Residual effect of chlorhexidine gluconate in 4‐day plaque regrowth crossover trials, and its implications for study design

The efficacy of oral hygiene agents in preventing the accumulation of plaque from a zero baseline is conveniently evaluated in the 4-day plaque regrowth model. In many studies a panel of volunteers has been used to compare several agents according to a highly efficient Latin square based crossover design. Often chlorhexidine gluconate is included as a positive control; there is concern that the effect of this potent agent might persist for longer than the 3-day washout period often employed. To test this hypothesis of residual effect, we put together the evidence relating to possible carryover from 12 studies. The residual effect of chlorhexidine differs from that of an inert rinse such as saline or water. Consequently, a longer washout period, such as 10 days, is preferable. Studies omitting chlorhexidine are worth considering. Designs should be balanced for residual effects, at least from the preceding treatment period; several useful designs with this property are presented.