Depression is a widespread and debilitating disorder, but developing effective treatments has proven challenging. Despite success in animal models, many treatments fail in human trials. While various factors contribute to this translational failure, standardization practices in animal research are often overlooked. This paper argues that certain standardization choices in behavioral neuroscience research on depression can limit the generalizability of results from rodents to humans. This raises ethical and scientific concerns, including animal waste and a lack of progress in treating human (...) patients. To address these issues, animal ethics committees can establish reasonable expectations for preclinical research and highlight the impact of standardization on generalizability. Such efforts can help improve translation from animal models to human patients and ultimately benefit those suffering from depression. (shrink)

Biomarker-based predictive tests for subjectively asymptomatic Alzheimer’s disease (AD) are utilized in research today. Novel applications of artificial intelligence (AI) promise to predict the onset of AD several years in advance without determining biomarker thresholds. Until now, little attention has been paid to the new ethical challenges that AI brings to the early diagnosis in asymptomatic individuals, beyond contributing to research purposes, when we still lack adequate treatment. The aim of this paper is to explore the ethical arguments put forward (...) for AI aided AD prediction in subjectively asymptomatic individuals and their ethical implications. The ethical assessment is based on a systematic literature search. Thematic analysis was conducted inductively of 18 included publications. The ethical framework includes the principles of autonomy, beneficence, non-maleficence, and justice. Reasons for offering predictive tests to asymptomatic individuals are the right to know, a positive balance of the risk-benefit assessment, and the opportunity for future planning. Reasons against are the lack of disease modifying treatment, the accuracy and explicability of AI aided prediction, the right not to know, and threats to social rights. We conclude that there are serious ethical concerns in offering early diagnosis to asymptomatic individuals and the issues raised by the application of AI add to the already known issues. Nevertheless, pre-symptomatic testing should only be offered on request to avoid inflicted harm. We recommend developing training for physicians in communicating AI aided prediction. (shrink)

Animal research has long been a source of biomedical aspirations and moral concern. Examples of both hope and concern are abundant today. In recent months, as is common practice, monkeys have served as test subjects in promising preclinical trials for an Ebola vaccine or treatment 1 , 2 , 3 and in controversial maternal deprivation studies. 4 The unresolved tension between the noble aspirations of animal research and the ethical controversies it often generates motivates the present issue of the (...) Cambridge Quarterly of Healthcare Ethics. As editors of this special section, we hope that these original and timely articles will push the professional discussion of animal research ethics in a positive direction that will benefi t research scientists and others interested in moral problems in animal research. We also look forward to a day when animal research will genuinely meet both appropriate scientifi c and appropriate ethical criteria—criteria that themselves can be improved by critical scrutiny. Animal research—that is, the use of live animals as experimental subjects in biomedical and behavioral fi elds of learning—has been deeply entrenched for well over half a century. One signal development was the enactment in the late 1930s of federal product safety legislation in the United States and other nations that required animal testing of food, drugs, and medical devices prior to use by human subjects or consumers. 5 Another development was the publication of codes of research ethics that called for animal research prior to human research. The Nuremberg Code, published by an American military tribunal in 1947–48 after scrutiny of Nazi medical atrocities, stated that experiments involving the use of human subjects should be " based on the results of animal experimentation. " 6 The Declaration of Helsinki, fi rst published in 1964, reaffi rmed this assumption and added, rather imprecisely, that " the welfare of animals used for research must be respected. " 7 Against the background of such statements, the institutionalization and widespread acceptance of animal research in the twentieth century rested on two basic assumptions, one factual and one moral. The factual assumption was that animal research is suffi ciently reliable as a basis for predicting the effects of drugs, products, and other materials on human beings that animal trials can be expected to yield signifi cant scientifi c conclusions and medical benefi ts to humanity. (shrink)

Translation failure occurs when a treatment shown to be safe and effective in one type of population does not produce the same result in another. We are currently in a crisis involving the translatability of preclinical studies to human populations. Animal trials are no better than a coin toss at predicting the safety and efficacy of drugs in human trials, and the high failure rate of drugs entering human trials suggests that most of the suffering of laboratory animals is (...) futile, creating no commensurate benefit for human patients. Here, I argue that animal ethics committees have a role to play in getting us out of this crisis. Inadequate representation is a known contributor to translation failures and is a matter of both scientific and ethical concern. Ethical review committees have the authority to address it by reprioritising the values already enshrined in their guiding principles. (shrink)