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Submission Process

IRB approval must be obtained prior to initiating any research activity that meets either the DHHS definition of research involving human participants or the FDA definition of clinical investigation involving human participants and prior to implementing amendments to previously approved research (except when necessary to eliminate apparent immediate hazards to participants). The IRB will publish submission deadlines for studies requiring review by the convened board at the start of each semester. New submissions requesting expedited review or exempt status can be submitted at any time and are reviewed on an on-going basis.

All forms required for an IRB submission are available on the IRB website. The PI is responsible for submitting complete forms and required supporting documentation. The PI must sign all submissions. Students are required to sign the submission when the research is student initiated (research is related to the doctoral dissertation or master’s degree). The signature of the Department Head or Dean is required for all submissions unless the research is funded by an external grant or contract. The signature of the medical monitor is required for interventional studies that are monitored by a physician. The IRB staff and reviewer reserve the right to return any submission that is incomplete or on out-dated forms.

 

Determination of Level of Review

Investigators make an initial determination for which type of review is appropriate for their study (full board, expedited, or exempt) and submit the required number of copies of the protocol and supporting documentation. Upon receipt, the IRB staff, in consultation with the Chair or an IRB member, screens the protocol to verify the PI’s initial determination. The protocol is then placed into the appropriate queue for review. The Chair, or his/her designee, makes the final determination of the type of review required and the appropriate expedited or exempt category.

 

When Submission to the IRB is Required

A protocol application must be submitted to the IRB for any study for which research is the intent and the researcher proposes to use or involve any of the following:

  • identifiable data collected for non-research purposes (e.g., academic or medical records);
  • interaction (communication or interpersonal contact between investigator and participant) through interviews, surveys, and other forms of communication;
  • intervention (physical procedures by which data are gathered and manipulations of the participant or the participant’s environment that are performed for research purposes);
  • student research projects conducted as part of Research Methods Courses;
  • access to medical records and data through the medical information systems;
  • pathological specimens (directly identifiable or identifiable via codes);
  • diagnostic specimens (directly identifiable or identifiable via codes).

The IRB reviews projects when the research:

  • is sponsored by the institution;
  • is conducted by or under the direction of an employee or agent of the institution in relation to his/her institutional responsibilities;
  • is conducted by or under the direction of an employee or agent of the institution using resources of the institution; or
  • involves the use of the institution’s non-public information (i.e. alumni, students, staff, etc.) to identify or contact human research participants or prospective participants.

 

Pilot Research and Protocol Development

Per 45 CFR 46.102, Research means a systematic investigation, including research development, testing and evaluation, designed to develop or contribute to generalizable knowledge. Activities which meet this definition constitute research for purposes of this policy, whether or not they are conducted or supported under a program which is considered research for other purposes. For example, some demonstration and service programs may include research activities.

In some cases, the UConn IRB must review pilot research and protocol development, including but not limited to the following activities:

  • Development and testing of instruments or measures on human subjects* (even if it is just one subject);
  • Testing of research procedures on human subjects*;
  • Procedures done on human subjects* for the purpose of refining research design.
  • Data collected that will be used solely or in combination with other data for purposes of publication, reports or presentation;
  • Development and testing procedures on human subjects* involving needles, catheters, radiation, drugs or devices that are swallowed or inserted in an orifice require IRB approval.
    *Please note that the Office for Human Research Protections (OHRP) considers the Principal Investigator as well as all research personnel to be human subjects if testing procedures are to be conducted on them. Therefore, even when pilot tests are conducted on study personnel, the protocol must be reviewed and approved by the IRB prior to initiation. Please refer to the policy on the Involvement of UConn Students and Employees in Research.

Pilot studies should be identified as such in applications to the IRB. The informed consent process must explain to subjects that the research is a pilot study.

Procedures that are not considered to be pilot research and do not need to be reviewed by the IRB include, but may not be limited to, the following:

  • Training programs designed to teach proven methods that will be used during the conduct of research (i.e., blood drawing training, interview techniques training);
  • Refining data collection procedures or preparation of an instrument, such as a survey. For instance, “How could this survey question be misunderstood?”, or “In what order should survey instruments be distributed?” This type of study development does not contribute to generalizable knowledge, and therefore is not considered research and does not require IRB review. Such data cannot be used in publications or reports.

 

Meeting Schedule and Submission Deadlines

The meeting schedule and submission deadlines are posted on the web. Adjustments to the meeting schedule may be made due to holidays or other issues. Adjustments will either be noted in the published meeting schedule (when known in advance) or announced via e-mail. The submission deadline for full board reviews is 10 working days prior to the meeting date.

Material requiring full-board review must be submitted by the published submission deadlines to provide sufficient time for screening and review prior to the meeting date. The IRB staff will send the agenda and material to IRB members via hand delivery or express mail within 2 – 3 working days after the submission deadline to allow members to have at least 7 working days for review of the material prior to the meeting date.

Under unusual circumstances, the Chair may call an emergency meeting of the board. However, such a meeting will not be called due to the negligence of the investigator to submit material on time. An emergency meeting may be called, for example, when a quorum for the originally scheduled meeting was not met and review is required to prevent lapse of a study, or if an investigator is faced with a situation beyond his/her control. If not already distributed, material must be distributed to members as soon as possible to allow for sufficient review. The investigator may be asked to attend the meeting to address questions, or provide additional information or clarification.

Under unusual circumstances, the IRB staff, in consultation with the Chair, may also add an item to the agenda after the submission deadline. Such circumstances generally involve situations in which an investigator is faced with a situation beyond his/her control and an amendment must be made to the protocol. The material must be distributed (via hand delivery, e-mail or express mail) to members as soon as possible to allow for sufficient review.

 

Submission of New Applications

The PI is responsible for submitting a complete protocol and relevant supporting documentation. The required number of copies for each category of review and the types of supporting documentation required are listed in the instructions for the protocol application. Investigators have the option of submitting applications in hard copy or via the on-line InfoEd submission process.

For studies using devices or substances not yet approved by the FDA, the IRB may require copies of IND submission and FDA opinions depending on the anticipated risks to participants. All substances used in clinical trials are to be human grade materials, and the PI must provide evidence of compliance with Good Manufacturing Practice. For some studies, especially those involving substances not yet approved by the FDA, substances not requiring FDA approval or substances being used for a purpose other than the approved indication, the IRB may require investigators to strengthen the literature review regarding previous studies and potential side effects.

 

Eligibility for Principal Investigator (PI) Status

In most cases, only faculty of UConn Storrs (including those at the regional campuses, the School of Law, and School of Social Work) and the UConn Storrs Health Center qualify to serve as PIs on IRB protocols. Only one person may be designated as the PI. Students may be designated as co-investigators but not PIs. On occasion, staff members of UConn Storrs may also qualify to serve as PIs on IRB protocols. In rare circumstances, requests by someone not affiliated or employed by the University (a collaborating independent investigator) to serve as PI will be reviewed on a case-by-case basis by the RCC in consultation with the IRB Chair. The intended PI must submit written requests for an exception to the RCC. Such requests will involve two parts. The first part is a request to the RCC from the individual seeking appointment as the PI. The request must include 1) a description of the level and nature of involvement s/he has with the University, 2) how that involvement relates to the mission of the University, 3) appointment of a UConn Storrs faculty member to serve as a co-investigator and 4) if applicable, to what data s/he is requesting access. The RCC will inform the PI via copy of the memo noting the approval, if such a request is approved. In addition, the IRB will enter into an Individual Investigator agreement with the PI, who is acting as a collaborating independent investigator, to extend the applicability of its FWA in accordance with OHRP’s January 31, 2005 guidance. The DRC is a designee of the IO to sign these documents.

 

Submission of Request for Amendments/Amendments

A PI may amend his/her approved protocol by submitting an IRB-3 Amendment Review form. Requests for amendment must be submitted for IRB review and approval prior to being implemented. The PI is responsible for providing the necessary number of copies and all material requested on the instructions. An exception may be made when the changes are necessary to eliminate apparent immediate hazards to the participants. Such changes must be reported to the IRB using the IRB-6 Protocol Deviation Report form and, when applicable, to the FDA within 5 business days. The Protocol Deviation Report form is to be accompanied by the consent form and any other document affected by or related to the change that was instituted. IRB staff, in consultation with the IRB Chair, will determine whether the change was consistent with ensuring the participant’s continued welfare and will also determine whether the change should be reviewed by the full IRB. The convened IRB will determine whether the event requires reporting as an unanticipated problem or serious or continuing noncompliance if the change is found to be inconsistent with ensuring the welfare of the participant.

 

Submission of Requests for Continuation (Re-approval)

Continuing review and approval must be obtained prior to the end of the day on which approval expires. Continuing review is required through all follow-up and data analysis activity (data is being maintained, and/or analyzed, and the identity of participants has not been separated from the research data), even if the study is closed to enrollment and research related interventions are complete. Continuing review is also required for studies that have been suspended, in whole or in part. Requests for continuation are submitted using the IRB-2 Re-Approval/Completion form. A request for approval of an amendment may be incorporated into a request for continuation. The PI must indicate that an amendment is being made at time of continuing review and submit the IRB-3 Amendment Review form along with supporting documentation. As a courtesy, the IRB staff will send one reminder notice by e-mail to the PI to request continuation approximately 6 weeks before the study approval expires. The PI retains the responsibility for submitting requests for continuation. A request for continuation requiring full board review that is submitted early will be placed on the agenda of the next regularly scheduled IRB meeting. The approval period by which subsequent continuing review must occur will be adjusted accordingly. Requests for expedited continuation will be forwarded by the IRB staff to the Chair or IRB member for review and approval as they are received.

 

Submission of Requests for Closure/Completion

A PI may close his/her approved protocol by submitting an IRB-2 Re-Approval/Completion form to the IRB. A summary of the findings must be provided on the form or on an attached document. Requests for completion should be submitted at the time the next continuation application is due or within 30 days after data analysis is complete, the identity of participants has been separated from the research data, and there is no additional research beyond the original intent planned for this data. Requests for completion are typically reviewed by IRB staff.

 

Categories of Review/Process of Review and IRB Decision

 

Initial Review of All Submissions
IRB staff screen all submissions for completeness. PIs will be notified by phone or e-mail if a submission is missing documentation or necessary signatures. The IRB staff, in consultation with the Chair or an IRB member, screens the protocol to verify the PI’s initial determination for exempt, expedited or full board review. Any questions concerning the appropriate review level, applicability of the definition of human participants and/or the definition of research, jurisdiction of IRB, or otherwise relating to necessity of review are directed to the IRB Chair.

 

Exempt Procedures (New Protocol Submissions)
The PI must complete and submit the IRB-5 Request for Exemption from Continuing Review protocol form to the ORC. Exempt research must be minimal risk. Only the IRB Chair, IRB member, or IRB staff (acting as a designee of the Chair), may determine if a protocol is granted exempt status under the six categories described in 45 CFR 46.101(b). In most cases, an IRB staff member reviews the protocol application and all of the material required for submission for exempt studies. The IRB staff member may contact the PI directly to resolve any questions or concerns, or to require amendments prior to approving the exempt status. Contact will generally be made via e-mail to provide documentation of the correspondence. The IRB staff, after consultation with the IRB Chair or an IRB member, may determine that the research qualifies for expedited or full-board review, but may not deny the project. The PI will be notified via e-mail or by letter if expedited or full board review is required, be given the reasons why it is required, and be asked to resubmit the study on the IRB-1 Protocol Application form. Requests for Exemption from Continuing Review are generally reviewed within two weeks of receipt.

Although the regulations do not require informed consent for exempt research, the IRB has determined that informed consent is ethically appropriate to ensure that prospective participants are informed of the research and have an opportunity to decide for themselves whether or not to participate. In most cases, the IRB will waive written consent and ask that the PI prepare an information sheet according to the requirements set forth under 45 CFR 46.116.

If the study qualifies for exempt status, the IRB staff will notify the PI via the standard exempt approval letter. As a designee of the Chair, the IRB staff will issue the approval letter on behalf of the Chair and sign or initial the Chair’s name. The approval letter describes the exempt category under which the study was approved. The letter will also inform the PI that the study is subject to audit by the IRB Monitor. A list of exempt approvals is provided to the IRB for review and approval by the IRB at each meeting. Any member can request to review the entire IRB file for an exempt study.

For administrative purposes of maintaining the InfoEd database and files, the IRB staff may periodically contact the PIs of exempt studies during the three year approval period to determine if the study is still active.

 

Categories of Research that May be Reviewed by the IRB Through an Exempt Review Procedure
Federal regulations allow six specific categories of human participant research to be exempt from continuing IRB review. Although these six categories do involve research with human participants, the research does not expose participating participants to psychological, social or physical risks. Per 45 CFR 46.101(b), the exempt research categories are:

      1. Research conducted in established or commonly accepted educational settings, involving normal educational practices, such as (i) research on regular and special education instructional strategies, or (ii) research on the effectiveness of or the comparison among instructional techniques, curricula, or classroom management methods.
      2. Research involving the use of educational tests (cognitive, diagnostic, aptitude, achievement), survey procedures, interview procedures or observation of public behavior, unless:
        • information obtained is recorded in such a manner that human participants can be identified, directly or through identifiers linked to the participants; and
        • any disclosure of the human participants’ responses outside the research could reasonably place the participants at risk of criminal or civil liability or be damaging to the participants’ financial standing, employability, or reputation.
      3. Research involving the use of educational tests (cognitive, diagnostic, aptitude, achievement), survey procedures, interview procedures, or observation of public behavior that is not exempt under paragraph (b)(2) of this section, if:
        • the human participants are elected or appointed public officials or candidates for public office; or
        • Federal statute(s) require(s) without exception that the confidentiality of the personally identifiable information will be maintained throughout the research and thereafter.
      4. Research involving the collection or study of existing data, documents, records, pathological specimens, or diagnostic specimens, if these sources are publicly available or if the information is recorded by the investigator in such a manner that participants cannot be identified, directly or through identifiers linked to the participants.
      5. Research and demonstration projects which are conducted by or participant to the approval of Department or Agency heads, and which are designed to study, evaluate, or otherwise examine:
        • Public benefit or service programs;
        • procedures for obtaining benefits or services under those programs;
        • possible changes in or alternatives to those programs or procedures;
        • or possible changes in methods or levels of payment for benefits or services under those programs
      6. Taste and food quality evaluation and consumer acceptance studies,
        • if wholesome foods without additives are consumed or
        • if a food is consumed that contains a food ingredient at or below the level and for a use found to be safe, or agricultural chemical or environmental contaminant at or below the level found to be safe, by the Food and Drug Administration or approved by the Environmental Protection Agency or the Food Safety and Inspection Service of the U.S. Department of Agriculture.

Category 4 applies to retrospective studies of specimens and/or data that have already been collected. The materials must be “on the shelf” (or in the freezer) at the time the protocol is submitted to the IRB. Research that involves the ongoing collection of the specimens and/or data does not meet the criteria for category 4. Category 5 pertains only to studies sponsored or funded by DHHS. Research participant to FDA regulations does not qualify for exemption categories 1 – 5.

Per 45 CFR 46.101(i), the exemptions at 45 CFR 46.101(b) do not apply to research involving prisoners, subpart C. Also, the exemption at 45 CFR 46.101(b)(2), for research involving survey or interview procedures or observation of public behavior, does not apply to research with children, subpart D, except for research involving observations of public behavior when the investigator(s) do not participate in the activities being observed.

In addition, although not required by regulations, IRB polices and procedures do not allow exemption of most research involving deception, audio or video taping, or HIV+ individuals.

 

Initial Review by Expedited Procedures
The PI must complete and submit the IRB-1, IRB-7 or IRB-9 Protocol Application for the Involvement in Human Participants in Research protocol form to the ORC. Expedited research must be no more than minimal risk. As defined in the federal regulations, “minimal risk” means that 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 (45 CFR 46.102(i)). Only the IRB Chair or an IRB member may determine if a protocol is granted expedited status under seven of the nine categories as published in the federal register as 45 CFR 46.110 and 21 CFR 56.110. Categories 8 and 9 do not pertain to initial review.

Only the Chair or an IRB member can make one of the following three determinations in regard to the protocol and consent forms:

APPROVED: IRB approval indicates that the IRB reviewer(s) has concluded that the research and consent forms meet the federal criteria for approval.

MODIFICATIONS REQUIRED IN ORDER TO SECURE APPROVAL: The IRB reviewer(s) withhold approval pending submission of revisions/additional information.

FULL REVIEW REQUIRED: The IRB reviewer(s) may determine that the protocol requires full review by the IRB at a convened meeting.

The Chair or IRB member may not disapprove any research reviewed using the expedited procedure. An IRB staff member screens the protocol and material required for submission for completeness and corresponds with the PI by e-mail and/or phone until the submission is complete. Once the submission is complete, an IRB staff member conducts a preliminary review of the protocol application and material required for submission of expedited studies. The staff member may also complete the Primary Reviewer Checklist. The preliminary review consists of the following: (1) a review of the protocol to determine if there is missing information or information that requires further clarification, (2) a review of the consent form to see if it contains the required elements set forth in 45 CFR 46.116 and 117 and University policy, (3) a review of the recruitment procedures, (4) approval category, (5) if applicable, permissible categories and required findings for vulnerable populations and/or waivers or alterations of the consent process, and (6) a recommendation regarding one of the three determinations described above. The IRB staff does not review scientific issues such as the study design, feasibility of specific aims or data analysis plans. IRB staff prepares a draft review letter to the PI. The IRB staff, in consultation with the IRB Chair, selects an experienced IRB member (the “Reviewer”) with appropriate scientific experience to review the protocol and material required for submission as well as the draft review letter. The Reviewer may contact the PI directly to discuss questions or concerns. The Reviewer may complete the Primary Reviewer Checklist. The purpose of the checklist is to assist the reviewer. It is an unofficial document that does not become part of the study file.

The preliminary review and the review conducted by the IRB Chair or IRB member Reviewer is conducted in accord with the criteria set forth in 45 CFR 46.111 and 21 CFR 56.111. In addition, the Reviewer must also determine 1) that the research is minimal risk, 2) that if identification of the participants and/or their responses reasonably place them at risk of criminal or civil liability or could be damaging to the participants’ financial standing, employability, insurability, or reputation, or be stigmatizing there are reasonable and appropriate protections that will be implemented so that risk related to invasion of privacy and breach of confidentiality are no greater than minimal, and 3) that the research is not classified or does not involve prisoners, with the exception that the expedited review of minor amendments for approved studies involving prisoners may be used.

If the Reviewer determines the protocol is approved, the IRB staff will notify the PI or correspondent via the standard expedited approval letter. The IRB staff will issue the approval letter on behalf of the Reviewer and sign or initial his/her name. The approval letter describes the expedited category under which the study was approved. The letter will also inform the PI that the study is subject to audit by the IRB Monitor. The approval period for studies approved through expedited review will be for one year from the date the initial approval or approval for continuation is granted. Approval is valid through the expiration date (also known as ‘valid through’ date) noted in the approval letter. For example, an expedited study given approval (either initially or for continuing review) on October 8, 2007 would be approved as valid through October 8, 2008, meaning that research is approved to be conducted on October 8, 2007, but will no longer be approved on October 9, 2008, and may not be conducted on or after that date without continuing approval by the IRB. A list of studies approved via the expedited mechanism during the interim between agenda dates is provided to the IRB for review and approval IRB at each meeting. Any member can request to review the entire IRB file for an expedited study.

If the Reviewer determined the protocol requires modifications to secure approval, he/she reviews and may revise the draft preliminary review letter prepared by IRB staff. The Reviewer may add comments to the letter directly or provide comments about the protocol and letter to IRB staff by e-mail. The IRB staff incorporates the revisions and sends the letter by e-mail to the PI or correspondent listed on the protocol. If the research is student directed, the student will also receive a copy of the letter by e-mail. If the requested revisions or clarifications are minor, the PI may be notified by e-mail to provide documentation of the correspondence. The PI responds to revisions requested by the IRB in writing and sends the response to the ORC. PIs are encouraged to submit a point by point response to the IRB’s initial determination letter to facilitate review. The PI must submit one copy of the protocol and/or consent form with the revisions highlighted and one copy of the protocol “clean,” without revisions highlighted, to expedite review of the revisions. The IRB staff member who conducted the preliminary review will review the revisions to determine if the Reviewer’s concerns were properly addressed. Any requested revisions involving the addition or deletion of specific elements is eligible to be reviewed by IRB staff. Any revisions that involve controverted issues or pertain to the scientific review will be reviewed by the Reviewer rather than IRB staff. In addition, any new procedures added to the protocol that result from the IRB’s review will be reviewed by the Reviewer. In most cases, the IRB staff member will forward the revisions to the Reviewer by e-mail. If the IRB staff and/or the Reviewer determines that all concerns have been addressed, the IRB staff will issue the approval letter on behalf of the Reviewer and sign or initial his/her name. The approval letter describes the expedited category under which the study was approved. The letter will also inform the PI that the study is subject to audit by the IRB Monitor. The approval period for studies approved through expedited review will be for one year from the date the initial approval or approval for continuation is granted. If the Reviewer and the investigator cannot agree on the amendments required for approval, the research will be sent to the convened IRB for review. The PI will be notified by the IRB staff via e-mail or by phone if full board review is required, given the reasons as to why it is required, and may be asked to submit additional copies.

 

Continuing Review (Re-Approval) by Expedited Procedures
To request re-approval, the PI must complete and submit the IRB-2 Re-Approval/ Completion form along with any required material as described in the instructions. An IRB staff member screens the IRB-2 form and, if applicable, the protocol, consent form or material required for completeness and corresponds with the PI by e-mail and/or phone until the submission is complete. To be eligible for expedited review, the research protocol must satisfy the criteria set forth in 45 CFR 46.111 and 21 CFR 56.111 for the IRB to approve the protocol for continuation. The IRB may only use expedited review procedures for continuation review under the following circumstances:

      1. The study was initially eligible and continues to be eligible for expedited review procedures; OR
      2. The research is permanently closed to the enrollment of new participants; all participants have completed all research-related interventions; and the research remains active only for long-term follow-up of participants; OR
      3. Where no participants have been enrolled and no additional risks have been identified either at the University or at any site if the research involves a multi-site study; OR
      4. The research involves the study of drugs and/or medical devices AND either does not require an Investigational New Drug (IND) (21 CFR Part 312) and/or an Investigational Drug Exemption (IDE) (21 CFR Part 812) and/or the device is approved for marketing and being used in accordance with the approved labeling. The IRB must also have determined and documented at a convened meeting that the research is no greater than minimal risk and no additional risks have been identified.

Categories 1 through 9, excluding 8b, apply to continuing review. In accord with federal requirements, the IRB approval period can extend no longer than one year after the start of the approval period. The PI may not continue research after expiration of IRB approval; continuation is a violation of federal requirements specified in 45 CFR 46.103(a) and 21 CFR 56.103(a). If the IRB approval has expired, the PI must cease all research activities and may not enroll new participants in the study after the expiration of the IRB approval. However, if the IRB determines that an overriding safety concern and/or ethical issue is involved or that it is in the best interests of the individual participants to continue participating in the research activities, the IRB may permit the participants to continue in the study for the time required to complete the re-approval process.

If the request for re-approval meets the circumstances defined above, the continuing review is conducted in the same manner as a new expedited protocol submission whereby IRB staff conduct a preliminary review and forwards the review to the IRB Chair or an IRB member.

Continuing review and approval for expedited studies must be obtained prior to the end of the day on which IRB approval expires. Any amendments that are made at the time of re-approval will be reviewed in accord with the procedures for Review of Amendments to Previously Approved Research by Expedited Procedures.

For expedited review, the outcomes of continuing review are the same as the options outlined under Initial Review by Expedited Procedures.

 

Review of Amendments to Previously Approved Research by Expedited Procedures
A PI may amend his/her approved protocol by submitting an IRB-3 Amendment Review form. An IRB staff member screens the IRB-3 form and, if applicable, the protocol, consent form or material required for submission for completeness and corresponds with the PI by e-mail and/or phone until the submission is complete. The IRB staff, in consultation with the IRB Chair or an IRB member, conducts a preliminary review of the IRB-3 to determine if the requested amendment is eligible for review under expedited procedures. To be eligible for review under the expedited procedures the amendment must be minor. A minor change is one which makes no substantial alteration in:

      • The level of risk to participants;
      • The research design or methodology;
      • The participant population;
      • Qualifications of the research team;
      • The facilities available to support the safe conduct of the research; or
      • Any other factor which would warrant review of the proposed changes by the convened IRB.

If the IRB Chair or an IRB member determines that the research qualifies for expedited review, the amendment is reviewed in the same manner as a new expedited protocol submission whereby IRB staff conducts a preliminary review and forwards the review to the IRB Chair or an IRB member. Amendments of research involving vulnerable populations may be approved via the expedited process. However, for research involving prisoners, the prisoner advocate will also be asked to review the requested change or addendum to determine that it meets the definition of minor change to previously approved research.

For expedited review, the outcomes of review of amendments are the same as the options outlined under Initial Review by Expedited Procedures..

 

Categories of Research that May be Reviewed by the IRB through an Expedited Review Procedure
Federal regulations allow nine specific categories of human participant research to be reviewed through an Expedited Review Procedure. Per 45 CFR 46.110 and 21 CFR 56.110, the research should present no more than minimal risk to human participants and involve only procedures listed in one or more of the following categories:

      1. Clinical studies of drugs and medical devices only when condition (a) or (b) is met.
        1. Research on drugs for which an investigational new drug application (21 CFR Part 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.)
        2. Research on medical devices for which (i) an investigational device exemption application (21 CFR Part 812) is not required; or (ii) the medical device is cleared/approved for marketing and the medical device is being used in accordance with its cleared/approved labeling.
      2. Collection of blood samples by finger stick, heel stick, ear stick, or venipuncture as follows:
        1. From healthy, nonpregnant adults who weigh at least 110 pounds. For these participants, the amounts drawn may not exceed 550 ml in an 8 week period and collection may not occur more frequently than 2 times per week; or
        2. From other adults and children1 considering the age, weight, and health of the participants, the collection procedure, the amount of blood to be collected, and the frequency with which it will be collected. For these participants, the amount drawn may not exceed the lesser of 50 ml or 3 ml per kg in an 8 week period and collection may not occur more frequently than 2 times per week.
      3. Prospective collection of biological specimens for research purposes by noninvasive means. Examples: (a) Hair and nail clippings in a nondisfiguring manner; (b) deciduous teeth at time of exfoliation or if routine patient care indicates a need for extraction; (c) permanent teeth if routine patient care indicates a need for extraction; (d) excreta and external secretions (including sweat); (e) 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; (f) placenta removed at delivery; (g) amniotic fluid obtained at the time of rupture of the membrane prior to or during labor; (h) 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; (i) mucosal and skin cells collected by buccal scraping or swab, skin swab, or mouth washings; (j) sputum collected after saline mist nebulization.
      4. 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: (a) 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 participant or an invasion of the participant’s privacy; (b) weighing or testing sensory acuity; (c) magnetic resonance imaging; (d) electrocardiography, electroencephalography, thermography, detection of naturally occurring radioactivity, electroretinography, ultrasound, diagnostic infrared imaging, doppler blood flow, and echocardiography; (e) moderate exercise, muscular strength testing, body composition assessment, and flexibility testing where appropriate given the age, weight, and health of the individual.
      5. 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: Some research in this category may be exempt from the HHS regulations for the protection of human participants. 45 CFR 46.101(b)(4). This listing refers only to research that is not exempt.)
      6. Collection of data from voice, video, digital, or image recordings made for research purposes.
      7. 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: Some research in this category may be exempt from the HHS regulations for the protection of human participants 45 CFR 46.101 (b)(2) and (b)(3). This listing refers only to research that is not exempt.)
      8. Continuing review of research previously approved by the convened IRB as follows:
        1. Where (i) the research is permanently closed to the enrollment of new participants; (ii) all participants have completed all research-related interventions; and (iii) the research remains active only for long-term follow-up of participants; or
        2. Where no participants have been enrolled and no additional risks have been identified; or
        3. Where the remaining research activities are limited to data analysis.
      9. Continuing review 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.

 

Initial Review by the Full Board
Proposed research that does not qualify for either exempt status or expedited review will be sent to the convened board for review. The PI must complete and submit the IRB-1 Protocol Application for the Involvement in Human Participants in Research form to the ORC. The application form used for expedited and full board review is the same. If the PI indicates that he/she believes the research is more than minimal risk and requires review by the convened board, the original and 15 copies of the protocol and material are submitted. This packet is set aside for the next IRB meeting. Prior to the meeting, the IRB staff, in consultation with the IRB Chair or an IRB member, reviews the protocol to determine if the PI’s assessment is correct. If the submission is determined to be of no greater than minimal risk and satisfies the criteria for expedited review, the protocol is added to the queue for review by expedited procedure.

Protocols that do not qualify for either exempt or expedited review are assigned a primary reviewer for initial review at the convened meeting. Each member of the IRB receives a complete copy of the protocol submission. The Chair and primary reviewer also receive a copy of the grant application, when applicable. In cases where the standardized assessment measures are substantial, only the Chair and primary review will receive copies. IRB members are informed that the packet they receive is not complete and may request a copy of the material by contacting the ORC. The full file is also available to all IRB members at the meeting. The primary reviewer is responsible for the following: (1) comparing the detailed grant application or industry protocol with the IRB application; (2) informing the full IRB of any discrepancies between the detailed protocol and the summary application materials; and (3) conducting an in-depth review. Any member of the IRB may request to see additional information, including all of the information presented to the primary reviewer, the IRB file and previous minutes related to the study. Each reviewer is provided with the Primary Reviewer Checklist and other review sheets as an aid to making determinations. These work sheets are unofficial documents that do not become part of the study file. The determinations of the convened board are noted in the minutes.

At the convened meeting, the primary reviewers will present a summary of the study, any concerns with specific items on the reviewer sheet and any additional concerns or comments. Discussion and voting will follow. IRB members are expected to be familiar with all items on the agenda and contribute toward the discussion or each item. If the primary reviewer is absent, the review will be presented by the Chair or Vice-Chair.

Full Board reviews are conducted in accord with the criteria set forth in 45 CFR 46.111 and 21 CFR 56.111. The Board can make one of the following four determinations in regard to the protocol and consent forms:

APPROVED: IRB approval indicates that the Board has concluded that the research and consent forms meet the federal criteria for approval.

MODIFICATIONS REQUIRED IN ORDER TO SECURE APPROVAL: A vote for amendments required indicates the IRB has given the meeting Chair the authority to approve the minor revisions. The IRB withholds approval pending submission of minor revisions/additional information.

DEFERRED: The IRB withholds approval pending submission of major revisions / additional information. For some studies, the IRB may appoint one or more members of the IRB to discuss the reasons with the investigator. Once the revisions have been made by the PI and submitted to the ORC, the revised protocol is added to the next IRB meeting agenda for review.

DISAPPROVED: Disapproval of a protocol usually occurs when the IRB determines that the risk of the procedures outweighs any benefit to be gained or if the proposed research does not meet the federal criteria for IRB approval.

If the full board determines the protocol is approved, the IRB staff will notify the PI or correspondent via the standard full board approval letter. The IRB staff will issue the approval letter on behalf of the individual chairing the meeting and sign or initial his/her name. The letter will also inform the PI that the study is participant to audit by the IRB Monitor. During the convened meeting, the IRB determines the approval period, as appropriate to the degree of risk but not less frequently than once per year. The IRB will generally set a shorter approval period for high risk protocols or protocols with high risk/low potential benefit ratios. When a protocol receives final approval, the IRB staff assigns the start of the approval period as the date of the convened IRB meeting. If a protocol was determined to require amendments to secure approval and the PI completes the revisions, the approval period starts from the meeting date of the convened IRB at which the protocol was initially reviewed.

If the full board determined the protocol requires modifications to secure approval, the IRB staff prepares a draft determination letter based upon the IRB’s discussion at the meeting. The letter describes the revisions requested by the IRB. If the revisions requested are particularly controverted or complex, the staff may first e-mail the draft letter to the primary reviewer for review and comment. The draft letter is then e-mailed to the meeting Chair for final review and approval. The primary reviewer and Chair may add comments to the letter directly or provide comments about the protocol and letter to IRB staff by e-mail. The IRB staff incorporates the revisions and sends the letter by e-mail to the PI or correspondent listed on the protocol. If the research is student-directed, the student will also receive a copy of the letter by e-mail. A hard copy of the letter is sent as a follow-up. The PI responds to revisions requested by the IRB in writing and sends the response to the ORC. PIs are encouraged to submit a point by point response to the IRB’s initial determination letter to facilitate review. The PI must submit one copy of the protocol and/or consent form with the revisions highlighted and one copy of the protocol “clean,” without revisions highlighted to expedite review of the revisions. If the revisions are straightforward and minor, the IRB staff may review the revisions to determine if they were addressed. Any revisions that involve controverted issues or pertain to the scientific review will be reviewed by the primary reviewer or meeting Chair rather than IRB staff. In addition, any new procedures added to the protocol that result from the IRB’s review will be reviewed by the primary reviewer or meeting Chair. The Chair or primary reviewer may request that the new procedures be reviewed by the full board. In most cases, the IRB staff member will forward the revisions by e-mail. If the IRB staff, primary reviewer and/or the meeting chair determines that all concerns have been addressed, the IRB staff will issue the approval letter on behalf of the meeting Chair and sign or initial his/her name. The letter will also inform the PI that the study is subject to audit by the IRB Monitor. During the convened meeting, the IRB determines the approval period, as appropriate to the degree of risk but not less frequently than once per year. The IRB may set a shorter approval period for high risk protocols or protocols with high risk/low potential benefit ratios. When the protocol was determined to require modifications to secure approval and the PI completes the revisions, the approval period starts from the meeting date of the convened IRB at which the protocol was initially reviewed. If the IRB and the investigator cannot agree on the modifications required for approval, the research will be sent to the convened IRB for further review. The PI will be notified by the IRB staff via e-mail or by phone if full board review is required, given the reasons as to why it is required, and may be asked to submit additional copies.

If the full board determines that a protocol must be deferred, the IRB staff will prepare a draft determination letter based upon the IRB’s discussion at the meeting. The letter lists the reasons for the deferral and includes a description of the revisions or clarifications requested. The draft letter is reviewed according to the same procedures described above. The approved letter is sent by e-mail to the PI or correspondent listed on the protocol. If the research is student directed, the student will also receive a copy of the letter by e-mail. A hard copy of the letter is sent as a follow-up. The PI responds to revisions requested by the IRB in writing and sends the response to the ORC. PIs are encouraged to submit a point by point response to the IRB’s initial determination letter to facilitate review and to met with IRB staff to discuss revisions. The PI must submit one clean copy of the protocol and/or consent form and 15 copies of the protocol and/or consent form with the revisions highlighted. The protocol is then added to the agenda for the next scheduled IRB meeting. When a protocol that was initially deferred receives final approval, the IRB staff assigns the start of the approval period as the date of the meeting the protocol was approved or required modifications to secure approval.

If the full board determined the protocol must be disapproved, the IRB prepares a draft determination letter based upon the IRB’s discussion at the meeting. The draft letter is reviewed and approved in the same manner as described above. The approved letter is sent to the PI by hard copy. If the research is student-directed, the student will also receive a copy of the determination letter. A copy of the disapproval determination letter is also sent to the IO, AVPR, the PI’s Department Head, the Office of Sponsored Programs (if applicable), and other University offices, as necessary.

 

Continuing Review (Re-approval) by the Full Board
To request re-approval, the PI must complete and submit the IRB-2 Re-Approval/ Completion form along with any required material as described in the instructions. The application form used for continuing review for expedited and full board review is the same. A primary reviewer system is used for continuing review. Reviewers are selected in the same manner as described for Initial Review by the full board. Each member of the IRB receives a complete copy of the protocol submission. The Chair and primary reviewer each receive a copy of the grant application. In cases where the standardized assessment measures are substantial, only the Chair and primary reviewer will receive a copy. IRB members are informed that the packet they receive is not complete and may request a copy of the material by contacting the ORC. The full protocol file is available at the meeting. The research protocol must satisfy the criteria set forth in 45 CFR 46.111 and 21 CFR 56.111 for the IRB for the IRB to approve the protocol for continuation.

If a request for continuation is received early, the study will be reviewed at the next convened meeting and the review cycle will be adjusted accordingly based on that meeting date. The instructions for the request for continuation form describe in detail the requirements for submission.

For full review, the outcomes of continuing review by the convened board are the same as the options outlined under Initial Review by the Full Board.

 

Review of Amendments to Previously Approved Research by the Full Board
A PI may amend his/her approved protocol by submitting an IRB-3 Amendment Review form. The application form used for amendments for expedited and full board review is the same. Minor changes can be approved by expedited review. All other changes will be reviewed by the full board. A primary reviewer system will be used to review requests for amendments to determine whether the modified research continues to fulfill the criteria for approval. Reviewers are selected in the same manner as described for Initial Review by the full board. Each member of the IRB receives a complete copy of the protocol submission. The Chair and primary reviewer each receive a copy of the grant application. In cases where the standardized assessment measures when are substantial, only the Chair and primary review will receive a copy. IRB members are informed that the packet they receive is not complete and may request a copy of the material by contacting the ORC. The full protocol file is available at the meeting. The instructions for the request for amendment form describe in detail the requirements for submission.

For full review, the outcomes of review of amendments by the convened board are the same as the options outlined under Initial Review by the Full Board.

 

Human Participant Research Determination

The IRB Chair, IRB member, or IRB staff (acting as a designee of the Chair), may determine if a proposed project using human materials/data constitutes human participant research. Investigators are encouraged to submit their proposed project to the IRB using the IRB-5 Request for Exemption from Continuing Review protocol form. The form will be reviewed and a final determination will be made as to whether a study meets the definitions of human participant research set forth in 45 CFR 46.102(d)(f). If the determination is that the project does not constitute human participant research, a letter of determination will be sent to the investigator and the ORC/IRB will have no further involvement. If the determination is that the research does involve human participants, the IRB-5 will be reviewed and approved in accordance with the exemption process described above. An IRB-1 application may be required if the research project does not qualify for exempt status. The IRB staff will send a written determination regarding the proposed project to the PI.

 

Lapse In Approval

If continuing approval is not obtained, or will not be obtained due to failure to meet submission deadlines, by the end of day on the expiration date, the IRB staff will send the investigator the standard notification letter or e-mail that a lapse in approval has occurred. The letter informs the investigator that all research-related activity must stop until IRB re-approval is obtained. For studies requiring full board review, if review does not occur by the next convened meeting, the study is administratively closed by the IRB. For studies requiring expedited review, if review has not been obtained within 30 days after the expiration date the study is administratively closed by the IRB staff. The IRB staff sends written notification to the PI of administrative closures. This type of study closure is not considered a suspension or termination that is reportable to the IO or agency heads.

The PI may appeal the requirement to stop all research related activity or the administrative closure if continuation of an activity is required due to it being in the best interest of the participant. The appeal must be submitted in writing to the IRB Chair, must request permission for continuation of specific activity(ies), and explain why the continuation of the activity is in the best interest of the participant. The PI must also confirm that continuation is actively being sought. The IRB Chair reserves the right to deny the appeal and require that a new application be submitted for review and approval.

Investigators must respond to the IRB’s letter which outlines the modifications required in order to secure approval within six months, or the initial application is withdrawn. An investigator may request additional time. In the case of modifications related to continuing approval, the study is administratively closed by the IRB staff if a response is not received within 1 month. The IRB staff will notify the investigator in writing of such closures.

 

Criteria for Approval

In order to grant approval to a research study, the IRB must find and document that the following criteria are met, per 45 CFR 46.116(a)(b), at the time of initial approval and sustained through continuing review and requests for an amendment:

  • risks to participants are minimized: (i) by using procedures which are consistent with sound research design and which do not unnecessarily expose participants to risk, and (ii) whenever appropriate, by using procedures already being performed on the participants for diagnostic or treatment purposes;
  • risks to participants are reasonable in relation to anticipated benefits, if any, to participants, 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 participants 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 (for example, the possible effects of the research on public policy) as among those research risks that fall within the purview of its responsibility;
  • selection of participants 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 and should be particularly cognizant of the special problems of research involving vulnerable populations, such as children, prisoners, pregnant women, mentally disable persons, or economically or educationally disadvantaged persons. For example vulnerable populations in proposed studies selected as populations of convenience is not acceptable;
  • informed consent will be sought from each prospective participant or the participant’s legally authorized representative, in accordance with, and to the extent required by regulations (or a request to waive or alter the elements of consent must be approved);
  • informed consent will be appropriately documented, in accordance with, and to the extent required by regulations (refer to informed consent section);
  • when appropriate, the research plan makes adequate provision for monitoring the data collected to ensure the safety of participants (refer to data safety monitoring section); and
  • when appropriate, there are adequate provisions to protect the privacy of participants and to maintain the confidentiality of data (this criterion applies to all studies).
  • when some or all of the participants are likely to be vulnerable to coercion or undue influence, such as children, prisoners, pregnant women, mentally disabled persons, or economically or educationally disadvantaged persons, additional safeguards have been included in the study to protect the rights and welfare of these participants.
  • when biomedical research procedures are included in a research study, the IRB requires that information be provided by the PI that documents the specific training/credentials for each individual identified as key personnel that qualifies them to perform each procedure.

 

Review of Studies Involving Vulnerable Populations

Studies proposing the involvement of vulnerable populations are reviewed to ensure that inclusion of these participants is justified and, if so, that adequate procedures are in place to minimize the risks related to physical harm, psychological harm and breach of privacy and confidentiality. The research must be relevant to the vulnerable population and not otherwise capable of being carried out with a non-vulnerable population. The IRB will fulfill the additional duties required by Federal Regulations outlined in Subparts B, C and D of 45 CFR 46 regardless of the source of funding for initial and continuing review by expedited or full board proceedings. For studies requiring full board review, a member or consultant who is knowledgeable about or experienced in working with vulnerable populations must review all material and be present (in person or via teleconference) at the meeting. The IRB Chair may use the IRB roster to identify such members and/or consultants to assign as reviewers. Consultants may participate in the discussion but may not vote. For studies requiring full board review, any decision made by a convened board will supersede the opinion of an individual reviewer. The minutes will reflect the determinations of the convened board regarding the required findings.

Vulnerable populations include those defined 45 CFR 46 Subparts B (Pregnant Women, Human Fetuses and Neonates), Subpart C (Prisoners), and Subpart D (Children), and those mentioned in 45 CFR 46.111(b): mentally disabled persons, or economically or educationally disadvantaged persons. The IRB also considers UConn students, employees, and HIV+ individuals to be vulnerable populations. The IRB may also require additional protections for any other group not specified in this policy but determined to be vulnerable by the IRB. Such additional protections may include, but are not limited to, the witnessing of the consent process, more frequent continuing review, or additional review by someone with a specific expertise.

 

Pregnant Women, Fetuses or Neonates
Proposed studies involving pregnant women, fetuses or neonates may qualify for exempt or expedited review when no more than minimal risk is involved. The Chair or an IRB member will make the final determination. Studies requiring full board review will be reviewed and approved in accordance with the criteria of 45 CFR 46 Subparts A and B. The primary reviewers will be provided with the standard reviewer sheet that addresses Subpart A and information provided by the investigator that outlines the additional duties/findings required of the IRB under Subpart B. Unavailability of the father as related to consent issues is interpreted to mean that he is either deceased or that his whereabouts are not known and cannot be determined with a reasonable amount of effort.

Note: The regulations specified in Subpart B apply when investigators engage in human participants research conducted or supported by any federal department or agency that has adopted the Federal Policy for the Protection of Human Subjects unless the research is otherwise exempt from the requirements of the Common Rule or a department covered by a separate assurance. In cases where clinical research is not supported by the federal government, as described above, the University will apply equivalent standards when 45 CFR 46.204 applies. However, this may not always be possible in social/behavioral research because such research (while the risk is not greater than minimal risk) may not directly benefit the pregnant woman and/or the fetus. In order to engage in social/behavioral research involving pregnant women, the IRB determined that it will allow pregnant women to be enrolled in research involving interview, focus group, survey or similar procedures. These studies will be reviewed by the IRB following equivalent standards as set forth in the Common Rule.

Pregnant women or fetuses may be involved in research only if the IRB finds that:

      1. where scientifically appropriate, preclinical studies, including studies in pregnant animals, and clinical studies, including studies on pregnant women, have been conducted and provide data for assessing potential risks to pregnant woman and fetuses;
      2. the risk to the fetus is caused solely by interventions or procedures that hold out the prospect of direct benefit for the woman or the fetus; or, if there is no such prospect of benefit, the risk to the fetus is not greater than minimal and the purpose of the research is the development of important biomedical knowledge which cannot be obtained by any other means;
      3. any risk is the least possible for achieving the objective of the research;
      4. the woman’s consent is obtained in accordance with the provisions of Subpart A if the research holds out 1) the prospect of direct benefit to the pregnant woman, 2) the prospect of a direct benefit to both the pregnant woman and the fetus, or 3) no prospect of direct benefit for the woman nor the fetus when risk to the fetus is not greater than minimal and the purpose of the research is the development of important biomedical knowledge that cannot be obtained by any other means;
      5. if the research holds out the prospect of direct benefit solely to the fetus then the consent of the pregnant woman and the father is obtained in accord with the informed consent provision of Subpart A. The father’s consent need not be obtained if he is unable to consent because of unavailability, incompetence, or temporary incapacity or the pregnancy resulted from rape or incest;
      6. each individual providing consent under paragraph d or e of this section is fully informed regarding the reasonably foreseeable impact of the research on the fetus or neonate;
      7. for children who are pregnant, assent and permission are obtained in accord with the provisions of Subpart D – children involved as participants in research; (Subpart D is described under the section for children)
      8. no inducement, monetary or otherwise, will be offered to terminate a pregnancy;
      9. individuals engaged in the research will have no part in any decisions as to the timing, method, or procedures used to terminate a pregnancy; and
      10. individuals engaged in the research will have no part in determining the viability of neonates.

Neonates of uncertain viability and nonviable neonates may be involved in research if all of the following conditions are met:

      1. where scientifically appropriate, preclinical and clinical studies have been conducted and provide data for assessing potential risks to neonates.
      2. each individual providing consent is fully informed regarding the reasonably foreseeable impact of the research on the neonate.
        • For neonates of uncertain viability, the legally effective informed consent of either parent of the neonate or, if neither parent is able to consent because of unavailability, incompetence or temporary incapacity, the legally effective informed consent of the either parent’s legally authorized representative is obtained in accordance with Subpart A, except that the consent of the father or his legally authorized representative need not be obtained if the pregnancy resulted from rape or incest.
        • For nonviable neonates, the legally effective informed consent of both parents of the neonate is obtained in accord with Subpart A. The provisions to request a waiver or alteration of consent described in Subpart A do not apply. If either parent is unable to consent because of unavailability, incompetence, or temporary incapacity, the informed consent of one parent of a nonviable neonate will suffice. The consent of the father need not be obtained if the pregnancy resulted from rape or incest. The consent of a legally authorized representative of either or both of the parents of a nonviable neonate will not suffice.
      3. individuals engaged in the research will have no part in determining the viability of a neonate.
      4. the following requirements have been met as applicable to neonates of uncertain viability.
        • until it has been ascertained whether or not a neonate is viable, a neonate may not be involved in research unless the IRB determines that 1) the research holds out the prospect of enhancing the probability of survival of the neonate to the point of viability, and 2) any risk is the least possible for achieving that objective; or 1) the purpose of the research is the development of important biomedical knowledge which cannot be obtained by other means and 2) there will be no added risk to the neonate resulting from the research;
        • the legally effective informed consent of either parent of the neonate or, if neither parent is able to consent because of unavailability, incompetence or temporary incapacity, the legally effective informed consent of the either parent’s legally authorized representative is obtained in accordance with Subpart A, except that the consent of the father or his legally authorized representative need not be obtained if the pregnancy resulted from rape or incest.

Nonviable neonates: After delivery a nonviable neonate may not be included in research unless all of the following additional conditions are met:

      1. vital functions of the neonate will not be artificially maintained;
      2. the research will not terminate the heartbeat or respiration of the neonate;
      3. there will be no added risk to the neonate resulting from the research;
      4. the purpose of the research is the development of important biomedical knowledge that cannot be obtained by other means; and
      5. the legally effective informed consent of both parents of the neonate is obtained in accord with subpart A of this part. The provisions for a waiver or alteration of consent (46.116 c and d) do not apply. However, if either parent is unable to consent because of unavailability, incompetence, or temporary incapacity, the informed consent of one parent of a nonviable neonate will suffice. The consent of the father need not be obtained if the pregnancy resulted from rape or incest. The consent of a legally authorized representative of either or both of the parents of the nonviable neonate will not suffice.

Viable neonates: A neonate, after delivery, that has been determined to be viable may be included in research only to the extent permitted by and in accord with the requirements of subparts A and D, Additional Protections for Children Involved as Participants in Research, describe in subsequent sections.

Research involving, after delivery, the placenta, the dead fetus, or fetal material may be conducted only if the IRB finds that:

      1. research involving, after delivery, the placenta; the dead fetus; macerated fetal material; or cells, tissue, or organs excised from a dead fetus, shall be conducted only in accord with any applicable Federal, State or local laws and regulations regarding such activities.
      2. if information associated with material described in paragraph a of this section is recorded for research purposes in a manner that living individuals can be identified, directly or through identifiers linked to those individuals, those individuals are research participants and must be afforded the applicable protections of 45 CFR 46 its subparts as applicable.

Research involving pregnant women, fetuses or neonates that does not fit into one of the above categories may only be conducted if the IRB finds that the research presents a reasonable opportunity to further the understanding, prevention, or alleviation of a serious problems affecting the health or welfare of pregnant women, fetuses or neonates and after the Secretary has consulted with an expert panel and there has been opportunity for public review and comment. The required findings for such research are that the research does present the aforementioned opportunity, the research will be conducted in accord with sound ethical principles and informed consent will be obtained.

 

Prisoners
The full board must initially review all studies involving prisoners. The membership of the board will be such that the majority of members have no association with the prisons involved and at least one member will be a prisoner, or a prisoner representative. Such membership constitutes compliance with 45 CFR Subpart C 46.304, Composition of Institutional Review Boards where prisoners are involved. A prisoner representative will be assigned as the primary reviewer. The primary reviewer will be provided with the standard reviewer sheets that address Subpart A and information provided by the investigator that outlines the additional duties/findings required of the IRB under Subpart C.

Minimal risk as related to studies proposing to involve prisoners is defined as the probability and magnitude of physical or psychological harm that is normally encountered in the daily lives, or in the routine medical, dental or psychological examination of healthy persons. In assessing the level of risk involved in a study, the IRB will not use risks that face prisoners in the prison setting as the standard for acceptable risk, and will only allow risks that are commensurate with those that would be accepted by non-prisoner volunteers. The IRB must find that the involvement of prisoners as participants is justified.

Requests for amendments to approved studies that are administrative in nature and/or that pose no change to the involvement of the prisoner or to the level of risk, for example corrections of typographical errors in consent documents or additional data elements in a file review study, may be approved through the expedited review process by the Chair or the prisoner representative. However, the Chair or the prisoner representative reserves the right to require full board review of any request for modification.

Continuing review of studies involving prisoners will require full board review unless no participants have been enrolled and no additional risks have been identified or the remaining activity is limited to data analysis in which case the PI may request expedited review under category 8(b) or (c).

Per 46.305(a)(1), when reviewing proposals involving prisoners the IRB will ensure that the research is permissible under one of the categories of 46.306(a)(2) which are:

      • study of the possible causes, effects, and processes of incarceration, and of criminal behavior, provided that the study presents no more than minimal risk and no more than inconvenience to the participants;
      • study of prisons as institutional structures or of prisoners as incarcerated persons, provided that the study presents no more than minimal risk and no more than inconvenience to the participants;
      • research on conditions particularly affecting prisoners as a class (e.g., vaccine trials and other research on hepatitis which is much more prevalent in prisons than elsewhere; and research on social and psychological problems such as alcoholism, drug addiction and sexual assaults) provided that the study may proceed only after the Secretary has consulted with appropriate experts including experts in penology medicine and ethics, and published notice in the Federal Register of his intent to approve such research; or
      • research on practices, both innovative and accepted, which have the intent and reasonable probability of improving the health or well-being of the participant. In cases in which those studies require the assignment of prisoners in a manner consistent with protocols approved by the IRB to control groups which may not benefit from the research, the study may proceed only after the Secretary has consulted with appropriate experts including experts in penology medicine and ethics, and published notice in the Federal Register of his intent to approve such research.

Per 46.305(a)(2-7), the IRB will also determine that the following additional criteria for approval have been satisfied:

      • any possible advantages accruing to the prisoner through his or her participate in the research, when compared to the general living conditions, medical care, quality of food, amenities and opportunity for earnings in the prison, are not of such a magnitude that his or her ability to weigh the risks of the research against the value of such advantages in the limited choice environment of the prison is impaired;
      • the risks involved in the research are commensurate with risks that would be accepted by non-prisoner volunteers;
      • procedures for the selection of participants within the prison are fair to all prisoners and immune from arbitrary intervention by prison authorities or prisoners. Unless the PI provides to the Board justification in writing for following some other procedures, control participants must be selected randomly from the group of available prisoners who meet the characteristics needed for that particular research project;
      • the information is presented in a language which is understandable to the participant population; (note: use a 5th grade reading level as a benchmark)
      • adequate assurance exists that parole boards will not take into account a prisoner’s participation in the research in making decisions regarding parole, and each prisoner is clearly informed in advance that participation in the research will have no effect on his or her parole; and
      • where the Board finds there may be a need for follow-up examination or care of participants after the end of their participation, adequate provision has been made for such examination or care, taking into account the varying lengths of individual prisoner’s sentences, and for informing participants of this fact.

When funding is from DHHS, the institution shall certify to the Secretary, in such form and manner as the Secretary may require, that the duties of the Board under Subpart C have been fulfilled. The certification letter will be sent from the RCC or DRC on behalf of the IRB.

 

Epidemiologic Research Involving Prisoners
Effective June 20, 2003, the Secretary of the DHHS may also approve epidemiologic research involving prisoners as participants under a provision allowing for a waiver of the applicability of provisions 46.305(a)(1) and 46.306(a)(2) as set forth above. While prisoners may be included in such studies, they cannot be the only population included within the study. The epidemiologic research can present no more than minimal risk and no more than inconvenience to the prisoner-participants. To qualify for such a waiver the epidemiologic study must meet the following criteria:

      • the sole purposes are to describe the prevalence or incidence of a disease by identifying all cases, or to study potential risk factor associations for a disease, and
      • for DHHS supported research, the IRB, via the RCC or DRC, must include in the certification letter to OHRP that the additional criteria of 46.305(a)(207), as described above, have been satisfied.
      • that the research presents no more than minimal risk and no more than inconvenience to the prisoner-participants, and
      • prisoners are not a particular focus of the research

Studies for which the waiver may apply include epidemiological research related to chronic disease, injuries, and environmental heath.

 

Children
Research that involves children is subject to the additional requirements of Subpart D. Under DHHS and FDA regulations “children” are persons who have not attained the legal age for consent to treatments or procedures involved in the research, under the applicable law of the jurisdiction in which the research will be conducted.

When research is conducted in Connecticut, persons who meet the above definition are all individuals under 18 years of age with the following exceptions:

      1. Individuals between 16 and 18 years of age adjudicated as emancipated by a probate court
      2. All individuals under 18 years of age, if the research procedures are limited to:
        • HIV testing, counseling, and treatment
        • Outpatient mental health services
        • Testing or treatment for sexually transmitted diseases
        • Treatment or rehabilitation for alcohol or drug dependence
        • Abortion counseling and treatment
      3. All individuals between 16 and 18 years of age, if the research procedures are limited to:
        • Inpatient mental health services
      4. All individuals between 17 and 18 years of age, if the research procedures are limited to donation of blood or any component thereof and to the withdrawal of blood in conjunction with any voluntary blood donation program.

Proposed studies involving children may qualify for exempt or expedited review if the study falls into one of the federally-approved categories defined in 45 CFR 46.101 or in the guidance published in the Federal Register for categories for which expedited review is acceptable. Exemption categories 1-5 do not apply to FDA regulated studies. Also the exemption noted at 45 CFR 46.101(b)(2) for research involving survey or interview procedures or observations of public behavior does not apply to research involving children unless the research involves the observation of public behavior and the investigator(s) do not participate in the activities being observed. The Chair will make the final determination regarding approval status and categories. Studies requiring full board or expedited review will be reviewed and approved in accordance with the regulatory criteria as summarized below. The primary reviewers will be provided with the standard reviewer worksheets that address Subpart A and information provided by the investigator within the protocol that outlines the additional duties/findings required of the IRB under Subpart D.

For research not involving greater than minimal risk, the IRB must find and document that adequate provisions are made for soliciting the assent of the children and permission of their parents or guardians.

For research involving greater than minimal risk but presenting the prospect of direct benefit to the individual participants the IRB must find and document:

      • the risk is justified by the anticipated benefit to the participants;
      • the relation of the anticipated benefit to the risk is at least as favorable to the participant as that presented by available alternative approaches; and
      • that adequate provisions are made for soliciting the assent of the children and permission of their parents or guardians.

For research involving greater than minimal risk and no prospect of direct benefit to individual participants, but likely to yield generalizable knowledge about the participant’s disorder or condition the IRB must find and document:

      • the risk represents a minor increase over minimal risk;
      • the intervention or procedure presents experiences to participants that are reasonably commensurate with those inherent in their actual or expected medical, dental, psychological, social, or educational situations;
      • the intervention or procedure is likely to yield generalizable knowledge about the participant’s disorder or condition which is of vital importance for the understanding or amelioration of the participant’s disorder or condition; and
      • that adequate provisions are made for soliciting the assent of the children and permission of their parents or guardians.

For research not otherwise approvable that presents an opportunity to understand, prevent, or alleviate a serious problem affecting the health or welfare of children the IRB must find and document:

      • the research presents a reasonable opportunity to further the understanding, prevention, or alleviation of a serious problem affecting the health or welfare of children, and
      • for studies funded by DHHS, the Secretary, after consultations with a panel of experts in pertinent disciplines and following opportunity for public review and comment, has determined either that the research in fact satisfies one of the set of conditions described above, or the following:
      • the research presents a reasonable opportunity to further the understanding, prevention or alleviation of a serious problem affecting the health or welfare of children;
      • the research will be conducted in accordance with sound ethical principles; and
      • adequate provisions are made for soliciting the assent of the children and permission of their parents or guardians.
      • for studies regulated by the FDA, the Commissioner of Food and Drugs, after consultations with a panel of experts in pertinent disciplines and following opportunity for public review and comment, has determined either that the research in fact satisfies one of the set of conditions described above, or the following:
      • the research presents a reasonable opportunity to further the understanding, prevention or alleviation of a serious problem affecting the health or welfare of children;
      • the research will be conducted in accordance with sound ethical principles; and
      • adequate provisions are made for soliciting the assent of the children and permission of their parents or guardians.

The IRB must determine that adequate provisions are made for soliciting the assent of the children when in the judgment of the IRB the children are capable of providing assent. In determining whether children are capable of assenting, the IRB shall take into account the ages, maturity, and psychological state of the children involved. The judgment may be made for all children to be involved in research under a particular protocol, or for each child. When the IRB determines that assent is required, it shall also determine whether and how assent must be documented.

Assent is not a necessary condition for proceeding with the research if the IRB determines that the capability of some or all of the children is so limited that they cannot reasonably be consulted or that the intervention or procedure involved in the research holds out a prospect of direct benefit that is important to the health or well-being of the children and is available only in the context of the research. The IRB may also waive the assent requirement under provisions noted in 45 CFR 46.116 and/or 21 CFR 50.55(d)(1-4). Examples when assent might be waived include certain school-based behavioral studies or studies that meet the criteria under 45 CFR 46.101(b)(1).

In accordance with and to the extent that consent is required under regulation, the IRB shall determine that adequate provisions are in place for soliciting the permission of each child’s parents or guardian. Under DHHS regulations, “guardian” means an individual who is authorized under applicable State or local law, to consent on behalf of a child to general medical care. Under FDA regulations “guardian” means an individual who is authorized under applicable State or local law to consent on behalf of a child to general medical care when general medical care includes participation in research, or an individual who is authorized to consent on behalf of a child to participate in research. When research is conducted in Connecticut, the persons who meet the definition of guardian are court-appointed guardians with the authority to consent to major medical, psychiatric or surgical treatment with specific authorization to consent to research.

Where parental permission is to be obtained, the IRB may find that the permission of one parent is sufficient for research not involving greater than minimal risk or research involving greater than minimal risk but presenting the prospect of direct benefit to the individual participants. If the research is greater than minimal risk and offers no prospect of direct benefit to individual participants, but is likely to yield to generalizable knowledge about the participant’s disorder or condition or is not otherwise approvable but presents an opportunity to understand, prevent, or alleviate a serious problem affecting the health or welfare of children and permission is to be obtained from parents, both parents must give their permission unless one parent is deceased, unknown, incompetent or not reasonably available, or when only one parent has legal responsibility for the care and custody of the child.

In addition to the provisions for waiver of consent contained in DHHS regulations, if the IRB determines that a research protocol is designed for conditions or for a participant population for which parental or guardian permission is not a reasonable requirement to protect the participant (e.g., neglected or abused children) it may waive the consent requirements in 45 CFR 46 provided an appropriate mechanism for protecting the children who will participate as participants in the research is substituted, and provided further that the waiver is not inconsistent with Federal, state or local law. The choice of an appropriate mechanism would depend upon the nature and purpose of the activities described in the protocol, the risk and anticipated benefit to the research participants, and their age, maturity status and condition. This is not applicable to FDA regulated studies.

Permission by parents or guardians shall be documented in accordance with and to the extent required by regulations. FDA regulated studies do not qualify for the exception to the requirement to document consent noted at 46.117(c)(1).

Per regulations, children who are wards of the state or other agency, institution, or entity can be included in research involving greater than minimal risk and no prospect of direct benefit to the individual participants, but likely to yield generalizable knowledge about the participant’s disorder or condition, or research that is not approvable under a defined regulatory category but that presents an opportunity to understand , prevent , or alleviate a serious problem affecting the health or welfare of children only if the research is 1) related to their status as wards, 2) conducted in schools, camps, hospitals, institutions, or similar settings in which the majority of children involved as participants are not wards. If the research is approved, the IRB will require appointment of an advocate for each child who is a ward, in addition to any other individual acting on behalf of the child as guardian or in loco parentis. One individual may be the advocate for more than one child. The individual acting as the advocate shall have the background and experience to act in, and agrees to act in, the best interests of the child for the duration of the child’s participation in the research and who is not associated in any way (except as the advocate or IRB member) with the research, the investigators, or the guardian organization.

 

Economically or Educationally Disadvantaged
Economically or educationally disadvantaged individuals may be particularly vulnerable to the risks of research. The IRB may require additional protections. For example, the IRB may require the use of a witness to the consent process or videotaping the consent process.

Educationally disadvantaged participants may not be able to fully understand the concepts presented by the research and the investigator must take extra precautions to ensure that the participants fully understand what is being asked of them.

Similarly, economically disadvantaged participants may be easily persuaded to participate in research if the economic compensation is so great that it would result in the participant ignoring or disregarding the research risks because of the income offered by the study. In such cases investigators must be careful to set economic compensation at a meaningful level that compensates the participant for her/his time, but it not so great that it unduly influences a participant’s decision to enroll. It is also important in such cases that the risks to the participants be made clear to the participants.

 

UConn Storrs Students
Studies that focus on UConn students as participants may raise concerns with issues of coercion, undue influence and privacy. While these studies may qualify for exempt or expedited review, the Chair, Vice Chair or authorized designee reserves the right to require full board review. The IRB may consult with students when considering approval of a study that involves them as participants.

Each application that involves students as participants must outline procedures to ensure that the students will not be subject to undue influence or coercion and to ensure that the student’s privacy will be respected. While a PI may use his/her own students as participants, it is preferable for the PI to recruit students with whom he/she does not have a direct relationship. If it is not possible or practical to recruit from the general population of students due to the nature of the research (e.g., research on teaching methods or curriculum development) the study must be designed in such a way that any element of undue influence or coercion is minimized.

Suggestions to minimize elements of undue influence and coercion include anonymous data collection methods and the use of an independent third party to collect data or consent participants (a graduate teaching assistant in the class in which the student/participant is enrolled does not qualify as a third party for collecting the data on behalf of the instructor). In this way, the instructor does not know who did or did not participate. Another is to hold off seeking consent until after course grades have been determined. For example, if the research project involves evaluating the effectiveness of a new teaching method, once final grades are determined, consent from the student should be sought as to whether his/her individual information can be used in the research study. In this way, the element of coercion is minimized since grades would already have been determined. Students should also be recruited by a general announcement, central posting or announcement mechanism and should include a clearly written description of the project and a statement of the proposed student participation. In addition to being provided with the traditional information and consent forms, the student should also be provided with the name and contact information of a neutral third party to contact should they feel coerced at any time during the process. Note: The PI is required to submit the proposed study to the IRB prior to implementing the new teaching method that is the subject of the research and at that time may request the IRB’s approval to delay the consent process. Also, the IRB suggests that when students are the targeted population, any payment for participation should be proportionate to the expense incurred with participation, for example parking expenses. Because students are often under financial constraints, larger payments may influence decisions to enroll.

As with all participants, participation must be voluntary and based on disclosure of complete and accurate information. Students should not be asked to participate in any study that will interfere with their curricular activities and obligations. A student’s decision to participate or not participate can not have any bearing on grades awarded by the instructor.

If extra credit is awarded for participation in a study, other comparable means of earning the same amount of extra credit must be available to those students who choose not to participate. Examples of other comparable means include: short papers, special projects, book reports, and brief quizzes on additional readings, research seminars, or completing a similar project. These projects should be comparable in terms of time, effort and educational benefit to participation as a research participant to ensure that students are not being pressured or coerced into becoming participants.

Whenever possible, researchers should avoid data collection during regular class meetings. When study participation consumes a significant portion of a class section, loss of instructional time for both participants and non-participants may be considered a loss of benefits. Also, when research participation is expected during the same session at which participation is invited, students may be unduly influenced to take part due to peer pressure, perceived stigmatization from non-participation, or a sense of having otherwise wasted time by attending that day’s class.

Since there are special risks of confidentiality in the close environment of the university, special attention should be given to full disclosure of these risks in the consenting of a student to participate. The plan for handling research data should also be designed to minimize the risk that confidentiality will be breached. When instruments call for the disclosure of information which participants may view as personal or sensitive, data should be collected in a manner that minimizes the chance of one participant learning the response of another.

Students must be allowed to withdraw from the study at any time. The informed consent statement should make clear the consequences of withdrawing from a project prior to completion. In general, it is favorable to give credit if the participant withdraws, unless the student withdraws immediately or there is evidence of bad faith on the part of the student.

If the research is such that data are collected from a group project or perhaps a videotape of the group interaction, each student’s consent is necessary for the use of that data in the instructor’s research. If one student does not consent, the data may be used only if the non-consenting student’s data can be effectively excluded.

Students have the right to full disclosure as soon as possible. Whenever possible a teaching opportunity in the form of an “educational debriefing” should be employed. Students should know something about the rationale for the study, the process of data collection, and intent of the researcher. In exceptional circumstances, the full or true purpose of the research may not be revealed to the participants until the completion of data collection. In such cases, students must not be subjected to undue stress or embarrassment and must have the right to full disclosure of the purpose of the study as soon as possible after the data have been collected. During the debrief students should be told why the use of deception was necessary to carry out the research and be given an opportunity to decide whether the researcher(s) can use the data collected (refer to Informed Consent Requirements with Use of Deception in Research).

Research conducted by graduate students in a class in which the researcher teaches, assists in the class, or does any grading will be subject to the same restraints described above.

 

Psychology Department Participant Pool
Undergraduate students enrolled in Psychology 1110, 1101 or 1103 are required to participate in research studies as a learning experience. The IRB provides guidance and oversight of the participant pool and reviews all research requesting participant pool participation. The IRB reviews bi-annually the pre-screening measures to be used. All student participation in participant pool research must be completely voluntary. The department provides participants with research participation credits as an incentive. For example, Psychology 1110 students must earn 5 credits of research participation (each credit = ½ hour of participation). Students have the option of earning 7 additional credits as extra credit for the course. Alternatives to research participation must meet the guidelines established for UConn Students. The IRB notes that access to participant pool students is limited to Psychology department faculty members and graduate student researchers and that the department has established an internal review panel that reviews research studies, after receiving IRB approval, before opening the studies for participation. For more information about the Psychology Department Participant Pool, refer to the Psychology Department website.

 

UConn Storrs Employees
Studies that focus on UConn employees as participants may raise concerns of coercion, undue influence and privacy. While these studies may qualify for exempt or expedited review, the Chair, Vice Chair or authorized designee reserves the right to require full board review. The IRB may consult with employees when considering approval of a study that involves them as participants.

Within each application that involves employees as participants, the PI must outline procedures to ensure that the employees will not be subject to undue influence or coercion and to ensure that the employee’s privacy will be respected. While a PI/supervisor may use his/her own direct report employees as participants, the preference of the IRB is that the PI recruit employees with whom the PI does not have a direct relationship. For example, if the research study is an analysis of the performance evaluation process, the PI may recruit employees from the general population of the institution as opposed to employees from the PI’s department. If colleagues or subordinates will be recruited the PI must provide a rationale for their recruitment other than for convenience sake.

Additional suggestions to minimize concerns of coercion, undue influence and privacy include the general recruitment of participants through IRB approved advertisements, collection of data in an anonymous method, the use of an independent third party to recruit, consent and/or collect data. The IRB will also closely review how study data is reported back to management.

The employee’s participation must be voluntary and based on disclosure of complete and accurate information. Employees should not be asked to participate in any study that will interfere with their job obligations. An employee’s decision to participate or not participate can not have any bearing on the employee’s performance evaluation.

The IRB will follow these same policies and procedures when it reviews research studies that seek to enroll non-UConn employees in research.

 

Decisionally Impaired
Individuals considered to be decisionally impaired may include those with psychiatric, cognitive or developmental disorders, substance abuse problems or individuals in chronic pain. Studies involving decisionally impaired participants may qualify for exempt or expedited review. However, the Chair, Vice Chair or designee reserves the right to require full board review. Individuals who are decisionally impaired may still be capable of providing consent. If evidence is present that they are incapable of providing informed consent, for example, due to the incapacity to understand, an individual who is legally authorized to consent for them must sign and date the consent document. The IRB will make a determination as to whether the target participant population is capable of providing consent or whether a legally authorized representative must provide consent. The IRB may also require additional protections such as a witness to the consent process or requiring the PI to determine on an individual basis whether an individual is capable of providing consent, e.g., the IRB may require that the PI ask the participant to articulate in his/her own words the purpose of the study, the risks involved with the study, the benefits of the study and may request that those responses be documented. If the participant cannot answer such questions, consent from a legally authorized representative must be obtained.

When reviewing protocols that focus on decisionally impaired participants as the target population, the IRB must find that they are an appropriate participant population for the study, that the research question focuses on an issue unique to this population, that the level of risk is appropriate to the study and that, unless a waiver or alteration of consent has been approved, the provisions for obtaining informed consent from a legally authorized representative and the assent of the participant are adequate.

The IRB will use the additional protections set forth in Subpart D 46.404 (Research not involving greater than minimal risk), 46.405 (Research involving greater than minimal risk but presenting the prospect of direct benefit to the individual participants), 46.406 (Research involving greater than minimal risk and no prospect of direct benefit to individual participants, but likely to yield generalizable knowledge about the participant’s disorder or condition) or 46.407 (Research not otherwise approvable via 404, 405 or 406 which presents an opportunity to understand, prevent or alleviate a serious problem affecting the health or welfare of the individuals) as guiding standards for the review process. Legally authorized representative will be substituted for reference to parent or guardian made in subpart D. Research involving decisionally impaired adults that would fall under category 407 will not require a Secretarial consult but the IRB may call upon consultants with additional expertise.

The provisions for obtaining the assent of an individual with impaired decision making ability are based on those set forth in subpart D. The IRB shall determine that adequate provisions are made for soliciting the assent of the decisionally impaired individual, when in the judgment of the IRB the individuals are capable of providing assent. In determining whether the individuals are capable of assenting, the IRB shall take into account the maturity and psychological state of the individual involved. This judgment may be made for all individuals to be involved in research under a particular protocol, or for each individual, as the IRB deems appropriate. If the IRB determines that the capability of some or all of the individuals is so limited that they cannot reasonably be consulted or that the intervention or procedure involved in the research holds out a prospect of direct benefit that is important to the health or well-being of the individual and is available only in the context of the research, the assent of the individual is not a necessary condition for proceeding with the research. Even where the IRB determines that the participants are capable of assenting, the IRB may still waive the assent requirement under circumstances in which consent may be waived in accord with 46.116(d)(1-4). For FDA regulated studies, assent may be waived in accordance with 50.55(d)(1-4).

The IRB may impose additional protections. For example, the IRB may require the use of a witness to the consent process or videotaping the consent process. The IRB may also require that the investigator consider the following issues and address each issue as appropriate:

The investigator should explain how he/she plans to determine competency to consent. Observed deficits in cognitive or mental status testing may indicate need to evaluate participant’s decision making in more detail. Cognitive functions related to competency are attention, abstraction, judgment, reasoning, memory, learning, comprehension, language expression, mood and affect. In addition, severe decisional impairment to the extent that institutionalization (nursing home, hospitalization) is probable or actual for the potential participant should be considered a criterion in the determination of competency to consent. Components of the research consent capacity should be evaluated and documented during the consent process.

The investigator should address how he/she will separate the roles of clinician and clinical investigator, if applicable.

It should be recognized that decision-making capacity may fluctuate, requiring ongoing assessment during the course of the research. The consent process should be ongoing and periodic reconsent may be needed. The investigator should describe his/her process for reconsent or reassent or reassessment of willingness to continue participation.

As impairment increases, along with risks and discomforts, safeguards should increase according to a sliding scale, i.e., protections should be proportional to the severity of capacity impairment, or to the magnitude of experimental risk, or both.

 

HIV-Infected Individuals
HIV-infected individuals will be considered a vulnerable population because of the risks of social stigma, employability and insurability facing them if their HIV status were revealed. The University will comply with federal and state guidelines, including those concerning notification of seropositivity, counseling, and safeguarding confidentiality where research activities directly or indirectly involve the study of human immunodeficiency virus (HIV).

All research with HIV-infected individuals is reviewed by the full IRB to ensure that the participants’ rights and privacy are thoroughly safeguarded. At such a review the IRB may determine that a particular research study is sufficiently low in risk so as to allow continuing review to be conducted on an expedited basis. Research about HIV/AIDS that does not include HIV-infected individuals may be considered exempt or expeditable.

In addition, the IRB will consider the guidelines set forth from OHRP with regards to AIDS/HIV Related Research (OHRP: Institutional Review Board Guidelines, Chapter 5, Section F). When necessary the IRB may call upon consultants with additional expertise in this area.

 

Members of the Armed Forces
Studies that focus on military personnel may also raise concerns of coercion, privacy and, in particular, undue influence. While these studies may qualify for exempt or expedited review, the Chair, Vice Chair or authorized designee reserves the right to require full board review. The IRB may consult with military personnel when considering approval of a study that involves them as subjects.

Within each application that involves military personnel as participants, the PI must outline procedures to ensure that personnel will not be subject to undue influence or coercion and to ensure that the employee’s privacy will be respected. The IRB suggests that PIs review the Department of Defense (DoD) directive 3216.2 (Reissued March 25, 2002). While this directive concerns clinical research studies, it describes additional protections for certain categories of research that go beyond those outlined in 32 CFR 219 (the DoD implementation of the “Common Rule” Federal Policy) and are relevant for social and behavioral research. The directive includes the following requirements (see section 4.3) to minimize concerns of coercion, undue influence and privacy as they apply to more than minimal risk studies. The requirements include ensuring that unit officers and noncommissioned officers (NCOs) shall not influence the decisions of their subordinates to participate or not to participate as research participants. Unit officers and senior NCOs in the chain of command shall not be present at the time of research subject solicitation and consent during any research recruitment sessions in which members of units under their command are afforded the opportunity to participate as research subjects. When applicable, officers and NCOs so excluded shall be afforded the opportunity to participate as research subjects in a separate recruitment session. During recruitment briefings to a unit where a percentage of the unit is being recruited to participate as a group, an ombudsman not connected in any way with the proposed research or the unit shall be present to monitor that the voluntary nature of individual participants is adequately stressed and that the information provided about the research is adequate and accurate. These requirements should also be taken into consideration for studies not supported by the DoD. The IRB will also closely review how study data is reported back to officers.

The service member’s participation must be voluntary and based on disclosure of complete and accurate information. Military personnel should not be asked to participate in any study that will interfere with their responsibilities. A service member’s decision to participate or not participate can not have any bearing on the service member’s performance evaluation.

 

Non-English Speaking Individuals
The involvement of non-English speaking individuals in research studies raise concerns with issues of informed consent as well as their inclusion and exclusion in research. While these studies may qualify for exempt or expedited review, the Chair, Vice Chair or authorized designee reserves the right to require full board review.

Investigators must be aware that individual participants, and sometimes significant portions of the potential participant population, may not speak English. Investigators must plan for populations that are likely to be recruited into the research and incorporate translations into the study design to allow for appropriate recruitment and enrollment. When applicable, the PI must outline in the protocol application procedures to recruit non-English speaking participants as well as procedures to translate study material and consent documents. The protocol must also describe procedures for ensuring that informed consent is presented to participants in a language understandable to them. Procedural requirements for the informed consent process for these participants can be found in the informed consent section of the policies (see Consent for Participants Not Fluent in English).

Non-English speaking participants, who meet enrollment criteria, may not be excluded because they cannot understand or read English. Non-English speaking participants may not be excluded from research that may have direct potential benefits. If non-English speaking participants will be specifically excluded from research, the PI must provide an ethical and scientific explanation for doing so.

 

Types of Research Conducted at UConn Storrs

While FDA-regulated and other biomedical studies are conducted on campus, the research conducted at UConn Storrs is primarily social/behavioral in nature. Although Federal regulations for the protection of human participants cover both biomedical and social/behavioral research, they are not specific regarding the various types of social/behavioral research. Therefore, the IRB developed the guidance to assist in the development and review of Qualitative/Ethnographic, Focus Groups, Oral History and other types of social/behavioral research. The guidance is available on the IRB website.

 

Review of Studies Conducted in Foreign Countries

Research conducted by UConn investigators in foreign countries remains under UConn purview and guidelines. While adjustments may be made to some requirements to respect cultural differences, our standards for ethical conduct are not relaxed.

The IRB may require that research projects be approved by the local equivalent of an IRB before the IRB will grant final approval. Where there is no equivalent board or group, investigators must rely on local experts or community leaders to provide approval. The PI must provide the IRB with documentation of this “local approval” and documentation of the authority and expertise of the individual or group who granted approval. There must also be detailed plans in place for local monitoring of studies that pose more than minimal risk to participants. Researchers must describe what, if any, knowledge or experience they possess regarding the language and culture of the country in question. If the IRB is not satisfied with the review of local experts and/or the plans for continued monitoring there is the possibility that the study will not be approved.

The IRB may seek guidance first from OHRP’s International Compilation of Human Subject Research Protections or it may contact OHRP to determine whether procedures described by a foreign institution afford protections that are at least equivalent to U.S. regulations 45 CFR 46.101(h) and may be substituted for the U.S. regulations. Under this provision, OHRP investigates the foreign country’s guidelines for human participants research, and if the foreign guidelines are found to be equivalent to U.S. regulations, the investigator is permitted to substitute those foreign procedures.

Note that the “HHS regulations for the protection of human subjects, in 45 CFR 46, implement Section 491(a) of the PHS Act and provide a framework, based on established, internationally recognized ethical principles, to safeguard the rights and welfare of individuals who participate as subjects in research activities supported or conducted by the NIH or other HHS components.  The HHS regulations stipulate that the grantee organization(s), whether domestic or foreign, bears ultimate responsibility for safeguarding the rights and welfare of human subjects in HHS-supported activities (46.101(a) and 46.103(a)). Grantee institutions “engaged” in human subjects research must obtain a Federalwide Assurance (FWA) with the HHS Office for Human Research Protections (OHRP), and establish appropriate policies and procedures for the protection of human subjects.”  Refer to the NIH Policy here.

 

Research Requiring Review More Frequent Than Annually

The IRB will require that continuing review occur more often than annually in the following circumstances:

  • The research involves the use of procedures that have not been studied in humans.
  • The research is expected to result in a high frequency of morbidity or mortality.
  • The investigator has a history of serious or continuing noncompliance that the IRB believes necessitates closer monitoring.
  • Any other situation in which the IRB believes that more frequent continuing review is warranted.

 

Verification from Sources Other Than Investigators:

The IRB will require independent verification from sources other than the investigator that no material changes (i.e. changes that are both relevant and consequential) have occurred since previous IRB review in the following situations:

  • When there is inconsistency in the information presented by the investigator to the IRB and those inconsistencies cannot be easily resolved.
  • When the IRB questions the ability or the willingness of the investigator to provide accurate information.
  • When concerns have been raised, via continuing review or from other sources, that material changes have been implemented without IRB approval.
  • Other circumstances for which the IRB deems independent verification is needed.

In most cases the Research Compliance Monitor will conduct the verification. The monitor has access to all research data and may observe the research and consent process. The IRB may require that an ad-hoc consultant with particular expertise review the research activity. Such consultants will not have a professional or financial interest in the research. The IRB Chair may determine who will act as the consultant and will also confirm that no conflicts exist. The individual performing the verification will provide the IRB staff with a written statement of the verification. The IRB staff will make this information available to the IRB members and also place a copy in the IRB study file.

 

Scientific Review

The Common Rule and corresponding FDA regulations require the IRB to determine that the study is designed so that risks to participants are minimized and justified by potential benefits (refer to 45 CFR 46.111(a)). Therefore, the IRB will carefully consider the study design and overall scientific quality of each study, particularly those studies that are investigator-initiated and/or unfunded. In evaluating the scientific design, the primary reviewer (exempt and expedited studies) or the primary reviewer and convened IRB (full board studies), will consider the following:

  • clarity of the research question
  • appropriateness and efficiency of design
  • rigor and feasibility of methods
  • qualifications and expertise of the research team
  • scholarship and pertinence of background material and rationale
  • adequacy of sample size and relevance of controls and
  • the validity of the statistical analysis plan.

When necessary the IRB may ask consultants with additional expertise to review the research study.

 

Categories of Study Status

Submissions to the IRB will fall into one of the status categories noted below:

Approved
This decision is used when a study is given final approval either through the exempt, expedited, or full board review process. Final approval of a full board study means that all modifications initially required have been addressed. If the study is approved through the expedited or exempt review process, the specific category by which expedited or exempt review is permissible is noted. A study can begin only after final approval is granted. This category is also used to reflect approval of requests for continuations and amendments.

Modifications Required in Order to Secure Approval
This decision is used when the full board has reviewed a study at a convened meeting and requires minor modifications before final approval will be given. This category may also be used for expedited review, requests for continuation (re-approval), and amendments. Upon satisfactory response to the request for modifications, the Chair or his/her designee is authorized to grant final approval without re-review by the full board.

The IRB may also request that the PI make modifications to an application for initial or continuing expedited or exempt review. This is communicated to investigators through letters from the IRB. Final approval of an expedited or exempt study means that the requested modifications initially identified have been satisfactorily addressed.

Deferred
This decision is used when the full board has reviewed a study at a convened meeting and has significant concerns with the protocol, consent document or other relevant material, or requires substantive clarifications on issues that relate to the required criteria for approval. For example, if the protocol contains insufficient information to assess the nature and purpose of the study, or if the IRB requires clarification as to why a procedure is being followed in the study, the study will be deferred until the convened IRB can determine that risks to participants are minimized. The PI is encouraged to make a point-by-point response in writing, and must resubmit the application for full board review. This category may also be used for requests for continuation and amendments.

Disapproved
This decision is used when the full board reviews a study and determines that one or more of the elements required for approval (refer to Criteria for Approval section) has not been met, and in the Board’s opinion, cannot be satisfied through revisions to the application (for example, if the Board determines that balance of risks to benefits is unacceptable). This category may be used for requests for continuation and amendments. The decision is made by the convened IRB. Protocols may not be disapproved by the expedited or exempt review mechanism.

Tabled
This category is used only when a study is not reviewed at the meeting for which it was originally scheduled, for example, due to loss of quorum. This category may also be used for requests for continuation and amendments.

Closed
This decision is used to reflect that a study is closed/completed. An investigator may request closure of a study when the research project will no longer be pursued, or when data analysis is finished, and the essential work of the study is completed.

Terminated
This decision is used to reflect that a study has been closed by the IRB. A study may be terminated due to failure to request continuing review beyond a 30-day grace period after the study expiration date. The IRB may terminate a study for noncompliance or due to the occurrence of serious or unexpected risks to participants. Termination of previously approved research is defined as a permanent withdrawal of study approval that requires all study related activity to cease. The investigator will be notified of studies terminated by the IRB. Terminations are not reportable events.

Suspended
This decision is used to reflect the imposition of a temporary hold on any or all research activity associated with a study, or a permanent stop to some portion of a previously approved research activity.

 

IRB Decision Appeals Process

In the event that an application is disapproved, suspended, or terminated by the IRB, the PI may appeal the decision in writing to the IRB. The appeal must include information that supports the PI’s position. The appeal may be referred to the full board for consideration.

At the discretion of the Chair, the PI may be invited to attend the next regularly scheduled IRB meeting or one convened specifically for the appeal purpose. The PI will explain to the IRB why the appeal is being made, provide justification for the appeal, and approval/reinstatement of approval for the study, and may engage in discussion with the IRB to provide additional information. The PI will be excused prior to deliberations and voting. The PI will be informed in writing of the final decision of the IRB. The letter will be prepared by the IRB staff for signature by the Chair.

When the IRB has determined that serious or continuing noncompliance or issues that expose participants to unnecessary risks are present, the decision of the IRB to terminate or suspend approval of such a study is effective immediately upon such determination. An investigator must comply with the decision, but may make an appeal to the convened IRB to lift the suspension or termination.

The investigator may also appeal modifications required by the IRB for approval. The initial appeal will be through a written response to the requested modifications, explaining why the modifications identified by the IRB are not appropriate. The Chair may elect to agree with the investigator, disagree with the investigator and still require that modifications be addressed, or refer the matter back to a full board meeting for review, e.g., if the Chair and investigator cannot come to an agreement. This procedure also applies to expedited reviews.

 

Request for Permission to Recruit on Campus

Researchers who are unaffiliated with the University but wish to recruit participants on the UConn Storrs campus, the five regional campuses, the School of Social Work, or the School of Law, must request permission from the IRB before recruiting students or employees on UConn campuses (via poster, flyer, email announcement or newspaper ad).

Unaffiliated researchers must submit one copy of the full packet of materials submitted to the IRB of their own institution, including the letter of IRB approval for the project. The packet should include, but may not be limited to, the IRB protocol application, consent form or information sheet, recruitment flyer or ad, instruments or measures to be used, and any supporting documentation.

The IRB Chair or his/her designee will review the request and issue a letter of permission to recruit on campus. The IRB reserves the right to have requests for permission to recruit on campus go to the full board for review and approval, should the Chair or Vice Chair decide that the nature of the study requires the independent scrutiny of the IRB to protect its students and employees.

 

Conflicts of Interest

In conducting human participant research, a conflict of interest is defined as a situation in which an investigator or key personnel (or someone in his/her immediate family – spouse, children, and any other person living in the same household) has a significant financial, professional or personal, interest in the approval or outcome of a study and the interest could affect decisions related to either the design, conduct or reporting of the research, or adversely affect the rights and welfare of research subjects. This applies to all research protocols regardless of funding source, including those that are unfunded. Such conflicts must be identified and managed appropriately.

The Conflict of Interest (COI) Committee serves as the resource with respect to matters involving individual conflicts of interest in research. Its responsibilities include the identification and management, mitigation or elimination of specific conflicts of interest. The Institutional Policy on Individual Conflicts of Interest in Research can be viewed in its entirety at http://research.uconn.edu/fcoi-home/. The Policy provides guidelines for relationships between the University and its investigators with private industry, federal and state government, and the nonprofit sector that will help to assure the primacy of academic integrity. This Policy applies to all investigators, key personnel, and IRB members.

 

What Must Be Disclosed by Investigators, Coordinators, Persons Obtaining Consent and Persons Involved in the Design, Conduct or Reporting of the Research
Individuals must disclose interests in public and non-public companies, including interest in the specific article or service being researched. The following interests must be disclosed to the IRB if the individual or an immediate family member holds the interest:

  • Any ownership interest, stock options, or other financial interest related to the research unless it meets the following four criteria:
    • <$10,000 when aggregated for immediate family
    • publicly traded on a stock exchange
    • value will not be affected by the outcome of the research
    • <5% interest in any one single entity
  • Any compensation related to the research unless it meets two tests:
    • <$10,000 in the past year when aggregated for immediate family
    • the amount will not be affected by the outcome of the research
  • Any proprietary interest related to the research including, but not limited to, a patent, trademark, copyright or licensing agreement.
  • Any board or executive relationship related to the research, regardless of compensation

Disclosure and Management Procedures for Investigators, Key Personnel, and Persons Involved in the Design, Conduct or Reporting of the Research
All faculty members must complete the Significant Financial Interest Review Form and submit it to the COI. The IRB-1 protocol application asks investigators to disclose whether a significant financial interest has been reported to the COI. If “yes”, then a copy of the Significant Financial Interest Review Form(s) must be attached to the IRB-1. The IRB staff will bring it to the attention of the IRB Chair and the primary reviewer. The COI will determine whether the conflict represents a significant financial interest and if so, a management plan will be developed. The IRB staff will also provide the COI management plan to the Chair and reviewers. Approval for a study cannot be given until a response, and if applicable, a plan has been received from the COI and reviewed by the convened IRB. The convened IRB reserves the right impose management strategies in addition to those outlined by the COI. The convened IRB also makes the final determination as to whether the conflict can be managed sufficiently to allow for approval of the research.

At the convened meeting the IRB will discuss disclosures of conflicts and the measures in place to manage, reduce or eliminate the conflict. The convened IRB is responsible for taking the appropriate action(s), i.e.:

  1. Reviewing the nature of the conflict and the management plan developed by the COI.
  2. Determining whether the COI plan is sufficient to properly oversee and manage the conflict(s), or whether additional management strategies are required, taking into consideration the possible remedies as outlined below.
  3. Determining whether the conflict can be sufficiently managed to ensure protection of participants is not affected and to allow for approval of the research.
  4. Informing the investigator and the COI of the actions and decisions of the IRB, including restrictions.

Restrictions that might be imposed to manage a conflict of interest to prevent it from adversely affecting the rights and welfare of participants, include, but are not limited to:

  1. Monitoring of the research by independent reviewers;
  2. Modification of the research plan;
  3. Disqualification from participation in all or a portion of the activities affected by the conflict;
  4. Divestiture of significant financial interests, or;
  5. Severance of relationships that create the conflict.

Any financial benefit to the investigator must be disclosed in the consent form and during the consent process. However, disclosure alone is not sufficient to manage a conflict that might affect the rights and welfare of participants.
Sanctions
Failure of an investigator to comply with the requirements of disclosure or a management plan may lead to disciplinary action. Such actions may include, but are not limited to:

  1. Letter or reprimand;
  2. Notification to funding agencies and/or professional journals or societies;
  3. Reassignment of duties;
  4. Suspension or termination of a research project;
  5. Recommendations for suspension or termination of employment.

In determining the appropriate course of action, consideration will be given to whether the Noncompliance has biased the design, conduct or reporting of the research or compromised the safety or welfare of participants. The IRB may make recommendations for suspension or termination of employment but cannot impose that action.
What Must Be Disclosed by IRB Members

  • All items listed above for investigators and key personnel;
  • Any involvement of the IRB member or the member’s family member in the design, conduct or reporting of the research;
  • Other reasons for which an IRB member believes he or she cannot objectively review the research, e.g. a sponsor is a client of a community member’s law firm.
    • The subordinate / supervisor relationship, or someone’s departmental or center affiliation with a project, does not necessarily create a conflict of interest. The IRB member is expected to exercise his/her judgment and is encouraged to solicit advice from the IRB to determine whether or not to review/vote on a study.

Procedure for Disclosing and Managing IRB Member Conflict of Interest
An IRB member or consultant may not participate in the IRB’s initial or continuing review of any project in which the member or consultant has a conflict of interest, except to provide information requested by the IRB.

A conflict of interest of an IRB member (or consultant) generally includes the following. The aggregate interest of the member (or consultant) and his/her immediate family (investigator’s spouse, minor children, and any other persons living in the same household) is considered.

  1. Participation in a project (IRB member is listed as an investigator on the project or is a member of the research team);
  2. Supervision of a project (IRB member is a faculty sponsor of the Protocol Director, or a situation in which any investigator must report to or is under the professional supervision of the IRB member);
  3. Significant financial interest as described in the University of Connecticut Financial Disclosure Policy;
  4. Personal relationship with investigator (IRB member has an immediate family relationship or other close personal relationship with the investigator);
  5. Fiduciary relationship to sponsor (IRB member serves as a consultant to a company sponsoring the research, or serves on the company’s board of directors);
  6. Other non-financial interests that may be conflicting interests, such as (a) the IRB member has an interest that he/she believes conflicts with the member’s ability to review a project objectively; or (b) the IRB member is in direct competition with the investigator for limited resources, funding, sponsorship, or research participants, or the IRB member is considered a personal or professional adversary of the investigators (for (b), the IRB member must disclose the circumstances to the IRB Chair or DRC for a determination of whether a conflict of interest exists);
  7. Any other reason for which the IRB member believes he or she has a conflict of interest with the research.

IRB members will determine if a conflict exists by reviewing the agenda that lists the names of all investigators and sponsors. The following statement is read at the start of each convened meeting by the IRB Chair or Vice-Chair, and it is also printed on the meeting agenda:

“Any member who has a conflict with any of the protocols discussed at this meeting should either recuse her/himself from the discussion and vote for that protocol or else abstain from the vote. If you are unsure whether you have an actual conflict, or are unsure as to what constitutes a conflict, you are welcome to discuss it with me (IRB Chair) in private and our conversation will be considered confidential.”

Members will make disclosures orally and the IRB staff will note them in the minutes. If a conflict is disclosed, when the study is reviewed, the member with the conflict is required to leave the meeting for the deliberation and voting. If assigned as a reviewer for a study in which the member has a conflict, the member is responsible for contacting the IRB Office so that another reviewer may be assigned. This policy also pertains to reviews conducted through the expedited process.

IRB members receive initial and on-going education to ensure their awareness of institutional policies regarding non-financial conflicts of interest.