Methods
Dispensing records from the University of North Carolina (UNC) Health System home delivery pharmacy were used to assess all filled prescriptions for PwCF prescribed CFTR modulator therapy from Nov 2016 to Aug 2021. To restrict the analysis to those who regularly filled modulators through our pharmacy, the population was limited to those who filled ≥3 modulator prescriptions over that time frame. Data was obtained for medication fills for dornase alpha (Dorn), hypertonic saline (HTS), and pancreatic enzymes (PERT), and inhaled tobramycin. The study was approved by the institutional IRB (#21-1137).
Medication utilization was measured as medication possession ratio (actual months filled/prescribed months, MPR). For each individual, MPR was calculated over a time interval beginning with the first prescription of any of these medications and ending with the last prescription and were calculated separately for the pre- and post-ETI intervals. For inhaled tobramycin, infrequent pharmacy fills (typically prescribed every other month) plus intermittent use for acute exacerbations raised doubts about the accuracy of MPR values, and this medication was not evaluated further. To exclude individuals who did not receive medications regularly from our home delivery pharmacy, individuals with fewer than six total fills for a given medication within the interval were excluded. For longitudinal evaluation, the number of pharmacy fills for a given month pre- or post-ETI was determined for all individuals prescribed the medication. Medications dispensed for 55-60 days were counted as filled for two months total, and medications dispensed for 85-90 days counted as three months. MPRs for the group were calculated as the total number of fills in a given month for the medication divided by the number of individuals prescribed the medication in that month.
For associations to lung function, percent predicted FEV1 (ppFEV1) was extracted from UNC access to the CF Foundation Patient Registry. To ensure sufficient data to calculate accurate changes over time, subjects were limited to those who had at least three ppFEV1 values over at least one year before and three ppFEV1 values over at least one year after initiation of ETI. Slope ppFEV1 was calculated by linear regression separately in both pre- and post-ETI intervals for each individual. Between group analyses were performed using Student’s T-test, and correlation analyses by linear regression.