Adverse or Unanticipated Events

• Overview
• Definitions
• When and How to Report Events to the CHS
• When there is a Data Safety Monitoring Board or Committee (DSMB/C)

Overview

In the course of a research project, various problems arise some of which may affect the research participants in varying degrees of severity. It is important that the CHS be aware of any problems that arise so that a determination can be made by the CHS whether such problems are anticipated or unanticipated and involve risks to participants or others with resultant corrective actions. Investigators must contact the CHS office via phone or email as soon as possible but not less than 48 hours upon learning of a problem within their research program. All calls and emails are handled confidentially by CHS staff. The convened CHS will decide, as described below, which of the problems are anticipated or unanticipated involving risks to participants or others and subsequently determine whether any corrective actions need to be taken including, in extreme cases, suspension of the research with notification to participants.

Definitions

Definitions and examples are provided below. However, the Investigator must report the following to the CHS as soon as possible, but in all cases within 48 hours:

• Any adverse event (any harm experienced by a participant regardless of whether the event was internal (on-site) or external (off-site) and regardless of whether the event meets the FDA definition of “serious adverse event”) which in the opinion of the Investigator are both unexpected and related.
  • Unexpected is defined as an event whose specificity and severity are not accurately reflected in the human studies application, protocol, consent form, current investigational brochure or medical device/medication package insert.
  • Related to the research procedures is defined as an event which in the opinion of the Investigator, was more likely than not to be caused by the research procedures or if it more likely than not affects the right and welfare of current participants.
• Information that indicates a change to the risk or potential benefits of the research , such as
  • An interim analysis or safety monitoring report indicates that frequency or magnitude of harms or benefits might be different from those initially presented to the CHS;
  • A paper is published from another study that shows that the risks or potential benefits of the research might be different from those initially presented to the CHS.
• Breach of confidentiality.
• Change in FDA labeling or withdrawal from marketing of a drug, device, or biologic used in a research protocol.
• Change to the protocol taken without prior CHS review to eliminate an apparent immediate hazard to a research participant.
• Incarceration of a participant in a protocol not approved to enroll prisoners.
• Any event that requires prompt reporting to the sponsor
• Sponsor imposed suspension for risk.
• Complaint of a participant when the complaint indicates unexpected risks or which cannot be resolved by the research team.
• Protocol violation (meaning an accidental or unintentional change to the CHS approved protocol) that harmed participants or others or that indicates participants or others may be at risk of increased harm.
• Unanticipated Adverse Device effect: 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 participants.
• Serious Adverse Event (SAE): (used interchangeably with Adverse Event (AE) in many settings) is defined as any adverse event occurring that results in any of the following outcomes:
  • Death;
  • A life threatening adverse drug experience;
  • In-patient hospitalization or prolongation of existing hospitalization;
  • Persistent or significant disability/incapacity;
  • Prolonged hospitalization;
  • Congenital anomaly/birth defect;
  • Any important medical event that may not result in death, be life-threatening, or require hospitalization may still be considered a serious adverse event when, based upon appropriate medical judgment, they may jeopardize the patient or participant and may require medical or surgical intervention to prevent one of the outcomes listed in this definition.
• Unanticipated Problem involving Risks to Participant or Others is defined as a problem that is (1) unforeseen and (2) indicates that participants or others are at increased risk of harm. The majority of the studies reviewed by CHS involve social and behavioral research and thus, these events may be sometimes difficult to determine. As stated above, all problems should be reported to the CHS office for evaluation by the CHS staff, CHS Chair or CHS.

When and How to Report Events to the CHS

The CHS adheres to 45 CFR § 46.103(b)(5)(i) and 21 CFR § 56.108(b)(1), which require IRBs to have written procedures for ensuring prompt reporting to the IRB, appropriate institutional officials, and the federal department or agency head of any unanticipated problems involving risks to research participants or others.

Investigators should report any research problems involving human participants or research staff via telephone or email immediately but not more than 48 hours upon learning of the problem (as defined above). After the initial contact with the CHS Office, Investigators are required to file an Unanticipated Problem/Adverse Event form (and/or a separate written report to the CHS office, as well as to study sponsor or FDA (if applicable), within five working days of the eventunless otherwise specified (depending on the severity of the event) by the CHS office.

When there is a Data Safety Monitoring Board or Committee (DSMB/C)

DSMB/Cs can be relied upon by the CHS to review serious adverse events occurring at other study sites in a clinical trial, but the CHS must still receive and review reports of local adverse events. If a study has a DSMB/C, the Investigator should submit the data safety monitoring report to the CHS office as soon as it is available. DSMB/C reports should include a statement indicating that the data have been reviewed, the date of review and a summary of specific findings of the research study.

If you are unsure whether an event meets one of the definitions outlined above or requires reporting to the CHS office, please call us at 617.432.3071.

Updated: 21-Oct-2009