CHAPTER 5 Conducting Clinical Research 67

If you were hoping to have six participants in each group, you won’t be pleased if

you end up with three participants receiving the drug and nine receiving the

placebo, because it’s unbalanced. But unbalanced patterns like this arise quite

often from 12 coin flips. (Try it if you don’t believe us.) A better approach is to

require six participants in each group but shuffle those six Ds and six Ps around

randomly, as shown in Figure 5-2.

This arrangement is better because there are exactly six participants assigned to

drug and placebo each. But this particular random shuffle happens to assign more

drugs to the earlier participants and more placebos to the later participant (which

is just by chance). If the recruitment period is short, this would be perfectly fine.

However, if these 12 participants were enrolled over a period of five or six months,

seasonal effects may be mistaken for treatment effects, which is an example of

confounding.

To make sure that both treatments are evenly spread across the entire recruitment

period, you can use blocked randomization, in which you divide your subjects into

consecutive blocks and shuffle the assignments within each block. Often the block

size is set to twice the number of treatment groups. For instance, a two-group

study would use a block size of four. This is shown in Figure 5-3.

You can create simple and blocked randomization lists in Microsoft Excel using

the RAND() built-in function to shuffle the assignments. You can also use the web

page at https://www.graphpad.com/quickcalcs/randomize1.cfm to generate

blocked randomization lists quickly and easily.

Selecting the analyses to use

You should select the appropriate analytic approach for each of your study hypoth-

eses based on the type of data involved, the structure of the study, and the require-

ments of the hypothesis. The rest of this book describes statistical methods to

FIGURE 5-2:

Random

shuffling.

© John Wiley & Sons, Inc.

FIGURE 5-3:

Blocked

randomization.

© John Wiley & Sons, Inc.