Safety Reporting for Sites

The eMedicus IRB in accordance with the regulations 21 CFR 56.108(b)(1) and 45 CFR 46.103(b)(5) requires reporting of all events that may represent any unanticipated problems involving risk to human subjects or others. In addition, any new safety information relating to the study or the study products must be reported. Reportable events and other study information must be reported to the eMedicus IRB within 10 working days of becoming aware of the event.

Adverse Event

Any untoward or unfavorable medical occurrence in a human subject, including: 

• any abnormal sign (for example, abnormal physical exam or laboratory finding), symptom, or disease, 
• temporarily associated with the subjects participation in the research, whether or not considered related to the subjects participation in the research

Two Types of Adverse Events

• Internal adverse event – adverse events experienced by subjects enrolled by the investigator at the site or institution
• External adverse event – adverse events experienced by enrolled subjects at other sites or institutions participating in the research study

Reportable Internal Adverse Events that occur at the investigator site

• serious adverse event, protocol deviation or violation
• complaint from a research subject or study personnel regarding the conduct of the study
• any adverse audit findings or actions taken against the principal investigator
• any other unanticipated problems occurring at the site including incarceration of a subject or breech of patient confidentiality

Reportable External Adverse Events that did not occur at the investigator site but are reported to the principal investigator

• IND safety reports, CIOMS, SUSAR or MedWatch reports
• New or updated safety information
• Publications, interim findings or DSMB reports
• Clinical holds, recalls, or early study termination

Non-Reportable Events

• Minor protocol deviations such as study visits or laboratory tests performed slightly out of window
• Adverse events that according to the PI’s judgment are not related to the study
• Adverse events that are anticipated or expected during participation in the research study
• External adverse event reports such as IND Safety Reports that according to the PI’s judgment do not adversely affect the conduct of the study at the PI’s site or institution 

Serious Adverse Event

Any adverse event temporarily associated with the subject’s participation in the research that meets any of the following criteria:

1. results in death
2. is life-threatening (places the subject at immediate risk of death from the event as it occurred)
3. requires inpatient hospitalization or prolongation of existing hospitalization
4. results in persistent or significant disability/incapacity
5. results in congenital abnormality/birth defect; or
6. any other adverse event that, based upon appropriate medical judgment, may jeopardize the subject’s health and may require medical or surgical intervention to prevent one of the other outcomes listed in this definition (examples of such events include allergic bronchospasm requiring intensive treatment in the emergency room or home, blood dyscrasia or convulsions that do not result in inpatient hospitalization, or the development of drug dependency or drug abuse).

Unanticipated Problem

An unanticipated problem involving risks to subjects and others is any incident, experience or outcome that meets all of the following criteria:

1. unexpected in terms of nature, severity, or frequency given

1. the research procedures that are described in the protocol-related documents, such as the IRB approved research protocol and informed consent document; and
2. the characteristics of the subject population being studied

1. related or possibly related to participation in the research

1. possibly related means there is a reasonable possibility that the adverse event, incident, experience, or outcome, may have been caused by the procedures involved in the research; and

1. suggests that the research places subjects or others at greater risk of harm (including physical, psychological, economic, or social harm) related to the research than was previously known or recognized

Please Note: Only a small subset of adverse events occurring in human subjects participating in research, will meet the above three criteria for an unanticipated problem.

Adverse Event Reporting Resources

FDA – Adverse Event Reporting Guidance for Clinical Investigators, Sponsors, and IRBs – Adverse Event Reporting to IRBs – Improving Human Subject Protection – January 2009 Procedural

OHRP – Adverse Event Reporting Guidance on Reviewing and Reporting Unanticipated Problems Involving Risks to Subjects or Others and Adverse Events – Dated: January 15, 2007