The Protocol Deviation, Non-compliance and Protocol Exception Form must be used to report major protocol deviations, issues of non-compliance and protocol exceptions, defined as the following:
Definitions
A protocol deviation is defined as a variation from the IRB approved research plan that happens without prior review and approval of the IRB (e.g., study visit outside protocol window, blood work drawn outside protocol window, etc.). Protocol deviations can be major or minor. Depending on the details, protocol deviations may be determined to be non-compliance (serious, continuing, or otherwise).
Non-compliance is defined as failure to adhere to federal, state, or local regulations governing human subject research, organizational policies related to human subject research, or the requirements or determinations of the IRB. Non-compliance may be minor or sporadic or it may be serious or continuing.
Protocol deviations and non-compliance may or may not be intentional and may or may not be under the control of the study team.
Major Protocol Deviations and Non-compliance
Protocol deviations and non-compliance issues should be reported if it meets any of the following criteria:
- May represent a serious failure on the part of the study team to comply with the protocol, standard operating procedures, GCPS, federal, state or local regulations.
- May represent a continuing failure on the part of the study team to comply with the protocol, standard operating procedures, GCPS, federal, state or local regulations.
- Significant negative impact to subject safety or alters risks to subjects. The deviation/noncompliance may or may not result in actual harm to the subjects. Risk or actual harm may be clinical, emotional social, financial, etc. The risk/potential risk to the subject present by this deviation is deemed to be greater than minimal risk.
- Significantly damages the completeness, accuracy and reliability of the data collected for the study.
Serious non-compliance. Serious non-compliance is defined as non-compliance that, in the judgment of the convened IRB, creates an increase in risks to subjects, adversely affects the rights, welfare or safety of subjects, or adversely affects the scientific integrity of the study. Willful violation of regulations and/or policies may also constitute serious non-compliance.
Continuing non-compliance. Continuing non-compliance is defined as a pattern of non-compliance that, in the judgment of the convened IRB, suggests a likelihood that instances of non-compliance will continue unless the IRB or organization intervenes.
Examples of major deviations and noncompliance that should be reported to the IRB. These examples may or may not be serious or continuing non-compliance.
- There is evidence of willful or knowing misconduct on the part of the investigator(s), or study team
- Implementing non-exempt human subject research prior to IRB-HSR approval.
- Inappropriate documentation of consent or failure to obtain informed consent prior to initiating study procedures. (i.e., there is no documentation of informed consent, or informed consent is obtained after initiation of study procedures)
- Major deviations involving failure to document informed consent, including:
- Missing subject or parental signature and source documents are not available to indicate the subject/parent voluntarily agreed to participate in the study and understood the risks.
- Use of invalid consent form where there was a change in the study procedure that increased risk to subjects, subject requirements, cost to subject, or risks of the study as described in the consent form and the subject was not re-consented prior to exposure to the new risk.
- Failure to obtain 2 parent signatures if required by the IRB and the reason for the missing second parent signature is “not appropriate”. Acceptable reasons for missing second parent signature could be that the second parent has lost legal custody, is oversees in a war zone, is in a coma, etc.
- Enrollment of a subject who did not meet all inclusion/exclusion criteria without prior approval from the sponsor or the study DSMB.
- Implementing a modification prior to IRB approval, except in certain specific cases where modifications must be implemented to protect subject safety.
- Failure to report serious unanticipated problems/adverse events to the sponsor/DSMB or whoever is responsible for reviewing safety on an ongoing basis.
- Failure to perform study procedures outlined in the protocol where subject safety or data integrity may be significantly and negatively impacted.
- Drug/study medication dispensing or dosing error where the subject is negatively affected/potentially negatively affected. (i.e. risk or potential risk is increased in a significant way, subject visit/procedure falls outside of the window of time indicated by the protocol resulting in significant increase in potential for risk to the subject or damage to the integrity or completeness of the data).
- Subject visit/procedure is not done per protocol resulting in significant increased potential for risk to the subject or significant damage to the integrity or completeness of the data.
- Missing safety labs where the study team ordered the correct tests but for some reason the test was not performed, or there was a lab processing error AND subject safety was significantly and negatively affected.
Reporting Timelines for Deviations and Serious/Continuing Noncompliance:
All major protocol deviations and issues of noncompliance must be reported to the IRB-HSR immediately upon discovering them, and no later than seven (7) calendar days from the time the study team receives knowledge of the event.
Protocol deviations that meet the definition of Unanticipated Problem
Some protocol deviations may also meet the definition of or result in an unanticipated problem. The link below provides information on unanticipated problems:
IRB Reporting of Serious/Continuing Noncompliance and Unanticipated Problems
The IRB is required by federal regulations to report issues of Serious and/or Continuing noncompliance and issues meeting the definition of Unanticipated Problem to federal agencies (OHRP, FDA as appropriate), institutional officials (department chairs, Risk Management etc.) and in some cases the funding source (when DHHS funding is supporting the study).
Definition of a Minor Deviations:
A minor deviation is a deviation that does not impact participant safety, compromise the integrity of study data and/or affect the participant’s willingness to participate in the research. Minor deviations do not need to be reported to the IRB.
Examples of minor deviations may include, but are not limited to:
- Implementation of unapproved recruitment procedures that would have been approved by IRB-HSR if submitted according to the recruitment procedures.
- Missing signed and dated consent form, however, there is source documentation the subject willingly consented to the study.
- Missing pages of executed consent form and subject was later re-consented with a complete consent.
- Inappropriate documentation of informed consent, including:
- Missing subject or parental signature; however, source documents indicate the subject/parent voluntarily agreed to participate in the study and understood the risks.
- Missing investigator signature
- Copy not given to the person signing the form
- Someone other than the subject dated the consent form
- Individual obtaining informed consent/study procedures not listed on IRB-HSR approved key personnel list
- Use of invalid consent form, i.e. consent form without IRB-HSR approval stamp, or outdated/expired consent form (unless there was a change in the study procedure that increased risk to subjects, subject requirements, cost to subjects, or risks of the study as described in the consent form).
- Failure to follow the approved study procedure that does not affect subject safety or data integrity
- Study procedure conducted out of sequence
- Omitting an approved portion of the protocol
- Failure to perform a required lab test for efficacy
- Missing lab results
- Study visit conducted outside of required timeframe
- Over enrollment of more subjects than number approved by IRB
- Subject visit/procedure falls outside of the window of time indicated by the protocol and there is no increased potential for risk to the subject or any damage to the integrity or completeness of the data.
- Subject visit/procedure is not done per protocol and there is no increased potential for risk to the subject or any damage to the integrity or completeness of the data
- Minor dosing errors where the potential risk to the subject is not increased or the increased risk is felt to be minor.
- Procedures not completed at a participant’s request.
Why Minor Deviations do NOT require reporting to the IRB
Minor deviations do not need to be reported to the IRB. These issues have been deemed to present less than minimal risk to the subject. The IRB recommends however that a record or log be kept of minor deviations and/or suggests the use of Notes to File for the research records to document when these sorts of issues are discovered. If you wish to use the log format the IRB has provided a template for you called Minor Deviation Log and it is available under FORMS.
If you or your sponsor feel it is necessary to submit these minor deviations to the IRB-HSR you are welcome to do so. You will receive acknowledgement of receipt of these submissions. Please make sure that any minor deviations submitted include the following statement or similar wording: I verify that the minor deviation(s) recorded on this form do not meet the IRB reporting criteria for major deviation, serious and/or continuing or unanticipated problem.
Protocol Exceptions
Protocol/Research Plan exceptions are circumstances in which the investigator wishes to deviate from eligibility criteria or one or more of the specific procedures called for in a research plan. Unlike modifications that apply to all subsequent subjects in the research, a protocol/research plan exception only applies to a specific subject or group of subjects. Exceptions are planned, and the investigator gets approval from the sponsor ahead of time.
Submission Instructions for “Protocol Deviation, Noncompliance or Protocol Exception Reporting Form”
Send one (1) completed “Protocol Deviation, Noncompliance or Protocol Exception Reporting Form” (signed and dated by the PI) along with any additional documentation to IRB-HSR office to Box # 800483 with IRB-HSR Routing Form
For additional information please see the IRB-HSR Learning Shot: Reporting to the IRB Part 2: Protocol Deviation, Noncompliance and Protocol Exceptions