Human Participants Research – IRB Presentation November 3, 2010 Office of Research Assurances...

Human Participants Research – IRB

Presentation November 3, 2010

Office of Research Assurances (ORA)University of Idaho

Overview

• Historical Context for Ethics in Research

• University of Idaho IRB

• IRB Processes for Exempt, Expedited, Full Board Reviews

• Some Commonly Asked Questions

• Contact Information

Historical Context for Ethics in Research

Ethical Consideration

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Working with people in research is a privilege, not a right.

Institutions and investigators who enroll human participants in research take on the moral obligation to protect the rights and welfare of those who agree to participate in such research.

• Nuremberg Trials • Tuskegee Syphilis Study• Milgram Experiment• Brooklyn Jewish Chronic Disease Cancer Study• Willowbrook Hepatitis Study• Stanford Prison Experiment

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Examples of Historical Ethical Violations

Nuremberg Trials

During the Nuremberg War Crimes Trials, 23 German doctors were charged with war crimes against humanity for “performing medical experiments upon concentration camp inmates and other living human subjects, without their consent, in the course of which experiments the defendants committed the murders, brutalities, cruelties, tortures, atrocities, and other inhumane acts.”

“Trials of War Criminals before the Nuremberg Military Tribunals under Control Council Law No. 10. Nuremberg”, October 1946 - April 1949. Washington D.C.U.S.G.P.O,1949-1953.

• First international document to advocate voluntary participation and informed consent

Consists of Ten Rules:• Voluntary consent• Anticipate scientific benefits• Benefits outweighing risks• Animal experiments need to come first • Protection of subjects against remote possibility of injury• Experiments should only be conducted by scientifically qualified

personnel • Subjects have ability to withdraw• Avoid suffering• No intentional death or disability• Stop the study if harm occurs

Nuremberg Code (1949)

PHS Study in Macon County, Alabama

1932: Recruited 300 black males

1933: 300 Controls were added

1943: Penicillin available for the military

Subjects taken off of WWII Draft List

1949: The Nuremberg Code came about

1951: Penicillin was made available to the public

1966: Local ethics committee reviewed study

RESULTS:

•28 Deaths

•100 Cases of disability

•19 Cases of congenital syphilis

Tuskegee Syphilis Study

http://images.google.com/imgres?imgurl=http://www.anairhoads.org/graphics/tuskegee.jpg&imgrefurl=http://www.anairhoads.org/govexperiments/tuskegee.shtml&h=236&w=345&sz=239&hl=en&start=5&tbnid=eZoeKtqY1S1pBM:&tbnh=82&tbnw=120&prev=/images%3Fq%3DTuskegee%2Bsyphilis%2B%26gbv%3D2%26svnum%3D10%26hl%3Den

Milgram Experiment (1961)

– (1963)– Indigent, elderly subjects were injected

with live cancer cells without their consent

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The Brooklyn Jewish Chronic Disease Cancer Study

The Willowbrook Hepatitis Study

– (1963-1966) – New York – Conducted on mentally retarded,

institutionalized children– Involved systematically infecting the

children with hepatitis– Parents were coerced into

consenting

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Willowbrook Hepatitis Study

Zimbardo’s Stanford Prison StudyAugust 1971

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9 College Men Assigned to be “Guards”

9 College Men Assigned to be “Prisoners”

1971-A psychology study of how ordinary people, college students, can behave in aggressive and dehumanizing ways based on the situation

Originally this experiment was to be two weeks long, but it had to be cut short after 6 days because “guards” were beginning to abuse the “prisoners” and prisoners were showing signs of depression and trauma.

The Declaration of Helsinki (1964)

• Principles established by the World Medical Association to guide physicians conducting medical research involving humans subjects

Differentiated between therapeutic and non-therapeutic research:

• Therapeutic research gives patients the opportunity to receive an experimental treatment that might have beneficial results.

• Non-therapeutic research is conducted to generate knowledge for a discipline, and might have positive results in future patients.

• Prominent researcher and anesthesiologist

• Chronicled 22 unethical studies

• “Ethics in Clinical Research”, published in the New England Journal of Medicine, June 1966.

• Beecher’s revelations led to IRBs and informed consent

Henry Knowles Beecher 1904-1976

Basic Ethical Principles

Respect for Persons• Individuals should be treated as

autonomous agents • Persons with diminished autonomy are

entitled to protection

Beneficence• The potential risks inherent in a project

must be justified by the potential benefits • Do good, not just avoid harm

Justice• Those who assume the risks of research

should be representative of those who stand to benefit from the research.

Belmont Report (1979)

Summary of Ethical Principles for Research with Humans

Nat. Commission for Protection of Human Subjects of Research

Dept. Health, Ed., Welfare

Federal Regulations

The Common Rule (Federal Policy for the Protection of Human Subjects, 56 FR 28003, June 18, 1991) :

45 CFR 46 (HHS implementation of the Common Rule)

• 45 CFR 46 – Department of Health and Human Services (HHS) regulations concerning protection of human research participants

• 21 CFR 51, 56 – FDA policies for human subjects research• Federal Wide Assurance (FWA) – Each institution

receiving federal funding has an assurance, which is a contract with the government regarding the protection of human subjects. Allows UI to do research w/out direct approval from Office for Human Research Protection (OHRP)

• HIPAA – Health Insurance Portability & Accountability Act - Protecting Personal Health Information

Federal Regulations

Timeline of Critical Events

• Broad ethical guidelines that assist scientists, subjects and society in understanding the ethical issues related to human subject research.

• These historical guidelines have evolved since the 1940s and serve as a framework for current regulations.

-Nuremberg code 1949-U.S. Scandals 1960

-Declaration of Helsinki 1964-Early NIH Policy 1966

-Tuskegee in open 1972-National Research Act 1974

-Belmont Report 1979-Common Rule 1991

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IRB at University of Idaho

HTTP://WWW.UIDAHO.EDU/ORA/COMMITTEES/IRB

HTTP://WWW.HHS.GOV/OHRP/HUMANSUBJECTS/GUIDANCE/DECISIONCHARTS.HTM

http://www.uidaho.edu/ora/committees/irb

The mission of the ORA is to facilitate and assist UI researchers in identifying and complying with all pertinent regulations and guidelines. We work collaboratively with researchers to develop and implement policies and procedures which assure compliance with minimal impact on research programs. This Office is part of the overall effort of UI to ensure the responsible conduct of research.

The ORA was established in 2008.

Office of Research Assurances (ORA)

IRB is charged with providing independent,objective review of research involving humanparticipants in order to: • protect the rights and welfare of human research

participants, and• ensure compliance of human participant research

with established ethical standards and federal, state, and local regulations and policies.

IRB at University of Idaho

• Surveys• Observation• Interviews• Accessing Private Records• Taste Testing• Clinical Trials• Therapeutic Evaluations• Experimental Treatments

Human Subjects Research Methods Human Subjects Research Methods

Human Participants/Research DefinitionsHuman Participants/Research Definitions

Research – a systematic investigation including research development, testing and evaluation,designed to contribute to generalizableknowledge

Human Subject – a living person about whom an investigator conducting research obtains

1) data through an intervention or interaction with the individual, or

2) identifiable private information

More DefinitionsMore Definitions

• Living Individual-The Specimen (s)/data/information must be collected from live subjects.

• About whom- A human subject research project requires that the data received from the living individual is about the person.

• Intervention-Includes physical procedures, manipulations of the subject, or manipulations of the subject’s environment for research purposes.

• Interaction- Includes communication between the investigator and the subject. This includes face-to face, mail, and phone interaction as well as other modes of communication

• Identifiable private information- Identifiable means the information contains one or more data elements that can be combined with other reasonably available information to identify an individual ( e.g. Social security #)

What Activities Require IRB Review?

Specific Populations

• Children under 14 years outside established educational settings

• Neonates/ Fetuses• Prisoners• Pregnant women• Decisionally impaired• HIV/AIDS patients• Native American Tribes

• Crime victims• Students or employees

under the supervisory or evaluative authority of the researcher

• Substance abusers• Non-English speakers• Terminally ill• Institutionalized

individuals

Doesn’t Need IRB Approval

• Quality Assurance/Quality Improvement/Research Practica : http://www.uidaho.edu/ora/committees/irb/irbpolicies

• Samples from deceased individuals

• Not Sure? Not Sure? Call 885-6162 or Email [email protected]

IRB Processes for Exempt/Expedited/Full Board Reviews

Three Types of IRB Review

Exempt (45 CFR 46.101)• Limited categories of research exempt from Federal regulation

and IRB review and oversight.

Expedited Review (45 CFR 46.110)• Review by one or more IRB members of research that within

certain prescribed categories and presents no more than minimal risk. Full review standards are applied.

Full Board Review• Convened meeting of board, usually reserved for protocols

presenting more than minimal risk, research that cannot be expedited, or projects presenting issues not previously considered by IRB.

Student Review Process OverviewStudent Review Process Overview

Student

Faculty(Faculty Advisor)

IRB

• Exempt research must meet at least one of six specific criteria (slides follow with more information)

• PI needs to inform ORA of post exempt certification protocol changes to ensure that project still qualifies as exempt

Exempt Research

1. Research conducted in established or commonly accepted educational settings, involving normal educational practices, such as i. research on regular and special educational instructional strategies, orii. research on the effectiveness of or the comparison among instructional techniques, curricula, or classroom management methods.

Exemption also applies to children.

Exempt Research in the Regulations

2. Research involving the use of educational tests (cognitive, diagnostic, aptitude, achievement), survey procedures, interview procedures or observation of public behavior, unless:i. information obtained is recorded in such a manner that human participants can be identified, directly or through identifiers linked to the participants; andii. any disclosure of the human participants ' responses outside the research

could reasonably place the participants at risk of criminal or civil liability; oriii. be damaging to the participants ' financial standing, employability, or reputation.Exemption also applies to children (if anonymous) for educational tests. Exemption does not apply to children for survey procedures, interview procedures or observation of public behavior (observation of public behavior may apply to children if the researcher does not participate in the activities being observed).


3. Research involving the use of educational tests (cognitive, diagnostic, aptitude, achievement), survey procedures, interview procedures, or observation of public behavior that is not exempt under category (2) of this section, if:i. the human participants are elected or appointed public officials or candidates for public office; ore.g. public official: mayor but a city planner would not be a public official. Chief of police is an elected public official but a police officer would not.

ii. federal statute(s) require(s) without exception that the confidentiality of the personally identifiable information will be maintained throughout the research and thereafter.


4. Research involving the collection or study of existing data, documents, records, pathological specimens, or diagnostic specimens, if these sources are publicly available or if the information is recorded by the investigator in such a manner that subjects cannot be identified, directly or through identifiers linked to the participants.


5. Research and demonstration projects which are conducted by or subject to the approval of department or agency heads, and which are designed to study, evaluate, or otherwise examine:i. public benefit or service programs;ii. procedures for obtaining benefits or services under those

programs;iii. possible changes in or alternatives to those programs or

procedures;iv. possible changes in methods or levels of payment for benefits or services under those programs.

(Narrowly construed under Federal Regulations e.g. WIC, Disability Benefits)


6. Taste and food quality evaluation and consumer acceptance studies:i. if wholesome foods without additives are consumed orii. if a food is consumed that contains a food ingredient at or below the level and for a use found to be safe, or

agricultural chemical or environmental contaminant at or below the level found to be safe, by the Food and Drug Administration or approved by the Environmental Protection Agency or the Food Safety and Inspection Service of the U.S. Department of Agriculture.


Protocol (IRB) Approval Process for Protocol (IRB) Approval Process for Exempt ProjectsExempt Projects::

Changes (if needed) Changes noted by ORA

Submission of Project Proposal Form(Principal Investigator/Faculty Advisor)


Review of Protocol(Staff at ORA)

Review of Protocol(Staff at ORA)

Contact PI for necessaryChanges to protocol

Not Certified as Meeting an ExemptionNot Certified as Meeting an ExemptionExempt CertificationExempt Certification

Communicated(E-mail Notification)

Communicated(E-mail Notification)

PI ChangesPI Changes

Re-submissionRe-submission

Expedited/Full Board ReviewExpedited/Full Board Review

Preliminary Review of Project Proposal(Staff at Office of Research Assurances)

Preliminary Review of Project Proposal(Staff at Office of Research Assurances)

Expedited Review

Two general categories of research available for expedited review (46.110(b)):

1)Research activities presenting no more than minimal risk and listed in NIH adjunct list of categories qualifying for expedited review

2)“minor changes in previously approved research during the period (1 year or less) for which the approval is granted”

Protocol (IRB) Approval Process for Protocol (IRB) Approval Process for Expedited ProjectsExpedited Projects::




Review by 1- 2 IRB Members Review by 1- 2 IRB Members

Email, phone callto PI if more infois needed

Feedback:Approved or Deferred

Approval deferred pending specific changesApproval deferred pending specific changesApproval grantedApproval granted

Approval CommunicatedE-mail Notification




ApprovalApproval

Preliminary Review of Project Proposal(Staff at ORA)


Full Board Review

• Evaluation of application for protocol presenting more than minimal risk to subjects by IRB members.

• Research involving Human Participants that does not qualify for expedited review.

• Investigator has opportunity to provide answers to questions at the full IRB committee meeting

Protocol (IRB) Approval Process for Protocol (IRB) Approval Process for Full Board ProjectsFull Board Projects::




Approval deferred pending specific changesApproval deferred pending specific changes Approval deniedApproval deniedApproval grantedApproval granted





ApprovalApproval



Pre-review by IRB Members Pre-review by IRB MembersEmail, phone callto PI if more infois needed

Avoiding Common PitfallsAvoiding Common Pitfalls• Key Concerns of Reviewers:

• Are subjects protected from harm/embarrassment?• Confidentiality/anonymity of data• Risk/benefit ratio and scientific validity• Special populations

• Abstract - too much theory, not enough on methods• Stating data as anonymous, but it’s confidential• Stating there are no risks in your study (see next slide)• Overstating benefits of study• Not attaching consent, & well-labeled survey materials• Poorly constructed consent form

Common Research Risks Common Research Risks (Non-medical)(Non-medical)

• Disclosure of private/confidential information • Psychological risks (insult, trauma)• Social risks (embarrassment, rejection by peers)• Economic risks (loss of job, credit, insurance)• Legal risks (subpoena, fine) • Inconvenience/intrusiveness (boredom, frustration)

Avoiding Common PitfallsAvoiding Common Pitfalls

Anonymity vs. Confidentiality • Anonymity - Providing anonymity of information collected from research

participants means that either the project does not collect identifying information of individual subjects (e.g., name, address, Email address, etc.), or the project cannot link individual responses with participants’ identities. A study should not collect identifying information of research participants unless it is essential to the study protocol.

• Confidentiality - Maintaining confidentiality means that only the investigator(s) or individuals of the research team can identify the responses of individual subjects; however, the researchers must make every effort to prevent anyone outside of the project from connecting individual subjects with their responses.

Informed ConsentInformed Consent

What is the purpose of informed Consent????

To make sure the potential research participant has adequate decision making capacity, and that they are able to make a voluntary choice to be in or out of the study

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Informed Consent ShouldInformed Consent Should

• Give subjects all the information that they may need to make a decision. The information

should be factual, complete, and accurate.• Ensure that subjects understand the information.

– Should be written at a level to provide understanding by the subject population.

• Give subjects an opportunity to consider participation in the study on an initial and ongoing basis.

Elements of Informed ConsentElements of Informed ConsentChecklistChecklist

Basic Elements• Statement that the

study involves research• Purpose of the study• How long the

participant will be involved

• Description of procedures

• Identification of experimental procedures

• Description of reasonably foreseeable risks or discomforts

• Description of benefits to the subjects or others


• Disclosure of alternative treatments that might be advantageous to the subject

• Statement describing the extent, if any, to which confidentiality of records will be maintained

• Explanation of whether or not compensation or treatment are available in the event of an injury

• Whom to contact regarding research and subjects' rights or in the event of an injury


• Statement that participation is voluntary, refusal is not penalized, and the subject can withdraw at any time

• Additional Elements• Unforeseeable risks• Termination by

investigator

• Additional costs to subjects

• Orderly procedures for withdrawal

• New findings• Number of participants

Informed Consent – Waiver of Informed Consent – Waiver of DocumentationDocumentation

An IRB may waive the requirement of a signed consent form for all or some of the subjects, if:

1) The only record linking the subject and the research would be the consent document and the principle risk would be potential harm resulting from a breach of confidentiality.

2) The research presents no more than minimal risk of harm to the subjects and involves no procedures for which written consent is normally required outside the research context.

Informed Consent – Waiver of Informed Consent – Waiver of DocumentationDocumentation

If the IRB approves waiver of written documentation of consent, it may still require:

• Statement at the beginning of the survey/interview that incorporates the elements of informed consent

• Written consent statement at the initial screen or cover letter of a survey (web/mail)

• Consent elements in invitation to participate in survey (e-mail communication/mailing)

• Oral consent prior to initiating an interview (with subsequent written statement)

• Statement at the conclusion of survey/interview• Oral consent prior to initiating an interview (with subsequent written

statement)

Child AssentChild Assent

• Parents must give consent for their children to participate, but the children must assent to participate.

• Assent is an affirmative action on the part the child indicating willingness to participate.

• A child is a person who has not attained the legal age of consent, 18 years in the state of Idaho.

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Child Assent Child Assent (cont.)(cont.)

• The child assent form must include the same elements as the consent form, but must be written at the appropriate age level for comprehension

• Ages 3-7: verbal assent must be obtained and documented by the researcher

• Ages 7- below18: This age group must sign a separate assent document

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Some Commonly Asked Questions

Parental consent is sufficient to involve minors in studies.• False;False; it is necessary, but not sufficient• Must also have assent of child participant (> 3 yrs. old)

Class projects that involve human participants research are exempt from review.• False;False; all research is reviewed

Written consent is necessary for all studies involving human participants.• False;False; in some cases (phone survey, anonymous survey, illiterate populations), other forms of consent may be better

Common Questions? ?

The primary reason for IRB review is to protect UI from legal suits by participants.• False, it is to protect participants.• Participants still retain their legal rights

All research involving humans poses some risk.• True;True; even if it is considered minimal.

Participants can be assured of confidentiality.• False, While there are many measures that can be taken to protect confidentiality, UI is a state institution and data collected by faculty, staff and students can be requested through the Public Records Act.

Common Questions? ?

Training in human subjects research required at UI.• True • Training link: http://phrp.nihtraining.com/users/login.php Training link: http://phrp.nihtraining.com/users/login.php

All protocols need to be reviewed by Full Board.• False;False; most qualify for exempt or expedited status.• Depends on risk• Your protocol may be bumped up from exempt to expedited or

from expedited to full board if a reviewer feels it is appropriate

Common Questions? ?

When a participant signs a consent form, he/she is committing to the entire research project.• False;False; participants can withdraw at any time without penalty

Federal, state, and university regulations regarding human participants research change frequently.• True;True; as new areas of research and new issues arise

UI’s IRB has authority to create policies beyond federal and state regulations.• True;True; it will never go against those regulations, but it may add additional guidelines

Common Questions? ?

WebsitesWebsites• Declaration of Helsinki

–http://ohsr.od.nih.gov/guidelines/helsinki.html • Federal Regulations -

http://www.hhs.gov/ohrp/humansubjects/guidance/45cfr46.htm

• HIPAA –http://www.hhs.gov/ocr/privacy/

• Nuremburg Codehttp://www.ushmm.org/research/doctors/Nuremberg_Code.htm

• Belmont Reporthttp://ohsr.od.nih.gov/guidelines/belmont.html

• University of Idaho IRB -http://www.uidaho.edu/ora/committees/irb

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Traci CraigInstitutional Review Board

[email protected]

Lorraine McConnellResearch Assurance Manager

[email protected]

Julie HaddoxResearch Assurance Specialist

[email protected]

Who to Contact with Questions:Who to Contact with Questions:

Human Participants Research – IRB Presentation November 3, 2010 Office of Research Assurances...

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