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HRPP Policy - IRB review process
About This Policy
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IU Human Subjects Office
This policy applies to all non-exempt human subjects research and exempt human subjects research requiring limited institutional review board (IRB) review under the oversight of the IU IRBs.Back to top
The IU IRBs are charged with protecting the rights and welfare of human research subjects, specifically ensuring that those individuals participating in research are not subject to undue or inappropriate risks, that participation remains a voluntary right, and that the conduct of research is upheld as a privilege.
IU follows the ethical principles established by the Belmont Report to ensure the ethical conduct of research. These principles - autonomy/respect for persons, beneficence, and justice - form the cornerstone of federal regulations involving human subjects.
IU applies the federal regulations for protection of human subjects (45 CFR 46, Subpart A, Protection of Human Subjects, also known as "the Common Rule") when research is sponsored or overseen by a federal agency.
When studies do not receive funding from, or are not otherwise regulated by, a federal agency, IU has adopted policies and procedures to accommodate differences in types of research and to reduce unnecessary administrative burdens. In these instances, IU has adopted equivalent protections for subjects.
Additional federal, state, and local laws, regulations, and requirements may apply. When laws or regulations differ or conflict, the stricter requirements are followed.
Pursuant to 45 CFR 46.103(a), each institution engaged in research that is governed by the Common Rule (45 CFR 46) and conducted or supported by a federal department or agency shall provide written assurance satisfactory to the department or agency head that it will comply with the requirements set forth in the regulations. IU and their affiliates provide this assurance in the form of a Federalwide Assurance approved by the Office for Human Research Protections (OHRP).
Authority to develop, implement, and monitor all human subjects protection programs has been designated by the President of Indiana University to the Vice President for Research, who serves as the institutional official (IO) for research. The IU IRBs are authorized by the IO to review human subjects research in accordance with the IU Policy on Research with Human Subjects. The IRB functions independently of other organizational entities in protecting research subjects.
Prior to research initiation, the IRB review must find that all criteria for IRB approval outlined below are met, or grant exemption, as applicable. The IRB evaluates whether resources are adequate to protect subjects' rights and welfare.
The IRB may approve, require modification to secure approval ("provisionally approve" or "table"), or disapprove research proposals covered by this policy, including exemptions requiring the IRB conduct a limited IRB review to make the determination required by the IU Human Research Protection Program (HRPP) Policy on Exempt Research.
No official or office of the institution may approve a research activity that has been disapproved by the IRB, and no external body or official may override IRB disapprovals, nor apply undue pressure on the IRB to approve a research study or reverse a decision. IRB members or Human Subject Office (HSO) staff who feel they are being unduly influenced should report this to the University Director, HRPP or to the Research Integrity Officer. Either of these officials may investigate and take corrective action, as necessary.
Research which is approved by the IRB may be disallowed by the institution. If research is approved by the IRB but not permitted by the institution, the appropriate institutional authority will promptly notify research personnel and the IRB that the research cannot be conducted, including the reasons for that determination.
The IRB may suspend, place restrictions upon, or terminate approval of research activities falling within its jurisdiction that are not being conducted in accordance with IRB requirements or that have been associated with unexpected serious harm to subjects.
The IRB may have the consent process or the research procedures of any research study under its jurisdiction observed by a third party if the IRB determines that such observation is indicated. This is typically done by the IU Quality Improvement Office.
Deliberations, decisions, findings, and actions of the IRB associated with research activities are considered confidential, except as appropriate. This information is reported to appropriate institutional officials as required by law and/or policies of the IRB. Failure to adhere to this provision may be cause for removal of a member from the IRB. See the Indiana Public Access Counselor (http://in.gov/pac/) for additional information regarding the Open Door Law and Public Records Act.
Based on the IRB's review of information provided by the study team, and in accordance with appropriate regulations and IU and IU HRPP Policies and procedures, the IRB may grant approval of research, including initial review, continuing review, and modifications to previously approved research, if it determines that all of the following requirements are satisfied:
- Risks to subjects are minimized by using procedures that (1) are consistent with sound research design and that do not unnecessarily expose subjects to risk, and (2) whenever appropriate, by using procedures already being performed on the subjects for diagnostic or treatment purposes.
- Risks to subjects are reasonable in relation to anticipated benefits, if any, to subjects, and the importance of the knowledge that may reasonably be expected to result. In evaluating risks and benefits, the IRB should consider only those risks and benefits that may result from the research (as distinguished from risks and benefits of therapies/procedures/activities subjects would receive even if not participating in the research). The IRB should not consider possible long-range effects of applying knowledge gained in the research (e.g. the possible effects of the research on public policy) as among those research risks that fall within the purview of its responsibility.
- Selection of subjects is equitable. In making this assessment, the IRB should take into account the purposes of the research and the setting in which the research will be conducted. The IRB should be particularly cognizant of the special problems that involves a category of subjects who are vulnerable to coercion or undue influence, such as children, prisoners, adult individuals lacking consent capacity, or economically or educationally disadvantaged persons.
- Informed consent will be sought from each prospective subject or the subject's legally authorized representative in accordance with and to the extent required by relevant regulations and IU HRPP Policies and procedures.
- Informed consent will be appropriately documented, or appropriately waived, in accordance with relevant regulations and IU HRPP Policies and procedures.
- When appropriate, the research plan makes adequate provision for monitoring the data collected to ensure the safety of subjects.
- When appropriate, there are adequate provisions to protect the privacy of participants and to maintain the confidentiality of data.
- When some or all the subjects are likely to be vulnerable to coercion or undue influence, such as children, prisoners, pregnant women, adult individuals lacking consent capacity, or economically or educationally disadvantaged persons, additional safeguards have been included in the research proposal to protect the rights and welfare of these subjects.
The IRB may use an expedited review procedure to review any of the following:
- Research which involves only procedures listed in one or more of the Expedited Research Categories below, unless the reviewer determines that the research involves more than minimal risk
- Renewals or modifications to research previously approved under expedited procedures provided the research continues to meet the Expedited Research Categories below and any modifications do not substantially increase risk to subjects
- Minor changes in research previously approved by the convened IRB
- Research granted exemption but requiring a limited IRB review under the IU HRPP Policy on Exempt Research
The IRB may not use an expedited review procedure to review any of the following:
- Research in which identification of the subjects and/or their responses would reasonably place them at risk of criminal or civil liability or be damaging to their financial standing, employability, insurability, reputation, or be stigmatizing, unless reasonable and appropriate protections will be implemented so that risks related to invasion of privacy and breach of confidentiality are no greater than minimal
- Classified research involving human subjects
- Studies involving randomized use of drugs, devices, or biologics. All such studies are reviewed by the convened IRB.
Research involving prisoners may be reviewed via expedited procedures, unless subject to Department of Defense requirements, if:
- For research involving interaction with prisoners, the primary IRB reviewer and the prisoner representative determine the research is minimal risk for the prison population being studied or included.
- For research that does not involve interaction with prisoners, the primary IRB reviewer determines the research poses minimal risk for the prison population being studied or included.
Clinical studies of drugs and medical devices only when either condition below is met:
- Research on drugs for which an investigational new drug application (21 CFR 312) is not required. Note: Research on marketed drugs that significantly increases the risks or decreases the acceptability of the risks associated with the use of the product is not eligible for expedited review; or
- Research on medical devices for which (1) an investigational device exemption application (21 CFR 812) is not required; or (2) the medical device is cleared/approved for marketing and the medical device is being used in accordance with its cleared/approved labeling.
Collection of blood samples by finger stick, heel stick, ear stick, or venipuncture as follows:
- From healthy, nonpregnant adults who weigh at least 110 pounds. For these subjects, the amounts drawn may not exceed 550ml in an 8 week period and collection may not occur more frequently than 2 times per week; or
- From other adults and children, considering the age, weight, and health of the subjects, the collection procedure, the amount of blood to be collected, and the frequency with which it will be collected. For these subjects, the amount drawn may not exceed the lesser of 50ml or 3ml per kg in an 8 week period and collection may not occur more frequently than 2 times per week.
Prospective collection of biospecimens for research purposes by noninvasive means. Examples include:
- Hair and nail clippings in a nondisfiguring manner;
- Deciduous teeth at time of exfoliation or if routine patient care indicates a need for extraction;
- Permanent teeth if routine patient care indicates a need for extraction;
- Excreta and external secretions (including sweat);
- Uncannulated saliva collected either in an unstimulated fashion or stimulated by chewing gumbase or wax or by applying a dilute citric solution to the tongue;
- Placenta removed at delivery;
- Amniotic fluid obtained at the time of rupture of the membrane prior to or during labor;
- Supra- and subgingival dental plaque and calculus, provided the collection procedure is not more invasive than routine prophylactic scaling of the teeth and the process is accomplished in accordance with accepted prophylactic techniques;
- Mucosal and skin cells collected by buccal scraping or swab, skin swab, or mouth washings; or
- Sputum collected after saline mist nebulization.
Collection of data through noninvasive procedures (not involving general anesthesia or sedation) routinely employed in clinical practice, excluding procedures involving x-rays or microwaves. Where medical devices are employed, they must be cleared/approved for marketing. (Studies intended to evaluate the safety and effectiveness of the medical device are not generally eligible for expedited review, including studies of cleared medical devices for new indications). Examples include:
- Physical sensors that are applied either to the surface of the body or at a distance and do not involve input of significant amounts of energy into the subject or an invasion of the subject's privacy;
- Weighing or testing sensory acuity;
- Magnetic resonance imaging;
- Electrocardiography; electroencephalography, thermography detection of naturally occurring radioactivity, electroretinography, ultrasound, diagnostic infrared imaging, doppler blood flow, and echocardiography;
- Moderate exercise, muscular strength testing, body composition assessment and flexibility testing where appropriate given the age, weight, and health of the individual.
Research involving materials (data, documents, records, or specimens) that have been collected or will be collected solely for nonresearch purposes (such as medical treatment or diagnosis). Note that some research in this category may be exempt from the federal regulations or IU HRPP Policy and procedure. This listing refers only to research that is not exempt.
Collection of data from voice, video, digital, or image recordings made for research purposes.
Research on individual or group characteristics or behavior (including, but not limited to, research on perception, cognition, motivation, identity, language, communication, cultural beliefs or practices, and social behavior) or research employing survey, interview, oral history, focus group, program evaluation, human factors evaluation, or quality assurance methodologies. ; Note that some research in this category may be exempt from federal regulations or IU HRPP Policy and procedure. This listing refers only to research that is not exempt.
Continuing review (i.e., renewal) of research previously approved by the convened IRB as follows:
- where (i) 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
- where no subjects have been enrolled and no additional risks have been identified; or
- where the remaining research activities are limited to data analysis.
Continuing review (i.e., renewal) of research, not conducted under an investigational new drug application or investigational device exemption, where categories two (2) through eight (8) do not apply but the IRB has determined and documented at a convened meeting that the research involves no greater than minimal risk and no additional risks have been identified.
The IRB conducts continuing review of research at intervals appropriate to the degree of risk, but not less than once per year for:
- Non-exempt studies subject to FDA regulations
- Research requiring review by the convened IRB, except as described below
The IRB is not required to conduct renewal for the following:
- Research granted exemption, including exempt research requiring a limited IRB review per the IU HRPP Policy on Exempt Research
- Research that is not subject to FDA regulations and is eligible for expedited review under Categories 1-7 above
- Research that is not subject to FDA regulations and requires review by the convened IRB, but has progressed to the point that it involves only one or both of the following:
- Data analysis, including analysis of identifiable private information or identifiable biospecimens (i.e., data analysis only)
- Accessing follow-up clinical data from procedures that subjects would undergo as part of clinical care (i.e., clinical follow-up)
The IRB may require renewal for this research on a case-by-case basis as it deems appropriate. If renewal is required, the IRB must document the rationale for such requirement.
Any proposed changes in approved research must be reviewed and approved by the IRB prior to implementation to ensure that the modified research continues to meet the criteria for approval, except when it is necessary to implement changes to eliminate apparent immediate hazards to the subjects. In this situation, the changes must be promptly reported in accordance with the IU HRPP Policy on Reportable Events.
Closure of all non-exempt research must be reported to the IRB within a reasonable time frame (i.e., prior to study expiration, when applicable).
- For FDA-regulated research and greater than minimal risk research, research personnel must provide a final accounting of subject recruitment, withdrawals, adverse events, deviations, and changes to risk/benefit ratio. The closure is approved by an IRB member via the expedited review process and is reported to a convened IRB.
- Minimal risk research which is not FDA-regulated may be closed by an HSO staff member and does not require reporting to a convened IRB.
When the principal intent of the medical device (or other product regulated as a device) is to develop information about the product's safety or efficacy, submission of an Investigational Device Exemption application (IDE) is ordinarily required. However, in certain circumstances, the FDA does not require an IDE.
Investigations of devices fall into one of three categories: exempt from IDE requirements, studies of nonsignificant risk (NSR) devices subject to abbreviated IDE requirements, or significant risk (SR) devices subject to full IDE requirements. The assessment of whether a device is exempt from IDE requirements, NSR subject to abbreviated IDE requirements, or SR subject to full IDE requirements is initially made by the investigator and/or the sponsor. The IRB must agree with the assessment based on the proposed use of the device in the research and not on the device alone; however, the FDA has the ultimate decision in determining if a device is IDE exempt, NSR, or NSR.
- Exempt from IDE Requirements: The IRB must agree with the justification of exemption; otherwise, the investigator will be required to follow the full or abbreviated IDE requirements. Review the full FDA regulations at 21 CFR § 812 for applicability for exemption.
- NSR Device: If the investigator and/or sponsor determines that a device is NSR, the convened IRB considers the explanation of its determination and any other information that may assist in evaluating the risk of the device. The convened IRB may agree or disagree with the assessment of NSR.
- SR Device: In deciding if a device poses a SR, the IRB considers the nature of the harm that may result from use of the device. If the IRB determines that the device is SR, the investigator is notified and the study cannot be approved and/or conducted until the investigator has provided the IRB with documentation of FDA approval of an IDE application, FDA determination that the device is NSR, or FDA IDE exemption determination.
Drugs or Biological Products
If the study involves a drug or biological product used in humans in any way other than in the course of medical practice, an Investigational New Drug application (IND) is required unless certain exemptions apply. The assessment of whether a drug or biological product requires an IND or is exempt from IND requirements is initially made by the investigator and/or the sponsor. The IRB must agree with the assessment based on the proposed use of the drug or biological product in the research; however, the FDA has the ultimate decision in determining if the study of the drug or biological product requires an IND. Review the full FDA regulations at 21 CFR § 312 for applicability for exemption.
Criteria for Approval
Privacy and confidentiality provisions must take into consideration the requirements of privacy standards including the HIPAA Privacy Rule and the Privacy Action of 1974, 5 U.S.C. 552a; VA Claims Confidentiality Statue, 38 U.S.C. 5701; Confidentiality of Drug Abuse, Alcoholism and Alcohol Abuse, Infection with Human Immunodeficiency Virus (HIV), and Sickle Cell Anemia Medical Records, 38 U.S.C. 7332; and Confidentiality of Healthcare Quality Assurance Review Records, 38 U.S.C. 5705.
The VA Research and Development Committee defers the scientific review for research conducted at or funded by the VA to the IRB.
Amendments to VA research involving issues related to biosafety or radiation safety must first be approved by the appropriate committee or subcommittee prior to granting final IRB approval.
If IRB approval expires, research personnel must immediately submit to the IRB Chair a list of research subjects who could be harmed by stopping study interventions or interactions. The IRB Chair must determine within two (2) business days whether or not such interventions or interactions may continue.
IRB-approved research activities may be disapproved by the IU or VA IO, the Research & Development (R&D) Committee, or ORD.
IRB disapprovals or required modifications to the research cannot be overruled by any other entity.
The R&D Committee must provide the final approval before the research can be initiated.
When conducting DoD sponsored survey research or survey research conducted within the DoD, review and approval is typically required by the DoD, and when appropriate, the research should be reviewed and approved by the IRB prior to DoD approval.
Research conducted within the Bureau of Prisons must have an adequate research design and contribute to the advancement of knowledge about corrections.
The IRB is not expected to have expertise in regulations or cultures outside of the U.S. The IRB reviews issues with transnational research based on the information provided by the study team via the human subjects application, including as applicable:
- Whether there is additional risk to subjects due to their location or inclusion in a culture
- Whether modifications to the informed Consent document are appropriate
- Whether the study team has sufficient knowledge and understanding of the target country to conduct research
The day-to-day operations of the IRB are administered and supported by the IU HSO. No individual responsible for business development at IU or its affiliates may participate in the day-to-day operations of the IRB review process.
The IRB has given HSO staff the authority to conduct preliminary review of all research submitted to the IRB in order to ensure that it is in an acceptable form for the IRB to review.
The IU HSO certifies the review and approval of human subjects research to external funding agencies, as required.
The IRB has delegated authority to HSO staff to provide guidance to research personnel as to whether an activity requires IRB review; however, HSO staff may consult with members of the IRB with any questions.
HSO staff notify the PI and Student, Fellow, Resident PI in writing of IRB actions taken on research.
The study team provides protocol-specific information via the human subjects application and submits the following additional materials, as applicable:
- Data collection instruments
- Recruitment materials
- Informed consent or assent documents, unless a waiver of consent or assent is being requested.
The IRB may take appropriate action to protect human subjects when reviewing a research study or submission, including new studies, amendments, renewals, and FYI items. All actions and determinations made by the IRB are conveyed to the PI and Student, Fellow, Resident PI in writing. Appropriate actions may include:
- Approval No changes are needed. The research may proceed.
- Provisional Approval Specific revisions, stipulated by the convened IRB and requiring simple concurrence by research personnel need to be made. After revisions have been made, final approval may be granted by the IRB Chair or designee. In the event of extensive changes or questions, reviewers may request subsequent review at a convened IRB meeting. The approval of research contingent on specific minor revisions is documented in the minutes of the first IRB meeting that takes place after the date of approval.
- Table Major concerns exist that impact the protection of human subjects, or clarifications or modifications regarding the research or consent process that are directly relevant to the determinations required by the convened IRB are necessary. This action can be taken only by the convened IRB, and the response must be reviewed by the convened IRB at a subsequent meeting.
- Disapprove Significant study concerns exist such that the IRB does not feel the project can be conducted as currently proposed. Specific reasons for disapproval are included in meeting minutes and communicated to the research personnel in writing. The study cannot be resubmitted in the same format. This action can be taken only by the convened IRB.
- Accept the item with no further action required (i.e., protocol continues as previously approved and/or the proposed corrective and preventative action plans are adequate)
- Refer to or consult with other institutional entities (e.g., department head; University General Counsel, Chief Compliance Officer, or Privacy Officer; IRB Executive Committee)
- Restrict use of research data collected
- Audit the research study(ies)
- Modify the research protocol and/or informed consent process/form
- Request notification to or re-consent of past and/or current subjects if the report may relate to their willingness to continue to take part in the study
- Withdraw currently enrolled subjects if it is determined to be in their best interest
- Require additional training of the research personnel and/or research team
- Modify the renewal schedule
- Require increased reporting by research personnel and/or increased monitoring of the research and/or informed consent process
- Restrict privileges of the PI or research personnel to conduct human subjects research
The IRB may, upon the request of research personnel or on its own initiative, reconsider any proposal and reverse its own determination. Research personnel may appeal a decision made by the IRB by responding in writing to concerns posed by the IRB. These appeals should be addressed to the HSO, which will provide this information to the IRB. The IRB may choose to invite research personnel to a meeting to address the concerns or may reject the appeal based on initial concerns with the research.
Research studies that are tabled or disapproved by the IRB cannot be resubmitted to a different IRB in an attempt to bypass the original IRB's decision.
Research that is not being conducted in accordance with the IRB's requirements or has been associated with unexpected serious harm to participants may also be suspended (temporary cessation of some or all research activities) or terminated (permanent withdraw of IRB approval for all research activities).
Although research personnel make a preliminary determination about whether research meets the criteria for expedited review procedures, the IRB makes the final determination. If the IRB does not concur with the study team's determination, it may request modification to the research or require that the research be submitted for convened IRB review. If the IRB determines that research appearing in the categories in 2.5 above is more than minimal risk, the IRB must document the rationale.
Individuals who are appointed as regular or alternate members of an IRB may be designated by the Chair to review research that qualifies for review under expedited procedures when at least one of the following criteria have been satisfied:
- Minimum of two (2) years of service as a regular member of the IRB
- Minimum of twenty (20) full board reviews with mentorship from experienced IRB members
- Minimum of eight (8) new expedited study reviews in collaboration with an experienced IRB member
- In the case of HSO staff IRB members, having attained Certified IRB Professional (CIP) certification and completed the applicable training per the HSO staff manual.
Any IRB member who has a conflicting interest in a submission cannot review that submission as an expedited reviewer. Examples of conflicting interests include:
- Participation in the project
- Financial interest as defined by the IU Policy on Financial Conflicts of Interest in Research
- Certain non-financial interests, including having supervision over the PI of the project or participating in a project that is in direct competition with the project
- Any other real or perceived conflict
In conducting an expedited review, the IRB reviewer may exercise all of the authorities of the convened IRB, except that he/she may not disapprove the research. Research may only be disapproved by the convened IRB.
Consultants with specific expertise may be utilized to assist in the review of expedited research, when appropriate. Their comments are documented and forwarded to an IRB member for review and final approval.
Approval of research under the expedited review procedure, including the relevant expedited category, is reported to the convened IRB.
Scientific review, which addresses whether the research uses procedures consistent with sound research design that will yield the expected knowledge, is conducted on all non-exempt human subjects research submitted to the IRB. Scientific review may be conducted by external committees as described below. When scientific review is not conducted by one of these committees, the IRB conducts scientific review as part of determining that the research meets the criteria for IRB approval.
IU Simon Cancer Center (IUSCC) Scientific Review Committee (SRC)
This committee provides scientific review for prospective cancer-related research utilizing IUSCC patients or resources. Documentation of the IUSCC SRC approval must be obtained before IRB approval is granted.
Indiana Clinical and Translational Science Institute (CTSI)
New studies which are greater than minimal risk, require review by the convened biomedical IRB, and have not undergone a peer-review process must be submitted to the CTSI SRC for scientific review. Documentation of CTSI SRC approval must be obtained before IRB approval is granted.
- Peer review may include review of the protocol by an external funder, such as a federal agency or established not-for-profit research foundation, or protocol development by a commercial sponsor, such as a pharmaceutical or medical device company.
- When deemed necessary by an IRB Chair or HSO Associate Director, other protocols requiring convened IRB review may be required to obtain CTSI SRC approval prior to IRB approval.
The CTSI-sponsored Project Development Teams (PDTs) assist research personnel in developing ideas/hypotheses into well-designed translational research projects. This goal is accomplished by helping research personnel with protocol development (including scientific review); provision of pilot funding; facilitation of collaboration with other research personnel; and access to certain CTSI Core Resources. Research personnel may request scientific review from the PDTs.
If renewal is required, KC IRB reflects the current expiration date for the protocol. The HSO notifies research personnel of the need to renew a study well in advance of the expiration date.
- Upon notification, research personnel should submit for IRB review the appropriate renewal information, including any necessary protocol attachments.
- Submission for renewal is made through the online KC IRB system. Research personnel complete a questionnaire and, depending on the nature of the research, may also be required to provide additional materials for the IRB's review.
Review of Renewals
The following information must be provided by research personnel at time of renewal and is reviewed by the IRB, as applicable:
- The number of subjects accrued, including a summary of any withdrawal of subjects from the research since the last IRB review and the reasons for withdrawal, if known
- Summary of minor deviations and/or noncompliance since the last IRB review
- Statement whether adverse events have occurred in excess of the expected frequency and level of severity as documented in the research protocol, the informed consent document, and investigator's brochure and, if so, a summary
- Most recent data safety monitoring results, if applicable
- Summary of the progress of the research
- Any relevant information, published or unpublished, since the last IRB review, especially information about risks associated with the research. Relevant information may include literature publications, audits, subject complaints, interim findings.
- The latest version of the IRB-approved protocol and informed consent document(s)
- A brief summary of any amendments to the research approved by the IRB since the last IRB review (compiled by the HSO on the study team's behalf)
- Any proposed modifications to the informed consent document or protocol
- For VA studies, the study team's assessment based on research results, the gender and minority status of those entered into the research, number of subjects considered as members of specific special populations, and an assurance that all serious or unexpected adverse events had been reported as required
When the IRB reviews the current informed consent/assent documents at the time of renewal, it ensures that they are still accurate and complete. If any significant new findings are identified that may relate to the subject's willingness to continue participation in the research, the IRB requires that the information be provided to subjects in accordance with regulations.
The IRB determines whether additional verification from sources other than the study team are necessary to ensure that no material changes have occurred since the last review based upon the type of research, risks to subjects, and/or previous noncompliance concerns.
When renewal is required, there are no provisions for any grace period extending the conduct of the research beyond the expiration date of IRB approval. Additionally, where the convened IRB issues a provisional approval, renewal must occur no more than one year after the date the research was reviewed by the convened IRB. It is the study team's responsibility to ensure that the research is reapproved prior to the study's expiration date.
- If the study team fails to submit a renewal to the IRB or the IRB has not reviewed and approved a research study by 11:59 p.m. on the last date the protocol is approved, research activities must cease, including enrollment of new subjects, interventions on/interactions with current subjects, and analysis of identified data.
- However, if the study team is actively pursuing renewal with the IRB and the IRB believes that an overriding safety concern or ethical issue exists such that it is in the best interest of individual subjects for the research to continue, the IRB may permit this while the review process is completed. Enrollment of new subjects, however, cannot occur after the expiration of IRB approval.
- Lapse in IRB approval need not be reported to OHRP as a suspension of IRB approval under HHS regulations.
Submissions for amendment are made through the online KC IRB system. The study team provides information about the proposed changes and submits revised IRB-approved documents or new materials, as applicable.
Amendments to Expedited Research
Amendments to research previously approved under expedited procedures are reviewed under expedited procedures provided the changes continue to meet the expedited category(ies). If the proposed changes to the research involve addition of procedures which are not described by the expedited category(ies) or involve greater than minimal risk, the research must be reviewed by the convened IRB.
Amendments to Research Previously Approved by the convened IRB
Pursuant to 45 CFR §46.110(b)(2), minor changes in research previously approved by the convened IRB may be reviewed and approved under an expedited review procedure. Major changes (e.g., those that involve increased risks or discomforts to subjects or decreased potential benefit) are reviewed and approved by the convened IRB. Refer to the IU HSO website for additional information and examples.
Changes in key personnel are considered amendments to previously approved research which require prospective IRB approval; however, study teams may make changes to the list of non-key research personnel by prospectively submitting a notification of the change to the HSO. These notifications are not considered amendments and do not require prospective IRB review and approval.
Research personnel may request the IRB reopen a research study that was prematurely closed/expired. In reviewing this request, the IRB may require modifications to the research prior to reopening and/or enrolling subjects, as necessary. The study team may need to submit a new research application to restart/continue the previously closed/expired research study at the discretion of the HSO.
Suspensions of research are typically made at a convened IRB meeting; however, they can also be made on an urgent basis by either an IRB Chair or designee, if necessary. Any suspension or termination includes a statement of the reasons for the IRB's action and is reported promptly to the PI, appropriate institutional officials, and/or the department or agency head.
Suspensions can be lifted only by the convened IRB. If an IRB Chair or designee suspends research, it is reported to the full IRB for consideration and possible action. Termination of research can be made only by the convened IRB. Suspensions and terminations cannot be overturned by Institutional Officials.
When the IRB suspends or terminates a research study, it considers whether the suspension or termination requires that subjects be withdrawn from the study and/or places them at risk of harm.
- When subjects must be withdrawn from a study, the IRB considers the safety, rights, and welfare of subjects and determines necessary termination procedures (e.g., drug tapering, final visit, lab tests, other follow-up, and/or arrangements for continued care).
- If the IRB determines that the suspension or termination will place subjects at risk of harm and/or follow-up of subjects for safety reasons is permitted or required, the IRB determines which subjects are to be notified (e.g., current or past subjects) and the manner in which they are to be notified (e.g., in writing or by telephone). Depending upon the reasons for the suspension or termination and the design of the study, the IRB may require that any of the following individuals be notified of the suspension or termination:
- All subjects who have been or who are currently enrolled;
- Only subjects who are currently enrolled and active; or
- Only subjects who participated in a certain aspect of the study.
- Research personnel may request to attend an IRB meeting to discuss a suspension or termination in order to provide clarification of the issues.
Revisions to 45 CFR 46 (Common Rule) are effective January 21, 2019 (2018 requirements).
As of July 19, 2018, non-exempt research which meets all of the following criteria is transitioned and considered in compliance with and subject to the 2018 Requirements:
- Progressed to the point that it involves only data analysis, including analysis of identifiable private information or identifiable biospecimens (i.e., data analysis only)
- Not also subject to FDA or VA regulations
A list of this research will be maintained by the HRPP.
Research which is federally-funded or otherwise subject to the Common Rule but not transitioned under the paragraph above may be subjected to the 2018 Requirements at initial review or time of renewal or other submission at the discretion of the institution and/or IRB. If previously-approved non-exempt research is transitioned to the 2018 Requirements under this paragraph, the IRB will document the application of the 2018 Requirements at time of approval.
Individuals found to be in violation of this policy may be subject to sanctions relating to their participation in research with human subjects, up to and including permanent suspension or debarment from engaging in research with human subjects at IU.Back to top
IU HRPP Guidance
Related Guidance Documents
IU HRPP Documents
Related IRB Questionnaires
- Conflicts of Interest
- A – Level of Review Assessment
- B – Lay Summary & Research Design
- C – Sites & Collaborations
- D – Recruitment Materials
- E – Risks, Benefits, Protections
- F – Data Safety Monitoring
- G1 – Children
- G2 – Individuals Lacking Consent Capacity
- G3 – Prisoners
- G4 – Transnational Research
- H – Informed Consent Process
- J – Child Assent & Parental Consent Process
- K – HIPAA
- L – VA Research
- Reportable Event (FYI)
- Study Closure/Closeout Report
Related Forms and Templates
- Drug or Biological Product Form
- Medical Device Form
- AAHRPP Standards
- Standard I-1, Elements I.1.A I.1.B, I.1.C, I.1.D, I.1.F, I.1.G,
- Standard I-7 , Elements I.7.A, I.7.B,
- Standard II-1, Elements II.1.C, II.1.D, II.1.E
- Standard II-2, II.2.D, II.2.E, II.2.G,
- Standard II-3, II.3.A, II.3.B, II.3.C, II.3.D, II.3.E
- Standard II-4, Elements II.4.A
- 21 CFR 56
- 21 CFR 312
- 21 CFR 812
- 45 CFR 46
- DoD Instruction 3216.02 – Protection of Human Subjects and Adherence to Ethical Standards in DoD-Supported Research
- FDA Guidance:
- Information Sheet Guidance for IRBs, Clinical Investigators, and Sponsors: Significant Risk and Nonsignificant Risk Medical Device Studies
- Guidance for Clinical Investigators, Sponsors, and IRBs: Investigational New Drug Applications (INDs) Determining Whether Human Research Studies Can Be Conducted Without an IND
- Guidance for Clinical Investigators, Sponsors, and IRBs: IRB Responsibilities for Reviewing the Qualifications of Investigators, Adequacy of Research Sites, and the Determination of Whether an IND/IDE is Needed
- International Council for Harmonisation of Technical Requirements for Pharmaceuticals for Human Use (ICH): Guideline for Good Clinical Practice E6(R2), especially section 3
- OHRP Guidance:
- VHA Directive 1200.05 Requirements for the Protection of Human Subjects in Research
2018 requirements Federal Policy for the Protection of Human Subjects, effective January 21, 2019, available at 45 CFR 46
adverse event Any untoward or unfavorable occurrence, including medical, physical, and psychological harms, in a human subject associated with the subject’s participation in the research, whether or not considered related to the subject’s participation in the research.
assent An individual's affirmative agreement to participate in research obtained in conjunction with permission of the individual's parents, guardian, or legally authorized representative. Mere failure to object should not, absent affirmative agreement, be construed as assent.
audit (see also for-cause (directed) audit, internal audit, and not-for-cause (scheduled) audit) A systematic and independent examination of study-related activities and documents to determine whether the evaluated study-related activities were conducted, and the data were recorded, analyzed, and accurately reported, according to applicable federal regulations, state laws, and institutional policies. Includes audits, monitoring visits, and compliance inspections.
authorization Per the Privacy Rule, an individual's permission to allow a covered entity to use or disclose the individual’s protected health information (PHI) described in the authorization for the purpose(s) and to the recipient(s) stated in the authorization.
biological product or biologic As regulated by the FDA, a virus, therapeutic serum, toxin, antitoxin, vaccine, blood, blood component or derivative, allergenic product, protein (except any chemically synthesized polypeptide), or analogous product, or arsphenamine or derivative of arsphenamine (or any other trivalent organic arsenic compound), applicable to the prevention, treatment, or cure of a disease or condition of human beings; regulated as a drug.
biospecimen A quantity of tissue, blood, urine, or other human-derived material. A single biopsy may generate several biospecimens, including multiple paraffin blocks or frozen biological material. The molecular makeup of such specimens reflects the physiologic or pathologic condition of the person from whom they derive; therefore, they provide sensitive and specific insight into the biologic state of the donor. Examples of biospecimens include: subcellular structures (e.g., DNA), cells, tissue (e.g., bone, muscle, connective tissue, and skin), organs (e.g., liver, bladder, heart, and kidney), blood, buccal swabs, gametes, embryos, fetal tissue, saliva or other body fluids, and waste (e.g., urine and stool). Portions or aliquots of a biospecimen are referred to as samples.
confidentiality The assurance that certain information about individuals, which may include a subject's identity, health, behavior, or lifestyle information, or a sponsor's proprietary information, will not be disclosed without permission from the subject or sponsor.
corrective action Action taken to correct a noncompliant situation that has occurred.
department or agency head The head of any federal department or agency and any other officer or employee of any department or agency to whom authority provided by the Common Rule to the department or agency head has been delegated.
device (medical device) As regulated by the FDA, an instrument, apparatus, implement, machine, contrivance, implant, in vitro reagent, or other similar or related article, including any component, part, or accessory, which is: 1) recognized in the National Formulary, or the United States Pharmacopeia, or any supplement to them; 2) intended for use in the diagnosis of disease or other conditions, or in the cure, mitigation, treatment, or prevention of disease, in man or other animals; or 3) intended to affect the structure or any function of the body of man or other animals, and; which does not achieve its primary intended purposes through chemical action within or on the body of man or other animals and which is not dependent upon being metabolized for the achievement of its primary intended purposes. See FDA Guidance for Industry and FDA Staff on Classification of Products as Drugs or Devices and Additional Product Classification Issues.
drug As regulated by the FDA, A) articles recognized in the official United States Pharmacopoeia, official Homoeopathic Pharmacopoeia of the United States, or official National Formulary, or any supplement to any of them; and B) rticles intended for use in the diagnosis, cure, mitigation, treatment, or prevention of disease in man or other animals; and C) articles (other than food) intended to affect the structure or any function of the body of man or other animals; and D) articles intended for use as a component of any articles specified in clause (A), (B), or (C). See FDA Guidance for Industry and FDA Staff on Classification of Products as Drugs or Devices and Additional Product Classification Issues.
enrollment Enrollment begins at the time of consent for the study. For research for which consent is not required, enrollment begins at time of data collection or when the subject agrees to participate.
exempt from IDE requirements There are several categories of device studies that are exempt from investigational device exemption (IDE) requirements if certain criteria are met: (A) certain studies of custom devices; (B) studies involving certain device modifications, combinations, or consumer preference testing of already-approved or cleared devices; (C) studies involving non-invasive diagnostic devices; and (D) studies involving already cleared or approved devices.
federally-funded Supported, either directly or indirectly, by funds provided by the federal government. This includes federal pass-through funding (i.e., received as a subrecipient through subcontracts). Use of administrative services funded by a federal grant, alone, is not sufficient to consider research federally-funded.
federalwide assurance (FWA) Written assurance of compliance with the Common Rule to OHRP from institutions engaged in non-exempt human subjects research conducted or supported by HHS.
HIPAA The Health Insurance Portability and Accountability Act of 1996. See also Privacy Rule.
identifiable private information Private information for which the identity of the subject is or may readily be ascertained by the research personnel or associated with the information.
informed consent An ongoing process by which a subject (or his/her legal representative) voluntarily confirms his or her willingness to participate in a particular research project in accordance with the IU HRPP Policy on Informed Consent.
interaction Includes communication or interpersonal contact between research personnel and the subject.
intervention Includes both physical procedures by which information or biospecimens are gathered (e.g., venipuncture) and manipulations of the subject or the subject’s environment that are performed for research purposes.
investigational device exemption (IDE) As regulated by the FDA, authorization allowing an investigational device to be used in a clinical investigation in order to collect safety and effectiveness data.
investigational new drug application (IND) Request for authorization from the FDA to administer an investigational drug or biological product to humans.
investigator (FDA, see also research personnel, IU-affiliated research personnel, key personnel, non-key personnel, non-affiliated research personnel, principal investigator (PI), student, fellow, resident PI, site-specific PI) In research subject to FDA regulations, an individual who actually conducts a clinical investigation, i.e., under whose immediate direction the test article is administered or dispensed to, or used involving a subject, or, in the event of an investigation conducted by a team of individuals, is the responsible leader of that team.
IRB-approved protocol Refers to all IRB-approved study information, including the human subject application, formal protocol document, consents, etc.
key personnel (see also research personnel, Investigator, IU-affiliated research personnel, non-key personnel, non-affiliated research personnel, principal investigator (PI), student, fellow, resident PI, site-specific PI) research personnel, other than the PI, who are responsible for the conduct and/or reporting of research. Such individuals may include, among others: Individuals making critical decisions regarding eligibility of subjects; Individuals obtaining consent for a study that is greater than minimal risk (Full Board); Individuals listed on Form FDA 1572 or the investigator agreement.
legally authorized representative (LAR) An individual or judicial or other body authorized under applicable law to consent on behalf of a prospective participant to the participant’s participation in the procedure(s) involved in the research. For definition of LAR in Indiana, see the IU HRPP Policy on Adult Individuals Lacking Consent Capacity.
minimal risk The probability and magnitude of harm or discomfort anticipated in the research are not greater in and of themselves than those ordinarily encountered in daily life or during the performance of routine physical or psychological examinations or tests.
noncompliance (see also continuing noncompliance, minor noncompliance, observed or apparent noncompliance, serious noncompliance) Any action or activity associated with the conduct or oversight of research involving human subjects that fails to comply with federal or state regulations, requirements of VHA Handbook 1200.05, or institutional policies governing human subjects research or the requirements or determinations of the IRB.
noninvasive When applied to a diagnostic device or procedure, means one that does not by design or intention: 1) penetrate or pierce the skin or mucous membranes of the body, the ocular cavity, or the urethra, or 2) enter the ear beyond the external auditory canal, the nose beyond the nares, the mouth beyond the pharynx, the anal canal beyond the rectum, or the vagina beyond the cervical os. Blood sampling that involves simple venipuncture is considered noninvasive, and the use of surplus samples of body fluids or tissues that are left over from samples taken for noninvestigational purposes is also considered noninvasive.
nonsignificant risk (NSR) device Investigational device that does not meet the definition for a significant risk device.
principal investigator (see also research personnel, Investigator, IU-affiliated research personnel, key personnel, non-key personnel, non-affiliated research personnel, student, fellow, resident PI, site-specific PI) Responsible leader of a team of research personnel who has the ultimate responsibility for the conduct of the research.
prisoner Any individual involuntarily confined or detained in a penal institution. The term is intended to encompass individuals sentenced to such an institution under a criminal or civil statute; individuals detained in other facilities by virtue of statutes or commitment procedures that provide alternatives to criminal prosecution or incarceration in a penal institution; and individuals detained pending arraignment, trial, or sentencing. Examples of individuals considered prisoners are available in the OHRP Prisoner Research FAQs.
privacy Refers to persons and their interest in controlling the access of others to themselves.
privacy rule Federal Rule found at 45 CFR 160, and 164 subparts A and E, which establishes national standards for protection of individuals’ medical records and other personal health information; applies to covered entities.
private information Includes information about behavior that occurs in a context in which an individual can reasonably expect that no observation or recording is taking place, and information that has been provided for specific purposes by an individual and that the individual can reasonably expect will not be made public (e.g., medical records).
protected health information (PHI) Health information, including demographic information collected from an individual, that is created or received by a health care provider, health plan, employer, or health care clearinghouse; and relates to the past, present, or future physical or mental health or condition of an individual, or to the provision of health care to an individual.
recruitment Initial identification and contact with potential subjects, which may include both direct interactions with individuals and/or accessing identifiable data or specimens for the purpose of determining whether an individual or their data or specimen may participate or be included in a study.
research A systematic investigation, including research development, testing, and evaluation, designed to develop or contribute to generalizable knowledge (Synonymous with clinical investigation For research subject to FDA regulations, any experiment that involves a test article and one or more human subjects, and that either must meet the requirements for prior submission to the FDA under §505(i), §507(d), or §520(g) of the Food, Drug & Cosmetic Act, or need not meet the requirements for prior submission to the FDA under these sections of the act, but the results of which are intended to be later submitted to, or held for inspection by, the FDA as part of an application for a research or marketing permit. The term does not include experiments that must meet the provisions of part 58 regarding nonclinical laboratory studies (21 CFR 50.3(c)).) The following activities are deemed not to be research under this definition: Scholarly and journalistic activities (e.g., oral history, journalism, biography, literary criticism, legal research, and historical scholarship), including the collection and use of information that focus directly on the individuals about whom the information is collected; Public health surveillance activities, including the collection and testing of information or biospecimens, conducted, supported, requested, ordered, required, or authorized by a public health authority. Such activities are limited to those necessary to allow a public health authority to identify, monitor, assess, or investigate potential public health signals, onsets of disease outbreaks, or conditions of public health importance (including trends, signals, risk factors, patterns in diseases, or increases in injuries from using consumer products). Such activities include those associated with providing timely situational awareness and priority setting during the course of an event or crisis that threatens public health (including natural or man-made disasters); Collection and analysis of information, biospecimens, or records by or for a criminal justice agency for the activities authorized by law or court order solely for criminal justice or criminal investigative purposes; Authorized operational activities (as determined by each agency) in support of intelligence, homeland security, defense, or other national security missions.
research personnel (See also investigator, IU-affiliated research personnel, non-key personnel, non-affiliated research personnel, principal investigator (PI), Student, Fellow, Resident PI, site-specific PI) Individuals engaged in human subjects research; specifically, individuals who interact or intervene with human subjects or access identifiable information for research purposes. May also be called investigators.
significant risk device Per 21 CFR 812.3(m), investigational device that: (1) is intended as an implant and presents a potential for serious risk to the health, safety, or welfare of a subject; (2) is purported or represented to be for a use in supporting or sustaining human life and presents a potential for serious risk to the health, safety, or welfare of a subject; (3) is for a use of substantial importance in diagnosing, curing, mitigating, or treating disease, or otherwise preventing impairment of human health and presents a potential for serious risk to the health, safety, or welfare of a subject; or (4) otherwise presents a potential for serious risk to the health, safety, or welfare of a subject.
sponsor An individual, company, institution, or organization that takes responsibility for the initiation, management, and/or financing of research.
student, fellow, resident PI (see also research personnel, Investigator, IU-affiliated research personnel, key personnel, non-key personnel, non-affiliated research personnel, principal investigator (PI), site-specific PI) Student responsible for design and/or conduct of the research under the mentorship of a PI in order to complete an education requirement.
suspension Temporary cessation of some or all activities in a currently approved research study.
termination Determination made by the IRB to permanently withdraw approval for some or all activities of a currently approved research study.
test article Any drug for human use, biological product for human use, medical device for human use, human food additive, color additive, electronic product, or any other article subject to regulation under the Food, Drug, and Cosmetic Act or under §351 or §§354-360F of the Public Health Service Act.
transnational research Any human subject research conducted at international sites (not within the United States, its territories, or commonwealths) or research using either human biological specimens or human data originating from an international site.
written/in writing Writing on a tangible medium (e.g. paper) or in an electronic format.Back to top