Assessing cognitive toxicity in early phase trials - What are we missing?

Area of Science:

• Oncology
• Clinical Pharmacology
• Neuroscience

Background:

• Phase I clinical trials evaluate novel therapies like small molecule inhibitors and immunotherapies.
• A primary goal of Phase I trials is to establish a toxicity profile, with a strong emphasis on safety.
• Cognitive toxicity is a poorly understood and potentially under-reported concern in this trial phase.

Purpose of the Study:

• To review evidence of cognitive assessment and toxicity in Phase I trial reports.
• To identify confounding factors influencing cognitive function in Phase I trial participants.
• To explore potential mechanisms linking novel therapy actions to cognitive impairment.

Main Methods:

• A scoping review methodology was employed.
• Searches were conducted across Embase, MEDLINE, and Clinicaltrials.gov.
• Data were screened, categorized, charted, and synthesized into a narrative.

Main Results:

• Robust cognitive assessment tools are not routinely used in early clinical trials.
• Limited reports indicate a proportion of Phase I trial patients experience cognitive impairment.
• Potential links exist between novel therapy mechanisms and cognitive impairment mechanisms.

Conclusions:

• There is a clear need for research into cognitive function in Phase I trials.
• Current evidence suggests cognitive impairment occurs in a subset of patients.
• Formal cognitive assessment should be considered in early clinical trials.