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
-
Coumarins as Antioxidants
Current Medicinal Chemistry Preface: Developments in Understanding of Alzheimer Disease
Current Alzheimer Research Anti-Inflammatory Effects of Antidepressants: Possibilities for Preventives Against Alzheimers Disease
Central Nervous System Agents in Medicinal Chemistry Genistein as a Potential Anticancer Agent Against Head and Neck Squamous Cell Carcinoma
Current Topics in Medicinal Chemistry Disrupted Functional Connectivity Related to Differential Degeneration of the Cingulum Bundle in Mild Cognitive Impairment Patients
Current Alzheimer Research Alzheimer’s Disease Risk and Progression: The Role of Nutritional Supplements and their Effect on Drug Therapy Outcome
Current Neuropharmacology A Case of Neurosarcoidosis Mimicking Brain Tumor
Current Medical Imaging Anorexia Nervosa and the Use of Total Parenteral Nutrition Refeeding
Current Nutrition & Food Science Targeting the Pleiotrophin/Receptor Protein Tyrosine Phosphatase β /ζ Signaling Pathway to Limit Neurotoxicity Induced by Drug Abuse
Mini-Reviews in Medicinal Chemistry Tetrahydroxystilbene Glucoside Improves Neurotrophic Factors Release in Cultured Astroglia
CNS & Neurological Disorders - Drug Targets Development of Novel Therapeutics Targeting Isocitrate Dehydrogenase Mutations in Cancer
Current Topics in Medicinal Chemistry Mechanisms of Inhibitory and Regulatory Effects of Methylenedioxyphenyl Compounds on Cytochrome P450-Dependent Drug Oxidation
Current Drug Metabolism Adipose Tissue and Bone Marrow as Sources for Cell-based Therapeutic Angiogenesis in Ischemic Tissues: Biological Foundation and Clinical Prospects for Age-related Vascular Disease
Immunology, Endocrine & Metabolic Agents in Medicinal Chemistry (Discontinued) New Horizons in the Treatment of Neurological Disorders with Tailorable Gold Nanoparticles
Current Drug Metabolism α7 Nicotinic Acetylcholine Receptor Subunit in Angiogenesis and Epithelial to Mesenchymal Transition
Current Drug Targets The Role of Endocannabinoids in Pain Modulation and the Therapeutic Potential of Inhibiting their Enzymatic Degradation
Current Pharmaceutical Biotechnology Potential Use of Nanomedicine for Drug Delivery Across the Blood-Brain Barrier in Healthy and Diseased Brain
CNS & Neurological Disorders - Drug Targets A Potential Role for the Existence of Pericytes in the Neurovascular Unit of the Sexually Dimorphic Nucleus of the Rat Preoptic Area to Control Blood-Brain Barrier Function
Current Neurovascular Research Resilience to Alzheimer's Disease: The Role of Physical Activity
Current Alzheimer Research Editorial (Thematic Issue: Update on Inflammatory Targets Modulating Atherogenesis)
Current Drug Targets