How the prospect of a clinical trial impacts decision-making for predictive genetic testing in amyotrophic lateral sclerosis

Objective Genetic testing practices are rapidly evolving for people living with, or at-risk for, amyotrophic lateral sclerosis (ALS), due to emerging genotype-driven therapies. This study explored how individuals at-risk for familial ALS (fALS) perceive the opportunity to participate in a clinical trial, and to better understand how that may influence the decision-making process for predictive genetic testing. Methods This study used both quantitative and qualitative data analyses. Data were collected through an online questionnaire, followed by semi-structured interviews conducted with twelve (n=12) individuals at-risk for either SOD1- or C9orf72 -ALS who had predictive testing prior to study participation. Interview data were analyzed using reflexive thematic analysis. Results Three overarching themes were conceptualized from the data: i) the psychosocial impact of fALS; ii) perspectives of at-risk individuals on research involvement; and iii) predictive genetic counselling and testing considerations. These results contribute perspectives of the lived experience to inform predictive genetic counselling and testing practices for individuals at-risk for fALS. Conclusion Individuals at-risk for fALS view potential participation in a presymptomatic clinical trial as an actionable measure that may increase their desire for predictive genetic testing. Genetic counselling was identified as a critical component of the predictive testing process given the life-changing implications associated with a positive result. Increased access to genetic counselling, and in a timely manner, is a significant need in the ALS population given potential access to gene-specific therapies in the presymptomatic stage.