title: Discrepancies between registered and published primary outcome specifications in analgesic trials: ACTTION systematic review and recommendations.
abstract: The National Institutes of Health released the trial registry ClinicalTrials.gov in 2000 to increase public reporting and clinical trial transparency. This systematic review examined whether registered primary outcome specifications (POS; ie, definitions, timing, and analytic plans) in analgesic treatment trials correspond with published POS. Trials with accompanying publications (n = 87) were selected from the Repository of Registered Analgesic Clinical Trials (RReACT) database of all postherpetic neuralgia, diabetic peripheral neuropathy, and fibromyalgia clinical trials registered at ClinicalTrials.gov as of December 1, 2011. POS never matched precisely; discrepancies occurred in 79% of the registry-publication pairs (21% failed to register or publish primary outcomes [PO]). These percentages did not differ significantly between industry and non-industry-sponsored trials. Thirty percent of the trials contained unambiguous POS discrepancies (eg, omitting a registered PO from the publication, "demoting" a registered PO to a published secondary outcome), with a statistically significantly higher percentage of non-industry-sponsored than industry-sponsored trials containing unambiguous POS discrepancies. POS discrepancies due to ambiguous reporting included vaguely worded PO registration; or failing to report the timing of PO assessment, statistical analysis used for the PO, or method to address missing PO data. At best, POS discrepancies may be attributable to insufficient registry requirements, carelessness (eg, failing to report PO assessment timing), or difficulty uploading registry information. At worst, discrepancies could indicate investigator impropriety (eg, registering imprecise PO ["pain"], then publishing whichever pain assessment produced statistically significant results). Improvements in PO registration, as well as journal policies requiring consistency between registered and published PO descriptions, are needed.
authors: Department of Anesthesiology, University of Rochester School of Medicine and Dentistry, Rochester, NY, USA School of Medicine, Case Western Reserve University, Cleveland, OH, USA California Pacific Medical Center Research Institute, San Francisco, CA, USA United States Food and Drug Administration, Silver Spring, MD, USA Purdue Pharma LP, Stamford, CT, USA University of Pennsylvania, Philadelphia, PA, USA Departments of Anesthesiology and Perioperative Medicine and Biomedical and Molecular Sciences, Queen's University, Kingston, ON, Canada Analgesic Solutions, Natick, MA, USA Tufts University, Boston, MA, USA Departments of Biostatistics and Computational Biology and Neurology, University of Rochester School of Medicine and Dentistry, Rochester, NY, USA Depomed, Newark, CA, USA Department of Anesthesiology and Pain Medicine, University of Washington, Seattle, WA, USA Departments of Anesthesiology and Neurology and Center for Human Experimental Therapeutics, University of Rochester School of Medicine and Dentistry, Rochester, NY, USA.
authors: Shannon M
authors: SM
authors: Smith
authors: Anthony T
authors: AT
authors: Wang
authors: Anthony
authors: A
authors: Pereira
authors: Daniel R
authors: DR
authors: Chang
authors: Andrew
authors: A
authors: McKeown
authors: Kaitlin
authors: K
authors: Greene
authors: Michael C
authors: MC
authors: Rowbotham
authors: Laurie B
authors: LB
authors: Burke
authors: Paul
authors: P
authors: Coplan
authors: Ian
authors: I
authors: Gilron
authors: Sharon H
authors: SH
authors: Hertz
authors: Nathaniel P
authors: NP
authors: Katz
authors: Allison H
authors: AH
authors: Lin
authors: Michael P
authors: MP
authors: McDermott
authors: Elektra J
authors: EJ
authors: Papadopoulos
authors: Bob A
authors: BA
authors: Rappaport
authors: Michael
authors: M
authors: Sweeney
authors: Dennis C
authors: DC
authors: Turk
authors: Robert H
authors: RH
authors: Dworkin
mesh_terms: D000700:Analgesics / Q000627:therapeutic use*; D002986:Clinical Trials as Topic / Q000379:methods / Q000592:standards*; D006801:Humans; D017410:Practice Guidelines as Topic / Q000592:standards*; D017594:Publication Bias; D012042:Registries / Q000592:standards*; D016896:Treatment Outcome
chemical_list: D000700:Analgesics
keywords: Analgesic medications; Clinical trials; Primary outcomes; Registry; Systematic review
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