1. Good Research, Bad Choices? Mary Coombs

2. What Makes Something Research Rather Than Treatment?

3.  Primary Goal is to Answer a Research Question

4. What Makes Something Research Rather Than Treatment?  Subject welfare isn’t primary goal: “risks to subjects must be reasonable in relation to anticipated benefits, if any, to subjects and the importance of the knowledge that may reasonably be expected to result”

5. What Makes Something Research Rather Than Treatment? Decisions are based on protocol in first instance Not on contextual best interests of this person

6. What Makes Something Research Rather Than Treatment? Usually requires testing and procedures beyond those needed for treatment

7. What Makes Something Research Rather Than Treatment? Usually/ ideally is RCT Neither subject nor researcher know if is getting treatment A or treatment B

8. Proposed: “The main purpose of a clinical trial is to benefit future patients rather than the patients in the trial” Do you think this is true?

9. Proposed: “The main purpose of a clinical trial is to benefit future patients rather than the patients in the trial” What did doctors at a (Boston-based) academic institution think?

10. Proposed: “The main purpose of a clinical trial is to benefit future patients rather than the patients in the trial” What did doctors at a (Boston-based) academic institution think? Yes: 45.9% Unsure: 29.5% No: 24.6%

11. This misunderstanding is common enough to have a name: Therapeutic Misconception

12. Law and Ethics of Treatment (a very summary summary!!)

13. Law and Ethics of Treatment Option A: Standard Treatment Informed Consent needed

14. Law and Ethics of Treatment Option B: Reasonable Experimental Treatment More Detailed Informed Consent needed

15. Law and Ethics of Treatment Option C: Unreasonable Experimental Treatment Not permitted “Consent” Irrelevant

16. Law and Ethics of Treatment There is Potential Tort Liability if 1) there is a bad outcome and 2) there was a. Unreasonable Experimental Treatment or b. Insufficient Informed Consent or c. Execution of Treatment fell below standard of care

18. How Can Research Study be a “Bad Choice”? Phase One Trial Consider: Risk to subject Benefit to subject Benefit to knowledge/future patients

19. How Can it be a “Bad Choice”? Phase One Trial Risk to subject  Significant: more toxic dose than previously given to humans

20. How Can it be a “Bad Choice”? Phase One Trial Benefit to subject?  Minor in fact  Protocol not designed to test efficacy

21. How Can it be a “Bad Choice”? Phase One Trial Benefit to knowledge/future patients?  Subjects say are doing to find a cure for themselves  Are either altruistic or misunderstand the “free rider” option

22. Downsides of being a Subject: Other Clinical Trials  Apart from Randomization Rigidity of protocol Risks/Inconveniences of Additional Testing Not told of interim results

23. Upsides of being a Subject: Other Clinical Trials  Apart from Randomization Access to better quality care than P might otherwise obtain  Academic medical center trials  Effect of limits on health insurance

24. Upsides of being a Subject: Other Clinical Trials  Apart from Randomization Possible Access to Drug/Treatment not otherwise available  If new drug  If (some) doctors won’t provide off-label  If new technique not available outside trial setting

25. Upsides/Downsides of being a Subject: Randomization  Must be “clinical equipoise” What might be differences between standard and new treatment?

26. Possible Differences [to be tested by study]  Effectiveness  Expected Mild-to-Moderate Side Effects  Level of Risk of Serious Side Effects  Convenience  Cost

27. Possible Outcomes [after study]  New treatment is clearly as good or better on all dimensions  Standard treatment is clearly as good or better on all dimensions  Two treatments are in equipoise: incommensurable (known) differences

28. Clinician decisions [after study]  New treatment is clearly as good or better on all dimensions: USE NEW  Standard treatment is clearly as good or better on all dimensions: USE STANDARD

29. Clinician decisions [after study]  Two treatments are in equipoise: incommensurable (known) differences Choose what is best given specifics of this patient Engage patient to help choose given subjective preferences  E.g. risk vs. efficacy  E.g. cost vs mild/moderate likely side effects

30. Clinician decisions [before study] (if new treatment available outside study Two treatments are in equipoise: incommensurable (unknown) differences Choose what is best given specifics of this patient Engage patient in choice given subjective preferences E.g. risk vs. efficacy E.g. cost vs mild/moderate likely side effects

31. Is informed consent the answer to the “bad choices/good study” dilemma? Are people free to be altruistic? Are people free to make “bad choices”? Should we be skeptical that bad choices are freely made and fully informed?

32. Does Informed Consent Form Matter?  written documentation matters  Research form is more important than treatment form  Research form is easier to prepare than treatment form  Liability: “I always tell people; I must have told Ms. X”

33. What might a subject want to know?  That is a research study  Potential future benefits of research study  Intervention being studied  Alternative [standard care? placebo?]  Are there third alternatives available?  Risks of Standard Care  Risks of Proposed New Treatment

34. What might a subject want to know?  Benefits of Standard Care  Benefits of New Treatment  Risks/discomforts inherent in participation  Obligations of being a subject  What happens if leave study prematurely

35. What might a subject want to know?  What recompense ($$) for participating?  What consequence if things go wrong? Who pays for what?  Facts about person offering to enroll me might be relevant to determining his/her motivations

37. Are these all in the standard forms?  Research study/ purposes/benefits: yes  Treatment being tested and randomized alternative: yes  Availability of third alternatives? Sometimes Often doesn’t include option of study treatment outside research study

38. Are these all in the standard forms?  Risks/discomforts inherent in study Generally included Tests may be referred to as “routine” This may be understood as “risk-free” rather than common outside the research protocol

39. Are these all in the standard forms?  Obligations/effect of leaving prematurely? Usually covered Doesn’t indicate that won’t be told of interim results

40. Why might a subject want to know – and a researcher not want to reveal this?? Results show new treatment more efficacious Confidence interval overlaps null hypothesis Compare researcher interest and patient interest

41. Are these all in the standard forms?  Risk/benefit of standard and alternative? Yes, but boiler-plate COST study of laparoscopic surgery for colon cancer  Form language: “it is possible that the new technique may change the way the tumor grows back after surgery if it does”  Vs. Benefits of “smaller incisions and faster recovery”

42. Are these all in the standard forms?  Financial Issues Payment to P for time/inconvenience? Y Coverage of Medical Costs during trial? Y Compensation for damages from trial?  Usually not included/not covered Incentives to Researcher/Doctor to Include P in trial?  No

43. Can we do needed research if we tell the truth and the whole truth? Can we treat subjects with something like the ethics we use for patients?