TABLE 3.
Description of seven observational studies of the effects of interventions on study outcomes using various statistical methods for handling immortal time bias (ITB).
| References | Country | Study size | Study subjects | Interventions* | Outcomes | Statistical methods | HR (95% CI) |
| Suissa (49) | Canada | 3,524 | COPD | Inhaled corticosteroids | All–cause mortality | Time–fixed | 0.72 (0.58–0.88)# |
| Time–dependent | 0.94 (0.81–1.09)# | ||||||
| Shintani et al. (50) | USA | 224 | Mechanically ventilated patients | Delirium in the ICU | ICU length of stay | Time–fixed | 1.90 (1.30–2.70) |
| Time–dependent | 1.10 (0.70–1.60) | ||||||
| Lévesque et al. (11) | Canada | 11,661 | Diabetes | Statins | Disease progression | Time–fixed | 0.74 (0.58–0.95) |
| Time–dependent | 1.97 (1.53–2.52) | ||||||
| Mi et al. (28) | USA | 52,741 | COPD | Inhaled corticosteroids | 3 years mortality | Time–fixed | 0.55 (0.53–0.57) |
| Exclusion | 0.66 (0.64–0.69) | ||||||
| Time–dependent | 0.97 (0.93–1.00) | ||||||
| 3 months landmark | 0.94 (0.90–0.97) | ||||||
| 6 months landmark | 0.99 (0.95–1.03) | ||||||
| 9 months landmark | 1.02 (0.97–1.06) | ||||||
| 12 months landmark | 1.01 (0.97–1.07) | ||||||
| Weberpals et al. (12) | Germany | 9,876 | Prostate cancer | Beta–blockers | All–cause mortality | Time–fixed | 0.68 (0.60–0.77) |
| Time–dependent | 1.13 (1.00–1.28) | ||||||
| Colorectal caner | Time–fixed | 0.51 (0.47–0.57) | |||||
| Time–dependent | 1.15 (1.05–1.26) | ||||||
| Lung caner | Time–fixed | 0.42 (0.38–0.46) | |||||
| Time–dependent | 1.04 (0.96–1.13) | ||||||
| Pancreatic cancer | Time–fixed | 0.34 (0.22–0.51) | |||||
| Time–dependent | 1.10 (0.84–1.44) | ||||||
| Wallis et al. (33) | Canada | 38,340 | Men aged ≥ 66 years | Tertile 1; exposure of TRT ≤ 120 days | All–cause mortality | Time–fixed | 1.23 (1.14–1.33) |
| Time–dependent | 1.11 (1.03–1.20) | ||||||
| Tertile 2; exposure of TRT 121–510 days | Time–fixed | 1.02 (0.95–1.11) | |||||
| Time–dependent | 0.90 (0.83–0.97) | ||||||
| Tertile 3; exposure of TRT ≥ 511 days | Time–fixed | 0.56 (0.52–0.61) | |||||
| Time–dependent | 0.67 (0.62–0.73) | ||||||
| Choi et al. (51) | Korea | 16,769 | Ulcerative colitis | 5–Aminosalicylic acid | Incidence of colorectal cancer | Time–fixed | 0.18 (0.09–0.35) |
| 6 months landmark | 0.58 (0.35–0.97) | ||||||
| 1 year landmark | 0.59 (0.32–1.09) | ||||||
| 2 years landmark | 0.55 (0.25–1.19) |
*“Intervention” might be an intervention, treatment, or exposure.
#Rate ratio; ITB, immortal time bias; COPD, chronic obstructive pulmonary fibrosis; ICU, intensive care unit; TRT, testosterone replacement; HR, hazard ratio; CI, confidence interval.