Betsy Ripley, MD, MSProfessor of Medicine Division of NephrologyVCU IRB Senior ChairVCU Clinical Research Compliance OfficerAssociate Chair Faculty Development for IMElizabeth.ripley@vcuhealth.org804-828-1955

Must adhere to Federal regulations

Monitored by local Institutional Review Boards (IRBs)

The Belmont Report: Ethical Principles and Guidelines for the Protection of Human Subjects of Research (1979)Three basic principles should govern the

conduct of research involving human subjects:Respect for personsBeneficenceJustice

The Belmont Report. National Commission for the Protection of Human Subjects of

Biomedical and Behavioral Research. 1979.

“Respect for persons incorporates at least two ethical convictions: first, that individuals should be treated as autonomous agents, and second, that persons with diminished autonomy are entitled to protection.”

The Belmont Report. National Commission for the Protection of Human Subjects of

Biomedical and Behavioral Research. 1979.

Treat individuals as autonomous agentsDon’t use people solely as a means to an

endLet people make their own decisionsProvide additional protections for those

with diminished autonomyPractical applications:

Informed consentInformationComprehensionVoluntariness

Privacy and confidentialityThe Belmont Report. National Commission for

the Protection of Human Subjects of Biomedical and Behavioral Research. 1979.

“Beneficence is understood…as an obligation. Two general rules have been formulated as complementary expressions of beneficent actions in this sense: do no harm, and maximize possible benefits and minimize possible harms.”

The Belmont Report. National Commission for the Protection of Human Subjects of

Biomedical and Behavioral Research. 1979.

Don’t merely be niceDo no harmPromote welfareMaximize possible benefitsMinimize risks of harmsPractical applications:

Study designRisk/benefit analysisQualified and competent investigators

The Belmont Report. National Commission for the Protection of Human Subjects of

Biomedical and Behavioral Research. 1979.

Justice requires that we treat persons fairly and we give each person what he is owed

The principle requires that both benefits and burdens be distributed fairly

Practical applications:Selection of subjects is equitableRecruitmentPopulations under study

The Belmont Report. National Commission for the Protection of Human Subjects of

Biomedical and Behavioral Research. 1979.

1. Risks minimized2. Favorable risk-potential benefit analysis3. Equitable selection4. Informed consent sought5. Informed consent documented6. Data monitored for safety7. Privacy protected; confidentiality

maintained8. Safeguards for vulnerable individuals

The tension was anticipated and expectedSubjective judgment calls will often be

requiredReasonable people will disagree

45CFR46 “The Common Rule” * HHS research regulations OHRP

21CFR50, 56 * FDA research regulations Federal-wide assurance (FWA)

Responsible conduct of research * Office of Research Integrity

Established to provide ethical review of research

Assure that federal regulations are followedMembers include researchers, non-

researchers and members of the local community

5 IRBs at VCURegulatory and ethical charge: review and

approve ‘human subjects research’

RESEARCH –A systematic investigation designed to develop or

contribute to generalizable knowledge. 45 CFR 46.102(d)

HUMAN SUBJECTA living individual about whom an investigator…

conducting research obtains 1) data through intervention or interaction with the

individual, or 2) identifiable private information

45 CFR 46.102(f)

‘Systematic’: use of data analyses, scientific methods – (can include ‘nonresearch’ projects)

AND What about ‘generalizable’?

Considerations:

Intent to publish/present does not necessarily define a project as research – what is the intent?

Is the intent to contribute to the knowledge base of your profession/discipline by drawing conclusions and/or to make generalizable claims based on systematic methods?

If so, it is ‘research’

A major goal of (non-therapeutic) research is to benefit people other than the immediate research subjects

Quality improvement/ QA projects – designed with goal of improving institutional/organizational practice

Resource utilization reviewCase report or case series – if no systematic

investigation, i.e. no statistical or data analysis; no outcome measures

Public health practice – surveillance, program evaluation

Survey/questionnaire development – no data retained for research purposes

More straightforward Interventions or interactions with living personsAccess to identifiable personal data

Secondary data sets without ANY identifiers or codes generally do not involve human subjects

*Note difference between de-identified and anonymized

Chart/medical record reviews to address hypothesis or research question(s)

Surveys, including Internet-based surveys Randomized intervention and control group Creating data registries/tissue banks Data analysis of primary or secondary data

from data registries or tissue repositories that contain identifiers or codes

Interventions/procedures that utilize randomization or a control group

HOWEVER, if …- there is a question- a project might become research- there is potential to publish or present

THEN…

- Contact ORSP or OECO or IRB member with questions

- Submit to the IRB if unsure: protect your ability to present or publish and ensure subjects are protected

Think about your project.

Do you have any ethical concerns about your project? Are their changes or clarifications or safety measures that could mitigate those concerns?

Does it involve Human Subjects Research? Why or Why not?

Website –Institutional Review Board (IRB) https://irb.research.vcu.edu

RamsIRB

Level of potential risk to subjects determines type of review

Exempt ------ Expedited ------ Full board Low risk ------------ High risk(click on “forms” on the IRB website to receive guidance on

determining review type:

www.research.vcu.edu/forms/vcuirb.htm)

“Minimal Risk” means that the probability and magnitude of harm or discomfort anticipated in the research are not greater in and of themselves than those ordinarily encountered in daily life or during the performance of routine physical or psychological examination or tests.

Kinds of Risk

Just plain inconvenience and hassle

Emotional or psychological risk

Social riskPhysical riskEconomic riskLegal risk

Risk To Whom?

The subjectThe subject’s

institutionThe familyThe communityThe researcher & his

institutionScienceSociety

Joan Sieber

Reviewed for exemption from informed consent requirement and continuing IRB reviewInvolves a non-vulnerable population (does

not generally include children, prisoners, decisionally impaired,

economically or educationally disadvantaged)Low-risk researchDoes not include recorded identifiers or

codesQuestions generally are not sensitiveFits one of 6 categories of research

1. Typical educational practices

2. *Educational tests, surveys, interviews, or observation of public behavior (non-sensitive, no identifiers) No children for surveys, interviews or obs of public behavior where research is involved.

3. Research with elected public officials, appointed public officials,candidate for public office)

4. *Existing data, documents, pathological specimens, if publicly available or recorded to be unidentifiable

5. Evaluation of public benefit service programs

6. Taste and food quality evaluation and consumer acceptance studies

EXAMPLES: medical record review; surveys/questionnaires with no recorded identifiers or codes

Meets federal criteria for minimal risk research (considers risk of criminal/civil liability, financial risk, employment risk, stigmatization, insurability, and embarrassment)

May include identifiers (direct or indirect) but topics not sensitive OR

May include some sensitive topics, but confidentiality securely protected

Need to consider a formal informed consent process OR justify a waiver of consent

Clinical studies: IND/IDE NOT required

Blood sample collection (routine methods –small amounts)

Prospective collection of biological samples—noninvasive means

Data collected though noninvasive means (routinely practiced in clinical settings)

Materials (data, documents, specimens etc.) have been collected or will be collected for non-research purposes

Collection of voice, video or digital data for research purposes

Individual or group behavior, surveys, interviews, oral histories

What is the risk level of your study? Why?Does your study qualify for exempt,

expedited, or full board review? Remember it must fit completely within that category.

Click on the help icon in RAMSIRBSeek consultation from someone on the IRB

from your area or from an experienced researcher

Call the IRB office or OREC for consultationReview the WPPs and IRB guidance on the

website (links on application)Call/email me Elizabeth.ripley@vcuhealth.org,

804-828-1955