Closing Time: The Dos and Don’ts of Study ClosureJune/July 2022 Issue(Note: this article is an update of an article published in September 2014) Author(s):
When Do I Close a Study?The short--but accurate--answer is, “When what you are doing no longer constitutes human subjects research. In previous editions of the CR TIMES, we wrote about what is and what is not human subjects research, and when active IRB oversight is needed. In this month’s article, we will cover how a similar analysis can be used to let you know when it is acceptable to close a study that previously involved human subjects research. Once a study involving human subjects research has been approved or determined to be exempt, oversight by the IRB continues until the investigator provides information that the study qualifies for closure. This IRB oversight consists of continuing review (and re-approval of a research project) at least annually for studies with expiration dates, and a status check-in at least every 3 years for all other studies. OHRP considers a research project to continue to involve human subjects as long as the investigators conducting the research continue to obtain:
At first reading, you might think that once you have finished interacting with subjects and are no longer collecting identifiable private information, then at that point you are no longer doing human subjects research and, therefore, can close the study. This is because the OHRP (and our HRPP) also considers using, studying, or analyzing identifiable private information or identifiable biological specimens to constitute human subject research. However, once the information or specimens are no longer identifiable, then using, studying, or analyzing the information or specimens is not human subject research. The OHRP’s definition of identifiable is that the identity of the subject is or may readily be ascertained by the investigator or associated with the information (or specimens). This definition is not the same as the HIPAA definition of “de-identification.” The HIPAA definition of de-identification is that the data do not contain any of the 18 HIPAA identifiers; or a statistical expert has determined that the risk is very small that the information could be used by a recipient to identify the individual(s). There will be situations in which a data set may meet the definition of HIPAA de-identification, but the identity of the subjects would still be known to the investigators. In such a case, analysis of the data would constitute human subjects research, and continuing review or status check-in by the IRB is required. For example, in a study involving interviews with a small number of individuals, the investigator who conducted the interviews can readily recall which subject provided which answers, even if the data set do not contain any of the HIPAA identifiers, because of the small number of subjects. The analysis being done by the investigator is still considered human subject research because the participants are identifiable, so continued oversight by the IRB is required. For the rest of this article, let’s use the example of a research study where:
The only activity that remains is analysis of the data, which IS human subjects research if the data are identifiable; and is NOT human subjects research if the data are not identifiable. At this point, it should be determined whether the study is no longer human subjects research and is eligible for closure. Two obvious situations where data are no longer identifiable are (1) if all raw data have been erased and only aggregate data remain; and (2) if data are coded (a study ID number replaces all direct identifiers), and the linking code has been destroyed.
You can also close your study if you continue to maintain the data (even if it is identifiable), but are no longer doing analysis or otherwise accessing the data. Simply maintaining individually identifiable private information without using, studying, or analyzing such information is not human subjects research and, thus, does not require continuing oversight by the IRB. Note that the maintenance/storage of identifiable private information must be consistent with the IRB-approved research plan, and the Investigator must continue to honor any confidentiality protections of the data that are in the approved protocol or application.
How Do I Close a Study?Final reports must be submitted when a study is closed, including when a study is terminated by the Principal Investigator or the sponsor prior to the anticipated end of the protocol. To close a study, submit a Final/Closure Report form in INSPIR prior to the expiration or status check-in date, rather than using the Continuing Review form. The Final/Closure Report form asks some questions related to the study closure which are not found in the Continuing Review Submission form. The submission information for closure of approved non-exempt research includes enrollment; demographics; auditing or monitoring results; adverse events, deviations, and subject complaints; closure processes (including plans for destroying or anonymizing study data and whether data or specimens will be moved into a repository); study status (never started or closed); and new risks. Please make sure that you answer all of the questions in the Final/Closure Report form, or it will be returned to you with a request to complete missing sections. The submission information for closure of exempt or ceded research must simply include that research activities are no longer occurring. The closure letter indicates that the effective date of the closure is the date when the Final Report was submitted in INSPIR. The IRB endeavors to process Final Reports on a routine basis; yet, Final Reports are not high on the priority list, when compared to forms for studies that actively involve human subjects. Therefore, please send an email to medirb@bu.edu if you have a time-sensitive need for the closure letter (for example, for the Sponsor or for funding purposes). If you have closed a study where you are maintaining but not analyzing identifiable data, and at a later date, you wish to go back to do further analysis of the previously-collected identifiable data to answer a different study question, you would then have to submit a new protocol describing your plan, and wait until you receive IRB approval before you use or analyze the identifiable data. Alternatively, you can submit an amendment to your closed study to re-open it for further analysis of identifiable data. Please check with the IRB first to see whether it would be more appropriate to re-open your old study with an amendment, or submit a new study to use the data. If the data are not identifiable, or you are still maintaining a master-code but do not need to access the master-code to do your new analyses, then you do not need IRB oversight. This is because using or analyzing non-identifiable data is not human subjects research, as discussed earlier. Please note that letting a study lapse by failing to submit a Final Report or Status Check-In Report does not fulfill the requirement to close a study. The IRB will check new submissions to determine whether the Principal Investigator (PI) is responsible for any lapsed studies as PI or Supervising Principal Investigator (SPI). If the PI does have a lapsed study, the PI will be informed that the new study will not be considered by the IRB until the lapsed study has been closed.
What Are My Responsibilities for Keeping the Data After Study Closure?It is the PI’s responsibility to maintain all study records (including source documentation) according to institutional, sponsor, and federal requirements. Study records must be retained for a minimum of 7 years after the end of the study, according to Boston Medical Center policy #39.04.455 and Boston University policy #FA-002. The end of the study is the date that you submitted your Final/Closure Report form. This effective closure date will appear in the closure letter that the IRB sends you. A longer retention period may be required by the sponsor of the study or because of other circumstances, such as a pending investigation. Sponsor-investigators with INDs must assure that the retention period complies with requirements based on the date of marketing application approval or notification to the FDA, and sponsor-investigators with IDEs must ensure that the retention period complies with requirements based on the date of communications to the FDA. Specific information about these FDA requirements may be found in Section 6.6.7.1 of the HRPP Policies and Procedures. When you destroy records after the retention period is over, you must ensure that you use a method for destruction that ensures there is no possibility of reconstruction of the information. Boston Medical Center policy notes that appropriate methods include shredding, burning, pulping and pulverizing. Boston University policy describes specific methods and tools for destruction of physical and electronic data here under ‘Data Protection Standards - Additional Guidance’. If you ever have a question about retaining your research records after study closure; for example, how long to retain records or in what format, please reach out to the IRB at medirb@bu.edu.
What Do I Do About Closing My Study if I am Leaving the Institution?If a PI leaves Boston Medical Center (BMC) or Boston University (BU) Medical Campus and/or is no longer a member of the BMC or BU Medical Campus faculty or staff, then human research activities cannot continue at BMC or BU Medical Campus unless a new qualified individual accepts responsibility as the PI. If the responsibility is not transferred to a qualified individual as PI, then the study must be closed. Closure is also appropriate when the departing PI wishes to move the study in its entirety to a new institution. Such a transfer cannot take place, however, until the IRB of the new institution has issued its approval or exemption determination. If the PI leaves before such approval is obtained, a new PI at BMC or BU Medical Campus must be designated until IRB approval has been obtained at the new institution and a Final/Closure Report can be submitted to close the study at BMC or BU Medical Campus. If the human subjects activities at BMC or BU Medical Campus will cease after PI departure, and the study does not need to be left open until the study has IRB oversight at the new institution, PIs are required to submit a Final/Closure Report for all active studies *prior* to leaving the institution. It is not appropriate to simply leave and let the study expire or miss its status check-in due date.
ConclusionThe IRB often receives Continuing Review or Status Check-In submissions that indicate that the only ongoing activities involve the analysis of non-identifiable data and/or completing the manuscript for publication (with no further need to access identifiable data). As explained in this Feature Article, analysis of non-identifiable data is not human subjects research, and, therefore, does not require continuing IRB oversight. Instead, these studies can be closed. Conversely, studies that have completed all interactions with subjects but do still require analysis of identifiable data, need to remain open with active IRB oversight. By knowing when you are permitted to close a study, you can remain in compliance with HRPP policy while allocating the appropriate time and effort to attending to the requirements of your IRB submissions.
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