Training Clinical Data

Managers
A Joint Industry-Academic
Perspective

Society for Clinical Trials

2007 Annual Meeting
Montreal, Canada

James R. Johnson, PhD

Adjunct Professor of Clinical Research, Campbell
University
Director-Planning and Documentation, BioCryst
Pharmaceuticals, Inc.

Department of Clinical Research

 Questions and Objectives

• How do we train Clinical Data

Managers for work in Industry?
– CROs
– Pharmaceutical and Biotechnology Companies
– Data Coordination Centers (Joint Academic-
Industry Collaborations)

• What are the essential elements

of a training program?

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 Elements of Data Management
Training Center with Good Data
Management Practices

1. Study Design
 Sets the ground work for establishing Good Data Management
Practices
2. Study Methods
 Implementing data mgt practices consistent with ensuring that
study methods are robust and accurately implemented.
Concerned primarily with Data Collection Methods, and
validation of the data collection methodology.
3. Study Analysis
 Poor data mgt practices leads to “questionable” study analysis,
whereas solid data mgt methodology generally results in
observations that are true to the experiment.
4. Feedback Loop
 The Study Analysis serves to provide a check on the Original
Study Design. Is an indicator of how well the design, data
management, and statistical practices were established and
implemented.
1
STUDY DESIGN

2
STUDY
METHODS

4 3
STUDY
ANALYSIS

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 Where Does Good Data Management
Practice fit into a Clinical Study?
What training is essential?

Protocol Review
Data Dictionary Design
CRF Design, Edit Specifications
Data Management Plan

STUDY DESIGN

Data Entry
Query Generation and Mgt.
STUDY Coding: AEs and Medications
METHODS
Laboratory Data Management

STUDY
ANALYSIS

Medical and Statistical

Review
Database Auditing
Locking the Database
Formal Planned Analysis
Archiving

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 Goals and Objectives for training
Clinical Data Managers for work in
Industry

• Goals • Objectives
– To provide the Data – To present principles
Manager with a of data management
for:
comprehensive
understanding of the • Study Design,
Planning,
principles of data Randomization, and
management as a Data Collection
discipline. Methodology
– To provide practical • Case Record Form
Design
skills that allow the
• Data Quality
data manager to take
measures
the principles
• Data Validation
presented and apply
issues
them across a wide
• Coding Dictionary
array of clinical Use/Abuse
research projects.
• Medical/Statistical
– To provide review of trial data.
Regulatory Compliant • Closure/Archiving
training for the Data • Good Data
Manager to provide Management
“data” that may be Practices &
used for submissions Guidelines

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 Clinical Data Manager

• Roles and responsibilities of a

Clinical data Manager vary with the
setting and scope of the Clinical
Research Program. Some generalities
do apply to a general role.
– Who are these people?
– What Roles and Responsibilities do
they Assume?
– How do they interact with other
Clinical Trials Specialists (e.g.
statisticians, CRAs, etc.)?
– What kind of training and experiences
do professional data managers need to
be successful?

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 Clinical Data Management: Roles and
Responsibilities

• Clinical Data Managers are

Responsible for:
– Providing strategic DM leadership and expertise to
the clinical development team. (Protocol and CRF
Development)
– Proactive Communication with the Clinical
Development Team for all Data Management
Activities.
– Manage DM activities (and partners) for adherence
to project timelines.
– Review and approve DM related documents.
– Monitor Data Quality for adherence to GCP and
defined quality standards.
– Proactively monitor DM activities to provide
continuous process improvement with data
collection and processing methods.
– Overall responsibility for delivering high quality,
regulatory compliant clinical data bases for
regulatory submissions and publication of study
results.

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 Clinical Data Management
Responsibilities

• Clinical Data Managers Manage

Processes for:
– Collection of appropriate study data, in line with
study objectives and endpoints.
– Efficient entry and cleaning of CRF data, minimizing
unnecessary work.
– Quality to provide maximum benefit of study data.

• Note the manuscript presenting the

thesis regarding the statisticians
active role in DM process.
– Grobler AC, Harris SL, Jooste HL. The role of the
statistician in the data management process. Drug
Information Journal 2001;35:665-670

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 Clinical Data Management:
Responsibilities

• Clinical Data Managers Tasks May

Include:
– Case Record Form Development
– Data Base Design and Setup.
– Data Entry and Verification.
– Edit Specification Programming.
– Query Generation and Resolutions.
– Data Base Corrections and Audit Trails.
– Integration of external data sets (e.g. clinical laboratory
investigations, imaging data, ECG data)
– Medical Coding (MEDRA), Rx Coding (WHOMED).
– Data Base Quality Control.
– Data Base Auditing.
– Electronic Delivery of study data sets for interim monitoring
and medical review.
– Delivery and Archiving of of Final Study Data Sets.

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 Clinical Data Management: Training
and Experiences

• Clinical Data Manager Training &

Experience Includes:
– Educational Background in the Life Sciences
(Biology, Medicine, Biochemistry, etc.).
– Training and Understanding in Clinical/Medical
Terminology
– Working knowledge of clinical databases (relational
database technology), and appropriate programming
functions.
– Superior communications (oral and written) skills,
and the ability to work collaboratively on cross-
functional clinical development teams.
– Must be highly detailed oriented, with experience
reviewing and solving complex interdependent data-
relationships and problems.
– Very Flexible, Adaptable, and Resilient to the
evolving environment of DM technology, and best
data management practices.
– Good Project Management Skills

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 Study Design:
Training the Data Managers to Ask
Questions!

• At Study Design the concept of rational CDM

practices must be started.
• Critical Data Management questions that must be
address at the conception of a Research Protocol.
– What is the “Clear” Objective of the study?
– What is the Target Variable(s) to be assessed in
the study?
– How are the Target Variable(s) measured?
– Can Target Variable measurements be
reproduced and validated.
– Are the Target Variables:
• Objective Assessments by an Independent
Assessor or Instrument?
• Subject Assessments supplied by the Subject
or Observation?

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 Training Data Managers to utilize
“standards”
Key Identifiers Critical to Data
Management

• Key Identifiers
– Protocol
– Investigator
– Site (if applicable)
– Subject
– Visit
– Random Code (Treatment ID)
• The unique combination of these identifiers allows
for identification of a subject, at a point in time,
with the planned treatment assignment.
• No two identifiers are identical for any given
subject.

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 Training Data Managers to utilize
“standards”
Principles of CRF Design

• Key Principles for developing a

paper based Case Record Form.
– Follow the principles of K.I.S.S. (Keep it Simple for
Silly People!)
– Use Standard Headers for Key Attributes
– Put important data collection date/time in the
Top of the form.
– Never Mix data collection unless absolutely
necessary

• Similar principles apply for

training on the use of electronic
data capture methods.

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 Training Data Managers
Quality Data Management as a
Discipline

Organization/Interdiscplinary Data Management System Specific

Documentation Documentation

Data Management Handbook, Position

Policies, Guidelines, and
Principles Descriptions, Operational Policies for
Interpretations
Data Management

Standard Operating Procedures Functional Roles and

(SOPs) High-Level Instructions Responsibilities, CV and Training
Documentation

Working Practices, Forms

and Templates, Content Function Specific
Guides Instruction Details
Manuals

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 Elements of a Quality Management
System
for Clinical Data Management

• Documented
– Roles and Responsibilities of Data Managers
– CV (Resume) and Training Records
Demonstrating Competency for specified Role
and Responsibility.
– Standard Operating Procedures (SOP):
Organizational and Departmental
– Data Management Departmental Level
Handbook of Policies and Procedures.
– Operating Manuals (OM), sometimes called
Working Practices (WP), for each “Major”
Function identified in an SOP.
– Clearly Defined and Documented Procedures
for document development, review, and
approval.

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 Training Data Managers:
Quality Implementation through SOPs

• Roles & • Corresponding SOP

Responsibilities: (WP):
– – SOP 1.04.04-01
Case Record Form
Development – SOP 1.04.05-02 (WP 1.04.05-
02)
– Data Base Design and
– SOP 1.04.06-03
Setup.
– – SOP 1.04.07-01 (WP 1.04.07-
Data Entry and Verification.
01)
– Edit Specification – SOP 1.04.08-12
Programming.
– SOP 1.04.09-07
– Query Generation and
– SOP 1.04.10.09
Resolutions.
– SOP 1.04.11.04
– Data Base Corrections and
Audit Trails. – SOP 1.04.11.02
– – SOP 1.04.12.07
Integration of external data
sets. – SOP 1.04.13.02
– Medical Coding (MEDRA), – SOP 1.04.14.02
– Rx Coding (WHOMED). – SOP 1.04.15.09
– – SOP 1.04.16.18
Data Base Quality Control.
– – SOP 1.04.17.02
Data Base Auditing.
– Data Base Monitoring &
medical review.
– Database Locking and
Approval
– Delivery and Archiving of
Final Study Data Sets.

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 Training Data Managers
Project Specific Data Management
Plan

• Outlines the specific elements to be

completed for a project.
• Is the basis for establishing Data
Quality & acceptance at the project
level.
• Identifies any and all expected
deviations from SOPs or WPs for the
project.

• Remember If is ain’t written down

it did not happen!!

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 Training Data Managers:
CT Information Platforms: RDBMS &
Data Warehouses

Clinical Portals

Study
Paper EDC Labs Images Site Mgt PV Reporting
Setup

Clinical Acquisition Clinical Intelligence

Applications Applications

Clinical Acquisition Clinical Intelligence

Framework Framework
Data Data Data Data
RDBMS Safety MetadataDictionary Marts Marts Marts Marts

Clinical Trials Data Warehouse

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 Training Data Managers:
Relational Database Design
Principles

• Relational Database Design Principles

PROTOCOL

INVESTIGATORS

SITES

SUBJECTS

ONE

VISITS

TO MANY
TREATMENTS ASSESSMENTS

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 Training Data Managers:
Medical and Statistical Review
Principles

Biostatistics and Statisticians

Statistical Programmers
Data Sciences
Medical and Statistical Review Audiences

Data Managers

Clinical Research and Study Physicians (M.D.’s)

1o Medical Affairs
Clinical Research Scientists (PharmD, Ph.D., MPH, RN’s, etc)
Clinical Trial Managers (Operational Positions)

Writer’s (CSR or Manuscripts: M.D.’s, PharmD, Ph.D. BS, MS, MPH,

Medical Communications RN’s, etc.)

Regulatory Directors and Managers (M.D.’s, PharmD, Ph.D. BS, MS,

Regulatory Affairs MPH, RN’s, etc.)

Clinical Pharmacology
2o
and Pharmacokinetics
Pharmacology Scientists (PharmD, Ph.D.)

Marketing and Market Planners

Market Research Market Research Scientists

Statisticians (Internal and External Consultants)

Regulatory Agencies Medical Reviewers (M.D.’s)
Project Managers

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 Training Data Managers to
Begin with the End in Mind

• Patient Disposition Figure in all Study

Reports (ICH E3) (CONSORT)
INFORMED CONSENT / SCREENED
(N=XXX)

SCREEN FAILURES
(N=XXX)

RANDOMIZED
(N=XXX)

WITHDRAWLS
(N=XXX)

SAFETY POPULATION FULL ANALYSIS SET (ITT)

(N=XXX) (N=XXX)

MAJOR PROTOCOL VIOLATIONS

(N=XXX)
SAFETY SUBGROUP(S)
(N=XXX)
PER-PROTOCOL(PP)
(N=XXX)

EFFICACY SUBGROUP(S)
(N=XXX)

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 Advanced Data Management Course
Syllabus
(10-12 Weeks: Principles and
Practices)

• Overview, Definitions, Data Types,

• Roles and Responsibilities of Data Mgt in CR
• Study Design, Data Management Planning,
Randomization Principles,
• Data Collection Methodologies
• Processes and Procedures for Addressing Data Quality,
SOPs and Working Practices.
• Data Validation: Systematic Error, Controlling for Biases,
Edit Specifications
• Data Base Management Systems
• Form and Function of Coding Dictionaries
• Electronic Data Capture: Clinical Laboratory
Investigations
• Medical and Statistical Review of Study Data
• Data Base Closure, Reporting, and Archiving
• Communication Strategies: Oral and Written
• Computer Skills: Programming and RDBMS utilization

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 Questions

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