Centre effects and case-mix in early rheumatoid arthritis observational cohorts: a narrative review

OBJECTIVES: Observational cohort studies in early RA are a key source of evidence, despite inconsistencies in methodological approaches. This narrative review assesses the spectrum of methodologies used in addressing centre-level effect and case-mix adjustment in early RA observational cohort studies. METHODS: An electronic search was undertaken to identify observational prospective cohorts of >100 patients recruited from two or more centres, within 2 years of an RA or early inflammatory arthritis diagnosis. References and author publication lists of all studies from eligible cohorts were assessed for additional cohorts. RESULTS: Thirty-four unique cohorts were identified from 204 studies. Seven percent of studies considered centre in their analyses, most commonly as a fixed effect in regression modelling. Reporting of case-mix variables in analyses varied widely. The number of variables considered in case-mix adjustment was higher following publication of the STrengthening the Reporting of OBservational studies in Epidemiology (STROBE) statement in 2007. CONCLUSION: Centre effect is unreported or inadequately accounted for in the majority of RA observational cohorts, potentially leading to spurious inferences and obstructing comparisons between studies. Inadequate case-mix adjustment precludes meaningful comparisons between centres. Appropriate methodology to account for centre and case-mix adjustment should be considered at the outset of analyses.