What is Clinical

Data Management
Clinical Data Management is involved
in all aspects of processing the clinical
data, working with a range of computer
applications, database systems to
support collection, cleaning and
management of subject or trial data.
• Clinical Data Management is the
collection, integration and validation of
clinical trial data

• During the clinical trial, the investigators

collect data on the patients' health for a
defined time period. This data is sent to
the trial sponsor, who then analyzes
the pooled data using statistical
analysis.
Data management plan design
•data to be gathered from trial participants,
•existing data that can be integrated,
•data formats,
•metadata and its standards,
•storage and backup methods,
•security measures to protect confidential information,
•data quality procedures,
•responsibility assignments across team members,
•access and sharing mechanisms and limitations,
•long-time archiving and preservation procedures,
•the cost of data preparation and archiving, and
•compliance with relevant regulations and requirements.
 Why CDM
• Review & approval of new drugs by Regulatory Agencies is
dependent upon a trust that clinical trials data presented are
of sufficient integrity to ensure confidence in results &
conclusions.

• Presented by pharma company, important to obtaining

that trust is adherence to quality standards &
practices.

• Hence companies must assure that all staff involved in

the clinical research are trained & qualified to perform
data management tasks.
 Key Members
The Key members involved in Data Management

• Project Manager /Data Manager

• Database Administrator
• Database Programmer / Developer
• Clinical Data Associate
CLINICAL TRIAL OVERVIEW
Multidisciplinary Teams in Clinical Trials

1. Clinical Investigator 9. Ethics committee

2. Site coordinator 10. Regulatory affairs
3. Trial Pharmacists 11. Clinical Data Management
4. Biostatistician 12. Pharmacovigilance
5. Lab Coordinator 13. IT/IS personnel
6. Project manager 14. Clinical supply
7. Clinical Research 15. Auditor/Compliance
Manager/Associate
8. Monitor
 Responsibilities of CDM
Study Setup
• CRF design and development (paper/e-CRF)
• Database build and testing
• Edit Checks preparation and testing
Study Conduct
• Data Entry
• Discrepancy Management
• Data Coding (using MedDRA and WHODDE
dictionaries)
• Data review (Ongoing QC)
• SAE Reconciliation
• Data Transfer
Study Closeout
• SAE Reconciliation
• Quality Control
• Database Lock
• Electronic Archival
• Database Transfer
CDM Process Overview
 Study Start Up Process Review

C R F design

Database
Pr o t o c o l
design

Validation/
der iv ation
Procedures

Ac t iv a t e d d a t a b a s e
r e a d y to a c c e p t
production data
 CRF Design/Review
• A representation of the study as outlined in the protocol is made
(including CRF completion guidelines if necessary). Therefore, a final
protocol needs to be available before this activity can be initiated.
• CRF design usually takes about three rounds: First draft (rough without
detail but correct content), second draft (as good as we can get it) and
final version.
• We need input from our sponsor to correct draft versions and to
approve the final version.

QA DATA EDC
• Traditional Paper Based Case Report Forms
• e-CRF (Electronic Case Report Form)- Study information directly
entered into computer.
Paper CRF e-CRF
How many CRFs do you need?
• Eligibility or Screening
• Randomisation
• Physical Exam / Vitals
• Medical History
• Follow-up Visit
• AE form/ SAE form
• Concomitant therapy form
• Laboratory test form
• Status Evaluation
Data Base Design
Data from a clinical trial will be
collected and stored in the CDMS

A database is simply a structured

set of data.

A collection of rows and

columns.
--QAData CDMS
DBMS:
MS Access, MS Excel Oracle Clinical,
Clintrial, Phaseforward InForm ,
medidata Rave
 CRF Annotation
• An annotated CRF is generally defined as a blank CRF with
markings, or annotations, that coordinate each data point
in the form with its corresponding dataset name.
• Essentially, an annotated CRF communicates where the
data collected for each question is stored in the database.
• CRF Annotation is the first step in translating the
CRFs into a database application.
• CDM annotates the CRFs by establishing variable names for
each item to be entered.
• Reviewed by CDM and Statistician
Validation Checklist:
 Edit specifications list describes in detail which data
shall be checked and queried if necessary.
 The programming of the checks occurs according to
this list.
 Before the programming starts, the sponsor will be
asked to give approval of this list.
 Test subjects are entered in the database to test the
entry screens and the programming.
 The exact number of test subjects is not standard,
but every check has to pass and fail (negative and
positive proof) at least once.
Database set up and testing
 Database setup and testing are always performed in a
secure, non study data environment (test site).
 Only when a database has been reviewed and fully
tested, will it be set in ‘production’, a separate
environment where only study data will be entered.
 Changes in structure or programming will always
first be performed and tested in the non study data
environment before they are made effective in the
‘production’ database.
 CRF Tracking
• Logistic way if it is paper based study. EDC-electronic data
capture if it is e-CRF. Data Entry

• Data Entry
• Data entry is a process of entering/transferring data
from case report form to the Clinical Data
Management System (CDMS).
• Data Entry: 1) Single data Entry
• 2) Double Data Entry
Discrepancy Management
Discrepancy management is a process of
cleaning subject data in the Clinical Data
Management System (CDMS), it includes
manual checks and programmed checks.

Trivial discrepancies are closed as per self

evident correction method or Internal rulings
and discrepancies which require response
from the site are queried by raising Data
Clarification Forms (DCF).
 Medical Coding
The medical coding for a study is done
as per the project specific protocol
requirement. The dictionaries used for
a study are:

Adverse Events: MedDRA (Medical

Dictionary for Regulatory Activities)
Medications: WHODD (World
Health Organization – Drug
Dictionary)
SAE Reconciliation
• Serious Adverse Event (SAE)
data reconciliation is the
comparison of key safety data
variables between Clinical Data
Management System (CDMS)
and Sponsor PV.
• Reconciliation is performed to
ensure that events residing in
both systems are consistent.
 Quality Control
• Quality Should be maintained for overall study by
performing Quality checks at intervals for all data points
(Critical & Non- Critical) prior to database lock.
• QC helps to ensure that all the data processed is
accurate, clean and correct.
 Database Lock
The database lock for a study is
done to ensure no manipulation
of study data during the final
analysis.
Database lock for a study is done once
all data management activities are completed.
This includes the database lock checklist
which ensures the same.
Some of the activities included in
database lock checklist are-
All discrepancies closed, DCFs received
and updated, coding complete, SAE
Reconciliation process complete etc.
• CDM is a vital vehicle in Clinical Trials to ensure:

• The Integrity & quality of data being transferred from trial

subjects to a database system
• That the collected data is complete and accurate so that
results are correct
• That trial database is complete and accurate, and a true
representation of what took place in trial
• That trial database is sufficiently clean to support statistical
analysis, and its subsequent presentation and
interpretation
 Importance of CMD
CDM has evolved from a mere data entry process to
a much diverse process today

• It provides data and database in a usable format

in a timely manner
• It ensures clean data and a ‘ready to
lock’ database
CDM Professionals
• ICH.E6.5.5.1: Utilize qualified individuals
to:
• Supervise overall conduct of trial (Project
Manager)
• To handle and verify the data (Data
Manager)
• To conduct the statistical analysis
(Biostatistician)
• To prepare study reports (Medical
Writer)
DM Role in Clinical Research
 The data management function provides all data
collection and data validation for a clinical trial
program

 Data management is essential to the overall clinical

research function, as its key deliverable is the data to
support the submission

 Assuring the overall accuracy and integrity of the

clinical trial data is the core business of the data
management function
DM Role in Clinical Research
 Data management starts with the creation of
the study protocol

 At the study level, data management ends

when the database is locked and the Clinical
Study Report is final

 At the compound level (of the drug), data

management ends when the submission
package is assembled and complete
Mission of CDM Consistency
Accuracy
Validity
Archiving
DATA MANAGEMENT WORKFLOW

Data Clarification
Form
(DCF)
 Data Manager
• Investigator-initiated trials usually have a Data Manager within the
Sponsor-Investigator’s central coordinating trial team.
• Responsibilities may include:

Development of the Data Management Plan and any other SOPs or

guidelines to ensure data management activities are in accordance with
GCP.
Coordinate the design, build, test and validation of the Case Report Form
(CRF) or clinical database.

Coordinate process for integrating other systems for Electronic Data

Capture (EDC).

Develop CRF Completion Guidelines for participating sites.

 Continue…
Assign database user permissions in accordance with PI approval

Enter data from paper CRFs into database.

Perform data cleaning, resolve data queries.

Generate datasets for interim analysis (if applicable) or reporting

and final analysis (after database lock).

Archive trial data at end of trial.

 Clinical Trial Systems –
Technology Usage
• Protocol Development –
– Word Processing software such as Word, Adobe
– Document Management Solutions such as Documentum for
organizing and standardizing the process of protocol development
– Protocol Authoring / Modeling tools
– Simulation software
• Investigator/Site Selection and Trial Preparation
– Excel Sheets
– In House Tracking systems to track receipt/ approvals of
documents
– Internet based software systems
 Clinical Trial Systems –
Technology Usage – Cont…
• Subject Identification and Enrollment
– Media Advertisements
– Databases from local hospitals -
– Call centers
– Publicly available subject data from organizations such as Center
Watch
• Collection, Monitoring and Processing of Data
– Clinical Data Management Systems (Paper based)
– Electronic Data Capture
• First Generation EDC tools
– OCR and OMR (Post Marketing Trials)
– Remote Data Entry
– IVRS (Interactive Voice Response Systems)
 Clinical Trial Systems –
Technology Usage – Cont…

• Second Generation EDC tools

– Integrated functionalities with much more clinical trial
process functionalities
– Extensive usage of internet
– Hybrid systems with 2 modes of operations, online and
offline
– Enhanced IVRS
– ePRO systems
 Integrated
CTMS
Regulatory Compliant

Study Site Staff

Management Management Management

Offline and Online Capability

Subject Contracts Data
Management Management Management
Secure

Document Patient Diary

Medical Coding
Management Integration

Adverse Supplies
Monitoring Event Reporting Management

LAB Data External Interfaces Randomization

Data Standards
compatible
Alternative Views of CTMS systems
Thank You