Ethical Principles of Ethical Principles of Human Subjects Human Subjects

ResearchResearchHuman Subjects Protection ProgramHuman Subjects Protection Program

Office of the Vice President for ResearchOffice of the Vice President for ResearchUniversity of MinnesotaUniversity of Minnesota

Minneapolis, MNMinneapolis, MN

NurembergNurembergDuring the Nuremberg During the Nuremberg War Crimes Trials, 23 War Crimes Trials, 23 German doctors were German doctors were charged with crimes charged with crimes against humanity foragainst humanity for ““performing medical performing medical experiments upon concentration camp inmates and other experiments upon concentration camp inmates and other living human subjects, without their consent, in the course living human subjects, without their consent, in the course of which experiments the defendants committed the of which experiments the defendants committed the murders, brutalities, cruelties, tortures, atrocities, and murders, brutalities, cruelties, tortures, atrocities, and other inhuman acts.other inhuman acts.””

The Nuremberg Code (1947)The Nuremberg Code (1947)As part of the verdict, the Court enumerated some As part of the verdict, the Court enumerated some

rules for "Permissible Medical Experiments", now rules for "Permissible Medical Experiments", now known as the known as the ““Nuremberg CodeNuremberg Code””. These ten rules . These ten rules include:include:

Voluntary consentVoluntary consent Yield fruitful results otherwise unobtainableYield fruitful results otherwise unobtainable Based on animal experimentsBased on animal experiments Avoid physical and mental sufferingAvoid physical and mental suffering Not done if injury expectedNot done if injury expected Risk less than importance of problemRisk less than importance of problem Protect subject from injuryProtect subject from injury Conducted by qualified peopleConducted by qualified people Termination by subjectTermination by subject Termination by investigatorTermination by investigator

Brief History of IRB: 1940s: A series of research abuses starts in Tuskegee, Alabama. In one study on the natural history of untreated syphilis, poor, black males are uninformed of their disease and denied treatment even after a treatment is found in 1947. The abuses are revealed in 1972. 1950s:Willowbrook Hepatitis Studies. Intentionally infecting otherwise healthy children with hepatitis; parents were told children could not be enrolled into the institution unless children agreed to be in the research study

1960s:Jewish Chronic Disease Hospital Studies. Studies on chronically ill, mostly demented patients in the Chronic Disease Hospital in NYC. All the subjects had compromised immune systems so researchers injected live cancer cells into the bloodstream of the subjects so doctors could see how a weakened immune system would influence the spread of cancer.

History, continuedHistory, continuedMilgram Studies of Obedience. The researcher wanted to understand the Nazis and

the “just following orders” mentality. The subjects questioned other subjects and if they gave a wrong answer they were to give them a shock; the shock was increased with each wrong answer. Shock actually wasn’t given but the subject on the other end acted like it was.

Holmesburg Prison Experiments. 1950s to mid-70s. 33 pharmaceutical companies tested 153 experimental drugs. Albert Kligman, “acres of skin,” dermatology experiments. Psychotropics, eye drops, radioactive isotopes.

Stanford Prison Experiment. Two week study to look at personality and obedience. Randomized into prisoners and guards. Research lost control, ended after 6 days.

Tearoom Trade Study. Research on male/male sexual encounters in publics restrooms. Researcher observed, did not indicate he was a researcher, wrote down license plate numbers and followed men home, often married.

National Research Act

1974: The National Commission for the Protection of

Human Subjects of Biomedical and Behavioral Research is established and the National Research Act is passed by Congress. This Act requires all research involving human participants to be regulated.

The Belmont ReportThe Belmont ReportEthical Principles and Guidelines for the Ethical Principles and Guidelines for the

Protection of Human Subjects of Protection of Human Subjects of ResearchResearch

The National Commission for the Protection of The National Commission for the Protection of Human Subjects of Biomedical and Behavioral Human Subjects of Biomedical and Behavioral

ResearchResearchApril 18, 1979April 18, 1979

The Belmont ReportThe Belmont ReportBasic Ethical Principles:Basic Ethical Principles: Respect for PersonsRespect for Persons

– Individual autonomyIndividual autonomy– Protection of individuals with reduced autonomyProtection of individuals with reduced autonomy

BeneficenceBeneficence– Maximize possible benefits and minimize Maximize possible benefits and minimize

possible harmspossible harms– Do not harmDo not harm

JusticeJustice– Equitable distribution of research costs and Equitable distribution of research costs and

benefitsbenefits

Respect for PersonsRespect for Persons Treat individuals as autonomous agentsTreat individuals as autonomous agents Do not use people as a means to an Do not use people as a means to an

endend Allow people to choose for themselvesAllow people to choose for themselves Give extra protection to those with Give extra protection to those with

limited autonomylimited autonomy– Informed consentInformed consent– Respect for privacyRespect for privacy

BeneficenceBeneficence Acts of kindness or charity that go beyond Acts of kindness or charity that go beyond

dutyduty Obligations derived from beneficenceObligations derived from beneficence

– Do not harmDo not harm– Prevent harmPrevent harm– Prevent evilPrevent evil– Promote goodPromote good

Good research designGood research design– Competent investigatorsCompetent investigators– Favorable risk-benefit analysisFavorable risk-benefit analysis

JusticeJustice Treat people fairlyTreat people fairly Fair sharing of burdens Fair sharing of burdens

and benefits of researchand benefits of research Distinguish procedural Distinguish procedural

justice from distributive justice from distributive justicejustice

Equitable selection of Equitable selection of subjectssubjects

Defining Human Subjects Defining Human Subjects Research Research What is research?What is research?

Federal research regulations define it Federal research regulations define it as: (1) a as: (1) a systematic investigationsystematic investigation, , including research development, including research development, testing, and evaluation, (2) designed testing, and evaluation, (2) designed to develop or contribute to to develop or contribute to generalizable knowledgegeneralizable knowledge

[45 CFR 46.102(d)][45 CFR 46.102(d)]

What does that mean?What does that mean? (1) systematic investigation(1) systematic investigation

hypothesis testing; multiple subjects, same set of hypothesis testing; multiple subjects, same set of questions; comparison over time vs. single story or questions; comparison over time vs. single story or case; no set hypothesis; phenomenological activitycase; no set hypothesis; phenomenological activity(where ever the conversation goes)(where ever the conversation goes)

(2) generalizable knowledge (2) generalizable knowledge draw general conclusions about multiple draw general conclusions about multiple cases/stories; apply knowledge broadly to a group cases/stories; apply knowledge broadly to a group vs. describing one story/case; anecdotal informationvs. describing one story/case; anecdotal information

Must be both of these; this is only the first stepMust be both of these; this is only the first step

Next Step: Human SubjectNext Step: Human Subject Federal research regulations define a Federal research regulations define a

human subject as: a living individual human subject as: a living individual about whom about whom an investigator an investigator conducting research obtains (1) data conducting research obtains (1) data through through intervention or interactionintervention or interaction with the individual or (2) with the individual or (2) identifiable identifiable private informationprivate information

[45 CFR 46.102(f)(1),(2)][45 CFR 46.102(f)(1),(2)]

Human Subject definition, broken Human Subject definition, broken downdown

Intervention Intervention both physical procedures by which both physical procedures by which data are gathered (for example, venipuncture) data are gathered (for example, venipuncture) and manipulations of the subject or the subjectand manipulations of the subject or the subject’’s s environment that are performed for research environment that are performed for research purposespurposes

InteractionInteraction communication or interpersonal communication or interpersonal contact between investigator and subjectcontact between investigator and subject

What does that mean?What does that mean? Private informationPrivate information includes information includes information

about behavior that occurs in a context in which about behavior that occurs in a context in which an individual can an individual can reasonably expect that no reasonably expect that no observation or recording is taking placeobservation or recording is taking place, and , and information which has been provided for specific information which has been provided for specific purposes by an individual and which the purposes by an individual and which the individual can reasonably expect will not be individual can reasonably expect will not be made public (for example, a medical record). made public (for example, a medical record). Private information must be individually Private information must be individually identifiable in order for obtaining the information identifiable in order for obtaining the information to constitute research involving human subjects.to constitute research involving human subjects.

Human Subjects ResearchHuman Subjects Research In order for a project to require IRB In order for a project to require IRB

review, it must be both research and review, it must be both research and involve human subjectsinvolve human subjects

Exempt Expedited FullExempt Expedited Full

Review Continuum

Low Risk High

(not exempt from review, (not quick) (also not quick!!) per Institutional policy)

Level of risk determines route of review

Exemptions federal criteria for low-risk researchfederal criteria for low-risk research six categories of researchsix categories of research non-vulnerable populationnon-vulnerable population usually short durationusually short duration no identifiers (no permanent record no identifiers (no permanent record

of individual)of individual)PROCESS: PROCESS:

file form with IRB by emailfile form with IRB by emailallow 5-10 business days for reviewallow 5-10 business days for review

Expedited Review

federal criteria for minimal risk federal criteria for minimal risk research (nine categories)research (nine categories)

non-vulnerable populationsnon-vulnerable populations non-sensitive topicsnon-sensitive topics

PROCESS: PROCESS: file form with IRB by file form with IRB by emailemail, 2-3 weeks, 2-3 weeks

Full Committee Review

vulnerable populationsvulnerable populations invasive procedures (physically or invasive procedures (physically or

psychologically invasive)psychologically invasive) sensitive topicssensitive topics investigational products (FDA)investigational products (FDA)

PROCESS: PROCESS: file form with IRB by file form with IRB by email, 4-6 weeksemail, 4-6 weeks

Who is on the IRB? UMN Faculty (all campuses)UMN Faculty (all campuses) UMN StaffUMN Staff UMN StudentsUMN Students Fairview System EmployeesFairview System Employees Community RepresentativesCommunity Representatives

– (non-affiliated members)(non-affiliated members)

Number of Meetings per Number of Meetings per monthmonth

5 Medical Meetings (including one 5 Medical Meetings (including one continuing review meeting)continuing review meeting)

1 Faculty Social/Behavioral Sciences 1 Faculty Social/Behavioral Sciences meetingmeeting

1 Student Social/Behavioral Sciences 1 Student Social/Behavioral Sciences meetingmeeting

Committee ActionsCommittee Actions Approved as SubmittedApproved as Submitted

SuggestionsSuggestions

Stipulations must be metStipulations must be met

DeferralDeferral

Not ApprovedNot Approved

IRBs give special IRBs give special consideration to:consideration to: Vulnerable Subjects:Vulnerable Subjects:

– childrenchildren– prisonersprisoners– mentally disabled personsmentally disabled persons– economically disadvantaged personseconomically disadvantaged persons– educationally disadvantaged personseducationally disadvantaged persons

Other considerations Other considerations when defining when defining ““VulnerableVulnerable””:: LanguageLanguage

CultureCulture Current Events or Incidents Current Events or Incidents Age (elderly)Age (elderly) Age (adolescents)Age (adolescents) Transient Cognitive ImpairmentTransient Cognitive Impairment Chemical UseChemical Use Health StatusHealth Status Students/EmployeesStudents/Employees

Sensitive TopicsSensitive Topics:: sexual practicessexual practices substance use/abusesubstance use/abuse illegal behaviorillegal behavior religionreligion economic status of subject or family economic status of subject or family

membermember perceived sanction for perceived sanction for

participation/non-participationparticipation/non-participation

Risks Common to Conducting Risks Common to Conducting ResearchResearch Social & MedicalSocial & Medical

Invasion of privacyInvasion of privacy Loss of confidentialityLoss of confidentiality Psychological traumaPsychological trauma Indirect physical harmIndirect physical harm Embarrassment or stigmaEmbarrassment or stigma Group stereotypingGroup stereotyping Failure of full disclosureFailure of full disclosure RecruitmentRecruitment Informed consentInformed consent Risk-benefit considerationsRisk-benefit considerations

Informed Consent:Informed Consent: What it is:What it is:

– ongoing process of communication and mutual understandingongoing process of communication and mutual understanding What it isnWhat it isn’’t:t:

– a piece of papera piece of paper– a moment in timea moment in time– a contract a contract

Elements of Informed Elements of Informed ConsentConsent

45 CFR 46.11645 CFR 46.116

11.. Study involves researchStudy involves research Purpose of researchPurpose of research Expected duration for subjectExpected duration for subject Description of proceduresDescription of procedures Identification of experimental proceduresIdentification of experimental procedures

Elements of Informed Elements of Informed ConsentConsent

45 CFR 46.11645 CFR 46.1162.2. Reasonably foreseeable risks or discomfortsReasonably foreseeable risks or discomforts3. Reasonably foreseeable benefits-subject/others3. Reasonably foreseeable benefits-subject/others4. Alternative procedures or treatments4. Alternative procedures or treatments5. Confidentiality5. Confidentiality6. Compensation for research related injury6. Compensation for research related injury7. Who can answer questions7. Who can answer questions

a. about study & about research related injurya. about study & about research related injuryb. about subjectb. about subject’’s rightss rights

8. Voluntary participation8. Voluntary participation

Whole process of consent:Whole process of consent: Recruitment is Recruitment is

considered part of considered part of consent processconsent process plans and materials should plans and materials should

be reviewed by IRBbe reviewed by IRB ““Public ServicePublic Service””

announcements and news announcements and news stories may be considered stories may be considered recruitment processesrecruitment processes

Whole process of consent:Whole process of consent: New information as it becomes available New information as it becomes available

should be shared uniformly with subjects should be shared uniformly with subjects and should be documented for IRB recordsand should be documented for IRB records

Re-visiting consent decision over time Re-visiting consent decision over time should be required in long term studies should be required in long term studies and for instances where capacity to and for instances where capacity to consent may changeconsent may change

Longitudinal studies with children and Longitudinal studies with children and adolescents should have a mechanism for adolescents should have a mechanism for ““re-consentingre-consenting”” when age of majority is when age of majority is attainedattained

Hints and Advice from a Hints and Advice from a Student ResearcherStudent Researcher Background, take your time, specific Background, take your time, specific

research questions, hypothesis, study research questions, hypothesis, study designdesign

Do not copy and paste from an Do not copy and paste from an abstract, write in lay languageabstract, write in lay language

Who is contacting the subjects? Are Who is contacting the subjects? Are these people in a position of authority? these people in a position of authority? Do they have a conflict of interest?Do they have a conflict of interest?

Hints and Advice from a Hints and Advice from a Student Researcher, cont.Student Researcher, cont.

Will the subjects be Will the subjects be ““singled outsingled out””?? Do the subjects have the capability to Do the subjects have the capability to

understand the study, given the understand the study, given the information you provide during consent information you provide during consent process?process?

Do you have an outline for the informed Do you have an outline for the informed consent process?consent process?

Are the appropriate consent and assent Are the appropriate consent and assent forms submitted?forms submitted?

Advising AdvisorsAdvising Advisors The advisorThe advisor’’s job: ensure that s job: ensure that

students recognize potential risks, students recognize potential risks, learn to follow ethical standards, learn to follow ethical standards, protect their subjectsprotect their subjects

Ultimate focus needs to be protecting Ultimate focus needs to be protecting research subjects, not interpreting the research subjects, not interpreting the rulesrules

Encourage contact with the IRB staff, Encourage contact with the IRB staff, colleagues and chairscolleagues and chairs

http://www.research.umn.edu/irb/guidance/social.html

IRB Application in a NutshellIRB Application in a Nutshell Committee is concerned with the Committee is concerned with the

researcherresearcher’’s interface with the s interface with the research subjectresearch subjectRecruitmentRecruitmentInterviewerInterviewer’’s experience and expertises experience and expertiseHow subjects are debriefedHow subjects are debriefedHow subjects are informed about the How subjects are informed about the

study and expectationsstudy and expectationsApplications need to be as informative Applications need to be as informative

as possibleas possible

Questions?Questions?