Workshop on the Protection of Human Subjects in Research

Texas Christian University August 24, 2012

Brian Gladue, PhD, CIPDirector, Office the Protection of Human Subjects

(OPHS)\Chair, Institutional Review Board (IRB)

Human Research Subject Protection

Human Research Protection Program: an organization-wide system to assure comprehensive and far-ranging protection of human subjects in research

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Human Research Subject Protection…Why is it important?

• Historical Basis/Core Principles of Ethical Research• Federal Regulations and Laws Protecting Human

Subjects• University Commitment to Sound Ethical Practices and

Research

Ethical Research = Quality Research

Federal Regulation & Law

In USA, human subject protection regulated by Federal Law (CFR)• FDA: 21 CFR 50, 56-

• Drug & device rules (IND, IDE, HDE, etc.)• OHRP: 45 CFR 46 –

• Rules for review of studies, Education of IRB members• Adequate IRB staff, appropriate investigator training• Implementation of Belmont Report Principles

At the “local level” the IRB is mandated by federal law to oversee human subject research

Roles of an IRB…

• Protect Human Subjects• Assure that the Institution (and its investigators,

students and staff) are “in compliance” with federal human subject research regulations / state law / university policies

• Assist Investigators to Enhance the Research Enterprise

• “The IRB (and IRB Office) is Your Friend”

University Commitment and Policy

ALL research projects involving human subjects require a priori review by the Department Review Board (DRB), and subsequently, by the university’s Institutional Review Board (IRB).

FWA (FederalWide Assurance)…an agreement by TCU with the federal

government to comply with the requirements of the Department of Health and Human Services (HHS) Protection of Human Subjects regulations, 45 CFR part 46 when conducting human subject research.

University’s FWA and commitment to human subject protection includes all university personnel (students, staff, faculty) … no matter where they are conducting research (on or off-campus).

Is it Research involving Human Subjects?

• ResearchA systematic investigation, including research development, testing andevaluation, designed to develop or contribute to generalizable knowledge.

• Human subjectsLiving individual(s) about whom an investigator (whether professional orstudent) conducting research obtains (1) data through intervention or

interaction with the individual, or (2) identifiable private information.

• Benefit: A valued or desired outcome; an advantage.

• Risk: The probability of harm or injury (physical, psychological, social, or economic) occurring as a result of participation in a research study. Both the probability and magnitude of possible harm may vary from minimal to

significant. Federal regulations define only "minimal risk.."

• Vulnerable Populations: Populations, such as children, prisoners, pregnant women, mentally disabled persons, or economically or educationally disadvantaged persons.

How do I know if what I am doing is “Research” and needs IRB review and Approval ?

1. Publish If you plan to publish your inquiry (even if it is 10 years from now), IRB review and approval is required.

2. Present If you think you will present your data at a professional meeting, conference, or setting, including local research presentation events

now or in the future, IRB review and approval is required.

3. Recognition or Promotion If you want your research or achievements as an investigator) recognized by someone such as your Department Head, Dean, or Major Professor, IRB review and approval is required.

4. Graduation If your project will be used for a degree program (Masters, Dissertation, Honors project, etc.) or to meet the requirements of a residency program, IRB review and approval is required.

WHO decides what is / isn’t “Research” that would need IRB review and Approval ?

The investigator is not the “final decision maker" as to whether or not something is research...

Departmental Review Boards can assess the scientific merit, attention to regulatory aspects, operational issues and general “do-ability” of a project…

TCU policy and procedures (and good ethical practice) is for an independent group to make the overall “research” determination…in this case, the IRB is that group

General “rules of thumb”:• If you think your project is (research)...then it probably is... • If you are not sure...it probably still is (research)…• and if you think it is NOT...confirm that with the IRB

In any case, the IRB makes the call

So, if we decide it is research…what is the harm? Determining if a study is “minimal risk”…

Federal Definition:Minimal Risk: "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 examinations or tests" (from 45 CFR 46.102(i)

When making a decision about minimal risk of research:Two Kinds of “Risk” to be Managed:• Procedural Risk – associated with the actual process or procedures

associated with the study• Informational Risk: breach of privacy, confidentiality risk, document

access, risk of embarrassment and other “risks” related to how sensitive information is stored, accessed, managed.

Why is determining “minimal risk” important?

Regulations specify that EXEMPT category projects must be minimal risk…also

EXPEDITED category projects must be “minimal risk”…

If it is more than minimal risk…then it goes to a convened meeting of the IRB.

On

Once again: Minimal Risk: "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 examinations or tests" (from 45 CFR 46.102(i)

Evaluating Scientific Merit and Research Design

• 45 CFR 46 §46.111 Criteria for IRB approval of research. (a) (1) Risks to subjects are minimized: (i) by using procedures which are consistent with sound research design and which do not unnecessarily expose subjects to risk

Currently, OHRP determinations rule that the IRB is the ONLY body authorized to make this evaluation for a given protocol.

A departmental or college level “scientific review committee” may “OK” a research study or design…but if the IRB determines that study design is an issue or concern, it must be addressed prior to approval.

Review of Human Subjects Research

· Exempt

· Expedited

· Full Board

· Continuing Review

· Amendments

Exempt Category Research

Language can be tricky…“Exempt” does NOT mean what you think it does…In the language of the IRB (and the Federal government) Exempt category research means that the project is “Exempt from Full Board Review”, but at most institutions (including UNTHSC and TCU) the protocol STILL HAS TO BE REVIEWED AND CERTIFIED BY A INSTITUTIONALLY DESIGNATED GROUP (USUALLY THE IRB) THAT THE PROJECT MEETS FEDERAL CRITERIA FOR “EXEMPT” STATUS…

• Minimal risk• Falls under of the categories listed by the Federal Regulations

…once approved, the project is then EXEMPT from further IRB surveillance and consideration

Some Examples of Exempt Research

• Secondary analysis of de-identified data (e.g., publically available databases, vital statistic records, student records, etc.)

• Anonymous surveys or interviews• Analyses of discarded pathological specimens without

patient identifiers (retrospective analyses) • Retrospective Record or Chart Review (no use of a

master list of identifiers)

“Expedited” Research

In IRB parlance , “Expedited” does NOT mean fast, streamlined or quickly reviewed (although it can be).

EXPEDITED research refers to protocols that are no more than minimal risk and are also not exempt category research, but can be reviewed by an “Expedited Review Procedure”…where one or more experienced IRB members designated by the IRB Chair review the protocol

AND from a list of specially (9) designated categories of research published in the Federal Register

Some Examples of Expedited Research

• Studies involving the collection of hair, saliva, or dental plaque samples,

• Studies of blood samples from healthy subjects,• Studies of existing pathological specimens with subject

identifiers• Focus group studies• Retrospective Chart Reviews with a master list• Prospective Chart Reviews• Analysis of audio or video recordings

Full Board Review

• Everything else…and all research that is “more than minimal risk”

IRB Protocol Review process…

Departmental review (if offered)Pre-Consultation with the IRB Office (where available)Submit IRB Application

• IRB Form• Protocol Synopsis• Consent Document(s)• Related documents: recruiting materials, ads, survey

questionnaires, etc,Pre-review by IRB Staff (time permitting)IRB Review : Chair (Exempt/Expedited), convened Board (“Full”)Determination / Approval

IRB Full Board Review…Determination

Discussion by IRB members: summary and Pre-reviewPrincipal Investigator Presentation / Discussion / Q & AFollow-Up Discussion by IRB Members

• Level of Risk• Special Findings• Technical Findings

Determination:• APPROVAL with no changes• APPROVAL CONTINGENT on minor (technical) modifications• DEFER (many modifications / significant changes needed)• DISAPPROVE (study not do-able in present form)

After the Approval…

Continuing Review … protocols can only be approved for one year (or less)…often called “Progress Reports”

Final Report (Close-Out)…submitted at any timeAmendments / Modifications to a protocol…any change to the IRB-

Approved protocol (or consent forms, or any aspect of the research project) must be approved by the IRB prior to implementation

Protocol Exception (requests)…seeking IRB approval for a “one-time”/rare deviation from the protocol BEFORE implementing it

Protocol Violations (Deviations)… an unauthorized change in protocol or documentation [ AVOID – but report to IRB immediately if it happens].

Unanticipated Problems / Serious Adverse Event (SAE) Reports

Being the Principal Investigator

Key Responsibilities…· Research Project Manager: Direct initiation and coordination,

supervision of all aspects of the research project· Personnel Manager: Training, supervision and management of all

personnel associated with the research project, especially student projects

· Compliance Manager: Need to meet all university, state and federal laws, policies and regulations.

In a phrase: “The Principal Investigator is responsible for Everything!”

Being the Principal Investigator

Other ResponsibilitiesNeed to “think through and develop” an effective and ethical

Research Protocol

Record retention (especially consent forms)

Hold for a minimum of 3 years after project ENDS

Crafting “correct” Consent Form(s)

Subject recruiting schemes, ads, flyers, documents

Discussion Items:

Subject Fees and Incentives• Fair and Balanced (a good thing)• Coercive / Unduly Influential ( NOT a good thing)• Follow institutional policy (ALWAYS a smart thing)

Changes to Protocols must be approved by IRB prior to implementation … watch out for ambitious ambitious / creative students and staff

Tips and Suggestions on working with an IRB

Key Points for IRB Submissions…

Tips for Successful reviews (minimizing approval delays):1. Write clearly and accurately – step by step process, listing,

bullet points, flow charts, etc.2. Think of research needs first before fitting the design to a

“standard” protocol template3. Include all needed documentation – approval from recruitment

sites, ads, web links, letters of support from key stakeholders (sample providers, affiliated agencies, etc.)

4. Allow enough time for review…build in time for a possibly higher level of review, modification or design changes

Key Points for IRB Submissions…

When drafting your protocol ask yourself…

WHO?WHAT?

WHEN?WHERE?

WHY? ANDHOW?

Additional Tips

• Discuss materials, recruitment flyers, and instruments in the Protocol, Application, and Consent Form!

• Describe study variables and identifiers data security/ confidentiality & management…if it’s de-identified, describe de-identification process

• Use simple language (at 8th grade reading level) in the consent form

• Use consistent “person” in the consent form.

• Watch for grammar and typographical errors that affect comprehension (& avoid jargon and awkward prose).

Additional Tips (cont.)

• Provide enough information about the study so that IRB staff and IRB members (who may not be experts in your field) will know what the investigators want to do.

• Provide all needed signatures (student, faculty, etc.)

• Obtain a Pre-review /Approval from DRBs before sending to the IRB

Take Home Message # 1Doing Human Subject Research? Whatever is planned, it’s going to

need IRB REVIEW

TCU’s FWA and commitment to human subject protection includes all university personnel (students, staff, faculty)…no matter where they are conducting research (on or off-campus).

Failure (of ALL personnel) to submit protocols to IRB for evaluation jeopardizes the

entire University!

Take Home Message # 2(The End All Be All)

“The Principal Investigator is Responsible for Everything...”

Take Home Message # 3

The IRB is your friend…and is a key component in enhancing the research enterprise while protecting

human subjects (as well as investigators) …