p





Presentation for IRB Members

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M
remberg War Trib
nal (1947) - Criminal proceedings against
23 leading German physicians and administrators for their willing
participation in war crimes and crimes against h
manity. Horrifying
proced
res were cond
cted for research p
rposes on tho
sands of
concentration camp prisoners witho
t their informed consent.

M yphilis t
dy in T
skegee, GA (1932

(1932--1972) ² As part of a
research project cond
cted by the U.. P
blic Health ervice, 600
low--income African
low African--American males, 400 of whom were infected
with syphilis, were monitored for 40 years. Free medical
examinations were given; however, participants were not told abo
t
their disease. Even tho
gh a proven c
re (penicillin) became
available in the 1950s, the st
dy contin
ed
ntil 1972 with
participants being denied treatment. In some cases, when
participants were diagnosed as having syphilis by other physicians,
researchers intervened to prevent treatment. Many participants died
of syphilis d
ring the st
dy. The st
dy was stopped in 1973 by the
U.. Department of Health, Ed
cation, and Welfare only after its
existence was p
blicized and it became a political embarrassment.
 m
 



 

M Thalidomide
se - Thalidomide was
sed in the 1950s to combat

npleasant symptoms associated with pregnancy. At the time it was
being
sed it was not
s
ally disclosed to patients that the dr
g was
investigational and still in the testing phase of the reg
latory process.
After women in E
rope, Canada, and the U.. were treated with the
dr
g it was discovered that the dr
g had teratogenic effects, ca
sing
severe deformities in the fet
s. Thalidomide was soon banned
worldwide. Unfort
nately, approximately 12,000 babies were born
with severe deformities d
e to thalidomide.

M Radiation experiments (1940s ² 1960s) - U.. officials st
died

the effects of radiation thro
gh experiments on hospital patients,
pregnant women, mentally disabled children, and enlisted military
personnel. Few of the participants of the experiments gave informed
consent; most had no knowledge that they were being s
bjected to
radioactive materials. Manhattan Project officials a
thorized the
wartime experiments to establish health and safety standards for the
tho
sands of workers in atomic bomb plants.








  



M azi atrocities in World War II drew attention to the lack of
international standards on research with h
man participants and led
to the form
lation of the
remb
rg Code (1948).

M The thalidomide disaster led to the adoption of the "Kefa
ver

"Kefa
ver
Amendment"" (1962) to the Food, Dr
g and Cosmetic Act, req
iring
Amendment
dr
g man
fact
rers to prove to the FDA the safety and effectiveness
of their prod
cts and physicians to obtain informed consent from
potential s
bjects before administering investigational medications.
M The Declaration of Helsinki drafted by the world Medical Association
in 1964 (most recently
pdated in 2000) b
ilds on the
remberg
Code and is the basis for Good Clinical Practices
sed today.

M The ational Research Act (1974) passed primarily in response to the

syphilis st
dy, codified the req
irement that h
man participants in
research m
st be protected and set the stage for the iss
ance of the
Belmont Report.
ë 


   (1974)
M D
e to the p
blicity from the yphilis t
dy, the
ational Research Act of 1974 was passed.
M The ational Research Act created the ational
Commission for the Protection of H
man 
bjects of
Biomedical and Behavioral Research.
M The Commission charge was to identify the basic
ethical principles that sho
ld
nderlie the cond
ct of
biomedical and behavioral research involving h
man
participants and to develop g
idelines which sho
ld be
followed to ass
re that s
ch research is cond
cted in
accordance with those principles.
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m 

 
 

 



M Carrying o
t its charge, the Commission prepared the
Belmont Report in 1979.

M The Belmont Report is a statement of basic ethical

principles and g
idelines that provide ´an analytical
framework to g
ide the resol
tion of the ethical problems
arising from research with h
man s
bjects.µ

M The framework of the Belmont Report is presented in

three disc
ssion topics: bo
ndaries between practice and
research; basic ethical principles, and applications.
 





 




M The distinction between practice and research is
bl
rred; often beca
se they occ
r together.

M The IRB m
st ens
re that the researcher (and the

participant) disting
ishes practice from research in
both social science and biomedical research

M Minimize the potential for therape
tic misconception ²

when one believes the p
rpose of clinical research is to
treat rather then to gain knowledge
 
  



M Respect for Persons
² Individ
als sho
ld be treated as a
tonomo
s agents
² Individ
als with diminished a
tonomy are entitled to
protections
M Beneficence
² Do not harm
² Maxim
m possible benefits, and minimize potential
harms
M 
stice
² Fair distrib
tion of b
rdens and benefits of research








M Treat individ
als as a
tonomo
s persons; allow
individ
als to choose for themselves

M Persons with limited a
tonomy need additional

protection, even to the point of excl
ding them from
activities that may harm them. The extent of
protection sho
ld depend
pon the risk of harm, and
the likelihood of benefit.

M The j
dgment that any individ
al lacks a
tonomy

sho
ld be periodically re-
re-eval
ated, and will vary
across sit
ations.
 

 


M The IRB sho
ld determine whether the risks to s
bjects
are reasonable in relation to anticipated benefits

M bligations of beneficence affect both the researcher

and society ²
ü investigators are req
ired to give foretho
ght on
maximization of benefits and red
ction of risk that
may be involved in the research

ü society sho
ld recognize the longer term benefits

and risk that may res
lt from the improvement of
knowledge, and from the development of novel
medical, psychological, and social processes and
proced
res
 
 

M Treat people fairly

M Do not exploit those who are readily available

or malleable

M Fair distrib
tion of the risks and the benefits of

research based
pon the problem/iss
e
nder
investigation


  




 



M Consideration of the three general principles in
the cond
ct of research lead to the
consideration of:
ü Informed Consent process

ü Risk/Benefits assessment

ü election of research participants

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M Informed Consent Process
ü Information - Does the consent form provide all the information
necessary for the individ
al to make a reasoned decision?
ü Comprehension - Is the consent form crafted in lang
age

nderstandable to the potential participant?
ü Vol
ntariness - Does the consent form and clearly indicate that
participation in the research is vol
ntary?
ü What additional protections can be in place to protect those with
limited a
tonomy?
ü How to determine whether one lacks the a
tonomy to make a
reasoned decision?


  



 


M Assessment of Risks and Benefits
ü Risk refers to the probability of harm; when considering risk, one
sho
ld consider both the probability and the severity of the
envisioned harm; while the term, benefit refers to something that
promotes health, well-
well-being, or welfare.

ü What are the risks of harm to the participants (consider physical,

psychological, social, and economic harms)? Are the risks j
stified?
Can they be minimized?

ü Can the research design be improved to minimize risk and

maximize benefit?

ü What are the benefits (to the participant; to society)?



  


 

M election of 
bjects
ü Is the potential s
bject pool appropriate for the
research?
ü Is it appropriate to involve v
lnerable pop
lations
(e.g., economically disadvantaged; limited cognitive
capacity) in the research or are they being enrolled
beca
se it is convenient or beca
se they are easily
manip
lated as a res
lt of their sit
ation?
ü Are the recr
itment proced
res fair and impartial?
ü Are the incl
sion and excl
sion criteria fair and
appropriate?
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M Altho
gh never officially adopted or endorsed by Congress
or DHEW (now DHH), the Belmont Report has served as
an ethical framework for protecting h
man s
bjects for
over 25 years. Many of it recommendations have been
incorporated into DHH Title 45 CFR Part 46 and FDA Title
21 CFR Part 50.

M To obtain a f
ll appreciation of the Belmont Report, IRB

Members are strongly enco
raged to read it in its
entirety. The report can be fo
nd @
http://www.fda.gov/oc/ohrt/IRB/belmont.html
 A

 


Please contact:
ü Karen Allen
Director of Research Protections
@ kallen@
ci.ed
or 949-
949-824
824--1558