Crossover study design

Finally, trials can follow parallel or crossover study designs. In a parallel trial, patients are assigned to a therapy that they remain on, and they are compared with patients in alternate therapy groups. In a crossover trial, patients switch or change therapy assignments during the course of the trial. 

Table 4.4 Crossover study design with two alternating cohorts of eight subjects and a 6 2 restricted randomisation to active drug (A) or placebo (P) - each subject receives A on three occasions and P on one occasion ...

Controlled trials can be conducted under matched pairs, parallel, crossover, group comparisons, or mixed design conditions. Parallel and crossover study designs each have advantages and disadvantages. Both can be used to compare two or more treatments, one of which may be placebo. In a crossover study, all treatments to be compared are administered to every enrolled patient in a carefully designed and blinded sequence with an interim drug washout period. Each patient receives all treatments and thus serves as his or her own control. 

Finally, a crossover study design can be employed such that study participants are randomized to placebo or treatment on one occasion and to the alternate regimen on a second occasion, assuring an adequate washout period between the two occasions. The endogenous concentrations determined in the same persons after placebo administration can be subtracted from the matching sample collected after treatment administration. This design accommodates the intraperson variability and variations in endogenous concentrations due to pulsatile secretion, but assumes that the two separate study days are similar. 

Due to the large inter- and intrasubject variability in QT/QTc (see later for variability discussion), the sample size for crossover study design would typically be about 60-80 subjects (typically 65 subjects) exposed per treatment. This is to ensure... 

The 20 healthy participants were randomized to a three-period crossover study design, where they received three of the six study drugs or placebo in an incomplete block design that resulted in each study drug being administered to nine participants and placebo being administered to six participants in separate periods. 

Consiglio GP, Burden AM, Maclure M, McCarthy L, Cadarette SM (2013) Case-crossover study design in pharmacoepidemiology systematic review and recommendations. Pharmacoepidemiol Drug Saf 22 1146-1153... 

---