title: Reporting of primary analyses and multiplicity adjustment in recent analgesic clinical trials: ACTTION systematic review and recommendations.
abstract: Performing multiple analyses in clinical trials can inflate the probability of a type I error, or the chance of falsely concluding a significant effect of the treatment. Strategies to minimize type I error probability include prespecification of primary analyses and statistical adjustment for multiple comparisons, when applicable. The objective of this study was to assess the quality of primary analysis reporting and frequency of multiplicity adjustment in 3 major pain journals (ie, European Journal of Pain, Journal of Pain, and PAIN®). A total of 161 randomized controlled trials investigating noninvasive pharmacological treatments or interventional treatments for pain, published between 2006 and 2012, were included. Only 52% of trials identified a primary analysis, and only 10% of trials reported prespecification of that analysis. Among the 33 articles that identified a primary analysis with multiple testing, 15 (45%) adjusted for multiplicity; of those 15, only 2 (13%) reported prespecification of the adjustment methodology. Trials in clinical pain conditions and industry-sponsored trials identified a primary analysis more often than trials in experimental pain models and non-industry-sponsored trials, respectively. The results of this systematic review demonstrate deficiencies in the reporting and possibly the execution of primary analyses in published analgesic trials. These deficiencies can be rectified by changes in, or better enforcement of, journal policies pertaining to requirements for the reporting of analyses of clinical trial data.
authors.affiliation: Department of Anesthesiology, University of Rochester School of Medicine and Dentistry, Rochester, NY, USA United States Food and Drug Administration, Silver Spring, MD, USA School of Professional Psychology, Pacific University, Hillsboro, OR, USA Analgesic Solutions, Natick, MA, USA Tufts University, Boston, MA, USA Department of Biostatistics and Computational Biology, University of Rochester School of Medicine and Dentistry, Rochester, NY, USA Department of Anesthesiology and Pain Medicine, University of Washington, Seattle, WA, USA.
authors.forename: Jennifer S
authors.initials: JS
authors.lastname: Gewandter
authors.forename: Shannon M
authors.initials: SM
authors.lastname: Smith
authors.forename: Andrew
authors.initials: A
authors.lastname: McKeown
authors.forename: Laurie B
authors.initials: LB
authors.lastname: Burke
authors.forename: Sharon H
authors.initials: SH
authors.lastname: Hertz
authors.forename: Matthew
authors.initials: M
authors.lastname: Hunsinger
authors.forename: Nathaniel P
authors.initials: NP
authors.lastname: Katz
authors.forename: Allison H
authors.initials: AH
authors.lastname: Lin
authors.forename: Michael P
authors.initials: MP
authors.lastname: McDermott
authors.forename: Bob A
authors.initials: BA
authors.lastname: Rappaport
authors.forename: Mark R
authors.initials: MR
authors.lastname: Williams
authors.forename: Dennis C
authors.initials: DC
authors.lastname: Turk
authors.forename: Robert H
authors.initials: RH
authors.lastname: Dworkin
mesh_terms: D000700:Analgesics / Q000627:therapeutic use*; D006801:Humans; D016032:Randomized Controlled Trials as Topic / Q000379:methods; D012107:Research Design / Q000592:standards*; D013223:Statistics as Topic / Q000379:methods / Q000592:standards*; D016896:Treatment Outcome
chemical_list: D000700:Analgesics
keywords: Multiplicity; Primary analysis reporting; Systematic review