Enhancing Informed Consent: Lessons from Studies in Childhood Cancer

1. Enhancing Informed Consent: Lessons from Studies in Childhood Cancer Eric Kodish, MD Department of Bioethics Lerner College of Medicine Cleveland Clinic SACHRP October 28, 2009

2. Pediatric Ethics “A branch of bioethics that analyzes moral aspects of decisions made relating to the health care of children.” Lyren and Kodish Encyclopedia of Bioethics 3rd Edition

3. A Misnomer Informed Consent in Pediatrics = Parental Permission + Assent of the Child

4. The Beginning: Questions • about Informed Consent • What is better informed consent? • A higher consent rate / better accrual numbers? • A lower consent rate suggesting freedom to decline? • Enhanced compliance with federal regulations? • Improved understanding of the study by subjects? • Empowered participants in control of the research decision?

5. Project on Informed Consent (PIC): • Research Strategy, 1999-2002 • Describe current practice using direct observation methodology • Learn from parents of children with cancer and collaborate to improve the consent process. • Two Sources of Information • Direct Observation of Informed Consent Conferences (ICCs) and Parent Interviews • PIC is the 1st informed consent study to include direct observation • Parental Recommendations for Improving Informed Consent • Focus Groups and the Parent Advisory Group on Informed Consent (PAGIC)

6. Project on Informed Consent: Research History Year 4 N = 9 PAGIC Year 3 N = 72 FOCUS GROUPS Year 1- 2 DIRECT OBSERVATION N = 140

7. The Informed Consent Process Clinical Event Disclosure and consent conferences Treatment End Treatment at 4-6 months Diagnosis Telephone Interviews Observed/taped conference(s) and interviews Focus Groups PAGIC Notification Research Event

8. Results: Randomization was explained by physicians in 83% of cases and consent document was presented during the conference in 95% of cases. Interviews after the conference demonstrated that 68 (50%) of 137 parents did not understand randomization. Parents of racial minority and lower socioeconomic status were less likely to understand randomization (P<.001 for each). Discussion of specific clinical trial details and the presence of a nurse during the conference were associated with understanding. Eighty-four percent of children were enrolled in a leukemia trial. Conclusions: Despite oral and written explanation, half of the parents in this study did not understand randomization for childhood leukemia trials. To make informed consent more effective, future research must seek to improve communication during this critical interchange. JAMA, 2004;291:470-475 www.jama.com

9. Parental Understanding: Choice • On a conceptual level, understanding choice is more than just understanding that trial participation is voluntary. • Understanding choice requires that parents/patients have a clear appreciation of the alternative(s) to study participation. 33% of parents did not understand that they had a choice between participation in the RCT and off-study therapy.

10. Hiatus of Informed Consent, PIC Study Explained Understood by Cliniciansby Parents Choice: 89% 67% Randomization: 83% 49%

11. Deficits in Parental Understanding • Source/cause of deficits in parental understanding is not clear • Whatever the cause, this evidence suggests that data driven interventions to improve the process of communication and information exchange can positively affect: • Parental comfort level • Parental understanding • Parental involvement

12. Learning from Parents: The PAGIC Model What is Leukemia? Understand? 1st Meeting No Yes Current Treatment 1st or 2nd Meeting Depending Upon Parents Understand? No Yes Randomized Clinical Trial 2nd Meeting Understand? No Yes Decision

13. Increased Interactivity Intervention Better Understanding Why is interactivity important? 1) c/w conceptual ideal (bidirectional ICP) 2) Data from PIC show question asking a/w better parental understanding

14. The MUlti-Site Intervention Study to Improve Consent • (MUISIC)2003-2007 • Intervention phase of MUISIC builds on accomplishments of the PIC study • Previous research identified deficits in informed consent. MUISIC tests 2 (subsequently 3) rationally-designed interventions that may improve outcomes for informed consent

15. Specific Aims of MUISIC • To utilize our scientific understanding of the informed consent process in childhood leukemia trials to further develop, test and implement three data-based interventions to improve informed consent: • Physician-directed – teaching improved management of the informed consent conference • Parent-directed – delivered by nurse educators and based on the model of anticipatory guidance for informed consent • Parent-directed – delivered via DVD and based on the model of anticipatory guidance for informed consent

16. Specific Aims of MUISIC, cont. • 2) To conduct a clinical trial to test the effect of each intervention on three specific outcomes: • Parental comprehension of choice and alternative to clinical trial participation • Parental understanding of randomization • Parental participation during the informed consent process as measured by the number and quality of questions asked by parents • 3) To determine if any one intervention is superior to a control group, and how the three interventions compare to one another.

17. Study Design Philadelphia Physician-Directed Intervention Washington, D.C. Cleveland Parent-Directed Intervention (Nurse) MUISIC Los Angeles Atlanta (Eg) Parent-Directed Intervention (DVD) Pittsburgh Oakland Control/ No Intervention Atlanta (SR)

18. Description of Intervention Models – Parent-Directed Nurse Intervention Target ofTarget ofContent ofIntervention TrainingInterventionInterventionOutcome Nurse Parents Support and anticipatory guidance regarding informed consent conference Improved understanding of consent (parents); enhanced involvement of parents in the consent process, relative to controls

19. Description of Intervention Models – Parent-Directed DVD Intervention Target ofTarget ofContent ofIntervention TrainingInterventionInterventionOutcome DVD Parents Support and anticipatory guidance regarding informed consent conference Improved understanding of consent (parents); enhanced involvement of parents in the consent process, relative to controls

20. Description of Intervention Models – Physician-Directed Intervention Target ofTarget ofContent ofIntervention TrainingInterventionInterventionOutcome Physician Physicians Communication; listening skills; management of consent conference Improved understanding of consent (parents); enhanced involvement of parents in the consent process, relative to controls

21. Study Design Philadelphia Physician-Directed Intervention Washington, D.C. Cleveland MUISIC Parent-Directed Intervention (Nurse) Los Angeles Parent-Directed Intervention (DVD) Atlanta (Eg) Pittsburgh Control/ No Intervention Oakland Atlanta (SR)

22. Distribution by Site • Parent (Nurse Delivered) Intervention Sites • CL 14 • LA 10 • AI 12 • Parent (DVD Delivered) Intervention Site • PI 12 • Physician Intervention Sites • PH 36 • DC 22 • Control Sites • AT 33 • OA 7 • -------------------------------------------- • Total N = 146

23. Demographics For All Cases

24. Features of the ICC – MUISIC Study

25. Diagnosis Communicating Prognosis in the ICC

26. Physician Training Seminars: Participant Numbers* *Seven physicians at CNMC and thirteen from CHOP attended booster seminars conducted after these full day seminars.

27. Enrollment and group assignment

28. Observed Features of ICC

29. Observed Features of ICC

30. Parent Interviews: Understanding by Parents * Excludes participants offered non-randomized trials

31. MUISIC vs. PIC:Understanding Randomization • Comparing PIC study with MUISIC study control group: • Understanding randomization was only 50% in PIC study with the larger group size of N=140. • Understanding randomization was 78% in MUISIC study for the smaller control group sample size of N=26.

32. Learning from Parents: The PAGIC Model What is Leukemia? Understand? 1st Meeting No Yes Current Treatment 1st or 2nd Meeting Depending Upon Parents Understand? No Yes Randomized Clinical Trial 2nd Meeting Understand? No Yes Decision

33. Sequence Analysis • * The first six coded variables were considered to be part of “What is leukemia?” and were noted as discussed during the ICC prior to discussion of current therapy more often in the PDI than control group cases. • † Side effects of therapy, outline treatment plan and length of treatment were items coded if they were discussed prior to description RCT

34. Fidelity to PAGIC Model

35. Question asking by Parents

36. Parent Interview Data: Understanding by Parents * Excludes participants offered non-randomized trials

37. Data on Parental Understanding Outcomes • Parental Understanding: Choice • 85% of parents at physician-directed intervention sites (trained physician) and 81% of parents at parent-directed intervention sites understood that they had a choice between RCT and off-study therapy • Only 62% of parents at control sites understood that they had a choice between RCT participation and off-study therapy • Parental Understanding: Randomization • 77% of parents at physician-directed intervention sites (trained physician) and 63% of parents at parent-directed intervention sites understood that their child would be randomly assigned to one of RCT multiple arms • 78% of parents at control sites understood that their child would be randomly assigned (remember this was 50% in PIC, with larger sample)

38. Key Summary Points • With attention to sequence, choreography and communication science, we can improve the informed consent process. • The lessons we have learned may not apply to other contexts. • More research is needed. Support from NIH R01 CA 083267