The clinical effectiveness and cost-effectiveness of enzyme replacement therapy for Gaucher's disease: a systematic review

摘要: OBJECTIVES The aim of this review is to determine the clinical effectiveness and cost-effectiveness enzyme replacement therapy (ERT) in treatment symptomatic Gaucher's disease. DATA SOURCES Major electronic databases were searched from their inception August 2003; updated January 2003 July/August 2004. REVIEW METHODS Databases for studies that met criteria selected data extracted evaluated. Studies assessed relevance UK context objective. bibliographic also identify existing cost studies, economic evaluations models. A Markov decision model was constructed based on patients moving between states defined by modified Severity Score Index (SSI). Most parameters derived published literature. ERT assumed restore full health base case. RESULTS Sixty-three included, all suggestive benefit with ERT. However, way which effects translate into patient well-being survival or need services resources has not been reliably estimated. Quality life improvements have reported. Nonetheless, Short Form 36 (SF-36) indicate treated continue reduced health-related quality (HRQoL) compared general population. No study attached utility values measures ERT-treated patients. Thirty-one relevant natural history disease found. Sixteen looked at multiple characteristics a cohort type I There considerable within-study between-study heterogeneity, but showed progressive condition. Some suggested may become more indolent adulthood; however, discrepant point. diagnosed adulthood, although about one-quarter presented childhood, these having most severe symptoms greatest rate progression. Modelling undertaken using five papers reported SSI each patient, along patient-level age, age diagnosis, splenectomy status genotype, address question whether stabilises adulthood degree correlation phenotype genotype. Analysis available progression likely slow markedly genotype useful predictor expression Five life. Data topic obtained registries. evidence suggests vast majority little impact subjective HRQoL therefore people be Bone skeletal contribute morbidity can lead pain immobility. mean per approximately pounds sterling 86,000 annum England Wales. varied considerably dose. Four found, calculated very high quality-adjusted life-year (QALY). Using model, estimated incremental QALY [incremental ratio (ICER)] case ranged 380,000 476,000 QALY, depending Univariate sensitivity analyses examined restoring health, untreated cohort, only treating severely affected These produced ICERs 1.4 million, 296,000 275,000 respectively. base-case unit drug 2.975. would had ten-fold, 0.30, obtain an ICER 30,000 QALY. At 1 120,000 CONCLUSIONS Although 'average' exceeds normal upper threshold seen NHS policy decisions over some argue since orphan legislation encouraged manufacture Cerezyme, as disease, option provide it, despite its great expense. More information required before generalisability findings determined. used wherever possible, thin indeed. even large errors estimates distribution genotype--phenotype associations, numbers will reduce anywhere near level treatments usually considered cost-effective. Further research could help clarify many uncertainties exist. doing so interest, it questionable whether, within current pricing environment, such any substantive decisions. It highly improbable that, whatever research, brought down orders magnitude make efficient use service resources. (The possible exception investigating alternative strategies paediatric population only.) Moreover, if under equity considerations diseases feels important drug, regardless cost-effectiveness, then refining precision estimate becomes superfluous.