# Risk willingness in multiple system atrophy and Parkinson’s disease understanding patient preferences

## TL;DR

The study explores how patients with multiple system atrophy and Parkinson’s disease are willing to take risks for potential cures, finding significant differences between the two groups.

## Contribution

The study introduces a novel approach to quantifying patient risk willingness in α-synucleinopathies using standard gamble scenarios.

## Key findings

- MSA patients accepted a median 1% risk of sudden death for a 99% chance of cure, while PD patients accepted a median 0.055% risk.
- MSA patients' risk willingness was associated with life satisfaction and nonmotor disease burden, whereas PD patients' risk willingness was linked to age and disease duration.
- The study highlights the need for individualized approaches to assessing therapy-associated risk willingness in MSA and PD patients.

## Abstract

Disease-modifying therapeutics in the α-synucleinopathies multiple system atrophy (MSA) and Parkinson’s Disease (PD) are in early phases of clinical testing. Involving patients’ preferences including therapy-associated risk willingness in initial stages of therapy development has been increasingly pursued in regulatory approval processes. In our study with 49 MSA and 38 PD patients, therapy-associated risk willingness was quantified using validated standard gamble scenarios for varying severities of potential drug or surgical side effects. Demonstrating a non-gaussian distribution, risk willingness varied markedly within, and between groups. MSA patients accepted a median 1% risk [interquartile range: 0.001–25%] of sudden death for a 99% [interquartile range: 99.999–75%] chance of cure, while PD patients reported a median 0.055% risk [interquartile range: 0.001–5%]. Contrary to our hypothesis, a considerable proportion of MSA patients, despite their substantially impaired quality of life, were not willing to accept increased therapy-associated risks. Satisfaction with life situation, emotional, and nonmotor disease burden were associated with MSA patients’ risk willingness in contrast to PD patients, for whom age, and disease duration were associated factors. An individual approach towards MSA and PD patients is crucial as direct inference from disease (stage) to therapy-associated risk willingness is not feasible. Such studies may be considered by regulatory agencies in their approval processes assisting with the weighting of safety aspects in a patient-centric manner. A systematic quantitative assessment of patients’ risk willingness and associated features may assist physicians in conducting individual consultations with patients who have MSA or PD by facilitating communication of risks and benefits of a treatment option.