Human Research: Laws, Privacy, and Confidentiality

Human Laws and Regulations

• A human subject is a living individual
• Intervention refers to physical procedures collecting data, or manipulations of a subject's environment for research, like venipuncture
• Interaction involves interpersonal contact between an investigator and a subject

Private vs Identifiable Information

• Private information relates to behavior in a context where an individual expects no observation or recording
• It includes data provided for specific purposes, with a reasonable expectation of non-disclosure, like a medical record
• Identifiable information is data that can individually identify a person
• It involves the subject's identity and associated information accessible to the investigator

Privacy vs Confidentiality

• Privacy is an individual’s desire to control access to themselves, including personal information
• Confidentiality is an investigator’s agreement on how a research participant’s identifiable private information will be managed and disseminated, including storage details

Pure Food and Drug Act (Wiley Act)

• Defined “misbranding” and adulteration in food and drugs
• Required drug labels list any of 10 "addictive" or "dangerous" ingredients
• Led to the creation of the Food and Drug Administration (FDA)

Events Leading to Pure Food and Drug Act

• Problems with adulteration involved added chemicals/ingredients in food; drugs were not correctly labeled or proven safe
• "The Jungle" highlighted diseased animals being processed into food
• Formaldehyde was used to preserve milk, causing organ damage
• Whiskey, coffee, and tea had dyes; some contained methanol, leading to blindness and death

Substances and Penalties

• Regulates food and drugs
• Violations resulted in minor financial penalties; goods in violation were seized

Federal Food, Drug, and Cosmetic Act

• Empowered the government to inspect plants and manufacturers
• Required manufacturers to file a New Drug Application for marketing
• Requires proof of safety, but not necessarily effectiveness, following the Kefauver-Harris amendment
• Labels should not have false efficacy and purity information

Events Leading to Federal Food, Drug, and Cosmetic Act

• Response to multiple poisonings, including elixir sulfanilamide poisoning which killed over 100 people, primarily children becaus testing was not required

Scope of Federal Food, Drug, and Cosmetic ACt

• Now regulates food (including gum), food additives, dietary supplements, drugs, cosmetics, and tobacco products
• Also includes medical devices: Class 1 (low risk), Class 2 (moderate risk), Class 3 (high risk)
• Originally regulated food, drugs, and cosmetics

FDA Enforcement and Penalties

• Enforces both civil and criminal law clauses
• Penalties can include fines and jail time, especially for repeated, intentional, or fraudulent violations

Nazi Medical Experiments

• Nazi medical experiments included twin experiments and exposing prisoners to extreme conditions like freezing, seawater immersion, and altitude changes
• Included deliberately infecting patients with diseases like tuberculosis and malaria

Nuremberg Trial

• The Nuremberg Trial involved the prosecution of Nazi leaders and physicians for crimes against humanity, mainly against Jews
• The Nuremberg Code is not law in the US, but serves as a principle for ethical guidelines
• Voluntary human consent is the primary tenet

Kefauver Harris Amendment

• Thalidomide, meant to relieve pregnancy symptoms and sold OTC, was the catalyst
• The FDA didn't approve thalidomide due to safety concerns, after it caused phocomelia
• It added the requirement of "proof of effectiveness" to the FDAC

Declaration of Helsinki

• The Declaration of Helsinki establishes internationally agreed ethical standards for human research subjects
• It emphasizes respect for the individual, their right to self-determination, and autonomy
• States that vulnerable groups should only be in research if there are specific health needs of that population that cannot be addressed otherwise

Vulnerable Populations

• Includes children, prisoners, pregnant women, the mentally disabled, the economically disadvantaged, the educationally disadvantaged, workers, and students
• Children, prisoners, and pregnant women receive additional federal protections

Enforcement of Declaration of Helsinki

• The FDA has adopted most versions; it cannot "break" the Declaration, but based its laws on the recommendations

National Research Act

• The Tuskegee syphilis study led to its creation
• The act established the National Commission for the Protection of Human Subjects in Biomedical and Behavioral Research aimed to describe important components of ethical research
• This commission's work was documented in the Belmont Report and then turned into law by the Common Rule

Belmont Report

• Outlines components of ethical research.
• Respect for persons, beneficence, and justice are core

Respect for Persons

• Respect for persons includes treating subjects as autonomous agents and protecting those with diminished autonomy via informed consent
• An example of violation is the Humphry study, where a PhD student acted as a "watch queen" for homosexual acts in public restrooms

Beneficence

• Beneficence dictates subjects should not be harmed
• Maximize benefits and reduce possible burdens through a risk/benefit assessment
• Tuskegee study exemplifies a violation

Justice

• Justice entails fair distribution of research benefits and risks
• Consider which groups should receive research funds and how subjects are chosen
• Subject groups should benefit from the research
• Examples of violations include Tuskegee, Nazi Experiments, Willowbrook, and Holmesburg prison experiments

Common Rule

• The Common Rule enforces principles set by the Belmont report
• Resulted in the creation of Institutional Review Boards (IRBs)

Institutional Review Board (IRB) Role

• IRBs are required for institutions undertaking federally funded research
• They evaluate proposed experiments via risk/benefit analysis

IRB Powers

• IRBs can approve, disapprove, and modify research
• Can conduct continuing reviews, observe changes, and suspend or terminate approvals

IRB Oversight

• IRBs continuously monitor approved experiments, review studies at least annually, conduct full-board reviews when required
• Must approve amendments or modifications; problems must be notified within 24 hours
• There are risks to subjects, incidents of noncompliance, and deviations from the approved study plan and violations

3 Types of IRB Review

• Full Board/Review is for studies ineligible for expedited review/exemption status and involves greater than minimal risks
• Requires convened meeting, majority presence for approval, and written notification of decisions

Expedited IRB REview

• Expedited review is for studies involving no more than minimal risk that fall into one of 9 federally defined categories
• Minimal risk examples include blood samples from healthy adults and data collection through routine non-invasive methods

Exempt IRB Review

• Exempt review means a very fast review, with just one or two people signing off
• Includes research in educational settings, using anonymous tests, involving public officials, and studying existing data
• Studies including prisoners or children are never exempt

IRB Requirements

• Anyone working on human studies experiments needs IRB approval
• Approvals require minimized risks reasonable to benefits, equitable subject selection, documented informed consent, and protection of privacy and confidentiality

Consequences of Not Following Rules

• Suspension, inability to publish data, debarment by FDA, loss of funding, IRB oversight, termination, and shut-down of all research are possible

IRB Membership Guidelines

• Requires 5+ members with diverse backgrounds (gender, race, cultural sensitivity), but no IRB member may participate in reviewing their own project

Key Features for Informed Consent

• Disclosure of needed information, facilitation of understanding, and promoting the voluntariness of the research
• Must be obtained prior to research

Informed Consent Process

• Informed consent must be obtained from capable adults or a legally authorized representative
• For children, one or both parents/guardians are needed, with the child's assent in age-appropriate language
• Participants can withdraw, but assent is not required is the child is unable to provide it

What constitues Informed Consent?

• The consent must describe the overall experience, benefits, and alternatives
• It must detail the extent to which private information is protected and explain compensation if research-related injury has occurred
• People must be shown to retain the right to withdraw

Types of Research Risk

• Minimal risk: The probability and magnitude of harm/discomfort are no greater than daily life
• Research greater than minimal risk requires full review

Study Preparation

• Experiments/events require knowing the victims, procedures, laws broken, belmont violations, and regulations influenced

Studies to Consider

• Patent medicine/snake oil/jungle had unethical conditions for products; Elixir Sulfanilamide was toxic with no drug testing prior
• Nazi Medical Experiments- Hypothermia Studies lacked justice, consent, autonomy, and beneficence
• Willowbrook Hepatitis Study had justice violation by infecting uninfected children
• Thalidomide harmed children's health from the birth defects (phocomelia)
• Tuskegee Syphilis Study failed beneficence/justice, as penicillin was hindered, withheld condition details, and allowed the spread of illness

Studies that involved Prison Population

• Holmesburg Prison Experiments gave no justice; prisoners have reduced autonomy
• In the prison system, the prisoners are offered incentives, but confidentiality has limits to escape
• MK Ultra manipulated mental states using LSD, and sometimes resulted in death
• Stanford Prison Experiment involved harm to the volunteers, which violated a failure to protect from harm
• Henrietta Lacks involved a family without consent of compensation

Animal Laws: Vivisection

• Vivisection is first identified animal experimentation
• It includes surgery on living organisms for experimental purposes (humans and animals)
• Coronary circulation and surgery practice both examples of vivisection

Cruelty to Animals Act

• The act emerged after anti-vivisectionist movements protested against using animals for entertainment
• Experiments are only allowed for teaching purposes/to save/prolong human health
• Anesthesia must be provided to animals
• The bodies of the animals must only be used one time and destroyed after

Role of Federal Food, Drug, and Cosmetic Act in Animal Experiments

• Safety must be proven prior to public release
• This caused medical testing on animals and created NIH oversight that was largely guideless

Animal Welfare Act

• The act was made to reduce kidnapping that took animals from homes for science
• Federal law that sets standards for housing, sanitation, food, water, and veterinary care
• Amended eight times
• Enforced by USDA through APHIS, including unannounced inspections, fines, and license suspension

Scope of animal welfare

• AWA protects living vertebrates, except for farm animals, cold-blooded species, horses, fish, invertebrates, rats, and mice

AWA requirements

• Entities dealing with animals must be licensed/registered
• Required vet care: animal must consult a vet to minimize pain

3 R's of Animal testing

• Replacement: Conscious animals replaced with unconscious material or less sentient species.
• Reduction: Use as few animals as possible
• Refinement: Minimize harm to animal subjects

ARRIVE Testing

• Mandates that ethical 3Rs must create reproducible research
• Published results must contain housing information
• It also prevents harm to animals and ensures data is utilized

Silver Springs Monkeys

• Edward Taub + The use of The Silver Springs Monkeys was the catalyst for the IACUC
• PETA became a national group
• The IACUC must: approve protocols (3R's), undergo monitoring, and yearly reviews
• The Silver Springs Monkeys involved cutting sensory nerves in a monkey’s arm and forcing relearning with the good arm constrained, ethical violations included not providing proper care and house monkeys

Key Criteria of IACUC

• It needs 3 min members, a Committee Chair appointee and a Veterinarian, a Scientist experienced with the research and a non-scientist member
• It must not be affiliated with the institution

Endagered Species Act

• The act came to be due to the endangerment of species
• The act provides protection to prevent extinction
• Enforced U.S. Fish and Wildlife Service

Criteria

To be listed:

• There has to be threatened present day habitat curtailment.
• There has to be an overuse of species by humans
• The species is declining due to disease/predation
• The is the inadequacy of regulating
• There are outside internal pressures for the curtailment
• It can be delisted only in recovery

Animal Testing and roles for Chimpazees

• Chimps used to be used for research for most genetic relationships
• Now in most cases they can't develop full blown AIDS and the money for testing is phased out, they are also retired to laboratories.

Environments and attitudes

Nature has a value, but that is for our use. There should be protection and preservation. Tragedy can occur

Early grassroots

• Sierra club promotes green policies and responsible use of the earth's ecosystem
• Audubon Societies: Bird conservation and habitats
• Migratoary Birds act prevents slaughter of birds for feathers for millinery

Testing for toxicity

• A Sand Country Almanac states that the environment has a value outside of humanity. DDT declined bird population

DDT

• There was toxicity for DDT, it killed more than just mosquitos, and humans had too much of it from being resistant. This also caused air pollution

Air Pollution Act

• 1st air policy that provides money
• Clean air act controls pollution w/fines and enforces method for control measures
• EPA EnFORCE CAA

Penalties for Violations

• Penalties for violations:Citizen lawsuits and Civil cleanup

Domoara Smog

• Had 20 deaths and caused toxicity for the environment
• Mauna Loa is important because it monitors the air and monitors pollution level
• Carbon dioxide leads to H iodine increase. Pterodons unable to produce shells

Fed Waster Pollution Act. 1948 -

• The first laws to address pollution
• Clean water act: US waterways wear unfit and it regulates discharges. Point source- single discharge (Ex factories)
• Endocrine disrupter screening program

Other important regulations

In the Flint crisis there was the switch from lake Huron to Flint river and there was too much corrosion. There was death and people instructed to use bottled water.

• The epa in force laws. And manages waste

Overview of human research subject regulations, focusing on defining human subjects, intervention, and interaction. Explains private versus identifiable information, privacy rights, and researcher confidentiality agreements. Covers ethical considerations in research.