Problems and Reportable Events in Research

Protocol Violations or Deviations and Unanticipated Problems

  • A protocol violation is a failure to comply with the study protocol as approved by the IRB. A violation is a serious non-compliance with the protocol that can result in the exclusion of a patient or their results in the study and in some cases a charge of research misconduct;
  • A protocol deviation is a less serious non-compliance with the approved study protocol. A protocol deviation presented in advance of the event may be considered acceptable by the sponsor (if any) and the IRB.
  • An unanticipated problem is not limited to physical harms.  They can include breaches of confidentiality or emotional harms (such as the emotional distress that could be triggered by questions about traumatic life events). Some unanticipated problems involve social or economic harm instead of the physical or psychological harm associated with adverse events.  Unanticipated problems that do not involve adverse events but must be reported are listed under the HHS regulations at 45 CFR 46.103(a) and 46.103(b) (5).

Please consult the Prompt Reporting Requirements policy for reporting of Protocol Violations, Deviations or Unanticipated Problems.

Examples of Violations

  • Failure to obtain informed consent
  • Informed consent obtained after the initiation of study procedures
  • Omitting study procedure(s) required by approved protocol
  • Performing a study procedure that is not outlined in the IRB-approved protocol
  • Failure to report a Serious Adverse Event
  • Drug dispensing/dosing error
  • Failure to securely control the study product
  • Enrolling participants outside of inclusion criteria
  • Failure to follow a Safety Monitoring plan
  • Study visit outside of window, only if in the opinion of the investigator, if affects the safety or welfare of the subject or others, the rights of subjects or other or the integrity of the study design. (eg. subject is on study drug and PK values are vital to data collection and subject safety)
  • Use of an unapproved consent form

Examples of Deviations

  • Study visit outside of window, if in the opinion of the investigator, it does not affect the safety or welfare of the subject or others, the rights or participants or other or the integrity of the study design. (eg. usually within a week or in long windows, within 2 weeks)
  • Failure to report a withdraw of a subject in adequate time
  • Use of expired recruitment materials

Examples of Unanticipated Problems

  • Unresolved subject complaints
  • Adverse audit or enforcement actions
  • Breaches of privacy/confidentiality
  • Unauthorized use or disclosure of protected health information (PHI)
  • Loss of study records
  • Disappearance of study drug
  • Research staff misconduct affecting the research
  • Incarceration of a subject
  • Injury sustained by research staff relating to the study
  • Suspension of principal investigator’s medical license
  • Higher than expected volume of adverse events
  • Higher than expected volume of protocol deviations
  • Higher than expected volume of subject drop-out rates
  • Complaint from a subject involving an unanticipated risk that cannot be resolved by the research staff