Amendment	Protocol deviations/violations
Request protocol exception	Serious Adverse Events (SAEs)
Change in principal investigator/study staff	Re-opening a closed study

Amendment

If the changes do not fall within the minimal risk criteria, the amendment needs to go to full committee.

• Amendment form.
• Research personnel form.

Protocol deviations/violations

Protocol deviations

Any alteration or modification to the IRB-approved protocol. The protocol includes the detailed protocol, summary, consent form, recruitment materials, questionnaires and any other information relating to the research study. Some deviations such as alteration of eligibility criteria may be approved by the HRRB if requested as an exception.

Protocol exception

Any temporary protocol deviation that is approved by the IRB prior to its initiation, such as enrollment of a subject who does meet the eligibility criteria. Any permanent change to the protocol constitutes an amendment that must be submitted to the IRB for approval prior to initiation.  

Protocol violation

Any protocol deviation that is not approved by the IRB prior to its initiation or implementation.

• A major violation impacts subject safety, affects the integrity of study data and/or affects subjects' willingness to participate in the study.
• A minor violation does not impact subject safety, compromise the integrity of study data and/or affect subjects' willingness to participate in the study. 
• Deviation or violation: Major.
• Deviation or violation: Minor.

Request protocol exception

Researchers may request an exception to an approved protocol if it is known that a deviation will likely occur in a planned situation. These are not permanent changes to the protocol.

Examples: 

• If a potential study subject meets all eligibility requirements except one, a researcher may request an exception to allow that subject into the study. 
• If an enrolled subject will be out of town at the time of protocol-directed tests or treatments, an exception request may be filed to allow this one time variation from protocol, allow the event to occur either before or after the planned date. 

Exceptions should be submitted in letter format explaining the requested exception and why it is necessary. The letters should be submitted via IRBnet and will be reviewed by the HRRB chair.

SAES

• On-site SAEs
  All serious adverse events that occur in subjects enrolled in research protocols approved by Children's Hospital of Wisconsin's Human Research Review Board must be reported to the HRRB in a timely fashion using the on-site SAE form.
• Off-site SAEs
  If the HRRB-approved protocol has a Data Safety Monitoring Board/Safety Committee to evaluate all adverse events for indications of new risks, the HRRB does not need to see every External SAE sent by sponsors or Medwatch. These can be summarized by the researchers and submitted at continuing review. Any safety reports sent from the DSMB's or safety review panels must promptly be submitted to the HRRB for review.
  If the HRRB-approved protocol does not have a DSMB/safety committee, all off-site SAE reports must be submitted to the HRRB in a timely fashion using the off-site SAE form. 

Change in principal investigator/study staff

• Accessing research data after leaving Children's Hospital and/or The Medical College of Wisconsin:
  • HIPAA request for privacy board waiver.
  • Limited data set user agreement.
• Amendment form.

Re-opening a closed study

• If the study is expedited or just being re-opened to data analysis only, then a letter explaining why the study should be re-opened needs to be submitted along with any revised documents.
• If the study is full committee and being re-opened to enrollment, a letter of explanation and the entire protocol needs to go back to full committee for review.
• If you are resubmitting due to the continuing review not being submitted, then a Continuing Review Form also needs to be completed.
• If the study originally was in paper format, you must submit it via IRBNet along with a new Registration Page (using the IRBNet Wizard). We then pull the old file from the warehouse and scan in any old documents.