Main aim: To examine the (expected or perceived) impact of knowing when symptoms will appear on carriers’ lives and life choices, including on reproductive choices, and decision-making with regard to clinical research and (pre-symptomatic) treatment or trial participation.

WP leader: Ineke Bolt (Erasmus MC)

Objectives: The overall objective of WP6 is to provide ethics and psychological guidance for researchers, healthcare professionals and policy makers dealing with new prognostic information involving carriers of neurodegenerative diseases and to formulate the conditions for implementation of prognostic information and personalized medicine in an ethically responsible way. HD is the first adult onset disease for which presyptomatic DNA-testing became possible and considered world-wide as a major breakthrough; medical treatment would soon become possible. From the start a psychological research programme was added into the attitudes, psychological functioning and adjustment after disclosure of test results. The ethical issues have also been extensively explored. Thus, much knowledge has been acquired about the psychological and ethical implications of presymptomatic DNA-testing. However, the development of a predictive model of AO and POD and personalized treatment for HD and SCA1 and SCA3 creates a new layer of uncertainty and again raises new psychological and ethical issues.

Psychological issues: if prognostic information becomes available to carriers, they would not only face the question to be tested and if so, to adjust to the certainty of being (not) a carrier of HD but also have to consider whether they want to know when they will get the first symptoms and how severe the course of the disease will be. Will it benefit them or be a burden? How does prognostic information affect important decisions of carriers regarding relationships, reproduction, study/training, and work? How do carriers respond when they learn that the predicted AO is at age 25, 40, or 60? The answers to these questions are necessary to provide adequate guidance for genetic counseling of carriers regarding AO and POD as well as to inform the ethical study.

Ethical issues: three different types of ethical questions need to be studied. First, normative questions about the reliability and accuracy of the predictive model and ethics of AI: when is the prognostic model sufficiently reliable to be used in research and clinical practice; what level of uncertainty between prediction and true onset, course and severity of disease is acceptable (e.g., to predict with a margin of 2, 5 or 10 years when a carrier will end up in a wheelchair); should the model be fully transparent to practitioners? Second, questions about genetic testing and the right (not) to know: is it justified to make prognostic information a precondition for access to trials and treatment? Do eligible individuals have the right not to receive prognostic information without being excluded from treatment? Presymptomatic DNA-testing of children for late onset genetic conditions is currently not recommended: should professional guidelines be changed given the opportunity of prognostic models? Third, prognostic information may have societal consequences: the interest of insurers and employers in prognostic information may reignite the debate and policy on disclosure of information in order to get access to supplemental health care insurance, disability and life insurance.