Decentralised clinical trials: ethical opportunities and challenges.

Fuelled by adaptations to clinical trial implementation during the COVID-19 pandemic, decentralised clinical trials are burgeoning. Decentralised clinical trials involve many digital tools to facilitate research without physical contact between research teams and participants at various stages, such as recruitment, enrolment, informed consent, administering study interventions, obtaining patient-reported outcome measures, and safety monitoring. These tools can provide ways of ensuring participants' safety and research integrity, while sometimes reducing participant burden and trial cost. Research sponsors and investigators are interested in expanding the use of decentralised clinical trials. The US Food and Drug Administration and other regulators worldwide have issued guidance on how to implement such adaptations. However, there has been little focus on the distinct ethical challenges these trials pose. In this Health Policy report, which is informed by both traditional research ethics and digital ethics frameworks, we group the related ethical issues under three areas requiring increased ethical vigilance: participants' safety and rights, scientific validity, and ethics oversight. Our aim is to describe these issues, offer practical means of addressing them, and prompt the delineation of ethical standards for decentralised trials.

Research Ethics during Pandemics: How IRBs Can Prepare.

The Covid-19 pandemic has raised a range of complex challenges for the research community in the United States. This essay uses Covid-19 as a model pandemic illness to consider two such issues that have yet to be fully explored in the ethics literature: first, whether the informed consent process should include a discussion of pandemic risks and, if so, how precisely these risks should be conveyed to potential research participants and, second, whether and under what circumstances vaccination status should be taken into consideration when enrolling subjects in non-pandemic-related studies during a pandemic.

Ethics committees in the time of COVID-19.

BACKGROUND: ethics committees (ECs) protect the rights, safety, and well-being of research participants and ensure the scientific correctness of clinical research. COVID-19 pandemic and the lockdown from 9 March to 16 May 2020 have potentially influenced several activities, including ECs. OBJECTIVES: to assess the impact of COVID-19 outbreak on Italian ECs and their performance during the lockdown. DESIGN: cross-sectional survey. SETTING AND PARTICIPANTS: the survey was conducted in mid-June 2020 in Italy contacting all the 90 local ECs. MAIN OUTCOME MEASURES: amount and kind of activities performed during the lockdown, characteristics of submitted studies and adoption of standard protocols of evaluation of research applications during the pandemic. Chi-square test was used to estimate the differences between territories with higher incidence (HI) and lower incidence (LI) of COVID-19. RESULTS: 258 questionnaires were collected from 46 ECs that participated in the study. Ten were excluded due to missing substantial data. Responses were divided into two groups according to location of EC: the HI (125 responses) and the LI (123 responses). Seventy-five percent of the HI describe an increase in the number of studies submitted, while 53% of the LI does not (p=0.001). Due to the pandemic and its effects on research, the 15% of participants belonging to HI territories reported that consideration and respect of research-related and general ethical principles could have decreased, as well the adoption of standard protocols of evaluation of research applications. EC secretariats located in HI Regions moved to smart working more than in LI ones (75% vs 59%; p=0.001). Where the EC workload increased significantly, it was reported that it was impossible to perform an accurate analysis of the submitted documentation, with the effect of providing a favorable opinion to studies of not excellent quality, though always ensuring the respect of ethical principles and patients' safety. CONCLUSIONS: COVID-19 impact on ECs has been heavier in HI territories, but smart working has been effective in ensuring EC activities and the subsequent activation of clinical studies potentially useful to face the pandemic. Clear differences arise between ECs belonging to the Italian Regions that have recorded a HI of COVID-19 cases compared to those located in Regions with a LI of cases. In some EC members' perception, the high number of studies in the most affected Regions together with the emergency experienced during the lockdown may have exposed ECs to the risk of decreasing the adoption of ethical principles and standard protocols of evaluation of research applications.

Challenges in developmental psychology research during the COVID-19 pandemic / Desafios da pesquisa em psicologia do desenvolvimento durante a pandemia da COVID-19 / Desafíos de la investigación en psicología del desarrollo durante la pandemia de COVID-19

The COVID-19 pandemic brought a series of restructurings necessary for research in Developmental Psychology. The aim of the manuscript is to discuss adaptations we made in our research in this context during the COVID-19 pandemic and to present strategies to adequate research protocols originally designed to occur in person. Although some contexts do not allow the continuity of studies, research at this time can bring essential contributions in this extreme period. This article explores the strategies for adapting recruitment procedures, suggesting dissemination platforms, and using social networks for this purpose. Guidelines are suggested for conducting non-face-to-face interviews with caregivers, ways of assessing the interaction of the mother-child pairs, and problematizing ethical issues. The procedures for returning the results, an ethical researcher commitment, may be improved by resources such as automatic reports. Besides, strategies for better dissemination of the results for the participants are suggested. (AU)

A pandemia COVID-19 trouxe uma série de reestruturações necessárias à pesquisa em Psicologia do Desenvolvimento. O objetivo deste artigo é discutir as adaptações que realizamos em pesquisas neste contexto durante a pandemia de COVID-19 e apresentar estratégias para adequação de protocolos de pesquisa originalmente planejados para ocorrer de forma presencial. Embora alguns contextos não permitam a continuidade dos estudos, pesquisas nesse momento podem trazer importantes contribuições sobre este período ímpar. No presente artigo são exploradas estratégias de adaptação dos procedimentos de recrutamento, sugeridas plataformas de divulgação e como melhor usar as redes sociais para esse fim. Também são descritos procedimentos para realização de entrevistas não presenciais com responsáveis, formas de avaliação da interação das duplas mãe-criança e problematizadas questões éticas. Os procedimentos de devolução dos resultados, um compromisso ético dos pesquisadores, podem ser facilitados por recursos como relatórios automáticos. Além disso, sugerimos estratégias para melhor divulgação dos resultados ao público participante. (AU)

La pandemia del COVID-19 trajo una serie de reestructuraciones necesarias para la investigación en Psicología del Desarrollo. El objetivo de este artículo es discutir las adaptaciones realizadas en las investigaciones en este contexto durante la pandemia de COVID-19 y presentar algunas estrategias para la adaptación de los protocolos de investigación originalmente planeados para ser presenciales. Si bien algunos contextos no permitan la continuidad de los estudios, la investigación en este momento puede aportar importantes avances sobre estos tiempos de crisis. Este artículo explora las estrategias para adaptar los procedimientos de contratación, sugiriendo algunas plataformas de difusión y la mejor manera de utilizar las redes sociales para este fin. También se describen los procedimientos para la realización de entrevistas no presenciales con padres o tutores legales, las formas de evaluar la interacción madre-hijo y las cuestiones éticas. Los procedimientos para la devolución de los resultados, un compromiso ético de los investigadores, pueden verse facilitados por funciones como informes automáticos. Además, se recomienda estrategias para una mejor difusión de los resultados al público participante. (AU)

Strengthening research ethics governance and regulatory oversight in Central America and the Dominican Republic in response to the COVID-19 pandemic: a qualitative study.

BACKGROUND: Good governance and regulatory supervision are required to conduct research in an international public health emergency context and to ensure compliance with ethical standards. The "Strengthening research ethics governance and regulatory oversight in Central America and the Dominican Republic in response to the COVID-19 pandemic" study is a regional effort in which research ethics stakeholders participated in addressing research ethics governance and preparedness response challenges to the COVID-19 pandemic in Central America and the Dominican Republic. METHODS: A qualitative action research study was conducted following a participatory approach. Research ethics stakeholders in Central America and the Dominican Republic were mapped; a regional webinar and three virtual workshops were conducted discussing research ethics governance, ethics review and collaborative research practice during the pandemic. A roundtable session presented results and obtained feedback on a draft of a policy to strengthen regional research ethics governance. RESULTS: Countries across Central America and the Dominican Republic are at different stages in their development of research ethics systems. Countries with more established systems before COVID-19 were better organized and prepared to respond. This finding argues against improvisation and supports further work on strengthening governance of research ethics systems. Community engagement in research ethics public policy-making is practically absent in the region. Research and research ethics collaboration schemes are lacking amongst the countries; however, there are incipient initiatives in the region, such as the Central America and Caribbean Network of Research Ethics Committees. A policy brief with recommendations on how to advance towards strengthening the governance of research ethics systems was prepared and submitted to the Central American Integration System for analysis and possible approval. CONCLUSION: National research ethics systems in Central America and the Dominican Republic were unprepared to respond to the COVID-19 pandemic with respect to research oversight and effective collaboration. In most cases, national research ethics systems were found to be weak, and regional research collaboration was practically absent. To promote collaboration, a joint strategy needs to be developed with a regional vision towards sharing knowledge and best practices.

"We're already doing this work": ethical research with community-based organizations.

BACKGROUND: Public health research frequently relies on collaborations with community-based organizations, and these partnerships can be essential to the success of a project. However, while public health ethics and oversight policies have historically focused on ensuring that individual subjects are protected from unethical or unfair practices, there are few guidelines to protect the organizations which facilitate relationships with - and are frequently composed of - these same vulnerable populations. As universities, governments, and donors place a renewed emphasis on the need for community engaged research to address systematic drivers of health inequity, it is vital that the ways in which research is conducted does not uphold the same intersecting systems of gender, race, and class oppression which led to the very same health inequities of interest. METHODS: To understand how traditional notions of public health research ethics might be expanded to encompass partnerships with organizations as well as individuals, we conducted qualitative interviews with 39 staff members (executive directors and frontline) at community-based organizations that primarily serve people who use drugs, Black men who have sex with men, and sex workers across the United States from January 2016 - August 2017. We also conducted 11 in-depth interviews with professional academic researchers with experience partnering with CBOs that serve similar populations. Transcripts were analyzed thematically using emergent codes and a priori codes derived from the Belmont Report. RESULTS: The concepts of respect, beneficence, and justice are a starting point for collaboration with CBOs, but participants deepened them beyond traditional regulatory concepts to consider the ethics of relationships, care, and solidarity. These concepts could and should apply to the treatment of organizations that participate in research just as they apply to individual human subjects, although their implementation will differ when applied to CBOs vs individual human subjects. CONCLUSIONS: Academic-CBO partnerships are likely to be more successful for both academics and CBOs if academic researchers work to center individual-level relationship building that is mutually respectful and grounded in cultural humility. More support from academic institutions and ethical oversight entities can enable more ethically grounded relationships between academic researchers, academic institutions, and community based organizations.

The integrity of the research record: a mess so big and so deep and so tall.

SUMMARY: Poor research integrity is increasingly recognised as a serious problem in science. We outline some evidence for this claim and introduce the Royal College of Psychiatrists (RCPsych) journals' Research Integrity Group, which has been created to address this problem.

Ethical Issues in Social Media Recruitment for Clinical Studies: Ethical Analysis and Framework.

BACKGROUND: Social media recruitment for clinical studies holds the promise of being a cost-effective way of attracting traditionally marginalized populations and promoting patient engagement with researchers and a particular study. However, using social media for recruiting clinical study participants also poses a range of ethical issues. OBJECTIVE: This study aims to provide a comprehensive overview of the ethical benefits and risks to be considered for social media recruitment in clinical studies and develop practical recommendations on how to implement these considerations. METHODS: On the basis of established principles of clinical ethics and research ethics, we reviewed the conceptual and empirical literature for ethical benefits and challenges related to social media recruitment. From these, we derived a conceptual framework to evaluate the eligibility of social media use for recruitment for a specific clinical study. RESULTS: We identified three eligibility criteria for social media recruitment for clinical studies: information and consent, risks for target groups, and recruitment effectiveness. These criteria can be used to evaluate the implementation of a social media recruitment strategy at its planning stage. We have discussed the practical implications of these criteria for researchers. CONCLUSIONS: The ethical challenges related to social media recruitment are context sensitive. Therefore, social media recruitment should be planned rigorously, taking into account the target group, the appropriateness of social media as a recruitment channel, and the resources available to execute the strategy.

The Ethics of Human Challenge Trials Using Emerging Severe Acute Respiratory Syndrome 2 Variants.

The world's first coronavirus disease 2019 human challenge trial using the D614G strain of severe acute respiratory syndrome 2 (SARS-CoV-2) is underway in the United Kingdom. The Wellcome Trust is funding challenge stock preparation of the Beta and Delta variant for a follow-up human challenge trial, and researchers at hVIVO are considering conducting these trials. However, little has been written thus far about the ethical justifiability of human challenge trials with SARS-CoV-2 variants of concern. We explore 2 specific characteristics of some variants that may initially be thought to make such trials unethical and conclude that SARS-CoV-2 variant challenge trials can remain ethical.

Formulating Hypotheses for Different Study Designs.

Generating a testable working hypothesis is the first step towards conducting original research. Such research may prove or disprove the proposed hypothesis. Case reports, case series, online surveys and other observational studies, clinical trials, and narrative reviews help to generate hypotheses. Observational and interventional studies help to test hypotheses. A good hypothesis is usually based on previous evidence-based reports. Hypotheses without evidence-based justification and a priori ideas are not received favourably by the scientific community. Original research to test a hypothesis should be carefully planned to ensure appropriate methodology and adequate statistical power. While hypotheses can challenge conventional thinking and may be controversial, they should not be destructive. A hypothesis should be tested by ethically sound experiments with meaningful ethical and clinical implications. The coronavirus disease 2019 pandemic has brought into sharp focus numerous hypotheses, some of which were proven (e.g. effectiveness of corticosteroids in those with hypoxia) while others were disproven (e.g. ineffectiveness of hydroxychloroquine and ivermectin).

An ongoing science-society-ethics experiment: The human challenge trial debate in COVID-19 pandemic: The human challenge trial debate in COVID-19 pandemic.

Human challenge trials to deliberately infect volunteers with SARS-CoV-2 should inspire wider debates about research ethics and participants' motivations to take part in such studies.

Social Researchers' Approaches to Research Ethics During the COVID-19 Pandemic: An Exploratory Study.

The global COVID-19 pandemic and quarantine/distancing measures have forced researchers to cope with a new situation. This paper aimed to analyze how the pandemic and its associated constraints have affected social researchers' approach to research ethics. Drawing on an online qualitative survey with 193 Polish social researchers conducted in April and May 2020, we distinguished three approaches: nothing has changed, opportunity-oriented, and precautionary. According to the first, the pandemic was not regarded as a situation that required additional reflection on ethical issues or changes in research approaches. By contrast, the other two were based on the assumption that the pandemic affected research project ethics. The difference was in the assessment of changes in the area of ethics. The pandemic presented an opportunity and a threat to the ethicality of research, respectively. We discuss the implications of all three approaches for research and education.

Governance frameworks for COVID-19 research ethics review and oversight in Latin America: an exploratory study.

BACKGROUND: Research has been an essential part of the COVID-19 pandemic response, including in Latin American (LA) countries. However, implementing research in emergency settings poses the challenge of producing valuable knowledge rapidly while upholding research ethical standards. Research ethics committees (RECs) therefore must conduct timely and rigorous ethics reviews and oversight of COVID-19 research. In the LA region, there is limited knowledge on how countries have responded to this need. To address this gap, the objective of our project is to explore if LA countries developed policies to streamline ethics review and oversight of research in response to the pandemic while ensuring its adherence to ethical standards, and to analyze to what extent these governance frameworks are in accordance with international guidance. METHODS: We conducted a descriptive and exploratory study assessing the COVID-19 research ethics governance frameworks of 19 LA countries, considering 4 dimensions based on international COVID-19 ethics guidance documents: (i) ethics review organizational model adopted, (ii) measures to coordinate between RECs and other research stakeholders, (iii) operational guidance for RECs, and (iv) key ethical issues for review and oversight of COVID-19 research. RESULTS: 10 out of 19 LA countries have some policy to streamline ethics review of COVID-19 research. Of these countries only 6 issued comprehensive documents following international guidance that contemplate strategies with recommendations for concrete actions for a timely and rigorous review. CONCLUSION: LA countries adopted partial strategies and operational guidance that may demonstrate a lack of a comprehensive view of research ethics for the review and oversight of COVID-19 research. Continuing efforts should be directed to strengthen LA countries' research capacity to respond timely and ethically to future health emergencies. Past lessons and the ones from this pandemic should be the basis to develop international standards and operational guidelines for ethics review and oversight of any research for public health emergencies.

Comparison of COVID-19 studies registered in the clinical trial platforms: A research ethics analysis perspective.

BACKGROUND: The coronavirus disease (COVID-19) treatment must be based on scientific methods such as clinical trials. Trials involving human subjects and those requiring a risk-benefit analysis may occasionally face challenges owing to the time limitations in the pandemic. METHODOLOGY: This study analyses the WHO's International Clinical Trials Registry Platform and clinicaltrials.gov, where most COVID-19 clinical trials are registered, according to ethical criteria including study design, conflicts of interest, enrollment of healthcare workers, study locations, site-, design-, and participant-related issues. The discussion is based on three aspects: the quality of the information to be produced, the relevance to significant health problems, and the creation or evaluation of interventions, policies, or practices that promote individual or public health. RESULTS: There were significant differences between the two platforms regarding the investigational medicinal product (IMP), the comparator, ethics committee/institutional review board approval, plan to share individual participant data, study phase, site, IMP, and design-related issues. Conflict of interest, sponsor information, and management of vulnerable groups were the main areas wherein both platforms lacked sufficient information. CONCLUSION: With this analysis, we aimed to define a minimum set of ethical criteria for clinical trial platforms to obtain standardization between these two platforms.

A Call for Better, Not Faster, Research Ethics Committee Reviews in the Covid-19 Era.

With the rapid spread of SARS-CoV2 has come a rapid proliferation of clinical research studies, resulting in considerable strain on research ethics committees (RECS), which need to review study proposals. RECs are pressured to move through the review process quickly so that studies can get underway to address the pandemic. These committees are also asked to increase efficiency without relaxing the standards for ethical review. RECs are accustomed to external pressure for approval from investigators; however, in the Covid-19 era, this pressure is coming from not only the sponsors and investigators but also many other stakeholders, including world leaders, the community, the media, and professional organizations. Drawing on the authors' experiences on a central REC reviewing complex multicenter Covid-19 studies, this commentary describes challenges that are inherent to Covid-19 research studies, such as the difficulty of obtaining informed consent from patients ill with the highly infectious virus. The commentary recommends several steps that RECs can take to ensure ethical review of research studies during the Covid-19 pandemic and future infectious disease outbreaks.