Competence to Consent to Research: Concepts and Assessment

1. Competence to Consent to Research: Concepts and Assessment Paul S. Appelbaum, MD Dollard Professor of Psychiatry, Medicine & Law Director, Division of Psychiatry, Law & Ethics Department of Psychiatry Columbia University

2. History of Concern with Research Ethics • Birth of research ethics often traced back to Nazi atrocities and the Nuremberg trials after WW II. • But even before then investigators seem to have recognized the importance of subjects’ competent consent to research. • 1st known consent form: Walter Reed’s yellow fever experiments in Cuba (1898).

3. Example of Early Recognition of Importance of Consent to Research • Just over 100 years ago, George Bernard Shaw was writing Pygmalion (later My Fair Lady). • Consider this dialogue that occurs just as Prof. Henry Higgins is about to begin his experiment of turning the flower-girl, Eliza Doolittle into a “lady.”

4. Col. Pickering: Excuse me, Higgins; but I really must interfere… If this girl is to put herself in your hands for six months for an experiment in teaching, she must understand thoroughly what she’s doing.

5. Prof. Higgins:How can she? She’s incapable of understanding anything. Besides, do any of us understand what we are doing? If we did, would we ever do it?

6. Col. Pickering:Very clever, Higgins, but not sound sense.

7. Prof. Higgins:No use explaining. As a military man, you ought to know that. Give her her orders: that’s what she wants.

8. Nature of the Study Eliza: You are to live here for the next six months, learning how to speak beautifully, like a lady in a florist’s shop. If you’re good and do whatever you’re told, you shall sleep in a proper bedroom, and have lots to eat, and money to buy chocolates and take rides in taxis. If you’re naughty and idle, you will sleep in the back kitchen among the black beetles, and be walloped by Mrs. Pearce with a broomstick.

9. Risks At the end of six months, you shall go to Buckingham Palace in a carriage, beautifully dressed. If the King finds out you’re not a lady, you will be taken by the police to the Tower of London, where your head will be cut off as a warning to other presumptuous flower girls.

10. Benefits If you are not found out, you shall have a present of seven-and-sixpence to start life with as a lady in a shop.

11. Right to Withhold Consent If you refuse this offer, you will be a most ungrateful and wicked girl and the angels will weep for you. Now are you satisfied, Pickering?

12. Doctrine of Informed Consent • Three elements: • Disclosure – Pickering’s concern • Competence – Higgins’ focus and our topic today • Voluntariness – Liza’s bottom line Liza: You’re a big bully you are. I won’t stay here if I don’t like. I won’t let nobody wallop me.

13. Role of Competence Requirement • Right to make decisions is key value in liberal societies • But balanced against concern that some people lack capacity to make decisions consistent with their interests • Hence, informed consent doctrine creates exception for persons lacking competence

14. Core Characteristics of Competence • Task specific – Can be competent for some decisions, but not others (e.g., focal delusions). • Time specific – May be competent at one point but not earlier or later. • Responsive to demand characteristics of decision – Riskier decisions may require higher level of capacity.

15. Criteria for Competence to Consent to Research • Evidencing a choice • Understanding disclosure of information • Appreciation of the nature of the situation and its consequences • Reasoning (ability to weigh risks and benefits)

16. What is Different About Competence to Consent to Research and to Treatment? Subjects must appreciate the differences between the two contexts. Treatment: Primary goal is the provision of “personal care.” Research: Primary goal is the production of generalizable knowledge.

17. Research Methods that Favor Validity Over Patients’ Interests • Random assignment to treatment • Placebos • Double blind procedures • Adherence to protocol to determine dosages • Limitations on adjunctive treatments

18. Subject #50 Interviewer: Do you know how treatment in this study is different from ordinary care? Did they say what your treatment would be if you weren’t in the study? Subject: No, no. Interviewer: They didn’t discuss what the treatment would be? Subject: No, no, I’ll leave that up to them. I want them to give me the best treatment for what I have. Interviewer: Do you think by being in the study this is the best treatment you could get? [continued]

19. Subject #50[continued] Subject: Okay, if they don’t, then I’ll drop out. Interviewer: Hopefully they will give you the best treatment you can get? Subject: Right, right. Interviewer: So you are not sure they have different groups or anything? As far as you know if they did have different groups, would the doctors decide which is the best one for you? Subject: I would assume he would decide which one was the best one for me.

20. Therapeutic Misconception Study: Participants 243 participants from 44 clinical research studies at 2 academic medical centers Age (mean) 53.1 years (range 18-32) Gender (female) 69.8% Race (white) 90.5% Education (mean) 14.2 years

21. Therapeutic Misconception Study: Dependent Variables Incorrect belief that participant’s individualized needs would determine assignment to treatment conditions or lead to modification of the treatment regimen (Individualization) Unreasonable belief about the nature or likelihood of medical benefit based on misunderstanding of research design (Benefit)

22. Therapeutic Misconception Study: Frequency of TM (n=243) Individualization 31.1% (n=70) Benefit 51.1% (n=115) Total 61.8% (n=139)

23. Role of Therapeutic Misconception in Impairing Competence • Subjects who don’t appreciate the differences between research and treatment contexts can’t make meaningful decisions about participation • Therapeutic misconception is highly prevalent among potential research subjects and needs to be considered in competence evaluation

24. How Competent are Research Subjects with Conditions That May Impair Capacity? • Data available on subjects with schizophrenia, depression, Alzheimer’s disease • Most studies use MacCAT-CR; many compare with normal populations • Both hypothetical and in vivo studies

25. Diagnosis and Competence • Performance on competence measures: normals > depression > schizophrenia > Alzheimer’s disease.

26. Schizophrenics vs. Normals Pre-test Means Normal Schizophrenia Comparison Subjects (n=24) Group (n=24) P Understanding (0-26) 12.9 (8.5) 20.2 (3.8) 0.001 Reasoning (0-8) 3.5 (2.8) 5.5 (1.4) 0.002 Appreciation (0-6) 2.3 (2.0) 4.4 (1.5) 0.0001 Choice (0-2) 1.6 (0.7) 1.9 (0.3) 0.06 Carpenter, et al. Arch Gen Psychiatry 57: 533-8, 2000

27. Correlates of Impaired Competence • Positive and negative psychotic symptoms have weak or no correlations with performance on competence measures. • Neuropsychological variables consistently show the strongest correlations with impairment

28. Cognitive Impairment and Competence

29. Effectiveness of Remedial Interventions • Puzzle of Carpenter, et al. data • Many subjects with impaired capacity respond well to additional education • Special teaching techniques may be helpful (e.g., multimedia) • After intervention, many subjects able to make decisions for themselves

30. Example of Effects of Additional Education Pre Post P Understanding (0-26) 8.35 18.35 <0.00001 Appreciation (0-6) 1.35 3.25 <0.0001 Reasoning (0-8) 2.35 3.7 <0.04

31. Many Patients with Psychiatric or Neurologic Disorders Are Competent to Consent to Research • There is great heterogeneity within diagnostic categories, but many persons in every diagnostic category (fewest in AD) retain decisional competence. • Proportions of competent patients will vary depending on diagnosis, clinical state, and nature of research study.

32. Data from CATIE Study - 1 • Kim (2003) had 3 psychiatrists assess competence of sample of schizophrenic subjects and compared with MacCAT-CR scores • Cut-offs were established using ROC analyses.

33. Data from CATIE Study - 2 • Of 900 subjects in preliminary analysis, approximate % falling below cut-offs were: • Understanding: 9% • Appreciation: 16% • Reasoning: 24% • Conclusion: vast majority of chronic schizophrenic subjects in this study are competent to consent—but not all

34. Approaches to Impaired Capacity • Screening increasingly prevalent in higher risk studies (e.g., placebo-controlled) • Can be done with: • Clinical interview • Symptom measures (e.g., MMSE, BPRS) • Competence screening instruments (e.g., MacCAT-CR)

35. MacCAT-CR Overview • Assesses understanding, appreciation, reasoning, and choice • Series of disclosures followed by questions and reasoning tasks • Takes approximately 20-25 minutes • Provides quantitative scores, but not competent/incompetent decision

36. MacCAT-CR Understanding MacCAT-CR Disclosure U-1 (ii) Disclosure (Procedures of Project)— Patients who agree to be in this study will do the following things: - First, they will stop all medications for schizophrenia for 2 weeks; this is called the washout period - Second, after the washout period, they will receive either the new medication or the old medication for 8 weeks; this is called the treatment phase of the study - Altogether, the study lasts 10 weeks; 2-week washout and an 8-week treatment phase

37. MacCAT-CR Understanding MacCAT-CR Questions • “Do you have any questions about what I just said?” • “Can you tell me your understanding of what I just said?” • If subject fails to mention spontaneously, ask • “How long will the research study last?” • “What will happen to your medication at the beginning of the study?” • “ What medication will your receive in the study?”

38. Understanding - Scoring • 2 Subject recalls content of item and offers fairly clear version. • 1 Subject shows some recollection of item content, but describes in a way that renders understanding uncertain, even after efforts to clarify • 0 Subject does not recall, is clearly inaccurate, or seriously distorts meaning

39. MacCAT-CR Appreciation • A-1 – “Do you believe that you have been asked to be in this study primarily for your personal benefit?” • Then ask: “What makes you believe that this (was/wasn’t) the reason you were asked?”

40. Appreciation - Scoring • 2 Subject acknowledges being recruited for reason unrelated to personal benefit • 1 Subject says recruited both for and not for personal benefit; or for personal benefit with plausible reason • 0 Subjects maintains being recruited only for personal benefit

41. MacCAT-CR - Choice • “As you know, you have been invited to participate in a research project testing a new medication for the treatment of schizophrenia. Do you think you are more likely to want to participate or not to want to participate?”

42. Choice - Scoring • 2 Subject states a choice • 1 Subject states more than one choice, seems ambivalent • 0 Subject does not state a choice

43. MacCAT-CR Reasoning • R1/R2 - “You think that you are more likely to want (to participate/not to participate) in the study. Tell me what it is that makes that option better than the other.” • Probe to explore reasoning process.

44. Reasoning – Scoring(Consequential Reasoning) • 2 Subject mentions at least 2 specific consequences • 1 Subject mentions only 1 specific consequence • 0 Subject mentions no specific consequences, even after direct probe

45. Use of Screening Instruments • Thresholds can be set based on data from similar populations or a priori judgments • Failure can trigger clinical evaluation and/or remediation • Retesting after remediation allows participation for those able to improve performance

46. Who Should Do the Screening? • NBAC (1999) suggested independent evaluation • But use of objective measures may allow clear documentation of decisions and obviate the need for outside assessor

47. What If Impairment is Detected? • Presence of impairment doesn’t imply subject should be excluded from study • Proper response is remediation, e.g., • Repetition of disclosure • Videotape/computer programs • Group discussions with former subjects • Still likely that some subjects will have to be excluded, unless someone else can make decision

48. Use of Proxy Decision Makers • Status unclear in US • Federal rules allow “legally authorized representative” • But case law suggests usual proxies in treatment settings (e.g., family members, guardians) may not be authorized to consent to research • However, without proxy consent, some disorders will never be understood (e.g., AD)

49. NBAC Recommendations for Use of Proxies • NBAC suggested use of proxies in minimal risk research, or more than minimal risk but with some prospect of benefit (e.g., treatment trials) • But this would disallow proxies in studies seeking understanding of pathophysiology (e.g., PET studies, indwelling catheters)

50. Reasonable Approach to Proxies • Permit persons authorized to consent for medical treatment to consent to research, so long as some prospect of benefit or risk represents no more than minor increment over minimal.