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Table 3 Frequency and statistical analyses of interim analyses, early stopping and prior Phase II RCTs in adult critical care RCTs showing increased mortality in the intervention groups

From: Trials in adult critical care that show increased mortality of the new intervention: Inevitable or preventable mishaps?

References Interim analyses (frequency) Interim statistical test RCT D/C’d early Prior Phase II RCT (n) DSMB
Hayes [10] Yes (every 50 patients) Chi-square Yes Yese No
Fisher [15] No NA No No Not stated
Sloan [14] Yes (after 10, 25, 50 and 75 % enrollment) Possibly Log rank 28 daya Yes Yesf Yes
Takala [13]g Yes (group sequential trials; 150 then every 40 patients) Chi-square Yes Yesc Yes
Edwardsd [17] Annually Chi-square Yes Yes$ Yes
Perner [12] Yes (after 400 patients) Chi-square No Yes Yes
Ferguson [16] Yes (pilot phase after 94, 300, 500 and 700 for safety, 800 for efficacy) Mantel–Haentszel Chi-square Yes Yes (N = 25) Yes
Finfer [8]b Yes (after 1500 and 4000 patients) Chi-square No Yesg Yes
Lopez [11] Yes Triangular test with Christmas tree correction at stopping boundaries Yes Yes (n = 312) Yes
Gao Smith [9] Yes (every 12 months) 95 % CI Yes Yes (n = 40) Yes
  1. Two parallel RCTs in Finland and in Europe (UK, the Netherlands, Belgium and Sweden) are reported together [13]. Because of slow recruitment due to the unexpectedly high incidence of exclusion criteria, the design was changed before the first interim analysis. The revised design was a fixed-sample analysis of 170 and 190 patients in the Finnish and multinational studies
  2. D/C’d discontinued, NA not available in primary publication
  3. aThe interim analyses methods were not stated. The primary analysis was log rank to 28 days
  4. bPrior to the NICE SUGAR RCT [8], van den Berghe et al. [19] had published a similar RCT of intensive versus conventional insulin treatment in critically ill patients
  5. cPrior small RCTs in burns, postoperative surgical patients, trauma, sepsis and critically ill non-septic patients
  6. dMany prior small RCTs in head injury
  7. eSeveral prior RCTs in septic shock, high-risk surgical, trauma and critically ill patients
  8. fSeveral prior RCTs in trauma and critically ill patients
  9. gSeveral prior trials of intensive insulin