Evidence, regulation and “rational” prescribing: the case of gabapentin for neuropathic pain.

Rationale, aims and objectives: In 2004, the pharmaceutical company Warner-Lambert paid US$430million to resolve criminal and civil legal liability for aggressive off-label marketing of gabapentin. Perhaps surprisingly, however, regulatory and legal concerns regarding the marketing of gabapentin has not significantly impacted upon the attitude of physicians towards using gabapentin for neuropathic pain. In this paper we attempt to understand the reasons for this discrepancy between clinical practice and regulatory/legal concerns through an analysis of published discussions about gabapentin prescribing. Methods: We performed a qualitative empirical analysis of the published clinical debate surrounding the use of gabapentin for the management of neuropathic pain. Results: The ongoing use of gabapentin for neuropathic pain use was primarily driven by the perception that it was a safe, non-addictive drug with few drug interactions, by possible similarities between the physiology of chronic pain and other neurological conditions, by the well-established clinical precedent of using antiepileptic drugs in pain management, and by the lack of alternative options available in the market. Emerging evidence of lack of effectiveness and controversies about the integrity of the scientific record appeared to be of relatively little importance to practicing clinicians. Conclusions: Those who want to promote “rational” prescribing need to recognise that prescribing is driven by many factors other than epidemiological data and regulatory indications and that even intensely negative publicity about medicines may not penetrate clinical reasoning. This suggests that a range of measures may be needed to ‘incentivise’ rational prescribing and to promote research integrity. Regulators must be more sensitive to the contextual issues that are relevant to clinical practice when evaluating drugs for approval and developing guidelines. KEYWORDS: Chronic Pain; Neuralgia; Pain Management; Off-Label Use; Drug Industry; Physician’s Practice Patterns.NHMRC Project Grant (APP1059732); Wendy Lipworth is supported by a NHMRC Career Development Fellowship APP106356

The Contemporary Significance of the Holocaust for Australian Psychiatry.

In this paper we survey briefly the components of the Holocaust directly relevant to the psychiatric profession and identify the main themes of relevance to contemporary psychiatry. The euthanasia program, the persecution of lesbian, gay, bisexual, transgender and intersex (LGBTI) citizens and the complex relationship between the psychiatric profession and Nazi state are the main themes to emerge from this survey. We then compare this period with key themes in the history of Australian psychiatry and link these themes to some of the contemporary ethical challenges the profession faces

Challenges to pharmaceutical policymaking: lessons from Australia’s National Medicines Policy

Objective: National medicines policies (NMPs) provide a means for governments to achieve their objectives in relation to pharmaceuticals and other medicines. This research aimed to identify challenges to implementing the objectives of the Australian NMP from the perspective of key stakeholders. Methods: In 2012 and 2103, we conducted 30 semi-structured interviews with stakeholders involved in the discovery, clinical testing, regulation and funding of medicines in Australia. We asked participants to describe their careers and to give their opinions on specific issues surrounding drug development, clinical research, regulation and subsidisation in Australia. Data were analysed using Morse’s outline of the cognitive basis of qualitative research and Charmaz’s outline of data analysis in grounded theory. The initial phase of “open coding”, revealed findings that could be mapped to three of the four objectives of the NMP. We then conducted “focused coding” for themes relevant to these objectives. Results: Participants identified many issues relevant to the ongoing evolution of the NMP, relating primarily to ongoing tensions between the commercial objective of ensuring a viable medicines industry, and the non-commercial objectives of ensuring that medicines are safe, effective and affordable. There were also a number of other challenges identified to the achievement of both the commercial and non-commercial objectives of the NMP. These included limits to government funding, globalisation, consumer advocacy, changing scientific paradigms and new information technologies. Conclusions: There are many issues that need to be addressed if policymakers are to achieve the best outcomes from the NMP. Tensions between the commercial and non-commercial objectives of the NMP suggest the need to ensure that one stakeholder group’s imperatives do not stifle those of other groups. At the same time, there are a number of emerging issues that are likely to concern all stakeholders equally, and these are both challenges and opportunities for new kinds of collaboration

Dilemmas in the Compassionate Supply of Investigational Cancer Drugs

In Australia, patients who want to access medicines that are not yet approved have only two options: to enrol in a clinical trial if they are eligible, or obtain their medicine through ‘compassionate supply’, which is provided at the discretion of the manufacturer. In this article, we explore ethical issues associated with the provision of oncology medicines that are still in development, either prior to regulatory approval or government reimbursement. Keywords: ethics; evidence-based medicine; health services accessibility; oncolog

Psychiatry, genocide and the National Socialist State: lessons learnt, ignored and forgotten.

The genocide of European Jews perpetrated by the National Socialist (Nazi) regime in Germany and its satellites was a distinctly modern event. The bureaucratised and industrialised nature of the Nazi plan (the Endlösung or Final Solution) is generally considered the defining characteristic of the Nazi regime’s genocide. It placed that particular genocidal endeavour in a modernist context, unparalleled in human history. Prior to the establishment of extermination camps in Poland, the Nazi regime had perpetrated or fomented both sporadic massacres and a militarised program of executions in Eastern Europe, in what has been termed “Holocaust by bullets” (Desbois, 2008). Yet despite the murder of 1.5 million Jews by SS and police mobile killing squads (Einsatzgruppen), the defining symbol of the Holocaust was the industrialised killing centre at Auschwitz-Birkenau. Importantly, the gas chambers of the Reinhard camps (Belzec, Sobibor, and Treblinka II) and Auschwitz-Birkenau did not appear de novo for the purposes of killing Europe’s Jews (Friedlander, 1995). The medical profession, in collusion with Adolf Hitler’s Chancellery (KdF), had developed and refined a large scale, state-financed and well-concealed program of victim selection and mass transportation to dedicated killing centres with effective techniques of gassing and disposal of victims’ remains. The template for the Endlösung evolved as a medical procedure, developed primarily by psychiatrists (Burleigh M, 2002)

Is Gly16Arg β₂ Receptor Polymorphism Related to Impulse Oscillometry in a Real-Life Asthma Clinic Setting?

PURPOSE: We evaluated whether Gly16Arg beta2-receptor genotype relates to impulse oscillometry (IOS) in a real-life clinic setting. METHODS: Patients with persistent asthma taking inhaled corticosteroid ± long-acting beta-agonist (ICS ± LABA) were evaluated. We compared genotype groups comprising either no Arg copies (i.e. GlyGly) versus one or two Arg copies (i.e. ArgArg or ArgGly). IOS outcomes included total airway resistance at 5 Hz (R5), central airway resistance at 20 Hz (R20), peripheral airway resistance (R5–R20), reactance at 5 Hz, area under reactance curve (AX) and resonant frequency (RF). In addition, we recorded ACQ-5 and salbutamol use. RESULTS: One hundred and twelve ICS-treated asthmatic patients (mean ICS dose 1238 µg/day), mean age 43 years, ACQ 2.34, FEV1 82 %, R5 177 % were identified—89 were also taking LABA. 61 patients were GlyGly, while 14 were ArgArg and 37 were ArgGly. There were no significant differences in IOS outcomes, ACQ or salbutamol use between the genotypes. The allelic risk (as odds ratio) for less well-controlled asthma (as ACQ > 1.5) was 1.1 (95 % CI 0.72–1.68) in relation to each Arg copy with a corresponding odds ratio for abnormal R5–R20 > 0.07kPA/l.s being 0.91 (95 % CI 0.57–1.44). 71 % of patients had an ACQ > 1.5 in the GlyGly group, versus 67 % in GlyArg/ArgArg group, with corresponding figures for abnormal R5–R20 > 0.07 kPa/l.s being 69 versus 73 %. CONCLUSION: In a real-life clinic setting for patients with poorly controlled persistent asthma taking ICS ± LABA, we found no evidence of any relationship of Gly16Arg to IOS, ACQ or salbutamol use

Globalisation and the ethics of transnational biobank networks

Biobanks are increasingly being linked together into global networks in order to maximise their capacity to identify causes of and treatments for disease. While there is great optimism about the potential of these biobank networks to contribute to personalised and data-driven medicine, there are also ethical concerns about, among other things, risks to personal privacy and exploitation of vulnerable populations. Concepts drawn from theories of globalisation can assist with the characterisation of the ethical implications of biobank networking across borders, which can, in turn, inform more ethically sophisticated responses. Using the China Kadoorie Biobank as a case study, we show how distinguishing between the subnational, transnational, supranational and extranational spheres of operation and influence can help researchers, institutions and regulators to understand and manage the ethical issues raised by the globalisation of biobanking.National Health and Medical Research Council (Australia

A case-control study of lactation and cancer of the breast.

We have examined the relation of lactation, by total duration, with breast cancer risk among pre- and post-menopausal women. In a hospital-based case-control study conducted in Athens (1989-91), involving 820 patients with confirmed breast cancer and 795 orthopaedic patient controls and 753 hospital visitor controls, logistic regression was used to analyse the data controlling for demographic, nutritional and reproductive factors, including parity and age at any birth. Among post-menopausal women, there was no association between breastfeeding and breast cancer risk, but among premenopausal women those who has breastfed for > or = 24 months had an odds ratio of 0.50 (95% confidence interval 0.23-1.41). A reduction of the odds ration was also evident among premenopausal women who had breastfed between 12 and 23 months (odds ratio 0.70; 95% confidence interval 0.34-1.60). In conjunction with several other recent reports these results support the hypothesis that breastfeeding of prolonged duration may reduce the risk of breast cancer among premenopausal women but not among post-menopausal women. The biology underlying this different effect remains unknown, and the practical implication of the finding is a marginal importance

Beyond platitudes: a qualitative study of Australian Aboriginal people's perspectives on biobanking.

BACKGROUND: Biobanks are vital resources for genetics and genomics, and it is broadly recognised that for maximal benefit it is essential that they include samples and data from diverse ancestral groups. The inclusion of First Nations people, in particular, is important to prevent biobanking research from exacerbating existing health inequities, and to ensure that these communities share in the benefits arising from research. AIMS: To explore the perspectives of Australian Aboriginal people whose tissue - or that of their family members - has been stored in the biobank of the National Centre for Indigenous Genomics (NCIG). METHODS: Semi-structured interviews with 42 Aboriginal people from the Titjikala, Galiwinku, Tiwi Islands, Yarrabah, Fitzroy Crossing, Derby, One Arm Point and Mulan communities, as well as a formal discussion with A. Hermes, an Indigenous Community Engagement Coordinator at the NCIG who had conducted the interviews. The interviews and the structured discussion were double coded using a procedure informed by Charmaz's outline of grounded theory analysis and Morse's outline of the cognitive basis of qualitative research. RESULTS: In this article, we report on A. Hermes' interviews with members from the above Aboriginal communities, as well as on her personal views, experiences, and interpretations of the interviews she conducted with other community members. We found that participation in the NCIG biobank raised issues around broken trust, grief and loss, but also - somewhat unexpectedly - was perceived as a source of empowerment, hope and reconnection. CONCLUSIONS: This research reminds us (again) of the need to engage deeply with communities in order to respond appropriately with respect for their cultural values and norms, and to develop culturally relevant policies and processes that enhance the benefits of biobank participation and minimise potential harms