Was Phenserine a Failure or Were Investigators Mislead by Methods?

Robert      E. Becker; Nigel      H. Greig

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