Pasta DJ, Rasouliyan L. A mixed-effects piecewise linear model of the rate of lung function decline before and after inhaled corticosteroids in an observational study of children with cystic fibrosis. Poster presented at the International Society of Pharmacoeconomics and Outcomes Research 3rd Latin America Conference; September 2011. Mexico City, Mexico. [abstract] Value Health. 2011 Nov; 14(7):A564. doi: 10.1016/j.jval.2011.08.1691.

OBJECTIVES: To evaluate the change in the rate of lung function decline before and after initiation of inhaled corticosteroids (ICS) in children enrolled in the Epidemiologic Study of Cystic Fibrosis (ESCF) through a multivariable mixed-effects piecewise linear model.

METHODS: The primary outcome measure was the long-term rate of change in percent predicted forced expiratory volume in 1 second (pp FEV1). Patients aged 6-17 years who had been enrolled in ESCF for 2 years, when initially treated with ICS therapy, were selected if they remained on treatment for at least 80% of their visits during the following 2 years. A comparator group included patients aged 6-17 who did not receive ICS for 4 consecutive years. The index date was defined as date of ICS initiation (ICS group) or the patient’s even-numbered (8th- 16th) birthday (comparator group). For each patient we estimated the annual rate of decline in pp FEV1 before and after index using a mixed-effects piecewise linear model adjusted for age, gender, pulmonary exacerbations, routine therapies, and nutritional supplements. Model results were used to draw comparisons within and between study groups.

RESULTS: Before initiation of ICS, mean FEV1 decline was -1.52 pp/year (95% CI: -1.96, -1.08 pp/year). After initiation of ICS therapy, mean FEV1 decline was -0.44 pp/year (95% CI: -0.85, -0.03 pp/year), which was a significant change (p0.002). In contrast to our observations in the ICS group, patients in the comparator group had a mean FEV1 decline of -1.01 pp/year (95% CI: -1.27, -0.75 pp/year) before index, which marginally worsened (p0.046) after index to -1.44 pp/year (95% CI: -1.70 to -1.19 pp/year).

Initiation of ICS was associated with a significantly slower subsequent rate of FEV1 decline in children with cystic fibrosis. Mixed-effects piecewise linear models are valuable for analyzing observational studies by demonstrating changes in key disease measures corresponding to the times of interventions.

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