Introduction to

Data Management

DIPEN KHANNA
Manager – Data Review
Pfizer Pharmaceutical India Pvt. Ltd.

21 April 2005
What is Data Management?
 Historically, Data Management has been
thought of as “running edit checks” and
“writing queries”.

 While these two aspects of Data Management

still exist as very important functions, Data
Managers are responsible for many other
aspects of managing the data, which may
include…

21 April
2005
What is Data Management?
 Setting up complex checks in either the Clinical Trial
database or Data Browser programs
 Managing a vendor who is performing the data management
for a study
 Interacting with other specialty outsource vendors (e.g.,
Central Labs)
 Acting as a key contributor to the larger Clinical Project
team
 Oversight of Case Report Form and database development
 Knowledge of several complex systems for overseeing the
data and data quality (e.g., OC, OC RDC, etc.)
 Others???

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2005
What is Data Management?

Defined simply, Data Management is…

The entire process involved with taking

original raw data from the clinical sites
and compiling and validating it, so that it
is suitable for reporting.

21 April
2005
What is Data Management?
Ways in which data are managed:
 Monitoring and Source Document Verification
 Validation checks within a database
 EDC auto-hits at the clinical site
 Manual data checks
 Double data entry of all CRF data
 Blinded data review (BDR)
 Issue and resolve site queries
 Code Adverse Event & Medication terms
 Review of data listings
 Database QC audit
 Others???
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2005
 Data Management Responsibilities

Study Start-up:
 Coordinate Protocol and CRF development
 Develop data management documents
– CRF Completion Guidelines
– Data Management Plan
– Self-evident Corrections
– Data Entry Guidelines

21 April
2005
 Data Management Responsibilities
Study Start-up:
 Oversee database development
– I*NET
– Oracle Clinical
 Identify, oversee development, and test validation procedures
 Oversee Imaging system set-up
 Perform/oversee lab set-up

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2005
 Data Management Responsibilities

Study Conduct:
 Maintain data management study
documents and ensure they are in the TMF
 Oversee data management activities
performed by a CRO/FSP and provide
necessary study specific documents
 Generate, distribute, and resolve queries

21 April
2005
 Data Management Responsibilities

Study Conduct:
 Participate in dictionary coding
– Adverse Events
– Medications
– Medical History
 Request and track batch validations
 Oversee electronic data loads

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2005
 Data Management Responsibilities

Study Conduct:
 Perform CRF page tracking
 Oversee data flow
 Participate in blinded data reviews (BDRs)

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2005
 Data Management Responsibilities

Study Close-out:
 Test break blind program
 Oversee QC Audits
 Perform database release and re-release
 Document post-database release changes

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2005
How Does DM Fit into Clinical Research?
• The data management function
supports/oversees 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.
21 April
2005
How Does DM Fit into 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, data management ends

when the submission package is assembled and
complete

21 April
2005
 How Does DM Fit into Clinical Research?

ICH Guidelines for Good Clinical Practice list requirements for how
clinical trial data shall be validated and updated.
 ICH GCP 5.5
 ICH GCP 8.3.14
 ICH GCP 8.3.15

Example:
5.5.1 “The sponsor should utilize appropriately qualified
individuals to supervise the overall conduct of the trial,
to handle the data, to verify the data, to conduct the
statistical analyses, and to prepare the trial reports.”

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2005
Additional Guidelines -

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2005
Importance of Effective Data Management

The quality of a clinical study is

only as good as the weakest data
point…

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2005
 Importance of Effective Data Management
Statistical analysis
– an accurate database is the basis for drug approval by the FDA
– Adherence to federal regulation and guidelines mandate the safety
and welfare of patients participating in trial and ultimately, the
safety of patients prescribed the approved drug
Marketing the drug
– It is important for patients and physicians to clearly understand the
indication for the treatment, potential side effects, and
contraindications for the use of the product
Post marketing surveillance
– Drug companies are required to send safety information to the
FDA after the drug has been approved and marketed
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2005
 Ensuring Quality Data

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2005
The CRF or Other Data Collection Tool (DCT)…

We all know the saying…

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2005
The CRF or Other Data Collection Tool (DCT)
…
Protocol to CRF:
• The study protocol dictates what data need to be
collected.

• The CRFs or DCTs should be designed to collect only

the data required to answer the study protocol’s
research question(s).

• Collecting the “nice to have” data that is not specified

in the protocol should be avoided.

• Standards should be adhered to.

21 April
2005
The CRF or Other Data Collection Tool (DCT)…
CRF to database:
• The CRF defines the overall design and structure of
the clinical trial database.

• Data should only be collected in one place. Multiple

sources of the same data introduces additional
possibilities for error.

• If a data point must be summarized it must be

captured as a numeric or coded value. Free text cannot
be summarized.
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2005
 The Clinical Trial Database

Oracle Clinical (OC):

Storing and validating the clinical trial data.
An industry standard for managing clinical trial data.

OC is a fully validated system:

Conforms to the software development life cycle (SDLC)

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2005
The Clinical Trial Database

Excel spreadsheets or Access databases should never

be used to capture the clinical trial data, as they
are not validated for that purpose and do not
conform to GCP Guidelines.

• Excel and Access are not set up to require 1st and 2nd
pass data entry

• Excel & Access have no audit trail to track data

changes

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2005
Oracle Clinical Structure
OC is set up to allow for
easy data entry and data
retrieval.
The data entry screens are
actually set up in sequential
order of the CRFs, so that a
Data Entry operator can
enter the data quickly.

Oracle Clinical
21 April
2005
Data Verification

 Verification: check that what is in the

source doc is on the CRF and what is on the
CRF is in the database

 Verification ensures that data are reported

accurately on the CRFs and are consistent
with the source data.

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2005
Data Verification

 Data Verification is performed:

– At the site via source document
verification
– In-house via:
Double data entry

Data reviews – BDRs, listings, etc.

21 April
2005
Data Validation

 Validation: check that what is in the database is

logical, consistent, and analyzable

 Validation ensures that data are:

 Complete

 Correct

 Allowable

 Valid

 Consistent

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2005
 Data Validation

 Data Validation is performed:

– At the site via CRF review for consistency and validity
– In-house via:
Programmed data checks within Oracle Clinical

Manual data review via listing or edit check

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2005
Verifying and Validating the Data

 Potential Sources for Error

– People
– Data entry
– Coding process

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2005
Verifying and Validating the Data

 Possible Types of Error

– Erroneous Data
– Protocol Deviations
– GCP Violations

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2005
 Data Management Documentation
 Data Management Plan may include:
– Lists checks performed
– Identifies which discrepancies can be solved in-
house (self-evident changes or no action required)
– Identifies which must be queried to the
investigator
– Lists any assumptions that can be made during
review/coding process

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2005
 Data Management Documentation

Self-Evident Corrections (SEC):

–Lists all changes that can be made to the data

by sponsor without a query to the Investigator

–Site is sent document prior to start of

discrepancy management and at least one more
time once the study has ended

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2005
When to Query the Site

• Only a very limited number of corrections can

be made to the data, without querying the
clinical site.

• For any data discrepancies that cannot be

corrected as self-evident and are clearly data
errors, a query, or Data Clarification Form
(DCF) must be sent to the site.

21 April
2005
Data Queries
 Definition
– Individual questions sent to investigative site
concerning a data discrepancy
– Should be generated on ongoing basis
– Should be resolved as early as possible
– Query cycle time consuming and expensive
 Commonly quoted each query cost

$50-$75 to resolve
 Query generation/resolution typically takes

up 50% of the total data processing time

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2005
 Data Queries
 Data Discrepancy Flow
Data Discrepancy

Generate Query Self-Evident

Correction

Send to Site Data Manager makes

Change to Database
Site Responds
with Answer
Data Manager makes
Change to Database
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2005
 When are the Data Considered Clean?
• All data has been received and entered

• All DCFs and OC discrepancies have been addressed and resolved

• A final QC has been performed across the entire study database

• At this point the database may be locked and unblinding

information is added.

• Checks are run to validate the unblinding information.

• The database is then frozen and released for analysis.

• All SAEs are reconciled with the safety database.

21 April
2005
Database Release
Making any post-release changes
is highly discouraged, unless
significant data issues are
identified.
There are very clear & detailed
procedures on how to make a
post-release change, should it be
necessary.

21 April
Oracle Clinical
2005
 Reporting the Data---Data Out
A1 2 3 4 5 6 L is tin g o f B e s t S u b je c t R e s p o n s e w ith D e m o g ra p h ic D a ta
S u b je ct In itia lsAg e Sex R a ce T re a tm e n t Be st Re sp o n se Du ra tio n o f Re sp o n se
ABC 56 M C auc as ian O ur Drug S table D is eas e 36 week s
DE F 48 F A fric an-A m eric anO ur Drug P artial R es pons e 22 week s
G HI 62 F A s ian O ur Drug P artial R es pons e 19 week s
K LM 46 F C auc as ian Com petitor Drug P artial R es pons e 13 week s
NO P 53 M H is panic Com petitor Drug S table D is eas e 17 week s
RS T 38 M A s ian O ur Drug P artial R es pons e 35 week s
UV W 59 F A fric an-A m eric anCom petitor Drug P rogres s ive Dis eas eN/A

• This is a sample listing for the fictitious Oncology

study A123456.
• This may be one of many tables used to perform
the overall analysis of this trial’s data.

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2005
 Summary

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2005
 Flow Chart of Activities
Detailed
Detailed statistical
statistical
Protocol
Protocol Design
Design CRF
CRF Design
Design Database
Database setup
setup analysis
analysis plan
plan written
written
and
and validation
validation
procedures
procedures

Data
Data entry
entry Indexing
Indexing Scanning
Scanning Monitored
Monitored CRFs
CRFs
received
received

Data
Data verification
verification Data
Data Entry
Entry audit
audit Online
Online dictionaries
dictionaries
Merge
Merge data
data into
into
automatically
automatically
database
database
applied
applied

Update
Update database
database Send Generate
Generate queries
queries Batch
Batch validation
validation
Send to
to sites
sites thro’
thro’
with
with resolutions and
resolutions and CRAs/
CRAs/ DMs
DMs
close
close out
out queries
queries

Database
Database audit
audit Database Programming
Programming for for Tables
Tables generated
generated
Database closure
closure for
for
reporting all
all safety
safety &
& efficacy
efficacy
reporting 100%
100% QC
QC of
of tables
tables
tables
tables completed
completed

CSR Issue
Issue of
of final
final Review
Review of
of reports,
reports, Statistical
Statistical report
report
biometrics
biometrics tables
tables tables
tables by
by clinical
clinical on
on methodology
methodology
and
and report
report text
text and
and biometrics
biometrics and
and findings
findings
21 April 2005 teams
teams
 Data Management Workflow
 Define project specific data management
requirements
 With Study Start Up:
– Develop CRFs
– Develop database
– Develop validation checks
 CRF computerized tracking, entry and
verification
 Tracking electronic data loads
21 April
2005
Data Management Workflow
 Validation checks and data listings generated
 Data review, coding, and query generation
 Query resolution and database changes
 Final database updates and verification
 Final database quality check
 Database lock and delivery to reporting
 Post-release change management

21 April
2005
 Whew!!!

21 April
2005
 Q&A

21 April
2005
 Thank you for your
participation today!!!

21 April
2005