Ethical Considerations Ethical Considerations in Human Subjects in Human Subjects

ResearchResearch

Stacey Berg, M.D.Texas Children’s Cancer

Center

• Definitions

• IRB review

• Informed consent

• Confidentiality + HIPAA

• Human material

• Chart reviews

Definition of ResearchDefinition of Research

• Research means a systematic investigation, including research development, testing and evaluation, designed to develop or contribute to generalizable knowledge

Publication plans irrelevant

Definition of SubjectDefinition of Subject

• Human subject means a living individual about whom an investigator (whether professional or student) conducting research obtains:

(1) data through intervention or interaction with the individual

(2) identifiable private information

Subjects involved?Subjects involved?

Interaction due to research?

Yes No

Identifiable info?

Subjects involved

No subjects

Human Subjects Human Subjects ResearchResearch

• IRB approvalfull boardexpedited

• Informed consentfull written consentaltered or waived consent

Research Exempt from Research Exempt from ApprovalApproval

• Educational testing

• Some surveys

• Some studies of existing data or specimens

• Study of public service programs

• Taste and food quality evaluationIRB, not investigator,

decides

What does an IRB do?What does an IRB do?

• Review, approve, require modifications or disapprove research

• Review informed consent

• Conduct continuing review

• Have authority to observe consent process and research

45 CFR 46

Criteria for approvalCriteria for approval• Risks to subjects are minimized• Risks to subjects are reasonable relative to benefits

• Selection of subjects is equitable• Provisions made for data, safety monitoring • Provisions made to protect confidentiality• Safeguards in place for vulnerable subjects• Informed consent will be sought, documented

Risks minimizedRisks minimized

• Background/importance of problem

• Study design issuesGood endpointsJustifiable sample sizeAppropriate biologic correlates

Leverage clinical procedures

• Less risky way to get answer?

Risk-benefit ratio Risk-benefit ratio favorablefavorable

• How much risk?To individualTo family?To society?

• How much benefit?To individual To society

• Adequate data analysis planProtocol endpointsSafety monitoring

Informed consentInformed consent

• Tell people why you’re doing this and what’s going to happen to them!

• Risks (not underestimated)

• Benefits (not oversold)

• 7th grade language

Informed consentInformed consent

• What the research is

• Procedures involved

• Risks, benefits

• Treatment/compensation for injury

• Alternatives

• Right to withdraw

• Confidentiality

• Contacts for questions

Basic elements

Informed consentInformed consent

• Unforeseeable risks

• Circumstances for termination of participation

• Additional costs

• Procedures for withdrawal

• Notification of new findings that might affect willingness to participate

• Approximate number of subjects

Additional elements

ConfidentialityConfidentiality• Consider subject privacy

Where you’ll talkHow intrusive?

• Safeguard confidentiality of dataLocked doorsPassword protected files

• Consider risks if confidentiality breachedGenetic info- parentage, insurancePsychological harmJob status

• Who gets access, what circumstances• What happens to samples

HIPAAHIPAA

• Privacy rule

• “Limiting the ways that health plans, pharmacies, hospitals and other covered entities can use patients’ personal medical information.”

• Authorization to use PHI usually part of consent form

• Applies in some settings where research regs don’t

Waiver of Consent?Waiver of Consent?

Special types of Special types of researchresearch

• Tissue samples onlyTissue banks complex

• DatabasesDo not need IRB approval for operational use

DO need IRB approval for research on data

• Chart reviewsNeed IRB approval (HIPAA)

Consult with IRB

Tissue BanksTissue Banks

• Critical research resourceGenomicsProteomicsFuturomics

• Samples held indefinitely

• Future uses unpredictable

• Sample used in other studies

• Clinical correlation valuable

Research specimen from subject

Repository

CollectionLocal PISubjectLocal IRBConsent

Bank SOPsAdvisory Board

Bank IRBConsent Form

DistributionDistal PI

Usage agreementDistal IRB No consent

Types of sampleTypes of sample

• AnonymousNo links exist anywhere

• CodedA link existsTissue recipient does not have key

Repository does

• IdentifiedTissue recipient can connect tissue to donor

Defined by link to donor

Kinds of IRB reviewKinds of IRB review

• Anonymous samplesCan be exempt from IRB review

• Coded or identified samplesIRB review requiredExpedited review may apply if minimal risk

• Samples all from decedentsExempt from IRB review (not human subjects)

Still need HIPAA review

Determined by type of sample

Consent considerationsConsent considerations

• Informed consent required• Special considerations

Subject contact:What PHI being collected?Duration of follow-upRecontact re: future studies?

Sample use:This study only?Any study related to condition?Unspecified future studies?

Prospective sample acquisition

Waiver of consent?Waiver of consent?• Only if minimal risk

Confidentiality well protectedNo release of PHIRights of subject not compromisedAdequate plan to reveal important findings

• AND impracticable to get consent

Most applicable to previously banked specimens

Few good reasons if prospective collection

Tissue Collection Tissue Collection Exempt?Exempt?

Chart ReviewsChart Reviews

• IRB approvalusually expeditable

• Informed consent?- Not (usually) if retrospective review*Justify waiver of consent and authorization in IRB application

- Yes if prospective data collection

• “Dear colleague” letterpassive approval from other MDs

DatabasesDatabases

• If for TPO (or education), no IRB or HIPAA issue

• If collecting PHI but not for research, need authorization (or waiver)

• If collecting PHI for research, need informed consent (or waiver)

QI/QAQI/QA• Effectiveness of programs

• Improvements in health care delivery in particular settings

• Not usually research if intended for internal program evaluation without generalization

• Difficulty is in deciding when insight becomes “generalizable”

Lynn, Ann Intern Med. 2007;146:666-673

http://brain-prod.bcm.tmc.edu/brainlogin.asp

Helpful linksHelpful links

• 45 CFR 46 http://www.hhs.gov/ohrp/humansubjects/guidance/45cfr46.htm#46.111

• Belmont Report http://www.hhs.gov/ohrp/humansubjects/guidance/belmont.htm

• NIH guide on informed consent http://www4.od.nih.gov/oba/rac/ic/appendix_m_iii_b.html

• Data monitoring http://grants.nih.gov/grants/guide/notice-files/not98-084.html

• IRB Manual https://intranet.bcm.tmc.edu/apps/research/oor/a_c/document/irb_manual.pdf