#Polio, #AIDS, and #Ebola: A Recurrent #Ethical #Dilemma (Clin Infect Dis., abstract)

[Source: Clinical Infectious Diseases, full page: (LINK). Abstract, edited.]

Clin Infect Dis. 2019 Jul 24. pii: ciz662. doi: 10.1093/cid/ciz662. [Epub ahead of print]

Polio, AIDS, and Ebola: A Recurrent Ethical Dilemma.

Kazanjian P1.

Author information: 1 University of Michigan Michigan Medicine, Department of Internal Medicine, Division of Infectious Diseases, University Hospital South, Medical Center Drive Ann Arbor, MI, United States of America.

 

Abstract

During the 2014 West African outbreak, a dilemma emerged about the ethics of conducting randomized placebo-controlled trials in the midst of a rapidly spreading, devastating epidemic for which there was no effective treatment. The dilemma has in fact has deep historic roots; it has appeared in several previous fearsome epidemics-during the poliomyelitis epidemic in the 1930s-1950s, and again during the AIDS epidemic in the1980s-1990s. Moreover, ethical and social questions characterizing each of these epidemics-the increased risks of withholding potentially life-saving drugs for people assigned to a control arm and the damaging effect on eroding community trust-were conceptualized beforehand in the 1925 novel Arrowsmith. A historical analysis both reaffirms that rigorous placebo controlled trials remain indispensable tools in epidemic settings and also provides guidance on how to approach the ethical and social issues that will likely arise when these trials are carried out in future epidemic emergencies.

© The Author(s) 2019. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail: journals.permissions@oup.com.

KEYWORDS: AIDS; Ebola; Epidemics; Ethical dilemma; Placebo-controlled trial; Polio

PMID: 31339992 DOI: 10.1093/cid/ciz662

Keywords: Emerging Diseases; Bioethics.

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#Conceptions within #misconceptions: #Pluralisms in an #Ebola #vaccine #trial in West Africa (Glob Public Health., abstract)

[Source: US National Library of Medicine, full page: (LINK). Abstract, edited.]

Glob Public Health. 2019 Jun 25:1-9. doi: 10.1080/17441692.2019.1632368. [Epub ahead of print]

Conceptions within misconceptions: Pluralisms in an Ebola vaccine trial in West Africa.

Alenichev A1,2, Peeters Grietens K3, Gerrets R1.

Author information: 1a Department of Anthropology , University of Amsterdam , Amsterdam , Netherlands. 2b The Barcelona Institute for Global Health , Barcelona , Spain. 3c Department of Public Health , Institute of Tropical Medicine , Antwerp , Belgium.

 

Abstract

Ensuring that biomedical information about research procedures is adequately understood by participants and their communities is key for conducting ethical research. This article explores participants’ understanding of trial procedures for an experimental vaccine against Ebola virus disease (EVD) in a West African context. We found that some trial participants believed there was a chance of contracting Ebola and other sicknesses from the vaccine, and others believed both the vaccine and the placebo control would be able to prevent other illnesses than EVD. While these beliefs might be understood as misconceptions about the vaccine trial, this paper shows that such a conclusion is problematic because it excludes local explanatory health models and logics of causality. The paper invites bioethicists to work with anthropologists to take seriously different models of health knowledge in global health research. Investigating and addressing such differences could be the key to understanding human subjects’ motives for participation, and to creating space for studies of empirical ethics.

KEYWORDS: Ebola; clinical trial; misconceptions; pluralism

PMID: 31237180 DOI: 10.1080/17441692.2019.1632368

Keywords: Ebola; Vaccines; Society; Africa region; Bioethics.

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#RTS,S #malaria #vaccine pilot studies: addressing the #human #realities in large-scale clinical trials (Trials, abstract)

[Source: Trials, full page: (LINK). Abstract, edited.]

Commentary / Open Access / Open Peer Review

RTS,S malaria vaccine pilot studies: addressing the human realities in large-scale clinical trials

Machteld van den Berg, Bernhards Ogutu, Nelson K. Sewankambo, Nikola Biller-Andorno and Marcel Tanner

Trials, 201920:316 / DOI: https://doi.org/10.1186/s13063-019-3391-7

©  The Author(s). 2019

Received: 18 December 2018 – Accepted: 2 May 2019 – Published: 31 May 2019 – Open Peer Review reports

 

Abstract

A malaria vaccine as part of the integrated malaria control and elimination efforts will have a major impact on public health in sub-Sahara Africa. The first malaria vaccine, RTS,S, now enters pilot implementation in three African countries. These pilot implementation studies are being initiated in Kenya, Malawi, and Ghana to inform the broader roll-out recommendation. Based on the malaria vaccine clinical trial experiences, key ethical practices for effective clinical trial research in low-resource settings are described. For successful vaccine integration into malaria intervention programs, the relational dynamics between researchers and trial communities must be made explicit. Incorporating community values and returning to research practices that serve the intended benefactors are key strategies that address the human realities in large-scale clinical trials and pilot implementation, leading to positive public health outcomes.

Keywords: Malaria vaccine – Pilot studies – Low-resource settings – Community engagement – Ethics – Transnational clinical trials

Keywords: Malaria; Vaccines; Bioethics.

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Too Many #Patients…A #Framework to Guide Statewide #Allocation of Scarce Mechanical #Ventilation During #Disasters (Chest, abstract)

[Source: US National Library of Medicine, full page: (LINK). Abstract, edited.]

Chest. 2018 Oct 11. pii: S0012-3692(18)32565-0. doi: 10.1016/j.chest.2018.09.025. [Epub ahead of print]

Too Many Patients…A Framework to Guide Statewide Allocation of Scarce Mechanical Ventilation During Disasters.

Daugherty Biddison EL1, Faden R2, Gwon HS3, Mareiniss DP4, Regenberg AC2, Schoch-Spana M5, Schwartz J6, Toner ES5.

Author information: 1 Johns Hopkins University School of Medicine. Electronic address: Lee.biddison@jhmi.edu. 2 Johns Hopkins Berman Institute of Bioethics. 3 Johns Hopkins Medicine. 4 Georgetown University School of Medicine. 5 Johns Hopkins Bloomberg School of Public Health. 6 University of Maryland Carey School of Law.

 

Abstract

The threat of a catastrophic public health emergency causing life threatening illness or injury on a massive scale has prompted extensive federal, state, and local preparedness efforts. Modeling studies suggest that an influenza pandemic similar to that of 1918 would require ICU and mechanical ventilation capacity that is significantly greater than what is available. Several groups have published recommendations for allocating life-support measures during a public health emergency. Because there are multiple ethically permissible approaches to allocating scarce life-sustaining resources and because the public will bear the consequences of these decisions, knowledge of public perspectives and moral points of reference on these issues is critical. Here we describe a critical care disaster resource allocation framework developed following a state-wide community engagement process in Maryland. It is intended to assist hospitals and public health agencies in their independent and coordinated response to an officially declared catastrophic health emergency in which demand for mechanical ventilators exceeds the capabilities of all surge response efforts and in which there has been an executive order to implement scarce resource allocation procedures. The framework, built on a basic scoring system with modifications for specific considerations, also creates an opportunity for the legal community to review existing laws and liability protections in light of a specific disaster response process.

PMID: 30316913 DOI: 10.1016/j.chest.2018.09.025

Keywords: Disaster Preparedness; Pandemic Preparedness; Public Health.

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Synthetic #horsepox viruses and the continuing #debate about dual use #research (PLoS Pathogens, summary)

[Source: PLoS Pathogens, full page: (LINK). Summary, edited.]

OPEN ACCESS / OPINION

Synthetic horsepox viruses and the continuing debate about dual use research

Ryan S. Noyce, David H. Evans

Published: October 4, 2018 / DOI: https://doi.org/10.1371/journal.ppat.1007025

Citation: Noyce RS, Evans DH (2018) Synthetic horsepox viruses and the continuing debate about dual use research. PLoS Pathog 14(10): e1007025. https://doi.org/10.1371/journal.ppat.1007025

Editor: Carolyn B. Coyne, University of Pittsburgh, UNITED STATES

Published: October 4, 2018

Copyright: © 2018 Noyce, Evans. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

Funding: The HPXV project is supported by funding from Tonix Pharmaceuticals Ltd. Long-term research support from the Canadian Institutes for Health Research, Natural Sciences & Engineering Research Council, and the Canada Foundation for Innovation is also gratefully acknowledged. These funders had no role in study design, data collection and analysis, decision to publish, or preparation of this manuscript.

Competing interests: The authors are paid consultants for Tonix Pharmaceuticals and are identified as co-inventors on patent applications relating to synthetic poxviruses.

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On January 19, 2018, a paper describing the complete synthesis of a horsepox virus was published in PLOS ONE [1]. This is the largest virus assembled to date, and it shows that no viral pathogen is likely beyond the reach of synthetic biology. The paper and reports of its contents have attracted much comment [2–4]. As the two authors who conducted these experiments, we thank PLOS Pathogens for giving us the opportunity to address some of the issues arising from this work.

At the heart of the discussion lies the fact that this is dual use research of concern (DURC) [5] because any method that can be used to assemble horsepox virus could be used to construct variola, the virus that causes smallpox. This renders our work of special relevance for the agencies tasked with ensuring that smallpox remains a disease of history. Although the world’s known variola stocks are securely stored in Russia and the United States, synthetic biology compromises this approach for securing any agent. This was shown by the reconstruction of poliovirus in 2002 [6] and has been discussed within WHO [7]. Whether secret or lost [8] stocks of variola virus still exist is unknown, but countermeasures are still stockpiled because of this recognized threat.

(…)

Keywords: Biological Hazards; Bioethics; Bioterrorism; Syntetic Biology; Horsepox virus.

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Inoculating #science against potential #pandemics and #information #hazards (PLoS Pathogens, abstract)

[Source: PLoS Pathogens, full page: (LINK). Abstract, edited.]

OPEN ACCESS / OPINION

Inoculating science against potential pandemics and information hazards

Kevin M. Esvelt

Published: October 4, 2018 / DOI: https://doi.org/10.1371/journal.ppat.1007286

 

Abstract

The recent de novo assembly of horsepox is an instructive example of an information hazard: published methods enabling poxvirus synthesis led to media coverage spelling out the implications, efficiently disseminating true information that might be used to cause harm. Whether or not the benefits justified the risks, the horsepox saga provides ample reason to upgrade the current system for screening synthesized DNA for hazardous sequences, which does not cover the majority of firms and cannot reliably prevent the assembly of potentially pandemic pathogens. An upgraded system might leverage one-way encryption to confidentially scrutinize virtually all commercial production by a cooperative international network of servers whose integrity can be verified by third parties. Funders could support participating institutions to ease the transition or outright subsidize the market to make clean DNA cheaper, while boycotts by journals, institutions, and funders could ensure compliance and require hardware-level locks on future DNA synthesizers. However, the underlying problem is that security and safety discussions among experts typically follow potentially hazardous events rather than anticipating them. Changing norms and incentives to favor preregistration and advisory peer review of planned experiments could test alternatives to the current closeted research model in select areas of science. Because the fields of synthetic mammalian virology and especially gene drive research involve technologies that could be unilaterally deployed and may self-replicate in the wild, they are compelling candidates for initial trials of early-stage peer review.

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Citation: Esvelt KM (2018) Inoculating science against potential pandemics and information hazards. PLoS Pathog 14(10): e1007286. https://doi.org/10.1371/journal.ppat.1007286

Editor: Carolyn B. Coyne, University of Pittsburgh, UNITED STATES

Published: October 4, 2018

Copyright: © 2018 Kevin M. Esvelt. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

Funding: I gratefully acknowledge support from Burroughs Wellcome Fund IRSA 1016432, and NIH R00-DK102669-04 and DP2-A136597-01. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.

Competing interests: The author has declared that no competing interests exist.

Keywords: Synthetic Biology; Biological Hazards; Bioterrorism; Bioethics; Pandemic Preparedness.

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Why Do Exceptionally #Dangerous #GOF #Experiments in #Influenza (Methods Mol Biol., abstract)

[Source: US National Library of Medicine, full page: (LINK). Abstract, edited.]

Methods Mol Biol. 2018;1836:589-608. doi: 10.1007/978-1-4939-8678-1_29.

Why Do Exceptionally Dangerous Gain-of-Function Experiments in Influenza?

Lipsitch M1.

Author information: 1 Departments of Epidemiology and Immunology and Infectious Diseases, Center for Communicable Disease Dynamics, Harvard TH Chan School of Public Health, Boston, MA, USA. mlipsitc@hsph.harvard.edu.

 

Abstract

This chapter makes the case against performing exceptionally dangerous gain-of-function experiments that are designed to create potentially pandemic and novel strains of influenza, for example, by enhancing the airborne transmissibility in mammals of highly virulent avian influenza strains. This is a question of intense debate over the last 5 years, though the history of such experiments goes back at least to the synthesis of viable influenza A H1N1 (1918) based on material preserved from the 1918 pandemic. This chapter makes the case that experiments to create potential pandemic pathogens (PPPs) are nearly unique in that they present biosafety risks that extend well beyond the experimenter or laboratory performing them; an accidental release could, as the name suggests, lead to global spread of a virulent virus, a biosafety incident on a scale never before seen. In such cases, biosafety considerations should be uppermost in the consideration of alternative approaches to experimental objectives and design, rather than being settled after the fact, as is appropriately done for most research involving pathogens. The extensive recent discussion of the magnitude of risks from such experiments is briefly reviewed. The chapter argues that, while there are indisputably certain questions that can be answered only by gain-of-function experiments in highly pathogenic strains, these questions are narrow and unlikely to meaningfully advance public health goals such as vaccine production and pandemic prediction. Alternative approaches to experimental influenza virology and characterization of existing strains are in general completely safe, higher throughput, more generalizable, and less costly than creation of PPP in the laboratory and can thereby better inform public health. Indeed, virtually every finding of recent PPP experiments that has been cited for its public health value was predated by similar findings using safe methodologies. The chapter concludes that the unique scientific and public health value of PPP experiments is inadequate to justify the unique risks they entail and that researchers would be well-advised to turn their talents to other methodologies that will be safe and more rewarding scientifically.

KEYWORDS: Evolution; Ferret; Gain-of-function; Influenza; Passage; Potential pandemic pathogen; Selection; Transmissibility; Virulence

PMID: 30151594 DOI: 10.1007/978-1-4939-8678-1_29

Keywords: Pandemic Influenza; Influenza A; Pandemic Preparedness; Biosafety; Biological Hazards; Bioethics.

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