Comparison of two drugs by multiple stage sampling using Bayesian decision theory

The general problem considered in this thesis is to determine an optimum strategy for deciding how to allocate the observations in each stage of a multi-stage experimental procedure between two binomial populations (e.g., the numbers of successes for two drugs) on the basis of the results of previous stages. After all of the stages of the experiment have been performed, one must make the terminal decision of which of the two populations has the higher probability of success. The optimum strategy is to be optimum relative to a given loss function; and a prior distribution, or weighting function, for the probabilities of success for the two populations is assumed. Two general classes of loss functions are considered, and it is assumed that the total number of observations in each stage is fixed prior to the experiment.

In order to find the optimum strategy a method of analysis called extensive-form analysis is used. This is essentially a method for enumerating all the possible outcomes and corresponding strategies and choosing the optimum strategy for a given outcome. However, it is found that this method of analysis is much too long for all but small examples even when a digital computer is used.

Because of this difficulty two alternative procedures, which are approximations to extensive-form analysis, are proposed.

In the stage-by-stage procedure one assumes that at each stage he is at the last stage of his multi-stage procedure and allocates his observations to each of the two populations accordingly. It is shown that this is equivalent to assuming at each stage one has a one stage procedure.

In the approximate procedure one (approximately) minimizes the posterior variance of the difference of the probabilities of success for the two populations at each stage. The computations for this procedure are quite simple to perform.

The stage-by-stage procedure for the case that the two populations are normal with known variance rather than binomial is considered. It is then shown that the approximate procedure can be derived as an approximation to the stage-by- stage procedure when normal approximations to binomial distributions are used.

The three procedures are compared with each other and with equal division of the observations in several examples by the computation of the probability of making the correct terminal decision for various values of the population parameters (the probabilities of success}. It is assumed in these computations that the prior distributions of the population parameters are rectangular distributions and that the loss functions are symmetric} i.e., the losses are as great for one wrong terminal decision as they are for the other. These computations show that, for the examples studied, there is relatively little loss in using the stage-by-stage procedure rather than extensive-form analysis and relatively little gain in using the approximate procedure instead of equal division of the observations. However, there is a relatively large loss in using the approximate procedure rather than the stage-by-stage procedure when the population parameters are close to 0 or 1.

At first it is assumed there are a fixed number of stages in the experiment, but later in the thesis this restriction is weakened to the restriction that only the maximum number of stages possible in the experiment is fixed and the experiment can be stopped at any stage before the last possible stage is reached. Stopping rules for the stage-by- stage and the approximate procedures are then derived.