Interim Analyses. There are no plans to conduct an interim analysis and no criteria by which the study would be terminated early based upon statistical determination.
Interim Analyses. The first interim analysis will be done when the recruitment of 40 patients have been completed and followed up for 12 weeks (or progressed or died prior to 12 weeks). The interim analysis will be based on efficacy variables i.e. change in tumour size at 12 weeks. The description of statistical analysis at the interim will be same as section 4.2. Additionally, the following variables will be summarised (frequency and percentage) by treatment groups for overall population. • Response rate at week 12 • Best Objective response • Percentage of patients without progression The above stated analysis will be performed for overall population, PIK3CA mutation-positive patients and non-detected patient population separately. The second interim analysis will be conducted when at least 38 PFS events across both PIK3CA mutation subgroups have been achieved and 30 PIK3CA mutation detected patients have completed 12 week follow up period (or progressed prior to 12 weeks). The 2nd interim analysis will be conducted upon the following efficacy endpoints for the overall population, PIK3CA mutation detected and PIK3CA mutation not detected subgroups : • Change in tumour size at week 12 • Progression-free survival • Duration of response Additionally the following variables will be summarised: • Progression status • Progression free survival • Best objective response More details on the interim analysis can be found in the interim SAP.
Interim Analyses. The planned interim efficacy analyses will focus on the dual composite endpoint of all-cause death or mechanical assist. (No hypothesis testing of the co-primary quad endpoint will be conducted on interim data sets). Two interim reviews are planned to occur after roughly 50% and 70% of the planned 113 events for the dual co-primary endpoint (57and 80 events, respectively). Futility assessments will be conducted at the same meetings. The guidelines for the futility assessment will recommend stopping the study if the all-cause death endpoint and both co-primary endpoints have odds ratios > 1.0 suggesting better outcomes for the control group. The interim efficacy analyses will be assessed using a one-sided O’Xxxxx Xxxxxxx (OBF) type spending function on the dual co-primary endpoint of death or mechanical assist.59, 60 Recommendations for stopping for efficacy will include crossing the O’Xxxxx Xxxxxxx boundary in analysis of the dual co-primary endpoint of all-cause mortality and mechanical assist AND having at least a 1% benefit for levosimendan for the all-cause death endpoint at 30 days. An independent DSMC will be established to monitor the progress of the study and ensure that the safety of subjects enrolled in the study is not compromised. The DSMC will review enrollment and safety data at regular intervals. The first DSMC review will be conducted after the first 200 enrolled patients have completed 30 days of follow-up. In addition to reviewing patient safety, the DSMC will review event rates. Should the event rate in the control arm be below the planned 32%, the DSMC may recommend an increase in the percentage of patients with LVEF ≤20% to bring the event rate to the planned 32%. Additional reviews will be conducted after 50% and 70% of the113 study events for the co-primary endpoint of all-cause mortality or mechanical assist (57 and 80 events, respectively). Additionally the DSMC will conduct the interim efficacy and futility reviews described above.
Interim Analyses. An independent DSMC will be established to monitor the progress of the study, ensure that the safety of subjects enrolled in the study is not compromised, and determine if the study should be stopped for futility/efficacy or the study population should be enhanced with a higher percentage of patients with lower baseline LVEF to meet the initial event rate assumptions included in calculations of study sample size/power. The DSMC will not be otherwise involved in the conduct of the study. See Section 3.3, Study Committees and Section 12.2.5, Processing Primary Clinical Endpoint Safety Events for additional information on the DSMC.
Interim Analyses. Version: 1.0; CURRENT; Most-Recent; Effective There are no plans to conduct an interim analysis and no criteria by which the study would be terminated early based upon statistical determination.
Interim Analyses. The first IA occurs 14 days after approximately 74 patients are randomized. This IA is for futility only. The futility boundary p-value will be calculated using the Xxx XxXxxx spending function with the X’Xxxxx-Xxxxxxx type of boundary based on the actual number of patients who have completed 14 days on study at the time of the IA. The second IA happens 14 days after approximately 124 patients are randomized. This IA is for futility and sample size reestimation. An unblinded sample size re-estimation (SSR), is planned to be performed at this IA. The unblinded SSR will be based on the method of conditional power (CP). It is defined as the probability to detect a statistically significant difference for the primary endpoint at the end of study given the current data observed at this IA, assuming this interim trend continues. The CP will be calculated for the primary endpoint at this IA using East software with CHW method (Cui 1999). The odds ratio and associated p-value will be obtained for the primary endpoint OSI between two arms based on the observed data at this IA, then the CP will be calculated using East. The calculated CP will be assigned to one of the 3 zones:
Interim Analyses. To ensure that appropriate ethical consideration is given to the welfare of the patients enrolled in the study, NINDS-NIH has appointed a Data and Safety Monitoring Board (DSMB). The DSMB will review the incidences and circumstances of adverse events that occur during the course of the trial. Formal interim analyses will occur after 25%, 50%, and 75% of patients have been enrolled. The objectives of the DSMB are ordered as follows:
Interim Analyses. No formal interim analyses are planned for this study other than the safety assessments and scheduled external review.
Interim Analyses. An interim analysis will be performed when all subjects complete Visit 3A (20-40 days post 2nd eye implantation) in order to support the study publication plan of the test articles for near, intermediate and distance visual acuity, contrast sensitivity, defocus curves and adverse events. The interim analysis results will be distributed to a limited audience to limit potential bias in Visit 4A assessments. The clinical trial team with the exception of the Brand Lead will be masked to the interim analysis results.
Interim Analyses. There are no plans to conduct an interim analysis and no criteria by which the study would be terminated early based upon statistical determination. Printed By: Print Date: Alcon - Business Use Only Protocol - Clinical Effective Date: 01-Mar-2018 Document: TDOC-0054838 Status: Effective Version: 2.0; Most-Recent; Effective; CURRENT Serious Adverse Device Effect (USADE) severity or outcome has not been identified in the risk management file. Use Error Act or omission of an act that results in a different medical device response than intended by manufacturer or expected by user. Note: This definition includes slips, lapses, and mistakes. An unexpected physiological response of the subject does not in itself constitute a use error.
