Bridging the Chasm Between Scientific Discovery and a Pivotal Clinical Trial for a CNS Disorder: A Checklist

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Abstract

The central nervous system (CNS) is difficult to treat effectively after damage, whether the situation is congenital, traumatic, or degenerative. The effective translation of a novel preclinical discovery to a clinically meaningful human treatment is demanding and initially governed by fundamental achievements at the preclinical development level. Good laboratory practices (GLPs) are increasingly being adopted, as they provide all neurological investigators with increased confidence for the results. GLPs are demanding and ask scientists to adhere to many of the demanding criteria intrinsic to human studies. The subsequent preclinical development of a therapeutic is equally important and outlines the safety, dose, fate, window of opportunity, and route of administration.

Human trials are channeled by established guidelines, but CNS clinical studies involve target populations that are heterogeneous and often rely on subjective (ordinal) outcome tools that can be questioned for their ability to accurately and sensitively discern subtle treatment effects. Improved solutions for the following concerns are evolving quickly:
  1. 1.

    What is the most appropriate type of participant to enroll in each phase of a trial program?

     
  2. 2.

    What would be the most accurate, sensitive, and reliable outcome measure for the chosen clinical target?

     
  3. 3.

    How is a clinical endpoint threshold selected to determine whether the therapeutic provides a meaningful clinical benefit?

     

Keywords

Good laboratory practice Therapeutic development Human study Subject heterogeneity Clinical outcome measures Stroke Spinal cord injury 
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Copyright information

© Springer Science+Business Media New York 2016

Authors and Affiliations

  1. 1.International Collaboration on Repair Discoveries (ICORD)University of British Columbia and Vancouver Coastal HealthVancouverCanada
  2. 2.Blusson Spinal Cord CentreVancouver General HospitalVancouverCanada

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