CLINICAL DATA MANAGEMENT SYSTEMS

KAMAL AKHTAR
Background and Introduction

Paper based methods of data management involve more cost, effort and time.

The advent of PC based systems that can validate data has brought dramatic reduction in cost
and time.

In addition to a front end system a backend system is needed to:

-Collect the data from the front end system
-Audit the transfer of data from the front end system to it and otherwise.
-Clean the data and code the medical terms
-Resolve discrepancies between data values
-Broadcast object changes to the front end system

A system that incorporates the capabilities of both front end and back end systems within its
framework hence providing data entry , medical coding, query management, auditing and data
analysis functionality dynamically within an integrated system can be called a CDMS.

Today most of the CDMS are huge complex centralized databases having a friendly front end
interface over the web.

Examples of widely used CDMS are Oracle Clinical and Clintrial.

CLINICAL DATA MANAGEMENT SYSTEMS

A CLINICAL OVERVIEW
 Origin of Data Management in Clinical Trials

Clinical Data Management originated in the need to:

Generate accurate Generate statistically The regulatory requirement

data significant, clean and that all data should be
In a timely fashion. audited data. traceable to its source.

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Paper based method Electronic method Computer based method

Client Server
-Error prone -Different data standards
-Time consuming -Real time analysis not -Large cost on hardware
-Resource consuming possible -Networking issues for
multi centric trials
What is a CDMS?

A Clinical Data Management System (CDMS) is a standardized, 21 CFR Part

11 compliant, validated database management system specifically designed for
managing all aspects of a clinical trial including clinical study planning,
preparation, performance and reporting.
 What is a CDMS used for?

Investigator
Relationship
Management

Re a ollm
Pa ruit d nt
An Dat

t ie m e
c n e
al a

nt nt
En
ys

r
is

Protocol preparation and documentation

Costs CDMS CRF development and management

ing FUNCTIONS Documentation (planning, distribution, tracking)
Clinical Track Management
Supplies DCF development and management

Rep
orti oring
ng nit
Mo

AE
Quality
SAE
IRB approval and decision status
What are the advantages of CDMS over legacy systems?

Legacy systems Intermediary between paper based methods and CDMS

Example: Winchester Business Systems, SAS

Weaknesses:

Could not provide long term support for underlying software

Steep operating and support costs
Costly and risky for long term use
Availability of original system experts slowly reduced
Not compliant with regulatory standards.

CDMS The new standard of clinical data management

Example: Oracle Clinical

Advantages:

Compliant with regulatory standards (21 CFR Part 11, CDISC)

Cost effective (hardware costs is reduced)
Reliable
System experts only required at the application support side
CLINICAL DATA MANAGEMENT SYSTEMS

A TECHNICAL OVERVIEW
 What are the CDISC data standards to be met by a CDMS?
ODM
(Operational Data Model)
SDM
(Submission Data Model)
ADaM
CDISC (Analysis Data Set Model)
Clinical Data Interchange
SEND
Standards Consortium
Standard for the exchange
of Non-Clinical Data
Standards for exchange, CRT-DDS
Storage, archival and Case Report Tabulation-
Submission of clinical Data Definition Specification
Data.
Lab Standard
Protocol Standard
Format for storage, exchange and archival
Format for submission of clinical data to FDA
-Provides metadata models
-Analysis datasets to generate statistical
results
Organization, structure an format for non-
clinical data
-Data definition specification for CRT as XML
- Enhances speed of processing by
regulators
-Also called define.xml
- Exchange of Lab data
-Still under development
-To describe study protocol in machine
readable format.
-Allow automated database setup, computer
based workflows
 DATA FLOW USING CDISC STANDARD

Electronic Health Record

Patient Info

ODM XML Clinical Trial ODM XML

Data

Protocol Patient Info Integrated

Representation Administrative,, Reports
Tracking,
ODM Clinical (CRF) ODM ODM XML
Trial Design Lab Acquisition SDM Data,
XML Trial Data XML Define.xml
Analysis Plan Info Analysis Data,
(SDM) (defined by SDM)
Metadata
CRF, Analysis
Data
(e) Source Regulatory
Clinical Trial Protocol
Document Operational and Submission
Analysis Databases s

SDM and Protocol Source

ODM
Analysis Data Information Data
The following roadmap shows the various standards being applied and the standards that
are yet to be implemented:

BRIDG

LAB

ODM A
SDM
LAB &
SDM
B
ODM

Define.xml
LAB,ODM,
Define.xml,
C
SDM
ADaM

LAB,ODM,
Define.xml, CDISC
D
ADaM, SDM Standard
PROTOCOL

2005 2005-2006 2006 2007-2010

ROADMAP TIMETABLE
 What are the components of a CDMS?

CDMS

RDBMS Features/Tools

THIRD PARTY TOOLS

API
e.g. RDC

The RDC (Remote Data Capture) module is generally not a part of a CDMS with the exception of
Oracle Clinical.

For other systems the RDC and other third party applications have to be patched with the CDMS
using a specific Application Programming Interface (API) which depends on the architecture of
the CDMS.
CLINICAL DATA MANAGEMENT SYSTEMS

VENDORS
What are the types of CDMS used by Pharmaceutical companies?

CDMS may be of three types:

In-House Systems
- These are systems that have been designed in-house
- Modules/applications can be modified as per need
- Have issues being regulatory compliant due to flexibility
-Relatively cheaper to develop

Vendor Systems
- These are CDMS designed by third part/company specifically to be licensed/sold to industry
players
- They have been validated as per regulatory guidelines (21 CFR Part 11 etc.)
- Modules/applications cannot be modified at the core but integrated using a validated API
- Very costly to implement

Open Source CDMS

- By far the only open source CDMS available is OpenClinica
- It is 21 CFR Part 11 compliant, supports HIPAA guidelines
- It is free of cost
- Has issues of security
Which are the various CDMS available in the market?

The various CDMS available today are:

Oracle Clinical

Phase Forward

Siebel Clinical

eResearch Technology

Paraxel / Perceptive Informatics

MediData

NexTrials

SAS Drug Development

ClinSource
What is the market share of various CDMS being used?

Market shares of the top 7 participants among the commercial, vendor supplied CDMS.

These vendors make up 60% of the CDMS market.

Additional 40% of the systems are homegrown.

CLINICAL DATA MANAGEMENT SYSTEMS

CASE STUDY ORACLE CLINICAL

 Overview of Oracle Clinical

Oracle clinical has 27%

market share in the vendor
supplied CDMS market.
The most integrated CDMS
available in the market.

comprehensive solution
for management of
clinical data.

The only CDMS having a RDC

(remote data capture) application
integrated with it.

Allows standardization of data definitions across a global operation

enabling consistent management and interpretation.
What are the various components of Oracle Clinical and their
application in Clinical Data Management ?

Oracle Clinical is the CDMS component OPA (Oracle Pharmaceutical Applications), an

integrated suite of applications provided by Oracle.

The other components of OPA are:

- RDC for entering and managing data from the investigator site.

-TMS for classifying investigator terms against medical dictionaries

-AERS for managing product safety

 The Core Clinical Data Management Engine (RDBMS)

ORACLE CLINICAL
(CDMS)

Laborator Data Study

Administr Plannin Global Desig Data
y Definitio Condu
ation g Library n Extract
Reference n ct
Ranges

The CDMS subsystems as in

Oracle Clinical v 4.5

ARCHITECTURAL SUBSYSTEMS OF ORACLE CLINICAL

 Study Design
& - Designing protocols and amendments
Management - Specifying method of tracking patients (by site/visit etc.)

-Enables trials to be managed multi-centrically

-Global library stored definitions for standard clinical data elements, code
Study Data lists, CRF data entry layouts, validation and derivation criteria and data
Definition extract specifications.
-Laboratory reference range management
Oracle -Validation (uses a library of re-usable procedures)
Clinical
-Globally distributed data capture
Data Capture - Automatic validation during data entry
& - Tracking discrepancies
Validation - Real time data capture integration using Microsoft C++ API

-Storage of data in universal format

Access & - Ability to extract data into SAS for analysis
Reporting - Query Management
- Create multiple reports in various formats (PDF, HTML, Postscript, RTF)

Functional Subsystems/Components of Oracle Clinical

 What is the basic architecture of Oracle Clinical?

OPA Integrated Architecture

Clinical trials are set up and managed by Sponsor/CRO and site using Clinical Trial Minder and
Clinical Site Minder (CTMS)

TMS is the central coding system for both Oracle Clinical (CDMS) and Oracle AERS (Safety
System)

Oracle AERS pulls AEs and metadata from CDMS thus reducing reconciliation efforts.

The AERS reconciliation engine compares the CDMS and AERS and flags any differences in reports.

Oracle Clinical RDC can be said to be a different front end of Oracle Clinical. Data entered through
the RDC goes directly into the same tables as data entered from Oracle Clinical

Oracle Clinical and RDC use the same data definitions, screen layouts and edit checks.
 Oracle
Site / Trial Minder
(CTMS)

Oracle
AERS Oracle AERS
Clinical Oracle Clinical
Reconciliation (Safety System)
RDC (CDMS)
Engine

Oracle TMS
(Dictionary Management)

ARCHITECTURE OF OPA (ORACLE PHARMACEUTICAL APPLICATIONS)

What is SAS?

Online Compilers Interfaces

Statistical Data Warehouse
Graphics Data for for
Analysis Visualization Administration
Entry C - programming WWW

Functionalities of SAS

Latest version is SAS 9.1.3

Worldwide Leader in Statistical Analysis

The SAS Workspace
What is the SAS Drug Development platform?

Ability to make informed Assess Collaborate across

Business decisions. safety trials
and efficacy

Managing Reporting
Functionalities
Analyzing Reviewing

SAS/ACCESS Modules
SAS/STAT

SAS 9 Architectural Components CDMS

Base Package (RDBMS)
What are the various components of SAS Drug Development?

-Support structure for all components

- Provides basic repository object model
Collaborative - Mechanism for analysis and reporting
Framework -Transactions performed over SSL -128 bit
- Follows 21 CFR Part 11

- Means of extracting data from CDMS

Data - Reorganizing data for reporting and analysis
Warehousing - Transforming the extracted data
- Enriching the data with metadata
- Documenatation Management- 21CFR Part 11 compliant

-Extraction of custom analysis data structures

Analysis - Integration of third party analysis tools
And - Run batch programs without intervention
Reporting

-Prepare SAS transport files of analysis data sets for submission

Regulatory -Access reports, tables, figures, listing due to integration with
Submissions Document management system.
Support - Validation of the analysis results
What are the advantages of using SAS Drug Development ?
Collaborative Framework
Real time collaboration
Security
Interim reviews
Centralized repository
Regulatory compliance
Data Warehousing
Build common repositories of
standardized, analysis ready data
sets in a validated controlled
enviornment.
Automatically generate
Documentation for the process
Analysis and Reporting
Report Codes management
User level management of
Reports
Framework for integration of
third party tools
Regulatory Submissions Support
Reduced errors rates
Integrated enviornment for
validating results
Audit Trailing to document
compliance
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