Document ID: EPA-HQ-ORD-2006-0384-0061
Agency: epa
Document Type: Supporting & Related Material
Title: 
Posted Date: 2006-07-12T04:00Z

1
Ethics
Review
of
Ethics
Review
of
AHETF
Template
Protocol
AHETF
Template
Protocol
and
Study
Protocols
and
Study
Protocols
John
M.
Carley
2
Summary
Summary

The
AHETF
template
protocol
is
a
true
template
into
which
values
are
substituted
to
develop
an
executable
protocol

Specific
protocols
follow
the
template
very
closely

Primary
focus
of
this
ethics
review
is
on
the
template
protocol

Most
comments
apply
to
all
AHETF
protocols

A
few
comments
are
specific
to
the
individual
study
protocols
3
AHETF
Framework
AHETF
Framework
­
1
1.
Value

AHETF
studies
will
enhance
the
completeness
and
accuracy
of
the
database
EPA
uses
to
assess
handler
exposure
in
agriculture

Reliable
data
about
dermal
and
inhalation
exposure
of
workers
who
handle
agricultural
pesticides
can
improve
the
quality
of
EPA
risk
assessments
and
support
appropriately
protective
regulation

Use
of
standardized
scenarios,
methods,
and
surrogate
chemicals
permits
broad
extrapolation
of
results
2.
Scientific
Validity:
Defer
to
others
4
AHETF
Framework
AHETF
Framework
­
2
3.
Subject
Selection

Subjects
are
workers
with
specific
experience
in
the
tasks
to
be
performed

Pregnant
women
and
children
are
excluded

Subjects
are
recruited
through
their
employers 
growers
or
providers
of
pesticide
application
services

IRB
required
 
extra
care
in
the
consent
process
to
avoid
any
coercion
or
undue
influence
to
participate
in
the
research 


The
protocols
do
not
specify
how
this
extra
care
will
be
ensured
5
AHETF
Framework
AHETF
Framework
­
3
4.
Risk­
Benefit
Ratio

Exposures
measured
for
workers
doing
their
usual
job
the
usual
way

Negligible
increase
in
risk
to
subjects 
if
any 
for
pesticide
exposure

Some
increase
in
risk
of
heat­
induced
illness

Discussion
of
expected
benefits
of
each
study
and
to
whom
they
would
accrue
is
limited
but
acceptable

No
discussion
of
how
expected
benefits
weigh
against
the
potential
risks
to
subjects

Subjects
are
paid
$
100/
day
6
AHETF
Framework
AHETF
Framework
­
4
5.
Independent
Ethics
Review

Individual
protocols
reviewed
and
approved
by
Western
Institutional
Review
Board,
Inc.,
of
Olympia
WA

WIRB
is
registered
with
OHRP
and
is
independent
of
the
investigators

Approvals
conditioned
on
"
extra
care"
in
recruitment
and
consent
process
to
minimize
coercion
or
undue
influence
7
AHETF
Framework
AHETF
Framework
­
5
6.
Informed
Consent

Protocol
promises
to
obtain
informed
consent
of
all
subjects

Protocol
is
silent
about
the
circumstances
and
procedures
for
informing
potential
subjects
and
seeking
their
consent,
and
the
 
extra
care 
called
for
by
WIRB

Informed
Consent
document
is
included
for
each
specific
protocol,

in
English
only

Investigator
requested
Spanish
translation
from
WIRB
for
AHE­
38
7.
Respect
for
Subjects

Subject
privacy
would
not
be
compromised

Subjects
would
be
free
to
withdraw
8
Applicable
Standards
Applicable
Standards

These
are
3rd­
party
studies
intended
for
submission
to
EPA
under
the
pesticide
laws.

They
may
involve
intentional
exposure.

The
applicable
standards
are:


40
CFR
26,
Subparts
K
and
L

FIFRA
§
12(
a)(
2)(
P)


In
some
cases,
California
Code
of
Regulations
Title
3,

Section
6710
9
Deficiencies
Noted
Deficiencies
Noted
­
1
 
All
protocols
should
acknowledge
the
applicable
ethical
standards,
and
the
investigators'
obligation
to
report
any
amendments
to
or
deviations
from
the
approved
protocol
to
the
cognizant
IRB
and,
if
the
research
is
conducted
in
California,
to
the
California
Department
of
Pesticide
Regulation
10
Deficiencies
Noted
Deficiencies
Noted
­
2
 
The
meaning
of
the
reference
in
section
5.3
of
the
protocol
to
exclusion
of
subjects
with
a
conflict
of
interest
is
unclear,
and
no
mention
of
conflict
of
interest
is
made
in
the
Informed
Consent
(
IC)
materials.

 
Section
5.3
of
the
protocol
promises
a
description
of
the
"
worker
selection
process"

for
IRB
review.
It
does
not
appear
to
be
present.
11
Deficiencies
Noted
Deficiencies
Noted
­
3
 
The
Informed
Consent
materials
should
include
a
statement
about
the
pesticide
use
pattern
involved
in
the
study,
as
is
provided
in
section
5.6.
b
of
the
protocol.

 
The
MSDS
and
label
should
be
made
available
to
the
subjects
as
well
as
to
the
investigators,

as
promised
in
section
5.6.
c
of
the
protocol.
12
Deficiencies
Noted
Deficiencies
Noted
­
4

The
provision
in
section
5.9
for
altering
dilution
or
application
rates
to
extend
the
time
of
exposure
may
make
the
exposure
scenario
atypical
or
inconsistent
with
the
label,
and
could
undermine
the
justification
for
the
research.
Investigators
should
ensure
that
plots
selected
for
treatment
in
the
research
are
large
enough
to
meet
the
design
requirement
for
at
least
4
hours
exposure.
13
Deficiencies
Noted
Deficiencies
Noted
­
5

Sections
8.1
and
12
of
the
protocol
should
acknowledge
the
requirement
to
fully
document
the
ethical
conduct
of
the
research
consistent
with
40
CFR
26.1303,
including:


the
recruiting
process
(
and
the
"
extra
care"
required
by
the
IRB)


informing
potential
subjects

obtaining
subject
consent

reporting
deviations
or
amendments

reporting
any
adverse
events
14
Deficiencies
Noted
Deficiencies
Noted
­
6

The
generic
statement
of
purpose
in
the
template
is
inadequately
informative
for
the
Informed
Consent
materials
in
specific
studies,
which
should
specify:

the
formulation
and
the
active
ingredient(
s)
of
the
pesticide

the
site
to
which
it
will
be
applied

the
equipment
that
will
be
used

Subjects
should
be
told
they
are
being
asked
to
participate
because
they
are
experienced
at
performing
those
activities
as
part
of
their
job
15
Deficiencies
Noted
Deficiencies
Noted
­
7
 
A
bullet
for
state
government
agencies
should
be
added
under
the
heading
of
"
Confidentiality"
to
the
list
of
organizations
which
may
see
personal
information,
particularly
when
research
is
conducted
in
California.

The
relationship
between
"
Payment
for
Participation"

and
"
Voluntary
Participation/
Withdrawal"
is
not
clear
in
the
Informed
Consent
material.
Would
a
subject
withdrawing
early
from
the
research
be
entitled
to
full
payment?
16
Deficiencies
Noted
Deficiencies
Noted
­
8

The
discussion
of
"
Compensation
for
Injury"
in
the
Informed
Consent
material
promises
to
pay
for
treatment
of
injuries
resulting
from
being
in
the
study,
but
excludes
injuries
"
resulting
from
your
normal
activities."
Since
the
studies
are
designed
to
measure
exposure
of
workers
while
they
perform
their
normal
activities,
this
exclusion
is
unacceptable
exculpatory
language.

It
would
be
appropriate
to
translate
the
generic
Informed
Consent
materials
into
Spanish,
and
perhaps
into
other
languages
as
well.
17
Specific
Comments
Specific
Comments

AHE­
34:
Closed
System
Mixing
and
Loading
of
Liquid
Malathion
in
California

"
Investigator's
Confirmation
of
Board
Requirements"

form
provided
by
the
WIRB
is
not
signed

AHE­
36:
Airblast
Application
of
Malathion
to
Grapes
in
California

On
p.
7
the
protocol
says
there
will
be
13
"
replicates";
on
page
14
the
protocol
says
there
will
be
9
"
workers
(
or
replicates)"
18
Specific
Comments
Specific
Comments

AHE­
37:
Airblast
Application
of
Diazinon
to
Grapes
in
New
York

On
p.
7
the
protocol
says
there
will
be
13
 
replicates ;
on
page
14
the
protocol
says
there
will
be
9
 
workers
(
or
replicates) 

AHE­
38:
Closed
Cab
Airblast
Application
of
Carbaryl
to
Orchards
in
Georgia

Item
36
in
the
application
to
the
WIRB
requests
a
Spanish
translation
of
the
IC
materials.
No
translation
was
included
in
the
submitted
package.


 
Investigator s
Confirmation
of
Board
Requirements 
form
provided
by
the
WIRB
is
not
signed
19
Charge
Questions
Charge
Questions

Is
this
proposed
research
likely
to
generate
scientifically
reliable
data,
useful
for
assessing
the
exposure
received
by
agricultural
pesticide
handlers?

Does
this
proposed
research
appear
to
comport
with
the
applicable
requirements
of
40
CFR
part
26,
subparts
K
and
L?