clinical data management plan_katalyst hls

CDM Process Overview

1Data Management PlanClinical Data Management2/21/2017Katalyst Healthcares & Life Sciences

A data management plan ensures compliance with good clinical data management practices throughout the entire clinical trial.

Data Management plan is a document which defines all data management activities, to promote consistent, efficient and effective data management practices for each individual study.

Data management plan not only describes data management activities, but also provide an agreement among all parties concerning responsibilities and deliverables related to clinical data management.

Data Management Plan : Overview22/21/2017Katalyst Healthcares & Life Sciences

After completing this training you will be able to:

Understand how a Data Management Plan is created in compliance with good clinical data management practices

Describe all study specific data management activities, roles and responsibilities

Understand how DMP acts as central reference for the supporting documentation and processes used during the life cycle of the study

Data Management Plan : Objectives32/21/2017Katalyst Healthcares & Life Sciences

The DMP describes the database structure and the procedures that will be used for system testing and validation and also for data entry, edit checks, data coding, data queries and query resolution.

It serves as a document for planning, communication and reference tools for clinical study teams

It provides continuity for data management activities when personnel changes occur

It also provides a record of the data handling activities to be performed for a given study along with the timelines

It also define Roles & responsibility of the different stake-holders involved in DM Activities

What is Data Management Plan?42/21/2017Katalyst Healthcares & Life Sciences

A primary goal of the DMP is to communicate to all stakeholders the necessary knowledge to create and maintain a high-quality database ready for analysis

All of the CDM process require documentation in a Data Management Plan. DMP is a crucial document and serves as a master document enlisting all the processes and quality of the clinical data Management of a clinical trial. And all the versions of the DMP and the DMP components will be made available throughout the study to all the individuals involved.

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The DMP components will be made available to all members of the Study team throughout the study

This document is a global reference, is to be read thoroughly once and used as a reference on an ongoing basis

The components once created will be distributed to the study team for review and approval

The DMP components are living documents and will be updated as study circumstances evolve, and will only be complete when the study has been terminated or closeout activities are completed

The Lead Data Manger is responsible for creating the components of the DMP

DMP Creation and Distribution52/21/2017Katalyst Healthcares & Life Sciences

Many people are involved in handling data throughout the course of a clinical study, so it is imperative that all parties refer to the DMP for a consistent approach to the processes and guidelines for conducting data management activities.

The DMP should be created during the setup phase of each study and should contain information relating to all aspects of data management activities to be performed.

The DMP document addresses to answer any process related queries about the CDM activity of the trial as well help to adhere to the regulatory requirement. DMP may be amended and revised time to time during the course of the data Management.The DMP is an auditable document often asked for by regulatory inspectors and should be written in a manner that is professional and of high quality. During an audit, the inspectors may also seek to ascertain the degree to which the project team adheres to the processes described in the DMP.

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DMP Components vary from 1 study/client to another. On a broader level, information on the following areas need to be collected within the DMP:Data FlowData CaptureStudy SetupData EntryData TransferData Processing/ ManagementCodingSafety Data (Serious Adverse Events)External dataAny milestones if applicable or Database Lock and Unlock processArchival of Clinical DataReportsQuality

DMP Components62/21/2017Katalyst Healthcares & Life Sciences

Each component of the DMP will be governed by an SOP as applicable which should be followed.6

Data Flow7This process flow will cover the following points

Data from source documents> Data entry in Trial databaseAutoquery/DM review/Monitor/CRA reviewQuery issue>site response>query resolution/re-querySource data verification, if applicableCRF freeze CRF sign offCRF and database lock Process for Database unlock2/21/2017Katalyst Healthcares & Life Sciences

Regardless of whether youre running a small, single Phase I trial or many, complex Phase III or phase IV trials you look for ways to ensure that your organization is collecting and managing clinical data reliably, efficiently and in compliance with industry and government regulations

Data Capture8DATA CAPTUREPaper Data CaptureRemote Data CaptureElectronic Data Capture2/21/2017Katalyst Healthcares & Life Sciences

Types of Data Capture9

Paper Case Report forms/Case Report Form

Remote Data Capture (RDC): Paper CRFs are used however the data entry and storage is done at the site or at a central location for multiple sites within a geographic region

Electronic Data Capture (EDC): Study information is entered directly into a computer without any paper trail

2/21/2017Katalyst Healthcares & Life Sciences

This covers all the documents that are required for setting up/building a study:CRF Creation Guidelines: Provide guidance to CRF designer on creation of eCRF.CRF data standards: Provides details of standard to be used while designing a CRF to CRF designer.Annotated CRF: Blank CRF with marking, or annotations that coordinate each data point in the eCRF form with its corresponding dataset name.Paper Case Report Form: Data collection tool used in clinical trials to support investigators and coordinators in capturing all protocol-required information. CRF Completion guidelines: Provides detailed guidelines to the site staff to fill in the paper CRFs. Guidelines help to bridge the gap between the study protocol and the users in regards to CRF completion, correction, signing and handling procedures.Study Set Up102/21/2017Katalyst Healthcares & Life Sciences

Annotated CRF: Gives the information about the structure of clinical data. Annotated CRF document the tables,variable item names, forms, visits and any other objects. It also includes codelists. It should also contain images of the entryscreens (provided in PDF). This is the first step in translating the CRFs into a database application.

CRF completion guidelines: General and protocol specific guideline on how the sponsors are expecting forms to be completed at the investigative site CRF completion guidelines should ensure that all required fields are completed, and thatthe data provided within these forms are logical within the scope of the study protocol. The CRF completion guidelines document is a tool that should be available to all members of the multidisciplinary team participating in a clinical trial, andshould be referenced to ensure accurate and consistent entry and interpretation of data. These guidelines help train site staff on proper form completion, and also aide Clinical Research Associates (CRAs) on how to review data on the completed forms.

Edit Check Specifications: Document created to identify a number of different types of data inconsistencies or potential data errorsMost edit checks are programmed into the database or CDMS and are triggered automatically when predefined conditions are not met

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Monitoring Plan: Provides detailed guidelines to Monitor/CRA on how to review CRFs and provides reference to Study specific monitoring plan where monitoring method(s), intervals between on-site visits, and other details associated with monitoring are provided.

Database design manual/eCRF specification: Provides guidance to Clinical Programmers by the DM on the Edit Checks for each data point on the CRF

Edit Check Specifications: Describes all checks (manual and electronic) that will be applied to the study data to ensure that data is fit for reporting purposes

Study Set Up112/21/2017Katalyst Healthcares & Life Sciences

This session of the DMP describe the data entry guidelines which will be followed throughout the study conduct

Data EntryData Entry Guidelines: Describes the process to enter data into the Database

Data Entry122/21/2017Katalyst Healthcares & Life Sciences

For external data transfers, the DMP should describe the data type (e.g., safety lab data), the entity providing or receiving the data and any applicable agreements, the format, the frequency of transfers, and contact information for all those involved with the data transfer

Data TransferData Load Specification: Variable/element specifications used in the studyType of the Data to be received: for example PK, Biomarker, ECG, etcSource of the data: Recipient of data (site, sponsor, data safety monitoring board (DSMB),statisticians, etc.)Reference Ranges: Reference range used in the study in case of local LabQuality control processes to be followed: Validation steps performed to maintain the integrity of the data

Data Transfer132/21/2017Katalyst Healthcares & Life Sciences

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This section of the DMP describes the Data Management documents used to ensure that the data is accurate and clean throughout the course of the study. This review allows data analysis to be performed at pre-defined study timelines as defined in the study protocol.

This section enlist:- the essential requirements on Data review- Provides variables for cleaning or provides reference of Data review plan/Data Review guidelines where instructions on data cleaning activities are captured for DM/CRA/Monitor/safety review.- This should also mention how queries are trackedEg. DM review: If action taken is Concomitant medication on AE form, check if Medication form is updated.

Data Processing/Management142/21/2017Katalyst Healthcares & Life Sciences

This section of the DMP give the details about how the Coding and Safety data will behandled during the study conductCoding ProceduresTerms to be coded: Indicate which terms will be coded, e.g. Adverse Events, Medications and Medical History, and in which modules they are foundDictionaries used: Indicate which dictionaries (and version numbers) will be usedCoding method and Responsibilities: Indicate the method and responsibility of a coderCoding Tools: Name of the tool used for the study for coding activitySafety Data Handling Safety Data: Indicates the frequency at which SAE reconciliation will be performed, for e.g. (monthly, weekly etc)Handling SAE queries: Indicate the process of how the SAE queries will be handled during the study conduct

Coding and Safety Data152/21/2017Katalyst Healthcares & Life Sciences

This section of the DMP give the details about how external data will be handled during the study conductExternal data type: Type of data collected & maintained by external vendorExternal data vendors: The point of contact, TPV details etc will be providedData transfer specifications: The attributes of the data which will be received by the vendorFrequency of reconciliations: The rounds of review of to be done & Frequency of the external data reviewAny primary or secondary reconciliation variablesEscalation path: How to follow up for unresolved issuesTrackers & Metrics if any: If any template to be followed or metrics to be generated post reconciliationQuality control: Any QC involved in the External data reconciliation will be included hereExternal data handling162/21/2017Katalyst Healthcares & Life Sciences

This section of the DMP give the details about the process to lock and unlock the database.

This section provides details on how and when to have interim and final database lock by listing the different endpoints in the study. Also provides reference to DB lock checklist that need to be used to ensure all the activities related to lock are completed. Interim locks can be used to track the level of cleanliness for the study.

It lists the milestones that need to be included in DB lock timelines.

It provides details on which level the lock should be performed eg. Datapoint/ CRF/casebook

It also provides the process to be followed when DB need to be unlocked,

Database lock and Unlock172/21/2017Katalyst Healthcares & Life Sciences

This session of the DMP gives the information regarding the organizations procedures for archiving the electronic records and list of available reports for dissemination throughoutthe life of the studyArchival of Data Method of archiving original documents: Describe when and how the archival process followed for original documents. e.g. CRFsMethod to archive documents or data related to account and database access management: document process when and how the archival process occur for account and database related accessMethod to access and retrieve the audit trail-Access management and retrieval process

Reports: Details about lists of available reports available of a particular study for use or DM/CRA/etc

Archival of Data and Reports182/21/2017Katalyst Healthcares & Life Sciences

This session of the DMP give the details regarding the quality assurance (QA) plans and quality control (QC) process steps

Quality QC Plan: Helps in fulfilling both regulatory and GCP requirement by creating the plan and detailing what documents will record the conduct of the studyPercentage of patients to be involved in QC: Sample sizeData points that will be audited: data point to be checked during quality checkAcceptable error rate: acceptable allowable error rateAction plan for resolution of audit: Details about process to handling post QC/QA findings

Quality192/21/2017Katalyst Healthcares & Life Sciences

This section speak about the related documents such as quality control plan sent alongwith the DMP as appendix

Study Specific Data handling document/Study Decision log - DynamicSelf Evident corrections (SEC)Quality control planCRF Completion Guidelines (CCGs)Study Design/eCRF SpecificationDatabase Testing PlanEdit Check SpecificationsData Entry GuidelinesData Flow Activities

DMP Documents/Elements20


Protocol A Clinical Trial Protocol is a document that describes the objective(s), design, methodology, statistical considerations, and organization of a clinical trial. The protocol also contains a study plan on which the clinical trial is based. The protocol describes, among other things, details on patient population; the schedule of tests, procedures, medications, and dosages/ devices; and the length of the study.

DMP Documents/Elements21


Study specific Data handling Document/Study Decision log Details decisions made in agreement with the study team, around the handling of certain data items whose resolution either no longer requires a DCF to be sent to the site and is specific to the study

Self Evidence Corrections Details permissible corrections or changes that can be made to subject data without issuing a Data Clarification Form (DCF) to the Site. These are changes that use data that already exists in the CRF and/or source documents attached to the CRF, e.g., laboratory report and do not impact the meaning of the data

DMP Documents/Elements222/21/2017Katalyst Healthcares & Life Sciences

Quality Control Plan Describes the process to perform a quality review or audit in order to ensure consistent quality of the database

CRF completion Guidelines Provides detailed guidelines to the site staff to fill in the paper CRFs

Study Design/eCRF Specification Provides specifications for each data point to design database Details decisions made in agreement with the study team, around the design of the Case Report Form and study database


Database Testing Plan Contains the plan and checklist to Qc the database that has been built

Edit check Specifications Describes all edit checks that will be applied to the study data to ensure that data is clean and fit for reporting purposes

Data Entry Guide Describes the process to enter data into the Database


Sample DMP documents will be discussed by the Trainer (You can also use the search engine to look up more samples)

Lets see how these look?25


Timeline included in the DMP or document referenced by the DMP lists expected completion targets for all deliverables. For example, database validation could be targeted for completion a specified number of weeks from the time the protocol is finalizedTimelines may vary based on parameters of the study, such as between paper-based studies and those utilizing electronic data capture (EDC)

DMP Timelines26


Work to be done and responsibilities are clearly stated at the start of the study so that everyone knows what is expectedExpected documents are listed at the start of the study so they can be produced during the course of, rather than after, the conduct of the studyDocument helps everyone fulfill regulatory requirements.Data management tasks become more visible to other groups when the DMP is made available to the project teamProvides continuity of process and a history of a project.Particularly useful for long-term studies and growing data management groups

DMP Benefits272/21/2017Katalyst Healthcares & Life Sciences

What do you mean by DMP?

Why is DMP essential in the CDM process?

Name and explain any 5 Components in DMP?

Name and explain any 3 DMP Documents?

How may types of Data Capture are there? Name themTest Your Understanding28


In summary the DMP Documents helps:Act as a backbone of overall Quality System of Data Management (DM)In study planningIn having SOPs and Working Instructions in placeProvide a focus for identifying work to be performed Provide details on the Roles and responsibilitiesProvide details of documentation or output to be collectedIn communicating with the entire study team

Summary292/21/2017Katalyst Healthcares & Life Sciences

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Thank You&Questions2/21/201730Contact:Katalyst Healthcares & Life SciencesSouth Plainfield, NJ, USA 07080.E-Mail: [email protected]

Controlled Copy Clinical Data Management Procedure

Enter study codeData Quality Control Plan

TITLE PAGE

ContentsTITLE PAGE11.0QUALITY ASSURANCE AND CONTROL PROCESS31.1Quality Assurance31.2Quality Control31.2.1Quality Control Plan for Study 42.0Revision History4

QUALITY ASSURANCE AND CONTROL PROCESSQuality Assurance

Define the timelines for QA activities for the study.The DMTL, in collaboration with the SDT members, performs an early check on data quality for the study to identify any systematic errors or misunderstandings. The DMTL ensures that the following early quality checks are performed : A check of the critical variables for a selection of clean subjects (5-20% of the subjects depending on study population) Ensure that all the critical variables including the critical dates are mentioned.The critical variables have to be defined by the SDT as per the critical data definition and in accordance with any project standards in the Project Data Management Information Package.Spot checks on clean subjects (review of all data for a random sample of clean subjects to detect systematic errors/misunderstandings on other than the critical variables). The pre-defined critical variables are the following:Module NamePre-defined critical variables

>>

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These early quality checks do not include a manual comparison between the data entered into the eCRF in the study database and the pCRF forms (ie, to detect data entry errors). This is checked as part of formal QC procedures applicable to paper-based data collection. These early quality checks do include a review of the data from a clinical perspective to check that data are complete, logical and consistent across modules/visits/subjects.

If all data are captured via eCRF, add N/A directly after the heading and delete the contents of section 1.2. In case of studies using paper components, complete the details.The DMTL ensures that appropriate actions taken based on the early quality check findings, including updating any data validation procedures included in the study level data management documents or ensuring that data queries are raised by the DMC to clarify/resolve any discrepancies.Please refer to the standard Quality Assurance process described in SWP_SC_SCO 010.

Quality ControlQuality Control (QC) is defined as the operational techniques and activities that exist within the quality assurance system to ensure that all quality requirements are met. (ICH E6). Quality control is an on-going process. It begins when the first CRFs are entered into the database and continues through database lock activities. The Quality Control (QC) process is applicable for all studies using paper-based data collection. The QC consists of a manual comparison of pCRF data (including data query resolutions and data entry instructions) to the data in the study database (or resultant SAS datasets).The Data Management Team: Mention the % of sample depending on the study population.Performs QC for a random selection of of the randomized subjects Documents any errors found and actions taken in the QC Report Corrects all errors found during the QC Enter study codeDecides what further actions are required if the error rate is greater than 0.5 % for non-critical data or more than 0% for critical data.Quality Control Plan for Study QC #Timing (25, 50, 75, 100%) Estimated Date (Start date of QC)Responsible for Execution (DMTL)Sample SizeCritical Modules

Indicate if QC will be conducted on complete subjects or at specified time points or visits, on batches and/or on a complete study .

Revision HistoryDateVersionAuthorChanges/Comments

For any changes made to this document during its lifecycle, post approval, details of the changes should be included in this table in the format suggested to enable track changes.

Clinical Data Management Procedure

Data Management Plan (DMP)

TITLE PAGE

Drug Substance

Project

Study Code

DMP Version Number

Date

Approval Page

Study DMP Owner- Lead Data Manager (LDM):

(Sign-off within 14 days post Go-live)

Date (Day Month Year)

Study DMP Owner- Data Management Team Leader (DMTL):

(Sign-offat the time ofFinal Database Lock)>

Date (Day Month Year)

Study DMP Reviewer- Study Delivery Team Leader (SDTL):

TABLE OF CONTENTSTITLE PAGE11.0TABLE OF CONTENTS32.0LIST OF ABBREVIATIONS43.0OBJECTIVE54.0STUDY TEAM MEMBERS65.0STUDY TIMELINES66.0STUDY DATA MANAGEMENT DELIVERABLES77.0COLLECTION OF DATA107.1Data Capture107.2Imaging118.0DATA VALIDATION119.0EXTERNAL / THIRD PARTY VENDOR DATA119.1Handling TPV Data119.1.1TPV data reconciliation129.1.2Laboratory Reference Ranges139.2Treatment Revealing/ Unblinding Data1310.0CODING AND DICTIONARY MANAGEMENT1311.0SAE RECONCILIATION1412.0QUALITY ASSURANCE AND CONTROL PROCESS1413.0DATABASE LOCK1413.1Protocol Deviations1413.2Declaring Clean File1413.2.1Clean file for interim analyses1513.3Database Lock1514.0EXTRACTION OF STUDY DATA1515.0ARCHIVING1516.0COMMUNICATIONS1617.0OTHER PROCESSES1617.1Support And Upgrades Of Data Management Systems1617.1.1DM Systems Support1617.1.2Upgrading of systems1817.2Training And Support1818.0DM SOPs/SWPs/SWIs1818.1Standard Operating Procedures (SOPs)1818.1.1For all studies1818.1.2Specific to this study1918.2Standard Working Procedures (SWPs)1918.3Standard Working Instructions (SWIs)1918.3.1For all studies1918.3.2Specific to this study2018.4Other Guidelines2019.0APPENDIX2119.1List of Appendix2120.0REVISION HISTORY21

LIST OF ABBREVIATIONSAbbreviationAbbreviation for

AEAdverse Event

ATCAnatomical Therapeutic Chemical

AZAstraZeneca

AZACAstraZeneca AutoCoder

AZACIOAstraZeneca AutoCoderIn and Out

AZDDAZ Drug Dictionary

BORBusiness Object Reports

CD/DVDCompact Disc/ Digital Video Disc

CRFCase Report Form

CRF DENCase Report Form - Data Editing Notation

CSPClinical Study Protocol

DBLDatabase Lock

DEIData Entry Instruction

DESData Extraction Specification

DMData Management

DMData Management Center

DMEData Management Enablement

DMPData Management Plan

DMPLData Management Project Leader

DMTLData Management Team Leader

DVSData Validation Specifications

ePROElectronic Patient Reported Outcome

GCPGood Clinical Practices

IVRS/IWRSInteractive Voice / Web Response System

LDMLead Data Manager

MCMarketing Company

MedDRAMedical Dictionary for Regulatory Activities

MIPSMedical Image Processing System

PDPharmacodynamics

PKPharmacokinetics

QCQuality Control

QoLQuality of Life

SAESerious Adverse Event

SASStatistical Analysis Software

SDTStudy Delivery Team

SDTLStudy Delivery Team Leader

SMFStudy Master File

SOPStandard Operating Procedures

SSUStudy Set-Up

SWIStandard WorkingInstructions

SWPStandard Working Procedures

TPVThird Party Vendor

UATUser Acceptance Testing

WBDCWeb Based Data Capture

OBJECTIVE To describe all study specific data management activities, roles and responsibilities and act as a central reference for the supporting documentation and processes used during the life cycle of the study. The DMP serves as a planning, communication, and reference tool for the study, providing a record of the data handling activities for a given study and continuity for data management activities when personnel changes occur. All the versions of the DMP and the DMP components will be made available throughout the study to all the individuals involved. The LDM is the owner of the DMP in set-up phase and should always use the standard template provided. The ownership will be transferred to the DMTL in conduct & close-out phase. The DMP and the associated components will be developed by DM Data Manager (DM), reviewed by the LDMand then distributed to the relevant Study Delivery Team (SDT) members for review. The DMP is approved by the LDM. The DMP components are living documents and will be updated as study circumstances evolve. However the version 1.0 of the DMP should be ready within 14 days post Go-liveandthe final version will be signed-off by the DMTLat the time of final database lock . This document is to be read thoroughly and used as a reference by all DM personnel working on a study on an ongoing basis. The DMP components include data management information and activities from the study start-up phase through CRF submissions and archival. All studies should follow the global CISGO standards. Any project specific standards or information can be found in Project Data Management Information Package provided by DMPL.

STUDY TEAM MEMBERSFor AstraZeneca and Data Management Center (DM) study team members and Third Party Vendor details and contacts, please refer of DMP. STUDY TIMELINESThe total sites, enrolled subjects and randomized subjects are planned in the study. For Study Deliverable timelines please refer to Study Project Plan provided by SDT and Data Management Project Plan provided by LDM in set-up phase and by DMTL in conduct and closeout phase.Study milestones Planned Date(dd-mmm-yyyy)Actual Date(dd-mmm-yyyy)

Receipt of Good copy CSP

Go- live

First Subject In

Last Subject In

Last Subject Last Visit

Last eCRF Data In

Last pCRF Data In

Last eCRF/pCRF Lock

Final TPV Data In

Final TPV Data Clean

Clean File

Treatment Revealing Data Available

Final DBL

Interim DBL (I)

Data Cut-off date for Interim DBL (I)

TPV Data Infor Interim DBL (I)

TPV Data Clean for Interim DBL (I)

Clean File for Interim DBL (I)

Treatment Revealing Data Available for Interim DBL (I)

Interim DBL(I)

Interim DBL (II)

Data Cut-off date for Interim DBL (II)

TPV Data Infor Interim DBL (II)

TPV Data Clean for Interim DBL (II)

Clean File for Interim DBL (II)

Treatment Revealing Data Available for Interim DBL (II)

Interim DBL (II)

STUDY DATA MANAGEMENT DELIVERABLESAll the final electronics versions of the DM related documents are/will beplacedin .

The final versions of the relevant study data management deliverables will be provided to the SDT for filing in the SMF. See SWP_SC_SCO_010 for information on the archiving requirements for study data management deliverables.For roles, responsibilities and timelines please refer to the Study Project Plan and Data Management Project Plan.Data Management Deliverable Tick(if applicable) Tick(if to be placed in eRoom as applicable)

DM Project Plan

DM Section of CSP

Data Management Plan (DMP)

Unique Ecrf

Data Standards Document (DSD)

Expanded eCRF

Visit Matrix

eCRF/pCRF Instructions

eCRF Review Manual (optional)/ Data Review Instructions

SAE Reconciliation (Ongoing and Final)

Dictionary CodingNA

Final Raw SAS Datasets

Clean File Form

Database Lock Checklist

Database access List

QC Report of CDs / DVDs of eCRF PDFs

Archival of eCRFsNA

Rave Validation Plan

Rave Test Plan

Rave Traceability Matrix

Rave Test Script

Rave Test Issue and Resolution Log

Rave Test Review Meeting Minutes

Rave Test Report

Rave Validation Report

Rave User Requirement Specification

Rave eCRF Configuration Report

Data Validation Specification

Custom Function Specification

Rave Report Specification

Data Extraction Specification (DES)

SAE email alert integration specification

pCRF components(delete rows that are not applicable)

Subject Questionnaire(s)(Including user instructions)

Subject Diary Cards(Including user instructions)

Data Entry Instruction (DEI) (for paper components)

Data Entry (for paper components)NA

Local Quality Control Report (if applicable) (for paper components)

Archival of paper componentsNA

TPV data(delete rows that are not applicable)

Data Transfer Logs

Data Load Logs

TPV Data: Load Specifications and Validation Documentation

TPV Data: Extraction Specification & Validation Documentation

TPV Data: Transfer Specifications

TPV data: Integration specifications and validation documentation

Test Data TransferNA

ePRO(electronic Patient Reported Outcomes)(delete rows that are not applicable)

ePRO Kick-Off Meeting Checklist

ePRO Translation Tracking Log

ePRO Device Tracking Log ePRO Device Tracking - between ePRO Service Provider and MC / Local Depot / Study Site

ePRO Device Tracking Log ePRO Device Tracking - between Study Site and Subject

ePRO Training Plan

Investigator / Study Site Personnel ePRO Training Checklist

Subject ePRO Training Checklist

Approval for ePRO to go live

ePRO Data Change Request Form

ePRO Data Closure Form

Confirmation of Receipt of ePRO Data Archive / Investigator Receipt of Archival eCRF / ePRO Data

ePRO Validation and Change Control Documentation

Database Access List for Subjects

ePRO System Validation Plan

ePRO System Validation Report

ePRO System Validation Test Plan

ePRO System Validation Test Script

ePRO System Validation Traceability Matrix

Data Report

Study Work Specification

IVRS / IWRS(delete rows that are not applicable)

IVRS / IWRS Kick-off Meeting Checklist

IVRS / IWRS Key Functionality Checklist

IVRS / IWRS User Requirements Specification Checklist

IVRS / IWRS Validation Plan

IVRS / IWRS User Acceptance Test (UAT) Plan

IVRS / IWRS User Acceptance Test Report

IVRS / IWRS User Acceptance Test Script

IVRS / IWRS Traceability Matrix

IVRS / IWRS Test Issue & Resolution Templates

IVRS / IWRS Approval to Go Live

Delete the pCRF section, if there are no paper components in the study.IVRS / IWRS Validation Report

IVRS / IWRS Risk log

IVRS / IWRS Maintenance Plan

Test Data

Validation Timelines

IWRS/IVRS-RAVE Integration Specification

Other Study Specific Documents(delete rows that are not applicable)

DM Risk Log

DM Action and Decision Log

COLLECTION OF DATAData CaptureWBDC: The Investigator or delegate will enter the data into the Rave eCRF within the timelines agreed in the CSA and in accordance with the eCRF Instructions.The subjects who have signed the informed consent will be assigned enrollment codes. If any enrolled subjects do not satisfy inclusion/exclusion criterion as specified in the CSP, they will not be randomized in the study. These subjects will be considered as Screen Failures.Minimum required data for Screen Failures: VISIT, DEM, CRIT, AE, TERM, SIGN, and, if applicable, SERAE together with MED and HISM/HISS..The Data Manager requests the Site Monitor to inactivate any module/s received for Screen Failures that is/are not required for the study.

Imaging will be used for scanning and indexing the images of paper components.The scanning and indexing will be done as per the SOP for Scanning, Indexing, Data Entry Activities, SWI_Receiving and Scanning of CRFs_SC_SCO_12 and SWI_Indexing and Data_Entry_SC_SCO_013DATA VALIDATIONThe data validation activities will be carried out as per SOP for Data Validation Activities in LS-BPO, SWI_Discrepancy Management and Closeout (WBDC)_SC_SCO_015.Please refer for data validation specifications.Please refer for the study/module specific data validation instructions.For local labs, as a part of validation activities, DM will send the out of range lab values to study physician for review and as per comments, required actions are taken.The DM will perform consistency checks for missing lab IDs, values, reference ranges and units. In addition to this, DM will also perform consistency check for sampling and visit date, as per study plan.For central labs, the DM will perform reconciliation of lab data as mentioned in section 9.1EXTERNAL / THIRD PARTY VENDOR DATAHandling TPV DataType of TPV data

Tick(if to be handled in this study)Frequency of TransferData HandlingFields to be reconciled

Subject IDVisit No.Sample IDSample DateOther

Safety LAB data(foreg Glucose, Calcium, etc.)Loaded/ IntegratedHeld externally

Electrocardiogram (ECG) data(Eclysis or non-Eclysis) Loaded/ IntegratedHeld externally

IVRS/IWRS dataLoaded/ IntegratedHeld externally

ePRO dataLoaded/ IntegratedHeld externally

Imaging DataLoaded/ IntegratedHeld externally

Loaded/ IntegratedHeld externally



Please refer to the respective Data Transfer Specifications, for each type of TPV data.TPV data reconciliationThe DM will reconcile the above mentioned fields between the database and TPV data. The DM will be responsible for handling discrepancies either with the site or with the third party supplier.TheTPV data reconciliation will be done as per Third Party Vendor Data Reconciliation Process Map,SWI_PK_SC_SCO_020, SWI_Lab_SC_SCO_021,SWI_ECG Eclysis Data processing_SC_SCO_022, SWI_ECG_TPV data processing (Non eclysis)_SC_SCO_023, SWI_e-PRO_SC_SCO_024Laboratory Reference RangesThe SDT will be responsible for providing signed laboratory reference from the sites. In case new ranges are provided, the updates will be done by DM/SSU to the RAVE database as per the . The new reference ranges will be applied only to data received after the date of reference range update or on all data depending on the validity date of the reference ranges.Treatment Revealing/ Unblinding DataType of Treatment Revealing Data

Tick(if to be handled in this study)Frequency of TransferData HandlingFields to be reconciled

Subject IDVisit No.Sample IDSample DateOther

PKLoaded/ IntegratedHeld externally

PDLoaded/ IntegratedHeld externally

Biomarker data Loaded/ IntegratedHeld externally


Please refer to the respective Data Transfer Specifications, for each type of treatment revealing data and how it will be merged and reconciled with the clinical study data.CODING AND DICTIONARY MANAGEMENTThe modules and terms to be coded will be taken from the Project Data Management Information Package provided by the DMPL.The coding and dictionary management activities will be carried out as mentioned in the SOP for Coding Activities and SWI_Coding_SC_SCO_016.Terms to be codedModule nameDictionary Used (This will be the latest version used inthe study)

Adverse events

Medications

SAE RECONCILIATIONThe SAE reconciliation will be performed manually. The Business Object Reports (BOR) from Sapphire will be used as safety database listings. This data will be reconciled with relevant AE/SAE listings from clinical study database. The SAE reconciliation activities will be carried out on a basis and at the clean file as described in the SOP for Serious Adverse Event Reconciliation Activities and SWI_SAE_Reconciliation_SC_SCO_017QUALITY ASSURANCE AND CONTROL PROCESSQuality Assurance(QA) process involves data review which includes checks to ensure data are complete, logical and consistent across modules/visits/subjects.QA will be performed for all modules with emphasis on critical modules .Depending on the phase/complexity of the study, data for all critical modules will be reviewed by the Quality Audit Team at periodic intervals. For the list of critical variables/ modules in the study and further details please refer to the Data Quality Control Plan Document provided as of the DMP.DATABASE LOCKProtocol DeviationsThe SDT reviews the protocol deviations to be included in the Clinical Study Report regularly and provide direction to the Monitors and Data Management Team as needed. To facilitate this review the DMTL works with the DM team to ensure that the SDT are provided with a listing of all important protocol deviations on a regular basis.For more details refer Declaring Clean FileDMTL will set up the Clean File meeting and coordinate the completion of the Clean File Form.Clean File will be declared by DMTL and SDT, AZ R&D > and documented on the Clean File Form as per the SWI_Discrepancy Management and Closeout(WBDC) _SC_SCO_015.The DMTL will ensure that all study data have been write protected by restricting access, as soon as the Clean File Form has been signed.The system accesses will be handled as described in the Access Management Guidelines.Clean file for interim analysesThe interim analysis will take place at All DM pre-Clean File checks be applicableDMTL will set up the Clean File meeting for interim analysis and coordinate the completion of the interim Clean File Form.Interim Clean File will be declared by DMTL and SDT, AZ R&D > and documented on the Interim Clean File Form as per the SWI_Discrepancy Management and Closeout(WBDC) _SC_SCO_015.The data used for the interim analysis will be protected by means of .Database LockThe final study database will be protected from changes by restricting access after the Clean File Form has been signed and the treatment revealing data have been included.Details for DB lock procedure can be referred in SWI_Discrepancy Management and Closeout(WBDC) _SC_SCO_015.DMTL will lock the final study database.EXTRACTION OF STUDY DATAClinical study data is made available to Data Management Enablement (DME), AZ R&D at during the study.After database lock final raw data is provided to DME, AZ R&D .ARCHIVINGThe DM documents, final clinical study database, , programs will be archived according to SWP_CZ_CRF Archivingand SWI Archiving of Study Documents in CZ DMand the Study Master File (SMF)index. Any additional documentation will be archived according to the local procedures.The DM generates submission and archival PDFs and is responsible for creating the site-specific CDs containing eCRF PDFs and sample PDFand providing it to SDT. This will be performed as per SOP for Submission Ready Activities in LS BPOThe DM documents during the set-up phase need to be providedby LDM to SDT for archival within 1 month of Go live . The DM documents during conduct and close-out phases will be provided by DMTL to SDT for archival within 1 month of DB lock.

COMMUNICATIONSData Management kick off meetings and update meetings will be held as agreed between LDM and SDT during set up phase and , between DMTLand SDTL during handover meeting and during conduct phase >.Please refer to the DM kick-off meeting presentation for study communication plan details.

OTHER PROCESSESSupport And Upgrades Of Data Management SystemsDM Systems SupportSystem Tick(if used in this study)DetailsSystem Support provided by

Rave

Rave is a web-based data capture (WBDC) tool for data capture, monitoring and validation of data

Medidata

JReview

JReview is a data review tool, which is an add-on application to Rave that allows users to view reports and graphs of clinical data. JReview accesses the clinical views.

Medidata

SAS

SAS is used for study specific programming such as data checks, reports and ad hoc programs. SAS is the format for data transfers and extracts.IBM Helpdesk

AstraZeneca AutoCoder (AZAC)

AZAC is a web-based auto encoding tool.

IBM Helpdesk

AZACIO

AZACIO Intermediate tool for data flow between Rave and AZAC.

IBM Helpdesk

CRF DEN

An application used to index, search, retrieve, view and print CRFs in US. This electronic repository contains completed patient specific documentation generated during clinical trials.

IBM Helpdesk (US)

PSI

An application used for scanning, indexing &imaging . It is capable of delivering publishing ready pdf post all pages are indexed.CAMT/Bluestone tec.

Clinstore

Clinstore is an electronic repository for eCRF data (both Archive PDF & Submission PDF), blank eCRF and annotated eCRF.IBM Helpdesk

Sapphire BO Reports

Business Object Reports (BOR) from Sapphire will be used as safety database listings.

IBM Helpdesk

CAVE

Cave/Structure Data Storage (SDS) All study data will be stored as SAS datasets in write protected area in study SDS folder in CAVE.

IBM Helpdesk

WBDC: The SDTL is the first point of contact for the study site for support on study specific and related issues. Upgrading of systemsUpgrades to new versions of the system/programs used will be decided during the study. Any updates will be coordinated from AstraZeneca .

Training And SupportAll personnel involved in the data management of this study must have adequate experience in accordance with the Procedure for Quality Controland Procedurefor Training.

DMSOPs/SWPs/SWIs

All the DMSOPs/SWPs/SWIs are available in the below link.

Standard Operating Procedures (SOPs)Standard Operating Procedures (SOP) Tick(if applicable)

For all studies

SOP for Clinical Data Management Activities in LS BPO

SOP for Serious Adverse Event Reconciliation Activities

SOP for IS Security Policy

Procedure for Training

Procedure for Quality Control

SOP for SSU Activities in LS-BPO

SOP for Scanning, Indexing, Data Entry Activities

SOP for Coding Activities

SOP for Submission Ready Activities in LS BPO

SOP for Data Validation Activities in LS-BPO

Specific to this study

SOP for External Data Set-Up and Data loading Activities in LS-BPO

Standard Working Procedures (SWPs)Standard Working Procedures (SWP) Tick(if applicable)

SWP_SC_SCO 010

SWP_SR_ 010

SWP_SSU 010

Standard Working Instructions (SWIs)Standard Working Instructions (SWI) Tick(if applicable)

For all studies

SWI_Coding_SC_SCO_016

SWI_CZ_Database Quality Control_SC SCO_025

SWI_Discrepancy Management and Closeout (WBDC)_SC_SCO_015

SWI_Rave_eCRF Development_SSU_020

SWI_Rave_eCRFTesting _SSU_028

SWI_Rave_Edit Check build & Unit testing_SSU_029

SWI_Rave_Formal Testing of Edit Checks_SSU_030

SWI_Rave_Output Development_SSU_026

SWI_Rave_Output QC_SSU_032

SWI_Rave_Report QC_SSU_033

SWI_Rave_Reports Development_SSU_027

SWI_Rave_SAE Email_SSU_025

SWI_Rave_Site_and_User_Administration_AM_010

SWI_SAE Reconciliation_SC&SCO_017

SWI_SST_SSU_016

Specific to this study

SWI_ECG_Eclysis_DA_SC_SCO_022

SWI_ECG _NE_TPV data processing (Non eclysis)_SC_SCO_023

SWI_ePRO_SC_SCO_024

SWI_Lab_SC_SCO_021

SWI_PK_SC_SCO_020

SWI_Receiving and Scanning of CRFs_SC_SCO_12

SWI_Indexing and Data Entry_SC_SCO_013

SWI_PCRF_Development_Printing_SSU_010

SWI_Rave_Batch Uploader_SSU_024

SWI_Rave_Custom Function_SSU_023

SWI_Rave_Test Plan Writing_SSU_031

Other GuidelinesDM Guidelines Tick(if applicable)

Access Management Guidelines

Rave Lab Reference Update Process Map

Third Party Vendor Data Reconciliation Process Map

AZ Guidelines

Project Data Management Information Package

APPENDIXList of AppendixAppendix no.Name of Appendix

AStudy Team Details (AZ, DM and TPV)

BRave Data Validation Specifications

CData Quality Control Plan

DData Review Instructions

REVISION HISTORYThe following amendment(s) have been made to this document since the finalization of version 1.0.

Date(dd-mmm-yyyy)VersionAuthorChanges/Comments

clinical data management plan_katalyst hls

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