Human Subjects Research

Hippocrates

believed health was a balance between blood, phlegm, yellow bile, and black bile

believed diseases were caused naturally, not supernaturally

do no harm, benefit the sick

Galen

developed Hippocrates’ humorist theory

dissected and experimented on animals

advanced anatomy significantly

Scientific Revolution

16th-18th century

dissection and documentation of the human body

Edward Jenner

founder of immunology

developed smallpox vaccine

William Beaumont’s Digestion Experiments

founder of gastric physiology

WWII Experiments

thousands of human subjects

no consent, poor design, not conducted by researchers

hypothermia studies, wound healing, infection, endurance, twin studies

Tuskegee Syphilis Study

participants not told they had syphilis, treatment was withheld

Health and Disability Commissioner Act

promote and protect the rights of health consumers and disability services consumers

HDC Code of Health and Disability Services Consumers’ Rights Regulation

closure 1: establishes the duties and obligations of providers to comply with the code and to promote its awareness

closure 2: the rights of consumers and duties of provider

closure 3: sets out provider compliance requirements and states that where the rights cannot be met then the onus is on the provider to show that it was reasonable in the circumstances not to have done so

Five Elements of Valid Consent

disclosure, understanding, voluntariness, competence, and the act of consent itself

Placebos are Acceptable When:

no established effective intervention exists

withholding treatment causes at most temporary discomfort or delay

there are compelling scientific reasons and no risk of serious or irreversible harm from not receiving the best proven intervention

Vulnerability

compromised decision making capacity and lack of power

Decision Making Capacity (DMC)

the psychological ability to make reasonable choices, distinct from legal competence

Willowbrook Hepatitis Experiments

state school where mentally disabled children were housed and cared for

researchers tested anti-hepatitis antibodies as therapy

newly admitted children were deliberately infected with hepatitis after receiving antibodies

consent was obtained from parents, framed deliberate infection as prevention

Dan Markingson and the CAFE Study

Markingson recruited into the study, an AstraZeneca sponsored trial comparing three antipsychotic drugs

Markingson enrolled despite questionable competence

His condition worsened, eventually killed himself

AstraZeneca paid the department at UMN for each subject that completed the study

Study team ignored the mother’s warnings

Key Protections for Vulnerable Subjects

use of legally authorize representatives when subjects cannot consent

assent from subjects who cannot formally consent but can cooperate

independent assessment of DMC for higher-risk research

limits on permissible risk levels for specific vulnerable groups

legitimate scientific justification required for including vulnerable subjects

ethics committee members with relevant expertise in the vulnerable population

NEAC on Vulnerability

do not exclude patients because they are vulnerable

include the least vulnerable participants consistent with study aims

valance inclusion with reduction of unnecessary risk and exploitation

provide all potentially vulnerable participants with support

balance rights and potential benefits against increased risk of harm

research must include Māori participants unless valid justification for exclusion exist

Explotation

taking unfair advantage of another person or group

failure of justice

unfair distribution of benefits and burdens in a transaction or relationship

three elements: injustice, disrespect, harm

Pfizer/Trovan Trial in Nigeria

Pfizer tested a new antibiotic during a meningitis epidemic on 200 children, the control group received standard therapy

inadequate consent, dose given to control group was reduced to bias results, lead investigator provided a falsified letter of ethics committee approval, 11 children died

The AZT Trials

15 sub trials in sub saharan Africa tested whether a cheaper, shorter course of AZY could reduce mother to child HIV transmission

the control group received placebos, not the 076 protocol (established protocol in developed nations)

case against the trials: the trials exploited the fact that participants lacked access to AZT, it was unethical to not offer the control group a treatment

case for the trials: participants in the control group were not being denied treatment they would otherwise receive. participation did not make them worse off. trials were approved by local authorities, WHO, and more. within a year, the trials allowed the production of a treatment that would actually be accessible to developing nations

Universal Standard of Care

control groups should receive the best proven intervention available anywhere

Local Standard of Care

control groups should receive whatever is actually available in the host country. what matters is whether participation makes subjects worse off

Capacity Building

a responsibility to contribute to local research and health capacity when conducting research in settings with limited resources

it is a direct beneft to the host country that partially addresses the exploitation concern and a strong local oversight is itself a protection