Document ID: EPA-HQ-OPP-2003-0132-0238
Agency: epa
Document Type: Supporting & Related Material
Title: 
Posted Date: 2005-09-02T04:00Z

The
Belmont
Report
Office
of
the
Secretary
Ethical
Principles
and
Guidelines
for
the
Protection
of
Human
Subjects
of
Research
The
National
Commission
for
the
Protection
of
Human
Subjects
of
Biomedical
and
Behavioral
Research
April
18,
1979
AGENCY:
Department
of
Health,
Education,
and
Welfare.

ACTION:
Notice
of
Report
for
Public
Comment.

SUMMARY:
On
July
12,
1974,
the
National
Research
Act
(
Pub.
L.
93­
348)
was
signed
into
law,
there­
by
creating
the
National
Commission
for
the
Protection
of
Human
Subjects
of
Biomedical
and
Behavioral
Research.
One
of
the
charges
to
the
Commission
was
to
identify
the
basic
ethical
principles
that
should
underlie
the
conduct
of
biomedical
and
behavioral
research
involving
human
subjects
and
to
develop
guidelines
which
should
be
followed
to
assure
that
such
research
is
conducted
in
accordance
with
those
principles.
In
carrying
out
the
above,
the
Commission
was
directed
to
consider:
(
i)
the
boundaries
between
biomedical
and
behavioral
research
and
the
accepted
and
routine
practice
of
medicine,
(
ii)
the
role
of
assessment
of
riskbenefit
criteria
in
the
determination
of
the
appropriateness
of
research
involving
human
subjects,
(
iii)
appropriate
guidelines
for
the
selection
of
human
subjects
for
participation
in
such
research
and
(
iv)
the
nature
and
definition
of
informed
consent
in
various
research
settings.

The
Belmont
Report
attempts
to
summarize
the
basic
ethical
principles
identified
by
the
Commission
in
the
course
of
its
deliberations.
It
is
the
outgrowth
of
an
intensive
four­
day
period
of
discussions
that
were
held
in
February
1976
at
the
Smithsonian
Institution's
Belmont
Conference
Center
supplemented
by
the
monthly
deliberations
of
the
Commission
that
were
held
over
a
period
of
nearly
four
years.
It
is
a
statement
of
basic
ethical
principles
and
guidelines
that
should
assist
in
resolving
the
ethical
problems
that
surround
the
conduct
of
research
with
human
subjects.
By
publishing
the
Report
in
the
Federal
Register,
and
providing
reprints
upon
request,
the
Secretary
intends
that
it
may
be
made
readily
available
to
scientists,
members
of
Institutional
Review
Boards,
and
Federal
employees.
The
two­
volume
Appendix,
containing
the
lengthy
reports
of
experts
and
specialists
who
assisted
the
Commission
in
fulfilling
this
part
of
its
charge,
is
available
as
DHEW
Publication
No.
(
OS)
78­
0013
and
No.
(
OS)
78­
0014,
for
sale
by
the
Superintendent
of
Documents,
U.
S.
Government
Printing
Office,
Washington,
D.
C.
20402.

Unlike
most
other
reports
of
the
Commission,
the
Belmont
Report
does
not
make
specific
recommendations
for
administrative
action
by
the
Secretary
of
Health,
Education,
and
Welfare.
Rather,
the
Commission
recommended
that
the
Belmont
Report
be
adopted
in
its
entirety,
as
a
statement
of
the
Department's
policy.
The
Department
requests
public
comment
on
this
recommendation.
National
Commission
for
the
Protection
of
Human
Subjects
of
Biomedical
and
Behavioral
Research
Members
of
the
Commission
Kenneth
John
Ryan,
M.
D.,
Chairman,
Chief
of
Staff,
Boston
Hospital
for
Women.

Joseph
V.
Brady,
Ph.
D.,
Professor
of
Behavioral
Biology,
Johns
Hopkins
University.

Robert
E.
Cooke,
M.
D.,
President,
Medical
College
of
Pennsylvania.

Dorothy
I.
Height,
President,
National
Council
of
Negro
Women,
Inc.

Albert
R.
Jonsen,
Ph.
D.,
Associate
Professor
of
Bioethics,
University
of
California
at
San
Francisco.

Patricia
King,
J.
D.,
Associate
Professor
of
Law,
Georgetown
University
Law
Center.

Karen
Lebacqz,
Ph.
D.,
Associate
Professor
of
Christian
Ethics,
Pacific
School
of
Religion.

***
David
W.
Louisell,
J.
D.,
Professor
of
Law,
University
of
California
at
Berkeley.

Donald
W.
Seldin,
M.
D.,
Professor
and
Chairman,
Department
of
Internal
Medicine,
University
of
Texas
at
Dallas.

***
Eliot
Stellar,
Ph.
D.,
Provost
of
the
University
and
Professor
of
Physiological
Psychology,
University
of
Pennsylvania.

***
Robert
H.
Turtle,
LL.
B.,
Attorney,
VomBaur,
Coburn,
Simmons
&
Turtle,
Washington,
D.
C.

***
Deceased.

Table
of
Contents
Ethical
Principles
and
Guidelines
for
Research
Involving
Human
Subjects
A.
Boundaries
Between
Practice
and
Research
B.
Basic
Ethical
Principles
1.
Respect
for
Persons
2.
Beneficence
3.
Justice
C.
Applications
1.
Informed
Consent
2.
Assessment
of
Risk
and
Benefits
3.
Selection
of
Subjects
Ethical
Principles
&
Guidelines
for
Research
Involving
Human
Subjects
Scientific
research
has
produced
substantial
social
benefits.
It
has
also
posed
some
troubling
ethical
questions.
Public
attention
was
drawn
to
these
questions
by
reported
abuses
of
human
subjects
in
biomedical
experiments,
especially
during
the
Second
World
War.
During
the
Nuremberg
War
Crime
Trials,
the
Nuremberg
code
was
drafted
as
a
set
of
standards
for
judging
physicians
and
scientists
who
had
conducted
biomedical
experiments
on
concentration
camp
prisoners.
This
code
became
the
prototype
of
many
later
codes(
1)
intended
to
assure
that
research
involving
human
subjects
would
be
carried
out
in
an
ethical
manner.

The
codes
consist
of
rules,
some
general,
others
specific,
that
guide
the
investigators
or
the
reviewers
of
research
in
their
work.
Such
rules
often
are
inadequate
to
cover
complex
situations;
at
times
they
come
into
conflict,
and
they
are
frequently
difficult
to
interpret
or
apply.
Broader
ethical
principles
will
provide
a
basis
on
which
specific
rules
may
be
formulated,
criticized
and
interpreted.

Three
principles,
or
general
prescriptive
judgments,
that
are
relevant
to
research
involving
human
subjects
are
identified
in
this
statement.
Other
principles
may
also
be
relevant.
These
three
are
comprehensive,
however,
and
are
stated
at
a
level
of
generalization
that
should
assist
scientists,
subjects,
reviewers
and
interested
citizens
to
understand
the
ethical
issues
inherent
in
research
involving
human
subjects.
These
principles
cannot
always
be
applied
so
as
to
resolve
beyond
dispute
particular
ethical
problems.
The
objective
is
to
provide
an
analytical
framework
that
will
guide
the
resolution
of
ethical
problems
arising
from
research
involving
human
subjects.

This
statement
consists
of
a
distinction
between
research
and
practice,
a
discussion
of
the
three
basic
ethical
principles,
and
remarks
about
the
application
of
these
principles.

[
RETURN
TO
TABLE
OF
CONTENTS]

Part
A:
Boundaries
Between
Practice
&
Research
A.
Boundaries
Between
Practice
and
Research
It
is
important
to
distinguish
between
biomedical
and
behavioral
research,
on
the
one
hand,
and
the
practice
of
accepted
therapy
on
the
other,
in
order
to
know
what
activities
ought
to
undergo
review
for
the
protection
of
human
subjects
of
research.
The
distinction
between
research
and
practice
is
blurred
partly
because
both
often
occur
together
(
as
in
research
designed
to
evaluate
a
therapy)
and
partly
because
notable
departures
from
standard
practice
are
often
called
"
experimental"
when
the
terms
"
experimental"
and
"
research"
are
not
carefully
defined.

For
the
most
part,
the
term
"
practice"
refers
to
interventions
that
are
designed
solely
to
enhance
the
well­
being
of
an
individual
patient
or
client
and
that
have
a
reasonable
expectation
of
success.
The
purpose
of
medical
or
behavioral
practice
is
to
provide
diagnosis,
preventive
treatment
or
therapy
to
particular
individuals.(
2)
By
contrast,
the
term
"
research'
designates
an
activity
designed
to
test
an
hypothesis,
permit
conclusions
to
be
drawn,
and
thereby
to
develop
or
contribute
to
generalizable
knowledge
(
expressed,
for
example,
in
theories,
principles,
and
statements
of
relationships).
Research
is
usually
described
in
a
formal
protocol
that
sets
forth
an
objective
and
a
set
of
procedures
designed
to
reach
that
objective.

When
a
clinician
departs
in
a
significant
way
from
standard
or
accepted
practice,
the
innovation
does
not,
in
and
of
itself,
constitute
research.
The
fact
that
a
procedure
is
"
experimental,"
in
the
sense
of
new,
untested
or
different,
does
not
automatically
place
it
in
the
category
of
research.
Radically
new
procedures
of
this
description
should,
however,
be
made
the
object
of
formal
research
at
an
early
stage
in
order
to
determine
whether
they
are
safe
and
effective.
Thus,
it
is
the
responsibility
of
medical
practice
committees,
for
example,
to
insist
that
a
major
innovation
be
incorporated
into
a
formal
research
project.(
3)

Research
and
practice
may
be
carried
on
together
when
research
is
designed
to
evaluate
the
safety
and
efficacy
of
a
therapy.
This
need
not
cause
any
confusion
regarding
whether
or
not
the
activity
requires
review;
the
general
rule
is
that
if
there
is
any
element
of
research
in
an
activity,
that
activity
should
undergo
review
for
the
protection
of
human
subjects.

Part
B:
Basic
Ethical
Principles
B.
Basic
Ethical
Principles
The
expression
"
basic
ethical
principles"
refers
to
those
general
judgments
that
serve
as
a
basic
justification
for
the
many
particular
ethical
prescriptions
and
evaluations
of
human
actions.
Three
basic
principles,
among
those
generally
accepted
in
our
cultural
tradition,
are
particularly
relevant
to
the
ethics
of
research
involving
human
subjects:
the
principles
of
respect
of
persons,
beneficence
and
justice.

1.
Respect
for
Persons.
­­
Respect
for
persons
incorporates
at
least
two
ethical
convictions:
first,
that
individuals
should
be
treated
as
autonomous
agents,
and
second,
that
persons
with
diminished
autonomy
are
entitled
to
protection.
The
principle
of
respect
for
persons
thus
divides
into
two
separate
moral
requirements:
the
requirement
to
acknowledge
autonomy
and
the
requirement
to
protect
those
with
diminished
autonomy.

An
autonomous
person
is
an
individual
capable
of
deliberation
about
personal
goals
and
of
acting
under
the
direction
of
such
deliberation.
To
respect
autonomy
is
to
give
weight
to
autonomous
persons'
considered
opinions
and
choices
while
refraining
from
obstructing
their
actions
unless
they
are
clearly
detrimental
to
others.
To
show
lack
of
respect
for
an
autonomous
agent
is
to
repudiate
that
person's
considered
judgments,
to
deny
an
individual
the
freedom
to
act
on
those
considered
judgments,
or
to
withhold
information
necessary
to
make
a
considered
judgment,
when
there
are
no
compelling
reasons
to
do
so.

However,
not
every
human
being
is
capable
of
self­
determination.
The
capacity
for
selfdetermination
matures
during
an
individual's
life,
and
some
individuals
lose
this
capacity
wholly
or
in
part
because
of
illness,
mental
disability,
or
circumstances
that
severely
restrict
liberty.
Respect
for
the
immature
and
the
incapacitated
may
require
protecting
them
as
they
mature
or
while
they
are
incapacitated.

Some
persons
are
in
need
of
extensive
protection,
even
to
the
point
of
excluding
them
from
activities
which
may
harm
them;
other
persons
require
little
protection
beyond
making
sure
they
undertake
activities
freely
and
with
awareness
of
possible
adverse
consequence.
The
extent
of
protection
afforded
should
depend
upon
the
risk
of
harm
and
the
likelihood
of
benefit.
The
judgment
that
any
individual
lacks
autonomy
should
be
periodically
reevaluated
and
will
vary
in
different
situations.

In
most
cases
of
research
involving
human
subjects,
respect
for
persons
demands
that
subjects
enter
into
the
research
voluntarily
and
with
adequate
information.
In
some
situations,
however,
application
of
the
principle
is
not
obvious.
The
involvement
of
prisoners
as
subjects
of
research
provides
an
instructive
example.
On
the
one
hand,
it
would
seem
that
the
principle
of
respect
for
persons
requires
that
prisoners
not
be
deprived
of
the
opportunity
to
volunteer
for
research.
On
the
other
hand,
under
prison
conditions
they
may
be
subtly
coerced
or
unduly
influenced
to
engage
in
research
activities
for
which
they
would
not
otherwise
volunteer.
Respect
for
persons
would
then
dictate
that
prisoners
be
protected.
Whether
to
allow
prisoners
to
"
volunteer"
or
to
"
protect"
them
presents
a
dilemma.
Respecting
persons,
in
most
hard
cases,
is
often
a
matter
of
balancing
competing
claims
urged
by
the
principle
of
respect
itself.

2.
Beneficence.
­­
Persons
are
treated
in
an
ethical
manner
not
only
by
respecting
their
decisions
and
protecting
them
from
harm,
but
also
by
making
efforts
to
secure
their
well­
being.
Such
treatment
falls
under
the
principle
of
beneficence.
The
term
"
beneficence"
is
often
understood
to
cover
acts
of
kindness
or
charity
that
go
beyond
strict
obligation.
In
this
document,
beneficence
is
understood
in
a
stronger
sense,
as
an
obligation.
Two
general
rules
have
been
formulated
as
complementary
expressions
of
beneficent
actions
in
this
sense:
(
1)
do
not
harm
and
(
2)
maximize
possible
benefits
and
minimize
possible
harms.

The
Hippocratic
maxim
"
do
no
harm"
has
long
been
a
fundamental
principle
of
medical
ethics.
Claude
Bernard
extended
it
to
the
realm
of
research,
saying
that
one
should
not
injure
one
person
regardless
of
the
benefits
that
might
come
to
others.
However,
even
avoiding
harm
requires
learning
what
is
harmful;
and,
in
the
process
of
obtaining
this
information,
persons
may
be
exposed
to
risk
of
harm.
Further,
the
Hippocratic
Oath
requires
physicians
to
benefit
their
patients
"
according
to
their
best
judgment."
Learning
what
will
in
fact
benefit
may
require
exposing
persons
to
risk.
The
problem
posed
by
these
imperatives
is
to
decide
when
it
is
justifiable
to
seek
certain
benefits
despite
the
risks
involved,
and
when
the
benefits
should
be
foregone
because
of
the
risks.
The
obligations
of
beneficence
affect
both
individual
investigators
and
society
at
large,
because
they
extend
both
to
particular
research
projects
and
to
the
entire
enterprise
of
research.
In
the
case
of
particular
projects,
investigators
and
members
of
their
institutions
are
obliged
to
give
forethought
to
the
maximization
of
benefits
and
the
reduction
of
risk
that
might
occur
from
the
research
investigation.
In
the
case
of
scientific
research
in
general,
members
of
the
larger
society
are
obliged
to
recognize
the
longer
term
benefits
and
risks
that
may
result
from
the
improvement
of
knowledge
and
from
the
development
of
novel
medical,
psychotherapeutic,
and
social
procedures.

The
principle
of
beneficence
often
occupies
a
well­
defined
justifying
role
in
many
areas
of
research
involving
human
subjects.
An
example
is
found
in
research
involving
children.
Effective
ways
of
treating
childhood
diseases
and
fostering
healthy
development
are
benefits
that
serve
to
justify
research
involving
children
­­
even
when
individual
research
subjects
are
not
direct
beneficiaries.
Research
also
makes
it
possible
to
avoid
the
harm
that
may
result
from
the
application
of
previously
accepted
routine
practices
that
on
closer
investigation
turn
out
to
be
dangerous.
But
the
role
of
the
principle
of
beneficence
is
not
always
so
unambiguous.
A
difficult
ethical
problem
remains,
for
example,
about
research
that
presents
more
than
minimal
risk
without
immediate
prospect
of
direct
benefit
to
the
children
involved.
Some
have
argued
that
such
research
is
inadmissible,
while
others
have
pointed
out
that
this
limit
would
rule
out
much
research
promising
great
benefit
to
children
in
the
future.
Here
again,
as
with
all
hard
cases,
the
different
claims
covered
by
the
principle
of
beneficence
may
come
into
conflict
and
force
difficult
choices.

3.
Justice.
­­
Who
ought
to
receive
the
benefits
of
research
and
bear
its
burdens?
This
is
a
question
of
justice,
in
the
sense
of
"
fairness
in
distribution"
or
"
what
is
deserved."
An
injustice
occurs
when
some
benefit
to
which
a
person
is
entitled
is
denied
without
good
reason
or
when
some
burden
is
imposed
unduly.
Another
way
of
conceiving
the
principle
of
justice
is
that
equals
ought
to
be
treated
equally.
However,
this
statement
requires
explication.
Who
is
equal
and
who
is
unequal?
What
considerations
justify
departure
from
equal
distribution?
Almost
all
commentators
allow
that
distinctions
based
on
experience,
age,
deprivation,
competence,
merit
and
position
do
sometimes
constitute
criteria
justifying
differential
treatment
for
certain
purposes.
It
is
necessary,
then,
to
explain
in
what
respects
people
should
be
treated
equally.
There
are
several
widely
accepted
formulations
of
just
ways
to
distribute
burdens
and
benefits.
Each
formulation
mentions
some
relevant
property
on
the
basis
of
which
burdens
and
benefits
should
be
distributed.
These
formulations
are
(
1)
to
each
person
an
equal
share,
(
2)
to
each
person
according
to
individual
need,
(
3)
to
each
person
according
to
individual
effort,
(
4)
to
each
person
according
to
societal
contribution,
and
(
5)
to
each
person
according
to
merit.

Questions
of
justice
have
long
been
associated
with
social
practices
such
as
punishment,
taxation
and
political
representation.
Until
recently
these
questions
have
not
generally
been
associated
with
scientific
research.
However,
they
are
foreshadowed
even
in
the
earliest
reflections
on
the
ethics
of
research
involving
human
subjects.
For
example,
during
the
19th
and
early
20th
centuries
the
burdens
of
serving
as
research
subjects
fell
largely
upon
poor
ward
patients,
while
the
benefits
of
improved
medical
care
flowed
primarily
to
private
patients.
Subsequently,
the
exploitation
of
unwilling
prisoners
as
research
subjects
in
Nazi
concentration
camps
was
condemned
as
a
particularly
flagrant
injustice.
In
this
country,
in
the
1940'
s,
the
Tuskegee
syphilis
study
used
disadvantaged,
rural
black
men
to
study
the
untreated
course
of
a
disease
that
is
by
no
means
confined
to
that
population.
These
subjects
were
deprived
of
demonstrably
effective
treatment
in
order
not
to
interrupt
the
project,
long
after
such
treatment
became
generally
available.

Against
this
historical
background,
it
can
be
seen
how
conceptions
of
justice
are
relevant
to
research
involving
human
subjects.
For
example,
the
selection
of
research
subjects
needs
to
be
scrutinized
in
order
to
determine
whether
some
classes
(
e.
g.,
welfare
patients,
particular
racial
and
ethnic
minorities,
or
persons
confined
to
institutions)
are
being
systematically
selected
simply
because
of
their
easy
availability,
their
compromised
position,
or
their
manipulability,
rather
than
for
reasons
directly
related
to
the
problem
being
studied.
Finally,
whenever
research
supported
by
public
funds
leads
to
the
development
of
therapeutic
devices
and
procedures,
justice
demands
both
that
these
not
provide
advantages
only
to
those
who
can
afford
them
and
that
such
research
should
not
unduly
involve
persons
from
groups
unlikely
to
be
among
the
beneficiaries
of
subsequent
applications
of
the
research.

Part
C:
Applications
C.
Applications
Applications
of
the
general
principles
to
the
conduct
of
research
leads
to
consideration
of
the
following
requirements:
informed
consent,
risk/
benefit
assessment,
and
the
selection
of
subjects
of
research.

1.
Informed
Consent.
­­
Respect
for
persons
requires
that
subjects,
to
the
degree
that
they
are
capable,
be
given
the
opportunity
to
choose
what
shall
or
shall
not
happen
to
them.
This
opportunity
is
provided
when
adequate
standards
for
informed
consent
are
satisfied.

While
the
importance
of
informed
consent
is
unquestioned,
controversy
prevails
over
the
nature
and
possibility
of
an
informed
consent.
Nonetheless,
there
is
widespread
agreement
that
the
consent
process
can
be
analyzed
as
containing
three
elements:
information,
comprehension
and
voluntariness.

Information.
Most
codes
of
research
establish
specific
items
for
disclosure
intended
to
assure
that
subjects
are
given
sufficient
information.
These
items
generally
include:
the
research
procedure,
their
purposes,
risks
and
anticipated
benefits,
alternative
procedures
(
where
therapy
is
involved),
and
a
statement
offering
the
subject
the
opportunity
to
ask
questions
and
to
withdraw
at
any
time
from
the
research.
Additional
items
have
been
proposed,
including
how
subjects
are
selected,
the
person
responsible
for
the
research,
etc.

However,
a
simple
listing
of
items
does
not
answer
the
question
of
what
the
standard
should
be
for
judging
how
much
and
what
sort
of
information
should
be
provided.
One
standard
frequently
invoked
in
medical
practice,
namely
the
information
commonly
provided
by
practitioners
in
the
field
or
in
the
locale,
is
inadequate
since
research
takes
place
precisely
when
a
common
understanding
does
not
exist.
Another
standard,
currently
popular
in
malpractice
law,
requires
the
practitioner
to
reveal
the
information
that
reasonable
persons
would
wish
to
know
in
order
to
make
a
decision
regarding
their
care.
This,
too,
seems
insufficient
since
the
research
subject,
being
in
essence
a
volunteer,
may
wish
to
know
considerably
more
about
risks
gratuitously
undertaken
than
do
patients
who
deliver
themselves
into
the
hand
of
a
clinician
for
needed
care.
It
may
be
that
a
standard
of
"
the
reasonable
volunteer"
should
be
proposed:
the
extent
and
nature
of
information
should
be
such
that
persons,
knowing
that
the
procedure
is
neither
necessary
for
their
care
nor
perhaps
fully
understood,
can
decide
whether
they
wish
to
participate
in
the
furthering
of
knowledge.
Even
when
some
direct
benefit
to
them
is
anticipated,
the
subjects
should
understand
clearly
the
range
of
risk
and
the
voluntary
nature
of
participation.

A
special
problem
of
consent
arises
where
informing
subjects
of
some
pertinent
aspect
of
the
research
is
likely
to
impair
the
validity
of
the
research.
In
many
cases,
it
is
sufficient
to
indicate
to
subjects
that
they
are
being
invited
to
participate
in
research
of
which
some
features
will
not
be
revealed
until
the
research
is
concluded.
In
all
cases
of
research
involving
incomplete
disclosure,
such
research
is
justified
only
if
it
is
clear
that
(
1)
incomplete
disclosure
is
truly
necessary
to
accomplish
the
goals
of
the
research,
(
2)
there
are
no
undisclosed
risks
to
subjects
that
are
more
than
minimal,
and
(
3)
there
is
an
adequate
plan
for
debriefing
subjects,
when
appropriate,
and
for
dissemination
of
research
results
to
them.
Information
about
risks
should
never
be
withheld
for
the
purpose
of
eliciting
the
cooperation
of
subjects,
and
truthful
answers
should
always
be
given
to
direct
questions
about
the
research.
Care
should
be
taken
to
distinguish
cases
in
which
disclosure
would
destroy
or
invalidate
the
research
from
cases
in
which
disclosure
would
simply
inconvenience
the
investigator.

Comprehension.
The
manner
and
context
in
which
information
is
conveyed
is
as
important
as
the
information
itself.
For
example,
presenting
information
in
a
disorganized
and
rapid
fashion,
allowing
too
little
time
for
consideration
or
curtailing
opportunities
for
questioning,
all
may
adversely
affect
a
subject's
ability
to
make
an
informed
choice.

Because
the
subject's
ability
to
understand
is
a
function
of
intelligence,
rationality,
maturity
and
language,
it
is
necessary
to
adapt
the
presentation
of
the
information
to
the
subject's
capacities.
Investigators
are
responsible
for
ascertaining
that
the
subject
has
comprehended
the
information.
While
there
is
always
an
obligation
to
ascertain
that
the
information
about
risk
to
subjects
is
complete
and
adequately
comprehended,
when
the
risks
are
more
serious,
that
obligation
increases.
On
occasion,
it
may
be
suitable
to
give
some
oral
or
written
tests
of
comprehension.

Special
provision
may
need
to
be
made
when
comprehension
is
severely
limited
­­
for
example,
by
conditions
of
immaturity
or
mental
disability.
Each
class
of
subjects
that
one
might
consider
as
incompetent
(
e.
g.,
infants
and
young
children,
mentally
disable
patients,
the
terminally
ill
and
the
comatose)
should
be
considered
on
its
own
terms.
Even
for
these
persons,
however,
respect
requires
giving
them
the
opportunity
to
choose
to
the
extent
they
are
able,
whether
or
not
to
participate
in
research.
The
objections
of
these
subjects
to
involvement
should
be
honored,
unless
the
research
entails
providing
them
a
therapy
unavailable
elsewhere.
Respect
for
persons
also
requires
seeking
the
permission
of
other
parties
in
order
to
protect
the
subjects
from
harm.
Such
persons
are
thus
respected
both
by
acknowledging
their
own
wishes
and
by
the
use
of
third
parties
to
protect
them
from
harm.

The
third
parties
chosen
should
be
those
who
are
most
likely
to
understand
the
incompetent
subject's
situation
and
to
act
in
that
person's
best
interest.
The
person
authorized
to
act
on
behalf
of
the
subject
should
be
given
an
opportunity
to
observe
the
research
as
it
proceeds
in
order
to
be
able
to
withdraw
the
subject
from
the
research,
if
such
action
appears
in
the
subject's
best
interest.

Voluntariness.
An
agreement
to
participate
in
research
constitutes
a
valid
consent
only
if
voluntarily
given.
This
element
of
informed
consent
requires
conditions
free
of
coercion
and
undue
influence.
Coercion
occurs
when
an
overt
threat
of
harm
is
intentionally
presented
by
one
person
to
another
in
order
to
obtain
compliance.
Undue
influence,
by
contrast,
occurs
through
an
offer
of
an
excessive,
unwarranted,
inappropriate
or
improper
reward
or
other
overture
in
order
to
obtain
compliance.
Also,
inducements
that
would
ordinarily
be
acceptable
may
become
undue
influences
if
the
subject
is
especially
vulnerable.

Unjustifiable
pressures
usually
occur
when
persons
in
positions
of
authority
or
commanding
influence
­­
especially
where
possible
sanctions
are
involved
­­
urge
a
course
of
action
for
a
subject.
A
continuum
of
such
influencing
factors
exists,
however,
and
it
is
impossible
to
state
precisely
where
justifiable
persuasion
ends
and
undue
influence
begins.
But
undue
influence
would
include
actions
such
as
manipulating
a
person's
choice
through
the
controlling
influence
of
a
close
relative
and
threatening
to
withdraw
health
services
to
which
an
individual
would
otherwise
be
entitle.

2.
Assessment
of
Risks
and
Benefits.
­­
The
assessment
of
risks
and
benefits
requires
a
careful
arrayal
of
relevant
data,
including,
in
some
cases,
alternative
ways
of
obtaining
the
benefits
sought
in
the
research.
Thus,
the
assessment
presents
both
an
opportunity
and
a
responsibility
to
gather
systematic
and
comprehensive
information
about
proposed
research.
For
the
investigator,
it
is
a
means
to
examine
whether
the
proposed
research
is
properly
designed.
For
a
review
committee,
it
is
a
method
for
determining
whether
the
risks
that
will
be
presented
to
subjects
are
justified.
For
prospective
subjects,
the
assessment
will
assist
the
determination
whether
or
not
to
participate.

The
Nature
and
Scope
of
Risks
and
Benefits.
The
requirement
that
research
be
justified
on
the
basis
of
a
favorable
risk/
benefit
assessment
bears
a
close
relation
to
the
principle
of
beneficence,
just
as
the
moral
requirement
that
informed
consent
be
obtained
is
derived
primarily
from
the
principle
of
respect
for
persons.
The
term
"
risk"
refers
to
a
possibility
that
harm
may
occur.
However,
when
expressions
such
as
"
small
risk"
or
"
high
risk"
are
used,
they
usually
refer
(
often
ambiguously)
both
to
the
chance
(
probability)
of
experiencing
a
harm
and
the
severity
(
magnitude)
of
the
envisioned
harm.

The
term
"
benefit"
is
used
in
the
research
context
to
refer
to
something
of
positive
value
related
to
health
or
welfare.
Unlike,
"
risk,"
"
benefit"
is
not
a
term
that
expresses
probabilities.
Risk
is
properly
contrasted
to
probability
of
benefits,
and
benefits
are
properly
contrasted
with
harms
rather
than
risks
of
harm.
Accordingly,
so­
called
risk/
benefit
assessments
are
concerned
with
the
probabilities
and
magnitudes
of
possible
harm
and
anticipated
benefits.
Many
kinds
of
possible
harms
and
benefits
need
to
be
taken
into
account.
There
are,
for
example,
risks
of
psychological
harm,
physical
harm,
legal
harm,
social
harm
and
economic
harm
and
the
corresponding
benefits.
While
the
most
likely
types
of
harms
to
research
subjects
are
those
of
psychological
or
physical
pain
or
injury,
other
possible
kinds
should
not
be
overlooked.

Risks
and
benefits
of
research
may
affect
the
individual
subjects,
the
families
of
the
individual
subjects,
and
society
at
large
(
or
special
groups
of
subjects
in
society).
Previous
codes
and
Federal
regulations
have
required
that
risks
to
subjects
be
outweighed
by
the
sum
of
both
the
anticipated
benefit
to
the
subject,
if
any,
and
the
anticipated
benefit
to
society
in
the
form
of
knowledge
to
be
gained
from
the
research.
In
balancing
these
different
elements,
the
risks
and
benefits
affecting
the
immediate
research
subject
will
normally
carry
special
weight.
On
the
other
hand,
interests
other
than
those
of
the
subject
may
on
some
occasions
be
sufficient
by
themselves
to
justify
the
risks
involved
in
the
research,
so
long
as
the
subjects'
rights
have
been
protected.
Beneficence
thus
requires
that
we
protect
against
risk
of
harm
to
subjects
and
also
that
we
be
concerned
about
the
loss
of
the
substantial
benefits
that
might
be
gained
from
research.

The
Systematic
Assessment
of
Risks
and
Benefits.
It
is
commonly
said
that
benefits
and
risks
must
be
"
balanced"
and
shown
to
be
"
in
a
favorable
ratio."
The
metaphorical
character
of
these
terms
draws
attention
to
the
difficulty
of
making
precise
judgments.
Only
on
rare
occasions
will
quantitative
techniques
be
available
for
the
scrutiny
of
research
protocols.
However,
the
idea
of
systematic,
nonarbitrary
analysis
of
risks
and
benefits
should
be
emulated
insofar
as
possible.
This
ideal
requires
those
making
decisions
about
the
justifiability
of
research
to
be
thorough
in
the
accumulation
and
assessment
of
information
about
all
aspects
of
the
research,
and
to
consider
alternatives
systematically.
This
procedure
renders
the
assessment
of
research
more
rigorous
and
precise,
while
making
communication
between
review
board
members
and
investigators
less
subject
to
misinterpretation,
misinformation
and
conflicting
judgments.
Thus,
there
should
first
be
a
determination
of
the
validity
of
the
presuppositions
of
the
research;
then
the
nature,
probability
and
magnitude
of
risk
should
be
distinguished
with
as
much
clarity
as
possible.
The
method
of
ascertaining
risks
should
be
explicit,
especially
where
there
is
no
alternative
to
the
use
of
such
vague
categories
as
small
or
slight
risk.
It
should
also
be
determined
whether
an
investigator's
estimates
of
the
probability
of
harm
or
benefits
are
reasonable,
as
judged
by
known
facts
or
other
available
studies.

Finally,
assessment
of
the
justifiability
of
research
should
reflect
at
least
the
following
considerations:
(
i)
Brutal
or
inhumane
treatment
of
human
subjects
is
never
morally
justified.
(
ii)
Risks
should
be
reduced
to
those
necessary
to
achieve
the
research
objective.
It
should
be
determined
whether
it
is
in
fact
necessary
to
use
human
subjects
at
all.
Risk
can
perhaps
never
be
entirely
eliminated,
but
it
can
often
be
reduced
by
careful
attention
to
alternative
procedures.
(
iii)
When
research
involves
significant
risk
of
serious
impairment,
review
committees
should
be
extraordinarily
insistent
on
the
justification
of
the
risk
(
looking
usually
to
the
likelihood
of
benefit
to
the
subject
­­
or,
in
some
rare
cases,
to
the
manifest
voluntariness
of
the
participation).
(
iv)
When
vulnerable
populations
are
involved
in
research,
the
appropriateness
of
involving
them
should
itself
be
demonstrated.
A
number
of
variables
go
into
such
judgments,
including
the
nature
and
degree
of
risk,
the
condition
of
the
particular
population
involved,
and
the
nature
and
level
of
the
anticipated
benefits.
(
v)
Relevant
risks
and
benefits
must
be
thoroughly
arrayed
in
documents
and
procedures
used
in
the
informed
consent
process.

3.
Selection
of
Subjects.
­­
Just
as
the
principle
of
respect
for
persons
finds
expression
in
the
requirements
for
consent,
and
the
principle
of
beneficence
in
risk/
benefit
assessment,
the
principle
of
justice
gives
rise
to
moral
requirements
that
there
be
fair
procedures
and
outcomes
in
the
selection
of
research
subjects.
Justice
is
relevant
to
the
selection
of
subjects
of
research
at
two
levels:
the
social
and
the
individual.
Individual
justice
in
the
selection
of
subjects
would
require
that
researchers
exhibit
fairness:
thus,
they
should
not
offer
potentially
beneficial
research
only
to
some
patients
who
are
in
their
favor
or
select
only
"
undesirable"
persons
for
risky
research.
Social
justice
requires
that
distinction
be
drawn
between
classes
of
subjects
that
ought,
and
ought
not,
to
participate
in
any
particular
kind
of
research,
based
on
the
ability
of
members
of
that
class
to
bear
burdens
and
on
the
appropriateness
of
placing
further
burdens
on
already
burdened
persons.
Thus,
it
can
be
considered
a
matter
of
social
justice
that
there
is
an
order
of
preference
in
the
selection
of
classes
of
subjects
(
e.
g.,
adults
before
children)
and
that
some
classes
of
potential
subjects
(
e.
g.,
the
institutionalized
mentally
infirm
or
prisoners)
may
be
involved
as
research
subjects,
if
at
all,
only
on
certain
conditions.

Injustice
may
appear
in
the
selection
of
subjects,
even
if
individual
subjects
are
selected
fairly
by
investigators
and
treated
fairly
in
the
course
of
research.
Thus
injustice
arises
from
social,
racial,
sexual
and
cultural
biases
institutionalized
in
society.
Thus,
even
if
individual
researchers
are
treating
their
research
subjects
fairly,
and
even
if
IRBs
are
taking
care
to
assure
that
subjects
are
selected
fairly
within
a
particular
institution,
unjust
social
patterns
may
nevertheless
appear
in
the
overall
distribution
of
the
burdens
and
benefits
of
research.
Although
individual
institutions
or
investigators
may
not
be
able
to
resolve
a
problem
that
is
pervasive
in
their
social
setting,
they
can
consider
distributive
justice
in
selecting
research
subjects.

Some
populations,
especially
institutionalized
ones,
are
already
burdened
in
many
ways
by
their
infirmities
and
environments.
When
research
is
proposed
that
involves
risks
and
does
not
include
a
therapeutic
component,
other
less
burdened
classes
of
persons
should
be
called
upon
first
to
accept
these
risks
of
research,
except
where
the
research
is
directly
related
to
the
specific
conditions
of
the
class
involved.
Also,
even
though
public
funds
for
research
may
often
flow
in
the
same
directions
as
public
funds
for
health
care,
it
seems
unfair
that
populations
dependent
on
public
health
care
constitute
a
pool
of
preferred
research
subjects
if
more
advantaged
populations
are
likely
to
be
the
recipients
of
the
benefits.

One
special
instance
of
injustice
results
from
the
involvement
of
vulnerable
subjects.
Certain
groups,
such
as
racial
minorities,
the
economically
disadvantaged,
the
very
sick,
and
the
institutionalized
may
continually
be
sought
as
research
subjects,
owing
to
their
ready
availability
in
settings
where
research
is
conducted.
Given
their
dependent
status
and
their
frequently
compromised
capacity
for
free
consent,
they
should
be
protected
against
the
danger
of
being
involved
in
research
solely
for
administrative
convenience,
or
because
they
are
easy
to
manipulate
as
a
result
of
their
illness
or
socioeconomic
condition.

(
1)
Since
1945,
various
codes
for
the
proper
and
responsible
conduct
of
human
experimentation
in
medical
research
have
been
adopted
by
different
organizations.
The
best
known
of
these
codes
are
the
Nuremberg
Code
of
1947,
the
Helsinki
Declaration
of
1964
(
revised
in
1975),
and
the
1971
Guidelines
(
codified
into
Federal
Regulations
in
1974)
issued
by
the
U.
S.
Department
of
Health,
Education,
and
Welfare
Codes
for
the
conduct
of
social
and
behavioral
research
have
also
been
adopted,
the
best
known
being
that
of
the
American
Psychological
Association,
published
in
1973.

(
2)
Although
practice
usually
involves
interventions
designed
solely
to
enhance
the
well­
being
of
a
particular
individual,
interventions
are
sometimes
applied
to
one
individual
for
the
enhancement
of
the
well­
being
of
another
(
e.
g.,
blood
donation,
skin
grafts,
organ
transplants)
or
an
intervention
may
have
the
dual
purpose
of
enhancing
the
well­
being
of
a
particular
individual,
and,
at
the
same
time,
providing
some
benefit
to
others
(
e.
g.,
vaccination,
which
protects
both
the
person
who
is
vaccinated
and
society
generally).
The
fact
that
some
forms
of
practice
have
elements
other
than
immediate
benefit
to
the
individual
receiving
an
intervention,
however,
should
not
confuse
the
general
distinction
between
research
and
practice.
Even
when
a
procedure
applied
in
practice
may
benefit
some
other
person,
it
remains
an
intervention
designed
to
enhance
the
well­
being
of
a
particular
individual
or
groups
of
individuals;
thus,
it
is
practice
and
need
not
be
reviewed
as
research.

(
3)
Because
the
problems
related
to
social
experimentation
may
differ
substantially
from
those
of
biomedical
and
behavioral
research,
the
Commission
specifically
declines
to
make
any
policy
determination
regarding
such
research
at
this
time.
Rather,
the
Commission
believes
that
the
problem
ought
to
be
addressed
by
one
of
its
successor
bodies.