UConn Health’s HSPP Reaccreditation from the

Association for Accreditation of Human Research Protection Program (AAHRPP)

On March 27-28, 2024, UConn Health Human Subjects Protection Program (HSPP) underwent a Site Visit evaluation as part of the process of reaccreditation by the Association for Accreditation of Human Research Protection Programs (AAHRPP).  After the HSPP responds to the Site Visit report the application will be reviewed by the AAHRPP Council in June 2024.  This process required team work from many stakeholders. The Director of the Human Subjects Protection Program and the Associate Vice President for Research Integrity & Compliance extend their gratitude to the faculty, staff, IRB members and members of the Scientific Review and Conflicts of Interest Committees, Office of Clinical and Translational Research Services, Sponsored Program Services, Research Pharmacy and Research Safety, and many others who committed their time to the Site Visit and who ensure that we have an outstanding human subjects program every day.

FDA Regulated Research

Overview of Human Subjects Research with Devices

The U.S. Food and Drug Administration (FDA) regulates drugs, biologics, and devices used in the diagnosis, mitigation, treatment, or prevention of diseases.

 Investigators who will be conducting clinical investigations in which the purpose of the study is to obtain data about a medical device (e.g., data on its safety and effectiveness), should become familiar with the information provided below to determine whether: (a) the device is exempt from an investigational device application (IDE), (b) the device fulfills the requirements for an abbreviated IDE, or (c) the device needs an IDE issued by the FDA.

Investigators should only think about these determinations when research participants of a clinical investigation will become part of the group in which a medical device will be used or part of the control group, and the device is the object of the investigation/research study.

Unless the sponsor of the device has made the determination that the device is exempt from the requirements of Part 812.2 (c), the study may be conducted under an abbreviated IDE or the investigator must submit an IDE application to FDA. See Table 1 below.

An investigational device exemption (IDE) is a regulatory status granted by the FDA that allows researchers to conduct clinical investigations on medical devices that have not yet received FDA approval. However, not all device studies are required to submit an IDE application to the FDA.  If a device is determined to be a non-significant device (NSR) in concurrence with the IRB, then an IDE is not necessary.

An IRB may determine that a device is a non-significant device because it does not meet the definition for a significant risk device (SR) (see definition of SR below) and does not present a potential for serious risk to the health, safety, or welfare of participants.

The sections below explains when and how an investigator makes a determination that a device could be used in a clinical investigation under an abbreviated IDE or under an Investigational Device Exemption (IDE).

Abbreviated Investigational Device Exemption

The sponsor makes the initial determination of SR or NSR for the device. However, it is important to note the IRB will make the final determination for NSR devices. If the research study is investigator initiated, then the investigator is also acting as the sponsor.

NSR device studies may not require submission to the FDA providing they comply with the abbreviated requirements of the regulations described in the IRB Policy 2011-021.0.pdf – Investigational Device Studies 

The FDA considers an investigation of a non-significant risk device to have an approved IDE (Abbreviated Investigational Device Exemption) when an IRB concurs with the initial non-significant risk determination of the sponsor or investigator and approves the study. See Table 1 below.

Investigational Device Exemption (IDE)

If either the investigator or the IRB has made a determination that the device is a significant risk device an IDE application is to be submitted to the FDA.

To obtain an IDE approval by the FDA, the sponsor or manufacturer of the device must properly fill out an IDE application. This application should be submitted proposing a human clinical researcher to study an unapproved significant risk device or a cleared or approved device for use other than its approved indication or intent.

The application should provide information about the investigational device, including its design, manufacturing process, and intended use. A clinical investigational protocol that outlines study objectives, methodology, patient population, and end points should also be included.  In addition, the sponsor must demonstrate in the application that there is reason to believe that the risks to human subjects from the proposed investigation are outweighed by the anticipated benefits to subjects, the importance of the knowledge to be gained, that the investigation is scientifically sound, and that there is reason to believe that the device as proposed for use will be effective.

An IDE application can be considered approved 30 days after it has been reviewed by the FDA, unless otherwise indicated. The FDA may inform the sponsor of approval, approval with conditions, or disapproval prior to 30 calendar days from the date of receipt.

Once FDA approval is granted, and the IRB has approved the study the sponsor and/or investigator may proceed with the clinical investigation. See Table 1 below.

The FDA grants permission so a device that otherwise would be required to comply with a performance standard or to have premarket approval can be shipped lawfully for the purpose of conducting investigations of that device. This FDA permission is evidenced by the assignment of an IDE number.

Additional Points to Consider About Research Studies with Medical Devices

• Studies of SR Devices require review of the convened IRB.
• NSR device studies generally will require full board review but may be approved through the expedited review procedure if the study falls within a designated approvable category and is minimal risk.
• IRB approval must be obtained before any clinical investigation can begin, and for studies with a SR Device, both FDA and IRB approval must be obtained before any subject can be enrolled.

Definitions-

 Clinical investigation means any experiment that involves a test article and one or more human subjects and that either is subject to requirements for prior submission to the Food and Drug Administration under section 505(i) or 520(g) of the act, or is not subject to requirements for prior submission to the Food and Drug Administration under these sections of the act, but the results of which are intended to be submitted later to, or held for inspection by, the Food and Drug Administration as part of an application for a research or marketing permit. The term does not include experiments that are subject to the provisions of part 58 of this chapter, regarding nonclinical laboratory studies.

Significant Risk (SR) Device: A device that presents a potential for serious risk to the health, safety, or welfare of a subject and 1) is intended as an implant, or 2) is used in supporting or sustaining human life, or 3) is of substantial importance in diagnosing, curing, mitigating or treating a disease, or otherwise prevents impairment of human health, or 4) otherwise presents a potential for serious risk to the health, safety, or welfare of a subject.          

     Table 1

Resources for investigators:
ReGARDD – Regulatory Guidance for Academic Research of Drugs and Devices

Device Advice: Comprehensive Regulatory Assistance | FDA

UConn Health IRB Forms and Polices Revisions

&

Educational Resources

The following forms have been updated:

• Instructions for Requesting Reliance Upon Advarra IRB.docx(2/13/2024, updated contacts at Advarra and consent template injury language section)
• Request for UConn Health as a Recruitment Site -Without Engagement(*new form as of 3/20/24)

The following policy has been updated:

• 2011-008.2.pdf– Informed Consent – Waivers and Alterations (1/22/2024) (including the FDA final rule that allows IRBs to approve an informed consent procedure that does not include or that alters certain informed consent elements, or to waive the requirement to obtain informed consent, for certain minimal risk clinical investigations).

The following links were added to the IRB website under online resources for investigators:

• Regulatory Guidance for Academic Research of Drug and Devices 
• Is my Device Study Exempt from Investigational Device Exemption (IDE) Regulations?

Upcoming Changes in at the HSPP/IRB

Education & Development Specialist of HSPP:  As of 4/5/2024, Mayra Cagganello has transferred to a new position within UConn Health.  Mayra has worked for the HSPP for almost 13 years and her dedication and support to the HSPP and research community will be missed!

Investigators who need education, guidance on IRB submission and/or training with the IRIS submission system should contact the IRB at irb@uchc.edu

We wish Mayra the best in her new role!

 Bibliography

 2011-007.0.pdf – Definitions Applied to Policies

2011-021.0.pdf – Investigational Device Studies

Frequently Asked Questions about Medical Devices

OCTOBER, NOVEMBER, DECEMBER, 2023 – HSPP NEWSLETTER

The HIPAA Privacy Rule & Human Subjects Research – Overview

The HIPAA Privacy Rule (the “Privacy Rule”) may impose additional requirements to the federal human subjects protection regulations applied to all human subjects research.

 The purpose of this overview is to clarify concepts and apply them to commonly seen human subjects research activities/studies. Specifically, the sections below highlight some of the main provisions of the Privacy Rule as they relate to human subjects research.

A series of questions and answers explain the scope of the Privacy Rule, the difference between an Authorization, a Waiver of HIPAA Authorization and an Alteration of HIPAA Authorization.  In addition, several sections explain how to address the Privacy Rule in recruitment activities, and when using specimens for research studies.  Examples of research activities and the appropriate HIPAA forms are included in some of those sections.

The Privacy Rule regulates the way certain organizations called covered entities under the Rule handle protected health information (PHI). Since UConn Health is a covered entity, investigators conducting research with UConn Health PHI need to address HIPAA.

Question: How do I know if I need to address the Privacy Rule in my research study?

Answer: The Privacy Rule affects research and researchers when either:

Research creates or generates PHI, or research requires access to and/or use of PHI.

If your study involves the use of PHI you must address the Privacy Rule within your application for approval. PHI means individually identifiable health information transmitted or maintained in any form (electronic means, on paper, or through oral communication) that relates to the past, present or future physical or mental health or condition of an individual. Health information is not considered PHI if it has been de-identified in accordance with the Privacy Rule (i.e., by expert analysis or by removing all identifiers specified in the Privacy Rule of the individual or of relatives, employers, or household members of the individual).

Examples of research studies for which the HIPAA regulations apply are:

• Studies using individually identifiable health information that is generated as part of a health care service.
• Studies gathering individually identifiable health information that is entered into a medical record.
• Studies gathering individually identifiable health information that is used to make treatment decisions.
• Retrospective or Prospective research studies involving the review of medical records.
• Research studies involving surveys, questionnaires or focus groups, which obtain PHI from patients receiving treatment.

 Question: When does the Privacy Rule not apply to research?

Answer: Research studies that do not use, disclose or create PHI are not subject to HIPAA regulations.

Examples of studies that are not subject to HIPAA:

• Studies that use tests that do not go into the medical record because they are part of a basic research study and the results will not be disclosed to the subject.
• Studies that review de-identified health information.
• Studies that obtain data from records open to the public.

• Interviews, focus groups, and surveys studies that collect information that is not considered health information (e.g., opinions, beliefs, wants/preferences, etc.)

 Question: What is the difference between HIPAA “Authorization” and Informed Consent?

Answer: An informed consent is the individual’s volunteer permission to participate in the research. The requirement to obtain the legally effective informed consent of individuals before involving them in research is one of the central protections provided for under the HHS regulations at 45 CFR part 46 ( AKA as the Common Rule).  The Common Rule’s focus is in protecting the safety of the individuals, their privacy, and confidentiality. To do so, the investigators need to include in the consent forms the applicable elements /information described in the Main Consent Form Checklist.doc .

The Privacy Rule, a different regulation, focuses on protecting the privacy and security of PHI. The Privacy Rule generally requires subjects to give written Authorization before a covered entity may use or disclose patients’ PHI for research. A signed HIPAA Authorization represents an individual’s agreement to the use and disclosure of the individual’s PHI for the specified research purpose.

An authorization must contain several required elements and statements, including but not limited to a description of the PHI to be used and disclosed, the person authorized to make the use or disclosure, the  researcher may make the disclosure, an expiration date, and, in some cases, the purpose for which the information may be used or disclosed.

The IRB may approve a HIPAA authorization process which does not include, or which alters some or all of the elements of a valid written authorization, or waives the requirement for written HIPAA authorization if the IRB finds and documents that the use of the subjects’ PHI meets the criteria for a waiver.

In granting an alteration or waiver of HIPAA authorization, the IRB must determine that the alteration or waiver, in whole or in part satisfies each of the following criteria:

• The use or disclosure of PHI involves no more than minimal risk to the privacy of individuals, based on, at least, the presence of the following elements:
• an adequate plan to protect the identifiers from improper use and disclosure;
• an adequate plan to destroy the identifiers at the earliest opportunity consistent with the conduct of the research, unless there is a health or research justification for retaining the identifiers or such retention is otherwise required by law; and
• adequate written assurances that the PHI will not be reused or disclosed to any other person or entity, except as required by law, for authorized oversight of the research study, or for other research for which the use or disclosure of PHI would be permitted (i.e., under the HIPAA regulations).
• The research could not practicably be conducted without the waiver or alteration; and
• The research could not practicably be conducted without access to or use of the PHI.

  Question: What is the difference between a partial and complete Waiver of HIPAA Authorization?

 Answer: A waiver of HIPAA authorization is a determination that is made by the IRB.  An IRB can waive in full or in part the individual authorization required by the Privacy Rule to use and disclose PHI for research purposes.

Example of research study for which the IRB may grant a complete waiver of the Authorization:

• A research study limited to a retrospective review of medical records (HIPAA Waiver for the entire study).

Example of research study for which the IRB may grant a partial waiver of the Authorization:

• A research study collecting information during telephone screening (HIPAA Waiver for a portion of the study).

To request a waiver of HIPAA authorization the investigator must complete pages 1 and 2 of the HIPAA Request for Alteration or Waiver of Authorization.doc form and submit this document to the IRB for review and approval prior to using and/or disclosing PHI.

Question: Is it possible to get a HIPAA waiver to screen patient charts without having each patient first sign an Authorization form?

Answer: Yes. The Privacy Rule allows for certain activities regarding screening, recruiting or determining eligibility (e.g. chart reviews for determining eligibility) to occur without obtaining a HIPAA authorization.

The investigator must submit a HIPAA Request for Alteration or  Waiver of Authorization.doc . The waiver must be granted by the IRB before charts are screened.

Question: What is a HIPAA Alteration of the Required Elements and/or Statements?

Answer: A HIPAA Alteration of the Required Elements and/or Statements is a regulatory determination that is made by the IRB.  An IRB can approve to omit (waive), or change (alter) in part the individual authorization required by the Privacy Rule to use and disclose PHI for research purposes.

When investigators are planning to obtain an individual’s authorization to access their information, and they need to either remove (waive), or change (alter) some of the core elements or statements of an authorization, they must complete and submit Appendix A.  Appendix A is in the fourth page of the HIPAA Request for Alteration or Waiver of Authorization.doc form   The IRB must approve this request prior to the use and/or disclosure of PHI.

Example of an alteration of the authorization:

• An authorization that requires to remove (waive) the element that describes each purpose of the requested use or disclosure because providing the purpose of the study would affect the results of the study.

Examples of studies withholding information about the study purpose and/or reason for procedures, in order to prevent biasing the results:

• Subjects are asked to take a quiz for research but they are not told that the research question involves how background noise affects their ability to concentrate.
•  To further understanding of how representations of same sex couples depicted in commercials influence consumer behavior, subjects are exposed to advertisements featuring gay couples and straight couples while their heart rate, facial muscle movement, and sweat responses are recorded. Subjects are informed that their reactions to the commercials are being studied, but not that the researchers are examining if the sexual orientation of characters in commercials influences them.

 To request to alter the HIPAA authorization, the investigator needs to submit a HIPAA Request for Alteration or Waiver of Authorization.doc  and Appendix A.

 Example of research study that requires waiving documentation/signature of the authorization:

• Research on sensitive topics, such as domestic violence or illegal activities where the only link of a subject to the study is their signature on the authorization, and there is a risk of breach of confidentiality.

 To request a waiver of the participant’s signature on the HIPAA authorization, the investigator needs to submit a HIPAA Request for Alteration or Waiver of Authorization.doc  and Appendix A.

Because the federal definition of human subjects research extends to people who are sources of biological specimens and identifiable private information, research with these materials often requires review and approval by the IRB. The level of IRB review  is based on the level of risk the study poses.

The risks of research with specimens potentially include one or both of the following:

• The risk of harm from procedures used to obtain specimens, and/or
• The risk associated with the loss of privacy and confidentiality due to personally identifiable information that may be associated with specimens.

Common questions involving research using human specimens are summarized below.

Question:  What type of IRB review is required for a research project using existing specimens? What HIPAA form do I need to submit?

  Answer: It depends on whether the existing specimens are identifiable. Existing specimens means the  specimens were collected for clinical purposes or for research studies other than the proposed research study.

If the existing specimens are not identifiable, and if the investigator will make no effort to re-identify the specimens, the specimens do not meet the definition of a human subject and IRB review would not be required.

On the other hand, if the specimens are identifiable, or efforts will be made to re-identify the samples, IRB review is required.

Research that only involves the use of existing identifiable specimens may qualify for exemption if one of the following is true:

• the specimens are publicly available
• Information is recorded in such a manner that the identity of the human subject cannot readily be ascertained directly or through identifiers linked to the subjects, the investigator does not contact the subjects, and the investigator will not re-identify subjects. In this case, the research may qualify for exempt status under Category 4.ii.

To address HIPAA submit a HIPAA Certification of De-Identification.doc

On the other hand, research involving previously collected specimens that have identifiers associated most likely qualifies for expedited review under category 5.  Use of specimen-associated identifiers must be restricted and privacy protection measures must be in place.

To address HIPAA submit HIPAA Request for Alteration or  Waiver of Authorization.doc

Question:  What type of IRB review is required for a research project using specimens that will be collected for research purposes by noninvasive means? What HIPAA form do I need to submit?

Answer: Research that involves the collection of specimens for research purposes by noninvasive means may qualify for Expedited review- under Category 3.

Examples of these noninvasive collections of specimens are:

1. Hair and nail clippings in a non-disfiguring manner
2. Deciduous teeth at time of exfoliation or if routine patient care indicates a need for extraction
3. Permanent teeth if routine patient care indicates a need for extraction
4. Excreta and external secretions (including sweat)
5. Un cannulated saliva collected either in an unstimulated fashion or stimulated by chewing gum base or wax or by applying a dilute citric solution to the tongue
6. Placenta removed at delivery
7. Amniotic fluid obtained at the time of rupture of the membrane prior to or during labor
8. 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
9. Mucosal and skin cells collected by buccal scraping or swab, skin swab, or mouth washings
10. Sputum collected after saline mist nebulization.

You will need to submit a HIPAA Authorization to Use and Disclose PHI for Research Purposes.doc

Question:  What type of IRB review is required for a research project using specimens collected for research purposes by invasive means? What HIPAA form do I need to submit?

Research that involves the collection of specimens for research purposes by invasive means/using procedures that pose greater than minimal risk to participants must undergo full committee review by the IRB.

Examples of these invasive collections of specimens are:

• Collection of specimens through  a skin Biopsy
• Collection of specimen through a bronchoscopy, amniocentesis or colonoscopy.

You will need to submit a HIPAA Authorization to Use and Disclose PHI for Research Purposes.doc

Question: My research study involves collecting sputum and lung aspirates from clinical procedures involving chronic smokers that are otherwise going to be thrown away.  The specimens will be provided by the pathology department without identifiers. The pathologist will not be involved in the research.  Do I have to get IRB review?  If so, what HIPAA form do I need to submit?

 Answer: You do not need to submit an application for IRB review nor you need to submit a HIPAA form. Your research is considered secondary research that is not human subjects research because: (a) the specimens were originally collected for clinical care and not specifically for the purpose of the investigator’s current research, (b) the specimens do not come with individually identifiable information, and (c) there is no interaction or intervention done specifically for the research.

The IRB may approve a research proposal in which an investigator will obtain information for the purpose of screening, recruitment or determining the eligibility of prospective subjects without the prospective subject’s HIPAA authorization, however the following conditions must be met:

• The investigator will obtain information related to screening, recruiting or determining eligibility through oral or written communication with the prospective subject.
• The investigator will obtain identifiable information or identifiable biospecimens for screening, recruiting or determining eligibility by accessing records or stored identifiable biospecimens.
• In order to access records or specimens for such purposes, there must be an established relationship between the investigator and the individuals whose records /specimens will be reviewed.  The investigator may delegate the review to designated UConn Health research staff.

Question: At what point in recruitment may we gather information about a potential participant (e.g., if a potential participant calls our office after seeing a flyer, may we screen that person/ ask them about their history, or do we need the person to complete a written HIPAA Authorization prior to screening)?

Answer: If the IRB has approved your recruitment plan, including a partial waiver of Authorization to permit you to collect PHI for screening without written Authorization, you may take the person’s contact and screening information.  Investigators must also submit to the IRB a phone script using the Sample Phone Script for Screening Prior to Consent.doc . The IRB must approve the script prior to collecting information from potential participants over the phone.

The potential participant should know that in order to evaluate whether he or she is a candidate for the research, the researcher will need to share the caller’s information, and the caller may need to share information, with a limited number of others who staff the study.  If the person is deemed qualified for the study, then he/she will be asked to come in to sign an informed consent and a HIPAA Authorization. To protect the privacy of the potential participant all the information they provide will be kept only if he/she qualifies to proceed and decides to participate in the study.

  Question: HIPAA specifies18 identifiers that must be removed to “de-identify” health information.  Is any one of these identifiers, all by itself, PHI?

 Answer: Not necessarily. PHI is information, including demographic information, which relates to (i) the individual’s past, present, or future physical or mental health or condition; (ii) the provision of health care to the individual; or (iii) the past, present, or future payment for the provision of health care to the individual, and that identifies the individual or for which there is a reasonable basis to believe can be used to identify the individual.  If the only identifier you have is a DOB and that DOB is not linked to any other health information and could not be sourced to a provider (e.g., UConn Health), the DOB alone would not be PHI.  However, if the DOB is coupled with other information, such as “a patient at UConn Health,” or “was one of 15 enrollees in a particular study,” this combination would be PHI.

 Question: What coded information or coded specimens means?

The Office of Human Research Protections (OHRP) has defined coded as:

•  identifying information (such as name or social security number) that would enable the investigator to readily ascertain the identity of the individual to whom the private information or specimens pertain has been replaced with a number, letter, symbol, or combination thereof (i.e., the code);

and

• a key to decipher the code exists, enabling linkage of the identifying information to the private information or specimens.

 OHRP considers the term investigator to include anyone involved in conducting the research. OHRP does not consider the act of solely providing coded private information or specimens (for example, by a tissue repository) to constitute involvement in the conduct of the research. Note that if the individuals who provide coded information or specimens collaborate on other activities related to the conduct of this research with the investigators who receive such information or specimens, then OHRP would consider such additional activities to constitute involvement in the conduct of the research.

Examples of such additional activities include, but are not limited to:

(1) The study, interpretation, or analysis of the data resulting from the coded information or specimens; and

(2) Authorship of presentations or manuscripts related to the research.

Question: Is coded information identifiable?

 Answer: The Privacy Rule considers coded information to be de-identified if the 18 specific identifiers of the individual or of relatives, employers, or household members of the individual, listed below are coded and the person cannot reasonably be identified.

However, that code needs to be assigned by someone other than the investigator.  The code cannot be derived from any identifiable piece of information or combination of pieces of identifiable information.  The key to the code cannot be accessible to the investigator or research personnel using the de-identified data.

• Names;
• Address (including street address, city, county, zip code). The initial three digits of a zip code may be used if, according to the current publicly available data from the Bureau of Census: 1) the area formed by combining all zip codes with the same three initial digits contains more than 20,000 people; and 2) the initial three digits of a zip code for a region containing 20,000 or fewer people is changed to 000;
• All elements of dates (except year) for dates directly related to an individual (birth
• date, admission date, discharge date, date of death), and all ages over 89 and all elements of dates (including year) indicative of such age, except that ages and  elements may be aggregated into a single category of age 90 or older;
• Telephone numbers;
• Fax numbers;
• Electronic mail addresses;
• Social Security numbers;
• Medical record numbers;
• Health plan beneficiary numbers;
• Account numbers (bank, retirement, credit card, etc.);
• Certificate/license numbers;
• Vehicle identifiers and serial numbers, including license plate numbers;
• Device identifiers and serial numbers;
• Web Universal Resource Locators (URLs);
• Internet Protocol (IP) address numbers;
• Biometric identifiers, including finger and voice prints;
• Full face photographic images and comparable images; and
• Any other unique identifying number, characteristic or code.

REFERENCES

 HIPAA Privacy Rule and Its Impacts on Research (nih.gov)

• Coded Private Information or Specimens Use in Research, Guidance (2008)

• 2011-014.0.pdf– Health Insurance Portability and Accountability Act (HIPAA) in Research 

• Use and Disclosure of Protected Health Information.pdf

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.

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.

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

FDA Warning Letter Regarding the Failure to Submit INDs for the Conduct of Clinical Investigations 

with an Investigational Product that met the Definition of a Combined Product.

Inspections of clinical trials are conducted as a part of the U.S. Food and Drug Administration (FDA)’s Bioresearch Monitoring Program.  These inspections are designed to evaluate the conduct of research and to help ensure that the rights,   safety, and welfare of human subjects have been protected.  Below you will find a short summary of a warning letter issued because of the failure to submit an investigational new drug application.

Warning Letter to Dr. David M. Lubeck/Arbor Centers for EyeCare

 On November 18, 2022, the FDA issued a warning letter to Dr. David M. Lubeck/Arbor Centers for EyeCare.  The FDA officials inspected Dr. Lubeck study and concluded that the investigator did not adhere to the FDA regulations governing the conduct of clinical investigations and the protection of human subjects. Specifically, the investigator failed to submit an Investigational New Drug application (IND) for the conduct of a clinical investigation with investigational new drugs that is subject to 21 CFR 312.2(a) [21 CFR 312.20(a), 312.20(b), and 312.40(a)].

The FDA argued that the investigational product used in combination with another drug comprised  both a drug and a device components and was therefore a combination product within the meaning of section 503(g) of the FD&C Act (21 U.S.C. 353(g)).

Furthermore, the FDA underlined that because the primary mode of action of the investigational combination product was attributable to the product and because the product met the definition of a drug under section 201(g) of the FD&C Act, an IND was required for any clinical investigation of the investigational combination product used in such Protocol.

Among other important issues noted in this investigation was that the investigator did not wait the 30 days to enroll subjects in the study.  An IND does not go into effect upon FDA’s receipt of the IND submission. Rather an IND generally goes into effect 30 days after FDA receives the application, or on earlier notification by FDA that the clinical investigation in the IND may begin (21 CFR 312.40(b)). The FDA emphasized that FDA regulations require a sponsor to submit, and to have in effect, an IND before initiating a clinical investigation that must be conducted under an IND in accordance with 21 CFR 312.40.

For more details about the inspection of this study and the findings of the FDA please review the Warning Letter to Dr. Davd M. Lubeck.

Developing a Mobile Health App?

Updated FTC-HHS online tool helps developers understand which federal laws apply

The Federal Trade Commission (FTC) in conjunction with the Department of Health & Human Services (HHS) Office for Civil Rights (OCR), the HHS Office of the National Coordinator for Health Information Technology (ONC), and the Food and Drug Administration (FDA) have updated the Mobile Health App Interactive Tool. This tool is designed to help developers of health-related mobile apps understand what federal laws and regulations might apply to them.   The guidance tool asks developers a series of high-level questions about the nature of their app, including about its function, the data it collects, and the services it provides to users. Based on the developer’s answers to those questions, the guidance tool will point the app developer toward detailed information about certain federal laws that might apply to the app. These include the FTC Act, the FTC’s Health Breach Notification Rule, the Children’s Online Privacy Protection Act (COPPA), the Health Insurance Portability and Accountability Act (HIPAA), the Federal Food, Drug and Cosmetics Act (FD&C Act), and the 21st Century Cures Act and ONC Information Blocking Regulations.

Developers and others seeking more information about how the HIPAA Rules might apply to their health apps should visit OCR’s HIPAA and Health Apps page, which contains information on how HIPAA applies to a range of example health app scenarios and offers key questions to consider in determining when HIPAA’s regulations cover a particular health app.

IRB Forms – Update

The following forms were updated in the IRB website:

1. Sample Cover Letter for a Survey Study.docx (09/02/2022)
2. Application Checklist for Initial and Continuing Review Full Board.docx (09/02/2022 – New Contact Information for Institutional Biosafety Committee )
3. Application Checklist – Single Patient Expanded Access .docx(9/22/2022)
4. Request for Exemption Form .doc(09/30/2022)
5. Guidance for Completing Continuation Form.docx (10/12/2022)
6. Guidance for Preparing a Chart Review Study .docx(10/12/2022)
7. HIPAA Authorization to Use and Disclose – Spanish.doc (11/7/2022)

The following forms were added to the IRB website:

• Instructions for Facilitated Review for Collaborative Research with Neighboring Facility .docx(10/12/2022)

• Request for UConn Health as a Recruitment Site -Without Engagement(12/14/2022)

The following educational resources were added to the IRB website:

• NIH Policy for Data Management and Sharing (effective 1/25/2023)
• NIH Guide for Writing a Data Management & Sharing Plan
• Data Storage Finder (tool from Cornell University)

National Institute of Health (NIH) Policy for Data Management and Sharing

Investigators Resources

The National Institute of Health (NIH) has posted a one-page handout “The Who, What, Where and When of the NIH Data Management and Sharing (DMS) Policy” summarizing the most important information for investigators regarding the NIH Policy for Data Management and Sharing.  Click on the image to go to their website and explore the info/links in the handout.

The University of Pennsylvania has shared the following resources on its website to aid investigators to comply with the National Institute of Health (NIH) Policy for Data Management and Sharing

• DMS Plan Format Page

NIH’s checklist that walks researchers through the elements of a DMSP

• NIH FAQs on the DMSP

NIH is constantly updating its FAQ page on the DMSP. Check back for your questions.

• NIH Webinars

Includes NIH webinar recordings and registration information for upcoming presentations.

• NIH Guidance for Informed Consent

Provides points to consider and sample language for informed consent documents of research studies which plan to store and share data and/ or biospecimens for future use.

• DMPTool Guide

Penn Libraries uses DMPTool to assist with writing data management plans. DMPTool is a resource researchers can use to draft data management plans. The new NIH DMSP template is available in the tool. We can provide comments on your DMSP if you need assistance. See our contact information on this page.

• NIMH Sample DMSPs

The National Institute of Mental Health (NIMH) has developed four example DMSPs that are consistent with NIMH and NIH requirements.

• NIH Institute and Center Data Sharing Policies

NIH institutes and centers may have other data sharing requirements in addition to the NIH DMS Policy. Make sure to read your applicable policy carefully.

• NIH DMS Policy: Applicable Activity Code

A comprehensive listing of all NIH activity codes that generally require applicants to submit a Data Management & Sharing Plan

• ICPSR’s Guide to Sharing NIH Data

Provides an overview of ICPSR’s NIH funded archives and recommendations for designating ICPSR for your data to meet the requirements of the NIH DMSP.

• Working Group on NIH DMSP Guidance

Created by librarians and other research support professionals, this working group has created a variety of resources that researchers can use to prepare for the NIH DMS Policy implementation. Resources include glossaries, a DMSP checklist for researchers, and an example DMSP for the 2023 expectations.

• Ten simple rules for maximizing the recommendations of the NIH data management and sharing plan

Recent article on the NIH DMSP policy that covers 10 key recommendations for creating a DMSP that is both maximally compliant and effective.

• Data Management Resources

Research Data & Digital Scholarship Data Sharing Services

NIH Repositories

Cornell University has excellent resources and tools on its website to aid investigators to comply with the National Institute of Health (NIH) Policy for Data Management and Sharing.

In addition, the NIH National Library of Medicine has posted the following resources:

• NIH CDE Repository
• NIH Data Sharing Repositories
• NIH Data Sharing Policies

Office of Human Research Protection (OHRP) Luminaries Lectures Series

Educational Resources for Investigators

The Office of Human Research Protection  Luminaries Lectures Series features videos by esteemed individuals with thought-provoking insights on diverse aspects of human research protections.

Some of the recently added videos are listed below.  These videos are covering the challenges of research during public health emergencies and research studying usual care practices, as well as thoughts from representatives in the research community on how to promote diversity and engagement in research participation:

• “The Covid Drug Wars” – What We Learned from the Front Lines
• “Unusual Practices Masquerading as Usual Care”
• “Vulnerability, Justice, Equity, and Engagement: A Conversation About Public Health and Human Subjects Research”

Click here and start watching!

Changes in the HSPP/IRB

Administrative Manager and Deputy Director of HSPP: Julia Blair has been named Administrative Manager of the HSPP, after filling the role on an interim basis since June following Deb Gibb’s retirement.  She can be reached at jblair@uchc.edu and (860) 679-7555.

HSPP- July, August, September, 2022 – Newsletter

Revision to Exemption Category 4 (iii)

To ensure the protection of identifiable private information (IPI) at UConn Health in compliance with The Privacy Rule, the HSPP will limit use of the exemption 45 CFR 46.104(d)(4)(iii):
Secondary research uses of identifiable private information, [when] the research involves only information collection and analysis involving the investigator’s use of identifiable health information (not biospecimens) when that use is regulated under [HIPAA].
Exemption 4(iii) applies to secondary research ‘use’ of the IPI which is protected under HIPAA, however the release, transfer or provision of access to a non-covered entity / third party would constitute a ‘disclosure’ where the IPI is no longer protected and the exemption would not apply.
Effective October 1, 2022, to ensure compliance with HIPAA and the Common Rule (45 CFR 46), the UConn Health HSPP will restrict the use of exempt category 4(iii) to studies where the Principal Investigator is UConn Health faculty (whose home/primary institution is UConn Health) and the data is not shared outside UConn Health or with non-UConn Health personnel.
New applications to the IRB seeking approval for secondary research use of identifiable private information which do not qualify for exemption under category 4 should request expedited review by the IRB. More information on exempt and expedited submissions can be found on the HSPP website or by contacting the HSPP Education Specialist, Mayra Cagganello at x8802 or cagganello@uchc.edu.

National Institute of Health (NIH) Policy for Data Management and Sharing

The National Institute of Health (NIH) Data Management and Sharing policy was published on October 29, 2020, and will go into effect on January 25, 2023. The two year delay in implementation was planned to give time to institutions to learn and prepare for enactment of the policy.

This policy applies to all research funded (in whole, or in part) or conducted by NIH that results in generation of scientific data. The goal of this NIH Data Management and Sharing policy is to benefit everyone, namely investigators, funding agencies, the scientific community, and, most importantly, the public. Data sharing provides more effective use of NIH resources by avoiding unnecessary duplication of data collection. It also conserves research funds to support more investigators. As stated in this policy “data sharing enables researchers to rigorously test the validity of research findings, strengthen analyses through combined datasets, re-use hard-to-generate data, and explore new frontiers of discovery.”

The NIH DMS Policy requires researchers to submit a plan to preserve, to share the data and to show compliance with said plan.

The NIH has made available multiple educational materials to inform and educate researchers about this policy at sharing.nih.gov. Below please find the links to the webinars

Webinar I: Understanding the New NIH Data Management and Sharing Policy –
o Resource Slide Deck
o Webinar Recording

Webinar II: Diving Deeper into the New NIH Data Management and Sharing Policy
o Resource Slide Deck

To access the frequently asked questions regarding this policy please click on 2023 Data Management & Sharing Policy

Uconn Health – Research Participant Feedback Form
Now available in Redcap

The Human Subjects Protection Program (HSPP) is responsible for ensuring that studies are conducted in compliance with internal policies, federal regulations and ethical standards. When research participants complete and submit a Research Participant Feedback Form, the HSPP is able to learn about the study volunteer experiences.

Participants can access the Research Participant Feedback form in two ways:
1) Download the form from the IRB website at http://research.uchc.edu/rcs/hspp/volunteers/. Forms must be completed and emailed or faxed following the instructions on the form.
2) *NEW* Research participants may submit this form electronically by accessing the REDCap form at https://redcap.link/UConnHealth-Feedback-Research from a computer or mobile device.

The IRB and HSPP encourage the research community to help research volunteers to complete this form.

IRB Forms – Update

The following updates have been made to IRB forms:

Added new contact information to the following forms:
• Application Checklist for Initial and Continuing Review Full Board.docx (09/02/2022 – New Contact Information for Institutional Biosafety Committee)
• IRB Website : Related Departments and Committees-
Institutional Biosafety Committee (IBC): Investigators must obtain approval from the IBC prior to seeking local IRB approval for research studies that deal with recombinant DNA. Investigators may contact Vijayasmitha Rayadurg in the Office of Research Safety for additional information.

Added new template language to the following form:
• Sample Cover Letter for a Survey Study.docx (09/02/2022)

Changes to the Requests for Exemption form to limit Exempt Category 4 (iii) to researchers and activities internal to UConn Health.

• Request for Exemption Form .doc (09/30/2022)

Continuing Review Guidance

Considerations for When the IRB Evaluates the Progress of a Research Study

According to Robert J. Amdur & Elizabeth A. Bankert. IRB Management and Function. 2nd Edition., Jones & Bartlett, 2006, “Continuing review is a monitoring mechanism that assures that continuing safeguards are in place to protect the rights and welfares of research participants.”

When a Protocol/study is submitted for renewal or continuing review the investigator is to report the study progress and findings. When conducting the continuing review, OHRP recommends that IRBs evaluate the following issues to determine whether the study’s approval should be renewed:

Consistent with the IRB-approved Protocol
The IRB should confirm that the information provided by the investigator at the time of continuing review is consistent with the research protocol previously approved by the IRB.

Total Subject Enrollment
Evaluating information about the number of subjects enrolled in the research at the time of continuing review may allow the IRB to ascertain whether enrollment is consistent with the planned number of subjects described in the IRB-approved protocol. Has accrual progressed as planned? If not, will this affect the ability of the researchers to complete the study?

A marked difference between the actual and expected rates of enrollment may indicate a problem with the research project that requires further evaluation, including whether the research project is likely to provide sufficient data to answer the scientific question(s) being posed.

Subject Withdrawals
Subjects may discontinue their participation in research at any point for various reasons (e.g., serious adverse events, conflicts with the investigators, transportation problems, etc.).
The IRB’s continuing review procedures in general should provide for review of:
• The number of subjects who discontinued their participation; and
• A summary of the reasons for the withdrawals, if known.
IRB review of this information may shed light on problems related to the conduct of the research.

To provide an accurate account of the enrollment data, UCONN Health IRB recommends that prior to completing a Continuation form in the iRIS submission system, the Principal Investigator should have the enrollment information for the study available. If this is not the first request for continuation (e.g. study has been open form more than one year), the enrollment data should build off of the previously submitted request for continuation. Investigators should use the enrollment data in the previously approved continuation form as a starting point. The Enrollment Guidance.docx should be reviewed to provide an accurate account of enrollment numbers, screen failures or withdrawals.

Office of Human Research Protection (OHRP) – Resources
Luminaries Lecture Series

OHRP continues to add new videos to help the research community learn about multiple topics.
Click here to view the latest videos of distinguished speakers from OHRP’s Research Community Forum co-sponsored with Northwell Health this past May.
New additions include:
• The COVID Drug Wars That Pitted Doctor vs. Doctor
• Improving Health Equity in Clinical Research
• Vulnerability, Justice, Equity, and Engagement, A Conversation Public Health and Human Subjects Research
• Unusual Practices Masquerading as Usual Care

HSPP Newsletter – April, May, June, 2022

FDA Warning Letter Regarding the Failure to Ensure IRB Continuing Review and Approval of Protocol

Inspections of clinical trials are conducted as a part of the U.S. Food and Drug Administration (FDA)’s Bioresearch Monitoring Program.  These inspections are designed to evaluate the conduct of research and to help ensure that the rights, safety, and welfare of human subjects have been protected.  Below you will find a short summary of a warning letter issued because of the failure to obtain continuing review of a study and failure to perform study procedures as required by the protocol.

Warning letter to Sabine S. Hazan, M.D.

On February 28, 2022, the FDA issued a warning letter to Dr. Hazan.  The FDA officials who inspected the study concluded that the investigator did not adhere to the FDA regulations governing the conduct of clinical investigations and the protection of human subjects.  Dr. Hazan failed to obtain continuing review and approval for her study.  Specifically, her study IRB approval lapsed. During the course of this lapsed period, she enrolled and randomized subjects into the protocol, and administered investigational drugs to subjects. In addition, she was unable to provide a corrective action plan to prevent the recurrence of this type of violation in the future.

The FDA emphasized that the failure to ensure continuing IRB review and approval, impeded the IRB’s ability to determine the adequacy of the application to conduct the protocol.  This raised significant concerns about the extent to which subjects’ rights and welfare were protected at that site during the lapse in approval.

For more details about the inspection of this study and the findings of the FDA please review the Warning Letter – Sabine S. Hazan, M.D. February 28, 2022

 Warning letter to Smitha C. Reddy, M.D. / ACRC Studies, LLC

On May 27, 2022, the FDA issued a warning letter to Dr. Reddy.  The FDA officials who inspected the study concluded that the study as it was implemented raised significant concerns about the safety of subjects enrolled and the reliability of data at that site.

Dr. Reddy failed to ensure that the investigation was conducted according to the investigational plan. Specifically, the investigator did not ensure subjects randomized to an assigned treatment arm received the correct drug for that group, and there was a failure to adhere to procedures for the blinding of staff.

The FDA emphasized that the principal investigator is ultimately responsible to ensure that the study is conducted properly and in compliance with FDA regulations, both to protect the rights, safety, and welfare of study subjects and to ensure the integrity of study data.  Additionally, the FDA required corrective actions to include retraining of the investigator on study drug administration, not just study staff.

For more details about the inspection of this study and the findings of the FDA please review the FDA Warning letter to Smitha C. Reddy, M.D./ACRC Studies, LLC

Office of Human Research Protection (OHRP) – Resources

The Office of Human Research Protection (OHRP) has launched two interactive programs to help explain the expectations for investigators in applying the Common Rule review criteria of equitable selection of subjects in research and minimizing research risks for participants. These resources are valuable for investigators to understand and fulfill these specific requirements for protecting human participants in research.

To access these interactive programs click on links below.

Equitable Selection of Subjects : This is a 30-minute scenario which examines how investigators could apply the concept of equitable selection of subjects in research

Minimizing Risks in Research : This is a 30-minutes scenario which examines the concept of research risks and how these risks to participants could be identified and minimized.

Human Subjects Training – Frequently Asked Questions

 I am a new resident/student at UCONN Health and I completed CITI Training under my affiliation with a former institution.  Is that CITI Certificate valid at UConn Health?

If an individual is to be included in an IRB application and that person has recently become affiliated to UConn Health (e.g. a new student), that person should attach the CITI Training certificate completed under his/her former affiliation.  If the courses previously completed are comparable to the ones required by UCONN Health IRB that individual will not need to complete additional training.  If not, he/she must complete training under his/her affiliation to UConn Health.  The CITI Program will give credit for any modules he/she have completed under other institution’s affiliation and will require completion of modules that are specific to UConn Health.

To affiliate an account in the CITI Program with UConn Health, individuals should log into the CITI program, and click on “Add Affiliation” listed under the “Courses” Menu.  To

find UConn Health in the drop down box, the following words “University of Connecticut“ must be typed.  Then, select “University of Connecticut Heath Center”.  To complete the process, check the box next to the statement: “I AGREE to the Terms of Service for accessing CITI Program materials”   and check the box with the statement: “I affirm that I am an affiliate of University of Connecticut Heath Center.” Last, click on “Continue.”

To select the correct learning group and courses, follow the “Course Enrollment Questions” posted at  https://ovpr.uchc.edu/services/rics/hspp/citi-instructions/

Recent Articles Published by a Central IRB

ADVARRA IRB:  

 What do I do about Incidental Findings in Research? If you are conducting research that has a potential to uncover an incidental finding, it is best to plan ahead for how you’ll treat the result and if you plan to return that result to a participant. This article describes the plans and consideration to communicate incidental findings to research participants.

eClinical Regulatory Trends Impacting Clinical Research   For the past two years, the clinical research industry has seen an acceleration in staff shifting to a remote, work from home model. While this was initially in an effort to keep everyone safer from the COVID-19 pandemic, many organizations are permanently moving toward a remote or hybrid work model for their staff.  This article discusses how has this shaped current regulatory trends, the benefits of eClinical suite, and the consideration when adopting an eClinical suite.

IRB Forms – Update

Added new contact information to the following forms:

• Human Subject Research Determination Form.doc
• dbGaP Access Request Form for IRB Certification.docx
• Participant Feedback Form.doc
• Participant Feedback Form in Spanish.docx
• HIPPA Assurance of Preparatory to Research or Decedent Research .doc
• Instructions for Students Residents or Fellows Doing Research_at_Hartford HealthCare_or_CT Children’s Medical Center.docx

Added Federal required Overview section to:

• Sample Consent for Registry (05/10/2022).doc

Upcoming changes in at the HSPP/IRB and the OVPR

• Vice President for Research: Dr. Pamir Alpay has been appointed Interim Vice President for Research, Innovation & Entrepreneurship while Dr. Radenka Maric is serving as Interim President of the University of Connecticut.
• Associate VPR and Institution Official: Dr. Victor Hesselbrock has been named Interim Associate Vice President for Research Integrity and Regulatory Affairs and Institution Official following Dr. Byerly’s departure.
• Manager and Deputy Director of HSPP: Deb Gibb retired June 1, after 19 years with the HSPP.  Julia Blair will serve as interim manager of the HSPP.

HSPP – January, February, March, 2022- Newsletter

How to Write a Low Literacy Informed Consent Form

Obtaining informed consent in non-exempt research is a process required by federal regulations –the U.S Department of Health and Human Services ( HHS) at 45 CFR 46 and the U.S. Food and Drug Administration (FDA) at 21 CFR 50.   The consent process typically includes providing a written consent document containing the required information along with an oral presentation of that information to prospective participants. However, for a consent process to empower individuals to voluntarily participate in a study or not, the information in the consent document must be presented in a language they can understand.   The readability of a consent form is essential to enable potential participants to have sufficient comprehension of the elements that facilitate a decision. The language used in consent forms should not be complex.   An 8^th grade reading level is the suggested benchmark to use as the readability index.

Investigators conducting clinical trials should consider literacy of potential participants when preparing consent documents.

John Hopkins Office of Human Subjects Research  and Elizabeth Winslow offers the following guidance for preparing consent forms:

• Recommendations to lower the reading level of consent forms:

 Words

• Use words familiar to the non-medical reader.
• If possible, keep words to 2- 3 syllables or fewer.
• Use common, familiar words

Sentences/Paragraphs/Print Size & Type:

• Write short, simple, and direct sentences.
• Keep paragraphs short and limited to one idea.
• Use active verbs.
• Use the second person (you) not third person (the participant) to increase personal identification.
• Avoid contractions.
• Use page numbers
• Use at least 12-point font and consider a larger font based on your audience.
• Check the text to see if each idea is clear and logically sequential.
• Avoid large blocks of printed text.

 Avoid Complex Medical Terminology

• Avoid medical Terminology. If a medical term must be used, define /explain it
• Be consistent with use of all terminology, such as drug names and abbreviations.
• Use the appropriate abbreviation the first time a drug name is used in the consent.

 Abbreviations:

• Spell out abbreviated terms the first time you use them
• Abbreviation terms such as DNA, HIV and AIDS that have come to be accepted as standard by your proposed study population need not be spelled out.
• Do not use e.g. or etc., use instead, “for example,” “so forth.”
• Spell out acronyms when first used.

 Pictures

• Use photos, graphics, tables, illustrations or diagrams if they will help clarify procedures.

Numbers

• Use numerals rather than words for numbers, e.g., “10” instead of “ten,” “1 out of 4” instead of “one out of four.”

Tips to Describe Study Procedures

• Consent forms for projects that involve collection of blood or other fluids should include the amount(s) to be taken.  Do not use ml. or cc. as a volume measure; give a volume equivalent in teaspoons or tablespoons. Rather than abbreviating such words as teaspoon and tablespoon, please spell them out.
• Do not use symbols such as “>”; use “greater than.”
• Describe study design procedures such as “double blind,” “randomized,” and “placebo/controlled” when the concept(s) is/are first introduced. Example: “A placebo is an inactive substance that looks like the study drug, but contains no medication.”
• Do not use the words “treatment” or “therapy” to describe an investigational drug, device or procedure. Use the term “study drug” not “study medication” when the drug is investigational.  The word “medication” or “medicine” should only be used if the drug is commercially available for that particular condition.
• Do not use the term “treatment” or “therapy”” if one of the study arms will be a placebo. Instead, use words like: “study product”, “study drug or placebo”,  “study regimen” or “study procedure
• Do not describe investigational drugs, devices or procedures as “new.”For investigational drugs or devices, state they are investigational or “experimental” and describe that term (e.g., the word “investigational” means the study drug is not approved by the U. S. Food and Drug Administration (FDA) and is still being tested in research studies.) Be consistent in using “investigational” throughout the consent form.
• Use “research study,” instead of “trial.”
• Use the word “participant” in the consent form instead of “patient” since this is research.  However, you may use “patient” when referring to the person prior to his/her entering the study.
• When describing randomization for 2 groups use, “like the flip of a coin,” for more than 2 groups, use “like drawing numbers from a hat.”

To check the grade level of a consent document, the investigator can implement the following steps. 

For Microsoft Word:

1. on the “File” tab, click the “Options” button;
2. on the “Proofing” tab, under “When correcting spelling and grammar in Word”, make sure “Check grammar with spelling” is selected;
3. under “When correcting spelling and grammar in Word”, select the “Show readability statistics” check box.  Click on OK
4. Click on the “Review Tab”
5. Click on “Spelling & Grammar”

After the grammar check is complete, Word displays a message box showing you the readability grade-level.

D- The following websites and word substitution file are helpful for drafting consent forms:

1. a)  Glossary of medical words: (http://kidshealth.org/kid/word/)
   b)  Clinical Research Glossary: (http://www.firstclinical.com/icfglossary/)
   c)  Glossary of lay terms: (http://humansubjects.stanford.edu/general/glossary.html)

• The following Checklist for Low Literacy Informed Consent Forms .pdf has been posted in the UCONN Health IRB website

ResearchMatch, an Online Recruitment Tool

ResearchMatch.org is a national online recruitment tool for health research, funded by the National Institutes of Health and maintained at Vanderbilt University. ResearchMatch connects health researchers with individuals interested in volunteering through its secure online matching tool, available in English and Spanish. UConn Health is part of the ResearchMatch Network and there is no cost to UConn Health researchers to use ResearchMatch. There are currently over 160,000 (and counting!) registered volunteers across the country.

To see if ResearchMatch might be useful to you, register now to conduct a feasibility analysis:

Register here: https://www.researchmatch.org/researchers/. (You do not need to be a Principal Investigator to register.) The registration process takes less than 10 minutes. Registration grants you “feasibility access” to search the current ResearchMatch volunteer population for demographic and health information of volunteers within a designated geographic area.

 Then, if you decide to use ResearchMatch to conduct participant recruitment, you will need IRB approval. Once approved, you may request “recruitment access” in ResearchMatch and upload your IRB approval letter and your IRB-approved contact message. Recruitment access will give you the ability to send your contact message to volunteers that you select. If a volunteer agrees, you will be given access to his/her contact information in order to contact about possible study participation.

 The next ResearchMatch Training is April 14, 2022 at 3:00 pm.

For questions about how to use ResearchMatch for your health research, please contact ResearchMatch Liaison, Ellen Ciesielski eciesielski@uchc.edu or visit https://ovpr.uchc.edu/services/rics/hspp/resources/researchmatch/.

Office of Human Research Protection (OHRP) – Resources

• OHRP New Informational Resource Flyer with its Very Own QR Code!

OHRP’s new Informational Resource Flyer includes a QR code allowing anyone with a smart phone access to a free online library of trusted resources about research and research participation. Print, display, and distribute this flyer at your centers for the benefit of prospective research participants!

Find the flyer here together with other informational materials (in English and Spanish) that you may wish to print and provide for potential research participants! These resources are free and you do not need permission to distribute them.

• New Interactive Training Programs on IRB Reviews!

OHRP launched two interactive training programs on considerations for reviewing and designing research involving human participants.

OHRP created these programs to enable investigators and IRB reviewers to be cognizant of the importance of diversity, inclusion, and risk minimization in research participation.

Click here to access our other scenarios!

• Recordings of OHRP Presentations on Human Subjects Research and Investigator Responsibilities for Protecting Participants in Research!

What is Human Subjects Research? A Review of the Common Rule and its Application provides helpful explanation on the complex concept of human subjects research and how to address related considerations in the NIH grant application process.

 What Investigators Need to Know About IRB Review helps investigators understand the thoughts and considerations needed for writing a successful plan to protect human research participants that would pass the muster of reviewers.

These videos will help investigators with the NIH grant application and IRB review process.

HSPP- October-November-December, 2021- Newsletter

FDA Warning Letter Regarding the Failure to Submit INDs for the Conduct of Clinical Investigations with an Investigational New Drug

Inspections of clinical trials are conducted as a part of the U.S. Food and Drug Administration (FDA)’s Bioresearch Monitoring Program.  These inspections are designed to evaluate the conduct of research and to help ensure that the rights, safety, and welfare of human subjects have been protected.  Below you will find a short summary of warning letters issued because of the failure to submit investigational new drug applications.

Warning letter to Kaleido Biosciences, Inc

On September 7, 2021, the FDA issued a warning letter to Kaleido Biosciences, Inc.   The FDA officials inspected two of Kaleido’s studies and concluded that investigators did not adhere to the FDA regulations governing the conduct of clinical investigations and the protection of human subjects.

Kaleido investigators thought that the product used in their investigations was subject to regulations as medical food but not subject to regulations as a drug.  However, the FDA inspectors concluded that the product was intended for use as a drug, and not as a food.

The argument established by the FDA to support their conclusion is based in the definition of food vs a drug in the use of a clinical investigation.  The FDA argued that the purposes of this clinical investigation was to evaluate the efficacy of a food product as treatment of a disease and, consequently, the food in this trial was seen as a drug.   Therefore, use of the food product in the clinical trial is not exempt from the investigation new drug requirements.

For more details about the inspection of these studies and the findings of the FDA please review the warning letter to Kaleido Biosciences, Inc.

Warning letters  to Jon B. Cole, MD, and Lauren R. Klein, MD., MS.

The FDA regulations require a sponsor to submit, and to have in effect, an investigational new drug application (IND) before initiating a clinical investigation of a drug in human subjects, unless the clinical investigation qualifies for an exemption (see 21 CFR 312.20 and 312.40(a)).

The FDA determined that Dr. Cole  and Dr. Klein failed to comply with these requirements while using marketed drugs in two studies.

The investigators thought that an IND was not needed, and argued that the medications administered to subjects were not part of a research intervention but were provided only for clinical purposes.   In addition, the investigators stated that if their clinical investigations were subject to FDA jurisdiction, they met the criteria for exemption from the investigational new drug requirements.

Contrary to the investigators, the FDA auditors concluded that the studies were designed to study the safety and efficacy of those marketed drugs products. In addition, the FDA determined the drugs were not delivered in the course of medical practice, but for research purposes. “The FDA underlined that whenever an investigator limits his choices, his patients’ choices, and the choices of the people working for them in the treatment of patients, then he/she is conducting a clinical investigation. This is different from the practice of medicine, where the primary intent is to treat the individual patient.”

Moreover, the FDA inspectors determined these clinical investigations did not meet the criteria for exempt since these investigations increased the risks or decreased the acceptability of the risks associated with the use of the drug products.

For more details about the studies mentioned above, the FDA’s thinking regarding IND requirements for market drugs and FDA views of clinical use vs. clinical investigation, please click on the links to the warning letters seen below:

• Warning letter to Jon B. Cole, MD
• Warning letter to Lauren R. Klein, MD., MS

Medical Devices

 Medical device products are regulated by the FDA’s Center for Medical Devices and Radiological Health (CDRH).  Depending on the device classification and other factors, the Code of Federal Regulations, Title 21, defines the requirements to approve or clear devices sold in the United States.

Investigators planning to conduct research with medical devices should learn the FDA status of a device.  The investigator should determine whether the device has been approved, cleared for marketing, or whether it is an investigational device. When used in research it is important that the informed consent form accurately identify the type of device being used as approved, cleared, or investigational (see FDA guidance).

Reviewing the following information will allow investigators to understand the process by which the FDA classifies devices, clears devices, and approves devices. The sections below includes excerpts from the document titled Is it really FDA approved? and the FDA webpage on the Premarket Notification 510(k) clearance process.

Overview of Device Regulation

FDA classifies devices, or more accurately device types, in order to identify the degree of regulations for that product area.  Classification is based on two factors:  the device description/its physical characteristics, and the intended use.

FDA classifies devices into Class I, II, or III.  The class of the device generally increases with its degree of risk. Regulatory control increases from Class I to Class III. The device classification regulation defines the regulatory requirements for a general device type. Most Class I devices are exempt from Premarket Notification 510(k); most Class II devices require Premarket Notification 510(k); and most Class III devices require Premarket Approval.

A description of device classification and a link to the Product Classification Database is available at “Classification of Medical Devices.”  To learn more about how medical devices are classified, please watch the FDA educational video titled: How is my Medical Device Classified?

Note – A registration number with the FDA only means the FDA is aware of the manufacturer and device, and does not mean the device is ‘FDA cleared’ or ‘approved.’ (see more info here)

Cleared Devices

The FDA may clear a device for marketing through the 510(k) process, when the manufacturer demonstrates the device is substantially equivalent to a predicate device. A claim of substantial equivalence does not mean the device(s) must be identical. Substantial equivalence is established with respect to intended use, design, energy used or delivered, materials, performance, safety, effectiveness, labeling, biocompatibility, standards, and other applicable characteristics.  The 510K clearance process does not require submission of clinical data to support the claim.

A device which is “cleared” to market should not be deemed the same as a device that has been “approved” by the FDA through a Premarket Approval (PMA) application.

Approved Devices 

To receive FDA approval to market  devices, manufacturers must demonstrate with sufficient, valid scientific evidence (i.e., submitting clinical data to support a claim) that there is a reasonable assurance that the devices are safe and effective for their intended use.

Investigational Devices

An investigational medical device is one that is the subject of a clinical study designed to evaluate the effectiveness and/or safety of the device.  An application for an Investigational Device Exemption (IDE) is to be submitted by the Sponsor or investigator to use the investigational device/unapproved device in a clinical study.

Data collected during these clinical studies is to be included in a future marketing application. The IDE application enables manufacturers to ship a device from one state to another when conducting a clinical study on the device without being subject to most other provisions of the Federal Food, Drug, and Cosmetic Act.

An IDE application may also be required for a legally marketed device that has been modified and/or intended for a new use.

Clinical studies with investigational devices of significant risk must be approved by FDA and by an Institutional Review Board (IRB) before the study can begin. Studies with devices of no significant risk must be approved by the IRB only before the study can begin.

Investigators conducting research with medical devices are to include in their initial application and informed consent forms whether their devices are approved devices, cleared devices or investigational devices.

Inclusion of Certificate of Confidentiality Language in Consent Forms for NIH funded Studies

In October 2017, NIH updated its Policy for issuing Certificates of Confidentiality (Certificates or CoCs) for NIH-funded and conducted research. These Certificates protect the privacy of participants by limiting the disclosure of identifiable, sensitive information.

Informed consent forms of NIH funded studies must include the required language regarding the Certificate of Confidentiality (CoC) and the protections it offers. This requirement is already listed in the Main Consent Form Template .doc (page 8) and the Main Consent Form Checklist.doc  (Page 4)

More information about Certificates of Confidentiality is available at https://grants.nih.gov/policy/humansubjects/coc.htm

IRB Forms – Update

The submission checklists for IRB applications have been updated.

The updates include:

• Changing the point of contact for I.T. security
• Clarifying details regarding the need for letters of permission to conduct research
• Clarifying details regarding the FERPA verification form
• Clarifying details regarding the use of recruitment tag lines for on-line postings

HSPP- July-August-September, 2021- Newsletter

Informed Consent- Process & Documentation

 The informed consent process is one of the central components of the ethical conduct of non-exempt research with human subjects.  The consent process typically includes providing a written consent document containing the required information along with an oral presentation of that information to prospective participants.  The informed consent process involves the “who”, “what”, “when’, “where”, and “how” that results in a valid, and effective informed consent being obtained from a participant.

The following section presents a general overview of an effective informed consent process and its documentation. Exceptions to this process may be granted by the IRB.  Those exceptions are described in IRB policy 2011-008.2.pdf – Informed Consent – Waivers and Alterations.

Who can obtain consent?    

The Principal investigator or designated individuals listed on the materials approved by the IRB. Any personnel authorized to obtain consent must comply with human subjects protection training requirements.  Individuals who are approved to obtain consent must be knowledgeable of the protocol and prepared to answer questions that may be posed by the potential subjects.

Study personnel who will be obtaining consent should be familiar with the following IRB policies:

• 2011-008.0.pdf– Informed Consent – Forms
• 2011-008.1.pdf – Informed Consent – Process
• 2011-008.5.pdf – Informed Consent – Providing and Obtaining Informed Consent  

Who can provide consent? 

Consent is to be obtained from an individual who has authority to give consent.  If the prospective participant is an adult who has capacity to consent, it is that individual who should give consent.  When an individual is unable to consent on his or her own behalf, consent must be obtained from a person who has the authority to do so. Investigators should be aware of the provisions described in the IRB Policy 2011-008.5.pdf  regarding the conditions and requirements to obtain consent from adults, minors, and legally authorized representatives.

The study protocol and initial study application should identify who will be providing consent (i.e., adult subjects, legally authorized representative (LAR)).  If the individual to provide consent is a LAR, documentation of this status must be obtained except when the LAR is the parent of a participant who has not yet reached the age of majority, or attests to being the next of kin. One exception to the next of kin provision is that adults with intellectual disabilities who have been declared incompetent must have an appointed legal guardian provide consent to participate in research. The natural parents of the adult are not authorized to give permission unless they have been appointed legal guardian(s).

When Consent Process must occur?

An informed consent process must be conducted with a potential subject prior to any involvement of the subject in non-exempt research (e.g., prior to any procedures that are done solely for research purposes).  It must happen before any interaction/interventions to collect data to ensure that the subject has an appreciation for the study in which s/he may enroll.

The process of consent should continue throughout the study, for example by explaining  each visit as it occurs and ensuring the subject is still willing to participate, or by providing new information to subjects as it is learned to ensure they are still willing to participate.

Where Consent Process must occur?

The consent process must be conducted in a setting that affords sufficient privacy to the potential subject. Privacy refers to an individual’s desire to control who has access to him/herself. The setting where the potential participants will interact with the researcher team must be protected from access to the public.

What do you need to obtain Consent from a prospective participant?

The individual obtaining consent must present the subject with a written informed consent form that contains the key information that is most likely to assist a subject in understanding the research, what is expected of them, and the potential risks of harm and potential benefits, if any. The consent form must be written in a language that is understandable to the subject or subject’s LAR, and should be written in lay language using an 8^th grade literacy level as a benchmark.  The informed consent template and informed consent checklists available on the IRB website should be used to ensure the consent document contains the regulatory and local required elements of consent.

The individual obtaining consent should ensure that the most recently approved and stamped version of the consent form is used when obtaining consent.

 How should a consent process be conducted?

The Principal investigator must describe the proposed process of consent in the material provided to the IRB.

This process should begin with allowing the potential subject time to review the consent document, and then a discussion of the key elements of a research study in the subject-preferred language.

The process must be free of any coercion (e.g. a threat of something bad happening if the subject declines participation), and free of undue influence (e.g. a sense of pressure to say yes, because the person obtaining consent is also the clinical provider).  The subject must receive the following information:

• that consent is being sought for research and participation is voluntary;
• the purpose of research;
• expected duration of participation and procedures to be followed;
• the risks or discomforts and the potential for benefits to the prospective subject or to others; and
• the appropriate alternatives procedures or courses of treatment, if any, that might be advantageous to the prospective subject.

The consenter should provide ample time for questions, and may ask the subject questions about the research to assess his/her understanding of the study.

In most cases, unless the IRB has waived the requirement to document consent, at the conclusion of the consent process and after the subject has decided to participate, investigators are to obtain a signature and date of signature from the participant on an IRB approved informed consent document.  The IRB also require that the person obtaining consent sign and date the form.  At this time, a copy of the signed and dated consent form must be provided to the subject along with the Research Participant Feedback Form

The original signed consent form must be stored in accordance with the plans for storage described in the study application and protocol (e.g., consent form is to be filed in a research folder, or in separate secure location apart from research record, or in the medical record).

Notes in a research chart indicating on-going discussions with the subject at subsequent study visits may supplement documentation of the informed consent process.

Educational Resources for Investigators at UConn Health – Informed Consent Process and Documentation

Checklist and Weekly WebEx Sessions

Investigators may use this Self-Audit /Checklist tool along with the IRB Policies listed above to ensure the consent process and its documentation comply with UConn Health IRB Policies.

The HSPP is offering a one-hour WebEx “Informed Consent Process and Documentation” education session every Thursday and Friday at noon time for study coordinators, investigators, first time principal investigator, and students who plan to conduct Human Subjects Research at UConn Health.  To register for these sessions please email Mayra Cagganello at cagganello@uchc.edu

Educational Resources for Investigators –OHRP –Simplifying Informed Consent Video

 The Office of Human Research Protection (OHRP) has posted a video titled: “Simplifying Informed Consent.”  In this video OHRP representatives discuss what goes into a meaningful informed consent. Practical examples are used to illustrate how to discern meaningful information for potential participants, and how to present information simply in consent documents and materials to ensure consent processes fulfill their goal of enabling potential participants to make informed decisions about whether to participate in the research.

To access this Simplifying Informed Consent video please click here

Informed Consent – Process & Documentation – Frequently Asked Questions

Why do I need to use the Main Consent Form Checklist to create my Consent Form?

UConn Health IRB created and posted the Main Consent Form Checklist .doc to assist investigators and research staff when creating consent documents. This checklist outlines the basic and additional elements of a consent form.

Although, not all elements of the informed consent form template will be required for every study, as applicable to a study, the IRB recommends inclusion of all relevant elements noted on this form and reserves the right to require additional elements.

In addition, as applicable to the study design, investigators must use additional consent checklists along with the above one when creating their Consent forms.    For example, if the study involves genetic research the investigator must also complete the Consent Checklist – Genetic Research Addendum If the research involves the use of stem cells  the Consent Checklist – Stem Cell Research Addendum.doc must also be used.  When funding for a study comes from the National Institute of Justice, the Consent Checklist – National Institute of Justice Requirements Addendum.doc. must be used along with the main consent checklist.

Do I need to use the Consent Form Template?

UConn Health IRB created and posted the Main Consent Form Template .doc  to assist investigators and research staff when creating consent documents.  The IRB strongly recommends investigators to use the standard UConn Health Main Consent Form Template .doc  because this template contains all the basic elements, and is tailored to multiple study designs (e.g., consent for federal funded research, consent for genetic research, consent for research subject to FDA oversight). However, this template may not cover all nuances for various studies.  You may need to add, delete and/or edit sections to make them applicable to your study.

What should I do if I realized I have not documented the consent process correctly (e.g., the subject did not incorporate the date when signing the Informed Consent Form)?

In the event that an informed consent (IC) form is found to be undated, if the error is not discovered while the subject is present, the research staff should prepare a note to file attesting to the fact that they witnessed the signing of the form, and the date that it was witnessed.

Since this incident was under the control of the study team, this event should be reported to the IRB within 5 days of becoming aware of the non-compliance.  The investigator should complete and submit a problem report form via iRIS system.

To avoid this type of issues, investigators obtaining consent should review the IC forms once they are signed/completed, and before the subject leaves that day to ensure that all signatures and dates are properly entered on the forms.

Who may provide consent when a subject is unable to provide consent?

When a potential subject is unable to provide consent because of impaired competency, consent must be obtained from a legally authorized representative (LAR) of the subject. Documentation of this status must be obtained except when the LAR is the parent of a participant who has not yet reached the age of majority, or attests to being the next of kin. One exception to the next of kin provision is that adults with intellectual disabilities who have been declared incompetent must have an appointed legal guardian provide consent to participate in research. The natural parents of the adult are not authorized to give permission unless they have been appointed legal guardian(s).

The investigator obtaining consent from a LAR must be knowledgeable of the IRB Policy 2011-008.5.pdf – “Informed Consent – Providing and Obtaining Informed Consent” which describe in detail who in Connecticut meet the definition of a legally authorized representative.

How far in advance of research participation, can informed consent be obtained?

The U.S. Department of Health & Human Services (HHS) do not identify how far in advance of study entry a subject can provide consent. They explain that the amount of time required by a subject to make a decision would presumably depend on the nature of the study, taking into account, among other factors, the degree of risk, potential benefits, alternatives, and desire to consult with family members or others. HHS recommends reviewing the information contained in the consent form with the subject again if a prolonged period elapses from the date of consent to the date of entry into the study.

 FDA Regulated Studies -Compliance with 21 CFR Part 11

 Title 21 CFR Part 11 is the portion of the Code of Federal Regulations that provides standards determined by the Food and Drug Administration (FDA) on electronic records and electronic signatures.   During the COVID-19 pandemic, an FDA enforcement discretion of Part 11 was implemented, which is still in effect.  However, this enforcement discretion will eventually end.

If any FDA regulated studies at UConn Health are using work-around solutions from the FDA Guidance on Conduct of Clinical Trials of Medical Products During the COVID-19 Public Health Emergency these systems will need to be discontinued when the Public Health Emergency is declared over.

FDA Sends Warning Letter to Individual Investigator for  Clinicaltrials.gov Non-Compliance

 For the first time, the FDA sent a warning letter to a principal investigator for a ClinicalTrials.gov record that was not updated in accordance with the law. Civil money penalties currently stand at $12,316 per day until the violation is corrected. Previous warning letters were sent to industry sponsors, but this is the first time the FDA has sent a letter to an individual investigator for non-compliance.

For any questions related to ClinicalTrials.gov, please contact UConn Health’s ClinicalTrials.gov Administrator, Ellen Ciesielski (eciesielski@uchc.edu) for assistance.

HSPP- April-May-June, 2021- Newsletter

What is Exempt Human Subjects Research?

Exempt human subject research is a project that does constitute human subjects research but is exempt/excused from satisfying the requirements of the Department of Health and Human Services (HHS) policy for the protection of human research.  Research activities that involves no more than minimal risk are exempt from the human research protection regulations when the only involvement of human subjects falls within one or more of the exempt categories described in the Request for Exemption Form .doc. While the research may be exempt from certain regulatory requirements, human subject protections, such as plans for protection of privacy and confidentiality of data, are still applied per accreditation standards and internal policies.

As per UConn Health’s Human Subjects Protection Program Policy 2011-009.2.pdf – Institutional Review Board – Exemptions, investigators cannot make the determination as to whether a human research project meets the criteria of exempt research.  This determination is to be made by the Institutional Review Board (IRB).

To aid those who need to decide if an activity is research involving human subjects that must be reviewed by the IRB for Exempt determination, the Office of Human Research Protection (OHRP) published graphic charts titled Is the Research Involving Human Subjects Eligible for Exemption Under 45 CFR 46.104(d)? .

What is Non-Exempt Human Subjects Research?

If the project does not fall within one or more of the defined categories of exemption, then it is not exempt and must satisfy the regulatory criteria for approval.   Non-Exempt human subject research may be a project for which research activities involve no more than minimal risk to subjects and all of the procedures in the research are described in the categories of research that may be reviewed by the expedited procedure.  The expedited review procedure means that only one member of the IRB needs to conduct the review. This type of research is reviewed on a daily basis and there are no submission deadlines.

Non-Exempt human subject research may also be a research project involving greater than minimal risk and/or involving procedures not described in the categories for exempt status or expedited review.  This type of research would have to be reviewed by the convened IRB committee and submission deadlines will apply.

In order to obtain IRB review investigators must complete and submit an on-line Application in the iRIS submission system and attach to that application the relevant submission checklist and corresponding documents.

IRB Frequently Asked Questions

 Q: Who is consider “Key Study Personnel” in a Human Subjects Research Study?

A: The key study personnel (KSP) are those people designated by the Principal investigator as back–up principal investigator, co-investigators, study coordinators, data managers, or consenters on an application submitted to the IRB for review and approval.   The KSP often include individuals involved in the study through an interaction or intervention with research subjects for research purposes or those reviewing or accessing identifiable data for the research.  Individuals who will be interacting with research subjects during the course of a study, but only in their regular non-research employment capacity (e.g. a nurse or phlebotomist) should not be listed as KSP if they are not associated with the study as researchers.

Q: Do key study personnel added to a study need to complete Human Subjects Training? 

A: Yes. All key study personnel listed on an IRB application must complete training in the protection of human subjects.  Training completed through the Collaborative IRB Training Initiative (CITI) is the most used method of training to fulfill this requirement. Training must have been completed within the past three years to be considered current.

Q: I have little experience in IRB submissions.  Where can I find information about the IRB process for a new proposed study?

A: The Human Subjects Protection Program offers a one-hour general educational session for study coordinators and investigators who plan to conduct Human Subjects Research at UConn Health. This training provides an overview of the research proposal submission and maintenance process. Registration is required. Interested staff should e-mail Mayra Cagganello at cagganello@uchc.edu.  Individuals who need study specific guidance on preparing IRB submissions are encouraged to request assistance from the Education Specialist as noted above. WebEx orientation sessions are available on a daily basis.

Recent Articles Published by a  Central IRB

ADVARRA IRB:  

FDA Inspections of Clinical Investigators: Understanding the Process and What to Expect: This article provides answers to a series of questions regarding FDA inspections process.

Among the questions answered in this article are:

• What is the likelihood an investigator-initiated Investigational New Drug application (IND) and non-IND study would undergo an FDA inspection at an academic center?
• For multisite studies, does FDA inspect all sites, or might one specific site be selected to be monitored?
• How do you suggest research staff/coordinators educate clinical investigators (CIs) that they need to pay attention to study oversight and the FDA will not hold coordinators responsible by FDA if things go awry in the study conduct?
• Do you anticipate inspections to pick back up as more people become vaccinated and COVID-19 cases decrease? Will the FDA catch up on missed investigations?

Cell and Gene Therapy vs Small Molecule Research: Understanding the Difference Cell and gene therapy’s popularity has grown exponentially in the past year. This article provides an overview of how cell and gene therapy research is different from traditional drug development. Among the issues discussed in this article is that sites need to build the required infrastructure for conducting cell and gene therapy research safely and successfully.

 Educational Resources for Investigators

OHRP Luminaries Lecture Series

The Office of Human Research Protection (OHRP) has posted a series of lectures on human subjects research protections titled: “Luminaries Lecture Series.”  Many of these lectures are recordings of keynote addresses at OHRP-sponsored Research Community Forum (RCF) events.  Among the topics presented in these lectures are “Use of eConsent in Human Subjects Research,”  “Making Mobile Clinical Trials a Reality” and “Big Data, Privacy, and the Public Good.” To access these Luminaries Lecture Series please click here.

HSPP-Newsletter January-February-March 2021

NIH Releases New Policy for Data Management and Sharing

On October 29, 2020, the National Institute of Health (NIH) published the final policy for data management and sharing (DMS).  This policy applies to all research funded or conducted by NIH that results in generation of scientific data.  As stated in this policy  “data sharing enables researchers to rigorously test the validity of research findings, strengthen analyses through combined datasets, re-use hard-to-generate data, and explore new frontiers of discovery.”  The NIH DMS Policy requires researchers to submit a plan to preserve, to share the data and to show compliance with said plan.

To learn more about the scope of this policy and the details of data management and sharing plans, please review the Final NIH Policy for Data Management and Sharing.

Limited Data Sets and Data Use Agreements

A limited data set (LDS) contains protected health information that is associated with indirect identifiers as defined in the HIPAA privacy rule.  The indirect identifiers that may be included in an LDS are: town, city, state and five digit or more zip code, dates directly related to an individual such as date of birth, admission date, discharge date and date of death.

Before an LDS can be received by a UConn Health employee or disclosed to another institution, a data use agreement (DUA) must be in place between the sender and receiver of the LDS.   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: Cherron Payne chpayne@uchc.edu
• If the DUA is  unrelated to a Clinical Trial contact: Jennifer Pomales pomales@uchc.edu

 IRB Forms – Update

The   Main Consent Form Template .doc  has been revised to include instructional text about the option to decline payment for participation. The Main Consent Form Checklist .doc has also been revised to reflect this option.

Which Initial Application Form is the Correct One for Your Study?

 Once an investigator has determined that his/her project is a human subject’s research project, the next step for the investigator is to submit the project for review and approval to the IRB. This task will require that the investigator complete the “Initial Study Application Form” within the Integrated Research Information System (iRIS).

The investigator creating a new study application in iRIS will need to select one of the three available Initial Study Application Forms listed below:

• Application for a General Study
• Application for a Humanitarian Use Device
• Application for a Registry and /or a Repository

The following section provides a description of the three Initial Application Forms available in iRIS along with examples of when each one should be selected.

Application for a Humanitarian Use Device (HUD):

According to the U.S. Drug and Food Administration (FDA) a Humanitarian Use Device (HUD) is defined as a medical device intended to benefit patients in the treatment or diagnosis of a disease or condition that affects or is manifested in not more than 8,000 individuals in the United States per year. An HUD is an FDA approved device.  Because the HUD device is approved for use in such a small population, the FDA regulations requires that an IRB approve the use of the HUD in accordance with its approved label even though the use of the HUD is not research.

If you are requesting approval for use of an HUD, select the application specific for HUDs.

Application for a Registry and /or a Repository:

A registry/repository is used for the collection and maintenance of information/biospecimens on individuals who have a similar condition and who will consent to being contacted for future studies.  The investigator must develop a protocol that describes how the data/biospecimens will be collected, how they will be maintained, and how release of information from the registry or biospecimens from the repository will occur.

If you are requesting approval for a Registry and /or a Repository, select the application specific for Registry/Repository.

Application for a General Study:

The Application for a General Study form is the most commonly used application type. The investigators should select it when their research is categorized as either biomedical research, social & behavioral research or community based participatory research.  These projects may qualify for Exempt Status or Expedited review in accordance with regulatory criteria, or otherwise they will be review by the convened board.

Examples of human subject research projects that should be submitted with this General Application Form are:

• Minimal risk studies (e.g. studies limited to a survey, studies limited to a retrospective or prospective data review, clinical studies of drugs and medical devices when the conditions for expedited review are met, studies 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).
• Studies submitted for full board review (e.g., investigational new drug (IND) studies, investigator new device (IND) studies, social & behavioral studies including more than minimal risk to subjects).

Research with Children

When children are to be involved in non-exempt research, the investigator must address the additional protections for the inclusion of children in research.  The investigator does this by completing IRB Form D – Additional Protections for Children Involved as Subjects in Research.   The additional requirements set forth on this form are derived from DHHS and FDA regulations.

On Form D the investigator makes the initial assessment of risk level and sets forth plans for obtaining parental permission and assent.  The IRB reviews this form and makes the final determination as to whether the requirements for additional protections have been satisfied.  Depending on the level of risk of the study, UConn Health IRB will determine whether one or both parents (or legally authorized representatives) must give their permission.  The IRB will also make the final determination as to whether assent of the child is required and if so how that assent will be obtained.  In making this determination the IRB will take into consideration the age and maturity of the children, and the psychological state of the children involved.

Per UConn Health policy, 2011-006.3.pdf – Additional Protections – Children the additional protections for children apply to all non-exempt research (e.g., Expedited and Full Board Submissions) that is federally funded or supported, and/or that involves an intervention or interaction with a child regardless of funding source. Therefore, the additional protections do not apply to non-federally funded or supported chart review studies that qualify for exempt status.

OHRP New Video

Research with Children:  What Parents Need to Know

The Office of Human Research Protection (OHRP) has posted a new video on its public outreach website. This short video titled “Research with Children: What Parents Need to Know” is for parents/legal authorized representatives who may be or have been approach about permitting their children to participate in research.  It provides an explanation as to why research-involving children is necessary, its importance and what parents should expect if considering enrolling their child in a study. This video is found under the category of Videos on Protecting Human Research Volunteer

HSPP- October, November, December, 2020- Newsletter

 Accessing and Signing-off Submissions in iRIS

In order for a member of the study team to be notified that there is an IRB submission that requires the study team member’s sign-off, there must be a valid e-mail address associated with the study member’s account in iRIS.  Therefore, it is important to verify the validity of email addresses when selecting the members of a study team.  For UConn Health faculty, staff, students and residents, iRIS is linked to the LDAP active directory at UConn Health; so if a user does not have an e-mail in that directory there will likely be problems notifying them of the required sign-off task in iRIS.  In addition to verifying addresses by using the active directory; at the time of adding study team members to the form in iRIS there should be an email address listed next to the team member’s name in iRIS.  Lack of a valid e-mail address prevents the submission from being routed to the study team member for sign-off and from being submitted to the IRB for review and approval.

To avoid these problems, the person creating the study form in iRIS should follow the steps described in pages 7 and 8 of the iRIS user manual entitled “Basics for Creating a New Study Submission- Manual 1.”  The manual is available in the help section within iRIS.

FAQ about Facilitated Review – Reliance on External IRB

Q: What changes do I have to report to the UConn Health IRB when my study has been approved by an external IRB?

 A: When the UConn Health IRB has elected to rely on an external IRB, the external IRB is referred to as the IRB of Record.  Per the IRB Reliance Agreement in place, with one exception, only the IRB of Record for your study is responsible for all reviews of your study, inclusive of continuing reviews, requests for study modifications or amendments, and for reviews of non-compliance and unanticipated problems.

The one exception is that changes to UConn Health study personnel must still be processed through the UConn Health IRB by submitting a request for modification form through the iRIS system.

OHRP Determination of Exception to the Single IRB Review Requirements for Certain HHS-Conducted or – Supported Cooperative Research Activities Subject to the 2018 Requirements During the Coronavirus Disease 2019 (COVID-19) Public Health Emergency

 To ensure that institutions conducting cooperative research are able to take advantage of the most appropriate IRB review structure, the Office for Human Research Protections (OHRP) in the Office of the Assistant Secretary for Health of the Department of Health and Human Services has determined that, for studies that are conducted or supported by HHS and subject to the 2018 Requirements, and for purposes of 45 CFR 46.114(b) (2)(ii), an exception to the requirement to use a single IRB is appropriate for the following category:

Cooperative research:

1. that is ongoing or initially reviewed by the IRB during the Coronavirus Disease 2019 (COVID-19) public health emergency, as declared by the Secretary of Health and Human Services here.
2. where reliance on a single IRB would not be practical; and
3. for which the HHS division supporting or conducting the research approves of the use of this exception.

This exception applies for the duration of the HHS-conducted or supported research.

OHRP has made this exception determination due to concerns regarding the application of the single IRB requirement to cooperative research subject to the 2018 Requirements when this research is initially reviewed or ongoing during the COVID-19 public health emergency. The COVID-19 public health emergency has created unprecedented burdens and disruption to the research enterprise, while at the same time requiring urgent research responses that necessitate flexible approaches to oversight in order to provide vital information and to allow other research to continue where possible. This exception represents an effort to prioritize the health and safety of both research subjects and investigators, and provides flexibility to institutions in seeking IRB review due to the unique challenges created by the COVID-19 outbreak.

The exception includes some scenarios for which OHRP anticipates it may not be practical to rely on use of a single IRB for multi-site, cooperative research trials during the ongoing COVID-19 pandemic. This exception determination can be accessed here.

OHRP’s November 2019 Determination of Exception and related background information can be accessed here.

NIH Policy on Registration/Results Posting Of Basic Experimental Studies with Humans (BESH)

NIH’s clinical trial definition includes prospective basic science studies involving human participants. Basic Experimental Studies with Humans (BESH) use an intervention to understand fundamental aspects of a phenomenon without specific application towards processes or products in mind. NIH published case studies with examples of BESH (cases 9, 14, 40 & 41).

NIH funded clinical trials, including BESH, are required to register and post results in ClinicalTrials.gov.

On December 7, 2020, the Acting Director of ClinicalTrials.gov, presented the results of the National Library of Medicine analysis of challenges and considerations for registration and results information reporting of BESH in ClinicalTrials.gov. The recording of this webinar is available at https://videocast.nih.gov/watch=40141

For more information about ClinicalTrials.gov, including assistance with registration, please contact Research Compliance Monitor, Ellen Ciesielski at eciesielski@uchc.edu.

Recent Articles Published by Central IRBs

ADVARRA IRB:  

Beginner’s Guide to Investigator-Initiated Trials  This article describes the basic concepts an investigator must understand about “investigator initiated clinical trials” and how they fit into the clinical research landscape.

Western IRB (WCG):

Virtual Clinical Trials: Best Practices in moving Toward a Patient-Centric Research Model

This article defines virtual clinical trials, describes the potential benefits/risks of this new paradigm, and best practices for maintaining regulatory and Institutional Review Board (IRB) compliance.

Informed Consent Process and Documentation

 One of the most important aspects of conducting non-exempt human subject research is obtaining the legally effective informed consent of the subject or the subject’s legally authorized representative (LAR) before involving the subject in the research.  Study personnel who will be obtaining consent should be familiar with the following IRB policies

• 2011-008.0 – Informed Consent Forms
• 2011-008.1 – Informed Consent Process
• 2011-008.5 – Informed Consent, Providing and Obtaining Informed Consent

Exceptions to the above noted policies may be granted by the IRB if certain criteria are met.  Those exceptions are described in IRB policy 2011-008.2.pdf – Informed Consent, Waivers and Alterations.

The following section presents a general overview of a correct informed consent process and documentation of consent.  Examples of non-compliance with the process and documentation of consent are also provided.

Informed consent process and documentation:  

• The consent process occurs in a private setting.
• The consent process starts with a potential participant being given the opportunity to review the informed consent form and is followed by a discussion about the research.
• The process is free of coercion or undue influence.
• The process occurs under circumstances that provide the prospective subject, sufficient time to discuss, ask questions and consider whether or not to participate.
• Once an individual has had all his/her questions answered and has had ample time to consider the information s/he decides whether or not to participate.
• Unless documentation of consent has been waived by the IRB, the informed consent process is documented by use of an IRB approved informed consent form.
  • The IRB approved consent form must be signed and dated by the subject (or legally authorized representative) and the person obtaining consent.
  • All names, signatures and dates should be entered in the document on the same date and at the same time.
  • After the signatures are obtained the participant must be provided with a copy of the complete signed informed consent document.
  • Documentation of the initial informed consent process may be supplemented by notes in a research chart that indicate on-going discussions with the subject at subsequent study visits.
  • At the conclusion of the consent process investigators should provide a Research Participant Feedback form to the subjects.

Examples of Non-Compliance with the Consent Process

• Consent for participation obtained from next of kin, spouse or other individual in a study that does not have IRB approval to obtain consent from a legally authorized representative (LAR).
• Consent obtained from individual who is not part of the approved study team.
• Research interventions occurred prior to obtaining consent.

Examples of Non-Compliance with Documentation of Consent

• Consent form is not signed by the subject
• Consent form is not signed by the person obtaining consent.
• Dates of signature are either missing, incomplete or incorrect.
• The original consent document is not retained.
• Dates contained corrections, which obscured the original entry.
• The most recent version of the approved consent form was not used when consent was obtained

Mayo Clinic Expanded Access Program (EAP) – Update

 On August 23, 2020, the US Food and Drug Administration (FDA) issued an Emergency Use Authorization (EUA) for convalescent plasma for the treatment of hospitalized COVID-19 patients. Click here for more information regarding the Emergency Use Authorization (EUA) announcement.  The Emergency Use Authorization (EUA) is currently active and represents the preferred means of administering convalescent plasma.

For additional information, please consult the US FDA fact sheet for health care providers, available at: https://www.fda.gov/media/141478/download

New patient enrollment in the Mayo Clinic EAP is not authorized after August 28, 2020.

Order of convalescent plasma under the Mayo Clinic EAP is not authorized after August 31, 2020.

Participating sites are required to complete data follow-up forms for all patients enrolled in the Mayo Clinic Expanded Access Program (EAP).

 Please visit our website for additional information:https://www.uscovidplasma.org/

Expanded Access for Treatment Use, Including Single Emergency Use – IRB Policy Update

Uconn Health‘s Human Subjects Protection Program (HSPP) policy 2011-022.2.pdf – Investigational Drug/Biologic – Expanded Access for Treatment Use, Including Single Emergency Use  has been revised.  This revision is to inform clinicians who intend to use the Expanded Access Program in a single emergency case that if time permits, prior to the emergency use, the prescribing clinician should complete an application for expedited review in the iRIS submission system.  The application in iRIS -Section 1, should indicate the type of research as: “Expanded Access –Single Patient.”

Within the online application the clinician must also describe his/her intent to utilize an investigational drug for a therapeutic reason at least 24 hours prior to the planned date of the first administration of the drug.  In addition, an email notification should also be sent to a Regulatory Specialist (RS) within the office (IRB contact information available at http://research.uchc.edu/rcs/hspp/) to alert the IRB of the situation such that the submission can be prioritized for review.

If prior review is not possible, the submission in iRIS is to be made within 5 business days of the drug administration.

Expedited review may be requested also for a single patient COVID-19 Expanded Access request for which a waiver of the requirement for full board review has been granted by the FDA in accordance with the FDA guidance that review by the IRB Chair or designee is sufficient.

The documents required for an Expanded Access Expedited submission are described in detail in the new published Application Checklist – Single Patient Expanded Access .docx

IRB Forms – Update

 The Application Checklists have been updated to reference when additional approvals from I.T. may be required to ensure that data security measures are adequate.

The application checklists for Exempt status, Expedited review, Full board review and Facilitated review, now include the following requirement:

If Institutional standards for data security, inclusive of standards for use of data encryption, are not being used on all devices (e.g. desktop, laptop, thumb-drive, other mobile devices) used to store/transfer data, approval from I.T. for use of alternate data security plan.  Contact Carrie Gray with questions (860) 679-2295, cagray@uchc.edu.  If not provided the IRB application should indicate data encryption is being used and implies Institutional standards are being followed.

The Initial Application form in iRIS now contains this note:  Study personnel must be aware of and comply with relevant IRB policies and institutional policies for data security. Links to IRB and UConn Health policies are available from the HSPP website at https://ovpr.uchc.edu/services/rics/hspp/policies/ and https://ovpr.uchc.edu/services/rics/hspp/policies/uch-policies/

Institutional data security standards, inclusive of standards for use of encryption, must be followed unless approval from I.T. to deviate from Institutional standards is obtained.  Contact Carrie Gray with questions (860) 679-2295, cagray@uchc.edu

 The Main Consent Form Template .doc  has been revised to include text in the sections regarding confidentiality for studies that use the medical record.  This was added because of the ability to share EMRs across institutions.   New submissions must use the latest revised consent form template. Approved studies are not required to change their consent forms.  The revision to that section includes that any clinical/provider that subjects see, whether at UConn Health or elsewhere, may potentially have access to the information in their medical record.

New FDA Guidance for Civil Money Penalties for ClinicalTrials.gov- Non-Compliance

On August 14, 2020, the Food and Drug Administration (FDA) published new guidance titled “Civil Money Penalties relating to the Clinical Trials.gov Data Bank.” The guidance clarifies how the FDA identifies whether responsible parties have failed to submit required clinical trial registrations or results to ClinicalTrials.gov, or knowingly submitted false or misleading information, and details the applicable fines, including “$10,000 for each day that the violation continues” and potential civil or criminal penalties.

Applicable clinical trials include those evaluating at least one drug, biological, or device product regulated by the FDA.

If your NIH-funded study involves human subjects, you can use the NIH decision tree to determine if it meets the NIH’s broad definition of a clinical trial and will therefore require registration and results posting.

For more information about ClinicalTrials.gov, including assistance with registration, please contact Research Compliance Monitor, Ellen Ciesielski at eciesielski@uchc.edu

HSPP- April- May-June, 2020- Newsletter

The Integrated Research Information System (iRIS ) is the electronic system used by research personnel and the Institutional Review Board (IRB) for the submission and review of research projects involving human participants.  On March 21, 2013, iRIS was successfully implemented.   To support said implementation, one on one training of researchers as well as weekly group sessions were carried out.  These training sessions are still available to all investigators as are iRIS-training manuals.  To schedule a training session e-mail Mayra Cagganello (cagganello@uchc.edu). To obtain a training manual click on the Help button found in your iRIS Homepage.

This present Newsletter has been prepared to address the most common and current difficulties observed when investigators navigate the system.   In the majority of the cases, these difficulties have caused delays in approval.   In addition to the training options noted above, it is highly recommended that all iRIS users read this newsletter to increase knowledge of the system thus preventing delays in approvals.

 The Most Common Mistakes with Revisions of Documents in iRIS

Once a submission is received by the IRB in iRIS, an IRB Regulatory Specialist (RS) conducts a  pre-review of that submission.  If the RS determines that corrections or additional documentation is needed before the submission can be formally reviewed by the IRB, the RS will return the submission to the study team either in a Submission Correction Form or in a Submission Response Form describing the corrections that are necessary.

The following section describes the major issues observed when investigators are submitting revised documents in the above mentioned submission forms.

Issue #1: Investigators upload revised documents to the system section for Protocol items rather than to the Submission Form .

The corrections requested must be made within the Submission form sent by the IRB (e.g., the Submission Correction Form or the Submission Response Form).  The IRB does not have access to your Study’s Protocol items. The IRB will only see and review documents uploaded/attached to the Submission Forms.

Issue #2: Investigators upload edited documents to the Submission Form as brand new documents instead of creating an iRIS revision.

If a contingency requires you to revise a document that you have submitted in previous rounds, you should follow the steps found in the iRIS User Manuals to revise the documents that are in the system.

• If you have received a Submission Correction Form, please use the instructions found in the iRIS User Manual titled:   Responding to a Correction Task- Manual 3.
• If you have received a Submission Response Form, please use the instructions found in the iRIS User Manual titled:   Responding to a Response Task – Manual 4.

iRIS Sign –off Notifications

 Once a submission form has been routed for sign off, the iRIS system generates emails to notify the research team members and principal investigator that they need to log into iRIS and apply their sign off.

Depending on whose signature is required, the e-mail sent to the study team members will have a different message.

Below are two possible messages the study team can receive when sign off are required. The subject line of the notification indicates who needs to sign off.

• A “Protocol Sign-off Notification” is sent to all members of the study team with a subject line stating:  Member of Research Team – Initial Notification for Review and Signoff.  In this case, all members of the study team need to log into iRIS and sign off (e.g., an initial submission application form).

The body of the email will specifically state that the study is in need of signatures from one or more team members of the team in order to continue the submission process to the IRB.

• A “Principal Investigator Signoff Notification” is sent to all members of the study team.
• However, the subject line indicates that this is a Principal Investigator Signoff Notification.  In this case, the submission has been routed only to the Principal Investigator for sign off (e.g., a Response form, an initial Modification Form, Continuation Form, Problem Report Form, and Closure Form,).  Even though the PI sign off is the only one required, all study team members receive the notification so that they are aware that the PI needs to do so.

The body of the email will state PI Signoff Needed.

Investigators should review the content of the notifications to determine whether to log into iRIS to sign off.  Many investigators log into iRIS with the intention to sign off on a submission, however, their signatures are not required.

iRIS Frequently Asked Questions (FAQ)

Q: Who needs to request an account to access iRIS?

A: If you are affiliated to UConn Health (e.g., if you are a student, a resident, a fellow, a faculty member, or staff), by virtue of said affiliation you already have the ability to log in to iRIS.  Your UConn Health network’s credentials are to be used to log into iRIS.

Individuals who are external to UConn Health (e, g., a UCONN Storrs student or faculty, a Hartford Hospital physician, etc.) who need access to iRIS should request an external account in iRIS.   An online request form must be completed by clicking on the Request New Account option found in the iRIS logging page. The person requesting the account should provide an explanation as to why the account is necessary and with whom at UConn Health the researcher will be associated.

An email request to create an account in iRIS is not adequate to generate an account in iRIS.  The information provided in the on-line request form is necessary to build an account for an external user.  To avoid inaccurate information this online request form should be completed by the person in need of the account.

Q: I am unable to log into iRIS.  What should I do? 

A: Internal Users (Investigators Affiliated to UConn Health):  If you are having trouble accessing iRIS with your UConn Health network credentials, please try to verify the following prior to contacting the HSPP/IRB office:

• Your network credentials are case sensitive.  Check the basics such as cap lock or number lock issues.
• Ensure that your UConn Health password has not expired (you can test this by rebooting your personal computer).
• If you recently changed your password, please try rebooting your personal computer before logging into IRIS.
• Make sure you are not coping and pasting your credentials into the iRIS’s log in boxes.  Your user ID and password must be typed into the iRIS log in boxes.
• If you are still experiencing problems using your UConn Health credentials, please contact the UConn Health help desk at x4400.

External Users (Investigators NOT Affiliated to UConn Health):  If you are having trouble accessing iRIS with the credentials provided when your account was created, you do not need to request another account. Please, do the following:

• The iRIS accounts of external users are active for a maximum of an 18-month period.   If you have not used iRIS for a long time and you think your account has expired, send an email to Mayra Cagganello ( cagganello@uchc.edu ) requesting an extension of your account.
• If your account is active ( is not expired) but you forgot your iRIS User ID, send an email to Mayra Cagganello ( cagganello@uchc.edu ) requesting your iRIS User ID.
• If you know your iRIS User ID but can’t remember your password, you will need to retrieve your password from iRIS.  To do so, click on the “I forgot my Password” tab found in the iRIS logging page . Enter your iRIS User ID in the box provided, and then click on the “Send Password” tab.    The IRIS system will send your password to the e-mail address found in your iRIS account.
• If you have tried to retrieve your password but have not received an email from iRIS with your password, it may be that your email address in your iRIS account is no longer valid.    If you  have a new email address, email your new email address to  Mayra Cagganello ( cagganello@uchc.edu ) with a request to update your email address in iRIS.

Q:  Who Needs to Sign off on Submissions in iRIS?

The table below explains:

When a Submission form is routed for sign off and other members of the study team are checked for sign-off, you should uncheck the boxes next to their names to deselect them as shown in the screen shot below.  Likewise, initial continuations, modifications, problem reports and closure forms only require the Principal Investigator (PI) sign off.  If other members of the study team are listed in the routing sign off sheet, you can uncheck the boxes to deselect their names .

Q: I am submitting a modification form to add new personnel to an approved study. However,   when routing the modification form for sign off I am unable to find the name of the new investigators in the Sign off Submission Routing list.

A: When a Modification Form is created in iRIS, such form works as a “request” made to the IRB.    Only principal investigators are required to sign off on an initial Modification Form.

When routing this form for sign off, the investigator working on the form will not find the names of the new personnel in the Sign off Submission Routing list.  This is because this request will be granted after the IRB has verified that the new personnel has complied with the human subjects protection training (e.g., CITI Training) requirement.    Moreover, the iRIS the system verifies whether the new added personnel has a valid iRIS account.

After the IRB staff and IRIS system have confirmed that the new personnel has met these requirements, an IRB Regulatory Specialist will add the names of the new personnel to the Key Personnel section of the study allowing the new investigator access to the study.

The IRB Regulatory Specialist then returns the Modification Form to the study team in a Correction Form with a contingency for approval.  The contingency will require that the new personnel sign off to accept his/her role in the study.   At this point, the study team working in the Correction Form will find the names of the new personnel in the Sign off Submission Routing list. 

Q: I routed a submission form to the IRB a while ago.  I have not hear from the IRB.   I see that the track location of the form states that is “Waiting for Finalization of Routing List.”  What should I do?

 A: In order for a form to arrive to the IRB queue in IRIS, the person submitting the form must complete several steps to route the form for sign off.   When all sign offs on the form have been completed, the system moves the submission form to the Submission box of the IRB in IRIS.

Whenever an investigator sees a yellow square under the “Track Location” that means that the form built in iRIS was never routed for sign off .

In the example below, the submission Correction Form is waiting for someone from the study team to route the form for signatures.

To route the form to the person who has responded to the contingencies, the following steps must be completed.  Begin by clicking click on the magnifier glass located on the yellow box under the Track Location.   Second, click on the “Routing Assignment List” (icon with the two heads).  Manually uncheck the boxes next to the names of the other members of the study team to deselect them.  Then, click on Save and continue twice.  If you are not the person who needs to sign off, log out. The submission will be in the iRIS homepage of the person whose signoff is required.

If you are the person who needs to sign off you will see the “approve” radio button.  Click on the approve radio button and enter your credentials to sign off.   Finally, click on Save to save your sign off.

Q:  How do I know if the IRB received my submission.

A:  Your  submissions forms are in the IRB inbox in iRIS when you see a green box under the Track Loction stating “Routing in Process.”

New iRIS users should use the iRIS User Manuals to ensure all the steps for routing submissions to  the IRB have been completed.

Office of the Vice President for Research (OVPR)

COVID-19 Guidance for the UConn Health Research Community

The Office for the Vice President for Research (OVPR) website has posted a COVID-19 Guidance for the research community at UConn Health.  Information about the impact and changes caused by the COVID-19 outbreak on research activities are described on this guidance.  Information on this web site is updated frequently.

IRB Policies – Revisions

 IRB Policy 2011-015.0. -Recruitment and Payment and policy 2011-011.0- Research Personnel have been revised to better outline the requirements and expectations for recruitment of UConn Health patients.  The policies denote, among other items, that the person who first approaches a patient about research participation must be someone with an existing treatment relationship with the patient and that members of the study team (e.g., principal investigators, co-investigators, study coordinators, consenters, etc.) interacting with the patient-participant must be affiliated with UConn Health (e.g. faculty appointment, employee, student, intern, volunteer).

If the study submitted for review has a Principal Investigator who is not a paid UConn Health faculty member, there must be a paid faculty member from UConn Health as a co-investigator on that study who is responsible for patient involvement.

IRB Forms – Update

The following forms have been revised:

• Consent checklist – Addendum for Genetic Research – This form was revised to clarify wording and to re-order the elements of consent.
• Main Consent Checklist – This form was revised to add elements for inclusion of any requirements imposed by a specific funding Institute, Office or Center within NIH related to data sharing (added in the NIH section of the checklist)
• Main Consent template – This template was revised to add instruction for investigators to check whether the funding entity has any specific requirements regarding data sharing language and if so to include it.    The NIAAA suggested language was provided as an example.

Connecticut Law Raises Legal Age to Buy Smoking Products to 21

 As of October 1, 2019, the State of Connecticut change the legal age for smoking from 18 to 21. UConn Health investigators who are conducting studies with tobacco products should review their studies and as needed revise them to comply with this new law in Connecticut.

NIH Update: Guidance for NIH-Funded Clinical Trials and Human Subjects Studies Affected By Covid-19

The National Institute of Helath ( NIH) has published the following guidance NOT-OD-20-087 outlining the flexibilities available to recipients impacted by COVID-19 for delays to ongoing research, delays to research progress for NIH-funded clinical trials and human subject studies, and unanticipated costs.

Disclosure Form for Work Submitted to Medical Journals

As stated by Darren B. Taichman, MD, PhD; Joyce Backus, MSLS; and Christopher Baethge, MD; et al, in their published article titled “A Disclosure Form for Work Submitted to Medical Journals.  : A Proposal from the International Committee of Medical Journal Editors” the International Committee of Medical Journal Editors (ICMJE) adopted the “ICMJE Form for the Disclosure of Potential Conflicts of Interest” as a mechanism for collecting and reporting authors’ relationships and activities that readers might consider relevant to a published work.

The ICMJE has proposed changes to this disclosure form to enhance transparency and accuracy in the information captured by this form. The ICMJE is requesting feedback about the proposed new form.  Comments received by April 30, 2020 will be consider for the finalization of the revised version.  The current ICMJE Form for the Disclosure of Potential Conflicts of Interest is available and downloadable in PDF at their website.  To enter your comments on the proposed form, please click here.

Recent Articles Published by Central IRBs

ADVARRA IRB:  

Key Biosafety Considerations for Coronavirus Research: This article provides an overview of the coronavirus and describe strategies for developing medical countermeasures to combat the recent outbreak.  A description of the opportunities, risks, and risk mitigation strategies for coronavirus are also discussed in this article.

Beyond the Regulations: More Considerations for Emergency Research: this article describes what the researchers and research organization must know about “Emergency Research.” The authors explain emergency research is only feasible if a plan is in place.  These plans include but are not limited to the establishment of a front-line staff communication plan, an evaluation of clinical operations, and a plan to respond to media inquiries.

Western IRB (WCG):

Your 5 Questions About Enrollment Assistants Answered: In this article WCG describes the services they provide through “Enrollment Assistants” (EAs) for recruitment, and enrollment in clinical studies.  Mark Summers, president of patient engagement from WCG addresses the following questions: (1) how can a person from outside the study team legally work at a site? (2) How accepting are sites of EAs–especially sites that have never worked with one? (3) Are EAs trained onsite or by WCG Three Wire? (4) Would an Enrollment Assistant be more beneficial to, say, a large academic center than to a small standalone research site? (5) How do you keep track of your enrollment performance metrics?

COVID-19 Preparedness for Health Care Institutions: Insights Paul Biddinger, MD and Scott Gottlieb, MD:  This article is a summary of takeaways and key points from the March 13, 2020 webinar sponsored by WCG.

Regulatory Framework for Research with Mobile Applications

The following information was drawn in large part from the CITI Program’s module titled “Mobile Apps and Human Subject Research.” The content of this module is copyright.  Uconn Health obtained permission to use this module from the CITI Program.

A mobile application (mobile app or app) is a type of application software designed to run on a mobile device, such as a smartphone or tablet computer.  Medical mobile apps (MMAs) are medical devices that are mobile apps, meet the definition of a medical device and are an accessory to a regulated medical device or transform a mobile platform into a regulated medical device.

Research with apps may be subject to multiple federal regulations such as 45 CRF 46 (The Common Rule), the U.S. Food and Drug Administration (FDA) regulations (including 21 CFR 11), and the Health Insurance Portability and Accountability Act (HIPAA) rule.  Specifically, the FDA regulates mobile health technologies that meet the definition of a medical device.  When a covered entities or business associates use software and mobile applications store or transmit protected Health information (PHI) this falls within the jurisdiction of the Office of Civil Rights (OCR) under the Department of Health and Human Services (HHS).   Researchers may use the information provided on the FDA website to determine if an app meets the definition of a medical device regulated by the FDA. Researchers may use the interactive tool developed by the Federal Trade Commission (FTC), in conjunction with HHS, the Office of the National Coordinator for Health Information Technology, the OCR, and the FDA to determine which laws apply to mobile health applications

When using apps in research investigators should consider the following points:

• If Consent occurs via an app the investigator should be aware that the consent document must contains all the required elements required by the Common Rule. The risk of hacking posed by the electronic consent is to be described in the consent document.
• The requirements of the IRB for an electronic informed consent process are described in the IRB Policy #  2011-008.1.pdf – Informed Consent – Process –page 4.
• Ample time to contemplate participation and ask questions will also be applicable to electronic consent, therefore  app-based consent should contain a functionality to satisfy this requirement described in the IRB Policy # 2011-008.5.pdf – Informed Consent – Providing and Obtaining Informed Consent  
• Because mobile apps may use, collect, store, and share data, researchers should communicate the risks of the mobile device security to the subjects and the measures in place to minimize the chance of a breach of confidentiality.   If a mobile app is being used to collect protected health information the researcher must obtain an assessment from UConn Health’s I.T. department that the app is HIPAA compliant.

• The “Terms of Services” (TOS) and/or “End-User License Agreements” (EULAs) associated with the mobile apps, and devices are between the user and the service/provider, not the user and the researchers.  Agreeing to TOS/EULA is different from consenting to participation in research. These agreements may require review by the IRB because they are materials for the subjects, and may include information that would affect a subjects’ decision to enroll in a study.  Differences between these documents and the consent form should be communicated to the subject.

• When the research may result in collection of incidental data (e.g. use of a mobile fitness app), the researchers must indicate to the IRB what incidental data they may collect, and if this data will be disclosed to subjects.  In addition, investigator should clarify whether they will keep that data and if so provide the plans to protect that data.

UConn Health Institutional Policy for Mobile Devices &  Consequences of Non-Compliance with HIPAA Rules

 According to UConn Health Institutional Policy # 2008-03 –  Mobile Computing Devices (MCD) Security, confidential or restricted data is not authorized to be stored on either a UConn Health or non-UConn Health Mobile Computing Devices ( MCDs) unless all the criteria below are met:

1. The device stores only the minimum data necessary to perform the function necessitating storage on the device.

2. Information is stored only for the time needed to perform the function.

3. The device requires a password for access and is encrypted using methods authorized by the UConn Health IT Department.

In addition, users may not bypass or disable UConn Health required security mechanisms, and unauthorized physical access, tampering, loss or theft of an MCD must be reported to UConn Health Public Safety.

Failure to adhere to this institutional policy and associated procedures may result in sanctions as per applicable UConn Health policy.   Failure to adhere to this policy could also lead to monetary fines imposed by the Office of Civil Rights  should a breach occur.  For example, the University of Rochester Medical Center ( URMC) filed a breach reports with the Office for Civil Rights (OCR) of the U.S. Department of Health and Human Services (HHS) in 2013 and 2017 following its discovery that protected health information (PHI) was impermissibly disclosed through the loss of an unencrypted flash drive and theft of an unencrypted laptop, respectively.  To settle the violations of the Health Insurance Portability and Accountability Act (HIPAA) privacy and security rules, the URMC agreed to pay $3 million to the Office for Civil Rights and follow a corrective action plan.  A description of their corrective action plan and the two years of compliance monitoring have been posted in the HHS website.

To learn the provisions/controls defined by UConn Health IT Security when using institutionally owned devices or personally owned devices and the MCD’ user responsibilities, please review the Mobile Computing Devices (MCD) Security Institutional Policy # 2008-03.

Clarifying the CDA Process: A  Researcher’s Guide to Handling Confidentiality Agreements

 By Dr. Cherron Payne, Esq.

Introduction

The administration of a research study may be an arduous process for researchers and staff.  Moreover, the legal aspect concerning research agreements may also be equally perplexing. Thus, this article is intended to clarify the proper procedure for handling confidentiality agreements.

Confidentiality Agreements

 The nomenclature of confidentiality agreements is varied; some agreements are called confidential disclosure agreements, non-disclosure agreements or NDAs, and mutual disclosure agreements.  Although the title of the agreement may vary, the agreement serves the general purpose of protecting the confidential information that is disclosed by research sponsors. Confidentiality agreements will hereafter be referred to as a “CDA”.

Before a study commences, the sponsor needs to disclose information for the researcher to evaluate his or her interest in the study.  The disclosed information is often confidential because it contains proprietary information or trade secrets often in the form of models, prototypes, notes, diagrams, documents, reports, memoranda, and other forms of intellectual property. Therefore, it is imperative that researchers manage confidential information in accordance with the terms and expectations of the CDA.  A researcher’s failure to properly safeguard confidential information may impose serious legal ramifications upon UConn Health.  Moreover, breaching the terms of a CDA, or improperly disclosing confidential information, may also cause study sponsors to cease sponsoring UConn Health’s research.

Procedural Steps for Researchers

 In order to avoid legal pitfalls, there are specific steps that a researcher or principal investigator “PI” must follow when a confidentiality agreement is received.

1. The PI should first e-mail the CDA to the proper contract specialist.  The PI should also e-mail the research sponsor’s contact information to the contract specialist.  If the researcher is uncertain as to the appropriate contract specialist, then the researcher may contact Sponsored Program Services at 860-679-4040, by e-mail at sps@uchc.edu, or by reviewing the website of the Office of the Vice President for Research at   https://ovpr.uchc.edu.  The PI should never sign a CDA or agree to its terms without a contract specialist negotiating the agreement.
2. If a PI receives a research study agreement without receiving a CDA, the researcher should (a) ask the study sponsor to send a CDA or (b) ask the contract specialist to request the CDA. The study agreement should not be negotiated before the CDA has been negotiated and signed.
3. While negotiating the CDA, the contract specialist may have questions for the researcher or may require additional information. Researchers must furnish said information in a timely manner to avoid a delay in the negotiation.
4. After the CDA has been negotiated, it is sent to the principal investigator for signature.  The PI should read the agreement before signing, in order to be cognizant of the CDA terms and to properly safeguard confidential information.  If there are any questions regarding the terms of the agreement, a PI may ask the following contacts for clarification:  (a) the contract specialist, (b) the Director of Sponsored Program Services at hudobenko@uchc.edu, or (c) the Executive Director, Sponsored Program Services and Faculty Services at laura.kozma@uconn.edu.
5. After the CDA has been reviewed, the researcher signs the agreement and promptly returns it to the contract specialist.

When the contract specialist receives the fully executed CDA, a copy will be returned to the researcher or the research staff.  A fully executed copy of the CDA should be retained by the researcher to ensure compliance with the agreement.

 Recent Articles Published by Central IRBs

ADVARRA IRB:

Reporting to the IRB: What NOT to Report:  This article provides an overview of what the regulations do and do not say about IRB reporting requirements. 

Should Social Media Be Part of Your Research Toolbox?    This article discuss the benefits, the risk and the applicable regulatory requirement when using social media for recruitment and retention:

Western IRB (WCG):

 An Overview of the Recent SACHRP Recommendations Around Payments in Clinical Research The U.S Department of Health and Human Services Secretary’s Advisory Committee on Human Research Protections (SACHRP) has approved two sets of recommendations regarding payments in research.  The first set of recommendations identified a number of considerations for IRBs when evaluating the acceptability of incentives payments.   The second set of recommendations addresses those studies that ask potential research participants to bear some or all of the cost of the research.  SACHRP’s issued several questions prospective subjects and IRBs should ask when participants are required to pay for access to the experimental intervention.

How to Mitigate Placebo Response, Test, Train and Control Expectations in Analgesic clinical trials   This article discusses the importance of training patients to be able to report their symptoms more accurately and the importance of staff training.

IRB Forms – Update

The Pharmacy section of Appendix A.to the application and the application checklists have been revised to reflect the change in pharmacy contact to Jennifer Czerwinski, 860-679-2085, jczerwinski@uchc.edu

 The HIPAA Request for Alteration or Waiver of Authorization.doc was modified to allow a brief description of the PHI to be used/accessed with reference made to documents within the submission that describe the information in more detail.

 The HIPAA authorization form was revised to delete reference to the Office of Research Compliance as it is no longer a stand-alone office and to change reference to John Dempsey Hospital to UConn Health and to change HSPO to HSPP.

 The Human Subject Research Determination form was revised to provide more instruction regarding the attachment of documents related to the funding source of a project.

The instructions for reliance on ADVARRA IRB were revised to reflect changes to the consent language template and the instructions for reliance upon WIRB were revised to add reference to the site number assigned to UConn Health.

Why should I register my study on ClinicalTrials.gov?

• If you wish to comply with the ICMJE policy (followed by the BMJ, JAMA and many others journals) requiring registration as a condition of consideration for publication, you may voluntarily register your study with ClinicalTrials.gov. You must register prior to subject enrollment.

• If your clinical trial is NIH funded, in whole or in part, you are required to register the study and report results on ClinicalTrials.gov.

• If your clinical trial is funded by a Federal department or agency, the Revised Common Rule requires that your consent form be posted on a public platform, like ClinicalTrials.gov, after the trial is closed to recruitment, and no later than 60 days after the last subject visit.
• If your clinical trial evaluates at least one drug, biological, or device product regulated by the FDA (See this decision checklist for more details), regardless of funder, you are required to register and post results on ClinicalTrials.gov.

For assistance with ClinicalTrials.gov, see our webpages and contact UConn Health’s ClinicalTrials.gov Administrator, Ellen Ciesielski (860.679.6004) in Research Integrity and Compliance Services.

Research Advertisement Reminder

All methods and materials to recruit participants for research require IRB review prior to implementation. Please be sure all recruitment materials (e.g., text of announcement) are IRB-approved before submitting an announcement for publication.  Announcements must include IRB# and name of approving IRB (if not the UConn Health IRB).  For guidance, visit: UConn Health IRB  and  Guidelines for submitting recruitment announcements  

Managing Research Studies

 Managing research studies efficiently and effectively requires leadership, planning, collaboration, and communication.

The Principal Investigator (PI) is responsible for the overall management of an approved study. Management of a study encompasses the ethical, technical, administrative and fiscal elements of the research study.

The PI is responsible for ensuring that the research team is oriented to the protocol and aware of their responsibilities. The study team should have specific details about the plans to accomplish the goals and procedures of the study, inclusive of plans for recruitment, consenting of subjects, data and safety monitoring, and protections for privacy and confidentiality.

The PI is also responsible for ensuring that adequate resources are available to conduct the study, including equipment, supplies, and storage space at UConn Health and in any outpatient facilities. Prior to seeking IRB approval, the PI should communicate with the leadership of any ancillary areas that may become involved with the research to ensure the area can commit the necessary resources (e.g. staff, hospital beds, equipment etc.).

Communicating with appropriate areas to ensure resources are available and educating all members of the research team on their roles and responsibilities will help to ensure that the research is implemented in a safe and compliant manner.

Human Subjects Training- Educational Requirements

I completed CITI Training under my affiliation with a former institution.  Is that CITI Certificate valid at UConn Health?

CITI Training completed within the last three years may satisfy the UConn Health IRB requirements.  However, the IRB reserves the right to require that an individual complete additional modules.

The IRB encourages individuals who are new to UConn Health (e.g. a new student, new faculty member) to complete CITI training under their new affiliation with UConn Health. When completing modules under the new affiliation to UConn Health the CITI Program will provide credit for any overlapping modules completed under another institutional affiliation and will require completion of any modules that are specific to UConn Health requirements.

To affiliate one’s account in the CITI Program with UConn Health, individuals should log into the CITI program, and click on “Add Affiliation” listed under the “Courses” Menu.  To find UConn Health in the drop down box, the following words “University of Connecticut” must be typed.  Then, select “University of Connecticut Health Center”.  To complete the process, check the box next to the statement: “I AGREE to the Terms of Service for accessing CITI Program materials”   and check the box with the statement: “I affirm that I am an affiliate of University of Connecticut Heath Center.” Last, click on “Continue.”

To select the correct learning group and courses, follow the “Course Enrollment Questions” posted at  https://ovpr.uchc.edu/services/rics/hspp/citi-instructions/

I will be conducting a Clinical Trial at UConn Health.  Should I complete the “Good Clinical Practice (GCP)” course?

It depends on whether or not the clinical trial is supported by the National Institutes of Health (NIH). The GCP training is a requirement if the clinical trial is an NIH funded trial.  The Human Subjects Protection Program/IRB strongly encourages researches who are involved in clinical research trials not supported by the NIH to complete the GCP course.

Reporting Non-Compliance to the IRB

Principal Investigators are responsible for being knowledgeable of and following the IRB policy for reporting non-compliance (i.e.  Policy 2009-002.0.pdf – Reporting Non-Compliance to the Institutional Review Board).   Noncompliance is defined in Policy 2011-007.0 as any action that is taken or occurs that is not in accordance with an IRB approved study, IRB polices or regulations or that represents a failure to follow the requirements and/or determinations of the IRB.

Principal investigators (PIs) should report to the IRB any non-compliance that was within the control of the research team within 5 business days of becoming aware of the event.  To do so, PIs should complete and submit a Problem Report Form through the IRB online submission system, iRIS.  When the non-compliance was not within the control of the research team it should be reported at the time of continuing review.  If continuing review is no longer a requirement, non-compliance that was not within the control of the research team should be documented and tracked by the study team and available for review should the study be selected for audit.

Whenever any non-compliance is reported, the investigators should describe the details of the event, the underlying causes of the noncompliance and the actions that have been taken or will be taken to correct the problem and to prevent a subsequent occurrence. PIs should also describe whether the occurrence suggests that subjects or others are placed at an increased risk of harm.  This information allows the IRB to accurately assess the situation to determine whether the non-compliance rises to the level of serious and or continuing non-compliance as defined in IRB Policy 2011-007.0 – Definitions Applied to Policies. If the event does rise to the level of serious and/or continuing non-compliance there may be additional reporting required if the research is Federally funded or subject to FDA oversight.

If there is any question about whether reporting is required it is always better to err on the side of caution and report the issue.   PI’s are also encouraged to contact one of the Regulatory Specialists to discuss any questions about reporting requirements.

 Are you responsible for updating a ClinicalTrials.gov record?

 Are you responsible for updating a ClinicalTrials.gov record? You may want to subscribe to the new ClinicalTrials.gov bulletin “Hot off the PRS!” The bulletin details recent updates to the Protocol Registration and Results System (PRS) as well as new resources for PRS users. Enter your email address next to “Receive Updates” at the top of their webpage to subscribe. For help with registering your record or related questions, contact UConn Health’s PRS Administrator, Ellen Ciesielski at 860.679.6004 or eciesielski@uchc.edu.

IRB Forms – Update

 The Instructions for Requesting Reliance Upon Advarra IRB.docx  have been update to reflect the new contact names at Advarra IRB.  Investigators may contact Kathleen Rankin or Ashley Carpenter for guidance in making a submission to Advarra IRB.

Recent Articles Published by Central IRBs

Advarra IRB:

• Gene Therapy: Gene therapy research is at the forefront of a coming boom in the clinical setting. Understand the  growth, risks, and regulatory requirements by reading How Centralized IBC Review Can Benefit Gene Therapy Research
• IRB Review of Participant Compensation: IRBs are in charge of reviewing the amount of payment, as well as the method and timing of disbursement, to ensure that the payment plan does not present potential undue influence. Participant compensation is often a complicated matter, what an IRB should consider is discussed at Compensating Clinical Trial Participants: The Basics  

Western IRB (WCG):

• Participants Training has a direct impact in achievement the objectives in Clinical trials: Lack of training, particularly for patients, creates variability detrimental to trial findings, says Nathaniel Katz, founder and chief science officer of WCG Analgesic Solutions. To learn more about this topic click on: Lack of Training Compromises Trial Results.
• Recruitment: Recruitment is what drives a study. No patients, no research, right? Sites, sponsors and CROs know they need to do it, but they don’t really consider all the implications or differing strategies to recruitment .To learn more about this topic click on: What You Don’t Know About Patient Recruitment Can Impede the Success of Your Trial

Reporting Race and Ethnicity Data when Requesting Continuing Review

 “Researchers assumed that what they learned about white male participants could safely applied to anybody, regardless of gender, race, ethnicity or other variables.  We now know that this is not true.  When you are communication about research results, it’s vital not only to explain how a study was done, but was being studied,” says Dr. Eliseo J. Perez-Stable, Director of the National Institute on Minority Health and Health Disparities in his article titled: Communicating the Value of Race and Ethnicity in Research.

In August of 2001, The National Institute of Health (NIH) issued a policy which adopted the 1997 Office of Management and Budget (OMB) revised minimum standards for maintaining, collecting, and presenting data on race and ethnicity for all grant applications, contract and intramural proposals and for all active research grants, cooperative agreements, contract and intramural projects.  The goal of this policy is to ensure that the distribution of study participants by sex/gender, race and ethnicity reflects the population needed to accomplish the scientific goals of the study.

UConn Health IRB Main Consent Form Template .doc contains an Addendum Form titled “Personal Census Data”.  This form provides a mechanism for capturing the representation from  racial and ethnic groups in research studies conducted at UConn Health. This addendum form provide instructions to investigators, to present this form to subjects at the time of consent for completion.

The categories and definitions in the “Personal Census Data Sheet” are commonly used for federal data collection purposes. The form’s standards consist of two categories for ethnicity: “Hispanic or Latino” and “Not Hispanic or Latino” and five categories for race: American Indian or Alaska Native, Asian, Black or African American, Native Hawaiian or Other Pacific Islander, and White.

Investigator with full board studies or expedited submissions requiring continuing review are required to report this data at the time of request for continuing review.

Investigator should count all subjects who provided consent since the start of the study, including subjects who were screen failures or withdrew.  Investigators should indicate by gender the number in each racial/ethnic group. The total reported numbers should equal the total reported since the start of the study in the first table (e.g. first request for continuing review).

The table to be completed within the continuation form in IRIS is provided here for reference.

UConn Health’s Human Subjects Protection Program Receives Reaccreditation from the Association for the Accreditation of Human Research Protection Programs (AAHRPP)

 The Association for Accreditation of Human Research Protection Programs (AAHRPP) completed a site visit at UConn Health in April 2019.  During this visit, IRB members and staff, investigators and study coordinators, and others involved with research oversight were interviewed, and study research records were reviewed.  In June 2019, the AAHRPP Council on Accreditation awarded full reaccreditation to UConn Health’s Human Subjects Protection Program (HSPP), confirming that all standards for re-accreditation were fulfilled.   This reaccreditation is for five additional years. The final report issued by AAHRPP commends the HSPP for demonstrating an unusually high degree of integration among the areas responsible for research oversight.

Documentation of Consent

Unless the requirement to document consent has been waived by the IRB, the IRB approved consent form must be signed and dated by the subject (or legally authorized representative) and the person obtaining consent.

Notes in a research chart that indicate on-going discussions with the subject at subsequent study visits may supplement documentation of the initial informed consent process.

The following are examples of issues found with documentation of consent during recent internal audits at UConn Health.

• The date of consent differs between the subject and the person obtaining consent.
• The date of consent is left blank by the subject and/or the person obtaining consent..
• The date of signature is incomplete or incorrect.
• The informed consent form is missing the signature of the person obtaining consent.
• The person obtaining consent enters the date of the subject’s signature.
• Consent for participation obtained from legally authorized representatives when the study approval requires the subject to provide consent.
• Consent was obtained by people not approved as consenters by the IRB.
• Subjects consented with expired consent documents.
• Consent forms containing a correction to the signature and/or date which obscured the original entry.

To ensure consent is appropriately documented the following points should be considered:

• The principal investigator and study team members should use the most recently approved stamped and dated consent form when obtaining consent.
• Subjects should sign the consent form in the presence of, and at the same time as, the consenter.
• Persons obtaining informed consent should review the forms once they are signed/completed and before the subject leaves that day, to ensure that all signatures and dates are properly entered on the forms.
• In the event that a form is found to be incomplete (e.g., a date is missing) if the error is not discovered while the subject is present, the research staff should prepare a note to file attesting to the fact that they witnessed the signing of the form, and the date that it was signed.  The original consent form must be retained, and the subject should make the corrections at the earliest opportunity.
• Any problem with documentation of informed consent should be reported to the IRB using a problem report form within five days of becoming aware of the non-compliance.
• Approved consenters should review HSPP Policy 2011-008.1.pdf – Informed Consent – Process  and Policy 2011-008.5.pdf – Informed Consent – Providing and Obtaining Informed Consent  

Guidance for Posting Clinical Trial Consent Forms

Last January 2019, the revised version of 45 CFR 46, the federal regulation for the protection of human subjects in research, which is also known as the Common Rule, went into effect.  One of the revisions requires that for any clinical trial conducted or supported by a Common Rule department or agency, one IRB-approved consent form that was used to enroll subjects be posted on a publicly available federal website within a specific time frame.   UConn Health IRB has posted a Guidance for Posting Clinical Trial Consent Forms to help the research community to fulfill this obligation.

IRB Forms – Update

 Investigators should always use the latest version of the IRB forms posted in the IRB website.  Listed below, are the forms revised during the past three months. Within the parenthesis is the date when forms were revised.

• Instructions for Requesting Reliance Upon Advarra IRB.docx (4/24/2019 – template consent language updated per Advarra requirement)
• Confirmation of Resources for Inpatient Stays.docx (4/25/2019 – added comment section in sign-off area)
• Request for Full or Partial Waiver Informed Consent.doc (4/25/2019 – added note that approval of waiver not applicable to information/samples if original consent stated there would be no future use of information/samples)
• Application Appendix A.doc (CRC Resource Request) (5/21/2019 by CRC)
• Application Checklist for Initial and Continuing Review Full Board.docx (6/25/2019 – changed pharmacy contact)
• Application Checklist for Initial Exempt Application .doc(5/1/2019 – removed CICATS references)
• Application Checklist for Initial and Continuing Review Expedited .doc (6/25/2019 – changed pharmacy contact)
• Application Checklist to Request Facilitated Review for Industry or Cooperative Group Sponsored Study, or study utilizing the SMART IRB Initiative.docx (6/25/2019 – changed pharmacy contact)
• Main Consent Form Template .doc (6/12/2019 – changed reference Health One to EPIC, added reminder about mobile device security, rather than instructional text/samples about when FDA/DHHS/Sponsor can inspect records changed to “as may be applicable” and reference all three.)
• HIPAA Authorization to Use and Disclose.doc (6/28/2019 – deleted instructional text at top of form)
• HIPAA Authorization to Use and Disclose – Spanish.doc 6/28/2019 )

Personnel Changes to the Scientific Review Committee

 Dr. Doug Peterson who has served as the Chair of the Scientific Review Committee (SRC) for over a decade has stepped down as Chair. Dr. Julie Wagner is now the SRC Chair and Dr. Peterson will continue to serve on the SRC as a member until November 1.

The following three faculty members have been appointed to serve on the SRC.

• Dr. Efthimia Ioannidou, Professor/Clinical, Periodontology
• Dr. Ivo Kalajzic, Professor/Basic Science, Center for Regenerative Medicine
• Dr. Tannin Schmidt, Associate Professor/Basic Science, BioMedical Engineering

In Memoriam – Pamela Engelson Colwell

Our dear friend and colleague, Pamela E. Colwell (Pam) passed away on Wednesday, June 26, 2019.  Pam worked for the IRB for the last 15 years as a Regulatory Specialist and IRB member. Pam was an amazing team member, taught multiple IRB members, and played a pivotal role in the implementation of the iRIS submission system.  Please refer to the following link for information regarding services and memorial donations. http://northhavenfuneral.com/obituary/pamela-engelson-colwell/

ResearchMatch.org is a national online recruitment tool, funded by the National Institutes of Health and maintained at Vanderbilt University. ResearchMatch connects researchers with individuals interested in participating in research studies, through its secure, online matching tool. There is no cost to UConn Health researchers to use ResearchMatch.

To learn more about using ResearchMatch for your studies, register for the free ResearchMatch Researcher Webinar Training/Live Demo on Thursday, July 12, 2018 from 3:00 p.m. – 4:00 p.m. The training is open to all research staff. After registering, you will receive a confirmation email with instructions on joining the training.

The team at ResearchMatch will show you how to register your studies, create a cohort of potential volunteers and send out contact messages and surveys. They will also cover how to send a pre-screening (eligibility) survey, contact the volunteers that replied ‘yes’ to your initial message, and manage your enrollment continuum.

To register for the training, click here:

https://attendee.gototraining.com/r/9112903382698216193

For additional information, contact Ellen Ciesielski (eciesielski@uchc.edu; 860-679-6004).

Delay of Revised Common Rule and Revised UConn Health IRB Policies  

Implementation of the revised version of the Federal regulation governing federally funded/supported research (i.e. 45 CFR 46, also known as the Common Rule) has been delayed until July 19, 2018. In spite of this delay, the UConn Health IRB has moved forward with implementing several changes that aim to reduce regulatory burden on investigators while still offering protection to research participants, complying with current regulatory requirements and being prepared to comply with the revised requirements.

Several IRB forms, templates and policies have been revised. Understanding the reasons for these changes, what has been changed and to what type of research these changes apply may aid investigators in complying with IRB polices as well as with federal regulations.

The following table lists the UConn Health IRB polices that have been changed, a description of the change and the IRB forms that have been modified due to the policy revisions.

Frequently Asked Questions Related to CITI Training, IRIS System and Facilitated Review

I completed my CITI human subject’s protection training recently.  Should I submit my CITI Training Certificate to the IRB?

If an external investigator completed CITI training through another institution, s/he must submit proof of having completed human subject’s protection training to the IRB because the IRB does not get automatically notified of such completions.

If the investigator is affiliated with UConn Health, he/she does not need to submit a certificate of completion. The IRB staff receives the CITI Training certificates one day after individuals have completed the training. Designated IRB staff enter the course completion information into a master training list (Excel) posted in the IRB website and into IRIS. This master training list (Excel) is updated every two weeks. Therefore, investigator should check this list often. In order for the IRB to update the training records in the IRIS system investigators affiliated with UConn Health must have logged into IRIS at least once. Therefore, investigator who have never before log into IRIS should do so right after they have completed the CITI Training. To log into IRIS investigator should click on the following link: https://imedris.uchc.edu , enter their UConn Health network credentials in the ID and PW boxes found in the IRIS logging page, and click on Log in.

I am going to submit an application to UConn Health IRB for review and approval.

Do I need to request an account in IRIS?

Every individual who is affiliated with UConn Health can use the UConn Health ID and password to log into IRIS. Therefore, individuals affiliated with UConn Health (faculty, staff, students, residents, and fellows) do not need to request an account in IRIS.

On the other hand, individuals external to the UConn Health will need to request an account in IRIS. To do so the external investigator must complete the online request form accessible from the IRIS home page. Investigators must complete all the required fields on the form indicating why the account is necessary and with whom at UConn Health he/she will be working. The IRB designated staff may contact the person in UConn Health to confirm that the creation of this account is necessary. Accounts will be created within 1-2 business days.

I have completed an application for IRB review in IRIS. I do not see the sections that allow me to attach documents for review? What should I do?

Unfortunately, the IRIS system currently has a glitch that does not transition the application form to the submission package where you can attach documents.  Follow the steps listed below when you get to the last section of the application for initial review and you see a sign stating: “Study Application Completion. You have completed the Study Application process. Click here to go to the …”

• click on the “Back Button” ( located in the upper right hand corner)
• Click on “Study Assistant” menu
• click on “My Studies” sub-menu,
• Open the study, and there you will find Section 1- Submission Packet to the Review Board.
• Click on “Save and Continue to the Next Section” to build the following sections of the forms that will allow you to attach documents.

I am affiliated with UCONN Health (e.g. faculty member, student, employee, or resident, fellow) and I will be part of a study conducted at another institution. That institution has reviewed and approved the study. Do I need approval from the UConn Health IRB?

Yes, if you are affiliated with UConn Health and you are acting in that capacity, your involvement in a research study engages UConn Health in the research and therefore the UConn Health IRB must be involved.   However, as opposed to conducting a formal review the UConn Health IRB may elect to rely on the IRB of the other institution. To determine if the UConn Health IRB will do this you, you must submit an application for facilitated review to the UConn Health IRB. By submitting this application you will obtain an official determination from the UConn Health IRB as to whether oversight for the study will be deferred to the external IRB. In order for the UConn Health IRB to defer oversight a written agreement must exist between to the two institutions.  This agreement is referred to as an IRB Reliance Agreement.  Investigators may contact the IRB to determine if such an agreement is in place or needs to be established.

The Office of the Vice President for Research would like to announce that the 2017 Individual Financial Disclosure in Research reporting period has started today. In order to remain in compliance with university policy and federal regulations, UConn Health employees who are involved in research are required to complete an annual questionnaire in the UConn Health COI-SMART electronic disclosure system.

An automated e-mail inviting applicable employees to complete the questionnaire should be in your inbox. The sender name on the e-mail is UConn Health Financial Disclosure in Research.

If you did not receive an automated e-mail invitation and believe you need to complete the form, or if you have any questions regarding the form or the disclosure requirements, please contact Gus Fernandez-Wolff in the Office of the Vice President for Research, Research Compliance Services at x8125 or gfernandez@uchc.edu.

Thank you for your cooperation.

For more information, contact: Gus Fernandez-Wolff at x8125 or gfernandez@uchc.edu