Transcript Human Research

Human
Research
Vaughn Chapter 6
For historical perspective, click image, watch two
minutes of life at The Knickerbocker Hospital in
NYC…
Human Research Only a
Utilitarian Could Love?
 Nazi experimentation on
prisoners and civilians
 US Public Health Service study
of syphilis using poor black
men from Macon County, AL
 US government Cold War
studies of radiation effects on
thousands of human subjects
from 1944-74
 Willowbrook State Hospital in
NY study of hepatitis,
infecting mentally retarded
children
Negative public reaction to the
above events, and others,
produced:
• The Nuremburg Code (guidelines
for ethical research), 1947
• Declaration of Helsinki,
embraced by the World Medical
Association (WMA) in 1964
• Belmont Report, 1979, of the
National Commission for the
protection of Human Subjects of
Biomedical and Behavioral
Research
• 1993 guidelines from World
Health Organization (WHO), and
Council for International
Organizations of Medical
Sciences (CIOMS)
• Prompted President Bill Clinton’s
public apology, 1997
Clinical Trials
Clinical Trial = “[a] scientific
study designed to test a
medical intervention in
humans ...” –Vaughn, 194
Clinical trials …
 exist to determine
whether a given drug or
procedure is safe and
effective
 are the best available
method to determine that
Vaughn mentions 3 virtues of
clinical trials:
1.maximize objectivity
2.minimize bias
3.avoid errors
What kinds of value to 1 - 3
have?
Intrinsic?
Instrumental?
Combination?
Clinical Trials
Composition:
1. Experimental group
 the group getting the
new treatment
2. Control group
 the group(s) not getting
the new treatment
Placebo control =
group gets a sugar pill
or equivalent
Active control =
group gets a standard
treatment already
known to work (to
some degree)
Clinical Trials
Blinding = keeping
experimental and control
group membership secret
 single-blind study = test
subjects are kept in the
dark regarding group
membership
Randomization = assigning
experimental and control
group membership randomly
•to ensure the variety of
test subjects are evenly
distributed between
groups
 double-blind study =
both test subjects and
researchers are kept in the
dark as to who is in which
group
•eliminate researcher bias
Clinical Trials
Phases I
 small group
 adverse reactions
 safe doses
 non-therapeutic / no
testing for efficacy
Phase II
 medium group
 safety
 preliminary
effectiveness study
Phases III
 large group (thousands)
 therapeutic (hopefully,
to those in
experimental group)
 success here qualifies
the drug or procedure
for widespread use
Phase IV
 not universally used
 done after procedure or
drug is marketed
 long-term effects
Beneficence, Science, and
Placebos
Beneficence = doing good
for others
in the context of medical
science (treatment of
patients and test
subjects),
 beneficence = the duty
to help others
 non-malfeasance = the
duty not to harm others
Science = in Vaughn,
science is presented as
in occasional conflict
with the duties of
beneficence and nonmalfeasance
Question: why present the
conflict this way, rather
than between duties to
present and future
patients?
Beneficence, Science, and
Placebos
Beneficence vs. ‘Science’
“… conflict with the aim of doing science.” para2, p197
“… treated merely as a means to the end of
scientific knowledge.” –para3, p197
“ … beneficence and science collide.” –last
paragraph, p198
Is this a trumped up conflict?
Is it really some abstract love of science
researchers are motivated by when
researching drugs and procedures? (See
previous slide for another possible motive …
can you think of still others?)
Watch this melodrama
between Dr. Crusher
(seated) & Utilitarian
researcher … When Dr.
Crusher says ‘you take
shortcuts’ … can’t the
shamed researcher
respond, ‘Yeah,
because slow research
kills people’?
Beneficence, Science, and
Placebos
The main question of this section (Beneficence, Science, and
Placebos), is …
How can a physician recommend a patient for clinical trials
over prescribing the best known treatment?
Problem:
“As a physician, she has an obligation to act in the best
interests of her patients, which requires that she offer to
them only those treatments she judges to be the best. But
in clinical trials, patients are randomized into
experimental and control groups where they may not
receive the treatment that the physician believes is best.” –
para1, p198
Beneficence, Science, and
Placebos
Reply to problem:
Physicians can recommend participation in clinical trials
because they don’t know which treatment is better; they
are in a state of equipoise (“rationally balanced between
the alternatives” –para2, p198), and so cannot be
recommending a treatment they know to be inferior
Defense of problem:
Physicians owe their patients their best judgment, and if there
is just a hunch that a standard treatment is better than a
new one, physicians cannot recommend, they are not in a
state of equipoise
Beneficence, Science, and
Placebos
Reply to Defense:
Equipoise is not subjective … it is the state of scientific
knowledge where the relative merits of 2 or more
treatments are unknown. When those are unknown,
including patients in randomized trials is permissible
So, is there any conflict between 1, physicians revealing their
honest treatment preferences and 2, offering patients a
chance to participate in clinical trials? –para2, p198
Vaughn suggests that as long as full disclosure is met and
informed consent is gained, the answer is ‘no’.
Beneficence, Science, and
Placebos
Placebos raise another problem:
“Can the deliberate nontreatment of patients be justified?” –para1, p199
The book says ‘Yes’, although:
1.
No, if there is an effective treatment already available, a placebo
controlled human study is “unethical”…
2.
Also, when lack of treatment is life-threatening, the above rule is at its
strongest
3 Questions:
1.
2.
3.
Did the AZT placebo-controlled trial violate proviso #1? –see
quotation on p199
If the lack of treatment results in minor harm, is a placebocontrolled trial permissible under any conditions, according to
Vaughn?
Is equipoise possible in a placebo-controlled trial?
Science and Informed
Consent
Vaughn provides a checklist (from CIOMS and WHO) of what
research scientists owe clinical trial participants (see p200-201)
Main worries about the possibility of getting meaningful informed
consent:
1.
subjects are not able to comprehend enough science to give
informed consent
2.
subjects may, in some cases, consent out of desperation, fear, or
wishful thinking, … all of which threaten informed consent
3.
subjects may be coerced or exploited by payments for helping in
the research
You should know Vaughn’s responses to these objections (1 & 3 … he
gives no reply to 2)
Research on the Vulnerable
Problematic special cases are clinical trials that involve those
who cannot give informed consent and are at the mercy of
others:





children
mentally disabled
prisoners
minorities
people in developing countries
Vaughn tells us many effective therapies that help children, for
example, could only be developed by studies on children, as
their physiology and pathologies differ substantially from
adults …
Research on the Vulnerable
According to Vaughn, “most official policies” follow these
guidelines:
 “… research in children is morally acceptable if it is
conducted for their sake, if it is done to generate the
therapies they need.” (individually, or as a group?)
 consent is required (age of consent is controversial)
 a proper balance of risk and reward for the research
subjects
“[t]he child’s refusal to participate in research must always
be respected unless according to the research protocol
the child would receive therapy for which there is no
medically acceptable alternative.” –p203, (Vaughn
cites CIOMS and WHO)
Research on the Vulnerable
The previous slide is about the justification of therapeutic
research on children.
 What about non-therapeutic research using children?
 Is that ever morally permissible?
See Vaughn’s discussion on p203 … as risk to the research
subject goes up, so do requirements for …
 meaningful consent,
 better balance of reward vs. risk, and
 therapeutic benefit for the child undergoing the tests
Research on the Vulnerable
The guidelines for treatment of the mentally disabled are
similar to those for children, but with special concern
for susceptibility to exploitation:
1. conditioned to defer to authority figures
2. fear punishment from caretakers for refusing to
participate
3. desperation for change of routine or special attention
might amount to coercion
Research on the Vulnerable
Vulnerable subjects in Third World countries …
Vaughn provides this scenario:
1.
AZT is a drug that reduces HIV transmission from women to their fetuses
2.
The dose of the drug was too high to be affordable in these countries (Thailand and
some African countries)
3.
Placebo-controlled trials were conducted to determine if a lower, cheaper dose would
work
4.
Because placebo-controlled trials guarantee some women will not get the experimental
dose, those women’s children are virtually guaranteed to get HIV
5.
The results of the trials were positive; the lower dose worked in reducing HIV
transmission
Compare Marcia Angell’s condemnation of these trials to Baruch Brody’s defense of them
(p204-205); who is right?