Unanticipated problem reporting

All unanticipated problems must be reported to the IRB within five working days of learning of the event. Evaluating whether an event is an unanticipated problem is the responsibility of the principal investigator.

An unanticipated problem involving risk to subjects or others (UP) is any event that meets all of the following three criteria:

1. Was not anticipated or foreseen
2. Was possibly, probably or definitely related to, or caused by, the research activity in the judgment of the investigator
3. Suggests that the research places subjects or others at greater risk of harm (including physical, psychological, economic or social harm) than was previously known or recognized

It is important to note that only those AEs that meet all three criteria above are unanticipated problems that need to be reported promptly to the IRB.

Read more about identifying unanticipated problems in WPP VII-6.

Other reporting

Noncompliance in the conduct of the research must be reported to the IRB. There may also be times when a sponsor requires reporting to the IRB or there is other information the investigator feels the IRB should know, in which case a report may be submitted to the IRB.

Submitting a report in RAMS-IRB

• Log in to RAMS-IRB and open the workspace for the study needing a report
• Click the “New Report to IRB” button
• Complete a report form and upload relevant documentation

Please see the RAMS-IRB Submission System Guide for details on submitting a report.

Reporting requirements for studies approved by non-VCU IRBs

Once an initial submission is approved an external, non-VCU IRB such as NCI Central, Western IRB, Advarra or another academic IRB, the principal investigator is responsible for directly submitting all reportable events to that external IRB, including unanticipated problems, in accordance with that IRB's policies. All unanticipated problem determinations made by an external IRB regarding a VCU research setting should subsequently be submitted in a report to the VCU IRB via the procedure described above.

For questions regarding research reviewed by external, non-VCU IRBs contact irbreliance@vcu.edu or visit the IRB reliance webpage.

Amending exempt research

Most modifications to exempt research may be done at the discretion of the principal investigator without prior IRB approval. Some changes do require IRB approval before being implemented. For a list of changes that must be submitted to the IRB for review and approval, see the conditions of approval attached to your initial exemption letter from the IRB or refer to WPP X-1.

Amending expedited research

All proposed changes to expedited research must be submitted for IRB review and approval prior to initiating the change.

Amending full board research

All proposed changes to full board research must be submitted for IRB review and approval prior to initiating the change. Some types of minor changes to full board studies may be reviewed in an expedited fashion by a single reviewer. This determination is made by the IRB reviewer, not the principal investigator.

Changing the Principal Investigator (PI) on a study

If you need to amend a study to change the Principal Investigator (PI) for the study, you must submit this change in an amendment in RAMS-IRB. In addition, you must also complete the VCU IRB PI Change Instrument in REDCap. The IRB is requiring use of the REDCap PI Change Instrument because it is important for the new PI to be aware of what they are taking on when they agree to be the PI, and the RAMS-IRB system does not have a mechanism for documenting that the new PI certified to all of the PI responsibilities outlined in WPP IX-1. Instructions for use of this instrument are contained within the REDCap form.

This instrument must be used in tandem with an amendment submitted in RAMS-IRB. This instrument must be used for all studies proposing a change of PI, including exempt, expedited, and full board research that is reviewed by the VCU IRB. This instrument is not applicable to studies reviewed by an IRB other than VCU's IRB (i.e.: WIRB). When changing the PI on an externally-reviewed study, email irbreliance@vcu.edu for guidance.

Submitting an amendment in RAMS-IRB

• Log in to RAMS-IRB and open the workspace for the study needing an amendment
• Click the “New Amendment” button
• Fill out the amendment cover sheet
• Modify the smartform
• Upload redline and clean copies of any revised documents to the study workspace

Please see the RAMS-IRB Submission System guide for details on submitting an amendment.

Ongoing submissions for Western IRB approved research

Once an initial submission is approved by WIRB, the principal investigator is responsible for directly submitting all future submissions to WIRB, including changes in research (amendments).

A copy of all submissions must be provided to the Human Research Protection Program via IRBIntake@vcu.edu, as well as to WIRB.

Be aware that WIRB updates its submission forms as much as twice yearly to improve the review of research and protection of human subjects. When preparing to submit research for review, be sure to use the most current versions of WIRB submission forms by referring directly to the WIRB forms site.

All full board research must be re-reviewed by the IRB at least annually through a continuing review process. Some, but not all, expedited research also requires continuing review. Exempt research does not require continuing review. Well in advance of an expiration date, reminders are sent to investigators prompting preparation and submission of a continuing review submission. For more information on continuing review, see WPP VIII-4.

Submitting a continuing review in RAMS-IRB

• Log in to RAMS-IRB and open the workspace for the study needing continuing review
• Click the “New Continuing Review” button
• Complete a continuing review form and upload relevant documentation such as DSMB reports

Please see the RAMS-IRB Submission System Guide for details on submitting a continuing review.

Maintaining approval for Western IRB approved research

Once an initial submission is approved by WIRB, the principal investigator is responsible for directly submitting all future submissions to WIRB, including:

• Changes in research (amendments)
• Unanticipated problems
• Continuing reviews
• Study closure

A copy of all submissions must be provided to the Human Research Protection Program via IRBIntake@vcu.edu, as well as to WIRB. WIRB will send continuing review reminder notices to principal investigators. Please pay close attention to the reminders. WIRB strictly enforces deadlines.

Be aware that WIRB updates its submission forms as much as twice yearly to improve the review of research and protection of human subjects. When preparing to submit research for review, be sure to use the most current versions of WIRB submission forms by referring directly to the WIRB forms site.

Status updates of IRB-approved expedited research

Expedited research that does not require ongoing continuing review must submit a status update to the IRB at least annually through RAMS-IRB. Well in advance of an expiration date, reminders are sent to investigators prompting submission of a status update.

For expedited studies, investigators can tell whether their study requires continuing review by the current state listed for their study in RAMS-IRB.

• If a study requires continuing review

 Pre 2018 Common rule Continuing Review [View Image]

• If a status update is required

2018 common rule status update [View Image] 

NOTE: Certain expedited studies require continuing review. If your study requires a continuing review, see accordion above titled, "Continuing review of approved IRB study."

Submitting a status update in RAMS-IRB

1. Log in to RAMS-IRB (https://irb.research.vcu.edu) with your VCU eID.
   Tip: Remember to connect through RAMS VPN first if you are off campus.
2. Go to the “My IRB Studies” tab.
   My IRB Studies tab displayed [View Image]
   Tip: If your study is expired or closed, locate it under the “Archive” tab.
3. Click on the title of the study for which you want to submit a continuing review.
4. Click the “Submit Status Update” button.
   My activities, Submit status update [View Image]
5. Complete the three to five question status update form in the pop-out window.
6. Click OK to close the pop-out window and submit the status update.

You will receive an email with either:

• An automatic acknowledgement of your study’s ongoing status or
• A request to submit any necessary report or amendment to the IRB

If the issue(s) noted in the status update are not resolved with the VCU IRB prior to the expiration date, then the study will expire, and all research activities (including data analysis) must stop. 

Allowing the study to expire may result in the IRB making a determination of noncompliance. 

If your status update prompts you to submit a closure request

RAMS-IRB will not allow you to submit the status update if you indicate in your status update that the study is ready to close. You will be prompted to submit a closure request instead of a status update. 

For more information about study closure, please review WPP X-4 Closure of Study from VCU IRB Oversight.

For instructions on how to submit a closure request, see next accordion panel, "Study close out."

If your status update prompts you to submit a report

If your status update indicates that the study has had an unanticipated problem that has not already been submitted to the IRB, you will be required to submit a report to the IRB within five working days.  

The expiration date for your study will be extended by 30 days to give you time to submit the report and for the IRB to review it before the study expires.

To determine whether a problem is an unanticipated problem, the following questions should be asked:

• Is the problem unexpected?
• Is the problem related or possibly related to participation in the research?
• Does the problem suggest that the research places subjects or others at a greater risk of harm than was previously known or recognized?

If the answer to all three questions is yes, then the problem is an unanticipated problem and must be reported to the IRB immediately. 

For more information about unanticipated problems, please review WPP VII-6 Required Reporting of Unanticipated Problems Involving Risk.

For instructions on how to submit a report, see first accordion on this page, "Problem reporting."

If your status update prompts you to submit an amendment

If your status update indicates that the study has made changes to the study protocol, procedures or study documents that have not already been approved by the VCU IRB, you will be required to submit an amendment to the IRB as soon as possible. 

One of the conditions of IRB approval is that investigators must “obtain approval from the VCU IRB before implementing any changes in the approved research.” This applies for any site (VCU or non-VCU) that is under the VCU IRB’s oversight.

The expiration date for your study will be extended by 30 days to give you time to submit the amendment and for the IRB to review it before the study expires.

For more information about amendments, please review WPP VIII-5 Review of Modifications to Research.

For instructions on how to submit an amendment, see second accordion panel on this page, "Amending an approved study."

If you filled out your study’s status update incorrectly:

Call the IRB coordinator assigned to your study before the study’s expiration date. The IRB coordinator’s name is listed in RAMS-IRB in the header information of your study, and their direct contact information is available at Contact ORSP. You may also call the IRB’s main phone number, (804) 828-0868. 

When a study meets the criteria for closure, IRB oversight is no longer needed and a study may be closed with the IRB.

VCU IRB oversight may end (following a request for closure) only when ALL of the following conditions are met:

• The research is permanently closed to enrollment at the site(s) under the VCU IRB approval.
• All interactions/interventions with subjects, or access to a subject’s personally identifiable information, (including identifiable biological specimens) for the purpose of research data collection is complete.
• All use, study and/or analysis of identifiable private information at the research site(s) under the VCU IRB approval is complete.

  Note regarding multicenter studies: Continuing review of the research by the VCU IRB is no longer required once the above conditions are met (following a request for closure), even if (i) interactions or interventions with subjects may be occurring at study sites other than those under the VCU IRB approval; or (ii) data analysis of identifiable private information is ongoing at another central site (site other than those under the VCU IRB approval) that collects and analyzes data from all study sites. For studies closed with the VCU IRB under these conditions, investigators may still respond to queries from the statistical center at the other institution regarding previously collected data about subjects who were enrolled under the VCU IRB approval.

As a reminder, principal investigators should retain all VCU IRB correspondence, approved documents and raw data for a minimum of five years; longer retention may be necessary based on applicable regulatory requirements and/or sponsor requirements. Refer to the VCU Research Data Ownership, Retention and Access policy and the VCU Record Retention Policy for specific requirements. Data security must be ensured even after study closure if identifiable information (including coded data) is retained.

Submitting a closure request in RAMS-IRB

• Log in to RAMS-IRB and open the workspace for the study that is ready to close
• Click the “New Study Closure” button
• Complete the closure form and upload relevant documentation such as DSMB reports

Alternatively, a study can be closed at the time of continuing review by selecting the close study option within the continuing review activity.

Please see the RAMS-IRB Submission System Guide for details on submitting a closure request.

Maintaining approval for Western IRB approved research

Once an initial submission is approved by WIRB, the principal investigator is responsible for directly submitting all future submissions to WIRB, including study closure requests.

A copy of all submissions must be provided to the Human Research Protection Program via IRBIntake@vcu.edu, as well as to WIRB.

Be aware that WIRB updates its submission forms as much as twice yearly to improve the review of research and protection of human subjects. When preparing to submit research for review, be sure to use the most current versions of WIRB submission forms by referring directly to the WIRB forms site.

The purpose of the program is to assist the university and investigators in conducting human research that is of the highest ethical quality and is compliant with federal, state and local requirements. The PAMQuIP staff works toward this goal by improving investigator/IRB performance through monitoring, education and measurement of the overall quality, effectiveness and efficiency. In addition, the PAMQuIP staff acts as a resource for the VCU/health system research community by offering help through problem-solving tips, templates, focused educational services, external/internal audit preparation and referrals.

Types of visits

For cause

Visits requested by the IRB, Human Research Protection Program staff, institutional official and department chairs, etc., are generally due to concerns regarding study compliance and/or subject rights and welfare. For cause visits may also be initiated due to complaints, repeated errors or a lack of responsiveness by the principal investigator to IRB/Human Research Protection Program requests.

Examples of the types of for-cause reviews are:

• Focused
  More narrow reviews of research activities that concentrate on direct research subject impact. The informed consent process (including documentation, observation), recruitment or treatment outcomes could each be object of a focused review. This type of review is not prompted by a specific concern or issue and is similar to routine review.

• Investigations
  Occasionally the IRB/Human Research Protection Program will request an in-depth investigation of an investigator’s studies or study conduct. This may be due to a noncompliance determination and/or significant regulatory problems were found during review.
  
  This investigation may involve significant time on site reviewing study documentation and processes.

Routine

Visits to studies that are not initiated by any cause for concern. Studies may be selected based on any number of criteria, including:

• Risk level of the study
• Studies enrolling vulnerable populations
• Studies involving investigational new drugs or devices
• Studies involving an investigator held IND-IDE
• Studies involving complex procedures
• A high number of studies conducted by a PI or managed by a study coordinator
• Randomly from all active studies

Examples of routine visits are:

• Targeted
  Visits or document reviews targeted toward a particular type of study such as studies reviewed by an external IRB, expedited research or IRB review of studies involving a vulnerable population.

• Preventative/educational
  Visits requested by the PI, study staff, IRB, Human Research Protection Program staff and department chairs, etc., to address a perceived educational need related to study conduct. This is often requested when there are new study staff/PIs as part of the onboarding process.

Preparatory review

This type of visit is often requested by the PI or research staff to assist with preparation for an external audit or in anticipation of the start of recruitment.

Overview of the QA review process

Most visits follow the process outlined below. Educational visits or those otherwise requested by the study staff may have a slightly different process.

1. The QI/QA Staff contacts the investigator via email to request the visit. A mutually acceptable time is agreed upon to conduct the visit. Visits should take place within a week or two of suggested dates.
2. In the visit request letter, the QI/QA staff includes links so the PI can complete the Post Approval Monitoring Study Evaluation Tool (PAM SET), CITI certification, Risk Mitigation Table and the VCU data security classification survey. Links to or attachments of these documents are included in the visit request email. These completed documents are emailed to the Staff a minimum of one week before the visit.
3. The PI, study coordinator and QI/QA staff meet to discuss questions arising from the IRB documentation and PAMSET. This visit usually takes 90-120 minutes depending on questions/issues that PI and study coordinator want to discuss or the complexity of the questions that arose from the pre-visit document review.
4. The QI/QA staff may return on another day to observe the consent process, clinical processes and/or to do an in-depth documentation review, etc.
5. Following the visit, the QI/QA staff will email a final report to the PI and study coordinator noting required actions and recommendations. The required actions constitute the corrective action plan. A PI response form will be attached to the email. The PI response form should be completed and returned within a week of receipt. This does not mean that the required changed need to be completed within a week, but the PI response form denotes the PI’s intentions and commitment to fulfilling those intentions within a stated period of time and/or before the next continuing review.
6. The QI/QA staff will upload the final report, questions and completed PI response form to the secure server in the Office of the Vice President for Research and Innovation and to RAMS IRB for IRB review.
7. If there is a possibility of the PI being cited for noncompliance (general, serious and/or continuing), the QI/QA manager will discuss the report and PI response with the executive director of the Human Research Protection Program. The findings and response will be referred to the full IRB panel if the executive director believes there may be continuing and/or serious noncompliance.
8. If applicable, the QI/QA staff may offer up to six hours of consulting time to help the PI and staff resolve issues, comply with the corrective action plan and help the study move through the IRB process more smoothly.

The QI/QA staff will make an effort to give an overview of recommendations and required changes that will be included in the final report before leaving the final meeting with the PI and staff.

There may be communication back and forth after the visit to clarify any additional questions that arise while the report is being written.

Preparing for a visit

Visits will be completed in a timely fashion and flow more smoothly if the following preparation is done prior to the scheduled visit:

1. Complete the required pre-visit documentation return it to the QI/QA staff (QI/QA STAFF). This includes:
   • Post-approval Monitoring Study Evaluation Tool (PAM SET)
   • CITI Certification Table
   • Risk Mitigation Table
   • VCU Data Security Classification survey
2. Reserve a conference room with a table for the visit/record review to occur.
3. Have applicable research records ready for review, including:
   • IRB submissions
   • Protocols
   • Recruitment materials
   • Subject screening and enrollment logs
   • Signed consent forms
   • DSMB reports
   • FDA visit reports
   • Monitoring reports
   • Communication from sponsor/funder

Education, consulting and assistance

The Quality Improvement and Quality Assessment Office is available for education and consulting sessions, as well as assistance.

Education

The QI/QA office staff has unique skills in understanding how to adjust study procedures/processes to comply with federal, state and institutional policies. The staff will offer recommendations for increasing compliance while maintaining or increasing good research design.

Consulting

The office staff is available for research design and compliance consulting. The process usually takes this form:

The PI contacts the PAMQuIP office by email to request a consult. The PI emails specific questions for review at least a week prior to RAMS IRB submission or a consulting meeting. A meeting is scheduled to discuss the study. The meeting takes place. A consulting report is sent to the PI if needed and uploaded to the RAMS/Human Research Protection Program's secure server if appropriate. The report includes questions and recommendations.

Assistance

The staff can offer up to six hours of assistance after a visit/consultation. This usually takes the form of advice regarding upcoming submissions/amendments, researching PI questions and conversations with the PI about research design enhancements for current or upcoming research.

Schedule a consultation

Please use the "Schedule a consultation" button above to reserve a time to meet with a member of the PAMQuIP Team for education, consulting, or assistance. You can also contact PAMQuIP at pamquip@vcu.edu with questions or requests for additional information.

Resources

• Post-Approval Monitoring and Quality Improvement Program Self-Evaluation Tool (PAMQuIP SET)
• WPP X-3: Post Approval Monitoring of IRB-Approved Protocols

Study conduct toolkit

Click here to view the study conduct toolkit, which contains a wide variety of templates to assist investigators and study coordinators with study organization and conduct.