Table A4.
Adverse Event Incidence Differences Under Systematic Subsampling Methods for Adjuvant Disease Studies
| CALGB 89803 (n = 1,263), Adverse Event, Active Arm Rate Excess in Full Study | Sampling Method | Subsample Size (total No. of patients) |
||||
|---|---|---|---|---|---|---|
| 200 | 300 | 400 | 500 | 600 | ||
| Grade 3+ events | ||||||
| Thrombosis embolism, 4.2% | Biggest centers* | NA | NA | NA | NA | NA |
| First patients enrolled | 5.2 | 7.3 | 5.6 | 5.9 | 5.2 | |
| Grade 1 to 2 events | ||||||
| Sweating (diaphoresis), 5.8% | Biggest centers* | NA | NA | NA | NA | NA |
| First patients enrolled | 6.2 | 6.0 | 4.6 | 5.9 | 6.3 | |
| Constipation, 6.9% | Biggest centers* | NA | NA | NA | NA | NA |
| First patients enrolled | 3.4 | 8.7 | 8.6 | 7.6 | 9.4 | |
| HERA (n = 3,386), Adverse Event, Active Arm Rate Excess in Full Study | Sampling Method | Subsample Size (total No. of patients) |
||||
|---|---|---|---|---|---|---|
| 600 | 900 | 1,200 | 1,500 | 1,800 | ||
| Grade 3+ events | ||||||
| Ejection fraction decreased,†‡ 2.4% | Biggest centers* | 2.2 | 1.7 | 1.9 | 1.6 | 1.9 |
| First patients enrolled | 2.7 | 3.4 | 3.4 | 3.2 | 2.9 | |
| Grade 1 to 2 events | ||||||
| Fatigue, 5.1% | Biggest centers* | 4.6 | 3.6 | 5.5 | 5.1 | 5.4 |
| First patients enrolled | 7.1 | 6.8 | 5.8 | 5.7 | 6.6 | |
| Headache,† 6.8% | Biggest centers* | 5.3 | 4.4 | 5.9 | 6.3 | 6.7 |
| First patients enrolled | 10.1 | 10.2 | 9.6 | 9.2 | 8.6 | |
| BIG 1-98 (n = 7,963), Adverse Event, Active Arm Rate Excess in Full Study | Sampling Method | Subsample Size (total No. of patients) |
||||
|---|---|---|---|---|---|---|
| 600 | 1,200 | 2,000 | 4,000 | 6,000 | ||
| Grade 1 to 2 events: Hypercholesterolemia, 21.2% | Biggest centers* | 18.2 | 20.9 | 16.9 | 19.8 | 21 |
| First patients enrolled | 28.4 | 23.7 | 24.1 | 19.3 | 20.1 | |
NOTE. To account for their substantially larger safety databases, the HERA study (n = 3,386) and BIG 1-98 study (n = 7,963) were evaluated using larger subsamples. Adverse events 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 the subsampling. Results from 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%. Incidence differences in boldare ≥ 2 for grade 3+ adverse events and ≥ 5 for grade 1 to 2 adverse events.
Abbreviations: CALGB, Cancer and Leukemia Group B; NA, not applicable; HERA, HERceptin Adjuvant; BIG, Breast International Group; ECOG, Eastern Cooperative Oncology Group.
Sample sizes are approximate. Enough centers were selected to meet or exceed the target subsample size.
Known from previous trials.
Identified as known in candidate trial from analysis of adverse events to be collected in all patients (see Methods).