Crossover and self-controlled designs in clinical research.

Crossover studies (clinical trials in which each patient receives two or more treatments in sequence) and self-controlled studies (in which each patient serves as his or her own control) can produce results that are statistically and clinically valid with far fewer patients than would otherwise be required. We investigated the use of the crossover design in the 13 crossover studies that appeared in the Journal during 1978 and 1979. We considered the following important features of design and analysis as they applied to these studies: the method by which patients were assigned to initial treatment (only 7 of 13 studies used random assignment); the determination of when to switch treatments (10 of the 13 used a time-dependent rule, and 3 a less appropriate disease-state-dependent rule); blinding of the crossover point (in only 3 of the 13 studies was the crossover point concealed, but in 4 of the remaining 10 concealment was impossible); assessment of the effects of the order of treatments (included in only 1 of the 13 studies); and the use of at least minimally acceptable statistical analysis (11 of the 13 studies had such an analysis). We also report briefly on 28 additional studies of a single treatment each, in which each patient served as his or her own control before or after treatment or both. The scientific issues were much the same as in crossover studies except that self-controlled comparisons of treatments tended to be less precisely designed and conducted and to focus on clinical problems and patient groups that are especially difficult to study.