A Delphi Consensus Document on the Use of Single-Inhaler Fixed-Dose Triple Therapies in COPD Patients

Figures & data

Figure 1 Results of the degree of agreement among the panelists after the 1st and 2nd Delphi rounds. (N) number of panelists that participated in the Delphi round.

Table 1 Results of the Degree of Agreement Among the Panelists with the Statements Regarding Efficacy of Single-Inhaler Fixed Triple Therapy vs LABA/LAMA, LABA/ICS and Open Triple Therapy After the two Delphi Rounds

#	Statement	% Agreement	Round*	Final Results
a. Efficacy of single-inhaler fixed triple therapy vs double therapy LABA/LAMA
1	In a non-exacerbator COPD patient, with eosinophilia ≥300, single-inhaler fixed triple therapy is indicated before dual LABA/LAMA.	55.56% Disagreement	2	Divergence
2	When deciding to use single-inhaler fixed triple therapy vs dual LABA/LAMA therapy, the COPD phenotype of the patient is taken into account.	91.11% Agreement	1	Consensus
3	Single-inhaler fixed triple therapy is more effective than dual LABA/LAMA therapy to improve the pulmonary function	44.44% Agreement	2	Divergence
4	Single-inhaler fixed triple therapy is more effective than dual LABA/LAMA therapy to improve dyspnea in symptomatic patients (CAT>10), independently of FEV1 and of the number of previous exacerbations.	80.00% Disagreement	2	Consensus
5a	Single-inhaler fixed triple therapy significantly improves the health-related quality of life (measured by the St. George’s Respiratory Questionnaire (SGRQ)) compared to dual LABA/LAMA therapy.	62.22% Agreement	2	Divergence
5b	In your clinical practice, the single-inhaler fixed triple therapy improves the health-related quality of life when compared with dual LABA/LAMA therapy.	46.67% Agreement	2	Divergence
6a	Single-inhaler fixed triple therapy is more effective than dual LABA/LAMA therapy to reduce the number of exacerbations in a patient with COPD and FEV1 < 50%	62.22% Agreement	2	Divergence
6b	Single-inhaler fixed triple therapy is more effective than dual LABA/LAMA therapy to reduce the number of exacerbations in a patient with COPD and frequent exacerbations.	77.78% Agreement	2	Majority
7	In COPD patients treated with dual LABA/LAMA therapy hospitalized because of one severe or two moderate exacerbations, the treatment must be escalated to single-inhaler fixed triple therapy independently of the number of eosinophils.	84.44% Agreement	2	Consensus
8	In COPD patients treated with dual LABA/LAMA therapy hospitalized because of one severe or two moderate exacerbations and with a number of eosinophils <100, the treatment must be escalated to single-inhaler fixed triple therapy	51.11% Agreement	2	Divergence
9a	Single-inhaler fixed triple therapy improves COPD patients’ survival compared to dual LABA/LAMA therapy	44.44% NAND	2	Divergence
9b	Single-inhaler fixed triple therapy improves survival of COPD patients with frequent exacerbations compared to dual LABA/LAMA therapy	66.67% Agreement	2	Majority
b. Efficacy of single-inhaler fixed triple therapy vs dual LABA/ICS therapy
10	In a COPD patient receiving monotherapy LABA or LAMA it is correct to escalate to single-inhaler fixed triple therapy skipping dual LABA/ICS therapy	62.22% Disagreement	2	Divergence
11	Single-inhaler fixed triple therapy is more effective than dual LABA/ICS therapy to improve pulmonary function	84.44% Agreement	1	Consensus
12	Single-inhaler fixed triple therapy is more effective than dual LABA/ICS therapy to improve the symptoms	95.56% Agreement	2	Consensus
13	Single-inhaler fixed triple therapy is more effective than dual LABA/ICS therapy to improve dyspnea in symptomatic patients (CAT>10), independently of FEV1 and of the number of previous exacerbations	95.56% Agreement	2	Consensus
14a	Single-inhaler fixed triple therapy significantly improves the health-related quality of life (measured by the SGRQ questionnaire) compared with dual LABA/ICS therapy	95.56% Agreement	2	Consensus
14b	In your clinical practice, single-inhaler fixed triple therapy significantly improves health-related quality of life compared to dual LABA/ICS therapy	75.56% Agreement	2	Majority
15a	Single-inhaler fixed triple therapy is more effective than dual LABA/ICS therapy reducing the number of exacerbations in a COPD patient with FEV1 < 50%	84.44% Agreement	2	Consensus
15b	Single-inhaler fixed triple therapy is more effective than dual LABA/ICS therapy reducing the number of exacerbations in a COPD patient with frequent exacerbations	93.33% Agreement	2	Consensus
16	In COPD patients treated with dual LABA/ICS therapy hospitalized because of one severe or two moderate exacerbations, the treatment must be escalated to single-inhaler fixed triple therapy, independently of the number of eosinophils	80.00% Agreement	2	Consensus
17	In COPD patients treated with dual LABA/ICS therapy hospitalized because of one severe or two moderated exacerbations and with a number of eosinophils < 100, the treatment must be escalated to single-inhaler fixed triple therapy	68.89% Agreement	2	Majority
18a	Single-inhaler fixed triple therapy improves survival in COPD patients compared to dual LABA/ICS therapy	57.78% Agreement	2	Divergence
18b	Single-inhaler fixed triple therapy improves survival in COPD patients with frequent exacerbations compared to dual LABA/ICS therapy	62.22% Agreement	2	Divergence
c. Efficacy of single-inhaler fixed triple therapy
19	Based on your clinical experience, currently efficacy differences exist among the known single-inhaler fixed triple therapies	57.78% NAND^2	2	Divergence
20	Single-inhaler fixed triple therapy is more effective than open triple therapy in improving the pulmonary function	46.67% NAND^2	2	Divergence
21	Single-inhaler fixed triple therapy is more effective than open triple therapy in improving dyspnea	64.44% Agreement^2	2	Divergence
22	Single-inhaler fixed triple therapy is more effective than open triple therapy in improving quality of life	62.22% Agreement^2	2	Divergence
23	Single-inhaler fixed triple therapy is more effective than open triple therapy in reducing the number of moderate and severe exacerbations	42.22% Disagreement^2	2	Divergence
24	In the subgroup of patients suffering >1 moderate-severe exacerbation in the 12 previous months, the single-inhaler fixed triple therapy is more effective than open triple therapy in reducing the number of moderate-severe exacerbations	44.44% Agreement^2	2	Divergence

Notes: The final results were determined considering the degree of agreement among the panellists meant consensus: ≥80%; majority ≥66%; or divergence (<66%). NAND: neither agreement nor disagreement. *Indicates the round where the degree of agreement shown was reached. In bold those words changed from round one to round two.

Table 2 Results of the Degree of Agreement of the Panelists with the Statements Regarding Safety of Single-Inhaler Fixed Triple Therapy vs LABA/LAMA, LABA/ICS and Open Triple Therapy After the two Delphi Rounds

#	Statement	% Agreement	Round*	Final Results
a. General safety of single-inhaler fixed triple therapy
25	Based on your clinical experience, currently differences exist in the safety profile of the different known single-inhaler fixed triple therapies	62.22% Disagreement^2	2	Divergence
b. Safety of single-inhaler fixed triple therapy vs dual LABA/LAMA therapy
26	Single-inhaler fixed triple therapy has the same risk of producing pneumonia than dual LABA/LAMA therapy	86.67% Disagreement^2	2	Consensus
27	Single-inhaler fixed triple therapy produces similar cardiovascular adverse effects to those produced by dual LABA/LAMA therapy	82.22% Agreement^1	1	Consensus
28	Single-inhaler fixed triple therapy produces similar local adverse effects to those produced by dual LABA/LAMA therapy	82.22% Disagreement^2	2	Consensus
c. Safety of single-inhaler fixed triple therapy vs dual LABA/ICS therapy
29	Single-inhaler fixed triple therapy causes more pneumonia cases than dual LABA/ICS therapy	80.00% Disagreement^1	1	Consensus
30	Single-inhaler fixed triple therapy produces similar cardiovascular adverse effects to those produced by dual LABA/ICS therapy	88.89% Agreement^2	2	Consensus
d. Single-inhaler fixed triple therapy vs open triple therapy
31	Single-inhaler fixed triple therapy causes more pneumonia cases than open triple therapy	86.67% Disagreement^1	1	Consensus
32	Single-inhaler fixed triple therapy produces similar cardiovascular adverse effects to those produced by open triple therapy	82.22% Agreement^1	1	Consensus
33	Single-inhaler fixed triple therapy produces similar local adverse effects to those produced by open triple therapy	84.44% Agreement^1	1	Consensus

Notes: The final results were determined considering the degree of agreement among the panelists: consensus ≥80%; majority ≥66%; or divergence (<66%). NAND: neither agreement nor disagreement. *Indicates the round where the degree of agreement shown was reached. In bold are words changed from round one to round two.

Table 3 Results of the Degree of Agreement Among the Panelists with the Statements Regarding Treatment with Single-Inhaler Fixed Triple Therapy in Specific Patient Types After the two Delphi Rounds

#	Statement	% Agreement	Round*	Final Results
34	In high risk, non-exacerbator COPD patients, with a number of eosinophils > 300, single-inhaler fixed triple therapy is indicated as starting therapy	73.33% Disagreement	2	Majority
35	In patients with more than wo exacerbations and a number of eosinophils < 100, single-inhaler fixed triple therapy is indicated as starting therapy	75.56% Disagreement	2	Majority
36	In patients with very severe obstruction (FEV1 <30%) who do not present exacerbations, single-inhaler fixed triple therapy is indicated as starting therapy	42.22% Disagreement	2	Divergence
37	The use of single-inhaler fixed triple therapy needs to be indicated by the pneumologist	62.22% Disagreement	2	Divergence
38	To make the decision of using single-inhaler fixed triple therapy, it must be taken into account if the patient has pneumonia precedent	75.56% Agreement	2	Majority

Notes: The final results were determined considering the degree of agreement among the panelists: consensus ≥80%; majority ≥66%; or divergence (<66%). NAND: neither agreement nor disagreement. *Indicates the round where the degree of agreement shown was reached. In bold are those words changed from round one to round two.

Table 4 Results of the Degree of Agreement Among the Panelists with the Statements Regarding the Different Device Options After the two Delphi Rounds

#	Statement	% Agreement	Round*	Final Results
39	The Ellipta^® device has shown a lesser number of critical errors compared to other devices that use triple therapy	93.33% Agreement^2	2	Consensus
40	The fine particle with Modulite^® technique has shown bigger pulmonary deposit in peripheral airways than other devices that use triple therapy	82.22% Agreement^2	2	Consensus
41	The pulmonary deposit originated by the single-inhaler fixed triple therapy is similar to the one originated by the dual LAMA/LABA therapy	51.11% Agreement^2	2	Divergence
42	The pulmonary deposit originated by the single-inhaler fixed triple therapy is similar to the one originated by the dual LABA/ICS therapy	60.00% Agreement^2	2	Divergence
43	Single-inhaler fixed triple therapy leads to a higher decrease in the number of critical errors than open triple therapy	93.33% Agreement^1	1	Consensus
44	Single-inhaler fixed triple therapy leads to higher adherence to the treatment than open triple therapy	93.33% Agreement^1	1	Consensus
45	The administration pattern of single-inhaler fixed triple therapy every 12 hours is more effective than every 24 hours pattern	84.44% Disagreement^2	2	Consensus
46	The administration pattern of single-inhaler fixed triple therapy every 24 hours improves the adherence compared to every 12 hours pattern.	84.44% Agreement^2	2	Consensus

Notes: The final results were determined considering the degree of agreement among the panellists: consensus ≥80%; majority ≥66%; or divergence (<66%). NAND: neither agreement nor disagreement. *Indicates the round where the degree of agreement shown was reached.

Table 5 Results of the Degree of Agreement Among the Panelists with the Statements Regarding Costs of the Diverse Therapeutic Options for the COPD Patients After the two Delphi Rounds

#	Statement	% Agreement	Round*	Final Results
47	In patients with symptomatic COPD, the single-inhaler fixed triple therapy is more cost-effective than the dual LABA/ICS therapy	75.56% Agreement	2	Majority
48	In high-risk patients according to the GesEPOC definition, the single-inhaler fixed triple therapy is more cost-effective than the dual LABA/LAMA therapy	53.33% NAND	2	Divergence

Notes: The final results were determined considering the degree of agreement among the panelists: consensus ≥80%; majority ≥66%; or divergence (<66%). NAND: neither agreement nor disagreement. *Indicates the round where the degree of agreement shown was reached. In bold are those words changed from round one to round two.