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SOURCE DATA
CLINICAL DATA MANGEMENT • RECORDS

(CDM) • ORIGINAL RECORDS OF CLINICAL FINDINGS

• OBSERVATIONS IN CLINCAL TRIALS
• RECONSRTUCTION AND EVALUATION OF THE TRIAL
• SOURCE DATA ARE CONTAINED IN SOURCE
DOCUMENTS

SOURCE DOCUMENTS SOURCE DOCUMENTS

• ORIGINAL DOCUMENTS,DATA,RECORDS • MICROFICHES,PHOTOGRAPHIC NEGATIVES
• HOSPITAL RECORDS,CLINICAL & OFFICE CHARTS • MICROFILM OR MAGNETIC MEDIA
• LABORATORY NOTES & FINDINGS,MEMORANDA • X-RAYS
• SUBJECT’S DIARIES OR EVALUATION CHECKLISTS • SUBJECT FILES
• PHARMACY DISPENSING RECORDS • RECORD KEPT AT PHARMACY
• RECORDED DATA FROM AUTOMATEDINSTRUMENTS • RECORDS AT THE LABORATORIES
• COPIES OR TRANSCRIPTIONS CERTIFIED AFTER • MEDICOTECHNICAL DEPARTMENTS INVOLVED
VERIFICATION AS BEING ACCURATE COPIES IN THE CLINICAL TRIAL
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Source Document: The electronic record to used INTRODUCTION

to keep together a collection of eSource data
• CRO’s
items for capture, transmission, storage, • DATA GENERATION & PRESENTATION
and/or display; and serving as a source • ACCURACY OF TRAILS & REGULATORS
• INFORMATION TECHNOLOGY (IT)
document for a clinical investigation.

Raw Data: Data as originally collected. Distinct COMPUTERIZED SYSTEM (REMOVAL OF

TRADITIONAL SYSTEM PAPER WASTAGE )
from derived. Raw Data includes original • GROWTH & REQUIREMENTS OF GOOD DATA
MANAGEMENT SYSTEMS THAT COMPANIES WHICH
observations, measurements and activities
ARE OTHERWISE IT-BASED

• HAVE FULL FLEGED CLINICAL TRIAL DATA MANAGEMNET Good Clinical Data Management
SYSTEMS WHICH BRING THEM A GOOD AMOUNT OF Practice (GCDMP)
BUSINESS AND REVENUE • The objective of GCDMP is to generate high quality
database devoid of errors and omissions
• CDM is a fundamental process which controls data
• ICH GUIDELINES
accuracy of each trial besides helping the timelessness to • US FDA REGULATIONS
be achieved. DRUG AND DEVICE DEVELOPMENT PROCESS
• It helps in linking clinical research co-ordinator = who The Society of Clinical Data Management (SCDM) has
created a comprehensive document- Good Clinical
monitor all the sites & collects the data Data Management Practices (GCDMP) (Version 4.0 is
the most recently updated version published in May
• Link with biostatisticians = who analyze, interpret and
2007)- that provides guidance on accepted practices of
report data in clinically meaningful way. Clinical Data Management (CDM)
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SYSTEMIC APPROACH FOR CDM

• INITIAL PLANNING
SPONSOR or INVSTIGATOR or CRO
Standardized database management system
CRF CASE RECORD FORMAT
CRF as per database need, setting realistic
dates for receipt, verification, query
resolution, corrections, Final editing and
release of data and finally resource
mobilization

• Preparing for Incoming Data Data • Establishing systems for tracking of CRF;s like
management study master file SOP’s should Barcodes, deciding which CRF copy to be
be established to ensure operational working copy (usually second copy)
documentation for computers, system • Validating CRF and other data transfer
reliability, Validation and accuracy. procedures.
• System security for hardware software and • Data Transfer may be on Paper or Electronic
data from theft and sabogate.
• Adequate access code and back up of the
data.
• Indexes & Checklists for CRF’s
• Designing data entry screens
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INITIAL DATA REVIEW AND

INCOMING DATA
VERIFICATION
• Data received continuously and in a timely • DATA REVIEW COMMITTEE MEMBERS
manner • MAINTAINING BLINDING DURING REVIEW AND
• Helps in data testing methodology, validates ENTRY OF THE DATA
data base management system (DBMS), helps in • ERROR DETECTION IS AN IMPORTANT STEP TO BE
checking accuracy and completeness of CRF DONE BEFORE AND DURING DATA REVIEW AND
VERIFICATION
• Timely clarification of errors and omissions with • THE VARIOUS ERRORS THAT ONE CAN EXPECT
the investigators. DURING THIS STAGE CAN RANGE FROM MISSING
• It is also important to decide on unambiguous DATA, FAULTY COMPLETION OF
Codes for subject identification that allow FORMS,QUESTIONABLE VALUES (E.G. HEIGHT 20
identification of all the data of any subject. FEETS), TREND TESTS TO GROSS PROTOCOL
VIOLATIONS

• SUBSEQUENT ERRORS CAN ALSO BE DETECTED DATA ENTRY, VERIFICATION AND

AT VARIOUS STAGES LIKE DURING COMPUTER
ENTRY, ERRONEOUS CODING OR VALIDATION
INVESTIGATOR’S CORRECTIONS NOT BEING • The Data entry person should be defined for the
TAKEN INTO ACCOUNT. specific trial & specified in a data management
• DATA MONITORING COMMITTEE HELPS IN plan.
ASSESSING THE PROGRESS OF TRIALS AT • For transcription from paper CRF to electronic
INTERVALS TO RECOMMEND WHETHER TO CRF different procedures are used:
CONTINUE, MODIFY OR STOP THE TRIALS.  Double Data Entry form (one person)
• IT ALSO EVALUATES SAFETY DATA AND CRITICAL  Double Data Entry form (two persons)
EFFICIACY END POINTS.
 Single entry with second look
• THERE SHOULD BE WRITTEN OPERATION
PROCEDURES AND MAINTENANACE OF ALL  Single data entry with reading aloud
MEETING RECORDS  Single data entry with source verification
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• Double data entry is not required by regulation by

good practice. CODING
• Data entry process should be chosen based on the
skills of the personnel, this will give good impact on • FOR Adverse Events
to the resources in the project and the reflected
evaluation of key variables.  COSTART (Coding Symbols for Thesaurus of
Adverse Reaction Terms)
• Only authorized persons should be entitled to do
entry and corrections on the data entry screens.  WHO-ART (Adverse Reaction Terminology)
• Verification and Validation is done by Data  SNOMED (Systematized Nomenclature of
Reviewers, automated computer checks (an error Medicine)
message like when a value is outside the acceptable  MedDRA (Medical Dictionary for Regulatory
norms) and during audit
Activities)
• It has been that errors in entry is 1 % by good
operator.  In House Codes
• This Decreases to 0.1% by double entry of data by
two different operators.

• FOR concomitant diseases: international

classification of diseases version 10 (ICD-10) • To minimize errors only qualified and trained
• FOR concomitant medications: WHO Drug staffs should be employed in the process the
Dictionary data entry operators should insist on legible
• Medical Term ----- Preferred term(s)----- Code filling of CRFs.
ERRORS IN CODING
• Misunderstanding about medical terms, • It can also be minimized by keeping a log
misinterpretation of hand writing, defective book of difficult coding cases, doing
translation, foreign Language of CRF, wrong translation-retranslation and centralizing of
choice of preferred terms and difficulties in the final coding
transcoding.
This errors leads to inconsistencies in
final report, decreased credibility of report,
delay in report writing and represent evidence
of negligence
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DATA QUERIES Query Tracking and Resolution

Problems faced by data entry operators • A proper SOP has to be made in place of query
• Subject has to go back to investigator tracking and solving
• Operators are failure to check the inclusion and exclusion criteria
• Inconsistent Calendar Dates • Operator should draw a list of QUERIES
• Illegible entries • This List should be sent to investigators who
• Unfamiliar Drugs Names verifies, corrects, signs and corrects the dates
• Text in unfamiliar Language the query
• Entries in incorrect place at CRFs
• Failure to specify indication for concomitant medication
• Three copies should be send to the same format
• Lack of reason for change in medication then
• Inconsistencies in physical examination at start and finish • To the data entry operator who operates the
• Incomplete information on Adverse Events same
• Varying Units & Normal ranges in case of Laboratory Data.

• At the end a validation program is done and DATA OUTPUT, REVIEW & FREEZING
run to follow the program and check the • As the data comes the manager and
editing done. stastician finalizes the data and queries are
resolved.
• Any change or correction must be readily
• Thereafter a final audit is performed, data is
spottable and is called as AUDIT TRIAL.
frozen and sent to the statistician.
• This Trial may be given in the computers • Goal of perfectly accurate database is usually
where computers saves the date and time of unrealistic.
correction, new value along with old value • It is preferable to set acceptable limits of
and access code used to make changes or on error that do not alter the validity of
paper statistical analysis and results and
conclusions drawn from the study
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ARCHIVING PATIENT DATA

BUDGET/BILLING PHARMACEUTICAL
• Data mangers and statistician are responsible PROTOCOL CLINICAL RESEARCH ASSOCIATE
for archiving the electronic database, TRAINING TRIAL MONITOR
associated computer programs, Data REGULATORY FORMS CONTRACT RESEARCH

monitoring conventions, audit trials and final RESEARCH

INVESTIGATOR
SITE MANAGER /

report.
• They also maintain also all sponsor-specific
essential documents as per regulatory
requirements. CLINCAL DATA MANAGEMENT
SOLUTION GATHERS AND CENTRALIZES
DATA

REQUIREMENTS FOR ACQUIRING/ CAPTURING/

COPYING SOURCE DATA • In the case of eSource data, of course, this is
not possible.
• In general data & documents containing source data • A copy of eSource data shall be accepted in
must first be specified in the trial protocol. place of eSource data, if the copy hass been
• Source Data are the original data, the recordings produced and verified against the eSource
and all information regarding Clinical Investigations,
Laboratory findings, anamnesis, interviews, patient data based on procedures defined in a SOP
diaries and other sources. for acquiring data duplication and
verification.
• The original documents have to be archived. • Appropriate handling is also required for
• Copies have to be dated and signed by a scanning source documents.
responsible person (Certified copies)
• If the original data is stored electronically, a • The Scanning process has to be validated
printout has to be made or a list of dates and prior to implementation in a trial to ensure
versions of stored documents signed/dated by the integrity of the generated record
Principal Investigator.
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• In the CRF is the source document (e.g., in

psychiatric instruments like psychometric pCRF to eCRF Transfer
scales ) this has to be defined in the protocol.
• If work has been used as a transcription • In this scenario, clinical data are at first collected
instrument (e.g., Transitional documentation with a pCRF.
prior to electronic data entry), these are to • Investigator has less time or has to move
be considered as informal source data sheets between locations (e.g. emergency ward,
and have to be filed and quality checked operation theatre)
appropriately. • In a remote data entry scenario, it is often not
• In general, source data must be accessible the investigator, but special assistance personnel
and verifiable and the quality of digitisation who enters data from the pCRF into the eCRF
must be carefully controlled using • This transcription step must be quality assured.
appropriately defined SOPs.

• Type of personnel needed (i.e., for data • Personnel responsible for different phases of
entry, for data review, etc.) pCRF entry must be traked as well as all the
• Criteria chosen to qualify them must be changes.
clearly defined.
• Because the investigator’s signature is
• For using eCRF, specific training programs for
required, he is responsible for the correct
investigators and assistance personnel must
be included. transcription of the data.
• Appropriate quality control steps have to be • Appropriate workflow support should be
implemented and double data entry may be implemented in the Electronic Data Capture
prformed. (EDC) system.
• pCRF transfer as well as status (arrived, re-
viewed, non-correct, requested queries,
correct, closed) must be clearly tracked.
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ESSENTIAL REQUIREMENTS • Change Control

1. Risk Assessment of any change in the system.
GOOD CDM SYSTEM
2. Controlled processes of making changes to the
• System evaluation and provider/vendor system, consisting of announcement,
selection. assessment and approval of the change.
• System Security
• System installation, setup and configuration.
1. Password policy.
• System configuration management
2. Firewall configuration.
(Configuration of Audit Trial e.g. reson for
3. Physical & Logical security, in particular also at
change optional or not?). the sites (EDC).
• System access and profile management. 4. System controls.
5. Network security for remote access.

• Database and communication security 4 Regulation of access to electronic or paper

1. Encryption of data storage, data Transfer. based data storage.
2. Electronic signature has to comply also with 5 Particularly strict standards for genetic data.
national regulations [EDC].
• Data protection
6 Secure data handling procedures.
1. Handling of personally identifiable data (e.g., 7 Use of pseudonyms/anonyms where
blinding of additionally submitted identifying appropriate.
data; sites should eliminate personal identifiers 8 Secure cross-border data transfer.
from source documents prior to submission).
2. Specification of minimum subject identifiers.
• Data backup and recovery
3. Safeguarding that (future) use of data is in • Disaster system recovery
accordance with informed consent. • Database security
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8 Report on data completeness at respondent and

• Data Archiving variable level.
1. Database specification. 9 Secure Storage and access control.
• Business continuity
2. Data files. • Migration of data/meta-data (in case of system
3. Audit Trial. retirement)
• System Validation.
4. Clinical Data (open standards – vendor • Risk management.
independent, e.g., CSV, XML, PDF, ODM, 1. All components of the system have to be judged
from CDISC) according to their risk to violate GCP.
2. GCP-compliance has to be guaranteed especially for
5. Archiving reports. high-risk components.
6. Scanned paper CRFs. 3. Maintenance of GCP-compliance even after updates
or other changes to the system.
7. Content and Variable definitions (metadata).

• Periodic review/audits. • New hardware's like PCs, Electronic

• Safeguard of Blinding. notebooks
• Help Desk. • Remote data entry.
• Optical mark recognition like bar codes.
CONCLUSION • Optical character recognition like
The importance of CDM can be realized from fingerprints.
the fact a lot of pure IT companies are • Facsimile.
involved in CDM activities and this • Smart cards for each patient.
contributes a big share in their revenue.
• Computer assisted new drug application
Some of the advances in CDM are:
[CANDA] by FDA.