Influences on the Sponsors Choice of These Values

As we have discussed, when conducting a sample-size estimation, the researcher has to choose values for a and p and has to come up with a standardized treatment effect, which is in turn the result of finding the best possible estimates of a clinically significant difference and its variation. What are the influences that lead the sponsor to choose certain values for a, p, and the standardized treatment effect  

For financial, time demand, and logistical reasons, a smaller sample size is preferable to a sponsor than a larger one. There are also ethical factors that need to be borne in mind. It is unethical to choose a sample that can reasonably be considered either too small or too large (see Section 9.2). The optimum sample size can be considered to be the smallest sample size that can reasonably be expected to answer the primary research question, i.e., evaluating the primary objective as stated in the study protocol. 

What might influence the sponsor s choice of a and P It was noted in Section 9.5.1 that a typical value for a is 0.05 and a typical value for P is 0.10 (i.e., a typical power is 90%). Circumstances in which it may make sense to choose different values include the following  

While either action, i.e., reducing a or p, will increase the value of N given by the sample-size estimation and therefore result in additional cost to the sponsor, the sponsor may well decide that, in the overall balancing act of estimating sample size, there are good reasons to do this in cases such as these examples. 

At each stage of the drug development program and for each trial within that stage, sponsors need to be aware of the implications of their choice of a and their choice of p and the acceptability of these implications. The implications of each choice and the acceptability of these implications may change throughout the course of a clinical development program. 

---