P atients’ E xperiences in E mergency R esearch

1. Patients’ Experiences in Emergency Research Neal Dickert, MD, PhD Victoria Mah, MPH Rebecca Pentz, PhD

2. Introduction What do people think about EFIC? Available data on views: General public Participants in community consultation sessions People with the condition Subjects for whom surrogates gave consent

3. Introduction Why does it matter what enrollees think? Critical to the ethical validity of EFIC “There should be no compelling reason to think that the experimental intervention conflicts with patients’ values or interests.” Largent, et al. Arch Int Med. 2010. What level of acceptance is necessary is unclear Strongest reason for community consultation May provide opportunities to improve experience, minimize harms, improve trust, etc.

4. General Public McClure et al. Acad Emerg Med, 2003

5. Community Consultants • Biros et al. Resuscitation. 2009.

6. Community Consultants • Bulger et al. Ann Emerg Med. 2009.

7. Community Consultants • Contant et al. Crit Care Med. 2008.

8. People with condition under study 66% (n=277) of parents of children with mild head trauma willing to enroll Baren et al.Acad Emerg Med 1999 TBI patients, stroke survivors, and young people Good understanding of research and EFIC General acceptance of EFIC Particular concern over randomization and use of placebo Kasner et al. Ann Emerg Med 2010 Survivors of Sudden Cardiac Death None opposed to EFIC altogether Accepting of studies comparing existing treatments Central concern is risk of “experimental” treatments Challenging to explain core concepts Dickert and Kass. Soc Sci Med 2009

9. Subjects/Surrogates Kamarainen, et al. Resuscitation. 2011.

10. Subjects/Surrogates Kamarainen, et al. Resuscitation. 2011.

11. Major Gaps No published study has assessed the views of EFIC enrollees/family members Arguably the most relevant population Don’t know if CC predicts their responses/concerns Significant variation in existing studies Existing data lack depth

12. PEER Specific Aims Assess views of enrolled patients regarding acceptability of EFIC and RAMPART enrollment Provide baseline/benchmark data Identify patient and study factors that predict satisfaction/acceptance: Conversations w investigators, understanding of research, prior experience, demographics Risk level, randomization, alternatives Assess whether Community Consultation elicits concerns of enrollees. Links to RAMPART CC studies.

13. Population Population= enrollees or surrogates Identified by site Generally whoever consented for participation Initially restricted to adult enrollees, expanded to allow surrogates of pediatric enrollees Spanish-speaking interviewers available 5 sites- Emory/Grady, University of Pennsylvania, University of Minnesota, UCSF, and University of Cincinnati Target n= 100

14. Recruitment and Conduct • Eligible subjects identified by local site • Asked permission to be contacted about PEER participation or sent opt-out letter • Trained interviewer at each site • Interviews over the phone or in-person • Audio recorded • Paid $35 for participation

15. Interview Methods Structured, interactive interviews Principal goals Quantitatively meaningful data with reliable estimates of prevalence of particular views and concerns Qualitative assessment of reasons for responses and level of understanding

16. Interview Methods • Introduction of content and opportunity for clarification • Allow participants to understand the content, develop views, and ask questions • Standard Likert-scale question • to provide quantitative data • Follow-up questions regarding reasons for responses • Allow insight into participants’ understanding • Deeper knowledge of reasons for response

17. Interview Example 3.3 When researchers do research studies to test treatments for emergencies like seizures, they can’t ask patients for their permission or consent. This is because patients are very out of it or are unconscious. In addition, family members are not always around and decisions about how to treat people with these conditions have to be made very, very quickly. Does it make sense why researchers who do research like the RAMPART study have to include patients without asking them or their family members for consent or permission?

18. Interview Example 3.5 I want to ask you now for your opinion about (your family member) being included in the RAMPART study. On a scale of 1 to 5 with 1 being strongly agree and 5 being strongly disagree, how would you rate the following statement? I think that it was ok for researchers to include (your family member) in the RAMPART research study without asking me or (your family member) first for permission. Strongly Agree 1      2       3       4       5 Strongly Disagree Everyone then asked “How did you decide on this answer?”

19. Interview Domains Prior research experience & attitude toward research Knowledge of the study Views on having been included in the study Views on acceptability of EFIC in research- in this study and in general Views on randomization Views on conversations with investigators/study staff Views on community consultation Impact of public disclosure Trust in researchers and in clinical research Demographics and medical background

20. Data Management • Interviews transcribed verbatim • Redacted for errors • Coded quantitative data and pre-defined codes for text data entered into ACCESS database • Text data entered into MAXQDA for qualitative analysis

21. Quantitative Data Analysis Entry into online database Analyzed using SAS 9.3 Statistics Descriptive statistics Bivariate analysis (Chi-square)

22. Qualitative Data Analysis MAXQDA software used to manage the data Principal analytic method = qualitatitve description Low-inference method Multi-level coding strategy employed given size of the database Content-based codes to allow sorting A priori/deductive codes Inductive coding Codebook built through initial inductive coding Second round using complete codebook Reliability assessment- 15 challenging interviews

23. PEER Study-Population • 62 interviews conducted • 1 recording failure • 2 interviews terminated early • 59 fully analyzable interviews • Reasons for low enrollment • Challenging population • Failure to contact > refusal • Rapid RAMPART recruitment and delayed start

24. PEER Study-Population

25. PEER vs. RAMPART

26. Site Distribution

27. Views on RAMPART and EFIC

28. Views on RAMPART and EFIC

29. Acceptance- Patient vs. Surrogate

30. Acceptance- Race

31. Acceptance- Education

32. Acceptance- Sex

33. Acceptance- Age

34. Reasons for Positive Views Direct medical benefits (31, 51%) ”… the medicine stopped him from having so many seizures. It helps him control his seizures." 1-068 Often misunderstood Trust in researchers and doctors to do what is best (15, 25%) "I don’t think y’all would do a study that’s not going to help him." 1-346 Wanting to save patients’ lives (12, 20%) "If it is going to save their life… you go ahead and then you talk to them about it later and tell them what you had to do about it, to save their life." 1-346

35. Reasons for Positive Views Recognizing the inability to get consent given the situation (12, 20%) " I didn’t have a problem with it because I understood, just as you were saying. I was seizing at the time, so, it wasn’t like I could give a yes or no and it was something that could be beneficial, like pull me out of the seizure quicker." 4-004 Importance of research (11, 18%) "Well, I would have to think about that. All research is important. You know that and I do too. Whether it is about seizures or anything else, you have to research it in order to get any type of cure for it or medication that helps it.” 4-005

36. Reasons for Positive Views Desire to improve scientific knowledge and help others (10, 16%) "So, going through the process, it can be a good thing. We can get better medical skills on how to help patients." 1-179 Positive interaction with study staff (10, 16%) "She let me know a lot about the study and she let me know something about the drug. She said, it hasn’t been approved or something yet, she said. I was a little concern about that, but, I got comfortable with it. The longer she talked, I got a little more comfortable with it." 1-235

37. Reasons for Negative Views Concerns about consent (17, 28%) “If somebody wants to sit up there and let them do that or be tested for it, that’s cool. But, people who that are not knowing about it, they shouldn’t go through that because if they want to do an experiment, why don’t they do it on themselves first... They have to ask people first. They need to tell them what they are giving them and doing to make people decide if they want to do it.” 5-012 Dissatisfaction with amount of information given (11, 18%) Like I said, I disagree with that because of my problem, because they didn’t tell me and let me know. 1-179

38. Reasons for Negative Views Other people may not be as accepting (9, 15%) “Some people feel different than I do. The situation that my mom was in, I am glad they did what they did. Some people don’t want that because maybe it is an invasion or whatever of privacy.” 1-382 Concerns about allergies/interactions (7, 11%) "I was kind of bothered because I am very sensitive to medication. I had already stopped breathing a couple of times... they should have asked the people that I was with if I was allergic to anything… and especially since I am high risk patient, they could have made everything turn worse." 1-459

39. Randomization • I think that it was acceptable for researchers to assign treatments at random like this in this study? • Agree= 50 (86%), neutral= 3 (5%), disagree= 5 (9%) • Reasons • Positive: avoids bias, okay since both are seizure meds • Negative: inappropriate to randomize with lives at stake, wants specific medicine • At least a quarter did not understand the concept after repeated explanation

40. Opt-Out Bracelet People who heard about the study could call in and get a wrist band that would let people know that they didn’t want to be included in this study if they had a seizure and were picked up by the ambulance. Is that something you would have done if you had known about the study? Yes = 4 No = 47 1 not okay with study, but wouldn’t bother w bracelet Difficult question to understand

41. Community Consultation Do you think community consultation sounds like something important to do? Yes= 56 (98.25%) No= 1 (1.75%) Who should be consulted for EFIC seizure studies? People who have seizures and their families= 35 Doctors and nurses, people in medical community= 10 General public= 10 Other= 27 Examples; underprivileged people, racial/ethnic minorities, churches, elderly people, support/health groups, and community members

42. Public Disclosure Researchers also tried to inform communities about the RAMPART study so that they would know it was going on. Were you aware of the RAMPART study (the one in which (your family member) was enrolled) before (your family member ) was brought to the hospital? Yes= 2 (3.57%)- 1 repeat enrollee, 1 got a letter from epilepsy foundation No= 54 (96.43%)

43. Trust in Researchers/Doctors Reverse coded, mean is 16.04. RAMPART CC participants’ mean was 14.4; mean In national sample in which scale was validated was 12.4.

44. Discussion/Conclusion Acceptance of EFIC personally and in general are reasonably high (73 and 67%) and consistent with data from CC populations Similar to RAMPART data with meetings/FGs CC does not overestimate acceptance No clear demographic associations with particular views. Most remarkable trend is less positive response among non-whites No major differences between surrogates vs. patient

45. Discussion/Conclusion • Principal reasons for acceptance included perception of benefit and understanding that consent is not possible. • Often inappropriate perception of benefit… • Concerns about consent often expressed. Not always translated into view that EFIC is unacceptable. • Concerned about harms, but few felt harmed • Post-enrollment interactions matter • When someone present, involvement appreciated

46. Limitations Poor understanding of study and EFIC This study was very difficult to do Recruitment in this population Interview standardization Also, the results are hard to interpret Shifting responses (standard approach to this) Large volume of qualitative data) Small sample size, below target

47. Thanks Sites/Co-Investigators Jill Baren, Michelle Biros, PrashaGovindarajan, Art Pancioli, David Wright Luke Farmer and Peggy Waymeyer NETT and RAMPART leadership Robert Silbergleit and Bill Barsan HSP working group members NINDS R03 NS066378-01

49. PEER-RAMPART vs. PEER-PROTECT