Table 1.
Randomized Aldactone Evaluation Study (RALES) comparing spironolactone to placebo: observed and projected number of deaths and summary statistics at the interim analyses
| Observed | |||||||||
| Data | Meeting | Estimated | z-value | Observed | |||||
| Look | cutoff | date | Placebo | Treatment | Relative | information | P | ||
| no. | (d-mo-y) | (d-mo-y) | deaths | deaths | risk | time* | Critical | Observed | (two-sided) |
| Interim analysis cut-offs with the sweeps as they occurred | |||||||||
| 1 | 09-8-96 | 24-8-96 | 70 | 52 | 0.76 | 0.12 | 6.38 | 1.58 | 0.11 |
| 2 | 10-3-97 | 17-3-97 | 136 | 109 | 0.83 | 0.24 | 4.43 | 1.69 | 0.092 |
| 3 | 14-8-97 | 25-8-97 | 224 | 175 | 0.80 | 0.34 | 3.67 | 2.55 | 0.011 |
| 4 | 26-3-98 | 30-3-98 | 304 | 241 | 0.81 | 0.48 | 3.04 | 3.02 | 0.0026 |
| 5 | 14-8-98 | 24-8-98 | 351 | 269 | 0.78 | 0.57 | 2.79 | 3.75 | 0.00018 |
| Estimated interim analysis cutoffs without the sweeps† | |||||||||
| 4a | 26-3-98 | 30-3-98 | 281 | 222 | 0.81 | 0.45 | 3.16 | 2.93 | 0.0034 |
| (275-289) | (214-228) | (0.76-0.85) | (2.33-3.69) | ||||||
| 5a | 14-8-98 | 24-8-98 | 333 | 256 | 0.79 | 0.55 | 2.81 | 3.59 | 0.00034 |
| (325-341) | (248-264) | (0.74-0.83) | (2.87-4.33) | ||||||
| Interim analysis cutoffs that would have occurred if we had known the true numbers and times of deaths | |||||||||
| 1b | 09-8-96 | 24-8-96 | 81 | 59 | 0.75 | 0.14 | 5.88 | 1.80 | 0.072 |
| 2b | 10-3-97 | 17-3-97 | 189 | 140 | 0.76 | 0.26 | 4.24 | 2.75 | 0.0060 |
| 3b | 14-8-97 | 25-8-97 | 257 | 201 | 0.80 | 0.38 | 3.46 | 2.82 | 0.0048 |
| 4b | 26-3-98 | 30-3-98 | 330 | 254 | 0.79 | 0.51 | 2.95 | 3.56 | 0.00038 |
| 5b | 14-8-98 | 24-8-98 | 383 | 283 | 0.76 | 0.60 | 2.72 | 4.46 | 0.000008 |
This three-panel table shows (a) the data observed in the RALES trial at each of the five interim analyses; (b) simulated data for the fourth and fifth interim analysis had the sweeps not occurred; and (c) the data that would have been observed had all the deaths been reported within 24 h of their occurrence, as specified by the protocol. *No. of events that have occurred divided by the no. of events that will occur up to the planned end of the trial. Because the number of events that will occur is unknown at the time of a DSMB meeting, one must estimate it on the basis of data observed thus far and assumptions made about the future. †Observed values are median number of events (in 1000 simulated iterations of the trial), with ranges shown in parentheses. The 1000 iterations of the simulation assuming neither sweep showed a probablility of 18% and 100% that the data would have first crossed the prespecified stopping boundary at the fourth and fifth interim analyses, respectively. These numbers refer to looks 4a and 5a (data not shown).