This guidance is not meant to be governing and, as with all research, the Indiana University Institutional Review Board (IRB) has independent authority to approve or disapprove any research. For questions regarding specific protocols, please contact IU Human Subjects Research Office via the information listed under 'Contact Us' to the left of this page.

Most of the research reviewed by the IU IRBs falls within the broad categories of biomedical or social-behavioral science research. While it is difficult to draw a clean line between these two broad categories, this guidance is intended to help the IU research community in defining in which category research falls. This categorization is important because the regulations governing human subjects research require that an IRB with appropriate expertise review research. Indiana University’s Human Research Protection Program (IU-HRPP) includes two (2) social-behavioral science IRBs and four (4) biomedical IRBs. For purposes of this guidance, when defining biomedical vs. social-behavioral research, consideration is given to: the research field, characteristics of the subjects, the research procedures or interventions being employed, and the nature of the research risks.

Social-Behavioral Science
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Biomedical
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IRB Review
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In addition to concerning itself with risk, the IRB must consider the subject's consent to participate in the research project. An underlying ethical principle of the Federal regulations is that human subjects enter into research voluntarily and with adequate information. (Also see The Belmont Report, 1979)  Thus, consent must be informed and voluntarily given. A subject's consent is "informed" if he/she has a reasonable comprehension of that to which he/she is consenting. The investigator must use language appropriate to the subject's ability to comprehend. Generally, the consent form should be written at the 8th grade reading level. Nondisclosure of information to subjects must not be used simply to assure their participation in the research. It is desirable, but not mandatory, that the investigator, rather than an assistant, obtain the consent.

To ensure that subjects' consent is voluntary, the IRB considers whether any undue pressures will be brought to bear on potential subjects. Such pressure may be subtle as, for example, when a teacher asks his or her own students to become subjects of his or her research.  Excessive compensation or no payment for withdrawals is viewed by the IRB as pressure.

In order to obtain informed consent the investigator must provide an informed consent statement. An Informed Consent Statement Template is available on the IRB Forms & Checklists page to assist investigators in the preparation of the consent form. The template reflects both requirements of the Federal regulations and customary language adopted by the IU Human Subjects Office. Use of the template will facilitate the review process. Each subject must be given a copy of the signed consent form.

The consent statement (or information sheet) that is approved by the IRB will be stamped with two dates, the approval date and the expiration date. Before the form has expired it must be submitted for reapproval by the IRB. Exempt level documents will be stamped for the time period of the study. Expedited and full committee documents will be stamped for the time period of the approval (no longer than one year). The stamped version must be used to make the copies for the subjects.

For additional information regarding informed consent, please view the IU IRB SOP on Informed Consent. The SOP document is available on the Policies & Procedures page.

Who can give consent?

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Waiver of Consent

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Minors

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Cognitively Impaired

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Deception

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Web-based Studies

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This document provides guidance on determining whether a project may be considered and exempt, and considerations when designing your project.

• IU IRB Guidance – Exempt Status Requests (v12/01/12)

This flow chart provides guidance on determining the appropriate IRB submission for an activity involving research with existing information or specimens (non-genetic).

• IU IRB Guidance - Research with Existing Data

*Special thanks to Jessica Roy of the IU Simon Cancer Center for providing this language.*

Below is suggested template language to utilize when seeking an opinion from the FDA regarding drug exemption.

Please note this does not replace the IND process, but is only intended for use when contacting the FDA for an opinion regarding potential exempt status.

Three paper copies of this inquiry should be mailed to:

Food and Drug Administration
Center for Drug Evaluation and Research
Central Document Room
5901-B Ammendale Rd
Beltsville, MD 20705-1266

For further information regarding drug and device development, please contact the Indiana Clinical Translational Sciences Institute (CTSI) at: invdrdev@iu.edu.

• FDA Opinion Letter

The IRB reviews a number of protocols from faculty proposing to recruit students from their classes to serve as research participants.  While this practice is not prohibited, whenever possible, faculty should avoid using their own students if another population of subjects is equally suited to the research question, e.g. another class section not taught by the researcher, recruitment by another instructor, or blinded/coded data collected by an associate so that subjects are not identifiable to the instructor.  When it is determined to be appropriate to recruit students, several key issues should be considered.

Use of Researcher's Students as Subjects

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Primary and Secondary School Subjects

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Use of Student Academic Records

If a researcher wishes to gain access to identifiable student academic records, signed consent may be required. Please contact the IU Human Subjects Office for additional guidance.

Any individuals who interact with subjects or have access to identifiable subject information should be listed as investigators on the Investigator List.

Please see: IU IRB Guidance – Quick Guide to Investigators

Collaborations between investigators at different institutions are becoming increasingly common.  In many of these cases, two or more IRBs may have jurisdiction over the research project.  In order to facilitate review of research collaborations, the IU IRBs may defer review of some research to another institution or may agree to provide review for individuals at external institutions.  Generally, the IU IRBs will take this step only for minimal risk research.  Please also note that all research conducted in an IU Health facility must be reviewed by the IU IRB.

Deferrals of IRB review between institutions must be documented by an IRB Authorization Agreement.  HSO staff will facilitate the agreement using the IRB Authorization Agreement form which is available on the IRB Forms & Checklists page under Additional Resources.

Research with Non-IU Affiliated Investigators

As always, IRB review is only required when investigators are considered engaged in human subjects research. The IU IRBs recognize several specific situations where non-affiliated investigators are not considered engaged and do not need to obtain IRB approval. For example, investigators who will not have access to identifiable data and will not have any interaction with human subjects are not engaged in research. Most commonly, these investigators receive deidentified data or specimens for analysis. Please see the Quick Guide to Collaborating with External Investigators for more information.

Investigators who are not part of an affiliated institution but would like to collaborate on an IU IRB protocol may request that the IU IRBs provide review of their participation in the research.  Non-affiliated investigators must:

• Be added to the Investigator List at time of initial review or via an Amendment
• Be listed on the Investigator List in Section I, part D. 
• Complete a COI disclosure
• Complete required CITI modules if interacting with subjects or if they are considered key personnel
• Provide contact information for his/her local IRB, if his/her institution has a local IRB
• Submit a Non-Affiliated Investigator Agreement form* signed by the investigator and the PI, if his/her institution does not have a local IRB

*The Non-Affiliated Investigator Agreement form is available on the IRB Forms & Checklists page under Additional Resources.

HSO staff will work with the external IRB when applicable to complete the required agreements.  The appropriate submission (initial review or amendment) will be approved when these requirements are met.

Collaborating Institutions

The IU IRBs have entered into cooperative agreements with several institutions with which IU investigators commonly collaborate. These agreements allow the institutions to accept IRB approval from each other with minimal additional requirements.

Franciscan St. Francis Health (FSFH)

• If investigators from FSFH are collaborating on an IU protocol, follow the instructions for non-affiliated investigators above. During review, HSO staff will contact FSFH and obtain written approval that the research meets FSFH ethical requirements. 
• If an IU investigator is collaborating on an FSFH protocol, please contact HSO for additional instructions.

IU Health Bloomington Hospital

• The IRB application should be submitted to the Principal Investigator’s IRB. After approval, the application packet and approval letter will be submitted to the deferring institution, which will provide written agreement to the study team that they may begin the research.

Mayo Clinic

• Please contact HSO for additional instructions.

Medical College of Wisconsin

• Please contact HSO for additional instructions.

Notre Dame University

• The IRB application should be submitted to the PI’s home institution. If the research involves an IU Health facility, the application should be submitted to the IU IRBs. The investigator should include the IU-PU Request for Deferral form with their application. During review, HSO staff will send it to the deferring institutional for approval and signature.

Purdue University

• The IRB application should be submitted to the PI’s home institution. If the research involves an IU Health facility, the application should be submitted to the IU IRBs. The investigator should include the IU-PU Request for Deferral form* with their application. During review, HSO staff will send it to the deferring institutional for approval and signature.

* The IU-PU Request for Deferral form is available on the IRB Forms & Checklists page under Additional Resources.

University of Wisconsin Madison

• Please contact HSO for additional instructions.

The Request to Defer Review form is available on the IRB Forms & Checklists page under Additional Resources.

Requesting that IU defer to another institution

If you are collaborating with researchers at another institution not listed above who have already obtained IRB approval, IU may defer its review of your participation to the external IRB. To request such a deferral, submit the following information to the Human Subjects Office:

• Request to Defer Review
• External IRB approval
• All study documents approved by the external IRB
• Contact information for the external IRB

HSO staff will contact the external IRB to complete the required agreement and the signed Request to Defer Review will be returned to the investigator when all requirements are complete.

The following guidance has been adopted by the Human Subjects Office in order to provide guidance for investigators and IRB members on conduct and review of research involving exercise testing and training. In general, the main points of discussion and possible contention during IRB review include:

1. Screening for appropriate participation
2. Appropriate safeguards during exercise intervention
3. Determining whether the research is minimal risk or greater than minimal risk

While investigators and IRB members agree that exercise testing does involve risk, there is very little data about the actual level or incidence of the risk and whether those risks can be fully prevented by any level of protection procedures. Bright-line rules regarding appropriate screening procedures and required safeguards for all exercise-related research are impossible to identify. As such, the IRBs will assess each protocol involving exercise testing individually and determine appropriate requirements on a case-by-case basis, taking into consideration study subjects, procedures, and possible risks.

Minimum expectations for exercise-related research are described below; however, the IRBs may request additional requirements. In addition, investigators are welcome to propose and justify alternative procedures or safeguards if the expectations below are inappropriate for particular protocols.

Screening for Appropriate Participation
In general, risks of participation in exercise testing are caused by the presence of known or unknown cardiovascular, pulmonary, or metabolic diseases. As such, investigators conducting research involving exercise testing must conduct screening procedures to identify the presence, signs, symptoms, and/or risk factors of such diseases in potential subjects.

For purposes of these guidance, subjects which screen positively for the presence, signs, symptoms, and/or risk factors of cardiovascular, pulmonary, or metabolic diseases will be considered and referred to as higher risk subjects, and appropriate safeguards must be conducted to avoid occurrence of adverse events and other risks.

Screening procedures must include the following, at a minimum, for all subjects:

• a questionnaire designed to discover the subjects health history and identify known symptoms and risk factors for cardiovascular, pulmonary, or metabolic disease
• pulse to ensure that an unknown symptom or risk factor does not exist
• at least one blood pressure test to ensure that an unknown symptom or risk factor does not exist

The IRB application should include the following information regarding screening:

• list of proposed screening procedures
• justification if the screening process does not include the above minimum procedures
• whether subjects will be enrolled if the screening process determines them to be higher risk
• if the study is designed to test higher risk subjects, an assessment of risk factors or diseases which make the population higher risk

Additional thoughts on risk stratification and screening may be found in the American College of Sports Medicine’s Guidelines for Exercise Testing and Prescription; however, investigators are not required to follow the recommendations therein.

Appropriate Safeguards during Exercise Intervention
It is the responsibility of the investigator to propose an appropriate plan for safeguarding subjects during the exercise intervention, given the proposed procedures and subject population. Some research involving higher risk subjects may require that the study team have access to physician supervision or other medical expertise during exercise intervention. In those situations, utilization of a local emergency response team (e.g. 911) may be appropriate, while other studies may necessitate a specified physician to be present onsite.

In order for the IRB to assess whether the proposed plan is appropriate, the investigator should include the following information in the IRB application:

• whether higher risk subjects will be enrolled and, if so, an assessment of the risk
• whether the investigators conducting the exercise intervention have been trained in CPR or other first aid, and, if so, the training received
• access to medical emergency equipment, if any, during the exercise intervention
• assessment of the local emergency response units and whether use of these units during an adverse event is appropriate

Identifying Minimal Risk vs. Greater than Minimal Risk Research
Unless additional concerns are raised, the IRBs may utilize the following guidance when determining whether exercise-related research should be considered minimal risk or greater than minimal risk. When making this determination, the IRB should consider the characteristics of potential subjects and the intensity of the proposed exercise intervention. For example, walking the length of a standard hallway would be considered minimal risk for most healthy subjects, but may be greater than minimal risk for elderly subjects or those recovering from knee surgery.

The following research should be considered minimal risk:

• sub-maximal exercise testing in healthy, asymptomatic subjects (not higher risk)
• research involving maximal and sub-maximal exercise testing in athletes
• research involving muscle stimulation; however, the IRB will need to make this determination on a case by case basis, considering the specific muscle group(s) to be stimulated and the method used to stimulate.

The following research should be considered greater than minimal risk:

• maximal exercise testing in non-athletes
• research which is intended to cause fatigue, exhaustion, or muscle soreness beyond that which would normally be experienced by the proposed subjects

Minimal risk means that the probability or 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 (as defined by 45 CFR 46.102(i)).

The IU IRBs provide IRB review for several area hospitals and medical groups.  If you are employed by one of these affiliated organizations, you are obligated to submit your research to the IU IRBs for review.  The following institutions are considered “affiliated” for the purposes of IRB review:

• Health & Hospital Corporation of Marion County/Wishard Hospital
• Indiana State Department of Health
• Indiana University
• Indiana University Health, including:
  • Emergency Medical Group
  • IU Health Bedford Hospital
  • IU Health Goshen Hospital
  • IU Health LaPorte Hospital
  • IU Health Methodist Hospital
  • IU Health Methodist Beltway Surgery Center
  • IU Health North
  • IU Health Saxony Hospital
  • IU Health University Hospital
  • IU Health West Hospital
  • Methodist Sports Medicine
  • Riley Hospital for Children at IU Health
  • Riley Hospital for Children at IU Health North Hospital
• Larue D. Carter Memorial Hospital
• Regenstrief Institute
• Richard L. Roudebush Veterans Affairs Medical Center

The IRB reviews a number of research studies that take place in an international (non-US) setting. Research conducted outside of the US can pose some unique risks, specifically concerning the political, cultural or economic conditions of the research site.

Risk

When evaluating risk, different considerations may apply to research conducted outside the US  Specifically:

• research methods that have virtually no risk in the US might have risk when conducted in other countries;
• questions that may be innocuous in the US could be offensive in other countries;
• breach of confidentiality could have much more dangerous consequences than in the US;
• assuring and maintaining confidentiality in foreign countries may be difficult; and/or
• there may be dangers to the researcher that may not be present under the same conditions in the US.

Local Research Context

If not already knowledgeable, researchers must become knowledgeable in local context issues that are relevant to the specific research.  Specifically, researchers may need to:

• consult with community leaders and stake holders who may be able to provide important insights about the local research context including information about local customs, norms and laws;
• communicate and coordinate with local IRBs or Ethics groups as well as work with their US IRB;
• develop local collaborative relationships to assist in the approval, design, and conduct of the research;
• identify and communicate with a local contact who is fluent in the local language; and/or
• provide approval documentation for the research received by the PI from the local IRB or ethics group, as applicably defined by the specific community in which the research will be taking place.  Examples of acceptable documentation include: local IRB or Ethics group approval documents, letters from community leaders and stake holders, etc.

Informed Consent

Consideration should be given to the most appropriate method of obtaining informed consent, including literacy levels, confidentiality concerns, and cultural norms.  Different cultures have different authority structures for approval and consent.  Researchers should be aware of and honor different cultural attitudes regarding consent.  These attitudes may include differences with regard to autonomy and coercion, e.g. what we might consider to be coercive in the US may not be so in a different culture and vice versa.

In some cases, a waiver of documentation of written consent (verbal consent) may be more appropriate because signing a consent document would put participants at greater risk.  In some cases, even when a consent document is appropriate, it may not be appropriate to include some of the required information in the document.  For example, e-mail or phone numbers in consent documents may not be realistic or feasible in a foreign country.

Consent is best obtained using the language that is most familiar to the prospective participant and ideally the researcher or research team is fluent in the local language.  If not, the investigator might seek collaborators or hire assistants who are fluent in the local language.  A third option is to hire interpreters.

When hiring interpreters, the following elements should be considered:

• In a small population, the relationship between the interpreter and the participants must be considered;
• The interpreter might exert influence or undue pressure which could lead to selection bias
• The interpreter may not relay information in a clear and unbiased manner, e.g., they may leave out information they believe is unpleasant or culturally inappropriate.
• In addition to the initial consent process, fluent researchers or interpreters should be available to answer questions, address complaints, or relay instructions throughout the conduct of the study.
• Some languages are not written and sometimes people speak a language but may not be able to read or write it.
• There may not be any translations of important words like ‘placebo’ or ‘randomization.’
• It may be culturally inappropriate to ask for a signature and may indicate a lack of trust.
• It may be appropriate to use alternative consent procedures like the use of a short form and witness, use of pictures or videos or other alternate forms of documentation.

Research with Children

Children may have different statuses in foreign countries than in the US.  Questions that may need to be considered are:

• What is the age of majority?
• What is the relationship between parents and their children in that country?
• What is an acceptable and effective parental permission process?
• What is an acceptable and effective child assent process and are there laws pertaining to orphans in that country?

Levels of Review

Through consultation with experts, the IRB must ensure that the risk assessment holds true at the foreign site. Thus, knowledge of local context is important even in research which may be exempt.  Even in exempt research, informed consent, parental permission, or child assent may still be ethically appropriate and/or required under local law.  The researcher should include information in the research submission to address the local community ethical standards where the study will be conducted.  This information should include details regarding local review (as applicable) and the investigator’s experience with the locality. This information will be considered when approving exempt research conducted at a performance site outside of the US.

To assist researchers who are conducting expedited or full Board research in a foreign country, the IRB requires that the Transnational Research Request Form be completed.  This allows the researcher to consider and detail relevant political, social, cultural, and economic norms or issues and gives the IRB a sense of how knowledgeable the researcher is about the region where the research will take place.