Using serum urate as a validated surrogate end point for flares in patients with gout: protocol for a systematic review and meta-regression analysis

Melanie Birger Morillon, L. Stamp, E W Taylor, J. Fransen, N. Dalbeth, J A Singh, Robin Christensen, M. Lassere

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Abstract

INTRODUCTION: Gout is the most common inflammatory arthritis in men over 40 years of age. Long-term urate-lowering therapy is considered a key strategy for effective gout management. The primary outcome measure for efficacy in clinical trials of urate-lowering therapy is serum urate levels, effectively acting as a surrogate for patient-centred outcomes such as frequency of gout attacks or pain. Yet it is not clearly demonstrated that the strength of the relationship between serum urate and clinically relevant outcomes is sufficiently strong for serum urate to be considered an adequate surrogate. Our objective is to investigate the strength of the relationship between changes in serum urate in randomised controlled trials and changes in clinically relevant outcomes according to the 'Biomarker-Surrogacy Evaluation Schema version 3' (BSES3), documenting the validity of selected instruments by applying the 'OMERACT Filter 2.0'.

METHODS AND ANALYSIS: A systematic review described in terms of the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) reporting guidelines will identify all relevant studies. Standardised data elements will be extracted from each study by 2 independent reviewers and disagreements are resolved by discussion. The data will be analysed by meta-regression of the between-arm differences in the change in serum urate level (independent variable) from baseline to 3 months (or 6 and 12 months if 3-month values are not available) against flare rate, tophus size and number and pain at the final study visit (dependent variables).

ETHICS AND DISSEMINATION: This study will not require specific ethics approval since it is based on analysis of published (aggregated) data. The intended audience will include healthcare researchers, policymakers and clinicians. Results of the study will be disseminated by peer-reviewed publications.

TRIAL REGISTRATION NUMBER: CRD42016026991.

Original languageEnglish
JournalBMJ Open
Volume6
Issue number9
Number of pages7
ISSN2044-6055
DOIs
Publication statusPublished - 20. Sept 2016

Bibliographical note

ISI Document Delivery No.: EG8JL Times Cited: 0 Cited Reference Count: 26 Morillon, Melanie B. Stamp, Lisa Taylor, William Fransen, Jaap Dalbeth, Nicola Singh, Jasvinder A. Christensen, Robin Lassere, Marissa Christensen, Robin/0000-0002-6600-0631 Oak Foundation Musculoskeletal Statistics Unit at the Parker Institute is supported by grants from the Oak Foundation. 0 Bmj publishing group London

Keywords

  • threshold effect ste hierarchical levels evaluation schema management survival trials metaanalysis criteria cancer hyperuricemia General & Internal Medicine
  • SURROGATE
  • BIOMARKER
  • OUTCOME
  • GOUT
  • RHEUMATOLOGY
  • Gout/blood
  • Reproducibility of Results
  • Humans
  • Uric Acid/blood
  • Systematic Reviews as Topic
  • Biomarkers/blood
  • Research Design

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