Renee Wilson

Sham surgery controls in Parkinson's disease clinical trials: Views of participants

Sham surgery controls are increasingly used in neurosurgical clinical trials in Parkinsons disease (PD) but remain controversial. We interviewed participants of such trials, specifically examining their understanding and attitudes regarding sham surgery.

Trust in early phase research: therapeutic optimism and protective pessimism

Bioethicists have long been concerned that seriously ill patients entering early phase (‘phase I’) treatment trials are motivated by therapeutic benefit even though the likelihood of benefit is low. In spite of these concerns, consent forms for phase I studies involving seriously ill patients generally employ indeterminate benefit statements rather than unambiguous statements of unlikely benefit. This seeming mismatch between attitudes and actions suggests a need to better understand research ethics committee members’ attitudes toward communication of potential benefits and risks of early phase studies to potential subjects. We surveyed the members of two U.S. research ethics committees using a phase I gene transfer study scenario, and compared the results to a previous survey of potential subjects’ perceptions and attitudes toward benefit and risk for the same protocol. The results show that there is indeed a gap between the subjects’ perceptions and the committee members’ views on what is appropriate to be communicated to research subjects. This discrepancy is the product of both the commonly assumed optimism of the subjects and to a “protective pessimism” of the research ethics committee members. We discuss this discrepancy using “frameworks of trust” and demonstrate the need to incorporate these frameworks into the existing model of informed consent.

Are therapeutic motivation and having one's own doctor as researcher sources of therapeutic misconception?

Background Desire for improvement in ones illness and having ones own doctor functioning as a researcher are thought to promote therapeutic misconception (TM), a phenomenon in which research subjects are said to conflate research with treatment. Purpose To examine whether subjects’ therapeutic motivation and own doctor functioning as researcher are associated with TM. Methods We interviewed 90 persons with advanced Parkinsons disease (PD) enrolled or intending to enrol in sham surgery controlled neurosurgical trials, using qualitative interviews. Subjects were compared by motivation (primarily therapeutic vs primarily altruistic or dually motivated by altruistic and therapeutic motivation), and by doctor status (own doctor as site investigator vs not) on the following: understanding of purpose of study; understanding of research procedures; perception of chance of direct benefit; and recollection and perceptions concerning the risks. Results 60% had primarily therapeutic motivation and 44% had their own doctor as the site investigator, but neither were generally associated with increased TM responses. Overall level of understanding of purpose and procedures of research were high. Subjects responded with generally high estimates of probability of direct benefit, but their rationales were personal and complex. The therapeutic-motivation group was more sensitive to risks. Five (5.6%) subjects provided incorrect answers to the question about purpose of research, and yet, showed excellent understanding of research procedures. Conclusions In persons with PD involved in sham surgery clinical trials, being primarily motivated by desire for direct benefit to ones illness or having ones own doctor as the site investigator were not associated with greater TM responses.

Comparison of Enrollees and Decliners of Parkinson Disease Sham Surgery Trials

Concerns have been raised that persons with serious illnesses participating in high‐risk research, such as PD patients in sham surgery trials, have unrealistic expectations and are vulnerable to exploitation. A comparison of enrollees and decliners of such research may provide insights about the adequacy of decision making by potential subjects. We compared 61 enrollees and 10 decliners of two phase II neurosurgical intervention (i.e., cellular and gene transfer) trials for PD regarding their demographic and clinical status, perceptions and attitudes regarding research risks, potential direct benefit, and societal benefit, and perspectives on the various potential reasons for and against participation. In addition to bivariate analyses, a logistic regression model examined variables regarding risks and benefits as predictors of participation status. Enrollees perceived lower risk of harm while tolerating higher risk of harm and were more action oriented, but did not have more advanced disease. Both groups rated hope for benefit as a strong reason to participate, whereas the fact that the studys purpose was not solely to benefit them was rated as “not a reason” against participation. Hope for benefit and altruism were rated higher than expectation of benefit as reasons in favor of participation for both groups. Enrollees and decliners are different in their views and attitudes toward risk. Although both are attracted to research because of hopes of personal benefit, this hope is clearly distinguishable from an expectation of benefit and does not imply a failure to understand the main purpose of research.

Are patients with amyotrophic lateral sclerosis at risk of a therapeutic misconception

Objectives To assess whether persons with amyotrophic lateral sclerosis (ALS) are at risk of a therapeutic misconception (TM) in which they misconceive research as treatment or overestimate the likelihood of its benefit. Methods 72 patients with ALS recruited via academic and patient organisations were surveyed using a hypothetical first-in-human intervention study scenario. We elicited their understanding of the purpose of the study (‘purpose-of-research question’) and then asked how they interpreted the question. We then asked for an estimate of the likelihood that their ALS would improve by participating and asked them to explain the meaning of their estimates. Results Although 10 of 72 (14%) subjects incorrectly said that the intervention study was ‘mostly intending to help [me]’ in response to the purpose-of-research question, 7 of those 10 thought that the question was asking them about their own motivations for participating. Overall, only one of 72 respondents (1.4%) both understood the purpose-of-research question as intended and gave the incorrect response. Subjects’ mean estimate of likelihood of benefit was 31% (SD 26). This was due to 29 of 72 of respondents providing high estimates (50%–54% likelihood), which they said were expressions of hope and need for a positive attitude; among those who said their estimates meant ‘those are the facts’ or ‘there is a lot of uncertainty’, the estimates were much lower (12.6% and 18.5%, respectively). Conclusions In this group of patients with ALS considering a hypothetical first-in-human intervention study, apparent TM responses have alternative explanations and the risk of true TM appears low.

“It is not guaranteed that you will benefit”: True but misleading?

Background: Participants of early-phase intervention trials for serious conditions provide high estimates of likelihood of benefit, even when informed consent forms do not promise such benefits. However, some technically correct, negatively stated benefits statements—such as “it is not guaranteed that you will benefit”—could play a role in raising expectations of benefit because in ordinary English usage such statements denote a likely but not a certain-to-occur event. Methods: An experimental online survey of 584 English-speaking adults recruited online. They were randomized to receive one of two benefit statements (“not guaranteed” vs “some but very small chance”), using a hypothetical scenario of an early-phase clinical trial testing an intervention to treat amyotrophic lateral sclerosis. We assessed respondents’ willingness to consider participating in the amyotrophic lateral sclerosis trial, their estimates of likelihood of benefit, and their explanations for those estimates. Results: The two arms did not differ in willingness to consider participation in the amyotrophic lateral sclerosis trial. Those receiving “not guaranteed” benefit statement had higher estimates of benefit than those receiving “some but very small chance” statement (35.7% (standard deviation 20.2) vs 28.3% (standard deviation 22.0), p < 0.0001). A total of 43% of all respondents chose expressions of positive sentiment (hope and need to stay positive) as explanations of their estimates; these respondents’ estimates of benefit were higher than others but similar between the two arms. The effect of benefit statements was greatest among those who chose “Those are just the facts” as the explanation for their estimate (31.0% (standard deviation 22.4%) in “not guaranteed” arm vs 18.9% (standard deviation 21.0%) in comparison arm, p = 0.008). Conclusion: The use of “not guaranteed” language in benefit statements, when compared to “small but very small chance” language, appeared to increase the perception of likelihood of benefit of entering an early-phase trial, especially among those who view their estimates of benefits as “facts.” Such “no guarantee” benefit statements may be misleading and should not be used in informed consent forms.