Background
Methods
Selection of RCTs and study population
Selection criteria for RCTs |
a. Recruiting patients with COPD |
b. Phase III or Phase IV randomised, double-blind, placebo-controlled trial, testing i. Long-acting muscarinic antagonist (LAMA) OR ii. Long-acting β-agonist (LABA) OR iii. LAMA/LABA combination |
c. Primary outcomes were i. spirometry parameter(s) OR ii. COPD exacerbations OR iii. mortality |
d. Duration of treatment was ≥24 weeks post-randomisation |
e. Enrolled ≥100 patients with COPD |
f. Medicine was tested at licensed dose |
Selection of patients with COPD from the OPCRD database |
a. Quality and Outcomes Framework (QOF) approved diagnostic code of COPD, which includes the requirement for a post-bronchodilator FEV1/FVC <0.70 [31] |
b. Registered in OPCRD with data extracted from general practice at least once after 1 January 2011. The index date was defined as the date of the last data extraction |
c. ≥1 year of data available prior to the index date to define RCT inclusion/exclusion criteria |
d. FEV1 and FVC recorded within 5 years of the index date |
e. mMRC score recorded within 5 years of index date |
f. Recorded valid blood eosinophil count ever |
g. Age ≥40 years |
Data source
Methods of analysis
Results
Inclusion/exclusion criteria reported in RCTs
Generic name drug tested | RCT | Trial name | Sample size | Twin studya
| Start datec
| Publication date | % Male | Age mean ± SD or median (IQR) | FEV1 % predicted mean ± SD | Reference |
---|---|---|---|---|---|---|---|---|---|---|
Tiotropium | NCT02172287 | 410 | NCT02173691 | Feb-99 | Jul-02 | 75 | 64.9 ± 7.9 | Not available | [32] | |
NCT00274014 | 1010 | Oct-00 | Mar-06 | 88 | 64.8 ± 9.3 | 35.6 ± 12.6 | [27] | |||
NCT00274547 | 1829 | Sep-01 | Sep-05 | 99 | 67.9 ± 8.6 | 39.4 ± 13.5 | [33] | |||
NCT00277264 | 913 | Jan-02 | Nov-07 | 60 | 66.9 ± 8.9 | 39.4 ± 12.0 | [34] | |||
NCT00144339 | UPLIFT | 5993 | Dec-02 | Oct-08 | 75 | 64.5 ± 8.5 | 45.3 ± 13.6 | [12] | ||
NCT00387088 | 3991 | NCT00168844/NCT00168831 | Sep-06 | Oct-10 | 78 | 64.8 ± 9.1 | 49.3 ± 13.2 | [35] | ||
NCT00563381 | POET-COPD | 7376 | Jan-08 | Mar-11 | 75 | 62.4 ± 9.0 | 48.3 ± 13.9 | [36] | ||
NCT01126437 | 17 135 | May-10 | Oct-13 | 72 | 65.0 ± 9.1 | 47.9 ± 12.7 | [37] | |||
NCT01455129b
| 839 | Nov-11 | Feb-14 | Not available | [38] | |||||
Formoterol | NCT00134979 | 847 | Oct-04 | Nov-08 | 78 | 62.6 ± 8.9 | 51.2 ± 13.1 | [39] | ||
Aclidinium | NCT00363896 | ACCLAIM/COPD I | 843 | NCT00358436 | Aug-06 | Apr-11 | 79 | 62.3 ± 8.3 | 53.6 ± 15.2 | [40] |
NCT01001494 | ATTAIN | 828 | Oct-09 | Oct-12 | 67 | 62.4 ± 8.0 | 52.5 ± 14.1 | [41] | ||
NCT01044459 | 605 | Nov-09 | Dec-13 | 58 | 63.6 ± 9.7 | 52.3 ± 13.2 | [42] | |||
Indacaterol | NCT00463567 | 1683 | Apr-07 | Jul-10 | 63 | 63.6 ± 9.1 | 55.6 ± 14.7 | [43] | ||
NCT00567996 | 1002 | Nov-07 | Jun-11 | 75 | 63.6 ± 8.8 | 53.3 ± 13.9 | [44] | |||
NCT00792805 | 563 | Nov-08 | Feb-14 | 94 | 65.4 ± 8.8 | 49.9 ± 12.1 | [45] | |||
NCT00845728 | INVIGORATE | 3444 | Mar-09 | Sep-13 | 77 | 64.0 (40–91) | 40.5 ± 6.0 | [46] | ||
Olodaterol | NCT00782210 | 624 | NCT00782509 | Nov-08 | Jun-14 | 73 | 64.9 ± 8.4 | 48.9 ± 15.4 | [28] | |
NCT00793624 | 904 | NCT00796653 | Jan-09 | Jul-14 | 78 | 63.8 ± 8.7 | 51.2 ± 14.7 | [29] | ||
Glycopyrronium | NCT00929110 | GLOW2 | 1066 | Jun-09 | Nov-12 | 64 | 63.7 ± 8.8 | 56.0 ± 13.3 | [47] | |
NCT01005901 | GLOW1 | 822 | Oct-09 | Dec-11 | 82 | 63.9 ± 9.2 | 54.5 ± 12.9 | [48] | ||
NCT01566604 | GLOW7 | 460 | Mar-12 | Jan-15 | 96 | 64.8 ± 8.1 | 51.0 ± 12.4 | [49] | ||
Indacaterol + Glycopyrronium | NCT01120691 | SPARK | 741 | Apr-10 | May-13 | 75 | 63.3 ± 8.0 | 37.2 ± 8.1 | [25] | |
NCT01202188 | SHINE | 2144 | Sep-10 | Dec-13 | 75 | 64.0 ± 8.8 | 55.2 ± 13.1 | [50] | ||
NCT01315249 | ILLUMINATE | 259 | Mar-11 | Mar-13 | 71 | 63.3 ± 8.0 | 60.3 ± 10.6 | [51] | ||
NCT01709903 | LANTERN | 676 | Nov-12 | June-15 | 91 | 65.1 ± 7.9 | 51.8 ± 12.9 | [52] | ||
NCT01782326 | LANTERN | Jul-13 | Recruiting | [26] | ||||||
Vilanterol + Umeclidinium | NCT01313650 | 1532 | NCT01313637 | Mar-11 | Oct-13 | 71 | 63.0 ± 8.9 | 47.4 ± 13.1 | [53] | |
NCT01316900 | 1141 | NCT01316913 | Mar-11 | Jun-14 | 69 | 62.9 ± 9.0 | 47.7 ± 13.0 | [54] | ||
NCT01777334 | 905 | Jan-13 | Dec-14 | 68 | 62.3 ± 8.5 | 46.4 ± 12.9 | [55] | |||
Tiotropium + Olodaterol | NCT01431274 | 2624 | NCT01431287 | Sep-11 | Apr-15 | 73 | 64.0 ± 8.3 | 45.0 ± 11.7 | [30] |
Distribution of reported criteria in the OPCRD population
Characteristic | |
---|---|
Age, mean (SD) | 71.3 (10.6) |
Male, n (%) | 19 478 (52.8) |
FEV1 % predicted, mean (SD) | 62.5 (20.0) |
GOLD category of airflow limitation, n (%) | |
GOLD 1: FEV1 ≥ 80 % | 19.3 % (7 118) |
GOLD 2: 50 % ≤ FEV1 < 80 % | 53.5 % (19 755) |
GOLD 3: 30 % ≤ FEV1 < 50 % | 23.0 % (8 468) |
GOLD 4: FEV1 < 30 % | 4.2 % (1 552) |
mMRC score grade ≥2, n (%) | 17 075 (46.3) |
Pack years of smoking, n (%): | |
≥ 10 | 34 758 (94.2) |
≥ 20 | 34 232 (92.8) |
Maintenance therapya prescribed within 6 months, n (%) | 25 594 (69.4) |
Symptomaticb, n (%) | 29 579 (80.2) |
History of ≥ 1 exacerbation in the last year, n (%) | 18 373 (49.8) |
Proportion of OPCRD patients eligible for inclusion in RCTs
Step | Criterion for sequential selection | NCT02172287 | NCT00274014 | NCT00274547 | NCT00277264 | NCT00144339 | NCT00387088 | NCT00563381 | NCT01126437 | NCT01455129 | Median |
---|---|---|---|---|---|---|---|---|---|---|---|
1 | FEV1
| 46.8 | 50.3 | 46.8 | 56.3 | 65.8 | 46.8 | 65.8 | 65.8 | 72.8 | 56.3 |
2 | Other inclusion criteria | 38.5 | 20.6 | 44.5 | 23.2 | 54.4 | 44.5 | 26.1 | 55.6 | 64.7 | 44.5 |
3 | COPD-related exclusion criteria | 37.8 | 19.9 | 41.6 | 21.8 | 53.4 | 43.8 | 25.8 | 54.4 | 59.8 | 41.6 |
4 | Concomitant pulmonary disease | 35.6 | 19.9 | 41.6 | 20.2 | 47.3 | 41.1 | 25.5 | 48.2 | 52.9 | 41.1 |
5 | Asthma, allergic diseases and atopy | 23.8 | 14.3 | 32.9 | 14.7 | 37.5 | 29.8 | 19.6 | 38.2 | 39.1 | 29.8 |
6 | Comorbidities | 16.7 | 11.2 | 30.7 | 9.6 | 28.8 | 27.9 | 15.2 | 29.3 | 31.4 | 27.9 |
7 | Other relevant conditions | 15.7 | 11.2 | 30.7 | 9.5 | 27.1 | 27.9 | 14.4 | 27.5 | 29.2 | 27.1 |
8 | Final eligible proportion (%) | 15.7 | 11.2 | 25.1 | 9.5 | 22.5 | 27.8 | 11.8 | 22.9 | 25.0 | 22.5 |
Step | Criterion for sequential selection | NCT00134979 (Fa) | NCT00363896 (Aa) | NCT01001494 (A) | NCT01044459 (A) | NCT00463567 (Ia) | NCT00567996 (I) | NCT00792805 (I) | NCT00845728 (I) | NCT00782210 (Oa) | NCT00793624 (O) | NCT00929110 (Ga) | NCT01005901 (G) | NCT01566604 (G) | Median |
---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
1 | FEV1
| 63.9 | 80.7 | 76.5 | 76.5 | 76.5 | 76.5 | 76.5 | 23.0 | 80.7 | 80.7 | 76.5 | 76.5 | 76.5 | 76.5 |
2 | Other inclusion criteria | 51.4 | 68.3 | 64.9 | 64.9 | 71.4 | 72.3 | 72.3 | 12.5 | 76.4 | 76.4 | 59.1 | 72.3 | 57.8 | 68.3 |
3 | COPD related exclusion criteria | 50.5 | 67.1 | 64.3 | 63.8 | 57.8 | 68.8 | 65.0 | 10.1 | 75.6 | 74.9 | 56.5 | 70.2 | 51.1 | 64.3 |
4 | Concomitant pulmonary disease | 44.8 | 60.8 | 58.3 | 57.9 | 52.6 | 62.4 | 58.3 | 8.8 | 74.8 | 70.9 | 51.0 | 62.7 | 46.2 | 58.3 |
5 | Asthma, allergic diseases and atopy | 34.7 | 43.8 | 46.0 | 45.7 | 42.0 | 44.6 | 46.0 | 6.8 | 72.5 | 66.5 | 38.0 | 49.2 | 34.2 | 44.6 |
6 | Comorbidities | 26.5 | 42.6 | 44.7 | 38.2 | 32.0 | 36.0 | 43.3 | 6.5 | 55.0 | 61.9 | 28.3 | 47.8 | 25.7 | 38.2 |
7 | Other relevant conditions | 26.3 | 41.5 | 44.7 | 38.2 | 31.7 | 34.9 | 43.3 | 6.5 | 55.0 | 57.6 | 28.1 | 47.8 | 25.2 | 38.2 |
8 | Final eligible proportion (%) | 26.3 | 41.5 | 44.6 | 38.1 | 26.2 | 34.9 | 43.3 | 6.5 | 55.0 | 57.6 | 23.1 | 39.2 | 20.7 | 38.1 |
Step | Criterion for sequential selection | NCT01120691 (I + Ga) | NCT01202188 (I + G) | NCT01315249 (I + G) | NCT01709903 (I + G) | NCT01782326 (I + G) | NCT01313650 (V + Ua) | NCT01316913 (V + U) | NCT01777334 (V + U) | NCT01431287 (T + Oa) | Median |
---|---|---|---|---|---|---|---|---|---|---|---|
1 | FEV1
| 27.2 | 76.5 | 67.6 | 76.5 | 43.5 | 65.8 | 65.8 | 65.8 | 80.7 | 65.8 |
2 | Other inclusion criteria | 15.0 | 59.1 | 50.2 | 33.9 | 13.8 | 32.9 | 32.9 | 32.9 | 76.4 | 32.9 |
3 | COPD related exclusion criteria | 9.5 | 42.7 | 18.4 | 21.5 | 10.7 | 28.5 | 28.2 | 31.8 | 74.9 | 28.2 |
4 | Concomitant pulmonary disease | 8.4 | 38.2 | 16.7 | 19.4 | 9.4 | 25.3 | 25.1 | 27.8 | 70.9 | 25.1 |
5 | Asthma, allergic diseases and atopy | 5.4 | 24.9 | 11.4 | 14.9 | 7.0 | 20.0 | 24.4 | 27.0 | 68.7 | 20.0 |
6 | Comorbidities | 4.1 | 19.2 | 9.0 | 11.2 | 5.0 | 14.8 | 18.2 | 20.1 | 52.2 | 14.8 |
7 | Other relevant conditions | 4.0 | 18.5 | 8.9 | 11.1 | 4.8 | 13.7 | 16.7 | 18.5 | 48.9 | 13.7 |
8 | Final eligible proportion (%) eligible | 3.5 | 15.2 | 7.2 | 8.6 | 3.9 | 13.7 | 13.2 | 14.7 | 48.9 | 13.2 |