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):
  • subject complaints
  • unanticipated problems involving risk to subjects or others,
  • unexpected profile of adverse events in terms of frequency and/or severity,
  • non-compliance with or deviation from the approved protocol or procedures,
  • audits, inspections or monitoring visits by internal or external personnel.
  • 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:
  • The research is permanently closed to the enrollment of subjects
  • The subjects have completed all research-related interventions
  • The research is no longer active for long-term follow up of subjects
  • 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 – 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.  Per the State of Connecticut records retention schedules, the retention period for signed research authorizations is six years after the study closure date, unless a longer retention period is specified in a contract with a sponsor/funding source in which case, the longer retention period specified in the contract must be followed.

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

Purpose:  This policy is intended to ensure that appropriate provisions have been made for pre-, intra-, and post-operative care of animals undergoing surgical procedures as defined in the Animal Welfare Act, the Guide for the Care and Use of Laboratory Animals, UConn Health’s Assurance with NIH, and AAALAC-i guidelines.

Attending Veterinarian (AV) Responsibilities:
1. Meet with the Principal Investigator, or his/her designee, prior to the submission of an IACUC protocol in which surgical procedures will be performed;
2. Provide support for surgeries involving USDA-regulated non-rodent species pre-,intra-, and post-surgery; and
3. Final determination of classification of survival surgery being major or minor (see table 1).

Principal Investigator (PI) Responsibilities:
1. Consult with the AV prior to submitting an animal care and use protocol in which surgical procedures will be performed;
2. Perform surgical procedures only as described in the approved protocol;
3. Provide pre- and post-surgical care of rodent, amphibian, and fish species and documentation of care given to all animals subjected to any surgical procedure: and
4. Provide training on the surgical procedure to all research personnel expected to perform the surgery.

Definitions:
Major Survival Surgery
Major survival surgery is defined as a procedure that will:
1. Penetrate and expose a body cavity (cerebral, thoracic, or abdominal);
2. Produce substantial impairment of physical or physiological function; and/or
3. Cause extensive dissection or transection of tissue.

Minor Survival Surgery
Minor survival surgery is defined as a surgery that will not:
1. Penetrate and expose a body cavity; and/or
2. Produce substantial impairment of physical of physiological function.

N0n-survival Surgery
Non-survival surgery is defined as a surgical procedure that is performed in which animals will be euthanized prior to any recovery from anesthesia.

Multiple Major Survival Surgery (MMSS)
MMSS is defined as one animal experiencing more than one major survival surgical procedure.

Action:
All survival surgery requires the following:

Preparation of Location and Instruments
1. Surface area cleaned with a disinfectant (e.g., 10% Clidox) prior and after the surgery.
2. Disinfection of all instrumentation to be used (e.g., autoclaving prior to use, cold sterilization by the use of an appropriate aldehyde).  Please refer to the CCM SOPO for aseptic rodent surgery and the CCM SOP for surgery on USDA covered species for specific requirements.
3. Surgery in rodents, amphibians, and fish may be performed in the PI laboratory if approved in the animal care and use protocol.  Surgery in non-rodent USDA-regulated species must be performed in a dedicated CCM OR room unless the performance in another space is approved by the IACUC.
4. In general, if multiple surgeries are performed in a single day, the use of separate sterile packs of instruments should be used.  If not possible, instruments should be sterilized in-between animals using a hot bead sterilizer.  Please refer to the CCM SOP for aseptic rodent surgery and the CCM SOP for surgery on USDA covered species for specific requirements.

Preparation of Animals
1. Acclimation to the facility is required; refer to the IACUC Policy on Animal Stabilization for specific requirements.
2. Assessment for normal well-being (e.g., smooth and glossy hair coat, good body condition, normal and unobstructed breathing pattern).
3. Pre-operative fasting.  This is generally not required for rodents (rodents cannot vomit); however, for gastrointestinal surgeries, this may be helpful.
4. Hair from surgical site is required to be removed.  Please refer to the CCM SOP for aseptic rodent surgery and the CCM SOP for surgery on USDA covered species for specific requirements.

Preparation of Surgeon
1. Surgeons must wear a clean lab coat over their regular street clothes.  Alternately, surgeons may don scrubs, but a clean lab coat is still required.
2. Surgeons must scrub hands with an antiseptic surgical scrub preparation and done sterile surgical gloves.  CCM SOP for aseptic rodent surgery and the CCM SOP for surgery on USDA covered species for specific requirements.
3. Sterile gloves should be changed between surgeries and after contact with non-sterile areas.
4. If surgeries are performed in a CCM procedure rom, standard personal protective equipment (PPE) must be worn.
5. All surgeons must be appropriately trained in the surgery to be performed.

Documentation of Post-surgical Animal Care
1. There must be written documentation for all post-surgical monitoring performed on animals.  For non-rodent USDA regulated species, this documentation must be in the animals’ medical record.
2. Animals may not be returned to facility housing until they have recovered from anesthesia.  Procedure cards must be placed on the cage cards stating what surgical procedure has been performed and the date of performance.
3. Post-surgical monitoring must be performed as described in the approved animal care and use protocol.

Special Considerations:

Non-survival Surgery
1. Non-survival surgery does not require the use of sterilized instruments or sterile surgical gloves.  Instruments must be clean but need not be sterile.
2. Animal acclimation times for non-survival surgery are not as stringent as those for survival surgery.  Refer to the IACUC Policy on Animal Stabilization for specific requirements.
3. Adequate anesthesia is required for non-survival surgeries.
4. If the non-survival surgery is of an extended duration, attention to aseptic technique may be more important in order to ensure stability of the model and a successful outcome.

Multiple Major Survival Surgery
1. MMSS requires approval by the IACUC.
2. Researchers wanting to perform MMSS must provide justification in order to have IACUC approval.  Examples of acceptable justification includes:
a. MMSS being related components of a single research objective;
b. MMSS being used to conserve scarce animal resources; or
c. MMSS being used for clinical teaching purposes
3. PIs may need to provide information on the timing between the surgical procedures, justification of animal numbers subject to MMSS, and the potential significance of findings to be obtained from performing MMSS in order to obtain IACUC approval.

Surgery on Fish and Amphibians
1. Fish and amphibians must be kept moist during surgical procedures by use of sterile saline.
2. Pharmaceutical grade Tricaine is to be used for anesthesia.

References:
The Guide for the Care and Use of Laboratory Animals, current edition
CCM SOP Guidelines for Aseptic Rodent Surgery
CCM SOP Surgery Guidelines for USDA Covered Species
IACUC Policy on Animal Stabilization

Effective Dates:          February 23, 2023 through December 31, 2025

This policy has been approved by a majority vote of the IACUC Members

Table 1:  Examples of Major and Minor Surgical Procedures

Major Surgical Procedure	Minor Surgical Procedure
Laparotomy/Laparoscopy	Wound Creations
Thoracotomy	Subcutaneous Implantations
Craniotomy	Superficial Vascular Cutdown
Joint Replacement	Castration
Limb Amputation	Percutaneous Biopsy
Orthopaedic Surgeries
Intracranial Sterotaxic injections

Your Potential Risks

Based on the species you are working with, you should be aware of the following potential health risks:

• Asthma and Allergy in Animal Handlers
• Bites and Scratches
• Campylobacteriosis
• Giardiasis
• Influenza
• Rabies
• Ringworm (fungal infection)
• Salmonellosis
• COVID-19
• Preventing Asthma in Animal Handlers

 

What you should do 

1. Be knowledgeable about the potential for developing allergies and/or asthma due to animal handling – especially if you are already allergic.  When seeking any medical advice for illness, inform your health care provider that you work with ferrets.
2. Consider using an N95 respirator when working with ferrets.  These respirators have been show to reduce the chance of developing animal allergies.  In order to use a respirator, you must have a fit test through Environmental Health & Safety.
3. Perform procedures in a laminar flow hood whenever possible.  Minimize wearing protective clothing, such as lab coats, outside of animal areas.  Use disposable supplies whenever possible.  Sanitize laboratory work areas after animal work.
4. Know proper handling techniques for ferrets.  Proper ferret handling training is available through the Center for Comparative Medicine.
5. Always wash your hands after coming in contact with ferrets or their saliva, urine, blood, feces, and or bedding materials.  This is the primary method of preventing laboratory acquired infections associated with the use of ferrets – even if you use gloves.
6. Merck Manual has a good general overview of using ferrets in the laboratory on their webpage.

EpicCare® Link at UConn Health is a secure web portal that offers site monitors easy access to clinical trial study data. There is no cost to access the portal, and there’s no software or hardware to maintain. EpicCare Link is available 24/7 via any computer with an Internet connection and an up-to-date browser. Supported browsers include Chrome version 50 or later, Microsoft Edge version 79 or later, and Internet Explorer version 11.

In order to provide a site monitor with access to EpicCare link and a specific clinical trial, an EpicCare Link Agreement between the sponsor and UConn Health needs to be completed first. Once the agreement is executed, we will add the sponsor to the EpicCare Link. A site monitor can be added once the sponsor is added to EpicCare Link. You can learn more about our process via the following documents:

• EpicCare Link Process Flow When No Master Agreement is in Place
• EpicCare Link Process Flow When Master Agreement is in Place

To start the process, please complete the EpicCare Link Request Form and send it to octrclinicaltrial@uchc.edu.

If you any questions, please contact us at octrclinicaltrial@uchc.edu.

To access a Safety Data Sheet (SDS), search for it either with a general search engine, such as Google, or use of the specific manufacturer’s or SDS service websites listed below. Specific instructions for each website are listed in the table below.

COMPANY	SITE INSTRUCTIONS
Google, Yahoo, MSN, etc.	Enter the search criteria: SDS + product name + manufacturer (if known) and SEARCH button to bring up link to SDS.
3M	Under Search, down arrow until you find “with Product Name/Number” and under the search (magnifying glass) type in the product you are searching for and on the magnifying glass.
Acros Organics	Type in the product name in the “Product Code” box and “Go”.
Avantor Performance Materials, Inc	“Certificate/SDS search” and type product name in the “text search” box under SDS and “SDS Search”.
Bio-Rad Laboratories	Please enter the catalog number, product name or chemical name. You may filter the results by selecting SDS in the Documents filter group on the left-hand side.
Certol International, LLC	Search by Product Number or Product Name.
Eastman Kodak Company	Enter product name and search for SDS.
ECOLAB	Type in product name and search for SDS.
Fisher Scientific	Type in SDS product you are searching for SDS
GC America Inc.	Look for product name you are searching for SDS.
Thermo Fisher Scientific	Search by typing in product you are looking for and scroll down to find the SDS.
Ivoclar Vivadent	Search for product you are looking for. Click on product and to get information.
Lang Dental Manufacturing Company, Inc.	Search by product name for SDS.
Promega	Search by product name under “Search SDS”.
Pharmco-Aaper	Find the product name to get SDS.
Sigma-Aldrich	Search Type by Product Name, CAS number or Product Number.
Sterilex	Find product name, “Learn More” and “Resources” to get SDS.
Steris Corporation	Search by product name, product number, document title, or key word and “Search SDS”.
Temrex Corporation	Click on product name for SDS.