The objective of this study was to assess safety, tolerability, and explore efficacy (proof-of-concept).
The majority (80%) of phase III failures were caused by a lack of efficacy [ 152, 154– 156] that resulted from a lack of efficacy proof-of-concept in humans and a lack of objective biomarkers capable of reporting such efficacy [ 152, 154].
While the later stages of the PhAT deal with the clinical validation of the therapeutic hypothesis, early preclinical experiments are essential to define a number of the PhAT parameters, including identification of biomarkers and early demonstration of efficacy and proof of mechanism.
However, such knowledge has not translated into a significant improvement in the clinical management of the disease, with EGF-R or PDGF-R inhibitors lacking clinical efficacy in proof of concept studies (Mathy et al, 2005; Garland et al, 2007).
If this reduction were seen in a therapeutic approach that was designed to inhibit Aβ production, it would have been an encouraging sign of efficacy and proof of mechanism.
We conclude that gabapentin and tramadol were effective in the treatment of painful SFN and that this experimental enrichment paradigm is attractive to screen potential neuropathic pain compounds for efficacy in proof-of-concept studies.
The ability to develop novel anti-fibrotic therapies and analyse their efficacy in proof-of-concept (POC) studies is partly impeded by limitations in currently available animal models used to study this disorder in vivo.
A main driver behind the growing investments in Systems Pharmacology is the recognition that novel, innovative approaches are required to improve productivity in pharmaceutical research and development, specifically tackling attrition due to insufficient efficacy in proof-of-concept/phase II studies, which is increasingly seen as the main bottleneck.
The bispecific virus retained the original oncolytic efficacy, while providing proof of concept for a strategy to counteract issues of resistance development.
