On large sample sequential analysis with applications to survivorship data

Although his work on the application of invariance concepts to the sequential testing of composite hypotheses is better known, Cox (1963) has also outlined a large sample approach to the same problem. His method is based on Bartlett's (1946) recognition that the sequence of maximum likelihood estimates (MLE) of the parameter of interest, calculated from an increasing number of observations, resembles asymptotically a random walk of normally distributed variables. However, the large sample theory needed to justify this approach rigorously is left largely implicit. At the end of his paper, Cox suggests that these msthods may be extended to yield a sequential comparison of survival curves (Armitage (1959)), a suggestion which has been reiterated as a research problem in the monograph of Wetherill (1966). In this paper we first present a general theoretical framework in which the asymptotic validity of a wide class of large sample sequential tests may be examined, thus making explicit the justification for Cox's approach. The results of this section are fairly straightforward consequences of the increasingly well known theory of convergence in distribution for random variables which take values in separable metric spaces. Next we illustrate the theory by re-examining Cox's results on the comparison of two binomial parameters. Finally, and of greater consequence from the practical point of view, we present a large sample solution to the problem of the sequential comparison of exponential survival