Maintaining IRB Approval

All changes to the research protocol must be submitted for prospective IRB approval unless a change needs to be implemented immediately to remove or minimize an imminent harm to subjects.  In the latter situation, such changes should be submitted promptly to the IRB for review and approval, even though out of necessity they were already implemented.  Any change to the protocol, even for one subject, must be submitted for prospective IRB approval (e.g., change of a specific inclusion or exclusion criterion altering a subject's treatment that is prescribed by the protocol, etc.).  If such a change is identified at the time of enrollment and IRB approval is needed quickly, notify the staff of the appropriate IRB, in addition to submitting the modification in RASCAL. 

To submit a modification in Rascal, please follow these steps:

1. Go to the Rascal home page at https://www.rascal.columbia.edu.
2. Select 'Human Subjects (IRB)' under 'Compliance'.
3. Log in with your UNI and password.
4. Retrieve your protocol by number.
5. Select the 'Create Modification' link from the menu on the left side.
6. Complete and submit your modification.

Be sure to:

• Explain why the modification is requested (in the Summary of Changes section).
• Revise the protocol, consent forms, or other documents & fields as necessary.
• Attach new documents, if applicable.
• Review the personnel section to ensure that the list is still current.

Renewals and Annual Reports

Designation of the need to submit a Renewal or an AR

Calculation of the due date or expiration date

Frequently Asked Questions (FAQs)

• FAQ 1: Is the renewal for my protocol, which was initially reviewed at a convened meeting of a Columbia IRB, eligible for expedited review?
• FAQ 2: Is the renewal for my protocol, which was initially reviewed by IRB EXP, eligible for expedited review?

Recommended Timeline for Submission of Renewals

Renewal Review process

Annual Report Review process

Creating and submitting your Renewal in Rascal

Creating and submitting your Annual Report in Rascal

Renewals and Annual Reports

Renewal (referred to as “continuing review” in federal policies for the protection of human subjects)

• Federal regulations at 45 CFR 46.109(e) (DHHS) and 21 CFR 56.109(f) (FDA) require an IRB to conduct continuing review of certain non-exempt human subject research studies and FDA-regulated studies at intervals appropriate to the degree of risk, but not less than once per year. The IRB may require more frequent continuing review.
• During continuing review, the IRB will consider any new information about the study, confirm the implementation of its monitoring as planned to minimize risks, evaluate the number of subjects, and will review the consent document(s) to confirm that they include up-to-date information about the research.
• Documentation of the requirement to submit a Renewal, as continuing review forms are called at Columbia, and the approval period are reflected in Rascal upon initial review of the Protocol and upon approval of each Renewal.
• Updates in 2018 to the DHHS regulations allow that certain types of studies no longer require a continuing review by the IRB.  Such types are listed in the “Annual/Progress Report” section below.
• Non-exempt research at Columbia is generally approved for intervals of one year. Exempt research at Columbia is generally approved for intervals of five years, and submission of an AR is required at the end of each interval for research that remains active.

Annual/Progress Report (AR)

For the following types of studies initially approved on or after January 21, 2019 (2018 requirements) and not conducted under FDA regulations, and unless an IRB decides otherwise, a renewal is not required for:

• Research that is eligible for expedited review as determined by the IRB
• Research that has progressed to the point that it involves only data analysis of identifiable private information or identifiable biospecimens
• Research that has progressed to the point that it only involves accessing follow-up clinical data from procedures that subjects would undergo as part of clinical care
• All exempt research, including research reviewed under a limited IRB review

Columbia requires the submission of an Annual/Progress report (AR) in Rascal for these studies to facilitate reporting of subject enrollment and tracking of all active human subject research.

No changes can be submitted with the AR. If changes to the protocol need to be made, a modification will need to be submitted either before or after the submission of the AR.

The AR submission allows only the attachment of the following types of documents:

• The Cancer Center Renewal Form (required for oncology non-therapeutic studies)
• Documentation of the reviewing IRB approval/site approvals

Designation of the need to submit a Renewal or an AR

The determination of whether a study is eligible for elimination of continuing review, and therefore only requires submission of an AR, or whether the study requires a renewal, is made by the IRB upon initial review of the protocol and will be reflected in Rascal.

For studies that are relying on review by an external IRB under a reliance agreement, the reviewing IRB’s determination will be reflected in Rascal by HRPO staff.  For studies that don’t require a renewal, the external reviewing IRB may not require an annual progress report. In such a case, an AR report should still be submitted in Rascal by the due date that will be reflected in Rascal.

Notifications that the Renewal or AR is due are sent automatically by the Rascal system to the PI and coordinators at 90, 60 and 30 days prior to the due date.

Calculation of the due date or expiration date

Annual Reports:

• For studies initially eligible for expedited review: the due date is calculated by adding 1 year to the date on which the Protocol or previous AR was approved and subtracting one day.
• For research determined to be exempt: the due date is calculated by adding 5 years to the date on which the initial Protocol or previous AR was approved and subtracting one day.
• For studies relying on an external IRB review, if a due date was specified by the external IRB, it will be reflected in Rascal. If not, the due date is calculated by adding 1 year to the date on which the initial Protocol or previous AR was approved and subtracting one day.

Renewals:

• For studies reviewed at a convened IRB meeting: The expiration date is calculated by adding 1 year to the IRB meeting date on which the submission was reviewed and subtracting one day.
• For studies eligible for expedited review: the expiration date is calculated by adding 1 year to the date on which the submission (initial or previous renewal) was approved and subtracting one day.
• For studies relying on an external IRB review: the expiration date set by the external IRB will be reflected in Rascal.

Frequently Asked Questions (FAQs)

FAQ 1: Is the renewal for my protocol, which was initially reviewed at a convened meeting of a Columbia IRB, eligible for expedited review?

Click this link to view schematic

FAQ 2: Is the renewal for my protocol, which was initially reviewed by IRB EXP, eligible for expedited review?

Click this link to view schematic

Recommended Timeline for Submission of Renewals

The Principal Investigator and research team are responsible for maintaining IRB approval of their studies and submitting a renewal in time for review and approval. Sufficient time to accommodate for IRB review and other ancillary* reviews needs to be considered. The following timeline for submission provides recommended intervals to avoid a lapse of IRB approval.

Important note: The timeline below may not apply for studies relying on an external IRB review because documentation of the external IRB’s renewal approval may not be received until just before the expiration date. However, the renewal should be submitted no later than 30 days before the expiration date. If approval documentation from the external IRB is not available before the expiration date, please specify this in the datasheet. Please follow up with the HRPO staff reviewer when documentation of approval is received. Approval will not be reflected in Rascal until that documentation is received.

* Concurrent review by another Columbia University research compliance office/committee (i.e., ancillary review)

Click this link to view Timeline for Submission of Renewals

Renewal Review process

The progress of the renewal review is reflected in the Renewal History Page in Rascal.

Click this link to view the Renewal Review Process

Annual Report Review process

The progress of the annual report review is reflected in the Annual Report History Page in Rascal.

Click this link to view the Annual Report Review Process

Creating and submitting your Renewal in Rascal

1. Go to the Rascal home page at https://www.rascal.columbia.edu.
2. Select 'Human Subjects (IRB)'.
3. Log in with your UNI and password.
4. Retrieve your protocol by number.
5. You can find the expiration date on the Protocol Overview page or on the determination letter of the most recent approved event.
6. Select the 'Create Renewal' link from the Protocol Overview Page below the table
7. Complete the Renewal Information Page
8. Update the Subjects page to reflect the current enrollment/accrual information.

Review the Enrollment/Accrual definitions below:

Enrollment: All individuals who agree to participate in a study, even if just for screening/assessment purposes, and all individuals about whom data and/or specimens were collected under a waiver of informed consent (e.g., in the course of a record review, or when using residual specimens), are considered to be enrolled in the study, and are considered to be human subjects.

Accrual: For an interventional study with a screening procedure to determine eligibility that occurs after consent is obtained, subjects who are confirmed to be eligible for the intervention. This number is a subset of the number of participants "enrolled."

9. Update the modification summary -if modification is submitted with the renewal- and relevant sections
10. Submit your renewal. All information that is required for a new protocol submission must be entered into Rascal for the renewal, e.g., the latest version of the sponsor protocol or grant application, investigator brochure, study instruments, and consent documents (both the last stamped consent and clean version(s) to be stamped (pdf format) for the next approval period). Include a copy of the Certificate of Confidentiality approval letter, if applicable and not previously submitted in Rascal.
11. Be sure the latest versions of all relevant material are attached: e.g., funding proposal (grant or contract), sponsor protocol, investigator brochure (if the study involves an investigational drug), study instruments [i.e., questionnaire(s) or survey(s)], IND/IDE documentation, non-CU site approvals (e.g., permission to conduct the study), and consent forms.
12. If the approved protocol includes monitoring by a Data Monitoring Committee (DMC). Data and Safety Monitoring Board (DSMB), or other monitoring entity, please attach the most recent report.

Be aware that a pending modification may impede the submission of a renewal request. It may be necessary to withdraw pending modifications if submitting a renewal, and to incorporate the changes in the renewal study description.  If this becomes necessary, notify relevant IRB staff before proceeding.  Be sure to explain changes in any case, either in the study description or in a cover letter. 

Please file your renewal sufficiently in advance of the expiration date to allow time for the IRB review process. (At least 60 days in advance for studies that will required convened review, i.e., review at an IRB meeting; at least 30 days in advance for all others)

Research activities may continue uninterrupted ONLY if the renewal request is approved by the IRB prior to the expiration date. All research activities must cease on the expiration date if the renewal is filed, but not yet approved. When the IRB approves the renewal request, research activities may continue.

Creating and submitting your Annual Report in Rascal

1. Go to the Rascal home page at https://www.rascal.columbia.edu.
2. Select 'Human Subjects (IRB)'.
3. Log in with your UNI and password.
4. Retrieve your protocol by number.
5. You can find the due date on the Protocol Overview page or on the determination letter of the most recent approved event.
6. Select the 'Create Annual Report' link from the Protocol Overview Page below the table
7. Review the Annual Report Information Page
8. Update the Subjects page to reflect the current enrollment/accrual information.

Review the Enrollment/Accrual definitions below:

Enrollment: All individuals who agree to participate in a study, even if just for screening/assessment purposes, and all individuals about whom data and/or specimens were collected under a waiver of informed consent (e.g., in the course of a record review, or when using residual specimens), are considered to be enrolled in the study, and are considered to be human subjects.
Accrual: For an interventional study with a screening procedure to determine eligibility that occurs after consent is obtained, subjects who are confirmed to be eligible for the intervention. This number is a subset of the number of participants "enrolled."

9. Submit your annual report.

If the annual report is not approved by the due date, IRB approval does not lapse and research activities may continue. However, it is expected that the annual report will be submitted in order to facilitate accounting of all human subject research at Columbia. The protocol overview page will show a lapse if the annual report is not submitted and approved by the due date.

Protocol Deviations & Violations

Columbia IRB policy requires that all protocol deviations/violations and/or instances of noncompliance with Columbia policies or IRB determinations be reported to the IRB by the Principal Investigator.  A protocol violation/deviation occurs when there is a variance in a research study between what is described in the protocol (reviewed and approved by the IRB) and the actual activities performed by the research team.

The IRB defines a protocol deviation as a change in the protocol for one or more subjects that is identified by the research team before the change is implemented.   A protocol violation is defined by the IRB as a protocol change or modification that was not approved by the IRB and is identified by the research staff after the change was implemented.  Protocol violations may be considered as noncompliance with the federal regulations for the protection of human subjects. 

How to Report a Protocol Deviation/Violation to the IRB:

If the Protocol Deviation/Violation is unanticipated and involves risks to subjects or others, submit it to the IRB within one week (5 business days) as an Unanticipated Problem Report in RASCAL. (see instructions above under "Reporting Unanticipated Problems Involving Risks to Subjects or Others").

Protocol Deviations/Violations that do not involve risks to subjects or others should be submitted promptly as a Modification in RASCAL (see instructions above under "Modifying an Approved Protocol").

Whether you are submitting the Protocol Deviation / Violation as an Unanticipated Problem or as a Modification, be sure to include the following information:

• A complete description of the deviation/violation;
• An explanation of why the deviation is necessary, or why the violation occurred;
• Whether the deviation affected/violation affects the:
  1. risk/benefit ratio for the subject(s)
  2. integrity of the research data
  3. subject's willingness to continue study participation; and
• If a protocol violation, a description of the corrective measures that will be taken to prevent the recurrence of the violation and indicate what steps will be taken to avoid similar problems in the future.

Interim Analysis of Data / DSMB Reports:

• Submit promptly as a modification in RASCAL, providing a summary of findings "Summary of Changes" section and attaching all relevant documents.

Suspensions:

• Submit promptly as a modification in RASCAL, providing a summary of findings "Summary of Changes" section and attaching all relevant documents.

• A study should not be terminated until all subjects have completed the study and research-related activity has ceased, including subject follow-up, data collection, and/or data analysis.
• Notification of 'Closure to Enrollment' should be submitted as a modification rather than a termination unless the above criteria are fulfilled.

To terminate a protocol in Rascal, please follow these steps:

1. Go to the Rascal home page at https://www.rascal.columbia.edu.
2. Select 'Human Subjects (IRB)' under 'Compliance'.
3. Log in with your UNI and password.
4. Retrieve your protocol by number.
5. Select the 'File Termination Report' link from the menu on the left side.
6. Complete and submit your termination.

The termination report should include:

• Cumulative enrollment data and demographics
• Summary of Amendments
• Summary of Adverse Events
• Patient Problems or Complaints
• Protocol Deviations/Violations
• Synopsis of Study Results
• Papers Pending or Published (attach)