Introducing OpenClinica

1. Introducing OpenClinica

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

3. 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)

4. 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

5. 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

6. 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, MySQL • Used by major IT players eg Google, HP & IBM • Has been argued provides better software • saved the Human Genome Project according to Lincoln Stein

7. Introducing OpenClinica 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

8. Submit data Module; Web-based Data entry and validation Clinical Case Report Forms (CRF) OC - DataBase CRF Design, validation and import Define CRFs in Excel Temp. Creating Data Bases in OpenClinica Designing a database in OC; requirement and flow of data.

9. Data Base Creating in OpenClinica A part of CRF Excel Template: “Some tricks”.

10. Creating Databases in OpenClinica 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.

11. The Back End of OpenClinica • Developed using Java J2EE framework • Application Server- Tomcat 5.x • Uses JDBC with JSP based front-end. • Database PostgreSQL 8.x or Oracle 10g • custom ports to DB2, SQL Server, or MySQL also possible • Has 74 related tables

12. Important Features of OpenClinica • 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

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

15. Uploading CRFs The excel sheet is then uploaded onto OpenClinica

16. Event Definition

18. Data Entry

19. Data Extraction

20. System End of OpenClinica

21. NAS1 Database Database server The Back Up Setting • 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. PgDump utility Creates a backup file on the secondary HDD on the main server. File automatically copied to NAS1

22. Restore Process • Installing Application Stack I.E. Postgresql, Apache Jarkata Tomcat,J2SE runtime environment and Deploying OpenClinica • 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

23. 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.

24. Working with OpenClinica • 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

25. GCP Regulations and OpenClinica • 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

26. 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.

27. 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.