Continuing Review of an Approved and Ongoing Protocol Quizlet

What is the purpose of continuing review?

Continuing Review is the process by which the IRB re-evaluates whether a protocol is being conducted in compliance with the criteria for approval that are applied during initial review. Continuing approval is required for all submissions classified as either expedited or convened review at least annually (364 days of approval). The expiration date for a submission is noted in the original approval letter and will be provided on the stamped informed consent form (if applicable).

If a study lapses in approval at any time, no research related activities may occur, unless the PI contacts the IRB in advance and it is determined that continuation during expiration is appropriate for subject safety. If any activity has occurred during the lapse in approval, those activities should be documented in the appropriate section of the continuing review form.

Extension of the IRB expiration date may only be achieved by submission of a continuing review. Other submission types (modification, exception request, deviation) cannot serve as a renewal submission.

"Enrolled" Participant Definition

The Penn IRB defines "enrolled" as an appropriately informed individual agreeing to participate in a study. In other words, an enrolled participant is an individual who may be eligible for participation, has provided informed consent, and may have participated in some or all study procedures including procedures that determine eligibility (if applicable). It is this definition of enrolled that should be used to determine the number of participants to be enrolled as indicated on all study documents. This definition allows for consistency of enrollment review across all projects and ensures that for studies that may include "screening procedures" or "pre-screening procedures," the individual is "enrolled" in the study to allow these study procedures to be done.

Current federal guidelines include that at the time of continuing review, "the IRB's responsibility to protect human subjects should include the IRB's review of trial progress. For example, expected rates of enrollment and dropout are generally identified for most studies. A marked difference between the actual and expected rates of enrollment or dropout, either at an individual site or in the study as a whole, may indicate a problem requiring further investigation."

The IRB recognizes that commercial sponsors, and others, may have a different definition, such as considering an individual "enrolled" in a study when the participant has been assigned to a study arm or has taken their first dose of the study drug. If the sponsor provides such definition, the study team may include that description and expected number in the HSERA application and continuing review progress report.

However, as noted above, the study documents including the Continuing Review Form must reflect the enrollment number of those individuals who are appropriately informed and agree to participate in a study. Study teams may differentiate between screen failures and eligible subjects in their progress reports.

Can I submit a modification while my Continuing Review is pending approval by the IRB?

The system will also allow a modification to be submitted concurrently while a continuing review is pending (or vice versa). However, a soft stop and a warning will appear but you may proceed.However,the IRB recommends that study teams do not submit concurrent modification / continuing review submissions, unless absolutely necessary, due to complications that can occur, as detailed below.

However, if you are waiting on a modification approval and your continuing review expiration date is approaching, DO NOT WAIT to submit your continuing review submission.

If you must submit concurrent modification / continuing review submissions, please note the following:

1. You must reach out to the IRB staff to faciliate the processing of these submissions and ensure that the correct documents are approved in the continuing review submission.  For greater than minimal risk studies requiring convened board review, please email BOTH the coordinator and administrator for the study's assigned board. For minimal risk research, please email the IRB PO Box.
2. It is the recommendation of the IRB that you create and submit the modification first before creating the Continuing Review (CR) application. This is to make sure that changes made within the HSERA modification submission are carried over into the continuing review application. If you do not do this, you may lose changes you made in HSERA if the create the CR first. It is preferred that the continuing review application be created after the approval letter for the modification has been uploaded for this reason.

Steps for Creating a Continuing Review in HSERA

1. After completing the submission form, save it to your desktop (be sure to update the file name to indicate the protocol number, that it is a continuing review form, and the date).

2. Go to HSERA.

3. In the blue menu on the left side of your screen look for "Create" under "My Submissions".

4. After clicking "Create" you will be brought to a new screen where the various application types are available. Click "Continuing Review"

5. After clicking "Continuing Review" you will be brought to a screen with a list of all HSERA studies for which you are listed as either PI, Co-PI or Study Contact (note that Key Personnel cannot create submissions). Check to make sure your filter is clear. Then enter the protocol # you wish to make a continuing review for and click "Filter".

6. After clicking "Filter" with the specific protocol number entered, you should see one entry with columns showing the PI name, Submission date, Title, and a Select column - click the white and yellow "Select" button.

7. After clicking the "Select" button you will be taken to the first page of the Continuing Review submission. There are 3 pages to complete:

• Page 1 requires that users indicate the level of review required for this continuing review. This decision is based on the risk level of the study. Please refer to your Initial approval letter to determine whether your study is expedited or convened if you are not sure. The next field after selecting level of review is where you attach your completed continuing review form that you downloaded from this page.
• Page 2 contains only the standard question about financial conflicts of interest. You should enter the same responses you provided in the attached form. Other offices in the University rely on the HSERA responses so this question will continue to appear in both places.
• Page 3 is where you will attach the appropriate documents related to the continuing review. Please be mindful to upload documents under the appropriate header to facilitate the IRB's review of these documents.

Safety Monitoring and Adverse Event Reporting (Greater Than Minimal Risk Research)

Safety Monitoring

It is the expectation of the IRB that all Greater Than Minimal Risk research protocols will include a plan for safety monitoring and submission of unanticipated problems posing risk to subjects or others. The IRB will no longer require a summary of the safety monitoring plan in your progress report. Please answer the questions in the continuing review form and provide clarifying information as directed. It is also the IRB's expectation that the study team will be aware of who is conducting safety monitoring for each study in order to answer these questions appropriately. Please refer to your protocol as you answer the questions in the form.

Reporting of Adverse Events

All study teams should record and assess all internal adverse events in their research records when they occur. The assessment should include seriousness, expectedness, and relatedness. Per IRB SOP RI 801, an investigator is responsible for the accurate documentation, investigation and follow up of all adverse events that are possibly study related. Please see the table below for IRB reporting criteria of adverse events. Definitions of Expectedness and Relatedness are fully explained in the How to Submit:Reportable Event page

Please answer the questions in the Continuing Review form and provide clarifying information as directed. Additionally, please provide a summary of applicable events as described in the table above within your progress report. The summary of these events is required so that the convened board may review aggregated information to confirm that :

• Risks to subjects remain minimized
• Risks remain outweighed by, or appropriately balanced by, potential benefits
• When appropriate, the research plan makes adequate provision for monitoring the data collected to ensure the safety of subjects

There is no required structure for the adverse event summary. It will vary depending on the complexity of the study. Please ensure your summary mentions relatedness and seriousness / grading of the events. Please provide any new information related to these events, if available. Summarize the impact of these unexpected events on the risk - benefit ratio of the study. Summarize any actions taken in response.

Study Monitoring, Quality Control, & Deviation Reporting (Greater Than Minimal Risk Research)

It is the expectation of the IRB that all Greater Than Minimal Risk research protocols will include a plan for site monitoring, quality control and deviation reporting for noncompliance assessments. Some clinical trials require an independent study monitor to review the quality of the study activities. The study monitor conducts quality controlby inspecting study records. Some clinical trials may also be audited by one or more entities for quality assurance. See the Penn Manual for more detail about study monitoring.

The study team should know who is conducting study monitoring in order to answer the questions correctly in the continuing review form. Please refer to your protocol to assist you in answering the questions in the form.

A summary of quality control monitoring is no longer required. Please answer the questions in the continuing review form and provide clarifying information as directed.

Pathway A

If the study has a regulatory sponsor that is responsible for the oversight and conduct of the protocol and the sponsor has appointed an individual to conduct quality control monitoring, Pathway A within the form should be followed. This will apply to most industry - sponsored research (i.e., the industry sponsor authored the protocol)

Pathway B

If the study is investigator-initiated (i.e., the protocol was designed and/or authored by the principal investigator, a sub-investigator, or a faculty member at Penn or another academic institution) and does not have a sponsor appointed monitor to conduct quality control, Pathway B within the form should be followed.

Reporting of Deviations

All study teams should record, assess and develop corrective actions for all deviations that occur during the conduct of the research study. Deviations should be assessed in the context of the protocol and it should be determined whether expedited IRB reporting is required. Events that require expedited IRB reporting are those that have an adverse impact on the following:

• subjects' rights, OR
• subjects' welfare / safety (including any potential or actual substantive harm), OR
• the scientific integrity of the study

More information about deviations is available on the How to Submit:Deviations page

If there is no sponsor appointed monitor conducting quality control monitoring, at the time of continuing review the study team should review deviation logs to ensure all recorded deviations have been assessed appropriately, and reported in an expedited fashion when necessary.

Please answer the questions in the continuing review form under Pathway A or B (as applicable) and provide clarifying information as directed. Additionally, please provide a summary of deviations within your progress report as directed within the applicable pathway. The summary of these events is required so that the convened board may review aggregated information to confirm that:

• There are adequate resources to conduct the study
• Risks to subjects remain minimized
• When appropriate, the research plan makes adequate provision for monitoring the data collected to ensure the safety of subjects

There is no required structure to deviation summaries. It will vary depending on the complexity of the study and the number of deviations. Note that the summary requirements are different depending on whether Pathway A or B is required within the continuing review form. Please follow the requirements as directed in the form. Regardless of structure or format the summary must include:

1. when each deviation ocurred
2. a description of the deviation
3. if and when the deviations were previoulsy reported to the IRB
4. assessments of each deviation to determine whether it adversely affected: subjects' rights, OR subjects' welfare /safety (including any potential or actual substantive harm), OR the scientific integrity of study
5. any corrective actions put in place in response to each deviation

Submitting Continuing Review When Penn Serves as the IRB of Record for Multiple Sites (Reliance Agreements/Central IRB Review)

Submitting Continuing Review for studies where Penn serves as the central IRB requires specific documentation from each site. Please download and review our guidance prior to submitting continuing review for these studies.

Reliance Agreement Guidance for Post Approval Submissions

Associated forms can be downloaded from the IRB forms page: https://irb.upenn.edu/forms. Please note: The Relying Site Supplement has been updated as of 7/22/20 to collect additional information on recruitment. Submissions utilizing older versions of these forms will be returned starting 9/1/2020.

What if my study is expired?

If your study is expired the IRB will expect the following information to accompany your continuing review request:

• A description of all activity that has ocurred during the lapse in approval
• an explanation for what lead to the delayed submission of the continuing review
• a corrective action plan to avoid expiration in the future
• If a study has expired more than once please comment on whether the existing corrective action plan needs to be corrected
• If your research is greater than minimal risk and activities need to occur during the lapse for the benefit or safety of participants, an exception request should be submitted. Please see https://irb.upenn.edu/Exception

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Source: https://irb.upenn.edu/continuing-review

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