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It is unclear whether or not grant winning should count towards authorship credit in the sciences. In this paper, I argue that under certain circumstances grant winning can count for credit as an author on subsequent works. It is a mistake to think that grant winning is always irrelevant to the correct attribution of authorship. [ABSTRACT FROM AUTHOR]

A growing number of bioethics papers endorse the harm threshold when judging whether to override parental decisions. Among other claims, these papers argue that the harm threshold is easily understood by lay and professional audiences and correctly conforms to societal expectations of parents in regard to their children. English law contains a harm threshold which mediates the use of the best interests test in cases where a child may be removed from her parents. Using Diekema's seminal paper as an example, this paper explores the proposed workings of the harm threshold. I use examples from the practical use of the harm threshold in English law to argue that the harm threshold is an inadequate answer to the indeterminacy of the best interests test. I detail two criticisms: First, the harm standard has evaluative overtones and judges are loath to employ it where parental behaviour is misguided but they wish to treat parents sympathetically. Thus, by focusing only on 'substandard' parenting, harm is problematic where the parental attempts to benefit their child are misguided or wrong, such as in disputes about withdrawal of medical treatment. Second, when harm is used in genuine dilemmas, court judgments offer different answers to similar cases. This level of indeterminacy suggests that, in practice, the operation of the harm threshold would be indistinguishable from best interests. Since indeterminacy appears to be the greatest problem in elucidating what is best, bioethicists should concentrate on discovering the values that inform best interests. [ABSTRACT FROM AUTHOR]

Background: Doctors sometimes encounter parents who object to prescribed treatment for their children, and request suboptimal substitutes be administered instead (suboptimal being defined as less effective and/or more expensive). Previous studies have focused on parental refusal of treatment and when this should be permitted, but the ethics of requests for suboptimal treatment has not been explored.Methods: The paper consists of two parts: an empirical analysis and an ethical analysis. We performed an online survey with a sample of the general public to assess respondents' thresholds for acceptable harm and expense resulting from parental choice, and the role that religion played in their judgement. We also identified and applied existing ethical frameworks to the case described in the survey to compare theoretical and empirical results.Results: Two hundred and forty-two Mechanical Turk workers took our survey and there were 178 valid responses (73.6%). Respondents' agreement to provide treatment decreased as the risk or cost of the requested substitute increased (p<0.001). More than 50% of participants were prepared to provide treatment that would involve a small absolute increased risk of death for the child (<5%) and a cost increase of US$<500, respectively. Religiously motivated requests were significantly more likely to be allowed (p<0.001). Existing ethical frameworks largely yielded ambiguous results for the case. There were clear inconsistencies between the theoretical and empirical results.Conclusion: Drawing on both survey results and ethical analysis, we propose a potential model and thresholds for deciding about the permissibility of suboptimal treatment requests. [ABSTRACT FROM AUTHOR]

This paper proposes an ethical framework for evaluating biosafety risks of gain-of-function (GOF) experiments that create novel strains of influenza expected to be virulent and transmissible in humans, so-called potential pandemic pathogens (PPPs). Such research raises ethical concerns because of the risk that accidental release from a laboratory could lead to extensive or even global spread of a virulent pathogen. Biomedical research ethics has focused largely on human subjects research, while biosafety concerns about accidental infections, seen largely as a problem of occupational health, have been ignored. GOF/PPP research is an example of a small but important class of research where biosafety risks threaten public health, well beyond the small number of persons conducting the research.We argue that bioethical principles that ordinarily apply only to human subjects research should also apply to research that threatens public health, even if, as in GOF/PPP studies, the research involves no human subjects. Specifically we highlight the Nuremberg Code's requirements of 'fruitful results for the good of society, unprocurable by other methods', and proportionality of risk and humanitarian benefit, as broad ethical principles that recur in later documents on research ethics and should also apply to certain types of research not involving human subjects. We address several potential objections to this view, and conclude with recommendations for bringing these ethical considerations into policy development. [ABSTRACT FROM AUTHOR]

Clinical Study Agreements (CSAs) can have profound effects both on the protection of human subjects and on the independence of investigators to conduct research with scientific integrity. Sponsors, institutions, and even investigators may fail to give adequate attention to these issues in the negotiation of CSAs. Despite the key role of CSAs in structuring ethically important aspects of research, they remain largely unregulated and unreviewed for adherence to ethical norms. Academic institutions routinely enter into research contracts that fail to meet adequate ethical standards. This is a failing that can have serious consequences. Accordingly, it is necessary that some independent body have the authority both to review research contracts for compliance with norms of subject protection and ethical integrity, and to reject studies that fail to meet ethical standards. Such review should take place prior to the start of research, not later. Because of its expertise and authority, the institutional ethics review board (IRB or REB) is the appropriate body to undertake such review. Much recent commentary has focused on contractual restrictions on the investigator's freedom to publish research findings. The Olivieri experience, and that of other investigators, has brought freedom of publication issues into sharp focus. Clinical study agreements also raise a number of other ethical issues relating to human subjects and research integrity, however, including disclosures relating to patient safety, data analysis and reporting, budget, confidentiality, and premature termination of the study. This paper describes the ethical issues at stake in structuring such agreements and suggests ethical standards to guide institutional ethics review. [ABSTRACT FROM AUTHOR]

Must medical experiments with human subjects offer them a 'favourable risk-benefit ratio', that is, more expectation of benefit than harm or burden, if they are to be judged as ethically justified? Ethical justification is easier for experiments that do offer net benefit to subjects, but ethical justification is possible also for some experiments that do not. Basic science experiments with healthy volunteers and 'Phase I' drug trials that seek to determine tolerable dosage levels are routinely approved by ethical review committees; moreover, guidance they receive from government funding agencies specifically asks them to weigh risks to subjects against benefits to subjects and also benefits to those who may benefit from the knowledge gained in the experiment. If a puzzle remains, it is why there remains any assumption that research ethics requires a 'favourable risk-benefit ratio' for the individual research subject. [ABSTRACT FROM AUTHOR]

Reflecting on the contribution by Rahul Kumar to the symposium, I consider the following topics in relation to risks in research: (1) treating someone as a mere means; (2) aggregation; (3) different conceptions of contractualism; (4) uncertainty; (5) paternalism and complicity. [ABSTRACT FROM AUTHOR]

We analysed the authorship policies of a random sample of 600 journals from the Journal Citation Reports database. 62.5% of the journals we sampled had an authorship policy. Having an authorship policy was positively associated with impact factor. Journals from the biomedical sciences and social sciences/humanities were more likely to have an authorship policy than journals from the physical sciences, engineering or mathematical sciences. Among journals with a policy, the most frequent type of policy was guidance on criteria for authorship (99.7%); followed by guidance on acknowledgments (97.3%); requiring that authors make substantial contributions to the research (94.7%); requiring that authors be accountable for the research as a whole (84.8%); guidance on changes in authorship (77.9%); requiring that authors give final approval to the manuscript (77.6%); requiring that authors draft or critically revise the manuscript (71.7%); providing guidance on corporate authorship (58.9%); prohibiting gift, guest or ghost authorship (31.7%); requiring authors to describe their contributions (5.3%); limiting the number of authors for some types of articles (4.0%) and requiring authors to be accountable for their part in the research (1.1%). None of the policies addressed equal contribution statements. Journals that do not have authorship policies should consider adopting or developing ones. [ABSTRACT FROM AUTHOR]

Introduction: Patients require an accurate knowledge about placebos and their possible effects to ensure consent for placebo-controlled clinical trials is adequately informed. However, few previous studies have explored patients' baseline (ie, pretrial recruitment) levels of understanding and knowledge about placebos. The present online survey aimed to assess knowledge about placebos among patients with a history of back pain.Design: A 15-item questionnaire was constructed to measure knowledge about placebos. Additional questions assessed sociodemographic characteristics, duration and severity of back pain, and previous experience of receiving placebos.Setting: Participants recruited from community settings completed the study online.Results: 210 participants completed the questionnaire. 86.7% had back pain in the past 6 months, 44.3% currently had back pain. 4.3% had received a placebo intervention as part of a clinical trial and 68.1% had previously read or heard information about placebos. Overall knowledge of placebos was high, with participants on average answering 12.07 of 15 questions about placebos correctly (SD=2.35). However, few participants correctly answered questions about the nocebo effect (31.9% correct) and the impact of the colour of a placebo pill (55.2% correct).Conclusions: The findings identified key gaps in knowledge about placebos. The lack of understanding of the nocebo effect in particular has implications for the informed consent of trial participants. Research ethics committees and investigators should prioritise amending informed consent procedures to incorporate the fact that participants in the placebo arm might experience adverse side effects. [ABSTRACT FROM AUTHOR]

The ability of adolescents to access safe and effective new products for HIV prevention and treatment is optimised by adolescent licensure at the same time these products are approved and marketed for adults. Many adolescent product development programmes for HIV prevention or treatment products may proceed simultaneously with adult phase III development programmes. Appropriately implemented, this strategy is not expected to delay licensure as information regarding product efficacy can often be extrapolated from adults to adolescents, and pharmacokinetic properties of drugs in adolescents are expected to be similar to those in adults. Finally, adolescents enrolled in therapeutic HIV prevention and treatment research can be considered adults, based on US Food and Drug Administration (FDA) regulations and the appropriate application of state law. The FDA permits local jurisdictions to apply state and local HIV/sexually transmitted infection minor treatment laws so that adolescents who are HIV-positive or at risk of contracting HIV may be enrolled in therapeutic or prevention trials without obtaining parental permission. [ABSTRACT FROM AUTHOR]

It is not uncommon for multiple clinical trials at the same institution to recruit concurrently from the same patient population. When the relevant pool of patients is limited, as it often is, trials essentially compete for participants. There is evidence that such a competition is a predictor of low study accrual, with increased competition tied to increased recruitment shortfalls. But there is no consensus on what steps, if any, institutions should take to approach this issue. In this article, we argue that an institutional policy that prioritises some trials for recruitment ahead of others is ethically permissible and indeed prima facie preferable to alternative means of addressing recruitment competition. We motivate this view by appeal to the ethical importance of minimising the number of studies that begin but do not complete, thereby exposing their participants to unnecessary risks and burdens in the process. We then argue that a policy of prioritisation can be fair to relevant stakeholders, including participants, investigators and funders. Finally, by way of encouraging and helping to frame future debate, we propose some questions that would need to be addressed when identifying substantive ethical criteria for prioritising between studies. [ABSTRACT FROM AUTHOR]

: Genetic research into ageing, longevity and late-onset disease is becoming increasingly common. Yet, there is a paucity of knowledge related to clinical actionability and the return of pathogenic variants to otherwise healthy elderly individuals. Whether or not genetic research in the elderly should be managed differently from standard practices adapted for younger populations has not yet been defined. In this article, we provide an overview of ethical and practical challenges in preparing for a genetic study of over 14 000 healthy Australians aged 70 years or older enrolled in the ASPirin in Reducing Events in the Elderly (ASPREE) Healthy Ageing Biobank. At the time of consent, all participants in this study were free of life-threatening illness, cardiovascular disease or cognitive impairment. ASPREE is thus a cohort of healthy elderly individuals with seemingly minimal burden of genetic disease recruited without ascertainment bias. The cohort presents a unique opportunity to address the penetrance of known pathogenic variants in a population without disease symptoms; however, it also raises a number of ethical concerns regarding the interpretation and disclosure of variants with known clinical actionability. Some of the challenges include (a) how to manage the interpretation, disclosure and actioning of pathogenic variants found in otherwise healthy elderly adults without disease symptoms, (b) whether or not to disclose findings for the benefit of family members rather than elderly consented donors themselves, (c) how to manage the return of genetic findings to the elderly individuals who are now in severe cognitive decline or terminal illness, (d) how to ensure quality of information and clinical service upon disclosure of results to this demographic and (e) how to prepare for the insurance implications of disclosing genetic information under Australian law. We discuss these and other dilemmas and propose a defensible plan of management.Trial Registration Number: ISRCTN83772183. [ABSTRACT FROM AUTHOR]

During the 2014-2015 Ebola outbreak in Guinea, Liberia and Sierra Leone, many opposed the use of individually randomised controlled trials to test candidate Ebola vaccines. For a raging fatal disease, they explained, it is unethical to relegate some study participants to control arms. In Zika and future emerging infections, similar opposition may hinder urgent vaccine research, so it is best to address these questions now. This article lays out the ethical case for individually randomised control in testing vaccines against many emerging infections, including lethal infections in low-income countries, even when at no point in the trial do the controls receive the countermeasures being tested. When individual randomisation is feasible-and it often will be-it tends to save more lives than alternative designs would. And for emerging infections, individual randomisation also tends as such to improve care, access to the experimental vaccine and prospects for all participants relative to their opportunities absent the trial, and no less than alternative designs would. That obtains even under placebo control and without equipoise-requiring which would undermine individual randomisation and the alternative designs that opponents proffered. Our arguments expound four often-neglected factors: benefits to non-participants, benefits to participants once a trial is over including post-trial access to the study intervention, participants' prospects before randomisation to arms and the near-inevitable disparity between arms in any randomised controlled trial. [ABSTRACT FROM AUTHOR]

Combination antiretroviral therapy (cART) is highly effective at preventing morbidity and mortality due to infection with human immunodeficiency virus (HIV), but does not eradicate the virus. Consequently, cART must be administered life-long. Recent progress has stimulated research towards a cure of HIV infection. Approaches under investigation include hematopoietic stem cell transplantation, latency reactivating agents, immune based therapies, and cell-based therapies. Each of these approaches carries potential risks that must be weighed against the availability of safe and effective cART. Balancing the risks and benefits of this research poses unique challenges to potential study participants, clinicians and investigators. [ABSTRACT FROM AUTHOR]

Ethical guidelines recommend that experimental interventions should be tested in adults first before they are tested and approved in children. Some challenge this paradigm, however, and recommend initiating paediatric testing after preliminary safety testing in adults in certain cases. For instance, commentators have argued for accelerated testing of HIV vaccines in children. Additionally, HIV cure research on the use of very early therapy (VET) in infants, prompted in part by the Mississippi baby case, is one example of a strategy that is currently being tested in infants before it has been well tested in adults. Because infants' immune systems are still developing, the timing of HIV transmission is easier to identify in infants than in adults, and infants who receive VET might never develop the viral reservoirs that make HIV so difficult to eradicate, infants may be uniquely situated to achieve HIV cure or sustained viral remission. Several commentators have now argued for earlier initiation of HIV cure interventions other than (or in addition to) VET in children. HIV cure research is therefore a good case for re-examining the important question of when to initiate paediatric research. I will argue that, despite the potential for HIV cure research to benefit children and the scientific value of involving children in this research, the HIV cure agenda should not accelerate the involvement of children for the following reasons: HIV cure research is highly speculative, risky, aimed at combination approaches and does not compare favourably with the available alternatives. I conclude by drawing general implications for the initiation of paediatric testing, including that interventions that have to be used in combination with others and cures for chronic diseases may not be valuable enough to justify early paediatric testing. [ABSTRACT FROM AUTHOR]

The patient empowerment movement, spurred by AIDS activism in the 1980s, quickly evolved to encompass how study participants are considered and treated in clinical research. Initially, people fearing death of AIDS sought early access to experimental medications that had not undergone rigorous testing in hopes of extending their lives. Thirty years on, scientists are asking a different set of ethical questions about clinical research, this time in the pursuit of either a sterilising cure or long-term remission for HIV. Instead of hastening access to experimental drugs for the sickest, researchers are now testing interventions for eradicating or controlling the virus in typically very healthy HIV-positive individuals who have the most to lose from such interventions if something goes wrong. While clinical researchers and ethicists debate the merits and limits of this type of research they should avoid discounting altruistic motivations as a powerful factor in a prospective study participant's decisions to assume risks. My conversations with four men who participated in HIV cure studies confirmed the capacity of these people to make carefully considered decisions about risks and the sometimes substantial influence/sway of non-clinical benefits that may come from participation in cure-oriented research. Studies must undergo ethical and clinical review before proceeding, and not all participants of such studies will be able to weigh or understand risks and benefits as those profiled here. But respecting the self-agency of people living with HIV should be a goal in the design and conduct of cure research. [ABSTRACT FROM AUTHOR]

Some early phase clinical studies of candidate HIV cure and remission interventions appear to have adverse medical risk-benefit ratios for participants. Why, then, do people participate? And is it ethically permissible to allow them to participate? Recent work in decision theory sheds light on both of these questions, by casting doubt on the idea that rational individuals prefer choices that maximise expected utility, and therefore by casting doubt on the idea that researchers have an ethical obligation not to enrol participants in studies with high risk-benefit ratios. This work supports the view that researchers should instead defer to the considered preferences of the participants themselves. This essay briefly explains this recent work, and then explores its application to these two questions in more detail. [ABSTRACT FROM AUTHOR]

Moral evaluation of risk/benefit in early phase studies requires assessing the clinical promise of a candidate intervention using preclinical evidence. Yet, there is little to guide ethics committees, investigators, sponsors or other stakeholders morally charged with making these assessments ('evaluators'). In what follows, we draw on published guidelines for preclinical study design to develop a structured process for assessing the clinical promise of new interventions. In the first step, evaluators gather all relevant preclinical studies, assess the magnitude of treatment effects and determine clinical promise in light of various threats to valid clinical inference. In the second step, evaluators adjust the assessments of clinical promise from preclinical studies by examining how other agents in the same reference class-and supported by similar evidence-have fared in clinical development. Assessments of clinical promise can then be fed into the moral evaluation of risk and benefit in early phase trials. Though our approach has limitations, it offers a systematic and transparent method for assessing risk/benefit in early phase trials of novel interventions. [ABSTRACT FROM AUTHOR]

Withdrawal of artificially delivered nutrition and hydration (ANH) from patients in a permanent vegetative state (PVS) requires judicial approval in England and Wales, even when families and healthcare professionals agree that withdrawal is in the patient's best interests. Part of the rationale underpinning the original recommendation for such court approval was the reassurance of patients' families, but there has been no research as to whether or not family members are reassured by the requirement for court proceedings or how they experience the process. The research reported here draws on in-depth narrative interviews with 10 family members (from five different families) of PVS patients who have been the subject of court proceedings for ANH-withdrawal. We analyse the empirical evidence to understand how family members perceive and experience the process of applying to the courts for ANH-withdrawal and consider the ethical and practice implications of our findings. Our analysis of family experience supports arguments grounded in economic and legal analysis that court approval should no longer be required. We conclude with some suggestions for how we might develop other more efficient, just and humane mechanisms for reviewing best interests decisions about ANH-withdrawal from these patients. [ABSTRACT FROM AUTHOR]

Purpose: To identify the specific needs, preferences and expectations of the stakeholders impacted by returning neuroimaging incidental findings to research participants.Methods: Six key stakeholder groups were identified to participate in focus group discussions at our active neuroimaging research facility: Participants, Parents of child participants, Investigators, Institutional Review Board (IRB) Members, Physicians and Community Members. A total of 151 subjects attended these discussions. Transcripts were analysed using principles of Grounded Theory and group consensus coding.Results: A series of similar and divergent themes were identified across our subject groups. Similarities included beliefs that it is ethical for researchers to disclose incidental findings as it grants certain health and emotional benefits to participants. All stakeholders also recognised the potential psychological and financial risks to disclosure. Divergent perspectives elucidated consistent differences between our 'Participant' subjects (Participants, Parents, Community Members) and our 'Professional' subjects (IRB Members, Investigators and Physicians). Key differences included (1) what results should be reported, (2) participants' autonomous right to research information and (3) the perception of the risk-benefit ratio in managing results.Conclusions: Understanding the perceived impact on all stakeholders involved in the process of disclosing incidental findings is necessary to determine appropriate research management policy. Our data further demonstrate the challenge of this task as different stakeholders evaluate the balance between risk and benefit related to their unique positions in this process. These findings offer some of the first qualitative insight into the expectations of the diverse stakeholders affected by incidental finding disclosure. [ABSTRACT FROM AUTHOR]

Objectives Disclosures of funding sources and conflicts of interests (COI) in published peer-reviewed journal articles have recently begun to receive some attention, but many critical questions remain, for example, how often such reporting occurs concerning research conducted in the developing world and what factors may be involved. Design Of all articles indexed in Medline reporting on human subject HIV research in 2007 conducted in four countries (India, Thailand, Nigeria and Uganda), this study explored how many disclosed a funding source and COI, and what factors are involved. Results Of 221 articles that met the criteria, 67.9% (150) disclosed the presence or absence of a funding source, but only 20% (44) disclosed COI. Studies from Uganda were more likely, and those from Nigeria were less likely to mention a funding source (p<0.001). Of articles in journals that had adopted International Committee of Medical Journal Editors (ICMJE) guidelines, 56% did not disclose COI. Disclosure of funding was more likely when: ≥50% of the authors and the corresponding author were from the sponsoring country, the sponsor country was the USA, and the articles were published in journals in which more of the editors were from the sponsoring countries. Conclusions Of the published studies examined, over a third did not disclose funding source (ie, whether or not there was a funding source) and 80% did not disclose whether COI existed. Most articles in ICMJE-affiliated journals did not disclose COI. These data suggest the need to consider alteration of policies to require that published articles include funding and COI information, to allow readers to assess articles as fully as possible. [ABSTRACT FROM AUTHOR]

This is an afterword to the JME symposium on the benefit/risk ratio challenge in clinical research, and the case of HIV cure. It notes implications of the symposium for research ethics in general. [ABSTRACT FROM AUTHOR]