Questions Related to the Need for IRB Review

Q: Does a case study / case series require IRB review?

A:  Research is defined as a systematic investigation, including research development, testing and evaluation, designed to develop or contribute to generalizable knowledge. Consistent with many other institutions, UConn Health does not consider a write up of a single case, or two or three cases, as constituting research. The retrospective summary of such a few number of cases is not considered to meet the definition of research.  A review of four or more cases is considered to meet the definition of research and prospective IRB review is required.

Q: When should I submit a Human Subject Research Determination Form?

A: The Human Subject Research Determination Form can be submitted when an individual is considering a project that s/he does not think constitutes human subject research, but would like an official determination made by the IRB prior to initiating the project.  A representative of the IRB will review the form and make the final determination as to whether the proposed activity meets the definition of human subject research. If the reviewer determines the project does not constitute human subject research the IRB will have no further involvement. If the reviewer determines that the project does constitute human subject research a complete IRB application will be required. Determination are usually made within two weeks of the date the IRB received the request for determination.

Q: Does a student project involving humans require IRB review?

A: If the project meets both the definition of research and human subject IRB review is required.   The definition of research is often key in determining if a student project needs IRB review.  Research is defined as a systematic investigation designed to develop or contribute to generalizable knowledge.  If a student project is not designed to develop or contribute to generalizable knowledge (e.g. it will be used only to satisfy a curricular requirement), it would not meet the definition of research.  Master’s or Doctoral proposals are typically designed to develop or contribute to generalizable knowledge so IRB review for such is typically required if the project also involves human subjects.   IRB approval cannot be granted retrospectively. Students are therefore encouraged to complete a Human Subject Research Determination Form prior to starting any activity for which a question exists as to whether it constitutes human subject research.  That form can be used to self-determine whether IRB review is required; or it can be thoroughly completed and submitted to the IRB for a formal determination.

When students at UConn Health are involved in the conduct of human subjects research at an external institution, please consult this engagement guidance document to ensure any IRB requirements at UConn Health are addressed.

Q: What type of IRB review is required for a research project using existing specimens?

A: It depends on whether the existing specimens are identifiable.  If not, and if the investigator will make no effort to re-identify the specimens, the specimens do not meet the definition of human subject and IRB review would not be required.   If the specimens are identifiable, or efforts will be made to re-identify the samples, IRB review is required.  Research that only involves the use of existing identifiable samples may qualify for exemption if one of the following is true:

• the specimens are publicly available
• information is recorded in such a manner that the identity of the human subject cannot readily be ascertained directly or through identifiers linked to the subjects, the investigator does not contact the subject and the investigator will not re-identify subjects.

Q: Does a pilot study have to be reviewed by the IRB?

A: Yes. Any study involving human subjects, regardless of the number of subjects to be involved, must be reviewed and approved by the IRB prior to initiation.  Because the purpose of a pilot study is to test the feasibility of a design that is intended to be used on a larger scale a pilot study is considered be “designed to develop or contribute to generalizable knowledge”.

Q: If I am going to do research on excess specimen samples (i.e., urine, blood, skin, etc.) that are being collected for a clinical purpose and that are otherwise going to be thrown away, do I have to get IRB review?

A: If the samples are to be used for a research purpose, and if at any point in time the investigator can link a sample (directly or through codes) to the individual from whom it came, IRB review is required. If information is record in such a way that individuals from whom the sample came cannot be identified the research may qualify for exempt status.

Q: If I am doing research on cadavers or on samples obtained from cadavers, do I have to get IRB review?

A:  IRB review is not needed as the definition of human subject pertains to living individuals. However, if personal identifying information is linked to the materials, then HIPAA must be appropriately addressed.  The Assurance of Using Decedent Information form must be submitted to the IRB, which also acts as the HIPAA privacy board for research purposes.

Q: If I want to make a change to my study after I’ve received approval, do I need IRB approval again?

A: Yes. Any change to a previously approved non-exempt study must be reviewed and approved by the IRB prior to implementation. This includes changes to any document related to the study (e.g. informed consent form, surveys, advertisements, recruitment letters, etc.) You will need to submit the form to request a modification / addendum to a previously approved study. The only exception to this is that a change can be implemented if it is needed to eliminate immediate harm to subjects or others. Such changes must be reported to the IRB within 5 business day.  Investigators are encouraged to seek approval for any modification to an exempt study to ensure that the change does not invalidate the exempt status of the study.

Q: How does the mandate for single IRB review for multi-site federally supported research apply?

A: The NIH has published a list of frequently asked questions pertaining to the requirement for single IRB review.  Please review this list.   If your question is not addressed by this list, you may contact the IRB.  Please note, the UConn Health IRB does not intend to act as the single IRB for NIH funded multi-site research.  IRB reliance agreements are in place between UConn Health and commercial IRBs that are willing to act as the single IRB, and additional IRB Reliance agreements can be entered into if needed.

Questions Related to IRB Submissions:

Q: Once I submit my application, how long does the IRB review process take?

A: Review of exempt and expedited applications occurs on an on-going basis. Screening of the application will generally occur within 7 to 10 business days of receipt. Any concerns will be communicated to the investigator through iRIS. Once all concerns have been addressed the application will be forwarded for official review. Studies requiring full board review must be submitted by the published deadline. This allows sufficient time for the committee to review the application prior to the meeting. After the meeting the minutes must be prepared and approved by the committee before letters are sent to the investigators. Therefore, investigators should not expect an official letter until 7 to 10 business days after the meeting. Note that you may not begin your research until you have received final, unconditional approval from the IRB.

Q: Can I e-mail my IRB materials to the IRB office?

A: IRB forms (applications, requests for continuation, requests for modifications, problem reports) and supporting documents should be submitted through the iRIS system. For UConn Health employees and students, your UConn Health username and password can be used to access iRIS.

Q: What is my IRB number?

A: After you have submitted your application to the IRB for review, the IRB will assign an IRB number to your study.  The IRB number can be used to search for the study within iRIS.  The first two digits represent the latter part of fiscal year that the study was submitted, the next three digits represent the sequential order of receipt, and the last digit represents the panel to which the study was assigned. If there is an X after the first two digits it indicates the research was determined to qualify for exemption. If there is a letter appended after the three sequential numbers the letter indicates that UConn Health is acting as the IRB for another institution.  For example an IRB number of 19-001C-2 reflects receipt of the study in fiscal year 2018/2019, that it was the first study received within the fiscal year and that Connecticut Children’s Medical Center is relying on the UConn Health IRB for oversight of the research, and that the submission was reviewed by Panel 2.

Note that any e-mail written or phone inquiry should make reference to the IRB number of the study. This will enable the IRB to quickly locate any required information.

Q: Why should I have a version number on my protocol and consent form?

A: It should always be possible to quickly determine which version of the protocol was current when the ICF was signed. Investigators are encouraged to maintain a link between the consent document and current protocol. For example, if you submit a modification that affects the informed consent form, but not version 1.0 of the protocol, the informed consent version reference should be revised, by adding a number after the version reference, e.g., Version 1.1. This indicates that the informed consent form is still linked to version 1 of the protocol.

Revising the version number also helps investigators to differentiate between copies of the protocol that have been modified. For example, if a modification was made to procedures in the protocol but both versions were labeled as version 1 (as opposed to 1 and 2 or 1 and 1.1) it would be easier for the investigator to follow the incorrect version of the protocol.

Q: I am not sure how to answer some questions in the application; can I leave them blank?

A: The IRB expects the investigator to respond to relevant items on the IRB application. Providing complete responses will make it less likely that the application will be returned for corrections.  If you have a question as to how to respond you are encouraged to contact a Regulatory Specialist within the IRB for guidance.

Q: Can I submit my application without the signature of the Principal Investigator?

A: No, the application must be signed by the Principal Investigator. With the implementation of the iRIS system, the PI can access the system from any place with internet access in order to sign the submission.

Q: What documents do I need to submit to the IRB for review of my study?

A: Because every study is unique it is not possible to provide directions that will address every situation.  The relevant IRB application checklist should be used as guide in determining the submission requirements.  You may also want to review the table “What Documents to Submit” at https://ovpr.uchc.edu//rcs/hspp/resources/expedited-exempt/ . The documents common to all new expedited and exempt submissions are noted in the first row and additional documents that are often associated with specific study designs follow. Some projects may combine characteristics of more than one study type.

Q: Are there any protocol templates in the IRB/HSPP web-site that can guide me in preparing my study protocol?

A: A protocol template is available on the IRB forms page.

Q: My study was deferred at the IRB meeting held on Monday night. Can I have an extension to the submission deadline so that my study can be reviewed at the next regularly scheduled meeting of that panel?

A: Yes, you can have a one week extension on the submission deadline. This is allowed for two reason. First because the IRB recognizes that the turn-around-time without the extension is quite difficult to meet. Second, because the reviewers have already seen the initial version of the protocol and discussed it at the board, allowing the reviewer one week to re-review is sufficient. Note that if you study was deferred it must be reviewed by the same IRB panel that conducted the initial review.

Q: Do I have to submit every single protocol deviation (e.g. instance of non-compliance with the protocol) to the IRB?

A: Yes, however the timing of when you report the non-compliance may differ. If the non-compliance was within the control of the research team (e.g. a follow-up appointment was scheduled by the research team outside of the study window) it should be reported within 5 business days of becoming aware of it using the problem report form available in iRIS.  All reports should contain a description of the deviation, why and when it occurred, and corrective action implemented, if any, to prevent future occurrence. If the non-compliance was not within the control of the research team it and it does not place a subject at risk (e.g. the subject canceled a scheduled appointment and had to be rescheduled outside of the study window) the event can be reported at the time of continuation.  However, if the event was not within the control of the research team but has in impact on subject safety or data integrity it should still be reported within 5 business days of becoming aware of it. If possible, investigators should allow for “windows” within the protocol design to reduce the instances of non-compliance. For example, rather than stating that a second visit will occur in 2 weeks state that second visits will occur within 10 to 18 days.

Q: How do I know which HIPAA form to submit?

A: You must address HIPAA within your application if your study will involve the use of protected health information. Protected health information means individually identifiable health information transmitted or maintained in any form (electronic means, on paper, or through oral communication) that relates to the past, present or future physical or mental health or conditions of an individual. In general,

• if you are obtaining informed consent you will also need to obtain a HIPAA Authorization, or
• if you are seeing, but not recording any identifiable information you will submit a request for Waiver of HIPAA authorization and a Certification of Deidentification form, or
• if you need to keep some identifiable information, and you cannot obtain an Authorization, you will apply for a Waiver of HIPAA Authorization.

Q: If the sponsor requires that a safety report be submitted to the IRB, but the adverse event reporting policy requires that it be reported only at the time of continuation (e.g., it is a non-serious event), should I still submit it to the IRB?

A: You should inform the sponsor that our reporting policy is that non-serious events will be submitted in summary format at the time of continuation. The IRB will not review individual non-serious reports.

Q: If my project will most likely qualify for exempt status do I still have to submit the entire IRB application, write a protocol, and make sure everyone has completed training in the protection of human subjects?

A: Yes.  The IRB is the only office that can determine if a research project qualifies for exemption and must have sufficient information in order to make that determination; and training requirements pertain regardless of the type of review conducted.

Q: I submitted an application for expedited review three days ago. Why haven’t I heard from the IRB yet?

A: Expedited review does not mean a quicker review. It simply means that only the Chair or an IRB member designated by the Chair has to review the project. All of the same criteria for approval still apply and applications are reviewed with the same level of scrutiny as a full board review.

Q: I will be doing research that will involve individuals who speak a foreign language. If the IRB approved the English version of the consent form do I have to submit a translated version for approval?

A: Yes. The IRB must approve all translated documents that will be presented to subject, e.g. the informed consent form and surveys. Investigators may either use a professional translation service or the back translation process. The full details are available in the Human Subjects Protection Office/IRB operating policies. Information on companies that provide translation services is available on the Information for Investigators page.

Questions Related to Continuing Review:

Q: How do I know when my study is due for continuing review?

A: When the IRB grants you final approval the approval letter will include the date by which your request for continuation is due.   The iRIS system should send 30, 60 and 90 day reminders to you to request continuing review. However, the investigator retains the responsibility for seeking continuation of an approved study and the IRB encourages you to add reminder notices to your outlook calendar.

Q: What happens if I miss the submission deadline for my continuation that requires full board review?

A: A lapse in IRB approval for the study will occur if continuing approval is not granted by the end of day on the expiration date of approval.  For example if the expiration date of a study is May 1st, research activity could occur on May 1st, but could not occur on May 2nd unless continuing approval had been obtained.  If a lapse in approval occurs, all research related activity must cease until approval for continuation is obtained.  If a subject is on active treatment and will be exposed to harm if treatment is withheld during the lapse in approval, you must request in writing approval from the IRB Chair to continue to treat the subject. You must also confirm that you are seeking continuation and will meet the next submission deadline.

Q: Why must I request continuation in less than one year when my colleagues’ studies where given approval for a full year?

A: When continuing review is a requirement, regulations require that continuing review occur at least annually. However, the IRB has the authority to require that review occur more frequently. Example scenarios of when the IRB may exercise this option include studies that pose a high risk to subjects or studies for which the investigator does not have extensive experience in the field.

Q: Why do I have to submit the complete protocol again at the time of continuing review if I haven’t changed it since the initial approval?

A: Federal guidance states that in order for continuing review to be meaningful and substantive the IRB must review the complete protocol. Attaching the protocol at the time of continuing review includes it in a master pdf file that the iRIS system creates for the assigned IRB reviewer. This facilitates the review process for them.

Questions Related to Informed Consent:

Q: What is informed consent?

A: Informed consent reflects an individuals voluntary agreement to participate in a research study. In order to make this agreement the individual must have adequate knowledge and understanding of the relevant information (purpose of the study, risks and benefits of the study, methods to be used, etc.). the process of informing a subject about a study is documented using the informed consent form.

Q: Who can provide informed consent?

A: Individuals who have reached the age of majority and who are competent can provide informed consent to participate in a research study. If the subject is either a minor or lacks the capacity to provide informed consent, a surrogate person (i.e. a legally authorized representative) must provide consent and the subject will generally be asked to provide assent. The policy to provide surrogate consent for research studies follows the same standards as providing surrogate consent for clinical care.

Q: What does a research subject need to be informed of during the consent process?

A: The informed consent checklist outlines the regulatory requirements of the informed consent form and these requirements are incorporated into the IRB sample consent form.  If these documents are used as a guideline, you should address all required elements within your consent document. However, consent is more than a document. Consent must be a process in which the research subject has the right to read and discuss the form and to ask any questions regarding the study and have them answered in a satisfactory manner.

Q: Is informed consent always required?

A: In the majority of non-exempt studies informed consent is required. However, there are situations in which the requirement to obtain informed consent may be waived or altered. A retrospective chart review study is an example of when the requirement to obtain consent may be waived. The form to request a waiver or alteration of informed consent must be completed and submitted to the IRB for review and approval. The form describes the criteria that must be satisfied in order for the IRB to grant approval to the request.

Questions Related to Closure of Human Subject Research Studies:

Q: When  should I close my study? 

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

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

A closure form allows the IRB to have a summary of the following information:

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

The Guidance on Closure of Human Subject Research Studies.docx  explains the circumstances in which a non-exempt human research study may be closed from IRB oversight, as well as ongoing researcher responsibilities that apply to closed studies.