title: Intention-to-treat and transparency of related practices in randomized, controlled trials of anti-infectives.
abstract: Intention-to-treat (ITT) analysis is commonly recommended for use, due to its benefits on external validity, in randomized, controlled trials (RCTs). No published reports describe how ITT analysis, as well as alternative approaches, are used in anti-infective RCTs. The purpose of this study is to describe the extent to which ITT analysis and alternative data approaches are used, the practices used to handle missing subject data, and whether non-inferiority trials present both ITT and per protocol (PP) analyses. Results of this analysis will help guide end users of infectious diseases primary drug literature.
  
  
  
  A cross-sectional study of RCTs of anti-infectives published from January 1, 2013 through December 31, 2014 was conducted. A PubMed search identified relevant articles published in five specialty infectious diseases journals and four general medical journals. Each article was reviewed by two independent investigators with discrepancies resolved by consensus. Descriptive statistics were used to quantify results.
  
  
  
  One hundred four articles met study criteria. The most common medication classes represented in the RCTs were hepatitis C antivirals (26 %), antibacterials (25 %), and antiretrovirals (21 %). Thirty studies (29 %) were non-inferiority trials. Most studies (77 %) described use of ITT or modified ITT (mITT) in their methods. Of the ITT and mITT studies, most (73 %) did not describe practices used to handle missing data. Most (97 %) non-inferiority trials described use of ITT, mITT, or both; however, only 15 (50 %) also described use of PP.
  
  
  
  RCTs of anti-infectives commonly employ ITT and mITT. Most do not describe how missing data were addressed. Non-inferiority trials of anti-infectives do not consistently employ both ITT and PP populations.
authors.affiliation: Manchester University College of Pharmacy, Natural, and Health Sciences, 10627 Diebold Road, Fort Wayne, IN, 46845, USA. rdbeckett@manchester.edu.
authors.forename: Robert D
authors.initials: RD
authors.lastname: Beckett
authors.affiliation: Columbus Regional Health, 2400 17th Street, Columbus, IN, 47201, USA.
authors.forename: Kathryn C
authors.initials: KC
authors.lastname: Loeser
authors.affiliation: CVS Pharmacy, 1221 W Monroe Street, Decatur, IN, 46733, USA.
authors.forename: Kathryn R
authors.initials: KR
authors.lastname: Bowman
authors.affiliation: Manchester University College of Pharmacy, Natural, and Health Sciences, 10627 Diebold Road, Fort Wayne, IN, 46845, USA.
authors.forename: Trent G
authors.initials: TG
authors.lastname: Towne
mesh_terms: D000890:Anti-Infective Agents / Q000627:therapeutic use*; D003430:Cross-Sectional Studies; D030881:Disclosure; D006801:Humans; D057194:Intention to Treat Analysis / Q000379:methods*; D039781:PubMed; D016032:Randomized Controlled Trials as Topic / Q000379:methods* / Q000592:standards*; D012107:Research Design / Q000592:standards; D058028:Research Report / Q000592:standards; D016896:Treatment Outcome
chemical_list: D000890:Anti-Infective Agents
keywords: Anti-infectives; Clinical trial evaluation; Intention-to-treat; Per protocol