Neuroscience
Becker RE & Greig NH. Alzheimer's disease drug development in 2008 and beyond: Problems and opportunities. Current Alzheimer Research. 2008 Aug; 5(4): 346-357.
Drug Design & Development Section, Laboratory of Neurosciences, Intramural Research Program, National Institute on Aging, National Institutes of Health, Baltimore, MD 21224, USA.
Recently, a number of Alzheimer's disease (AD) multi-center clinical trials (CT) have failed to provide statistically significant evidence of drug efficacy. To test for possible design or execution flaws we analyzed in detail CTs for two failed drugs that were strongly supported by preclinical evidence and by proven CT AD efficacy for other drugs in their class. Studies of the failed commercial trials suggest that methodological flaws may contribute to the failures and that these flaws lurk within current drug development practices ready to impact other AD drug development [1]. To identify and counter risks we considered the relevance to AD drug development of the following factors: (1) effective dosing of the drug product, (2) reliable evaluations of research subjects, (3) effective implementation of quality controls over data at research sites, (4) resources for practitioners to effectively use CT results in patient care, (5) effective disease modeling, (6) effective research designs. New drugs currently under development for AD address a variety of specific mechanistic targets. Mechanistic targets provide AD drug development opportunities to escape from many of the factors that currently undermine AD clinical pharmacology, especially the problems of inaccuracy and imprecision associated with using rated outcomes. In this paper we conclude that many of the current problems encountered in AD drug development can be avoided by changing practices. Current problems with human errors in clinical trials make it difficult to differentiate drugs that fail to evidence efficacy from apparent failures due to Type II errors. This uncertainty and the lack of publication of negative data impede researchers' abilities to improve methodologies in clinical pharmacology and to develop a sound body of knowledge about drug actions. We consider the identification of molecular targets as offering further opportunities for overcoming current failures in drug development.
PMID: 18690832 [PubMed - indexed for MEDLINE]
Download the full article: Link
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Neuroscience
Neuropsychology Abstract of the Day: Alzheimer's Disease Drug Development
Becker RE & Greig NH. Alzheimer's disease drug development in 2008 and beyond: Problems and opportunities. Current Alzheimer Research. 2008 Aug; 5(4): 346-357.
Drug Design & Development Section, Laboratory of Neurosciences, Intramural Research Program, National Institute on Aging, National Institutes of Health, Baltimore, MD 21224, USA.
Recently, a number of Alzheimer's disease (AD) multi-center clinical trials (CT) have failed to provide statistically significant evidence of drug efficacy. To test for possible design or execution flaws we analyzed in detail CTs for two failed drugs that were strongly supported by preclinical evidence and by proven CT AD efficacy for other drugs in their class. Studies of the failed commercial trials suggest that methodological flaws may contribute to the failures and that these flaws lurk within current drug development practices ready to impact other AD drug development [1]. To identify and counter risks we considered the relevance to AD drug development of the following factors: (1) effective dosing of the drug product, (2) reliable evaluations of research subjects, (3) effective implementation of quality controls over data at research sites, (4) resources for practitioners to effectively use CT results in patient care, (5) effective disease modeling, (6) effective research designs. New drugs currently under development for AD address a variety of specific mechanistic targets. Mechanistic targets provide AD drug development opportunities to escape from many of the factors that currently undermine AD clinical pharmacology, especially the problems of inaccuracy and imprecision associated with using rated outcomes. In this paper we conclude that many of the current problems encountered in AD drug development can be avoided by changing practices. Current problems with human errors in clinical trials make it difficult to differentiate drugs that fail to evidence efficacy from apparent failures due to Type II errors. This uncertainty and the lack of publication of negative data impede researchers' abilities to improve methodologies in clinical pharmacology and to develop a sound body of knowledge about drug actions. We consider the identification of molecular targets as offering further opportunities for overcoming current failures in drug development.
PMID: 18690832 [PubMed - indexed for MEDLINE]
Download the full article: Link
- Clinical Trials: Evp-6124 Phase 2b Clinical Trial In Schizophrenia
From Drug Discovery & Development: Positive Study Results for Schizophrenia Drug Drug Discovery & Development December 05, 2011 "EnVivo Pharmaceuticals announced the analysis of a completed Phase 2b clinical trial of EVP-6124, a novel, orally bioavailable...
- Alzheimer's: The Current Pipeline
FierceBiotechResearch has an article which presents a very brief overview of the current Alzheimer's disease drug pipeline: It is available at the link below: Making sense of the Alzheimer's drug pipeline FierceBiotechResearch March 15, 2011 —...
- Upcoming Event:alzheimer's Drug Discovery (jersey City, Nj, 14-15 September)
The 10th international conference on Alzheimer's disease drug discovery takes place next week on the 14th and 15th in Jersey City, NJ. From the conference website: "The 10th International Conference on Alzheimer's Disease Drug Discovery is presented...
- Upcoming Event: Alzheimer Disease (las Vegas, 29-30 Oct 2009)
2nd Conference on Clinical Trials on Alzheimer’s Disease (CTAD) From the conference website: "Dear Colleague, "It is a great pleasure for us to invite you to attend the 2nd conference Clinical Trials on Alzheimer’s Disease (CTAD), which will take...
- The Placebo Effect Is Stronger Than Ever
The September 2009 issue of Wired has a terrific article about the placebo effect / response. Steve Silberman writes in "Placebos Are Getting More Effective. Drugmakers Are Desperate to Know Why" that the placebo effect in drug clinical trials has been...