Lecture 1

Introduction and
Data Management Plan
What are Clinical Trials?
 Why do people participate?
• Healthy volunteers say they participate to help others
and to contribute to moving science forward.

• Participants with an illness or disease also

participate to help others, but also to possibly receive
the newest treatment and to have the additional care
and attention from the clinical trial staff.

• Clinical trials offer hope for many people and an

opportunity to help researchers find better treatments
for others in the future.
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References & further reading

• ICH GCP, E 6, Consolidated Guideline. Geneva, 1996

• Code of Federal Regulations, Title 21, Volume 1, Part 11.

Washington, DC: US Government Printing Office, 1998

• Guidance for Industry: Computerized Systems Used in

Clinical Investigations. US Department of Health and
Human Services, Food and Drug Administration (FDA),
Office of the Commissioner, May 2007
Data Management Plan
 DMP

References & further reading

• ICH GCP, E 6, Consolidated Guideline. Geneva, 1996

• Code of Federal Regulations, Title 21, Volume 1, Part 11.

Washington, DC: US Government Printing Office, 1998

• Guidance for Industry: Computerized Systems Used in

Clinical Investigations. US Department of Health and
Human Services, Food and Drug Administration (FDA),
Office of the Commissioner, May 2007
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Clinical Data Management

• What does it stand for?
• CDMS – Clinical Data Management System
– A CDMS is used in clinical research to manage the
data of a clinical trial; the clinical trial data gathered at
the investigator site in the case report form are stored
in the CDMS; processes/work flows related to data
capture up to data analysis are summarized in the
term clinical data management
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Data Management Plan (DMP)

• Study protocol contains the overall clinical plan
for a study
• Some key areas should/may have in addition a
separate plan to document adherence to certain
standards
– Road map of how to handle data under any
foreseeable circumstances
– Establishes processes for how to deal with
unforesseen issues
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Data Management - Goal

• Database that is
– Accurate
– Secure
– Reliable
– Ready for analysis
• Many people are involved in handling data
throughout the course of the trial
– Imparative that all parties refer to the DMP for a
consistent approach to processes related to data
management activities
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DMP – to be considered
• DMP – auditable document
– Often asked for by regulatory authorities
– Consequently to be written in high quality
– Inspectors may also seek to ascertain the
degree to which the study adheres to the
processes described in the DMP!
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Scope
• Style and format differs from organization
to the next
• Here: minimal components to be
addressed
– Contained in DMP itself
– DMP refers to other study documents for
further detail (attention: controlled document?)
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Minimum Standards
• Draft to be completed prior to enrollment of first
subject
• Compliance with applicable regulations
• Identification and definition of personnel and
roles involved (with decision making)
– Data collection, data handling, data quality control
• Period from study initiation until database
closure must be covered
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Best Practices
• Development together with stakeholders to
ensure agreement
• DMP template – consistency and
standardization across different trials
• DMP must be kept current, incl. proper
versioning
• Approved and signed-off version must be
available prior to starting on the work it
describes
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Purpose of the DMP

• Serves as the authoritative resource,
documenting data management practices and
decisions agreed to during study setup

• Should also address any procedural or protocol

updates made during study conduct
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Creation and maintenance

• General comment:
– DMP is based on study protocol, work scope,
[contract], analysis plans, case report forms
(CRFs) [other supporting documents], if
appropriate
– Upon conclusion of the study, DMP is to be
archived with the TMF
– Living document throughout the life cycle of a
study!
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Living document
• Requirements:
– Unique identification (to be captured on each
page, e.g. study code)
– Subject to version control
• Each version must be documented and must
include:
– Date, author, reason for change and individual version
identifier
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Organization of a DMP
• Typically made up with the following
sections:
– Approval page
• Incl. date of approval
• Work should NOT begin until signatures are
present!
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Organization of a DMP [cont.]

• Protocol summary (optional)
– Short synopsis of the study protocol, e.g.
• Visit schedule,
• Critical data and variables
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Organization of a DMP [cont.]

• Dictionary and coding management
– Which coding dictionary (e.g. MedDRA, WHO Drug
etc.) and which version of it?
– References to documents providing instructions
• E.g. for handling dictionary updates,
– Description of auto-encoding or study specific
conventions, if appropriate
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Organization of a DMP [cont.]

• Definitions and acronyms
– List of acronyms as used in the protocol and
the DMP
• Personnel/role identification/training
– Key personnel with roles and responsibilities
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Organization of a DMP [cont.]

• Timelines (vary from company to the next!)
– Expected completion targets for all deliverables
• E.g. database validation could be targeted for completion a
specified number of weeks from time the protocol is finalized!
– Following are examples of milestones:
• Protocol finalization, CRF development, database design
and UAT, first patient first visit, last patient last visit, last CRF
received, last query solved, safety data reconciliiation
completed, medical coding completed, interim analysis,
database lock, study data archiving
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Organization of a DMP [cont.]

• Case report forms (CRF)
– ICH E6 „A printed, optical, or electronic document
designed to record all of the protocol-required
information to be reported to the sponsor on each trial
subject“
– Following are areas to be elucidated:
• CRF design process – ref. SOP CRF development
• CRF instructions – guidelines for CRF completion
• CRF changes – process for managing changes, query
handling!
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Organization of a DMP [cont.]

• Database design, creation and maintenance
– Reference to database validation plan!
– Inclusion of description of how the database is
created and maintained, description of data and table
naming convention
– ! Title 21, CFR Part 11 mandates that procedures and controls be in
place to ensure appropriate control of and access to documentation as
well as revision and change control procedures to maintain an audit trail
of modifications to documentation!
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Organization of a DMP [cont.]

• Database archive
– Specific information for archiving electronic
records (company standard)
• Database roles and privileges
– Profiles for available database roles
– Assignment of privileges to those roles
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Organization of a DMP [cont.]

• Database security
– Security of network equipment and servers
– Security features of the electronic records
– Maintenance of user roles and access rules
– Database backup
• Procedures
• Frequency
– Reference to company´s desaster recovery plan!
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Organization of a DMP [cont.]

• Data entry and processing
– Data entry guidelines
• Entry of various data elements (who and how)
• Handling of missing data
• Self-evident changes (criteria for corrections by DM-personnel, who,
how authorized)
– Data discrepancy conventions
– Data receipt
• Type of receipt (paper, EDC) expected frequency, tracking of data
receipt
– Data reconciliation (as required)
– Database lock
• Definition of criteria for database lock
• Process of database locking
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Organization of a DMP [cont.]

• Data validation and UAT
– Validation test procedures (to ensure integrity of
study-specific components), e.g.
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Organization of a DMP [cont.]

• Serious Adsverse Event (SAE) Data
Reconcilation
– Description or reference to a document that
describes the protocol specific SAE
reconciliation plan
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Organization of a DMP [cont.]

• Quality assurance / control processes
– Level of checks
• Depends on regulatory importance of the study
– Frequency of quality controls
• ICH E 6: „Quality control should be applied to each
stage of data handling to ensure that all data are
reliable and have been processed correctly“
– Documentation of checks performed
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Organization of a DMP [cont.]

• External data transfer
– Description of data type (safety, lab data etc.)
– Entity to provide /to receive data
– Data format and method of transfer
• SAS datasets, ASCII-files, XML-files etc
• Encrypted e-mail, File Transfer Protocol (FTP), CD etc.
– Freqency of transfers
– Reference to written agreements, if any
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Organization of a DMP [cont.]

• Audit plan(s)
– Interim and final database audits as planned
– Any further „QA“-activities as planned during
the course of the study
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Organization of a DMP [cont.]

• Reports
– List of reports for dissemination during the
study
• With target audience
• Content of the report
• [Planned] date of data extraction
• Mechanism for distribution (e.g. e-mail, posting
electronically)
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Organization of a DMP [cont.]

• Other processes
– In general: every study is to some degree
unique, and there may be processes so far
not covered in this lecture!
– Note: if a study involves other processes, they
should be described in detail in the DMP!
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Organization of a DMP [cont.]

• Additional processes, if applicable
– DSMB requirements – Data Safety Monitoring
Board
– Business rules, such as IT maintenance which
may limit server access
– Blind data review specification
– Record retention „process“
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Lecture end
• Any question?
• Today´s take home message!
• CDM, DMP, goal, scope, purpose,
minimum standards, best practices,
components