Laura Guidry-Grimes, PhD

Assistant Professor of Medical Humanities and Bioethics

■ Extra time, resources, approvals

■ Might not receive enough volunteers for important research

■ If subjects are allowed to back out of research and refuse

their previously acquired data, then some research will never
achieve large enough ‘n’ for useful results.

■ The “good of the state” or good of the many might seem

really urgent
FIRST, SOME HISTORY
Ethical Codes Arise Out of Tragedy
■ Aimed at survival of Axis military
– Determine max. altitude from which crews could survive by parachute;
freezing to find hypothermia solutions

■ Pharmaceutical and treatment methods for military personnel

– Immunization compounds for malaria, typhus, TB, typhoid, yellow fever,
infectious hepatitis; mustard gas antidotes

■ Advance racial and ideological tenets of Nazism

– Twin studies; serological tests to determine how different “races” withstood
contagion
“Nazi Medical Experiments” by US Holocaust Memorial Museum
■ Voluntary consent
■ Fruitful results, unprocurable by other methods
■ Prior animal studies
■ Avoid all unnecessary pain, suffering, injury
■ No experiment where already reason to believe death or disabling injury
will occur
■ Degree of risk proportionate to humanitarian importance
■ Proper facilities and preparations to minimize harm
■ Only scientifically qualified persons allowed to conduct studies
■ Subjects at liberty to end participation at any time
■ End any study the moment the harms outweigh possible benefits
“The Nuremberg Code was conceived in reference to Nazi atrocities
and was written for the specific purpose of preventing brutal excesses
from being committed or excused in the name of science. The code ...
is in our opinion not necessarily pertinent to or adequate for the
conduct of medical research in the United States”

Joseph Gardella, MD (1962)

Assistant Dean of Students, Harvard Medical School
■ African American men in AL selected for study of “bad blood”
– 399 w/syphilis, 201 w/o as control group
– Not told they had syphilis
– Prevented from knowing when penicillin became readily available in 1947

■ Researchers claimed to be conducting “study in nature” as passive

observers
– Believed this population was unlikely to seek treatment anyway (racist
assumptions)

■ Inducements to maintain participation over the years

– Free meals, “free treatment” for “bad blood,” burial expenses
– Researchers justified 40-year long study on basis that this was better medical
care than these people would otherwise receive (again, racist assumptions)
■ Thousands of children with a variety of psychiatric, cognitive,
and neurological conditions lived in Willowbrook
 overcrowding, poor facilities, inadequate staff
contributed to hepatitis outbreaks

■ Researchers intentionally infected children w/ hepatitis

– Justified by researchers because any non-infected child was already at
high risk for contracting it and because subjects had special staff
attention and lived in isolated units
– Parents given bare consent with manipulative elements (see prior slide)
– Led to significant innovations in hepatitis vaccines
■ 1966 publication of 22 ethically problematic published
research trials
– Injecting cancer cells into non-consenting elderly
patients
– Exposing institutionalized children to hepatitis
– No-therapy control groups in serious, treatable
diseases
■ Some highlights:
– “While the primary purpose of medical research is to
generate new knowledge, this goal can never take
precedence over the rights and interests of individual
research subjects.”
– Risks must be continually monitored and minimized.
– Vulnerable groups should receive “specifically considered
protection,” including in consenting practices.
■ National Research Act of 1974 
Commission for the Protection of Human
Subjects of Biomedical and Behavioral Research

■ Experts from multiple disciplines meet at Belmont

Conference Center
– Report leads to revisions of Code of Federal Regulations 
Adopted by 14 other federal agencies in 1991 
the Common Rule is born
■ BENEFICENCE
– Strict obligation to 1) do no harm + 2) maximize
potential benefits and minimize potential harms

■ JUSTICE
– Equals ought to be treated equally + fair distribution

■ RESPECT FOR PERSONS

– Respect autonomous decisions + protect those with
diminished autonomy
■ Human Subjects Research and IRBs (45 CFR Subpart A)
■ Additional protections for pregnant women, fetuses,
neonates (45 CFR Subpart B)
■ Additional protections for prisoners (45 CFR Subpart C)
■ Additional protections for children (45 CFR Subpart D)

* Note: revisions underway… Take a look

 RESEARCH DESIGN
Yes, There Are Ethical Components to This.
 Could subjecting participants
to any amount of risk be
worth it based on foreseeable
benefits and possible harms?

■ Valid and important question?

■ Sound methodology?
■ Solid plan for protecting private information?
■ Not exploiting vulnerable population?
■ Clinical equipoise – no one intervention is known to
be better for this group?
■ Plans and remedies in case of harm or error?
■ Benefits considered according to..
– Directly beneficial or nonbeneficial
– Probability
– Participant’s individual considerations

■ Actively minimize risks

– Continual monitoring of adverse events and protocol deviations
– Responsible reporting (IRB, DSMB, funding agency, compliance
office)
– Transparency when anything shifts benefit-risk balance for
participants, including critical findings
– Protect identifiable sensitive information about the participants
and any third parties
■ Recruitment techniques
– Manipulative? Taking advantage of vulnerable persons? Fair
and sensible?

■ Inducement
– None vs. reimbursement vs. compensation vs. incentive
■ Clear and respected right of exit
■ Access to participation and to benefits
– Systematic exclusion of population that could benefit from
findings? Likelihood that study group could benefit at all from
the findings?
CONSENT & ASSENT
Some Basics…and Some Complexities
1. Disclosure

2. Conversation ONGOING PROCESS

not a single event,
not merely signing a form
3. Authorization
■ That this is a research study.
■ Purpose of the study
■ What their participation involves at each stage
■ Their rights and responsibilities
■ Possibility of not receiving study intervention
■ Risks and benefits of participating
■ Cannot always tailor to informational and autonomy needs of
particular participant

■ Limitations in information processing, understanding, health literacy

■ Therapeutic misconceptions

■ Research study designs

– Consenting to a survey vs. specific experimental device vs. biobank
– Single- and double-blind studies
– Placebo control group
■ Positive agreement from participant who is incapable of giving
consent
– Still require consent from parent/guardian/LAR

■ IRBs can differ in their assent requirements

– Consider “age, maturity, and psychological state of the children
involved” (45 CFR, §46.408)
– Ethically can be reasonable to include in protocol, regardless of
IRB requirements

■ Dissent as ethically binding for nonbeneficial research, but not for

beneficial research
■ Autonomy and liberty rights
■ Protection against coercion, deception
■ Respecting individual as individual
– even a developing one
■ Building trust, therapeutic alliance
■ Helping to minimize/manage risks and harms
– From participant’s own perspective
SCENARIO TO CONSIDER
Imagine this…
■ There is a proposed study that could potentially make strides toward
eradicating non-lethal but prevalent STIs. The research design calls
for a large infected group that can be tested and retested at regular
intervals. The researchers cannot find volunteers in their local
community.
– The researchers find that they can obtain their results more
expediently by testing subjects in Guatemala.
– Prisoners, soldiers, patients in a psychiatric hospital, and
commercial sex workers are exposed to STIs, some with consent.
– Serology experiments are conducted without intentional
exposure on children from state-run schools, an orphanage, and
rural towns.
– What are some ethical concerns about this study? Should the
researchers or other interested parties be permitted to use their
data if they are able to complete this research?