Background
Methods
Bland-Altman limits of agreement
Primary hypothesis
Statistical test
Group-sequential testing with an α-spending function
Clinical example
Results
Bland-Altman limits of agreement
Number of interim analyses | Estimated mean difference and Bland-Altman limits of agreement at analysis time point | |||
---|---|---|---|---|
Interim analysis 1 | Interim analysis 2 | Interim analysis 3 | Final analysis | |
0 | – | – | – | 0.30 –1.78 to 2.38 (N = 45) |
1 | 0.47 –2.30 to 3.24 (N = 23) | – | – | 0.30 –1.78 to 2.38 (N = 45) |
2 | 0.25 –1.53 to 2.03 (N = 15) | 0.43 –2.03 to 2.89 (N = 30) | – | 0.30 –1.78 to 2.38 (N = 45) |
3 | 0.19 –1.85 to 2.24 (N = 11) | 0.47 –2.30 to 3.24 (N = 23) | 0.40 –1.92 to 2.73 (N = 34) | 0.30 –1.78 to 2.38 (N = 45) |
Fixed-sample analysis (N = 45)
Number of interim analyses | Observed standard deviation, P value (sample size), respective significance level, and upper confidence limit at analysis time point | |||
---|---|---|---|---|
Interim analysis 1 | Interim analysis 2 | Interim analysis 3 | Final analysis | |
0 | – | – | – |
SD = 1.060
P = 0.0022 (N = 45)
α
1
= 0.05
95% uCL 1.288
|
1 | SD = 1.415
P = 0.3900 (N = 23) α0.5 = 0.025 97.5% uCL 2.002 | – | – |
SD = 1.060
P = 0.0022 (N = 45)
α
1
= 0.05
95% uCL 1.288
|
2 |
SD = 0.909
P = 0.0162 (N = 15)
α
0.33
= 0.0167
98.33% uCL 1.495
| SD = 1.255
P = 0.1162 (N = 30) α0.67 = 0.0333 96.67% uCL 1.653 | – |
SD = 1.060
P = 0.0022 (N = 45)
α
1
= 0.05
95% uCL 1.288
|
3 | SD = 1.044
P = 0.0984 (N = 11) α0.25 = 0.0125 98.75% uCL 2.006 | SD = 1.415
P = 0.3900 (N = 23) α0.5 = 0.025 97.5% uCL 2.002 | SD = 1.185
P = 0.0452 (N = 34) α0.75 = 0.0375 96.25% uCL 1.519 |
SD = 1.060
P = 0.0022 (N = 45)
α
1
= 0.05
95% uCL 1.288
|
Sequential testing
Discussion
Statement of principal findings
Strengths and weaknesses of the study
Meaning of the study: possible mechanisms and implications for clinicians and policymakers
Number of interim analyses |
P value (sample size) and respective significance level at analysis time point | |||
---|---|---|---|---|
Interim analysis 1 | Interim analysis 2 | Interim analysis 3 | Final analysis | |
0 | – | – | – | 0.0189 (N = 100) α
1 = 0.05 |
1 | 0.1557 (N = 50) α
0.5 = 0.025 | – | – | 0.0189 (N = 100) α
1 = 0.05 |
2 | 0.0669 (N = 33) α
0.33 = 0.0167 | 0.0577 (N = 67) α
0.67 = 0.0333 | – | 0.0189 (N = 100) α
1 = 0.05 |
3 | 0.0174 (N = 25) α
0.25 = 0.0125 | 0.1557 (N = 50) α
0.5 = 0.025 | 0.0395 (N = 75) α
0.75 = 0.0375 | 0.0189 (N = 100) α
1 = 0.05 |