Clinical Outcome Assessments in Preclinical Alzheimer’s Disease: Considerations for Global Clinical Trials
November 28, 2019
Preclinical Alzheimer’s disease (AD) is classified in individuals who show abnormal levels of amyloid, tau or neurodegenerative biomarkers but who do not meet any clinical criteria for dementia or mild cognitive impairment. Current estimates indicate that this preclinical AD stage can last for more than 10 years and so it provides a unique opportunity to understand the clinical-pathological sequelae of very early AD. This information can be used to develop and implement therapeutic strategies that can slow or even halt these processes, so as to forestall the development of symptoms.
Selecting Cognitive & Behavioral Endpoint Measures for Trials in Rare Epilepsy and MPS Disorders
November 28, 2019
Clinical trials in patients with rare forms of epilepsy and mucopolysaccharidoses (MPS) disorders present considerable challenges, as patients with these conditions are heterogeneous and many are quite impaired. Further, comorbid sensory and motor deficits are common as are disruptive behaviors. Additionally, these diseases are often regressive, making the assessment of cognitive and behavior even more complex.
Using Cognition to Guide Decisions on the Safety and Tolerability of Drugs in Clinical Development
July 25, 2019
In clinical trials, changes in performance on cognitive tests can provide a sensitive index of the impact of a drug on the central nervous system (CNS). In such trials, the detection of decline in specific aspects of cognition, or in cognition in general, is important for making decisions about target engagement, maximum tolerated dose and pharmacodynamic profile. Observations of drug-related cognitive decline can also indicate areas for concern with clinical use, such as the potential effects on activities of daily living or the ability to operate a motor vehicle. In children, drug-related cognitive decline can indicate the potential for influence on neurodevelopment.
Measuring Cognitive Effects of Pediatric Oncology Treatments Using Computerized Assessments
May 15, 2019
In recent years the neurocognitive effects of treatments for pediatric cancers have been acknowledged in the scientific literature. However, in many cases the magnitude of these deficits and the long-term impact on cognitive maturation remain unclear. Children and adolescents present a particularly challenging population, given neurocognitive effects may impact developmental trajectories, and patients are often so unwell at the time of testing that brevity, flexibility and adaptability of the neuropsychological testing need to be considered. With the availability of computerized cognitive assessments, recent studies have more readily included longitudinal assessments of neurocognitive function.
Evaluating Cognition in Parkinson’s Disease Clinical Trials
March 20, 2019
The past two decades have seen multiple industry trials explore the impact of drug treatments (primarily dopaminergic therapies and cholinesterase inhibitors) on cognition in Parkinson’s disease (PD) and PD dementia (PDD).
How to Leverage eCOA for Improved Signal Detection in Pediatric & Rare Disorder Trials
March 4, 2019
Combining eSource Technology with Expert Clinical Science to Reduce Rater Errors on Cognitive, Behavioral and Developmental Assessments for Infants to Young Adults.
Selecting CNS Endpoint Measures in Pediatric and Rare Disease Clinical Trials: Key Considerations for Cognitive and Behavioral Assessments
May 21, 2018
Testing new medicines in children and patients with rare diseases presents considerable challenges, not the least of which is proper endpoint selection and measurement. With the recent rapid growth of pediatric and rare disease trials, the pharmaceutical industry is now particularly considering the assessment of cognition and behavior in pediatric populations.
The ABCs of Assessing Cognition in Oncology Clinical Trials: Applications, Benefits, and Considerations
May 17, 2017
Nearly all patients with central nervous system (CNS) and many patients with non-CNS cancers experience cognitive problems during the course of their disease and treatment that can result in diminished quality of life and functional independence. While overall survival and progression-free survival have been the most widely accepted clinical trial endpoints in evaluating oncology therapies, more recently, there has been a growing interest in patient-centered clinical outcome assessments (COAs) that measure the impact of disease and treatments on an individual’s overall functioning, including cognitive function.
Increasing the Precision of Cognitive Endpoints in Schizophrenia Clinical Trials
February 13, 2017
Cognitive impairment associated with schizophrenia (CIAS) is an important treatment target, and major unmet therapeutic need in the chronic stages of schizophrenia. Many studies have sought to ameliorate CIAS with new drugs but, as yet, no drug has been approved for treatment of CIAS. In acute stages of the illness the measurement of cognition has also been used to guide decisions about the safety and efficacy of new medicines. In this acute stage of the illness cognitive tests have been used successfully to show the benefits of new antipsychotic medicines.
Optimizing CNS Endpoints Using Technology-enabled Workflows
November 16, 2016
A principal challenge in CNS clinical trials are the subjective assessments prone to rater bias and variability that can cause failed or inconclusive trials. Even the most rigorous rater training programs and scientific oversight are not enough when they remain siloed and unconnected. But when learning management, data capture and central review are integrated and empowered by innovative fit-for-purpose technologies designed by clinical experts, dramatic improvements in endpoint reliability and rater-centricity are achieved.
The Preclinical Alzheimer Cognitive Composite: From Theory to Practical Application in Global Clinical Trials
September 6, 2016
Drug development strategies for early Alzheimer’s disease (AD) require clinical endpoints that are sensitive to the subtlest cognitive changes that may be occurring at even preclinical stages. Commonly used measures of cognition in clinical trials of treatments for Alzheimer’s disease, such as the Alzheimer’s Disease Assessment Scale-Cognitive subscale (ADAS-Cog) and the Clinical Dementia Rating (CDR), have inadequate measurement properties (e.g., ceiling effects, practice effects, restricted range, and/or skewed distributions), which render them insensitive to subtle change.