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6
HUMAN
RESEARCH
POLICY
NATIONAL
HEALTH
AND
ENVIRONMENTAL
EFFECTS
RESEARCH
LABORATORY
(
9­
27­
04)

1.
PURPOSE
This
document
presents
the
EPA
National
Health
and
Environmental
Effects
Research
Laboratory
(
NHEERL)
policy
on
the
general
requirements
and
responsibilities
for
initial
approval,
conduct,
and
oversight
of
human
research
activities
conducted,
or
supported,
by
NHEERL.
This
policy
covers
research
activities
that
involve
the
collection
or
study
of
data
or
samples
that
are
of
human
origin
or
are
otherwise
linked
to
human
data.
This
includes
both
the
collection
of
information
or
measurements
from,
or
about,
humans
and
the
analysis
of
existing
data
sets,
tissues,
or
other
specimens
of
human
origin.
Additional
guidance
for
specific
situations
and
study
types
is
available
in
an
accompanying
NHEERL
Human
Research
Guidance
document.
The
Guidance
document
provides
guidelines
for
approval
and
conduct
of
HSR
in
general,
as
well
as
for
controlled
human
exposure
studies,
epidemiology
studies,
human
tissue
studies,
and
studies
using
NHEERL
employees
as
subjects.

2.
APPLICABILITY
This
policy
applies
to
all
research
activities:
a.
Conducted
by
or
supported
by
NHEERL
or
in
which
NHEERL
employees
collaborate
with
other
institutions,
and
b.
Meeting
the
definition
of
research
involving
human
subjects
as
defined
by
the
Common
Rule
(
40
CFR
26.102)
and
given
below.

3.
DEFINITIONS
All
definitions
listed
in
EPA
Order
1000.17,
Change
A1
and
in
the
Common
Rule
(
40
CFR
26.102)
[
both
documents
found
at
http://
intranet.
epa.
gov/
rmpolicy/
ads/
orders/
1000_
17a.
pdf]
apply
to
this
policy.
Four
key
definitions
derived
or
summarized
from
these
documents
are
listed
below.

a.
Human
subject
[
40
CFR
26.102(
f)]
and
[
EPA
Order
1000.17,
Change
A1,
3(
d)]
means
a
living
individual
about
whom
an
investigator
conducting
research
obtains
(
1)
Data
through
intervention
or
interaction
with
the
individual,
or
(
2)
Identifiable
private
information.

b.
Research
[
40
CFR
26.102(
d)]
and
[
EPA
Order
1000.17,
Change
A1,
3(
a)]
means
a
systematic
investigation,
including
research
development,
testing,
and
evaluation,
designed
to
develop
or
contribute
to
generalizable
knowledge.
Activities
which
meet
this
definition
constitute
research
for
purposes
of
this
policy,
whether
or
not
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2
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they
are
conducted
or
supported
under
a
program
which
is
considered
research
for
other
purposes.

c.
Human
subjects
research
(
HSR)
or
Research
involving
human
subjects.
Research
activity
that
meets
the
definitions
of
both
research
and
human
subject
given
above
and
in
40
CFR
26.102
and
EPA
Order
1000.17,
Change
A1.

d.
Exempt
research
[
EPA
Order
1000.17,
Change
A1,
3(
b)].
Human
subjects
research
falling
into
one
of
several
categories
described
in
40
CFR
26.101
(
b),
which
is
exempt
from
the
Common
Rule.

4.
POLICY
a.
All
research
activities
meeting
the
definition
of
human
subjects
research
(
HSR)
conducted
or
supported
by
NHEERL
shall
comply
with
EPA
Order
1000.17,
Change
A1,
with
the
Common
Rule
(
40
CFR
26),
and
with
this
policy.
In
addition,
research
involving
pregnant
women,
fetuses,
and
neonates;
prisoners;
and
children
shall
comply
with
Subparts
B,
C,
and
D,
respectively,
of
the
Common
Rule,
as
codified
by
the
Department
of
Health
and
Human
Services
in
45
CFR
46
[
http://
www.
hhs.
gov/
ohrp/
humansubjects/
guidance/
45cfr46.
htm].

b.
All
research
activities
that
collect
or
use
data
or
materials
of
human
origin
must
be
classified
as
either
meeting,
or
not
meeting,
the
definition
of
HSR
by
the
Director
of
the
NHEERL
Human
Research
Protocol
Office
(
HRPO)
prior
to
the
initiation
of
any
research.

c.
All
HSR
must
be
approved
by
the
NHEERL
Associate
Director
for
Health
or
Ecology
prior
to
submission
to
the
Agency
Human
Subjects
Research
Review
Official
(
HSRRO).

d.
All
HSR
must
be
either
approved
or
determined
to
be
Exempt
Research
by
the
Agency
HSRRO
before
any
research
is
conducted
by
or
supported
by
NHEERL.

e.
The
NHEERL
HRPO
is
the
official
NHEERL
repository
for
protocol
packages
(
see
Section
5)
involving
human
research
activities.
Complete
copies
of
the
original
protocol
package,
amendments,
Institutional
Review
Board
(
IRB)
approval
letters,
consent
forms,
renewal
application
packages,
adverse
event
reports,
and
all
correspondence
to
and
from
the
IRB
must
be
provided
by
the
Principal
Investigator
to
the
HRPO
prior
to
the
conduct
of
(
additional)
research.

f.
Each
NHEERL
Division
conducting
HSR
shall
appoint
a
Division
Human
Research
Officer
(
DHRO)
who
serves
as
the
key
Division
resource
for
day­
to­
day
compliance
with
existing
Federal
regulations
and
with
this
NHEERL
human
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3
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research
policy.

g.
Any
violation
or
deviation
of
the
conduct
of
research
from
an
approved
HSR
protocol
or
any
occurrence
of
an
adverse
event,
including
subject
injury
or
unexpected
response,
must
be
immediately
reported
by
the
Principal
Investigator
to
the
IRB,
to
the
Director
of
the
NHEERL
HRPO,
and
to
NHEERL
management,
which
will
report
the
information
up
the
NHEERL
chain
of
command,
and,
if
indicated,
to
the
Agency
HSRRO.

h.
Each
NHEERL
employee
engaged
in
the
conduct
of
HSR,
or
in
the
HSR
approval
chain,
shall
complete,
each
calendar
year,
at
least
one
hour
of
relevant
training
that
must
be
approved
by
the
Director
of
the
NHEERL
HRPO.
Documentation
of
all
such
training
shall
be
provided
to
the
Director
of
the
NHEERL
HRPO.
Each
employee
engaged
in
a
human
subjects
research
protocol
must
also
meet
any
training
requirements
of
the
IRB
overseeing
the
specific
protocol.

5.
GENERAL
REQUIREMENTS
To
obtain
approval
for
an
HSR
study
from
the
appropriate
NHEERL
Associate
Director
(
AD),
a
human
subjects
research
protocol
package
must
be
prepared
that
includes
the
elements
shown
below.
Further
guidance
on
the
preparation
of
this
package
and
the
required
reviews
is
found
in
the
accompanying
NHEERL
Human
Research
Guidance
document.

a.
NHEERL
documents
(
1)
Cover
letter
(
2)
Sign­
off
sheet
(
3)
Fact
Sheet
(
4)
Study
Justification
Document
b.
IRB
package
(
1)
IRB
approval
letter
(
2)
Written
research
protocol
(
3)
Consent
forms
approved
and
stamped
by
the
IRB
(
4)
Questionnaires
and
advertising
approved
and
stamped
by
the
IRB
(
5)
HSR
training
certificates
c.
Reviews
(
1)
Any
required
extramural
scientific
reviews
with
written
responses
(
2)
Any
required
medical,
statistical,
or
other
reviews
with
written
responses
6.
RESPONSIBILITIES
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The
following
NHEERL
organizational
and
individual
responsibilities
apply
to
the
development,
management,
and
conduct
of
any
research
study
involving
human
subjects.

a.
Principal
Investigator
(
PI)
The
PI
is
responsible
for
all
aspects
of
the
study
and
must
be
exceedingly
knowledgeable
about
HSR
regulations,
the
science
supporting
the
proposed
study,
and
any
potential
risks
to
subjects.
The
PI
has
specific
responsibilities
to
the
EPA,
to
the
IRB,
and
to
the
subjects
participating
in
the
research.
The
PI
must:
(
1)
Understand
and
comply
with
EPA
and
NHEERL
human
research
policy.
(
2)
Understand
and
comply
with
the
requirements
of
all
IRBs
with
jurisdiction
over
a
particular
study.
(
3)
Prepare
a
protocol
package
that
clearly
and
accurately
presents
the
scientific
rationale
for
the
study,
the
potential
risks
to
the
subjects,
and
the
expected
benefits
of
the
study
so
that
scientific
and
ethical
reviewers
have
all
the
necessary
information
to
make
objective
judgements
about
the
protocol.
(
4)
Ensure
that
the
initial
review
and
approval
of
the
study
by
EPA
is
completed.
(
5)
Minimize
risk
and
ensure
the
safety
and
well­
being
of
the
subjects.
(
6)
Conduct
the
study
in
an
ethical
manner.
(
7)
Maintain
accurate
records,
including
documentation
of
informed
consent
and
current
IRB
approval,
and
send
copies
of
all
correspondence
with
the
IRB
of
record,
including
all
protocol
amendments
and
renewals,
to
the
NHEERL
HRPO.
(
8)
Report
any
adverse
effects
or
noncompliance
with
the
protocol
to
the
NHEERL
HRPO
Director,
NHEERL
line
management,
and
to
the
IRB.
(
9)
Oversee
study
staff.

b.
Branch
Chief
(
BC)
The
PI's
Branch
Chief
is
responsible
for
ensuring
that
the
composition
of
the
research
team
is
appropriate;
that
all
requirements
for
initial
reviews,
meetings,
and
written
responses
have
been
met;
and
that
the
written
protocol
is
scientifically
and
ethically
sound.
In
particular
the
BC
must:
(
1)
Ensure
that
the
PI
or
a
Co­
PI
has
significant
previous
HSR
experience.
(
2)
Ensure
that
the
research
team
has
appropriate
scientific
and
medical
expertise
to
safely
and
ethically
realize
the
goals
of
the
study.
(
3)
Ensure
that
required
meetings
among
the
PI
and
all
relevant
parties
(
e.
g.
medical
staff,
recruitment
staff,
etc.)
occur
prior
to
protocol
preparation
and
again
prior
to
study
commencement.
(
4)
Ensure
that
all
required
written
reviews
(
e.
g.
medical
review,
statistical
review,
extramural
peer
review,
etc.)
have
been
completed
and
that
the
PI
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has
adequately
addressed
the
reviewers
comments
in
writing.
(
5)
Review
the
protocol
and
consent
form
to
ensure
that
the
proposed
study
is
scientifically
sound
and
clearly
presented,
and
that
he/
she
is
satisfied
that
the
risks
to
subjects
have
been
accurately
presented
in
both
the
protocol
and
the
consent
form.

c.
Division
Human
Research
Officer
(
DHRO)
The
DHRO
will
review
the
proposed
protocol
and
consent
form
and
must:
(
1)
Ensure
that
they
are
consistent
with
the
requirements
of
both
the
EPA
and
the
IRB
and
that
EPA­
required
language
has
been
included
in
the
consent
form.
(
2)
Ensure
that
the
protocol
identifies
the
risks
to
subjects
and
the
measures
to
reduce
this
risk.
(
3)
Ensure
that
ethical
issues
which
should
be
clarified
or
addressed
prior
to
submission
to
the
IRB
are
identified.

d.
Division
Director
(
DD)
The
DD
will
ensure
that
all
lower­
level
reviews
have
been
completed
and
that
the
BC,
DHRO,
and
other
Division
reviewers
are
aware
of,
and
are
fulfilling,
their
HSR
review
responsibilities.

e.
Director,
NHEERL
Human
Research
Protocol
Office
(
HRPO)
The
Director
of
NHEERL
HRPO
is
responsible
for
initial
review
of
the
protocol
package
and
maintenance
of
NHEERL
records
for
HSR.
The
Director
will
(
1)
Ensure
that
the
protocol
package
contains
all
necessary
elements
for
approval
by
the
appropriate
Associate
Laboratory
Director
and
the
Agency
HSRRO.
(
2)
Ensure
that
all
required
reviews
have
been
completed
and
adequately
addressed
by
the
PI.
(
3)
Ensure
that
the
protocol
identifies
the
risks
to
subjects,
the
measures
taken
to
reduce
this
risk,
and
any
ethical
issues
that
must
be
further
addressed
by
the
PI.
(
4)
Ensure
that
the
consent
form
contains
any
specific
language
required
by
NHEERL.
(
5)
Maintain
all
HSR
records,
including
the
original
protocol
package
and
approval
letters,
subsequent
amendments
and
renewals
with
IRB
approval
letters,
and
any
other
correspondence
with
the
IRB.

f.
NHEERL
Associate
Director
(
AD)
for
Health
or
Ecology
The
appropriate
NHEERL
AD
provides
the
final
NHEERL
review
prior
to
Agency
review.
Specific
responsibilities
include:
(
1)
Review
of
the
protocol
package
to
ensure
clarity
of
information.
(
2)
Review
of
the
package
for
any
scientific,
policy,
or
ethics
issues
that
need
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6
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6
to
be
further
clarified.
(
3)
Transmission
of
the
approved
protocol
package
to
the
Agency
HSRRO.

g.
All
NHEERL
employees
All
NHEERL
employees
are
responsible
for
reporting
the
following
to
the
NHEERL
HRPO
and
the
appropriate
DD:
(
1)
Any
serious
or
unanticipated
harm
experienced
by
research
subjects.
(
2)
Any
deviations
of
HSR
from
the
approved
protocol.
(
3)
Any
unethical
or
unsafe
behavior
by
anyone
associated
with
HSR
conducted
in
or
supported
by
NHEERL.
