TY - JOUR
T1 - Cerebrospinal fluid biomarkers for Alzheimer's disease
T2 - A view of the regulatory science qualification landscape from the coalition against major diseases CSF biomarker team
AU - Arnerić, Stephen P.
AU - Batrla-Utermann, Richard
AU - Beckett, Laurel A
AU - Bittner, Tobias
AU - Blennow, Kaj
AU - Carter, Leslie
AU - Dean, Robert
AU - Engelborghs, Sebastiaan
AU - Genius, Just
AU - Gordon, Mark Forrest
AU - Hitchcock, Janice
AU - Kaplow, June
AU - Luthman, Johan
AU - Meibach, Richard
AU - Raunig, David
AU - Romero, Klaus
AU - Samtani, Mahesh N.
AU - Savage, Mary
AU - Shaw, Leslie
AU - Stephenson, Diane
AU - Umek, Robert M.
AU - Vanderstichele, Hugo
AU - Willis, Brian
AU - Yule, Susan
PY - 2016
Y1 - 2016
N2 - Alzheimer's disease (AD) drug development is burdened with the current requirement to conduct large, lengthy, and costly trials to overcome uncertainty in patient progression and effect size on treatment outcome measures. There is an urgent need for the discovery, development, and implementation of novel, objectively measured biomarkers for AD that would aid selection of the appropriate subpopulation of patients in clinical trials, and presumably, improve the likelihood of successfully evaluating innovative treatment options. Amyloid deposition and tau in the brain, which are most commonly assessed either in cerebrospinal fluid (CSF) or by molecular imaging, are consistently and widely accepted. Nonetheless, a clear gap still exists in the accurate identification of subjects that truly have the hallmarks of AD. The Coalition Against Major Diseases (CAMD), one of 12 consortia of the Critical Path Institute (C-Path), aims to streamline drug development for AD and related dementias by advancing regulatory approved drug development tools for clinical trials through precompetitive data sharing and adoption of consensus clinical data standards. This report focuses on the regulatory process for biomarker qualification, briefly comments on how it contrasts with approval or clearance of companion diagnostics, details the qualifications currently available to the field of AD, and highlights the current challenges facing the landscape of CSF biomarkers qualified as hallmarks of AD. Finally, it recommends actions to accelerate regulatory qualification of CSF biomarkers that would, in turn, improve the efficiency of AD therapeutic development.
AB - Alzheimer's disease (AD) drug development is burdened with the current requirement to conduct large, lengthy, and costly trials to overcome uncertainty in patient progression and effect size on treatment outcome measures. There is an urgent need for the discovery, development, and implementation of novel, objectively measured biomarkers for AD that would aid selection of the appropriate subpopulation of patients in clinical trials, and presumably, improve the likelihood of successfully evaluating innovative treatment options. Amyloid deposition and tau in the brain, which are most commonly assessed either in cerebrospinal fluid (CSF) or by molecular imaging, are consistently and widely accepted. Nonetheless, a clear gap still exists in the accurate identification of subjects that truly have the hallmarks of AD. The Coalition Against Major Diseases (CAMD), one of 12 consortia of the Critical Path Institute (C-Path), aims to streamline drug development for AD and related dementias by advancing regulatory approved drug development tools for clinical trials through precompetitive data sharing and adoption of consensus clinical data standards. This report focuses on the regulatory process for biomarker qualification, briefly comments on how it contrasts with approval or clearance of companion diagnostics, details the qualifications currently available to the field of AD, and highlights the current challenges facing the landscape of CSF biomarkers qualified as hallmarks of AD. Finally, it recommends actions to accelerate regulatory qualification of CSF biomarkers that would, in turn, improve the efficiency of AD therapeutic development.
KW - Alzheimer's disease
KW - biomarker qualification
KW - cerebrospinal fluid biomarkers
KW - Coalition Against Major Diseases
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U2 - 10.3233/JAD-160573
DO - 10.3233/JAD-160573
M3 - Review article
C2 - 27662307
AN - SCOPUS:84994644485
VL - 55
SP - 19
EP - 35
JO - Journal of Alzheimer's Disease
JF - Journal of Alzheimer's Disease
SN - 1387-2877
IS - 1
ER -