Transcript The Therapeutic Misconception and Consent in - CAREB

Therapeutic Misconception:
What difference does it
make?
Charles W. Lidz Ph.D.
What is the Therapeutic
Misconception (TM)?
The therapeutic misconception
occurs when a research subject fails
to grasp the distinction between
clinical research and ordinary
treatment and attributes therapeutic
intent to research procedures
Competing Commitments in
Clinical Research
 The
primary purpose of research is to
gather valid data that will provide an
answer to an important research
question
 Ethical rules require researchers to
protect patients
 Most clinical researchers also are
dedicated to good clinical care
Contrasting Clinical Trials
and Ordinary Treatment
 Treatment
 Individualized Tx
decisions
 Physician selects Tx
for pt. benefit
 Other treatments
used if thought helpful
 Dosage adjusted for
maximum benefit
 Clinical Trials
 Randomized
assignment
 Physician blinded
 Restrictions on other
treatments
 Limited adjustment of
dosage
These are Important
Restrictions on Treatment
 Researchers
do not impose these
limitations lightly
 They are essential for gathering
generalizable data
 Research staff often monitor care better
 Nonetheless,these are important risks that
subjects should consider when enrolling
The Discovery of TM
 Paul
Appelbaum and I were interviewing
subjects in clinical trials for a study of
informed consent
 Noticed that they seemed typically to
misunderstand what “research” meant
 Paul suggested I write it up. I agreed
 6 months later, when I hadn’t, Paul wrote
the paper.
First Study: Prevalence of the
Therapeutic Misconception (n=88)
Unaware of randomized assignment
69%
Expect assignment on basis of therapeutic needs
40%
Failed to recognize possiblygetting inactive treatment
44%
Unaware physician would be blind to medication
39%
Able to identify how protocol would limit treatment options 9%
Believe dosages would be adjusted to their clinical needs 50%
From: Appelbaum PS, Roth LH, Lidz CW, Benson P, Winslade W: False hopes and best data:
consent to research and the therapeutic misconception. Hastings Center Report 17(2):20-24,
1987.
A Second Study of TM

Appelbaum, Grisso and I studied the
frequency and the correlates of TM
 243 subjects, 44 different studies, 2 sites
 Semi-structured interviews
 Most, but not all, in phase III clinical trials
Age (mean)
53.1 years (range 18-32)
Gender (female)
69.8%
Race (white)
90.5%
Education (mean)
14.2 years
Disorders Targeted in Research Projects
Examined in this Study
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Disorders
Number of Studies
Asthma
1
ADHD
1
Cancer
13
Depression
8
Heart Disease
6
Hepatitis C
2
Osteoarthritis
3
Rheumatoid Arthritis 2
None
1
Other*
9
TOTAL
44
Number of Participants
13
19
38
51
27
4
16
21
19
17
225
* Includes acute respiratory distress syndrome, diabetes, hemophilia, HIV infection, plantar warts, polycystic ovary
syndrome, and Sjogren’s syndrome
Illustration: 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….if they
don’t, then I’ll drop out.
Interviewer: …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.
Illustration: From a study of advanced
non-small cell lung cancer
Interviewer: What does the project involve? The
research study. What does your participation involve?
Subject: Well, they choose an arm…one arm [subject
points to her arm]… for an operation…the other one for
the IV. If they choose the arm for the operation… I
mean for the IV, there’s no operation involved.
Interviewer: If they choose the arm for the IV…?
Subject: …There’s no operation…. If they choose the
other arm, then, there’s an operation [subject looking
at and pointing to her arms].
Interviewer: OK.
Subject: I don’t know what the idea of that is [laughs].
Measuring the Therapeutic
Misconception #1
 Extended
Interviews with Subjects
 Text of interviews was coded for two
features:
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the belief that the treatment would be
individualized to the subject
an unreasonable assessment of benefit (i.e.
one precluded by the design of the study)
Therapeutic Misconception Study:
Frequency of TM (n=243)
Individualization
Benefit
31.1%
51.1%
(n=70)
(n=115)
Either or both
61.8%
(n=139)
Demographic Variables Associated with
TM Summary Scores
Variable
Age
Education
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F Ratio
9.64
10.89
p Value
0.002
0.001
Effect*
>
<
All analyses are one-way ANOVAs.
Significance level was set at .01 due to the number of
variables tested.
SF-36 Variables Associated with TM
Summary Scores
Variable
F Ratio
General health
5.04
Physical Functioning
9.73
Role-Physical
16.53
Bodily Pain
1.99
Vitality
15.70
Social Functioning
25.31
Role-Emotional
21.14
Mental Health
10.24
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p Value
0.03
0.002
0.0001
0.160
0.0001
0.0001
0.0001
0.002
Effect*
<
<
<
<
<
<
<
All analyses are one-way ANOVAs.
Significance level was set at .01 due to the number of variables tested.
However all SF-36 variables are reported.
Subject #86:
All Subjects Treated the Same
Interviewer: Is the treatment the same for everyone in the study?
Subject: According to what the research nurse said that
everybody gets the same thing.
Interviewer: And one gets the double dose?
Subject: Everyone that had the angioplasty gets the same thing.
The same treatment I mean. There can’t be much of a variation
as far as I know…she says we are doing this to people who are
having angioplasty….
Interviewer: So everybody gets the double dose?
Subject: Everybody gets exactly the same.
Understanding of Risks
Interview Question: “What, if
any, are the risks or disadvantages of
being in this study”
 Coded entire text for statements
about risks and disadvantages
 Looked only at clinical trials N=149
 Critical
Hierarchically Organized
Risk Codes
 Risk
inherent in Research Design
 Risk inherent in Experimental
Treatment (i.e. side effects)
 Risk of Routine Tx (i.e. side effects)
 Incidental Disadvantages
 Risks Minimized or Partially Denied
 Complete Denial of Risk
Risks of Treatment
 23.9%
reported no risks or disadvantages
 2.6% noted only incidental disadvantages
 14.2% of sample reported only risks
associated with standard care
 Largest group (45.8%) reported side
effects of the experimental intervention
 None of these subjects had any apparent
awareness of risks associated with the
design of clinical trials
Risks of the Research Design
 13.5%
of subjects reported some
awareness of the risks involved with the
research design
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Examples:
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12 subjects expressed some concern about possibly
getting a placebo (including 4 who reported other
concerns about clinical trials)
 4 subjects expressed concerns about the double blind
design.
 Others expressed some diffuse concerns e.g. “there
are always risks”
How do Subjects Understand
Benefits: Questions
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What is the primary goal of this project?
Why are the researchers doing this project?
What might the researchers learn about treating
[the disease] if people decide to be in this
project?
In what way might the patient be better off
personally by being in this project?
Will this project be more helpful to the patient or
to others in the future?
Coding in Two Steps
Identified all statements relating to who
benefits or decision-making criteria for
entering the study
Code identified statements on two
dimensions:
1.
2.
1.
2.
Reasons for joining: personal benefit vs.
altruism
Purpose of study: research vs subject
benefit
Findings: Motives for Joining
Frequency
Percentage
Altruism
20
16.2
Personal Benefit
103
83.7
Total
123
100
Subject #BOS3:
Reason for Entering Project
Interviewer: Um, OK, what is the primary goal of
the project, meaning is it gonna help people in
the future or is it gonna help people in the
project? Or a combination of both?
Subject: Oh I expect it to help me…Um, I feel like I
am already cured. But I expect it to make
absolutely sure that I am…, and absolutely to
help people in the future so they can measure
my success. And you know, help people. Help
monitor. You know they need people to study.
Findings: Who Benefits from
the Project
Frequency
Percentage
Subject
58
50.6
Research
57
49.4
Total
115
100
What Should We Make of This
 Most
people join clinical trials because
they believe that they will benefit from
them
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This has been reported before
 About
half of the subjects have at least a
minimal understanding that clinical trials
are not simply treatment
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Other errors (e.g. not understanding control
groups or restrictions on treatment) are not
assessed in this data
Conclusions from Research
Findings
 Adds
to evidence that therapeutic
misconception is pervasive
 Suggests that we cannot easily identify
who will be susceptible
A Validated Measure of TM
 Recently
published new scale
 .Probably should be thought of as a
screen not a definitive measure
 Appelbaum PS, Anatchkova M, Albert K,
Dunn LB, Lidz CW. Therapeutic
misconception in research subjects:
development and validation of a measure.
Clin Trials. 2012 Dec; 9 (6):748-61
Methods
 220
participants in clinical trials at 4
medical centers
 Completed 28 item Likert questionnaire
 Thorough semi-structured interview
 Interview coded for three dimensions of
TM: Benefit, Purpose, Individualization
Results
 10
item scale
 3 strongly correlated factors
 Validated against coded interview
 Positive Predictive Value was 0.65 and
Negative Predictive Value was 0.68, with a
Positive Likelihood Ratio of 1.89, and a
Negative Likelihood Ratio of 0.47.
 That is the simple version of the results
Questions on the scale
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1. This study is designed to give everyone the type of treatment
and amount of treatment that best fits his or her individual needs.
2. When designing research, researchers must be sure that each
person in the study will get the best treatment available for that
person’s individual needs, just as though they were being treated
by their personal doctor.
3. Researchers always try to provide each person in a study the
treatment that best meets that person’s individual needs
4. The purpose of the [experimental study] is to provide the best
treatment available for me and the others in the study.
5. Research studies are designed primarily to help those people
who participate in them rather than primarily to help future
patients with the same disease
Scale Questions 2
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6. A researcher’s most important task is to make sure
that the research will help the people who participate.
7. The reason I was asked to be in this study is that it
will provide me with the best treatment available.
8. The treatment I am getting by being in this study is
the best treatment for me.
9. Being in a research study almost always provides
the best possible treatment for a sick person.
10. By participating in a research study, people will get
the best treatment for their medical problems.
A New Theory of TM
 Humans
understand their environment in
socially structured cognitive frames
 These frames help us understand each
other but they can also lead to
misunderstandings when they do not
match.
Researcher’s Primary Frame:
Science
 In designing clinical trials, researchers
generally approach the studies from what
can be called a “Scientific” cognitive frame.
 Based on an abstract concept of how the
efficacy of a treatment can be demonstrated.
 This abstract frame regards cases as units to
be managed according to a protocol that
guides the activities of the researcher.
Researcher’s Primary Frame
A
predetermined number of these units
need to be studied
 treatments being compared should have
equivalent groups and thus participants
must “be assigned” treatments at random
 Neither the treating physician nor the
participant should know which medication
the participant is getting to prevent bias
Researcher’s Primary Frame
 Dosages
are restricted to a predetermined
range so that the intervention is clearly
defined
 other medications that might also affect
the outcome are prohibited.
 This frame is independent of specific
patient needs
Participants’ Primary Frame:
Personal Needs
 Participants focus on the study from the
point of view of the individual units (i.e.,
themselves) and their medical needs.
 Coming for help with a problem and see the
study in that context.
 many participants either ignored design
features or made up reasons for them that
were consistent with a focus on their own
medical needs
Conflicting Frames - Eligibility
 For
researchers, eligibility is built into the
design of the trial. Usually trial designs
include tightly defined groups to reduce
extrinsic sources of variability in response
to the intervention.
 Participants tended to see eligibility as a
question of whether they personally would
be likely to benefit from the experimental
intervention
The role of secondary frames
 If
there were only primary frames,
researcher and clinician would quickly be
in conflict.
 Secondary frames are one of several ways
in which they can continue to
misunderstand each other.
Researcher’s Secondary
Frame
 Particularly
prominent among those
actively delivering tx to patients.
 Ethical commitments of clinical trials
require protecting participants and many of
our researcher-interviewees insisted that
they would never put participants at risk
 Besides: Excellent physicians, more time
for pt., better monitoring of condition
Participant’s Secondary
Frame
 Research
is important
 Research is hard to understand and
technical
 Researchers are “studying me” and how I
respond to treatment. That is, some see
the research as a series of single case
studies.
Secondary frames & TM
 The
researcher’s secondary frame allows
them to feel comfortable telling
participants that they will be very well
cared for.
 That reassurance combined with their own
misunderstanding of what research is,
allows participants in trials to have a
sustained therapeutic misconception
What Can Be Done
 Subjects
need to understand why not just
how treatment and research differ
 As much a part of disclosure as risks and
benefits of intervention
 Participants need to frame what they are
consent to as science
Example: About Placebos
“Some subjects will be selected by chance
to receive sugar pills that are not known to
help the condition you have; this is done
so we can find out whether the
experimental medication is really effective,
or if many people with your condition
would get better even with no active
medication at all."
Example: Standardized
Protocols
"Ordinarily doctors change the amount of
medication according to how their patients
are doing. Here, in order to test the
usefulness of the medications we are
trying out, we have to leave your dosage
at the same level for four weeks—unless
you suffer a severe reaction to it or decide
to withdraw from the study."
The costs and benefits of this
approach to TM
 Probably
reduce the flow of subjects
 Might require rethinking of some designs
 Will defend our research from critics who
simply don’t like this type of research