Presentation on theme: "Therapeutic Misconception: What difference does it make? Charles W. Lidz Ph.D."— Presentation transcript:
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 to grasp the distinction between clinical research and ordinary treatment and attributes therapeutic intent to research procedures 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 DisordersNumber of StudiesNumber of Participants Asthma 113 ADHD 119 Cancer 1338 Depression 851 Heart Disease 627 Hepatitis C 2 4 Osteoarthritis 316 Rheumatoid Arthritis 221 None 119 Other* 917 TOTAL * 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: the belief that the treatment would be individualized to the subject 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) an unreasonable assessment of benefit (i.e. one precluded by the design of the study)
Therapeutic Misconception Study: Frequency of TM (n=243) Individualization 31.1% (n=70) Benefit51.1% (n=115) Either or both 61.8% (n=139)
Demographic Variables Associated with TM Summary Scores Variable F Ratio p Value Effect* Variable F Ratio p Value Effect* Age > Age > Education < Education < 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 p Value Effect* General health < General health < Physical Functioning < Physical Functioning < Role-Physical < Role-Physical < Bodily Pain Bodily Pain Vitality < Vitality < Social Functioning < Social Functioning < Role-Emotional < Role-Emotional < Mental Health < Mental Health < 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 Critical 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
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 Examples: 12 subjects expressed some concern about possibly getting a placebo (including 4 who reported other concerns about clinical trials) 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. 4 subjects expressed concerns about the double blind design. Others expressed some diffuse concerns e.g. “there are always risks” Others expressed some diffuse concerns e.g. “there are always risks”
How do Subjects Understand Benefits: Questions 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 1. Identified all statements relating to who benefits or decision-making criteria for entering the study 2. Code identified statements on two dimensions: 1. Reasons for joining: personal benefit vs. altruism 2. Purpose of study: research vs subject benefit
Findings: Motives for Joining FrequencyPercentage Altruism Personal Benefit Total123100
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 FrequencyPercentage Subject Research Total115100
What Should We Make of This Most people join clinical trials because they believe that they will benefit from them This has been reported before This has been reported before About half of the subjects have at least a minimal understanding that clinical trials are not simply treatment Other errors (e.g. not understanding control groups or restrictions on treatment) are not assessed in this data 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 Dec; 9 (6):748-61Appelbaum PSAnatchkova MAlbert K Dunn LBLidz CW
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 That is the simple version of the results
Questions on the scale 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 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