The Value of Explicit, Deliberative, and Context-Specified Ethics Analysis for Health Technology Assessment: Evidence From a Novel Approach Piloted in South Africa.

OBJECTIVES: This article explores the perceived value, including associated strengths and challenges, of using a context-specified ethics framework to guide deliberative health technology appraisals. METHODS: The South African Values and Ethics for Universal Health Coverage (SAVE-UHC) approach, piloted in South Africa, consisted of 2 phases: (1) convening a national multistakeholder working group to develop a provisional ethics framework and (2) testing the provisional ethics framework through simulated health technology assessment appraisal committee meetings (SACs). Three SACs each reviewed 2 case studies of sample health interventions using the framework. Participants completed postappraisal questionnaires and engaged in focus group discussions. RESULTS: The SACs involved 27 participants across 3 provinces. Findings from the postappraisal questionnaires demonstrated general support for the SAVE-UHC approach and content of the framework, high levels of satisfaction with the recommendations produced, and general sentiment that participants were able to actively contribute to appraisals. Qualitative data showed participants perceived using a context-specified ethics framework in deliberative decision making: (1) supported wider consideration of and deliberation about morally relevant features of the health coverage decisions, thereby contributing to quality of appraisals; (2) could improve transparency; and (3) offered benefits to those directly involved in the priority-setting process. Participants also identified some challenges and concerns associated with the approach. CONCLUSIONS: The SAVE-UHC approach presents a novel way to develop and pilot a locally contextualized, explicit ethics framework for health priority setting. This work highlights how the combination of a context-specified ethics framework and structured deliberative appraisals can contribute to the quality of health technology appraisals and transparency of health priority setting.

Clinical trials and pregnancy.

Traditionally, there has been a reluctance to involve pregnant people in clinical trials due to complex ethical issues surrounding the risk to unborn babies. However it is crucial that new interventions are safe and effective for all patients and ensuring this can be difficult to achieve in the absence of clinical trials.

Defining the ethical considerations surrounding kidney transplantation for frail and cognitively impaired patients: a Delphi study of geriatric transplant experts.

BACKGROUND: Among adult kidney transplant (KT) candidates, 21% are frail and 55% have cognitive impairment, increasing the risk of pre- and post-KT mortality. Centers often assess frailty status and cognitive function during transplant evaluation to help identify appropriate candidate. Yet, there are no ethical guidelines regarding the use of frailty and cognitive function during this evaluation. We seek to develop a clinical consensus on balancing utility and justice in access to KT for frail and cognitively impaired patients. METHODS: Twenty-seven experts caring for ESRD patients completed a two-round Delphi panel designed to facilitate consensus (> 80% agreement). RESULTS: Experts believed that denying patients transplantation based solely on expected patient survival was inequitable to frail or cognitively impaired candidates; 100% agreed that frailty and cognitive impairment are important factors to consider during KT evaluation. There was consensus that health related quality of life and social support are important to consider before waitlisting frail or cognitively impaired patients. Experts identified important factors to consider before waitlisting frail (likely to benefit from KT, frailty reversibility, age, and medical contraindications) and cognitively impaired (degree of impairment and medication adherence) patients. CONCLUSIONS: Clinical experts believed it was ethically unacceptable to allocate organs solely based on patients' expected survival; frailty and cognitive impairment should be measured at evaluation when weighed against other clinical factors. Ethical guidelines regarding the use of frailty and cognitive function during KT evaluation ought to be developed.

Learning Health Care and the Obligation to Participate in Research.

This commentary responds to the article "Compulsory Research in Learning Health Care: Against a Minimal Risk Limit," by Robert Steel. Steel acknowledges that our ethics framework for a learning health care system, published in the 2013 special report Ethical Oversight of Learning Health Care Systems , includes an obligation on the part of patients to participate in learning activities, but he argues that this obligation does not go far enough. Steel, who provides an interesting justification for compulsory research participation in learning health care, claims that our obligation is limited to only minimal risk research. We take exception to that characterization insofar as it detracts from what we believe is most relevant for assessing learning activities, which is how much additional risk and burden a learning activity poses compared to clinical care alone. We also clarify that the level of additional risk is not the only morally relevant consideration in determining if a learning activity should be compulsory. Also important is whether the learning activity includes interventions or choices that engage values of importance to patients.

Streamlined versus traditional consent for low-risk comparative effectiveness trials: a randomized experimental study to measure patients' and public attitudes.

Aim: Streamlining consent for low-risk comparative effectiveness research (CER) could facilitate research, while safeguarding patients' rights. Materials & methods: 2618 adults were randomized to one of seven consent approaches (six streamlined and one traditional) for a hypothetical, low-risk CER study. A survey measured understanding, voluntariness, and feelings of respect. Results: Participants in all arms had a high understanding of the trial and positive attitudes toward the consent interaction. Highest satisfaction was with a streamlined approach showing a video before the medical appointment. Participants in streamlined were more likely to mistakenly think a signature was required. Conclusion: Streamlined consent was no less acceptable than traditional, signed consent. Streamlined and traditional approaches achieved similar levels of understanding, voluntariness and a feeling that the doctor-patient interaction was respectful.

Developing and piloting a context-specified ethics framework for health technology assessment: the South African Values and Ethics for Universal Health Coverage approach.

OBJECTIVES: While ethics has been identified as a core component of health technology assessment (HTA), there are few examples of practical, systematic inclusion of ethics analysis in HTA. Some attribute the scarcity of ethics analysis in HTA to debates about appropriate methodology and the need for ethics frameworks that are relevant to local social values. The "South African Values and Ethics for Universal Health Coverage" (SAVE-UHC) project models an approach that countries can use to develop HTA ethics frameworks that are specific to their national contexts. METHODS: The SAVE-UHC approach consisted of two phases. In Phase I, the research team convened and facilitated a national multistakeholder working group to develop a provisional ethics framework through a collaborative, engagement-driven process. In Phase II, the research team refined the model framework by piloting it through three simulated HTA appraisal committee meetings. Each simulated committee reviewed two case studies of sample health interventions: opioid substitution therapy and either a novel contraceptive implant or seasonal influenza immunization for children under five. RESULTS: The methodology was fit-for-purpose, resulting in a context-specified ethics framework and producing relevant findings to inform application of the framework for the given HTA context. CONCLUSIONS: The SAVE-UHC approach provides a model for developing, piloting, and refining an ethics framework for health priority-setting that is responsive to national social values. This approach also helps identify key facilitators and challenges for integrating ethics analysis into HTA processes.

Global disparities in public health guidance for the use of COVID-19 vaccines in pregnancy.

INTRODUCTION: Gaps in information about the safety and efficacy of COVID-19 vaccines in pregnancy have led to substantial global variation in public health guidance regarding the use of COVID-19 vaccines in pregnancy over the course of the pandemic. METHODS: We conducted systematic screenings of public health authorities' websites across 224 countries and territories every 3 weeks to track the development of policies on COVID-19 vaccine use in pregnancy. Policies were categorised using a 1-5 permissiveness scale, with 1 indicating policies that recommended use, and 5 indicating policies that recommended against use. RESULTS: As of 30 September 2021, 176 countries/territories had issued explicit guidance on COVID-19 vaccine use in pregnancy, with 38% recommending use, 28% permitting use, 15% permitting use with qualifications, 2% not recommending but with exceptions, and 17% not recommending use whatsoever. This represented a significant shift from May 2021, when only 6% of countries/territories with such policies recommended the use of COVID-19 vaccines in pregnancy (p<0.001). However, no policy positions could be found for 21% of all countries and territories, the vast majority being low and middle income. Policy positions also varied widely by vaccine product, with Pfizer/BioNTech and Moderna vaccines being most commonly recommended or permitted. CONCLUSION: Our study highlights the evolution of policies regarding COVID-19 vaccine use in pregnancy over a 5-month period in 2021, the role of pregnancy-specific data in shaping these policies and how inequities in access for pregnant people persist, both within countries and globally.

Disparities In County COVID-19 Vaccination Rates Linked To Disadvantage And Hesitancy.

We analyzed trends in adult COVID-19 vaccine coverage over time based on COVID-19 vaccine hesitancy and social vulnerability. We found that each of these variables carries an independent association with disparities across counties in COVID-19 vaccine coverage. Counties that score high on both hesitancy and vulnerability are especially likely to have lower COVID-19 vaccination rates compared with the rest of the country.

Pregnant Individuals' Views on Fetal Tissue Research in the United States.

OBJECTIVE: Fetal tissue research has driven significant medical advances but remains publicly contentious in the United States. The views of pregnant individuals in the United States regarding the donation of fetal tissue offer an important and previously unexplored perspective on this issue. METHODS: We conducted a secondary analysis of data from two separate, broader qualitative studies. Pregnant and recently pregnant individuals (N=79) from clinical sites at the University of North Carolina at Chapel Hill, Johns Hopkins University, and Massachusetts General Hospital were interviewed individually using a semi-structured guide addressing a range of issues related to infectious disease research and pregnancy, including the acceptability of fetal tissue research. Interviews were transcribed, coded, and analyzed for emergent themes. RESULTS: Among this sample of predominantly Black (61%), reproductive-aged pregnant and recently pregnant participants, the majority (72%) generally supported fetal tissue research. The following three themes were identified: choice, respect, and meaning. Respondents discussed the deeply personal nature of decisions surrounding fetal tissue research, emphasizing the importance of informed consent and respect for the person's emotional state when approaching for consent. The ways in which participants regarded how to respectfully handle fetal tissue also shaped views about the acceptability of donation, both for and against. For many participants, fetal tissue donation to research represented one way of ascribing meaning to pregnancy termination or loss. CONCLUSION: Among this diverse sample of pregnant and recently pregnant individuals, most were supportive of fetal tissue donation for research. A better understanding of pregnant individuals' views on this topic may lead to policies and practices that are congruent with the needs and values of people facing decisions regarding the disposition of fetal remains.

What Factors Predict Willingness to Join Low-Risk Pragmatic Clinical Trials?

Pragmatic clinical trials (PCTs) may improve the efficiency, relevance, and representativeness of research. While prior research has indicated that willingness to join a PCT is high, it is not universal among those asked in surveys exploring attitudes toward hypothetical PCTs. The objective of this study was to examine what factors predict willingness to join a hypothetical low-risk PCT comparing two blood pressure medicines. In our study, 2,618 respondents, recruited from three populations (adult patients from an academic health system, adult patients from an integrated delivery system, and adults from an online nationally representative panel), completed an online survey. Most respondents (90%) expressed willingness to participate in the hypothetical PCT. The two key predictors of expressed willingness to join low-risk PCTs were respondents' understanding of key features of PCTs, including how they differ from traditional research, and the degree of importance respondents perceived comparative research to have. Increasing awareness of the rationale for PCTs and understanding of these trials, including how they differ from explanatory trials, may increase prospective participants' willingness to contribute to this effort.

Pregnant women & vaccines against emerging epidemic threats: Ethics guidance for preparedness, research, and response.

Zika virus, influenza, and Ebola have called attention to the ways in which infectious disease outbreaks can severely - and at times uniquely - affect the health interests of pregnant women and their offspring. These examples also highlight the critical need to proactively consider pregnant women and their offspring in vaccine research and response efforts to combat emerging and re-emerging infectious diseases. Historically, pregnant women and their offspring have been largely excluded from research agendas and investment strategies for vaccines against epidemic threats, which in turn can lead to exclusion from future vaccine campaigns amidst outbreaks. This state of affairs is profoundly unjust to pregnant women and their offspring, and deeply problematic from the standpoint of public health. To ensure that the needs of pregnant women and their offspring are fairly addressed, new approaches to public health preparedness, vaccine research and development, and vaccine delivery are required. This Guidance offers 22 concrete recommendations that provide a roadmap for the ethically responsible, socially just, and respectful inclusion of the interests of pregnant women in the development and deployment of vaccines against emerging pathogens. The Guidance was developed by the Pregnancy Research Ethics for Vaccines, Epidemics, and New Technologies (PREVENT) Working Group - a multidisciplinary, international team of 17 experts specializing in bioethics, maternal immunization, maternal-fetal medicine, obstetrics, pediatrics, philosophy, public health, and vaccine research and policy - in consultation with a variety of external experts and stakeholders.

Rethinking "Elective" Procedures for Women's Reproduction during Covid-19.

Common hospital and surgical center responses to the Covid-19 pandemic included curtailing "elective" procedures, which are typically determined based on implications for physical health and survival. However, in the focus solely on physical health and survival, procedures whose main benefits advance components of well-being beyond health, including self-determination, personal security, economic stability, equal respect, and creation of meaningful social relationships, have been disproportionately deprioritized. We describe how female reproduction-related procedures, including abortion, surgical sterilization, reversible contraception devices and in vitro fertilization, have been broadly categorized as "elective," a designation that fails to capture the value of these procedures or their impact on women's overall well-being. We argue that corresponding restrictions and delays of these procedures are problematically reflective of underlying structural views that marginalize women's rights and interests and therefore threaten to propagate gender injustice during the pandemic and beyond. Finally, we propose a framework for triaging reproduction-related procedures during Covid-19 that is more individualized, accounts for their significance for comprehensive well-being, and can be used to inform resumption of operations as well as subsequent restriction phases.

Scarce Resource Allocation During Disasters: A Mixed-Method Community Engagement Study.

BACKGROUND: During a catastrophe, health-care providers may face difficult questions regarding who will receive limited life-saving resources. The ethical principles that should guide decision-making have been considered by expert panels but have not been well explored with the public or front-line clinicians. The objective of this study was to characterize the public's values regarding how scarce mechanical ventilators should be allocated during an influenza pandemic, with the ultimate goal of informing a statewide scare resource allocation framework. METHODS: Adopting deliberative democracy practices, we conducted 15 half-day community engagement forums with the general public and health-related professionals. Small group discussions of six potential guiding ethical principles were led by trained facilitators. The forums consisted exclusively of either members of the general public or health-related or disaster response professionals and were convened in a variety of meeting places across the state of Maryland. Primary data sources were predeliberation and postdeliberation surveys and the notes from small group deliberations compiled by trained note takers. RESULTS: Three hundred twenty-four individuals participated in 15 forums. Participants indicated a preference for prioritizing short-term and long-term survival, but they indicated that these should not be the only factors driving decision-making during a crisis. Qualitative analysis identified 10 major themes that emerged. Many, but not all, themes were consistent with previously issued recommendations. The most important difference related to withholding vs withdrawing ventilator support. CONCLUSIONS: The values expressed by the public and front-line clinicians sometimes diverge from expert guidance in important ways. Awareness of these differences should inform policy making.

Stakeholder perspectives regarding alternate approaches to informed consent for comparative effectiveness research.

INTRODUCTION: Traditional informed consent approaches, involving separate discussions and lengthy consent forms, may be an imperfect fit for comparative effectiveness research (CER) that is integrated into usual care and compares non-investigational treatments. However, systematic efforts to collect broad stakeholder perspectives about alternative streamlined approaches to disclosure and consent in this context have been limited. METHODS: We used a deliberative engagement method to solicit the views of a multi-stakeholder group regarding 3 alternative models of disclosure, consent, and authorization in CER studies: Opt-In, Opt-Out, and "General Approval". Participants considered the acceptability of these 3 models for observational and randomized CER studies of hypertension medications and for alternative treatments for spinal stenosis, all conducted in the context of a learning health care system. RESULTS: Fifty-eight stakeholders participated in the all-day deliberative engagement session. Following deliberation, a majority of stakeholders (67%) liked the General Approval model for the observational hypertension study, more than the number who reported liking Opt-Out or Opt-In (45% and 36%, respectively). Support was lower for General Approval model in the context of a randomized hypertension study, with 80% liking a traditional Opt-In approach, compared with 54% liking Opt-Out, and 11% liking General Approval. Similarly, for the spinal stenosis CER studies, while most stakeholders preferred a streamlined Opt-Out approach for the observational design, most preferred a traditional Opt-In approach for the randomized version. CONCLUSIONS: This multi-stakeholder group was more favorable towards streamlined models for disclosure and authorization for observational CER than randomized designs. These findings are consistent with arguments that informed consent requirements should be tailored to the context of the research design, rather than a standard "one size fits all" approach.