title: Use of band-pass filter analysis to evaluate outcomes in an antidepressant trial for treatment resistant patients.
abstract: Band-pass filtering is a novel statistical methodology that proposes that filtering out data from trial sites generating non-plausible high or low levels of placebo response can yield a more accurate effect size and greater separation of active drug (when efficacious) from placebo. We applied band-pass filters to re-analyze data from a negative antidepressant trial (NCT00739908) evaluating CX157 (a reversible and selective monoamine oxidase inhibitor-A) versus placebo. 360 patients from 29 trial sites were randomized to either CX157 treatment (n=182) or placebo (n=178). We applied two filters of<3 or>7 points (filter #1) or<3 and>9 points (filter #2) mean change of the total MADRS placebo scores for each site. Trial sites that had mean placebo MADRS score changes exceeding the boundaries of these band-pass filter thresholds were considered non-informative and all of the data from these sites were excluded from the post-hoc re-analysis. The two band-pass filters reduced the sample of informative patients from 353 patients in the mITT population to 62 in filter #1 and 152 in the filter #2 group. The placebo response was reduced from 31.1% in the mITT population to 9.4% with filter #1 and 20.8% with filter #2. MMRM analysis revealed a non-statistically significant trend of p=0.13 and 0.16 for the two filters in contrast to the mITT population (p= 0.58). Our findings support the band-pass filter hypothesis and highlight issues related to site-based scoring variability and inappropriate subject selection that may contribute to trial failure.
authors.affiliation: Clintara LLC, Boston, MA, United States. Electronic address: sdtargum@yahoo.com.
authors.forename: Steven D
authors.initials: SD
authors.lastname: Targum
authors.affiliation: PPD Inc., Wilmington, NC, United States.
authors.forename: Daniel J
authors.initials: DJ
authors.lastname: Burch
authors.affiliation: UCB Biosciences Inc., Raleigh, NC, United States.
authors.forename: Mahnaz
authors.initials: M
authors.lastname: Asgharnejad
authors.affiliation: Clintara LLC, Boston, MA, United States.
authors.forename: Timothy
authors.initials: T
authors.lastname: Petersen
authors.affiliation: Pharmacometrica, La Fouillade, France.
authors.forename: Roberto
authors.initials: R
authors.lastname: Gomeni
authors.affiliation: Massachusetts General Hospital, Boston, MA, United States.
authors.forename: Maurizio
authors.initials: M
authors.lastname: Fava
mesh_terms: D000328:Adult; D000368:Aged; D000928:Antidepressive Agents / Q000627:therapeutic use*; D003863:Depression / Q000188:drug therapy*; D004311:Double-Blind Method; D005163:Factor Analysis, Statistical; D005260:Female; D006571:Heterocyclic Compounds / Q000627:therapeutic use*; D006801:Humans; D008297:Male; D008875:Middle Aged; D017063:Outcome Assessment, Health Care; D016896:Treatment Outcome; D014481:United States; D055815:Young Adult
chemical_list: D000928:Antidepressive Agents; C551866:CX157; D006571:Heterocyclic Compounds
keywords: Band-pass filter analysis; MAO-A; Placebo response; Ratings reliability; Treatment resistant depression