Introduction to

Data Management
for
Clinical Research
Jaranit Kaewkungwal

www.biophics.org
 Biomedical Research Cycle

for clinical research New Ideas Design

Clinical Study
Care Utilize • Trial costing
Results for basic research • protocol authoring
• data mgmt plan
• CRF design
Protocol &
for patient Findings
care & policy Funding

• data processing & analysis

• reporting

Conduct Activate
Approval &
Study Preparation Study
• data acquisition & management • IRB approval
• GCP compliance • data/work flow preparation
• dmgt system setup

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Source: Ida Sim, UCSF
 Multidisciplinary Team in
Clinical Research Process

1. Clinical Investigator 10. Monitor

2. Site coordinator (CRC) 11. Safety Surveillance
3. Pharmacologist Associate (SSA)
4. Trialist/Methodologist 12. Regulatory affairs
5. Biostatistician 13. Clinical Data Management
6. Lab Coordinator 14. Clinical IT
7. Reference lab 15. IT/IS personnel
8. Project manager 16. Trial pharmacist
9. Clinical Research 17. Clinical supply
Manager/Associate 18. Auditor/Compliance

Adopted from: Shya TJ, Clinical Trial Unit, Clinical Research Center, www.biophics.org
 Data Management Definition
Project
What is Data Management? Initiation
Data Design

A process that begins with Data Acquisition

conception and design of a and
Quality Control
research project, continues
Data Manipulation
through data capture and and
Quality Assurance
analysis to publication, data
archiving and data sharing with Data Analysis
and
the broader scientific Interpretation

community. Data Access

and
Archiving
Publication

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 Primary Functions of
Clinical Data Management (CDM)
Time Results

Analysis

Clinic/Site Staff: Data Management Staff:

Data Closure Data Cleanup
Data Correction Clinic Data Data QC
Data Collection Data Entry
GCP Compliance Management Database Design

Study Initiation
Site Development
Protocol Development
Research

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 Data Management Workflow

Source: https://researchadmin.asu.edu/dmp

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Regulatory & Guidelines
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 Regulatory & Guidelines
GCP & Computer / Database Management Systems

• International Conference on Harmonisation of Technical Requirements

for Registration of Pharmaceuticals for Human Use (ICH)

• The European Agency for the Evaluation of Medicinal Products (EMEA)

• FDA Center for Drug Evaluation and Research (CDER)

• Human Subject Protections- Office of Human Subjects Research, NIH

(OHSR)

• WORLD MEDICAL ASSOCIATION

• Standard operating procedures for clinical investigators ( WHO GCP SOP)

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 Regulatory & Guidelines
GCP & Computer / Database Management Systems

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 Regulatory - Environment & Systems

GCP – E6 GCP – E2A GCP – E2B(R3)

(Data Management & (Data Elements &
Reporting) Transmission)

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 Regulatory - Environment & Systems
Computer Systems GCP – E9
DBMS (Data Analysis)
(21 CFR Part 11 – May 2007) GCDMP

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Society for Clinical Data Management
http://www.scdm.org

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 Regulatory & Guidelines

GCDMP

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 GCDMP

• Data Collection
• Data Acquisition
• Data Management Plan &
Database Setup
• Data Entry
• Data Quality
• Data Security
• Data Storage, Archival &
Transfer
• Training
• Project Management for DM

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Data Collection
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 Source Document & CRF

Hospital data
collection form

Medical records

Laboratory results

CRF(s)

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Source Document & CRF

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Source Document & CRF

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 Source Document & CRF
Vaccine Administration
Vaccination CRF -
Urine VADM
Pregnancy Log

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Design and Development of Data Collection Instruments
Minimum Standards
• Design CRFs to collect the data specified by the protocol.
• Document the process for CRF design, development,
approval, and version control.
• Document training of clinical site personnel on the
protocol, CRF completion instructions and data submittal
procedures prior to subject enrollment.
• Ensure CRFs are available at the clinical site prior to
enrollment of subjects.

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Design and Development of Data Collection Instruments
Best Practices
• Establish and maintain a library of standard forms and
associated edit checks (CRFs, CRF completion guidelines,
subject diaries, etc.).
• Use a multidisciplinary team to provide input into the CRF
design and review processes.
• Consult the protocol, study biostatistician(s) or review the
statistical analysis plan (SAP) (if available) to ensure all key
endpoints are collected.
• Keep the CRF’s questions, prompts, and instructions clear,
concise and conformant to CDISC CDASH standards, where
possible.
• Design the CRF to follow the data flow,
taking into account the flow of study procedures.

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 CRF Design Process

• Content
• Logistic
• Format

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 CRF Design Process

Operational
definition

Items in CRF

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 CRF Design Process
Pretest &
Version 1

Revised &
Version 2

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Form Design: Art & Science

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 Form Design: Art & Science
Please circle the face that best describes how well you feel
Happy today
Face
Scale

Likert
Type
Scale

Visual
Analogue
Scale

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 Item Design Technique

Close-ended
Question
(Fixed choice)

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 Item Design Technique
Close-ended Question (Check all that apply)

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 Item Design Technique

Open-ended
question

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 Item Design Technique
Fixed vs. Open Lab Units

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Schedule for Data Collection

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CRF Completion

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Data Acquisition
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 Simple Work /Data Flow
Between DMU and Clinical Sites
3 Clinical Sites DMU
3 Sites copy all
completed CRFs DataFax Double
Complete & Fill out CRF Verification
CRFs Binder Log Mail the whole CRF Image
Monthly CRF package
• Summary Report
to DMU via • DataSets for Sub-
Postal Parcel. study Analysis
(Per Request)
Edit
Check
Verification Fax only Corrected QCs to Primary Study
Source CRFs DMU by dial long distance Reports
Data
call Base

Error No Error
Corrected
QCs
Verification & Clean Data Sets/
Correction into Data
DMU faxes long distance Transport Files
both CRFs & Clarification
QCs QCs to each provincial Report
clinical sites within 7 days

QCs

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 Work /Data Flow Using Leased Line
Specimen Processing Centre &
Connecting with DMU
Central Laboratory
DMU - Data
Provincial Management Unit
Centers

48 Screening sites
8 Clinical Sites

Independent Statistician
DATA Team
CLARIFICATIONS
DataFax Double
Verification
CHONBURI
CRF Image
EDIT LOGIC
CHECKS
Leased Lines Data Coordinating
And Analysis Center

fax machines RAYONG Primary

Data
Base SAS Data Sets/
Transport Files

DMU Study MedDRA Coding Team

Monitoring
Reports
BANGKOK,
THAILAND
Ministry of Public Health
MARYLAND,
Study Center&
U.S.A
Study Collaborators

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 Work /Data Flow for
Electronic Data Capture (EDC)
Each Site is
Clinical Sites resolving his/her
complete their own own queries • Summary Report
Source Documents. through iDataFax • DataSets for Sub-
study Analysis
(Per Request)

Exported Data
Per requested
Each Site is Format. (i.e. SPSS,
doing his/her own Microsoft Excel)
Data
Data Entry to the Encrypted Data Clarification
Electronic CRFs transferred will be flagged
using iDataFax through an to any problem
Error
INTERNET to fields
DMU
Clean Data
Set
DMU validates
the data.
No Error
Database is backup
on a daily basis

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 Comparing Paper-based vs. EDC
Data Project
Manager Manager

CRA

Queries/ Database
DCFs

Data
Entry
Investigator
CRFs

Source: Jane Bentley, Breaking down the Barriers – Electronic Data Captur www.biophics.org
 Comparing Paper-based vs. EDC

Data
Manager Project
Manager

CRA

Investigator Database

Source: Jane Bentley, Breaking down the Barriers – Electronic Data Captur www.biophics.org
pCRF vs. eCRF

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 pCRF vs. eCRF
Paper-based CRF
eCRF (EDC)

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 Electronic Data Capture – Minimum Standards
• Ensure compliance with 21 CFR 11
• Stated quality standards should support the utilization of
automated data capture, management and archiving.
• Ensure requirements are defined for data transfers and
integration with other systems.
• Software systems validation should be scheduled and
completed prior to EDC study implementation.
• Verify training is provided for all users of the EDC systems
• Verify access to data is limited to authorized individuals.
• Ensure sites have access and control of data up to database
lock.

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 Electronic Data Capture – Best Practices
• Ensure systems are user-friendly and flexible for data entry.
• Ensure EDC systems do not restrict answers site staff can
provide in a way that introduces bias into the study.
• Ensure adequate edit check procedures and query
management tools are built into EDC software.
• Ensure data can be traced from the time of original input
through the reporting and analysis files via easily accessible
audit trails.
• Ensure your EDC system integrates as needed with other
databases
• Ensure change control procedures include complete
documentation.
• Provide an instruction manual for study workflow processes.
• Provide training customized to each user’s role.

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 21CFR Part 11 – IT System
GxP System Environment

Computerised System

Computer System Work Process

Hardware Network

Software People SOPs

Source: Validation Principles for GxP Regulated Computerized Systems, http://www.gcp.suite.dk/slides.ppt

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 21CFR Part 11 – CDMS
GxP System Environment

Computerised System

Computer System Work Process

Hardware Network

Software People SOPs

Source: Validation Principles for GxP Regulated Computerized Systems, http://www.gcp.suite.dk/slides.ppt

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 Password Policy
• US-FDA 21 CFR Part 11 Compliance including e-signatures, audit
trails, and rules for password complexity, aging and notification

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 System Authentication
• US-FDA 21 CFR Part 11 Compliance including e-signatures, audit
trails, and rules for password complexity, aging and notification

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Record Repository & Time Stamps

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Electronic Signatures

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Standard Operating Procedure (SOP)

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Data Management Plan
Database Setup
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Data Management Plan - Minimum Standards
• Complete a draft of the DMP prior to enrollment of
the first subject.
• Ensure the DMP supports compliance with applicable
regulations and oversight agencies.
• Identify and define the personnel and roles involved
with decision making, data collection, data handling
and data quality control.
• Ensure data management processes are described and
defined from study initiation until database closeout.

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 Data Management Plan - Best Practices
• Develop the DMP in collaboration with all stakeholders
to ensure that all responsible parties understand and
will follow the processes and guidelines
• Develop and maintain a DMP template for the
organization that ensures consistency and
standardization across all projects.
• Ensure the DMP for each study is kept current,
including proper versioning, and that all responsible
parties are aware of and agree to the current content.
• Ensure that an approved, signed version of the DMP is
completed prior to starting on the work it describes.

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Data Management Plan (DMP)

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Statistical Analysis Plan
SAP 4. Analysis Populations
Table of Content
1. Introduction 5. Protocol Implementation
5.A. Randomization and Blinding
2. Study Design And Plan 5.A.1. Method of Assigning Subjects to
2.A. Study Design Study Groups
2.B. Selection Of Study Population 5.A.2. Blinding Procedures
2.C. Study Vaccines/Drugs and Placebos and
Their Administration 6. Interim Data Monitoring
3. Objectives, Hypotheses, and Study Endpoints
3.A. Objectives 7. Analysis
3.A.1. Primary Objective 7.A. Enrollment and Baseline Characteristics
3.A.2. Secondary Objectives 7.B. Safety
3.B. Hypotheses 7.C. Risk Behaviors
3.B.1. Primary Hypotheses 7.D. Efficacy Analysis
3.B.2. Secondary Hypotheses 7.D.1. Methods
3.C. Study Endpoints 7.D.2. Primary Efficacy Results
3.C.1. Primary Efficacy Endpoint 7.E. Additional Analyses
3.C.2. Secondary Endpoints

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 Data Management Standards in Clinical Research
Minimum Standards
• Use the most current version of any standard,
if appropriate.
• Use standards required by regulatory agencies
in the country where the study is conducted.
• Do not modify published standards.

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 Data Management Standards in Clinical Research
Best Practices
• Use accepted standards whenever possible, and strive
for interoperability.
• Use all standards recommended by regulatory agencies
in the locale of the study.
• Review implementation guidelines for any standard
having associated guidelines documents.

CDISC MedDRA
HL 7 SNOMED CDISC

ICD 9 /10 WHO DD

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Clinical Data Interchange Standards Consortium
http://www.cdisc.org
Study Data Tabulaiton Model (SDTM)

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Medical Dictionary for Regulatory Activities
(MedDRA)

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 Database Structure
Features of Database Management System:
• Ease of data entry
• Automatic data validation
• Automatic error checking
• Alternative is a stack of paper forms
Multi-Table Relational Database:
• Eliminates redundancy

• Ensures data integrity

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 Source Docs (CRFs) & Data Files Design

one

many

many

one

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 Database Validation, Programming and Standards -
Minimum Standards
• Ensure the CDMS meets user/functional and regulatory
requirements
• Implement the CDMS carefully, testing according to
specifications, documenting all testing and issues
• Ensure documentation remains complete and current.
• Ensure that only qualified staff develop, maintain and
use the system.

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 Database Validation, Programming and Standards -
Best Practices
• Confirm that study-specific programming applications
perform as intended based on the user requirements
(data management plan requirements, CRF
requirements, database specifications, edit check
specifications, validation plan, etc.).
• Confirm accuracy, reliability, performance, consistency of
processing and the ability to identify invalid or altered
records. Confirm through testing and document.
• Confirm that the study-specific application has been
configured properly.

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 Related Documents about Validation

Data Spec
Data Entry
Edit Check

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 Related Documents about CDMS

QAS
• Document Control
DMS • Document Access
• Data Management Plan • Quality Assurance Procedure
• Study Set up • Internal Audit of IT & DM Sections
• Database Access Control • Training & Qualification
• Database Design & Testing • General Change Control
• Data Validation & Programming
• Data Entry & Verification
• Data Discrepancy & Resolution ITS
Management • System Change Control
• Database Quality assessment • Software Version Control
• Database Lock • Physical & Logical Security
• SAS Programming Practice • Backup & Archive
• SAS Program Validation • Disaster Recovery

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 Edit Check Design – Minimum Standards
• Finalize protocol and complete initial database specifications prior
to designing edit checks.
• Specify edit checks based on parameters of case report form (CRF)
• Specify edit checks for all primary study endpoints data.
• If applicable, specify edit checks with external data (e.g., laboratory
data) for reconciliation purposes.
• Ensure all edit checks are programmed, validated, and
documented
• Ensure all edit checks specification documents are appropriately
version controlled.
• Provide training to relevant personnel on the impact of edit checks
on their individual roles in entering and managing clinical data.

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 Edit Check Design – Best Practices
• Review edit checks with appropriate clinical and statistical
personnel to ensure edit checks meet study needs and help
identify inconsistencies in study endpoints.
• Develop a library of standard CRFs and edit checks based on
standards used, such as CDASH
• Perform a quality control review of edit check design and
specifications prior to performing user acceptance testing
(UAT) of edit checks.
• Evaluate the effectiveness of edit checks once in active use,
and modify, delete or create new edit checks accordingly.

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Type of Data Checks

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Example of Edit Check

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 Edit Check Requirements
QC report
Check with
Type of question
Form Section Item Specification/ Detail Gernera Inconsiste Addition
Remarks
Form Section Item Check with te nt Confirm
al
informati
(recheck)
on Type of question
(date of screening - date of birth +1) must be ≥ 18
DEM-plt1 Patient's
Demographics
Form
1. Age
Section DEM-plt1
Item
Screening/ baseline and Patient's
Demographics
date of screening and date of birth
Specification/ Detail x x

2. Date of birth DEM-plt1 Screening/ baseline and Patient's date of screening and age (date of screening - Date of birth + 1) must be ≥ 18 x Inconsistent
x Additional
Demographics Form Section Item (recheck)
Confirm
information
3. Sex Must select only one (male or female) x x
6. Date of admission DEM-plt1 Screening/ baseline and Patient's date of screening and date of diagnosis Must be occur before date of screening and date of diagnosis x x
IEC- Eligibility/ 4.2) Empirical Demographics
PANTI- Previous previous AB If 4.2 or 4.3 or 4.4 are x x
plt2 7. Diagnosis Inclusion NP-plt3, cIAI-plt4, cUTI-plt5 Specific criteria for NP,cIAI and cUTI
therapy: plt15 AB Must select only one (HAP, VAP, cIAI and cUTI) and mush be consistant with specific criteria page
therapy selected, previous anti x x

8. Date of diagnosis Criteria nosocomial

DEM-plt1 Patient's Demographics date of admission therapyShould be occur after or same day of admission date. For HAP and VAP, (dateAB of diagnosispage
- date of admissionmuch
+1) must be ≥ 2 daysbe x x x For NP, please confirm that the patient had 1) re-admission within 7 days; or 2)
re-admission within 30 days for resident of chronic care facilities; or 3) referral
infection with "yes" and provide patients form other hospital

9. Patient location failure of previous Must select only one (ICU or ward) previous AB treatment x x
10. Category of sepsis treatment
DEM-plt1 Patient's Demographics and
Must select only one (Sepsis or Severe sepsis) For Severe sepsis, it must be choosed ifof the4.4
at lest one is selected, x
organ dysfunction x x
Must select "yes" and age must be ≥ 18
IEC-plt2 Eligibility/Inclusion 1. Male or Female; 18 years old and above DEM-plt1 Patient's Demographics age and date of birth
check with initial x x
Criteria
2. Diagnosed NP, cIAI or cUTI 4.3) Modified PANTI- PreviousMust select "yes" previous AB
culture at study entry
3. Must have evidence of a SIRS with at least one of therapy: known plt15 AB therapy
3.1) Fever (BT > or = 38 C) or hyperthermia (BT < 36 C) PVLS-plt20 Vital sign temperature must has an organism x
pathogens with therapyIf it is selected "yes", temperature must be < 36 or >38 x
3.2) Elevated total peripheral WBC count > or = 12,000 cells/mm3 or PVLS-plt20 Laboratory test WBC If it is selected "yes", WBC must be < 4000 or ≥ 12000 cell/mm3 ESBL-producing strain x x
< 4,000 cells/mm3 resistance to
3.4) Increased pulse > 100 bpm and Respiratory rates > 20 bpm cephalosporin,
PVLS-plt20 Vital sign pulse rate and respiratory rate If it is selected "yes", pulse must be > 100 bpm and RR must be > 20 bpm
in the table x x
4. A candidate for treatment with carbapenems at least one of
aminoglycoside, If empirical and modified are selected together e.g., 4.1 with 4.3 or/and 4.4, 4.2 with 4.3 or and 4.4 x x Confirm the patients receive doripenem for both "Empirical Tx" and "Modified
Tx" condition
4.1) Empirical therapy: suspected infection caused by carbapenem- fluoroquinolone or
susceptible P. Aeruginosa or carbapenem-susceptible to A. baumannii
or MDR gram negative bacteria beta-lactam /
4.2) Empirical therapy: nosocomial infection with failure of previous betalactamase
PANTI-plt15 Previous AB therapy previous AB therapy If 4.2 or 4.3 or 4.4 are selected, previous anti AB page much be "yes" and provide previous AB treatment and if 4.4 is selected, check with initial culture x x x
treatment at study entry must has an organism ESBL-producing strain in the table
intibitor and
4.3) Modified therapy: known pathogens with resistance to PANTI-plt15 Previous AB therapy previous AB therapy
cephalosporin, aminoglycoside, fluoroquinolone or beta-lactam / susceptible to
betalactamase intibitor and susceptible to carbapenem
carbapenem
4.4) Modified therapy: known infection caused by ESBL-producing PANTI-plt15, MBIOS-plt30 Previous AB therapy, Culture at study entry previous AB therapy, oraganism at initial culture
gram negative bacteria
Eligibility/Exclusion 1. Pregnant or lactating females
4.4)
PVLS-plt20
Modified
Pregnancy test
PANTI-
pregnancy test
PreviousMust select "no" andprevious AB
result of pregnancy test must not be "positive" x x x
Criteria
5. Previous use of carbapenems within 7 days of study entry therapy:
PANTI-plt15 known
Previous AB therapy plt15,
previous AB therapy AB therapy,
Must select "no" and Imipenem or Meropenem or Doripenem or Ertapenam do not be appeared in previous anti AB page x x x

infection caused by MBIOS- therapy, oraganism

6. Patients are taking probenecid
ESBL-producing
OCT-plt85 Other concomitant therapy
plt30
other concomitant therapy
Culture Mustatselect "no" andat initial
probenecid do not be appeared in other concomitant page x x x
gram negative study culture
bacteria entry

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From Edit Check Requirements
to Validation Plan

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Manual Queries

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Data Entry
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 Standard Data Management Flow

Database Lock

Paper Double
CRF Data Entry
Data Validation Data Analysis
Data Collection
& Report
Paper
DCF
Data Clarification

Internet Database Lock

eCRF Web Server
Internet
Data Validation Data Analysis
Data Collection
& Report
eDCF
(eSubmission)
Data Clarification
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 Guidelines for all CRFs
EDC and Paper CRF Studies
• Ensure that all required fields on each CRF are completed.
• Provide contact information if questions arise while
completing the CRF.
• Ensure that all free text entries are spelled correctly and are
clinically appropriate.
• Provide a list of acceptable abbreviations, which may vary
between studies or indications

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 Guidelines for Paper CRF Studies
• Ensure the use of permanent media (blue or black ink).
• Ensure that all items captured in the CRF are legible.
• Specify procedures for making corrections to data.
• Provide instructions for the process flow of completed
documents, including shipping address, which copies of
the CRF to ship, etc.

Guidelines for EDC Studies

• Do not share user IDs or passwords with anyone.
• Do not record and/or store user IDs and/or passwords in
non-secure locations.

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 Data Entry Options
Traditional Data Capture Electronic Data Capture
via Manual Forms
Use current Implement Store and Forward On line data
system for scanable forms using in home, capture using
manually entering hand held data internet based
forms entry tools data entry tools
Timefor
Time forsite
home
staff    
visitors
to to enter
enter data and
o
data CRF
send or send
\
forms
Timefor
Time fordata
CPCRG    
center to receive
to receive forms,
CRF, enter & verify
enter and verify
data
data
Ease of Data 

Entry    
-- Study
Countysite    
- Data center
   
- CPCRG
Cycle time from    
Data Entry    
through Data
Validation and
Availability www.biophics.org
 Data Entry Options
Traditional Data Capture Electronic Data Capture
via Manual Forms
Use current Implement Store and Forward On line data
system for scanable forms using in home, capture using
manually entering hand held data internet based
forms entry tools data entry tools


Staff Needed    
- Study
County
site    
Data center    
- CPCRG o

Development $ $$ $$$ $$$

Cost
Hardware and
Software cost $ $ $$$ $$
- Study
County
site
Data center $$ $$ $ $
- CPCRG
   
IS Support
Needs    
- User Support 



 

   
- System
Support
Technology and    
Training
Requirements www.biophics.org
Standards of Paper CRF Data Processing Workflow

Note: EDC data processing

workflow varies from one study
to another depends of SW used

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 Standard Data Entry Flow
Clinic Staff
CRFs completed and verified at site(s)

3rd Party (?)

Data Entry Clerk(s)
Independent double data entry

Entry Error Data Technician I

Compare double data entry
Logical Error
One-entry in corrected file, leaving audit trail

Data Technician II (?)

Check program runs and sign off code
Freeze data files (tables) for statistician/ clients

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Data Entry @ Site

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Data Problem: Data Entry @ Site

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Data Problem: Data Entry @ Site

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Data Quality
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Sources of Error

Source Data
Verification

Data Validation

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Data Problem:
Data Coding

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Data Problem:
Inconsistency

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Data Problem:
Illegibility

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 Data Problem:
Illegal Values (?)

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 Data Problem:
Unclear Data

Heart or Hurt?

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Data Quality Check

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 Assuring Data Quality - Minimum Standards
• Provide sufficient information in data-processing
documentation to reproduce final analyses from source
data.
• Assure data quality for all studies, whether submitted for
regulatory review or not (e.g., marketing studies,
observational studies or for publication-only studies).
• Ensure data quality is appropriate for study analyses
according to parameters laid out in a statistical analysis
plan, if one exists.

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 Assuring Data Quality - Best Practices
• Create and maintain documentation of all roles and
responsibilities involved in managing a clinical study.
• Use well-documented processes for data collection and
handling.
• Minimize the number of data-processing steps in order to
minimize potential sources of error.
• Ensure data quality audits assess compliance of procedures to
regulations, compliance of practices to written
documentation, conformance of data to source
documentation, and conformance of data to written
procedures.
• Ensure all data management personnel are trained on and
knowledgeable

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 General clinical data checks
• Endpoint checks
• Safety checks
• Protocol compliance

• Programmed checks
• Manual checks

• Listings checks
• External checks

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 Quality Assurance

Standard Quality Assurance Aspects:

• Study/Trial Conduct
• Study/Trial Monitoring
• Study/Trial Progress

Key questions:
• Violation / deviation from protocol or assumptions?
• Meet the study target /goal as planned?
• Chance to answer the study objectives/questions?

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 Data Assurance:
Trial Conduct/Monitoring

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 Data Assurance:
Trial Conduct/Monitoring

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 Data Assurance:
Trial Conduct/Monitoring

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 Data Assurance:
Trial Progress (Central Collaboration)

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 Quality Control
Data Management Perspective
Data Quality Characteristics Description Example Metric

Accuracy A quality of that which is free of Percent of values

error. A qualitative assessment of correct that are when
freedom from error, with a high compared to the
assessment corresponding to a actual value. For
small error. example, M=Male
when the subject is
Completeness Completeness is the degree to Percent of data fields
which values are present in the having values
attributes that require them. entered into them.

Consistency Consistency is a measure of the Percent of matching

degree to which a set of data values across
satisfies a set of constraints. tables/files/records.

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 Quality Control
Data Management Perspective
Data Quality Characteristics Description Example Metric

Timeliness As a synonym for currency, Percent of data

timeliness represents the degree available within a
to which specified data values are specified threshold
up to date. time frame (e.g.,
days, hours,
minutes).
Uniqueness The state of being the only one of Percent of records
its kind. Being without an equal or having a unique
equivalent. primary key.
Validity The quality of data that is founded Percent of data
on an adequate system of having values that
Classification and is rigorous fall within their
Enough to compel acceptance. respective domain of
allowable values.
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 Data Validation
Standards in data validation:
• Making sure that the raw data were accurately entered into a
computer-readable file.
• Checking that character variables contain only valid values.
• Checking that numeric values are within predetermined ranges.
• Checking for and eliminating duplicate data entries.
• Checking if there are missing values for variables where
complete data are necessary.
• Checking for uniqueness of certain values, such as subject ID's.
• Checking for invalid date values and invalid date sequences.
• Verifying that complex multi- file [or cross panel] rules have been
followed. For example, if an adverse event of type X occurs,
other data such as concomitant medications or procedures might
be expected.

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 Accuracy/Completeness Logical Check:
Unmatched Cases (Case – Specimen Tracking)

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 Time Logical Check :
Error or Illogical Dates

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Validity Logical Check:
Illogical Data

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Validity Logical Check:
Illogical Data

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Validity Logical Check:
Out of Range Data

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 Consistency Logical Check:
Data Consistency

Yes
No
Missing

Yes

Yes
No Sypmtoms
No
BUT Yes Itching!

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 Audit Trails
Definition
AUDIT is the procedure to compare source data with
data on case record forms (CRF) and interim and final
reports. This would include validation of data both
pre- and post-computer entry
The aim of audit is to confirm that:
• the data reported are the data analyzed.
• the data analyzed are the data recorded on CRF.
• the data on the CRF are the data generated.
• the data generated are in compliance with the protocol.
• the protocol and all aspects of the trial/experimental
preparation conduct and analysis are in compliance
with the standard operating procedures (SOPs).
(Definition: Richard K. Rondel, UK)
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 Audit Trail of Edit Changes:
Initial & Date

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 Standard Audit Trail:
Data Clarification Form (DCF)

Data
Correction
Form
(DCF)

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 Audit trails
• US-FDA 21 CFR Part 11 Compiance including e-signatures, audit
trails, and rules for password complexity, aging and notification

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 Threats to Data Quality
– Literature has suggested that
• up to 1% of data is in error, which could impact
findings
• Not all error is random
– Systematic error can often be attributed to:
• lack of resources
• lack of skills or knowledge
• lack of attention to details
• lack of clearly defined data elements
Derived from: Rita E. Adkins, Matthew G. Hile, Keith Eldridge, Missouri Institute of Mental Health,
Tools for Evidence: Building a Quality Dataset

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 Deviation & Violation

Deviation Log &

Exemption Report

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 Deviation & Violation

File Note
&
Memo

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Data Security
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Data Privacy – Minimum Standards
• Ensure all personnel (including vendors) who directly or indirectly
handle identifiable personal data are properly trained on data privacy
issues.
• Design data-collection instruments with the minimum subject
identifiers needed, including the design of case report forms (CRFs),
clinical and laboratory databases, data transfer specifications, and
any other area of data collection that may contain personal
information.
• Ensure personal data is not identifiable, other than subject identifiers
used to link documentation to a database record, from
documentation
• Review and update data management processes regularly to ensure
consistency with current company privacy policies and government
regulations.

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 Data Privacy – Best Practices
• Develop and maintain an environment that respects the privacy of research
subjects. Applying strict criteria when handling personal information, and
verification that procedures are in compliance with regulations.
• Implement procedures prior to data transfer between sites, departments,
subsidiaries, and countries to ensure all privacy considerations have been
considered, addressed, and documented.
• Implement procedures for using data for an alternate or new purpose
other than what was originally intended by the informed consent.
• Put stringent procedures in place to securely transfer, store, access, and
report on extremely sensitive data (e.g., genetic information).
• Maintain proper physical and electronic security measures. Data should be
stored in protective environments relevant to the type of media being
stored.

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 Security
Physical Security Logical Security
-Access control – Authorization
(Access Card) (Password Policy)

Database Security
– Protection of Records
(Tape backup & Safe Box)
(disaster recovery)

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Documentation - QA &
Access/Change Control

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Data Storage,
Archival, &
Transfer
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 Data Storage - Minimum Standards
• During the conduct of a clinical trial, store all original data
collected (e.g., case report forms and electronic
laboratory data) in secured areas such as rooms or file
cabinets with controlled access (e.g., locks).
• Document the procedures for granting access to database
servers, establishing system controls, and assigning
passwords.

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 Data Storage - Best Practices
• Store clinical data in such a way that backup copies can be
easily and frequently made. For example, paper documents
should be scanned and archived electronically.
• Use open formats for archival, storage, and transport of
data (e.g., ASCIISAS Transport, Portable Document Format
(PDF), and the CDISC ODM Model) whenever possible.

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 Data Archival
• Database design specifications
• Raw data
• Audit trail
• Final data: Preserved in a standard file format (e.g., ASCII,
SAS transport)
• Original study documents
• Procedural variation documentation: Memos and relevant
information about any variations from standard operating
procedures or working practices
• Database closure
• Site copies of data (may be required for audit purposes)

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External Data Transfers – Minimum Standards
• Establish the procedures for collecting, transferring, loading,
validating, and editing external data through sponsor and
vendor collaboration.
• Identify key individuals for communication and follow through.
• Maintain a documentation trail.
• Apply quality control procedures to each stage of data
handling to ensure that all data are reliable and have been
processed correctly.

External Data Transfers – Best Practices

• Validate all programs and systems used for processing
clinical trial data in a clinical research environment

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 Data Management - Collaborating Teams
Example: Phase III Efficacy Trial of Prime-Boost HIV Vaccine
Randomization Scheme

Cumulative Clinical Database Unblinded Safety Reports Protocol Execution

Team Thailand

Preparation and Submission of Locked Database Interim and Final Analyses

Independent Statistician
DSMB
Team

Cumulative Clinical Data Coordinating

Database
Data Management Unit and Database Quality Assessment
DMU Analysis Center
Primary Database Quality (DCAC Team) Blinded Safety Reports
Assessment USMHRP
Reports
SAE Reconciliation

MedDRA Coding Team

USMHRP ROC
Preparation and Submission of AE/SAE MedDRA Coding for AE/SAE
Verbatim Terms for MedDRA Coding Verbatim Terms

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System & Data Flow Set-up - (Open System)

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System & Data Flow Set-up - (Open System)

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Training
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Training – Minimum Requirements
• Review and update curriculum and individual course
offerings regularly, including applicable SOPs, to
ensure that content remains current and relevant.
• Train all CDM staff members to perform the job
functions that are currently required for their
assigned roles.
• Ensure that training documentation is maintained a

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 Training – Best Practices
• Document a role-specific training curriculum for each
position within the CDM organization.
• Ensure that a master training plan, which is regularly
reviewed and revised, documents and prioritizes training
needs of the CDM function.
• Perform job-needs analyses and audience analyses to
guide development
• of the training plan.

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Project Management
for DM
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Summary: Data Management Functions & Elements

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Project Management for the Clinical Data Manager
Minimum Standards
• Identify all data management study team members, stakeholders,
and respective alternates wherever possible and as early in study
setup as possible.
• Identify, define, and document all study-specific processes.
• Ensure clear, comprehensive, and technically feasible timelines of
scheduled tasks
• Assure a thorough assessment has been made of CDM team
members’ familiarity with clinical study processes, disciplines, or
functional lines.
• Ensure appropriate project- or study-specific training is delivered,
maintained and documented for all study personnel performing
CDM tasks.

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Project Management for the Clinical Data Manager
Best Practices
• Create a responsibility matrix that describes activities to
be conducted during the course of the study.
• Continually assess project processes and modify
processes as needed to function more efficiently.
• Ensure all process changes are communicated,
documented, and version controlled.

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Data Management Metrics

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 More Info - Visit:
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 The End
of
Introduction to
Data Management
for
Clinical Research

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