EPA'S
REVIEW
OF
DDVP:

ETHICAL
CONSIDERATIONS
Robert
J.
Levine,
MD
Professor
of
Medicine;
Lecturer
in
Pharmacology.

Co­
Director:
Yale
University's
Interdisciplinary
Bioethics
Center
EPA
HSRB,
Rosslyn,
VA,
04/
05/
06
OUTLINE
OF
PRESENTATION
°
Ethics
of
research
involving
children
as
subjects.

 
Consideration
of
data
derived
from
the
inclusion
of
children
and
pregnant
women
in
observational
studies.

°
Ethical
requirement
to
use
all
historical
data.
CHILDREN
AS
RESEARCH
SUBJECTS
°
Research
involving
children
and
pregnant
women
should
be
allowed.
(
National
Commission
for
the
Protection
of
Human
Subjects:
encouraged.)

°
Pesticides
will
inevitably
be
used
in
homes
and
in
other
settings
in
which
there
will
be
children
and
pregnant
women.

°
Forbidding
research
in
these
populations
virtually
guarantees
the
future
occurrence
of
Thalidomidelike
disasters.
CHILDREN
AS
RESEARCH
SUBJECTS2
°
Historical
`
therapeutic
orphan'
phenomenon.

 
A
class
injustice.

°
Led
to
development
of
45
CFR
46
SubParts
D
(
children)
and
B
(
pregnant
women).

 
These
regulations
inform
the
regulatory
activities
of
all
federal
agencies
other
than
EPA.

°
The
studies
in
question
today
are
mostly
observational
(
opportunistic).

 
Would
be
permitted
by
SubParts
B
and
D.

 
Nonbeneficial
procedures
presenting
minimal
risk.
HISTORICAL
DATA:

ETHICAL
CONSIDERATIONS
°
Use
of
historical
data
puts
no
new
subjects
at
risk.

°
NAS
recommended
use
of
such
data.

°
It
also
recommended
procedures
to
follow
in
the
case
of
research
that
did
not
satisfy:

 
Contemporary
ethical
standards.

 
Ethical
standards
in
place
at
the
time
the
research
was
done.
HISTORICAL
DATA:

ETHICAL
CONSIDERATIONS2
°
If
EPA
must
disqualify
data
from
children
and
pregnant
women
it
should
not
disqualify
data
from
non­
pregnant
adults
involved
in
the
same
studies.

°
Disqualification
of
any
historical
data
creates
ethical
problems.

°
Transparency
would
in
some
cases
require
public
statements
that
the
Agency
reached
a
regulatory
decision
that
was
incompatible
with
available
data.
HISTORICAL
DATA:

ETHICAL
CONSIDERATIONS3
°
In
case
the
data
from
disqualified
research
was
of
vital
importance
to
the
regulatory
decision,
it
would
be
unethical
to
repeat
the
research
under
otherwise
ethically
acceptable
conditions.

°
Such
repetition
would
violate
the
ethical
standard
that
risks
must
be
justified
by
anticipated
benefits
(
new
knowledge).

 
There
would
be
no
new
knowledge.
HISTORICAL
DATA:

ETHICAL
CONSIDERATIONS4
°
Meta­
analysis
(
weight­
of­
evidence)
is
an
acceptable
method
of
developing
a
probative
data
set
from
multiple
studies
when
each
of
the
studies
is
 
for
one
reason
or
another
 
unsuitable
for
the
intended
purpose.

°
Disregarding
evidence
obtained
from
metaanalysis
has
the
same
ethical
implications
as
disregarding
other
data
sets.
DEALING
WITH
ETHICAL
TRANSGRESSIONS
°
Public
exposure
of
errant
sponsors
and
investigators.

°
This
is
usually
sufficient
for
academics.

 
NIH
might
also
bar
their
service
on
committees
or
their
eligibility
for
grants.

°
FDA
may
also
impose
criminal
sanctions:
fines
and/
or
imprisonment.

 
Fines
are
responsive
to
EPA's
concern
about
financial
rewards
for
unethical
research.
