Introducing OpenClinica

Investigator Monitor

Involved Laboratories

Data Manager

Statistician

Clinician

RegulatoryAuthority

Subject

Diary

CRF

DCF

CRF DCFSample

LabResults

ClinicalData

NDA

It’s all about data

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, 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

Introducing OpenClinicaFree, 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

Designing a database in OC; requirement and flow of data.

Define CRFs in Excel Temp.

CRF Design, validation and import

Submit data Module; Web-based Data entry and validation

OC - DataBase

Clinical Case Report Forms (CRF)

Creating Data Bases in OpenClinica

A part of CRF Excel Template: “Some tricks”.

Data Base Creating 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 itemVALIDATION 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.

Creating Databases in 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

The Back End 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

Important Features of OpenClinica

Done in excel using a blank CRF template provided by Openclinica

Designing CRFs

The excel sheet is then uploaded onto OpenClinica

Uploading CRFs

Event Definition

Data Entry

Data Extraction

System End of OpenClinica

• 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

NAS1DatabaseDatabase

server

The Back Up Setting

• 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

Restore Process

• 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.

Deploying O/C for Multiple Sites

• 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

Working with 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

GCP Regulations and OpenClinica

• 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.

Technology 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.

Policy & Procedures Best Practices