Estimands in CNS trials - A review of strategies for addressing intercurrent events.

Background: The estimands framework represents a significant innovation for the design, conduct, analysis, and interpretation of clinical trials. An aim of the framework is to increase precision and transparency on the handling of intercurrent events (IEs), defined as events occurring after treatment initiation and affecting the endpoint. While the experience in constructing and reporting estimands in the published literature is limited, developers performing confirmatory studies are already making use of the new paradigm, allowing to survey the strategies proposed by applicants and endorsed by regulators.

Preferences about Future Alzheimer's Disease Treatments Elicited through an Online Survey Using the Threshold Technique.

Background: Treatments aiming at slowing down the progression of Alzheimer's disease (AD) may soon become available. However, information about the risks that people are willing to accept in order to delay the progression of the disease is limited.

Objective: To determine the trade-offs that individuals are willing to make between the benefits and risks of hypothetical treatments for AD, and the extent to which these trade-offs depend on individuals' characteristics and beliefs about medicines.

Developing medicines for the pre-symptomatic stage of degenerative neurological conditions: Challenges and opportunities.

Neurodegenerative disorders have a devastating disease course and an increasing prevalence due to prolonged life expectancy. In the last decades, it has become increasingly clear that these diseases often start much earlier, before the onset of symptoms, creating a potential window for pre-symptomatic treatment, a strategy that is desirable from both the biologic and the ethical point of view. However, studying treatments for a pre-symptomatic population presents objective difficulties.

Clinically Manifest Infections Do Not Increase the Relapse Risk in People with Multiple Sclerosis Treated with Disease-Modifying Therapies: A Prospective Study.

Background: Many factors are believed to be positively associated with the incidence of relapses in people with multiple sclerosis (MS), including infections. However, their role is still controversial. We aimed to investigate whether symptomatic infections in people with MS increase the risk of relapse in the short, medium, or long term.