OBJECTIVES: This three-year, international, multicentre, longitudinal, observational, cost-effectiveness study named RaDiCEA (RareDisease &Cost-EffectivenessAnalysis) will assess the economic evaluation (cost of illness - COI and cost-effectiveness analisys - CEA) of innovative therapies (i.e., anti IL-1 agents), quality of life (QoL) and effects of the prevention of otherwise irreversible central nervous system, eye, ear, kidney, and cartilage damages of different treatment strategies for cryopyrin-associated periodic syndromes (CAPS) of adults and children. METHODS: A virtual time-cohort approach and a Markov model simulating health states corresponding to different CAPS severity will be developed to assess the cost-effectiveness of either anti IL-1 agents or other than anti IL-1. Due to the lack of a CAPS-specific severity index/damage score, a linear combination of existing indexes and damage scores related to specific organs and systems will be used to rank patient’s health statu. Coefficients of the resulting function will be assigned following a top-down (Delphi) approach and an interim-ex post principal component analysis. The model quantifies resource utilization for patients’ care in the National Health Systems’ perspectives and a broader societal perspective. QoL will be evaluated using EQ-5D questionnaires. Robustness of outcomes wil be tested through univariate and probabilistic sensitivity analyses. RESULTS: The RaDiCEA project will assess the long-term effectiveness of different potentially life-long treatment strategies and COI, while exploring the feasibility of a new CEA model to be generated from a rare disease (CAPS) observational study. The economic outcomes will be given as the number of years spent in each health state, the related yearly costs and QoL. CONCLUSIONS: The importance and novelty of the model is twofold: i) in its application, adopting the cost-effectiveness approach for assessing the impact of CAPS therapies, and ii) in the methods, extending the analyses of the impact of CAPS therapies in reducing the speed of disease progression.