Using Cognition to Guide Decisions on the Safety and Tolerability of Drugs in Clinical Development

Life Sciences, Clinical Trials, Drug Safety,
  • Wednesday, July 24, 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.

The clinical relevance of any drug-related cognitive decline, or the absence thereof, can be operationalized and benchmarked using measures of effect size. For example, standardized scores can be compared with those for established sedative-hypnotic and cognitively impairing drugs such as alcohol or benzodiazepines, or with socially relevant challenges such as sleep restriction.

The application of cognitive tests in different experimental designs can provide unique information to guide decision-making in both single ascending dose (SAD) and multiple ascending dose (MAD) studies. The application of cognition can also elucidate the potential for additive or synergistic effects in drug-drug and drug-alcohol interaction trials. Additionally, trials with active controls can confirm the predicted absence of an effect: for example, through the comparison of central versus peripheral anticholinergic drugs.

In later development and post-approval, the assessment of cognition can inform the presence of deleterious effects in the context of long-term follow-up and in larger, more representative samples. In conducting such studies, it is important to derive distinct outcome measures for separate cognitive domains and ensure performance on these tests should remain stable with multiple assessments over short and long retest periods. Most importantly, the sensitivity of cognitive tests to pharmacological interventions is critical.

Sponsors need to consider all of these elements when assessing cognition as an output of safety and tolerability of an experimental drug. In this free webinar, attendees will learn about the following:

  • Clear specification of relevant objectives related to cognition
  • An understanding of how the data collected will be applied
  • How elements of trial design will influence these determinations
  • Careful selection of an appropriate battery of tests


Paul Maruff, Cogstate

Paul Maruff, Chief Science Officer, Cogstate

Professor Paul Maruff is a founder of Cogstate and a neuropsychologist with expertise in the measurement of subtle behavioral and cognitive dysfunction in neuropsychiatric disease, neurological disorders and in brain injury. Paul’s research integrates conventional and computerized neuropsychological testing with cognitive neuroscientific methods, neuroimaging, genetics and clinical assessment to guide decision-making about brain function in both clinical medicine and drug development. 

Paul has worked extensively to develop methods for assessing cognitive impairment and drug efficacy in Alzheimer’s disease, mild cognitive impairment and HIV dementia complex. He has extended these methods to the identification of cognitive dysfunction and the effects of treatment in psychiatric diseases such as schizophrenia, attention deficit disorder and obsessive-compulsive disorder, major depressive disorder and substance abuse in adults and children.

In addition to being responsible for the scientific progress at Cogstate, Paul is also appointed Professor at the Florey Institute for Neuroscience and Mental Health where he is an active member of the Alzheimer’s disease research group. He is currently clinical co-chair of the clinical committee in the Australian Imaging Biomarkers and Lifestyle (AIBL) study and also sits on the executive committee for that group. Paul has published over 300 research articles in international peer-reviewed scientific journals and has co-authored 10 book chapters.

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Chris Edgar, Cogstate

Chris Edgar, Senior Vice President, Clinical Science, Cogstate

Dr. Chris Edgar is an experienced leader in cognitive assessment and clinical endpoint strategy who provides expert guidance to Cogstate’s pharmaceutical customers throughout all stages of trial conduct, from study design and test selection through final analysis. He is also a key advisor to Cogstate’s commercial and product teams for the development of new technologies and approaches in line with industry needs. Dr. Edgar joins Cogstate from Roche where he oversaw clinical endpoint strategy for multiple neuroscience indications in the Patient-Centered Outcomes Research group. Dr. Edgar has held other strategic positions including Clinical Scientist at Roche on schizophrenia and Alzheimer’s disease drug development programs, Senior Clinical Lead for rater training and data quality at Bracket, and Scientific Director at Cognitive Drug Research Ltd., a computerized cognitive assessment company.

He holds a PhD in Psychopharmacology from Northumbria University and has nearly two decades of pharmaceutical industry experience. His current research interests include defining clinically meaningful progression and meaningful change estimates in neurodegenerative disease, cognitive screening for Alzheimer’s disease, application of survival analysis to neuroscience clinical trials and defining treatment benefit for negative symptoms associated with schizophrenia and measurement science topics relevant to regulators.

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Who Should Attend?

Executives, directors, scientists and managers from pharma, biotech and CROs responsible for the clinical development of CNS drug products, including:

  • Research and Development
  • Clinical Operations
  • Clinical Science
  • Outcomes Research
  • Outsourcing and Procurement
  • Project Management
  • Clinical Trial Planning and Optimization
  • Medical Affairs

What You Will Learn

Attendees will gain insights into:

  • Important elements of trial design and how to ensure clarity of objectives and decision-making
  • Use of effect size to characterize the nature and relevance of deleterious effects on cognition
  • Application of active controls to demonstrate the absence of adverse effects
  • Important characteristics of cognitive tests having utility in early phase medicine

Xtalks Partner

Cogstate Ltd

Cogstate Ltd (ASX:CGS) is a leading science and technology solutions provider dedicated to optimizing the measurement of cognition in clinical trials, academic research and healthcare. Cogstate provides enabling technologies and professional services for higher quality neuropsychological assessments and is a pioneer in commercializing rapid, reliable and highly sensitive computerized cognitive tests. Cogstate customers include the world’s leading biopharmaceutical companies; elite sporting organizations and military; physicians and patients; renowned academic institutions and public-private partnerships. For more information, please visit

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