title: A novel subject synchronization clinical trial design for Alzheimer's disease.
abstract: One of the challenges in developing a viable therapy for Alzheimer's disease has been demonstrating efficacy within a clinical trial. Using this as motivation, we sought to re-examine conventional clinical trial practices in order to determine whether efficacy can be better shown through alternative trial designs and novel analysis methods. In this work, we hypothesize that the confounding factors which hamper the ability to discern a treatment signal are the variability in observations as well as the insidious nature of the disease. We demonstrate that a two-phase trial design in which drug dosing is administered after a certain level of disease severity has been reached, coupled with a method to account more accurately for the progression of the disease, may allow us to compensate for these factors, and thus enable us to make treatment effects more apparent. Utilizing data from two previously failed trials which involved the evaluation of galantamine for indication in mild cognitive impairment, we were able to demonstrate that a clear treatment effect can be realized through both visual and statistical means, and propose that future trials may be more likely to show success if similar methods are utilized.
authors.affiliation: Janssen Pharmaceutical Companies of Johnson and Johnson, Raritan, NJ 08869, USA. tschult4@its.jnj.com
authors.forename: Timothy
authors.initials: T
authors.lastname: Schultz
authors.forename: Eric
authors.initials: E
authors.lastname: Yang
authors.forename: Michael
authors.initials: M
authors.lastname: Farnum
authors.forename: Victor
authors.initials: V
authors.lastname: Lobanov
authors.forename: Rudi
authors.initials: R
authors.lastname: Verbeeck
authors.forename: Nandini
authors.initials: N
authors.lastname: Raghavan
authors.forename: Mahesh N
authors.initials: MN
authors.lastname: Samtani
authors.forename: Gerald
authors.initials: G
authors.lastname: Novak
authors.forename: Yingqi
authors.initials: Y
authors.lastname: Shi
authors.forename: Vaibhav
authors.initials: V
authors.lastname: Narayan
authors.forename: Allitia
authors.initials: A
authors.lastname: DiBernardo
mesh_terms: D000544:Alzheimer Disease / Q000188:drug therapy* / Q000473:pathology* / Q000523:psychology; D002986:Clinical Trials as Topic / Q000379:methods* / Q000592:standards; D018450:Disease Progression; D005702:Galantamine / Q000627:therapeutic use*; D006801:Humans; D018697:Nootropic Agents / Q000627:therapeutic use*; D012107:Research Design / Q000592:standards
chemical_list: D018697:Nootropic Agents; D005702:Galantamine