Search

Discusses a strategy for randomised clinical trials in rare cancers. Need for randomised trials to establish that treatments are effective; Problems of small trials; Designing a new trial; Prior and posterior distribution.

Background: Approximately 20% of hepatocellular carcinoma (HCC) patients diagnosed in the early stages may benefit from potentially curative ablative therapies such as surgical resection, transplantation or radiofrequency ablation. For patients not eligible for such options, prognosis is poor. Sorafenib and Selective Internal Radiation Therapy (SIRT) are clinically proven treatment options in patients with unresectable HCC, and this study aims to assess overall survival following either SIRT or Sorafenib therapy for locally advanced HCC patients. Methods: This investigator-initiated, multi-centre, open-label, randomized, controlled trial will enrol 360 patients with locally advanced HCC, as defined by Barcelona Clinic Liver Cancer stage B or stage C, without distant metastases, and which is not amenable to immediate curative treatment. Exclusion criteria include previous systemic therapy, metastatic disease, complete occlusion of the main portal vein, or a Child-Pugh score of >7. Eligible patients will be randomised 1:1 and stratified by centre and presence or absence of portal vein thrombosis to receive either a single administration of SIRT using yttrium-90 resin microspheres (SIR-Spheres®, Sirtex Medical Limited, Sydney, Australia) targeted at HCC in the liver by the trans-arterial route or continuous oral Sorafenib (Nexavar®, Bayer Pharma AG, Berlin, Germany) at a dose of 400 mg twice daily until disease progression, no further response, complete regression or unacceptable toxicity. Patients for both the Sorafenib and SIRT arms will be followed-up every 4 weeks for the first 3 months and 12 weekly thereafter. Overall survival is the primary endpoint, assessed for the intention-to-treat population. Secondary endpoints are tumour response rate, time-to-tumour progression, progression free survival, quality of life and down-staging to receive potentially curative therapy. Discussion: Definitive data comparing these two therapies will help to determine clinical practice in the large group of patients with locally advanced HCC and improve outcomes for such patients. [ABSTRACT FROM AUTHOR]

This is an exploratory paper of the ethical implications for genomic research and mental illness with specific reference to Singapore. Singapore has a unique context due to its social and political systems, and although it is a relatively small country, its population is religiously and culturally diverse. The issues that we identify here, therefore, will offer new perspectives and will also shed light on the existing literature on psychiatric genomics in society. We contextualise issues such as risk and stigma in the identification and diagnosis of psychosis in the way they relate to Singaporean society, and use a current study (LYRIKS) as a case example. Genomic research has the potential to change significantly he practice of clinical medicine if, as expected, fast and inexpensive sequencing becomes a reality. It will likely also change how society thinks and acts in respect to multi-factorial diseases, conditions, traits, and syndromes that have a genetic component. Genomic research already raises a number of ethical concerns relating to the privacy of individuals, including the disclosure of research results and incidental findings, surreptitious tests, third party access to data, and the re-emergence of genetic determinism. These issues are potentially exacerbated when genomics - the study of whole genomes to understand complex illness and behavioural traits - is applied to psychiatric research, because of the stigma that is often attached to mental illness. In this paper, we discuss some of the issues that have arisen in the context of a study in Singapore that is currently investigating the genomics and biomarkers of psychosis. We argue that although a genomic study rarely creates data that is directly useful to the participant, it can have incidental benefits to the individual who is identified during the study as being at high risk of developing psychosis and its related states. Understanding these potential benefits requires us to examine the implications that this type of research may have on public understandings of genomic data and risk. [ABSTRACT FROM AUTHOR]

To investigate the relationship between body mass and health-related quality of life (HRQOL) among Singaporean adolescents. Variation in this relationship by age, gender and ethnicity, and association of HRQOL with change in body mass over time and with demographic, socioeconomic and health variables were also assessed. HRQOL was assessed for Singaporean adolescents aged 11–18 from their own ( N = 1,249) and their parent’s ( N = 948) perspective using PedsQL™ 4.0 generic core scales. Body mass, measured as body mass index z-score based on the WHO Reference 2007, was categorized as thin, healthy weight, overweight and obese. Multiple linear regression models assessed the relationship between current body mass and HRQOL, adjusting for demographic, socioeconomic and health variables. Differences between adolescent and parent-proxy reported HRQOL were also investigated. Obese adolescents (and their parents) reported significantly lower HRQOL, overall and in most domains, compared to healthy weight adolescents. Parents tended to report lower HRQOL for their adolescents than the adolescents did themselves; however, this difference was much larger and statistically significant for obese adolescents. Obesity is associated with reduced HRQOL among adolescents. The effect in these Singaporean adolescents is similar to that in populations with higher rates of obesity. Awareness of this relationship can make it easier for health professionals, teachers, parents and peers to be supportive of obese adolescents. [ABSTRACT FROM AUTHOR]

Background: A Royal Statistical Society Working Party recently recommended that "Greater use should be made of numerical, as opposed to verbal, descriptions of risk" in first-in-man clinical trials. This echoed the view of many clinicians and psychologists about risk communication. As the clinical trial industry expands rapidly across the globe, it is important to understand risk communication in Asian countries. Methods: We conducted a cognitive experiment about participation in a hypothetical clinical trial of a pain relief medication and a survey in cancer and arthritis patients in Singapore. In part 1 of the experiment, the patients received information about the risk of side effects in one of three formats (frequency, percentage and verbal descriptor) and in one of two sequences (from least to most severe and from most to least severe), and were asked about their willingness to participate. In part 2, the patients received information about the risk in all three formats, in the same sequence, and were again asked about their willingness to participate. A survey of preference for risk presentation methods and usage of verbal descriptors immediately followed. Results: Willingness to participate and the likelihood of changing one's decision were not affected by the risk presentation methods. Most patients indicated a preference for the frequency format, but patients with primary school or no formal education were indifferent. While the patients used the verbal descriptors "very common", "common" and "very rare" in ways similar to the European Commission's Guidelines, their usage of the descriptors "uncommon" and "rare" was substantially different from the EU's. Conclusion: In this sample of Asian cancer and arthritis patients, risk presentation format had no impact on willingness to participate in a clinical trial. However, there is a clear preference for the frequency format. The lay use of verbal descriptors was substantially different from the EU's. [ABSTRACT FROM AUTHOR]

So far, most Phase II trials have been designed and analysed under a frequentist framework. Under this framework, a trial is designed so that the overall Type I and Type II errors of the trial are controlled at some desired levels. Recently, a number of articles have advocated the use of Bayesian designs in practice. Under a Bayesian framework, a trial is designed so that the trial stops when the posterior probability of treatment is within certain prespecified thresholds. In this article, we argue that trials under a Bayesian framework can also be designed to control frequentist error rates. We introduce a Bayesian version of Simon's well-known two-stage design to achieve this goal. We also consider two other errors, which are called Bayesian errors in this article because of their similarities to posterior probabilities. We show that our method can also control these Bayesian-type errors. We compare our method with other recent Bayesian designs in a numerical study and discuss implications of different designs on error rates. An example of a clinical trial for patients with nasopharyngeal carcinoma is used to illustrate differences of the different designs. [ABSTRACT FROM AUTHOR]

Health-related quality of life instruments tend to include a great many items. This imposes a burden on the respondents as well as undermining response rate and data quality. In this study we developed a shortened version of the Functional Living Index—Cancer (FLIC), now called Quick-FLIC, and examined its measurement properties. A questionnaire package, self-administered by 140 patients, included the FLIC and the Functional Assessment of Cancer Therapy—General. A factor analysis and clinical judgement were used to shorten the FLIC, which included 22 items. Each subscale of FLIC was shortened to include two or three items only. The Quick-FLIC included a total of only 11 items. Nevertheless, the measurement properties of the Quick-FLIC and its subscales were comparable to those of the original FLIC. It is concluded that the shortening of established health-related quality of life instruments is viable in oncology research. [ABSTRACT FROM AUTHOR]