A Survey of Clinicians Who Provide Aid in Dying.

INTRODUCTION: Little is known about the identity and moral experience of clinicians who provide the option of aid in dying to terminally ill Americans. METHODS: In May 2023 we distributed an email survey to clinicians registered for the American Clinician's Academy on Medical Aid in Dying listserv. RESULTS: Of the 72 clinicians who responded, 90% were of white race, 50% were over 60 years old, and 47% had been in practice for over 20 years. Most clinicians report practicing primary care (39%) or hospice/palliative care (33%); 25% of clinicians had training in palliative medicine. 22% described their practice as a specialized "aid-in-dying practice" and 26% either "rarely" or "never" cared for the terminally ill outside the context of aid in dying. A majority (56%) of clinicians were either affiliated with an independent practice or unaffiliated. Before they began aid-in-dying work, 26% of clinicians reported having felt "somewhat" or "very" morally conflicted; after having written an aid in dying prescription, 96% felt "hardly" or "not at all" conflicted. On average, clinicians felt that aid-in-dying laws balance protection of patients with access; 39% believed that the laws were "somewhat" or "overly" protective. CONCLUSION: Many responding clinicians report caring for patients considering aid in dying in specialized practices or otherwise in unaffiliated or independent practice. Clinicians report that providing aid in dying (and writing an aid-in-dying prescription) resulted in less reported moral conflict toward aid in dying.

Challenges in Completing a Death Certificate after Voluntary Stopping of Eating and Drinking (VSED).

In recent years, health care providers and the general public in the United States have gained a greater awareness of Voluntary Stopping of Eating and Drinking (VSED) as a last resort option to escape from unbearable suffering, thanks to a growing number of publications, books, and documentaries. However, the challenges and issues that can arise in completing a death certificate after VSED are not well described in literature. In this article, we first present an example case of VSED in which the death certificate was issued listing suicide as the manner of death by the medical examiner. Then, we describe the challenges and issues related to death certificates in VSED cases. Because there is no consensus on whether VSED is natural death or suicide, the death certificate may need to be referred to a medical examiner in many jurisdictions, potentially resulting in suicide being designated as the manner of death. Such designations can cause reticence in providers and institutions that might otherwise support patients who choose VSED but are concerned about the legal or reputational implications of enabling a "suicide" at their facility. A suicide designation may also contribute to moral distress in health care staff and impose emotional and practical burdens on the patient's surviving loved ones. We suggest that there are 3 approaches to addressing challenges and issues associated with death certificates after VSED: (1) navigate the existing system with guidance developed by professional organizations, (2) make a legal exemption, and (3) change the death certification system. Debate involving a wide variety of experts is warranted.

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.

Empirical evaluation of the need for 'on-going consent' in clinical research.

OBJECTIVE: Some commentators argue that informed consent for clinical research should be an on-going process, which begins, rather than ends, with participants' initial consent. Lacking, however, are empirical data on whether there is a need for 'on-going consent'. DESIGN: Two self-administered surveys - a baseline survey at initial consent and a follow-up survey 2-3 years later - to assess whether participants remain informed over time. METHODS: Respondents were adults with HIV disease from Argentina, Brazil and Thailand enrolled in a long-term clinical trial. RESULTS: Respondents overall were well informed at baseline. At follow-up, many reported being not informed about aspects of the study central to their on-going participation. With respect to the possibility of withdrawal, 38.5% of respondents at follow-up reported being 'not at all' informed. At follow-up, 71.1% wanted more information. Yet, 62.8% had not asked any questions during the entire study. Reasons for not asking questions included not having an opportunity (16.4%) and not knowing whom to ask (15.5%). CONCLUSIONS: The standard consent process resulted in participants being well informed at enrollment. Yet, this process was not sufficient to keep them informed about aspects of the study central to their on-going participation. In addition, participants who wanted more information often did not ask for it. These findings provide empirical support for recommendations that clinical trials should consider including a process of 'on-going consent'.

Attitudes towards transfers of human tissue samples across borders: an international survey of researchers and policy makers in five countries.

BACKGROUND: Sharing of tissue samples for research and disease surveillance purposes has become increasingly important. While it is clear that this is an area of intense, international controversy, there is an absence of data about what researchers themselves and those involved in the transfer of samples think about these issues, particularly in developing countries. METHODS: A survey was carried out in a number of Asian countries and in Egypt to explore what researchers and others involved in research, storage and transfer of human tissue samples thought about some of the issues related to sharing of such samples. RESULTS: The results demonstrated broad agreement with the positions taken by developing countries in the current debate, favoring quite severe restrictions on the use of samples by developed countries. CONCLUSIONS: It is recommended that an international agreement is developed on what conditions should be attached to any sharing of human tissue samples across borders.

Benefits and burdens of participation in a longitudinal clinical trial.

SYSTEMATIC DATA ON THE IMPACT THAT longitudinal clinical trials have on patient participants are needed to ensure that all the risks and potential benefits of participating in clinical research are properly evaluated and disclosed. Recognizing the lack of systematic data on this topic, we surveyed 582 individuals from Argentina, Brazil, and Thailand who were participating in the ESPRIT study, a Phase III randomized trial of interleukin-2 in HIV disease. Respondents were asked about the benefits and burdens of participating in ESPRIT using a self-administered survey. We found that 91% of respondents in the IL-2 treatment arm and 79% in the no IL-2 control arm reported medical benefits from their participation. In addition, 68% in the IL-2 treatment arm and 60% of the no IL-2 controls reported non-medical benefits. Thirteen percent of the IL-2 respondents and 5% of the non-IL2 respondents reported problems with their jobs due to study participation. Given that respondents, including those in the control arm, reported medical and non-medical benefits and burdens from their research participation, investigators and review committees should be aware of and respond to the potential for research participants to experience benefits and burdens that are unrelated to the intervention being tested.

Why patients continue to participate in clinical research.

BACKGROUND: Clinical research exposes patient participants to unproved methods and research procedures in order to gather generalizable knowledge to benefit others. While some commentators argue that this process inappropriately exploits patient participants, there are few data available to evaluate this claim. METHODS: Human immunodeficiency virus (HIV)-infected individuals from Argentina, Brazil, and Thailand who had been participating in the Evaluation of Subcutaneous Proleukin (Interleukin-2) in a Randomized International Trial (ESPRIT) study for at least 6 months were invited to complete a self-administered survey on their experience and were asked why they continued to participate. The ESPRIT study is a phase 3, multinational, randomized trial comparing antiretroviral therapy plus interleukin 2 (IL-2) with antiretroviral therapy alone in individuals with HIV disease. RESULTS: From a list of 12 possible reasons regarding why patient participants continue to participate, 8 options were selected as "very important" by 75% or more of 582 respondents, including the possibility of benefiting personally and the potential to help others. When asked to indicate the most important reason from this list, respondents in the IL-2 arm (n = 292) selected (1) increasing their CD4 lymphocyte count (26%); (2) finding better treatments for patients with HIV in their home country (22%); and (3) getting IL-2 (12%). Respondents in the no-IL-2 arm (n = 290) selected (1) finding better treatments for patients with HIV in their home country (32%); (2) finding better treatments for HIV-infected patients in other countries (12%); and (3) increasing their CD4 lymphocyte count (11%). Also, 90% of the respondents indicated that participation in ESPRIT involved making a "major" or "moderate" contribution to society, and 84% felt "very" or "somewhat" proud to be making this contribution. CONCLUSIONS: Most respondents continue to participate in the ESPRIT study in hopes of benefiting personally. The majority also recognized that by participating in ESPRIT they were contributing to helping others; they experienced pride regarding this contribution and considered it an important reason to continue to participate. These results indicate that it is possible for patient participants, even those seeking treatment for a life-threatening illness, to recognize and embrace the goals of the research in which they participate. Future studies will be needed to determine to what extent these findings generalize to other studies and other countries and what steps can help patient participants recognize and embrace the goals of clinical research.

Risks and benefits associated with novel phase 1 oncology trial designs.

BACKGROUND: Although aggressive dose escalation strategies were designed to improve the risk-benefit profile of phase 1 oncology trials, they have not been adequately studied. The prevalence of several novel trial designs and their association with a variety of clinical endpoints was evaluated. METHODS: A review of the literature was performed to identify phase 1 oncology studies of cytotoxic agents published from 2002 through 2004. RESULTS: Of 955 phase 1 oncology articles initially identified, 149 studies, comprising 4532 patients, were analyzed. Only 34% of studies utilized aggressive dose escalation schemes, 22% permitted intrapatient dose escalation, and only 28% enrolled fewer than 3 patients to any dose level. Studies that allowed intrapatient dose escalation or used fewer than 3 patients per dose were not associated with different rates of response or toxicity, nor did they increase the number of patients who received the recommended phase 2 dose. However, aggressive dose escalations were associated with increased rates of both hematologic (17% vs 10%) and nonhematologic (17% vs 13%) toxicity with similar response rates. Only studies that used conservative dose escalation designs and those that studied U.S. Food and Drug Administration (FDA)-approved agents required fewer patients to complete a trial. Trials of FDA-approved agents were also associated with higher response rates than trials of non-FDA-approved agents (10% vs 2%), without an increased risk of toxicity. CONCLUSIONS: Several novel aggressive design strategies intended to improve the risk-benefit profile of phase 1 oncology trials are not associated with improved clinical outcome, and may be harmful in certain instances.