>> Christine Gordon: Welcome back to Part Two of Four.
In this section, we will discuss the following.
Overview of the data cycle
and how clinical research data is handled,
the purpose of source documentation,
what case report forms are, and data standards.
So how is data handled?
At a quick glance, data management
actually begins with adequate and accurate source
documents from which the data can be abstracted
or even electronically extracted onto a case report form.
After data quality checks by the research team,
a database, and a sponsor, if applicable,
the data can be cleaned and verified
for transfer to a data analysis software or to the sponsor.
So where does the data come from?
Well, let's start with what source documents are
and their purpose.
Source documents are the original source
that documents the raw data.
These sources document the existence of the subject,
they substantiate compliance
with the protocol and integrity of the study data,
and they serve as an audit trail,
which allows one to recreate the progression of the trial.
Source documents may be found in the subject's medical record,
hospital record or clinic chart.
Some examples include physical exam findings,
documentation of the consent process,
diagnostic reports, operative reports,
laboratory reports, data reported,
or data recorded from automated instruments.
Some source data, such as quality of life surveys
and other patient recorded outcomes
or PK worksheets may not be found in the medical record,
but rather in a research record; however, at a minimum,
there should be some notation in the medical record
that surveys were collected or when PKs were drawn.
Clinical research source documentation
in the medical record
contains a bit more detail than in general clinical practice.
For example in clinical research,
we need to document the start dates of concomitant medications
and their indication for use.
Also, research source documentation
is never by exception, meaning if normal,
there is no documentation. In clinical research
there must be documentation that something is normal
in order to capture accurate data.
Per good clinical practice, a case report form,
also known as the CRF, is a printed or electronic form
used in the trial to record information
about the participant
as identified by the study protocol.
CRFs allow us to record data in a manner
that is both efficient and accurate,
record data in a manner that is suitable for processing,
analysis and reporting.
Electronic or paper case report form creation
is a critical step in data management
because if the correct data is not collected,
it will impact the trial results.
Case report form should be created based on the protocol
and whenever possible,
the raw data versus the derived data should be collected.
For example collecting the date of birth
rather than the age will provide more information
because the age can be derived using other dates.
This will help facilitate exchange of data
across projects and organizations.
All CRFs should be accompanied by completion
or an instruction manual.
General considerations for CRF development include
collect data outlined in the protocol,
collect data required by regulatory agencies,
collect data with all users in mind,
be clear and concise with data questions, avoid duplication,
request minimal free text responses,
collect data that allows for efficient computerization,
and develop version control procedures.
The consequences of poorly designed forms include the data
actually needed for analysis of primary
and secondary endpoints is not collected,
the data collected at not part of the study protocol,
data collected that can easily be analyzed,
requesting the same information more than once,
eCRF screens that don't display all data in a single display,
for example, a scrollbar must be used
which may result in missing data,
and not using form or data standards.
Poorly designed CRFs will likely cost more in the long run
due to corrections
and modifications needed throughout the study.
There are pros and cons to developing CRFs
during protocol development and after protocol finalization.
Ideally though, CRF developments should begin as soon as possible
in the protocol development process
and should use the protocol visit schedule.
During a protocol development,
a pro may include identification of problems
with protocol procedures prior to protocol finalization.
A con may include numerous versions of CRFs
may be necessary. After protocol finalization,
a pro includes fewer versions of CRFs
and fewer reviews prior to finalization.
A con includes if issues between CRF and data
and protocol rights,
a protocol amendment may be required.
No matter when CRFs are developed,
all appropriate individuals need to be part of the process
or at least have an interdisciplinary review
such as the statistician, the investigator,
the site coordinator database designer or programmer,
clinical monitor and data management
and data entry personnel.
Even though data collection forms are based on the protocol,
they usually contain certain categories or data modules,
along with key identifiers
such as the site identification number,
protocol number, and unique patient identifier.
These modules include the header,
which usually includes key identifying information,
study number, center number, subject identification number.
Safety modules may include demographic information,
inclusion or exclusion criteria, adverse events, medical history,
or cancer history, physical exams,
including vital signs, concomitant medications,
laboratory tests, procedures drug accountability,
deaths in off study reasons.
Efficacy modules are typically unique modules
and they can be more difficult to develop.
The protocol would dictate which elements should be included,
and this could be a repeated battery of tests.
The module should define key efficacy endpoints in the trial,
mainly the primary/secondary endpoints,
additional tests to measure efficacy,
such as quality of life and required diagnostics,
and may include baseline measurements.
Standards are a document established
by consensus that provides rules, guidelines,
and characteristics for specific activities or results.
There are a number of organizations
developing standards and involved in standards
development initiatives. When developing CRFs,
using standards for both the data questions
and answers allows for rapid data exchange,
removes the need for data mapping during data exchange,
allows for consistent reporting across protocols
for across projects,
promotes monitoring and investigator staff efficiency,
allows the merging of data between studies,
provides increased efficiency and processing
an analysis of the clinical data.
Some of the more well-known
standards development organizations
are ISO, the International Organization
for Standardization, HL7, Health Level 7,
CEN, European Committee for Standardization and CDISC,
Clinical Data Integration Standards Consortium.
These organizations design standards for data structure
or modeling exchange and data semantics.
There are several types of standards
using clinical research, including data exchange.
This facilitates the ability for the sender to communicate
with the receiver of information on format and type of data.
Data format identifies the data and outlines
the location of the data in a dataset.
Semantic data elements,
which standardize the data element name,
defines the data element, and lists permissible values
or possible responses to question.
CDISC is an open, global, multidisciplinary,
nonprofit organization that has established standards
to support the acquisition, exchange, and submission
archive of clinical research, data and metadata.
CDISC standards are vendor neutral, platform independent
and freely available via the CDISC website.
Clinical Data Acquisition Standards Harmonization,
also known as CDASH,
is a standard for form development
that is now widely used in clinical research.
This will not only help developing quality forms,
but may enable researchers to aggregate data
from other studies using the standard.
The standard describes the basic recommended data
collection fields for 16 domains,
including demographics, adverse events,
and other domains that are common to most therapeutic areas
and phases of clinical research.
In this session, we learned that data management
actually begins with adequate and accurate source documents.
The purpose of source documents is to document the existence
of the subject, substantiate compliance with the protocol
and the integrity of the study data,
and also serves as the audit trail.
We also discussed that CRFs are printed or electronic forms
used in the trial to record information about
the participant as identified by the study protocol.
The use of CRFs allows to record data
in a manner that is both efficient and accurate,
record data in a manner that is suitable for processing,
analysis and reporting.
Ideally, CRF development begins as soon as possible
in the protocol development process
and should use the protocol visit schedule.
We covered that standards are a document established
by consensus that provide rules, guidelines,
or characteristics for specific activities or results
and when developing CRFs
using standards for both the data questions
and answers allows for rapid exchange of data,
removes the need for mapping through deep exchanges,
allows for consistent reporting across protocols and projects,
promotes monitoring and investigator staff efficiency,
and allows the merging of data between studies,
as well as provides increased efficiency and data
processing in analysis of the data.
Let's see if you can answer these questions.
What is the purpose of source documentation?
And what does the case report form?
Thank you for your time.