Lesson 17 · IRB and HRPP Administration: From Coordinator to CIP

17. Adverse Events vs Unanticipated Problems: The OHRP Test and FDA Safety Clocks

55 min

After this lesson you can

  • Define adverse event, serious adverse event, unexpected adverse event, and suspected adverse reaction
  • Apply the three-part OHRP test for an unanticipated problem involving risks to subjects or others
  • Distinguish which adverse events must be reported to the IRB and by whom
  • State the FDA safety reporting clocks in 21 CFR 312.32, 312.64, and 812.150
  • Describe the roles of data and safety monitoring plans and boards and how the IRB uses their reports

Video coming soon

Scheduled for release on October 3, 2026.

Adverse Events vs Unanticipated Problems: OHRP and FDA Rules separates two terms that IRBs and investigators confuse every day. Most adverse events are not unanticipated problems, and many unanticipated problems are not adverse events, so this lesson applies OHRP's three-part test and the FDA reporting clocks.

5 Key Facts from This Lesson

  1. An unanticipated problem must be unexpected, related or possibly related to the research, and suggest a greater risk of harm than was previously known, and all three conditions are required.
  2. Sponsors notify FDA of unexpected fatal or life-threatening suspected adverse reactions within 7 calendar days and file other IND safety reports within 15 calendar days.
  3. Investigators report unanticipated adverse device effects to the sponsor and the IRB within 10 working days under 21 CFR 812.150(a)(1).
  4. Investigators report serious adverse events to the sponsor immediately, whether or not they consider them related.
  5. Ordinary adverse events are not reported to OHRP, while unanticipated problems are, and OHRP's 2007 guidance expects that report within about one month.

Exam traps

The distinctions exam questions on this topic are most often built to test. Know them cold.

  • An event must be unexpected, related or possibly related, and suggest greater risk to be a UP; all three

  • 7 and 15 calendar days for drugs; 10 working days for devices

  • Investigators report serious adverse events to the sponsor whether or not related

  • Expected adverse events at expected frequency do not require individual prompt reporting to the IRB

  • Only UPs go to OHRP; ordinary adverse events do not

  • The IRB reviews DSMB reports; it does not run the interim analysis

Practice quiz

  1. Question 1
    According to OHRP's 2007 guidance, an unanticipated problem must be:
  2. Question 2
    Under 21 CFR 812.150, an investigator must report an unanticipated adverse device effect to the sponsor and IRB no later than:
  3. Question 3
    A sponsor must submit an IND safety report for a serious and unexpected suspected adverse reaction that is not fatal or life-threatening within:
  4. Question 4
    Which of the following is an unanticipated problem that is NOT an adverse event?
  5. Question 5
    45 CFR 46.111(a)(6) requires, when appropriate, adequate provision for:

Recap

  • Vocabulary: adverse event by temporal association; serious by six outcomes; unexpected against the documents; suspected adverse reaction by reasonable possibility
  • The OHRP three-part test: unexpected, related or possibly related, greater risk; all three
  • Reporting: UPs to the IRB promptly, one week for serious and two weeks for others by OHRP's suggestion; UPs to OHRP within about a month; expected events in aggregate at continuing review
  • FDA clocks: 7 and 15 calendar days for drugs; investigators report SAEs to sponsors immediately; 10 working days for device effects; 5 and 15 working days for sponsor termination
  • Monitoring: plans under criterion (a)(6), DSMBs for high-risk and blinded trials, the IRB relies on their reports

Coming next

Lesson 18, noncompliance, research misconduct, and suspensions.

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This course is for educational purposes only and is not legal, regulatory, or compliance advice. Regulations and guidance change, so confirm every requirement against the current eCFR text, OHRP and FDA guidance, and your institution's IRB policies before relying on it. CIP® is a registered certification mark of Public Responsibility in Medicine and Research (PRIM&R). This course is produced independently by Subthesis and is not affiliated with, endorsed by, or reviewed by PRIM&R or the CIP Council. The instructor is not a Certified IRB Professional. Completing this course does not confer CIP certification, satisfy CIP eligibility requirements, or count as CIP recertification continuing education.