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Development of Clinical trial application and its impact on the management of the Clinical trial organisations
Wallischová, Zuzana ; Vrzáček, Petr (advisor) ; Staňková, Eva (referee)
My diploma thesis deals with the Clinical trial in the Czech Republic in the period from 1989 to present and on its impact on management in organizations dealing with clinical trials. The aim of this thesis is to identify key changes that occurred in the clinical trial and to identify how these changes infuenced the management of clinital trial organizations. This will be done based on the qualitative research. The theoretical part provides information about the history of the clinical trial, about internation and the Czech legislation, including ethical principles, the submission process including description of institution that are reviewing the clinical research. The theory also explains the issue of management, its organizational developments and its expected development in the future. In the research part I described the chosen research method, which extend from the semi- structured interview after the pilot part to the use of the focus group method - in the combination with semi-structured interview. Based on these interviews and focus group have been evaluated 7 parts to describe the evolution of the clinical trial and its impact on the management of clinical trials, including one topic that addresses the expected development of this field in the future. Key words: clinical trial, clinical...
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Programmable nucleases in human therapy
Šlaufová, Marta ; Kašpárek, Petr (advisor) ; Černý, Jan (referee)
Most genome disorders cause severe symptoms and are usually incurable. Recent, rapid development of programmable nucleases (PNs) brought new possibilities for the treatment of many diseases, such as genetic disorders, infectious diseases or cancer. PNs are enzymes, which enable site specific DNA cleavage that can lead to targeted modification of desired genomic loci. They are composed of separable non-specific cleavage domain and DNA- binding domain. The DNA binding domain is in the form of modular DNA-binding proteins or complementarity-based pairing of the oligonucleotide. The non-specific cleavage domain mediates DSB stimulation, which is necessary for further genome editing. Development of zinc finger nucleases (ZFNs) followed by transcription activator-like effector nucleases (TALENs) enabled the first therapeutic approaches based on targeted manipulation of human genome. The clustered regularly interspaced short palindromic repeats (CRISPR)-Cas technology brought further simplification to the method and broadened the availability of PN-based toolkits. This thesis will provide a summary of the recent developments, application of PNs in the therapy of human patients and potential obstacles preventing their implementation in clinics.
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Tumor in vitro chemosensitivity and resistance assays (CSRA) using flow cytometry
Drozdová, Tereza ; Drbal, Karel (advisor) ; Balounová, Jana (referee)
In vitro chemosensitivity and resistance assay determine the sensitivity of a specific tumor after a specific treatment administration in an experimental setup. A heterogeneous population of cancer cells is exposed to various approved anticancer drugs in short-term ex vivo and their combination thereof. The effect of each drug is then determined based on the viability of specific tumor cells allowing for individual patient treatment using a precise combination of drugs. This approach is an example of the personalized medicine principle, which is focusing on the adjustment of diagnostic procedures and treatment of a specific patient. Therefore, its goal is to avoid treatment failure in patients with poor response to the statistically most effective treatments based on randomized clinical trials. The number of viable cells determined by the flow cytometry provides very accurate statistics for multiparametric analysis. A necessary prerequisite is the presence of dissociated cancer cells in a single cell suspension. This is different from cloning methods, where tumor colonies grow on agar media, or from histocultures, which are specific with its three-dimensional tissue cultivation. We can also sort cells from suspension based on their pre-defined attributes for their subsequent functional testing. The...
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Clinical trials of pharmaceuticals
Horáková, Kateřina ; Svoboda, Petr (advisor) ; Millerová, Ivana (referee)
Clinical trials of medicinal products is increasingly important area of pharmaceutical law. Number of clinical trials and amount of financial resources is constantly rising and therefore the rules and principles of the clinical trials itself are being clarified overtime. This diploma thesis aims to provide an overview of the basic aspects of clinical trials of medicinal products for human use from a legal point of view. The author focuses in particular on the national legislation of clinical trials, which is complemented by the legislation of the European Union and important sources of the international law. Author is more closely analysing the particular procedures performed within the clinical trials, especially from the point of view of the administrative law. Particular attention is paid to the ethical review of the clinical trials, their particular aspects and the overall concept. The thesis is divided into twelve chapters. In the introduction, the author focuses on the development of the clinical trials and mentions the crucial moments that contributed to the formulation of the basic rules of the clinical trials. The following chapter focuses on the sources of law. Firstly, sources of international law are described, where more general sources and specific sources of law of medicinal products...
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Clinical trials of medical products for human use in the Czech Republic
Baloušek, Filip ; Kryska, David (advisor) ; Svoboda, Petr (referee)
The issue of legislative and ethical requirements on research of innovative medicines became more intense in connection to the expansion of the pharmaceutical industry in last few decades. This master thesis aims to complexly describe and analyse theoretical bases of current legislative regulating the process of clinical trials of medicinal products for human use in the Czech Republic, as well as to take a closer look to the issue of ethical review administered by specialized ethical review committees. The author also deals with some specific responsibilities of the committees from the perspective of administrative law, especially focusing on aspects of legal nature of the positive opinions, which are one of the conditions for commencement of a clinical trial. The thesis is divided into nine chapters and the introductory chapter is focused on the general outline of the issue of clinical trials of medicines for human use in the Czech Republic. The aim of the second chapter is to define the basic concepts stated in the Czech medicinal products act, which are specific for this area of pharmaceutical law. The next chapter analyses the relevant competencies of individual state authorities over the clinical studies. The fourth chapter contains the list of sources of law, whereas a particular emphasis is...
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Immune response to experimental active immunotherapy DCVac/OvCa in patients with ovarian carcinoma in phase II clinical trials.
Ksandrová, Marie ; Sadílková, Lenka (advisor) ; Krulová, Magdaléna (referee)
The immunotherapeutic drug DCVAC/OvCa is being tested in the treatment of ovarian cancer patients within the SOV02 clinical trial (Eudra CT number: 2013-001323-38). Ovarian cancer belongs to gynaecological malignancies with the highest mortality rate. Around 60% of patients are diagnosed at advanced stages. Despite the initial successful treatment, relapses occur in most cases, and the disease often becomes resistant to chemotherapy. Effective therapy for relapsed or metastatic patients is still missing. The solution could be immunotherapeutic treatment. DCVAC is an active cellular immunotherapy based on autologous dendritic cells. The aim of this diploma thesis was monitoring of immune parameters in samples from clinical trial SOV02 patients during the time period defined in the study protocol. We have monitored the presence of antigen specific T lymphocytes, tumor specific antibodies, immunosuppressive populations of regulatory T cells and MDSC cells, and also the expression of inhibitory molecules on the surface of T lymphocytes. We observed higher levels of Her-2, Muc-1 and MAGE-A1 antibodies in the DCVAC/OvCa treated group of patients versus the control group. Significant differences in the other monitored parameters were not observed. However, a large amount of data have been obtained that...
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Clinical trials of pharmaceuticals
Nedvědová, Michaela ; Svoboda, Petr (advisor) ; Millerová, Ivana (referee)
This master thesis is a description of the clinical trial, which is part of medical law un- der the law aspects. This thesis is split to topic, whose a brief outline is in the introduction. Process of the clinical trial and their institutions are discussed under the law and medical aspects. Resources of this thesis are a professional literature, knowledge of experts from pharmaceutical company and my own experience from part-time job in this type of com- panies. Aim of the thesis is to bring more resources and information about that topic to experts and other people who are interested in. This thesis is devided into five chapters. First chapter is speaking about a general insti- tute in the clinical trial. There are listed sources of the law. In the next chapter I deal with the process of the clinical trial from the begining i.e. from the development of a new sub- stance through the clinical trial to the final registration. The chapter about the european law regulation is following. In the fourth chapter I deal with the ethical aspects, which are conected with clinical trial. In that part I emphasised the influence of the international ethical documents. The last chapter is conclusion, where I describe the goal of this master thesis and also I am linking to the opinions of authorities regarding the...
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Opening clinical trial in the Czech Republic
Kodat, Richard ; Melechovský, Jan (advisor) ; Čížek, Ondřej (referee)
This bachelor thesis deals with the management of a project entitled Start-up of clinical trials in the Czech republic. Methods and tools of project management are applied to provide the project s analysis. In the practical part the project is firstly described. The description includes the project s environment, the scope and targets and the basic activities. Activities and finally the whole project are analysed by MS Project (considering costs, time, resources). The analyses are described in relation to the theoretical part of the thesis. In the theoretical part the basic terms, methods and analyses are described. The project is planned to meet the general requirements in clinical trials in the Czech republic.
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