Determination of Sample Size. The sample size of this study is based on the results obtained with a randomized, double blind, study with Racecadotril in the treatment of hospitalized children aged 3-60 months suffering from acute watery diarrhea (Bio-Projet Study nr. 45, Xxxxxxx Xxxxx et al. 1998). A total of 135 subjects were analyzed in this study. Data of the study showed following recovery rates over time: Duration of treatment Percentage of recovered patients Placebo Racecadotril Sample size per group required for a power of 80% using log-rank test (+10% drop out rate) after 1 day (24 hours) 18.3% 46.6% 41 (46) After 2 days (50 hours) 35.8% 70.1% 36 (40) After 3 days (72 hours) 59.4% 84.2% 55 (62) After 4 days (96 hours) 76.3% 90.1% 119 (132) After 5 days (120 hours) 80.6% 94.7% 90 (100) The mean duration of diarrhea was 64 (±4.6) hours in the placebo group (median 64 hours) and 40 (±4.1) hours in the Racecadotril group (median 28 hours), Therefore an appropriate approach to investigate a difference between recovery rates of the two treatment groups would be after a treatment duration of at least 3 days (i.e 72 hours).When the sample size in each group is 55 (with a total number of recoveries of at least 26), the two-sided log-rank test for equality of survival curves will have 80% power to detect the difference between 84.2% rate of recovery in the Racecadotril group and the 59.4% rate of recovery in the placebo group after a treatment duration of 72 hours. Adding a 10% drop-out rate the sample size per groups would be 62 subjects i.e. 124 subjects in total. A minimum number of 20 subjects should be available in each age group (3 – < 24 months, 2 years to 11 years, 12 to < 18 years). A subgroup analysis per age group (3 – < 24 months, 2 years to 11 years, 12 to < 18 years) will be performed.
Determination of Sample Size. To reliably detect (p<0.05, statistical power >80%) a more than two-fold increase in the odds of achieving smoking reduction at 24 weeks among the active versus placebo groups, and assuming a smoking reduction rate of 15% in the placebo group versus 25% in the active snus group (corresponding to an odds ratio of 1.9), the target sample size can be estimated at 250 per group, that is, a total size of 500 study participants. In previous randomized studies of NRT versus placebo, NRT has resulted in an increased proportion of participants achieving short- to medium term smoking cessation with odds ratios in the order of 1.5-3. Epidemiological, cross-sectional studies from Sweden have indicated that snus might be more effective as an aid in smoking cessation than NRT. Against this background the mentioned target sample size should provide reasonable statistical power for current purposes.
Determination of Sample Size. It is expected that the responder rate for this study is approximately 80% based on the results of a pivotal study of a similar investigational product Juvéderm Volbella XC. The margin of error (associated with 95% CI) for estimating an 80% expected responder rate is 10%, which is desirable to attain by having a sample size of 60 subjects for the study. Patients’ dropout rate is expected to be negligibly small at Day 30 post-treatment when the primary efficacy assessment is collected, thus 60 subjects will be recruited into the study.
Determination of Sample Size. There is no formal sample size calculation. The sample size is based on qualitative considerations and is sufficient to provide safety evaluation of eteplirsen in the studied population.
