Human Research

1
Human Research

• Vaughn Chapter 6

For historical perspective, click image, watch
two minutes of life at The Knickerbocker Hospital
in NYC
2
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 Clintons public apology,
  1997

3
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
• maximize objectivity
• minimize bias
• avoid errors
• What kinds of value to 1 - 3 have?
• Intrinsic?
• Instrumental?
• Combination?

4
Clinical Trials

• Composition
• Experimental group
• the group getting the new treatment
• 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)
5
Clinical Trials

• Blinding keeping experimental and control group
  membership secret
• single-blind study test subjects are kept in
  the dark regarding group membership
• double-blind study both test subjects and
  researchers are kept in the dark as to who is in
  which group

• Randomization assigning experimental and
  control group membership randomly
• to ensure the variety of test subjects are evenly
  distributed between groups
• eliminate researcher bias

6
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

7
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 non-malfeasance Question why
present the conflict this way, rather than
between duties to present and future patients?
8
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 cant the shamed
researcher respond, Yeah, because slow research
kills people?
9
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

10
Beneficence, Science, and Placebos

• Reply to problem
• Physicians can recommend participation in
  clinical trials because they dont 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

11
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.

12
Beneficence, Science, and Placebos

• Placebos raise another problem
• Can the deliberate nontreatment of patients be
  justified? para1, p199
• The book says Yes, although
• No, if there is an effective treatment already
  available, a placebo controlled human study is
  unethical
• Also, when lack of treatment is life-threatening,
  the above rule is at its strongest
• 3 Questions
• Did the AZT placebo-controlled trial violate
  proviso 1? see quotation on p199
• If the lack of treatment results in minor harm,
  is a placebo-controlled trial permissible under
  any conditions, according to Vaughn?
• Is equipoise possible in a placebo-controlled
  trial?

13
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
• subjects are not able to comprehend enough
  science to give informed consent
• subjects may, in some cases, consent out of
  desperation, fear, or wishful thinking, all of
  which threaten informed consent
• subjects may be coerced or exploited by payments
  for helping in the research
• You should know Vaughns responses to these
  objections (1 3 he gives no reply to 2)

14
Research on the Vulnerable

• Problematic special cases involve 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
• To take children for example, Vaughn tells us
  many effective therapies that help children could
  only be developed by studies on children (as
  their physiology and pathologies differ
  substantially from adults)

15
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
• the childs 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)

16
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 Vaughns 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

17
Research on the Vulnerable

• The guidelines for treatment of the mentally
  disabled are similar as those for children, but
  with special concern for susceptibility to
  exploitation
• conditioned to defer to authority figures
• fear punishment from caretakers for refusing to
  participate
• desperation for change of routine or special
  attention might amount to coercion

18
Research on the Vulnerable

• Vulnerable subjects in Third World countries
• Vaughn provides this scenario
• AZT is a drug that reduces HIV transmission from
  women to their fetuses
• The dose of the drug was too high to be
  affordable in these countries (Thailand and some
  African countries)
• Placebo-controlled trials were conducted to
  determine if a lower, cheaper dose would work
• Because placebo-controlled trials guarantee some
  women will not get the experimental dose, those
  womens children are virtually guaranteed to get
  HIV
• The results of the trials were positive the
  lower dose worked in reducing HIV transmission
• Compare Marcia Angells condemnation of these
  trials to Baruch Brodys defense of them
  (p204-205) who is right?