Enhancing the Informed Enhancing the Informed Consent Process for Research: Consent Process for Research: “The answer is we don’t know”“The answer is we don’t know”

Laura B. Dunn, M.D. Laura B. Dunn, M.D.

Associate ProfessorDirector of Psycho-Oncology

Department of PsychiatryUniversity of California, San Francisco

AcknowledgmentsAcknowledgments

Barton Palmer, Ph.D.Paul Appelbaum, M.D.Paul Holtzheimer, M.D.

Laura Roberts, M.D.Dilip Jeste, M.D.

Research support (2001-present)NIMH Career Development Award (K23)

NARSAD Young Investigator AwardNational Institute on Aging (R01), NIMH (various)

Greenwall Foundation

OutlineOutline

• Problems with current informed consent practices and oversight

• Vulnerability in context of informed consent

• Enhancing informed consent– Evidence base

– Sample approaches

– Recommendations

Problems with Current Informed Problems with Current Informed Consent Practices & OversightConsent Practices & Oversight

• Ongoing problems with readability, length, complexity

• IRB issues (see Emanuel et al. Ann Intern Med 2004)

• Rigid requirements discourage experimentation with methods to better enact “process” model

• Distracts from more serious ethical problems in clinical research

Problems with Current Informed Problems with Current Informed Consent PracticesConsent Practices

“…IRBs often spend much time scrutinizing informed consent documents and producing excessively long detailed forms, even for relatively simple, minimal-risk research. This focus on informed consent documents negates the widely accepted notion that informed consent is a process, does not always improve the informed consent process, and diverts limited IRB time from consideration of other serious ethical issues.”

Emanuel et al. Ann Intern Med 2004)

“As consent forms become increasingly lengthy and complicated and come to include more and more information … the very existence of such consent forms may obstruct rather than improve the process of obtaining informed consent.”

- Roth et al., 1982

(Roth et al. Int J Law Psychiatry 1982;5:29-50)

Respect for PersonsRespect for Persons(Belmont Report)(Belmont Report)

Two Components

“individuals should be treated as autonomous agents”

“persons with diminished autonomy are entitled to protection”

• “any subject or class of subjects who are either unable to provide informed consent or who are at substantial risk of being unable to provide informed consent for a particular study” (Rosenstein & Miller, Psychopharmacology 2003)

• Evidence that some proportion of the population has difficulties with decision-making capacity

• Cognitive impairment, poor insight, instability (medical, psychiatric, cognitive)

Who is “vulnerable”?Who is “vulnerable”?

Methods of assessing Methods of assessing decision-making capacitydecision-making capacity

• Clinical interview

• Cognitive/Neuropsychological tests (e.g., MMSE)

• Decisional capacity scales or structured interviews:– Questionnaires

– Scales or structured interviews

Decisional capacity scalesDecisional capacity scales• 23 published in the literature (1980 to 2004)

(Dunn et al. Am J Psychiatry 2006)

– 10 assessing research consent capacity– 15 treatment-related capacity– (2 both) – Comprehensive assessment of all four

dimensions was rare among the instruments for research

• UCSD Brief Assessment of Consent Capacity (UBACC) (Jeste et al. Arch Gen Psychiatry, 2007)

– 10 items assessing understanding and appreciation

MacCAT-CRMacCAT-CR

• Semi-structured interview – adapt to specific protocol – takes 15-30 minutes

• Four subscales:– Understanding: 13 items – Appreciation: 3 items – Reasoning: 4 items– Expression of a Choice: 1 item

• Psychometrics: Reliability – ICCs 0.78-0.99• Samples have included: SCZ, MDD, AD, Ca,

HIV, DM, controls• Requires reliability training; manual available

MacArthur Competence Assessment Tool for Clinical Research (Appelbaum & Grisso, 2001)

Methods for enhancing informed Methods for enhancing informed consentconsent

• Consent forms• Briefer• Structured, reviews, advance organizers

• Educational sessions• Provision of multiple learning trials• Multi-modal/multi-media disclosure

• Computer aided disclosure • Hands on demonstrations• Visual presentation (video, DVD)

Dunn & Jeste, Neuropsychopharmacology, 2001

Informed consent: intervention studiesInformed consent: intervention studies

Wirshing et al., 1998

Repeated learning trials, corrected feedback improved comprehension/retention

Carpenter et al., 2000

Educational remediation improved impairments on MacCAT-CR Understanding subscale; Appreciation, Reasoning also improved.

Dunn et al., 2001, 2002

PowerPoint-enhanced consent associated w/better performance (20-item comprehension test) vs. routine paper consent

Informed consent: intervention studiesInformed consent: intervention studies

Wirshing et al., 2005

Improved understanding, using instructional videotape re: important aspects of informed consent

Dunn et al., 2006

Better understanding of placebo controls among schizophrenia patients who received educational module about placebos vs. those receiving routine information as part of consent

Moser et al., 2006

Simplified computer-based intervention led to better MacCAT-CR (Understanding and Reasoning) scores in SCZ group. Post-intervention, SCZ pts did not differ from controls on any of 4 domains of capacity

Assessment of Capacity to Assessment of Capacity to Consent to Research Among Older Consent to Research Among Older

Persons with Schizophrenia, Persons with Schizophrenia, Alzheimer Disease, or Diabetes Alzheimer Disease, or Diabetes

MellitusMellitus

Palmer BW, Dunn LB, Appelbaum PS, et al.

Arch Gen Psychiatry 2005 62:726-733.

Sample characteristicsSample characteristicsSCZ

(n=35)AD

(n=30)DM

(n=36)

Age (yrs) 66 (5) 77 (7) 71 (6)

Education (yrs) 12 (3) 15 (3) 14 (2)

% Men 57% 73% 97%

% Caucasian 80% 90% 72%

Age of onset (yrs)

29 (12) 72 (7) 54 (13)

Palmer et al. Arch Gen Psychiatry 2005; 61:230-6

3-item Questionnaire3-item Questionnaire• Consent process for hypothetical double-blind

placebo RCT of cognitive enhancer (“Plakmin”)

• 3 Item Questionnaire (3 Q)• (1) "What is the purpose of the study?“• (2) "What are the risks?“• (3) "What are the benefits?"

• Each item rated 0 (incapable), 1 (questionable/intermediate), or 2 (capable)

• MacArthur Competence Assessment Tool for Clinical Research (MacCAT-CR)

Palmer et al. Arch Gen Psychiatry 2005; 61:230-236

3 Q: Total scores by dx group3 Q: Total scores by dx group

0

5

10

15

20

25

30

35

40

45

0 0.5 to 1.5 2.0 to 2.5 3.0 to 3.5 4.0 to 4.5 5.0 to 5.5 6

Schizophrenia (n=35) Alzheimer Disease (n=30) Diabetes (n=36)

% o

f S

ub

jec

ts

3 Q Total (mean of two independent raters; possible range 0-6)

Sensitivity and specificity of 3 QSensitivity and specificity of 3 Q

0

10

20

30

40

50

60

70

80

90

100

0 0.5 1 1.5 2 2.5 3 3.5 4 4.5 5 5.5 6

Sensitivity Specificity Overall Correct

3 Q Total Mean Score

Per

cent

Implications of 3 Q studyImplications of 3 Q study

• Brief questionnaire may be a sensitive, and adequately specific, screening instrument for identifying potential research participants who warrant more in-depth capacity evaluation and/or educational interventions

• Can be easily integrated into consent process for any study

• Cut-point may need to be adjusted for different studies (i.e., more research needed)

Simple But Effective: Talk With Patients Simple But Effective: Talk With Patients or Potential Research Participantsor Potential Research Participants

• 7 Volunteer Protocols7 Volunteer Protocols• Reviewed each protocol Reviewed each protocol

to identify 5 essential to identify 5 essential elements, i.e.:elements, i.e.:– PurposePurpose– ProceduresProcedures– RisksRisks– BenefitsBenefits– VoluntaryVoluntary

• Pause during consent Pause during consent process, ask potential process, ask potential participant to paraphrase participant to paraphrase essential information.essential information.

• Re-explain missed infoRe-explain missed info• Re-evaluate Re-evaluate

understandingunderstanding• Re-explain againRe-explain again• Re-evaluateRe-evaluate

(Palmer et al. 2008; IRB: Ethics & Human Research)

Medication Adherence Among Medication Adherence Among People with Schizophrenia Ages People with Schizophrenia Ages ≥ ≥ 40 (N=63)40 (N=63)

Trial 1Trial 1 Trial 2Trial 2 Trial 3Trial 3

PurposePurpose 8484 9797 100100

ProcedureProcedure 7878 9494 9898

RiskRisk 7777 9797 100100

BenefitBenefit 7373 9090 100100

VoluntaryVoluntary 8787 9898 100100

(Palmer et al. 2008; IRB: Ethics & Human Research)

Exercise for Patients with Exercise for Patients with Osteoarthritis (N=10)Osteoarthritis (N=10)

Trial 1Trial 1 Trial 2Trial 2 Trial 3Trial 3

PurposePurpose 7070 9090 100100

VoluntaryVoluntary 100100

DurationDuration 100100

RisksRisks 100100

ConfidentialityConfidentiality 7070 9090 100100

(Palmer et al. 2008; IRB: Ethics & Human Research)

RCT Type II Diabetes (N=13)RCT Type II Diabetes (N=13)

Trial 1Trial 1 Trial 2Trial 2 N/AN/A

PurposePurpose 9292 100100

Procedure 1Procedure 1 6969 100100

RandomizationRandomization 7777 100100

RisksRisks 8585 100100

VoluntaryVoluntary 100100

(Palmer et al. 2008; IRB: Ethics & Human Research)

Blood Proteins in CHF (N=6)Blood Proteins in CHF (N=6)

Trial 1Trial 1 Trial 2Trial 2 N/AN/A

PurposePurpose 5050 100100

Procedure Procedure 6767 100100

RisksRisks 8383 100100

BenefitsBenefits 8383 100100

VoluntaryVoluntary 100100

(Palmer et al. 2008; IRB: Ethics & Human Research)

ImplicationsImplications

• Utility of brief assessment instruments for screening for issues with understanding of consent in diverse research studies

• Methods of administering consent can and should be used as educational opportunities

• Need more experimentation with other methods

• Premature to draw conclusions about what works best, for whom

• Consider cognitive impairment, physical limitations, pain, psychosocial issues, and subjects’ and families’ concerns

Images, video, multimediaImages, video, multimedia

• Useful for showing things that are hard to describe in text or are difficult concepts for many people

• study procedures

• probabilities

• Should not replace in person, individualized consent, but may be a helpful supplement.

Jeste, Dunn, Folsom et al., J Psychiatr Res 2007.

Key Study ProceduresKey Study Procedures

Screening Psychiatric Interview Blood Draw Spinal Tap Cognitive Testing MRI

Study Medication RisksStudy Medication Risks

Headache Bruising Dizziness Sleepiness Constipation Liver Damage/Death

Explaining randomizationExplaining randomization

Explaining randomizationExplaining randomization

Internet tools to enhance consentInternet tools to enhance consent

• Video consent process - ability to pause, review

• Online library of video/images for consent• Click through for more detailed information• Matching/tiling/multiple choice questions to

assess understanding of key facts, concepts• “Chat” functions with investigators• Need to fund this kind of research, while

simultaneously dismantling barriers to conducting research on informed consent itself

• Different individuals will prefer different methods of learning about studies

Informed consent as a process: Informed consent as a process: DBS for depressionDBS for depression

6 minutes into consent: Subject asks question about compatibility of two companies’ DBS devices, and whether she would be able to get a replacement part if needed.

Investigator: “Probably yes you will be able to get one, probably yes. Because the chance that nobody would--even if [Company A] decided to stop making it--we don’t know. The answer is we don’t know.”

Informed consent as a process: Informed consent as a process: DBS for depressionDBS for depression

29 minutes into consent:

(Following a question from subject’s significant other about mechanism of action of DBS.)

Investigator: “We’re probably providing a--and again, this is all conjecture--we’re probably providing essentially a pacemaker within some mood regulation network that prevents it from falling into a depressed rhythm.”

Informed consent as a process: Informed consent as a process: DBS for depressionDBS for depression

53 minutes into consent:

Investigator: “…We can’t say with any confidence that we know that this works versus doesn’t work. Even though the response rates are striking in this patient population, it could all be placebo. And I believe that. I mean I believe that that is a possibility. I don’t think it’s a probability, I believe that it’s a possibility. That said, there is no good evidence. There’s anecdotal evidence.”

Informed consent as a process: Informed consent as a process: DBS for depressionDBS for depression

Invest.: Improvement is by no means guaranteed, but it is a possibility...of...

Subj: Considering the type of people you are treating, 50 to 60% response rate is extremely impressive.

Invest.: We believe that in this population that that is a very good response rate. But from a patient's standpoint coming into the study, recognizing as I know you do that there's a chance you could do this and it'd be no different except for having two holes in your head.

Subj: I understand that.

Recommendations for informed consentRecommendations for informed consent

• Test for understanding of risks (likelihood, seriousness)

• Ask what the subject expects and hopes for in terms of benefits

• Assess perceptions of risks and benefits to ascertain if risks may be underestimated or benefits overestimated

• Ask about motivations for participation• Retest later (in ongoing protocols)• Highlight key differences between research and

usual clinical care

Dunn & Gordon, JAMA, 2005;293:609-612

Research Agenda: Research Agenda: Enhancing Informed ConsentEnhancing Informed Consent

• Emphasis on process and overall understanding, rather than on signature

• Allowing for innovation by researchers, departments, research units; allow for collection of data on informed consent (without requiring additional consent for such research)

• Effects of clarity re: “minimal risk” research for informed consent (i.e. allow waivers but collect data on understanding)

• Study IRB processes

Revitalize Informed ConsentRevitalize Informed Consent “Informed consent should be an ongoing

process that focuses not on a written form or a static disclosure event, but rather on a series of dynamic conversations between the participant and the research staff that should begin before enrollment and be reinforced during each encounter or intervention. Multidisciplinary approaches should be tailored to individual differences in participant education and learning capabilities.”

Institute of Medicine: Responsible Research: A Systems Approach to Protecting Research Participants (2002)

Revitalize Informed ConsentRevitalize Informed Consent “The informed consent process should be an

ongoing, interactive dialogue… involving the disclosure and exchange of relevant information, discussion of that information, and assessment of the individual’s understanding of the discussion. The informed consent conversation(s), as well as the written consent document, should not be obscured by language designed mainly to insulate the institution from liability. Rather, the process should ensure that participants clearly understand the nature of the proposed research and its potential risks and benefits to them and society.”

Institute of Medicine: Responsible Research: A Systems Approach to Protecting Research Participants (2002)

“Excessive literary production is a social offence.”

- George Eliot