Previously many people felt that it was too difficult to compute OS, but we have shown that this can now be accomplished for useful sample sizes.

Concurrent with our initial clinical trials work in 1991, using N=150, P. Jones (1992) noted that he could only handle N=25. Our results would have taken him approximately 100,000 times as long - i.e., his programs would still be running! (Please note that his programs were standard implementations, and the only reason he is explicitly pointed out is because his work was concurrent with ours and he explicitly mentioned what many other people only noted implicilty.) Since then, we have analyzed some problems with sample sizes as large as N=400.

Note that there has been no previous work on determining fully optimal few-stage designs. No one had obtained fully optimal stage sizes, nor had they even determined how to compute them.