Clinical Research: Phase 1 - Phase 4

3 Innovations Improving Neuropsychological Testing in CNS Drug Development

Although current limitations in neuropsychological testing may discourage development of treatments for central nervous system (CNS) disorders, some researchers see these unmet needs as an opportunity for innovation. Take a look at three strategies that are improving the validity and viability of neuropsychological testing.

Rater Training

Success or failure of a CNS trial can come down to how well study personnel are trained to collect data, including neuropsychological test administration. Establishing rater consistency between sites has been a major roadblock for CNS drug trials, especially in global studies where cultural and language differences can influence testing.

Because studies have shown that training improves rater competency at all levels of clinical experience, many trial design teams are focusing on increasing both the level and effectiveness of their rater training programs. These strategies include more thorough tutorials on scoring conventions as well as applied clinical training in which raters conduct interviews under the observation of an expert trainer.

Other Biomarkers

While currently lacking in concrete biomarkers for the evaluation of CNS disorders, neuropsychology is a rapidly changing field. In fact, CNS biomarkers are the fastest-growing niche in the overall biomarker development sector.

New advances in neuroimaging and molecular biomarkers may soon give researchers more objective metrics to work with. This identification and validation of anatomical and molecular biomarkers can then be used to complement neuropsychological tests.

As an example, new techniques allow researchers to directly observe a drug’s impact on brain activity or the rate of its distribution to targeted tissues. These metrics can be matched against changes in cognitive performance identified by neuropsychological testing to look for clinically significant correlations.

Computerized Testing

Traditional neuropsychological testing is time-consuming for both patients and test administrators. It can often require special equipment, dedicated testing areas and experienced professionals — all factors that increase cost and limit access. The increased use of computer testing may soon be able to reduce these drawbacks.

Computerized neuropsychological tests also have the potential to improve accuracy and reproducibility by minimizing the environmental and interpersonal factors that contribute to variability.

While some computerized tests are simple adaptations of traditional paper-and-pencil tests, others are completely novel techniques. Computerized testing can introduce useful elements that were difficult to implement in traditional neuropsychological tests, such as sound, motion tracking and complex images.

Although promising, the important aspects of computerized testing’s measurement validity in comparison with traditional tests in clinical trials still needs to be established. However, clinical studies of certain individual tests have demonstrated equivalence. Additionally, the FDA has already shown willingness to approve CNS drugs based on computerized cognitive tests.

What Next?

While testing innovations promise to improve data quality and reduce costs, sponsors must fully understand the current regulatory guidance involved in the clinical evaluation of neuropsychiatric drugs before these changes can be implemented. Luckily, the FDA has recognized the current challenges involved in CNS drug development and has taken steps to help encourage further innovation.

The continued research into accurate, specific and cost-effective neuropsychological assessments may prove to encourage a major boom in CNS drug development. Additionally, as researchers investigate alternative metrics for measuring the efficacy, safety and tolerability of experimental treatments, the underlying pathophysiology of these disorders may be one day brought to light.