Statistical Considerations. Standard statistical methods will be employed to determine primary and secondary efficacy and safety outcomes. Depending on the final study design, BioForm may consult with appropriate statistical authorities to both determine the effectiveness of the surgery and accurately assess a change over time using a 95% confidence interval. NUMBER OF INVESTIGATOR SITES & PATIENTS: BioForm expects to enroll up to [****] patients at up to [****] investigator sites. Standard screening and evaluation criteria may be employed to identify the appropriate patient population. POTENTIAL TIMELINE & BUDGET: Task Potential Date Cost [****] [****] [****] [****] [****] [****] [****] [****] [****] [****] [****] [****] [****] [****] [****] [****] [****] [****] [****] [****] [****] [****] [****] [****] [****] [****] [****] [****] **** Certain information on this page has been omitted and filed separately with the Securities and Exchange Commission. Confidential treatment has been requested with respect to the omitted portions.
Statistical Considerations. The statistical analyses will assess longer term safety, fracture incidence (including vertebral and non-vertebral fracture), and BMD change following treatment with alendronate for six months after the completion of a subject’s participation of 18 months in study BA058-05-003. The efficacy and safety analyses performed at six months will be used as a follow-up to the 18 month fracture endpoint for Study BA058-05-003. At this time-point, subjects will be analyzed based on the randomization assignment in the BA058-05-003 study.
Statistical Considerations. Statistical analysis will focus on longer term safety, fracture incidence, including vertebral fracture and BMD change following six months of standard-of-care osteoporosis treatment in subjects who have previously received 18 months of blinded treatment with BA058 Injection 80 µg/Placebo. The analyses will be performed based on the treatment arm they were randomized to in the BA058-05-003 study. The analyses performed on data collected at Month 12 and Month 24 will be descriptive in nature and will be summarized descriptively with number, percentage (for categorical variables), mean, standard deviation, median, minimum and maximum (for continuous variables). The analyses performed at six months will be used as a follow-up to the 18 month fracture endpoint for Study BA058-05-003. At this time-point, subjects will be analyzed based upon the randomization assignment in the BA058-05-003 study.
Statistical Considerations. This is a two-center study, with equal numbers of patients treated at each site. All patients receive CaPVax injections and act as their own controls. The treatment plan is presented in Section 5.0. 37
Statistical Considerations. 1. Is stratification/randomization involved? We propose using a cross-over design, because this will control for different degrees of refractive error, visual performance, and driving experience. Additionally, this will allow us to investigate “relative” and absolute benefits of toric contact lenses since subjects will serve as their own controls. ►IF YES, describe the stratification/ randomization scheme. The study is a block design with lens type (placebo, sphere, toric) counterbalanced over 3 sessions of driving and vision testing during the study visit. Driving and vision testing # of subjects Session 1 Session 2 Session 3 9 Placebo Sphere Toric 9 Placebo Toric Sphere 9 Sphere Toric Placebo 9 Sphere Placebo Toric 9 Toric Placebo Sphere 9 Toric Sphere Placebo ►IF YES, who will generate the randomization scheme? X Other: the PI
Statistical Considerations. Statistical analysis will focus on safety, fracture incidence, including vertebral fracture and BMD change following six months of alendronate treatment in subjects who have previously received 18 months of blinded treatment with Abaloparatide-SC/Placebo. Additional Protocol BA058-05-005 Amendment 4, Version 1 (24 August 2015) Radius Health, Inc. Confidential analyses will also be cumulatively at Month 12, 18, and 24 (i.e., Visit 4, 5, and 6). Full details of these analyses will be provided in the Statistical Analysis Plan. The efficacy and safety analyses performed at six months will be used as a follow-up to the 18 month fracture endpoint for Study BA058-05-003. Subjects will be analyzed based upon the randomization assignment in the BA058-05-003 study.
Statistical Considerations. This study uses an open-label, 2-cohort design. Among the Cohort 1 KTE-X19 subjects, with a target 50% response rate per independent review, an alternative hypothesis will be tested against a null hypothesis that the response rate is 25% or less. For the test of efficacy in the Cohort 1 KTE-X19 subjects, this study has 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 with a 1-sided alpha level of 0.025. No hypothesis will be tested on Cohort 1 axicabtagene ciloleucel subjects and on Cohort 2. Four interim analyses will be performed in Cohort 1, and 1 interim analysis will be performed in Cohort 2. One primary analysis will be performed after 60 Cohort 1 KTE-X19 subjects have been enrolled and treated and have had the opportunity to be assessed for response 6 months after the Week 4 disease assessment. 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 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 (Section 10.5) have been enrolled and treated with anti-CD19 CAR T cells and have had the opportunity to be evaluated for response 3 months after the investigational product (IP) infusion. This interim analysis will be for safety and efficacy (futility only). Cohort 1 interim analysis 3 will occur after 38 subjects treated with anti-CD19 CAR T cells in Cohort 1 have had the opportunity to be assessed for response 6 months after the IP infusion. Cohort 1 interim analysis 4 will be conducted after 44 subjects in Cohort 1 have been enrolled and treated with anti-CD19 CAR T cells and have had the opportunity to be followed for at least 30 days after the IP infusion. This interim analysis will assess safety only, with focus on the KTE-X19 subjects treated most recently in this cohort. Cohort 2 interim analysis will be conducted after 10 subjects in Cohort 2 have been enrolled and treated with KTE-X19 and have had the opportunity to be followed for 30 days after the KTE-X19 infusion. This interim analysis will assess safety and efficacy. The primary analysis will occur after 60 KTE-X19 subjects in the modified intent-to- treat (mITT) set of Cohort 1 have been enrolled and treated with KTE-X19 and have had the opportunity to be assessed for response 6 months after the Week 4 disease asses...
Statistical Considerations. Describe the statistical analyses that support the study design. As this is a pilot evaluation of the acceptability and feasibility of providing CBT4CBT in a Black church setting, data analyses will focus on determining whether the results warrant further adaptation of the existing CBT4CBT program. Criteria for this will include (1) measuring acceptability of treatment by giving each participant a post-intervention satisfaction survey as well as a qualitative exit interview, to fully assesses satisfaction with the intervention, perception of outcome, attitudes about spiritual practices accompanying CBT modules, and whether the participant would recommend this program to a friend. (2) Feasibility will be measured by at least 2/3 of participants (N=27) completing the CBT4CBT intervention. Secondary analyses will include significant reductions in drug use, as measured by mean change scores in the severity and quantity of substance use, and functioning over the course of treatment intervention. The proposed sample size (n=40) is adequate to detect this effect.
Statistical Considerations. 8.1 Trial Design This is a randomized, double blind, placebo-controlled clinical trial. Eligible patients will be randomized in a 1:1 ratio to one of two treatment arms: pembrolizumab + paricalcitol or pembrolizumab + placebo. Trial treatment will be administered every three weeks per the schedule as described in 4.2. The percent of patients with disease progression at six months will be the primary endpoint. Secondary endpoints will include: incidence of toxicities, overall survival, mutational landscape, transcriptional programs and cellular (immunity) VDR targets in the immune microenvironment.
Statistical Considerations. This is a two-center study, with equal numbers of patients treated at each site. All patients receive CaPVax injections and act as their own controls. The treatment plan is presented in Section 5.0. Safety Monitoring A serious adverse event (AE) has been defined on page 19. Consider the patients treated at one of the dose levels (DLs). Denote the probability of an adverse event (AE) at this DL by (theta). The maximum acceptable probability of an AE in a population of patients treated at any DL is .05. We assume that, a priori, (theta) follows a beta distribution with parameters (.10,1.9), which in particular has mean .05. The early stopping criterion is that the DL will be terminated if at any point in the trial Pr[(theta) > .05, data] > .90. Applying this criterion in sequence will terminate that DL if [# patients with an AE ]/ [# patients evaluated] is > or = 2/10, 3/22, 4/35, or 5/50. To apply this rule, note that the boundary "2/10" means that the DL will be discontinued if 2 AEs are observed at any point among the first 10 patients treated at that DL and evaluated, hence 2/2, 2/3, ..., up to 2/10 will cause the DL to be terminated. Similarly, for example, if there are 1/10 and then 2/11 AEs, so that the trial continues to treat patients at that DL at that point, but subsequently one more AE is observed in any patient thereafter up to the 22nd patient evaluated, then that DL is stopped. These rules pertain to all patients evaluated at that DL, including patients in the dose escalation stage. Thus, for example, a DL will be terminated if 2 patients among the first 3 or 6 treated in the dose escalation stage have an AE. 100 For a single dose level with up to 20 patients, this rule has the following operating characteristics: Sample Size 25th, 50th, 75th True Prob[AE] Prob[Early Termination] Percentiles ------------- ----------------------- ---------------------------- .01 .005 20 20 20 .05 .11 20 20 20 .10 .37 10 20 20 .20 .80 5 9 18 .25 .91 4 7 10 Although at most 20 patients will be treated at each dose level if none of the three DLs are terminated early, in the case that a DL is terminated early the remaining patients among the 60 in the trial will be randomized to the remaining dose levels. In this case, more than 20 patients may be treated on each of the remaining DLs. This is a simple "play the winners" strategy. It has the advantage that it is ethically desirable for the patients, since they are less likely to be treated at unsafe DLs, and it is s...
