Ethical issues in two parallel trials of personalised criteria for implantation of implantable cardioverter defibrillators for primary prevention: the PROFID project-a position paper.

AIM: To discuss ethical issues related to a complex study (PROFID) involving the development of a new, partly artificial intelligence-based, prediction model to enable personalised decision-making about the implantation of an implantable cardioverter defibrillator (ICD) in postmyocardial infarction patients, and a parallel non-inferiority and superiority trial to test decision-making informed by that model. METHOD: The position expressed in this paper is based on an analysis of the PROFID trials using concepts from high-profile publications in the ethical literature. RESULTS: We identify ethical issues related to the testing of the model in the treatment setting, and to both the superiority and the non-inferiority trial. We underline the need for ethical-empirical studies about these issues, also among patients, as a parallel to the actual trials. The number of ethics committees involved is an organisational, but also an ethical challenge. CONCLUSION: The PROFID trials, and probably other studies of similar scale and complexity, raise questions that deserve dedicated parallel ethics and social science research, but do not constitute a generic obstacle. A harmonisation procedure, comparable to the Voluntary Harmonization Procedure (VHP) for medication trials, could be needed for this type of trials.

Family and Community Medicine and its role in preventing health overuse (preventive, diagnostic, therapeutic and rehabilitative). / Medicina de Familia y Comunidad y su papel en evitar los excesos sanitarios (preventivos, diagnósticos, terapéuticos y rehabilitadores).

In Medicine, it is critical "to offer 100% of what is needed and avoid 100% of what is not needed." Unfortunately, this primary issue is challenging, and generally, more than required is offered, and everything that is unnecessary is not avoided. This is a nonsystematic review with a teaching objective that reviews the general issue in primary care and suggests ways to avoid overuse and shortcomings concerning preventive, diagnostic, therapeutic, and rehabilitative interventions. Knowing not to do is science and art that is hardly taught and practiced less. The overuse that harm are an almost daily part of clinical practice in prevention, diagnosis, treatment, and rehabilitation. It is essential to promote "the art and science of not doing".

En Medicina es clave "ofrecer el 100% de lo que se precisa y evitar el 100% de lo que no se precisa". Lamentablemente, es difícil cumplir con esta cuestión clave y generalmente se ofrece más de lo que se precisa y no se evita todo lo que no se precisa. Este texto es una revisión no sistemática con objetivo docente en que se revisa el problema general en atención primaria y se proponen formas de evitar los excesos y defectos respecto a intervenciones preventivas, diagnósticas, terapéuticas y de rehabilitación. Saber no hacer es ciencia y arte que se enseña poco y se practica menos. Los excesos que dañan son parte casi diaria de la práctica clínica, en prevención, diagnóstico, tratamiento y rehabilitación. Es imprescindible fomentar "el arte y la ciencia de no hacer".

Medicina de Familia y Comunidad y su papel en evitar los excesos sanitarios (preventivos, diagnósticos, terapéuticos y rehabilitadores) / Family and Community Medicine and its role in preventing health overuse (preventive, diagnostic, therapeutic and rehabilitative)

Resumen En Medicina es clave "ofrecer el 100% de lo que se precisa y evitar el 100% de lo que no se precisa". Lamentablemente, es difícil cumplir con esta cuestión clave y generalmente se ofrece más de lo que se precisa y no se evita todo lo que no se precisa. Este texto es una revisión no sistemática con objetivo docente en que se revisa el problema general en atención primaria y se proponen formas de evitar los excesos y defectos respecto a intervenciones preventivas, diagnósticas, terapéuticas y de rehabilitación. Saber no hacer es ciencia y arte que se enseña poco y se practica menos. Los excesos que dañan son parte casi diaria de la práctica clínica, en prevención, diagnóstico, tratamiento y rehabilitación. Es imprescindible fomentar "el arte y la ciencia de no hacer".

Abstract In Medicine, it is critical "to offer 100% of what is needed and avoid 100% of what is not needed." Unfortunately, this primary issue is challenging, and generally, more than required is offered, and everything that is unnecessary is not avoided. This is a nonsystematic review with a teaching objective that reviews the general issue in primary care and suggests ways to avoid overuse and shortcomings concerning preventive, diagnostic, therapeutic, and rehabilitative interventions. Knowing not to do is science and art that is hardly taught and practiced less. The overuse that harm are an almost daily part of clinical practice in prevention, diagnosis, treatment, and rehabilitation. It is essential to promote "the art and science of not doing".

Genetic Protection Modifications: Moving Beyond the Binary Distinction Between Therapy and Enhancement for Human Genome Editing.

The current debate and policy surrounding the use of genome editing in humans typically relies on a binary distinction between therapy and human enhancement. Here, we argue that this dichotomy fails to take into account perhaps the most significant potential uses of CRISPR-Cas9 genome editing in humans. We argue that genetic treatment of sporadic Alzheimer's disease, breast and ovarian cancer predisposing BRCA1/2 mutations, and the introduction of human immunodeficiency virus resistance in humans should be considered within a new category of genetic protection treatments. We suggest that if this category is not introduced, life-altering research might be unnecessarily limited by current or future policy. Otherwise ad hoc decisions might be made, which introduce a risk of unforeseen moral costs, and might overlook or fail to address some important opportunities.

Research participants' preferences for receiving genetic risk information: a discrete choice experiment.

PURPOSE: This study aims to determine research participants' preferences for receiving genetic risk information when participating in a scientific study that uses genome sequencing. METHODS: A discrete choice experiment questionnaire was sent to 650 research participants (response rate 60.5%). Four attributes were selected for the questionnaire: type of disease, disease penetrance probability, preventive opportunity, and effectiveness of the preventive measure. Panel mixed logit models were used to determine attribute level estimates and the heterogeneity in preferences. Relative importance of the attribute and the predicted uptake for different information scenarios were calculated from the estimates. In addition, this study estimates predicted uptake for receiving genetic risk information in different scenarios. RESULTS: All characteristics influenced research participants' willingness to receive genetic risk information. The most important characteristic was the effectiveness of the preventive opportunity. Predicted uptake ranged between 28% and 98% depending on what preventive opportunities and levels of effectiveness were presented. CONCLUSION: Information about an effective preventive measure was most important for participants. They valued that attribute twice as much as the other attributes. Therefore, when there is an effective preventive measure, risk communication can be less concerned with the magnitude of the probability of developing disease.

[Elaboration of prevention norms: Need for ethical reflection]. / Élaboration des normes de prévention : une réflexion éthique nécessaire.

INTRODUCTION: Public health tries to modify existing social norms by setting up strategies to promote the emergence of norms that are more adapted to the objectives of good health and well-being. Prevention policies and the corresponding interventions concern health behaviours and are designed to modify the individual's habits, and contribute to defining new ways of being, acting and living. Prevention therefore involves numerous personal, cultural, social and collective values. An ethical reflection concerning the meaning, rationale and justice of these actions is therefore essential. The objective of this study is to characterize the ethical reflection at the time of creation of public health norms. METHODS: A narrative review, based on the Web of Science database covering journals of the various disciplines concerned, was conducted to address this issue. RESULTS: Thirty-four publications were selected, illustrating the numerous definitions and types of norms used in public health intervention strategies. Many stakeholders are involved in the creation of public health norms specialists, opinion leaders, and social stakeholders. Finally, although some publications stress that the use of prevention norms raises a number of ethical issues, no publication refers to the presence of a structured ethical reflection as part of this process. CONCLUSION: Ethical reflection is an essential part of prevention interventions and tools. What is the best way of achieving the best results? How to resolve conflicts of interests? These issues must be addressed when developing policies or programmes and can more effectively guide public health strategies and help to improve their acceptability and efficacy in populations.

Ethical Approach to Prevention of Schizophrenia - Concepts and Challenges.

Patients with schizophrenia, nowadays chronic, frequently disabling mental disorder, get initial treatment after detection of a psychotic episode, seemingly late, potentially preventable stage of illness. As our knowledge about the nature of schizophrenia and other diseases of the spectrum is growing, so are the early interventions becoming more possible, and it is important to conceptualize the clinical, legal and moral issues emerging with new preventive treatments. Every intervention, especially in pre-clinical population, demands a careful risk-benefit assessment and having basic bioethical principles - primacy of patient's welfare, beneficience/non-maleficience, autonomy and justice - in mind. We believe that pharmacological treatments, considering today's drugs safety and effectiveness profiles, should stay reserved for cases with higly probable negative outcomes to patient's wellbeing, and that all other low-risk interventions, like psychosocial treatments, should be considered for reducing the conversion to disorder, if possible, or relieving the distress in vulnerable persons, when such vulnerability gets detected. How to recognize persons at risk before the start of the disorder, without missing the majority of cases or burdening healthy persons with stigma, is another challenge and not only mental health professionals should be included in finding the solutions. The broadest public, and especially the experts that will build the safety-net for the at-risk individuals, should get best possible appropriate education about the schizophrenia in order to stigmatize less and help more.

The evolution of public health ethics frameworks: systematic review of moral values and norms in public health policy.

Given the evolution of the public health (PH) and the changes from the phenomenon of globalization, this area has encountered new ethical challenges. In order to find a coherent approach to address ethical issues in PH policy, this study aimed to identify the evolution of public health ethics (PHE) frameworks and the main moral values and norms in PH practice and policy. According to the research questions, a systematic search of the literature, in English, with no time limit was performed using the main keywords in databases Web of Science (ISI) and PubMed. Finally, the full text of 56 papers was analyzed. Most of the frameworks have common underpinning assumptions and beliefs, and the need to balance PH moral obligation to prevent harm and health promotion with respect for individual autonomy has been specified. As such, a clear shift from liberal values in biomedical ethics is seen toward the community's collective values in PHE. The main moral norms in PH practice and policy included protecting the population against harm and improving PH benefits, utility and evidenced-based effectiveness, distributive justice and fairness, respect for all, privacy and confidentiality, solidarity, social responsibility, community empowerment and participation, transparency, accountability and trust. Systematic review of PHE frameworks indicates utilization of the aforementioned moral norms through an practical framework as an ethical guide for action in the PH policy. The validity of this process requires a systematic approach including procedural conditions.

Improving prevention, monitoring and management of diabetes among ethnic minorities: contextualizing the six G's approach.

OBJECTIVE: People from Black, Asian and Minority Ethnic (BAME) groups are known to have an increased risk of developing diabetes and face greater barriers to accessing healthcare resources compared to their 'white British' counterparts. The extent of these barriers varies by demographics and different socioeconomic circumstances that people find themselves in. The purpose of this paper is to present and discuss a new framework to understand, disentangle and tackle these barriers so that improvements in the effectiveness of diabetes interventions for BAME communities can be achieved. RESULTS: The main mediators of lifestyle behavioural change are gender, generation, geography, genes, God/religion, and gaps in knowledge and economic resources. Dietary and cultural practices of these individuals significantly vary according to gender, generation, geographical origin and religion. Recognition of these factors is essential in increasing knowledge of healthy eating, engagement in physical activity and utilisation of healthcare services. Use of the six G's framework alongside a community centred approach is crucial in developing and implementing culturally sensitive interventions for diabetes prevention and management in BAME communities. This could improve their health outcomes and overall wellbeing.

What is a good health check? An interview study of health check providers' views and practices.

BACKGROUND: Health checks identify (risk factors for) disease in people without symptoms. They may be offered by the government through population screenings and by other providers to individual users as 'personal health checks'. Health check providers' perspective of 'good' health checks may further the debate on the ethical evaluation and possible regulation of these personal health checks. METHODS: In 2015, we interviewed twenty Dutch health check providers on criteria for 'good' health checks, and the role these criteria play in their practices. RESULTS: Providers unanimously formulate a number of minimal criteria: Checks must focus on (risk factors for) treatable/preventable disease; Tests must be reliable and clinically valid; Participation must be informed and voluntary; Checks should provide more benefits than harms; Governmental screenings should be cost-effective. Aspirational criteria mentioned were: Follow-up care should be provided; Providers should be skilled and experienced professionals that put the benefit of (potential) users first; Providers should take time and attention. Some criteria were contested: People should be free to test on any (risk factor for) disease; Health checks should only be performed in people at high risk for disease that are likely to implement health advice; Follow up care of privately funded tests should not drain on collective resources. Providers do not always fulfil their own criteria. Their reasons reveal conflicts between criteria, conflicts between criteria and other ethical values, and point to components in the (Dutch) organisation of health care that hinder an ethical provision of health checks. Moreover, providers consider informed consent a criterion that is hard to establish in practice. CONCLUSIONS: According to providers, personal health checks should meet the same criteria as population screenings, with the exception of cost-effectiveness. Providers do not always fulfil their own criteria. Results indicate that in thinking about the ethics of health checks potential conflicts between criteria and underlying values should be explicated, guidance in weighing of criteria should be provided and the larger context should be taken into account: other actors than providers need to take up responsibility, and ideally benefits and harms of health checks should be weighed against other measures targeting (risk factors for) disease.

Eliminating latent tuberculosis in low-burden settings: are the principal beneficiaries to be disadvantaged groups or the broader population?

Tuberculosis (TB) remains a leading cause of morbidity and mortality worldwide, and the burdens of this disease continue to track prior disadvantage. In order to galvanise a coordinated global response, WHO has recently launched the End TB Campaign that aims to eliminate TB by 2050. Key to this is the introduction of population screening programmes in low-burden settings to identify and treat people who have latent TB infection (LTBI). The defining features of LTBI are: that it is not an active disease but confers an increased risk of disease; the socially disadvantaged are those most in danger and uncertainty persists as to who will be harmed or benefitted from screening-led prophylactic interventions. Systematic screening programmes that include surveillance, case-finding and treatment of asymptomatic individuals inevitably redistribute the risk of harms and the potential for benefits within a population. The extent to which those targeted within such programmes should be exposed to higher levels of risk in the pursuit of individual or community benefits requires careful consideration prior to implementation. As currently construed, it remains unclear who stands to benefit most from how LTBI screening in high-income countries is being organised, and whose health is being prioritised: members of disadvantaged groups or the broader community. Unless the aims of LTBI screening programmes in these settings are made transparent and their prioritisation ethically justified, there is a significant danger that such a targeted intervention will further disadvantage those who have the least capacity to bear the burdens of TB elimination.

Social values and the corruption argument against financial incentives for healthy behaviour.

Financial incentives may provide a way of reducing the burden of chronic diseases by motivating people to adopt healthy behaviours. While it is still uncertain how effective such incentives could be for promoting health, some argue that, even if effective, there are ethical objections that preclude their use. One such argument is made by Michael Sandel, who suggests that monetary transactions can have a corrupting effect on the norms and values that ordinarily regulate exchange and behaviour in previously non-monetised contexts. In this paper, I outline Sandel's corruption argument and consider its validity in the context of health incentives. I distinguish between two forms of corruption that are implied by Sandel's argument: efficiency corruption and value corruption While Sandel's thought-provoking discussion provides a valuable contribution to debates about health policies generally and health incentives specifically, I suggest the force of his criticism of health incentives is limited: further empirical evidence and theoretical reasoning are required to support the suggestion that health incentives are an inappropriate tool for promoting health. While I do not find Sandel's corruption argument compelling, this only constitutes a partial defence of health incentives, since other criticisms relating to their use may prove more successful.

HIV transmission law in the age of treatment-as-prevention.

Evidence that treating people with HIV early in infection prevents transmission to sexual partners has reframed HIV prevention paradigms. The resulting emphasis on HIV testing as part of prevention strategies has rekindled the debate as to whether laws that criminalise HIV transmission are counterproductive to the human rights-based public health response. It also raises normative questions about what constitutes 'safe(r) sex' if a person with HIV has undetectable viral load, which has significant implications for sexual practice and health promotion. This paper discusses a recent high-profile Australian case where HIV transmission or exposure has been prosecuted, and considers how the interpretation of law in these instances impacts on HIV prevention paradigms. In addition, we consider the implications of an evolving medical understanding of HIV transmission, and particularly the ability to determine infectiousness through viral load tests, for laws that relate to HIV exposure (as distinct from transmission) offences. We conclude that defensible laws must relate to appreciable risk. Given the evidence that the transmissibility of HIV is reduced to negligible level where viral load is suppressed, this needs to be recognised in the framing, implementation and enforcement of the law. In addition, normative concepts of 'safe(r) sex' need to be expanded to include sex that is 'protected' by means of the positive person being virally suppressed. In jurisdictions where use of a condom has previously mitigated the duty of the person with HIV to disclose to a partner, this might logically also apply to sex that is 'protected' by undetectable viral load.

Participant selection for preventive Regenerative Medicine trials: ethical challenges of selecting individuals at risk.

The innovative field of Regenerative Medicine (RM) is expected to extend the possibilities of prevention or early treatment in healthcare. Increasingly, clinical trials will be developed for people at risk of disease to investigate these RM interventions. These individuals at risk are characterised by their susceptibility for developing clinically manifest disease in future due to the existence of degenerative abnormalities. So far, there has been little debate about the ethical appropriateness of including such individuals at risk in clinical trials. We discuss three main challenges of selecting this participant model for testing RM interventions: the challenge of achieving a proportional risk-benefit balance; complexities in the trial design in terms of follow-up and sample size; and the difficulty of obtaining informed consent due to the many uncertainties. We conclude that selecting the model is not ethically justifiable for first-in-man trials with RM interventions due to the high risks and uncertainties. However, the model can be ethically appropriate for testing the efficacy of RM interventions under the following conditions: interventions should be low risk; the degenerative abnormalities (and other risk factors) should be strongly related with disease within a short time frame; robust preclinical evidence of efficacy needs to be present; and the informed consent procedure should contain extra safeguards with regard to communication on uncertainties.

Looking for Trouble: Preventive Genomic Sequencing in the General Population and the Role of Patient Choice.

Advances in genomics have led to calls for developing population-based preventive genomic sequencing (PGS) programs with the goal of identifying genetic health risks in adults without known risk factors. One critical issue for minimizing the harms and maximizing the benefits of PGS is determining the kind and degree of control individuals should have over the generation, use, and handling of their genomic information. In this article we examine whether PGS programs should offer individuals the opportunity to selectively opt out of the sequencing or analysis of specific genomic conditions (the menu approach) or whether PGS should be implemented using an all-or-nothing panel approach. We conclude that any responsible scale-up of PGS will require a menu approach that may seem impractical to some, but that draws its justification from a rich mix of normative, legal, and practical considerations.

Clinical Trial Design for HIV Prevention Research: Determining Standards of Prevention.

This article seeks to advance ethical dialogue on choosing standards of prevention in clinical trials testing improved biomedical prevention methods for HIV. The stakes in this area of research are high, given the continued high rates of infection in many countries and the budget limitations that have constrained efforts to expand treatment for all who are currently HIV-infected. New prevention methods are still needed; at the same time, some existing prevention and treatment interventions have been proven effective but are not yet widely available in the countries where they most urgently needed. The ethical tensions in this field of clinical research are well known and have been the subject of extensive debate. There is no single clinical trial design that can optimize all the ethically important goals and commitments involved in research. Several recent articles have described the current ethical difficulties in designing HIV prevention trials, especially in resource limited settings; however, there is no consensus on how to handle clinical trial design decisions, and existing international ethical guidelines offer conflicting advice. This article acknowledges these deep ethical dilemmas and moves beyond a simple descriptive approach to advance an organized method for considering what clinical trial designs will be ethically acceptable for HIV prevention trials, balancing the relevant criteria and providing justification for specific design decisions.