Unanticipated Problems, Protocol Deviations, and DSMB Reports

The IRB reintroduced Protocol Deviation report and DSMB report forms! The IRB noted that investigators requested a better method for reporting events required by sponsors or consortium groups. Some investigators told us that they would simply feel more comfortable by reporting this information. We listened, and we will now accept protocol deviation and DSMB reports.

Definitions

Data and Safety Monitoring Board (DSMB): A committee of scientists, physicians, statisticians, and others that collects and analyzes data during the course of a clinical trial to monitor for adverse effects and other trends (such as an indication that one treatment is significantly better than another, particularly when one arm of the trial involves a placebo control) that would warrant modification or termination of the trial or notification of subjects about new information that might affect their willingness to continue in the trial.

Protocol Deviation/Violation: Any incident involving non-adherence to the IRB-approved research plan.

Unanticipated Problems Involving Risks to Subjects or Others (UPIRTSO): Problems Involving Risk To Subjects or Others (UPIRTSO) as problems or events that, in the opinion of the local investigator, are:

  1. Unanticipated (in terms of nature, severity or frequency) given the nature of the research procedures described in protocol-related documents and the characteristics of the subject population being studied;
  2. Related to, or possibly related to, participation in the research; and
  3. Suggests that the research places subjects or others at a greater risk of physical, psychological, economic, or social harm than was previously known or recognized.

In general, UPIRTSO place subjects at greater RISK of harm, even when no harm occurs.

Note: A protocol deviation or DSMB Report may still meet the definition of Unanticipated Problem. If so, report the event using the Unanticipated Problem report form. The IRB does not otherwise require reporting of protocol deviations or DSMB meetings.

The majority of information on this webpage pertains to Unanticipated Problems reporting. For more examples and guidance, examine the NJH IRB SOP pertaining to Unanticipated Problems: http://spyderweb.njrc.org:88/dotNet/documents/?docid=1840&mode=view (on the NJH Spyderweb) or contact the IRB office

Examples of Unanticipated Problems

Examples of problems or events that may meet the definition of unanticipated problems involving risk to subjects or others include, but are not limited to:

  • Laboratory errors
  • Medication dispensing errors
  • Procedural errors
  • Enrollment of ineligible subjects
  • Incomplete/inadequate documentation of informed consent
  • Imminent threat of a reportable event that has not yet occurred
  • Unanticipated adverse device effect
  • Information indicating a change to the risk/benefit ratio of the research
  • Information resulting in a study hold or suspension
  • Change(s) in FDA labeling or withdrawal from marketing of a drug, device, or biologic used in a research protocol
  • Change(s) to the protocol taken without prior IRB review in order to eliminate an apparent immediate hazard to a research participant
  • Incarceration of a study subject
  • Event requiring prompt reporting to the sponsor
  • Breaches of confidentiality, including lost or stolen study documents
  • Subject complaint indicating unexpected risks or when the subject complaint cannot be resolved by the research team
  • Protocol deviation/violation, that in the opinion of the investigator:
    • Increases risk or decrease benefit, affect the participant's rights, safety, welfare, or affects the integrity of the resultant data, or
    • Has the potential to recur
  • Sponsor-initiated study hold, suspension or termination

When the problem or event involves any untoward or unfavorable medical occurrence (adverse event), including any abnormal sign, symptom, or disease, the problem or event could be considered an unanticipated problem if it meets the three criteria stated above.

Reporting Deadlines

Deadlines

  • Within 1 business day

    • Subjects exhibiting signs of high-risk behavior that can potentially cause harm to oneself or others. (The IRB Chairperson must be notified via phone or email within 1 business day. A written report must be submitted to the IRB office within 3 business days.)
  • Within 5 business days
    • Unanticipated Problem reports must be submitted to the IRB office within 5 business days of discovery.
  • Within 10 business days (recommended)
    • All other events or reports

Additional Information

For more guidance, review
OHRP guidance: www.hhs.gov/ohrp/policy/advevntguid.html
FDA guidance: http://www.fda.gov/downloads/RegulatoryInformation/Guidances/UCM126572.pdf
NJH IRB SOP: http://spyderweb.njrc.org:88/dotNet/documents/?docid=1840&mode=view (on the NJH Spyderweb or contact the IRB office for an emailed copy)

Forms

Unanticipated Problems Report Form (updated 25 Jun 2010)
Protocol Deviation Report Form (reintroduced 10 Aug 2011)
Data Safety Monitoring Report Form (reintroduced 10 Aug 2011)

If a protocol deviation or DSMB Report meets the definition of Unanticipated Problem, report the event/information using the Unanticipated Problem report form.


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