Assessing Cognitive Safety

Using cognitive assessment to guide safety and tolerability decision making in all phases of drug development.

Performance on cognitive tests can provide a sensitive assessment of the impact of a drug on the central nervous system (CNS).

Cogstate helps sponsors assess cognitive safety in all stages of drug development and across indications via our brief and reliable computerized cognitive testing.

Using cognitive testing for safety/tolerability in early trials provides insights into maximum tolerated dose and the duration and severity of any adverse effects. In later development stages and post-approval, cognitive assessment can be informative as to the presence of deleterious effects in the context of long-term follow-up, and in larger, more representative samples.

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Make Informed Cognitive Safety Decisions via Digital Assessments

The FDA have long recognized the potential of drugs to cause cognitive impairment and for effects on cognition to be an important guide to safety and tolerability. Furthermore, the FDA recognize that in assessing cognition, self-report may be inadequate. Inclusion of targeted, objective cognitive assessments helps study teams make informed decision on cognitive safety of an experimental therapeutic.

Using safety assessment to gather data on potential adverse cognitive effects can inform important elements such as dose-response relationships, differentiation from competitor drugs, and detection of off-target pharmacological effects. Cognitive safety assessments can provide different information at different stages of drug development. Short term studies such as SAD, MAD, drug-drug, and drug-alcohol interaction need different approaches than longer-term studies such as disease management and cognitive development in children.

Cogstate’s team of scientists have the expertise to advise your team on the strategic and appropriate use of cognitive assessments as safety measures, based on the stage and indication, to help answer key drug development questions. Cogstate solutions help sponsor teams assess potential cognitive impairment and approach trials with reduced risk.

Case Examples: Cogstate Digital Assessments Aid in Critical Safety Decision Making Across Indications

  • Cogstate supported the Phase 1, 2-period crossover study of intranasal esketamine to evaluate any potential cognitive effects from the administration of the therapeutic candidate. Subjects were tested using a Cogstate battery of digital assessments multiple times in short succession including at -1 hours, 40 minutes, 2 hours, 4 hours, and 6 hours after dosing. At 40-minutes post-dose there was a significant difference in cognition from placebo, and at 2-hours post-dose no significant difference in cognition was found between groups. This cognitive safety data contributed to the Risk Evaluation and Mitigation Strategy (REMS) of intranasal esketamine.*
  • Four Cogstate computerized tests were selected as safety outcomes for the pivotal, international Phase 3 pediatric trial of repatha, a drug to address hypercholesteremia. Cholesterol is important for the brain, so it was important to show the scientific community and regulators that the drug did not cause any problem with thinking. Data demonstrated that the drug reduced cholesterol levels and is safe in its effect on the brain.** Based on the data, the FDA approved the drug for treatment of hypercholesteremia in children aged 10+.
  • Cogstate supported safety assessment in a 24-month observational study of natalizumab in multiple sclerosis patients. 63 patients were treated and assessed prior to monthly infusions using a Cogstate battery and the Symbol Digit Modalities Test (SDMT). Using data from the Cogstate assessments, no patient showed evidence of sustained cognitive deterioration over the 24-month period. Data were relevant to ensuring long-term safety and sustained efficacy of treatment.***

*Bahr, R., et al., Pharmacy and Therapeutics, 2019: PMCID: PMC6534172

**R.D. Santos et al., New England Journal of Medicine: DOI 10.1056/NEJMoa2019910

*** Gaudet D., et al.,  Atherosclerosis, 2021: DOI: https://doi.org/10.1016/j.atherosclerosis.2021.06.789

Safety Batteries

Cogstate tests are organized into batteries that assess the cognitive domains relevant to safety assessment such as processing speed, attention, visual learning, and executive function.

Cogstate tests are rapid, reliable, simple, and sensitive. Each test has been shown to be valid for use in different cultures and language groups with comparative/normative data available for both clinical samples and healthy controls. Tests have been used in all phases of drug trials and maintain excellent reliability across repeated testing and cross-sectional research designs.

Battery recommendations vary depending on the study’s focus area. Pediatric versions of the Cogstate assessments are also available.

Cogstate Tests:Detection Test
Identification Test
One Card Learning Test
Groton Maze Learning Test
Length:Approx. 15 minutes
Administration:Standardized
Data Processing and Scoring:Automated
Application:Phase I
Culture and Language Neutral:Yes

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Data Quality Programs for Conventional Paper-and-Pencil Assessments

Rater-administered clinical assessments and performance-based assessments create the potential for variability in administration and scoring that may compromise data integrity. Cogstate supports all aspects of data quality programs with proven methodologies and leading technologies that drive endpoint reliability.

  • Rater Training – Reduces rater burden while ensuring data integrity with innovative eLearning-first delivery models and tailored certification pathways based on the experience level of the rater
  • Central Monitoring – Including strategic approaches for algorithmic data monitoring as well as targeted source review and audio recording review by clinical experts
  • eCOA Data Capture – For enhanced error preventions, in collaboration with our leading eCOA platform partners, which can include integration of Cogstate digital assessment and conventional assessments on a single device

Decentralized Clinical Trials

We help bring the trial to the patient

As more clinical trials realize the potential of decentralization, Cogstate digital endpoints are enabling at-home, self-administered assessment and our remote rating services are enabling at-home clinician-administered assessment to drive both enhanced data quality as well as patient enrollment, engagement and retention.

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Solutions for Every Stage of Your Study Development

Cogstate’s clinical trial services, coupled with innovative operational approaches, advanced analytics, and scientific consulting, help research teams draw conclusions from study data faster and with more accuracy. Learn how we can support your study:

Scientific Consulting

Computerized Cognitive Assessment

Rater Training

Central Monitoring

Scale Management

Remote / At-home Testing

How can we help you optimize the measurement of brain health?

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