Key criteria for the ethical acceptability of COVID-19 human challenge studies: Report of a WHO Working Group.
Ontology highlight
ABSTRACT:
SUBMITTER: Jamrozik E
PROVIDER: S-EPMC7598752 | biostudies-literature | 2021 Jan
REPOSITORIES: biostudies-literature
Publications
Key criteria for the ethical acceptability of COVID-19 human challenge studies: Report of a WHO Working Group.
Jamrozik Euzebiusz E Littler Katherine K Bull Susan S Emerson Claudia C Kang Gagandeep G Kapulu Melissa M Rey Elena E Saenz Carla C Shah Seema S Smith Peter G PG Upshur Ross R Weijer Charles C Selgelid Michael J MJ
Vaccine 20201028 4
This report of the WHO Working Group for Guidance on Human Challenge Studies in COVID-19 outlines ethical standards for COVID-19 challenge studies. It includes eight Key Criteria related to scientific justification, risk-benefit assessment, consultation and engagement, co-ordination of research, site selection, participant selection, expert review, and informed consent. The document aims to provide comprehensive guidance to scientists, research ethics committees, funders, policymakers, and regul ...[more]
Similar Datasets
Project description:COVID-19 poses an extraordinary threat to global public health and an effective vaccine could provide a key means of overcoming this crisis. Human challenge studies involve the intentional infection of research participants and can accelerate or improve vaccine development by rapidly providing estimates of vaccine safety and efficacy. Human challenge studies of low virulence coronaviruses have been done in the past and human challenge studies with severe acute respiratory syndrome coronavirus 2 have been proposed. These studies of coronaviruses could provide considerable benefits to public health; for instance, by improving and accelerating vaccine development. However, human challenge studies of severe acute respiratory syndrome coronavirus 2 in particular might be controversial, in part, for ethical reasons. The ethical issues raised by such studies thus warrant early consideration involving, for example, broad consultation with the community. This Personal View provides preliminary analyses of relevant ethical considerations regarding human challenge studies of severe acute respiratory syndrome coronavirus 2, including the potential benefits to public health and to participants, the risks and uncertainty for participants, and the third-party risks (ie, to research staff and the wider community). We argue that these human challenge studies can reasonably be considered ethically acceptable insofar as such studies are accepted internationally and by the communities in which they are done, can realistically be expected to accelerate or improve vaccine development, have considerable potential to directly benefit participants, are designed to limit and minimise risks to participants, and are done with strict infection control measures to limit and reduce third-party risks.
| S-EPMC7259898 | biostudies-literature
Project description:Human challenge trials (HCTs) may accelerate the development of treatments and vaccines, and deliver novel insights into the course and consequences of infection. However, HCTs are contentious because they involve purposely exposing volunteers to infection. Consultation with the public and other stakeholders is essential for understanding how HCTs can be most ethically and acceptably pursued. Previous research has found public support for COVID-19 HCTs, but little research has considered public attitudes towards HCTs in principle and the various factors making a trial more or less acceptable. Empirical data on the attitudes of research personnel is also missing. We generated an online survey covering overarching support/opposition towards HCTs, as well as factors of importance for deciding whether or not an HCT is ethically acceptable. Our sample of the US public represents the responses of 1500 participants sampled via Prolific, poststratified to be representative of the general US adult population. We additionally collected a convenience sample of 33 research personnel engaged in phase III clinical trials for infectious diseases. Estimates for the US public suggest substantial support for using HCTs to develop new vaccines, new treatments, and knowledge about diseases, with similarly high support among research personnel. The most important factors in determining acceptability of an HCT were the risk to participants and their comprehension of this risk. The general public, in particular, appear relatively unconcerned about participants' motivations, and favor higher payment in accordance with risk. This study adds to a growing body of public consultation surrounding HCTs, demonstrating high levels of support for their use in principle-not just in relation to COVID-19. The importance attributed to various ethically-relevant factors can help in designing HCTs with high public acceptance.
| S-EPMC11495607 | biostudies-literature
Project description:Human infection challenge studies (HCS) involve intentionally infecting research participants with pathogens (or other micro-organisms). There have been recent calls for more HCS to be conducted in low-income and middle-income countries (LMICs), where many relevant diseases are endemic. HCS in general, and HCS in LMICs in particular, raise numerous ethical issues. This paper summarises the findings of a project that explored ethical and regulatory issues related to LMIC HCS via (i) a review of relevant literature and (ii) 45 qualitative interviews with scientists and ethicists. Among other areas of consensus, we found that there was widespread agreement that LMIC HCS can be ethically acceptable, provided that they have a sound scientific rationale, are accepted by local communities and meet usual research ethics requirements. Unresolved issues include those related to (i) acceptable approaches to trade-offs between the scientific aim to produce generalisable results and the protection of participants, (iii) the sharing of benefits with LMIC populations, (iii) the acceptable limits to risks and burdens for participants, (iv) the potential for third-party risk and whether the degree of acceptable third-party risk is different in endemic settings, (v) the conditions under which (if any) it would be appropriate to recruit children for disease-causing HCS, (v) appropriate levels of payment to participants and (vi) appropriate governance of (LMIC) HCS. This paper provides preliminary analyses of these ethical considerations in order to (i) inform scientists and policymakers involved in the planning, conduct and/or governance of LMIC HCS and (ii) highlight areas warranting future research. Insofar as this article focuses on HCS in (endemic) settings where diseases are present and/or widespread, much of the analysis provided is relevant to HCS (in HICs or LMICs) involving pandemic diseases including COVID19.
| S-EPMC7476299 | biostudies-literature
Project description:In recent years, the number of approved and investigational agents that can be safely administered for the treatment of lymphoma patients for a prolonged period of time has substantially increased. Many of these novel agents are evaluated in early-phase clinical trials in patients with a wide range of malignancies, including solid tumors and lymphoma. Furthermore, with the advances in genome sequencing, new "basket" clinical trial designs have emerged that select patients based on the presence of specific genetic alterations across different types of solid tumors and lymphoma. The standard response criteria currently in use for lymphoma are the Lugano Criteria which are based on [18F]2-fluoro-2-deoxy-D-glucose positron emission tomography or bidimensional tumor measurements on computerized tomography scans. These differ from the RECIST criteria used in solid tumors, which use unidimensional measurements. The RECIL group hypothesized that single-dimension measurement could be used to assess response to therapy in lymphoma patients, producing results similar to the standard criteria. We tested this hypothesis by analyzing 47 828 imaging measurements from 2983 individual adult and pediatric lymphoma patients enrolled on 10 multicenter clinical trials and developed new lymphoma response criteria (RECIL 2017). We demonstrate that assessment of tumor burden in lymphoma clinical trials can use the sum of longest diameters of a maximum of three target lesions. Furthermore, we introduced a new provisional category of a minor response. We also clarified response assessment in patients receiving novel immune therapy and targeted agents that generate unique imaging situations.
| S-EPMC5834038 | biostudies-literature
Project description:The COVID-19 pandemic has led many countries around the world to take drastic measures. Regardless of the epidemiological impact, it is undisputed that these measures have had significant negative effects on scholastic attainment, psychosocial and physical health of children and adolescents. Given their consequences, such interventions evoke the question of their ethical justifiability. This article introduces the most common ethical theories and, building on them, discusses the ethical evaluation of the COVID-19-related school closures.
| S-EPMC9549434 | biostudies-literature
Project description:Empirical evidence suggests fishes meet the criteria for experiencing pain beyond a reasonable doubt and zebrafish are being increasingly used in studies of pain and nociception. Zebrafish are adopted across a wide range of experimental fields and their use is growing particularly in biomedical studies. Many laboratory procedures in zebrafish involve tissue damage and this may give rise to pain. Therefore, this FELASA Working Group reviewed the evidence for pain in zebrafish, the indicators used to assess pain and the impact of a range of drugs with pain-relieving properties. We report that there are several behavioural indicators that can be used to determine pain, including reduced activity, space use and distance travelled. Pain-relieving drugs prevent these responses, and we highlight the dose and administration route. To minimise or avoid pain, several refinements are suggested for common laboratory procedures. Finally, practical suggestions are made for the management and alleviation of pain in laboratory zebrafish, including recommendations for analgesia. Pain management is an important refinement in experimental animal use and so our report has the potential to improve zebrafish welfare during and after invasive procedures in laboratories across the globe.
| S-EPMC11264547 | biostudies-literature
Project description:The Banff Digital Pathology Working Group (DPWG) was established with the goal to establish a digital pathology repository; develop, validate, and share models for image analysis; and foster collaborations using regular videoconferencing. During the calls, a variety of artificial intelligence (AI)-based support systems for transplantation pathology were presented. Potential collaborations in a competition/trial on AI applied to kidney transplant specimens, including the DIAGGRAFT challenge (staining of biopsies at multiple institutions, pathologists' visual assessment, and development and validation of new and pre-existing Banff scoring algorithms), were also discussed. To determine the next steps, a survey was conducted, primarily focusing on the feasibility of establishing a digital pathology repository and identifying potential hosts. Sixteen of the 35 respondents (46%) had access to a server hosting a digital pathology repository, with 2 respondents that could serve as a potential host at no cost to the DPWG. The 16 digital pathology repositories collected specimens from various organs, with the largest constituent being kidney (n = 12,870 specimens). A DPWG pilot digital pathology repository was established, and there are plans for a competition/trial with the DIAGGRAFT project. Utilizing existing resources and previously established models, the Banff DPWG is establishing new resources for the Banff community.
| S-EPMC10614670 | biostudies-literature
Project description:Prior to the COVID-19 pandemic, the majority of clinical trial activity took place face to face within clinical or research units. The COVID-19 pandemic resulted in a significant shift towards trial delivery without in-person face-to-face contact or "Remote Trial Delivery". The National Institute of Health Research (NIHR) assembled a Remote Trial Delivery Working Group to consider challenges and enablers to this major change in clinical trial delivery and to provide a toolkit for researchers to support the transition to remote delivery. The NIHR Remote Trial Delivery Working Group evaluated five key domains of the trial delivery pathway: participant factors, recruitment, intervention delivery, outcome measurement and quality assurance. Independent surveys were disseminated to research professionals, and patients and carers, to ascertain benefits, challenges, pitfalls, enablers and examples of good practice in Remote Trial Delivery. A toolkit was constructed to support researchers, funders and governance structures in moving towards Remote Trial Delivery. The toolkit comprises a website encompassing the key principles of Remote Trial Delivery, and a repository of best practice examples and questions to guide research teams. The patient and carer survey received 47 respondents, 34 of whom were patients and 13 of whom were carers. The professional survey had 115 examples of remote trial delivery practice entered from across England. Key potential benefits included broader reach and inclusivity, the ability for standardisation and centralisation, and increased efficiency and patient/carer convenience. Challenges included the potential exclusion of participants lacking connectivity or digital skills, the lack of digitally skilled workforce and appropriate infrastructure, and validation requirements. Five key principles of Remote Trial Delivery were proposed: national research standards, inclusivity, validity, cost-effectiveness and evaluation of new methodologies. The rapid changes towards Remote Trial Delivery catalysed by the COVID-19 pandemic could lead to sustained change in clinical trial delivery. The NIHR Remote Trial Delivery Working Group provide a toolkit for researchers recommending five key principles of Remote Trial Delivery and providing examples of enablers.
| S-EPMC8665850 | biostudies-literature
Project description:Chronic graft-versus-host disease (GVHD) commonly occurs after allogeneic hematopoietic cell transplantation (HCT) despite standard prophylactic immune suppression. Intensified universal prophylaxis approaches are effective but risk possible overtreatment and may interfere with the graft-versus-malignancy immune response. Here we summarize conceptual and practical considerations regarding preemptive therapy of chronic GVHD, namely interventions applied after HCT based on evidence that the risk of developing chronic GVHD is higher than previously appreciated. This risk may be anticipated by clinical factors or risk assignment biomarkers or may be indicated by early signs and symptoms of chronic GVHD that do not fully meet National Institutes of Health diagnostic criteria. However, truly preemptive, individualized, and targeted chronic GVHD therapies currently do not exist. In this report, we (1) review current knowledge regarding clinical risk factors for chronic GVHD, (2) review what is known about chronic GVHD risk assignment biomarkers, (3) examine how chronic GVHD pathogenesis intersects with available targeted therapeutic agents, and (4) summarize considerations for preemptive therapy for chronic GVHD, emphasizing trial development, including trial design and statistical considerations. We conclude that robust risk assignment models that accurately predict chronic GVHD after HCT and early-phase preemptive therapy trials represent the most urgent priorities for advancing this novel area of research.
| S-EPMC8934187 | biostudies-literature
Project description:The European Working group on Sarcopenia in Older People recently updated the diagnostic criteria for sarcopenia. It is yet unclear how these modified criteria influence the rate of diagnosis in high risk populations, such as liver cirrhosis. We therefore assessed if the new diagnostic criteria for sarcopenia impacts on sarcopenia prevalence in liver cirrhosis. Within two years 114 cirrhotic patients were prospectively enrolled in the study. Sarcopenia was determined by muscle strength (handgrip strength), muscle mass (lumbal muscle index) and muscle performance (gait speed). Using the 2019 definition, the rate of pre-sarcopenia was significantly lower (30.7% versus 3.5%) due to the different starting points (2010 muscle mass, 2019 muscle strength) and cut-off values (muscle strength). The change in diagnostic criteria for sarcopenia drastically influences the rate of pre-sarcopenia diagnosis in cirrhotics. To evaluate, which diagnostic criteria should be chosen to diagnose sarcopenia in liver cirrhosis patients, prospective studies are needed.
| S-EPMC7071440 | biostudies-literature