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>> Christine Gordon: Welcome
back to Part Two of Four.

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In this section,
we will discuss the following.

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Overview of the data cycle

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and how clinical 
research data is handled,

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the purpose of 
source documentation,

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what case report forms are,
and data standards.

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So how is data handled?

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At a quick glance,
data management

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actually begins with 
adequate and accurate source

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documents from which the 
data can be abstracted

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or even electronically extracted
onto a case report form.

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After data quality checks
by the research team,

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a database,
and a sponsor, if applicable,

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the data can be 
cleaned and verified

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for transfer to a data analysis
software or to the sponsor.

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So where does 
the data come from?

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Well, let's start with
what source documents are

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and their purpose.

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Source documents
are the original source

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that documents the raw data.

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These sources document
the existence of the subject,

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they substantiate compliance

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with the protocol and 
integrity of the study data,

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and they serve
as an audit trail,

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which allows one to recreate
the progression of the trial.

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Source documents may be found
in the subject's medical record,

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hospital record or clinic chart.

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Some examples include
physical exam findings,

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documentation of 
the consent process,

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diagnostic reports,
operative reports,

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laboratory reports,
data reported,

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or data recorded
from automated instruments.

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Some source data,
such as quality of life surveys

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and other patient
recorded outcomes

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or PK worksheets may not be
found in the medical record,

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but rather in a research record;
however, at a minimum,

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there should be some notation
in the medical record

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that surveys were collected
or when PKs were drawn.

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Clinical research 
source documentation

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in the medical record

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contains a bit more detail than
in general clinical practice.

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For example
in clinical research,

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we need to document the start
dates of concomitant medications

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and their indication for use.

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Also, research 
source documentation

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is never by exception,
meaning if normal,

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there is no documentation.
In clinical research

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there must be documentation
that something is normal

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in order to 
capture  accurate data.

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Per good clinical practice,
a case report form,

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also known as the CRF,
is a printed or electronic form

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used in the trial
to record information

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about the participant

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as identified
by the study protocol.

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CRFs allow us to 
record data in a manner

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that is both 
efficient and accurate,

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record data in a manner
that is suitable for processing,

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analysis and reporting.

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Electronic or paper 
case report form creation

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is a critical step
in data management

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because if the correct 
data is not collected,

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it will impact
the trial results.

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Case report form should be
created based on the protocol

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and whenever possible,

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the raw data versus the derived
data should be collected.

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For example collecting
the date of birth

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rather than the age
will provide more information

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because the age can be 
derived using other dates.

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This will help 
facilitate exchange of data

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across projects
and organizations.

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All CRFs should be 
accompanied by completion

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or an instruction manual.

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General considerations for
CRF development include

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collect data outlined
in the protocol,

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collect data required
by regulatory agencies,

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collect data with 
all users in mind,

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be clear and concise with data
questions, avoid duplication,

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request minimal
free text responses,

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collect data that allows
for efficient computerization,

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and develop version
control procedures.

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The consequences of poorly
designed forms include the data

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actually needed for analysis
of primary

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and secondary endpoints
is not collected,

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the data collected at not part
of the study protocol,

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data collected
that can easily be analyzed,

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requesting the same 
information more than once,

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eCRF screens that don't display
all data in a single display,

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for example,
a scrollbar must be used

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which may result
in missing data,

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and not using form
or data standards.

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Poorly designed CRFs will likely
cost more in the long run

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due to corrections

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and modifications
needed throughout the study.

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There are pros and cons
to developing CRFs

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during protocol development
and after protocol finalization.

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Ideally though, CRF developments
should begin as soon as possible

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in the protocol
development process

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and should use the 
protocol visit schedule.

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During a protocol development,

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a pro may include
identification of problems

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with protocol procedures
prior to protocol finalization.

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A con may include
numerous versions of CRFs

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may be necessary.
After protocol finalization,

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a pro includes
fewer versions of CRFs

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and fewer reviews
prior to finalization.

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A con includes if issues
between CRF and data

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and protocol rights,

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a protocol amendment
may be required.

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No matter when CRFs
are developed,

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all appropriate individuals
need to be part of the process

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or at least have
an interdisciplinary review

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such as the statistician,
the investigator,

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the site coordinator
database designer or programmer,

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clinical monitor
and data management

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and data entry personnel.

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Even though data collection
forms are based on the protocol,

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they usually contain certain
categories or data modules,

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along with key identifiers

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such as the site
identification number,

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protocol number,
and unique patient identifier.

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These modules
include the header,

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which usually includes
key identifying information,

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study number, center number,
subject identification number.

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Safety modules may include
demographic information,

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inclusion or exclusion criteria,
adverse events, medical history,

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or cancer history,
physical exams,

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including vital signs,
concomitant medications,

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laboratory tests,
procedures drug accountability,

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deaths in off study reasons.

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Efficacy modules are
typically unique modules

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and they can be
more difficult to develop.

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The protocol would dictate which
elements should be included,

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and this could be
a repeated battery of tests.

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The module should define key
efficacy endpoints in the trial,

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mainly the 
primary/secondary endpoints,

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additional tests
to measure efficacy,

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such as quality of life
and required diagnostics,

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and may include
baseline measurements.

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Standards are a document
established

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by consensus
that provides rules, guidelines,

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and characteristics for
specific activities or results.

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There are a number
of organizations

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developing standards
and involved in standards

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development initiatives.
When developing CRFs,

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using standards for both
the data questions

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and answers allows
for rapid data exchange,

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removes the need for data
mapping during data exchange,

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allows for consistent
reporting across protocols

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for across projects,

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promotes monitoring and
investigator staff efficiency,

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allows the merging of data
between studies,

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provides increased 
efficiency and processing

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an analysis
of the clinical data.

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Some of the more well-known

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standards development organizations

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are ISO,
the International Organization

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for Standardization, 
HL7, Health Level 7,

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CEN, European Committee
for Standardization and CDISC,

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Clinical Data Integration
Standards Consortium.

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These organizations design
standards for data structure

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or modeling exchange
and data semantics.

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There are several types
of standards

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using clinical research,
including data exchange.

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This facilitates the ability
for the sender to communicate

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with the receiver of information
on format and type of data.

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Data format identifies
the data and outlines

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the location
of the data in a dataset.

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Semantic data elements,

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which standardize
the data element name,

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defines the data element,
and lists permissible values

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or possible 
responses to question.

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CDISC is an open, 
global, multidisciplinary,

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nonprofit organization
that has established standards

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to support the acquisition,
exchange, and submission

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archive of clinical research,
data and metadata.

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CDISC standards are vendor
neutral, platform independent

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and freely available
via the CDISC website.

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Clinical Data Acquisition
Standards Harmonization,

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also known as CDASH,

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is a standard
for form development

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that is now widely used
in clinical research.

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This will not only help
developing quality forms,

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but may enable researchers
to aggregate data

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from other studies
using the standard.

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The standard describes the basic
recommended data

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collection fields
for 16 domains,

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including demographics,
adverse events,

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and other domains that are
common to most therapeutic areas

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and phases of clinical research.

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In this session, we learned
that data management

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actually begins with adequate
and accurate source documents.

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The purpose of source documents
is to document the existence

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of the subject, substantiate
compliance with the protocol

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and the integrity
of the study data,

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and also serves
as the audit trail.

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We also discussed that CRFs
are printed or electronic forms

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used in the trial to record
information about

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the participant as identified
by the study protocol.

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The use of CRFs
allows to record data

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in a manner that is
both efficient and accurate,

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record data in a manner
that is suitable for processing,

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analysis and reporting.

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Ideally, CRF development 
begins as soon as possible

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in the protocol
development process

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and should use
the protocol visit schedule.

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We covered that standards are
a document established

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by consensus
that provide rules, guidelines,

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or characteristics for
specific activities or results

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and when developing CRFs

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using standards
for both the data questions

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and answers allows for 
rapid exchange of data,

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removes the need for mapping
through deep exchanges,

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allows for consistent reporting
across protocols and projects,

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promotes monitoring and
investigator staff efficiency,

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and allows the merging of 
data between studies,

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as well as provides
increased efficiency and data

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processing in 
analysis of the data.

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Let's see if you can 
answer these questions.

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What is the purpose
of source documentation?

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And what does
the case report form?

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Thank you for your time.