):

• Patient and visit information

• Image acquisition (series number burnt on the CD-ROM)

• Air waybill number

• Name and signature of Technologist

• Form to be faxed to Synarc before shipment of the entire data package

Good Clinical Practices– Use black or blue ink– Write clearly and legibly– Correct mistakes properly (strike

through error, put initials and date next to correction)

• Do NOT use correction fluid

– Fill out the forms properly– Use the labels provided for CD’s– Include proper signatures– Maintain subject and clinical

protocol confidentiality– Contact SYNARC for any

questions/problems

02-JAN-2006JUN

Error-MMS

03JUN06

Image Quality Control (1/2)

• Presence and readability of all documents (first check)– Presence of all the documents per visit (transmittal form and CD)– Verification of the readability of the documents (images format)

• Anonymity– If images not anonymised yet: anonymisation done by SYNARC

• Patient identity / Date of Acquisition of the scan– Proper labeling of the images in accordance with the transmittal form information

(patient and visit information)

• Complete scan– Compliance to the imaging protocol and presence of sequences required by the

protocol

• Imaging parameters

– Presence of the information required for the quantitative evaluation (slice thickness, …)

Image Quality Control (2/2): Query Management

Query Management:In case of missing information, missing image, discrepancy between the information …

SYNARC will send a Data Clarification Form by email to the site

The site will have to send back the Data Clarification Form filled by fax and if necessary with other documents

Central Reading (1/3):Eligibility Reading

SYNARCInvestigator’s center

IP Networ

k

IP Networ

k

Inclusion/exclusion

criteria

Feedbackto sponsor

Io Workstation Io Workstation Io Workstation

QC, Anonymization Randomization

Inclusion/exclusion

criteria

Inclusion/exclusion

criteria

Imaging Committee

Workstations

Central Reading (2/3):Safety and vessel status Reading

• Safety Reading:

– Central Reading pannel to assess the presence of Hemorrhage and/or Ischemic Oedema

• Vessel status and recanalization Reading:

– Central Reading pannel to assess the vessel status from baseline and 12-24h follow-up images

Central Reading (3/3):Quantitative Assessment

- Central Reading pannel to assess infarct volume- Validation or correction of the ROIs by the central Reader of the Imaging Committee- Automatic calculation of the volume using the imaging lab reading workstation (using information from DICOM header (slice thickness, slice position…)

Volume of the lesion

ROIs delineated on the images

Staying in touch

• Clemence Blondeau

Project Manager at Synarc

clemence.blondeau@synarc.com

• Jamal Smyej

Imaging specialist at Lundbcek

jsmy@lundbeck.com

Synarc Inc.7707 Gateway BoulevardBldg 5, 3rd FloorNewark, CA 94560USA

Thank you!

Any questions?