Table 1 Summary of Markov Model parameters included in the base-case and one-way deterministic sensitivity analyses

Baseline characteristics

 Age at start, mean

41.0 years

32.8/49.2 years

Gamma (Likely skewed nature of age, and its constraint to positive values)

SYGMA 2 [19]

Annual severe exacerbation rate

 As-needed budesonide-formoterol (95% CI)

0.11 (0.10–0.13)

0.088/0.132

Beta (α = 88.89, β = 719.20)

SYGMA 2 [19]

 Low-dose maintenance ICS + as-needed SABA (95% CI)

0.12 (0.10–0.14)

0.096/0.144

Beta (α = 87.88, β = 644.45)

Distribution of patients by severe exacerbation health states

 As-needed budesonide-formoterol

  SCS

81.9%

Dirichlet (The percentages across severe exacerbation management states must sum to 100%)

  ED + SCS

10.2%

SYGMA 2 [19]

  Inpatient hospitalization

7.9%

 Low-dose maintenance ICS + as-needed SABA

  SCS

78.4%

  ED + SCS

15.2%

  Inpatient hospitalization

6.4%

Annual moderate exacerbation rate

 As-needed budesonide-formoterol

Not included

0.07

N/A

SYGMA 1 [18]

 Low-dose maintenance ICS + as-needed SABA

Not included

0.06

Annual rate of withdrawal

 As-needed budesonide-formoterol

Not included

SYGMA 1: 0.8%, SYGMA 2: 0.7%

Dirichlet (The percentages across severe exacerbation management states must sum to 100%)

SYGMA 1 [18], SYGMA 2 [19]

 Low-dose maintenance ICS + as-needed SABA

Not included

SYGMA 1: 1.2%, SYGMA 2: 1.1%

Annual proportion of adverse events

 As-needed budesonide-formoterol vs low-dose maintenance ICS + as-needed SABA

N/A

SYGMA 2 [19]

  Viral URTI

7.4% vs. 8.0%

Beta (α = 95.53, β = 1157.83) vs. (α = 91.92, β = 1057.08)

  URTI

3.9% vs. 4.3%

Beta (α = 96.06, β = 2367.04) vs. (α = 95.66, β = 2128.92)

  Bronchitis

3.1% vs. 3.7%

Beta (α = 96.87, β = 3027.94) vs. (α = 96.26, β = 2505.44)

  Pharyngitis

2.4% vs. 3.0%

Beta (α = 97.58, β = 3968.09) vs. (α = 96.97, β = 3135.36)

  Headache

2.5% vs. 2.4%

Beta (α = 97.48, β = 3801.53) vs. (α = 97.58, β = 3968.09)

  Allergic rhinitis

2.4% vs. 2.1%

Beta (α = 97.58, β = 3968.09) vs. (α = 97.88, β = 4563.03)

  Influenza

1.6% vs. 2.1%

Beta (α = 98.38, β = 6050.62) vs. (α = 97.88, β = 4563.03)

Medication, inhalations/day

 As-needed budesonide-formoterol

0.52

N/A

Gamma (α = 100, β = 0.0052)

SYGMA 2 [19]

 Low-dose ICS

2.00

1.60/2.40

Gamma (α = 100, β = 0.02)

Fluticasone PI [54]

 As-needed SABA when combined with low-dose ICS

0.49

N/A

Gamma (α = 100, β = 0.0049)

SYGMA 2 [19]

Direct medical costs

 Severe exacerbation, per event^a

Gamma (Likely skewed nature of healthcare costs, and their constraint to positive values)

SYGMA 2 [19]

  SCS

$155.14

$124.11/$186.16

  ED + SCS

$490.81

$392.64/$588.97

  Inpatient hospitalization

$9399.94

$7519.95/$11,279.92

 Non-exacerbation health state (weekly)

$38.40

$30.72/$46.08

 Adverse events

 Viral URTI

$7909.00

 URTI

$7909.00

 Bronchitis

$157.00

 Pharyngitis

$157.00

 Headache

$157.00

 Allergic rhinitis

$157.00

 Influenza

$6038.00

Drug acquisition costs, per day

 As-needed budesonide-formoterol

$0.39

N/A

Fixed^b

SYGMA 2 [19]

 Low-dose maintenance ICS

$0.72

N/A

 As-needed SABA for patients on low-dose maintenance ICS

$0.01

N/A

Utility inputs for health states^c

 Utility of non-exacerbation

0.867

0.694/1.000

Beta (α = 12.43, β = 1.91)

SYGMA 2 (EQ-5D) [19]

 Disutility of severe exacerbation

  SCS

− 0.10

− 0.08/− 0.12

− Beta^d (α = 110.1, β = 1211.1)

Lloyd 2006[44]

  ED + SCS

− 0.15

− 0.12/− 0.18

− Beta (α = 115.15, β = 882.8)

Assumption

  Inpatient hospitalization

− 0.20

− 0.16/− 0.24

− Beta (α = 120.2, β = 721.2)

Lloyd 2006[44]

 Disutility of moderate exacerbation

Not included

− 0.04/− 0.06

− Beta (α = 105.05, β = 2206.05)

Assumption^e

Discount rate^f

1.5%

0.0%/3.0%

N/A