Sample Size Considerations. Sample size calculations based on various incidence rates in the control arm, relative vaccine efficacies for those in the MVA-NP+M1 arm, and alpha levels (two-sided) are provided in Table 7-1. Table 7-1 Sample Size Calculations (80% power, two-sided alpha levels) Rate of Influenza in Control Arm Relative Vaccine Efficacy Total Sample Size Required α=0.10 α=0.15 α=0.20 2% 30% 11478 9658 8360 35% 8188 6890 5964 40% 6082 5118 4430 50% 3652 3074 2660 3% 30% 7586 6382 5524 35% 5412 4554 3,942 40% 4022 3384 2930 50% 2416 2034 1760 4% 30% 5640 4746 4108 35% 4026 3386 2932 40% 2992 2516 2178 50% 1798 1512 1310 All calculations assume 80% power and given this is a proof of concept study an alpha of 0.1 is chosen for powering analyses. Based on the projected range of incidence rates in the control arm, a total sample size of approximately 5000 to 6000 participants over two influenza seasons is expected to provide approximately 80% power to detect a meaningful vaccine efficacy (approximately 35%) in the MVA-NP+M1 arm. After the first influenza season, which will enrol approximately 2,200 participants, a sample size recalculation may be performed on the basis of the observed relative vaccine efficacy of MVI-NP+M1 during the first influenza season. This will be described in more detail in the SAP.
Sample Size Considerations. The anticipated enrollment in this study is approximately 100 subjects. The primary efficacy endpoint and all analyses based on the response will be based on a mITT population consisting of all subjects who receive any dose of KTE-X19 in Phase 2. This study uses a single-arm design to test for an improvement in overall complete remission rate. For the test of efficacy this study has approximately 93% power to distinguish between an active therapy with a 65% true overall complete remission rate from a therapy with an overall complete remission rate of 40% or less with a 1-sided alpha level of 0.025. A step-down test of the secondary endpoint MRD-negative Rate will be performed against a MRD-negative rate of 30% if the testing of the overall complete remission rate is significant. In Phase 1, the SRT will review safety data after 3 subjects in the DLT evaluable set (see Section 10.5) have had the opportunity to be followed for 28 days after the KTE-X19 infusion. If the conditioning regimen and KTE-X19 dose evaluated in Phase 1 is determined to be safe based on the incidence of DLT, up to approximately 30 additional subjects may be enrolled to further evaluate safety prior to commencing Phase 2. Xxxxxx Xxxxx 0, one interim and one primary analyses will be performed. The interim analysis is for safety only and will occur after 20 subjects have been treated with KTE-X19 and have had the opportunity to be followed for 30 days after the KTE-X19 infusion. The primary analysis will occur when the overall study enrollment is complete and all subject in the mITT set have had the opportunity to complete the month 6 disease assessment. 65% Approximately 100 subjects may be enrolled into the entire study. At the time of the primary analysis, in the event that either less than or more than 50 subjects are eligible for the mITT set, all mITT eligible subjects will be included in the analysis.
Sample Size Considerations. This study uses an open-label, 2-cohort design to test for an improvement in XXX. Up to approximately 130 subjects with r/r MCL will be enrolled and treated with anti‑CD19 CAR T cells, including 10 axicabtagene ciloleucel subjects and up to approximately 80 KTE-X19 subjects in Cohort 1 and up to 40 KTE-X19 subjects in Cohort 2. The primary analysis will be conducted after 60 Cohort 1 KTE-X19 subjects have been enrolled and treated and have had the opportunity to be evaluated for response 6 months after the Week 4 disease assessment. For the test of efficacy, 60 KTE-X19 subjects in Cohort 1 will provide at least 96% power to distinguish between an active therapy with a 50% true response rate from a therapy with a response rate of 25% or less (undesirable response rate, for purposes of futility assessment) with a 1-sided alpha level of 0.025. No hypothesis will be tested in Cohort 1 axicabtagene ciloleucel subjects or Cohort 2 subjects. Exploratory analyses will be conducted on the data collected from these subjects. In Cohort 1, 4 interim analyses will be performed: Cohort 1 interim analysis 1 will be conducted after 10 subjects in Cohort 1 have been enrolled and treated with anti‑CD19 CAR T cells and have had the opportunity to be followed for 30 days. This interim analysis will be for safety only. Cohort 1 interim analysis 2 will be conducted after 20 subjects in Cohort 1 have been enrolled and treated with anti‑CD19 CAR T cells and have had the opportunity to be evaluated for response 3 months after treatment with anti‑CD19 CAR T cells. In this interim analysis, the DSMB will review data for both safety and efficacy (futility only). Cohort 1 interim analysis 3 will occur after 38 subjects in Cohort 1 have been treated with anti‑CD19 CAR T cells and have had the opportunity to be assessed for response 6 months after the treatment with anti‑CD19 CAR T cells. This interim analysis will be performed for a Kite internal review of the accumulating data of safety and efficacy. Cohort 1 interim analysis 4 will occur after 44 subjects in Cohort 1 have been treated with anti‑CD19 CAR T cells and have had the opportunity to be followed for at least 30 days. In this interim analysis, the DSMB will review data for safety only, with focus on the 6 KTE-X19 subjects treated most recently in this cohort. In Cohort 2, one interim analysis will be performed: Cohort 2 interim analysis will be conducted after 10 subjects in Cohort 2 have been enrolled and treated w...
Sample Size Considerations. Total of 280 patients in 2 groups of equal size (140 per group) Primary comparison: Obeticholic acid group vs. Placebo group Primary outcome measure: Histological improvement in NAFLD (defined above) Error protection: Type I= 0.05 and Type II= 0.10 (90% power) Missing data: 10% will not have 72 week biopsies and will be considered not improved Minimum clinically important difference: 50% higher relative rate of improvement in the obeticholic acid group vs. the placebo group Assumed response rates:
Sample Size Considerations. The design of the particular retrospective study has an observational character focusing on a specific disease i.e. breast cancer. The aim is to analyse the relationships between biological, psychological and social factors and their influence on resilience among breast cancer patients. Given the number and the heterogeneity of the clinical centres involved in the BOUNCE project, it is not possible to predict a priori the optimal sample size. The goal is to collect as many data sets as possible, in order to obtain the most representative sample.
Sample Size Considerations. Sample size is determined by the number of patients who participated in the previous phase III Study (RP103-03) and any additional patients, who did not complete the RP103-03 study, who enroll after all patients that participated in RP103-03 have completed and data have been analyzed.
Sample Size Considerations. In the Phase 1b dose escalation, at least 9 participants are expected to be enrolled. The sample size was determined empirically and is consistent with those used in this type of initial human clinical study. A total of at least 108 additional participants are expected to be treated in the Phase 2a (dose expansion) with OPT-302 at the MTD or highest dose tested from the Phase 1b, in combination with aflibercept (72 participants) or with aflibercept alone (36 participants). Increasing numbers of participants will be exposed in the various phases of the trial: • In the Phase 1b dose escalation, if 3 participants will be treated with OPT-302 per cohort (without dose limiting toxicity), a total of at least 9 participants will be treated in this phase of the trial. • In the Phase 2a dose expansion, 72 additional participants will be enrolled at the MTD or the highest dose level of OPT-302 (determined from the Phase 1b). In case one or more of these 72 participants are not evaluable, randomization will continue and more patients will receive the same dose. • A total of up to at least 81 participants receiving OPT-302 is anticipated to be enrolled in the trial (9 in Phase 1b and 72 in Phase 2a). The table below shows the true proportion of patients with an AE that can be ruled out at various confidence levels, assuming no such event is observed in the trial. Number of participants without adverse event Confidence level 80% 90% 95% 3 0.48 0.57 0.63 9 0.24 0.30 0.35 81* 0.04 0.05 0.06 * If more than 72 participants are randomized to the experimental arm (aflibercept + OPT-302) in Phase 2a, the confidence levels of the total group of participants receiving OPT-302 will be higher than N=81. In the Phase 2a dose expansion, subjects will be allocated in a 2:1 ratio to one of two treatment groups, aflibercept with OPT-302 or aflibercept with sham, with minimization for two baseline characteristics: BCVA (≤ 55 vs. > 55 letters) and CST (≤ 450 vs. > 450 µm). The primary outcome of the Phase 2a is the proportion of evaluable patients with a response of ≥ 5 letter gain in BCVA from baseline to week 12 according to ETDRS criteria in the combination aflibercept + OPT-302 group. The design of the trial is non-comparative in so far as the sample size is calculated for the aflibercept + OPT-302 arm only. A one-stage design is used for the primary outcome (Xxxxxxx 2001) of the aflibercept + OPT-302 arm. A formal rule allows for the assessment of the observed response rate as comp...
Sample Size Considerations. The primary endpoint is the percentage of patients progressing at 6 months. Based on a contemporary control of no maintenance after best response to prior chemotherapy8, the control arm with pembrolizumab alone is expected to have only 8% of patients with no progression at 6 months. To be of clinical interest, at least 58% of patients must be progression-free at 6 months on the pembrolizumab plus paricalcitol arm. A sample size of 12 patients per arm will provide 90% statistical power to detect this difference assuming a one-sided alpha level of 0.05. A one-sided test was selected as we are only interested in the combination if it decreases the percentage of patients progressing at 6 months. This sample size estimate was obtained using binomial enumeration of all possible outcomes to compare two independent binomial proportions (Xxxxxxx’x xxx-squared test) using PASS 15.18 A statistical concern is that the Xxxxxxx xxx-squared test does not guarantee the alpha level. We confirmed that we have adequate statistical power using the Miettinen & Nurminen 19 exact likelihood score method (89% power) using Pass 15.
