UIUC Human Subjects Module 1

Module 1 is intended to meet the basic training requirement for investigators receiving federal funding for human subjects research. Consult the UIUC Investigator Handbook, for detailed information and policies covering the topics in this module.

Contents

Section 1: Human Subject Research Definitions and Ethical Principles
Section 2: Campus Review of Human Subjects Research
Section 3: Principal Investigator Responsibilities and the Training of Research Personnel
Section 4: Institutional Review Board (IRB)
Section 5: IRB Office
Section 6: Protocol Preparation and Submission and the Review and Approval Process
Section 7: Modifications to Protocols
Section 8: Annual Renewal of Protocols
Section 9: Categories of Exempt Human Subject Research
Section 10: Informed Consent
Section 11: Risk/Benefit
Section 12: Recruitment of Subjects
Section 13: Confidentiality Issues
Section 14: Record Retention
Section 15: Special Subject Groups
Human Subjects Quiz
 

Section 1:  Human Subject Research Definitions and Ethical Principles

UIUC Human Subject Research Policy requires IRB review and approval prior to any involvement of human subjects in any research activity. Generally, any research involving living humans, human tissues, or humans' records that is conducted by any employee or agent of the University of Illinois at Urbana–Champaign (UIUC), or otherwise conducted at or sponsored by the UIUC, requires IRB review, irrespective of the risks, scope, funding, or location of the research. Specifically, IRB review is required for any human subjects research that

• is conducted by UIUC faculty, staff, student, or visiting researchers (including but not limited to intern, postdoctoral, and sabbatical researchers);
• is conducted on the premises of or is sponsored by the UIUC;
• is performed with or involves the use of facilities or equipment belonging to the UIUC;
• involves UIUC faculty, staff, students, or patients;
• satisfies a requirement imposed by the UIUC for a degree program; or
• is certified by a dean or department head to satisfy an obligation or a faculty appointment at the UIUC, including clinical and adjunct appointments.

As a condition of receipt of federal research funding, the University of Illinois, Urbana–Champaign has also given an Assurance that it will comply with the Department of Health and Human Services (DHHS) regulations for the protection of human research subjects. The Assurance also stipulates the composition of the IRB and organization of research administration as it relates to human subject research.

In 1991, federal departments and agencies that conduct, support, or regulate research adopted a common Federal Policy for the protection of human research subjects. This is known as the Common Rule and is found in the Code of Federal Regulations 45 CFR Part 46 and subsequent amendments.

Definition of Human Subject
See Figure 1, below. Human Subject means a living individual about whom an investigator conducting research obtains

1. data through intervention or interaction with the individual, or
2. identifiable private information.

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Definition of Research
Research means a systematic investigation, including research development, testing, and evaluation, designed to develop or contribute to generalizable knowledge.
 

Ethics is an essential part of research activity and professional responsibility. The foundation of ethical principles for human subjects research is embodied in the Belmont Report , which was produced in 1979 by the National Commission for the Protection of Human Subjects of Biomedical and Behavioral Research. The three tenets of that report are

• Respect for Persons: Subjects should be treated as autonomous agents and be fully informed about the research in which they participate. Persons with diminished autonomy (children, prisoners, the mentally handicapped, etc.) should be protected.
• Beneficence: Benefits of participation in the research should outweigh any potential harm or risk to subjects.
• Justice: Selection of research subjects should be fair and those asked to bear the burden of the research activity should also receive the benefits of the research.

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Section 2: Review of Human Subjects Research

All human subjects research must be reviewed and approved by the UIUC IRB or determined to be exempt by the IRB Office prior to any involvement of human subjects in the research. For all projects, an IRB-1 application or Application for Exemption, with relevant attachments, must be submitted to the IRB Office for review. The IRB-1 asks for information about the investigator(s), the nature of the research, the funding source, targeted subject groups, how subjects will be recruited, how informed consent will be obtained, how confidentiality will be protected, and the risks and benefits of the proposed research.

The IRB will determine the criteria for approval of human subjects research and the frequency of continuing review. The IRB Office has been delegated the day-to-day authority for determining the level of review needed for each case and for reviewing responses to the Board's stipulations for approval. New cases are categorized as follows:

Exempt

New cases that clearly meet one of the categories for exempt research, as provided in the federal regulations and as determined by the IRB or its Office, are not sent to a convened Board for review. These cases are reviewed and approved in the IRB Office only after the IRB application is satisfactorily completed by the investigator. The investigator may not make the determination of exemption—all human subjects research must be submitted for review before approval under an exemption can be made.

Expedited

An expedited review consists of a review by the IRB Chair, or designee(s) from among members of the IRB in accordance with the requirements set forth in Title 45 of the Code of Federal Regulations, Part 46 (45 CFR 46 ), §110. The IRB Office makes the initial determination of whether an expedited review is allowable. Assigned IRB member(s) make their recommendation(s) to the IRB Office. If the case is approved, the decision will be communicated to the investigator and also is reported at the next IRB meeting. IRB members may ask for discussion of expedited cases during any meeting.

Full Board

New cases that are neither exempt nor expedited are sent to the full Board for review and are assigned both a primary and a secondary reviewer by the IRB Office.

Upon completion of the review, a letter will be sent to the responsible project investigator (RPI) authorizing initiation of the project or containing stipulations that must be met before approval is granted. The involvement of human subjects may begin only after stipulations have been satisfactorily addressed and formal, written approval is given.

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Section 3: Principal Investigator Responsibilities and the Training of Research Personnel

The primary responsibility for the day-to-day protection of the rights and welfare of human subjects lies with the responsible principal investigator (RPI). Specifically, the RPI is charged with assuring that

1. the information provided in the IRB application is complete and correct.
2. as Responsible Project Investigator, she(he) takes ultimate responsibility for the protection of the rights and welfare of human subjects, the conduct of the study, and the ethical performance of the project.
3. she(he) will comply with all UIUC policies and procedures, the terms of its Federalwide Assurance, all applicable federal, state, and local laws, and policies of both the sponsoring agency and cooperating institutions, as applicable, regarding the protection of human subjects in research.
4. the project will be performed by qualified personnel according to the UIUC IRB-approved protocol.
5. The equipment, facilities, and procedures to be used in the research meet recognized standards for safety.
6. no change will be made to the human subjects protocol or consent form(s) until approved by the UIUC IRB.
7. legally effective informed consent or assent will be obtained from human subjects as required.
8. adverse events and effects, unanticipated problems, complications, and injuries involving subjects will be promptly reported to the UIUC IRB Office and to the appropriate Departmental Executive Officer.
9. She(he) is familiar with the latest edition of the UIUC Handbook for Investigators and will adhere to the policies and procedures explained therein.
10. student and guest investigators on the project are knowledgeable about the regulations and policies governing this research.
11. She(he) will meet with the project's other investigator(s) on a regular basis to monitor study progress.
12. if she(he) will be unavailable, as when on sabbatical or other leave, including vacation, she(he) will arrange for an alternate faculty sponsor to assume responsibility during her(his) absence and will advise the UIUC IRB by letter of such arrangements.
13. The proposed research has not been done, is not underway, and will not begin before IRB approval has been obtained.

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Section 4: Institutional Review Board (IRB)

The Institutional Review Board (IRB) is appointed by the Vice Chancellor for Research. The IRB is constituted as required by federal regulations to include members with effective knowledge of subject populations, with at least one unaffiliated community member and one nonscientist. The UIUC IRB is responsible for

1. providing initial and continuing review of human subjects research;
2. ascertaining the acceptability of the proposed research in terms of applicable regulations, policies, and procedures;
3. documenting that reviews are conducted according to applicable regulations, policies, and procedures;
4. appropriate oversight and monitoring of the research; and
5. providing advice and information to investigators engaged in research involving human subjects.

The UIUC IRB is additionally responsible for

1. developing policy, procedures, information, and instructions regarding human subjects research;
2. adjudicating differences and reviewing problems arising in research involving human subjects;
3. ensuring compliance with externally mandated policies and regulations; and
4. reporting to the appropriate institutional officials and, for research governed by HHS regulations, to the Secretary of HHS, any serious or continuing adverse events or investigator noncompliance with the requirements and determinations of the IRB.

The IRB may delegate certain responsibilities to IRB Office as appropriate.

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Section 5: IRB Office

The IRB Office is located in Suite 203 - 528 East Green Street (6th and Green Street). E-mail may be sent to irb@illinois.edu, and the phone number is 217.333.2670.

The responsibilities of the IRB Office are to

• provide information to investigators in preparation of human subject research protocols.
• receive from investigators all research protocols and submit them to the IRB.
• keep investigators informed of all IRB decisions.
• make final determination of exemption from full IRB review based on Section 101 of the Code Federal Regulations (45 CFR 46),
• forward certification of IRB approval to the appropriate funding agency, as requested.
• maintain and provide appropriate access to IRB records.
• ensure smooth communication between the IRB, investigators, department heads, and university administrators.
• receive inquiries from research subjects and resolve any issues that arise between subjects and investigators.
• provide education and information about federal and state regulations and ethical conduct of human subject research to the campus community, IRB members, and researchers.

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Section 6: Protocol Preparation and Submission, and the Review and Approval Process

To prepare and submit a protocol for review and approval of any human subjects research, do the following:

• Download the IRB-1 Form from this IRB Web site.
• Type all answers onto the form, using continuation pages as indicated.
• Answer all questions completely.
• Attach copies of all questionnaires, interview scripts, psychological instruments, and other relevant information or forms, as indicated on the application.
• If the research is part of an externally funded project, attach a copy of the complete funding proposal.
• Sign the IRB-1 form (responsible project investigator).
• Submit one complete, single-sided hard copy of the IRB-1, with attachments, to:

  IRB Office
  Suite 203, MC–419
  528 East Green Street
  Champaign, IL 61820
  



• Please call the IRB Office at 217.333.2670, if you have questions or need assistance in preparing your application materials.
• If a certification of approval is to be sent to the funding agency, the agency's name and address or FAX information should be provided on the IRB-1 form.

Deadlines for submission and dates of review are also listed on the IRB Web site Board Calendar. Submission prior to the deadline is critical; errors, omissions, or potential problems can not otherwise be identified before the protocol is sent to the IRB.

Within one week of formal IRB review, a letter is sent to investigators, either giving approval, requesting additional information, or indicating stipulations that the investigator must respond to before final IRB approval is given. Human Subject research may not be initiated until all such issues have been resolved and formal approval has been granted.

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Section 7: Modifications to Protocols

All modifications to human subjects research must receive prior IRB approval before subjects are involved in the revised protocol. Prior to implementation, modifications must be submitted on a Research Amendment Form and reviewed and approved by the IRB committee.

Minor modifications
Minor modifications to previously approved projects include those that do not alter the risk-benefit assessment for the research. Examples include changes in the investigators, minor wording or formatting changes in the consent form(s), recruiting materials, interviews, or questionnaires; minor changes in remuneration, time of participation, or subject recruitment; or the use of a new site that is not materially different from a previously approved site. Minor modifications may also include changes to other parameters, whereby the investigator provides the subjects with more accurate information as a result of additional experience with the protocol (such as how long a procedure takes).

Major modifications
Major modifications include significant protocol changes that would cause subjects to engage in activities not previously approved; or that involve an increased level of risk to the physical, emotional, or psychological well-being of participants (including the loss of confidentiality); or that involve a decreased benefit; or that otherwise result in alteration of the risk-benefit assessment for the research. For example, adding a new subject population, changing inclusion or exclusion criteria, changing the informed consent process, and changing procedures affecting subject confidentiality all constitute potentially major modifications.

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Section 8: Annual Renewal of Protocols

The UIUC IRB conduct continuing reviews of nonexempt research at intervals appropriate to the degree of risk, but at least once per year. Continuing cases are categorized as follows:

Renewal, Minimal Risk—Expedited without Full Board Review

Ongoing minimal risk projects receive annual, expedited, continuing reviews. Each of these has been previously reviewed and approved as a new project according new case procedures. The expedited continuing review is performed by the IRB Chair or designee(s). Approved cases are listed on the staff report of the next IRB meeting and IRB members may ask for discussion of these cases during the meeting.

Renewal, More than Minimal Risk—Full Board Review

Ongoing projects that have been determined to be more than minimal risk must receive full Board review. These cases are assigned primary and secondary reviewers from the Board and are reviewed at a convened meeting of the full board.

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Section 9: Categories of Exempt Human Subject Research

All human subjects research at UIUC, whether exempt or not, must be conducted in accordance with UIUC policies, the UIUC Federalwide Assurance, federal guidelines, and the ethical principles set forth in the Belmont Report. Unless it will involve prisoners as subjects or certain activities involving children, research may be exempt from the review of a convened IRB if the only involvement of human subjects will be in one or more of the six categories described in this section. The determination of exemption may not be made by the investigator. All human subjects research, whether exempt or not, must be reviewed and approved by either the campus IRB (or its Office). No involvement of human subjects may take place prior to formal, written approval from the IRB Office.

If a project meets any of the following six exemption categories it may be approved under an exemption. This determination shall be made by the campus IRB or the IRB Office after a complete review of the research protocol, associated measures and addenda, and the proposed consent process and relevant forms. Research involving more than minimal risk is not exempt.

1. Title 45 Code of Federal Regulations §46.101(b)(1) exempts research conducted in established or commonly accepted educational settings, involving normal educational practices, such as
   1. research on regular and special education instructional strategies, or
   2. research on the effectiveness of or the comparison among instructional techniques, curricula, or classroom management methods.


2. Title 45 Code of Federal Regulations §46.101(b)(2) exempts research involving the use of educational tests(cognitive, diagnostic, aptitude, achievement), survey procedures, interview procedures, or observation of public behavior can be exempt, unless
1. information obtained is recorded in such a manner that human subjects can be identified, directly or through identifiers linked to the subjects; and
2. any disclosure of the human subjects' responses outside the research could reasonably place the subjects at risk of criminal or civil liability or be damaging to the subjects' financial standing, employability, or reputation.

NOTE: Exemption 2 does not apply to the following types of research involving children: surveys, interviews, and observations of public behavior when the investigator is a participant in the activities being observed.

3. Title 45 Code of Federal Regulations §46.101(b)(3) exempts 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 paragraph (b)(2) of this section, if
   1. human subjects are elected or appointed public officials or candidates for public office; or
   2. federal statute(s) require(s) without exception that the confidentiality of the personally identifiable information will be maintained throughout the research and thereafter.

4. Title 45 Code of Federal Regulations §46.101(b)(4) exempts 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 subjects. NOTE: In order to be eligible for exemption 4, all of the materials have to exist at the time the research is proposed and must have been collected for purposes other than the proposed research.

5. Title 45 Code of Federal Regulations §46.101(b)(5) exempts research and demonstration projects that are conducted by or subject to the approval of department or agency heads, and that are designed to study, evaluate, or otherwise examine
   1. public benefit or service programs;
   2. procedures for obtaining benefits or services under those programs;
   3. possible changes in or alternatives to those programs or procedures; or
   4. possible changes in methods or levels of payment for benefits or services under those programs.

6. Title 45 Code of Federal Regulations §46.101(b)(6) exempts taste and food quality evaluation and consumer acceptance studies,
   1. if wholesome foods without additives are consumed; or
   2. 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 US Department of Agriculture.

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Section 10: Informed Consent

No investigator may involve a human being as a subject in research unless legally effective informed consent is first obtained from the subject or from their legally authorized representative. Investigators must seek consent only under circumstances that provide sufficient opportunity for the subject or their representative to consider whether or not to participate.

The IRB may consider a waiver or alteration of the informed consent requirement only if all four of the following are true:

1. The research involves no more than minimal risk to the subjects;
2. the waiver or alteration will not adversely affect the rights and welfare of the subjects;
3. the research could not practicably be carried out without the waiver or alteration; and
4. whenever appropriate, the subjects will be provided with additional pertinent information after participation.

Documentation of Informed Consent

Under federal regulations, informed consent must be documented by the use of a written form approved by the IRB and signed by the subject or their legally authorized representative. The consent form may be a comprehensive written document that embodies the federally required elements of informed consent, or a short form stating that the required elements of informed consent have been presented orally to the subject or their representative. In either case, a copy of the form must be given to the subject or their representative.

The IRB may consider a waiver or alteration of these requirements only if it finds either

1. that the only record linking the subject and the research would be the consent document and the principal risk would be potential harm resulting from a breach of confidentiality; or
2. that the research presents no more than minimal risk of harm and involves no procedures for which written consent is normally required outside the research context.

Within federal guidelines, the methods used to obtain consent may vary. They should be designed to fit the nature of the research, the nature and magnitude of the risks involved, the research setting, the nature of the subjects who will participate, and the requirements of applicable policies, laws, and regulations. If appropriate justification is given, an oral process may be approved by the IRB.

Essential Elements of Informed Consent

It cannot be overly stressed that the language used in every consent form or script must be understandable to the subject or their representative. Commonly, IRB approval of research is delayed over inadequate consent forms that have either too much or too little information, that are confusing, or that are written above the average subject's reading level. Consent forms should be written for the average participant's level of understanding, by keeping in mind the 8th grade reading level of the average American adult, and by being careful to avoid technical language or terminology. Every form should contain the essential elements as detailed in the Elements Of Informed Consent document.

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Section 11: Risk/Benefit

There are different risks inherent in different research procedures. All risks must be thoroughly described and assessed in the investigator's application for IRB approval, and minimized during the research. For purposes of safeguarding human subjects and according to federal guidelines, risks are classified as either minimal risk or more than minimal risk. Under minimal risk, the risks of harm in the proposed research are no greater, considering probability and magnitude, than those ordinarily encountered in the subject's daily life or during the performance of routine physical or psychological examinations or tests.

The potential for physical risk and the specific risks that are possible may be most obvious in procedures requiring physical intervention or involving strenuous exertion. The researcher must specifically describe such risks to both the IRB and to the subject who is considering participation in the research. If, during the course of the research, the researcher becomes aware of new information about risks, he or she must notify both the IRB and the subjects who are enrolled in the research so that they can reassess the risk-benefit ratio applicable to research participation.

There is a wide range of medical, social, and behavioral research protocols that may pose no immediate physical risk to the subject but that may involve varying degrees of emotional stress, deceit, or invasion of privacy. If a subject's dignity, self-respect, psyche, emotions, reputation, employment, financial standing, or criminal or legal status would be adversely affected through either participation in the research or as a result of a breach of confidentiality with regard to the research results, then the subject is at risk from the research.

It is the investigator's responsibility to minimize the risks associated with any research and to make clear to the research subjects any benefits that may result to them directly or more generally to society. Direct payments or other forms of remuneration to the research subject are not considered to be benefits of participation. Evaluation of the risk–benefit ratio is a primary consideration during the IRB review of research protocols.

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Section 12: Recruitment of Subjects

Subjects should not be selected for potentially beneficial research on the basis of favoritism, nor should risky research be directed to subjects who have limited autonomy.

No coercion, explicit or implicit, should be used to obtain or maintain cooperation. This is always a consideration when selection of subjects is from a UIUC course. Investigators should explicitly discuss in their research protocol steps to ensure that there will be no coercion to participate in a research activity conducted in a course, especially if the course instructor is also an investigator on the project. When participation as human subjects forms an integral part of any course, the official University course catalogue and timetable shall state that fact in the description of the course. There shall also be mechanisms in place to ensure that the subjects' participation in specific research is voluntary.

If access to research subjects is gained through cooperating institutions not under the control of the University of Illinois at Urbana–Champaign, the institution(s) must be identified on the IRB-1 form. For externally funded projects, it will be necessary to document review by an IRB with a current federal assurance at the cooperating institutions.

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Section 13: Confidentiality Issues

In all research involving human subjects, confidentiality of identifiable information is presumed and must be maintained unless the investigator obtains the express permission of the subject to do otherwise. That is, the anonymity of the subjects must be preserved in the disseminated research results. The more sensitive the material, the greater the care that must be exercised. Ordinarily, the following requirements must be met:

• Questionnaires, inventories, interview schedules, and other data-gathering instruments and procedures should be carefully designed to limit the personal information to be acquired to that which is essential, and should be administered using procedures that will protect the subject's privacy.
• Information that could reveal a subject's identity should be securely stored in files accessible only to the project investigator and authorized staff.
• As early as feasible, data should be coded to remove identifying information, and identifiers destroyed.
• The identity of subjects must not be released except with their express permission. This includes through the use of audio tapes, videos, photos, or other images (e.g., MRI, CT scan) that either show the subject's face or would divulge unique or identifying features. Subjects should always be told during the informed consent process if their likeness or other unique or identifying features will be imaged and how the images will be used. Explicit consent must be obtained for any public use of such images (including uses in the classroom, on the World Wide Web, or as part of a presentation of the research results), since publication would otherwise constitute a breach of the basic confidentiality requirement.
• Use of existing data that were originally obtained for different purposes and that involve identifiable subject information requires examination of the risks involved. There should be a determination of whether the new use is within the scope of the original consent or whether it is necessary or feasible to obtain additional consent.
• The identity of research subjects or research data can be sought under a subpoena. Any investigator served with a subpoena should immediately contact the Office of University Legal Counsel and the IRB Office for assistance. For studies involving the collection of data on sensitive matters or involving criminal activities, the investigator should consider obtaining a federally granted Certificate of Confidentiality, which will provide some protection even against a subpoena for research data.
• If research data is sought under the Freedom of Information Act, investigators should contact the University of Illinois Office of Public Affairs and the IRB Office.
• Mandated reporters are required by law to report instances of suspected child or elder abuse or neglect or instances where a research subject is in danger of harming himself/herself or others. The circumstances where confidentiality will be broken should be conveyed in the consent form. Any investigator may feel ethically bound to break confidentiality in case of suspected abuse or neglect, and this should be made clear to research participants.

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Section 14: Record Retention

All records relating to the IRB and to human subjects activities be retained for at least three years after completion of the research. Records, including signed consent forms and collected data, must be accessible for inspection at any time and for copying by authorized representatives of the UIUC, HHS, or the specific agencies sponsoring the research.

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Section 15: Special Subject Groups

The Office for Human Research Protections (OHRP) has identified populations in need of special protections in research. IRBs must give special consideration to recruitment, subject selection, informed consent, privacy, and confidentiality issues before approving research involving these populations:

• Children, Minors
• Decisionally Impaired Persons
• Elderly and Aged Persons
• International Research Subjects
• Minorities (including Women)
• Pregnant Women, Fetuses, and Neonates
• Prisoners
• Students and Employees
• Terminally Ill Patients
• Traumatized and Comatose Patients

Briefly,

• All research involving prisoners must be reviewed by the IRB. No research that involves prisoners as subjects is exempt from IRB review.
• In Illinois, the legal age for consent is 18 years. With rare exceptions, a parent or guardian must give consent for a child to participate in research activities, and the child must also assent to their own participation.
• Research protocols involving survey or interview procedures with children can not be exempted under federal regulations.
• Research protocols specifically directed toward pregnant women or fetuses must receive special consideration of additional regulatory requirements.
• Research involving decisionally impaired persons must not be of more than minimal risk, unless it holds out the prospect of direct benefit to the subject.
• Research that takes place in foreign countries must provide the same human subjects protection as research conducted in the United States. Research protocols should be designed with awareness of cultural differences.

 

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