ASSESSMENT OF RISK Karen M. Smith, PhD Office of Research Oversight Midwestern Region

1. ASSESSMENT OF RISK Karen M. Smith, PhD Office of Research Oversight Midwestern Region

2. RISK: The probability of harm or injury (physical, psychological, social, or economic) occurring as a result of participation in a research study. Both the probability and magnitude of possible harm may vary from minimal to significant. (OPRR IRB Guidebook, 1993)

3. RISK ASSESSMENT IS A FUNDAMENTAL DUTY OF THE IRB Research may be approved only if the IRB determines that: • The risks of the research are minimized [38 CFR 16. 111 (a)(1)] • Risks to subjects are reasonable in relation to anticipated benefits[38 CFR 16. 111 (a)(2)]

4. The IRB must ensure: • That subjects are completely and adequately informed about potential risks and discomforts [38 CFR 16.116(a)(2)] • That subjects are informed if the research involves risks to the subject (or to the embryo or fetus, if the subject is or may become pregnant) which are currently unforeseeable [38 CFR 16.116(b)(1)] • For research of greater than minimal risk, that subjects are informed if compensation or medical care will be available if injury occurs [38 CFR 16.116(a)(6)]

5. The IRB must determine • A term of approval based on degree of risk [38 CFR 16. 109(e)] • That adequate provisions are made for monitoring the data collected to ensure the safety of subjects[38 CFR 16.111(a)(6)] and to protect the privacy of subjects and to maintain the confidentiality of data [38 CFR 16.111(a)(7)] • When considering reports of adverse events and other problems, if the event represents an unanticipated problem posing risks to subjects or others [38 CFR 16.103(b)]

6. Exemption #2 also requires a risk determination to be made: (2) Research involving the use of educational tests (cognitive, diagnostic, aptitude, achievement), survey procedures, interview procedures or observation of public behavior, unless: (i) Information obtained is recorded in such a manner that human subjects can be identified, directly or through identifiers linked to the subjects; and  (ii) any disclosure of the human subjects' responses outside the research could reasonably place the subjects at risk of criminal or civil liability or be damaging to the subjects' financial standing, employability, or reputation.[38 CFR 16.101(b)(2)]

7. The only type of risk defined by the Common Rule is “minimal risk:” Minimal risk means that the probability and magnitude of harm or discomfort anticipated in the research are not greater in and of themselves than those ordinarily encountered in daily life or during the performance of routine physical or psychological examinations or tests. [38 CFR 16.102(i)]

8. Some procedural options hinge on a determination about minimal risk: • Expedited review • Waiver or alteration of some or all elements of consent • Waiver of documentation of consent In the VA, approval of research involving children also requires a determination that the risk is minimal.

9. RISK: The probability of harm or injury (physical, psychological, social, or economic) occurring as a result of participation in a research study. Both the probability and magnitude of possible harm may vary from minimal to significant.

10. The PROBABILITY of harm or injury… • Risk assessment is an estimate of the likelihood that certain events will happen. • This implies that all available information about the occurrence of past harm or injury, or about conditions that may increase the likelihood of harm or injury, will be weighed.

11. Sources of information: • Prior research (both human and animal) • Information about the properties of the experimental intervention (e.g., pharmacology of the investigational drug or of similar drugs) • Knowledge of the disease state to be studied • Information about the how the research will be carried out (e.g., the qualifications of the investigators, safety monitoring procedures to be used)

12. What if there’s no good risk information available? • The IRB may require procedures to minimize the likelihood of unknown risks. • The IRB may disapprove of the research pending more animal research. • The IRB may approve the research based on a best estimate of the likelihood of unforeseeable risks, taking into account the known risks and potential benefits. • In any case, the subject must be told if there may be unforeseeable risks.

13. The probability of harm or injury (PHYSICAL, PSYCHOLOGICAL, SOCIAL, OR ECONOMIC)… • Harm or injury from research may not be confined to physical harm. • Possibility of psychological, social or economic harm should be a standard part of risk assessment • Information must be elicited about these potential harms • Procedures for reporting and evaluating adverse events should also encompass the full range of possible harms.

14. The probability of harm or injury (physical, psychological, social, or economic) occurring as a RESULT OF PARTICIPATION IN A RESEARCH STUDY. • The IRB must isolate risks of research participation from those of • The clinical care the subject would receive regardless of participation • The underlying disease state

15. The IRB should also be aware of risks of participation that arise from the research context. • For instance: • Treatment schedules and dosages may not be individualized • There may be a possibility of assignment to a placebo arm • There may be drug washout periods during which symptoms may be exacerbated

16. The probability of harm or injury (physical, psychological, social, or economic) occurring as a result of participation in a research study. Both the probability and magnitude of possible harm may vary from MINIMAL TO SIGNIFICANT. • Risk occurs on a continuum. • IRBs should develop expertise in consistently identifying points along the risk continuum.

17. Beyond the Regs and Guidance: Challenges and Best Practices • Internal risk assessment guidelines • Problems with minimal risk • Risk perception

18. DEVELOPING INTERNAL RISK ASSESSMENT GUIDELINES • A way to locate points on the risk continuum • A way to ensure consistency in risk assessment • A way to develop and maintain expertise in assessing risk

19. PROBLEMS WITH MINIMAL RISK • Minimal risk means that the probability and magnitude of harm or discomfort anticipated in the research are not greater in and of themselves than those ordinarily encountered in daily life or during the performance of routine physical or psychological examinations or tests.

20. PROBLEMS WITH MINIMAL RISK • Whose daily life? • Which routine physical or psychological examinations or tests?

21. RISK PERCEPTION • Heuristics in risk perception • Expert versus lay perceptions

22. Heuristics: General inferential rules used to make judgments about risks in the face of incomplete statistical evidence. • Example: • Availability Heuristic: An event seems more likely or more frequent if it’s easy to imagine or recall (“Jaws”).

23. Experts and lay persons do not perceive risks the same way (Slovic, Fischoff and Lichtenstein, 1979). • Some characteristics of experts’ risk perceptions: • More accurate as to probability of death from an event; risk perceptions closely tied to this probability • Overconfident about current scientific knowledge • Overlook ways in which human error can affect technological systems • Fail to anticipate human response to safety measures • Focus on a narrow portion of a whole technological system

24. Some characteristics of laypersons’ risk perceptions: • More influenced by qualitative characteristics such as • the unknown nature of a threat • its controllability • its familiarity • the voluntariness of exposure • delayed effects • potential for catastrophe (e.g., many deaths)