Document ID: EPA-HQ-OPP-2003-0132-0004
Agency: epa
Document Type: Supporting & Related Material
Title: 
Posted Date: 2003-04-02T05:00Z

UNITED
STATES
ENVIRONMENTAL
PROTECTION
AGENCY
WASHINGTON
D.
C.,
20460
December
14,
2001
OFFICE
OF
PREVENTION,
PESTICIDES
AND
TOXIC
SUBSTANCES
Dr.
Bruce
Alberts
President
National
Academy
of
Sciences
2101
Constitution
Avenue,
NW
Washington,
D.
C.
20418
Dear
Dr.
Alberts:

I
am
writing
to
request
that
the
National
Academy
of
Sciences
(
NAS)
provide
recommendations
to
the
Agency
to
help
address
the
scientific
and
ethical
questions
related
to
whether
to
accept,
consider,
or
rely
on
research
involving
deliberate
exposure
of
human
subjects
to
toxicants
when
used
to
identify
or
quantify
toxic
endpoints.
The
Agency
asks
that
the
Academy
review
these
issues
and
provide
recommendations
that
will
help
EPA
develop
appropriate
factors
and
criteria
to
apply
when
it
makes
these
difficult
decisions.
The
advice
of
the
Academy
will
be
weighed
heavily
as
we
develop
and
implement
a
policy
to
govern
these
decisions
in
future.

The
Agency's
particular
focus
of
concern
is
on
studies
which,
since
they
are
not
conducted
or
supported
by
a
federal
agency,
may
not
be
performed
subject
to
regulations
that
protect
human
subjects,
such
as
EPA's
Protection
of
Human
Subjects
Rule
("
the
Common
Rule"),
40
CFR
26.
We
are
particularly
concerned
about
`
third­
party'
studies
submitted
by
regulated
entities
for
the
Agency's
consideration.
For
these
purposes,
EPA
is
considering
"
third­
party
studies"
as
studies
that
have
not
been
conducted
or
funded
by
a
federal
agency
pursuant
to
regulations
that
protect
human
subjects.
These
types
of
studies
generally
come
to
the
Agency's
attention
only
after
the
research
has
been
completed
and
reported.
At
this
point
it
is
generally
too
late
for
the
Common
Rule
requirements
to
apply
since
these
requirements
cover
prior
review
and
approval
of
proposed
research,
involving
fully
informed,
voluntary
consent
of
the
participants
to
protect
the
subjects
in
the
research.

One
particular
concern
of
the
Agency
is
for
determining
the
acceptability
of
third­
party
research
designed
to
identify
or
quantify
toxic
endpoints
in
human
subjects,
such
as
those
done
to
define
a
No
Observed
Adverse
Effect
Level
(
NOAEL)
or
No
Observed
Effect
Level
(
NOEL)
for
systemic
toxicity
in
humans.
Studies
of
this
kind
are
submitted
to
the
agency
from
time
to
time,
and
have
been
evaluated
prior
to
regulatory
decision
in
several
Agency
programs.
In
the
recent
past
most
such
submissions
have
been
of
studies
designed
to
define
a
NOAEL
for
pesticide
toxicity
in
humans.
2
EPA
asks
the
Academy
to
undertake
a
critical
review
of
appropriate
standards
for
the
scientific
and
ethical
assessment
of
research
entailing
deliberate
dosing
of
human
subjects
with
toxic
agents.
This
review
should
incorporate
and
be
informed
by
an
early
open,
public,
participatory
process
through
which
interested
people
can
express
their
suggestions
or
concerns
to
the
Academy
reviewers.

The
Agency
subscribes
fully
to
the
principles
of
the
Common
Rule
and
the
related
rules
of
other
federal
agencies,
as
they
protect
the
human
subjects
of
research
conducted
or
supported
by
the
federal
government.
We
are
pleased
with
our
record
of
compliance
with
the
Common
Rule
in
our
own
research,
and
of
the
favorable
review
by
our
human
subjects
protection
program
in
a
recent
survey
by
the
National
Bioethics
Advisory
Commission.

The
Agency
will
consider
the
Academy's
advice
resulting
from
this
review
as
we
develop
a
policy
to
guide
its
future
decisions
to
accept,
consider,
or
rely
on
such
studies
in
regulatory
decision
making.
As
the
Academy
evaluates
the
scientific
rationale
and
the
ethical
framework
for
these
studies,
it
would
be
most
helpful
if
the
Academy
would
include
in
its
general
advice
responses
to
the
following
questions:

$
What
factors
should
the
Agency
consider
in
determining
whether
to
accept,
consider,
or
rely
on
human
studies
performed
by
third
parties?
Are
there
clear
boundaries
between
acceptable
and
unacceptable
human
research?
If
so,
what
are
they?
If
not,
what
range
of
factors
should
the
agency
consider,
and
how
should
these
factors
be
applied
in
making
decisions
to
accept,
consider,
or
rely
on
specific
research?

$
What
range
of
information
should
the
Agency
consider
in
determining
whether
completed
research
with
human
subjects
conducted
by
third
parties
was
conducted
in
compliance
with
the
appropriate
ethical
standards,
such
as
the
Declaration
of
Helsinki,
which
may
be
cited
in
the
research
report?

$
Do
criteria
such
as
those
in
the
Common
Rule
provide
an
adequate
framework
for
assessing
the
scientific
and
ethical
acceptability
of
such
studies?
Should
such
a
standard,
designed
to
protect
human
participants
in
research,
be
applied
after
the
fact
to
completed
research
conducted
by
third
parties
to
determine
whether
it
is
acceptable
as
the
basis
for
regulatory
action?

$
Are
there
other
standards,
such
as
the
Declaration
of
Helsinki
or
various
standards
of
good
clinical
practice,
relevant
to
assessing
acceptability
of
research
to
define
or
quantify
toxic
endpoints
in
human
research
subjects?
Should
standards
intended
to
govern
human
safety
studies
for
diagnostic
or
therapeutic
agents
be
applied
to
research
involving
deliberate
exposures
to
environmental
toxins?

I
look
forward
to
meeting
with
you
soon
to
work
out
the
details
and
timing
of
your
review,
and
to
a
constructive
collaboration
on
this
project.

Sincerely,
3
Stephen
L.
Johnson
Assistant
Administrator
cc:
E.
William
Colglazier
Ann
Marie
Mazza