Prompt Reporting to the IRB

Events occurring during the research study at Stanford or at an external site relying on Stanford IRB, which in the opinion of the Monitoring Entity, Sponsor or the Protocol Director (PD) meet all of the following criteria:

a.  Unexpected in terms of nature, severity, or frequency, given (a) the research procedures described in the protocol-related documents such as the IRB-approved research protocol and informed consent document or the Investigator's Brochure, and (b) the characteristics of the subject population being studied;       

AND

b.  Related or Possibly Related to participation in the research or there is a reasonable possibility or likelihood that the incident, experience, or outcome may have been caused by the procedures involved in the research;   

AND

c.  Places Subjects or Others at a Greater Risk of Harm including physical, psychological, economic, or social harm than was previously known or recognized. 

UPs can include the following:

• events that require IND safety reporting, such as serious and unexpected suspected adverse reactions (SUSARs) or when there is an increased rate of occurrence of serious suspected adverse reactions
• deaths, life-threatening experiences and injuries that meet the above criteria
• privacy breaches
• serious and unexpected adverse events that occur prior to test article administration, during a washout period, or attributable to a screening period
• contaminated study medication
• untimely destruction or loss of study records 

Events that occur during the research study at an external sites and that meet the IND safety reporting requirements. The PD is notified of these events by the sponsor via Sponsor Safety Reports or Safety Memos (e.g. SUSAR reports). The PD is responsible for reviewing all IND safety reports received from sponsors and confirming they meet the UP criteria before submission to the Stanford IRB.  

An action, inaction, or activity, whether by the investigator, study staff, or others involved in human subject research, that is at variance with the approved IRB protocol, other requirements and determinations of the IRB, the HRPP Policy Manual and other applicable policies of Stanford University, SHC, LPCH, VAPAHCS (e.g., VHA Handbook 1200.5), Palo Alto Veterans Institute for Research (PAVIR) or relevant state or federal laws. The following are always considered noncompliance:

• Human subjects research conducted without IRB approval, or approved by an outside IRB, without prior notice to Stanford’s IRB (or Stanford IRB approval, if required under Stanford policies);
• Important Protocol Deviations as defined by the FDA which includes any deviation that might significantly affect the completeness, accuracy, and/or reliability of the study data or that might significantly affect a participant’s rights, safety, or wellbeing; or
• Change(s) to the research implemented without IRB approval except when necessary to eliminate apparent immediate hazards to the subject.

When the event is:

1. Possibly serious – Any behavior, action, inaction, or omission in the conduct or oversight of human research that, in the judgment of the IRB, has been determined to:

• adversely affect or compromise the rights or welfare of participants;
• harm or materially increase exposure to significant risk of harm to a research participant (the IRB does not have to find that harm has occurred, or was likely to occur, to make a determination of serious noncompliance);
• compromise the integrity or validity of the research.

2. Possibly continuing – A pattern of repeated instances of noncompliance that:

• Continues to occur after discovery of noncompliance or implementation of a preventive action plan; or
• Results from failure to implement a preventive action plan approved by the IRB; or  
• A circumstance in which an investigator or other study staff fails to cooperate with investigating or correcting non-compliance.

Any complaint unresolved by the research team.

When in the opinion of the PD it is in the best interest of the participant to remain on the study.

Any serious adverse effect on health or safety or any life-threatening problem or death caused by, or associated with, a device, if that effect, problem, or death was not previously identified in nature, severity, or degree of incidence in the investigational plan or application (including a supplementary plan or application), or any other unanticipated serious problem associated with a device that relates to the rights, safety, or welfare of subjects [21 CFR 812.3(s)].

Examples include: 

• a deviation intended to eliminate an immediate hazard to a participant,
• suicide or suicide attempt of a participant,
• Corrective Action Preventative Action (CAPA) plans,
• new information that indicates a change to the risks or potential benefits of the research or impacts the participant’s willingness to participate, and
• any other event that the IRB has determined requires reporting.  

Report only after consulting with the IRB Panel Manager to determine whether a prompt report or modification is needed.