Dissertations / Theses: 'Randomised controlled trials (RCTs)'

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Ferrante, di Ruffano Lavinia. "Using randomised controlled trials to evaluate the clinical effectiveness of diagnostic tests : how useful are test-treatment RCTs?" Thesis, University of Birmingham, 2013. http://etheses.bham.ac.uk//id/eprint/4269/.

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Background: Decisions on which tests to use should be informed by evidence that they do more good than harm. Test-treatment RCTs are recommended as the ‘gold–standard’ approach, but have attracted criticism that question whether they are fit for purpose. Confronting this question, the thesis investigates four key challenges by finding and analysing all identifiable test-treatment RCTs (2004–2007). Methods: Capture–recapture analysis estimated the total population of trials; descriptive analysis characterised the diagnostic questions evaluated by RCT; reviews of reporting and methodological quality investigated how informative and valid trials are; analytic induction was used to develop a theoretical framework linking tests to health outcomes, from which a tool was designed. Results: Published trials were poor quality, and found to be highly complex studies that will be challenging to evaluate reliably: interventions are difficult to capture and translate into protocols; several methods traditionally used to eliminate bias are more difficult to implement; test-treatment strategies impact on patient health in numerous and highly complicated ways. Conclusion: Test-treatment trials have the potential to be very useful instruments, and though highly challenging they could be both reliable and informative. However, it must be acknowledged that trials will not be suited to all comparisons.

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Watson, Hunna J. "Clinical and research developments in the treatment of paediatric obsessive-compulsive disorder." Thesis, Curtin University, 2007. http://hdl.handle.net/20.500.11937/2374.

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It is of crucial importance to identify and disseminate effective treatments for paediatric obsessive-compulsive disorder (OCD). OCD is time-consuming and distressing, and can substantially disable functioning at school, at home, and with peers (Piacentini, 2003). Children who do not receive treatment are at risk of psychological difficulties in adulthood, including continued OCD, clinical anxiety and depression, personality disorders, and social maladjustment (Wewetzer et al., 2001). Two-thirds of adult cases of OCD develop in childhood, and adults with OCD have lower employment, poorer academic achievement, and lower marital rates compared to non-OCD adults (Hollander et al., 1996; Koran, 2000; Lensi et al., 1996; Steketee, 1993). The distressing nature of OCD in childhood, accompanying psychosocial impairment and risk of future psychopathology, underscore the need to identify effective treatments. The primary aim of this thesis was to expand knowledge of evidence-based treatments for paediatric OCD. A mixed-methodology approach was employed to examine key issues in this area. The first study used meta-analytic methodology to determine the evidence supporting available treatments for paediatric OCD. An extensive literature search revealed over 100 published reports of treatments, encompassing a broad array of theoretical approaches and treatment strategies. Examples of treatments used for paediatric OCD included psychodynamic therapy, pharmacotherapy, cognitive-behavioural therapy (CBT), hypnosis, family therapy, immunotherapy, and homeopathy.Study 1 comprised the first known meta-analysis of randomised, controlled treatment trials (RCTs) for paediatric OCD. Included studies were limited to RCTs as they are the most scientifically valid means for determining treatment efficacy and provide a more accurate estimate of treatment effect by removing error variance associated with confounding variables. The literature search identified 13 RCTs containing 10 pharmacotherapy to control comparisons (N = 1016) and 5 CBT to control comparisons (N = 161). Random effects modelling yielded statistically significant pooled effect size (ES) estimates for pharmacotherapy (ES = 0.48, 95% CI = 0.36 to 0.61, p < .00001) and CBT (ES = 1.45, 95% CI = 0.68 to 2.22, p =.002). The results support the efficacy of CBT and pharmacotherapy, and confirm these approaches as the only two evidence-based treatments for paediatric OCD. Implications and suggestions for future research are discussed. The effectiveness of CBT provided impetus to further examine this treatment. Group CBT is an understudied treatment modality among children with OCD. It was hypothesised that group CBT would possess efficacy because of the effectiveness of individual CBT for children with OCD, the demonstrated effectiveness of group CBT among adults with OCD, the practical and therapeutic advantages afforded by a group treatment approach, and the embeddedness of the approach in robust psychological theory. The aim of the second study was to evaluate the efficacy of group CBT. The study comprised the largest known conducted randomised, placebo-controlled trial of group CBT for paediatric OCD.Twenty-two children and adolescents with a primary diagnosis of OCD were randomly assigned to a 12-week program of group CBT or a credible psychological placebo. Children were assessed at baseline, end of treatment, and at 1 month follow-up. Outcome measures included the Children’s Yale-Brown Obsessive-Compulsive Scale, global measures of OCD severity, Children’s Depression Inventory, and parent- and child-rated measures of psychosocial functioning. An intention-to-treat analysis revealed that children in the group CBT condition had statistically significantly lower levels of symptomatology at posttreatment and follow-up compared to children in the placebo condition. Analysis of clinical significance showed that 91% of children that received CBT were ‘recovered’ or ‘improved’ at follow-up, whereas 73% of children in the placebo condition were ‘unchanged’. Effect size analysis using Cohen’s d derived an effect of 1.14 and 1.20 at posttreatment and follow-up, respectively. These effects are comparable to results from studies of individual CBT. This study supported group CBT as an effective treatment modality for paediatric OCD and demonstrated that the effect extends beyond placebo and nonspecific treatment factors. In addition to treatment efficacy, the inherent worth of a treatment lies in its adoption by the relevant clinical population. Children with OCD are known to be secretive and embarrassed about symptoms, and there is often a long delay between onset of symptoms and treatment-seeking (Simonds & Elliot, 2001). An important observation during the course of conducting the RCT was that a high rate (39%) of eligible families declined participation.This led to the question, "What barriers prevent participation in group CBT for paediatric OCD?" Qualitative methodology was employed to address this research question. Eligible families that had declined participation in the RCT were contacted and invited to participate in semi-structured interviews that explored reasons for non-participation and positive and negative perceptions of group CBT. The average time between non-participation and interview was 1.33 years (SD = 3 months). Data were collected from nine families and thematic analysis methodology was utilised to identify emergent themes. Failure to participate was predicted by practical and attitudinal barriers. Practical barriers included a lack of time, distance, severity of OCD symptoms, financial, and child physical health. Attitudinal barriers included child embarrassment about OCD symptoms, child belief that therapy would be ineffective, fear of the social aspect of the group, lack of previous success with psychology, lack of trust in strangers, parental concern about the structure of the group, denial of a problem, and â€˜not being ready for itâ€™. Attitudinal barriers more frequently predicted treatment non-participation. Positive and negative perceptions of this treatment modality were informative. Parents showed no differences in preference for individual or group CBT. An important finding was that 56% of the children had not received treatment since parental expression of interest in the group CBT program. Application of the findings to methods that promote service utilisation is discussed.

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Watson, Hunna J. "Clinical and research developments in the treatment of paediatric obsessive-compulsive disorder." Curtin University of Technology, School of Psychology, Division of Health Sciences, 2007. http://espace.library.curtin.edu.au:80/R/?func=dbin-jump-full&object_id=115091.

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It is of crucial importance to identify and disseminate effective treatments for paediatric obsessive-compulsive disorder (OCD). OCD is time-consuming and distressing, and can substantially disable functioning at school, at home, and with peers (Piacentini, 2003). Children who do not receive treatment are at risk of psychological difficulties in adulthood, including continued OCD, clinical anxiety and depression, personality disorders, and social maladjustment (Wewetzer et al., 2001). Two-thirds of adult cases of OCD develop in childhood, and adults with OCD have lower employment, poorer academic achievement, and lower marital rates compared to non-OCD adults (Hollander et al., 1996; Koran, 2000; Lensi et al., 1996; Steketee, 1993). The distressing nature of OCD in childhood, accompanying psychosocial impairment and risk of future psychopathology, underscore the need to identify effective treatments. The primary aim of this thesis was to expand knowledge of evidence-based treatments for paediatric OCD. A mixed-methodology approach was employed to examine key issues in this area. The first study used meta-analytic methodology to determine the evidence supporting available treatments for paediatric OCD. An extensive literature search revealed over 100 published reports of treatments, encompassing a broad array of theoretical approaches and treatment strategies. Examples of treatments used for paediatric OCD included psychodynamic therapy, pharmacotherapy, cognitive-behavioural therapy (CBT), hypnosis, family therapy, immunotherapy, and homeopathy.
Study 1 comprised the first known meta-analysis of randomised, controlled treatment trials (RCTs) for paediatric OCD. Included studies were limited to RCTs as they are the most scientifically valid means for determining treatment efficacy and provide a more accurate estimate of treatment effect by removing error variance associated with confounding variables. The literature search identified 13 RCTs containing 10 pharmacotherapy to control comparisons (N = 1016) and 5 CBT to control comparisons (N = 161). Random effects modelling yielded statistically significant pooled effect size (ES) estimates for pharmacotherapy (ES = 0.48, 95% CI = 0.36 to 0.61, p < .00001) and CBT (ES = 1.45, 95% CI = 0.68 to 2.22, p =.002). The results support the efficacy of CBT and pharmacotherapy, and confirm these approaches as the only two evidence-based treatments for paediatric OCD. Implications and suggestions for future research are discussed. The effectiveness of CBT provided impetus to further examine this treatment. Group CBT is an understudied treatment modality among children with OCD. It was hypothesised that group CBT would possess efficacy because of the effectiveness of individual CBT for children with OCD, the demonstrated effectiveness of group CBT among adults with OCD, the practical and therapeutic advantages afforded by a group treatment approach, and the embeddedness of the approach in robust psychological theory. The aim of the second study was to evaluate the efficacy of group CBT. The study comprised the largest known conducted randomised, placebo-controlled trial of group CBT for paediatric OCD.
Twenty-two children and adolescents with a primary diagnosis of OCD were randomly assigned to a 12-week program of group CBT or a credible psychological placebo. Children were assessed at baseline, end of treatment, and at 1 month follow-up. Outcome measures included the Children’s Yale-Brown Obsessive-Compulsive Scale, global measures of OCD severity, Children’s Depression Inventory, and parent- and child-rated measures of psychosocial functioning. An intention-to-treat analysis revealed that children in the group CBT condition had statistically significantly lower levels of symptomatology at posttreatment and follow-up compared to children in the placebo condition. Analysis of clinical significance showed that 91% of children that received CBT were ‘recovered’ or ‘improved’ at follow-up, whereas 73% of children in the placebo condition were ‘unchanged’. Effect size analysis using Cohen’s d derived an effect of 1.14 and 1.20 at posttreatment and follow-up, respectively. These effects are comparable to results from studies of individual CBT. This study supported group CBT as an effective treatment modality for paediatric OCD and demonstrated that the effect extends beyond placebo and nonspecific treatment factors. In addition to treatment efficacy, the inherent worth of a treatment lies in its adoption by the relevant clinical population. Children with OCD are known to be secretive and embarrassed about symptoms, and there is often a long delay between onset of symptoms and treatment-seeking (Simonds & Elliot, 2001). An important observation during the course of conducting the RCT was that a high rate (39%) of eligible families declined participation.
This led to the question, "What barriers prevent participation in group CBT for paediatric OCD?" Qualitative methodology was employed to address this research question. Eligible families that had declined participation in the RCT were contacted and invited to participate in semi-structured interviews that explored reasons for non-participation and positive and negative perceptions of group CBT. The average time between non-participation and interview was 1.33 years (SD = 3 months). Data were collected from nine families and thematic analysis methodology was utilised to identify emergent themes. Failure to participate was predicted by practical and attitudinal barriers. Practical barriers included a lack of time, distance, severity of OCD symptoms, financial, and child physical health. Attitudinal barriers included child embarrassment about OCD symptoms, child belief that therapy would be ineffective, fear of the social aspect of the group, lack of previous success with psychology, lack of trust in strangers, parental concern about the structure of the group, denial of a problem, and â€˜not being ready for itâ€™. Attitudinal barriers more frequently predicted treatment non-participation. Positive and negative perceptions of this treatment modality were informative. Parents showed no differences in preference for individual or group CBT. An important finding was that 56% of the children had not received treatment since parental expression of interest in the group CBT program. Application of the findings to methods that promote service utilisation is discussed.

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4

Berrisford, Isabelle C. "Dual Agency of Physician-Researchers: The Role of Equipoise in RCTs in Preserving the Integrity of the Physician-Researcher Role During Public Health Crises." The Ohio State University, 2021. http://rave.ohiolink.edu/etdc/view?acc_num=osu1619164005499914.

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Relton, Clare. "A new design for pragmatic randomised controlled trials : a 'Patient Cohort' RCT of treatment by a homeopath for menopausal hot flushes." Thesis, University of Sheffield, 2009. http://etheses.whiterose.ac.uk/6644/.

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There is debate regarding the effectiveness of homeopathy and its continuing provision in the NHS, and despite 150+ clinical trials there are conflicting opinions as to what can be concluded from these trials. This thesis addresses the question: “What type of clinical trial design can provide the information needed to make decisions about the provision of homeopathy in a publicly funded healthcare system?” A critique of the methods used in existing clinical trial designs was undertaken which identified twelve key criteria for appropriate clinical trial design; methods from existing standard and alternative clinical trial designs were adapted in order to derive a new clinical trial design that has the potential to meet all twelve key criteria (the ‘Patient Cohort’ RCT design). A current clinical question was identified: ‘What is the clinical & cost effectiveness of treatment by a homeopath for women with menopausal hot flushes?” and a population based survey confirmed the importance of this question. The ‘Patient Cohort’ RCT design was piloted in an NHS setting in order to address this current clinical question. Seventy ‘with need’ women were recruited to the Hot Flush Cohort of whom forty-eight were eligible for the treatment, a proportion of whom were randomly selected to be offered the treatment. 70.8% of those offered treatment accepted the offer and completion of outcome measures was high (93.7%). The results indicate that a full trial of this treatment for this condition may be worthwhile conducting. A full RCT using this design would be an appropriate clinical trial design to provide answers as to the provision of homeopathy and other clinician delivered interventions in publicly funded healthcare system such as the NHS. The ‘Patient Cohort’ RCT design can be usefully applied to clinical questions that require very pragmatic approaches yet need the scientific rigour of randomisation.

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Ford, Shane Alwyn. "Delivering Acceptance and Commitment Therapy (ACT) for mental health disorders across group and guided self-help formats : a meta-analysis and randomised controlled trial." Thesis, University of Edinburgh, 2017. http://hdl.handle.net/1842/25924.

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Background: Acceptance and Commitment Therapy (ACT) has shown promise as an effective intervention in the treatment of mental health disorders. In the last decade, the delivery of ACT has expanded to include various formats (e.g. groups, self-help, online and phone apps). Further research is needed to evaluate whether such delivery formats are a viable extension of ACT. Furthermore, the existing evidence base of certain alternative delivery formats have yet to be reviewed. This thesis portfolio sought to contribute to this area of research. Methods: A systematic review of the literature was conducted to investigate the efficacy of group-based interventions for mental health disorders using ACT. Five databases were systematically searched, manual searches were conducted and corresponding authors were contacted. Studies which used a randomised-controlled design, with adult samples and investigated group-based ACT interventions for mental health disorders were included. A meta-analysis of the included studies was conducted for post-intervention and follow-up data. In the empirical study, an ACT manual was trialled using a randomised-controlled design to investigate the efficacy of using ACT in a guided self-help context. Participants with anxiety/depression were randomly assigned to receive either the ACT intervention or treatment as usual (TAU). Those in the ACT group were posted an ACT manual and received two telephone calls. Outcome measures were analysed after the six-week intervention. Results: From the meta-analysis, 18 randomised-controlled trials were identified, 14 of which focussed on anxiety and depression. The findings suggest that ACT-based groups have a large effect on symptom reduction when compared to non-active comparisons at post-treatment and a moderate effect when compared to non-active comparisons at follow-up. Additionally, there was a small effect in favour of ACT when compared to active treatment controls at post-treatment and equivalent effects when comparing ACT to active treatment controls at follow-up. Similar effects were found when separately comparing the 14 studies which focussed primarily on anxiety and depression. The empirical study revealed that guided self-help was found to be no more effective in improving quality of life or reducing psychological distress than the TAU group. However, such results should be interpreted with caution as the small sample size and high attrition rate indicates that further research with larger samples and follow-up are needed before strong conclusions can be made. Conclusions: The findings of this research indicate that group-based ACT interventions may be a suitable alternative delivery format for service providers in the provision of common mental health disorders, particularly anxiety and depression. Further research is needed before any strong conclusions can be made regarding the efficacy of guided self-help for anxiety/depression.

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Spieth, Peter Markus, Anne Sophie Kubasch, Ana Isabel Penzlin, Ben Min-Woo Illigens, Kristian Barlinn, and Timo Siepmann. "Randomized controlled trials - a matter of design." Saechsische Landesbibliothek- Staats- und Universitaetsbibliothek Dresden, 2017. http://nbn-resolving.de/urn:nbn:de:bsz:14-qucosa-215848.

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Randomized controlled trials (RCTs) are the hallmark of evidence-based medicine and form the basis for translating research data into clinical practice. This review summarizes commonly applied designs and quality indicators of RCTs to provide guidance in interpreting and critically evaluating clinical research data. It further reflects on the principle of equipoise and its practical applicability to clinical science with an emphasis on critical care and neurological research. We performed a review of educational material, review articles, methodological studies, and published clinical trials using the databases MEDLINE, PubMed, and ClinicalTrials.gov. The most relevant recommendations regarding design, conduction, and reporting of RCTs may include the following: 1) clinically relevant end points should be defined a priori, and an unbiased analysis and report of the study results should be warranted, 2) both significant and nonsignificant results should be objectively reported and published, 3) structured study design and performance as indicated in the Consolidated Standards of Reporting Trials statement should be employed as well as registration in a public trial database, 4) potential conflicts of interest and funding sources should be disclaimed in study report or publication, and 5) in the comparison of experimental treatment with standard care, preplanned interim analyses during an ongoing RCT can aid in maintaining clinical equipoise by assessing benefit, harm, or futility, thus allowing decision on continuation or termination of the trial.

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Spieth, Peter Markus, Anne Sophie Kubasch, Ana Isabel Penzlin, Ben Min-Woo Illigens, Kristian Barlinn, and Timo Siepmann. "Randomized controlled trials - a matter of design." Dove Medical Press, 2016. https://tud.qucosa.de/id/qucosa%3A29007.

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Randomized controlled trials (RCTs) are the hallmark of evidence-based medicine and form the basis for translating research data into clinical practice. This review summarizes commonly applied designs and quality indicators of RCTs to provide guidance in interpreting and critically evaluating clinical research data. It further reflects on the principle of equipoise and its practical applicability to clinical science with an emphasis on critical care and neurological research. We performed a review of educational material, review articles, methodological studies, and published clinical trials using the databases MEDLINE, PubMed, and ClinicalTrials.gov. The most relevant recommendations regarding design, conduction, and reporting of RCTs may include the following: 1) clinically relevant end points should be defined a priori, and an unbiased analysis and report of the study results should be warranted, 2) both significant and nonsignificant results should be objectively reported and published, 3) structured study design and performance as indicated in the Consolidated Standards of Reporting Trials statement should be employed as well as registration in a public trial database, 4) potential conflicts of interest and funding sources should be disclaimed in study report or publication, and 5) in the comparison of experimental treatment with standard care, preplanned interim analyses during an ongoing RCT can aid in maintaining clinical equipoise by assessing benefit, harm, or futility, thus allowing decision on continuation or termination of the trial.

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Ulucanlar, Selda. "Randomised controlled trials and equipoise." Thesis, University of Bristol, 2010. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.535188.

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Dakin, Helen A. "Economic evaluation of factorial randomised controlled trials." Thesis, University of Oxford, 2015. http://ora.ox.ac.uk/objects/uuid:77eda1f6-dd8c-439a-8871-75fd57a4c7f5.

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Factorial randomised controlled trials (RCTs) evaluate two or more interventions simultaneously, enabling assessment of interactions between treatments. This thesis presents literature reviews, methodological reviews, simulation studies and applied case studies that explore methods for assessing cost-effectiveness based on factorial RCTs. My systematic review suggests that factorial RCTs account for around 3% of trial-based economic evaluations, although there is currently no guidance or methodological work indicating the most appropriate methods. Around 40% of published studies assumed no interaction between treatments and many were poorly-reported. Various mechanisms are likely to produce large interactions within economic endpoints such as costs, quality-adjusted life-years (QALYs) and net benefits. Failing to take account of interactions can introduce bias and prevent efficient allocation of healthcare resources. I developed the opportunity cost of ignoring interactions as a measure of the implications of this bias. However, allowing for small, chance interactions is inefficient, potentially leading to over-investment in research if trial-based evaluations are used to inform decisions about subsequent research. Nonetheless, analyses on simulated trial data suggest that the opportunity cost of adopting a treatment that will not maximise health gains from the healthcare budget is minimised by including all interactions regardless of magnitude or statistical significance. Different approaches for conducting economic evaluations of factorial RCTs (including regression techniques, extrapolation using patient-level simulation, and considering different components of net benefit separately) are evaluated within three applied studies, including both full and partial factorials with 2x2 and 2x2x2 designs. I demonstrate that within both trial-based and model-based economic evaluation, efficient allocation of healthcare resources requires consideration of interactions between treatments, and joint decisions about interacting treatments based on incremental cost-effectiveness evaluated “inside-the-table” on a natural scale. I make recommendations for the design, analysis and reporting of factorial trial-based economic evaluations based on the results of this thesis.

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Kaur, Geetinder. "Recruitment to randomised controlled trials with children." Thesis, University of Liverpool, 2016. http://livrepository.liverpool.ac.uk/3002903/.

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Recruitment to randomised controlled trials is known to be difficult. Poor recruitment has several adverse consequences. It affects the validity of study findings, is a common cause of trial extensions and may result in premature termination of trials, which is a huge loss in terms of invested funds, resources and lost knowledge. Non-completion or delayed completion of studies maintains the uncertainty about the efficacy and safety of interventions, thereby delaying or preventing the use of effective interventions and prolonging the use of ineffective or potentially harmful treatments. Recruitment of children to randomised controlled trials is thought to be more challenging due to the vulnerability of the population and the fact that consent is provided by another person usually parents. This thesis aims to review the recruitment performance, i.e. comparison of achieved to anticipated recruitment, of randomised controlled trials with children and identify the factors associated with good or poor recruitment. We undertook a pilot systematic review of recruitment and retention in randomised controlled trials with children, in published literature, and found that few studies report recruitment information but those that do, report very high rates of percentage total recruitment achieved (%TR) and consent. It was not possible to obtain unbiased estimates of recruitment performance and consent rate due to the likelihood of selective reporting and/or non-publication of trials with unsuccessful recruitment. We subsequently conducted a review of recruitment of children to randomised controlled trials in the National Institute of Health Research (NIHR) Clinical Research Network (CRN) portfolio and found that under-recruitment and delayed recruitment are common problems in paediatric trials. Having a trial manager or coordinator was found to be significantly associated with successful recruitment. Other factors such as being an IMP (Investigational Medicinal Product) vs. non-IMP trial, trial of acute vs. chronic illness, having CTU (Clinical Trials Unit) involvement, pilot/feasibility study and additional trial demands had no statistically significant association with recruitment success. Since recruitment to a clinical trial can be affected by a number of internal and external factors, we conducted a survey with the clinical teams of a multi-centre randomised controlled trial with children, the MAGNETIC trial, to understand the various facilitators and barriers to recruitment. In order to identify the facilitators and barriers to recruitment and establish the recruitment experience of clinical teams in a systematic manner, we developed an evidence based recruitment survey tool. The survey tool is an online questionnaire that presents a comprehensive evidence based list of facilitators and barriers and free text space for responders to record the strategies applied to overcome these barriers and suggestions for change in organisation of trials to boost recruitment. The survey of clinical teams recruiting to the MAGNETIC trial found that a motivated clinical team with effective communication skills, effective coordination between study team members at site and between sites and CTU, trial management support, research experience of PI, presence of a research nurse and availability of a designated research team were imperative for trial recruitment success. Heavy clinical workload, shift patterns of work, lack of trained staff particularly out of hours, GCP training, local clinical arrangements and parental anxiety about the safety of experimental treatment were recognised as important barriers to recruitment. A trial specific barrier was difficulty faced by the clinicians in seeking consent from the parents of an acutely ill child in the emergency setting and suggestions were made for consideration of deferred consent. We concluded that recruitment to randomised controlled trials with children is challenging and poor recruitment and recruitment delays are a common problem. Reporting of recruitment and consent in paediatric trials is poor and needs improvement. Presence of a dedicated trial manager is significantly associated with successful recruitment and the various generic and trial specific facilitators and barriers to recruitment that have been identified can be used by trialists in planning and conducting future clinical trials with children.

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Caldwell, Patrina Ha Yuen. "The Recruitment of Children to Randomised Controlled Trials." University of Sydney. Paediatrics and Child Health, 2003. http://hdl.handle.net/2123/579.

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Abstract Background The randomised-controlled trial (RCT) provides the best evidence for evaluating treatment effects and is accepted as a gold standard for clinical and regulatory decision making (1;2). One of the major challenges to the conduct of RCTs is the recruitment of adequate numbers of participants. Inadequate numbers reduce the power of a study to detect statistically significant treatment effects, and may cause delays, increased costs and failure to complete trials. The need for clinical trials in children has been increasingly recognised by the scientific community, resulting in increased demands for the inclusion of children in trials. For several reasons, recruiting children to trials is more challenging than recruiting adults, as consent issues are more difficult because parents make decisions about trial participation on behalf of their child. Despite general professional and community support for paediatric clinical trials, parents and paediatricians express reluctance when their own child or patient is asked to participate. Although researchers working with children commonly experience difficulty with recruiting children to RCTs, little is known about this very important subject. The method by which potential participants are approached for trial participation, the influence of their health care provider and the attitude of potential participants (or their parents, in the case of children), are critical to the understanding of the decision making process for trial participation. This thesis is one of the first major attempts to explore the issues surrounding the recruitment of children to RCTs, and is divided into four studies which address these issues. Methods Recruitment strategies used to encourage participation in randomised controlled trials (systematic review) Eligible experimental and observational studies comparing methods of recruiting participants for RCTs were identified after a comprehensive search of Medline, Embase, the Cochrane Library and reference lists. Independent data extractions were completed by two reviewers who assessed the studies for eligibility and methodological quality. Outcome measures were consent rates, proportion enrolled by each method and cost of recruitment per participant. Summary estimators of effects were calculated using a random effects model and expressed as relative risk with 95% confidence intervals. Heterogeneity was analysed using the Q statistic. Paediatricians� attitudes to children�s participation in randomised controlled trials (focus group research) Qualitative analysis of focus group discussions involving 16 paediatricians and 5 trainees from a paediatric teaching hospital in Sydney was undertaken. Doctors varied in occupation, experience, research activity, age, gender, ethnicity and parenthood experience. A professional facilitator conducted the semi-structured group discussions. Recruitment ceased when informational redundancy was reached, after 4 focus groups involving 21 participants. The transcribed audiotapes were analysed by theme linkage using the constant comparative method. Australian paediatricians� and adult physicians� attitudes to randomised controlled trials (survey) A 44-item questionnaire was sent to 250 paediatricians and 250 adult physicians randomly selected from the membership list of the Royal Australasian College of Physicians. Questions assessing doctors� treatment philosophies and attitudes to trials were compared with demographic and practice variables. Parents� attitudes to children�s participation in randomised controlled trials (focus group research) Qualitative analysis of focus group discussions involving 33 parents from 5 different settings (representing parents of children with a life threatening, chronic or acute illness, with experience in trials and of healthy children) was undertaken. Parents varied in age, gender, ethnicity, level of education, research experience and their child�s health status. The transcribed discussions were analysed by theme linkage using the constant comparative method. Results Recruitment strategies used to encourage participation in randomised controlled trials (systematic review) Fifty papers were included (out of 8602 titles and abstracts searched) which described 8 RCTs, 2 quasi RCTs, 13 prospective cohort studies, 30 retrospective cohort studies and 2 before-after studies. These studies assessed how over 4 million people were approached for RCT participation using 87 different recruitment strategies, with 103,406 people enrolling in RCTs. Health care provider (HCP) referrals had the highest participant consent rates at the time of exposure to trial information (HCP referral versus target mailing: relative risk (RR) 1.84 (95% confidence interval (95%CI) 1.08, 3.13)). They also had the highest consent rates when potential participants respond to the recruitment material by further enquiry about the trial (HCP referral versus community presentation: RR 1.37 (1.06; 1.78); HCP referral versus worksite approach: RR 25.20 (20.19, 31.45); HCP referral versus general community approach: RR 2.53 (0.46, 14.05); HCP referral versus mailing: RR 3.29 (1.26, 8.60); HCP referral versus media: RR 2.66 (1.31, 5.41)). However, by the time potential participants attend eligibility assessment for trial participation, no difference in consent rates could be distinguished by method of recruitment. Higher proportions of study participants were recruited by methods that exposed larger numbers of potential candidates to trial information (despite their lower consent rates). The stated recruitment cost ranged from US$0 to $1108 per participant, with mailing being the most cost-effective method and community methods (such as community presentations, pamphlets and posters displayed at community sites) the least effective. Paediatricians� attitudes to children�s participation in randomised controlled trials (focus group research) From the focus group discussions, paediatricians thought parents balanced perceived gains and risks when deciding about trial participation. They also believed the child�s condition and parents� health beliefs and personal attributes influenced parents� decisions. Other factors thought to be important by paediatricians were the doctors� beliefs and their relationship with the investigators. Paediatricians perceived gains for trial participation including professional benefits for themselves, improved patient care, convenience for the families and themselves and scientific advancement. Perceived risks included inconvenience, inadequate resources and potential harms to the patient and the doctor-patient relationship. Paediatricians with previous research experience were most knowledgeable about RCTs and perceived greatest gains from trial participation. Paediatricians� personal treatment preferences hindered trial support. Australian paediatricians� and adult physicians� attitudes to randomised controlled trials (survey) Response rate from the paediatricians� and adult physicians� survey was 60% (300/500). Australian paediatricians and adult physicians are very similar in their treatment philosophies, and are clinician-oriented rather than research-oriented in their attitudes, with primary allegiance to their patients and preference for selecting treatment rather than referring for trial participation in the face of treatment uncertainty. Professional activities are clinically focused, with limited time assigned for research. Australian doctors perceive little reward for trial participation and claim that the opinions of referring doctors regarding RCTs does not influence them. Predictors of favourable attitudes to trial participation from the survey were time allocation for research, a history of referring patients to trials in the past and younger age (all p values less than 0.0001). Parents� attitudes to children�s participation in randomised controlled trials (focus group research) When parents were interviewed, they acknowledged balancing risks and benefits when deciding about trial participation for their child. Perceived benefits include the offer of hope, better care of their child, the opportunity to access new treatments, healthcare professionals and health information, meeting others in similar circumstances and helping others. Perceived risks include potential side effects, being randomised to ineffective treatments and the inconvenience of participation. The decision for trial participation is also influenced by parental factors (parents� knowledge, beliefs and emotional response), child factors (the child�s health status and preference about participation), trial factors (the use of placebos and the uncertainties of research) and doctor factors (doctor�s recommendations and communication of trial information). Conclusions There are many challenges to the successful conduct of RCTs. Ways of addressing these include: using effective methods of recruiting potential study participants (such as mailing of recruitment material to potential participants) and abandoning ineffective strategies (such as community methods): fostering greater willingness for trial participation by addressing parents� and paediatricians� concerns including enhancing communication between researchers, paediatricians and parents, and improving the gains-hazard balance (by increasing incentives while decreasing inconveniences); and reforming in the health care system to raise the priority placed on clinical research by restructuring clinical research in a clinically predominant workplace and with a clinically predominant workforce. The findings from this study have implications for researchers planning RCTs for children in the future. Careful consideration of the above will enhance RCTs participation for children improving efficiency, lowering costs and ultimately improving the future health care of children.

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Carragher, Raymond. "Detection of safety signals in randomised controlled trials." Thesis, University of Strathclyde, 2017. http://digitool.lib.strath.ac.uk:80/R/?func=dbin-jump-full&object_id=29239.

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The occurrence, severity, and duration of patient adverse events are routinely recorded during randomised clinical trials. This data is used by a trial's Data Monitoring Committee to make decisions regarding the safety of a treatment and may lead to the alteration or discontinuation of a trial if real safety issues are detected. There are many different types of adverse event and the statistical analysis of this data, particularly with regard to hypothesis testing, must take into account potential multiple comparison issues. Unadjusted hypothesis tests may lead to large numbers of false positive results, but simple adjustments are generally too conservative. In addition, the anticipated effect sizes of adverse events in clinical trials are generally small and consequently the power to detect such effects is low. A number of recent classical and Bayesian methods, which use groupings of adverse events, have been proposed to address this problem. We illustrate and compare a number of these approaches, and investigate if their use of a common underlying model, which involves groupings of adverse events by body-system or System Organ Class, is useful in detecting adverse events associated with treatments. For data where this type of grouped approach is appropriate, the methods considered are shown to correctly flag more adverse event effects than standard approaches, while maintaining control of the overall error rate. While controlling for multiple types of adverse event, these proposed methods do not take into account event timings or patient exposure time, and are more suited to end of trial analysis. In order to address the desire for the early detection of safety issues in clinical trials a number of Bayesian methods are introduced to analyse the accumulation of adverse events as the trial progresses, taking into account event timing, patient time in study, and body-system. These methods are suitable for use at interim trial safety analyses. The models which performed best were those that had a common body-system dependence over the duration of the trial.

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Schulz, Kenneth Fredrick. "Methodological quality and bias in randomised controlled trials." Thesis, London School of Hygiene and Tropical Medicine (University of London), 1994. http://researchonline.lshtm.ac.uk/4646508/.

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To evaluate the methodological quality of randomised trials in recently published articles and to examine the associations between methodological quality and bias, three related investigations were undertaken. First, to ensure the development of useful measures for the adequacy of randomisation, approaches to allocation were assessed as reported in 206 parallel group trials published in recent volumes of journals of obstetrics and gynaecology. Next, a study was conducted of associations between methodological quality and treatment effects. The material analysed came from 250 trials in 33 meta-analyses on pregnancy and childbirth topics. Finally, the reported approaches to blinding and handling of exclusions were assessed from a random sample of 110 of the 206 previously identified reports. In the 206 published trials, 77% reported either inadequately or unclearly concealed treatment allocation. Additional analyses suggest that non-random manipulation of comparison groups may have occurred. In the next study. compared with trials in which authors reported adequately concealed treatment allocation, trials in which authors reported inadequately or unclearly concealed allocation yielded larger estimates of treatment effects (p < 0.001). Odds ratios were distorted by 41% and 33%, respectively. Those associations likely represent bias and are particularly disconcerting in light of the results above from recently published trials. Lack of double-blinding in trials was also associated with larger treatment benefits. However, trials in which authors reported excluding 2 participants after randomisation were not associated with larger treatment effects. That lack of association appeared to be due to incomplete reporting. 3 The analysis of 110 recently published trials also supported the findings that some of the trials not reporting exclusions may actually have had exclusions. In practice, that incomplete reporting could lead to misinterpretations of trial quality. Moreover, only about half the trials that could have double-blinded actually did so. When investigators attempted double-blinding, only 16% provided any written assurances of successfully implementing blinding and only 6% tested its efficacy.

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McCann, Sharon Katrina. "Patients' perspectives on participation in randomised controlled trials." Thesis, University of Aberdeen, 2007. http://digitool.abdn.ac.uk/R?func=search-advanced-go&find_code1=WSN&request1=AAIU494624.

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The study had three components: (i) an overview of the literature on participant involvement in RCTs; (ii) a meta-ethnography focusing on factors impacting on participant recruitment to RCTs; and (iii) an embedded qualitative study investigating recruitment and participation in an ongoing UK multicentre trial. Non participant observation of trial recruitment consultations and in-depth interviews were conducted with patients invited to participate in the trial from two recruitment sites. Decisions about trial participation took part in a broad personal context, such as perceptions of treatment, levels of symptoms control, and prior experience of interventions. Views about the trial procedures, treatment interventions, and impressions of recruiting staff were also found to be salient. Although altruism was identified as a factor impacting on trial participation, this tended to be ‘conditional altruism’, dependent on expectations of personally benefiting from participating in a trial. Perceptions of benefiting personally from a trial were linked to the trial intervention(s) and also towards the trial process. Despite agreeing to be randomised it was apparent that some patients harboured a ‘preference’ for a treatment. However, people subsequently seemed able to adjust to their allocated treatment, although there were misconceptions about how treatment decisions had been reached. Perceptions of trial involvement, and having directly benefited from trial participation seemed particularly dependent on which treatment people were allocated to. Crucially, the findings have emphasised that trials are not simply an experimental tool operating in a vacuum, independent of the view and experiences of participants; and offer rich insights, which are likely to benefit people recruiting in future trials, and for future trial participants.

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Dodd, Susanna. "Modelling departure from randomised treatment in randomised controlled trials with survival outcomes." Thesis, University of Liverpool, 2014. http://livrepository.liverpool.ac.uk/2006887/.

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Randomised controlled trials are considered the gold standard study design, as random treatment assignment provides balance in prognosis between treatment arms and protects against selection bias. When trials are subject to departures from randomised treatment, however, simple but naïve statistical methods that purport to estimate treatment efficacy, such as per protocol or as treated analyses, fail to respect this randomisation balance and typically introduce selection bias. This bias occurs because departure from randomised treatment is often clinically indicated, resulting in systematic differences between patients who do and do not adhere to their assigned intervention. There exist more appropriate statistical methods to adjust for departure from randomised treatment but, as demonstrated by a review of published trials, these are rarely employed, primarily due to their complexity and unfamiliarity. The focus of this research has been to explore, explain, demonstrate and compare the use of causal methodologies in the analysis of trials, in order to increase the accessibility and comprehensibility by non-specialist analysts of the available, but somewhat technical, statistical methods to adjust for treatment deviations. An overview of such methods is presented, intended as an aid to researchers new to the field of causal inference, with an emphasis on practical considerations necessary to ensure appropriate implementation of techniques, and complemented by a number of guidance tools summarising the necessary clinical and statistical considerations when carrying out such analyses. Practical demonstrations of causal analysis techniques are then presented, with existing methods extended and adapted to allow for complexities arising from the trial scenarios. A particular application from epilepsy demonstrates the impact of various statistical factors when adjusting for skewed time-varying confounders and different reasons for treatment changes on a complicated time to event outcome, including choice of model (pooled logistic regression versus Cox models for inverse probability of censoring weighting methods, compared with a rank-preserving structural failure time model), time interval (for creating panel data for time-varying confounders and outcome), confidence interval estimation method (standard versus bootstrapped) and the considerations regarding use of spline variables to estimate underlying risk in pooled logistic regression. In this example, the structural failure time model is severely limited by its restriction on the types of treatment changes that can be adjusted for; as such, the majority of treatment changes are necessarily censored, introducing bias similar to that in a per protocol analysis. With inverse probability weighting adjustment, as more treatment changes and confounders are accounted for, treatment effects are observed to move further away from the null. Generally, Cox models seemed to be more susceptible to changes in modelling factors (confidence interval estimation, time interval and confounder adjustment) and displayed greater fluctuations in treatment effect than corresponding pooled logistic regression models. This apparent greater stability of logistic regression, even when subject to severe overfitting, represents a major advantage over Cox modelling in this context, countering the inherent complications relating to the fitting of spline variables. This novel application of complex methods in a complicated trial scenario provides a useful example for discussion of typical analysis issues and limitations, as it addresses challenges that are likely to be common in trials featuring problems with nonadherence. Recommendations are provided for analysts when considering which of these analysis methods should be applied in a given trial setting.

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Whitehead, Amy. "Sample size justifications for pilot trials of publicly funded randomised controlled trials." Thesis, University of Sheffield, 2016. http://etheses.whiterose.ac.uk/15822/.

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A sample size estimate for a clinical trial is an important issue as incorrectly estimating it could have both ethical and financial implications for the trial. Calculating the required sample size for a trial with a continuous outcome requires an estimate of the population variance. A pilot trial can be used to get an estimate of the population variance. However, pilot trials are often small and may give imprecise estimates; adjustment methods are discussed which allow for this imprecision. Theoretical minimum values for the overall trial sample size when using an adjustment method to design the main trial after an external pilot trial are provided. Using the results recommendations for external pilot trial sample size are presented which aim to minimise the overall trial sample size. It was found that the optimal pilot trial sample size increases with the size of the main trial, therefore stepped rules of thumb are proposed. For a 90% powered main trial this method indicates that the sample size for a two-armed pilot trial to minimise the overall sample size should be 150, 50, 30 and 20 for standardised effect sizes (δ) of δ < 0.1, 0.1 ≤ δ < 0.3, 0.3 ≤ δ < 0.7 and δ ≥ 0.7 respectively. The work is extended to allow for unequal cost per patient between the two trials. The results show that when the pilot trial is less expensive per patient than the main trial the optimal pilot trial sample size increases, giving more precision for the variance estimate and a relatively small main trial. The opposite is true when the main trial is less expensive than the pilot trial. For a 90% powered main trial this method indicates that the sample size for a two-armed pilot trial to minimise the overall sample size should be between 40- 260, 20-80, 20-40 and 20-30 dependent on the relative cost of the pilot and main trial per participant for standardised effect sizes (δ) of δ < 0.1, 0.1 ≤ δ < 0.3, 0.3 ≤ δ < 0.7 and δ ≥ 0.7 respectively. For internal pilot trials it is shown that the restricted sample size recalculation procedure raises the average sample size and power of the main trial. Aiming to minimise the overall trial sample size, it was found that the optimal pilot trial sample size rises as the main trial size increases. The work presented aims to help researchers choose sample sizes for pilot trials and to assess the impact selected methods have on the power and required sample size of the subsequent main trial.

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Walid, Rania. "Impact Evaluation in Post-conflict Environments : A Critical Appraisal of Randomised Controlled Trial (RCT)." Thesis, Linnéuniversitetet, Institutionen för samhällsstudier (SS), 2021. http://urn.kb.se/resolve?urn=urn:nbn:se:lnu:diva-104816.

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Impact evaluations in development interventions has been growing in recent years. The increasing demand for evidence-based outcomes has led to a debate of what methodology is best to evaluate the impact of development interventions. Accordingly, Randomised Controlled Trial (RCT) has been labeled as a gold standard for impact evaluations. The RCT method functions in a unique way, as it removes the selection bias and ensure high validity of a study. The aim of this research study is to critically assess the RCT as an alternative approach for impact assessment in relation to post-conflict countries; whether this claim holds in a conflict-affected environment or that the context-specific factors of post-conflict countries challenge the implementation of an RCT. This study implements mixed method approach by using simple descriptive statistics and semi-structured interview to answer the research questions. The findings of this study indicate that context-specific factors of post-conflict environments pose challenges on the implementation of an RCT. As a result, these challenges threaten the quality of the RCT method which lies in reliability, internal validity and external validity. The findings also indicate that feasibility of RCT which lies in ethics, logistics and security, cannot be addressed individually, as the feasibility has a direct impact on the quality of the RCT method.

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Hamad, Faten Fatehi. "Retrieval of sibling studies for clinical randomised controlled trials." Thesis, Aberystwyth University, 2013. http://hdl.handle.net/2160/55bc0889-17f1-4dc6-9e2b-26b998086c2c.

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Aims and objectives. For a particular randomised controlled trial, it is often useful to retrieve associated siblings - qualitative research, process and economic evaluations done alongside the randomised controlled trial (RCT). This thesis examines both the effectiveness and efficiency of search strategies, and the productivity of different databases, in retrieving sibling studies for an RCT. Methods. Five seed studies from different clinical areas were selected. A range of Boolean searches with simple subject term combinations with authors’ names, together with citation and similarity search strategies, were applied, on different databases that had different subject coverage and interests. Specialised search filters were combined with the simple search strategy and tested. The retrieval performances of the simple and sophisticated search strategies on PubMed were tested and compared using one of the seed studies as a case study. Recall, precision and odds estimators were used for all retrieval tests. Non-parametric statistical tests were used to test a set of hypotheses that set out to explore relationships underlying retrieval performance. Results. Neither one particular search strategy nor one database was an overall winner. The simple author-subject search provided a good recall with a readable retrieval size. The recall varied among seed studies and different databases. Search filters provided good recall for retrieving specific types of sibling, especially the qualitative filter. PubMed related articles strategy provided a good performance for some seeds, but not as good overall as the simple author-subject searching. Combining a similarity search with simple author-subject search provided complementary retrieval performance and therefore yields an optimal performance. Citing search did not perform well in terms of retrieving sibling studies. The simple author-subject search shows performance consistency, being the best search strategy among other strategies for all seed studies in terms of recall and precision. WoK and SCOPUS were the best databases for retrieving sibling studies. Conclusions. Simple author-subject search, especially when searching multiple databases, can yield an optimal performance in retrieving sibling studies.

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Begh, Rachna Aziz. "Randomised controlled trials of attentional bias retraining in smokers." Thesis, University of Birmingham, 2014. http://etheses.bham.ac.uk//id/eprint/4949/.

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Smokers attend preferentially to smoking-related cues in the environment, known as attentional bias. Evidence suggests that attentional bias is related to craving and relapse. Attentional retraining (AR) procedures have been used in laboratory studies to modify attentional bias and processes related to drug use, but investigations on the clinical value of AR in addiction are scarce. This thesis reports on two randomised controlled trials investigating the efficacy of AR with modified visual probe tasks in smokers. The first study explored the effects of varying the length of AR on attentional bias, craving, mood and withdrawal in current smokers. No retraining effects were observed after either a short, medium or long block of AR. The second study explored the efficacy of AR on attentional bias and smoking cessation outcomes in treatment-seeking smokers. While AR procedures were feasible to deliver within smoking cessation clinics, the intervention did not significantly reduce attentional bias, craving, withdrawal symptoms or the likelihood of relapse. These results and the literature in general show that there is no clear association between attentional bias and craving and relapse. Current AR procedures are not effective in smokers and should not be used in smoking cessation treatments, as they currently stand.

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Keeley, Thomas James Hier. "Capability as an outcome measure in randomised controlled trials." Thesis, University of Birmingham, 2014. http://etheses.bham.ac.uk//id/eprint/5269/.

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‘The capability approach is a broad, normative framework for the evaluation of well-being’(p.94)[1], which has attracted growing interest in health and health economics research. A broader measure of well-being may more accurately capture the effects of some interventions, than traditional health-related quality of life measures. The ICECAP-A and ICECAP-O are two measures of a person’s well-being, with a theoretical grounding in the capability approach, designed for use in health and social care research. This thesis reports qualitative and quantitative investigations into the validity and responsiveness of the ICECAP measures. A methodological review of existing validation studies was completed. Seventeen semi-structured interviews with health research professionals were carried out and an iterative, constant comparative, thematic analysis was completed to assess the content validity of the ICECAP-A. The construct validity and responsiveness of the measures were assessed using two randomised controlled trials: the BEEP trial (ISRCTN 93634563) and the Past BP trial (ISRCTN 29062286). Qualitative and quantitative results provide positive indications of validity. The qualitative work showed that research professionals viewed the ICECAP-A as a relevant and feasible measure for use in health research. The quantitative results confirmed the majority of a priori hypotheses in the validity analyses, while longitudinal data provided evidence that the measures are responsive to self-reported changes in health status. In conclusion, this thesis reports the first assessment of validity in a randomised controlled trial setting and the first analysis of responsiveness. While further testing of the ICECAP measures is required, results indicate that the measures are appropriate for use in health research.

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Martin, James Thomas. "Advancing knowledge in stepped-wedge cluster randomised controlled trials." Thesis, University of Birmingham, 2018. http://etheses.bham.ac.uk//id/eprint/8034/.

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This thesis aims to extend the existing knowledge and enhance the methodological quality of future stepped-wedge cluster randomised trial (SW-CRTs). A systematic review of published SW-CRTs shows that pre-trial sample sizes calculations display a poor standard of reporting, with little adherence to published guidelines. The methodological rigor is often substandard, with inappropriate methods often used to determine sample size. In SW-CRTs, it is assumed that the correlation between observations is independent of the timing of them. We test the validity of this assumption by outlining a method to estimate the within-period and inter-period correlation. A case study illustrates what these correlations may look like in practice. The impact of varying cluster size in a SW-CRT is then demonstrated by comparing a design with unequal cluster size to a design with equal cluster size. A simulation study provides evidence that the SW-CRT is affected less, on average, than a P-CRT by varying cluster size. However, the potential power in a SW-CRT with unequal cluster sizes is extremely variable. A practical method for estimated power in a SW-CRT with varying cluster size is then illustrated through a Stata function.

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Stobbart, Lynne. "Conducting randomised controlled trials in an acute stroke unit." Thesis, University of Newcastle upon Tyne, 2013. http://hdl.handle.net/10443/1944.

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Stroke is a major cause of death and disability in the UK. Few treatments exist and those that do, such as thrombolysis (‘clot-busting’ treatment) must be given urgently and are not risk-free. Large scale randomised controlled trials are crucial for the development of safe, effective, acute interventions, but progress has been limited, ostensibly due to ethical and regulatory difficulties. Theoretical work in this area has focussed primarily upon the requirement for prospective informed consent, but has also considered potential conflicts of interests inherent in the dual role of clinicianresearchers, and the notion that research and clinical practice are, can be, and should be conducted separately. Empirical evidence on this topic is lacking. By providing such evidence, this study examines claims made in the literature regarding the difficulties encountered or perceived in conducting emergency research. It also explores whether, how, and to what effect, the distinction between research and clinical activity advocated in the bioethical literature is maintained. Methods Ethnographic methods were employed, including participant observation, semistructured interviews, and audio-recording of research consent interactions in an acute stroke unit. Data were analysed drawing upon constant comparative and framework methods. Results and conclusion Whilst providing empirical evidence supporting some of the theoretical and conceptual literature, the data also furnish a detailed account of pragmatic issues encountered and managed daily by healthcare professionals in the acute stroke environment. Whilst attempts were made at the study site to separate, at least in part, clinical and research activity, it was observed that absolute separation of clinical activities is neither attainable, sustainable, nor desirable. Placement of research nurses within the clinical environment may promote transparency and greater understanding of their role, whilst simultaneously demystifying research concepts. Ultimately this may promote closer working relationships, contributing to enhanced recruitment, retention and management of research participants.

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Backhouse, Martin E. "Economic analysis and randomised controlled trials : an investment appraisal approach." Thesis, University of Nottingham, 2006. http://eprints.nottingham.ac.uk/11757/.

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Randomised controlled trials (RCTs) play a fundamental role in the development and marketing activities of pharmaceutical companies. They are the primary means of evaluating the tolerability, safety and efficacy of a drug, and for providing information relevant for pricing and reimbursement decisions and clinical decision-making. RCTs require a substantial investment by pharmaceutical companies and the financial consequences of poorly or sub-optimally designed trials are potentially substantial. Revenue does not materialise unless a licence to market a product is granted and sales may be restricted if a trial fails to provide evidence of sufficient strength or relevance for those involved in product adoption decisions. From a pharmaceutical company's perspective, the value of RCTs can therefore be judged on the contribution they make to the performance of a drug in the market and hence on their contribution to the performance of the firm. Consequently the design choices made in the planning of RCTs are effectively investment appraisal decisions. However, the application of investment appraisal techniques to RCT design has not previously been proposed. The purpose of this thesis is to consider how private sector investment appraisal methods might be applied to RCT design decision-making and to explore aspects of the practicalities of application. A general investment appraisal model is presented and its application to determine profit maximising RCT designs is illustrated. Considering the cost side of the investment appraisal equation, it is shown how decision-makers' requirements for cost-effectiveness evidence derived from trials could have a significant impact on the major determinants of cost (sample size and study duration) depending on their specific preferences for evidence defined over key components of RCT design. Considering the revenue side of the investment appraisal equation, it is shown how discrete choice analysis could be used to incorporate decision-makers' preferences for RCT designs into the planning of studies. Specifically, it is shown how the predicted probabilities derived from the application of this technique could be used within an investment appraisal framework. Directions for future research into the application of investment appraisal to RCT design are proposed.

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Robotham, D. J. "Participant opinions of randomised controlled trials within intellectual disability services." Thesis, University College London (University of London), 2010. http://discovery.ucl.ac.uk/19809/.

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OBJECTIVE: This study examined participants’ opinions and beliefs about Randomised Controlled Trials (RCTs) in an intellectual disability context. BACKGROUND: RCTs in this field require co-operation from various stakeholders, including carers and professionals from a variety of disciplines. However, previous research indicates that local stakeholders may have negative views regarding RCTs in this population, and that it may be difficult for researchers to gain access to participants. This is compounded by the potential problems surrounding communication with a proportion of the service users. METHOD: The present study builds upon an RCT for a behaviour therapy intervention for people with intellectual disability, which was situated within community based services in one county of South East England. Fifty-one individuals were interviewed; 11 paid carers, 7 family carers, 6 adults with mild intellectual disability, and 27 professionals from health and social care services. The interviews elicited opinions, beliefs and decision-making processes relating to stakeholder experiences of the RCT. Data was analysed through coding emergent categories into a framework, which evolved throughout the analysis. RESULTS: The data revealed that opinions about RCTs were shaped by several concerns. The most important of these included the following; continued ability to access interventions, the ethical concerns surrounding randomisation, perceptions of limited financial resources, and problems involving communication and consent. DISCUSSION: RCTs are ubiquitous in clinical research, including psychiatry. However, they present difficulties for researchers and participants in the field of intellectual disability. Good communication with all stakeholders is essential to ensure the successful conduct of an RCT. This study provides information for academics and clinicians who plan to conduct future research and RCTs with people who have intellectual disability. The findings may be used in future to develop appropriate strategies to assist with recruitment for RCTs in intellectual disability, and to increase stakeholders’ acceptance of the procedure.

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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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Hewitt, Catherine Elizabeth. "Selection bias in randomised controlled trials : which patient in which group?" Thesis, University of York, 2006. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.437588.

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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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McNellis, Jennie L. "Meta-analysis of Weight Change in the Placebo Arm of RCT’s for Weight Loss: Methods and Pilot Study." The University of Arizona, 2008. http://hdl.handle.net/10150/624315.

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Class of 2008 Abstract
Objectives: 1) To determine if data on weight change in the placebo arm of RCT's for weight loss were available, and 2) to conduct a pilot meta-analysis to estimate the average weight change in the placebo arm. Methods: Four randomized placebo controlled trials of rimonabant for weight loss were retrieved. A draft data extraction form was developed to record weight loss and demographic data. Potential for bias was assessed on design issues related to withdrawals, blinding, allocation procedure, adherence, and manufacturer influence. Based on available data, a forest plot was constructed and heterogeneity was assessed. The a priori alpha level was 0.05. Results: The placebo groups from all studies were similar. The pooled data indicated that individuals in the placebo arm lost an average of 3.3 kg, p < 0.001. One study had a significantly greater completion rate than the other studies. Participants were prescribed a hypocaloric diet and were instructed to increase physical activity but no data were reported on calories consumed or amount of physical activity. Weight loss of 5% ranged from 15-20% of participants. There was potential for bias relating to reported adherence, allocation concealment process, and manufacturer funding. Conclusions: Participants in the placebo arm of rimonabant trials lost an average of 3.3 kg, which was statistically significant. Little can be learned about weight loss in the placebo arm because no data on calories consumed, amount of exercise, or hunger were reported. Information from other RCT's is needed to provide additional data and to confirm the findings.

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Che, Hamzah Jemaima. "Assessment of glaucoma : using patient-reported outcome measures in randomised controlled trials." Thesis, University of Aberdeen, 2011. http://digitool.abdn.ac.uk:80/webclient/DeliveryManager?pid=186205.

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Background: Glaucoma is a chronic, progressive eye disease and the second cause of blindness in the world. To measure the patients’ perspective in randomised controlled trials (RCTs), patient-reported outcome measures (PROMs) are increasingly being used. However, the use of PROMs in glaucoma trials is low suggesting there may be a reluctance to use PROMs. Objectives: To explore three methodological challenges of using PROMs in RCTs in glaucoma: 1) PROM selection; 2) characterising glaucoma severity; and 3) interpreting PROM scores in terms of minimal important difference (MID). Methods: Vision PROMs used in glaucoma studies were identified and content validated using a systematic review approach and categorised by a new PROM taxonomy. Existing visual field staging systems (VFSSs) based on standard automated perimetry were systematically identified and quality assessed with a new tool developed for this review using a consensus method. The performance of four high quality visual field staging systems were evaluated and referenced against an experienced ophthalmologist in a diagnostic test accuracy study. A pilot study using the social comparison approach was undertaken to test the feasibility of an anchor-based approach in determining the MID of a vision PROM in a glaucoma population. Results: Thirty-three vision PROMs were identified and categorised, according to content into impairment, disability, status and satisfaction measures. Twenty-three VFSSs were identified but evaluation of quality assessment, particularly performance, was affected by poor VFSS reporting. The diagnostic accuracy study demonstrated suboptimal performance of the four highest quality staging systems. The pilot study to determine the MID for a vision PROM found the social comparison method to be a feasible approach in a glaucoma population. Conclusion: This thesis demonstrated how to select a PROM and identified difficulties with characterising glaucoma severity. Future research needs include development of robust methods for characterising glaucoma severity and full scale evaluation of MIDs in PROMs in glaucoma.

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Flynn, Terry Nicholas. "Design and analysis of randomised controlled trials : economic aspects of cluster randomisation." Thesis, University of Bristol, 2002. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.393952.

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Thompson, Douglas David. "Predicted risk of harm versus treatment benefit in large randomised controlled trials." Thesis, University of Edinburgh, 2015. http://hdl.handle.net/1842/15843.

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Most drugs come with unwanted, and perhaps harmful, side-effects. Depending on the size of the treatment benefit such harms may be tolerable. In acute stroke, treatment with aspirin and treatment with alteplase have both proven to be effective in reducing the odds of death or dependency in follow-up. However, in both cases, treated patients are subject to a greater risk of haemorrhage – a serious side-effect which could result in early death or greater dependency. Current treatment licenses are restricted so as to avoid treating those with certain traits or risk factors associated with bleeding. It is plausible however that a weighted combination of all these factors would achieve better discrimination than an informal assessment of each individual risk factor. This has the potential to help target treatment to those most likely to benefit and avoid treating those at greater risk from harm. This thesis will therefore: (i) explore how predictions of harm and benefit are currently made; (ii) seek to make improvements by adopting more rigorous methodological approaches in model development; and (iii) investigate how the predicted risk of harm and treatment benefit could be used to strike an optimal balance. Statistical prediction is not an exact science. Before clinical utility can be established it is essential that the performance of any prediction method be assessed at the point of application. A prediction method must attain certain desirable properties to be of any use, namely: good discrimination – which quantifies how well the prediction method can separate events from non-events; and good calibration – which measures how close the obtained predicted risks match the observed. A comparison of informal predictions made by clinicians and formal predictions made by clinical prediction models is presented using a prospective observational study of stroke patients seen at a single centre hospital in Edinburgh. These results suggest that both prediction methods achieve similar discrimination. A stratified framework based on predicted risks obtained from clinical prediction models is considered using data from large randomised trials. First, with three of the largest aspirin trials it is shown that there is no evidence to suggest that the benefit of aspirin on reducing six month death or dependency varies with the predicted risk of benefit or with the predicted risk of harm. Second, using data from the third International Stroke Trial (IST3) a similar question is posed of the effect of alteplase and the predicted risk of symptomatic intracranial haemorrhage. It was found that this relationship corresponded strongly with the relationship associated with stratifying patients according to their predicted risk of death or dependency in the absence of treatment: those at the highest predicted risk from either event stand to experience the largest absolute benefit from alteplase with no indication of harm amongst those at lower predicted risk. It is concluded that prediction models for harmful side-effects based on simple clinical variables measured at baseline in randomised trials appear to offer little use in targeting treatments. Better separation between harmful events like bleeding and overall poor outcomes is required. This may be possible through the identification of novel (bio)markers unique to haemorrhage post treatment.

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Tohotoa, Jennifer Lynn. "The development, implementation and evaluation of a father inclusive perinatal support intervention to increase breastfeeding duration : a randomised controlled trial." Thesis, Curtin University, 2012. http://hdl.handle.net/20.500.11937/1542.

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Breastfeeding is the biological norm for infant feeding and the most efficient and cost-effective method of giving the required nutrition to infants. The World Health Organization, the American Academy of Paediatrics and the National Health and Medical Research Council recommend exclusive breastfeeding for six months and the continuation of complementary foods for up to two years. Although most developed countries maintain high initiation rates, the duration rates fail to meet these recommendations. The promotion of breast milk substitutes, changing societal values, urbanization, and the erosion of traditional support systems pose threats to breastfeeding. In Australia the breastfeeding initiation rates are between 85%-95% but fall to 20%-45% by six months. There is some evidence that fathers, the primary support to their partners, influence the initiation and maintenance of breastfeeding by their partners. There has been little research in this area, however, with little known about the nature of a father’s support required by the mother and few interventions have specifically targeted fathers.The present thesis describes the development, implementation and evaluation of a father inclusive perinatal support intervention at six weeks postnatal. The project was conducted over three years as a randomised controlled trial (RCT) across eight public maternity hospitals in Perth, Western Australia.

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Acharya, Dev Raj. "Measuring the effectiveness of teaching sex education in Nepalese secondary schools : an outcome from a Randomised Controlled Trial (RCT)." Thesis, Aberystwyth University, 2014. http://hdl.handle.net/2160/7aed061b-668e-4789-879e-b30ba401b6c6.

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This study aimed to identify the effectiveness of delivering sex education in secondary schools in Hetauda (Nepal) by exploring the sexual health knowledge and understanding of young people, and parents' and teachers' views on sex education, in order to place the findings in the wider social, cultural and educational context of modern Nepal. The research selected four secondary schools pupils of diverse sociobackground characteristics in Hetauda municipality, central Nepal. This study was conducted by undertaking an intervention in control (2 schools) and experiment (2 schools) groups, and as such constituted the quantitative method. Semi-structured Key Informant Interviews (KIIs) with 14 key stakeholders (6 parents and 8 teachers) and 8 Focus Group Discussions (FGDs) with 78 pupils constituted the qualitative method. Quantitative and qualitative data were analysed separately by utilising statistical software (SPSS, 19) and thematic analysis, respectively. Outcomes were compared, combined and discussed. This study relies on a multiple theory platform (cognitive constructivism, social constructivism and social cognitive theory) to evaluate the effectiveness of sex education delivery in schools. The conventional teacher in the control school delivered the sex education programme in a didactic approach. The result had less impact on pupils' sexual health knowledge and understanding. In contrast, the health facilitator-led experimental schools used a participatory approach which showed a reasonable knowledge increment around sexual health. However, the pupils were still confused and uncertain about how to obtain sexual health information from relatives of a similar age and their family members. Many parents lacked the knowledge, iv confidence and skills to offer meaningful support to their children. This study noted four main important influential sexual health attitudes and behaviours of the pupils: ambiguous social roles leading to confusion; increased sexual awareness and curiosity about sex; significant gaps in knowledge and behaviour; and limited parental input. This study suggested several possible approaches that could be developed to improve sex education in Nepal. Young people need more information on the risk of Sexually Transmitted Infections (STIs) and unwanted pregnancies. This could encourage them to gain more sexual health knowledge which in turn could lead to increased engagement in safer sexual health practices. In particular, more young girls should be provided with access to sexual health knowledge and services in order to achieve real improvements in pupils' sexual health. Furthermore, attention needs to be given to rigorous research and appropriate sex education interventions in school. Integrating sex and relationship education, both in formal and informal education, could help to improve young people's sexual and reproductive health status.

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Nor, Aripin Khairun Nain Bin. "Drug toxicity in children : paediatric randomised controlled drug trials and global child health." Thesis, University of Nottingham, 2010. http://eprints.nottingham.ac.uk/11506/.

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Concern with potential toxicity due to the widespread use of unlicensed and off label drugs in children has led to regulatory changes aimed to strengthen the evidence base for paediatric drugs. This thesis examines paediatric randomised controlled trials (RCTs), the highest level of evidence, and assesses them in relation to global child health. A systematic review was performed using validated methods to search three major databases for paediatric RCTs published in 2007. More than 600 RCTs were identified involving more than 100,000 children. The RCTs appear to study the appropriate clinical areas however few studies involved neonates. The RCTs also seem to be of good methodological quality with a mean Jadad score of 3.22. The reporting of RCTs that involve both adults and children needs to be improved to add to the evidence base of paediatric medicines. More attention is also needed on the reporting of safety information from the RCTs to provide useful toxicity data. Although severe and moderate ADRs were seen in 25% of the RCTs, few RCTs (12%) established safety monitoring committees (SMCs). SMCs are vital to ensure patients in paediatric RCTs are protected from toxicity. The burden of childhood disease is heaviest in low and middle income countries (LMIC). A minority of the RCTs were performed in LMIC, although they are increasingly globalised. RCTs conducted in LMIC appear to have lower methodological quality, and reported less well on ethical approval and adverse events. In conclusion high quality, ethical paediatric RCTs should add to the evidence base for paediatric medicines. However they should correspond with the health needs of children on a global basis.

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Becque, Taeko Frieda. "Full probability modelling and regaining power in randomised controlled trials with non-compliance." Thesis, University of Cambridge, 2007. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.612766.

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Woodford, Joanne. "Development and feasibility randomised controlled trial of guided Cognitive Behavioural Therapy (CBT) self-help for informal carers of stroke survivors." Thesis, University of Exeter, 2014. http://hdl.handle.net/10871/17401.

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Background: One-in-three carers of stroke survivors experience depression with no psychological treatments tailored to meet their needs, such as barriers to attending traditional face-to-face psychological services. A cognitive behavioural therapy (CBT) self-help approach may represent an effective, acceptable solution. Methods: Informed by the MRC framework (2008) for complex interventions, six studies informed development, feasibility and piloting of a CBT self-help intervention for depressed carers of stroke survivors: Study One: Systematic review and meta-analysis of psychological interventions targeting depression and anxiety in carers of people with chronic health conditions; Study Two: Interviews to understand difficulties experienced by depressed and anxious carers; Study Three: Interviews to understand positive coping strategies used by non-depressed and non-anxious carers; Study Four: Drawing on results of Studies One to Three, iterative modelling to develop the CBT self-help intervention; Study Five: Feasibility randomised controlled trial to examine methodological and procedural uncertainties for a Phase III definitive trial; Study Six: Updated systematic review and meta-analysis. Results: Study One: 16 studies identified for inclusion yielding small and medium effect sizes for depression and anxiety respectively, with trends for individually delivered treatments over shorter session durations to be more effective for depression. Six additional studies were included in Study Six, replicating Study One results; Study Two: Depressed and anxious carers experience difficulties adapting to the caring role, managing uncertainty, lack of support and social isolation; Study Three: Non-depressed and non-anxious carers utilise problem-focused coping strategies to gain balance and adapt to caring role, use assertiveness, seek social support and positive reinterpretation; Study Four: Developed a theory-driven CBT self-help intervention; Study Five: Recruited 20 informal carers in 10-months, representing 0.08% of invited carers randomised with high attrition in the intervention arm. Lack of GP recognition, gatekeeping and barriers to accessing psychological support identified as reasons for poor recruitment. Conclusions: A greater appreciation is required concerning barriers experienced by informal carers of stroke survivors to accessing support for depression and type of acceptable psychological support.

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Walpole, Beverly. "Motivational Interviewing to Enhance Self-Efficacy and Promote Weight-loss in Overweight and Obese Adolescents: A Randomized Controlled Trial." Thesis, A portion of this thesis was published: Beverly Walpole, Elizabeth Dettmer, Barbara A. Morrongiello, Brian W. McCrindle, and Jill Hamilton. "Motivational Interviewing to Enhance Self-Efficacy and Promote Weight Loss in Overweight and Obese Adolescents: A Randomized Controlled Trial." in J. Pediatr. Psychol. first published online May 13, 2013 doi:10.1093/jpepsy/jst023 (10 pages), 2013. http://hdl.handle.net/10214/7261.

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Childhood obesity is associated with serious physiological and psychological consequences including type 2 diabetes, higher rates of depression and low self-esteem. With the population of overweight and obese youth increasing, appropriate interventions are needed that speak to the issue of motivation to maintain adherence to healthy behavior changes. The current investigation was a randomized controlled trial examining the efficacy of Motivational Interviewing (MI) as an intervention for promoting self-efficacy and weight-loss in a sample of overweight and obese youth. Participants (N = 42) ages 10-18, were randomly assigned to a control (social skills training) or treatment (MI) group. Both groups received individual therapy (~30 minutes/month) in addition to usual care of diet/exercise counseling. Pre and post (at 6 months follow-up) variables included measures of self-efficacy and anthropometrics. Results indicated that while significant between-group differences were not found, individuals in the MI group attended more sessions. Overall, participants in both groups showed significant increases in self-efficacy and a trend of decreased BMI z-scores. Though health benefits from participation in individual therapy may have been accrued, specific benefits attributable to MI were limited. Findings from the current study suggest that more than one type of counseling intervention (i.e., MI and social skills training) may be beneficial when providing integrative treatment for obese youth.
Canadian Institutes of Health and Research (CIHR)

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Hutchison, Catherine B. "A randomised controlled trial of an audiovisual patient information intervention in cancer clinical trials." Thesis, University of Stirling, 2008. http://hdl.handle.net/1893/442.

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Introduction and background Recruitment to cancer clinical trials needs to be improved, as does patient understanding about clinical trials, to enable patients to make an informed choice about whether or not to take part. The main reason that clinically eligible patients do not take part in clinical trials is because they refuse; poor understanding of the research has been associated with patient refusal. Audiovisual patient information (AVPI) has been shown to improve knowledge/understanding in various areas of practice but there is limited information about its effect in the cancer clinical trial setting, particularly in relation to recruitment rates. Understanding the research is necessary for informed consent, and it was hypothesised that if patient understanding about clinical trials was increased with AVPI, then this could result in a reduction in the number of patients refusing clinical trials, and therefore provide an ethical approach to improving recruitment. This study aimed to test the impact of an audiovisual patient information intervention on recruitment to randomised cancer clinical trials (refusal rates), patient understanding of the information given, and levels of anxiety. Reasons for patients’ decisions about trial participation were also assessed. Method An AVPI intervention was developed that aimed to address the common misconceptions associated with randomisation and clinical equipoise, as well as improve patient understanding generally of randomised cancer trials, and of other core clinical trial informational requirements, such as voluntariness. Patients were randomised to receive either AVPI in addition to the standard trial-specific written information, or the written information alone. A new questionnaire was developed to assess patient understanding (also referred to as knowledge) in the randomised trial setting and, following testing with patients and research nurses, this was shown to be reliable and valid. Patients completed self-report questionnaires to assess their understanding (new knowledge questionnaire) and anxiety (Spielberger State-Trait Anxiety Inventory), at baseline and after they had made their decision about clinical trial entry, when their perceptions of the intervention, as well as factors contributing to their decision were also determined (this tool incorporated Jenkins and Fallowfield’s (2005) questionnaire which assessed reasons for accepting and declining randomised cancer trials). Results A total of 173 patients with breast cancer (65%), colorectal cancer (32%) and lung cancer (3%) were entered into the main study. The median age was 60 (range 37-92 years). There was no difference in clinical trial recruitment rates between the two groups: 72.1% in the AVPI group and 75.9% in the standard information group. The estimated odds ratio for refusal (intervention/no intervention) was 1.19 (95% ci 0.55-2.58, p=0.661). Knowledge scores increased more in the intervention group compared to the standard group (U= 2029, p=0.0072). The change in anxiety score between the arms was also statistically significant (p=0.011) with anxiety improving in the intervention arm more than in the no-intervention arm. The estimated difference in the median anxiety change score between the groups is –4.6 (95% ci –7.0 to –2.0). Clinical trial entry was not influenced by tumour type, stage of cancer, age, educational qualifications or previous research experience, however, there was a modest association with deprivation status (p=0.046) where more affluent patients were the least likely to consent to a trial. Educational qualifications and stage of cancer were independently associated with knowledge: patients who were better educated had higher levels of knowledge about randomised trials, and patients who had limited stage of cancer had higher baseline knowledge than patients with advanced cancer. Acceptability of the intervention was high with 93% of those who watched it finding it useful, and 42% stating that it made them want to take part in the clinical trial. Personal benefit and altruism were key motivating factors for clinical trial participation, with reasons for refusal being less clear. Discussion and conclusions Although the potential for AVPI to increase clinical trial recruitment rates was highlighted in the literature, in this study, AVPI was not shown to have any effect on refusal rates to randomised cancer trials. However, by improving patient understanding prior to decision making, AVPI was shown to be a useful addition to the consent process for randomised cancer trials. AVPI addresses the fundamental ethical challenges of informed consent by improving patient understanding, and supports the ethical framework integral to Faden and Beauchamp’s (1986) theory of informed consent. The new knowledge questionnaire was shown to be a sensitive and effective instrument for measuring understanding of randomised clinical trials in the cancer setting, although it would benefit from further testing. The AVPI appears to reduce anxiety at the decision making time point and has been shown to be an acceptable medium for patients. This study confirms existing findings from studies assessing factors affecting decision making, with personal benefit and altruism being key motivating factors, and reasons for refusal being less clear. The need for further qualitative work in this area is highlighted to gain a deeper understanding of what is important to patients, in terms of why they refuse clinical trial participation. Implications for practice and further research Several implications for practice have been identified, including using AVPI as part of the standard information package for patients considering randomised cancer trials, and focussing on patient and staff education in this area. The knowledge questionnaire could be introduced to routine practice as a tool to determine patient understanding prior to decision making, allowing clinicians the opportunity to correct any misconceptions prior to consent. Further research focussing on AVPI specific to individual trials would be helpful, to determine if a more customised approach would be of benefit in terms of clinical trial recruitment. The importance of studying other aspects of the consent process such as the interaction between the clinician and the patient, in addition to more detailed exploration of the factors affecting patients’ decisions were highlighted.

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Lattimer, Valerie Ann. "A randomised controlled triage of nurse telephone trials in out of hours primary care." Thesis, University of Southampton, 1998. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.262872.

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Fisher, Helen. "'Held together with human glue' : understanding participation in non-therapeutic paediatric randomised controlled trials." Thesis, King's College London (University of London), 2013. https://kclpure.kcl.ac.uk/portal/en/theses/held-together-with-human-glue(51df0135-8f6f-4120-908e-1a742a0d49ec).html.

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Background: Successful recruitment, adherence and retention are essential for randomised controlled trials (RCTs) to produce robust and meaningful findings. Studies exploring trial participation predominantly focus on the characteristics and views of participants and staff and often reveal contradictory findings. To date little is known about adherence and retention to RCTs. Aim: To further understanding of recruitment, adherence and retention to non-therapeutic paediatric RCTs, with particular emphasis on the role of social context. Methods: An ethnographic approach was taken using two RCTs as case studies. Participant observation (130 hours) was conducted on a clinical trials unit. Twenty-six trial staff and 56 parents who considered or had participated in the RCTs were interviewed and relevant documents collected. Data were analysed using the principles of thematic analysis. Results: Drawing on Bourdieu’s (1977; 1990) ’Theory of Practice’ and Titmuss’ (1970) ’The Gift Relationship’ it was evident that recruitment, adherence and retention were influenced by the values and beliefs of parents and staff and by the wider context in which the RCTs were conducted. Recruitment and adherence were influenced by the degree of concordance between the philosophies of the trials’ fields and those of the wider fields of parenting, infant feeding, medical research and allergy healthcare. Perceptions of personal and societal benefit were relevant to participation but, reflecting the philosophy of the parenting field, families often prioritised personal benefit.
Conclusion: Open and regular personal communication between parents and staff was particularly important for retention. Trials that maximise personal contact may have more success retaining participants. Comparing recruitment, adherence and retention between the two RCTs illuminated the relevance of the wider context for participation, particularly recruitment and adherence. Conducting a thorough assessment of the context in which an RCT will take place will allow potential barriers to participation to be identified before trial commencement.

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Bryan, Gemma. "Randomised controlled trials of interventions to prevent oral mucositis in patients undergoingtreatment for cancer." Thesis, University of Manchester, 2011. https://www.research.manchester.ac.uk/portal/en/theses/randomised-controlled-trials-of-interventions-to-prevent-oral-mucositis-in-patients-undergoingtreatment-for-cancer(17316f4c-8e13-4d84-a192-c49833a02756).html.

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Introduction: Oral mucositis is an inflammatory and frequently ulcerative side effect of cancer therapy, which has been identified by patients as the most debilitating side effect of their treatment. Mucositis is a dose limiting toxicity which exerts a substantial clinical and economic impact and negatively affects patient quality of life. The patient experience of mucositis is under-reported in the literature. To date, no interventions have been identified that have proven successful in the prevention of mucositis for patients receiving all types of therapy. Vitamin E has shown conflicting results in clinical trials. This thesis combines appraisal of the literature and empirical research,and uses lessons learned from previous studies together with the results of a feasibility study to identify a best practice model for future trials. Methods: The Cochrane risk of bias (ROB) instrument was used to assess the ROB in the studies included in the Cochrane prevention review. A sensitivity analysis was conducted after studies assessed at unclear or high risk of overall bias were excluded. A systematic review of assessment instruments was conducted which identified 50 instruments. Consideration of the appropriateness of these instruments for the use in a clinical trial for the prevention of mucositis was based on the practicality, comparability, and reproducibility, and the impact of these instruments on patients. Three of these instruments were chosen for use in a clinical trial of adults undergoing stem cell transplant. Finally, a feasibility study was designed, developed and conducted which investigated vitamin E for the prevention of mucositis in patients undergoing conditioning for bone marrow transplantation. Through lessons learned from previous studies, consultations with medical professional, the MHRA, ethics committee and suppliers, a protocol was developed for a double blind RCT. The process of gaining MHRA and ethical approval, and the repackaging of intervention and placebo products to meet MA-IMP requirements are described. Results: 130 articles were assessed for risk of bias. Only ten studies were assessed as being at low overall risk of bias. Blinding of outcome assessors and adequate allocation concealment were identified to be important considerations in the planning of future studies. Although only nine patients were recruited into the feasibility study, a number of issues affecting the design and conduct of future trials were identified. Recruitment in particular was identified to be problematic. Strategies for overcoming this problem in future trials were discussed. The methods of blinding and allocation concealment employed were found to be feasible for use in future trials. Expected adverse events patients undergoing stem cell transplantation were also reported. Conclusion: Further studies are required to investigate interventions for the prevention of mucositis. It is of upmost importance that these trials are rigorous in both their methodology and subsequent reporting in order to elicit the maximum benefit for patients taking part in clinical trials, and future patients undergoing therapy for cancer.

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Boulind, Caroline Elizabeth. "Tests for the success of blinding in randomised controlled trials of non-pharmacological interventions." Thesis, University of Bristol, 2017. https://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.738309.

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Neyroud, Peter William. "Learning to field test in policing : using an analysis of completed randomised controlled trials involving the police to develop a grounded theory on the factors contributing to high levels of treatment integrity in Police Field Experiments." Thesis, University of Cambridge, 2017. https://www.repository.cam.ac.uk/handle/1810/268177.

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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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Snowdon, Claire. "Collaboration, participation and non-participation : decisions about involvement in randomised controlled trials for clinicians and parents in two neonatal trials." Thesis, London School of Hygiene and Tropical Medicine (University of London), 2005. http://researchonline.lshtm.ac.uk/682340/.

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Background: The ethical basis of randomised controlled trials is equipoise, whether at the collective or individual level. Neonatal intensive care trials are therefore conducted in a context of clinical uncertainty as well as stress and trauma. The theoretical literature suggests that tensions exist in the trials situation between the aims of care and research. Objectives: To improve understanding of decisions that clinicians and parents make about neonatal trial collaboration, participation and non-participation. Methods: Semi-structured interviews were conducted with 30 neonatologists and 63 parents from 5 UK hospitals who were offered enrolment in the INNOVO and/or CANDA trials. Qualitative analysis was aided by ATLAS-ti. Results: The neonatologists' interviews suggested an intermediate level of equipoise. A therapeutic orientation operated for the INNOVO Trial but not for the CANDA Trial. Neonatologists often did not connect trial participation and trial-related postmortem pathology studies. Most parents made very rapid decisions about trial participation. Perception of risk was independent of the trial under consideration but associated with a slower decision-making process. The 'therapeutic misconception' was present for parents in both trials. Many supported contributing to research. For some of the bereaved parents, this extended to contribution to trial-related pathology studies. Parents who declined the CANDA Trial saw risks in the trial situation. Conclusions: Decisions were complex and multi-tiered. The boundaries between care and research were often unclear for neonatologists and parents. Clarification of the nature of decisions at the heart of clinical trials is needed, so that those associated with research might be willing collaborators and participants, fully cognisant of the activity in which they are engage

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Strange, Vicki. "An investigation into the use of randomised controlled trials to evaluate social interventions : a case study of a randomised controlled trial of peer led sex education." Thesis, University College London (University of London), 2006. http://discovery.ucl.ac.uk/10020508/.

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White, Sarah Jane. "Examining alternative methodologies for the analysis of multi-site randomised controlled trials of complex interventions." Thesis, St George's, University of London, 2012. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.546782.

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Loveridge, Camilla. "Guided self-help interventions for Posttraumatic Stress Disorder : a meta-analysis of randomised controlled trials." Thesis, University of East Anglia, 2016. https://ueaeprints.uea.ac.uk/66545/.

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The current evidence base for the treatment of Posttraumatic Stress Disorder (PTSD) is based upon trauma-focused psychological therapy delivered on an individual, face-to-face basis with a therapist. Many barriers to accessing treatment exist, and if untreated, chronic PTSD can result in significant personal, occupational, social, financial, and health problems, reducing years and quality of life. In 2005, The National Institute for Health and Care Excellence recommended research into newly developed guided self-help (GSH) materials based on trauma-focused psychological interventions. Unlike other common mental health disorders, currently, there is no meta-analytical evidence available to support the implementation of GSH as a low intensity psychological intervention for PTSD. A metaanalysis of eight randomised controlled-trials, was conducted to review the effectiveness of trauma-focused GSH (TF-GSH) for adults with PTSD. These studies compared TF-GSH against active or passive control comparators, and seven of these studies delivered Internetbased interventions. Results show that at postassessment a large treatment effect is associated with TF-GSH in reducing symptoms of PTSD. A moderate effect size was found in favour of TF-GSH in reducing co-morbid symptoms of depression. The rate of dropouts from TF-GSH was comparable to current evidence-based treatments for PTSD. Sensitivity analyses revealed that the magnitude of effect remained when studies judged as at high risk of bias were removed. However, there was statistically significant and clinical heterogeneity present amongst studies, which could not be addressed with additional analysis due to the small number of studies included within the review. The quality of evidence was evaluated, as low and further research is required to increase confidence in estimating the treatment effect of TF-GSH for PTSD.

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Zhang, Dalu. "The conduct of randomised controlled trials in China : quality of trial reports and stakeholders’ views." Thesis, University of Birmingham, 2010. http://etheses.bham.ac.uk//id/eprint/885/.

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China is an emerging force in undertaking randomised clinical trials. The quality of trials from China may affect not only its own substantial population but also potentially contribute to health policy throughout the world. However, little is known about the quality of clinical trials conducted there. In this thesis, I will evaluate the quality of published Chinese randomised controlled trials (RCTs) by comparing them with Indian RCTs as well as a set of ‘gold standard’ trials reported in leading European and North American journals. I will also describe and contrast the quality and biases within Chinese RCTs. I then explore the reasons for these differences from the point of view of the major RCT stakeholders: Chinese clinicians and patients. The potential influences from Chinese traditional culture is also evaluated. Chinese medical journal editors need to undertake more training on the reporting of RCTs; all medical societies should take more concern about doctors’ research work; the Chinese public media should help the general population to understand more about RCT principles.

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Agrasada, Grace V. "Postnatal Peer Counseling on Exclusive Breastfeeding of Low-birthweight Filipino Infants : Results of a Randomized Controlled Trial." Doctoral thesis, Uppsala : Acta Universitatis Upsaliensis : Univ.-bibl. [distributör], 2005. http://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-6198.

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Dissertations / Theses on the topic 'Randomised controlled trials (RCTs)'

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