COPD Treatment Effectiveness Protocol

Full eligibility criteria for Study 207626 have been published previously.19 (link) Patients were eligible to participate if they had a post-bronchodilator FEV₁ of <50% predicted and COPD Assessment Test (CAT) score ≥10 or FEV₁ <80% predicted with a documented history of ≥2 moderate exacerbations or ≥1 severe exacerbation (requiring hospitalization) in the previous 12 months and a CAT score ≥10. Patients were required to receive daily maintenance treatment with TIO monotherapy for ≥3 months prior to screening.
Data for pooled baseline characteristics, based on the intent-to-treat (ITT) population of Study 2076260 (N=800)19 (link) were included in the model (Table 1). The mean age of the study population was 66.2 years and 32% were female.19 (link) Baseline FEV₁% predicted was 50.0%.
Table 1

Model inputs

	Total
	N=800a
Patient demographics (ITT population Study 207626)
Age, years, meana (SE)b	66.2a (0.3)
Sex, female, %	32.1
BMIc, %
Low	10.9
Medium	60.1
High	29.0
Any CVD comorbidity, %	54.8
Any other comorbidity, %	23.9
History of ≥1 exacerbationd, %	79.3
mMRC score ≥2e, %	48.1
Current smoker, %a	47.6a
Height, cm, mean (SE)b	169.7 (0.3)
Exacerbationsd in previous year, mean	1.4
Moderate exacerbations, mean	1.2
Severe exacerbations, mean	0.2
Baseline SGRQ, mean (SE)b	48.9 (0.6)
Baseline FEV1% predicted, meana (SE)b	50.0a (0.5)
Treatment effects (Study 207626)
Endpoint (12 weeks)	FF/UMEC/VI versus TIO
FEV1 increment, mean (95% CI) mL difference	95.0 (62, 128)
SGRQ change, mean (95% CI) score difference	−3.2 (−5.0, −1.4)
Exacerbation reduction, relative risk	No differencef

Notes: ^a19 (link)
^bCalculated as SD/√(N). ^cLow: <21, medium: ≥21 to ≤30, high: >30. ^dModerate or severe. ^eAssumed the same as CAT ≥21. ^fTreatment effect input on exacerbation reduction was set to “no difference” as the relative risk reduction of exacerbations was not included as an endpoint in Study 207626.

Abbreviations: BMI, body mass index; CAT, COPD Assessment Test; CI, confidence interval; COPD, chronic obstructive pulmonary disease; CVD, cardiovascular disease; FEV₁, forced expiratory volume in 1 second; FF, fluticasone furoate; ITT, intent-to-treat; mMRC, modified Medical Research Council; SD, standard deviation; SE, standard error; SGRQ, St George’s Respiratory Questionnaire; TIO, tiotropium; UMEC, umeclidinium; VI, vilanterol.

Model risk equations include, as covariates, baseline values for age, sex, body mass index, cardiovascular disease and other comorbidities, smoking status, fibrinogen level, modified Medical Research Council (mMRC) dyspnea scale score, FEV₁% predicted, prior exacerbation history, St George’s Respiratory Questionnaire (SGRQ) score, 6-minute walk test (6MWT), and height.
For parameters that were not available directly from Study 207626 data (ie baseline mMRC, fibrinogen, and 6MWT), estimates were made using risk equations or analogous data collected in the trial. Further details on the methods used to derive values for these parameters are provided in Supplementary Appendix 1.