Point-of-care clinical trials are randomized clinical trials designed to maximize pragmatic design features. The goal is to integrate research into standard care such that the burden of research is minimized for patient and physician, including recruitment, randomization and study visits. When possible, these studies employ Bayesian adaptive methods and data collection through the medical record. Due to the passive and adaptive nature of these trials, a number of unique challenges may arise over the course of a study. In this dissertation, adaptive methodology for Bayesian time-to-event clinical trials is developed and evaluated for studies with limited censoring. Use of a normal approximation to the study parameter likelihood is proposed for trials in which the likelihood is not normally distributed and assessed with respect to frequentist type I and II errors. A previously developed method for choosing a normal prior distribution for analysis is applied with modifications to allow for adaptive randomization. This method of prior selection in conjunction with the normal parameter likelihood is used to estimate future data for the purpose of prediction of study success. A previously published method for future event estimation is modified to allow for adaptive randomization and inclusion of prior information. Accuracy of this method is evaluated against final study numbers under a range of study designs and parameter likelihood assumptions. With these future estimates, we predict study conclusions by calculating predicted probabilities of study outcome and compare them to actual study conclusions. Reliability of this method is evaluated considering prior distribution choice, study design, and use of an incorrect likelihood for analysis. The normal approximation to non-normally distributed data performs well here and is reliable when the underlying likelihood is known. The choice of analytic prior distribution agrees with previously published results when equal allocation is forced, but changes depending on the severity of adaptive allocation. Performance of event estimation and prediction vary, but can provide reliable estimates after only 25 subjects have been observed. Analysis and prediction can reliably be carried out in point-of-care studies when care is taken to ensure assumptions are reasonable.

Women are thought to be under-represented as clinical trial participants and as clinical trialists in heart failure. We reviewed randomized controlled trials of heart failure published in high impact medical journals and examined the representation of women as both participants and authors. Furthermore, we explored clinical trial characteristics independently associated with women as clinical trial participants and as lead authors. Our analysis demonstrated that women are under-represented as both clinical trial participants and leaders, with no change in temporal trends over time. Addressing clinical trial characteristics associated with under-representation and developing strategies to overcome barriers may be a strategic way to improve the representation of women in heart failure research. / Thesis / Master of Science (MSc)

No description available.

No

Thesis (MCur)--Stellenbosch University, 2012. / ENGLISH ABSTRACT: Background Informed Consent (IC) has been proposed as the optimal method for ensuring the ethical entry of patients into clinical trials. IC is a vital part of the research process and as such entails more than obtaining a signature on a form. The IC must be given freely, without coercion, and must be based on a clear understanding of what participation involves. Aim The overall aim of this study was to attain an understanding of participants' knowledge regarding informed consent when participating in a research project. Methods The study was conducted at two public hospitals in a city in the Eastern Cape Province of South Africa. The quantitative study used descriptive survey design. A self administered questionnaire was used as a tool for data collection. Results The sample size consisted of 170 women with an average of 25.9 years. The majority had completed secondary level education. More than half of the participants did not have knowledge of the purpose of the original study. The majority of participants did not have knowledge of their responsibilities. Forty-two percent gave uninformative responses and 26% indicated they did not know their responsibilities. None of the participants understood the concept of randomization. The majority (85.9%) of participants indicated that information provided on the IC forms was sufficient for them to decide to participate. Conclusion Despite extensive efforts to ensure that participants understood their participation in the original studies, this study found poor recall of vital information for IC. A signed informed consent does not guarantee that participants understand information given. Recommendations The existing methods of communicating and obtaining of an informed consent seem to be insufficient for participants to make an informed decision. A new approach with more interactive features such as combination of audio-visual techniques might increase the possibilities of the understanding. / AFRIKAANSE OPSOMMING: Agtergrond Ingeligte toestemming (IT) is voorgestel as die optimale metode om die etiese toelating van die pasiënte vir kliniese toetse te verseker. IT is 'n belangrike deel van die navorsingsproses en as sodanig behels dit meer as die verkryging van 'n handtekening op 'n vorm. Die IT moet vrylik gegee word, sonder dwang en moet gebaseer wees op 'n duidelike begrip van wat die deelname behels. Doel Die algemene doel van hierdie studie is om 'n begrip van die deelnemers se kennis met betrekking tot ingeligte toestemming te bepaal, wanneer hulle deelneem aan 'n navorsingsprojek. Metodes Die studie is uitgevoer by twee openbare hospitale in ’n stad in die Oos-Kaap in Suid-Afrika. Die navorsingsontwerp is beskrywend van aard en ’n kwantitatiewe benadering is toegepas. ‘n Self-geadministreerde vraelys is as 'n instrument gebruik om data in te samel. Resultate Die steekproefgrootte het bestaan uit 170 vroue met 'n gemiddelde ouderdom van 25.9 jaar. Die meerderheid van die vroue het opleiding tot op sekondêre vlak. Meer as die helfte van die deelnemers het geen kennis van die doel van die oorspronklike studie gehad nie. Die meerderheid van die deelnemers het ook nie kennis van hul verantwoordelikhede gehad nie. Twee-en-veertig persent het nie toepaslike antwoorde gegee nie en 26% het aangedui dat hulle nie weet wat hul verantwoordelikhede in die studie is nie. Nie een van die deelnemers het die konsep van verewekansiging verstaan nie. Die meerderheid (85.9%) van die deelnemers het aangedui dat die inligting wat deur die IT verskaf word voldoende was om te besluit of hulle aan die studie wou deelneem. Gevolgtrekking Ten spyte van uitgebreide pogings om te verseker dat deelnemers hulle deelname verstaan het in die oorspronklike toetsing, het hierdie studie die swak herroeping van belangrike inligting aangaande IT bewys. ‘n Ondertekende ingeligte toestemming gee geen waarborg dat die deelnemers die inligting waarvoor toestemming geteken is, verstaan nie. Aanbevelings Die bestaande metodes van die kommunikasie en verkryging van ingeligte toestemming blyk onvoldoende te wees om deelnemers ingeligte besluite te laat neem. ‘n Nuwe benadering met meer interaktiewe eienskappe soos ’n kombinasie van oudio-visuele tegnieke mag die moontlikhede om te verstaan, meer duidelik maak.

The overall aim of this thesis was to study participants' understanding of clinical cancer trials, and their motivation for participation. Of particular interest was the question of whether the patients hoped for a cure resulting from the trial. The thesis was based on four studies and used three methods: interviews, a questionnaire, and empirical bioethics. The results of Study I indicated that the participants in phase 1 trials understood most of the information provided, but were unaware of both the very small potential for treatment benefit, and the risk of harm. Patients in phase 3 trials had a good understanding of the trial, except regarding side effects and their right to withdraw. Some found it hard to ask questions and felt they needed more information (Study III). The participants in phase 1 trials were strongly motivated by the generally unrealistic hope for therapeutic benefit (Study I). When the chances of a cure are minuscule, as for participants with end-stage cancer in phase 1 trials, hope can play an important, positive role and offer meaning to one’s remaining life. However, hope for an unrealistic outcome could also deprive patients of an opportunity to spend their remaining lives, as they would otherwise choose (Study II). The participants in phase 3 trials indicated that their motivation for participation was multifaceted; the most common motivations included hope of therapeutic benefit, altruism, access to extra clinical examinations or better care, and a wish to repay society for the help they had received (Study III). After stratifying and analysing the motivation data by gender, age, education and previous experience of trial participation, males and those aged ≥65 years were significantly more motivated to participate out of a desire to reciprocate the help they had received, either because of a sense of duty or because their families or friends considered that they should attend (Study IV). In conclusion, the informed consent process seems to work relatively well, with good results within most subgroups. However, patients with end-stage cancer who are participating in phase 1 trials are a vulnerable group as they have very little potential for treatment benefit coupled with a tangible risk of harm.

published_or_final_version / Community Medicine / Master / Master of Public Health

There is evidence that infaunal bivalves in New Zealand are not as abundant as they once were with overfishing and habitat modification contributing to the decline in density and health of cockles. The population biology and abundance of the bivalve Austrovenus stutchburyi (tuangi) in eight beds in four estuaries was assessed both seasonally (13 seasons) and annually (7 years) as little is known about the cockle beds in the Canterbury region of New Zealand. As with populations of similar species worldwide, there were site specific differences in population structure (density and size ranges) with the highest densities at Takamatua (>1500/m²), and the lowest at Port Levy (<350/m²). Gonad indices varied between male and female cockles. Male reproductive cycles were similar at all sites with male cockles being reproductively active year round, while females were more active in spring and summer. Temporal and spatial site specific differences occurred in cockle condition with high salinity sites having higher condition indices (CI) than low salinity sites. There were spatial and temporal variations in salinity (3-35ppt), sediment structure (fine sand through to predominantly silt), water temperature (6-20°C), nutrient supply (total volatile solids (TVS) 0.002- 0.15mg/L) and contaminant levels. Metal pollution indices (MPI) ranged between 3 and 11. Three cockle transplant trials were undertaken both within and between estuarine systems. Caged cockles survived well, and cage design needed to allow vertical movement of the bivalves within the substrate to reduce mortality. At the end of the 12 month trial, approximately 45% of the cockles remained in the plots. The condition of transplanted cockles was similar to naturally occurring cockles. Recommendations are made to optimise the success of cockle transplants. Large scale, un-caged placement of 25-30mm length cockles in the mid-low tide region of areas with stable, but not necessarily uncontaminated substrate, moderate salinity and temperature and with a reliable nutrient supply is recommended. The results from the thesis research can be applied to other infaunal bivalves in New Zealand allowing more successful restoration processes leading to increased species diversity and ecosystem functioning.

Based on the acreage, broccoli is the third largest vegetable crop in Yuma County, after head lettuce and romaine. It generates over 36 million dollars to Yuma's economy. Efforts are continuously made by growers, seed industry and the University of Arizona outreach program to produce better crops that respond to consumer’s choice. Selection of newly adapted varieties is made based on agronomic performance as well as commercial value. Stand uniformity disease resistance, vigor, head shape and head size are among characteristics that are evaluated. The objective of this demonstration trial is to evaluate the performance of newly developed varieties grown under standard cultural practices and to provide unbiased observations to growers and the seed industry. Fourteen varieties were tested on growers' fields in Yuma County. No incidence of disease was observed among varieties tested and the overall evaluation rating was greater than 4 indicating that most of varieties tested will grow well under similar growing conditions and planting date. Significant head diameter and plant height was observed among varieties evaluated.

Romaine lettuce plays an important role in Yuma’s economy. An estimated 10,000 acres are cropped to large number of varieties each year with planting season that spreads from September to March. The demonstration site was selected to compare new and existing varieties of romaine lettuce on growers’ fields using standard farming practices. Selected growth parameters were evaluated throughout the growing season. Results indicate that varieties tested at Barkley Farms in Yuma are expected to do well if grown under similar growing conditions and planting time. Varieties tested during this planting slot did not experience any incidence of diseases. There was no significant head size and head weight difference among varieties evaluated. Number of heads per bed and number of heads left after harvest were significantly different among varieties tested.