Transcript Therapeutic Misconception - Vanderbilt University Medical Center

Larry R. Churchill, PhD
Ann Geddes Stahlman Professor of Medical Ethics
Center for Biomedical Ethics and Society
Vanderbilt University Medical Center
“The belief that the purpose of a clinical trial is to
benefit the individual patient rather than to gather
data for the purpose of contributing to scientific
knowledge.”
“It is not a misconception to believe that participants
probably will receive good clinical care during
research, but it is a misconception to believe that
the primary purpose of clinical trials is treatment…”
---National Bioethics Advisory Committee (NBAC), 2001
“When a research subject fails to appreciate the
distinction between the imperatives of clinical
research and of ordinary treatment, and
therefore inaccurately attributes therapeutic
intent to research procedures.” (italics added)
---Lidz and Appelbaum, 2002
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Research subjects with “entirely therapeutic
orientations,” believe that procedures of
clinical trials are all designed solely to help
them, do not recognize research aims as
present and primary.
-- Appelbaum, Roth and Litz, 1982
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TM invalidates consent
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The first principle of The Belmont Report (1979),
which is the ethical basis for the U.S. federal
regulations, is “respect for persons”—persons have
the right to decide for themselves whether to
participate in research on the basis of information
about the nature of the trial, potential benefits and
harms, the alternatives, etc.
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“Subject Interview study” – 1,900 subjects
interviewed at 19 academic medical centers; 67%
responded that they had joined the trial “to get
better treatment” and “did not readily make
distinctions between research and medical
treatment”
---done in conjunction with the Human Radiation
Experiments National Commission Report, 1996.
Empirical studies of clinical trials,
predominantly early stage Ca trials, indicate
that subjects are often motivated to
participate in research by expectation of
direct medical benefit, and when asked, blur
the distinction between research and
treatment.
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Rodenhuis, S., W. J. van den Heuvel, et al. (1984). "Patient motivation and
informed consent in a phase I study of an anticancer agent." Eur J Cancer
Clin Oncol 20(4): 457-62.
Kodish, E., C. Stocking, et al. (1992). "Ethical issues in phase I oncology
research: a comparison of investigators and institutional review board
chairpersons." J Clin Oncol 10(11): 1810-6.
Tomamichel, M., C. Sessa, et al. (1995). "Informed consent for phase I
studies: evaluation of quantity and quality of information provided to
patients." Ann Oncol 6(4): 363-9.
Daugherty, C., M. J. Ratain, et al. (1995). "Perceptions of cancer patients
and their physicians involved in phase I trials." J Clin Oncol 13(5): 1062-72.
Daugherty, C. K., D. M. Banik, et al. (2000). "Quantitative analysis of
ethical issues in phase I trials: a survey interview of 144 advanced cancer
patients." Irb 22(3): 6-14.
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Schaeffer, M. H., D. S. Krantz, et al. (1996). "The impact of disease
severity on the informed consent process in clinical research." Am J Med
100(3): 261-8.
Yoder, L. H., T. J. O'Rourke, et al. (1997). "Expectations and experiences of
patients with cancer participating in phase I clinical trials." Oncol Nurs
Forum 24(5):891-6.
Itoh, K., Y. Sasaki, et al. (1997). "Patients in phase I trials of anti-cancer
agents in Japan: motivation, comprehension and expectations." Br J
Cancer 76(1): 107-13.
Joffe, S., E. F. Cook, et al. (2001). "Quality of informed consent: A new
measure of understanding among research subjects." Journal of the
National Cancer Institute 93(2): 139-147.
Churchill, L.R., Nelson, D.K., Henderson, G.E., King, N.M.P., Davis, A.M.,
Leahey, E., and Wilfond, B.S., “Assessing Benefit in Clinical Research:
Why Diversity in Benefit Assessment Can Be Risky,” IRB: Ethics and
Human Research 25 No. 3 (May-June, 2003), pp. 1-7.
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Joffe, S., E. F. Cook, et al. (2001). "Quality of informed consent in cancer
clinical trials: a cross- sectional survey." Lancet 358(9295): 1772-7.
Kass, N. E., M. R. Natowicz, et al. (2003). "The use of medical records in
research: what do patients want?" J Law Med Ethics 31(3): 429-33.
Meropol, N. J., K. P. Weinfurt, et al. (2003). "Perceptions of patients and
physicians regarding phase I cancer clinical trials: implications for
physician-patient communication." J Clin Oncol 21(13): 2589-96.
Weinfurt, K. P., L. D. Castel, et al. (2003). "The correlation between
patient characteristics and expectations of benefit from Phase I clinical
trials." Cancer 98(1): 166-75.
King, N.M.P., Henderson, G., Churchill, L., Davis, A., Hull, S., Nelson, D.,
Parham-Vetter, P., Rothschild, B., Easter, M., Wilfond, B., “Consent
Forms and the Therapeutic Misconception,” IRB: Ethics and Human
Research, Vol. 27, No. 1, 2005, pp. 1-8.
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Why participate in a clinical trial?
Participants in clinical trials can play a more
active role in their own health care, gain
access to new research treatments before
they are widely available, and help others by
contributing to medical research.
----from the NIH website,
http://www.clinicaltrials.gov/
( pre-2011)
From the NIH website: October 26, 2011
People participate in clinical trials for a variety of reasons.
Healthy volunteers say they participate to help others and to
contribute to moving science forward. Participants with an
illness or disease also participate to help others, but also to
possibly receive the newest treatment and to have the
additional care and attention from the clinical trial staff.
Clinical trials offer hope for many people and an opportunity
to help researchers find better treatments for others in the
future.
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Participants with an illness or disease also
participate to help others, but also to possibly
receive the newest treatment and to have the
additional care and attention from the clinical
trial staff. NIH website
People participating in clinical research have
access to experimental medications or
devices before they become available to the
general public. Univ. of Iowa website
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Contextual features: research done in same setting as medical care, by
many of the same personnel, researchers wear IDs that indicate they are
doctors, wear white coats, etc.—environment looks and feels
therapeutic.
Dual role issues: researchers are often also physicians, tend to think of
and describe their research as “care,” sometimes as “the best care,” or as
“new, or cutting edge treatments,” or present the long-range aims for a
line of research in therapeutic terms, which are interpreted by subjects as
benefits they may receive through participating…
Misleading, or ambiguous consent forms
Rebecca Dresser, “The Ubiquity and Utility of the Therapeutic Misconception,” Social Philosophy &
Policy 19:271-294, 2002.
_______________, When Science Offers Salvation, Oxford University Press, 2001
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Before 1990, 80% of clinical research
occurred in academic medical centers
Currently 75% of clinical research is
conducted in the clinics of community
practitioners.
Between 35-50% of all U.S. physicians have
conducted clinical trials
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Analysis of 321 consent forms for gene transfer research,
1990-2000; all early phase:
>’research’ and ‘treatment’ used as interchangeable terms
>surrogate endpoints (e.g., tumor shrinkage, immune
response) discussed but not distinguished from clinical
endpoints (e.g., survival time, improved quality of life)
>benefits to society and inclusion benefits not distinguished
from possible medical benefits for participants
---N. King, G. Henderson, L. Churchill, et al., “Consent Forms and the
Therapeutic Misconception: The Example of Gene Transfer Research,” IRB
(2005); 27,1:1-8.
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“You may or may not benefit.”
“Personal benefit cannot be guaranteed.”
“This trial is not intended to benefit you,
although we will monitor results for any
improvements in your condition.”
“You are unlikely to receive any lasting
benefit from joining this study.”
“Participating in this trial will not improve
your health.”
Classic TM:
Mistaking Research
for Medical Care
Overestimating
Benefit
Underestimating
Risk
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65 of 95 participants in Phase 1 oncology
trials did not know they were enrolled in
research.
89 of 95 participants in Phase 1 trials
estimated their chances of benefit as >20%,
or risk as 0.
--Pentz, White, Harvey et al., Cancer 118 (18):4571-78, 2012
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The subject knows it is research, but has an unrealistic
expectation of being helped by the trial. For example: the
investigator thinks the chances of a participant benefiting
from a Phase 1 Trial are remote (<2%)
but the subject thinks it is 50%.
When System 1 intuitions overwhelm System 2 logical thinking
Daniel Kahneman, Thinking: Fast and Slow, 2011.
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Does this jeopardize consent?
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Is the difference between ‘expectations’ and ‘hopes’ helpful
here?
Example: participant who is confident, after an explanation of risks, that
he/she is immune to harms, or tends to minimize them.
--from the MOMS trial:
1. “No harm will come to me. My grandfather (or God) is watching over me”
2. “I’m sure Vanderbilt wouldn’t be offering this trial if it weren’t safe.”
3. “I don’t want to hear about the possible problems. It will only upset me.”
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Do these jeopardize consent?
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Again, ‘expectations’ vs. ‘hopes’?
1. How confident are you that the experimental
therapy will control your Ca?
2. If 100 people were to participate in this
study, how many could expect to have their Ca
controlled as a result?
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Estimates were higher for 1 than 2, but both
still showed therapeutic overestimation.
--Weinfurt et al., J. Clin Oncol. 2012
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Nancy, M. P. King, Wake Forest
Gail Henderson, UNC-Chapel Hill
Ben Wilfond, Children’s Hospital, Seattle
Dan Nelson, UNC-Chapel Hill
[email protected]