Table 3.
Probability of Detecting AEs Under Random Subsampling Methods for Metastatic Disease Studies
| Study, AE, Active Arm Rate Excess in Full Study | Sampling Method | Subsample Size (total No. of patients) |
||||
|---|---|---|---|---|---|---|
| 200 (%) | 300 (%) | 400 (%) | 500 (%) | 600 (%) | ||
| Grade 3+ events | ||||||
| JMDB, anorexia*†, 2.1% | Random by patient | 62.4 | 61 | 63.3 | 60.4 | 61 |
| Random by center‡ | 50.6 | 49.9 | 52.7 | 56.7 | 56.4 | |
| AVAiL, weight decreased,2.1% | Random by patient | 63 | 65 | 66 | 68 | 79 |
| Random by center‡ | 51 | 54 | 52 | 59 | 65 | |
| ECOG 4599, infection without neutropenia, 2.4% | Random by patient | 63 | 67 | 68 | 72 | 75 |
| Random by center‡ | 57 | 60 | 63 | 68 | 70 | |
| EGF30001, leukopenia,2.4% | Random by patient | 68 | 70 | 79 | 86 | NA |
| Random by center‡ | 58 | 61 | 66 | 79 | NA | |
| EGF30001, nausea,2.4% | Random by patient | 66 | 68 | 73 | 84 | NA |
| Random by center‡ | 54 | 57 | 64 | 71 | NA | |
| ECOG 4599, proteinuria,* 3.0% | Random by patient | 87 | 91 | 94 | 96 | 98 |
| Random by center‡ | 78 | 85 | 90 | 93 | 98 | |
| AVF2107g, abdominal pain, 3.4% | Random by patient | 72 | 77 | 80 | 85 | 92 |
| Random by center‡ | 65 | 72 | 75 | 80 | 90 | |
| JMDB, nausea,*† 3.5% | Random by patient | 72.9 | 74.5 | 78.1 | 79.7 | 82 |
| Random by center‡ | 68.7 | 69.6 | 75.5 | 77.2 | 80.5 | |
| AVAiL, epistaxis,† 4.3% | Random by patient | 94 | 98 | 99.4 | 100 | 100 |
| Random by center‡ | 91 | 97 | 99.6 | 100 | 100 | |
| AVF2107g, leukopenia,6.7% | Random by patient | 79 | 88 | 92 | 97 | 99.4 |
| Random by center‡ | 77 | 85 | 90 | 96 | 98 | |
| Grade 1 to 2 events | ||||||
| AVAiL, stomatitis,* 6.4% | Random by patient | 76 | 76 | 88 | 92 | 99.5 |
| Random by center‡ | 67 | 70 | 78 | 87 | 97 | |
| AVAiL, headache,* 15.4% | Random by patient | 99.5 | 100 | 100 | 100 | 100 |
| Random by center‡ | 98 | 99.9 | 100 | 100 | 100 | |
NOTE. AEs in italics could be missed under patient subsampling. The other events are known events but are included here because the magnitude of the active arm rate excess versus the control arm illustrates the properties of AE subsampling. Results from the two missable events from ECOG 4599—hyponatremia with 2.4% excess and febrile neutropenia with 2.6% excess—were omitted because the subsampling results were similar to those for infection without neutropenia, which had a rate excess of 2.4%. Grade 3+ events are detected in a simulation when they appear in 2% excess over the control arm; grade 1 to 2 events are detected when they appear in 5% excess over the control arm. Rates of detection in bold are ≥ 75%.
Abbreviations: AE, adverse event; AVAiL, Avastin in Lung; ECOG, Eastern Cooperative Oncology Group; NA, not applicable.
Known from previous trials.
Identified as known in candidate trial from analysis of AEs to be collected in all patients (see Methods).
Sample sizes are approximate. The number of centers selected at random was determined to achieve an average number of patients at or above the target level.