Document ID: EPA-HQ-ORD-2006-0187-0101
Agency: epa
Document Type: Supporting & Related Material
Title: 
Posted Date: 2006-04-05T04:00Z

1
Summary
of
Summary
of
EPA
Ethics
Review
EPA
Ethics
Review
Moertel,
C.;
Ames,
M.;
Kovach,
J.;
et
al
(
1981)
A
Pharmacologic
and
Toxico­
logical
Study
of
Amygdalin.
JAMA
45(
6):
591­
594.

(
MRID
46769601)

Moertel,
C.;
Fleming,
T.;
Rubin,
J.;
et
al
(
1982)
A
Clinical
Trial
of
Amygdalin
(
Laetrile)
in
the
Treatment
of
Human
Cancer.
The
New
England
Journal
of
Medicine:
306(
4):
201­
206.
(
MRID
46769602)
2
Amygdalin
Clinical
Trial
Amygdalin
Clinical
Trial

Two
articles
report
on
the
same
body
of
research

A
clinical
trial
of
Laetrile
for
advanced
human
cancers

Conducted
at
four
centers
in
U.
S.
in
1980­
1981

Funded
by
NIH/
NCI

Conducted
under
FDA
IND
application
3
Amygdalin
Amygdalin
"
Framework
Framework"

1.
Value

Undertaken
to
resolve
widespread
public
and
scientific
debate
about
the
effectiveness
of
amygdalin

Results
were
published,
to
the
benefit
of
society
4
Amygdalin
Amygdalin
"
Framework
Framework"
­­

­­
2
2.
Scientific
Validity:
Defer
to
others
3.
Subject
Selection

178
Adult
male
and
female
volunteers
with
advanced
cancer
beyond
reach
by
any
conventional
therapy

standards
for
inclusion
or
exclusion
were
based
on
the
scientific
goals
of
the
study
5
Amygdalin
Amygdalin
"
Framework
Framework"
­­

­­
3
4.
Risk­
Benefit
Ratio

Societal
benefit
of
knowledge
expected
clearly
explained
5.
Independent
Ethics
Review

approved
by
the
FDA
under
an
Investigational
New
Drug
(
IND)
application

overseen
by
the
Human
Subjects
Committee
at
each
of
the
four
participating
centers
6
Amygdalin
Amygdalin
"
Framework
Framework"
­­

­­
4
6.
Informed
Consent

All
patients
were
fully
informed
about
the
experimental
and
unorthodox
nature
of
the
treatment
program
as
well
as
any
possible
alternative
treatment
available
to
them

All
patients
signed
an
informed
consent
7.
Respect
for
Subjects

Subjects'
privacy
was
not
compromised

Subjects
were
free
to
withdraw
7
Amydalin
Amydalin
Prevailing
Standards
Prevailing
Standards

Conducted
in
the
U.
S.
in
1980­
81

Funded
by
U.
S.
DHEW/
NIH,
so
subject
to
45
CFR
46

Conducted
under
FDA
IND
application,

so
subject
to
21
CFR
parts
50
and
56
8
Comparison
to
45
CFR
46
Comparison
to
45
CFR
46

Ethical
conditions
reported
much
more
completely
than
is
typical
of
published
articles
from
this
period

No
noteworthy
deficiencies
relative
to
DHEW
or
FDA
regulations
were
found
9
Amygdalin
Summary
Amygdalin
Summary

There
is
no
evidence
that
the
research
was
fundamentally
unethical.

There
is
no
evidence
of
significant
deficiency
relative
to
prevailing
ethical
standards.
10
Hydrogen
Cyanide/

Hydrogen
Cyanide/
Amygdalin
Amygdalin
Charge
to
the
HSRB
Charge
to
the
HSRB
When
sodium
cyanide
is
used
as
a
fumigant,

hydrogen
cyanide
is
generated
by
acidification.

Because
residues
of
HCN
may
remain
on
fumigated
citrus,
the
Agency
is
conducting
an
acute
dietary
risk
assessment
of
hydrogen
cyanide.
11
Hydrogen
Cyanide/

Hydrogen
Cyanide/
Amygdalin
Amygdalin
Charge
to
the
HSRB
Charge
to
the
HSRB
1.
Scientific
considerations:

The
Agency's
WOE
document
describes
a
lack
of
data
appropriate
for
developing
an
acute
dietary
risk
assessment
for
hydrogen
cyanide.
The
WOE
and
DER
present
the
results
from
a
clinical
trial
with
amygdalin
and
the
usefulness
of
this
clinical
trial
in
the
acute
dietary
risk
assessment
for
hydrogen
cyanide.
The
Agency
has
concluded
that
the
clinical
trial
is
appropriate
for
establishing
a
point
of
departure
in
the
acute
dietary
risk
assessment
for
hydrogen
cyanide.

Please
comment
on
the
scientific
evidence
that
supports
this
conclusion.
12
2.
Ethical
considerations:

In
its
ethics
review
of
this
research,
EPA
did
not
identify
any
deficiencies
with
respect
to
the
ethical
conduct
of
this
research.
The
Agency
asks
that
the
Board
provide
comment
on
the
following,
taking
into
account
all
that
is
known
about
the
ethical
conduct
of
this
study:


OPP's
conclusion
that
there
is
not
clear
and
convincing
evidence
that
the
conduct
of
the
research
was
fundamentally
unethical;
and

whether
there
is
clear
and
convincing
evidence
that
the
conduct
of
the
study
was
significantly
deficient
relative
to
the
ethical
standards
prevailing
when
the
study
was
conducted.

Hydrogen
Cyanide/

Hydrogen
Cyanide/
Amygdalin
Amygdalin
Charge
to
the
HSRB
Charge
to
the
HSRB