To date, there have been few studies reporting on attitudes toward, and experiences of, participation in CTs among patients with PD [7,8,9,10, 15], though some have been carried out among patients with very advanced PD on participation in trials involving sham surgery [16, 17]. To the best of our knowledge, ours is the first large-scale survey to assess how CTs are perceived by a random sample of patients with PD. Our study identified several clinical characteristics that are related to knowledge of, and willingness to participate in, CTs and revealed elements of how TM is associated with these issues.
Patients with PD had positive attitudes toward CTs, as is the case also with the general population [5, 18], patients e.g., with epilepsy [11], and cancer [19, 20]. Furthermore, more than 80% of the subjects in our study stated that patients with PD should be asked to participate in CTs. An important message for those who commission and conduct CTs is that the patients with PD were strongly in favor of the publication of the research results and indicated also that they were interested in learning the results themselves.
A large majority of the patients in our study were well aware of basic ethical issues and participant’s rights associated with CTs such as voluntary participation, informed consent, and the right to withdraw from a CT. Over 90% of the respondents supported the statement that the essential goal of CTs is to benefit future patients. However, at odds with that view is the fact that nearly 80% of the subjects thought that CTs are aimed primarily at seeking the best treatment for the participants. A similar observation has been made in another study with a different kind of PD population [16]. Patients may think that the combination of gathering scientific knowledge together with benefiting an individual study participant formulates the ultimate goal of the study. Clearly, understanding the purposes of CTs is complex, and, as Kim et al. [16] conclude, the issue is impossible to resolve fully with closed-ended items.
Overall, various methodological issues of CTs, such as randomization and the investigator physician’s ability to be aware of, or choose, the participant’s treatment, were correctly recognized by just 21–26% of the subjects. It is also important to note that nearly half of the respondents thought that all participants in CTs will receive effective study treatment. Furthermore, fewer than half of the subjects knew that CTs may include procedures deviating from standard care. In a group of PD patients who had all participated in CTs, 42% of the subjects thought that the study was part of the standard treatment [15]. Thus, subjects with PD share with other patient groups many difficulties in understanding the meaning and purposes of CT methods [18, 21, 22]. Our data further suggest that subjects with a low level of education and who are older in age are especially likely to have gaps in their knowledge of the principles of CTs. Indeed, a report on a survey of patients with PD who had participated in CTs [15] observed that less educated subjects had poorer comprehension of the study information. Our findings and those of previous research [22] highlight significant information needs of patients in relation to essential elements of informed consent for a CT.
With statements on issues such as information needs, study design, possible adverse effects, and altruistic interests, we explored some aspects of willingness to take part in CTs. As observed previously in patients with PD [7,8,9], altruism and contributing to science were also important factors in motivation to take part in CTs in this study. Study design, especially the use of placebos, and the high risk of adverse effects were negative motivating factors, as has been observed with other patient groups [23, 24], among them patients with PD specifically [7, 10]. A study of patients with PD who had taken part in a CT found that the subjects retained positive impressions of participation in placebo-controlled trials although they had wished to receive active treatment instead of a placebo [8]. Among our subjects, a higher level of education seemed linked to greater willingness to participate in CTs. An encouraging finding was that willingness to participate in CTs was positively correlated with knowledge of CTs.
The term TM was originally introduced almost 35 years ago by Applelbaum et al. – and still there remains uncertainty and disagreements regarding how it is defined and measured [25, 26]. The key point of TM is the mistaken belief that the purpose of CT is to benefit potential study subjects individually, as opposed to its real goal which is to gather scientific knowledge. This raises a number of specific problems – the validity of (informed) consent as well as overestimation of benefits, under-estimation of the risk of harm, and/or under-appreciation of alternatives to participation in CTs [27, 28]. However, TM is not coherently constructed, and several terms related to TM (e.g., therapeutic optimism, therapeutic mis-estimation, unrealistic optimism or expected therapeutic benefit) have been proposed [29,30,31,32]. TM is considered to be common among participants of CTs [27, 33,34,35] but this conclusion has been recently challenged [36, 37]. One issue in the assessment of TM has been that no universally accepted operational definitions or metrics for the phenomenon have been available or that it is the term argue for by scientists [28, 32]. However, a scale for the identification of TM among study subjects has recently been developed [38]. Our survey instrument included several items in parallel with that scale. Usually, issues related to TM are assessed in patients who have already been recruited to take part in CTs. Our data suggest that patients with PD, as potential study participants, have important preconceptions of CTs. Expectation of therapeutic benefits increases their willingness to participate in CTs. These expectations may place them at risk of TM, especially the older patients and those with a lower level of education, as observed previously [11, 27]. A possibly unexpected finding was that, in comparison with patients prescribed a higher number of PD medications, those with fewer drugs and, presumably, less severe PD, stated stronger indicators of TM. It might be that subjects who used more PD drugs and had more advanced disease had less expectation of therapeutic gains associated with CTs, or they may have gained fuller knowledge of their disease and hence shown realistic expectations of treatments overall. Our results suggest that level of general knowledge of CTs is not associated with degree of TM. However, poor understanding of specific methodological issues of CTs, as discussed above, may expose patients to misunderstanding of the main goals of research. Taken together, our findings suggest that patients’ preconceptions of CTs may lead to TM if adequate information is not given to, or appreciated by, the patients during the consent process. We agree with Lyons [32] that what really matters is the relationship and the discussion between the potential study participant and their physician/investigator before the patient can meaningfully consent in a study. We suggest that researchers should first enquire about patient preconceptions considering the CTs and then provide tailored information to the patient.
All of the statements linked to the “Therapeutic misconception” factor showed statistically significant correlation with the level of that factor. The highest scores were observed for statements pertaining to expected personal health benefits to participants, such as CTs offering new, or the best, medication and treatment, and continuation of the current health-care relationship. However, overall, most of the other statements receiving high scores had to do with issues related to personal benefit. Previous studies conducted both among the public at large and with various patient populations, PD patients among them, have shown that expectations of personal health benefits are the main factor behind participation in CTs [2, 5, 7, 9, 16]. In our study, the possibility of one’s own physician being the site investigator was associated with willingness to take part, but Kim et al. [16] did not find such an association. However, the study population in the latter study differed greatly from ours: the subjects were participants or subjects to be enrolled in a surgical trial. Therapeutic motivation in the case of participants in CTs may result from optimism that is not related to misunderstanding of the study information [31]; however, our study revealed that patients with PD do show deficiencies in their understanding of the purposes of CTs and the key methodological issues thereof.
Our study has some limitations. Firstly, the response rate (35%, after exclusion 34%) was quite modest. However, the number of survey forms (n = 681) accepted for the analyses was sufficient for statistical evaluations. The members of the FPA include about 50% of the Finnish patients with PD. These patients might be more than averagely motivated and interested in CTs and in their own condition. This issue needs to be taken into account since it can give a slightly more positive impression of the results. Our study population showed male predominance (see Table 4), as is also commonplace in many epidemiological studies [39,40,41,42]. Two thirds of the respondents had suffered from PD for at least 5 years, but patients aged at least 80 years accounted for only about 10% of the study subjects. Thus, the oldest PD patients seemed under-represented [43], an effect that may be due to their inability to complete the questionnaire themselves, arising from motor or cognitive deficits. A second issue to consider is the questionnaire which was developed for a study among patients with epilepsy [11] and then modified in light of the feedback from those patients, and also after pilot testing with patients diagnosed with PD. However, the questionnaire was not validated statistically or against in-depth interviews of the subjects. Assessing TM by means of questionnaires is challenging, because the items intended for measuring TM may not be understood as intended [36].