Consumer involvement in clinical research is an essential component of a comprehensive response during emergent health challenges. During the COVID-19 pandemic, the moderation of research policies and regulation to facilitate research may raise ethical issues. Meaningful, diverse consumer involvement can help to identify practical approaches to prioritize, design, and conduct rapidly developed clinical research amid current events. Consumer involvement might also elucidate the acceptability of flexible ethics review approaches that aim to protect participants whilst being sensitive to the challenging context (...) in which research is taking place. This article describes the main ethical challenges arising from pandemic research and how involving consumers and the community could enable resolution of such issues. (shrink)

The human and mouse genomes are complex from a genomic standpoint. Each cell has the same genomic sequence, yet a wide array of cell types exists due to the presence of a plethora of regulatory elements in the non‐coding genome. Recent advances in epigenomic profiling have uncovered non‐coding gene proximal promoters and distal enhancers of transcription genome‐wide. Extension of promoter‐associated H3K4me3 histone mark across the gene body, known as a broad H3K4me3 domain (H3K4me3‐BD), is a signature of constitutive expression of (...) cell‐type‐specific regulation and of tumour suppressor genes in healthy cells. Recently, it has been discovered that the presence of H3K4me3‐BDs over oncogenes is a cancer‐specific feature associated with their dysregulated gene expression and tumourigenesis. Moreover, it has been shown that the hijacking of clusters of enhancers, known as super‐enhancers (SE), by proto‐oncogenes results in the presence of H3K4me3‐BDs over the gene body. Therefore, H3K4me3‐BDs and SE crosstalk in healthy and cancer cells therefore represents an important mechanism to identify future treatments for patients with SE driven cancers. (shrink)

Objectives: To test the range of beliefs regarding the ethics of testing, in resource poor settings, new therapies that are less efficacious but more affordable and feasible than the best current therapeutic standard. Design: Using a web-based survey, we presented a hypothetical scenario proposing to test a therapy for HIV disease ("therapeutic inoculation") known to be less efficacious than highly active antiretroviral therapy (HAART). Respondents evaluated various trial designs as ethical or unethical. Participants: 604 subscribers to two listservs for individuals (...) interested in international health research ethics. Main outcome measures: Proportion of respondents endorsing trials testing this "substandard" therapy, and proportion endorsing placebo-controlled trials. Results: There were 215 respondents from 47 countries. Forty-five percent of respondents were from low or middle income countries; 96% devoted at least some time to research activities; and 75% had "some" or "considerable" research experience in developing countries. Of respondents, 97% (95% CI 94.7 to 99.4) endorsed testing therapeutic inoculation, without HAART, in patients with HIV disease; 86% (95% CI 81.4% to 90.7%) endorsed testing against placebo. Sixty-eight percent explicitly endorsed principles where the standard of care for subjects in clinical trials is determined by local, not universal, standards. There were no differences in responses based on respondent education-level or the income-level of their country of citizenship. Conclusion: There was broad agreement that a therapy of potential local benefit may be tested, even when that therapy is known to be inferior to the standard of care in wealthy countries. Most agreed that a placebo control may be used in some circumstances. (shrink)