Guidance on Presenting Noncompliance Reports to the IRB
Study teams are responsible for reporting potential noncompliance to the IRB so that it can determine whether the event constitutes noncompliance and, if so, whether the noncompliance is serious or continuing . This document serves as a guide for study teams when completing a noncompliance report for submission to a Health Sciences IRB in ARROW. It describes what information study teams need to include in the report, how information should be presented, and what additional steps may need to be taken both to gather information necessary to include in the report and to formulate an effective corrective action plan.
Submitting Noncompliance Reports in ARROW
After study teams discover the potential noncompliance, unless the event meets does not require reporting under the Health Sciences IRBs Protocol Exceptions and Deviations Guidance, they are responsible for informing the IRB within the required timeframes by submitting a noncompliance report in ARROW, how to complete reportable events. If potential noncompliance occurred on a study or project that is not active in ARROW (i.e., the noncompliance involves the conduct of research activities without prior IRB approval, or the study has been recently archived in ARROW), contact the Health Sciences IRBs office for instructions on how best to submit the report.
Completing the Noncompliance Report
The purpose of the noncompliance report form is to provide the IRB with the information necessary to make a determination as to whether noncompliance has occurred and, if so, whether it is serious and/or continuing as well as to ensure that appropriate actions have been or will be taken to ensure the rights and welfare of study participants. In order to provide the IRB with the details necessary to adequately evaluate the event, study teams may need to go through an information-gathering phase, which may include, for example, conduct of a root-cause analyses, audit of other studies, and development of a robust corrective and preventive action plan. If this phase cannot be accomplished within the required timeframes for reporting, at least a preliminary report should be submitted to the IRB within the required timeframe. This report should reflect the preliminary nature of the assessment of the event, describe the information-gathering activities that are ongoing related to the event, and provide an expected timeframe for completion of the investigation.
How should study teams complete the New Information, Noncompliance, Unanticipated Problems page in ARROW?
Q1.1 Describe the event or new information
This question serves as the main summary of the event being reported. A detailed description of the event should be provided and include enough context so as to be understandable without referring back to the protocol and/or IRB application. This may include the following information:
- Where and when the event(s) occurred (a timeline of events may be helpful)
- How the event(s) was discovered and by whom (e.g., study coordinator or study monitor)
How many subjects were involved or affected by the noncompliance
- A description of what should have happened versus what actually happened, with reference to specific sections of the protocol or other documents as necessary
Examples for summarizing a potential noncompliance event
Example 1: Dosing Error
Per protocol section 2.7 “All subjects will be dosed with 2.5mg/kg of body weight of study drug on Cycle 1 Day 1”. Subject A was seen in clinic on cycle 1 day 1 and weighed. The subject weighed 61kg and should have received 152.5mg of drug. The subject was inadvertently given 15.25mg of study drug, which was 1/10th of the dose the subject should have received. This dosing error was discovered the next day during the study coordinator’s review of the subject charts. All the subject charts for this study were reviewed and it was determined this was the only subject for whom a dosing error occurred.
Example 2: Informed consent error
Subject 1 was enrolled in the study on 12.30.2014 and signed an incorrect version of the consent form. Subject 1 signed version 1.0, dated 10.1.2014 of the study consent form. A change of protocol was recently approved by the IRB on 11.15.2014, which updated the consent form to version 2.0; dated 11.1.2014. The updates to the consent form from version 1 to version 2 included the following: increase in the study compensation amount from $100 to $250 and the addition of another research questionnaire for completion on visit 3. The study coordinator discovered this event after reviewing Subject 1’s chart prior to his first study visit. This was the first subject enrolled on study so no other subjects were affected. The study coordinator reviewed the new consent form with the subject, which the subject signed prior to completion of his first study visit.
Q1.3 Describe what effect the event or new information has or may have on the current research study.
The purpose of this question is to describe what actions may need to be taken regarding the conduct of the research study, based on the event/new information (e.g. halting the study to new enrollment, notifying subjects of information related to the event, closing a study arm, etc.)
Q1.4 Were subjects placed at increased risk of harm because of the event or new information? Provide rationale as to why or why not.
The purpose of this question is to assess the effect of the event on subject safety. Study teams are expected to provide a basis for any conclusions regarding the potential impact of the event on subject safety, specifically why subject safety was not likely to be affected and the empiric basis for this conclusion as well as how the study team ensured there were no adverse outcomes for other subject(s), if applicable, who could have been affected by the potential.
For example, if the event involves multiple missed safety labs for one subject, it is not sufficient to only state that subject safety was not affected and the subject experienced no side effects or adverse events. Instead, study teams should provide justification as to why subject safety was not likely to be affected. The study team might note that labs were drawn two days prior to the missed labs, and again the day following the missed labs and that these lab values were normal and the short time frame between the values is thought to have been sufficient to detect any abnormalities, even with the missed labs. Further, the study team should explain how it was ensured that there was no adverse outcomes, such as noting they followed up with the subject the same day that it was realized safety labs were missed and conducted additional monitoring (e.g., vitals, health history assessment, additional labs) to assess any potential problems the subject may have been having.
Q1.5 Was data integrity impacted by the event or new information? Provide rationale as to why or why not.
Data integrity refers both to the accuracy of data collected and the assurance that the data have not been altered or corrupted by the reported event. For example, inconsistencies in documentation or missing data points may impact data completeness and integrity such that the ability to meet the study's original aims/goals is compromised. Study teams should describe how data integrity may have been affected, if at all, as well as the basis for this assertion.
How should study teams complete the New Information, Noncompliance, Unanticipated Problems: Corrective and Preventative Actions ARROW page?
Q2.1 Describe the steps that have been or will be taken to mitigate the adverse effects on the subject(s) involved in the event (e.g. additional subject monitoring, laboratory tests, re-consenting subjects, etc.). If no steps have been taken, explain why.
This question addresses any steps the study team may have taken immediately to protect the rights and welfare of the subject(s) involved in the event, or actions taken to prevent the possibility of increased risk as a result of the event. Immediate steps may include outreach to subject(s) who were potentially affected by the noncompliance or suspension of study procedures. Follow-up steps many include an assessment to determine if additional subjects in the same study or other studies conducted by the research team could have been affected by the event, or provision of new information to subjects.
If no steps were taken, this should be stated along with an explanation as why this was the case. For example, no action was necessary as this was minor administrative noncompliance and did not place subjects at risk.
Q2.2 Describe the cause of the event. Depending on the complexity of the event, a root cause analysis may be necessary: CAPA Plans Guidance.
Study teams are expected to identify breakdowns in processes and systems that resulted in the potential noncompliance. Depending on the severity and complexity of the noncompliance, study teams may need to conduct a root cause analysis (RCA). The purpose of the RCA is to determine what happened, why it happened, what other factors may have contributed to the event, and finally, to determine what changes need to be made to prevent the event from occurring again, forming the basis of the corrective and preventive action (CAPA) plan.
For the purposes of report to the IRB, the study team should document the general findings of any RCA in question 2.1.
Q2.3 Describe the corrective actions taken to prevent similar events from occurring in the future. Include the following:
- A timeline for completing the corrective actions
- A description as to how it will be ensured the implemented corrective actions are effective
The purpose of this question is to provide the study team a place to describe the CAPA it developed in sufficient detail so that the IRB can evaluate its adequacy. Effective CAPA plans consist of two components: (1) the steps necessary to prevent the event from occurring in the future, and (2) a plan for ensuring that the corrective actions are implemented and effective.
Robust CAPAs address all factors that contributed to the event and may include:
- Additional education of the investigator and/or the research staff
- Additional monitoring of support staff by the investigator, including more frequent staff meetings or review of work by an auditor
- Creation of standard operating procedures (SOPs) or checklists
- Revisions to study documents or processes
- Conducting an audit of other studies to determine if the same or similar noncompliance occurred more widely
- Conducting a follow-up self-audit (or series of planned audits) to evaluate the implementation of the CAPA and its effectiveness in preventing similar errors
Q2.4 Will the information contained in the report result in a change to the study protocol, consent documents, or any other study materials?
Q2.4.1 If yes, briefly describe what changes will be proposed.
Q2.4.2 If no, provide justification for why no changes are necessary.
The responses to 2.4, 2.4.1, and 2.4.2 should describe any changes to the protocol and IRB application, consent documents or process, or any other study materials that will be made as a result of the event, as well as confirmation, when appropriate, that a change of protocol will be (or has been) submitted to the IRB. These changes may be included as part of the previously described CAPA, or may be in addition to the CAPA. If the event will not result in changes to study documents or procedures, provide justification as to why changes are not needed. For example, changes may not be warranted because the event was minor administrative noncompliance, did not result in risk to subjects, or enrollment in the study is now closed with all subjects off study.
How should study teams complete the New Information, Noncompliance, Unanticipated Problems: Assessment ARROW page?
Q3.1 Describe how the information in this report impacts the risk/benefit ratio of the study, if at all.
This response should provide an overall summary of how the event does or does not impact the risk/benefit ratio of the study. Specifically, the IRB is looking for information about whether the potential noncompliance suggests that the research presents increased risks to subjects beyond what the IRB approved or the potential benefit to subjects is altered. This assessment should consider the study as a whole, and not just the subject(s) that may have been directly involved in the event.