1.
Integrating
Trial
Data
Processes
Across
Functional
Authors:
Areas
using
Bill
Gluck,
PhD
DATATRAK,
VP
of
Clinical
and
Electronic
Data
Consulting
Services
Capture
(EDC)
Lorraine
D.
Ellis,
MS,
MBA
Research
Dynamics
Consulting
Technology
Group,
Ltd.,
CEO
2011

2. 2
of
8
Table of Contents
1
Introduction
...........................................................................................................................................
3
2
Process
Workflow
Changes
...................................................................................................................
3
2.1
Data
Collection
................................................................................................................................
4
2.2
Recording
Data
................................................................................................................................
5
2.3
Monitoring
......................................................................................................................................
5
2.4
Cleaning
Data
..................................................................................................................................
6
3
Summary
Overview
of
Process
Changes
and
Benefits
–
Focus
on
Clinical
Ops
and
CDM
Interactions
.
7
3.1
Investigator
Sites
Benefits
...............................................................................................................
7
3.2
Clinical
and
Monitor
Group
Benefits
...............................................................................................
7
3.3
Data
Management
Benefits
............................................................................................................
7
3.4
Statistical
Benefits
...........................................................................................................................
8
4
Conclusion
.............................................................................................................................................
8
Integrating
Trial
Data
Process
Across
Functional
Areas
using
Electronic
Data
Capture
(EDC)
Technology

3. 3
of
8
1 Introduction
One
common
theme
in
the
pharmaceutical,
biotechnology
and
medical
device
industry
is
the
constant
pressure
to
accelerate
development
of
drugs,
biologics
and
products
to
market.
Improvements
usually
tend
to
focus
on
one
aspect
of
the
development
workflow
at
a
time.
One
of
the
processes
that
is
the
most
time
and
effort
intensive
is
data
collection
and
management.
Clinical
data
workflows
have
traditionally
been
tweaked
especially
with
the
growing
acceptance
of
new
technology
and
more
contemporary
enterprise
eclinical
applications
(those
applications
that
include
clinical
trial
management
systems
(CTMS),
electronic
data
capture
(EDC),
randomization
and
drug
supply,
etc.).
Today
many
companies
are
viewing
procedures
not
only
within
but
across
functional
areas
as
a
necessity
to
streamline
data
flow
and
the
development
process.
This
white
paper
will
describe
some
of
the
process
re-­‐engineering,
role
modification
or
definition,
enhanced
communication
and
project
coordination
improvements
needed
to
implement
the
use
of
an
EDC
application
across
the
functional
areas
of
clinical
monitoring,
project
management,
Investigator
sites,
and
clinical
data
management
(CDM)
so
companies
can
maximize
the
benefits
of
today’s
technology.
Electronic
Data
Capture
technology
has
only
been
practiced
widely
in
the
industry
for
the
past
5-­‐to-­‐10
years
even
though
it
was
introduced
more
than
25-­‐years
ago.
Early
EDC
applications
were
more
remote
data
entry
stations
that
served
only
to
move
the
data
entry
process
to
the
sites;
there
were
not
many
procedural
or
process
changes.
Also,
early
EDC
software
lacked
the
extensive
functionality
to
evaluate
the
quality
of
the
data
that
are
found
in
today’s
systems.
As
the
EDC
application
matured,
it
became
evident
that
process,
role
and
procedural
changes
were
necessary
in
order
to
realize
the
full
benefits
of
the
technology.
These
changes
were
(are)
not
limited
to
changes
within
the
management
of
data
but
also
across
the
entire
clinical
trial
process.
2 Process Workflow Changes
Changing
from
a
paper-­‐based
data
collection
system
to
an
electronic-­‐based
data
collection
method
requires
changes
in
the
approach
to
data
collection,
processing,
and
management.
Processes
in
an
EDC
environment
must
be
re-­‐engineered
to
optimize
all
the
benefits
of
the
technology.
For
example,
roles
and
responsibilities
of
the
three
key
functional
groups
within
a
clinical
study:
the
Investigator
sites,
Clinical
Monitors
and
Clinical
Data
Managers
need
to
be
re-­‐defined
to
realize
the
benefits
of
the
technology.
Investigator
sites,
for
example,
no
longer
complete
paper
case
report
forms
as
they
enter
the
required
data
directly
into
the
EDC
application.
Monitors
now
modify
their
monitoring
procedures
to
review
data
before
they
go
to
the
site
so
they
can
be
more
efficient
in
managing
site
trial
performance
and
reviewing
data
against
source
documentation.
Clinical
data
management
too
must
adjust
internal
processes
and
procedures
as
there
are
many
differences
between
paper-­‐
based
approaches
to
collecting
data
versus
an
EDC
approach.
The
“flow”
of
the
data
must
be
evaluated
and
roles
and
responsibilities
of
each
task
adjusted.
For
example,
CDM
in
a
paper-­‐based
environment
would
be
responsible
Integrating
Trial
Data
Process
Across
Functional
Areas
using
Electronic
Data
Capture
(EDC)
Technology

4. 4
of
8
for
the
assignment
and
resolution
of
data
queries,
whereas
in
an
EDC
application
some
of
the
assignment
and
resolution
of
queries
may
be
distributed
across
CDM
and
the
clinical
monitoring
group.
To
discuss
the
revised
workflow
of
data
using
EDC,
we
have
broken
the
data
process
into
four
key
elements:
collection,
recording,
monitoring
and
cleaning.
2.1 Data Collection
The
data
collection
process
using
EDC
is
considerably
different
than
paper-­‐based
processes.
In
this
context,
data
collection
is
defined
as
the
design
of
the
eCRFs
and
the
underlying
clinical
database
files
during
the
start-­‐up
portion
of
the
study.
The
EDC
application
design
is
critical
as
it
needs
to
be
completed
in
advance
of
the
first
patient
being
screened
into
a
study;
it
must
conform
and
follow
the
study
protocol.
Since
the
Investigator
site
personnel
enter
data
into
the
eCRFS,
the
eCRFS
must
be
designed
for
the
workflow
of
the
Investigator
site
as
it
conducts
the
protocol
and
records
the
data.
The
EDC
application
should
be
designed
in
such
a
manner
to
facilitate
data
exports
to
meet
the
needs
of
the
staff
performing
the
analysis.
One
benefit
of
a
well-­‐designed
EDC
application
is
improved
protocol
compliance.
The
flow
of
the
EDC
application
from
one
eCRF
screen
to
another
should
follow
the
flow
of
the
study
protocol.
Thus,
site
coordinators
are
guided
through
the
study
not
only
by
the
protocol
itself
but
through
the
screens
of
the
application
as
they
are
completed.
The
eCRFs
should
contain
edit
checks
that
alert
the
Investigator
site
when
they
are
in
conflict
with
the
protocol
such
as
entering
an
ineligible
patient
or
forgetting
to
complete
a
procedure
and
record
the
results.
The
design
of
an
EDC
application
and
eCRFs
should
include
all
functional
groups
involved
in
a
clinical
study.
This
involvement
will
require
procedural
changes
that
are
different
from
paper-­‐based
studies
in
how
the
study
is
planned
and
initiated.
Not
only
does
the
team
need
to
identify
what
data
are
required
for
the
study
via
reviews
of
the
protocol
but
all
edit
checks
must
be
defined
and
programmed
into
the
application
during
the
study
design,
not
after
the
study
has
begun.
Clinical
staff
should
provide
input
on
the
flow
of
the
eCRF
to
match
clinical
procedures
and
whether
input
is
mandatory
or
voluntary.
Field
parameters,
labels
and
ranges
can
also
be
provided
by
the
clinical
staff
to
enhance
protocol
compliance.
Input
from
the
biostatisticians
is
essential
as
critical
data
fields
must
be
identified
and
included
in
the
design
specifications
and
programming.
Because
the
design
of
the
eCRFs
and
the
database
occurs
before
the
study
starts
and
is
a
team
effort,
the
clinical
staff
must
“test
drive”
the
draft
eCRFs
with
an
Investigator
site
to
ensure
that
the
questions
are
worded
appropriately,
the
field
size
and
parameters
are
suitable
for
the
data
entry,
and
the
order
of
the
questions
follows
the
protocol
procedures
for
easier
data
entry.
Because
of
the
abilities
of
EDC
to
prevent
inappropriate
questions
from
being
answered,
the
Clinical
group
also
contributes
to
the
decisions
of
when
questions,
such
as
pregnancy
tests,
should
be
answered.
Integrating
Trial
Data
Process
Across
Functional
Areas
using
Electronic
Data
Capture
(EDC)
Technology

5. 5
of
8
2.2 Recording Data
One
clearly
defined
difference
in
an
EDC
system
from
the
traditional
paper-­‐based
workflow
is
the
need
for
Investigator
site
staff
to
enter
their
own
patient
data
into
the
application.
EDC
systems
must
be
designed
to
facilitate
entry,
easy
to
understand
and
easy
to
navigate,
as
site
staff
do
not
have
the
time
to
learn
or
use
an
intricate
system.
An
advantage
of
most
EDC
systems
is
the
functionality
to
alert
the
site
staff
when
entries
are
entered
erroneously
and
easily
allows
them
to
revise
the
entry
without
generating
a
time-­‐consuming
query.
This
process,
only
available
when
using
EDC,
eliminates
many
of
the
queries
generated
when
paper
CRFS
are
used.
The
EDC
system
speeds
the
generation,
resolution
and
tracking
of
queries
by
providing
the
site
staff
the
ability
to
easily
make
data
corrections
online
instead
of
searching
for
and
manually
updating
paper
eCRFs.
The
process
of
documenting
protocol
compliance
also
becomes
easier
with
EDC,
as
well-­‐designed
eCRFs
prevent
the
entry
of
data
that
would
be
a
protocol
violation.
The
system
alerts
the
site
staff
to
improve
protocol
compliance
and
the
entry
of
protocol
compliant
data.
The
use
of
field
sizes,
edit
parameters
and
data
ranges
embedded
in
the
eCRFs
also
improves
the
recording
of
data
by
the
Investigator
site
staff,
as
these
items
provide
an
immediate
feedback
mechanism
on
the
accuracy
of
the
data
being
recorded.
Site
personnel
can
update
incorrect
or
incomplete
data
instantly
based
on
this
feedback
and
eliminate
queries.
Both
the
immediate
feedback
and
the
reduction
in
queries
change
the
processes
at
the
site
and
increase
site
efficiency.
2.3 Monitoring
The
monitoring
process
of
ensuring
data
quality
and
protocol
compliance
should
be
re-­‐engineered
to
obtain
the
benefits
of
an
EDC
system.
Instead
of
only
viewing
the
data
and
protocol
results
every
4-­‐to-­‐6
weeks
during
an
on-­‐
site
monitoring
visit,
the
Monitor
or
other
staff
member
can
review
the
data
in
real
time
as
it
is
entered
by
the
site.
As
data
is
reviewed
and
monitored
in
real
time,
errors
in
data
entry
by
the
site
can
be
identified
and
retraining
can
be
performed
to
prevent
further
and
often
more
costly
errors.
Also,
errors
in
eCRF
design
can
also
be
detected
and
changed
earlier
in
the
process
to
prevent
erroneous
data
from
being
recorded.
After
in-­‐house
data
review
through
the
EDC
system,
the
Monitor
is
better
prepared
for
the
on-­‐site
monitoring
visit
by
focusing
on
the
unique
problems
of
that
site
based
on
eCRF
review.
The
Monitor
can
verify
source
documentation
and
use
their
time
to
evaluate
the
site’s
study
conduct
and
provide
remedial
actions
for
any
performance
issues.
Site
performance
evaluation
can
also
be
completed
remotely
using
the
metrics
provided
by
the
EDC
system.
Site
metrics
within
and
across
sites
provide
information
such
as
speed
of
data
entry,
speed
of
query
correction,
number
of
protocol
violations,
etc.
that
document
how
well
the
site
is
conducting
the
study.
These
metrics
can
be
used
to
discuss
performance
with
the
site
and
if
necessary,
implement
a
remedial
action
plan
even
before
the
next
scheduled
on-­‐site
monitoring
visit.
Integrating
Trial
Data
Process
Across
Functional
Areas
using
Electronic
Data
Capture
(EDC)
Technology

6. 6
of
8
EDC
system
metrics,
such
as
time
to
eCRF
completion,
average
time
from
visit
to
data
entry
and
number
of
queries,
provide
a
‘window’
into
site
data
issues
in
real
time.
Anomalies
can
then
be
addressed
as
they
occur
instead
of
waiting
4-­‐to-­‐6
weeks
until
the
next
site
visit
to
discover
the
issue,
which
by
now,
has
usually
occurred
multiple
times,
and
then
correct
it.
2.4 Cleaning Data
The
data
query
process
also
needs
to
be
reengineered
when
using
EDC
systems.
Queries
can
be
generated
and
resolved
in
several
ways,
all
of
which
are
much
faster
than
paper-­‐based
systems.
One
major
advantage
is
the
change
in
the
tracking
of
generation
and
resolution
of
queries.
The
EDC
system
keeps
track
of
all
queries
that
are
generated
through
the
system,
so
time
and
resources
are
no
longer
necessary
for
query
tracking.
EDC
system
reports
provide
instant
up-­‐to-­‐date
metrics
on
queries
generated,
resolved,
outstanding
and
the
rate
of
correction
at
each
site.
Query
generation
and
resolution
can
also
be
completed
remotely
by
the
Clinical
group
to
prevent
further
similar
errors
in
data
entry.
The
Monitor
would
then
verify
the
correction
by
source
document
review
when
on
site.
The
Monitor
no
longer
has
to
spend
hours
locating
the
queries,
determining
if
they
have
been
addressed
and
verifying
the
eCRF
corrections.
Once
the
queries
are
resolved,
the
Monitor
just
needs
to
source
document
verify
the
changes.
Through
the
EDC
system,
the
Clinical
staff
also
has
access
to
any
queries
generated
by
Data
Management
and
can
monitor
the
resolution
of
these
queries
as
well.
Data
management
also
leverages
the
query
management
capabilities
of
EDC
systems,
especially
in
the
generation,
issuance,
and
subsequent
resolution
of
manual
queries.
By
adjusting
internal
processes,
Clinical
Data
Management
groups
can
optimize
the
core
functionality
of
EDC
systems
to
fire
automatic
queries
at
entry
in
order
to
reduce
data
entry
errors.
The
primary
focus
of
process
changes
will
affect
manual
queries
issued
by
the
Clinical
Data
Manager.
The
manual
queries
include
those
related
to
cross-­‐form
checks
as
well
as
safety
queries.
The
EDC
system’s
flexibility
provides
additional
benefits
by
creating
process
efficiencies
as
it
is
adapted
to
company’s
current
organizational
structure
and
business
workflows.
Since
all
queries
are
generated,
tracked
and
resolved
in
one
system,
the
data
cleaning
process
becomes
an
integrated
process
between
Clinical
Monitors
and
Data
Managers
which
improves
communication
between
these
groups
and
speeds
the
process.
Current
EDC
applications
also
allow
for
the
assignment
of
permissions
based
upon
company-­‐specific
workflows,
thereby
allowing
roles
and
responsibilities
to
better
align.
This
ability
accelerates
the
process
for
both
departments
as
well
as
the
study
for
faster
database
lock.
Integrating
Trial
Data
Process
Across
Functional
Areas
using
Electronic
Data
Capture
(EDC)
Technology

7. 7
of
8
3 Summary Overview of Process Changes and Benefits – Focus
on Clinical Ops and CDM Interactions
The
use
of
eCRFs
not
only
speeds
the
data
collection
process
but
also
provides
many
benefits
to
all
team
members.
3.1 Investigator Sites Benefits
As
the
concept
of
remote
data
entry
and
subsequent
adoption
of
EDC
applications
became
evident
there
was
push-­‐back
from
Investigator
sites
that
they
would
be
doing
more
work;
however,
there
are
benefits
that
the
sites
gain
through
the
use
of
EDC
applications
that
they
do
not
have
when
using
paper-­‐based
CRF’s.
The
large
reductions
in
the
number
of
queries
and
better
access
to
the
clinical
study
patient
data
are
two
main
benefits
for
the
Investigator
site.
Users
of
EDC
applications
have
documented
reductions
up
to
90%
of
queries,
which
translates
into
huge
time
savings
for
Investigator
site
personnel.
In
addition,
sites
also
have
access
to
patient
data
throughout
the
course
of
the
clinical
study,
which
provides
visibility
to
the
completion
of
clinical
milestones
and
can
lead
to
faster
payments
from
the
sponsoring
studies.
3.2 Clinical and Monitor Group Benefits
Being
able
to
design
the
eCRFs
to
enhance
protocol
compliance
decreases
the
number
and
types
of
protocol
violations
which
results
in
cleaner
data.
The
ability
for
the
clinical
staff
to
participate
in
eCRF
design
and
provide
only
applicable
questions,
set
response
range
limits,
and
prevent
inaccurate
data
saves
time
in
correcting
inaccurate
data.
The
ability
to
review
the
site’s
data
before
the
on-­‐site
monitoring
visit
provides
the
Monitor
insight
into
site
activities
so
they
can
correct
any
issues
in
real
time
instead
of
being
surprised
by
issues
that
are
brought
to
their
attention
when
they
arrive
for
the
next
on-­‐site
visit.
3.3 Data Management Benefits
Another
added
benefit
to
having
the
Investigator
site
enter
data
as
compared
to
having
Clinical
Data
Management
groups
transcribe
and
enter
data
into
Clinical
Data
Management
Systems
(CDMS)
is
that
the
sites
are
much
closer
to
the
data.
The
time
from
entry
to
query
generation
and
resolution
is
compressed
which
results
in
the
availability
of
‘cleaner’
data
faster
so
clinical
decisions
can
be
made
sooner.
Additionally,
safety
data
are
more
readily
available,
thus
increasing
awareness
of
patient
safety
throughout
the
course
of
clinical
studies.
Integrating
Trial
Data
Process
Across
Functional
Areas
using
Electronic
Data
Capture
(EDC)
Technology

8. 8
of
8
3.4 Statistical Benefits
In
addition
to
the
data
management
benefits
mentioned
above,
there
are
benefits
‘downstream’
for
Biostatistics
departments.
These
benefits
include
an
overall
streamlining
of
the
process
as
Biostatistics
are
involved
at
the
front-­‐end
of
the
data
collection
design
so
they
are
well
aware
of
the
data
items
to
be
collected
and
assist
in
the
definition
of
the
back-­‐end
export
data
structure.
This
allows
the
Biostatistical
programmers
to
begin
pre-­‐
programming
and
validation
for
the
study
tables,
listings
and
figures
much
earlier
in
the
process,
which
accelerates
the
study
timeline.
Through
the
active
participation
of
all
the
functional
members
of
the
study
team
earlier
in
the
study
process,
especially
Biostatisticians,
data
structures
and
edit
checks
are
better
understood,
thus
promoting
the
reliability
of
data
quality
amongst
the
team.
4 Conclusion
The
use
of
an
EDC
system
to
collect
and
manage
the
data
during
a
clinical
study
is
a
great
advance
in
the
clinical
trial
industry.
However,
the
processes
of
paper-­‐based
CRFs
must
be
evaluated
and
reengineered
to
obtain
maximum
benefit
from
the
EDC
technology.
Just
applying
an
EDC
technology
on
top
of
a
paper-­‐based
collection
process
is
simply
‘electrifying’
the
paper
process.
In
order
to
optimize
the
process,
a
company
must
review
and
understand
the
current
workflow,
identify
advances
in
technology
and
define
opportunities
where
process
changes
can
benefit
the
overall
organization.
The
introduction
of
EDC
systems
require
a
shift
in
the
roles
and
responsibilities
of
the
Site
Coordinators,
Clinical
Monitors,
Clinical
Data
Managers,
and
Safety
personnel
when
compared
to
the
roles
and
responsibilities
defined
for
personnel
when
using
traditional
paper-­‐based
data
collection
systems.
The
overall
goal
of
integrating
trial
data
processes
across
functional
areas
using
EDC
technology
is
to
streamline
the
company’s
processes;
however,
it
is
imperative
that
companies
also
realize
a
time
savings,
a
heightened
awareness
of
safety
issues
as
they
appear
during
the
course
of
a
clinical
study,
an
increase
in
the
reliability
of
the
clinical
data
collected
and
managed
and
an
overall
decrease
in
the
cost
to
achieve
the
previous
items.
Integrating
Trial
Data
Process
Across
Functional
Areas
using
Electronic
Data
Capture
(EDC)
Technology