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Table 1 Randomized Aldactone Evaluation Study (RALES) comparing spironolactone to placebo: observed and projected number of deaths and summary statistics at the interim analyses

From: Experience collecting interim data on mortality: an example from the RALES study

    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
  1. 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).