We reviewed the clinical measures used in rheumatoid arthritis (RA) economic evaluations with respect to their relevance and sensitivity to changes in survival, health-related quality of life (HR-QOL) and costs. We compared the measures from the economic perspective and discussed the validity of methods used to extrapolate beyond the trial data. Cost-effectiveness evaluations of disease-modifying antirheumatic drugs in RA were identified by searching MEDLINE, EMBASE, Econlit and NHS EED databases. Studies were retained if they extrapolated beyond randomized controlled trial evidence using relationships between clinical measures, costs and utilities. In the 22 studies identified, clinical severity was measured using the Health Assessment Questionnaire (HAQ) Disability Index, the American College of Rheumatology (ACR) response criteria, the Disease Activity Score (DAS) or a combination of the HAQ and DAS. The HAQ is correlated with mortality, costs and HR-QOL instruments, and several studies used linear relationships to model these associations. However, a polynomial relationship or discrete states may be more appropriate for patients at the extremes of the disease spectrum, and numerous HAQ health states may be required to capture differences in mortality risk. While the ACR response criteria is a more comprehensive measure than the HAQ, it is a relative measure, which creates difficulties when estimating absolute changes in HR-QOL, costs and mortality risk. The evidence base linking DAS scores with HR-QOL instruments, costs and mortality is less robust, possibly due to the comparatively recent development of the measure and the limited number of possible scores (mild/moderate/severe). While there is some evidence of a relationship between DAS scores and costs, the DAS does not capture all aspects of HR-QOL, and no significant relationship has been established with mortality risk. Evidence suggests the HAQ to be the primary clinical measure for use in economic evaluations as it is measured in almost all clinical studies, and is closely correlated to health utilities, mortality and costs. While new developments suggest the sensitivity of health states may be improved by combining the HAQ with measures such as the DAS, further research is required in this area. Further research is also required to explore the advantages in using either continuous or discrete health states.
