title: PRECISE--pregabalin in addition to usual care: statistical analysis plan.
abstract: BACKGROUND
  Sciatica is a severe, disabling condition that lacks high quality evidence for effective treatment strategies. This a priori statistical analysis plan describes the methodology of analysis for the PRECISE study.
  
  
  METHODS
  PRECISE is a prospectively registered, double blind, randomised placebo controlled trial of pregabalin compared to placebo, in addition to usual care in patients with sciatica. The aim of this study is to determine the efficacy and cost-effectiveness of pregabalin in reducing leg pain intensity (primary outcome). Secondary outcomes include disability (key secondary), back pain intensity, quality of life, participants' perceived global effect, work absenteeism and health utilisation. Information about medication usage and tolerability are also collected. Outcomes are collected over one year (weeks 2, 4, 8, 12, 26 and 52). Double data entry will be conducted for primary and key secondary outcomes. Other outcomes will be checked using a risk-based approach. Analyses will be consistent with the intention-to-treat principle. Statistical tests will be two-tailed with a p value <0.05 considered significant. Group allocation will remain masked until analyses and interpretation are finalised. Repeated-measure linear mixed models will assess the effect of treatment (pregabalin versus placebo) on primary and secondary outcomes at all time points. Fixed effects will include group allocation, visit as a categorical variable and the interaction between group and visit. Covariates will include baseline leg pain and symptom duration, with an interaction term between baseline leg pain and visit. Pairwise differences between groups will be tested at weeks 8 and 52. The number of serious adverse events and adverse events will be reported, and the proportion of patients per group who have at least one event will be compared using Fisher's exact test. An economic evaluation will be conducted if there is a treatment effect on the primary outcome at week 8. A subgroup analysis will assess whether presenting features of neuropathic pain at baseline modify the treatment effect of leg pain at week 8.
  
  
  CONCLUSIONS
  This statistical analysis plan provides detailed methodology for the analysis of the PRECISE study, which aims to deliver much needed evidence about effective and affordable management of sciatica.
  
  
  BACKGROUND
  Australian and New Zealand Clinical Trials Registry (ACTRN12613000530729. Registered 13 May 2013).
authors.affiliation: The George Institute for Global Health and Sydney Medical School, University of Sydney, P.O. Box M201, Missenden Road, Sydney, NSW, 2050, Australia. smathieson@georgeinstitute.org.au.
authors.forename: Stephanie
authors.initials: S
authors.lastname: Mathieson
authors.affiliation: The George Institute for Global Health and Sydney Medical School, University of Sydney, P.O. Box M201, Missenden Road, Sydney, NSW, 2050, Australia. lbillot@georgeinstitute.org.au.
authors.forename: Laurent
authors.initials: L
authors.lastname: Billot
authors.affiliation: The George Institute for Global Health and Sydney Medical School, University of Sydney, P.O. Box M201, Missenden Road, Sydney, NSW, 2050, Australia. cmaher@georgeinstitute.org.au.
authors.forename: Christopher G
authors.initials: CG
authors.lastname: Maher
authors.affiliation: Faculty of Pharmacy and Centre for Education and Research on Ageing, University of Sydney, Sydney, Australia. andrew.mclachlan@sydney.edu.au.
authors.forename: Andrew J
authors.initials: AJ
authors.lastname: McLachlan
authors.affiliation: The George Institute for Global Health and Sydney Medical School, University of Sydney, P.O. Box M201, Missenden Road, Sydney, NSW, 2050, Australia. jlatimer@georgeinstitute.org.au.
authors.forename: Jane
authors.initials: J
authors.lastname: Latimer
authors.affiliation: Department of General Practice, Erasmus University Medical Center, Rotterdam, The Netherlands. b.koes@erasmusmc.nl.
authors.forename: Bart W
authors.initials: BW
authors.lastname: Koes
authors.affiliation: Faculty of Human Sciences, Macquarie University, Sydney, Australia. mark.hancock@mq.edu.au.
authors.forename: Mark J
authors.initials: MJ
authors.lastname: Hancock
authors.affiliation: The South Western Sydney Clinical School, Faculty of Medicine, University of New South Wales, Sydney, Australia. ian.harris@sswahs.nsw.gov.au.
authors.forename: Ian
authors.initials: I
authors.lastname: Harris
authors.affiliation: St Vincent's Clinical School, Faculty of Medicine, University of New South Wales, Sydney, Australia. r.day@unsw.edu.au.
authors.forename: Richard O
authors.initials: RO
authors.lastname: Day
authors.affiliation: ACT NeuroSpine Clinic, Deakin, Australian Capital Territory, Australia. cjpik@tpg.com.au.
authors.forename: Justin
authors.initials: J
authors.lastname: Pik
authors.affiliation: The George Institute for Global Health and Sydney Medical School, University of Sydney, P.O. Box M201, Missenden Road, Sydney, NSW, 2050, Australia. sjan@georgeinstitute.org.au.
authors.forename: Stephen
authors.initials: S
authors.lastname: Jan
authors.affiliation: The George Institute for Global Health and Sydney Medical School, University of Sydney, P.O. Box M201, Missenden Road, Sydney, NSW, 2050, Australia. clin@georgeinstitute.org.au.
authors.forename: Chung-Wei Christine
authors.initials: CW
authors.lastname: Lin
mesh_terms: D000700:Analgesics / Q000627:therapeutic use*; D003627:Data Interpretation, Statistical; D004311:Double-Blind Method; D006801:Humans; D017063:Outcome Assessment, Health Care; D000069583:Pregabalin / Q000009:adverse effects / Q000627:therapeutic use*; D011446:Prospective Studies; D018401:Sample Size; D012585:Sciatica / Q000188:drug therapy* / Q000503:physiopathology
chemical_list: D000700:Analgesics; D000069583:Pregabalin
references.citation: Pain. 2009 Dec;146(3):238-44
references.pmid: 19836888
references.citation: N Engl J Med. 2007 May 31;356(22):2245-56
references.pmid: 17538084
references.citation: Curr Med Res Opin. 2006 Oct;22(10):1911-20
references.pmid: 17022849
references.citation: J Clin Nurs. 2005 Aug;14(7):798-804
references.pmid: 16000093
references.citation: Trials. 2013;14:213
references.pmid: 23845078
references.citation: J Clin Epidemiol. 2010 Jul;63(7):760-766.e1
references.pmid: 20056385
references.citation: Bull World Health Organ. 2003;81(9):671-6
references.pmid: 14710509
references.citation: Lancet Neurol. 2015 Feb;14(2):162-73
references.pmid: 25575710
references.citation: Am Heart J. 2014 Jan;167(1):51-58.e5
references.pmid: 24332142
references.citation: Spine (Phila Pa 1976). 1995 Sep 1;20(17):1899-908; discussion 1909
references.pmid: 8560339
references.citation: Med Care. 2004 Sep;42(9):851-9
references.pmid: 15319610