Proefschrift Rijksuniversiteit Limburg, Maastricht. / Met lit. opg. - Met samenvatting in het Nederlands.

Missing data is a potential source of bias in the results of randomised controlled trials (RCTs), which can have a negative impact on guidance derived from them, and ultimately patient care. This thesis aims to improve the understanding, handling, analysis and reporting of missing data in patient reported outcome measures (PROMs) for RCTs. A review of the literature provided evidence of discrepancies between recommended methodology and current practice in the handling and reporting of missing data. Particularly, missed opportunities to minimise missing data, the use of inappropriate analytical methods and lack of sensitivity analyses were noted. Missing data patterns were examined and found to vary between PROMs as well as across RCTs. Separate analyses illustrated difficulties in predicting missing data, resulting in uncertainty about assumed underlying missing data mechanisms. Simulation work was used to assess the comparative performance of statistical approaches for handling missing available in standard statistical software. Multiple imputation (MI) at either the item, subscale or composite score level was considered for missing PROMs data at a single follow-up time point. The choice of an MI approach depended on a multitude of factors, with MI at the item level being more beneficial than its alternatives for high proportions of item missingness. The approaches performed similarly for high proportions of unit-nonresponse; however, convergence issues were observed for MI at the item level. Maximum likelihood (ML), MI and inverse probability weighting (IPW) were evaluated for handling missing longitudinal PROMs data. MI was less biased than ML when additional post-randomisation data were available, while IPW introduced more bias compared to both ML and MI. A case study was used to explore approaches to sensitivity analyses to assess the impact of missing data. It was found that trial results could be susceptible to varying assumptions about missing data, and the importance of interpreting the results in this context was reiterated. This thesis provides researchers with guidance for the handling and reporting of missing PROMs data in order to decrease bias arising from missing data in RCTs.

Evidence-based policing (EBP) has emerged as a key strand of police innovation since Sherman’s (1998) Police Foundation lecture. However, for others EBP raises as many questions as answers. One of the most contentious areas is the role advocated for randomised controlled trials in testing practice and developing knowledge to support EBP. RCTs are controversial with some scholars who argue that policing is not comparable to medicine and that RCTs are unable to reflect the complexity of the police role and context. Even those who advocate the use of RCTs recognise that there are significant challenges in achieving the high dosage and high fidelity that a successful experiment requires. This dissertation responds to these challenges by analysing the completed randomised controlled trials in policing and using a case study, Operation Turning Point, to identify the factors that may contribute to the conduct and management of police field trials with high levels of treatment integrity. In the introduction, Chapter 1, the approach is set out, framed around grounded theory, to be developed in four, linked, chapters. Chapter 2 is focused on understanding treatment integrity in RCTs involving the police: A search for police RCTs is produced 122 Police RCTs completed and reported by 2016. The levels of treatment integrity are analysed. 78 of the 122 RCTs exceeded a 60% threshold, with 49 being above 90%. In Chapter 3, a “novice theory” is developed and tested as an explanation for levels of treatment integrity in police randomised controlled trials: Analysis of the 122 RCTs suggests that “novice theory” can provide an explanation for the general patterns of treatment integrity. Further detailed analysis suggested that there are, however, other factors which may be important in determining the treatment integrity. These are developed in Chapter 4, which centres on a case study of Operation Turning Point. Using published case studies and an analysis of juvenile justice RCTs, a potential framework of operational factors is developed that appear to be important in effective conduct and management. The Turning Point case study is used to develop and expand on those operational factors. Finally, taking the two together, the analysis concluded that, beyond the operational factors, there were some more strategic, “protective factors” that were also critical. These are developed in Chapter 5, by using the coding and analysis of interviews with a sample of key staff involved in Turning Point Our analysis suggests that novice theory needs to be understood in the context of both the operational and protective factors that we have identified. Taken together these findings indicate the potential advantages of building institutional frameworks in which the development of practitioners and researchers and the conduct and management of experimental research could be brought closer together. We conclude with ten recommendations designed to improve the treatment integrity of police RCTs.

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Background Loss to follow-up from randomised trials (RCTs) can affect the reliability of results. Objectives To quantify the effect of strategies to improve retention in RCTs, explore their use, and develop best practice guidance. Methods Systematic review: including retention RCTs nested in RCTs. Qualitative study: in-depth interviews with RCT personnel. Consensus development: workshops with RCT personnel. Results Systematic review: 38 RCTs evaluated RCT retention strategies. Most aimed to improve questionnaire response. Questionnaire response was improved by: adding monetary incentives (RR 1.18;1.09-1.28), higher value monetary incentives (RR 1.12;1.04-1.22) and offering monetary incentives (RR 1.25;1.14-1.38). There is some evidence that recorded delivery (RR 2.08;1.11-3.87), a specialised postal strategy (RR 1.43;1.22-1.67) and an open RCT design (RR 1.37;1.16-1.63) also improve questionnaire response. There is no clear evidence that, when compared to usual follow-up procedures, questionnaire response / retention is improved by: sending questionnaires early, more disease-relevant questionnaires, shorter, or long and clear questionnaires, offering charity donations, giving or offering gifts, "enhanced" letters, priority post, additional reminders, questionnaire order, reminders to sites, behavioural or case management strategies. There was no clear effect for monetary incentives when compared to offering entry into a prize draw, or telephone surveys when compared to a monetary incentive with a questionnaire. Qualitative study: Communication and incentive strategies are routinely used to improve retention / response. There was uncertainty about their effectiveness. Non-monetary incentives, although used, were not thought to be effective. Efforts are made to improve questionnaire layout. Other strategies are seldom used. Factors thought to impact upon retention were identified. Consensus development: Best practice guidance was agreed for monetary incentives and postage. Conclusion Giving and offering small monetary incentives can be used to improve questionnaire response in RCTs. Second class postage can also be used. Application of the results would depend on RCT context and follow-up procedures.

The use of shrimp processing waste with other cheap raw materials such as cassava was studied as a potential low cost animal feed, specially in developing countries. The impact on the economies of the shrimp industry and possible effects on the environmental were taken into consideration in developing the project.

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Antireligiously motivated trials in 1980s in Czechoslovakia The aim of my Master's degrese thesis is to point out specifics of the antireligiously motivated persecution in Czechoslovakia in 1980s. It differs from commonly known and reflected trials in the 1950s, which led to long lasting jail sentences and even death sentences. The strategy of communist Czechoslovakia in 1980s was more focused on less drastic but never stopping actions. The level of religious freedom in that time did't really exist, although the state submitted to several international pacts promising to be obliged by them. The first chapter deals with the historical context. It describes how the relationship between the communist regime and churches evolved after the World War Two. It focuses on the 1980s, describing some of the most important events in more detail. The second chapter deals with philosophical and political ideas on which the communist regime built its real policy. It quotes and comments various contemporary ideologists and tries to find the real meaining and purpose of the quoted material. The third chapter deals with the legal development of enactments relevant for this thesis. Also it tries to show how the law was applied. The fourth chapter deals with concrete case. There are four case studies, each chosen for a...

Philosophiae Doctor - PhD / Medicines for human use worldwide are generated in part through the conduct of clinical trials. This is done to ensure safety and efficacy. The involvement of human subjects in drug trials has raised concerns for the protection of human rights. As a consequence of the medical misadventures, the Declaration of Helsinki was formulated in 1964 and revised up to 2002. Today, the International Conference of Harmonization of Good Clinical Practice of 1996 guidelines are used worldwide (including South Africa) in the conduct of clinical trials. This study took place in South Africa. The objectives of the study were to first develop an instrument to be used in identifying the current good clinical practice knowledge and training needs of clinical researchers; secondly identify the knowledge level and training needs using the designed instrument and thirdly, based on the findings, develop a Good Clinical Practice training model so as to facilitate the achievement of quality standards for the conduct of clinical trials in South Africa. / South Africa

Randomization is the key element of any sensible clinical trial. It is the only way we can be sure that the patients have been allocated into the treatment groups without bias and that the treatment groups are almost similar before the start of the trial. The randomization schemes used to allocate patients into the treatment groups play a role in achieving this goal. This study uses SAS simulations to do categorical data analysis and comparison of differences between two main randomization schemes namely unrestricted and restricted randomization in dental studies where there are small samples, i.e. simple randomization and the minimization method respectively. Results show that minimization produces almost equally sized treatment groups, but simple randomization is weak in balancing prognostic factors. Nevertheless, simple randomization can also produce balanced groups even in small samples, by chance. Statistical power is also improved when minimization is used than in simple randomization, but bigger samples might be needed to boost the power.