Group Sequential Method
Pocock (1977) and O’Brien-Fleming (1979)
• Each stage contains equal increment (1/K) of
patients
– Pocock (1977): each stage is tested at a
constant boundary (or nominal significance
level)
– O’Brien-Fleming (1979): boundaries decrease
(or nominal significance levels increase) as the
study progresses
1
Haybittle-Peto Boundary
• Use a high critical value early on in order to spend most of α
level at the end.
2
O' Brien - Fleming, when t k  k K :
0


*
 t   2  2 Z
 

 2
t 0

t  0  t  1

Pocock, when t k  k K :
 * t    ln 1  e  1t
O’Brien Fleming
α-spending function
3