The article presents the advantages and limitations of adaptive clinical trials for assessing the effectiveness of medical interventions and specifies the conditions that contributed to their development and implementation in clinical practice. I advance two arguments by discussing different cases of adaptive trials. The normative argument is that responsible adaptation should be taken seriously as a new way of doing clinical research insofar as a valid justification, sufficient understanding, and adequate operational conditions are provided. The second argument is historical. The (...) development of adaptive trials can be related to lessons learned from research in cases of urgency and to the decades-long efforts to end the productivity crisis of pharmaceutical research, which led to the emergence of translational, personalized, and, recently, precision medicine movements. (shrink)

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 …. (shrink)

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... (shrink)

Disasters and public health emergencies raise a variety of ethical dilemmas, often including those that require balancing the best interests of individuals against those of groups or communities. The on-going COVID-19 pandemic provides examples of these ethical conflicts, as do other recent outbreaks. Decisions and actions in this context must address different ethical issues, ranging from those directly related to autonomy, consent, privacy and confidentiality to those related to interventions and technologies, such as efficacy, effectiveness, safety and fair access. This (...) paper aims to identify ethical conflicts with complex resolutions involving aspects related to values, rights and needs of individuals and the collective, and to suggest how such challenges could lead to more positive experiences and outcomes when confronted in future emergencies. (shrink)

In his article ‘The Ebola Clinical Trials: a precedent for research ethics in disasters’, Philippe Calain constructs a compelling case as to why and how experiences from the recent Ebola epidemic should be used to develop a framework for disaster research ethics. In particular, Calain proposes a useful model for assessing whether or not an unproven intervention could be suitable for human use in a disaster context, and makes a powerful argument against the separation of patient care from research goals. (...) In this commentary, I argue that the separation of patient care goals from research goals is also unhelpful in the context of other forms of participant disadvantage even when that disadvantage is less severe than an ongoing public health emergency. I contend that recognising that research in disadvantaged populations is an intervention that could and should aim to produce positive outcomes for participants, just as it should in disaster contexts, therefore seems a well-justified lesson that can be extrapolated from the experience of the Ebola epidemic. (shrink)

BackgroundThe West African Ebola virus epidemic from 2014 to 2016 is unprecedented in its scale, surpassing all previous and subsequent Ebola outbreaks since 1976. This epidemic provoked a humanitarian emergency that extended to different spheres of life, making visible ethical challenges in addition to medical, economic, and social ones. The present article aims to identify and differentiate the scope of ethical issues associated with the Ebola epidemic.MethodsAn online media analysis was performed on articles published from March 2014 to September 2015 (...) in ten preselected academic journals (scientific press) and two online newspapers (lay press). Two methodological approaches were combined: a systematic literature search and a qualitative content analysis. An additional keyword search was conducted on the PubMed database for the period after the end of the Ebola epidemic (2016-2020) to obtain an overview of research dealing with medical ethics due to the epidemic and to compare these results with the identified ethical challenges.ResultsA total of 389 articles dealing with the subject fields “Ebola epidemic” and “ethics” were researched. For qualitative content analysis, the time span with the highest article density was selected and a total of 64 articles were included (15 scientific articles, 49 popular articles). Five core ethical challenges of the Ebola epidemic emerged: 1. Responsibility and Accountability, 2. Spillover Effects, 3. Research and Development, 4. Health Communication, and 5. Resource Allocation. Articles in academic journals were dominated by the discussion of normative aspects in the area of “research and development”, while newspaper articles focused on aspects of “responsibility and accountability”.ConclusionAn ethical discussion of the Ebola epidemic requires an examination of as many of the ethical dimensions involved as possible. The presented investigation of the two types of media with regard to the Ebola epidemic offers this possibility of a more comprehensive insight into this diversity as a basis for ethical discussions. (shrink)

The circumstances of a public health emergency shape reasoning and decision-making in ways that deviate from routine circumstances, where adherence to established values, principles, and methodologies is expected. Understanding what drives these deviations is critical to assessing their ethical consequences. In this paper we describe four conditions that influence decision-making during PHEs, in particular regarding the deployment and conduct of research on experimental or novel biomedical interventions. These four conditions are politicization, urgency, uncertainty, and fear. We argue that taken together (...) these four conditions create pressure to address the most visible targets of immediate crisis events, driving emphasis on research and development of biomedical interventions. However, this emphasis raises ethical concerns regarding the extent to which attention to and investment in the underlying causes of PHEs, particularly impoverished global public health infrastructure, is diminished as a result. (shrink)

As the usual regulatory framework did not fit well during the last Ebola outbreak, innovative thinking still needed. In the absence of an outbreak, randomised controlled trials of clinical efficacy in humans cannot be done, while during an outbreak such trials will continue to face significant practical, philosophical, and ethical challenges. This article argues that researchers should also test the safety and effectiveness of novel vaccines in wild apes by employing a pluralistic approach to evidence. There are three reasons to (...) test vaccines in wild populations of apes: i) protect apes; ii) reduce Ebola transmission from wild animals to humans; and iii) accelerate vaccine development and licensing for humans. Data obtained from studies of vaccines among wild apes and chimpanzees may even be considered sufficient for licensing new vaccines for humans. This strategy will serve to benefit both wild apes and humans. (shrink)