The Prospective Huntington At-Risk Observational Study (PHAROS): The Emotional Well-Being, Safety and Feasibility of Long-Term Research Participation

Abstract

Background: There is limited understanding of the feasibility of conducting long-term research among undiagnosed (pre-symptomatic) adults at risk to develop Huntington disease (HD), while protecting their emotional well-being and safety.

Objective: To assess pre-specified events pertaining to emotional well-being, safety, and feasibility among healthy consenting adults at risk for developing HD who have chosen not to undergo genetic testing.

Methods: PHAROS research participants prospectively reported the occurrence of events pertaining to psychological distress (psychiatric evaluations, depression, suicidality) and feasibility (maintaining confidentiality, study attrition). PHAROS enrolled 1001 participants.

Results: Events pertaining to psychological distress were reported by 35% of participants. The most common events included heightened suicide risk (26%), new onset depression (12%), and new mental health evaluation (9%); all occurred significantly more frequently among participants with expanded trinucleotide CAG repeats (≥37). Five deaths occurred, none related to suicide. Forty-one percent of participants reported self-disclosure of their HD at-risk status, and 15% reported that someone else (usually a family member) had done so. Confidentiality of CAG test results was maintained by investigators. The withdrawal rate was largely uniform over the study period and did not differ significantly by gender or CAG status.

Conclusions: The potentially vulnerable research participants in PHAROS showed good emotional tolerability and safety. Individual CAG data were not disclosed, and confidentiality about disclosure of at-risk HD status was well maintained by others (family, friends, etc.). Long-term research participation of adults at risk for HD who choose not to undergo pre-symptomatic DNA testing is well tolerated, safe and feasible.

Keywords: Huntington’s disease; at risk; genetic privacy; observational trial; psychological stressors.