1. When Must Clinical Risks be Described in a Research Consent Document? Ron Kadden - September 10, 2008

2. The Question If a research study involves standard- of-care clinical interventions, that are being done for clinical reasons: must the risks of those clinical interventions be included in the research consent document (CD)? must the risks of those clinical interventions be included in the research consent document (CD)?

3. OHRP Guidance When an intervention (whether ‘standard of care’ or investigational) is dictated by a research protocol: then the reasonably foreseeable risks of that intervention are risks of the research, and must be described in the CD. then the reasonably foreseeable risks of that intervention are risks of the research, and must be described in the CD.

4. The Crucial Factor The research protocol must constrain the clinician’s judgment in some way: Randomization Randomization Selection of intervention Selection of intervention Timing of intervention Timing of intervention Dose/intensity of intervention Dose/intensity of intervention

5. The Crucial Factor If, on the other hand, the subjects will receive the intervention based entirely on clinician judgment: the risks of the intervention are NOT research risks the risks of the intervention are NOT research risks those risks should not be described in the CD those risks should not be described in the CD

6. Example #1 Subjects are to be randomized into 2 standard-of-care interventions: dental amalgams dental amalgams composite fillings composite fillings Since both interventions are standard- of-care, do their risks need to be described in the CD?

7. Example #1 YES! Since the clinician does not determine the assignment to the interventions: both standard-of-care treatments are considered research procedures both standard-of-care treatments are considered research procedures their risks must be described in the consent document their risks must be described in the consent document

8. Example #2 Similarly, the risks related to the use of 2 standard vascular stents, with random assignment, must be described in the CD because, here again, assignment is driven by the protocol, not by clinician judgment because, here again, assignment is driven by the protocol, not by clinician judgment

9. Example #2 What about other components of the intervention, such as the anesthesia associated with the standard catheterization procedures? the anesthesia associated with the standard catheterization procedures? the insertion of the catheter? the insertion of the catheter? Do their risks need to be described in the research CD???

10. Example #2 NO! As long as they are standard-of-care procedures, and the person was going to be getting a stent regardless of the research, those risks are not considered risks of the research and should NOT be described in the CD

11. Any Questions or Discussion?