Therapeutic misconception in research subjects: Development and validation of a measure

Abstract

Background Therapeutic misconception (TM), which occurs when research subjects fail to appreciate the distinction between the imperatives of clinical research and ordinary treatment, may undercut the process of obtaining meaningful consent to clinical research participation. Previous studies have found TM is widespread, but progress in addressing TM has been stymied by the absence of a validated method for assessing its presence. Purpose The goal of this study was to develop and validate a theoretically grounded measure of TM, assess its diagnostic accuracy, and test previous findings regarding its prevalence. Methods 220 participants were recruited from clinical trials at 4 academic medical centers in the U.S. Participants completed a 28-item Likert-type questionnaire to assess the presence of beliefs associated with TM, and a semi-structured TM interview designed to elicit their perceptions of the nature of the clinical trial in which they were participating. Data from the questionnaires were subjected to factor analysis and items with poor factor loadings were excluded. This resulted in a 10-item scale, with 3 strongly correlated factors and excellent internal consistency; the fit indices of the model across 10 training sets were consistent with the original results, suggesting a stable factor solution. Results The scale was validated against the TM interview, with significantly higher scores among subjects coded as displaying evidence of TM. ROC analysis based on a 10-fold internal cross-validation yielded AUC=.682 for any evidence of TM. When sensitivity (0.72) and specificity (0.61) were both optimized, 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. 50.5% (n=101) of participants manifested evidence of TM on the TM interview, a somewhat lower rate than in most previous studies. Limitations The predictive value of the scale compared with the “gold standard” clinical interview is modest, although similar to other instruments based on self-report assessing states of mind rather than discrete symptoms. Thus, although the scale can offer evidence of which subjects are at risk for distortions in their decisions and to what degree, it will not allow researchers to conclude definitively that TM is present in a given subject. Conclusions The development of a reliable and valid TM scale, even with modest predictive power, should permit investigators in clinical trials to identify subjects with tendencies to misinterpret the nature of the situation and to provide additional information to them. It should also stimulate research on how best to decrease TM and facilitate meaningful informed consent to clinical research.

Therapeutic misconception correlates with willingness to participate in clinical drug trials among patients with epilepsy; need for better counseling

“…Our study is consistent with previous literature in its findings that therapeutic misconception is a common phenomenon and that it should be considered in the recruitment of patients to be CT subjects [9,26,27]. The prevalence of therapeutic misconception of some extent has been found to be in the 55-74% range among CT participants [9,[26][27][28][29].…”

“…The prevalence of therapeutic misconception of some extent has been found to be in the 55-74% range among CT participants [9,[26][27][28][29]. The results of our study strongly support earlier research results in that selected patient groups appear to be at particular risk of therapeutic misconception [9].…”

When Does Therapeutic Misconception Affect Surrogates' or Subjects' Decision Making about Whether to Participate in Dementia Research?

“…Empirical studies have painted a detailed portrait of TM as pervasive across nearly all types of research studies and clinical populations [6][7][8][9][10]. The definition of TM has been discussed at length, with attempts at an expert consensus definition [11] as well as further refinement of the concept into several subtypes [6,12]. A recent article by Lidz and colleagues offered a conceptual basis for TM, in which the authors argued that TM does not primarily reflect inadequate disclosure or participants' incompetence.…”

“…Most recently, Appelbaum and colleagues have developed a psychometrically strong ten-item instrument to screen for TM based on semistructured interviews coded for the presence of several types of TM [12].…”

How not to test the prevalence of therapeutic misconception

“…Our initial approach to assessing TM involved extensive interviews with subjects that were transcribed and painstakingly scored 7. We subsequently developed a 10-item questionnaire that showed good correlations with the lengthier interview process 5. However, for a multidimensional construct like TM, we never have and never would rely on a single question about the purpose of the study, as Kim et al do here.…”