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.

 

SELF -AUDIT TOOL/CHECKLIST
INFORMED CONSENT PROCESS & DOCUMENTATION	Consenter Initials
The consent process was conducted using the latest approved and stamped consent form
The consent process occurred in a private setting
The consent process was conducted in a language understandable to the  subject
The consent process started with a potential participant being given the opportunity to review the informed consent form and it was followed by a discussion about the research
The process was  free of coercion or undue influence
The process provided the subject, sufficient time to discuss, ask questions and consider whether or not to participate
Once the subject had all his/her questions answered and had ample time to consider the information s/he decided whether or not to participate.
If documentation of consent was not waived by the IRB (e.g., informed consent form contains signature lines) informed consent process was documented in an IRB approved informed consent form.
The consent form was signed and dated by the subject (or legally authorized representative) in the section assigned to the participant
The consent form was signed and dated by the investigator in the section assigned to the investigator
All names, signatures and dates were entered in the document on the same date and at the same time
After the signatures were entered in the consent form the participant was  provided with a copy of the complete signed informed consent document
At the conclusion of the consent process, the investigator provided a Research Participant Feedback form to the subjects.
The signed consent form has been stored in accordance with the plans for storage described in the study application and protocol (e.g., consent form was filed in research folder, or in separate secure location apart from research record, or in the medical record).

 

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:

 

Form	Who is Required to Sign
Initial submission form for a new study	All key study personnel identified on the application form, excluding those who are listed only as a contact person.
Correction form	Any member of the study team, most often the study coordinator.
Response form	The Principal Investigator (PI)
Continuation Form	The Principal Investigator (PI)
*Modification Form	The Principal Investigator (PI)
Problem Report Form	The Principal Investigator (PI)
Closure Form	The Principal Investigator (PI)
When only the PI is required to sign the form on the routing sign-off sheet, the boxes next to the names of the other key study personnel should be unchecked.   *When new personnel are being added to the study through a request for modification, they will be asked by the IRB to sign off as a contingency for approval.

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.

 

Ethnic Category	Females	Males
Hispanic or Latino
Not Hispanic or Latino
Unknown
Racial Category
American Indian/Alaska Native
Asian
Native Hawaiian or Other Pacific Islander
Black or African American
White
More Than One Race
Unknown or Not Reported

 

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/