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Table 5 Results from the joint frailty model, including selected covariates, when applied to the pooled datasets

From: Improving the evaluation of COPD exacerbation treatment effects by accounting for early treatment discontinuations: a post-hoc analysis of randomized clinical trials

 Exacerbations (moderate/severe)Early treatment discontinuations
Pooled A-C
HR (95% CI)
Pooled D-E
HR (95% CI)
Pooled A-C
HR (95% CI)
Pooled D-E
HR (95% CI)
Demographics
 Age (+ 1 year)1.00 (0.99–1.00)1.00 (0.99–1.00)1.01 (1.00–1.02)1.01 (1.00–1.03)
 Sex (male vs female)  1.29 (1.06–1.56)1.24 (1.00–1.55)
Region
 Western Europe vs US1.10 (0.91–1.34)1.56 (1.28–1.90)0.59 (0.43–0.82)1.27 (0.86–1.87)
 Eastern Europe vs US0.49 (0.42–0.57)0.61 (0.52–0.71)0.21 (0.16–0.28)0.45 (0.34–0.61)
 Rest of the World vs US0.83 (0.70–0.99)0.83 (0.73–0.95)0.30 (0.22–0.41)0.50 (0.39–0.64)
Treatment
 BUD/FM 320 vs FM0.71 (0.61–0.82) 0.73 (0.56–0.94) 
 BUD/FM 160 vs FM0.71 (0.61–0.83) 0.75 (0.59–0.97) 
 BUD 320 + FM vs FM0.57 (0.42–0.77) 0.58 (0.36–0.94) 
 BUD 320 vs FM0.77 (0.58–1.04) 1.03 (0.65–1.64) 
 PBO vs FM1.20 (1.00–1.44) 1.12 (0.84–1.50) 
 SOC + RFL vs SOC 0.88 (0.80–0.97) 1.61 (1.34–1.94)
Disease related baseline factors
 Exacerbation history
 (+ 1 previous year)
1.16 (1.12–1.21)1.21 (1.14–1.28)  
 Smoking history
 (+ 10 pack-years)
1.02 (1.01–1.04)   
 ICS history (yes vs no)1.19 (1.06–1.34)   
 Bronchodilator history
 (yes vs no)
1.30 (1.16–1.46)   
 FEV1 (+ 100 mL)0.92 (0.90–0.93)0.52 (0.45–0.61)0.7 (0.53–0.93)0.551 (0.40–0.76)
 SGRQ total score (+ 10 points)1.04 (1.00–1.09) 1.01 (1.00–1.02) 
 Breathlessness (+ 1 point)1.11 (1.02–1.21)   
 CAT total score (+ 5 points) 1.09 (1.05–1.13) 1.02 (1.00–1.03)
 Use of rescue medication
 (+ 1 puff)
1.04 (1.03–1.06)1.03 (1.02–1.04)1.04 (1.01–1.06) 
Seasonality
 Spring vs Autumn0.76 (0.68–0.85)1.00 (0.90–1.11)  
 Summer vs Autumn0.69 (0.61–0.77)0.78 (0.70–0.87)  
 Winter vs Autumn1.07 (0.97–1.19)1.17 (1.06–1.29)  
Trial effect
 A vs C0.76 (0.65–0.89) 0.86 (0.67–1.10) 
 B vs C0.85 (0.70–1.03) 0.78 (0.57–1.07) 
 E vs D 1.08 (0.94–1.25) 1.64 (1.20–2.24)
 Association parameters*
 Pooled A-CPooled D-E
Frailty variance1.14 (SE = 0.07)0.67 (SE = 0.05)
Association (α)1.54 (SE = 0.15)0.95 (SE = 0.17)
  1. BUD budesonide, FM formoterol, RFL roflumilast, ICS inhaled corticosteroids, HR hazard ratio, CI confidence interval, SE standard error, US United States, * - all parameters significantly different from zero with p-value < 0.0001