Research Participants' "Irrational" Expectations

Common or Commonly Mismeasured?

Robert G. Holloway, MD, MPH; Karl Kieburtz, MD, MPH; Samuel Frank, MD; Sonali Parnami, MPH; Renee Wilson, MA; Raymond de Vries, PhD; Scott Y.H. Kim, MD, PhD

Disclosures

IRB. 2013;35(1) 

In This Article

Introduction

A longstanding concern of research ethics is that some clinical trial participants may confuse the goals of treatment with the goals of research and thus fail to understand certain key design elements of research that distinguish it from medical care.[1] One such element of research is random assignment to receive either the experimental or control intervention. Although most lay people understand randomization,[2] the findings of studies of prospective and actual participants' understanding of randomization is mostly discouraging, if somewhat mixed. In one study, only 50% of parents interviewed after informed consent discussions about enrolling their child in oncology randomized clinical trials reported that they understood the concept of randomization.[3] In another study of oncology trial participants, only 23% understood that they would be randomized to either the control or experimental intervention.[4] On the other hand, Simon and colleagues found that despite the fact that only 69% of adult oncology patients were explicitly told about randomization in the informed consent conversation, 93% understood that the intervention assignment would be randomized.[5]

These and other studies suggest that while some prospective and actual research participants may not understand randomization, actually measuring understanding about randomization is not straightforward, either. Indeed, some studies reveal that even when individuals seem to understand key concepts closely tied to randomization, they still seemed confused about its meaning.[6] Traditionally, many have worried that even if research participants intellectually comprehend the concept of research and its elements, their intense desire for a cure or the habitual perception that medical procedures are therapeutic (i.e., their therapeutically oriented mindset) may interfere with applying those facts to their own situation[7] —what Appelbaum and Grisso have described as the distinction between understanding and appreciation. As they point out, "understanding requires an ability to grasp the meaning of the information disclosed," and "appreciation involves the relevance of that information for one's own situation."[8] Indeed, in the first paper published on the concept of therapeutic misconception, Appelbaum and colleagues reported a dramatic and disturbing case of a woman who seemed to understand yet failed to appreciate that study participants received an intervention on the basis of randomization.[9] More recently, certain commentators have proposed that some research participants' "unrealistic optimism" about clinical trial participation—the expectation of benefit that cannot be statistically true—may be a form of lack of appreciation, in which understanding does not result in adequate appreciation of the probabilities of therapeutic benefit.[10]

In a recent study we conducted that examined how individuals made their decision about whether to enroll in a Parkinson's disease clinical trial that involved randomization to a gene-transfer or sham surgery arm, we included questions to examine the relationship between understanding and appreciation of randomization. We wanted to know whether prospective participants understood and appreciated the probability of being assigned to the sham or the gene transfer arm. Sham surgery controlled trials involving Parkinson's disease are particularly important and apt settings to examine the potential influence of therapeutic orientation on individuals' understanding and appreciation of research, for several reasons: 1) individuals with Parkinson's disease are older and have a serious and incurable illness, raising vulnerability concerns;[11] 2) a neurosurgical intervention has particularly elaborate trappings of "treatment;" 3) sham surgical controls in research continue to be controversial;[12] and 4) randomization involving a sham surgical arm is perhaps the quintessential "research design" feature that distinguishes research from treatment.

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