Abstract
Over 200 Alzheimer’s disease (AD) drug candidates have failed in development, and other neuropsychiatric trials have had their validity compromised. Studies suggest that methodological errors can be a source for these compromises and failures. We gained access to documentation for phenserine, an experimental AD drug that reached phase III clinical trials. The 06 Phase III trial was cited by the developers as grounds for their abandonment of the development. We compared evidence for interventions to control methodological errors and grounds for moving through phases of drug development to 40 other randomly selected AD developments we had studied. We analyzed methods and conditions of the 06 phenserine clinical trial, for biases able to account for its abandonment during development. The phenserine development failed to control error sources able to affect the outcomes. There are statistically significant relationships in the 06 clinical trial between outcomes at research sites and levels of variance, placebo group improvements and other factors. We conclude that phenserine was abandoned, at least in part, due to a clinical trial invalidated by relationships among its methods and outcomes.
Keywords: Neuropsychiatric drug development, placebo group improvement, variance, validity, phenserine, scientific practices in drug development, alzheimer’s disease, clinical translation, pharmacological activities
Current Alzheimer Research
Title:Was Phenserine a Failure or Were Investigators Mislead by Methods?
Volume: 9 Issue: 10
Author(s): Robert E. Becker and Nigel H. Greig
Affiliation:
Keywords: Neuropsychiatric drug development, placebo group improvement, variance, validity, phenserine, scientific practices in drug development, alzheimer’s disease, clinical translation, pharmacological activities
Abstract: Over 200 Alzheimer’s disease (AD) drug candidates have failed in development, and other neuropsychiatric trials have had their validity compromised. Studies suggest that methodological errors can be a source for these compromises and failures. We gained access to documentation for phenserine, an experimental AD drug that reached phase III clinical trials. The 06 Phase III trial was cited by the developers as grounds for their abandonment of the development. We compared evidence for interventions to control methodological errors and grounds for moving through phases of drug development to 40 other randomly selected AD developments we had studied. We analyzed methods and conditions of the 06 phenserine clinical trial, for biases able to account for its abandonment during development. The phenserine development failed to control error sources able to affect the outcomes. There are statistically significant relationships in the 06 clinical trial between outcomes at research sites and levels of variance, placebo group improvements and other factors. We conclude that phenserine was abandoned, at least in part, due to a clinical trial invalidated by relationships among its methods and outcomes.
Export Options
About this article
Cite this article as:
E. Becker Robert and H. Greig Nigel, Was Phenserine a Failure or Were Investigators Mislead by Methods?, Current Alzheimer Research 2012; 9 (10) . https://dx.doi.org/10.2174/156720512804142912
DOI https://dx.doi.org/10.2174/156720512804142912 |
Print ISSN 1567-2050 |
Publisher Name Bentham Science Publisher |
Online ISSN 1875-5828 |
Call for Papers in Thematic Issues
New Advances in the Prevention, Diagnosis, Treatment, and Rehabilitation of Alzheimer's Disease
Aims and Scope: Introduction: Alzheimer's disease (AD) poses a significant global health challenge, with an increasing prevalence that demands concerted efforts to advance our understanding and strategies for prevention, diagnosis, treatment, and rehabilitation. This thematic issue aims to bring together cutting-edge research and innovative approaches from multidisciplinary perspectives to address ...read more
Current updates on the Role of Neuroinflammation in Neurodegenerative Disorders
Neuroinflammation is an invariable hallmark of chronic and acute neurodegenerative disorders and has long been considered a potential drug target for Alzheimer?s disease (AD) and dementia. Significant evidence of inflammatory processes as a feature of AD is provided by the presence of inflammatory markers in plasma, CSF and postmortem brain ...read more
Deep Learning for Advancing Alzheimer's Disease Research
Alzheimer's disease (AD) poses a significant global health challenge, with an increasing number of individuals affected yearly. Deep learning, a subfield of artificial intelligence, has shown immense potential in various domains, including healthcare. This thematic issue of Current Alzheimer Research explores the application of deep learning techniques in advancing our ...read more
Diagnostic and therapeutic biomarkers of dementia
Dementia affects 18 million people worldwide. Dementia is a syndrome of symptoms caused by brain disease, usually chronic or progressive, clinically characterized by multiple impairments of higher cortical functions such as memory, thinking, orientation, and learning. In addition, in the course of dementia, cognitive deficits are observed, which often hinder ...read more
- Author Guidelines
- Graphical Abstracts
- Fabricating and Stating False Information
- Research Misconduct
- Post Publication Discussions and Corrections
- Publishing Ethics and Rectitude
- Increase Visibility of Your Article
- Archiving Policies
- Peer Review Workflow
- Order Your Article Before Print
- Promote Your Article
- Manuscript Transfer Facility
- Editorial Policies
- Allegations from Whistleblowers
- Announcements
Related Articles
-
Model Systems for Pulmonary Infectious Diseases: Paradigms of Anthrax and Tuberculosis
Current Topics in Medicinal Chemistry Neurotoxicity: The Broad Framework of Electron Transfer, Oxidative Stress and Protection by Antioxidants
Current Medicinal Chemistry - Central Nervous System Agents Imaging of Wallerian Degeneration in the Brain
Current Medical Imaging From Erythropoietin to Its Peptide Derivatives: Smaller but Stronger
Current Protein & Peptide Science Anti-inflammatory, Antioxidant, Lung and Liver Protective Activity of <i>Galaxaura oblongata</i> as Antagonistic Efficacy against LPS using Hematological Parameters and Immunohistochemistry as Biomarkers
Cardiovascular & Hematological Agents in Medicinal Chemistry Vascular Endothelial Growth Factor as an Anti-Angiogenic Target for Cancer Therapy
Current Drug Targets Current Perspectives of Healthy Mitochondrial Function for Healthy Neurons
Current Drug Targets Challenges and Successes Using Nanomedicines for Aerosol Delivery to the Airways
Current Gene Therapy The Basic Biology of BACE1: A Key Therapeutic Target for Alzheimers Disease
Current Genomics Clearance of Amyloid-β Peptide Across the Choroid Plexus in Alzheimer's Disease
Current Aging Science Anticonvulsant and Antinociceptive Actions of Novel Adenosine Kinase Inhibitors
Current Topics in Medicinal Chemistry Doxorubicin: The Good, the Bad and the Ugly Effect
Current Medicinal Chemistry Modulation of Anxiety Behavior by Intranasally Administered Vaccinia Virus Complement Control Protein and Curcumin in a Mouse Model of Alzheimers Disease
Current Alzheimer Research The Potential Use of Hormone-Based Therapeutics for the Treatment of Alzheimers Disease
Current Alzheimer Research Locus (Coeruleus) Minoris Resistentiae in Pathogenesis of Alzheimer’s Disease
Current Alzheimer Research Molecule of the Month
Current Topics in Medicinal Chemistry Blood Pressure Management in Acute Stroke
Current Hypertension Reviews KCa3.1 Channels and Glioblastoma: In Vitro Studies
Current Neuropharmacology Role of Connexins and Pannexins in Ischemic Stroke
Current Medicinal Chemistry Immunologic Modulations to Enhance Post-Stroke Recovery
Current Immunology Reviews (Discontinued)