title: Estimating effectiveness in an observational study: a case study of dornase alfa in cystic fibrosis. The Investigators and Coordinators of the Epidemiologic Study of Cystic Fibrosis.
abstract: Patients with cystic fibrosis (CF) receiving dornase-alfa had improved pulmonary function relative to a control group in a large randomized phase III controlled study. We reviewed data from a large observational phase IV study to estimate the observed drug effect in patients receiving dornase alfa as part of their routine care. Patients 6 years or older and with a baseline forced expiratory volume in 1 second (FEV1) of at least 40% predicted who had been enrolled for at least 18 months were included (n = 283). The control group consisted of 2382 patients who had never received dornase alfa. Patients in the study had a baseline spirometry and a second spirometry recorded 12 months later; a baseline observation period of 6 months preceded the initial spirometry, and dornase alfa had to have been started after the baseline spirometry (within 3 months) and to have continued through the 12-month follow-up spirometry. Patients treated with dornase alfa had lower pulmonary functions, more bacterial colonization, and more exacerbations at baseline (FEV1 : 76.0% vs 87.6%, Pseudomonas aeruginosa : 64.1% vs 46.7%, pulmonary exacerbations during the previous 6 months: 56.4% vs 22. 2%). Mean values of FEV1 for patients treated with dornase alfa improved by 3.9% of predicted compared with a decline of 1.6% in the untreated cohort. Covariate adjustment provided an estimated benefit of dornase alfa of 4.3% predicted FEV1 (SE = 0.9, P <.0001). This analysis provides evidence for the effectiveness of dornase alfa therapy in clinical practice.
authors.affiliation: Genentech, Inc, South San Francisco, California, Rainbow Babies and Children's Hospital, Cleveland, Ohio, USA.
authors.forename: C A
authors.initials: CA
authors.lastname: Johnson
authors.forename: S M
authors.initials: SM
authors.lastname: Butler
authors.forename: M W
authors.initials: MW
authors.lastname: Konstan
authors.forename: T J
authors.initials: TJ
authors.lastname: Breen
authors.forename: W J
authors.initials: WJ
authors.lastname: Morgan
mesh_terms: D002648:Child; D003550:Cystic Fibrosis / Q000188:drug therapy* / Q000503:physiopathology; D003850:Deoxyribonuclease I / Q000627:therapeutic use*; D005100:Expectorants / Q000627:therapeutic use*; D005260:Female; D005500:Follow-Up Studies; D005541:Forced Expiratory Volume; D006801:Humans; D008297:Male; D011446:Prospective Studies; D011994:Recombinant Proteins / Q000627:therapeutic use; D012044:Regression Analysis; D012720:Severity of Illness Index; D013147:Spirometry
chemical_list: D005100:Expectorants; D011994:Recombinant Proteins; C085693:DNASE1 protein, human; D003850:Deoxyribonuclease I