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 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.

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 DATA MANAGEMENT WORKFLOW

Receipt of CRFs
First Pass Second Pass
(CRF Tracking/Filing) Auto
Entry Entry Clinical Data
Management Coding

Batch
Validation

Data
Clarification
Form Thesaurus
(DCF)

DCF Discrepancy Manual

Resolutions Management Coding

SAE
Quality Control
Reconciliation
Plan
Database
Lock

Electronic
Archival
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.
KEY MEMEBERS:

The Key members involved in

Data Management:

➢ Clinical Data Manager

➢ Database Administrator

➢ Database Programmer

➢ Clinical Data Coordinator

➢ Clinical Data Associate

Bigger Picture
Clinical Trail Overview
MULTIDISCIPLINARY TEAMS IN CLINICAL
TRIALS

1. Clinical Investigator 11. Regulatory affairs

2. Site coordinator 12. Clinical Data Management
3. Pharmacologist 13. Clinical Safety Surveillance
4. Trialist/Methodologist Associate (SSA)
5. Biostatistician 14. IT
6. Lab Coordinator 15. IT/IS personnel
7. Reference lab 16. Trial pharmacist
8. Project manager 17. Clinical supply
9. Clinical Research 18. Auditor/Compliance
Manager/Associate
10. Monitor
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 RESPONSIBILITIES OF CDM

Study Setup
➢CRF design and development (paper/e-CRF)
➢Database built and testing
➢Edit Checks preparation and testing

Study Conduct
➢Data Entry
➢Discrepancy Management
➢Data Coding (using MEDRA and WHODD
dictionaries)
➢Data review (Ongoing QC)
➢SAE Reconciliation
➢Data Transfer
 Study Closeout
➢SAE Reconciliation
➢Quality Control
➢Database Lock
➢Electronic Archival
➢Database Transfer
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 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.

➢Traditional Paper Based Case Report Forms

➢e-CRF (Electronic Case Report Form)- Study information directly
entered into computer.
➢e-CRF is prepared by using:
➢ORACLE CLINICAL
➢CLINTRIAL
Paper CRF e-CRF
 HOW MANY CRFS DO YOU NEED?

•Eligibility or Screening form

•Physical Exam form
•Enrollment form
•Medical History form
•AE form/ SAE form
•Concomitant therapy form
•Blood test form
•Laboratory test form
•Follow-up Visit form
 DATA BASE DESIGN
Data from a clinical trial will be collected
and stored in some kind of computer
system.
A database is simply a structured set of
data.
A collection of rows and columns.
--Excel Spreadsheet
--Oracle application
DBMS:
MS Access XP, MS Excel XP
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:

Validation Checklist describes in detail which data shall be checked and

queried if necessary. The programming of the checks occurs
according to this checklist. Before the programming starts, the
sponsor will be asked to give approval of this Validation Checklist.

UAT: User Acceptance Test

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. 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.
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CRF Tracking
Logistic way if it is paper based study.
EDC-electronic data capture if it is e-CRF.

Data Entry
Data entry is a process of
entering/transferring data from case
report form to 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 Universal ruling 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)

Manual coding is performed using Thesaurus

Management System (TMS) which is integrated with
our Clinical Data Management System (CDMS).
 SAE RECONCILIATION

● Serious Adverse Event (SAE) data reconciliation is the comparison of key

safety data variables between Clinical Data Management System
(CDMS) and Master Drug Safety Database (MDSD). Reconciliation is
performed to ensure that events residing in both systems are
consistent.
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 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.
 OBJECTIVES OF CDM

Sufficiently clean to support statistical analysis, and its subsequent

presentation and 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 suffinterpretation
 IMPORTANCE OF CDM

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

➢CDM Professionals:
o Pharmacists
o Graduates/Post graduates in Life Sciences, IT, Statistics
o Graduates with post graduation diploma in Clinical Research
o Licensed Medical Practitioners

➢Utilize qualified individuals to:

o Supervise overall conduct of trial (Project Manager)
o To handle and verify the data (Data Manager)
o To conduct the statistical analysis (Biostatistician)
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o To prepare study reports (Medical Writer)
 DM ROLE IN CLINICAL RESEARCH

Data Management 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