Does pharmacogenomics provide an ethical challenge to the utilisation of cost-effectiveness analysis by public health systems?

Pharmacogenomics promotes an understanding of the genetic basis for differences in efficacy or toxicity of drugs in different individuals. Implementation of the outcomes of pharmacogenomic research into clinical practice presents a number of difficulties for healthcare. This paper aims to highlight one of the Unique ethical challenges which pharmacogenomics presents for the utilisation of cost-effectiveness analysis by public health systems. This paper contends that pharmacogenomics provides a challenge to fundamental principles which underlie most systems for deciding which drugs should be publicly subsidised. Pharmacogenomics brings into focus the conflict between equality and utility in the context of using cost-effectiveness analysis to aid distribution of a limited national drug budget.

Utilising survey data to inform public policy: Comparison of the cost-effectiveness of treatment of ten mental disorders

Background Mental health survey data are now being used proactively to decide how the burden of disease might best be reduced. Aims To study the cost-effectiveness of current and optimal treatments for mental disorders and the proportion of burden avertable by each. Method Data for three affective, four anxiety and two alcohol use disorders and for schizophrenia were compared in terms of cost, burden averted and efficiency of current and optimal treatment. We then calculated the burden unavertable given current knowledge. The unit of health gain was a reduction in the years lived with disability (YLDs). Results Summing across all disorders, current treatment averted 13% of the burden, at an average cost of AUS$30 000 per YLD gained. Optimal treatment at current coverage could avert 20% of the burden, at an average cost of AUS$18 000 per YLD gained. Optimal treatment at optimal coverage could avert 28% of the burden, at AUS$16 000 per YLD gained. Sixty per cent of the burden of mental disorders was deemed to be unavertable. Conclusions The efficiency of treatment varied more than tenfold across disorders. Although coverage of some of the more efficient treatments should be extended, other factors justify continued use of less-efficient treatments for some disorders. Declaration of interest None. Funding detailed in Acknowledgements.

A comparative analysis of entrepreneurial approaches within public healthcare organisations

This article examines the development of two distinct models of organising allied health professionals within two public sector health service organisations in Australia. The first case illustrated a mode of organising that facilitated a culture that focused on asset protection and whose external orientation was threat oriented because its disparate multiple identities operated as a fractured, fragmented and competitive set of profession disciplines. In this milieu, there was no evidence of entrepreneurial approaches being used. In contrast, the second case study illustrated a mode of organising that facilitated an entrepreneurial culture that focused on asset growth and an external orientation that was opportunity oriented because of the evolution of a strong superordinate allied health identity that operated as a single united health services stakeholder. This evolution was coupled with the emergence of a corporate boardroom model of management that is consonant with Savage et al. (1997) IDS/N model of management. Once this structure and strategy were in place, corporate entrepreneur ship became the modus operandi. Consequently, because the case study was a situation where corporate entrepreneurship existed in the public sector, it was possible to compare the factors that stimulate corporate entrepreneurship in Sadler's (2000) study with factors that were observed in our study.

Analysis of distinct tartrate-resistant acid phosphatase promoter regions in transgenic mice

The tartrate-resistant acid phosphatase (TRAP) is present in multiple tissues, including kidney, liver, lung, spleen, and bone. Recent study of (TRAP) gene expression has provided evidence for distinct promoters within the (TRAP) gene, suggesting that the gene has alternative, tissue-preferred mRNA transcripts. Examination of endogenous (TRAP) exon 1B and 1C mRNA transcripts revealed tissue-preferred transcript abundance with increased exon 1B transcripts detected in liver and kidney and increased exon 1C transcripts detected in bone and spleen. In this investigation, we have made transgenic mice that express a marker gene driven by two candidate promoters, designated BC and C, within the (TRAP) gene. The BC and C promoters are 2.2 and 1.6 kb, respectively, measured from the translation initiation site. Evaluation of BC transgenic lines demonstrated robust expression in multiple tissues. In contrast, significant transgene expression was not detected in C transgenic lines. Evaluation of transgene mRNAs in BC transgenic lines revealed that virtually all expression was in the form of B transcripts, suggesting that the tissue-preferred pattern of endogenous (TRAP) was not replicated in the BC transgenic line. Likewise, osteoclastogenic cultures from BC, but not C, transgenic bone marrow cells expressed the transgene following receptor activator of NFkappaB ligand/macrophage colony-stimulating factor stimulation. In conclusion, when compared with the 2.2-kb BC portion of the (TRAP) promoter region, the 1.6-kb C portion does not account for significant gene expression in vivo or in vitro; production of the bone- and spleen-preferred (TRAP) C transcript must depend on regulatory elements outside of the 2.2-kb promoter. As the majority of currently investigated transcription factors that influence transcriptional regulation of osteoclast gene expression bind within the 1.6-kb C portion of the (TRAP) promoter, it is likely that transcription binding sites outside of the 2.2-kb region will have profound effects on regulation of the gene in vivo and in vitro.

A simulation analysis of the market effect of the Australian Broadcasting Corporation

In this paper we utilise a stochastic address model of broadcast oligopoly markets to analyse the Australian broadcast television market. In particular, we examine the effect of the presence of a single government market participant in this market. An examination of the dynamics of the simulations demonstrates that the presence of a government market participant can simultaneously generate positive outcomes for viewers as well as for other market suppliers. Further examination of simulation dynamics indicates that privatisation of the government market participant results in reduced viewer choice and diversity. We also demonstrate that additional private market participants would not result in significant benefits to viewers.

Genome-wide analysis of mammalian promoter architecture and evolution

Mammalian promoters can be separated into two classes, conserved TATA box-enriched promoters, which initiate at a welldefined site, and more plastic, broad and evolvable CpG-rich promoters. We have sequenced tags corresponding to several hundred thousand transcription start sites (TSSs) in the mouse and human genomes, allowing precise analysis of the sequence architecture and evolution of distinct promoter classes. Different tissues and families of genes differentially use distinct types of promoters. Our tagging methods allow quantitative analysis of promoter usage in different tissues and show that differentially regulated alternative TSSs are a common feature in protein-coding genes and commonly generate alternative N termini. Among the TSSs, we identified new start sites associated with the majority of exons and with 3' UTRs. These data permit genome-scale identification of tissue-specific promoters and analysis of the cis-acting elements associated with them.

International symposium on career development and public policy: Synthesis of country papers

During the conference, country teams were asked to select and address selection of six themes: human capital, labour supply, employability skills, carer development services for workforce development, older workers or evidence based research. This synthesis of country papers covers the conceptual links between these themes. It then goes on to cover three reframed themes focusing on career development policies and services, but distinguishing three levels of such policies and services: workforce preparation, workforce adaptability and workforce re-integration.