Objective: To prospectively measure the lessebo effect using an expectancy questionnaire (EQ).

Background: The presence of a placebo arm in a randomized controlled trial has been associated with reduced efficacy in active treatment arms of PD trials, which was hypothesized to be secondary to a reduction in expectancy. This phenomenon was labelled lessebo effect. The lessebo effect has not been studied prospectively.

Method: The EQ was developed and administered to participants at the screening visit of two randomized placebo-controlled trials in PD: SURE-PD3 (inosine, disease-modification), NILO-PD (nilotinib, symptomatic cognitive and motor effect). The EQ includes items related to expectancy for active treatment, placebo, treatment preference, and change in expectancy due to possible placebo allocation. EQ data are presented with descriptive statistics, as well as correlations of EQ item responses with baseline clinical and demographic variables.

Results: The EQ was administered to 372 participants. In SURE-PD3 (n=297), 89.6 % preferred allocation to inosine (n=266), and 53.2 % (n=158) expected to be ‘somewhat better’ or ‘lot better’ with inosine. Worse cognitive performance (MoCA; r= – 0.19, p = 0.001) and older age (r: 0.19, p < 0.001) correlated with higher expectancy for allocation to inosine. In NILO-PD (n=75), 90.7% preferred allocation to nilotinib (n=68). 96.0 % (n=72) expected to have some level of benefit with nilotinib. Worse baseline MDS-UPDRS part III-OFF correlated with a greater expected benefit with nilotinib (r=0.23, p=0.04). In this trial, 42.6% (n=32) participants endorsed a reduction of expectation of benefit due to the possibility of placebo allocation. In both trials, most participants expected a negative outcome with placebo (SURE-PD3 – 73.4%, NILO-PD – 66.7%). The relationship between EQ item responses and efficacy outcome data will be presented.

Conclusion: To our knowledge, this is the first application of an expectancy questionnaire in PD trials. The results are consistent with a known patient preference for an experimental treatment compared with placebo and reveal unrealistic expectations for a disease-modifying effect. There is a negative view of placebos. The reduction of expectancy secondary to a possible placebo allocation endorsed by some participants will be tested for an association with efficacy outcome data and prospectively test the lessebo effect.

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MDS Abstracts - https://www.mdsabstracts.org/abstract/prospective-assessment-of-the-lessebo-effect-in-placebo-controlled-randomized-trials-using-an-expectancy-questionnaire/