Guidelines for calculating sample size in 2x2 crossover trials : a simulation study

Abstract

Abstract:In crossover trials, patients receive two or more treatments in a random order in different periods. The sample size determination is often an important step in planning a crossover study. This paper concerns sample size calculations in 2x2 crossover trials, with random patient effects and no interaction between the treatment and the patient under two scenarios, namely the exact and the large sample size approaches. Simulation was carried out for determining the sample size for both scenarios. For varying parameter values, simulation was used for generating samples of the required size and examining whether the significance level and power of the tests are maintained. The results indicate that when the sample size was ≤ 5, neither method maintained error rates and when the sample size was >5 and < 12 only the exact approach maintained error rates. However, when the sample size is approximately > 12 both methods maintained error rates. In addition it was found that a saving in sample size can be achieved depending on the extent of the correlation between the observations on the same patient. The simulation results indicate that crossover studies should not be conducted when the anticipated sample size is ≤ 5 and when a sample size of >5 and < 12 is anticipated, the exact method of determining sample size should be used. When larger sample sizes are anticipated either method can be used but the method based on large sample size approximation is simpler.

Effects of oral contraceptives on the quality of life of women with polycystic ovary syndrome: a crossover randomized controlled trial

“…As most crossover studies, and despite all of our approaches, there was a more loss to follow-up than initially expected; however, it should be kept in mind that patients left the study mostly because of unwillingness to continue treatment for non-medical reasons and they had no difference in their baseline characteristics, such as age and BMI. Although the loss to follow-ups extremely reduced the sample size, each study group had 7 or more participants; recent guidelines for calculating sample size in cross-over trials recommended having more than at least 5 participants in each study group [46]. GEE analysis can also partially overcome missing data [47].…”

Effects of oral contraceptives on the quality of life of women with polycystic ovary syndrome: a crossover randomized controlled trial

“…According to the recent International Evidencebased Guidelines for the Assessment and Management of PCOS, all women with PCOS should be screened and monitored for QOL status to prevent, identify, and manage their health concerns. While these guidelines recommended that improving the QOL of the patients should consider as an important goal of treatment [11,35,36], the effect of OCs on psychological health and QOL of PCOS has been investigated only in a limited number of previous studies [12][13][14][15]. Available data showed that treatment with OC was associated with a signi cant improvement in the QOL in a 16-week randomized controlled trial (RCT) [13], a 12-month RCT [12], and a 6-month observational trial [14].…”

Effects of oral contraceptives on the quality of life of women with polycystic ovary syndrome: a crossover randomized controlled trial

“…As most crossover studies, and despite all of our approaches, there was a more loss to follow-up than initially expected; however, it should be kept in mind that patients left the study mostly because of unwillingness to continue treatment for non-medical reasons and they had no difference in their baseline characteristics, such as age and BMI. Although the loss to follow-ups extremely reduced the sample size, each study group had 7 or more participants; recent guidelines for calculating sample size in cross-over trials recommended having more than at least 5 participants in each study group [36]. GEE analysis can also partially overcome missing data [37].…”