Feature Article

The Final Frontier: IRB Final Reports
January 2010 Issue

Eliana Meirowitz, BA
Senior IRB Analyst, Panel Blue
Author has nothing to disclose with regards to commercial support.

Educational Objectives:

At the end of this activity, participants should be able to:

• State how Final Reports relate to human subjects protection;
• Describe the requirements, both Federal Regulations and institutional policy, related to Final Reports;
• Explain how to complete a final report in INSPIR;
• Name two common errors investigators make when completing Final Reports.

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• Introduction
• When is a Final Report required?
• Are Final Reports actually that important?
• What do the regulations and BUMC policies say about Final Reports?
• What to include in a Final Report and how to write a Final Report
• Common Mistakes
• Studies that expire before a Final Report is submitted
• Conclusion
• Letter to the Editor
• References
• Quiz

Introduction

Final Reports are the last step in the IRB life cycle for research studies. The Final Report lets the IRB know that the research is complete, and gives the IRB the last details of how the study went before it was closed completely. The Office of Human Research Protections (OHRP), Food and Drug Administration (FDA), and BUMC IRB all have policies regarding completing Final Reports. The purpose of this article is to explain the importance of Final Reports, the regulation requirements related to Final Reports, and the essential components of a Final Report. The goal is for investigators to understand the necessity for completing timely and thorough Final Reports to the IRB.

When is a Final Report required?

Institutional Review Boards (IRBs) are required to review studies until all components of human subjects research are complete. The BUMC IRB Policies and Procedures state, “The Principal Investigator is required to notify the IRB when his/her study is completed. The IRB considers the study to be complete when the primary data analysis is complete and the study question is answered. Final Reports are also required when a study is closed or terminated by the PI or the sponsor prior to the anticipated end of the protocol.”

This means that for every non-exempt study, a Final Report must be submitted regardless of the size, risk level, or sponsorship of the study. Conversely, if the study is still in primary data analysis or manuscript preparation, or if the repository portion of the protocol is still open, then a Final Report can’t be submitted yet -- the study must remain open!

Are Final Reports actually that important?

The Final Report helps the IRB understand the entire history of the research project. They give the IRB the last picture of what happened in the study: How many subjects were enrolled overall? Did data get published? Did more adverse events occur than were expected? Most studies proceed as planned, and the Final Reports are simply a method of informing the IRB that studies have ended as expected.

Sometimes, however, a study takes an unexpected turn, such as being terminated early by a sponsor, ending because of failed recruitment efforts, loss of study staff or loss of funding, etc. In these situations, the Final Report is imperative so that the IRB can fulfill its responsibility in ensuring that appropriate measures have been taken so that subjects are not at placed at greater risk due to the early closure of the study. The IRB will also wants to ensure that all aspects of the study have been closed appropriately, the data has been de-identified (or destroyed if necessary), and any additional actions have been taken in accordance with the study plan (i.e., destruction of samples, final notification of subjects, etc.).

Final reporting is not just a regulatory concern. It is also a fundamental element of “Respect for Persons”. A Final Report is a respectful way to pay tribute to the individuals who have given their time and energy to your research. It shows that the investigators have considered the data which the research subjects have helped them to acquire, and helps to assure the IRB that the data is being put to its intended use.

What do the regulations and BUMC IRB policies say about Final Reports?

The FDA explains how a Final Report is relevant to the IRB review process. “IRBs are required to function under written procedures. One of these procedural requirements [21 CFR 56.108(a)(3)] requires ensuring prompt reporting to the IRB of changes in a research activity.” The completion of the study is a change in activity and should be reported to the IRB. Although subjects will no longer be “at risk” under the study, a Final Report allows it to close its files as well as provides information that may be used by the IRB in the evaluation and approval of related studies.

The Office of Human Research Protections (OHRP) explains that Final Reports must be submitted when all human subjects research activities have been completed. The guidance reads as follows:

“If all research-related interventions or interactions with human subjects have been completed, and all data collection and analysis of identifiable private information described in the IRB-approved research plan have been finished, then the human subjects research study has been completed. When a human subjects research study has been completed, the investigators no longer are required to obtain continuing review and approval of that study by the IRB. The investigators should follow any applicable institutional policies and procedures for notifying the IRB of the study's completion.

Once a study has been completed, investigators may keep the data they collected, including identifiable private data, if consistent with the IRB-approved research plan. Investigators should continue to honor any confidentiality protections of the data.

Investigators also should honor any other commitments that were agreed to as part of the approved research, for example, providing information about the study results to research subjects, or honoring commitments for compensation to research subjects for research participation.”

This means that if subjects were told that they would be given study results, then the time of the Final Report is also the time to inform the subjects about the results. If the data has been analyzed as planned, the manuscripts have been written, and there are no plans for additional use of the identifiable data (so the data has been de-identified), then it’s time to submit a Final Report. However, if primary analysis of identifiable data is still underway, or the manuscript is not completed, and there is a chance that an additional query of identifiable data may be needed to verify some results, then it is not time for Final Report submission -- the study must still remain open!

What to include in a Final Report and how to write a Final Report

Completing a Final Report is similar to completing a Progress Report. In fact, the exact same form is used! The most common problem seen by the IRB is that Final Reports are frequently improperly categorized as Progress Reports. By following the instructions below, investigators can ensure that their Final Reports are appropriately labeled as such by the INSPIR system:

• Open the “APPROVED” version of the protocol in INSPIR.
• Under “What would you like to do?”, select “Edit Progress Report/CR.”
• Complete the Progress Report as form as usual, completing all sections and providing the most accurate data about enrollment, reporting, AEs, and other study activities.
• Section PR5 is the transformative part of the form! This section contains several different templated options for protocol status. In order for the INSPIR system to flag this Progress Report as a Final Report, select the second-to-last option in Section PR5. This reads, ‘This is the FINAL REPORT. Research activities were never started OR all research activities (including all interventions, long-term follow-up and data analysis) have been completed. The study is closed.’ This is the *only* option that will turn this into a Final Report. If any other option is selected in PR5, the report will be electronically submitted to the IRB as a Progress Report (continuing review report) instead of a Final Report.
• Continue to complete the entire page as thoroughly and accurately as possible.
• If the study was never funded, it is important to explain this in PR6.
• If the study was completed or terminated, it is important to give a complete account of the status, including any reasons for termination, in Section PR6.
• Make sure that all promises, procedures, and policies set forth in the protocol and consent have been fulfilled or clearly explain why they have not. Have the data or identifiers been destroyed as described in the protocol? Have subjects been given information as promised? Were all the proposed analyses described in Section G performed? If all study activities have not yet been completed as set forth in the protocol, either complete those tasks before closing the study, or clearly and thoroughly explain in Section PR6 why the study is not being completed as planned.
• After a final check to ensure that the Final Report appropriately reflects the life of the study and all study activities have been completed (or there is a justification as to why they will not be finished), the Final Report is ready for submission.
• Only the Principal Investigator of the study has submit privileges in INSPIR and is allowed to submit the Final Report. This measure was designed into the system to help ensure accountability by the PI for the overall conduct of the study.

Common Mistakes

Here are some common mistakes observed by the IRB -- avoiding these will save the IRB time in processing Final Reports:

• If the sponsor closed the study before the study was complete, or an investigator’s individual site was closed before the overall study was completed, then this must be indicated in PR6! It is essential that information be included about why the study was closed, as well as the status of the subjects and how they were informed of the early termination of the research. Submit as much documentation of this decision as possible. If all the information will not fit in Section PR6, then supplemental information can be attached in Section S. ***Note: In some instances, the early closure of research is due to unanticipated problems and requires immediate notification of the IRB through the UPSER reporting process.
• If the study manuscript has been drafted but has not yet been accepted by the publisher, and there is a chance that the identifiable data may need to be queried further, then it is too early to submit a Final Report. All primary analyses of identifiable data must be done before submitting a Final Report.
• If the PI has left the institution and no additional research activities will be occurring at BU/BMC or with BU/BMC investigators, then this must be explained in detail in Section PR6. If the data are staying at BUMC, if analyses are happening at BUMC, if subjects are still at BUMC, then it may be necessary to keep the study open and assign a new BUMC PI to the study.
• Avoid the following approach, “Final Reports are too much work! Why don’t I just let the study expire and forget about it?” As detailed in this article, Final Reports are an integral part of the human subject protection regulations; and simply letting a study lapse is not a responsible way to end a study. Institutional policies requiring that investigators submit Final Reports are equal in importance to those requiring that investigators submit progress reports.
• Even if the study sponsor has conducted a closeout visit, this is not a substitute for a Final Report. Also, in all likelihood, the sponsor will want to verify that the Final Report has been approved by the IRB.
• If the study has never been funded and will never be conducted as was approved by the IRB, then a Final Report is still necessary to inform the IRB that the research will not be conducted. Sometimes it’s tempting for investigators to leave a study open, hoping that they may be able to initiate the research at some point in the future. However, this will require submitting regular progress reports to the IRB and explaining why there has been no progress on the project. If there is reasonable certainty that a study is not going to go forward as planned, then a Final Report should be completed.
• When preparing a Final Report, if investigators or study staff discover DSMB minutes, AEs, UPSERs, or Deviations that they neglected to submit previously, then these should be submitted at the time of the Final Report. The IRB needs as complete a record of the study as possible before approving the Final Report. Better late than never!

Studies that expire before a Final Report is submitted

Through the INSPIR system, the IRB can track all studies which investigators have allowed to expire without submitting a Final Report. These investigators then receive email notification of when their studies expire and are closed by the system. If an investigator becomes aware of a study that has expired and has been closed by the system, he/she still has a responsibility to complete a Final Report. In order to do so, he/she must contact Khaled Khattar in the IRB Office (617-638-7203) or kkhattar@bu.edu . Khaled will temporarily ”re-open” the study in INSPIR so that a Final Report can be created.

Conclusion

Final Reports give everyone the proper overview and sense of completion that is needed at the end of a study. Provided in this article is an explanation of the importance of submitting Final Reports, the regulatory requirements related to Final Reports, the contents of a Final Report, instructions for how to complete a Final Report in INSPIR, and a description of some common mistakes investigators make when completing Final Reports. Based on the regulatory requirements, most institutions, including BUMC, require investigators to submit Final Reports. Additionally, many sponsors require investigators to provide documentation that their Final Reports have been submitted and approved by their IRB.

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