Background
Methods
Data sources
Study design and cohort definition
Emulation of the target trial
Assessment of outcome
Assessment of negative control outcome
Assessment covariates
Statistical analysis
Results
Before propensity-score overlap weighting | After propensity-score overlap weighting | |||||
---|---|---|---|---|---|---|
BNT162b2 | ChAdOx1 | Standardized difference | BNT162b2 | ChAdOx1 | Standardized difference | |
Number | 536,371 | 774,704 | 163,716 | 163,716 | ||
Demographics | ||||||
Age, mean (SD), y | 46.37 (19.13) | 57.82 (14.82) | 0.669 | 58.32 (15.77) | 58.32 (16.75) | <0.001 |
Race (%) | 0.075 | <0.001 | ||||
White | 42.7 | 46 | 45 | 45 | ||
Other | 3.4 | 2.6 | 2.8 | 2.8 | ||
Missing | 53.9 | 51.3 | 52.2 | 52.2 | ||
Socioeconomic deprivation index score (%)a | 0.052 | <0.001 | ||||
1 | 15.5 | 15.8 | 16.7 | 16.7 | ||
2 | 18.5 | 19.7 | 19.8 | 19.8 | ||
3 | 19.7 | 20.1 | 19.8 | 19.8 | ||
4 | 18.6 | 18.6 | 17.7 | 17.7 | ||
5 | 15.5 | 14.9 | 14.2 | 14.2 | ||
Missing | 12.2 | 10.9 | 11.9 | 11.9 | ||
Female (%) | 52.9 | 50.3 | 0.052 | 52.2 | 52.2 | <0.001 |
BMI, mean (SD), kg/m2 | 27.44 (5.87) | 28.45 (6.30) | 0.165 | 27.98 (5.80) | 28.07 (6.00) | 0.015 |
Region | 0.105 | <0.001 | ||||
England | 14.8 | 13.6 | 15.1 | 15.1 | ||
Northern Ireland | 15.3 | 12.3 | 17.6 | 17.6 | ||
Scotland | 39.1 | 42.8 | 38.1 | 38.1 | ||
Wales | 30.8 | 31.4 | 29.2 | 29.2 | ||
Influenza vaccination (%)b | 31.8 | 45 | 0.272 | 49.1 | 49.1 | <0.001 |
Lifestyle factors | ||||||
Drinking (%) | 0.037 | <0.001 | ||||
None | 19.1 | 18.1 | 18.2 | 18.2 | ||
Past | 2.9 | 3.4 | 3.5 | 3.5 | ||
Current | 77.9 | 78.5 | 78.3 | 78.3 | ||
Smoking (%) | 0.134 | <0.001 | ||||
None | 62 | 55.8 | 56.9 | 56.9 | ||
Past | 21.7 | 26.8 | 27.5 | 27.5 | ||
Current | 16.2 | 17.4 | 15.6 | 15.6 | ||
Comorbidity (%) | ||||||
Hypertension | 18.2 | 28.7 | 0.249 | 30.5 | 30.5 | <0.001 |
Diabetes | 8.9 | 14 | 0.162 | 14.1 | 14.1 | <0.001 |
Chronic kidney disease | 3.0 | 5.0 | 0.102 | 5.5 | 5.5 | <0.001 |
Pneumonia or infection | 5.4 | 6.8 | 0.060 | 6.7 | 6.7 | <0.001 |
Chronic obstructive pulmonary disease | 2.3 | 4.4 | 0.112 | 4.6 | 4.6 | <0.001 |
Influenza | 3.1 | 3.6 | 0.030 | 3.6 | 3.6 | <0.001 |
Cancer | 6.3 | 9.2 | 0.106 | 10.4 | 10.4 | <0.001 |
Venous thrombosis | 1.5 | 2.6 | 0.079 | 2.5 | 2.5 | <0.001 |
Atrial fibrillation | 2.2 | 3.8 | 0.095 | 4.1 | 4.1 | <0.001 |
Ischemic heart disease | 4 | 6.7 | 0.120 | 7.3 | 7.3 | <0.001 |
Myocardial infarction | 1.8 | 3.2 | 0.088 | 3.3 | 3.3 | <0.001 |
Congestive heart failure | 1.1 | 2.0 | 0.075 | 2.0 | 2.0 | <0.001 |
Stroke | 1.4 | 2.6 | 0.085 | 2.6 | 2.6 | <0.001 |
Trauma | 0.9 | 1.1 | 0.025 | 1.0 | 1.0 | <0.001 |
Fracture | 31.2 | 33.3 | 0.044 | 32.6 | 32.6 | <0.001 |
Liver disease | 2.2 | 3.4 | 0.075 | 3.4 | 3.4 | <0.001 |
Fall | 5.8 | 7.8 | 0.079 | 8.0 | 8.0 | <0.001 |
Dementia | 0.6 | 1.1 | 0.053 | 1.1 | 1.1 | <0.001 |
Depression | 12.4 | 15.2 | 0.083 | 14.4 | 14.4 | <0.001 |
Medication (%)b | ||||||
Antihypertensive | 22.1 | 33 | 0.247 | 34.8 | 34.8 | <0.001 |
Antidiabetic | 4.5 | 7.9 | 0.142 | 7.6 | 7.6 | <0.001 |
Statin | 15 | 23.2 | 0.212 | 25.9 | 25.9 | <0.001 |
Loop diuretics | 2.0 | 3.9 | 0.117 | 3.8 | 3.8 | <0.001 |
Thiazide diuretics | 3.6 | 5.5 | 0.093 | 6.2 | 6.2 | <0.001 |
Glucocorticoids | 3.3 | 5 | 0.084 | 5.2 | 5.2 | <0.001 |
NSAIDs | 16.1 | 21.4 | 0.136 | 21.2 | 21.2 | <0.001 |
Opioids | 5.0 | 8.1 | 0.127 | 7.6 | 7.6 | <0.001 |
PPIs | 20.1 | 27.9 | 0.182 | 28.5 | 28.5 | <0.001 |
DMARDs | 1.1 | 1.7 | 0.051 | 1.9 | 1.9 | <0.001 |
Healthcare utilization, mean (SD)b | ||||||
Hospitalizationsb | 0.19 (0.70) | 0.24 (0.86) | 0.057 | 0.24 (0.82) | 0.24 (0.80) | <0.001 |
General practice visitsb | 1.69 (3.13) | 2.13 (3.95) | 0.123 | 2.13 (3.87) | 2.13 (3.53) | <0.001 |
Specialist referralsb | 0.21 (0.62) | 0.23 (0.66) | 0.026 | 0.24 (0.67) | 0.24 (0.69) | <0.001 |
Population | Number | No. of Events | Mean follow up, months | Incidence ratea, per 1000 person-months | Rate differencea (95%CI), per 1000 person-months | Hazard ratioa (95%CI) | ||||
---|---|---|---|---|---|---|---|---|---|---|
BNT162b2 | ChAdOx1 | BNT162b2 | ChAdOx1 | BNT162b2 | ChAdOx1 | BNT162b2 | ChAdOx1 | |||
Overall | 536,371 | 774,704 | 20,070 | 31,611 | 6.65 | 7.33 | 3.65 | 5.25 | -1.60 (-1.76, -1.43) | 0.69 (0.68, 0.71) |
Sex | ||||||||||
Male | 252,646 | 384,903 | 8,582 | 14,666 | 6.34 | 7.25 | 3.42 | 4.85 | -1.44 (-1.67, -1.20) | 0.70 (0.68, 0.73) |
Female | 283,725 | 389,801 | 11,488 | 16,945 | 6.93 | 7.40 | 3.85 | 5.59 | -1.74 (-1.98, -1.50) | 0.68 (0.66, 0.71) |
Age | ||||||||||
Age>=65 | 132,624 | 235,594 | 2,482 | 4,886 | 8.49 | 8.36 | 2.17 | 2.72 | -0.55 (-0.74, -0.36) | 0.79 (0.75, 0.84) |
Age<65 | 403,747 | 539,110 | 17,588 | 26,725 | 6.07 | 6.89 | 5.15 | 7.62 | -2.47 (-2.76, -2.19) | 0.67 (0.65, 0.70) |
Study period | ||||||||||
Alpha-variant predominance | 356,679 | 739,203 | 1,252 | 1,227 | 2.61 | 2.24 | 0.84 | 0.94 | -0.10 (-0.23, 0.04) | 0.89 (0.80, 1.00) |
Delta-variant predominance | 179,692 | 35,501 | 8,413 | 1,996 | 4.31 | 4.86 | 8.02 | 11.99 | -3.96 (-5.02, -2.90) | 0.67 (0.62, 0.72) |
Including prior infected population | 561,140 | 803,200 | 20,398 | 32,007 | 6.63 | 7.32 | 3.65 | 5.28 | -1.62 (-1.79, -1.47) | 0.69 (0.67, 0.71) |
Received two doses | 491,591 | 730,363 | 12,229 | 28,196 | 6.96 | 7.58 | 3.01 | 4.59 | -1.58 (-1.73, -1.42) | 0.65 (0.64, 0.67) |
Received one dose | 29,701 | 21,870 | 2,138 | 905 | 4.26 | 5.13 | 9.07 | 8.91 | 0.16 (-1.31, 1.64) | 1.01 (0.91, 1.14) |
Outcomes | BNT162b2 | ChAdOx1 |
---|---|---|
Number | 536,371 | 774,704 |
Hospitalisation for COVID-19 | ||
Event (n) | 603 | 1,432 |
Mean follow-up (months) | 6.74 | 7.41 |
Incidence ratea, per 1000 person-months | 0.17 | 0.26 |
Rate difference (95%CI) a, per 1000 person-months | -0.09 (-0.13, -0.05) | 0.00 (ref) |
Hazard ratio (95% CI) a | 0.65 (0.57, 0.74) | 1.00 (ref) |
Death from COVID-19 | ||
Event (n) | 42 | 112 |
Mean follow-up (months) | 6.74 | 7.41 |
Incidence ratea, per 1000 person-months | 0.018 | 0.022 |
Rate difference (95%CI) a, per 1000 person-months | -0.005 (-0.016, 0.006) | 0.00 (ref) |
Hazard ratio (95% CI) a | 0.66 (0.42, 1.04) | 1.00 (ref) |