Annette Rid

When making substituted judgments for incapacitated patients, surrogates often struggle to guess what the patient would want if they had capacity. Surrogates may also agonize over having the (sole) responsibility of making such a determination. To address such concerns, a Patient Preference Predictor (PPP) has been proposed that would use an algorithm to infer the treatment preferences of individual patients from population-level data about the known preferences of people with similar demographic characteristics. However, critics have suggested that even if such a PPP were more accurate, on average, than human surrogates in identifying patient preferences, the proposed algorithm would nevertheless fail to respect the patient’s (former) autonomy since it draws on the ‘wrong’ kind of data: namely, data that are not specific to the individual patient and which therefore may not reflect their actual values, or their reasons for having the preferences they do. Taking such criticisms on board, we here propose a new approach: the Personalized Patient Preference Predictor (P4). The P4 is based on recent advances in machine learning, which allow technologies including large language models to be more cheaply and efficiently ‘fine-tuned’ on person-specific data. The P4, unlike the PPP, would be able to infer an individual patient’s preferences from material (e.g., prior treatment decisions) that is in fact specific to them. Thus, we argue, in addition to being potentially more accurate at the individual level than the previously proposed PPP, the predictions of a P4 would also more directly reflect each patient’s own reasons and values. In this article, we review recent discoveries in artificial intelligence research that suggest a P4 is technically feasible, and argue that, if it is developed and appropriately deployed, it should assuage some of the main autonomy-based concerns of critics of the original PPP. We then consider various objections to our proposal and offer some tentative replies.

What is a just way of spending public resources for health and health care? Several significant answers to this question are under debate. Public spending could aim to promote greater equality in health, for example, or maximize the health of the population, or provide the worst off with the best possible health. Another approach is to aim for each person to have "enough" so that her health or access to health care does not fall under a critical level. This latter approach is called sufficientarian. Sufficientarian approaches to distributive justice are intuitively appealing, but require further analysis and assessment. What exactly is sufficiency? Why do we need it? What does it imply for the just distribution of health or healthcare? This volume offers fresh perspectives on these critical questions. Philosophers, bioethicists, health policy-makers, and health economists investigate sufficiency and its application to health and health care in fifteen original contributions.

This paper responds to the commentaries from Stacy Carter and Alan Cribb. We pick up on two main themes in our response. First, we reflect on how the process of setting standards for empirical bioethics research entails drawing boundaries around what research counts as empirical bioethics research, and we discuss whether the standards agreed in the consensus process draw these boundaries correctly. Second, we expand on the discussion in the original paper of the role and significance of the concept of ‘integrating’ empirical methods and ethical argument as a standard for research practice within empirical bioethics.

Background: Current practice relies on patient-designated and next-of-kin surrogates, in consultation with clinicians, to make treatment decisions for patients who lose the ability to make their own decisions. Yet there is a paucity of data on whether this approach is consistent with patients' preferences regarding who they want to make treatment decisions for them in the event of decisional incapacity. Methods: Self-administered survey of patients at a tertiary care center. Results: Overall, 1169 respondents completed the survey (response rate = 59.8%). Of the 229 respondents who had previously designated a surrogate, 78.2% wanted their surrogate to make treatment decisions in the event of decisional incapacity, whereas 21.8% wanted their doctors to make treatment decisions. Of the 822 respondents who had not designated a surrogate, 66.1% wanted their family to make treatment decisions, whereas 33.9% wanted their doctors to make treatment decisions. The most common explanation provided for why respondents wanted their surrogate or family to make treatment decisions for them in the event of decisional incapacity was the belief that loved ones knew the patient's treatment preferences. Conclusions: Contrary to current practice, 33.9% of respondents who had not designated a surrogate and 21.8% of those who had designated a surrogate indicated that they wanted their doctors to make treatment decisions for them in the event of decisional incapacity. Moreover, many of those who wanted their surrogates or family members to make treatment decisions explained this preference by citing a belief that loved ones knew the patient's treatment preferences. This belief is undermined by prior research that suggests that surrogates and family members frequently are unable to predict which treatments their charges would want. Future research should assess these two concerns with current practice and, where necessary, identify approaches to address them.

One of the key ethical requirements for biomedical research is that it have an acceptable risk-benefit profile (Emanuel, Wendler, and Grady 2000). The International Conference of Harmonization guidelines mandate that clinical trials should be initiated and continued only if “the anticipated benefits justify the risks” (1996). Guidelines from the Council for International Organizations of Medical Sciences state that biomedical research is acceptable only if the “potential benefits and risks are reasonably balanced” (2002). U.S. federal regulations require that the “risks to subjects” be “reasonable in relation to anticipated benefits, if any, to subjects and the importance of the knowledge” to be gained from the ..

Background: It is often claimed that a regulated kidney market would significantly reduce the kidney shortage, thus saving or improving many lives. Data are lacking, however, on how many people would consider selling a kidney in such a market. Methods: A survey instrument, developed to assess behavioural dispositions to and attitudes about a hypothetical regulated kidney market, was given to Swiss third-year medical students. Results: Respondents’ median age was 23 years. Their socioeconomic status was high or middle. 48 considered selling a kidney in a regulated kidney market, of whom 31 would sell only to overcome a particularly difficult financial situation. High social status and male gender was the strongest predictor of a disposition to sell. 32 of all respondents supported legalising a regulated kidney market. This attitude was not associated with a disposition to sell a kidney. 5 respondents endorsed a market and considered providing a kidney to a stranger if and only if paid. 4 of those 5 would sell only under financial duress. Conclusions: Current understanding of a regulated kidney market is insufficient. It is unclear whether a regulated market would result in a net gain of kidneys. Most possible kidney vendors would only sell in a particularly difficult financial situation, raising concerns about the validity of consent and inequities in the provision of organs. Further empirical and normative analysis of these issues is required. Any calls to implement and evaluate a regulated kidney market in pilot studies are therefore premature.

In controlled human infection (CHI) studies, investigators deliberately infect healthy individuals with pathogens in order to study mechanisms of disease or obtain preliminary efficacy data on investigational vaccines and medicines. CHI studies offer a fast and cost‐effective way of generating new scientific insights, prioritizing investigational products for clinical testing, and reducing the risk that large numbers of people are exposed to ineffective or harmful substances in research or in practice. Yet depending on the pathogen, CHI studies can involve significant risks or burdens for participants, pose risks to individuals or communities not involved in the research, and lead to public controversy. It is therefore essential to ensure that the risks of CHI studies are justified by their social value—that is, their potential to generate benefits for society—and that public trust can be maintained. In this paper, we aim to clarify how research sponsors, research ethics committees and other reviewers should judge the social value of CHI studies. We develop a list of relevant considerations for making social value judgments based on the standard view of social value. We then use this list to discuss the example of potentially conducting dengue virus CHI studies in endemic settings. We argue that dengue virus CHI studies in endemic settings would fall on the higher end of the spectrum of social value, mostly because of their potential to redirect all fields of future dengue research. Drawing on this discussion, we derive several general recommendations for how reviewers should judge the social value of CHI studies.

In controlled human infection studies (CHIs), participants are deliberately exposed to infectious agents in order to better understand the mechanism of infection or disease and test therapies or vaccines. While most CHIs have been conducted in high‐income countries, CHIs have recently been expanding into low‐ and middle‐income countries (LMICs). One potential ethical concern about this expansion is the challenge of obtaining the voluntary informed consent of participants, especially those who may not be literate or have limited education. In some CHIs in LMICs, researchers have attempted to address this potential concern by limiting access to literate or educated populations. In this paper, we argue that this practice is unjustified, as it does not increase the chances of obtaining valid informed consent and therefore unfairly excludes illiterate populations and populations with lower education. Instead, we recommend that investigators improve the informed consent process by drawing on existing data on obtaining informed consent in these populations and interventions aimed at improving their understanding. Based on a literature review, we provide concrete suggestions for how to follow this recommendation and ensure that populations with lower literacy or education are given a fair opportunity to protect their rights and interests in the informed consent process.

Several influential ethical guidelines and frameworks endorse the view that research with human participants is ethically acceptable only when it has “social value,” meaning that it generates knowledge which can be used to benefit society. For example, the Nuremberg Code requires that medical experiments on human beings “yield fruitful results for the good of society, unprocurable by other methods or means of study”. The Council for International Organizations of Medical Sciences guidelines hold that “health-related research with humans... must have social value” or the “prospect of generating the knowledge and the means necessary to protect and promote people’s health” (CIOMS...

Existing ethical frameworks for public health provide insufficient guidance on how to evaluate the risks of public health programs that compromise the best clinical interests of present patients for the benefit of others. Given the relevant similarity of such programs to clinical research, we suggest that insights from the long‐standing debate about acceptable risk in clinical research can helpfully inform and guide the evaluation of risks posed by public health programs that compromise patients’ best clinical interests. We discuss how lessons learned regarding the ethics of risk in one context can be fruitfully transferred to the other, using the example of a so‐called ‘rational antibiotic use’ guideline that limits antimicrobial prescribing in order to curb antimicrobial resistance.

What is a just way of spending public resources for health and health care? Several significant answers to this question are under debate. Public spending could aim to promote greater equality in health, for example, or maximize the health of the population, or provide the worst off with the best possible health. Another approach is to aim for each person to have "enough" so that her health or access to health care does not fall under a critical level. This latter approach is called sufficientarian. Sufficientarian approaches to distributive justice are intuitively appealing, but require further analysis and assessment. What exactly is sufficiency? Why do we need it? What does it imply for the just distribution of health or healthcare? This volume offers fresh perspectives on these critical questions. Philosophers, bioethicists, health policy-makers, and health economists investigate sufficiency and its application to health and health care in fifteen original contributions.

A new problem in health care priority‐setting is currently emerging for wealthy countries: what should be done when a new drug is considered cost effective but implementing it would still be unaffordable? The standard approach to setting priorities in health care rests on cost effectiveness. This approach is now being tested by new drugs that are highly effective but very costly. Because they are so effective, these drugs deliver “value for money” despite their high cost. However, when the targeted condition affects a sizeable number of patients, implementing the drugs becomes unaffordable. There are no easy alternatives. A key virtue of setting health care priorities with a presumptive cost‐effectiveness threshold is that it provides all patients a prima facie equal claim on the available resources, and alternative approaches to addressing affordability face their own challenges.

One of the fundamental ethical concerns about biomedical research is that it frequently exposes participants to risks for the benefit of others. To protect participants’ rights and interests in this context, research regulations and guidelines set out a mix of substantive and procedural requirements for research involving humans. Risk thresholds play an important role in formulating both types of requirements. First, risk thresholds serve to set upper risk limits in certain types of research. Second, risk thresholds serve to demarcate risk categories that streamline risk-adapted systems of ethical oversight. But although risk thresholds play such an important role in research governance, there is a need both to better define the existing risk thresholds and to delineate new thresholds in order to develop more risk-adapted systems of research oversight. The present paper examines the existing minimal risk threshold and the surrounding debates with the goal of deriving a systematic approach to setting thresholds of research risk.

In his stimulating target article, 1 Philippe Calain discusses how the traditional ethical framework for clinical research was challenged during the 2013–2016 Ebola epidemic in West Africa. One of his key claims is that conventional research ethics did not have the resources to address the ‘profound tension’ 1, between individual and public interests in clinical research during this epidemic. I agree with this claim, but would like to provide a modified argument in its support. As Calain points out, although a tension between individual and public interests in clinical research always exists, this tension was heightened during the Ebola epidemic. Ebola had an average fatality rate of 40%–60% in this outbreak and reached up to 90% in some locations. Appropriate personal protective equipment was not always available; the level of benefit from supportive care was contested; and there were no targeted treatments and vaccines for the...

In his stimulating target article,1 Philippe Calain discusses how the traditional ethical framework for clinical research was challenged during the 2013–2016 Ebola epidemic in West Africa. One of his key claims is that conventional research ethics did not have the resources to address the ‘profound tension’1, between individual and public interests in clinical research during this epidemic. I agree with this claim, but would like to provide a modified argument in its support. As Calain points out, although a tension between individual and public interests in clinical research always exists, this tension was heightened during the Ebola epidemic. Ebola had an average fatality rate of 40%–60% in this outbreak and reached up to 90% in some locations. Appropriate personal protective equipment was not always available; the level of benefit from supportive care was contested; and there were no targeted treatments and vaccines for the disease. Given this situation, patients with Ebola had a strong interest in accessing potential treatments even if they were unproven. This was especially true in the early phases of the epidemic when fatality rates were very high and seemingly safe ‘repurposed’ treatments were proposed for study. Individuals at high risk of contracting Ebola—for example, frontline workers or informal carers in the community—equally had a strong interest in accessing experimental vaccines, once their safety and ability to induce an immune response had been established in phase 1/2 testing. At the same time, the exponential spread of Ebola in the second half of 2014 created a strong public interest in rigorous research results that could support the rapid marketing authorization, mass production and widespread implementation of any proven effective treatments or vaccines, as well …

The current ethical and regulatory framework for research is often charged with burdening investigators and impeding socially valuable research. To address these concerns, a growing number of research ethicists argue that informed consent should be adapted to the risks of research participation. This would require less rigorous consent standards in low-risk research than in high-risk research. However, the current discussion is restricted to cases of research in which the risks of research participation are outweighed by the potential clinical benefits for the individual research participant. Furthermore, current proposals do not address the worry that risk-adapted informed consent may result in enrolling participants into research without their autonomous authorization. In this paper, we show how the standard view of informed consent – consent as autonomous authorization – can be adapted to risk even when the research does not have a favourable risk-benefit profile for the participant. Our argument has two important implications: first, it implies that current and proposed consent standards are not adequately calibrated to risk and, second, that consent standards also need to be adapted to factors other than risk.

The standard approach to treatment decision making for incapacitated patients often fails to provide treatment consistent with the patient’s preferences and values and places significant stress on surrogate decision makers. These shortcomings provide compelling reason to search for methods to improve current practice. Shared decision making between surrogates and clinicians has important advantages, but it does not provide a way to determine patients’ treatment preferences. Hence, shared decision making leaves families with the stressful challenge of identifying the patient’s preferred treatment option. To address this concern, the present paper proposes to incorporate the use of a “Patient Preference Predictor” (PPP) into the shared decision-making process between surrogates and clinicians. A PPP would predict which treatment option a given incapacitated patient would most likely prefer, based on the individual’s characteristics and information on what treatment preferences are correlated with these characteristics. Use of a PPP is likely to increase the chances that incapacitated patients are treated consistent with their preferences and values and might reduce the stress and burden on their surrogates. Including a PPP in the shared decision-making process therefore has the potential to realize important ethical goals for making treatment decisions for incapacitated patients. The present paper justifies this approach on conceptual and normative grounds

Norman Daniels’ theory of justice and health faces a serious practical problem: his theory can ground the special moral importance of health and allows distinguishing just from unjust health inequalities, but it provides little practical guidance for allocating resources when they are especially scarce. Daniels’ solution to this problem is a fair process that he specifies as "accountability for reasonableness". Daniels claims that accountability for reasonableness makes limit-setting decisions in healthcare not only legitimate, but also fair. This paper assesses the latter claim. Does accountability for reasonableness result in fair limit-setting decisions? It is argued that the answer to this question is not a clear yes. Daniels is remarkably unclear about the criterion of fairness that accountability for reasonableness satisfies. The paper discusses different options for resolving this lack of clarity and examines how they apply to Daniels’ accountability for reasonableness framework. It is concluded, first, that accountability for reasonableness is not a paradigm case of any of the classic notions of procedural justice; second, that what might be called "constrained pure procedural justice" best reflects how accountability for reasonableness results in fair limit-setting decisions; and third, that the procedural conditions of accountability for reasonableness must be further specified and amended to better achieve a fair process, and hence fair limit-setting decisions.

The World Medical Association's Declaration of Helsinki is one of the most important and influential international research ethics documents. Launched in 1964, when ethical guidance for research was scarce, the Declaration comprised eleven basic principles and provisions on clinical research. The document has since evolved to a complex set of principles, norms, and directions for action of varying degrees of specificity, ranging from specific rules to broad aspirational statements. It has been revised six times in an effort to maintain its influence. While all revisions were the result of vigorous debate, the 2000 revision and two subsequent notes of clarification spurred particular controversy surrounding the use of placebo in clinical research and the standard of care and post-trial obligations in research in developing countries. Several institutions opted to cite earlier versions of the Declaration, and the U.S. Food and Drug Administration recently removed all reference to the Declaration in its approval requirements for drugs and biological products that are studied outside the United States.

The use of prisoners as research participants is controversial. Efforts to protect them in response to past exploitation and abuse have led to strict regulations and reluctance to involve them as participants. Hence, prisoners are routinely denied the opportunity to participate in research. In the absence of comprehensive information regarding prisoners’ current involvement in research, we examined UK prisoners’ involvement through review of research applications to the UK National Research Ethics Service. We found that prisoners have extremely limited access to research participation. This analysis was augmented by a survey of those involved in research and research governance (UK researchers and Research Ethics Committee members). Our results suggest that pragmatic concerns regarding the perceived burden of including prisoners are far more prominent in motivating their exclusion than ethical concerns or knowledge of regulations. While prisoners may remain a vulnerable research population due to constraints upon their liberty and autonomy and the coercive nature of the prison environment, routine exclusion from participation may be disadvantageous. Rigorous ethical oversight and the shift in the prevailing attitude towards the risks and benefits of participation suggest that it may be time for research to be more accessible to prisoners in line with the principle of equivalence in prison healthcare. We suggest the necessary first step in this process is a re-examination of current guidance in the UK and other countries with exclusions.