Introduction to Research Involving Human Subjects

& the IRB at Florida Hospital

Presented by Janice Turchin, IRB Manager

Florida Hospital Institutional Review Board

Regulations and Oversight

• Why Does Research Need to be Regulated?

• What is IRB Oversight

Trigger Events

• The Nazi Experiments– Concentration Camps WWII

• Tuskegee Syphilis Study (1932-1972)– Infamous research to study the natural progression of

untreated syphilis

• Milgram’s Studies (1960’s)– Obedience Experiments – Participants believed they were delivering

“electrical shocks”

Johns Hopkins:A Cautionary Tale2001

• Healthy volunteer dies following participation in trial.

• Multiple failures on part of Medical School and Investigator.

• Johns Hopkins entire research program temporarily shut down.

• Criminal and Civil prosecutions.

Havasupai Indians and the Challenge of Informed Consent for Genomic Research• Dispute between Arizona State University and the Havasupai Indians

over the allegedly improper research use of DNA from members of the tribe

• Research a gene variant that might be contributing to the increasing rate of diabetes in the tribe.

• Research proved to be unfruitful. • Blood was used for other research purposes including searching tribe

members DNA for variants linked to schizophrenia. • Rights of research subjects can be violated when they are not fully

informed about how their DNA might be used. • $700,000 Settlement

Ethical Milestones • Nuremberg Code 1947 (Human consent is

essential.) • National Commission for the Protection of

Human Subjects Biomedical & Behavioral 1974 (First bioethical commission to shape Human Subjects Research.)

• Belmont Report 1978 • Common Rule 1991

The Belmont Report: Ethical Principles and Guidelines for the Protection of Human Subjects of Research, April 18, 1979• Respect for Persons (“Be courteous”)

• People should be autonomous and not used as a means to an end. • Allow informed choice where participants can choose for themselves. • Provide additional protections for those who need it. • Derived concepts: Informed consent, Respect for privacy.

• Beneficence (“Do good”) • We are obligated to protect persons from harm by clearly identifying and

maximizing anticipated benefits while minimizing possible risks of harm. • Derived concepts: Good research design, Competent investigators,

Favorable risk/benefit analysis.

• Justice (“Be fair.”) • Requires that the benefits and burdens of research be distributed fairly. • Derived concepts: Equitable selection of subjects.

Title 45 Code of Federal Regulations, Part 46

“The Common Rule”

• A federal policy regarding Human Subjects Protections that applies to 17 Federal agencies and offices.

• Subpart A: Outlines the requirements for: assuring compliance by research institutions (Federalwide Assurance [FWA]); obtaining and documenting informed consent; IRB membership, function, operations, review of research, and record keeping.

• Subparts B, C, D - Outline protections for vulnerable populations – Pregnant Women/Fetuses/Neonates, Prisoners, Children, respectively.

Food & Drug Administration (FDA) Human Research Regulations

• 21 CFR 11 Electronic Records/Signatures• 21 CFR 50 Protection of Human Subjects• 21 CFR 56 Institutional Review Boards• 21 CFR 312 Investigational New Drug Application • 21 CFR 312 Investigational Device Exemptions • ETC, ETC, ETC i.e. Licensing, Biological Products,

Premarket Approval of Devices . . . .

HIPAA – Privacy Rule for Research

• FH IRB acts as the “Privacy Board” for research

• Patient Authorization – IRB Consent form template includes HIPAA authorization

• Waiver of HIPAA Authorization – Retrospective chart reviews

What are Enforcement Options?

Fines and civil penalties

Oversight Suspension or termination of PI

Suspension or termination of

Institution

Loss of fundingCriminal penalties

Research Regulation is Needed

• How do we regulate Human Subjects research at Florida Hospital?

Institutional Review Board - IRB• Federal wide Assurance (FWA)

– FH has negotiated with the Office for Human Research Protections (OHRP) that all of the institution’s human subject research activities, regardless of funding, will be guided by the Belmont Report, will comply with the Common Rule, and other regulations as applicable.

• The purpose of an IRB is to review research involving human subjects to ensure their rights and welfare are adequately protected.

• Board consists of physicians, nurses, community members (i.e. clergy and study participants), non-scientists.

Authority & Responsibilities - IRB• Report, as required,

unanticipated problems involving risks to subjects or others; non-compliance; suspensions and termination to:– Sponsor – OHRP Office of

Human Research Protection

– FDA

• Federal Wide Assurance (FWA)• Assist and guide researchers to

help protect the rights of human subjects

• Charged with safeguarding the rights and welfare of human subjects

• Review all research studies involving human subjects under the Florida Hospital auspices.

• Audit research studies.

What do I do if I want to do research at Florida Hospital?

What is Human Subjects Research?Meets federal definition of “research” Systematic investigation designed to develop or

contribute to generalizable knowledge

+

Meets definition of “human subject(s)” The investigator will gather data about living

individuals through intervention or interaction OR The investigator will gather data about living individuals that is private AND identifiable.

IRB Review of Research All research projects are categorized into one of three categories for the IRB review process. Each category is different in the level of scrutiny and submission procedures. The IRB is responsible for making the final decision of which category a research project falls under.

• Full Board Review • Expedited • Exempt

Not sure if your research fits the definition of Research? Call IRB Office / Complete Determination Form

Criteria for IRB Approval• Risks are Minimized (Consistent with a sound research design

and does not unnecessarily expose subjects to risk) • Risks are Reasonable in Relation to Benefits • Selection of Subjects is Equitable • Informed Consent will be Sought for Each Prospective Subject • Informed Consent will Be Documented • Research Plan Adequately Provides for Monitoring the Data

Collected to Ensure Safety of the Subjects • Research Plan Adequately Protects the Privacy of Subjects and

Maintains Confidentiality • When some or all of the subjects are likely to be vulnerable to

coercion or undue influence, additional safeguards need to be included in the protocol to protect the rights and welfare of these subjects.

Levels of review- Exempt (reviewed by Chair or IRB designated member) • Minimal risk and fit into an “Exempt” category • Surveys or interviews UNLESS identifiers are recorded AND any

disclosure of responses could reasonably place the subjects at risk• Collection of existing data or specimens IF the information is

recorded in such a manner that subjects cannot be identified (directly or indirectly)

Levels of review- Expedited (reviewed by Chair or IRB designated member) • Minimal risk and fit into an “Expedited” category • Document review – Retrospective chart reviews• Surveys or interviews • Collection of specimens • Routine noninvasive procedures

Minimal Risk Definition

• Minimal risk is the probability and magnitude of physical or psychological harm that is normally encountered in the daily lives, or in the routine medical, dental, or psychological examination of healthy persons.

Full Board Protocol Review

• Protocols which are more than minimal risk • PI is invited to meeting to present study and clarify IRB

concerns • FH IRB meets twice a month• The Full Board has the authority to:

– Approve – Require modifications prior to approval – Table until major issues are clarified – Disapprove all research activities including proposed changes in previously

approved human subject research.

Advice for Common Errors with IRB Submissions• Forms - Go to IRBNet Library for each new submission

– Templates to help• Credentials – Ensure study team has completed requirements

– CITI training– CV– Volunteer descriptions

• Review protocol and consent form for clarity – Be clear about study processes/procedures – Content - Ensure all documents match in regards to study plans– Thorough Review – obtain review from others not affiliated with

study

IRB Classes

• IRB 101• HIPAA

For more information: checkout our calendar on the IRB Website.Stay tuned for new classes/lunch & learns.

Let us know what you are interested in knowing more about.

Emergency Use

• "Emergency Use” means the use of a test article on a human subject in a life-threatening situation in which no standard acceptable treatment is available, and where there is not sufficient time to obtain IRB approval, as stated in 21 CFR 56.102(d). Life-threatening, for the purposes of section 21 CFR 56.102(d), includes both life-threatening and severely debilitating conditions.

Emergency Use cont.

• IRB – Handbook– P/P’s being developed

• Florida Hospital has Policies/Procedures for use of Investigational Drugs

Emergency Use cont.

• Life-threatening means diseases or conditions where the likelihood of death is high unless the course of the disease is interrupted, and diseases or conditions with potentially fatal outcomes, where the end point of clinical trial analysis is survival. The criteria for life-threatening do not require the condition to be immediately life-threatening or to immediately result in death. Rather, the subjects must be in a life-threatening situation requiring intervention before review at a convened meeting of the IRB is feasible.

• Severely debilitating means diseases or conditions that cause major irreversible morbidity. Examples of severely debilitating conditions include blindness, loss of arm, leg, hand, or foot, loss of hearing, paralysis, or stroke.

Emergency Use cont.

• Regulations require that an emergency use of a test article be reported to the IRB within five working days (21 CFR 56.104(c)). Consequently, you must report an emergency use to the FH IRB within five working days of its occurrence, even if you communicated with the FH IRB prior to the emergency use.

• Use the form posted on IRBNet – “Form – Emergency Use Post-Use Report”.

On Your Road to Research, don’t think of Compliance as . . . . .

On Your Road to Research . . . . .

Questions?

Visit FH IRB Website

https://drupal02.floridahospital.org/irb/