Assessing the reproducibility of discriminant function analyses.

Data are the foundation of empirical research, yet all too often the datasets underlying published papers are unavailable, incorrect, or poorly curated. This is a serious issue, because future researchers are then unable to validate published results or reuse data to explore new ideas and hypotheses. Even if data files are securely stored and accessible, they must also be accompanied by accurate labels and identifiers. To assess how often problems with metadata or data curation affect the reproducibility of published results, we attempted to reproduce Discriminant Function Analyses (DFAs) from the field of organismal biology. DFA is a commonly used statistical analysis that has changed little since its inception almost eight decades ago, and therefore provides an opportunity to test reproducibility among datasets of varying ages. Out of 100 papers we initially surveyed, fourteen were excluded because they did not present the common types of quantitative result from their DFA or gave insufficient details of their DFA. Of the remaining 86 datasets, there were 15 cases for which we were unable to confidently relate the dataset we received to the one used in the published analysis. The reasons ranged from incomprehensible or absent variable labels, the DFA being performed on an unspecified subset of the data, or the dataset we received being incomplete. We focused on reproducing three common summary statistics from DFAs: the percent variance explained, the percentage correctly assigned and the largest discriminant function coefficient. The reproducibility of the first two was fairly high (20 of 26, and 44 of 60 datasets, respectively), whereas our success rate with the discriminant function coefficients was lower (15 of 26 datasets). When considering all three summary statistics, we were able to completely reproduce 46 (65%) of 71 datasets. While our results show that a majority of studies are reproducible, they highlight the fact that many studies still are not the carefully curated research that the scientific community and public expects.

Hippocratic obligation to shareholder profit? Medical treatment patents and the Australian High Court in Apotex Pty Ltd v Sanofi-Aventis Australia Pty Ltd [2013] HCA 50.

The method of treatment of suffering in patients, including through surgery and the administration of therapeutic drugs, are essential features of medical professionalism. Few, if any practitioners committed to developing the core professional virtue of loyalty to relief of patient suffering through consistently implementing the basic principles of medical ethics, would consider that such beneficial methods of practice are, or should be, the subject of a patent--requiring the practitioner utilising them to pay a royalty or risk infringement proceedings. Indeed a formal opinion of the American Medical Association declares "the use of patents, trade secrets, confidentiality agreements, or other means to limit the availability of medical procedures places significant limitation on the dissemination of medical knowledge, and is therefore unethical". Yet this could be the direction in which Australian patent law is heading. The decision of the High Court of Australia in Apotex Pty Ltd v Sanofi-Aventis Australia Pty Ltd [2013] HCA 50, upholding a patent over a method of using a known drug to prevent or treat psoriasis, may ultimately force practitioners to re-consider whether their basic ethical obligations to patients are secondary to a requirement to maximise profit for shareholders in companies holding medical patents. This column reviews this decision and its possible implications for health practitioners. It places it in context of other recent court decisions that have expanded the intrusion of corporate-owned intellectual property monopolies into Australian medical practices, and how legislative restrictions upon them in the Patents Act 1990 (Cth) places practitioners and patients at risk of more costly, ineffective or restricted health care. This column concludes by cautioning that Australia's scope to address policy problems caused by this case may be limited should it sign up to the Trans-Pacific Partnership Agreement, particularly if that preferential trade and investment deal includes an Investor-State Dispute Settlement clause that creates a mechanism for multinational corporations to challenge offshore, Australian federal and state policy decisions they perceive undercut their investments.

Planetary medicine and the Waitangi Tribunal Whanganui River report: global health law embracing ecosystem as patients.

A recent decision of the Waitangi Tribunal granted legal personhood to New Zealand's Whanganui River (appointing guardians to act in its interests). Exploring the impacts of this decision, this column argues that new technologies (such as artificial photosynthesis) may soon be creating policy opportunities not only for legal personhood to be stripped from some artificial persons, but for components of the natural world (such as rivers and other ecosystems) to be granted such enforceable legal rights. Such technologies, if deployed globally, may do this by taking the pressure off ecosystems to be exploited for human profit and survival. It argues that, by also creating normative space for such an expansion of sympathy, global heath law begins to incorporate the vision of planet as patient.

Government control over health-related not-for-profit organisations: Agency for International Development v. Alliance for Open Society International Inc 570 US_(2013).

The relationship between government and the not-for-profit (NFP) sector has important implications for society, especially in relation to the delivery of public health measures and the protection of the environment. In key health-related areas such as provision of medical services, welfare, foreign aid and education, governments have traditionally preferred for the NFP sector to act as service partners, with the relationship mediated through grants or funding agreements. This service delivery arrangement is intended to provide a diversity of voices, and encourage volunteerism and altruism, in conjunction with the purposes and objectives of the relevant NGO. Under the pretence of "accountability", however, governments increasingly are seeking to impose intrusive conditions on grantees, which limit their ability to fulfil their mission and advocate on behalf of their constituents. This column examines the United States Supreme Court decision, Agency for International Development v Alliance for Open Society International Inc 570 US_(2013), and compares it to the removal of gag clauses in Australian federal funding rules. Recent national changes to the health-related NFP sector in Australia are then discussed, such as those found in the Charities Act 2013 (Cth) and the Not-for-Profit Sector Freedom to Advocate Act 2013 (Cth). These respectively include the establishment of the Australian Charities and Not-For-Profit Commission, the modernising of the definition of "charity" and statutory blocks on "gag" clauses. This analysis concludes with a survey of recent moves by Australian States to impose new restrictions on the ability of health-related NFPs to lobby against harmful government policy Among the responses considered is the protection afforded by s 51l(xxiiiA) of the Australian Constitution. This constitutional guarantee appears to have been focused historically on preventing medical and dental practitioners and related small businesses being practically coerced into government or large-scale private corporate operations. As such, it may prohibit civil conscription arising not only from "gag clauses" in managed care contracts, but also from "gag clauses" in governmental ideological controls over taxpayer-funded, health-related NFPs.

Civil liberties and the critics of safe vaccination: Australian Vaccination Network Inc v Health Care Complaints Commission [2012] NSWSC 110.

Public immunisation programs have, time and again, demonstrated their effectiveness at reducing mortality and morbidity from vaccine-preventable diseases such as measles and pertussis. Governments, health agencies and almost all health practitioners regard vaccines as safe and cost-effective treatments with a low risk profile. Nevertheless, despite, or perhaps because of, their success, immunisation programs and vaccines have increasingly been questioned by various lobby groups, sceptical of the safety of vaccines and the motives of those who administer them. Whereas the reach of these groups would have once been limited by the cost of postage, the internet has delivered a global audience. The extent to which these anti-vaccination advocates are expected to comply with the ethical and professional standards applied to registered health professionals remains unresolved in Australia. As demonstrated in the case of Australian Vaccination Network Inc v Health Care Complaints Commission [2012] NSWSC 110, the ability of professional oversight bodies to regulate the information promoted by these lobby groups is limited by traditional conceptions of the doctor-patient relationship and the clinical setting in which medical advice is delivered. Acknowledging that vaccines, like all medical treatments, involve some level of risk, this article explores the relationship between the state, parents, family, medical professionals and such lobbyists within a human rights framework, suggesting that most public immunisation programs deliver benefits in "the best interest of the child" that, on balance, provide a good result for the civil liberties of Australians.

A bad trip for health-related human rights: implications of Momcilovic v The Queen (2011) 85 ALJR 957.

Momcilovic v The Queen (2011) 85 ALJR 957; [2011] HCA 34 arose from a prosecution for drug trafficking brought under the Drugs, Poisons and Controlled Substances Act 1981 (Vic). The Australian High Court held that the Charter of Human Rights and Responsibilities Act 2006 (Vic) (the Charter) validly conferred a power on the Victorian Supreme Court and Court of Appeal to interpret legislation in a manner consistent with a defined list of human rights. By a slim majority it also held that the Charter validly created a judicial power to "declare" a law inconsistent with one or more enumerated human rights. In reaching its decision, however, the majority supported a narrow interpretation likely to undermine the intended capacity of the Charter to act as a remedial mechanism to reform laws, regulations and administrative practices which infringe human rights and freedoms. Although Momcilovic involved interpretation of a specific State human rights law, the High Court judgments allude to significant problems should the Federal Government seek to introduce a similar charter-based human rights system. Momcilovic, therefore, represents a risk to future efforts to develop nationally consistent Australian human rights jurisprudence. This has particular relevance to health and medically related areas such as the freedom from torture and degrading and inhuman treatment and, in future, enforceable constitutional health-related human rights such as that to emergency health care.

Balancing public health, trade and intellectual monopoly privileges: recent Australian IP legislation and the TPPA.

Over the past year, several significant reforms to Australia's intellectual property regime have been proposed and passed by Parliament. The Intellectual Property Laws Amendment (Raising the Bar) Act 2012 (Cth) made various improvements to Australian patent law, including an improved threshold for patentability, greater clarity around "usefulness" requirements, and the introduction of an experimental use exemption from infringement. Another Bill, the Intellectual Property Laws Amendment Bill 2012 (Cth), currently out for public consultation, would implement a 2003 decision of the World Trade Organisation (WTO) General Council and the 2005 Doha Declaration on the TRIPS Agreement and Public Health (Doha Declaration). If enacted, this Bill would facilitate equitable access to essential medicines by amending the compulsory licensing regime set out in the Patents Act 1990 (Cth). The underlying intention of this Bill--meeting public health goals outlined in the 2005 Doha Declaration--stands in juxtaposition to proposed reforms to intellectual property standards pursuant to the Trans-Pacific Partnership Trade and Investment Agreement (TPPA) that Australia is involved in. Although at a preliminary stage, leaked drafts of relevant intellectual property provisions in the TPPA suggest a privileging of patent monopoly privileges over public health goals. This column weighs the sentiments of the proposed Bill against those of the proposed provisions in the TPPA.

Freedom of information applications as an "evergreening" tactic: Secretary, Department of Health and Ageing v iNOVA Pharmaceuticals (Australia) Pty Ltd (2010) 191 FCR 573; [2010] FCA 1442.

A recent decision of the Federal Court of Australia illustrates how patent-holding pharmaceutical companies are attempting to use Australia's Freedom of Information Act 1982 (Cth) to force Australian safety, quality and efficacy regulators to disclose whether generic competitors are attempting to enter the market. In Secretary, Department of Health and Ageing v iNova Pharmaceuticals (Australia) Pty Ltd (2010) 191 FCR 573; [2010] FCA 1442 a single judge of the Federal Court overturned a decision of the Administrative Appeals Tribunal (AAT) that would have compelled the Australian Therapeutic Goods Administration (TGA) to reveal whether they were in possession of an application to register generic versions of two iNova products: imiquimod and phentermine. In its justification to the AAT for refusing to confirm or deny the existence of any application, the TGA argued that to reveal the existence of such a document would prejudice the proper administration of the National Health Act 1953 (Cth) as it could compromise the listing of a generic on the Pharmaceutical Benefits Scheme. The AAT failed to appreciate the extent to which this revelation to a competitor would have undercut 2004 amendments to the Therapeutic Goods Act 1989 (Cth) that provided penalties for evergreening tactics involving TGA notifications to drug patent-holders and 2006 amendments to the Patents Act 1990 (Cth) which protected the right of generic manufacturers to "springboard". The decision of the Federal Court is one of the first to explore the use of freedom of information legislation by patent-holders as a potential "evergreening" technique to prolong royalties by marginalising generic competition. Because of the significant amounts of money involved in ensuring rapid market entry of low-cost generic products, the issue has considerable public health significance.

Should I stay or should I go? The Ectodysplasin locus is associated with behavioural differences in threespine stickleback.

Adaptive divergence may be facilitated if morphological and behavioural traits associated with local adaptation share the same genetic basis. It is therefore important to determine whether genes underlying adaptive morphological traits are associated with variation in behaviour in natural populations. Positive selection on low-armour alleles at the Ectodysplasin (Eda) locus in threespine stickleback has led to the repeated evolution of reduced armour, following freshwater colonization by fully armoured marine sticklebacks. This adaptive divergence in armour between marine and freshwater populations would be facilitated if the low allele conferred a behavioural preference for freshwater environments. We experimentally tested whether the low allele is associated with preference for freshwater by measuring the preference of each Eda genotype for freshwater versus saltwater after acclimation to either salinity. We found no association between the Eda low allele and preference for freshwater. Instead, the low allele was significantly associated with a reduced preference for the acclimation environment. This behaviour may facilitate the colonization of freshwater habitats from the sea, but could also hinder local adaptation by promoting migration of low alleles between marine and freshwater environments.

New Australian federal organ and tissue donation legislation: enhanced transplant services but no "opt-out".

Seriously ill people who could achieve many years of high-quality life with organ donation continue to die on waiting lists due to the scarcity of donated organs. Recent advances that suggest donor organs can be coated with host stem cells to reduce or remove the need for long-term recipient immunosupressive medication highlight the importance of encouraging such donation. A wide variation in organ donor rates in developed nations suggests this is one issue in which the right regulation can make a difference. Australia has now passed federal legislation on the topic. This column considers whether that legislation is headed in the right direction,