Cette thèse porte sur inférence statistique, les méthodes bootstrap et l’analyse multivariée dans le cadre des processus semi-markoviens. Les applications principales concernent un problème de la mécanique de la rupture. Ce travail a une contribution double. La première partie concerne la modélisation stochastique du phénomène de la propagation de fissure de fatigue. Une équation différentielle stochastique décrit le mécanisme de la dégradation et le caractère aléatoire inné du phénomène est traité par un processus de perturbation. Sous l'hypothèse que ce processus soit un processus markovien (ou semi-markovien) de saut, la fiabilité du modèle est étudiée en faisant usage de la théorie du renouvellement markovien et une nouvelle méthode, plus rapide, de calcul de fiabilité est proposée avec l'algorithme correspondant. La méthode et le modèle pour le processus markovien de perturbation sont validés sur des données expérimentales. Ensuite, la consistance forte des estimateurs des moindres carrés des paramètres du modèle est obtenue en supposant que les résidus du modèle stochastique de régression, dans lequel le modèle initial est transformé, soient des différences de martingales. Dans la deuxième partie de la thèse, nous avons abordé le problème difficile de l'approximation de la distribution limite de certains estimateurs non paramétriques des noyaux semi-markoviens ou certaines fonctionnelles via la méthode bootstrap pondérée dans un cadre général. Des applications de ces résultats sur des problèmes statistiques sont données pour la construction de bandes de confiance, les tests statistiques, le calcul de la valeur p du test et pour l’estimation des inverses généralisés. / The present dissertation is devoted to the statistical inference, bootstrap methods and multivariate analysis in the framework of semi-Markov processes. The main applications concern a mechanical problem from fracture mechanics. This work has a two-fold contribution. The first part concerns in general the stochastic modeling of the fatigue crack propagation phenomenon. A stochastic differential equation describes the degradation mechanism and the innate randomness of the phenomenon is handled by a perturbation process. Under the assumption that this process is a jump Markov (or semi-Markov) process, the reliability of the model is studied by means of Markov renewal theory and a new, faster, reliability calculus method is proposed with the respective algorithm. The method and the model for the Markov perturbation process are validated on experimental fatigue data. Next, the strong consistency of the least squares estimates of the model parameters is obtained by assuming that the residuals of the stochastic regression model are martingale differences into which the initial model function is transformed. In the second part of the manuscript, we have tackled the difficult problem of approximating the limiting distribution of certain non-parametric estimators of semi-Markov kernels or some functionals of them via the weighted bootstrap methodology in a general framework. Applications of these results on statistical problems such as the construction of confidence bands, the statistical tests, the computation of the p-value of the test are provided and the estimation of the generalized inverses.

Health technology assessment: case study on breast carcinoma treatment in the Czech Republic Bc. Lenka Šlegerová January 4, 2019 Abstract This thesis proposes an original method for assessing total costs of med- ical treatment. It defines the semi-Markov model with four states that are associated with specific costs of the treatment, and not with patients' health statuses. This method is applied to individuals' treatment data drawn from the Czech clinical practice in the treatment of the metastatic HER2+ breast cancer. The aim is to assess the cost-effectiveness of adding medication per- tuzumab to the combination of trastuzumab+docetaxel within first-line therapy and to examine whether using individual data on Czech patients and the economic conditions leads to different results from foreign stud- ies. Furthermore, employing censored data from the clinical practice in the thesis complicates the estimation of patients' overall survival in compari- son to clinical-trials data that form random samples. Therefore, survival functions were not only estimated by the Kaplan-Meier estimator but also using the Cox proportional hazard model and the Accelerated failure time model that both control for the effects of included covariates. The addition of pertuzumab does not result in significantly longer pa- tients'...

本研究以確定給付型退休基金為對象，建構廣義隨機評價模型，以衡量不確定情況下退休基金之財務風險。希望藉著模型建構的過程，適切地描述基金評價過程中所應考量的各項要素。 為了強調基金評價時同時考量內外部精算假設的重要性，本研究將模型分為存活函數、經濟函數和給付函數三部份討論；存活函數利用離散時間非同質性半馬可夫過程（Discrete Time Non-Homogeneous semi-Markov Process）描述成員狀態轉移的機率，把成員工作年資、年齡和及狀態納入評價過程，有別於傳統僅以年齡為假設基礎之精算方法；經濟函數則以隨機過程表達外部環境的不確定性，結合上述假設資訊預估未來給付後，成為半馬可夫隨機精算評價模型，此一般性的模型能推展至基金評價時所需的各項流程。因此，本研究將模型應用於我國公務人員退撫基金，針對公務人員退撫基金的給付特性發展財務評價公式，完整地描述基金精算成本計算、未來人力與現金流量結構模擬以及敏感度分析等過程。 最後，本研究撰寫公務人員精算評價資訊系統，具體化半馬可夫隨機精算評價模型，實證公務人員退撫基金財務評價公式。實證結果也顯示，不論基金的性質或外部經濟環境，都將影響退休基金財務評價結果，為基金評價時不可忽略的精算假設。 / This study focuses on constructing a generalized valuation model for the defined benefit pension schemes. Financial soundness and funding stability are critical issues in pension fund management. In this study, a realistic stochastic model is built to monitor the uncertainty factors in affecting the financial risk and cash flow dynamics along the decision process. In order to evaluate the importance of the interior and exterior actuarial assumptions in pension valuation. Detailed models in describing the turnover patterns, economic uncertainties and benefit structures are explored. Semi-Markov process proposed by Dominicis, Manca and Granata (1991) and Janssen and Manca (1997) is extended in structuring the transition pattern of the plan’s population and the economic based factors are generated through stochastic processes. Modifications according to classification and movements of the plan member and the plan’s turnover pattern are employed to improve its practical usefulness. Then the actuarial valuations, cash flow analyses and workforce projection are performed and investigated. We has explicitly formulated the plan’s realistic phenomenon and implemented the proposed mechanism into a risk management framework for pension finance. By using this realistic approach, the cost factors could be monitored throughout the valuation. Typically these analyses involve substantial assumptions. This article has outlined the procedure of building the proposed model. Finally, Taiwan Public Employees Retirement System is simplified to illustrate the proposed methodology in pension valuation. The results from this study show that the structure of the pension schemes and the assumed economic factors are the significant factors in pension valuation. It also indicated that the fund manager can evaluate these impacts through the proposed model.