Dissertations / Theses on the topic 'Clinical trials'
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Kim, Anne(Anne Y. ). "Optimizing clinical trials with Open Trial Chain." Thesis, Massachusetts Institute of Technology, 2018. https://hdl.handle.net/1721.1/121787.
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Thesis: M. Eng., Massachusetts Institute of Technology, Department of Electrical Engineering and Computer Science, 2019Cataloged from student-submitted PDF version of thesis.
Includes bibliographical references (pages 59-64).
The objective of this thesis is to study the challenges of data sharing in healthcare (namely clinical trials), and propose the use of Open Algorithms (OPAL) as a viable solution for research collaboration that allows for access to data without compromising data ownership (data is only used once for the intended purpose, raw data is never leaked, the value generated from the data is transferred to the owner). This thesis surveys the challenges unique to clinical trials, and highlights the various methods for privacy-preserving computation prior to this work. Through the overview of OPAL's solution in the space of privacy-preserving computation, we show the implementation details of how OPAL was applied to clinical trials in a project called Open Trial Chain, a platform for clinical trial data built for analytics, security, and incentivized sharing through technologies like federated learning and blockchain. With motivated examples derived from real-world reported problems in healthcare, we also demonstrate speed, accuracy, and security metrics. In the application, Open Trial Chain can drastically reduce clinical trial costs, reduce error, and increase quality of analysis diversity. Overall, this project shows promise for further extension in other health datasets for compliance in an ever-complicated move towards regulations that reflect for conscientiousness for data security, ownership, and provenance.
by Anne Kim.
M. Eng.
M.Eng. Massachusetts Institute of Technology, Department of Electrical Engineering and Computer Science
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Vickers, Andrew J. "Homoeopathy and clinical trials." Thesis, University of Oxford, 1999. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.302395.
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Zhang, Yifan. "Bayesian Adaptive Clinical Trials." Thesis, Harvard University, 2014. http://nrs.harvard.edu/urn-3:HUL.InstRepos:13070079.
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Bayesian adaptive designs are emerging as popular approach to develop adaptive clinical trials. In this dissertation, I describe the mathematical steps for computing the theoretical optimal adaptive designs in biomarker-integrated trials and in trials with survival outcomes. Section 1 discusses the optimal design in personalized medicine. The optimal design maximizes the expected trial utility given any pre-specified utility function, though the discussion here focuses on maximizing responses within a given patient horizon. This work provides absolute benchmark for the evaluation of trial designs in targeted therapy with binary treatment outcomes. While treatment efficacy can be measured by a short-term binary outcome in many phase II and phase III trials, patients' progression-free survival time is with significant importance in cancer clinical trials. However, it is often difficult to make a design adaptive to survival outcomes because of the long observation time. In Section 2, an optimal adaptive design is developed so that treatment assignment decision for later patients can be made with complete or partial survival outcomes of early patients. The design also maximizes the expected trial utility given any pre-specified utility function that is of clinical importance. In this section, the focus is on maximizing the expected progression-free survival time. Both Sections1 and 2 include examples of comparing adaptive designs, such as the bayesian adaptive randomization and the play-the-winner rule, in terms of the expected trial utility with respect to the best achievable result. In Section 3, a simulation-based p-value is proposed and can be used to conduct frequentist analysis of Bayesian adaptive clinical trials. The optimal Bayesian design is compared to the equal randomization design in terms of the Type I error and the statistical power. With a fixed trial size and Type I error, the power of the equal randomization design depends on the difference in treatment efficacy, meanwhile the power of the optimal Bayesian design also depends on the size of the patient horizon.
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Scarale, M. G. "RESPONSE - ADAPTIVE CLINICAL TRIALS." Doctoral thesis, Università degli Studi di Milano, 2015. http://hdl.handle.net/2434/344736.
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The question we posed at the beginning of this thesis was whether, in the presence of a clinical superiority of one of two possible treatments, it was possible to find an appropriate statistical methodology that would allow us to reach this goal. We were thus led to explore many possibilities to carry out this analysis and randomly assign patients to the two treatments, as required by the particular nature of these experiments. Specifically, we made a close examination of the methods of randomization, especially appreciating the flexibility of the adaptive responses, and could see the strengths of urn models. We started with the study of the urn for excellence, Polya's urn. Next, we analyzed some extensions and generalizations, focusing especially on two kinds of urns with random reinforcement. We exposed the results obtained throughout simulations concerning the convergence of the proportion of the best treatment, which came from the comparison of the models studied. In the end, we showed how the urn model works in a real case, comparing two treatments with continuous response in one ICU trial on Melatonin. We'll see how the properties demonstrated in theory are confirmed in practice.
The project ends by giving a hint of a new adaptive model that we have started to idealize in collaboration with the team of Prof. Parmigiani and Prof. Trippa of the "Biostatistics and Computational Biology" Department, Harvard T.H. Chan School of Public Health.
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Lui, Wai-fan. "Clinical trials research methodology current practice in Hong Kong and training programme development /." Click to view the E-thesis via HKUTO, 1998. http://sunzi.lib.hku.hk/HKUTO/record/B38628582.
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Čekanauskaitė, Asta. "Informedness about clinical trials of patients participating in placebo-controlled clinical trials in Lithuania." Doctoral thesis, Lithuanian Academic Libraries Network (LABT), 2013. http://vddb.laba.lt/obj/LT-eLABa-0001:E.02~2012~D_20130114_081952-77101.
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The dissertation aims to analyse the problem of informed consent in clinical drug trials. Understanding of the provided information is one of the basic components of a person’s sound and informed decision to participate in a clinical trial. Our research evaluated informedness about clinical trials of patients participating in clinical drug trials in Lithuania, with emphasis on the informedness about key elements of clinical trial design (placebo-control, double-blindness, and randomisation). An anonymous survey of patients participating in clinical drug trials was conducted for the purposes of this study. The results of the study reveal that the legal framework sets the basis for adequate informedness about clinical trials of clinical trial participants, however, patients participating in placebo-controlled clinical trials are insufficiently informed about clinical trials. Patients participating in placebo-controlled clinical trials are better informed about the rights of clinical trial participants than about clinical trial design, however, informedness about design is a more important condition for overall informedness. The majority of placebo-controlled clinical trial participants do not understand at least one of the three key elements of clinical trials design and they tend to interpret the scientific methods used in clinical trials therapeutically.Disertacijoje analizuojama informuoto asmens sutikimo įgyvendinimo klinikiniuose vaistinio preparato tyrimuose problema. Pateiktos informacijos supratimas yra viena svarbiausių asmens apsisprendimo dalyvauti klinikiniame tyrime sąlygų. Moksliname darbe vertinamas pacientų, dalyvaujančių placebu kontroliuojamuose klinikiniuose vaistinio preparato tyrimuose Lietuvoje (toliau – klinikinių tyrimų dalyviai), informuotumas apie klinikinius tyrimus, akcentuojant informuotumą apie klinikiniuose tyrimuose taikomus mokslinius metodus (placebo kontrolę, dvigubą aklumą, atsitiktinį tiriamųjų grupių sudarymą). Klinikinių tyrimų dalyvių informuotumas buvo tiriamas atliekant anoniminę apklausą. Mokslinio darbo rezultatai parodė, kad teisinis reglamentavimas sudaro prielaidas klinikinių tyrimų dalyvių informuotumui, tačiau jų informuotumas yra nepakankamas. Respondentai buvo geriau informuoti apie klinikinių tyrimų dalyvių teises nei apie klinikinių tyrimų metodologiją, tačiau informuotumas apie klinikinių tyrimų metodologiją yra svarbesnė prielaida bendram informuotumui. Dauguma klinikinių tyrimų dalyvių nesuprato vieno ar daugiau iš trijų pagrindinių klinikiniuose tyrimuose taikomų mokslinių metodų (placebo kontrolės, dvigubo aklumo, atsitiktinio tiriamųjų grupių sudarymo) ir buvo linkę suteikti jiems terapinę reikšmę. Tyrimo rezultatai sudaro prielaidas kryptingam klinikinių tyrimų dalyvių informuotumo gerinimui, informacijos apie klinikinius tyrimus viešinimui.
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Kehl, Victoria. "Responder Identification in Clinical Trials." Diss., lmu, 2002. http://nbn-resolving.de/urn:nbn:de:bvb:19-5908.
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Sydow, Victoria. "Clinical Trials - Competitive resource management." Thesis, KTH, Skolan för bioteknologi (BIO), 2012. http://urn.kb.se/resolve?urn=urn:nbn:se:kth:diva-149476.
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Murphy, Jeremy James. "Clinical trials in cerebrovascular disease." Thesis, University of Nottingham, 1991. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.293328.
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Machin, David. "Statistical aspects of clinical trials." Thesis, University of Southampton, 1987. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.257667.
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Lewis, Nigel da Costa. "Surrogate markers in clinical trials." Thesis, University of Cambridge, 2002. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.620204.
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Rahman, Najib. "Clinical trials in pleural disease." Thesis, University of Oxford, 2011. http://ora.ox.ac.uk/objects/uuid:930991f1-3424-4b96-984e-06df7f6e9204.
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The focus of this thesis is on practice changing clinical studies which impact upon the day to day treatment of patients with pleural infection, answering specific questions on several aspects of patient management. Specific areas of assessment in this thesis include: Assessment of the current evidence for optimal drain size choice in patients with pleural infection; Analysis and statistical modelling of a previous cohort of patients with pleural infection, in order to assess optimal drain size choice in pleural infection; The design, conduct and analysis of a 2 x 2 factorial multi-centre randomised, placebo controlled trial to assess the efficacy of two novel intrapleural agents (tPA and DNase) in aiding drainage in patients with pleural infection (The 2nd Multi-centre Intrapleural Sepsis Trial, referred to from here on as MIST2); Validation work informing the primary outcome measure of MIST2, assessing the relationship between chest radiograph imaging of infected pleural effusion and CT measured volume of pleural fluid using novel digital measurement strategies.
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Gatica, Diaz Escobar Gabriel. "Capacity planning under clinical trials uncertainty." Thesis, Imperial College London, 2004. http://hdl.handle.net/10044/1/8400.
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Verhagen, Arianne Petra. "Quality assessment of randomised clinical trials." [Maastricht] : Maastricht : Universitaire Pers Maastricht ; University Library, Maastricht University [Host], 1999. http://arno.unimaas.nl/show.cgi?fid=6863.
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Hee, Siew Wan. "Designing a series of clinical trials." Thesis, University of Warwick, 2012. http://wrap.warwick.ac.uk/50306/.
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This thesis presents designs for a series of clinical trials where instead of designing clinical trials individually, each of the trials is designed as part of a series of trials. The framework of the design is based on a combination of classical frequentist and Bayesian approaches which is sometimes known as the hybrid approach. The unknown parameter of the treatment efficacy is assumed to be random and follows a prior distribution in the design stage but at the end of the trial a frequentist test statistic is used on the observed data to infer the parameter. The design introduced in Chapter 5 aims to determine an optimum sample size for each trial by optimizing the average power of each trial and the overall resources while fixing the conventional type I error. The design has the exibility to either run sequentially or concurrently. The design is then extended to allow interim analyses in each trial (Chapter 6). The focus of the extended design is on a series of Bayesian decision-theoretic phase II trials and one frequentist phase III trial. At each interim stage, a decision is made based on the expected utilities of subsequent actions. There are four possible actions to choose from, namely, to continue the current trial by recruiting more patients, to initiate a new phase II trial, to abandon the development plan or to proceed to a phase III trial with this treatment against a control arm. For the last action, the phase III trial is designed with the hybrid methodology as described above. Finally, the prior distributions for each treatments are assumed to be correlated and as information is gathered from the previous and current trials, the current and following prior distributions are updated (Chapter 7).
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殷小曼 and Shiu-man Yolanda Yan. "Patient recruitment strategies in clinical trials." Thesis, The University of Hong Kong (Pokfulam, Hong Kong), 2001. http://hub.hku.hk/bib/B31970874.
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MaÌrquez, Elsa ValdeÌs. "Inference in covariate-adaptive clinical trials." Thesis, University of Sheffield, 2005. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.425222.
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Rothwell, Joanne C. "Quantifying effect sizes in clinical trials." Thesis, University of Sheffield, 2018. http://etheses.whiterose.ac.uk/20924/.
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Introduction: This thesis discusses the importance of the target effct size (ES) used in clinical trials of health interventions. It investigates the common methods of eliciting the target difference and whether target values are optimistic or unrealistic. Regression to the mean (RTM) is shown for trials in sequence, which is assessed through simulations and an adjustment developed to adapt for this bias. Research Question: Investigating currently used methods for eliciting the target difference and optimal methods for adjusting for RTM. Methods: Firstly, a review of the Health Technology Assessment (HTA) journal trial reports of parallel-group randomised controlled trials (RCTs) was performed. The standardised observed and target ES were compared for various clinical areas and elicitation methods. Second, performing simulations of trials in sequence to investigate the effect of RTM. A mathematical solution was evaluated to confirm these simulated results. Results: A review of 107 HTA reports showed the median standardised target ES is 0:30 (mean= 0:30), and the median standardised observed ES is 0:11 (mean= 0:19). Use of previous research was the most common method of elicitation. Simulations showed RTM occurs for trials in sequence, an adjustment method has been developed and proven mathematically, which depends only on the power of the first trial. Conclusions: This thesis demonstrates the most common method of target difference elicitation is the use of previous research. This method leads to RTM of the observed ES. An adjustment based on the power used in the initial trial power and the progression criteria in pilot studies has been developed and tested. If trialists adopt this adjustment then trial sample sizes, though slightly inflated, would potentially provide more realistic estimates of the target ES.
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Hodkinson, Alexander. "Assessments of harms in clinical trials." Thesis, University of Liverpool, 2015. http://livrepository.liverpool.ac.uk/2023762/.
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Introduction and Aims Healthcare interventions are usually associated with a risk of harmful events that must be balanced against the potential favorable outcomes. However reliable evidence on harms for interventions is often inadequate, and hampered by the many challenges that stem from the reporting, analysis and interpretation of harms data in clinical trials. This thesis addresses some of these issues. Methods Reporting of harms data is assessed in a systematic review of reviews and a case study investigating the additional value of harms data reported in clinical study reports (CSRs). A framework for searching and identifying relevant sources of harms data is outlined, and then explored further in a survey assessing current practices in clinical trial units (CTUs). Signal detection methods are introduced, and evaluated using simulated data to assess their performance when detecting safety signals in CTU databases. Results The systematic review highlights that the reporting of harms in RCTs is inconsistent, and often inadequate. In the case study, CSRs presented data on harms, including SAEs which are not reported or mentioned in publications, they also provide more detail about the design, conduct and analysis of the trial which facilitate the assessment of risk of bias in evidence synthesis. A wide range of sources for harms data have been identified, each with distinct strengths and limitations discussed. Selection of appropriate sources depends on the research question, and whether a hypothesis generating or hypothesis testing approach should be taken. Relevant sources have been identified for each approach, with examples of their exploitation in CTUs evaluated in the survey. The simulation study has shown that some of the current available signal detection methods are not able to control the false discovery rate well, and are only able to detect few safety signals for small or sparse data. Conclusions The work carried out within this thesis provides some recommendations to address the reporting, conduct, and analysis of harms in clinical trials. Wider adoption of recommendations made by the CONSORT-harms guideline will enhance the quality of reporting and improve subsequent evidence synthesis. Recent initiatives to promote open access to clinical trials data including CSRs is a major step towards supporting better data transparency. It is important to identify and consider different sources that are most likely to yield robust data on harms of interest, rather than relying on studies that cannot reliably detect harm. The survey identified published literature and systematic reviews as the most common source being used in the trial safety monitoring within CTUs. Signal detection methods are potentially unsuitable for use in CTUs. Further tools and guidelines for enhanced signal detection are needed in clinical trials.
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Yan, Shiu-man Yolanda. "Patient recruitment strategies in clinical trials." Hong Kong : University of Hong Kong, 2001. http://sunzi.lib.hku.hk/hkuto/record.jsp?B24872623.
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Henderson, Neil James Kerr. "Extending the clinical and economic evaluations of a randomised controlled trial the IONA study /." Connect to e-thesis, 2008. http://theses.gla.ac.uk/418/.
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Thesis (Ph.D.) - University of Glasgow, 2008.Ph.D. thesis submitted to the Department of Statistics, Faculty of Information and Mathematical Sciences, University of Glasgow, 2008. Includes bibliographical references. Print version also available.
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Ghersi, Davina. "Issues in the design, conduct and reporting of clinical trials that impact on the quality of decision making." Phd thesis, School of Public Health, 2006. http://hdl.handle.net/2123/6653.
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Chan, Hung-kin Clive. "A multi-dimensional survey and critical analysis of clinical trial regulations in Hong Kong and a comparison of the status of clinical trial regulations in some Asian countries/Regions." Click to view the E-thesis via HKUTO, 2004. http://sunzi.lib.hku.hk/hkuto/record/B31971465.
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Kilgore, Meredith L. "Effects of trial design on participation and costs in clinical trials : with an examination of cost analysis methods and data sources /." Santa Monica, Calif. : Pardee RAND Graduate School, 2004. http://www.rand.org/publications/RGSD/RGSD179.
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Zhao, Yufan Kosorok Michael R. "Reinforcement learning design for cancer clinical trials." Chapel Hill, N.C. : University of North Carolina at Chapel Hill, 2009. http://dc.lib.unc.edu/u?/etd,2857.
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Thesis (Ph. D.)--University of North Carolina at Chapel Hill, 2009.Title from electronic title page (viewed Jun. 4, 2010). "... in partial fulfillment of the requirements for the degree of Doctor of Philosophy in the Department of Biostatistics, School of Public Health." Discipline: Biostatistics; Department/School: Public Health.
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Millar, Joanne Ruth. "Early clinical trials in upper gastrointestinal cancer." Thesis, Queen's University Belfast, 2008. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.492011.
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On a worldwide basis, gastric and oesophageal cancer are the third and seventh most common causes of cancer respectively. The majority of patients either present with locally advanced I inoperable or metastatic disease, or develop recurrent disease after potentially curative management. Palliative chemotherapy is therefore a consideration for the majority of patients. Standard chemotherapy in this setting using cisplatin and fluorouracil based regimens does improve survival. However, to date, no randomised trial has shown survival beyond 12 months. There has therefore been considerable early trial activity in an attempt to improve outcomes and/or reduce toxicity of treatment in this palliative setting. An audit was conducted of all new cases of gastro-oesophageal cancer referred to the Northern Ireland Cancer Centre in the year 2003. This gave a broad overview of the current referral and management patterns employed, and their resulting outcomes. Two trials were performed in this treatment setting. The first was a phase II trial of the gemcitabine / cisplatin doublet in the treatment of advanced / metastatic oesophageal cancer. This regimen, used in other settings, had not been previously assessed in this patient group. A total of 42 patients were entered. The regimen was tolerable and yielded a response rate of 45% by intention to treat analysis. The second trial was a phase I trial using a new schedule of weekly docetaxel in combination with oxaliplatin, both drugs with promising activity in the treatment of gastro-oesophageal cancer. This trial was open to patients with all tumour types, but 15 of the 25 patients entered had gastro-oesophageal primaries. The response rate in this patient group was 40%. Toxicity was predictable and manageable, and the recommended phase II dose was established. .Pharmacokinetic analysis revealed no significant interaction. A phase II study of this regimen in gastro-oesophageal cancer has recently opened.
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Tan, Say Beng. "Bayesian decision theoretic methods for clinical trials." Thesis, Imperial College London, 1999. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.312988.
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Harwood, Susan Elizabeth. "Medication compliance in out-patient clinical trials." Thesis, University of Sunderland, 1989. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.330315.
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Bamias, Christina. "Analysis of clinical trials with rescue medication." Thesis, London School of Hygiene and Tropical Medicine (University of London), 2001. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.249574.
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Qian, Wendi. "Bayes methods in group sequential clinical trials." Thesis, University of Kent, 1997. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.263693.
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Todd, Susan Clare. "Methods of analysis for sequential clinical trials." Thesis, University of Reading, 1994. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.239477.
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Warne, David W. "Bayesian design and analysis of clinical trials." Thesis, University of Reading, 1991. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.303459.
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Burnett, Thomas. "Bayesian decision making in adaptive clinical trials." Thesis, University of Bath, 2017. https://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.760912.
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The key original contribution of this work is the use of a Bayes optimisation framework for the decision made at the interim analysis of Adaptive Enrichment trials. Adaptive Enrichment designs make efficient use of pre-identified patient sub-populations. They begin by recruiting from all eligible patients, then at a pre-planned interim analysis select which sub-populations will be recruited from for the remainder of the sample. We ensure strong control of the Familywise Error Rate whichever sub-populations are selected by constructing an overall hypothesis testing structure using both closed testing procedures and combination tests. This allows us to make interim decision by any method we choose. We find the Bayes optimal decision, recruiting the remainder of the trial to optimise the Bayes expected gain of the trial. We compare the Bayes optimal Adaptive Enrichment trials with fixed sampling designs to understand the overall advantage of using adaptive trials. This optimisation framework is very flexible, we evaluate the performance of Bayes optimal Adaptive Enrichment designs for different forms of data: delayed responses, longitudinal analysis and discuss the extension of these methods to survival data. Through this we see that although the information at the interim analysis is reduced the adaptive trials still offer some benefit. Additionally we investigate what may happen when we alter the pattern of recruitment of the Adaptive Enrichment trials, showing that adaptation may be useful in a broad range of scenarios.
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Miller, Michael G. (Michael Gahuse). "Optimal allocation of resources to clinical trials." Thesis, Massachusetts Institute of Technology, 1996. http://hdl.handle.net/1721.1/10670.
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Cotterill, Amy. "Novel methods for early phase clinical trials." Thesis, Lancaster University, 2015. http://eprints.lancs.ac.uk/75558/.
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Early phase clinical trials are conducted with limited time and patient resources. Despite design restrictions, patient safety must be prioritised and trial conclusions must be accurate; maximising a promising treatment’s chance of success in later largescale, long-term trials. Increasing the efficiency of early phase clinical trials, through utilising available data more effectively, can lead to improved decision making during, and as a result of, the trial. This thesis contains three distinct pieces of research; each of which proposes a novel, early phase clinical trial design with this overall objective. The initial focus of the thesis is on dose-escalation. In the single-agent setting, subgroups of the population, between which the reaction to treatment may differ, are accounted for in dose-escalation. This is achieved using a Bayesian model-based approach to dose-escalation with spike and slab priors in order to identify a recommended dose of the treatment (for use in later trials) in each subgroup. Accounting for a potential subgroup effect in a dose-escalation trial can yield safety benefits for patients within, and post- trial due to subgorup-specific dosing which should improve the benefit-risk ratio of the treatment. Dual-agent dose-escalation is considered next. In the dual-agent setting, singleagent data, including toxicity and pharmacokinetic exposure information, is available. This information is used to define escalation rules that combine the outputs of independent dose-toxicity and dose-exposure models which are fitted to emerging trial data. This solution is practical to implement and reduces the subjectivity that currently surrounds the use of exposure data in dose-escalation. In addition, escalation decisions and consistency of the final recommended dose-pair are improved. The focus of the third piece of research changes. In this work, Bayesian sample size calculations for single-arm and randomised phase II trials with time-to-event endpoints are considered. Calculation of the sample size required for a trial is based on a proportional hazards assumption and utilises historical data on the control (and experimental) treatments. The sample sizes obtained are consistent with those currently used in practice while better accounting for available information and uncertainty in parameter estimates of the time-to-event distribution. Investigating allocation ratio’s in the randomised setting provides a basis for deciding whether a control arm is indeed necessary. That is, in a randomised trial, whether it is necessary for any patients to be randomised to the control treatment arm.
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Oliveira, Liliana Cristina Santos. "Curricular training report about clinical trials monitoring." Master's thesis, Universidade de Aveiro, 2012. http://hdl.handle.net/10773/10578.
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Mestrado em Biomedicina FarmacêuticaO presente relatório propõe-se a apresentar as atividades desenvolvidas durante um estágio curricular de 10 meses na Datamedica CRO Full Service. A estagiária encontrava-se a desenvolver atividades de monitorização de ensaios clínicos na empresa recetora pelo que este será o principal enfoque deste trabalho. Após 6 meses de estágio curricular, a Astellas Farma Lda subcontratou à Datamedica a estagiária em questão para desempenhar a função de CRA o que permitiu conhecer o mundo dos ensaios clínicos de duas diferentes perspetivas - a das grandes empresas da indústria farmacêutica e a das CROs (empresas subcontratadas pela indústria farmacêutica para desenvolver atividades específicas). Este trabalho tenta mostrar a visão obtida e os pontos de vista da estagiária enquanto monitora de ensaios clínicos das duas empresas. Para além da monitorização, foi possível desenvolver outras atividades em outros departamentos da Datamedica, nomeadamente realização de testes de legibilidade e atividades de medical writing que serão também apresentadas neste relatório. Este trabalho encontra-se dividido em dois principais capítulos sendo que o primeiro capítulo pretende situar a empresa de acolhimento na dinâmica da investigação clínica farmacêutica e dar a conhecer o estado da arte dos ensaios clínicos a nível europeu e nacional, com ênfase para a crise na investigação clínica em ambos os níveis. O segundo capítulo constitui a apresentação dos procedimentos que são seguidos em cada área de trabalho desenvolvida durante o período de estágio e a identificação de todas as atividades realizadas pela estagiária. O relatório termina com a discussão e conclusão de todo o trabalho desenvolvido e verificação dos objetivos de aprendizagem definidos no início do estágio. Todo o trabalho desenvolvido durante o estágio curricular e o contacto com os diversos profissionais envolvidos na área da investigação clínica foram fundamentais para a aquisição de competências sociais e intelectuais que contribuíram para o melhor desempenho da estagiária e a prepararam para o mundo profissional da indústria farmacêutica.
This paper intends to present the activities developed during a 10-month internship at Datamedica Full Service CRO. The trainee was developing clinical trial monitoring activities at the host company, which will be the main focus of this report. After 6 months of internship, Astellas Farma Lda subcontracted the trainee from Datamedica to be one of their CRA’s, providing her with an opportunity to experience the world of clinical trials from two different perspectives - the major pharmaceutical companies and the CROs (companies subcontracted by the pharmaceutical industry to develop specific activities). This report tries to show the point of view of the trainee as clinical trial monitor of the two companies. Besides clinical trial monitoring it was possible to develop different activities from other Datamedica departments such as the realization of readability tests and medical writing activities that will also be presented in this report. This paper is divided in two main chapters, where the first chapter goal is to place the host company dynamics in the pharmaceutical clinical research environment and provide some knowledge about the clinical trials state of the art nationally and internationally, highlighting the clinical research crisis that is threatening the pharmaceutical world at both levels. The second chapter presents the procedures followed with the different activities performed divided by area of work and the identification/specification of each activity developed by the trainee. The report ends with a discussion and conclusion about the work developed and the verification of the learning outcomes defined at the beginning of the internship. The work developed during this curricular internship and the contact network developed through the contact with a variety of professionals involved in the clinical research area were essential in the acquisition of social and intellectual skills that contributed to the best performance of the trainee during the internship and prepared her to the professional work environment of the pharmaceutical industry.
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Al-Qasem, Leena. "Exploitation and clinical trials in developing countries." Thesis, Keele University, 2015. http://eprints.keele.ac.uk/1190/.
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This thesis discusses comprehensively the issue of exploitation from a normative perspective specifically relating to clinical trials within developing countries using a normative definition. Exploitation is defined from an unfairness perspective as the unfair use of an individual (group of individual) by another. In order to ease the flow of the arguments within this thesis, unfairness will be assessed from two different perspectives: a procedural perspective and an outcome perspective. The procedural perspective discusses whether the procedures followed when obtaining informed consent from the potential participants fulfilled the requirements of informed consent or failed to do so. Though the use of this approach it is concluded that informed consent is not a necessary condition for the avoidance of exploitation. Similarly, it is concluded that even if morally transformative, valid consent is given by potential participants, exploitation may still be lurking in the shadows of the interaction between the trial participants and the researchers/sponsors. The outcome perspective of unfairness focuses on the effect of the interaction on the parties involved within it and whether they benefit from their interaction with each other, are not affected by it, or are actually harmed as a result of the interaction. As an extension of this argument, the thesis will also consider the post-trial perspective of the interaction. The thesis concludes that post-trial access (reasonable availability) has a very narrow view of benefit and does not ensure that there is a fair share of the benefits between the parties involved. Instead of this narrow approach, a wider, post-trial benefit approach is adopted in order to prevent exploitation. Further discussion within the thesis will include, the requirements of an ethical review, the makeup of the review boards, and priority decision making in keeping with the current research ethics discussion in the literature.
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Thach, Chau Thuy. "Self-designing optimal group sequential clinical trials /." Thesis, Connect to this title online; UW restricted, 2000. http://hdl.handle.net/1773/9585.
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Kittelson, John Martin. "The design of group sequential clinical trials." Diss., The University of Arizona, 1996. http://hdl.handle.net/10150/290621.
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Group sequential clinical trials have become the accepted method for monitoring the results of an ongoing trial. These methods allows early termination of a trial based on the results of "interim analyses" that are conducted after each of the groups of subjects are entered on the study. Existing methods for designing these types of trials are currently comprised of several different constructions, each of which addresses a different clinical setting. The purpose of this dissertation is to unify these constructions into a single framework. This is accomplished by first proposing a general algebraic family of stopping rules for group sequential designs, and then constructing a statistical interpretation of the family. Both Bayesian and frequentist approaches are included in this unification. The properties of the unified family of designs is examined, which lends insight into the similarities and differences between existing approaches to group sequential designs. This work is motivated by several clinical examples, and the clinical application of these designs is given detailed consideration. A particular example is used to illustrate the application of these methods, and to describe how they would be implemented in an ongoing monitoring program for a clinical trial.
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Menezes, Prema Miller William C. "Is there a trial effect in HIV clinical trials? identifying who participates in clinical trials and assessing the effect of trial participation on the response to highly active antiretroviral therapy /." Chapel Hill, N.C. : University of North Carolina at Chapel Hill, 2008. http://dc.lib.unc.edu/u?/etd,2061.
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Thesis (Ph. D.)--University of North Carolina at Chapel Hill, 2008.Title from electronic title page (viewed Feb. 17, 2009). "... in partial fulfillment of the requirements for the degree of Doctor of Philosophy in the Department of Epidemiology, School of Public Health." Discipline: Epidemiology; Department/School: Public Health.
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Ali, Myzoon. "The Virtual International Stroke Trials Archive (VISTA) : promulgation of a clinical trial resource." Thesis, University of Glasgow, 2008. http://theses.gla.ac.uk/509/.
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Abstract Chapter 1 provides an introduction to stroke including its current prevalence both nationally and globally, aetiology, global importance and social & financial burden. We also describe here current acute stroke management practices, the role of clinical trials in the development of therapies, the richness of data within clinical trials and changes in regulatory thinking regarding data access. We provide recommendations for the use of trial data for novel exploratory investigations of clinical trial design and epidemiological studies. In Chapter 2 we describe the establishment of the Virtual International Stroke Trials Archive (VISTA) to address the need for reliable data on which to plan future clinical trials. This chapter details the methodology and logistics of establishing the resource, including details of regulatory policy for data collection and use, establishment of a Steering Committee and development of a constitution to safeguard data access and use. As of June 2008, VISTA contains 28 acute stroke clinical trials and one acute stroke registry. We collated data on over 27,500 patients with either ischaemic or haemorrhagic stroke. Patient age ranges from 18 to 103 years and outcome measures include Barthel Index, Scandinavian Stroke Scale, National Institutes of Health Stroke Scale, Orgogozo Scale, and modified Rankin Scale. Medical history and onset to treatment times are readily available and computed tomography (CT) lesion data are available for selected trials. We discuss the establishment and potential uses of this resource in the context of existing stroke resources. Chapter 3 demonstrates how we utilised VISTA to investigate natural history patterns in acute stroke. There are prominent differences in stroke incidence and outcome across different geographical locations; these are not confined to the Eastern- Western axis. We aimed to examine whether there were any differences in index stroke severity, stroke risk factors, and stroke outcome between geographical locations, after adjusting for case-mix. We found that patients who were enrolled in the USA and Canada had the worst index strokes, whilst patients enrolled in Austria and Switzerland had the mildest index stroke, and better functional (p=0.023) and neurological outcome (p=0.034) at 90 days. 90 –day survival was greater in patients who were enrolled in Spain and Portugal (p<0.0001). Chapter 4 demonstrates the use of VISTA to inform stroke clinical trial design by examining the impact of early follow up on adverse event and functional outcome profiles. We aimed to assess the contribution of adverse complications unrelated to stroke, to 30 and 90- day functional outcome. If fewer ‘stroke-unrelated’ adverse events were seen at later time points, and if the absence of these events appeared to influence functional outcome, then further investigation into shortening the follow up period of clinical trials with a view to minimizing complications may be warranted. We identified idiopathic post-stroke complications (deemed to be ‘stroke- unrelated’) but their absence did not beneficially alter outcome at either 30 days (p<0.0001, adjusted OR for good outcome =0.47, 95% CI [0.26, 0.67]), or 90 days (p=0.002, adjusted OR for good outcome =0.38, 95% CI [0.14, 0.61]). We concluded that shortening the follow up period with the aim of minimizing ‘stroke-unrelated’ complications did not benefit functional outcome, however further investigation is required. Chapter 5 illustrates the use of VISTA to investigate the natural history of complications after intracerebral haemorrhage (ICH). Treatments available for ICH remain limited. The use of haemostatic agents to promote local coagulation has had no significant benefit on outcome. However promising results from a subgroup analysis of patients from the FAST trial has raised the possibility of treatment with recombinant factor VIIa (rFVIIa) in patients with ICH. We sought to document the natural history of complications after ICH in order to inform safety in future trials of haemostatic agents for ICH. We found that the risk of thromboembolic complications after ICH was low (4 events affecting 2% of patients). The absence of these thromboembolic complications did not significantly affect the attainment of good functional outcome (p>0.05). The occurrence of haemorrhagic expansion was common, affecting 14% of patients, and significantly influenced attainment of good functional outcome at 90 days (p= p<0.0001, adjusted odds ratio for good functional outcome=21.9, 95% confidence interval [5.5, 88.3]). Although infection occurred in 11% of patients, this did not significantly influence attainment of good functional outcome at 90 days (p=0.8). The complications encountered in this investigation and their time to onset will serve to inform prophylaxis in future ICH clinical trials. Chapter 6 describes the processes involved in drug development from phase I, first- in – man studies to phase III efficacy trials and identifies a key area in the drug development process where use of VISTA as a historical comparator resource could be of benefit: phase II studies. We detail here the types of conventional comparator groups available for use in a phase II investigation, advantages and disadvantages of using each of these comparator groups, the potential for use of historical comparators in some scenarios where use of conventional comparator groups is infeasible, and possible solutions to address the limitations associated with use of historical comparators. Chapter 7 illustrates the use of VISTA as a resource for historical comparators in the context of an acute stroke device trial conducted by a small company with limited resources. BrainsGate, the manufacturers of the NeuroPath™ Device for treatment of ischaemic stroke, sought to collaborate with the VISTA group to examine initial efficacy of their device against outcomes derived from VISTA historical comparators. We discuss the example of this device in early phase testing, where VISTA was primed for use as a resource for historical comparators. We also describe the limitations associated with the use of historical comparators, how these limitations could be overcome in practice through use of matched patients, implementation of strict eligibility criteria and use of similar follow up periods and stroke scales, as well as the measures taken to ensure the validity of results. Chapter 8 describes a collaboration with the DESTINY trial group to investigate stroke outcomes after malignant middle cerebral artery occlusion (mMCAO). The DESTINY trial examined the impact of decompressive hemicraniectomy on outcome after mMCAO, compared with randomised controls. We compared the outcomes of operated patients from the DESTINY trial with historical comparators from VISTA to determine whether the findings could be replicated and if historical comparators could be used as an alternative in a situation where a randomised controlled trial (RCT) is infeasible or unethical. We found that fewer patients in the VISTA comparator group achieved a good functional outcome by mRS at final follow up (19%), when compared with the DESTINY surgical group (47%, Chi- Square test p=0.04). This difference persisted after adjusting for baseline NIHSS (logistic regression p=0.04). Analysis of Barthel Index at final follow up revealed no significant difference between the two groups and we also found no difference in 6 month survival rates between the surgical and VISTA comparator groups (Cox Proportional Hazards model p>0.05). We concluded that for effective replication of results, the database from which historical comparators are to be drawn should cover a similar or broader spectrum of patient prognostic factors. Chapter 9 discusses the implications of the investigations described in this thesis, outlines the scope for expanding the resource and proposes areas for future research.
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Leite, Diana Filipa Gomes. "Curricular training at a phase I clinical trials unit." Master's thesis, Universidade de Aveiro, 2014. http://hdl.handle.net/10773/13278.
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Mestrado em Biomedicina FarmacêuticaThis report describes a curricular training in a Phase I Clinical Trials Unit, Blueclinical Ltd, company with different business areas in clinical research. Regarding clinical research, an overview of the traditional and the new paradigm of pharmaceutical development is present as well Phase I and Bioequivalence clinical trials details, the European and Portuguese regulatory environment. During the training, I participated in nine clinical trial submissions to Portuguese Competent Authorities. I also participated in the conduction of five bioequivalence / bioavailability trials in healthy volunteers, in which I developed competences as clinical trial assistant and project manager. I performed complementary activities at the other business units of Blueclinical, such as Medical Writing and in Quality System Management, which broadened my competences in other areas of clinical research. Throughout the internship I felt a substantial improvement of my personal skills, such as time and tasks management and communications and leadership skills in the context of professional activities. This integrated curricular training in the master course enhanced my understanding of clinical research processes and enlarged my vision of work opportunities. It also allowed me to identify areas of interest that I intend to pursue in order to develop my career namely clinical research project manager.
Este relatório descreve o estágio curricular numa Unidade de Ensaios Clínicos de Fase I, Blueclinical Lda, empresa com diferentes áreas de negócio em investigação clínica. Tendo em conta a investigação clínica, é apresentado uma visão geral do tradicional e do novo paradigma de desenvolvimento farmacêutico, bem como informação detalhada sobre ensaios clínicos de Fase I e de Bioequivalência, e sobre o ambiente regulamentar Europeu e Português. Durante o período de estágio, participei em nove submissões de ensaio clínico às Autoridades Competentes nacionais. Participei também na condução de cinco ensaios de bioequivalência / biodisponibilidade em voluntários saudáveis, nos quais desenvolvi competências como assistente de ensaio clínico e gestora de projeto. Realizei atividades complementares noutras áreas de negócio da Blueclinical, como na Escrita Médica e no Sistema de Gestão da Qualidade, que alargaram as minhas competências em outras áreas da investigação clínica. Durante o estágio, senti uma melhoria significativa das minhas capacidades pessoais, nomeadamente na gestão de tarefas, de tempo e na capacidade de comunicação e espírito de liderança em contexto de atividades profissionais. Este estágio curricular integrado no curso de mestrado, aumentou a minha compreensão dos processos da investigação clínica e perspetivas de oportunidades de trabalho. Também me permitiu identificar áreas de interesse onde quero desenvolver a minha carreira, nomeadamente gestão de projeto.
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Hon, Wai-fan. "Fraud in clinical research : perceptions among clinical investigators and biomedical researchers /." View the Table of Contents & Abstract, 2007. http://sunzi.lib.hku.hk/hkuto/record/B38478584.
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Loudon, Kirstine. "PRECIS-2 : making trials matter : providing an empirical basis for the selection of pragmatic design choices in clinical trials." Thesis, University of Dundee, 2015. https://discovery.dundee.ac.uk/en/studentTheses/af271d88-4652-41e0-b280-4772cc30f8c4.
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Aim PRECIS (PRagmatic Explanatory Continuum Indicator Summaries 2009) is a tool with a simple wheel format that trialists can use when designing their trials to improve the applicability of results but users highlighted problems. The aim of the study was to produce an improved and validated version of PRECIS, called PRECIS-2 and test this tool out with trial teams designing primary care trials. Methods Brainstorming and a 2-round Delphi survey of authors who cited PRECIS plus user-testing of candidate PRECIS-2 models was followed by validity and reliability testing of the most promising PRECIS-2 candidate using a sample of 15 trials rated by 19 different trialists. The validated PRECIS-2 tool was then used to consider the risk of bias (internal validity) and estimates of treatment effect of a matched set of explanatory (ideal conditions) and pragmatic (real world) trials. The PRECIS-2 website was also created with a database of pragmatic trials and a toolkit for trial groups. This was tested out at the Pragmatic Clinical Trials Unit (PCTU) in London with trial teams designing primary care trials. Results Forty-two people responded to the Delphi and highlighted scoring, domain choice, and tool format as issues. An expert panel of 14 in Toronto provided the basis for a PRECIS-2 model that was then user tested by 19 other methodologists and trialists. After 13 iterations, a PRECIS-2 model with 9 domains (i.e. Eligibility, Recruitment, Setting, Organisation, Flexibility Delivery, Flexibility Adherence, Follow up, Primary Outcome, Primary Analysis) was tested for validity and reliability. Inter-rater reliability was generally good, with eight of nine domains having an ICC over 0.65. Discriminant validity was reasonable for all domains, though with wide confidence intervals. Matching trials taking pragmatic (‘real world’) and explanatory (‘ideal world’) approaches was challenging but we found no indication that a pragmatic approach compromises internal validity. We were unable to extract sufficient information for a planned analysis of estimates of treatment effect. At the PCTU, the tool highlighted differences in opinion with trial team members and demonstrated convergence of opinion following discussion. There was acknowledgment that scoring of PRECIS-2 domains assisted trials teams in considering the intended audience and creation of trials relevant to practice. Useful feedback was obtained to improve the PRECIS-2 tool software for users. Conclusions PRECIS was improved by the addition of scoring and additional domains after consultation with over 80 international trialists. We have a validated PRECIS-2, in the visually appealing wheel format with 9 spokes, which is being made available through an increasingly accessed website. Work at the PCTU improved the usability of the PRECIS-2 website and demonstrated that the tool increases transparency in trial design and assists trialists in considering applicability of trial results. More matching work on the impact of design approaches on effect size is needed, and further data to support the risk of bias results would be valuable.
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Salgueiro, Ana Cláudia Marques. "Curricular training in coordination of clinical trials in a clinical research unit." Master's thesis, Universidade de Aveiro, 2014. http://hdl.handle.net/10773/14285.
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Mestrado em Medicina FarmacêuticaThis report describes several activities and projects developed in the context of a curricular training in a clinical research unit, Centro de Investigação Clínica (CIC), led by Professor Joaquim Ferreira. The CIC is one of the research groups of Instituto de Medicina Molecular (IMM) and it is also a group of the Centro Académico de Medicina de Lisboa (CAML) consortium. The principal area of training was the coordination of clinical trials and observational studies. Additionally, other research activities were conducted during the training such as, pharmacovigilance, monitoring, data entry, medical writing and some language coordination activities in a European observational study about Huntington’s Disease founded by European Huntington’s Disease Network (EHDN). It is mention on the State of the Art the Research & Development Process of a new drug and it is characterised some issues about clinical research in Portugal, including advantages in the establishment and organisation of clinical networks. During the training, with the duration of 10 months (that started on 1st September 2013 and finished on 1st July 2014) I deepened my knowledge in clinical research area, understand the importance of the clinical research units, the importance and the role of the study coordinators and expand my areas of interest. The specific training focused in neurological clinical. I had opportunity to understand the practical and logistical difficulties that a research unit faces during the conduction of clinical studies I consider that this training was a valuable experience of introduction of the practice of clinical research. I finished this training with the motivation and interest in working in the area of coordination and monitoring of studies.
Este relatório descreve as actividades e projectos desenvolvidos no âmbito de estágio curricular numa unidade de investigação clínica, o Centro de Investigação Clínica (CIC), liderada pelo Professor Doutor Joaquim Ferreira. O CIC faz parte dos grupos de investigação do Instituto de Medicina Molecular (IMM) inserindo-se na iniciativa do consórcio Centro Académico de Medicina de Lisboa (CAML). A principal área de estágio foi a coordenação de ensaios clínicos e estudos observacionais. Adicionalmente foram abordadas outras actividades durante o estágio, tais como farmacovigilância, monitorização, preenchimento de bases de dados, escrita científica e algumas actividades de coordenação a nível nacional de estudo observacional europeu sobre a doença de Huntington financiado por European Huntington’s Disease Network (EHDN). Refere-se no estado da arte o Processo de Investigação e Desenvolvimento de novos medicamentos e caracteriza-se alguns aspectos da investigação clínica em Portugal incluindo vantagens na organização de redes clínicas de investigação. Ao longo do estágio, com 10 meses de duração (início a 1 Setembro de 2013 e fim a 1 de Julho de 2014) aprofundei o conhecimento na área de investigação clínica, percebi a importância de unidades de investigação clínica, a importância e papel de coordenadores clínicos e expandi as minhas áreas de interesse. O treino específico centrou-se em estudos clínicos na área da neurologia, nomeadamente ensaios de clínicos de fase II e III, e estudos observacionais. Tive ainda oportunidade de compreender a realidade prática e logística da condução de estudos clínicos num centro de investigação. Considero que este estágio foi uma experiência valiosa de introdução á prática de investigação clínica. Desta forma, termino o estágio com motivação e interesse em trabalhar na área de coordenação ou monitorização de estudos.
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Sakamoto, Junichi, and Satoshi Morita. "From Translational Research to a Large Randomized Clinical Trial : A Long and Streanuous Way from Bench to Bedside." Nagoya University School of Medicine, 2007. http://hdl.handle.net/2237/7473.
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Bari, Wasimul. "Analyzing binary longitudinal data in adaptive clinical trials /." Internet access available to MUN users only, 2003. http://collections.mun.ca/u?/theses,167453.
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Bailey, Stuart Michael. "Sequential adaptive designs for early phase clinical trials." Thesis, University of Sussex, 2007. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.445626.
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Zhang, Paul. "Multiple imputation of missing data in clinical trials." Thesis, National Library of Canada = Bibliothèque nationale du Canada, 2001. http://www.collectionscanada.ca/obj/s4/f2/dsk3/ftp05/NQ63596.pdf.
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Sjögren, Petteri. "Randomised clinical trials and evidence-based general dentistry /." Linköping : Univ, 2004. http://www.bibl.liu.se/liupubl/disp/disp2004/med865s.pdf.
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