The alternating-sequence design (or multiple-period crossover) trial for evaluating treatment efficacy in infertility.
OBJECTIVE
To determine whether a constant-sequence or an alternating-sequence design is better for the evaluation of infertility treatment efficacy when multiple cycles of treatment are undertaken.


METHODS
A simulation exercise using analytical methods.


METHODS
University medical center.


METHODS
A hypothetical, heterogeneous population of infertile patients participating in a randomized trial comparing an experimental treatment, with effectiveness of 2.0, to no treatment.


METHODS
Comparison of a constant-sequence design in which the subject receives the same intervention or the alternating-sequence design in which experimental and control treatments are crossed over after each successive cycle.


METHODS
Relative risks of pregnancy per cycle and overall after a maximum of five cycles of treatment.


RESULTS
With both designs, the pregnancy rates in experimental and control groups showed a consistent decrease with each successive cycle. The overall effectiveness in the constant-sequence design was underestimated at 1.83, whereas in the alternating-sequence design it was overestimated at 2.06. However, by restricting the analysis in the latter design only to the odd-numbered cycles, the relative risk was precisely correct at 2.00.


CONCLUSIONS
When multiple cycles of treatment are undertaken to evaluate the efficacy of infertility therapy, the alternating-sequence design with restriction of the analysis to only the odd-numbered treatment cycles provides an unbiased estimation of the treatment effect.
Norman
G R
GR
Department of Clinical Epidemiology and Biostatistics, McMaster University, Hamilton, Ontario, Canada.
Daya
S
S
D002986:Clinical Trials as Topic; D003198:Computer Simulation; D005260:Female; D006801:Humans; D007246:Infertility / Q000628:therapy*; D007247:Infertility, Female / Q000628:therapy; D011247:Pregnancy; D018873:Pregnancy Rate; D016032:Randomized Controlled Trials as Topic