Table 3 Comparison of simulated responder analysis results when 50% responses are missing using non-response imputation, impute-before-dichotomizing and dichotomize-then-impute multiple imputation1
Dropout model | Imputation method | % Responders Trt A | % Responders Trt B | Difference in proportions (95% CI) | % Bias | Coverage of the 95% CI | Power |
|---|---|---|---|---|---|---|---|
1: Lack of efficacy | NRI | 12.8 | 4.8 | 8.0 (0.3, 15.7) | − 46.8 | 55.6 | 0.52 |
DTI MI | 27.5 | 11.2 | 16.3 (5.7, 26.9) | 8.8 | 91.5 | 0.72 | |
DTI MI with CV | 24.2 | 9.7 | 14.5 (4.4, 24.6) | −3.2 | 90.6 | 0.66 | |
IBD MI | 25.8 | 11.1 | 14.8 (4.3, 25.2) | −1.5 | 94.1 | 0.59 | |
IBD MI with CV | 23.3 | 9.7 | 13.6 (3.5, 23.6) | −9.6 | 92.9 | 0.56 | |
2: Differing mechanism | NRI | 12.8 | 6.3 | 6.6 (−1.4, 14.6) | − 56.2 | 45.5 | 0.37 |
DTI MI | 27.5 | 10.9 | 16.6 (6.1, 27.2) | 11.0 | 86.9 | 0.71 | |
DTI MI with CV | 24.6 | 9.8 | 14.8 (4.7, 25.0) | − 1.2 | 88.7 | 0.65 | |
IBD MI | 25.9 | 11.1 | 14.8 (4.4, 25.3) | −1.1 | 92.9 | 0.58 | |
IBD MI with CV | 23.6 | 9.9 | 13.7 (3.6, 23.8) | −8.6 | 92.2 | 0.56 | |
3: Differing mechanism, reversed | NRI | 13.9 | 4.8 | 9.0 (1.1, 16.9) | − 39.8 | 66.5 | 0.62 |
DTI MI | 26.7 | 11.0 | 15.7 (5.1, 26.2) | 4.5 | 85.4 | 0.64 | |
DTI MI with CV | 23.9 | 9.7 | 14.2 (4.1, 24.2) | −5.4 | 86.1 | 0.61 | |
IBD MI | 26.1 | 11.1 | 15.1 (4.6, 25.6) | 0.7 | 92.0 | 0.58 | |
IBD MI with CV | 23.6 | 9.8 | 13.8 (3.7, 23.8) | −8.1 | 91.1 | 0.55 | |
4: Differential dropout rates | NRI | 18.3 | 1.8 | 16.5 (8.5, 24.4) | 10.0 | 93.9 | 0.99 |
DTI MI | 26.2 | 14.5 | 11.7 (0.9, 22.5) | −21.8 | 77.5 | 0.48 | |
DTI MI with CV | 24.0 | 11.1 | 12.9 (2.7, 23.1) | −13.8 | 84.1 | 0.58 | |
IBD MI | 25.7 | 11.8 | 13.9 (3.4, 24.5) | −6.9 | 92.8 | 0.49 | |
IBD MI with CV | 23.8 | 9.4 | 14.4 (4.4, 24.4) | −3.7 | 94.4 | 0.60 | |
5: Lack of efficacy, sensitivity of mechanism | NRI | 13.7 | 5.6 | 8.1 (0.1, 16.1) | − 45.9 | 59.9 | 0.53 |
DTI MI | 26.9 | 10.7 | 16.2 (5.7, 26.7) | 8.1 | 91.9 | 0.72 | |
DTI MI with CV | 24.2 | 9.5 | 14.7 (4.6, 24.8) | −2.1 | 92.6 | 0.67 | |
IBD MI | 25.9 | 10.9 | 15.0 (4.5, 25.4) | −0.2 | 94.1 | 0.62 | |
IBD MI with CV | 23.5 | 9.8 | 13.8 (3.7, 23.8) | −8.1 | 93.6 | 0.60 | |
6: Lack of efficacy and tolerability | NRI | 13.2 | 4.9 | 8.3 (0.5, 16.1) | − 44.6 | 59.5 | 0.57 |
DTI MI | 26.9 | 11.0 | 15.9 (5.4, 26.5) | 6.1 | 91.3 | 0.68 | |
DTI MI with CV | 24.1 | 9.7 | 14.4 (4.3, 24.5) | −4.0 | 91.2 | 0.65 | |
DTI MI with AE | 27.4 | 11.9 | 15.5 (4.8, 26.2) | 3.4 | 90.1 | 0.63 | |
IBD MI | 25.8 | 11.1 | 14.7 (4.2, 25.2) | −2.0 | 93.3 | 0.59 | |
IBD MI with CV | 23.5 | 9.8 | 13.6 (3.6, 23.7) | −9.0 | 92.5 | 0.57 | |
IBD MI with AE | 26.0 | 11.4 | 14.6 (4.1, 25.1) | −2.7 | 93.6 | 0.57 |