Pocock method

Pocock (1977) developed a procedure which divides the type I error rate of 5 per cent equally across the various analyses. In the example above with two interim looks and a final analysis, Bonferroni would suggest using an adjusted significance level of 0.017 (= 0.05 4- 3). The Pocock method however gives us the correct adjusted significance level as 0.022 and this exactly preserves the overall 5 per cent type I error rate. 

Pocock SJ. Group sequential methods in the design and analysis of clinical trials. Biometrika 1977 64 191-99. 

One area that we briefly mentioned was interim analysis, where we are looking at the data in the trial as it accumulates. The method due to Pocock (1977) was discussed to control the type I error rate across the series of interim looks. The Pocock methodology divided up the 5 per cent type I error rate equally across the analyses. So, for example, for two interim looks and a final analysis, the significance level at each analysis is 0.022. For the O Brien and Fleming (1979) method most of the 5 per cent is left over for the final analysis, while the first analysis is at a very stringent level and the adjusted significance levels are 0.00052, 0.014 and 0.045. 

Freedman LS, White SJ. 1976. On the use of Pocock and Simon s method for balancing treatment numbers over prognostic factors in the controlled clinical trial. Biometrics 32 691-694. 

Pfeffer MA, Claggett B, Diaz R, ELIXA Investigators et al (2015) Lixisenatide in patients with type 2 diabetes and acute coronary syndrome. N Engl J Med 373 2247-2257 Pocock SJ (1977) Group sequential methods in the design and analysis of clinical trials. Biometrika... 

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