PRECISE — pregabalin in addition to usual care: statistical analysis plan. Issue 1 (December 2016)

• Record Type: Journal Article
• Authors: Mathieson, Stephanie; Billot, Laurent; Maher, Christopher; McLachlan, Andrew; Latimer, Jane; Koes, Bart; Hancock, Mark; Harris, Ian; Day, Richard; Pik, Justin; Jan, Stephen; Lin, Chung-Wei
• Is Part Of: Trials. Volume 17:Issue 1(2016)
• Page Start: 1
• Page End: 10
• Publication Date: 2016-12
• Subjects: Sciatica -- Pregabalin -- Statistical analysis plan -- Randomised controlled trial -- Placebo; Group-randomized trials -- Periodicals; Randomized Controlled Trials -- Periodicals; 615.0727
• DOI: 10.1186/s13063-016-1174-y
• Languages: English
• ISSNs: 1745-6215

Abstract

Abstract Background Sciatica is a severe, disabling condition that lacks high quality evidence for effective treatment strategies. Thisa priori statistical analysis plan describes the methodology of analysis for the PRECISE study. Methods/design 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 ap 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. Discussion 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. Trial registration Australian and New Zealand Clinical Trials Registry (ACTRN12613000530729 . Registered 13 May 2013)