the institutional review board (irb) and its functions theresa m boyd associate professor of...
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The Institutional Review Board (IRB) and its functions
Theresa M BoydAssociate Professor of PathologyHoward University College of MedicineDirector Transfusion MedicineHoward University Hospital
Howard University IRB
Information
IRB Review Process
The government mandated purpose of IRBsThe singular purpose of the Howard
University IRB, as mandated by Federal Law, is to protect the rights and welfare of human research participants recruited to participate in research activities conducted under the auspices of Howard University.
This purpose can not be outweighed by any other consideration (i.e. time, money, research publications, graduation, etc.)
Why were/are IRBs needed?Tuskegee Syphilis Study (Alabama, 1932-
1972)Nazi Experiments (1930s-1940s)Stanley Milgram's experiment ."Obedience
and Individual Responsibility" (Yale, 1961-1963)
Willowbrook Study (New York, 1963-1966)Tearoom sex (Washington Univ., 1960s)Zimbardo Stanford Prison Experiment
1971Research conducted in prisoners, children
and other vulnerable populations
Guiding Ethical PrinciplesNuremberg Code of 1947Declaration of Helsinki, 1964
(last updated in 2004)Belmont Report 1979
Nuremberg CodeVoluntary consent of subject
must be obtained.Prior animal experimentation is
needed to assess risks.Human experimentation must be
performed by qualified individuals.
Belmont ReportRespect for persons
◦People are autonomous and have the right to self determination
◦Obtain informed consent, protect privacy and confidentiality
Beneficence◦Do no harm, provide benefit when
possible, limit risksJustice
◦Equitable selection of subjects◦Equal distribution of risks and benefits
The principles of the Belmont Report
govern all research supported by the
U.S. Government. The ethical
principles outlined in the report are
the basis for subsequent regulations
designed to ensure protection of
human subjects in research.
The Belmont Report
1. Respect for Persons
2. Beneficence
3. Justice
The Basic Principles of the Belmont Report
IRB Decision Matrix
BENEFICENCE JUSTICE
RESPECT FOR PERSONS
Privacy & ConfidentialityProtection of subjects (especially
vulnerable populations)
Informed consentSurrogate consent
Assent
Favorable Risk/Benefit AnalysisGood Experimental DesignCompetent &Qualified PI
Subject selection - equitableInclusion/exclusion
Recruitment
J. Cooper, Albany Medical Center
Respect for Persons
o Treat individuals as autonomous agents
o Do not use people as a means to an end
o Allow people to choose for themselves
o Provide extra protections to those with diminished autonomy (i.e., Prisoners, Children, Cognitively Impaired, etc.)
Beneficence
The two general rules formulated from the principle of beneficence are:
oFirst, do no harm
oSecond, maximize possible benefits and minimize risks
Justice
o Treat people fairlyo Fair sharing of burdens and
benefits of the research
An injustice occurs when:1. benefits to which a person is
entitled are denied without good reason, or
2. when burdens are imposed unduly.
The “Common Rule” is the set of regulations which were developed to ensure compliance with the principles of the Belmont Report. The regulations fall under the Department of Health and Human Services. These regulations have been adopted by many other federal departments which regulate human research.
There are many other regulations with which UVM/FAHC are required to comply, such as the Food and Drug Administration, but these are all in addition to the “Common Rule”.
The Common Rule
Historical Overview
The protection of the rights and privacy of human participants involved in research activities is mandated by federal law.
The National Research Act Public Law 99-158, The Health Research Extension Act of 1985, and the National Commission for the Protection of Human Subjects of Biomedical and Behavioral Research provide guidelines for research with human participants to ensure their protection in the design and conduct of research.
These federal regulations require that any institution requesting and receiving funds from a federal department or agency for research involving human participants must assure that such research is reviewed and approved by the institution's institutional review board (IRB).
Federal Regulations and Policy45 CFR 46 - Basic DHHS Policy for Protection
of Human Research Subjects Originally adopted May, 1974, Revised January 13, 1981, Revised June 18, 1991◦ Additional protections for vulnerable populations
in Subparts B-DFederal Policy for the Protection of Human
Subjects - “The Common Rule” June 18, 1991◦ Departments of Agriculture, Energy, Commerce,
HUD, Justice, Defense, Education, Veterans Affairs, Transportation, and HHS. NSF, NASA, EPA, AID, Social Security Administration, CIA, and the Consumer Product Safety Commission.
Regulations and GuidelinesDHHS: CFR 45 Part 46 (4CFR$^)FDA: CFR 21 Parts 50, 56, 312,
812National Research Act of 1974ICH Good Clinical Practice
◦The regulations are open to interpretation
◦45 CFR 46, OHRP is the interpreter◦21 CFR and it subparts are
interpreted by the FDA
Regulatory Requirements for IRB ApprovalRisks to subjects are minimized.Risks are reasonable in relation to
anticipated benefits – if any.Selection of subjects is equitable.Informed consent will be sought and
appropriately documented.When appropriate, the research plan
makes adequate provision for monitoring the data collected to ensure the safety of subjects.
Regulatory Requirements for IRB ApprovalWhen appropriate, there are adequate
provisions to protect the privacy of subjects and to maintain the confidentiality of data.
When some or all of the subjects are likely to be vulnerable to coercion or undue influence, such as children, prisoners, pregnant women, mentally disabled persons, or economically or educationally disadvantaged persons, additional safeguards have been included to protect the rights and welfare of these subjects.
More Recent Violations
In a totally unprecedented flurry of enforcement activity, the National Institutes of Health (NIH) Office for Protection from Research Risks (OPRR) stopped research at Rush-Presbyterian-St. Luke's Medical Center (AP 1998), the West Los Angeles Veterans Affairs Medical Center (Monmaney 1999; Hilts 1999a), Duke University (Stout 1999; Weiss 1999), the University of Illinois at Chicago (Guerrero and Herguth 1999; Grahnke and Ritter 1999), the University of Colorado (Hubler 1999), Virginia Commonwealth University (Mathews 2000), and most recently, the University of Alabama at Birmingham (Hansen and Spencer 2000; Hilts 2000).
While there have been some substantive concerns relating to subject enrollment and informed consent, most of these sanctions have been levied because of sloppy and inadequate operation of institutional review boards (IRBs) and slow or inadequate response to OPRR's concerns.
Violations
Researchers at Stanford University were permitted by the state in 1997 to test the use of Depakote in incarcerated adolescent males to see if the drug would reduce aggressive behavior (Weber 1999).
Researchers at the New York State Psychiatric Institute, the Mount Sinai School of Medicine, and the Research Foundation of the City University of New York came under fire for giving fenfluramine to young children, many of whom were Hispanic or African American. The children were at-risk younger siblings of child offenders identified by the researchers through court records (Hilts 1998a; Waldman 1999; Bernstein 1999).
In the early 1990s, plastic surgeons at the Manhattan Eye, Ear, and Throat Hospital performed a study in which different surgical face-lift techniques were used on the opposite sides of patients' faces without securing IRB approval and without express patient consent (Hilts 1998b).
Jesse Gelsinger and Gene Therapy (U. of Penn.)
In 1999-2000 the Food and Drug Administration stopped all gene therapy trials at the University of Pennsylvania, because of alleged shortcomings and violations of protocols, revealed in an audit .prompted by the death of Jesse Gelsinger
Gelsinger suffered from Ornithine transcarbamylase (OTC) deficiency, a rare metabolic disorder.
Gelsinger's death also prompted a revelation of at least six deaths in other gene therapy trials that had not been reported to the NIH, in violation of the law, because the investigators determined the deaths were caused by the subjects' disease and not the experimental therapy.
Several institutions and foundations sponsoring genetic therapy research halted trials because of concerns about patient safety. The public hearings also spurred the reporting to NIH of 652 adverse events in trials using modified adenoviruses (as used in the Penn trial), compared to only 39 that had been reported promptly as required by law.
Issues - Conflict of interest, did not meet the inclusion criteria, consent forms did not adequately discuss risks.
Research Regulations
In 1979, the federal government developed regulations of ethical principals underlying the current regulations and standards that are contained in the Belmont Report.
It was the capstone of the National Commission for the Protection of Human participants of Biomedical and Behavioral Research. It outlines the ethical principals upon which the ethics of a research study are evaluated in the United States.
The Belmont Report embodies the moral consensus upon which stand our present US Federal regulations governing the ethics of human participants research conduct with Federal funds from the majority of Federal agencies.
Our present regulations formulize The Belmont Report's requirements for informed consent and establish another Commission recommendation that formalized and extended the existing peer review system of that time, which has matured into the Institutional Review Board (IRB) system that we have today.
DefinitionsResearch - a systematic investigation
designed to develop or contribute to generalizable knowledge.
Human Subject - a living individual about whom an investigator conducting research obtains◦ data through intervention or interaction with the
individual, or◦ identifiable private information
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 Expedited Exempt Research Not Involving Human
Subjects
Types of Review
InitialContinuing ReviewAmendmentsSafety Information or
Unanticipated Problems to Subjects or Others
Noncompliance
Purpose of the IRB at Howard University Review research proposals, projects,
and activities that involve human participants;
Determine for each activity or proposed activity if human participants will be placed at risk;
if risk is involved, determine if the importance of the knowledge to be gained warrants allowing the participant to accept the risks;
Oversee protection of rights and welfare of participants.
Assess whether the researcher(s) is/are qualified to conduct research involving human participants.
In General
Applies to funded and unfunded research
Submission of a protocol and approval by the IRB is mandatory for any faculty, staff or student who will interact with a human being for purposes of conducting research
Research may not begin before approval from the IRB is given
IRB Membership
Each IRB shall have at least five members, with varying backgrounds to promote complete and adequate review of research activities commonly conducted by the institution.
Each IRB shall include at least one member whose primary concerns are in the scientific area and at least one member whose primary concerns are in nonscientific areas.
Each IRB shall include at least one member who is not otherwise affiliated with the institution and who is not part of the immediate family of a person who is affiliated with the institution.
No IRB may have a member participate in the IRB's initial or continuing review of any project in which the member has a conflicting interest, except to provide information requested by the IRB.
Every nondiscriminatory effort will be made to ensure that no IRB consists entirely of men or entirely of women, including the institution's consideration of qualified persons of both sexes, so long as no selection is made to the IRB on the basis of gender. No IRB may consist entirely of members of one profession.
What type of research requires review? Research which involves the administration of drugs
or other substances to participants Research involving pregnant women and/or fetuses in
utero Research involving participants with life-threatening
physical conditions Research involving physically intrusive procedures Research which previous experience (by the particular
investigator or other investigators) has shown to create a potential of risk to participants
Research which potentially could put the participant at risk for legal or civil liability or invade a participant's privacy in regard to sensitive aspects of his/her behavior (e.g., illegal conduct, drug use, sexual behavior, alcohol use).
Full Review One or more Committee member(s) are assigned to
review the complete protocol or amendment, consent form, Investigational Drug/Device Brochure and any other protocol materials.
These Primary & Secondary Reviewers summarize the protocol or amendment to the Full Committee at a convened meeting and answer questions during the discussion.
Expedited ReviewProtocols, amendments, or continuing
reviews that meet specific federal criteria qualify for an expedited review.
The complete protocol, consent form, and any other protocol materials receive review and approval by a Committee Chair.
Expedited does not mean “fast” it is a federal term used for research that must meet specific criteria (DHHS 45 CFR 46.110)
Some CommonExpedited Review CategoriesBlood collection – within limits.Collection of other biological
specimens.Collection of data through non
invasive procedures such as MRI, EKG.
Research on existing data, specimens, materials collected for NON research purposes.
Surveys, questionnaires.
Some CommonExpedited Review CategoriesContinuing Review when: the research
is permanently closed to the enrollment of new subjects; (ii) all subjects have completed all research-related interventions; and (iii) the research remains active only for long-term follow-up of subjects; or
(b) where no subjects have been enrolled and no additional risks have been identified; where the remaining research activities are limited to data analysis.
Exempt from IRB ReviewCommittee review is not required for
certain categories of research activities that involve little or no risk to human subjects.
To determine if your research qualifies for
exemption from formal committee review, complete the “Protocol Exemption Review and Determination Checklist.”
Only the IRB can make the determination of Exempt, this cannot be determined by researchers!
Some research can not be exempted!!!!
IRB Review and Determination of “Research Not Involving Human Subjects”
There is some research that involves coded private information or specimens that do not involve human subjects.
When conducting research using data or specimens, the level of review by the IRB depends primarily on one factor: whether the data or specimens are identifiable to the principal investigator or key personnel.
Determinations of whether research involving coded private information or biological specimens is considered to be “human subjects research” must be made by the IRB, not the investigator.
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.
The IRB has the authority to:
oApprove
oRequire modifications prior to approval
oTableoDisapprove all research activities including proposed changes in previously approved human subject research.
Determining an ActionApproval – the criteria for approval are met.Approve with Administrative Review– IRB
stipulates specific revisions requiring simple concurrence by the investigator, then the IRB Chair or another IRB member designated by the Chair subsequently approve the revised research protocol on behalf of the IRB.
Deferral - substantive clarifications or modifications required that are directly relevant to the criteria for approval.
Disapproval – major ethical or scientific issues – PI can respond to the IRB or start over.
Informed Consent
Beyond the Consent
Form
The Consent ProcessInformed consent is not a single event or
just a form to be signed -- rather, it is an educational process that takes place between the investigator and the prospective subject.
The basic elements of the consent process include:
full disclosure of the nature of the research and the subject's participation,
adequate comprehension on the part of the potential subjects, and
the subject's voluntary choice to participate.
• Information – includes research procedure, purpose, risks, benefits, alternatives, etc.
• Comprehension – function of intelligence, rationality, maturity and language, presentation of information must be adapted to the subject’s capacity
• Voluntariness –requires conditions free of coercion and undue influence
Informed Consent
Consent Form Required Elements
Statement that the study involves researchResearch is describedDescription of RisksDescription of BenefitsDisclosure of Alternatives Confidentiality If more than minimal risk, compensation
and/or medical treatmentParticipation is voluntaryWhom to Contact
Additional Elements of Informed Consento Unforeseeable riskso Early termination o Additional costs to subjectso Consequences of a subject's decision to
withdraw from study participationo Disclosing new findings which may impact
a subject's willingness to continue participation
o Number of subjects involved
Informed Consent Process
Informed Consent is more than just the IRB-approved document
Initial
Ongoing
Initial Informed Consent Take the time at the initial discussion with subjects
so that they have a thorough understanding of what they are making a commitment towards
Test subject comprehension◦ Research versus standard of care procedures◦ Time commitment◦ Randomization◦ Alternatives◦ Potential costs◦ Risks and Benefits
Taking time upfront with potential subjects most likely will improve subject understanding and improve retention
Ongoing ConsentEvery time you have an encounter with a
subject gives researchers an opportunity to continue the informed consent process
Discuss new information that may impact a subject’s willingness to continue study participation (i.e., new known risks, benefits, alternatives, changes in study design, etc.)
Remind subject of study goals and objectives this will improve subject compliance with the protocol and improve retention of subjects
Documentation of ConsentArticles in most popular magazines are at the
8th grade level. Factors that improve readability include the following:
Technical terms should be replaced with ordinary language;
Use active tense rather than passive tense verbs ("We did" rather than "It was done");
Write shorter sentences in general; andMake clear the links of logical sequences
and of cause-and-effect, even if doing so makes the sentence much longer. ("We will do this, because that happened".)
ResearchApproved
Most faculty regarded the new streamlined IRB Process as an improvement
Summary…Take home messageThe IRB is a key element in the
conduct of human participant research at the University.
But, it is the primary responsibility of the IRB to safeguard the rights and safety of human participants. It is not necessarily the role of the IRB to expedite research at the University at the expense of safety and human rights.
Last WordsWelcome and thank you.Please don’t be afraid to
communicate with our office.Please don’t be afraid to ask for
advice at the meetings.Please don’t be afraid to contact
Senior Administrators and the IRB Chair for assistance.