Power interim analysis

Timing of any interim analysis Reason for sample size Power of clinical study Level of significance Criteria for termination of study Procedure for missing and imused data Reporting procedures for deviations from statistical plan... 

This method of calculating the conditional power assumes that the observed difference between the treatments at the interim stage is the true difference, termed the conditional power under the current trend. It is also possible to calculate conditional power under other assumptions, for example, that the true treatment difference in the remaining part of the trial following the interim analysis is equal to d. These calculations under different assumptions about how the future data should behave will provide a broad basis on which to make judgements about terminating the trial for futility. 

The trial was, in fact, stopped at the interim analysis due to futility the conditional power, was well below 30 per cent. In addition, even though the formal boundary for safety was not crossed, the trend was in the direction of excess deaths in the ancrod group. 

Summers, W.A. (2003), Interim Project Report, Task A.l, Nuclear Hydrogen Plant Definition, NERI Project 02-0160, Centralized Hydrogen Production from Nuclear Power Infrastructure Analysis and Test-case Design Study, WSRC-TR-2003-00484, Savannah River Technology Center, Aiken, SC, USA. 

The code will be broken and data will be analyzed when the 12-mo follow-up has been completed for all patients. At that time, DHA therapy will be offered to all patients who desire to receive it. Clinical and laboratory studies will be monitored by an independent data and safety monitoring committee. This committee will also perform an interim analysis when 30 patients have completed assessment and has permission to terminate the study if there are significant favorable findings or unanticipated adverse outcomes. A determination of statistical power indicates that this sample size is sufficient to detect a major effect (0.862 standard deviations). With a more modest effect of 25%, however, the statistical power diminishes to 60%. The study has been approved by the Institutional Review Board at the Johns Hopkins Medical Institutions and is supported by a research grant from the Office of Orphan Products Development at the Food and Drug Administration. Fifty-two patients are enrolled in the study at this time. The code has not yet been broken. No adverse effects attributable to the medication have been observed. 

In keeping with the statistical plan, the next interim analysis of MACE events was performed after 550 events had occurred, resulting in a hazard ratio point estimate of 0.96 and an associated confidence interval upper bound of 1.17, demonstrating that alogliptin was noninferior but not superior to placebo. Since the conditional power to show superiority with 650 events was less than 20%, the trial was terminated. Prior to data lock, an additional 71 participants had a primary endpoint event. The final analysis of MACE yielded a hazard ratio of 0.96 and an associated confidence interval upper bound of 1.16 (p<0.001 for noninferiority p=0.32 for superiority), confirming that alogliptin did not unacceptably increase cardiovascular risk. 

More recently, there has been interest in adaptive designs where the sample size and number of events are increased based on an unblinded look at interim analysis results. For example, a trial might be initially sized based on the number of MACE outcomes needed to demonstrate noninferiority however, if superiority appears likely based on the conditional power available at the time of an interim analysis, the number of needed MACE outcomes and the sample size could be increased. Such adaptive designs require special statistical analyses to protect the alpha level and special provisions to minimize operational bias (FDA 2010). This approach reduces the risks to participants (and to the sponsor) associated with initiating a large superiority trial up-front, when there is limited information about the compound. 

Interim Reliability Evaluation Program Analysis of the kfillstone Point 1 Nuclear Power Plant... 

F) Anon, Experimental Analysis of Hybrid Rocket Fuels for MHD Pulse Power Generation Interim Tech Rept No 3, 2 Mar—2 Nov 66,... 

Also, the analysis plan should identify the statistical methods that will be used and how hypotheses will be tested (e.g., a p value cutoff or a confidence interval for the difference that excludes 0). And the plan should prespecify whether interim analyses are planned, indicate how issues of multiple testing will be addressed, and predefine any subgroup analyses that will be conducted. Finally, the analysis plan should include the results of power and sample size calculations. 

Ref. (61)]. The interim results confirmed the feasibility and safety of using E2F-I decoy. Analysis of the secondary endpoints using quantitative coronary angiography and three-dimensional intravascular ultrasound demonstrated increased patency and adaptive vessel remodeling characterized by reduction in neointimal size and volume in the treated group one year after treatment, leading to 40% reduction in critical stenosis. These results will now need to be confirmed in adequately sampled and powered phase III studies in patients with coronary and peripheral vessel disease in order to further... 

F) Anon, Experimental Analysis of Hybrid Rocket Fuels for MHD Pulse Power Generation , Interim Tech Rept No 3, 2 Mar—2 Nov 66, Contract DA-44-009-AMC-973(T), United Techgy Center, Sunnyvale (1966) G)Anon, R and D Abstracts, Vol 20, No 6,16-31 March 1967 , MinyAvn, London (1967) H) Anon, Research and Development Programs , Rept No APL-U-RQR/67-3, JHU/APL, Contract NOW-62-0604 (1967) I) A.C. Parmee S.F.W. Woodhouse, Assessment of Materials for Use as Nozzle Inserts in Solid Propellant Rocket Motors Part V, Tungsten , Rept No RPE-TR-67/17, Rocket Propn Estbmt, Westcott (Engl)... 

P. L. Hemmings and R. A. Perkins, Thermodynamic phase stability diagrams for the analysis of corrosion reactions in coal gasification/combusion atmospheres. Research Project 716-1, Interim Report, Palo Alto, CA, Lockheed Palo Alto Research Laboratories for Electric Power Research Insitute, December, 1977. 

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