P atients’ E xperiences in E mergency R esearch Neal Dickert, MD, PhD Victoria Mah, MPH Rebecca Pentz, PhD

Patients’ Experiences in Emergency ResearchNeal Dickert, MD, PhD

Victoria Mah, MPH

Rebecca Pentz, PhD

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

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.

General Public

ED Waiting Room patients (n= 530) % Agree

“There are times when it is so important to learn about a potential new treatment that it would be okay to enroll patients in a study before they are able to consent.”

45%

Willing to be enrolled “… if the risks were minimal and small compared to the risk for the serious disease.”

88%

McClure et al. Acad Emerg Med, 2003

Community ConsultantsMN State Fair Survey for RAMPART (n=1901)

Agree DisagreeNo

Opinion

“EFIC is acceptable for patient enrollment into an emergency research study when no surrogate is available to speak for the patient.”

36% 47% 18%

“EFIC is acceptable for research in our community.”

74% 4% 22%

“My own EFIC enrollment in this study would be acceptable.”

45% 19% 35%

Biros et al. Resuscitation. 2009.

Community ConsultantsROC- RDD Survey for Hypertonic Saline Study

Willingness to be included (n=2418) Yes“If you were severely injured, such that you had a 25-50% chance of dying with standard treatment, would you want this experimental fluid given to you without written consent, knowing that it might improve your chance for survival or recovery from head injury, but that there is a risk of allergic reaction or other unexpected sided effects.”

74%

Attitude toward EFIC (n=1005) Yes

“Do you believe that this exception to written consent is justified and in the best interests of the patients and community?”

81%

75%

Bulger et al. Ann Emerg Med. 2009.

Community ConsultantsComparative Study- CC for L-arginine in TBI

Influence of Method % Accept

Phone-Random Digit Dialing 71%

Interview 86%

Community Meeting 84%

Framing Effects % Accept

“If I or a close member of my family suffered a severe head injury, I would want to participate in the study.”

85%

“If I or a close member of my family suffered a severe head injury, I would NOT want to participate in the study.”

73%

Contant et al. Crit Care Med. 2008.

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

Subjects/SurrogatesEnrollees in Study of Pre-Hospital Hypothermia

Question Respondent Agree Disagree

My feelings regarding the study are positive

PatientSpouse

Physician

111613

000

Even in an emergency, consent from the patient or proxy is necessary to recruit…

PatientSpouse

Physician

5126

657

I believe the consent provider was capable to decide about participating in the trial…

PatientSpouse

Physician

11155

028

Kamarainen, et al. Resuscitation. 2011.

Subjects/SurrogatesEnrollees in Study of Pre-Hospital Hypothermia

Question Respondent Agree Disagree

If approved by an IRB, can be investigated without consent if treatment is considered beneficial

PatientSpouse

Physician

111513

010

I would accept may participation without consent if a trial were approved by an IRB

PatientSpouse

Physician

111613

000

IRB-approved study can be initiated w/o consent if delay would be harmful and consent obtained later

PatientSpouse

Physician

111613

000

Kamarainen, et al. Resuscitation. 2011.

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

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.

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

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

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

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

Interview Example3.3 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?

Interview Example3.5 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?”

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

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

Quantitative Data Analysis

• Entry into online database

• Analyzed using SAS 9.3

• Statistics• Descriptive statistics• Bivariate analysis (Chi-square)

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

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

ParticipantPatient 24 (39%)

Surrogate 37 (61%)

GenderFemale 40 (66%)

Male 21 (34%)

RaceWhite 13 (23%) Black 32 (57%) Other 11 (20%)

Age

< 30 10 (16%) 31-50 22 (36%) 51-70 26 (43%) 70 3 (5%)

EducationHigh School or Less 29 (54%)

Some College or More 25 (46%)

PEER Study-Population

PEER-RAMPART RAMPART

GenderFemale 40 (66%) 405 (45%)

Male 21 (34%) 488 (55%)

RaceWhite 13 (23%) 348 (39%)Black 32 (57%) 453 (51%)Other 11 (20%) 92 (10%)

Age (interviewed subject)

0-5 0 (0%) 61 (7%)6-10 0 (0%) 35 (4%)11-20 0 (0%) 49 (5%)21-40 20 (36%) 226 (25%)41-60 24 (43%) 338 (38%)>60 12 (21%) 184 (21%)

PEER vs. RAMPART

Site Distribution

PEER Study Sites # %Emory University/Grady Memorial Hospital 27 44%

University of Pennsylvania/York, PA site 2 3%

University of Minnesota/Hennepin County Medical Center 6 10%

University of Cincinnati Medical Center 15 25%

University of California-San Francisco/San Francisco General 11 18%

Total 61 100%

Views on RAMPART and EFICI am glad that I/(your family member) was included in this research study (before explicit EFIC discussion)

Agree 49 (82%)72%-91%

95% CINeutral 9 (15%)

Disagree 2 (3%)

It is important to do research comparing which treatments for seizures work best in the ambulance.

Agree 54 (95%)89%-100%

95%CINeutral 1 (2%)

Disagree 2 (3%)

Views on RAMPART and EFICI think that it was ok for researchers to include me/(your family member) in the RAMPART research study without asking me/(family member) first for permission.

Agree 43 (73%) 62%-84%95%CI95%CI

Neutral 6 (10%)

Disagree 10 (17%)

I think that it was ok for researchers to include people in this research study without asking them for permission.

Agree 39 (67%)55%-79%

95%CINeutral 10 (17%)

Disagree 9 (16%)

Acceptance- Patient vs. Surrogate

Patient Surrogate Total

Glad about inclusion in this study

Agree 16 (70%) 33 (89%) 49 (82%)

Not Agree 7 (30%) 4 (11%) 11 (18%)

Okay with personal enrollment under EFIC

Agree 17 (77%) 26 (70%) 43 (73%)

Not Agree 5 (23%) 11 (30%) 16 (27%)

Okay with EFIC usage in this study

Agree 15 (71%) 24 (65%) 39 (67%)

Not Agree 6 (29%) 13 (35%) 19 (33%)

Acceptance- RaceWhite Black Other


Agree 11 (85%) 27 (84%) 9 (82%)Not Agree 2 (15%) 5 (16%) 2 (18%)


Agree 11 (85%) 24 (75%) 6 (55%)Not Agree 2 (15%) 8 (25%) 5 (45%)


Agree 12 (92%) 20 (63%) 6 (55%)Not Agree 1 (8%) 12 (37%) 5 (45%)

Acceptance- EducationHigh School or < Some college or >


Agree 27 (93%) 18 (72%)

Not Agree 2 (7%) 7 (28%)


Agree 22 (76%) 17 (68%)Not Agree 7 (24%) 8 (32%)


Agree 18 (62%) 18 (72%)Not Agree 11 (38%) 7 (28%)

Acceptance- Sex

Male Female


Agree 16 (80%) 33 (83%)Not Agree 4 (20%) 7 (17%)


Agree 14 (74%) 29 (73%)Not Agree 5 (26%) 11 (27%)


Agree 11 (58%) 28 (72%)Not Agree 8 (42%) 11 (28%)

Acceptance- Age< 30 31-50 51-70 > 70


Agree 7 (78%) 17 (77%) 24 (92%) 1 (33%)Not Agree 2 (22%) 5 (23%) 2 (8%) 2 (67%)


Agree 6 (75%) 15 (68%) 20 (77%) 2 (67%)Not Agree 2 (25%) 7 (32%) 6 (23%) 1 (33%)


Agree 4 (57%) 15 (68%) 18 (69%) 2 (67%)Not Agree 3 (43%) 7 (32%) 8 (31%) 1 (33%)

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

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

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

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

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

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

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

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

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%)

Trust in Researchers/DoctorsMed/mean

Doctors who do medical research care only about what is best for each patient. 1 /1.58

Doctors tell their patients everything they need to know about being in a research study. 2 /2.21

I completely trust doctors who do medical research. 2 /2.22

Medical researchers treat people like "guinea pigs.” 4 /3.71

Total 9 /9.79*

Reverse coded, mean is 16.04. RAMPART CC participants’ mean was 14.4; meanIn national sample in which scale was validated was 12.4.

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

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

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

Thanks• Sites/Co-Investigators

• Jill Baren, Michelle Biros, Prasha Govindarajan, 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

PEER-RAMPART vs. PEER-PROTECT

DemographicsPEER RAMPART

PEER ProTECT

Participant Type

Patient 24 (39%) 31 (36%)Surrogate 37 (61%) 54 (64%)

GenderFemale 40 (66%) 46 (54%) Male 21 (34%) 39 (46%)

RaceWhite 13 (23%) 60 (76) Black 32 (57%) 11 (14%) Other 11 (20%) 8 (10%)

Age

< 30 10 (16%) 15 (18%) 31-50 22 (36%) 29 (35%) 51-70 26 (43%) 34 (40%) > 70 3 (5%) 6 (7%)

EducationHigh School or Less 29 (54%) 41 (48%) Some College or More 25 (46%) 44 (52%)

Documents

P atients’ E xperiences in E mergency R esearch Neal Dickert, MD, PhD Victoria Mah, MPH Rebecca Pentz, PhD