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The Win Ratio has gained significant traction in cardiovascular trials as a novel method for analyzing composite endpoints (Pocock and others, 2012). Compared with conventional approaches based on time to the first event, the Win Ratio accommodates the varying priorities and types of outcomes among components, potentially offering greater statistical power by fully utilizing the information contained within each outcome. However, studies using Win Ratio have largely been confined to fixed design, limiting flexibility for early decisions, such as stopping for futility or efficacy. Our study proposes a sequential design framework incorporating multiple interim analyses based on Win Ratio or Net Benefit statistics. Moreover, we provide rigorous proof of the canonical joint distribution for sequential Win Ratio and Net Benefit statistics, and an algorithm for sample size determination is developed. We also provide results from a finite sample simulation study, which show that our proposed method controls Type I error maintains power level, and has a smaller average sample size than the fixed design. A real study of cardiovascular study is applied to illustrate the proposed method., Comment: 36 pages, 1 figure, 5 tables

This article consists of three chapters.In Chapter 1, it is determined by the consecutive odd numbers, and study to the intrinsic properties of a class of matrix sequence. Through the establishment of matrix online number concept, characteristics and the online number column use mathematical induction to prove the some properties of this kind of matrix on the number of online features (Theorem 1). Finally, it is given a trial to prove the Goldbach conjecture (Theorem 6). This is the author in the years to explore prime properties in the process of research and discovery, and believe that this finding is of great significance.In Chapter 2, it is defined the concepts of matrix master characteristic number and the Matrix Master Characteristic Sequence (Definition 1). Firstly, we prove that any even number can be expressed as for the difference of two odd prime numbers at least two groups (Theorem 4). Secondly, we prove that there are infinitely many odd prime numbers separated by four (Theorem 9). Finally, we prove that if there is greater than 1 in the intersection by S(3) and s(2m+3) for any natural number m, so that there are infinitely many odd prime numbers separated by 2m(Theorem11). The results will undoubtedly promote the research for Polignac conjecture.In Chapter 3, mainly as a result of any odd natural number a, the intersection by S(a) and s(a+2) is not empty number set, and there are far more than 1 number in the set, where S(a)={k,If 2k+a be prime as k be natural number},and P is a prime number set, N is natural number set. we prove that there are an infinite number of twin prime, and then solve the problem of the twin primes in number theory., Comment: 32 pages. Prime numbers,Matrix master characteristic number,Matrix master characteristic sequence,Goldbach conjecture,Polignac conjecture,The twin prime conjecture