Research Ethics Committees (RECs) play a critical gatekeeping role in clinical trials. This role is meant to ensure that only those trials that meet certain ethical thresholds proceed through their gate. Two of these thresholds are that the potential benefits of trials are reasonable in relation to risks and that trials are capable of producing a requisite amount of social value. While one ought not expect perfect execution by RECs of their gatekeeping role, one should expect routine success in it. (...) This article reviews a range of evidence showing that substantial numbers of ethically tainted trials are receiving REC approvals. Many of the trials are early phase trials that evidence shows have benefits that may not be reasonable compared with their risks and many others are later trials that evidence shows may lack sufficient social value. The evidence pertains to such matters as methodologically inadequate preclinical studies incapable of supporting the inferences that REC members must make about the prospects for potential benefit needed to offset the risks in early phase trials and sponsorship bias that can cause improperly designed, conducted, analysed and reported later phase trials. The analysis of the evidence makes clear that REC practices need to be strengthened if they are to adequately fulfil their gatekeeping role. The article also explores options that RECs could use in order to improve their gatekeeping function. (shrink)

Recently, ethicists have posited that consideration of epigenetic mechanisms presents novel challenges to concepts of justice and equality of opportunity, such as elevating the importance of environments in bioethics and providing a counterpoint to gross genetic determinism. We argue that new findings in epigenetic sciences, including those regarding intergenerational health effects, do not necessitate reconceptualization of theories of justice or the environment. To the contrary, such claims reflect a flawed understanding of epigenetics and its relation to genetics that may unintentionally (...) undermine appeals to social justice. We provide a brief summary of epigenetic sciences, focusing on phenomena central to the current ethical discourse. We identify three fallacious modes of reasoning arising from the emergent literature on the ethical and policy implications of epigenetics, including mischaracterization, undue extrapolation, and exceptionalism. We end by discussing how these issues may work against mobilizing health equity policies and present a more modest claim regarding the value of new epigenetic knowledge to health justice by setting this discourse within the context of known themes in biomedical ethics and health policy. (shrink)

Launch of clinical investigation represents a substantial escalation in commitment to a particular clinical translation trajectory; it also exposes human subjects to poorly understood interventions. Despite these high stakes, there is little to guide decision-makers on the scientific and ethical evaluation of early phase trials. In this article, we review policies and consensus statements on human protections, drug regulation, and research design surrounding trial launch, and conclude that decision-making is largely left to the discretion of research teams and sponsors. We (...) then review what is currently understood about how research teams exercise this discretion, and close by laying out a research agenda for characterizing the way investigators, sponsors, and reviewers approach decision-making in early phase research. (shrink)

Between 2013 and 2016, West Africa experienced the largest ever outbreak of Ebola Virus Disease. In the absence of registered treatments or vaccines to control this lethal disease, the World Health Organization coordinated and supported research to expedite identification of interventions that could control the outbreak and improve future control efforts. Consequently, the World Health Organization Research Ethics Review Committee was heavily involved in reviews and ethics discussions. It reviewed 24 new and 22 amended protocols for research studies including interventional (...) and observational studies. WHO-ERC provided the reviews within on average 6 working days. The WHO-ERC often could not provide immediate approval of protocols for reasons which were not Ebola Virus Disease specific but related to protocol inconsistencies, missing information and complex informed consents. WHO-ERC considerations on Ebola Virus Disease specific issues are presented. To accelerate study approval in future public health emergencies, we recommend: internally consistent and complete submissions with information documents in language participants are likely to understand, close collaboration between local and international researchers from research inception, generation of template agreements for data and sample sharing and use during the ongoing global consultations on bio-banks, formation of Joint Scientific Advisory and Data Safety Review Committees for all studies linked to a particular intervention or group of interventions, formation of a Joint Ethics Review Committee with representatives of the Ethics Committees of all institutions and countries involved to strengthen reviews through the different perspectives provided without the ‘opportunity costs’ for time to final approval of multiple, independent reviews, direct information exchange between the chairs of advisory, safety review and ethics committees, more Ethics Committee support for investigators than is standard and a global consultation on criteria for inclusion of pregnant women and children in interventional studies for conditions which put them at particularly high risk of mortality or other irreversible adverse outcomes under standard-of-care. (shrink)

Background Between 2013 and 2016, West Africa experienced the largest ever outbreak of Ebola Virus Disease. In the absence of registered treatments or vaccines to control this lethal disease, the World Health Organization coordinated and supported research to expedite identification of interventions that could control the outbreak and improve future control efforts. Consequently, the World Health Organization Research Ethics Review Committee was heavily involved in reviews and ethics discussions. It reviewed 24 new and 22 amended protocols for research studies including (...) interventional and observational studies. WHO-ERC reviews WHO-ERC provided the reviews within on average 6 working days. The WHO-ERC often could not provide immediate approval of protocols for reasons which were not Ebola Virus Disease specific but related to protocol inconsistencies, missing information and complex informed consents. WHO-ERC considerations on Ebola Virus Disease specific issues are presented. Conclusions To accelerate study approval in future public health emergencies, we recommend: internally consistent and complete submissions with information documents in language participants are likely to understand, close collaboration between local and international researchers from research inception, generation of template agreements for data and sample sharing and use during the ongoing global consultations on bio-banks, formation of Joint Scientific Advisory and Data Safety Review Committees for all studies linked to a particular intervention or group of interventions, formation of a Joint Ethics Review Committee with representatives of the Ethics Committees of all institutions and countries involved to strengthen reviews through the different perspectives provided without the ‘opportunity costs’ for time to final approval of multiple, independent reviews, direct information exchange between the chairs of advisory, safety review and ethics committees, more Ethics Committee support for investigators than is standard and a global consultation on criteria for inclusion of pregnant women and children in interventional studies for conditions which put them at particularly high risk of mortality or other irreversible adverse outcomes under standard-of-care. (shrink)