Human Subjects Laws and Regulations

Human Subjects Laws and Regulations

• Laws and regulations exist to protect human subjects involved in research.
• The Department of Health and Human Services (HHS) defines a human subject as a living individual about whom a researcher obtains data through intervention or interaction or from individually identifiable information.

Human Subject Definition (HHS)

• A human subject is a living individual.
• Researchers (professionals or students) must obtain data through intervention or interaction with the individual or from individually identifiable information.
• Cadavers, decedents, and biospecimens are not considered human subjects.
• Additional rules exist regarding information and privacy.

Intervention and Interaction

• Intervention: Both physical procedures (e.g., venipuncture) and manipulations of the subject or their environment for research purposes.
• Interaction: Communication or interpersonal contact between the investigator and the subject.

Privacy vs. Confidentiality

• Privacy refers to an individual's desire to control access to their personal information. Factors to consider include how participants are contacted, the research setting, and the type of information collected.
• Confidentiality refers to how the researcher manages the participant's identifiable private information, including storage, protection, and dissemination.

Privacy versus Confidentiality

• Privacy concerns the people.
• Confidentiality concerns the data.

Privacy versus Confidentiality (Example)

• In a study on men's ice cream preferences, subjects signed consent forms stating that their answers would be kept in a locked cabinet.
• However, researchers failed to follow the procedure and left the surveys exposed on their desks, which does not maintain confidentiality despite not being visible to the public

History of Human Subjects Research

• Historical examples of unethical experiments, such as Nazi medical experiments and the Tuskegee syphilis study, informed current regulations in human subjects research.
• Early forms of medical practices (like Hippocratic traditions) focused on observations and experimentation in order to inform medical practices

Pure Food and Drug Act (Wiley Act) - 1906

• Led to the creation of the Food and Drug Administration (FDA).
• Harvey Washington Wiley spearheaded the law.
• Key definitions for misbranding and adulteration were included and were required on food and drug labels.
• Severe or egregious violations led to financial and physical penalties for those implicated or responsible for those violations

How did the Pure Food and Drug Act Come About?

• Food adulteration was a prevalent issue.
• Upton Sinclair's "The Jungle" was a notable factor in the formation of the act
• The Meat Inspection Act was passed on the same day.

Example of Food Adulteration (Prior to the Wiley Act)

• Milk adulteration was a major problem.
• Formaldehyde was added to preserve it but caused serious health problems, especially to children.
• Other types of food adulteration occurred as well. Food makers added dyes, sawdust, and other cheap fillers in order to make profitable products.

The Jungle

• Upton Sinclair's exposé of unsanitary conditions in Chicago's meatpacking industry.
• Inspired the FDA.
• Details unsanitary food preparation and handling practices of diseased animals that were incorporated into food products.

Federal Food, Drug, and Cosmetic Act - 1938

• Response to multiple poisonings, including the sulfanilamide poisoning incident.
• Increased regulation of drug safety and efficacy.
• Prior to this act, no new drug testing required.
• This act also regulated many other aspects of food preparation, labeling, and other practices.

Federal Food, Drug, and Cosmetic Act - 1938 (Continued)

• This act changed the way drugs were approved by requiring new drug testing in addition to increasing the amount of research needed.
• Overhauled the FDA for more safety testing prior to approval, in addition now requiring manufacturers to prove safety and effectiveness
• This act also prohibited the use of fraudulent labels or statements with regard to products efficacy and purity

Federal, Drug, and Cosmetic Act: What happens if you violate the FDAC now?

• Violators face both civil and criminal penalties (fines and jail time for severe cases)
• Repeated, intentional, or fraudulent violations are considered criminal acts

What Does FDA cover now?

• This act covers food, including gum, and food additives, dietary supplements, drugs, cosmetics, and tobacco products, medical devices with various classes (1, 2, & 3).

Class Question

In the example question of Alan and chocolate, this is an example of confidentiality, not privacy.

Nuremberg Code, 1946.

• First documented set of research ethics principles meant to prevent crimes like those committed by Nazis.
• Not legally binding in the U.S.
• Provided framework for ethical research practice

Kefauver Harris Amendment, 1962

• Response to thalidomide tragedy.
• Overhauled the FDA to require substantial additional safety testing before drug approval.
• Required manufacturers to prove the effectiveness of their drugs.
• Updated drug advertising to accurately represent side effects

Thalidomide

• A hypnotic/sedative that caused birth defects (phocomelia).
• Sold as an OTC medication in several countries.
• FDA failed to provide approval in the US due to insufficient safety testing.

How does thalidomide cause phocomelia?

• Metabolite of thalidomide has antiangiogenic effects.
• Given during critical limb development, causes phocomelia.
• Thalidomide is now used to treat leprosy and multiple myeloma.

Declaration of Helsinki, 1964

• Ethically guides human subjects research practices internationally.
• Does not have legal force in the U.S.
• States that researchers are ethically responsible to subjects

Declaration of Helsinki (DoH)-1964, Continued

• Not legally binding in the US for research with human participants
• Important guiding principles, laws, and ethical standards in other countries
• Still important guidelines that impact the ethical conduct of human subjects research

Declaration of Helsinki and Vulnerable Populations

• First set of regulations to consider unique needs of vulnerable groups.
• Vulnerable groups include, but are not limited to children, prisoners, pregnant women, mentally disabled, economically disadvantaged, educationally disadvantaged, workers, and students.

Willowbrook Hepatitis Study, 1956-1970

• Children with intellectual disabilities at a state institution, exposed to hepatitis to track virus development.
• Considered one of the most unethical experiments due to the deliberate exposure of uninfected children to hepatitis A.
• Practiced in unsafe conditions that contributed to widespread outbreaks and infection .

Tuskegee Syphilis Study, 1932-1972

• Followed the progression of syphilis in African American men without treatment.
• Men were not informed of their disease, and were not given necessary medical care.
• Considered one of the most unethical experiments.
• Termination occurred in 1972. Subsequent legal actions and settlements occurred

National Research Act- 1974

• Established the National Commission for the Protection of Human Subjects of Biomedical and Behavioral Research.
• Created the Belmont Report.

Belmont Report- 1979

• Set of ethical principles for human subjects research.
• Three core principles: Respect for persons, Beneficence, and Justice.

Understanding the Principles: Respect for Persons

• Subjects treated as autonomous agents.
• Subjects with diminished autonomy must be protected (e.g., informed consent).

Understanding the Principles: Beneficence

• Benefits of research should be maximized.
• Any possible harm should be reduced.

Understanding the Principles: Justice

• Benefits and risks of research are fairly distributed.
• How are subjects chosen?

Examples of Violations (Respect for Persons):

• A sociologist performing a secret study on homosexual men in public restrooms without their knowledge or consent.

Examples of Violations (Beneficence):

• Not providing necessary treatment to study participants.
• Exposing study participants to risks not proportional to expected benefits.

Examples of Violations (Justice):

• Using vulnerable populations (e.g., prisoners, children) as subjects when their needs were not adequately addressed, or not providing needed treatment.

IRB Approval

• Minimizing risks and protecting subject benefits.
• Equitable selection of subjects.
• Obtaining and documenting informed consent and maintaining confidentiality.
• Addressing needs of vulnerable subjects

Consequences if Regulations Not Followed

• Suspension or inability to use data or publish research.
• Debarment and inability to receive funding.
• Additional IRB oversight, Termination of employment, and loss of licences.
• Immediate shut down of research by the institution.

IRB Membership Guidelines

• At least 5 diversity members with a background of knowledge in their profession to promote a complete and adequate review of the research being conducted by the institution
• At least 1 person on the group that is not a member of the institution (i.e. a community representative).
• Should consist of both professionals from a wide-range of fields, to include but not limited to a scientist and a non-scientist.

Informed Consent

• Must be obtained prior to research, fully documented in writing.
• Disclosing necessary information and facilitating subject understanding.
• Promoting the voluntariness and freedom of research choices.
• Subject may withdraw at any point

Informed Consent (Continued)

• Adult capable of consenting gives consent
• Legally authorized representative makes consent for someone without the ability to give consent
• For research or procedures involving children, there must be parental consent and age-appropriate assent from minors

Additional Unethical U.S. Human Experiments:

• Holmesburg Prison Experiments -- Post WWII testing grounds. Subjects exposed to toxins and drugs.
• MKUltra - CIA mind control program. Subjects exposed to LSD, hypnosis, sleep deprivation.
• Stanford Prison Experiment -- Studied the effects of social roles and power.
• Tuskegee Syphilis Experiment -- African American men with syphilis were not treated.
• Henrietta Lacks - HeLa cells (cells from Henrietta Lacks) were taken without her knowledge and are essential to research today
• These experiments violated many principles, including informed consent and the use of vulnerable populations, and raised serious ethical concerns about human subject research.

Prisoners as a Vulnerable Group

• Subpart C defines prisoners as involuntarily detained individuals.
• Researchers must take additional steps to ensure proper protection and safeguard prisoners involved in research to prevent the exploitation of their vulnerability.
• Research involving prisoners must be only minimal risk
• Should include categories of research that takes into consideration the issues that may be faced by a prisoner

Prisoners Special Considerations

• Considerations regarding consent for prisoners to participate in research
• Financial incentives to participate in research(small incentives may seem significant to a prisoner on a low income)
• Confidentiality in the prison setting. Information about convictions and other sensitive topics should be treated with confidentiality and caution

Special Considerations—Breach of Confidentiality

• A researcher is studying child abuse history of pedophiles for treatment strategies and must ensure confidentiality to avoid further harm to the subject of the study
• Protecting the privacy of study subjects and protecting them from further harm.
• Even when information is public record, there are legal limits to confidentiality that must be addressed during the study.

Types of IRB Review

• Exempt: Largely administrative studies
• Expedited: Fewer ethical considerations; some risks may be involved.
• Full: Greater ethical considerations; more risk factors that may require full review

Additional Roles of the IRB

• Must re-review studies at least once per year in many circumstances.
• Must approve any modifications and additional considerations to the proposed experiment.
• Must be notified right away and within 24 hours if any adverse or unanticipated events occur or if there is non-compliance.

Institutional Review Boards (IRB)

• IRBs review research projects involving human subjects to ensure ethical conduct.
• They are required of all institutions receiving federal research funding.
• Their primary job is risk/benefit analysis.
• They approve, monitor, and review all scientific research

IRB Membership Training Requirement

• All participants in projects that include humans need special IRB certification to be involved and participate in certain roles involved in the research.
• Volunteer, students, and support personnel all must have IRB training if they are involved in research of human participants.

What Power Do IRBs Have

• Approve, disapprove, or modify research
• Conduct continuing reviews over the years
• Observe, verify, and/or suspend any changes made to the original research experiment.
• Observe the consent process and research procedures.

This quiz covers the laws and regulations designed to protect human subjects in research. It includes definitions from the Department of Health and Human Services and highlights the importance of intervention and interaction in research practices. Test your knowledge on the ethical considerations and guidelines governing human research.