Table 3 Adverse event reporting and harms

Adverse events (AEs)

Safety will be assessed using the FDA Guidance Document (2007): Toxicity Grading Scale for Healthy Adult and Adolescent Volunteers Enrolled in Preventive Vaccine Clinical Trial (http://www.fda.gov/BiologicsBloodVaccines/GuidanceComplianceRegulatoryInformation/Guidances/Vaccines/ucm074786.htm). Participants will be monitored up to Visit 2 (Day 7) for the occurrence and nature of any AEs.

All AEs will be entered in the appropriate eCRF (including seriousness, grade, severity, relationship to the IP, and action taken) and in the source documents. The hospital laboratory will perform investigational tests as specified in the trial schedule, including full blood count (with differential blood count and platelet count), liver panel (total bilirubin, ALP, ALT), renal panel (sodium, potassium, and creatinine), creatine kinase, troponin, and pregnancy test if indicated.

For out-of-range values, clinical laboratory reports must be reviewed by a physician within 24 h of receipt. Out-of-range values will be evaluated as either clinically significant (CS) or not clinically significant (NS). By definition, a value flagged as “CS” must be entered on the AE page in the CRF. The test may be repeated at the Investigator’s discretion. The Investigator may use his own judgment to determine whether the abnormal finding has sufficient reasons to immediately withdraw the participant from the study.

Collecting, recording, and reporting of “Unanticipated Problems Involving Risk to Subjects or Others” (UPIRTSO) events to the National Healthcare Group (NHG) Domain Specific Review Boards (DSRB)

UPIRTSO events refers to problems, in general, to include any incident, experience, or outcome (including AEs) that meets all of the following criteria:

1. Unexpected, in terms of nature, severity, or frequency of the problem as described in the study documentation (eg: Protocol, Consent documents, etc).

2. Related or possibly related to participation in the research. Possibly related means there is a reasonable possibility that the problem may have been caused by the procedures involved in the research; and

3. Risk of harm. This suggests that the research places participants or others at a greater risk of harm (including physical, psychological, economic, or social harm) than was previously known or recognized.

For urgent reporting, all problems involving local deaths, whether related or not, should be reported immediately – within 24 h after first knowledge by the NHG investigator. For expedited reporting, all other problems must be reported as soon as possible but not later than 7 calendar days after first knowledge by the NHG investigator.

Collecting, recording, and reporting of serious adverse events (SAEs) to the Health Science Authority (HSA)

A SAE is defined as any untoward medical occurrence that: results in death, is life-threatening (immediate risk of death), requires inpatient hospitalization or prolongation of existing hospitalization, results in persistent or significant disability/incapacity, results in congenital anomaly/birth defect, or is a medically important event. Medical and scientific judgment should be exercised in determining whether an event is an important medical event. An important medical event may not be immediately life-threatening and/or result in death or hospitalization. However, if it is determined that the event may jeopardize the subject and/or may require intervention to prevent one of the other AE outcomes, the important medical event should be reported as serious.

All SAEs that are unexpected and related to the study drug will be reported. The investigator is responsible for informing HSA no later than 15 calendar days after first knowledge that the case qualifies for expedited reporting. Follow-information will be actively sought and submitted as it becomes available. For fatal or life-threatening cases, HSA will be notified as soon as possible but no later than 7 calendar days after first knowledge that a case qualifies, followed by a complete report within 8 additional calendar days.