Ethical, regulatory, and practical barriers to COVID-19 research: A stakeholder-informed inventory of concerns

INTRODUCTION: SARS-CoV-2 (COVID-19) has caused death and economic injury around the globe. The urgent need for COVID-19 research created new ethical, regulatory, and practical challenges. The next public health emergency could be worse than COVID-19. We must learn about these challenges from the experiences of researchers and Research Ethics Committee professionals responsible for these COVID-19 studies to prepare for the next emergency. MATERIALS AND METHODS: We conducted an online survey to identify the ethical, oversight, and regulatory challenges of conducting COVID-19 research during the early pandemic, and proposed solutions for overcoming these barriers. Using criterion-based, convenience sampling, we invited researchers who proposed or conducted COVID-19 research to complete an anonymous, online survey about their experiences. We administered a separate but related survey to Institutional Review Board (IRB) professionals who reviewed COVID-19 research studies. The surveys included open-ended and demographic items. We performed inductive content analysis on responses to open-ended survey questions. RESULTS: IRB professionals (n = 143) and researchers (n = 211) described 19 types of barriers to COVID-19 research, related to 5 overarching categories: policy and regulatory, biases and misperceptions, institutional and inter-institutional conflicts, risks of harm, and pressure of the pandemic. Researchers and IRB professionals described 8 categories of adaptations and solutions to these challenges: enacting technological solutions; developing protocol-based solutions; disposition and team management; establishing and communicating appropriate standards; national guidance and leadership; maintaining high standards; prioritizing studies before IRB review; and identifying and incorporating experts. DISCUSSION AND CONCLUSIONS: This inventory of challenges represents ongoing barriers to studying the current pandemic, and they represent a risk to research during future public health emergencies. Delays in studies of a pandemic during a pandemic threatens the health and safety of the public. We urge the development of a national working group to address these issues before the next public health emergency arises

Are we ready to share qualitative research data? Knowledge and preparedness among qualitative researchers, IRB Members, and data repository curators

Data sharing maximizes the value of data, which is time and resource intensive to collect. Major funding bodies in the United States (US), like the National Institutes of Health (NIH), require data sharing and researchers frequently share de-identified quantitative data. In contrast, qualitative data are rarely shared in the US but the increasing trend towards data sharing and open science suggest this may be required in future. Qualitative methods are often used to explore sensitive health topics raising unique ethical challenges regarding protecting confidentiality while maintaining enough contextual detail for secondary analyses. Here, we report findings from semi-structured in-depth interviews with 30 data repository curators, 30 qualitative researchers, and 30 IRB staff members to explore their experience and knowledge of QDS. Our findings indicate that all stakeholder groups lack preparedness for QDS. Researchers are the least knowledgeable and are often unfamiliar with the concept of sharing qualitative data in a repository. Curators are highly supportive of QDS, but not all have experienced curating qualitative data sets and indicated they would like guidance and standards specific to QDS. IRB members lack familiarity with QDS although they support it as long as proper legal and regulatory procedures are followed. IRB members and data curators are not prepared to advise researchers on legal and regulatory matters, potentially leaving researchers who have the least knowledge with no guidance. Ethical and productive QDS will require overcoming barriers, creating standards, and changing long held practices among all stakeholder groups

Relative effects of mammal herbivory and plant spacing on seedling recruitment following fire and mining

<p>Abstract</p> <p>Background</p> <p>There is much debate concerning which ecological constraints are the most limiting factors to seedling recruitment in disturbed communities. We provide the first comparison between selective herbivory and plant competition effects among two post-mined forest ecosystems (primary succession) and one post-fire woodland ecosystem (secondary succession). Animal exclosure assessments of nine common species across eight sites were performed for comparison within three locations separated by up to 200 km. Additionally, we asked whether pre-browsed plants differed in nutrient content between or within species in the separate systems.</p> <p>Results</p> <p>Among the nine common species, seven of these were affected by mammal herbivory while five shared a similar vulnerability to predation regardless of system. One species was limited by competition (planting density). There was a strong linear correlation between herbivore selectivity (% browsed) and impact (biomass loss) on the fertilized minesites, but not post-fire sites. Phosphorus and potassium were higher for most species in the post-mined system. Principal components analyses revealed that nutrients in shortest supply may be the most likely components of selection within each system. Among all locations, species with highest levels of phosphorus, ADF and leaf water content were often favoured, while high tannins and nitrogen content were generally selected against.</p> <p>Conclusion</p> <p>Herbivory, rather than seedling competition, was the limiting factor for plant performance among post-fire and post-mined reclamation areas. The post-fire seedlings were smaller and more water and nutrient limited, nevertheless browsing prevalence was equivalent at all locations with nearly all seedlings predated. Kangaroo density in the post-fire community declined from the beginning of the experiment, while numbers in the post-mined revegetation increased fourfold within one year. Differences in water and nutrient availability may explain why herbivores are more likely to be attracted to post-mined communities.</p

Development of a resource guide to help patients receive appropriate care

After 10 years researching physician wrongdoing (i.e., sexual violations, improper prescribing, and unnecessary procedures), we developed a resource guide to help patients receive appropriate care and respond to inappropriate care. We gathered evaluative patient feedback, engaged physicians, and disseminated the guide. It is available at beforeyourvisit.org

Barriers and facilitators to qualitative data sharing in the United States: A survey of qualitative researchers

Qualitative health data are rarely shared in the United States (U.S.). This is unfortunate because gathering qualitative data is labor and time-intensive, and data sharing enables secondary research, training, and transparency. A new U.S. federal policy mandates data sharing by 2023, and is agnostic to data type. We surveyed U.S. qualitative researchers (N = 425) on the barriers and facilitators of sharing qualitative health or sensitive research data. Most researchers (96%) have never shared qualitative data in a repository. Primary concerns were lack of participant permission to share data, data sensitivity, and breaching trust. Researcher willingness to share would increase if participants agreed and if sharing increased the societal impact of their research. Key resources to increase willingness to share were funding, guidance, and de-identification assistance. Public health and biomedical researchers were most willing to share. Qualitative researchers need to prepare for this new reality as sharing qualitative data requires unique considerations

NADH dehydrogenase of Trypanosoma brucei is important for efficient acetate production in bloodstream forms

This work was supported by a grant from the National Institutes of Health (USA) [AI 5R01 AI069057] to MP and AS; a grant from the Medical Research Council (UK) [G0600129] to AS; grants from the Centre National de la Recherche Scientifique (CNRS, France), The Université de Bordeaux, The Agence Nationale de la Recherche (ANR) [ACETOTRYP of the ANR-BLANC-2010 call and GLYCONOV of the “Générique” call] and the Laboratoire d’Excellence (LabEx) ParaFrap [grant ANR-11-LABX-0024] to FB; and a grant from the Wellcome Trust [093228] to TKS.In the slender bloodstream form, Trypanosoma brucei mitochondria are repressed for many functions. Multiple components of mitochondrial complex I, NADH:ubiquinone oxidoreductase, are expressed in this stage, but electron transfer through complex I is not essential. Here we investigate the role of the parasite’s second NADH:ubiquinone oxidoreductase, NDH2, which is composed of a single subunit that also localizes to the mitochondrion. While inducible knockdown of NDH2 had a modest growth effect in bloodstream forms, NDH2 null mutants, as well as inducible knockdowns in a complex I deficient background, showed a greater reduction in growth. Altering the NAD+/NADH balance would affect numerous processes directly and indirectly, including acetate production. Indeed, loss of NDH2 led to reduced levels of acetate, which is required for several essential pathways in bloodstream form T. brucei and which may have contributed to the observed growth defect. In conclusion our study shows that NDH2 is important, but not essential, in proliferating bloodstream forms of T. brucei, arguing that the mitochondrial NAD+/NADH balance is important in this stage, even though the mitochondrion itself is not actively engaged in the generation of ATP.Publisher PDFPeer reviewe

Perceived barriers to assessing understanding and appreciation of informed consent in clinical trials: A mixed-method study

INTRODUCTION: Participants and research professionals often overestimate how well participants understand and appreciate consent information for clinical trials, and experts often vary in their determinations of participant\u27s capacity to consent to research. Past research has developed and validated instruments designed to assess participant understanding and appreciation, but the frequency with which they are utilized is unknown. METHODS: We administered a survey to clinical researchers working with older adults or those at risk of cognitive impairment ( RESULTS: We found that using a validated assessment of consent is relatively uncommon, being used by only 44% of researchers who had an opportunity. Factors that predicted adoption of validated assessments included not seeing the study sponsor as a barrier, positive attitudes toward assessments, and being confident that they had the resources needed to implement an assessment. The perceived barriers to adopting validated assessments of consent included lack of awareness, lack of knowledge, being unsure of how to administer such an assessment, and the burden associated with implementing this practice. CONCLUSIONS: Increasing the use of validated assessments of consent will require educating researchers on the practice and emphasizing very practical assessments, and may require Institutional Review Boards (IRBs) or study sponsors to champion the use of assessments

A randomized implementation trial to increase adoption of evidence-informed consent practices

INTRODUCTION: Several evidence-informed consent practices (ECPs) have been shown to improve informed consent in clinical trials but are not routinely used. These include optimizing consent formatting, using plain language, using validated instruments to assess understanding, and involving legally authorized representatives when appropriate. We hypothesized that participants receiving an implementation science toolkit and a social media push would have increased adoption of ECPs and other outcomes. METHODS: We conducted a 1-year trial with clinical research professionals in the USA ( RESULTS: Participants who engaged more with the toolkit were more likely to have tried to implement an ECP during the trial than participants less engaged with the toolkit or the active control group. However, there were no significant differences in the adoption of ECPs, intention to adopt, or positive attitudes. Participants reported the toolkit and social media push were satisfactory, and participating increased their awareness of ECPs. However, they reported lacking the time needed to engage with the toolkit more fully. CONCLUSIONS: Using an implementation science approach to increase the use of ECPs was only modestly successful. Data suggest that having institutional review boards recommend or require ECPs may be an effective way to increase their use

Enigmatic presence of mitochondrial complex I in Trypanosoma brucei bloodstream forms

The presence of mitochondrial respiratory complex I in the pathogenic bloodstream stages of Trypanosoma brucei has been vigorously debated: increased expression of mitochondrially encoded functional complex I mRNAs is countered by low levels of enzymatic activity that show marginal inhibition by the specific inhibitor rotenone. We now show that epitope-tagged versions of multiple complex I subunits assemble into α and β subcomplexes in the bloodstream stage and that these subcomplexes require the mitochondrial genome for their assembly. Despite the presence of these large (740- and 855-kDa) multisubunit complexes, the electron transport activity of complex I is not essential under experimental conditions since null mutants of two core genes (NUBM and NUKM) showed no growth defect in vitro or in mouse infection. Furthermore, the null mutants showed no decrease in NADH:ubiquinone oxidoreductase activity, suggesting that the observed activity is not contributed by complex I. This work conclusively shows that despite the synthesis and assembly of subunit proteins, the enzymatic function of the largest respiratory complex is neither significant nor important in the bloodstream stage. This situation appears to be in striking contrast to that for the other respiratory complexes in this parasite, where physical presence in a life-cycle stage always indicates functional significance