The Association for Accreditation of Human Research Protection Programs
UConn Health Human Subjects Protection Programs Preparation for Reaccreditation

The Association for Accreditation of Human Research Protection Programs (AAHRPP) is an independent, non-profit accrediting body that works to protect the rights and welfare of research participants and promotes high-quality research through an accreditation process.

AAHRPP’s accreditation standards meet or exceed U.S. federal regulatory requirements and the International Committee on Harmonisation –Good Clinical Practice (E6) guideline for protection, and are reasonable, attainable, and representative of current best practices.

UConn Health’s Human Subjects Protection Program (HSPP) achieved AAHRPP accreditation in 2006. As an accredited organization, our HSPP must periodically apply for re-accreditation every five years. This is a two-step process.

Step 1, consists of a self-evaluation of our program, followed by an AAHRPP review of our policies and procedures to ensure they meet regulatory and accreditation standards.

Step 2 is an onsite visit by AAHRP representatives to ensure that our policies and procedures are followed. Once our HSPP is scheduled for the reaccreditation visit an announcement will be sent to the research community.

To complete the reaccreditation step 1, the HSPP has revised multiple IRB policies to reflect our current practices, add required information and standards for accreditation.

In the tables below is a list of the IRB polices and forms that have been revised along with a short summary of the revisions.

If you have questions regarding those changes please send an email to either irb@uchc.edu or contact the Education Specialist at cagganello@uchc.edu , 860-679-8802.

2009-001.0.pdf – Reporting Unanticipated Problems to the Institutional Review Board: Edited section under “Self-Reporting” to clarify that the Principal investigators are to report to the IRB any noncompliance with the protocol or directives of the IRB that was within the control of the research team within 5 business days of becoming aware of the event.

2009-003.0.pdf – Imposing and Lifting Suspensions of IRB Approval or Imposing Terminations of IRB approval: Updated to reflect current guidance on diversity, equity and inclusion (change he/she to they, his/her to their) and minor punctuation and grammar changes.

2009-005.0.pdf – Monitoring of IRB Approved Studies: Updated to reflect current guidance on diversity, equity and inclusion (change he/she to they, his/her to their) and minor punctuation and grammar changes.

2011-006.1.pdf – Additional Protections – Pregnant Women, Fetuses or Neonates: Minor grammar changes.

2011-006.4.pdf – Additional Protections – Other Vulnerable Groups: Updated to reflect current guidance on diversity, equity and inclusion (change he/she to they, his/her to their) and minor punctuation and grammar changes.

2011-006.5.pdf – Additional Protections – Fetal Tissue Transplants: Updated to reflect current guidance on diversity, equity and inclusion (change he/she to they, his/her to their) and minor punctuation and grammar changes.

2011-007.0.pdf – Definitions Applied to Policies: Added definition of benign behavioral intervention. Edits to reflect current guidance on diversity, equity and inclusion (change he/she to they, his/her to their).  Included revised common rule.

2011-008.1.pdf – Informed Consent – Process The general section was revised to request information about the informed consent methods and documentation and to alert the investigator that prospective IRB approval is required for any subsequent modifications made to the methods of obtaining consent or documentation of informed consent whether they are done by hard copy or electronically.

• Changes to the process of obtaining consent by Phone / Fax to include that the individual obtaining consent must be approved by the IRB to consent and that such individual should have sufficient knowledge of the study to conduct the conversation and to answer any questions,; and the consent conversation should include an in-depth review of the consent document allowing sufficient time for questions to be asked and answered.
• The process for obtaining consent via videoconference (e.g., WebEx, Zoom) was added with an explanation of how this process must be conducted.
• A section about obtaining electronic documentation of consent was added with details of compliance expectations and acceptable methods and processes to obtain electronic signatures.
• A section about electronic informed consent process when consent is not witnessed by study personnel was added to alert researchers that the investigator planning to use this method should discuss this plan with the IRB prior to submitting this method for approval to ensure this method is appropriate for the research (e.g., in compliance with applicable regulations).
• Edits to reflect current guidance on diversity, equity and inclusion (change he/she to they, his/her to their).

2011-008.5.pdf – Informed Consent – Providing and Obtaining Informed Consent: Updated to reflect current guidance on diversity, equity and inclusion (change he/she to they, his/her to their) and minor punctuation and grammar changes.

2011-009.0.pdf– Institutional Review Board – Membership: Updated to reflect current guidance on diversity, equity and inclusion (change he/she to they, his/her to their) and minor punctuation and grammar changes.

2011-009.11.pdf – Institutional Review Board – Studies Conducted in Foreign Locations: Updated to reflect current guidance on diversity, equity and inclusion (change he/she to they, his/her to their) and minor punctuation and grammar changes.

2011-009.14.pdf – Institutional Review Board – Human Subject Research Determinations: Updated to reflect current guidance on diversity, equity and inclusion (change he/she to they, his/her to their) and minor punctuation and grammar changes.

2011-009.2.pdf – Institutional Review Board – Exemptions: Policy was edited to remove language related to pending adoption of the revised common rule and revisions to applicability of exemption 4(iii) at UConn Health.

2011-009.3.pdf – Institutional Review Board – Expedited Reviews : Policy was revised to include a complete list of the criteria for approval when conducting initial or continuing review for expedited submissions. In addition, when submissions are returned to the investigators with a status of “Approved Contingent,” the IRB reviewer can now add a deadline for the investigator to respond to the contingencies sent in a Response form.

2011-009.4.pdf – Institutional Review Board – Convened Meeting Operations: Policy was revised to add that when virtual IRB meetings are conducted the agenda item (inclusive of supporting documents) are shared on the screen in the videoconference.

2011-009.7.pdf – Institutional Review Board – Assignment of Status Codes: Policy was revised to clarify the IRB will assign the study status code “Closed by PI” to a study under oversight of an external IRB when the external IRB grants the request.  Under the status code title: “Inactive-Administratively Closed” the following was added: the IRB Administrator will assign this status code to exempt research after the anticipated completion date has passed.

2011-009.8.pdf – Institutional Review Board – Appeals Process: Policy was revised to indicate that when a principal investigator (PI) submits an initial appeal letter, it can be completed through a written correspondence (i.e., not limited to IRIS response).  Also, the letter sent by the IRB in response to the appeal made by the PI will contain a wet-ink or electronic signature of the IRB Chair.  In addition some edits were made to reflect current guidance on diversity, equity and inclusion (change he/she to they, his/her to their).

2011-009.10.pdf – Institutional Review Board – More Frequent Review: Policy Appendix -A was revised to remove Panel 3 and CICATS.

2011-009.12.pdf – Institutional Review Board – Criteria for Approval: Policy was revised to clarify that students can be considered subjects who are likely to be vulnerable to coercion or undue influence.  In addition, policy revised to remove language indicating ‘if’ the revised common rule is implemented (see section describing limited IRB review).

2011-009.13.pdf – Institutional Review Board – Lapse in IRB Approval: Policy was revised to describe that investigator are notified either by email or iRIS correspondence about the need to submit a request for extension of the anticipated completion date or close the study.

2011-009.15.a.pdf – Institutional Review Board – Reliance on UConn Health as IRB of Record: Policy was revised to indicate SMART IRB template may be used to execute reliance agreements. The Office of Human Research Protection reliance agreement template was removed as it not preferred since it does not meet AAHRPP standards.

2011-009.15.b.pdf – Institutional Review Board – Reliance on External IRB: Trinity Health was added as an institution with which UCONN Health has an established collaborative agreement for minimal risk studies conducted by a student, fellow or resident. Also, policy now contains that when requesting reliance on an external IRB for a student/resident/fellow project, UCONN Health IRB may request the original approval letter to ensure the research is minimal risk.

2011-011.0.pdf – Research Personnel: Policy revised to include principal investigator (PI) responsibility to ensure the confidentiality and security of research records and data as described to the IRB in the submission materials, and to cooperate with all aspects of internal or external audits and inspections.

2011-012.0.pdf – Conflict of Interest – Research Personnel: Updated to reflect current guidance on diversity, equity and inclusion (change he/she to they, his/her to their) and minor punctuation and grammar changes.

2011-012.1.pdf – Conflict of Interest – IRB Members: Updated to reflect current guidance on diversity, equity and inclusion (change he/she to they, his/her to their) and minor punctuation and grammar changes.

2011-015.0.pdf – Recruitment and Payment:  Policy was revised to indicate that external researchers looking to advertise recruitment in UConn Health broadcast (e.g., Lifeline) messages do not need HSPP/IRB permission. Also revised to include procedure to use UConn Health as a recruitment site when UConn Health is not engaged.   Added edits to reflect current guidance on diversity, equity and inclusion (change he/she to they, his/her to their).

2011-016.0.pdf – Scientific Review: Policy was revised to include the Clinical Research Center and funding foundation as acceptable entities who may have conducted the scientific review of studies submitted for full board review.

2011-020.0.pdf – Humanitarian Use Device: Updated to reflect current guidance on diversity, equity and inclusion (change he/she to they, his/her to their) and minor punctuation and grammar changes.

2011-022.0.pdf – Study Drug – General: Updated to reflect current guidance on diversity, equity and inclusion (change he/she to they, his/her to their) and minor punctuation and grammar changes.

2011-022.2.pdf – Investigational Drug/Biologic – Expanded Access for Treatment Use, Including Single Emergency Use: Updated to reflect current guidance on diversity, equity and inclusion (change he/she to they, his/her to their) and minor punctuation and grammar changes.

2011-023.0.pdf – Educational Requirements: Updated to reflect current guidance on diversity, equity and inclusion (change he/she to they, his/her to their) and minor punctuation and grammar changes.

2011-025.0.pdf – HSPP Evaluation / Institutional Support: Policy was revised to include minor updates to title of HSPP manager, and removing executive committee.

2014-034.0.pdf – Additional Requirements – Department of Education (Federal): Policy was revised to include that an email confirming with all of the information included in the FERPA verification form may be acceptable, provided the email is from the person at the school with the authority to grant the permission and sent from that individual’s institutional email address.  Added edits to reflect current guidance on diversity, equity and inclusion (change he/she to they, his/her to their).

Application Checklist for Initial Exempt Application  .doc: Exempt submission checklist Added the following requirements:  When submitting for Exempt determination under Exempt category 4.iii a confirmation that the data will remain protected under HIPAA for 4.iii is required.   If the protocol involves sharing data with indirect identifiers such as sharing a Limited Data Set with an external investigator the UConn Health investigators should provide confirmation they have in place a Data Use Agreement.    If the protocol involves sharing coded data the UConn Health investigators should provide confirmation they have a Don’t Ask /Don’t Tell agreement in place.

Application Checklist for Initial and Continuing Review Expedited .doc : Expedited submission checklist Added the following requirement:
When using electronic informed consent (eIC) (confirmation of part 11 compliance, hard copies of materials, access to eIC platform)
Application Checklist for Initial and Continuing Review Full Board.docx

Application Checklist for Initial and Continuing Review Full Board.docx : Added the following requirement : When using electronic informed consent (eIC) (confirmation of part 11 compliance, hard copies of materials, access to eIC platform).

Request for Exemption Form .doc: Request for Exemption Category 4.iii. was revised to be less restrictive but still ensure HIPAA protection for review as required under the exemption.

 

Guidance on Closure of Human Subject Research Studies

 

A research study should be closed by the Principal Investigator (PI) once all human research activities are completed regardless of whether a study is subject to the continuing review requirement. To do so, a closure form should be submitted to the IRB through the iRIS submission system for each non-exempt human research study (e.g., studies approved under Expedited review or Full Board review). The closure form should be submitted before the expiration of IRB approval, however, the PI can also submit a closure form after they have received a notice of lapse of approval.

If the study is an exempt study, the PI may allow the IRB approval to expire. When approval of an exempt study expires, the IRB will administratively close the study, but this does not invalidate the exemption. The research, as proposed to the IRB, may continue; it is not necessary to keep the exemption actively registered with the IRB.

A closure form allows the IRB to have a summary of the following information:
• the findings of the study
• the final enrollment data
• whether the study met the recruitment goals, and
• whether any of the following events occurred since the last approval (initial or continuing review):
o subject complaints
o unanticipated problems involving risk to subjects or others,
o unexpected profile of adverse events in terms of frequency and/or severity,
o non-compliance with or deviation from the approved protocol or procedures,
o audits, inspections or monitoring visits by internal or external personnel.
o any publications, presentations, trademarks, patents, etc. related to the study.

This guidance explains the circumstances in which a non-exempt human research study may be closed from IRB oversight, as well as ongoing researcher responsibilities that apply to closed studies.

Things to Consider before Closing Research Studies

• Investigators should honor wishes of the sponsor or funding source to keep the study open or to close the study. Some funding entities require IRB approval for the duration of the funding, even if human research activities are complete, or they may not allow the study to close without the sponsor’s permission. It is the PI’s responsibility to be aware of, and comply with, those requirements.

• Sponsors, contract research organizations (CROs), or coordinating center personnel may need to verify or monitor individually identifiable study data at a specific site where human subjects activities have been completed. The study team should verify whether these organizations require the studies to be open when conducting their monitoring visits. IRB approval must be maintained while these activities are occurring.

• Whenever possible, prior to closing a study, data should be permanently de-identified.

When to Close a Study

• For studies requiring continuing review (e.g., some Expedited studies and all full board studies ) a requests for closure should be submitted at the time the next continuation application is due or within 30 days after the completion of all study activity involving the use of private identifiable information or biospecimens, whichever comes first.

• Moreover, a closure form should be submitted to the IRB if the if the research study was not conducted or was canceled, or if each of the following conditions exist:
o The research is permanently closed to the enrollment of subjects
o The subjects have completed all research-related interventions
o The research is no longer active for long-term follow up of subjects
o Data has been de-identified.

• When a Principal Investigator terminates employment with UConn Health, the PI may submit a closure form to the IRB. Alternatively, the PI may submit a modification form requesting transfer of the study to another eligible Principal Investigator.
Retired investigators with Emeritus status at UConn Health may be permitted to keep the study open and continue as the PI with approval from the HSPP Director.

• When a student-led project is completed, the study should be closed with the IRB. This should occur prior to the student’s departure / graduation.

IRB Process of Expired studies, Lapsed Studies and Closure Forms

• Expired studies: If approval for continuation of non-exempt research is not sought, or a request to extend the expected completion date has not been received within a reasonable time frame (e.g., 30 days), IRB staff will administratively close the study and send a written notification to the Principal Investigator of the administrative closure. The research activity may not continue and a new application may be required to resume research activity.

• Lapsed studies: If approval of the study has lapsed due to lack of a response to contingencies or a request for continuing approval or to extend the completion date has not been received the study may administratively be closed. The IRB will send a written notification to the PI. Prior to closure the IRB will issue a final request for response by email to the PI and study contacts and the PI will be given a reasonable period within which to respond (e.g. one or two weeks).

• Closure forms: When a closure form is submitted, the IRB will review any new information provided in the closure form and determine whether any additional action is required on the part of the IRB or the investigator. Upon review of the closure form, the status of the study is changed in the iRIS system (e.g., “Closed by PI”) and an outcome letter is issued confirming the closure.

Principal Investigator Responsibilities with Closed Studies

The principal investigator (PI) continues to have responsibilities for a study even when IRB oversight of a study is no longer required. These responsibilities include:

• Verifying all research activities have been completed. The PI should ensure that all research-related activities, interventions or interactions with human subjects or individually identifiable data have been completed at the site(s) approved under the Principal Investigator’s IRB application at the time a closure form is submitted to the IRB or at the time of approval expiration, whichever occurs first.

If after a study is closed, the PI wishes to engage in an activity such that the criteria for closure listed above would no longer be met, the Principal Investigator must submit a new application for IRB review and approval for the use of the previously collected data.

• Record Retention Research data from the completed study should be stored and protected in the manner approved by the IRB and consented to by the research participant so as to maintain the privacy and confidentiality of the participants.

Per HSPP Policy 2011-024.0.pdf – File Requirements & Record Retention Requirements , investigators must maintain research records for three years beyond the completion/termination of the study. Investigators should be aware that other laws and requirements (e.g., funding agency) may require a longer record retention period. Per the HIPAA regulation, investigators are to retain documents relating to uses and disclosures, authorization forms for 6 years from the date of creation or the date when it last was in effect, whichever is later.

Investigator should be familiar with the record retention format described in the UConn Health HSPP Policy 2015-024.1.pdf – Record Retention Format .

Investigators should ensure that any specific regulatory and/or sponsor requirements are met for record retention or submission of reports.

• Confidentiality and Data Security. If the PI is maintaining identifiable private data or specimens, the protections described in the IRB application and to subjects must be maintained for the time frame described. The PI must continue to honor any commitments made to participants as part of the approved research (e.g., providing information about study results; payment for research participation).

• HIPAA authorization. The PI may have obtained HIPAA authorization from subjects to access their medical records, with an expiration date that is far in the future. If the PI still has permission to access medical records at the time they want to close the study that permission expires upon study closure.

 

 

U.S. Department of Health and Human Services Food and Drug Administration
Common Inspection findings from 2017-2022

 

The Food and Drug Administration (FDA) has released their Bioresearch Monitoring (BIMO) Fiscal Year 2022 Metrics. Below is a partial description of the common inspection findings from 2017-2022. The full report can be found here: https://www.fda.gov/media/165853/download

Common Sponsor-Investigator Inspectional Observations:
• Failure to maintain and/or retain adequate records in accordance with 21 CFR 312.57; accountability for the investigational product; Investigator Statement (FDA 1572); Financial disclosures.
• Failure to select qualified investigators and/or monitors, ensure proper monitoring of the study and ensure the study is conducted in accordance with the protocol and/or investigational plan.
• Failure to submit an Investigational New Drug (IND) application.
• Inadequate subject protection; informed consent issues.
• Failure to notify FDA of termination of investigator.

Common Sponsor/CRO Inspectional Observations:
• Failure to ensure proper monitoring of the study and ensure the study is conducted in accordance with the protocol and/or investigational plan.
• Failure to meet the abbreviated requirements for investigational device exemptions (IDEs).
• Failure to maintain and/or retain adequate records in accordance with 21 CFR 312.57; accountability for the investigational product; Investigator Statement (Form FDA 1572); Financial disclosures.
• Failure to submit an Investigational New Drug (IND) application; IND safety report.
• Failure to submit current list of all participating investigators to FDA at six-month interval after FDA approval of the study.

Common Clinical Investigator Inspectional Observations:
• Failure to comply with Form FDA 1572 requirements, protocol compliance
• Failure to follow the investigational plan; protocol deviations
• Inadequate and/or inaccurate case history records; inadequate study records
• Inadequate accountability and/or control of the investigational product
• Safety reporting; failure to report and/or record adverse events
• Inadequate subject protection; informed consent issues

 

Difference Between De-Identified Data Sets and Limited Data Sets
&
Limited Data Sets and Data Use Agreements

 

Under the Health Insurance Portability and Accountability Act (HIPAA) de-identified data is data from which all 18 HIPAA identifiers that could be used to identify an individual or the individual’s relatives, employers, or household members have been removed.

Unlike a de-identified data set, a limited data set is still considered Protected Health Information (PHI). As defined by HIPAA, limited data sets (LDS) are data sets stripped of certain direct identifiers that are specified in the Privacy Rule. They are not de-identified information under the Privacy Rule.

A limited data set is protected health information that excludes the following direct identifiers of the individual or of relatives, employers, or household members of the individual: (1) names; (2) postal address information, other than town or city, State, and zip code; (3) telephone numbers; (4) fax numbers; (5) e-mail addresses; (6) social security numbers; (7) medical record numbers; (8) health plan beneficiary numbers; (9) account numbers; (10) certificate/license plate numbers; (11) vehicle identifiers and serial numbers; (12) device identifiers and serial numbers; (13) web URLs; (14) Internet Protocol (IP) address numbers; (15) biometric identifiers, including fingerprints and voiceprints; and (16) full-face photographic images and any comparable images.

Distinct from de-identified data, a limited data set contains protected health information that is associated with indirect identifiers as defined in the HIPAA privacy rule. Protected health information in limited data sets may include the following indirect identifiers: town, city, state and zip code, and dates directly related to an individual, including birth date, admission date, discharge date and date of death.

The table below describe in detail the HIPAA identifiers that must not be present in a de-identified data set or in a limited data set.

 

 

DATA ELEMENT	DE-IDENTIFIED DATA SET	LIMITED DATA SET
Names.	Remove	Remove
Postal address information.	Remove	Remove
Town, city, state and zip code.	Remove	Can retain city, town, state or full zip code.
All elements of dates that are directly related to an individual, including birth date, admission date, discharge date, death date, and all ages over 89 and all elements of dates (including year) indicative of such age, except that such ages and elements may be aggregated into a single category of age 90 or older.	Remove	Remain
Telephone numbers, fax numbers; e-mail addresses, web URL addresses, IP addresses.	Remove	Remove
Social security number, medical record number, health plan beneficiary number, any account number, certificate or license number.	Remove	Remove
Vehicle identifiers and serial numbers, including license plate numbers, Device identifiers and serial numbers.	Remove	Remove
Full-face photographic images and any comparable images, Biometric identifiers, including fingerprints and voiceprints.	Remove	Remove
Any other unique identifying number, characteristic or code.	Remove	Remove

 

Limited Data Sets and Data Use Agreements

If indirect identifiers must be kept within a limited data set (LDS) in order to perform a research study and the information is to be disclosed outside of UConn Health, the principal investigator must enter into a Data Use Agreement (DUA) with the data recipient. A DUA may also be utilized when UConn Health is the  recipient of a LDS. Only after the agreement has been executed can the limited data set be used/disclosed.

This DUA is required under the HIPAA Privacy Rule. This agreement establishes the ways in which the information in the limited data set may be used, the purpose for which it was disclosed, and identifies who is permitted to use or receive the information.

Moreover, the DUA stipulates that the recipient will use appropriate safeguards to maintain the confidentiality and protect the data from further disclosures.

Since the data use agreements establish institutional obligations and bind the institution to the terms of the agreement, investigators are not authorized to execute research DUAs. UConn Health DUAs for research related activities are processed through the Office of Sponsored Programs Sponsored Program Services (SPS) or the Office of Clinical and Translational Research (OCTR). The specific contacts in these offices are listed below:

• If the DUA is related to a Clinical Trial contact: Donald Deyo, Contract Specialist (deyo@uchc.edu), or the OCTR main inbox (octrclinicaltrial@uchc.edu).

• If the DUA is unrelated to a Clinical Trial contact: Jennifer Pomales pomales@uchc.edu

The table below describes whether IRB review approval is required for a de-identified data set or for a limited data set, and when a Data Use Agreement is required.

 

	DE-IDENTIFIED DATA SET	LIMITED DATA SET
IRB Review/Approval	IRB and Investigator can determine the project /research is Not Human Subject research. May be used in any manner, not regulated under HIPAA.	If the data is not readily identifiable, IRB can determine Not Human Subject Research. IRB does not require HIPAA Authorization or Waiver.
Data Use Agreement	Not required.	Required. UConn Health DUAs for research related activities are processed through the Office of Sponsored Programs Sponsored Program Services (SPS) or the Office of Clinical and Translational Research (OCTR).

 

OHRP’s Common Rule Webinar

Join the introduction-level, webinar titled “Unlocking the Mysteries of the §46.111 Criteria for IRB Approval of Research.”

This presentation will explain the criteria for IRB approval of research and include case studies and interactive quizzes to demonstrate the way the criteria can be applied.
Date: Tuesday, July 11, 2023, 12:00 PM EDT
Spots are limited. Registration is required to attend and receive a certificate of attendance.

Register for this webinar at: https://www.zoomgov.com/webinar/register/WN_9RbRyAwjQY2N_kRxFPbT-w

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