Innovative technologies expedite cognition drug development

Dr Richard Keefe, PhD, is co-founder and CEO of NeuroCog Trials, a company that specialises in creating innovative tools and strategies to facilitate drug development and enhance assessment of cognition and functioning.

NeuroCog Trials, a company co-founded in 2004 by CEO Dr Richard Keefe and President Caren Gadigian, develops innovative methods to assess cognition and function in diseases such as schizophrenia, depression, Mild Cognitive Impairment, and Alzheimer’s disease. The overall philosophy of the company is to facilitate drug development with new tools and strategies to enhance signal detection in clinical trials. They do this by developing new approaches that utilise virtual reality and computerised tools to augment the delivery of clinical assessment.

Much of this technology has been used in schizophrenia treatment. Schizophrenia is a severe mental illness that affects most patients for their entire life. It impacts a person’s ability to engage with the world, affecting employment opportunities, the formation and maintenance of interpersonal relationships, and the ability to live independently. Although current antipsychotic drugs can help control some features such as hallucinations, they have little effect on the cognitive abilities of patients, so there is a drive to develop treatments that can assist in this domain.

NeuroCog Trials develops innovative technologies that utilise virtual reality and computerised assessments to augment the measurement of cognitive and functional abilities in clinical trials

As part of a consensus initiative, the Measurement and Treatment Research to Improve Cognition in Schizophrenia (MATRICS) project, recommendations were made to standardise the cognitive measures used in schizophrenia trials. As part of this, a set, or ‘battery’ of tests was developed that would accurately measure change in patients’ cognitive function, divided into seven cognitive domains: speed of processing, attention/vigilance, working memory (verbal and non-verbal), verbal learning, visual learning, reasoning and problem solving, and social cognition.

A Virtual Reality Assessment
The Virtual Reality Functional Capacity Assessment Tool (VRFCAT) is a computer- and web-based tool that assesses patients’ ability to perform tasks that are a common part of everyday life, such as travelling on public transport, paying for shopping etc. The battery aims to measure functional capacity, or “real-world functional improvements associated with cognitive change” [Keefe et al., 2016].

The VRFCAT differs from other assessment tools because it is computerised and performance-based. This means there is the potential for this test to be delivered remotely, and an outside observer or informant of a patient’s behaviour, such as a family member, is not required. Other tests, like the UCSD Performance-based skills assessment (UPSA), have previously relied on pen-and-paper tests, with a role-play component that requires patients to act out certain tasks. However, many of these tasks, such as writing cheques or calling a phone directory, are now somewhat out-dated. The VRFCAT has six alternative versions which allows the test to be administered repeatedly over time, without the patient’s scores improving simply because they have performed the test previously, the so-called ‘practice effect’.

How well does it work?
The NeuroCog Trials team assessed patients and healthy controls with a variety of different metrics to compare how well the VRFCAT performed at measuring functional capacity against other tests. The VRFCAT compares well with other measures, such as the UPSA, which has previously been used in trials. Different versions of the VRFCAT were used to measure the differences between them.

The high degree of correlation between the VRFCAT and UPSA suggests that the VRFCAT is a useful tool that accurately measures the functional capacity of users. There was clear differentiation between the scores of schizophrenia patients and healthy controls. Better test times were associated with lower degrees of cognitive impairment as measured on the Schizophrenia Cognitive Rating scale (SCoRS) and higher Specific Levels of Functioning (SLOF) scores.

Digitising Existing Tests
Another of NeuroCog’s innovative projects is the Brief Assessment of Cognition (BAC) App, which is a tablet-/app-based version of the pen-and-paper Brief Assessment of Cognition in Schizophrenia (BACS) test battery. The test measures a user’s ability to perform six tasks to assess their reasoning/problem solving, working memory, verbal memory, and processing speed.

In a paper co-written by Alexandra Atkins and others, Keefe and team compared the results of the BACS and BAC App methods. They found that there were no discernible differences between the traditional version of the test and the app version, and that there was a robust difference between schizophrenia patients and healthy controls. This supports the notion that the BAC App is appropriate for use in clinical trials.

Tablet-based methods are useful because they allow the incorporation of all the benefits of computerised methods, such as standardised algorithms and voiced-over instructions, while maintaining the interaction with the patient, which is important in cognitively-impaired or behaviourally-challenging populations such as patients with schizophrenia or Alzheimer’s disease.

Looking Beyond Schizophrenia
The VRFCAT and BAC App have potential applications beyond schizophrenia — for instance they are being tailored specifically for studies of patients with Mild Cognitive Impairment associated with Alzheimer’s disease, and are currently being used in trials of patients with depression and those at-risk for bipolar disorder.

Novel technologies such as virtual reality and simple apps are increasingly being recognised as effective methods to administer treatment and assist with diagnosis. NeuroCog Trials’ wealth of scientific expertise will enhance clinical outcomes associated with diseases like schizophrenia and Alzheimer’s that impair sufferers’ cognitive abilities.

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