A Personalized Patient Preference Predictor for Substituted Judgments in Healthcare: Technically Feasible and Ethically Desirable.

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.

Precarious hope: Ethical considerations for offering experimental fetal therapies outside of research after initial studies in humans.

OBJECTIVE: Risks and benefits of experimental fetal therapies can remain uncertain after initial clinical studies, especially long-term effects. Nevertheless, pregnant individuals may request them, hoping to benefit their future child. Guidance about offering experimental fetal therapies outside research (as "innovative therapy") is limited, despite their ethical complexity. We propose points for clinicians and reviewers to consider when deciding whether and how to offer experimental fetal therapies as innovative therapies after initial clinical studies. METHOD: We used conceptual analysis and a current case to develop points for consideration, grounded in broader debates on innovative therapy and the unique challenges associated with experimental fetal therapies. RESULTS: Clinicians should evaluate whether offering experimental fetal therapies as innovative therapy is appropriate for a pregnant individual and their fetus. The anticipated risk-benefit ratio for the fetus should be favorable. For the pregnant individual, risks may outweigh benefits, within reasonable limits. Medical resources should be sufficient to ensure appropriate care. Clinicians should support pregnant individuals in making informed choices. Clinicians offering innovative therapies with more than minimal risk should collect and report data on outcomes. Independent review should take place. CONCLUSION: Considering these points may advance the interests of fetuses, future children, and their families.

The Ethics of Conscientious Objection to Teaching Physician-Assisted Death.

The literature on the ethics of conscientious objection focuses on objections to participating in morally contested practices. This literature emphasizes the potential for participation to undermine objecting clinicians' moral integrity. Significantly less attention has been given to conscientious objection to teaching morally contested practices. Thus, it is unclear whether teaching morally contested practices has the potential to undermine objecting educators' moral integrity, and to the extent that it does, what steps can be taken to address this concern. We accordingly examine the ethics of conscientious objection to teaching morally contested practices, with a focus on teaching physician-assisted death (PAD) to trainees in US palliative care programs. We focus on three primary components of teaching PAD: (1) teaching the history and context of PAD; (2) teaching trainees how to understand and respond to requests for PAD; and (3) teaching trainees how to provide PAD. We argue that teaching components one and two has little potential to undermine objecting educators' moral integrity. Moreover, permitting objecting educators to opt out of teaching components one and two might undermine the education of trainees. In contrast, allowing objecting educators to opt out of teaching how to provide PAD may be important to preserving their moral integrity, and is unlikely to undermine trainees' education. We argue that educators should be permitted to opt out of teaching trainees how to provide PAD and describe policies that training programs can adopt to implement this approach.

Response to commentaries: 'autonomy-based criticisms of the patient preference predictor'.

The authors respond to four JME commentaries on their Feature Article, 'Autonomy-based criticisms of the patient preference predictor'.

Views of IRB members regarding phase 1 pediatric oncology trials.

There is significant debate over whether phase 1 pediatric oncology trials are ethical and approvable. We thus surveyed IRB members to answer four questions. First, do IRB members think the potential medical benefits of average phase 1 pediatric oncology trials justify the risks? Second, do they think these trials are ethically appropriate? Third, do they think these trials are approvable? Fourth, how do the views of IRB members on the first two questions compare to the views of the US public? Of the 80 respondents who answered the test questions correctly, 18.8% stated that the potential medical benefits of average phase 1 pediatric oncology trials outweigh the risks, 32.5% stated that the potential medical benefits and risks are about equal, and 48.8% stated that the risks outweigh the potential medical benefits. Compared to the general public, IRB members were significantly more likely to think the risks outweigh the potential medical benefits (p = 0.01). Finally, 68.8% of IRB members indicated that average phase 1 pediatric oncology trials are approvable, and 56.3% indicated that these trials are appropriate in children. These findings suggest two-thirds of IRB members believe average phase 1 pediatric oncology trials are approvable. Yet, almost half regard the risks as outweighing the potential medical benefits and almost half think these trials are inappropriate. These findings raise important questions regarding why IRB members and the general public evaluate the same risk/benefit profile differently, and whether it is possible to reconcile the two perspectives.

Distinguishing appropriate from inappropriate conditions on research participation.

Individuals do not have a right to participate in clinical trials. But, they do have a right against being denied participation for inappropriate reasons. Despite the widespread endorsement of these two claims, there has been little discussion regarding which conditions for participation in clinical trials are appropriate and which are inappropriate. The present manuscript attempts to address this gap in the literature. We first describe and then argue against the claim that conditions on enrollment or continued participation are appropriate only when they are needed to answer the scientific question(s) posed by the trial. We then offer an alternative view according to which the appropriateness of conditions depends on whether they help to satisfy the ethical requirements of clinical research. Because these requirements include social value, the present view implies that promoting social value is an acceptable reason to impose conditions on research participation. With this in mind, we explain why it is not coercive to require potential participants to accept conditions on enrollment that promote a trial's social value, even when the participants find those conditions unwelcome. We conclude by evaluating the present proposal's implications for the common practice of requiring participants to agree to the possible use of their leftover biospecimens in a broad range of future research. We argue, contra current regulatory policy, that this practice can be acceptable even when the present trial offers participants the prospect of clinical benefit and the samples are being reserved for future research that is unrelated to the present trial.

Suffering in Animal Research: The Need for Limits and the Possibility of Compensation.

Guidelines and regulations for medical research recognize that the experiences of humans and animals both matter morally. They thus set a presumption against harming research subjects, whether humans or animals, and mandate that the harms subjects experience should be the minimal necessary for achieving the scientific aims of the study. Beyond this, guidelines and regulations place upper limits on the extent to which human, but not animal, subjects may be harmed. They also mandate that human, but not animal, subjects should be compensated for the harms they experience. In this article, I argue that this common approach to regulating medical research is mistaken. In particular, there are upper limits on the extent to which animals may ethically be harmed in order to collect data to benefit others, and there are moral reasons to compensate them for the harms they experience. I conclude that guidelines and regulations for research with animals should be revised accordingly.

Deceiving Research Participants: Is It Inconsistent With Valid Consent?

It is widely assumed that the use of deception in research is always inconsistent with obtaining valid consent. In addition, guidelines and regulations permit research without valid consent only when it poses no greater than minimal risk. Current practice thus prohibits studies that use deception and pose greater than minimal risk, including studies that rely on deceptive methods to evaluate experimental treatments. To assess whether these prohibitions are justified, the present paper evaluates five arguments that might be thought to support the assumption that deception is always inconsistent with valid consent. Analysis of these arguments reveals that deception is frequently, but not always, inconsistent with obtaining valid consent for research. This conclusion suggests that, in order to avoid unnecessarily blocking valuable research, current policies and practice should be revised to recognize the conditions under which the use of deception can be consistent with obtaining research participants' valid consent.

Setting Risk Limits and Ensuring Fairness in Learning Health Care.

Historical abuses resulted in the segregation of clinical research and clinical care. While this approach has protected participants, it is extremely inefficient, leading commentators to propose (re)integrating research and care into learning health care systems. Previous commentators have argued that, in these systems, it could be appropriate to condition care on patients' consent to participation in research, but only when the added research risks are minimal. In the article "Compulsory Research in Learning Health Care: Against a Minimal Risk Limit," Robert Steel agrees about making research participation a condition for receiving care in these systems, but he argues that the limit to minimal risks is unfounded, and he offers compelling reasons to think that, in principle, permitting greater research risks could be fair and consistent with individual rights. Unfortunately, the nature of current institutions suggests that this approach is unlikely to be implemented fairly. We conclude that, to ensure fair learning health care systems, research and care may need to be reformed in more fundamental ways.

A new ethical framework to determine acceptable risks in fetal therapy trials.

OBJECTIVE: Fetal therapy trials pose complex ethical challenges because risks and benefits to both fetuses and pregnant persons must be considered. Existing regulatory guidance is limited and many proposed ethical frameworks have unnecessarily restrictive criteria that would block the development and implementation of important new fetal therapies. We aimed to develop a new ethical framework for assessing the risks and benefits of fetal therapy trials. METHODS: We reviewed existing regulatory and ethical guidance on fetal therapy trials. We used conceptual analysis to design a new ethical framework, which is grounded in general ethical principles for clinical research. RESULTS: We propose a new framework for assessing the risks and benefits of fetal therapy trials. We suggest that the potential benefits of a fetal therapy trial - for the fetus, the pregnant person, and society - should outweigh the risks for the fetus and the pregnant person. Furthermore, the risk-benefit profile for just the fetus and the risk-benefit profile for just the pregnant person should be appropriate. CONCLUSIONS: We hope that this new framework will permit important studies while protecting pregnant persons and fetuses from disproportionate harms.

The ethics of encouraging employees to get the COVID-19 vaccination.

The coronavirus pandemic continues to hinder the ability of businesses to operate at full capacity. Vaccination offers a path for employees to return to work, and for businesses to resume full capacity, while protecting themselves, their fellow workers, and customers. Many employers reluctant to mandate vaccination for their employees are considering other ways to increase employee vaccination rates. Because much has been written about the ethics of vaccine mandates, we examine a related and less discussed topic: the ethics of encouragement strategies aimed at overcoming vaccine reluctance (which can be due to resistance, hesitance, misinformation, or inertia) to facilitate voluntary employee vaccination. While employment-based vaccine encouragement may raise privacy and autonomy concerns, and though some employers might hesitate to encourage employees to get vaccinated, our analysis suggests ethically acceptable ways to inform, encourage, strongly encourage, incentivize, and even subtly pressure employees to get vaccinated.

Surrogate Perspectives on Patient Preference Predictors: Good Idea, but I Should Decide How They Are Used.

Current practice frequently fails to provide care consistent with the preferences of decisionally-incapacitated patients. It also imposes significant emotional burden on their surrogates. Algorithmic-based patient preference predictors (PPPs) have been proposed as a possible way to address these two concerns. While previous research found that patients strongly support the use of PPPs, the views of surrogates are unknown. The present study thus assessed the views of experienced surrogates regarding the possible use of PPPs as a means to help make treatment decisions for decisionally-incapacitated patients.This qualitative study used semi-structured interviews to determine the views of experienced surrogates [n = 26] who were identified from two academic medical centers and two community hospitals. The primary outcomes were respondents' overall level of support for the idea of using PPPs and the themes related to their views on how a PPP should be used, if at all, in practice.Overall, 21 participants supported the idea of using PPPs. The remaining five indicated that they would not use a PPP because they made decisions based on the patient's best interests, not based on substituted judgment. Major themes which emerged were that surrogates, not the patient's preferences, should determine how treatment decisions are made, and concern that PPPs might be used to deny expensive care or be biased against minority groups.Surrogates, like patients, strongly support the idea of using PPPs to help make treatment decisions for decisionally-incapacitated patients. These findings provide support for developing a PPP and assessing it in practice. At the same time, patients and surrogates disagree over whose preferences should determine how treatment decisions are made, including whether to use a PPP. These findings reveal a fundamental disagreement regarding the guiding principles for surrogate decision-making. Future research is needed to assess this disagreement and consider ways to address it.

Ethical and epistemic issues in the design and conduct of pragmatic stepped-wedge cluster randomized clinical trials.

Stepped-wedge cluster randomized trial (SW-CRT) designs are increasingly employed in pragmatic research; they differ from traditional parallel cluster randomized trials in which an intervention is delivered to a subset of clusters, but not to all. In a SW-CRT, all clusters receive the intervention under investigation by the end of the study. This approach is thought to avoid ethical concerns about the denial of a desired intervention to participants in control groups. Such concerns have been cited in the literature as a primary motivation for choosing SW-CRT design, however SW-CRTs raise additional ethical concerns related to the delayed implementation of an intervention and consent. Yet, PCT investigators may choose SW-CRT designs simply because they are concerned that other study designs are infeasible. In this paper, we examine justifications for the use of SW-CRT study design, over other designs, by drawing on the experience of the National Institutes of Health's Health Care Systems Research Collaboratory (NIH Collaboratory) with five pragmatic SW-CRTs. We found that decisions to use SW-CRT design were justified by practical and epistemic reasons rather than ethical ones. These include concerns about feasibility, the heterogeneity of cluster characteristics, and the desire for simultaneous clinical evaluation and implementation. In this paper we compare the potential benefits of SW-CRTs against the ethical and epistemic challenges brought forth by the design and suggest that the choice of SW-CRT design must balance epistemic, feasibility and ethical justifications. Moreover, given their complexity, such studies need rigorous and informed ethical oversight.

Acceptable Risks in Pediatric Research: Views of the US Public.

BACKGROUND AND OBJECTIVES: Critics argue that it is unethical to expose children to research risks for the benefit of others, whereas many regulations permit "net-risk" pediatric research but only when the risks are minimal. In the present survey, we assessed whether the US public agrees with these views and whether the US public's views regarding the acceptability of net-risk pediatric research are influenced by its social value. METHODS: A 15-minute survey of a nationally representative sample of US adults. Participants were randomly assigned to 1 of 4 hypothetical scenarios involving procedures that pose increasing levels of risk. To assess whether respondents' views on the acceptability of the risks is influenced by the social value of the research, in each of the 4 scenarios we described the respective procedure being used in 3 studies with increasing levels of social value. RESULTS: A total 1658 of the 2508 individuals who were sent the survey link participated (response rate = 66.1%). Approximately 91% approved of a research blood draw in minors, and ∼69% approved of a research bone marrow biopsy. The proportion who indicated that the respective procedure was acceptable increased as the study's social value increased. This effect was significantly stronger for studies which pose greater risks compared with studies with lower risks (P < .001). CONCLUSIONS: The vast majority of the US public supports net-risk pediatric research that poses minimal risk, and a majority supports net-risk pediatric research that poses somewhat greater risks, provided it has high social value. These findings offer important information for assessing when it is acceptable to conduct net-risk pediatric research.