SCDM EDC Concepts and Study Start-up 2023

EDC Study Start-up Minimum Standards

Ensure compliance with 21 CFR 11 and FDA Guidance,
standards for capture, management, and archiving,

Ensure requirements are defined for data transfers and data integration,

software validation and user acceptance testing prior to EDC study implementation,

EDC Study Start-up Minimum Standards

Verify training is provided to all users, documented and minimum competencies met,

Verify access to data is limited to authorized individuals,

Determine roles and responsibilities in data review and query Management,

Provide technical support with toll-free number

Ensure site access and control up to database lock

EDC Study Start-up Best Practices

Use business process analysts (possibly external, for objectivity) to establish EDC-specific workflow processes and identify required transitions from current processes.

Do not apply paper study processes to studies using ED

EDC Study Start-up Best Practices

Identify stakeholders in current processes, as well as additional
stakeholders required for new EDC processes.

Plan studies to avoid "last minute" system modifications that introduce errors and complexity to study-specific CRFs

EDC Study Start-up Best Practices

Develop CRFs or data collection tools with teams of individuals from monitoring, data management, statistics, regulatory affairs, and medical, ensuring adequate attention to the collection of safety data.

EDC Study Start-up Best Practices

Ensure systems are user-friendly and flexible for data entry.

Ensure EDC systems do not restrict answers site staff can provide in a way that introduces bias into the clinical study.

Ensure adequate edit check procedures and query management tools are built into EDC software

EDC Study Start-up Best Practices

Before the start of a study, conditions (e.g., SDV completed, all queries resolved) for locking forms and/or casebooks should be set according to a set of criteria, such as, all SDV complete, all data review complete, no outstanding queries or missing data exist.

When coding in an EDC environment it is recommended not to display coded terms back to the site user

EDC Study Start-up Best Practices

Ensure data can be traced from the time of original input through the reporting and analysis files via easily accessible audit trails.

Ensure ease and quality of all data transfers by testing data transfers prior to deployment of EDC systems.

Ensure your EDC system integrates as needed with other databases by testing integrations with your EDC system prior to initiating any trials using the system

EDC Study Start-up Best Practices

Ensure processes are defined to integrate laboratory and other non-CRF data with data obtained from the CRF.

Ensure all user acceptance tests are documented.

Ensure change control procedures include complete documentation.

Ensure all documentation for use by site staff is adequately reviewed before being provided to site staff

EDC Study Start-up Best Practices

If 24 x 7 x 365 support is not available, the help desk should cover the work days/times of all regions included in the study.

The help desk should support the minimum number of languages needed to communicate with all users and all languages, including local dialects

EDC Study Start-up Best Practices

Develop and follow SOPs for electronic data capture, data validation, and data archiving.

Assess current SOPs for potential impact created by EDC workflow processes and update SOPs as necessary.

Include SOP modification time in project plans for EDC implementation.

Assume that both the new workflow and SOPs will be in transition for some period of time as the staff interact with the EDC system following any modification of SOPs.

EDC Study Start-up Best Practices

Identify issues that merit periodic reminders, such as user ID and password security, and schedule recurring reminders.

Provide an instruction manual for study workflow processes.

Verify all users have documented training prior to being granted access to the system

EDC Study Start-up Best Practices

Create a training environment in which users can practice, and create training cases as examples that are pertinent to the study.

Provide a "Train the Trainer" program for clinical research associates (CRAs), data managers or others to be able to provide training to sites.

Provide training customized to each user's role. A study coordinator may need in-depth training of most system functions, while users with read
only access may need minimal instructions.

Document all training for trial master files as well as site files.

EDC Study Start-up Best Practices

Integrate metrics on process and cost/benefit into the EDC process to enable better EDC versus non-EDC comparisons and comparisons across EDC technologies.

CRF specifications should be finalized prior to finalization of edit check specifications, although development of both should be performed concurrently

EDC Training

Documentation for all users, training environment, train the trainer, role customization

Kinds Of Data Collection

offline / Paper, Online / EDC, hybrid

Data Collection Mode determination

Site readiness
Edit checking complexity
Audit trails - as stipulated in 21 CFR part 11
Subject population
Study timelines
Study management strategy
An assessment of the ability of the sponsor's clinical trials management system (CTMS) to interface with an EDC solution

Study Start-up Timelines 1

Revision of SOPs to support the EDC process

Define roles and access to data by authorized sponsor and site staff

User account management, which may include access control logs and account management documentation

Definition and creation of new or modified standard data collection forms

Study Start-up Timelines 2

Trial specific programming and UAT

Preparation of coding dictionaries and processes as needed

Design, programming, and testing of reports. Establish standard reports that can be reused across compounds

Communicating trial status impact on timelines

Definition and requirements testing for data transfers and integration with other systems or third party data. Utilize industry standards where possible (ODM, LAB, etc.)

Study Start-up Timelines 3

Selection of task-specific applications that
may need to be integrated with the EDC system

Site assessments for the ability to use EDC

EDC system- and trial-specific training

Help desk support for users

Disaster recovery planning

Start Up For EDC

Forms design, forms annotation edit check specifications, UAT, documentation, disaster recovery planning

Source Data Requirements

Complete, accurate, valid

Key Source Data

Primary Efficacy;
inclusion/exclusion;
medical and medication history;
physician exams and vital signs;
adverse events;
visit dates;
conmeds;
A record that the patient has entered a clinical study and the date of informed consent

Disasters Include

Fire, theft, weather, unavailability of key staff, insolvent EDC vendor

DRP Disaster recovery plans by increasing serverity, include:

- Localized failure—one system drive becomes nonfunctional
- Server failure—an entire server becomes nonfunctional
- Office building failure—all resources become unavailable at a building where business operations are conducted
- City failure—all resources become unavailable within a geographic region

BCP

Business continuity plan for study continuity during recovery

BCP Includes

Alternate processes for temporary or permanent unavailability

EDC Development Considerations

Understanding different types of software technology

Understanding different EDC system capabilities

Researching general information about vendors

Thick Client also known as a "fat client" or "rich client"

Software that performs the bulk of data processing operations and does not necessarily rely on the server, e.g. Word processing

Thick Client Advantages

Local processing
Less burden on server
Better multimedia performance
Flexibility
Thick clients allow sites with low bandwidth to still remain electronic and transmit their data on-demand

Thin Client

Server-dependent processing, e.g. EDC

Thin Client Advantages

Lower IT administrative costs to the project

Easier to secure

Lower hardware costs

Less network bandwidth

More efficient use of resources

Simple hardware upgrade path

ASP

Application service provider: vendor who owns and runs the software and hardware

advantages to using an ASP model for an EDC system

Little or no setup time is needed, and limited or no software integration is required to begin using the client software

Pay per use of the software or "pay as you go"

Costs for software development and upgrades are shared by multiple clients rather than solely by one client

In-house experience is not required, and niche employees do not need to be hired

advantages to using an ASP model for an EDC system

Vendor handles the challenges of system up-time, reliability, security, and scalability

IT costs are maintained at a predictable level, and fewer expensive or specialized IT staff are required

Installation of heavy infrastructure is not required

disadvantages to using an ASP model for an EDC system

Clients must usually accept the software "as is". Customizations usually do not occur unless several clients have made the same request and the vendor is willing to change the software

Loss of control of data: because the software is owned and maintained by the vendor, clients must ensure that proper service level agreements for system up-time and application availability are in place.

Technology Transfer

Software and hardware in-house

EDC System Capabilities Key features

Software Qualification and Validation
Support of Library Functionality
Electronic Investigator Signatures
Electronic CRF Archiving
Export Formats

EDC Integration

Clinical Data Management System (CDMS)
SAS
ePRO
CTMS
Paper Component
Laboratory Data
External, non- laboratory Data
Other (coding, IVRS, eHR)

International Study Considerations

Ascertain whether the local language can be used in a multi-national study

Plan early for CRFs that must be programmed in multiple languages

Ensure hardware deployment timelines are increased. Country specific laws may delay shipments significantly

Establish a plan to manage time zone differences, especially in relation to time and date stamping

International Study Considerations

Ensure hardware and software can be used at study sites, and that sites are prepared to use the tools that will be deployed to them

Develop a plan to manage system upgrades, which is particularly important if the system is being used 24 hours a day

Consider the wording of manual queries to ensure they will be understood by speakers of other languages

Consider issues posed by language barriers to staff training

EDC Assessments Checklist - Minimum

The types of data formats to export from the system

The formatting and process for final archived CRFs

The required software functionality, such as types of edit checks and the process for obtaining investigator signature

Details of service level agreements (SLAs)

Ecrf Archiving

Transferring data to read-only format

Export Formats

CDISC, Access, SAS, ASCII, character deliminated files, Oracle, extensible markup language (XML), SQL

Vendor SLAs and Performance Reports

sponsor must emphasize the writing and managing of service level agreements for performance. A contract should be established between the sponsor and vendor providing help desk services

Detailed Help Desk Planning

Tier-One Software Support
Providing Toll-Free Support
Multilingual Capabilities Required

Gap Analysis between Existing SOPs and EDC Requirements

The staffing evaluation plan should analyze the sponsor organization for any gaps between available resources and
the resources needed to conduct and manage the EDC study

Metrics and Performance Targets

Study build timeline metrics
Number of subjects screened and/or enrolled
Subject visit date to data entered in system for that visit
Current status and history of SDV
Number of queries outstanding (measure in number of days)
Percent of data/visits clean
Number of queries per site
Query frequency counts per da
Time from last patient visit (LPV) to all data entered and/or data cleaned
LPV date to data lock date

Reports to Support Study and Process Management

create a flow chart that outlines each report deliverable and the person responsible for approving that report design

Schedule meetings to review and obtain feedback

Determine the metrics important to the study and design reports to capture these metrics

If the study involves a CRO, consider what reports will be required from the CRO

Define CRO performance requirements and design a report to track performance of and provide feedback to the CRO

CDM Deliverables During Study Start-up for EDC

CRFs
Edit Checks
Coding

Site Evaluation and Qualification for EDC Study

Site Technical Capabilities
Site Connectivity, CRA Connectivity at Sites
Site Provisioning (Training)
Site Hardware and Broadband Provisioning

End User Preparation for EDC Study

Setting System Rights Determined by Roles and Privacy
User IDs and Passwords
Account Management
Training Prior to System Access

Recommended Sops For EDC

EDC Design Specifications
System Setup, Installation and Support
EDC Training
Medical Coding
Data Collection and Handling
Data Backup, Recovery, and Contingency Plans
Data Review and Validation
Prequalification Requirements including 21 CFR Compliance
User Access Creation, Modification and Revocation
Systems and Hardware Security
Guidelines for Outsourcing with Vendors/Vendor Management
Handling External Data
Coding Medical and Clinical Terms