CLINICAL DATA MANAGEMENT

Clinical data management (CDM) is a set of practices that handle

information generated during medical research. It aims to ensure
data quality, integrity, and compliance with internal protocols and
state regulations.
Also, the CDM process helps keep key clinical trial stakeholders on
the same page :

1. Sponsors — pharmaceutical companies, institutions, and other

organizations that initiate, monitor, and finance the trial.

2. CROs (control research organizations) — an organization

contracted by another company to take the lead in managing that
company's trials and complex medical testing responsibilities.

CRF design-Data manager Database design-Database designer

Data capture-Data entry associate Data validation-medical coder

Database lock-Quality control associate

Protocol review:reviewed done by the company team including data

manager along with other team members

Protocol amendments :Changes procedure in document

Data management plan:

DMP should be developed for each study and early during the setup of the
study

A data management plan or DMP is a document detailing all procedures,

tasks, milestones, and deliverables throughout the CDM lifecycle. It
gives a roadmap on how to work with information and handle possible
risks. Another important function is to clearly communicate what
happens in the course of the trial to each stakeholder.

INTRODUCTION 6
1.1 Purpose of the Data Management Plan (DMP) 6
1.2 Scope 6
2. SOPS 6
3. DATA MANAGEMENT TASKS 6
4. CORE/PRIMARY PROJECT TEAM MEMBERS 7
5. COMMUNICATION 7
5.1 Meetings 8
5.2 Status Reports/Metrics 8
6. CLINICAL DATABASE USED FOR PROJECT 8
7. TRAINING 8
8. DATA ENTRY 9
 8.1 Audit Trail 9
9. CRF COMPLETION GUIDELINES 9
10. CLINICAL DATABASE DESIGN AND TESTING 9
10.1 Clinical Database Specifications 9
10.2 Clinical Database Development 10
10.3 User Acceptance Testing (UAT) 10
11. EDIT CHECKS 10
11.1 System Checks 11
11.2 Manual Review

1. INTRODUCTION 6
1.1 Purpose of the Data Management Plan (DMP) 6
1.2 Scope 6
2. SOPS 6
3. DATA MANAGEMENT TASKS 6
4. CORE/PRIMARY PROJECT TEAM MEMBERS 7
5. COMMUNICATION 7
5.1 Meetings 8
5.2 Status Reports/Metrics 8
6. CLINICAL DATABASE USED FOR PROJECT 8
7. TRAINING 8
8. DATA ENTRY 9
8.1 Audit Trail 9
9. CRF COMPLETION GUIDELINES 9
10. CLINICAL DATABASE DESIGN AND TESTING 9
10.1 Clinical Database Specifications 9
10.2 Clinical Database Development 10
10.3 User Acceptance Testing (UAT) 10
11. EDIT CHECKS 10
11.1 System Checks 11
11.2 Manual Review 11
11.3 Query Prefaces 11
12. DATA FLOW 12
13. MEDICAL CODING 12
14. SAE RECONCILIATION 12
15. DATA IMPORT 13
 15.1 Vendor Reconciliation 14
16. DATA EXPORT 14
17. LOCAL LABS 14
17.1 Local Lab Data Entry 14
17.2 Local Lab Normal Ranges 14
18. DATA CUTS 15
19. INTERIM ANALYSIS 15
19.1 Data Cleaning Requirements 15
19.2 Post Analysis Unfreezing/Unlocking of data 15
20. QUALITY CONTROL AND DATABASE LOCK 16
20.1 Database Unlock 16
21. PROJECT DISPOSITION AND ARCHIVAL 17
The DMP typically describes the following aspects:

● data to be gathered from trial participants,

● existing data that can be integrated(how to mix,link,parts of data)
● 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 requirement
● Description of the data to be collected
● Data storage & backup.
● Data sharing & dissemination
● Data security & confidentiality
● Data preservation & archiving
The DMP must be ready at a trial design stage, before the first
participant is enrolled. This will ensure that data will be collected in the
correct format and properly organized. However, the plan is not
something immutable: It has to be updated across the trial, capturing any
changes that influence data management.
STUDY START UP/STUDY SET UP:
eCRF(case report form):
The case report form is a printed or electronic questionnaire for
collecting data from study participants and reporting it to trial sponsors.
The document is created specifically for each research project in
accordance with

​ the trial protocol, and

​ recommendations of the Clinical Data Acquisitions Standards
Harmonization (CDASH). They are developed by Clinical Data
Interchange Standards Consortium to streamline industry-wide
data exchange. Say, CDASH dictates dd/mm/yy format for
collecting dates. (Read our article on CDISC standards to learn
more.)

Well-designed case report forms collect only data necessary for the
particular study avoiding any redundancy. The fields to be filled in
may include

​ demographics (age, gender),

​ basic measurements (height, weight),
​ vital signs (blood pressure, temperature, etc.) captured at various
time points,
​ lab exams,
​ medical history,
​ adverse events, and
​ more, based on the research requirements.

Data managers create data entry screens and eCRF layouts in

collaboration with a database programmer. The design usually
goes through several review cycles before finalization.

● Crf pfd
● Compare crf pdf with protocol
● eCRF specification-prepare
● Explain ecrf spec to programmer
● Draft ecrf Review,updates and changes
● Final ecrf
● Ecrf in EDC(electronic data management)
● Compare ecrf spec with EDC
EDIT CHECK DOCUMENT:
Edit check document
 ● Edit check specification
● Manual query and automated query
● Dynamics
● Populate a query in edc
● Provide edit check specification parallel with ecrf
specification to programmer
● Compare edit check specifications with edc
UAT(user acceptance testing):
● Role testing: testing role for team members like access
● Screen testing
● Structural functionality
● Edit checks
● Any of the data which falls out of range it should
populate a query and for any thing which falls within a
range that it express should not populate a query
● LAB values-enter in UAT
● Sponsor DM—CRO DM—LNR(lower normal range)
template—Lead CRA(site)---Fill(template)---CRO
CM—EDC —---manual,automated
eCRF completion guidelines
STUDY CONDUCT:
Patient —site—assessments–enter edc
Company project manager or clinical operation manager send SHIPPING
MANIFEST to lab(vendor) – lab entry data in acquisition form
Lab—send test tubes—site
|
Pk samples–lab—analyze—send data to data manager
Lab 2 types
● Central
● Local
CENTRAL: Reference range values: lab maintain their own lab range
values
Set up: acquisition form =site data in vendor database
LOCAL: lab specific,site specific,sponsor specific
Set up: they do not maintain acquisition form
Data transfer specifications
Version
Table of contents
Contact details
Purpose
Data file structure
Data file transfer
Frequency = weekly or monthly
Data transfers will be cumulative or incremental
Date of file
File naming conventions=blinded,unblinded

Data deliver method

email,sftp(secure file portal) like passwords or client web portal
Test transfer
Data quality
Data receipt
Data file contents
Mapping tables =visit dates,codes
Data transfers:
● Mock data from vendors,IRT,SAE
Data transfer agreement:
Purpose
Type of data
File naming conventions
Data transfer mode
Data transfer type
 Frequency/Transfer frequency /schedule
● Vendor agreements
● Company agreements
Reconciliation :External data
● Vendor reconciliation : reconcile lab data eg:Pk,ECG etc..
● IRT reconciliation : reconcile header data eg:subjectid,site id
etc…
1. IRT=interactive response or randomization Technology
2. IRT helps clinical trial sponsors & site for manage the
patient & drug supply logistics—-->because =ability to offer
control & flexibility while increasing efficiency

3. IRT also helps to maintain blinding by making sure that

specific roles in a study do not know the treatment that
each patient is receiving
4. CDM reconcile below list:
Screening date
Re-screening date
Randomization number
● SAE reconciliation:reconcile SAE data:
Adverse event : Any effect/disease

Adverse event maybe : MILD,MODERATE,SEVERE

Serious adverse event

SAE →collected from→clinical trial & marketed products

Reporting containing SAE —>case—->goes to safety
department—>case of adverse effect
During clinical trial=SAE information also received through
CRF or EDC—>stored in ADVERSE EVENT—>DMS
 Stored in clinical & safety database
Important to match = SAE with data management
system—------->SAE reconciliation
During information following information are checked:
1. Cases found in the SAE system but not in the CDM
system—->(case of adverse effect)safety system.
2. Cases found in the CDM system but not in the SAE system
—>(adverse event)database system.
Death —>any case—>found only one system–>.(cases of
adverse effect) adverse event
Need of SAE reconciliation=compare SAE with CDM

SAE CDM
Less organized/defined more organized/defined
subject,investigate well defined in study data such as
data: eg: Subject & investigate ID age, sex information
| |
Collected information but collect collected separately adverse event are collected event
only events by event passociate each problem

Depends for
Companies—---->reports & manual comparison—-->SAEreconclliation
On
When the reporting system has access to the underlying
database
it might be possible to do
-------------------------------->

initial match on some information such as study ID,Sub ID etc…

Underlying database present in SAE system and CDM system.

SAE reconciliation-method SAE CDM

|required | |
 PLAN Data entered to create
|
Two lists for direct comparison
|then
1)events in both lists are cross checks
2)According to the plan,key data should be
Compared in each database
3)All discrepancy arise during reconciliation
Should be reviewed &resolved
Reconciliation issues:
● Ex: unschedule visit
MRI assessments
Accession ID
Query management:
Query management. In terms of clinical trials, a query is a request for
clarification from trial sponsors to researchers. Such requests are made
during data review, before database lock, and aimed at resolving errors and
inconsistencies. The query management feature facilitates communication
among data managers,sponsors, and other stakeholders. It helps faster
resolve all questions.
● Open queries : when site coordinator open query( seen the
query)
● Closed queries: when site coordinator opened ,answered query
and closed query
● Answered queries: when site coordinator opened and answered
query
● Canceled queries:when DM/biostatician/medical monitor/clinical
coder enter query in EDC and it can be canceled by these
people
● Queries prepare in excel sheet which discrepancy is present in
data(EDC)
● Query posting
 DM of CRO will provide weekly metrics
Sponsor DM will review meetrics
Metrics: can be open query by–DM,CRA,medical reviewer
Queries like eg:subject part,unconfirmed missed date etc..,
● Automated query—query populate in EDC when discrepancy is
entered by site coordinate–edit checks
Manual data listing
● SAS programme:
● \

● CRO will provide data listing-sponsor will review programme

listing
● If not possible sponsor will prepare programme listing from EDC
● EDC listing:
● EDC–installed modules–reporter–Data listing STUDY -

prod–submit==production clinical review

—-from:ad,cm,medical—run–DATA–download file
● Patient identifier
● J-review
● Spot fire
● illuminate
Manual data review
● Manual checks
● Ex : Compare adverse events with cocomident medication
Apply concatenate and vlookup
1. Create Unique ID : SUB ID
2. Concatenate:
Formula: Unique ID + the variable we want to compare (Record
number)
3. Create 2 concatenate records in both the listings
4. Vlook up:
 Formula:vlookup(first concatenate cell no 1,second concatenate
cell no 2 in different listing:$ columns name of the variable we
want to compare $ total no of rows/records,1,0).
5. Review coding dictionary MEDRA and WHO drug.

STUDY CLOSEOUT:
On the study completion, the database is locked so that no changes can be
done to the information. After that, clean data is submitted to stakeholders for
statistical analysis, reporting and, finally, publication of the results. However,
all these steps are beyond the clinical data management workflow.

● LPLV
● Database lock checklist:
1. Ensure data is complete (both ecrf&non-ecrf)
2. Perform final data listing review
● Data entry
● Data completion
● Last Data transfer
● Data review
● Last reconciliation
● Closing all discrepancies/issue trackers
● Open queries-all close out
● PI Signatures
● SDV status-100% SDV
1. SDV is completed for all CRDs by the CRA
After last patient last visit —-->data entry in ECRF —-->data
completion—->Last data transfer—->closing all discrepancies/issue
trackers in EDC—>Close out all open queries—->SDV(Source data
verification) done by the CRA in site—100%SDV
● Database lock checklist:
● Electronic archival:
1. Preparing archival(a collection of historical documents or records
providing information)
 2. It is done for secure retention maintaince & retrieval of data
which goes to the trial master file
●
TERMS
Go-live:
After study start up--Database ready in EDC--site --subject
enroll---Site PI(Doctor) enters patient details time from FPFV and
LPLV.
Split deployment:
In start up step skipping edit check document step and done with
remaining ecrf specification,UAT
Blinding:
Not aware of anything about drug
Open/Unblinding:
Aware of every thing about drug
Double blinding:
Nor subject/Doctor/the company aware of drug
SDV:
source data verification=CRA-->site-->verify site data with EDC
Randomization:IRT-->IRT ENTER DATA IN
Randomly assigning something to subjects
Example:oncology
study-->age:18-50-->100
subjects-->information-->computer-->computer gives each participant
a code-->code number are randomly assigned
1 2 3 4 5 subjects
computer assigned
3 5 1 2 4 subjects-->Treatment starts

Place-bo:
It looks like a drug but there is no therapeutic active due to minimize
patient bias
Screening:
example:Pass --10 subjects) enrollment different-->not possible of
above criteria-->changes
fail--40 subjects)
screening based on mainly only inclusion and exclusion certeria.
FPFV:
When approval got from IRB, the site started clinical trials. Beginning
of the clinical trial, the patient comes first to FPFV(first patient first
visit) and starts data entry in the database(EDC).
LPLV:
End of clinical trial which patient comes last for study
Disposition date:
When adverse event starts—> Treatment start—-->end of the treatment
(date){last day}
outsource
Outsourcing means that you hire outside resources to help you complete
tasks or projects. These might include freelancers or agencies that
specialize in performing a particular type of task or project. For example,
hiring a digital marketing agency is a way to outsource your social media
management.
Inhouse
In-house resources, on the other hand, are your existing employees —
including yourself. When you handle a task or project in-house, you
assign one or more of your team members to work on it.
Inclusion Criteria
Participants are eligible to be included in the study only if all of the
following criteria apply
Exclusion Criteria
Participants are excluded from the study if any of the following criteria
apply