Reporting Research Milestones in Click IRB
The Continuing Review (CR) submission form in the Click IRB review platform requires study activities to be reported through research milestones (described below). When selecting the applicable research milestone(s), keep the following points in mind:
Generally, the conduct of research involves: 1) enrolling subjects; 2) conducting study procedures; 3) collecting data; and 4) analyzing data. The first four research milestones identified in Click IRB reflect these four basic steps and, as such, should be selected in order, over the course of the research as each milestone is achieved (i.e. completed in its entirety). Once all four milestones have been achieved, Click IRB programming will facilitate IRB closure.
The two additional research milestones listed in Click IRB (‘remaining study activities are limited to data analysis’ and ‘study remains active only for long-term follow-up of subjects’) fall into a study’s lifecycle but, if selected, implicate specific IRB review pathways for research involving greater than minimal risk. Moreover, the wording of the last two milestones do not represent an endpoint or achievement. Rather, they are active, ongoing phases of the research (i.e., they may be selected when a study is within the course of the phase, not necessarily when the phase has been achieved/completed).
This confirms the study’s progress at the time of each continuing review and facilitates appropriate timing of study closure. Failing to select a milestone that was previously achieved implies that steps in the research have been skipped or the research is moving ‘backwards’ in the lifecycle, which is only accurate in very rare circumstances.
A milestone should only be selected when the milestone is achieved for all aspects of the research. This includes all subjects, all sub-studies, and all cohorts, as described in the study protocol. Individual subject status is no longer required to be routinely reported, with the exception of withdrawals, which are collected as part of Question #4. It is also possible that additional information regarding individual subject statuses may be requested by the Research Subjects Review Board (RSRB).
The research milestones are phrased in this manner to accommodate different types of research with varying subject engagement and to facilitate closure of approved studies that will not be completed. Generally, the first statement applies to traditional types of research where subjects enroll in the research and actively participate in study procedures. Whereas, the second statement applies to other types of research with no subject engagement (e.g., concept or umbrella studies) or when the research was approved but will not be conducted and submitted for closure.
The ‘Comments’ field in Question 5 of the continuing review form may be used when it is necessary to provide additional information about research milestones.
Research milestones
- Study is permanently closed to enrollment: All subjects (in all sub-studies and all cohorts, if applicable) have been enrolled in the research; no additional subjects will be enrolled in the future. Note: When considering secondary data analysis studies, chart reviews, and specimen analysis, ‘enrollment’ refers to records or specimens accessed/used.
OR
- Study was never open to enrollment: A) The study does not involve subject enrollment (e.g., concept or umbrella studies); OR B) The study never began (no subjects were enrolled and no data was collected) and the continuing review is being submitted to close the study.
- All subjects have completed all study-related interventions: All subjects (in all sub-studies and all cohorts, if applicable) have completed all study procedures. Note: In this case, the word ‘intervention’ should be broadly applied to encompass all study-related procedures and interactions (e.g., surveys, interviews, or task completion); the use of the word ‘intervention’ here is not limited to manipulations of the subject or subject’s environment.
OR
- Study-related interventions are not applicable: A) The study does not involve active engagement or participation of subjects (e.g., secondary data analysis, chart reviews, and specimen analysis); B) The study does not involve subject enrollment (e.g., concept or umbrella studies); OR C) The study never began (no subjects were enrolled and no data was collected) and the continuing review is being submitted to close the study.
Note: Generally, this milestone should only be true when the following additional milestone has been achieved (and selected in Click IRB):
- Study is permanently closed to enrollment OR was never open to enrollment.
- Collection of private identifiable information is complete: The collection and/or receipt of all identifiable data and specimens is complete (including the collection/receipt of coded data and specimens); no further data collection, editing, or queries will occur.
OR
- Collection of private identifiable information is not applicable: A) The study does not involve subject enrollment (e.g., concept or umbrella studies); OR B) The study never began (no subjects were enrolled and no data was collected) and the continuing review is being submitted to close the study.
Note: Generally, this milestone should only be true when the following additional milestones have been achieved (and selected in Click IRB):
- Study is permanently closed to enrollment OR was never open to enrollment; AND
- All subjects have completed all study-related interventions OR not applicable.
- Analysis of private identifiable information is complete: Analysis of identifiable data, as described in the study protocol, is complete (including the analysis of coded data).
OR
- Analysis of private identifiable information is not applicable: A) The study does not involve subject enrollment (e.g., concept or umbrella studies); OR B) The study never began (no subjects were enrolled and no data was collected) and the continuing review is being submitted to close the study.
Note: Generally, this milestone should only be true when the following additional milestones have been achieved (and selected in Click IRB) and the intention is to close the study:
- Study is permanently closed to enrollment OR was never open to enrollment;
- All subjects have completed all study-related interventions OR not applicable; AND
- Collection of private identifiable information is complete OR not applicable.
All subjects (in all sub-studies and all cohorts, if applicable) have been enrolled; all study-related interventions, procedures and interactions are complete; and all data have been collected BUT the analysis of the data, as described in the study protocol, is not yet complete.
Note: This milestone should only be true when the following additional milestones have been achieved, minimally (and selected in Click IRB):
- Study is permanently closed to enrollment OR was never open to enrollment;
- All subjects have completed all study-related interventions OR not applicable; AND
- Collection of private identifiable information is complete OR not applicable.
All subjects (in all sub-studies and all cohorts, if applicable) have been enrolled and the only remaining study-related procedures for active subject is limited to long-term follow-up only. Per HHS Office for Human Research Protections guidance, long-term follow-up includes: (continued on next page)
- “Research interactions that involve no more than minimal risk to subjects (e.g., quality of life surveys); and
- Collection of follow-up data from procedures or interventions that would have been done as part of routine clinical practice to monitor a subject for disease progression or recurrence, regardless of whether the procedures or interventions are described in the research protocol”.
Long-term follow-up does not include “research interventions that would not have been performed for clinical purposes, even if the research interventions involve no more than minimal risk” (HHS guidance).
Note: This milestone should only be true when the following additional milestone has been achieved (and selected in Click IRB):
- Study is permanently closed to enrollment OR was never open to enrollment.
Examples and common scenarios
No research milestones are selected
- Scenario A: Study is open to enrollment, but no enrollment has occurred.
- Scenario B: Subjects have enrolled but the accrual goal has not been reached. Enrolled subjects are actively participating in study procedures (some or all enrolled subjects may have completed or discontinued study participation).
- Scenario C: Enrollment is complete for one, but not for all cohorts. Enrollment in open cohort(s) continues; enrolled subjects are actively participating in study procedures (some or all enrolled subjects may have completed or discontinued study participation).
- Scenario D: Subjects have enrolled and were reported at the time of a previous continuing review, but no additional subjects were enrolled during the current reporting period; the study is continuing to enroll subjects. Enrolled subjects are actively participating in study procedures (some or all enrolled subjects may have completed or discontinued study participation).
- Scenario 1: The study has not been initiated, but will be initiated in the future.
- Scenario 2: Subjects/specimens for inclusion in the research have been identified; additional subject/specimen identification for inclusion may occur. Data collection or laboratory analysis on specimens may have begun but is not complete.
Study is permanently closed to enrollment…
Scenario E: Subject enrollment is complete (in all sub-studies and all cohorts, if applicable); no additional subjects will be enrolled. Enrolled subjects are actively participating in study procedures (some subjects may have completed or discontinued study participation).
Scenario 3: All subjects/specimens for inclusion in the research have been identified; no additional subjects will be identified. Data collection or laboratory analysis on specimens has begun but is not complete.
Study is permanently closed to enrollment…; AND
Study remains active only for long-term follow-up of subjects
Scenario F: Subject enrollment is complete and remaining study procedures for all active subjects (in all sub-studies and all cohorts, if applicable) is limited to long-term follow-up only.
Study is permanently closed to enrollment…; AND
All subjects have completed all study-related interventions…
Scenario G: Subject enrollment is complete and all subjects (in all sub-studies and all cohorts, if applicable) have completed all study procedures; no additional study procedures will be performed. Receipt of additional data may continue as test/procedure results are calculated/reviewed and/or data edits, queries or cleaning is completed.
Study is permanently closed to enrollment…;
All subjects have completed all study-related interventions…; AND
Remaining study activities are limited to data analysis
Scenario H: Subject enrollment is complete and all subjects (in all sub-studies and all cohorts, if applicable) have completed all study procedures. Data analysis has begun but is not complete. Additional data edits, queries or cleaning may still take place.
Scenario 4: All subjects/specimens for inclusion in the research have been identified; no additional subjects will be identified. All identifiable data/specimens have been accessed and/or collected. Laboratory analysis on specimens is complete. Additional data edits, queries or cleaning may still take place. Data analysis has begun but is not complete.
Study is permanently closed to enrollment…;
All subjects have completed all study-related interventions…;
Collection of private identifiable information is complete…; AND
Remaining study activities are limited to data analysis
Scenario I: Subject enrollment is complete and all subjects (in all sub-studies and all cohorts, if applicable) have completed all study procedures. No additional identifiable or coded data/specimens will be collected and/or accessed. Data analysis has begun but is not complete.
Scenario 5: All subjects/specimens for inclusion in the research have been identified; no additional subjects will be identified. No additional identifiable or coded data/specimens will be accessed and/or collected. No additional laboratory analysis on specimens will be completed. Data analysis has begun but is not complete.
Study is permanently closed to enrollment…;
All subjects have completed all study-related interventions…;
Collection of private identifiable information is complete…; AND
Analysis of private identifiable information is complete…
Note: Selecting all four of these milestones will close the study.
Scenario J: Subject enrollment is complete and all subjects (in all sub-studies and all cohorts, if applicable) have completed all study procedures. No additional identifiable or coded data/specimens will be collected and/or accessed. Data analysis, as described in the study protocol, is complete. Any further analysis of data will be limited to the analysis of de-identified data sets.
Scenario 6: All subjects/specimens for inclusion in the research have been identified. No additional identifiable or coded data/specimens will be collected and/or accessed. No additional laboratory analysis on specimens will be completed. Data analysis, as described in the study protocol, is complete. Any further analysis of data will be limited to the analysis of de-identified data sets.