KCR Data Management: Designed for Full Data Transparency

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KCR Data Management: Designed for Full Data Transparency 6% Observational 4% Phase IV 2% Device 11% Phase I 28% Phase II 49% Phase III 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

KCR knows that accurate clinical trial data is the lifeline of clinical studies KCR delivers all the support and tools to its clients that are necessary to make the correct decisions As an expert provider of a wide spectrum of clinical development support services, KCR has developed 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 budgets, all the while ensuring the meeting of all Good Clinical Practice (GCP) and ICH requirements. KCR DM Solution Knowledge Based Process Committed People Robust Technology KCR DM solution is based on a knowledge-based process borne by a committed team of expert people and a proven, secure and reliable technology designed for full data transparency. 2 www.kcrcro.com

Knowledge-based: Processes@KCR DM 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 constantly surveils its data management processes by applying a fully transparent and highly effective Quality Assurance (QA) process. 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 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. www.kcrcro.com 3

START-UP Processes Start-up processes at KCR are designed to set up the Electronic Data Capture (EDC) tool within a maximum of 1 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 1 launch period (Phase IIb psychiatry/psychology study) *Start up *Study phase Ii B *psychiatry/psychology *1 need to launch the study 234 planned patients enrolled 17 study visits per patient Data transfer between Central Lab, ECG data base and EDC ~96 automated validations ~47 real-data reports 9 study specific CRF modules designed; 9 standard modules used 1.47 DM FTEs involved 193 test cases to be passed before deployment Week 1 Week 3 Week 6 Week 9 Week 12 Protocol available Fpfv Creation of study documents in preparation for FPFV 1 st draft of ecrf after Protocol is recieved 2 ecrf review rounds with Sponsor ecrf finalization Configuration of additional features (e.g. randomization tool, encoding external data transfers, etc.) Configuration of automated validations, reports, workflows UAT of all features Site and user account creation 1 day Go live all features ready! 1 day CONDUCT Processes High quality data with timely delivery is crucial, given the competitiveness of the drug development environment and the meticulous focus on cycle timelines. The conduct processes at KCR ensure accurate prediction, prevention and dependable reaction on the data collected within a timely manner. 4 www.kcrcro.com

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: 1 Site - 7 days to enter visit data 5 Site - 7 days to resolve outstanding queries 2 DM - 7 days to review visit data - Issue queries 4 DM - 2 days to review responses - reissue or close queries 3 Site - 7 days to respond to issued queries Case Study II: Continuous data handling (Phase III rheumatoid arthritis study) *Conduct *Study phase III *Rheumatoid Arthritis Q Planned randomized patients 734 Q 77.8 avarage number of visits reviewed weekly 0.93 DM FTEs involved ME Avarage DM Query turnover less than 2 days Last Query Quality Assessments round error rate: 0% 79.3 avarage number of queries solved weekly Last Medical Encoding Quality Assessments round error rate: 0.02% Implementation of ProtoCol Amendment Changes day 1 day 10 Protocol Amendment Draft Approved Amendment Launch Changes Modify ecrf Risk Assessment of Protocol Amendment Implement Start up Activities Reconfigure EDC Additional Features EDC Update Modify Automated Validations UAT and Documentation Updates www.kcrcro.com 5

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 *Osteoartrithis *less than 8 weeks needed to lock the study 1481 screened patients 1261 randomized patients 7922 study visits 1.6 DM FTEs involved 112 044 lab results transferred from Central Lab to EDC 6.27 query per patients solved in 9.8 days (in avarage) Only 1 approved data deviation in locked database 8 weeks prior DBL 6 weeks Pre-lock meeting LPLV DBL Final DBL Accelerated Timelines Last Patient Last Visit occured Database locked and exported for statistical analysis purposes 25 days 15 days All signatures collected, database locked and archived 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: Project management Remote monitoring Training Centralized monitoring Quality assurance Risk assessment 6 www.kcrcro.com

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 similar 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 Robust: Technology@KCR KCR trained in-house experts take advantage of all possible capabilities of the tool to deliver a customized and transparent solution to each client. KCR uses Clincase, a secure, flexible and reliable EDC solution delivered by Quadratek and utilized by leading pharmaceutical companies across the globe. Flexible, customer-oriented ECRF design created inhouse by KCR DM Sponsor access to listings providing real-time view of data captured, thus enabling continued insight into the project Inbuilt randomization tool (IWRS) and medication inventory/drug supply feature, eliminating need for additional systems Automated edit checks rendering data cleaning process most efficient Inbuilt, fully customizable encoding tool, supporting commonly used medical dictionaries, e.g. WHO-DD and MedDRA Simplified data transfers between external databases and EDC e.g. Central Lab, ECG data All technology used by KCR Data Management is compliant with 21CFR Part 11 and all other industry standards including CDISC ODM and CDASH. www.kcrcro.com 7

KCR: Excellence in Clinical Trials Since 1997 KCR 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 KCR: We see human behind every number. 18 400 18 years of experience 400 clinical Trials executed 6% Observational 4% Phase IV 2% Device 11% Phase I 28% Phase II 3,000 30,000 49% Phase III Almost 3,000 Sites Contracted Over 30,000 patients recruited KCR CORPORATE Head office PERGAMON PALAIS am kupfergraben 4-4A De 10117 berlin, germany Email: info@kcrcro.com www.kcrcro.com Strategic Alliance Strategic Alliance Copyright 2015 KCR S.A. All rights reserved.