Betsy Ripley, MD, MS Professor of Medicine Division of Nephrology VCU IRB Senior Chair VCU Clinical Research Compliance Officer Associate Chair Faculty Development for IM

 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 persons Beneficence Justice The Belmont Report. National Commission for the Protection of Human Subjects of Biomedical and Behavioral Research

“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

Treat individuals as autonomous agents Don’t use people solely as a means to an end Let people make their own decisions Provide additional protections for those with diminished autonomy Practical applications: Informed consent Information Comprehension Voluntariness Privacy and confidentiality The Belmont Report. National Commission for the Protection of Human Subjects of Biomedical and Behavioral Research

“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

Don’t merely be nice Do no harm Promote welfare Maximize possible benefits Minimize risks of harms Practical applications: Study design Risk/benefit analysis Qualified and competent investigators The Belmont Report. National Commission for the Protection of Human Subjects of Biomedical and Behavioral Research

RiskBenefit

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 equitable Recruitment Populations under study The Belmont Report. National Commission for the Protection of Human Subjects of Biomedical and Behavioral Research

1. Risks minimized 2. Favorable risk-potential benefit analysis 3. Equitable selection 4. Informed consent sought 5. Informed consent documented 6. Data monitored for safety 7. Privacy protected; confidentiality maintained 8. Safeguards for vulnerable individuals

The tension was anticipated and expected Subjective judgment calls will often be required Reasonable 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 followed Members include researchers, non-researchers and members of the local community 5 IRBs at VCU Regulatory and ethical charge: review and approve ‘human subjects research’

RESEARCH – A systematic investigation designed to develop or contribute to generalizable knowledge. 45 CFR (d) HUMAN SUBJECT A 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 (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 review Case 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 persons Access 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) 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:

“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 risk Physical risk Economic risk Legal risk Risk To Whom? The subject The subject’s institution The family The community The researcher & his institution Science Society Joan Sieber

Reviewed for exemption from informed consent requirement and continuing IRB review Involves a non-vulnerable population (does not generally include children, prisoners, decisionally impaired, economically or educationally disadvantaged ) Low-risk research Does not include recorded identifiers or codes Questions generally are not sensitive Fits 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 RAMSIRB Seek consultation from someone on the IRB from your area or from an experienced researcher Call the IRB office or OREC for consultation Review the WPPs and IRB guidance on the website (links on application) Call/ me