Introducing Open Clinica Its all about data Subject

Introducing Open. Clinica

It’s all about data Subject Diary CRF DCF Investigator Monitor Sample CRF DCF Clinical Data Lab Results Involved Laboratories Statistician Data Manager Clinician NDA Regulatory Authority

What is CDMS? • A clinical data management system or CDMS is used in clinical research to manage the data of a clinical trial • It is set up to help with processing data from source through validation checks, analysis, reporting and storage; • Also useful for Coding (particularly for AEs and Medications) – MEDRA (Medical Dictionary for Regulatory Activities) – WHOART (WHO Adverse Reactions Terminology)

Institutional Approach • Setting up a specific CDMS requires institutional decision making at policy level • Whatever the choice, it comes with a cost • Requires infrastructure and equipment set up • Requires minimum core competencies • Dedicated time for learning and development • Opportunities to try out

Preferred Software characteristics • • • Standards based Well known many skilled practitioners available Readily mastered and modified Should run on any platform Should be affordable for small groups in resource constrained countries

Why an open source approach? • Potential advantages of Open Source solution – – – – – Cheaper More amenable to change No vendor lock in More able to be integrated with other systems Likely to be well documented Designed to be multilingual Open source software works eg R, Apache, My. SQL Used by major IT players eg Google, HP & IBM Has been argued provides better software • saved the Human Genome Project according to Lincoln Stein

Introducing Open. Clinica Free, open source, web-based software for EDC built by Akaza Research Features: – – Management of diverse clinical studies through a unified interface Clinical data entry and validation Data extraction Study oversight, auditing, and reporting

Creating Data Bases in Open. Clinica Designing a database in OC; requirement and flow of data. Submit data Module; Webbased Data entry and validation Clinical Case Report Forms (CRF) OC - Data. Base Define CRFs in Excel Temp. CRF Design, validation and import

Data Base Creating in Open. Clinica Page no Resp_Type Validation Required 1 1 text ST regexp: /[AZ]{3}/ 1 pidnu PAD No. 2 1 text ST regexp: /[0 -9, A 1 -Z]{7}/ 1 2 text REAL func: gte(-3. 0) WHZsco Wght/hght Z re score ons Resp_Valu es Date type Col_No Child Initials Resp_Lab el Resp_opti Label childini Units Item_name A part of CRF Excel Template: “Some tricks”. 1

Creating Databases in Open. Clinica Defining CRF on Excel Template §ITEM_NAME - This is the unique label or variable name for this data element. §DESCRIPTION_LABEL - give an explanation of the data element and the value(s) it captures. §UNITS - the units that the value of this data element should be captured in. §GROUP_LABEL - grouped items will display as a row within a table. §COLUMN_NUMBER - allow adjacent items or items with the same parent to be aligned together. §RESPONSE_OPTIONS_TEXT - list of the text values of the responses for this response set as a comma-delimited string. §RESPONSE_VALUES_OR_CALCULATIONS - comma-delimited list of the encoded values. §DATA_TYPE - data type; ST, INT, REAL, DATE. §VALIDATION - validation expression to run an edit check on this item §VALIDATION Expression - Expression Type: 1) regexp - Supports Java-style regular expressions. regexp: /regular expression/ e. g regexp: /[A-Z]{3}/, requires a three-letter string (all uppercase) 2) func - Supports built-in library of basic integer functions. func: func(args) e. g func: range(1, 10), func: eq(1), func: gte(10. 5) etc.

The Back End of Open. Clinica • Developed using Java J 2 EE framework • Application Server- Tomcat 5. x • Uses JDBC with JSP based front-end. • Database Postgre. SQL 8. x or Oracle 10 g – custom ports to DB 2, SQL Server, or My. SQL also possible – Has 74 related tables

Important Features of Open. Clinica • Organization of clinical research by study protocol and site. • Dynamic generation of web-based CRFs in portable Excel templates. • Management of longitudinal data for recurring patient visits • Data import/export tools for migration of clinical datasets. • Interfaces for data query and retrieval across subjects, time, and clinical parameters • Compliance with regulatory guidelines e. g. 21 CFR Part 11 • Built on robust and scalable technology infrastructure interoperable with relational databases

Designing CRFs Done in excel using a blank CRF template provided by Openclinica

Uploading CRFs The excel sheet is then uploaded onto Open. Clinica

Event Definition

Data Entry

Data Extraction

System End of Open. Clinica

The Back Up Setting Database server Database NAS 1 Pg. Dump utility Creates a backup file on the secondary HDD on the main server. File automatically copied to NAS 1 • Backups implemented via a scheduled command running as a batch file that writes out the data and metadata for each of the studies databases adding Timestamp information to the filename.

Restore Process • Installing Application Stack I. E. Postgresql, Apache Jarkata Tomcat, J 2 SE runtime environment and Deploying Open. Clinica • Using a suitable Postgres database GUI(e. g. pgadmin III) create a new blank database on the database server • Run the pg_restore command on the server and select the backup file to restore

Deploying O/C for Multiple Sites • OC is deployed a as Openclinica. war file “Web Application archive“. It is a JAR(JAVA ARCHIVE) file used to distribute a collection of Java Server Pages, servlets, Java classes, XML files, tag libraries and static Web pages (HTML and related files) that together constitute a Web application. • Standard Installation Process is well documented inside an instructions file that ships with the application. • To deploy separate instances, rename the Openclinica. war to [studyname]. war • Deploy as a normal OC application using the standard procedure and effect changes in database credentials inside the datainfo. properties of the deployed web Application.

Working with Open. Clinica • Policy determination needed • Required human and material resources allocated • When know-how is established, utilization requires only 5 main steps: – – – Designing Creating CRF’s Event definitions Data Entry Data Extraction

GCP Regulations and Open. Clinica • O/C by design, is compliant to the most stringent regulatory requirements • O/C is designed to be compliant to FDA 21 CFR Part 11 Electronic Records; Electronic Signatures • These are guidelines that govern the use of electronic records and signatures ; and can be summarized in two broad categories: – Technology best practice – Policy and procedures best practice

Technology Best Practices • Audit trail must be independently generated • Ensure that system maintains a “irrefutable link” between documents, metadata and the electronic signature. • Establish clear electronic signature manifestations for all electronic records. • Validate the system. • Establish role-based access and control. • Establish password and identification controls. • Series of signings. • Avoid hybrid systems, where practical. • Do not over customize technology solutions.

Policy & Procedures Best Practices • Establish corporate internal policies and guidelines for: – – – Validation and procedures Disaster recovery Revision and change control procedures System access and security procedures Training procedures Document control procedures • Develop a clear, comprehensive migration strategy. • Understand the impact of “open” or “closed” system definitions. • Establish retention policies based on current predicate rule requirements.