Ethical Considerations in Human Subjects Research Stacey Berg, M.D. Texas Children’s Cancer Center

Definitions IRB review Informed consent Confidentiality + HIPAA Human material Chart reviews

Definition 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 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? Interaction due to research? Yes No Identifiable info? Subjects involved No subjects

Human Subjects Research IRB approval full board expedited Informed consent full written consent altered or waived consent

Research Exempt from Approval Educational testing Some surveys Some studies of existing data or specimens Study of public service programs Taste and food quality evaluation IRB, not investigator, decides

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 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 minimized Background/importance of problem Study design issues Good endpoints Justifiable sample size Appropriate biologic correlates Leverage clinical procedures Less risky way to get answer?

Risk-benefit ratio favorable How much risk? To individual To family? To society? How much benefit? To individual To society Adequate data analysis plan Protocol endpoints Safety monitoring

Informed 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 consent What the research is Procedures involved Risks, benefits Treatment/compensation for injury Alternatives Right to withdraw Confidentiality Contacts for questions Basic elements

Informed 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

Confidentiality Consider subject privacy Where you’ll talk How intrusive? Safeguard confidentiality of data Locked doors Password protected files Consider risks if confidentiality breached Genetic info- parentage, insurance Psychological harm Job status Who gets access, what circumstances What happens to samples

HIPAA 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?

Special types of research Tissue samples only Tissue banks complex Databases Do not need IRB approval for operational use DO need IRB approval for research on data Chart reviews Need IRB approval (HIPAA) Consult with IRB

Tissue Banks Critical research resource Genomics Proteomics Futuromics Samples held indefinitely Future uses unpredictable Sample used in other studies Clinical correlation valuable Research specimen from subject

Repository Collection Local PI Subject Local IRB Consent Bank SOPs Advisory Board Bank IRB Consent Form Distribution Distal PI Usage agreement Distal IRB No consent

Types of sample Anonymous No links exist anywhere Coded A link exists Tissue recipient does not have key Repository does Identified Tissue recipient can connect tissue to donor Defined by link to donor

Kinds of IRB review Anonymous samples Can be exempt from IRB review Coded or identified samples IRB review required Expedited review may apply if minimal risk Samples all from decedents Exempt from IRB review (not human subjects) Still need HIPAA review Determined by type of sample

Consent considerations Informed consent required Special considerations Subject contact: What PHI being collected? Duration of follow-up Recontact re: future studies? Sample use: This study only? Any study related to condition? Unspecified future studies? Prospective sample acquisition

Waiver of consent? Only if minimal risk Confidentiality well protected No release of PHI Rights of subject not compromised Adequate plan to reveal important findings AND impracticable to get consent Most applicable to previously banked specimens Few good reasons if prospective collection

Tissue Collection Exempt?

Chart Reviews IRB approval usually expeditable Informed consent? -Not (usually) if retrospective review *Justify waiver of consent and authorization in IRB application -Yes if prospective data collection “Dear colleague” letter passive approval from other MDs

Databases 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/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:

Helpful links 45 CFR Belmont Report NIH guide on informed consent Data monitoring htmlhttp://grants.nih.gov/grants/guide/notice-files/not html IRB Manual nual.pdf