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Conducting CNS Clinical Trials? Overview and Considerations of the New Tools from NIH for Assessment of Neurological and Behavioral Function

Posted by Brook White on Tue, Apr 16, 2013 @ 09:29 AM

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neuropsychological assessments in clinical trialsIn recent years the National Institutes of Health (NIH) has undertaken several initiatives intended to advance neuroscience research by means of a multi-institute collaboration entitled “the Blueprint for Neuroscience Research.” Some of these initiatives involve standardization and sharing of cutting-edge technologies such as neuroimaging and genomics. Another of their initiatives, the NIH Toolbox, is a set of standardized neurobehavioral assessments that is useful to a broad research audience.   This article summarizes the development-of and uses-for the NIH Toolbox, and provides considerations for its current and future utility in drug development1.

Many central nervous system (CNS) clinical trials, as well as those in other therapeutic areas, require neurological or behavioral assessments.  Currently, investigators use a number of different assessments to assess the same construct, making it difficult to understand data across multiple studies.  In an effort to resolve this problem in 2004, the NIH formed a coalition to create a toolbox of neurological and behavioral assessments.  The coalition included multiple divisions at NIH and more than 250 scientists at more than 80 institutions.  The goals of the coalition were:

  • To develop and validate a set of standardized, psychometrically sound tools for neurobehavioral constructs
  • To be able to measure the same construct across the life span
  • To create tools that are royalty-free, and as close to cost-free as possible (most assessments currently in use are proprietary and often costly)
  • To create tools that are efficient to administerTo provide measures that facilitate the pooling of data across many studies

In October of 2012, the coalition released the toolbox to the public.  It includes:

  • Four domain level batteries
  • English and Spanish versions
  • 34 supplemental instruments
  • Training materials for administration of the assessments
  • Public data from the studies conducted during the development of the tools

The batteries are fully normalized for ages 3-85, and are essentially free to use.  Each domain takes 30 minutes to administer.  From the toolbox website, you can access the domain level batteries, supplemental assessments, and training materials including videos showing the assessments being conducted.

The four domains covered by the assessments are cognition, motor, sensation, and emotion. The cognitive domain includes working memory (short term buffer), executive function (planning and organizing), episodic memory (acquisition and retrieval), language, processing speed, and attention.  The motor domain includes standing balance, strength, dexterity, and speed/endurance.  The sensation domain includes audition, olfaction, pain, taste, vestibular, and vision.  The emotional domain includes psychological well-being, social relationships, stress and self-efficacy, and negative affect.

What will be the impact of the NIH toolbox on CNS clinical trials and the development of new treatments for CNS disorders?  They are not designed to capture pathology, and so far, they have been used primarily in health subjects. Therefore, the NIH Toolbox is unlike earlier initiatives such as the ECDEU assessment manual for psychopharmacology published in 1976, which had a profound effect on drug development through the late 1980s.  However, because of its focus on function in healthy subjects, the NIH Toolbox may provide a more precise and quantitative concept of “normal” against which pathology can be measured. As such, it will inevitably have utility throughout clinical research and drug development. 

It may take some time to gain broad acceptance in the CNS community.  For now, it seems risky to use one of these assessments alone as a primary end point for a clinical trial, and if you are considering doing so, you should probably proactively pursue agreement from the FDA. Another consideration is how you would use the assessments in a trial.  Most of the assessments are aimed at benchmarking a state of wellness.  While that doesn’t provide a direct measurement of disease state, these tests may be valuable in showing clinical significance.  

Have you used or considered using any of these assessments yet?  If so, share your experiences in the comments section.

For more information, see the NIH Toolbox website www.nihtoolbox.org where the assessments and training videos can be found.

1Information for this article was contributed by Nancy Yovetich, Ph.D., Senior Research Scientist, and Herbert Harris, M.D., Ph.D., Medical Director at Rho, Inc.  These contributors were not involved in the development or validation of the NIH Toolbox.  One of the authors did attend the launch of the NIH Toolbox in Bethesda, MD.  Both Dr. Yovetich and Dr. Harris have extensive backgrounds in clinical research and in psychology/psychiatry.

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