Comment by Professor Home on ACCORD,VADT and ADVANCE

Could I just pick up on the ACCORD, VADT, ADVANCE results and the comments in ENDODIABOLOGY please.Firstly there is twice a suggestion that CV deaths were increased in VADT. Though the results have not been published, my memory from the presentations is that there was no different between groups. CV deaths were numerically higher, but the power was way too low for this to be meaningful - indeed the very analysis is dangerous.
Secondly ACCORD did not show increased deaths. It was stopped because of a signal of increased death, which generated a p value of 0.04. This interim observational test should not be regarded as statistically significant. Indeed most of us would not have stopped the study on the basis of the results presented in the paper.
Thirdly you will have seen the UKPDS extension study published since. Attached for those who have not. It is important to realize that ACCORD, ADVANCE and VADT are all consistent with the UKPDS findings, but of course not statistically significant largely because underpowered (VADT always was, ACCORD because stopped early). The consistency and power problems can be seem by considering the headline CV risk reduction in each study :
study HR/RR p ACCORD 0.90 (0.78, 1.04) NS
VADT 0.86 (0.73, 1.04) NS
Advance 0.94 (0.84, 1.06) NS
UKPDS'08 0.84 (0.75, 0.97) 0.01
Someone will no doubt do a meta-analysis on this lot when VADT appears in print - my bet it that it will be statistically significant.Comments, as ever, welcome
Philip Home