Use of translational pharmacodynamic biomarkers in early-phase clinical studies for schizophrenia

2014 ◽  
Vol 8 (1) ◽  
pp. 29-49 ◽  
Author(s):  
Brett A English ◽  
Kelan Thomas ◽  
Jack Johnstone ◽  
Adam Bazih ◽  
Lev Gertsik ◽  
...  
Keyword(s):  
Clinical Studies ◽  
Early Phase ◽  
Pharmacodynamic Biomarkers

scholarly journals Targeting for Success: Demonstrating Proof-of-Concept with Mechanistic Early Phase Clinical Pharmacology Studies for Disease-Modification in Neurodegenerative Disorders

2021 ◽  
Vol 22 (4) ◽  
pp. 1615
Author(s):  
Maurits F. J. M. Vissers ◽  
Jules A. A. C. Heuberger ◽  
Geert Jan Groeneveld
Keyword(s):  
Clinical Trials ◽  
Failure Rate ◽  
Neurodegenerative Disorders ◽  
Early Phase ◽  
Proof Of Concept ◽  
Mesh Terms ◽  
Disease Modifying ◽  
Early Phase Clinical Trials ◽  
Pharmacodynamic Biomarkers ◽  
Response Biomarkers

The clinical failure rate for disease-modifying treatments (DMTs) that slow or stop disease progression has been nearly 100% for the major neurodegenerative disorders (NDDs), with many compounds failing in expensive and time-consuming phase 2 and 3 trials for lack of efficacy. Here, we critically review the use of pharmacological and mechanistic biomarkers in early phase clinical trials of DMTs in NDDs, and propose a roadmap for providing early proof-of-concept to increase R&D productivity in this field of high unmet medical need. A literature search was performed on published early phase clinical trials aimed at the evaluation of NDD DMT compounds using MESH terms in PubMed. Publications were selected that reported an early phase clinical trial with NDD DMT compounds between 2010 and November 2020. Attention was given to the reported use of pharmacodynamic (mechanistic and physiological response) biomarkers. A total of 121 early phase clinical trials were identified, of which 89 trials (74%) incorporated one or multiple pharmacodynamic biomarkers. However, only 65 trials (54%) used mechanistic (target occupancy or activation) biomarkers to demonstrate target engagement in humans. The most important categories of early phase mechanistic and response biomarkers are discussed and a roadmap for incorporation of a robust biomarker strategy for early phase NDD DMT clinical trials is proposed. As our understanding of NDDs is improving, there is a rise in potentially disease-modifying treatments being brought to the clinic. Further increasing the rational use of mechanistic biomarkers in early phase trials for these (targeted) therapies can increase R&D productivity with a quick win/fast fail approach in an area that has seen a nearly 100% failure rate to date.

Extemporaneous preparation strategy for early phase clinical studies

2018 ◽  
Vol 549 (1-2) ◽  
pp. 150-160 ◽  
Author(s):  
Rampurna P. Gullapalli ◽  
Carolyn L. Mazzitelli ◽  
Christina M. Charriez ◽  
David J. Carpenter ◽  
Rebecca D. Crean ◽  
...  
Keyword(s):  
Clinical Studies ◽  
Early Phase ◽  
Extemporaneous Preparation ◽  
Preparation Strategy

Association Between Pharmacodynamic Biomarkers and Clinical Events in the Early Phase After Kidney Transplantation: A Single-Center Pilot Study

2011 ◽  
Vol 33 (3) ◽  
pp. 341-349 ◽  
Author(s):  
Eberhard Wieland ◽  
Maria Shipkova ◽  
Yanina Martius ◽  
Georg Hasche ◽  
Corinne Klett ◽  
...  
Keyword(s):  
Kidney Transplantation ◽  
Pilot Study ◽  
Early Phase ◽  
Single Center ◽  
Clinical Events ◽  
Pharmacodynamic Biomarkers

Systematic analysis of early phase clinical studies for patients with breast cancer: Inclusion of patients with brain metastasis

2017 ◽  
Vol 55 ◽  
pp. 10-15 ◽  
Author(s):  
R. Costa ◽  
N. Gill ◽  
A.W. Rademaker ◽  
B.A. Carneiro ◽  
Y.K. Chae ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Brain Metastasis ◽  
Clinical Studies ◽  
Early Phase ◽  
Systematic Analysis

scholarly journals 2015 Guidance on cancer immunotherapy development in early‐phase clinical studies

2015 ◽  
Vol 106 (12) ◽  
pp. 1761-1771 ◽  
Author(s):  
◽  
Teruyo Arato ◽  
Takashi Daimon ◽  
Yuji Heike ◽  
Ken Ishii ◽  
...  
Keyword(s):  
Cancer Immunotherapy ◽  
Clinical Studies ◽  
Early Phase
Sign in / Sign up

Export Citation Format

Share Document