4%Phase IV

6%Observational

2%Device

11%Phase I

28%Phase II

49%Phase III

KCR Data Management: Designed for Full Data Transparency

The quality of study data relies first and foremost on the quality of the tool used to collect the data. If the data points specified in the protol are not accurately collected, a meaningful analysis of the study’s outcome will not be possible. Therefore, the design, development, and quality assurance processes of a CRF must receive the utmost attention.

— Good Clinical Data Management Practice, April 2011

2 www.kcrcro.com

KCR knows that accurate clinical trial data is the lifeline of clinical studies

As an expert provider of a wide spectrum of clinical development support services, KCR has develo- ped a supreme Data Management (DM) solution geared towards full data transparency as well as delivering the highest level of quality within the defined timelines and in adherence to study bud-gets, all the while ensuring the meeting of all Good Clinical Practice (GCP) and ICH requirements.

KCR delivers all the support and tools to its clients that are necessary to make the correct decisions

KCR DM solution is based on a knowledge-based process borne by a committed team of expert people and a proven, secure and reli-able technology designed for full data transparency.

KCR DM Solution

Knowledge Based Process

Committed People

Robust Technology

www.kcrcro.com 3

KCR constantly surveils its data management processes by apply-ing a fully transparent and highly effective Quality Assurance (QA) process.

All DM services offered by KCR are in strict alignment with our operating framework and structured around the three main phases of the clinical trial: start-up, conduct, and close-out.

KCR’s DM is guided by impeccable data management processes providing the know-how necessary to perform all activities throughout the lifecycle of a study to the highest quality possible. Our Standard Operating Procedures (SOPs) enable a clear audit trail for each process phase depending on stage of the study as well as a full index of documentation required of audits, inspections or for submission purposes.

KCR’s full package of DM services includes(but is not limited to):

→ eCRF design and validation → Automated validations programing → Programing of custom reports → User Acceptance Testing (UAT) → Continuous data cleaning → Randomization and Medication Inventory

/Drug Supply tool configuration, → External data set up, Lab, PK/PD, ECG etc.

data imports → SAE Reconciliation of Safety and Clinical

database → Coding of Adverse Events, Medical History

and Concomitant Medication → Study team EDC system training – including

e-learnings → Database QC (for data review and medical coding) → Listing of documents created for each service → Database Lock (DBL) and archive

Knowledge-based: Processes@KCR DM↵

4 www.kcrcro.com

CONDUCT Processes

The conduct processes at KCR ensure accurate prediction, prevention and dependable reaction on the data collected within a timely manner.

*Start up *Study phase Ii B

Protocol available

Creation of study documents in preparation for FPFV

Fpfv

*psychiatry/Psychology *12 weeks need to launch the study

193 test cases tobe passed before

deployment

1.47 DM FTEsinvolved

17 study visits perpatient

Data transfer betweenCentral Lab, ECG data

base and EDC

~96 automatedvalidations

~47 real-data reports

234 planned patientsenrolled

9 study speci�c CRFmodules designed;

9 standard modules used

Week 1 Week 3 Week 6 Week 9 Week 12

1 day

Go live –all features

ready!

2 weeks

1st draft ofeCRF afterProtocol isrecieved

2 weeks

2 eCRFreview roundswith Sponsor

Site anduser account

creation

2 weeks

Con�gurationof additionalfeatures (e.g.

randomizationtool, encodingexternal datatransfers, etc.) 2 weeks

Con�gurationof automated

validations,reports,

work�ows 2 weeks1 day

2 weeks

eCRF�nalization

UAT of allfeatures

High quality data with timely delivery is crucial, given the com-petitiveness of the drug development environment and the meticu- lous focus on cycle timelines.

→

→ START-UP Processes

Start-up processes at KCR are designed to set up the Electronic Data Capture (EDC) tool within a maximum of 12 weeks and to include the performance of two client eCRF review cycles as well as thorough User Acceptance Testing (UAT). Such a competitive timeline is made possible by utilizing pre-validated libraries of modules/forms, automated validations and reports. The processes ensure the EDC is available (with all features implemented) for First Patient First Visit (FPFV) to guarantee continued data entry from day one of the study.

Case Study I: Start-up process with a 12 weeks launch period

(Phase IIb psychiatry/psychology study)

www.kcrcro.com 5

4

Site - 7 days toenter visit data

DM - 7 days toreview visit data- Issue queries

2

Site - 7 days torespond to issued

queries

3DM - 2 days to reviewresponses - reissue

or close queries

1

Site - 7 days toresolve outstanding

queries

5

Case Study II: Continuous data handling (Phase III rheumatoid arthritis study)

*Conduct *Study phase III

Protocol Amendment Draft Approved Amendment Launch Changes

Implementation of ProtoCol Amendment Changes

day 1

*Rheumatoid Arthritis

day 10

Risk Assessmentof Protocol

Amendment

0.93 DM FTEsinvolved

Plannedrandomized

patients – 734

Avarage DMQuery turnoverless than 2 days

79.3 – avaragenumber of queries

solved weekly

Last QueryQuality Assessmentsround error rate: 0%

ImplementStart up

Activities

Modify eCRF

Recon�gure EDCAdditional Features EDC Update

Modify AutomatedValidations

UAT and DocumentationUpdates

77.8 – avaragenumber of visitsreviewed weekly

Q

Q

Last Medical EncodingQuality Assessments

round error rate: 0.02%

ME

Our experienced Data Management Protocol Leads meticulously control the data flow by help of statistical analysis tools and implemented risk based monitoring approach methods to ensure the highest quality of the data collected.

KCR’s Data Management ensures an ongoing data review within predefined timelines:

6 www.kcrcro.com

→ CLOSE-OUT Processes

KCR’s close-out processes are designed to maximize efficiency of Database Lock (DBL) activities and to ensure all DBL milestones are met. Our multi-step process facilitates a database lock within ~8 weeks from Last Patient Last Visit (LPLV) to final DBL without any need to unlock it at a later stage because of critical findings.

Case Study III: Data locked in less than 8 weeks (Phase IIIb osteoarthritis study)

*Close out *Study phase IiI B

8 weeks prior DBL

Pre-lock meeting

6 weeks

LPLV DBL Final DBL

*Osteoartrithis *less thAn 8 weeks needed to lock the study

AcceleratedTimelines

Last PatientLast Visitoccured

Database lockedand exportedfor statistical

analysis purposes

All signaturescollected,

database lockedand archived

1.6 DM FTEsinvolved

1481 screened patients 7922 study visits

112 044 lab resultstransferred from

Central Lab to EDC

6.27 query per patientssolved in 9.8 days

(in avarage)

Only 1 approveddata deviation

in locked database

25 days 15 days

1261 randomized patients

Committed: People@KCR

KCR DM team comprises experienced and reliable experts with a clear split of responsibilities. Every project has a designated Data Management Protocol Lead who ensures that study needs are met at all times.

KCR’s international team consists of professionals with an average of six years’ field experience and a range of expertise and background in:

Quality assurance

Project management Training

Centralized monitoring Risk assessment

Remote monitoring

↵

www.kcrcro.com 7

At KCR successful people never stop learning: we put significant emphasis on continuous and thorough training of our staff to ensure the delivery of highest quality services.

“Always Think Big”

We are convinced that innovations are the cornerstone for success, each member of our staff shares a sim-ilar mind-set and vision working towards the best results. Our DM team is personally liable for all actions and results, and follows one of our core values in all day-to-day activities.

“If it’s to be, it’s up to me”

KCR uses Clincase, a secure, flexible and reliable EDC solution delivered by Quadratek and utilized by leading pharmaceutical companies across the globe.

All technology used by KCR Data Management is compliant with 21CFR Part 11 and all other industry standards including CDISC ODM and CDASH.

KCR trained in-house experts take advantage of all possible ca-pabilities of the tool to deliver a customized and transparent solution to each client.

Flexible,customer-orientedECRF design createdinhouse by KCR DM

Inbuilt, fully customizableencoding tool, supporting

commonly used medicaldictionaries, e.g. WHO-DD

and MedDRA

Inbuilt randomization tool(IWRS) and medication

inventory/drug supplyfeature, eliminating

need for additional systems

Automated edit checksrendering data cleaningprocess most efficient

Sponsor access to listingsproviding real-time view

of data captured,thus enabling continuedinsight into the project

Simplified data transfersbetween external databases

and EDC e.g. Central Lab,ECG data

Robust: Technology@KCR↵

Strategic Alliance

PERGAMON PALAIS

am kupfergraben 4-4A

De–10117 berlin, germany

Email: info@kcrcro.com

www.kcrcro.com

Copyright © 2015 KCR S.A. All rights reserved.

18

3,000 30,000

40018 years of experience

Almost 3,000 Sites Contracted

400 clinical Trials executed

Over 30,000 patients recruited

Strategic Alliance

KCR CORPORATE Head office

KCR: We see human behind every number.

4%Phase IV

6%Observational

2%Device

11%Phase I

28%Phase II

49%Phase III

KCR: Excellence in Clinical Trials Since 1997KCR is a Contract Research Organization (CRO) with a dynamic team of over 300 professionals operating across 19 countries in Europe as well as the U.S. With 18 years of experience, almost 400 trials executed, 35,000 patients recruited and over 3,000 sites contracted, KCR is a strategic solutions provider and a reliable alternative to top tier CROs, delivering the all-important flexibility.

We provide services on long standing contracts to 12 out of the Top 20 Global Pharma companies, as well as biotech firms from Europe, Israel, and the U.S.

KCR offers full service capabilities via three types of professional product lines: • Trial Execution• Functional Service Provision (FSP)• Late Phase