title: Using comparative effectiveness design to improve the generalizability of bipolar treatment trials data: contrasting LiTMUS baseline data with pre-existing placebo controlled trials.
abstract: BACKGROUND
  Efficacy-based double-blind placebo controlled trials were conducted to establish efficacy and safety for FDA approval. Such designs allowed and encouraged the use of exclusion criteria to improve assay sensitivity and internal validity. The LiTMUS trial increased the representation of real-world individuals with bipolar disorder despite the acknowledgment that this compromises assay sensitivity.
  
  
  METHODS
  To maximize generalizability, LiTMUS used broad inclusion and narrow exclusion criteria: participants experiencing mood symptoms of sufficient intensity (at least with a CGI-BP ≥ 3) that would warrant a change in treatment, and that lithium treatment would be a reasonable therapeutic option if they were randomized to it. At baseline demographic, illness, clinical, and treatment characteristics were collected. The LiTMUS study design and baseline sociodemographic data were compared to previous efficacy studies.
  
  
  RESULTS
  As compared to the previous bipolar disorder efficacy studies, LiTMUS participants were of similar age, gender, weight and illness severity; however LiTMUS participants were more racially and ethnically representative of the general population, had a greater number of mood episodes in the past 12 months, more Axis I/II comorbidity, a greater number of prior suicide attempts, and higher functional capacity.
  
  
  CONCLUSIONS
  LiTMUS was a comparative effectiveness trial that had broad inclusion and minimal exclusion criteria that produced a more representative sample comprised of real-world participants. This design enables the results of the LiTMUS study to be a more representative of real world pharmacotherapuetic outcomes.
  
  
  CONCLUSIONS
  Limitations include possible selection bias, paucity of sociodemographic data in efficacy trials, and lack of a placebo.
authors.affiliation: University of Pittsburgh Medical Center, Pittsburgh, PA, USA. Electronic address: FriedmanE@upmc.edu.
authors.forename: E S
authors.initials: ES
authors.lastname: Friedman
authors.forename: J R
authors.initials: JR
authors.lastname: Calabrese
authors.forename: T A
authors.initials: TA
authors.lastname: Ketter
authors.forename: A C
authors.initials: AC
authors.lastname: Leon
authors.forename: M E
authors.initials: ME
authors.lastname: Thase
authors.forename: C L
authors.initials: CL
authors.lastname: Bowden
authors.forename: L G
authors.initials: LG
authors.lastname: Sylvia
authors.forename: M J
authors.initials: MJ
authors.lastname: Ostracher
authors.forename: J
authors.initials: J
authors.lastname: Severe
authors.forename: D V
authors.initials: DV
authors.lastname: Iosifescu
authors.forename: A A
authors.initials: AA
authors.lastname: Nierenberg
authors.forename: N A
authors.initials: NA
authors.lastname: Reilly-Harrington
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D018692:Antimanic Agents / Q000008:administration & dosage / Q000627:therapeutic use*; D001714:Bipolar Disorder / Q000188:drug therapy*; D057186:Comparative Effectiveness Research / Q000379:methods*; D005260:Female; D006801:Humans; D007406:Interview, Psychological; D018020:Lithium Compounds / Q000008:administration & dosage / Q000627:therapeutic use*; D008297:Male; D008875:Middle Aged; D011569:Psychiatric Status Rating Scales; D011788:Quality of Life / Q000523:psychology; D012107:Research Design; D016037:Single-Blind Method; D016896:Treatment Outcome; D055815:Young Adult
chemical_list: D018692:Antimanic Agents; D018020:Lithium Compounds
keywords: Baseline characteristics; Bipolar; Comparative effectiveness; Generalizability