Cognitive Testing in Clinical Drug Trials

By | September 8, 2010

Formal cognitive testing in pharmaceutical trials is relatively new.  Up until 2000, most drug trial designs did not include any form of baseline and end point cognitive testing, even for drugs that act directly on the central nervous system (CNS).

A significant push towards standardized cognitive assessments in clinical drug trials occurred in 2005 when the FDA, National Institute for Mental Health (NIMH), and several pharmaceutical companies agreed on a common protocol for cognitive testing as part of the MATRICS initiative.  MATRICS was designed to support the development of new drugs to help resolve serious cognitive impairments that are associated with schizophrenia.

This government-industry collaboration took more than three years of necessary analysis and consensus meetings to produce a recommendation for the MATRICS cognitive battery:

  • Reliable and valid assessment of all major cognitive domains (Speed of Processing, Attention/Vigilance, Working Memory, Verbal Learning and Memory, Visual Learning and Memory, Reasoning and Problem Solving, and Social Cognition)
  • Repeated test-retest reliability (little or no practice/training effect on retests, which can skew results)
  • Cognitive test results tied to functional outcome (do improved test results translate to better performance in daily activities?)
  • Practical test format (computer based, pencil and paper, how much time?)

The end result for a MATRICS cognitive test is the MATRICS Consensus Cognitive Battery, or MCCB.  The MCCB is a 90 minute, 10 test (1 computer-based, 9 pencil and paper), that must be administered by a skilled practitioner.  This “heavyweight” approach can make sense for some clinical drug trials, where the resources are plentiful and number of trial participants is relatively small.

It is unfortunate, however, that the MATRICS initiative did not include a view on generalizing the MCCB to a wider population that would benefit from a fully computerized version of a well validated cognitive assessment battery.

A more recent addition to cognitive testing in drug trials is the Neuropsychological
Test Battery (NTB) — a 45 minute, nine test (pencil and paper) cognitive battery that measures memory and executive function. The NTB is being used in several Alzheimer’s and dementia pharmaceutical trials.

There are several commercial companies that do provide full computer-based cognitive test batteries for clinical drug trials, including CANTAB by Cambridge Cognition, Brain Resource (IntegNeuro & WebNeuro), CNS Vital Signs, CogState, Cognitive Drug Research, and HeadMinder.  These companies provide cognitive test batteries that overlap the MCCB and NTB in some respects but are not exact copies.  The same can be said for company-to-company comparisons – there is some overlap on test batteries but each company has unique implementations and features.