Back to WHAT?:The role of research ethics in pandemic times

Abstract The Covid-19 pandemic creates an unprecedented threatening situation worldwide with an urgent need for critical reflection and new knowledge production, but also a need for imminent action despite prevailing knowledge gaps and multilevel uncertainty. With regard to the role of research ethics in these pandemic times some argue in favor of exceptionalism, others, including the authors of this paper, emphasize the urgent need to remain committed to core ethical principles and fundamental human rights obligations all reflected in research regulations and guidelines carefully crafted over time. In this paper we disentangle some of the arguments put forward in the ongoing debate about Covid-19 human challenge studies (CHIs) and the concomitant role of health-related research ethics in pandemic times. We suggest it might be helpful to think through a lens differentiating between risk, strict uncertainty and ignorance. We provide some examples of lessons learned by harm done in the name of research in the past and discuss the relevance of this legacy in the current situation

Framework to Support the Process of Decision-Making on Life-Sustaining Treatments in the ICU: Results of a Delphi Study

Objectives: To develop a consensus framework that can guide the process of decision-making on continuing or limiting life-sustaining treatments in ICU patients, using evidence-based items, supported by caregivers, patients, and surrogate decision makers from multiple countries. Design: A three-round web-based international Delphi consensus study with a priori consensus definition was conducted with experts from 13 countries. Participants reviewed items of the decision-making process on a seven-point Likert scale or with open-ended questions. Questions concerned terminology, content, and timing of decision-making steps. The summarized results (including mean scores) and expert suggestions were presented in the subsequent round for review. Setting: Web-based surveys of international participants representing ICU physicians, nurses, former ICU patients, and surrogate decision makers. Patients: Not applicable. Interventions: Not applicable. Measurements and Main Results: In three rounds, respectively, 28, 28, and 27 (of 33 invited) physicians together with 12, 10, and seven (of 19 invited) nurses participated. Patients and surrogates were involved in round one and 12 of 27 responded. Caregivers were mostly working in university affiliated hospitals in Northern Europe. During the Delphi process, most items were modified in order to reach consensus. Seven items lacked consensus after three rounds. The final consensus framework comprises the content and timing of four elements; three elements focused on caregiver-surrogate communication (admission meeting, follow-up meeting, goals-of-care meeting); and one element (weekly time-out meeting) focused on assessing preferences, prognosis, and proportionality of ICU treatment among professionals. Conclusions: Physicians, nurses, patients, and surrogates generated a consensus-based framework to guide the process of decision-making on continuing or limiting life-sustaining treatments in the ICU. Early, frequent, and scheduled family meetings combined with a repeated multidisciplinary time-out meeting may support decisions in relation to patient preferences, prognosis, and proportionality

Inter-physician variability in strategies linked to treatment limitations after severe traumatic brain injury; proactivity or wait-and-see

Background Prognostic uncertainty is a challenge for physicians in the neuro intensive care field. Questions about whether continued life-sustaining treatment is in a patient’s best interests arise in different phases after a severe traumatic brain injury. In-depth information about how physicians deal with ethical issues in different contexts is lacking. The purpose of this study was to seek insight into clinicians’ strategies concerning unresolved prognostic uncertainty and their ethical reasoning on the issue of limitation of life-sustaining treatment in patients with minimal or no signs of neurological improvement after severe traumatic brain injury in the later trauma hospital phase. Methods Interviews with 18 physicians working in a neurointensive care unit in a large Norwegian trauma hospital, followed by a qualitative thematic analysis focused on physicians’ strategies related to treatment-limiting decision-making. Results A divide between proactive and wait-and-see strategies emerged. Notwithstanding the hospital’s strong team culture, inter-physician variability with regard to ethical reasoning and preferred strategies was exposed. All the physicians emphasized the importance of team—family interactions. Nevertheless, their strategies differed: (1) The proactive physicians were open to consider limitations of life-sustaining treatment when the prognosis was grim. They initiated ethical discussions, took leadership in clarification and deliberation processes regarding goals and options, saw themselves as guides for the families and believed in the necessity to prepare families for both best-case and worst-case scenarios. (2) The “wait-and-see” physicians preferred open-ended treatment (no limitations). Neurologically injured patients need time to uncover their true recovery potential, they argued. They often avoided talking to the family about dying or other worst-case scenarios during this phase. Conclusions Depending on the individual physician in charge, ethical issues may rest unresolved or not addressed in the later trauma hospital phase. Nevertheless, team collaboration serves to mitigate inter-physician variability. There are problems and pitfalls to be aware of related to both proactive and wait-and-see approaches. The timing of best-interest discussions and treatment-limiting decisions remain challenging after severe traumatic brain injury. Routines for timely and open discussions with families about the range of ethically reasonable options need to be strengthened

Barriers and challenges in the process of including critically ill patients in clinical studies

Background Clinical research in severely ill or injured patients is required to improve healthcare but may be challenging to perform in practice. The aim of this study was to analyse barriers and challenges in the process of including critically ill patients in clinical studies. Methods Data from critically ill patients considered for inclusion in an observational study of venous thromboembolism in Norway were analysed. This included quantitative and qualitative information from the screening log, consent forms and research notes. Results Among 279 eligible critically ill patients, 204 (73%) were omitted from the study due to challenges and barriers in the inclusion process. Reasons for omission were categorised as practical in 133 (65%), medical in 31 (15%), and legal or ethical in 40 (20%) of the patients. Among 70 included patients, 29 (41%) consents were from patients and 41 (59%) from their next of kin. Several challenges were described herein; these included whether patients were competent to give consent, and which next of kin that should represent the patient. Furthermore, some included patients were unable to recall what they have consented, and some appeared unable to separate research from treatment. Conclusions Barriers and challenges in the inclusion process led to the omission of near three out of four eligible patients. This analysis provided information about where the problem resides and may be solved. The majority of challenges among included patients were related to issues of autonomy and validity of consent. Trial registration ClinicalTrials.gov (NCT03405766)

Treatment-limiting decisions in patients with severe traumatic brain injury in a Norwegian regional trauma center

Background Treatment-limiting decisions (TLD) for severe traumatic brain injury (sTBI) have been sparsely studied. This study determine prevalence, main reason for, categories and timing of TLDs in a Norwegian regional trauma setting. Methods A retrospective study of a 2-year cohort of 579 sTBI patients admitted to Oslo University Hospital (OUH). Prospectively collected data in the OUH Trauma Registry were combined with retrospective data from a chart review regarding TLDs. Results TLDs were documented for 101/579 sTBI patients (17%). The situation was evaluated as futile in 59 cases and as potentially inappropriate in 42 cases. The three most frequent types of TLDs were withholding of neurosurgery, do not resuscitate orders and withdrawing of organ support. In 70% of cases, the first TLD was made within 2 days after injury, while in 14%, the first TLD was made later than day 7. Twenty percent (20/101) of the first TLDs were later adjusted, revoked in 4 patients and broadening of TLDs in 16 patients. The median time from the decision to death was 2 days (range 1–652). TLDs were documented in 93% of in-hospital death cases (n = 79). In-hospital deaths occurred in 73% of TLD group cases and 1% of non-TLD group cases. Family interaction and multi-team discussions were documented in >88% of cases, but no advanced directives were found, and notifications of patients’ preferences were found in only 7% of cases. Discussion Clinicians should consider limiting treatment if continued treatment is not in the patients best interest. A range of different types of TLDs were applied for patients after sTBI in the trauma hospital setting. Conclusion TLDs were found in 17% of sTBI patients. Value considerations behind TLDs in this care context need to be further explored

Neurocritical care physicians’ doubt about whether to withdraw life-sustaining treatment the first days after devastating brain injury: an interview study

Background Multilevel uncertainty exists in the treatment of devastating brain injury and variation in end-of-life decision-making is a concern. Cognitive and emotional doubt linked to making challenging decisions have not received much attention. The aim of this study was to explore physicians´ doubt related to decisions to withhold or withdraw life-sustaining treatment within the first 72 h after devastating brain injury and to identify the strategies used to address doubt. Method Semi-structured interviews were conducted with 18 neurocritical care physicians in a Norwegian trauma centre (neurosurgeons, intensivists and rehabilitation specialists) followed by a qualitative thematic analysis. Result All physicians described feelings of doubt. The degree of doubt and how they dealt with it varied. Institutional culture, ethics climate and individual physicians´ values, experiences and emotions seemed to impact judgements and decisions. Common strategies applied by physicians across specialities when dealing with uncertainty and doubt were: 1. Provision of treatment trials 2. Using time as a coping strategy 3. Collegial counselling and interdisciplinary consensus seeking 4. Framing decisions as purely medical. Conclusion Decisions regarding life-sustaining treatment after devastating brain injury are crafted in a stepwise manner. Feelings of doubt are frequent and seem to be linked to the recognition of fallibility. Doubt can be seen as positive and can foster open-mindedness towards the view of others, which is one of the prerequisites for a good ethical climate. Doubt in this context tends to be mitigated by open interdisciplinary discussions acknowledging doubt as rational and a normal feature of complex decision-making

¿Volver a qué? El papel de la ética de la investigación en época de pandemia.

La pandemia de COVID-19 ha generado en todo el mundo una amenaza sin precedentes que no solo impone la urgente necesidad de reflexionar críticamente y de producir nuevo conocimiento, sino que también exige la acción inmediata, a pesar de las lagunas de información que aún prevalecen y la incertidumbre existente a múltiples niveles. En cuanto al papel de la ética de la investigación en estos tiempos de pandemia, algunos defienden el excepcionalismo mientras que otros, incluidos los autores de este artículo, hacen énfasis en la urgente necesidad de mantener el compromiso con los principios éticos fundamentales y con las obligaciones de derechos humanos más fundamentales, que se reflejan en las pautas y directrices para la investigación que han sido cuidadosamente elaboradas a lo largo del tiempo. En este artículo analizamos algunos de los argumentos que se plantean en el debate actual sobre los estudios de desafío humano o estudios de infección humana controlada (EIHC) y el papel concomitante de la ética de la investigación en temas de salud en épocas de pandemia. Sugerimos que resultaría útil pensar la cuestión a partir de la diferenciación entre riesgo, incertidumbre en sentido estricto y la ignorancia. Presentamos algunos ejemplos de casos en los que se causó daño en nombre de la investigación científica y discutimos la relevancia de este legado en la situación actual

Variations in end-of-life practices in intensive care units worldwide (Ethicus-2): a prospective observational study.

BACKGROUND End-of-life practices vary among intensive care units (ICUs) worldwide. Differences can result in variable use of disproportionate or non-beneficial life-sustaining interventions across diverse world regions. This study investigated global disparities in end-of-life practices. METHODS In this prospective, multinational, observational study, consecutive adult ICU patients who died or had a limitation of life-sustaining treatment (withholding or withdrawing life-sustaining therapy and active shortening of the dying process) during a 6-month period between Sept 1, 2015, and Sept 30, 2016, were recruited from 199 ICUs in 36 countries. The primary outcome was the end-of-life practice as defined by the end-of-life categories: withholding or withdrawing life-sustaining therapy, active shortening of the dying process, or failed cardiopulmonary resuscitation (CPR). Patients with brain death were included in a separate predefined end-of-life category. Data collection included patient characteristics, diagnoses, end-of-life decisions and their timing related to admission and discharge, or death, with comparisons across different regions. Patients were studied until death or 2 months from the first limitation decision. FINDINGS Of 87 951 patients admitted to ICU, 12 850 (14·6%) were included in the study population. The number of patients categorised into each of the different end-of-life categories were significantly different for each region (p<0·001). Limitation of life-sustaining treatment occurred in 10 401 patients (11·8% of 87 951 ICU admissions and 80·9% of 12 850 in the study population). The most common limitation was withholding life-sustaining treatment (5661 [44·1%]), followed by withdrawing life-sustaining treatment (4680 [36·4%]). More treatment withdrawing was observed in Northern Europe (1217 [52·8%] of 2305) and Australia/New Zealand (247 [45·7%] of 541) than in Latin America (33 [5·8%] of 571) and Africa (21 [13·0%] of 162). Shortening of the dying process was uncommon across all regions (60 [0·5%]). One in five patients with treatment limitations survived hospitalisation. Death due to failed CPR occurred in 1799 (14%) of the study population, and brain death occurred in 650 (5·1%). Failure of CPR occurred less frequently in Northern Europe (85 [3·7%] of 2305), Australia/New Zealand (23 [4·3%] of 541), and North America (78 [8·5%] of 918) than in Africa (106 [65·4%] of 162), Latin America (160 [28·0%] of 571), and Southern Europe (590 [22·5%] of 2622). Factors associated with treatment limitations were region, age, and diagnoses (acute and chronic), and country end-of-life legislation. INTERPRETATION Limitation of life-sustaining therapies is common worldwide with regional variability. Withholding treatment is more common than withdrawing treatment. Variations in type, frequency, and timing of end-of-life decisions were observed. Recognising regional differences and the reasons behind these differences might help improve end-of-life care worldwide. FUNDING None