Antenatal corticosteroids are given to pregnant people at risk of preterm birth to reduce newborn morbidity, including respiratory distress syndrome. However, there has been concern surrounding potential adverse effects on subsequent generations. Animal studies have demonstrated endocrine and metabolic changes in those exposed to corticosteroids in utero (F1) and in the second generation (F2). We aimed to assess the effects of parental antenatal corticosteroid exposure on health of the second generation (F2) of Auckland Steroid Trial (AST) participants. In the AST, women (F0) expected to birth between 24 and 36 weeks’ gestation were randomised to betamethasone or placebo. When their children (F1) were 50 years old, they and their children (F2) were followed up with a self-report questionnaire and data linkage. The primary outcome for this analysis was body mass index (BMI) z-score in the F2 generation. Secondary outcomes included respiratory, cardiovascular, neurodevelopmental, mental and general health, and social outcomes. Of the 213 F2 participants, 144 had BMI data available. There was no difference in BMI z-score between participants whose parent was exposed to betamethasone versus placebo (mean (SD) 0.63 (1.45), N = 77 vs 0.41 (1.28), N = 67, adjusted mean difference (95% confidence interval) = 0.16 (-0.37, 0.69)). There was no evidence of a difference in rates of overweight, diabetes, respiratory disease, cardiometabolic risk factors, neurodevelopmental difficulties, mental health difficulties and social outcomes between parental betamethasone versus placebo exposure groups, but confidence intervals were wide. These findings are reassuring regarding the intergenerational safety of antenatal corticosteroids.

Medicinal cannabis has been trialled for Tourette syndrome in adults, but it has not been studied in adolescents. This open-label, single-arm trial study evaluated the feasibility, acceptability and signal of efficacy of medicinal cannabis in adolescents (12–18 years), using a Δ9-tetrahydrocannabinol:cannabidiol ratio of 10:15, with dose varying from 5 to 20 mg/day based on body weight and response. The study demonstrated feasibility of recruitment, acceptability of study procedures, potential benefits and a favourable safety profile, with no serious adverse events. Commonly reported adverse events were tiredness and drowsiness, followed by dry mouth. Statistically significant improvement was observed in parent and clinician reports on tics (paired t-test P = 0.003), and behavioural and emotional issues (paired t-test P = 0.048) and quality of life as reported by the parent and young person (paired t-test P = 0.027 and 0.032, respectively). A larger-scale, randomised controlled trial is needed to validate these findings.

Current evidence underscores a need to transform how we do clinical research, shifting from academic-driven priorities to co-led community partnership focused programs, accessible and relevant career pathway programs that expand opportunities for career development, and design of trainings and practices to develop cultural competence among research teams. Failures of equitable research translation contribute to health disparities. Drivers of this failed translation include lack of diversity in both researchers and participants, lack of alignment between research institutions and the communities they serve, and lack of attention to structural sources of inequity and drivers of mistrust for science and research. The Duke University Research Equity and Diversity Initiative (READI) is a program designed to better align clinical research programs with community health priorities through community engagement. Organized around three specific aims, READI-supported programs targeting increased workforce diversity, workforce training in community engagement and cultural competence, inclusive research engagement principles, and development of trustworthy partnerships.

Significant improvements have been achieved to enhance the patient-centricity of clinical research, including the development and utilization of novel clinical trial endpoints. These include endpoints that harness outcomes that are important to patients and reflect the patients’ lived experiences. This may take the form of utilizing variables such as days alive and out of hospital (DAOH) and quality-of-life adjusted outcomes. The use of composite outcomes can be used to enrich patient-centricity by weighting or ranking events. These approaches have several nuances that should be considered including selecting appropriate events, defining outcomes, how to elicit or construct weights, and whose opinions to consider. After weights have been determined, a variety of approaches exist to combine weights with outcomes and make comparisons between groups. The approaches, including the win ratio, weighted win ratio, desirability of outcome ranking (DOOR), multicriteria decision analysis (MCDA), and variations of time-to-first composite event analyses, have unique advantages and challenges depending on the clinical scenario. While improving patient-centric outcomes is of high importance to multiple stakeholders, more comparative work is needed to characterize the implications of alternative approaches.

The risk of losing access to crucial means-tested programs — like Medicaid, Supplemental Security Income (SSI), the Supplemental Nutrition Assistance Program (SNAP), and Temporary Assistance for Needy Families (TANF) — poses a barrier to the enrollment of low-income Americans in clinical trials. This burden likely disproportionately affects members of racial and ethnic minority groups, people with disabilities, elderly individuals, and rural populations, and may frustrate efforts to reflect the US population in clinical trial enrollment. To help achieve representative clinical trials for myriad conditions, Congress should pass legislation excluding payments to clinical trial participants from gross income and expand the clinical trial compensation exclusions for means-tested programs established in the Ensuring Access to Clinical Trials Act of 2015.

Conducting scientific medical research with human subjects presents risks that raise both ethical and human rights concerns. We argue in this article that applying a human rights framework to the problems that arise in the context of scientific medical research can contribute to a better understanding of the impact on individuals, the related obligations of the State, and the avenues to make the State accountable when things go wrong. We start our analysis with a case brought to the European Court of Human Rights, which we use as an illustration throughout the article. We then discuss the relevance of human rights to the field of scientific medical research with a focus on the right to life and the right to health. The article draws on international human rights jurisprudence that deals with concrete disputes arising from the clinical reality. We use case law to highlight the role of human rights law in tackling the real-life problems that may occur during scientific medical research. Our analysis contends that human rights law can provide valuable guidance for healthcare professionals and equip them to handle concrete situations in the clinical reality when the safety of research subjects is at stake.

This paper provides an account of a specific operation – the removal of the thymus gland (thymectomy) to treat the rare neurological condition myasthenia gravis – from its first performance in 1936, by the American surgeon Alfred Blalock, to the publication in 2016 of an international multicentre randomised controlled trial (RCT) of the technique. Thymectomy was the subject of a transatlantic controversy in the 1950s, in which the main players were the English surgeon Geoffrey Keynes, and American neurologists and surgeons from New York, Boston, and the Mayo Clinic. The resolution of this controversy involved the use of increasingly sophisticated statistical techniques, but also crucially other influences including the social transformation of thoracic surgery, and competition between the leading American centres. The consensus achieved after this controversy was challenged in the late 1970s, eventually prompting the implementation of a trial acceptable to twenty-first-century evidence-based medicine. This account will demonstrate that surgical innovation in the period covered required increasing attention to the statistical basis of patient selection and outcome evaluation; that the processes of technical innovation cannot be regarded as separate from developments in the professional culture of surgery, and that one of the consequences of these changes has been the gradual eclipse of the prestigious autonomous surgeon.

The need for collaborative and transparent sharing of COVID-19 clinical trial and large-scale observational study data to accelerate scientific discovery and inform clinical practice is critical. Responsible data-sharing requires addressing challenges associated with data privacy and confidentiality, data linkage, data quality, variable harmonization, data formats, and comprehensive metadata documentation to produce a high-quality, contextually rich, findable, accessible, interoperable, and reusable (FAIR) dataset. This communication explores the experiences and lessons learned from sharing National Heart Lung and Blood Institute (NHLBI) COVID-19 clinical trial (including adaptive platform trials) and cohort study datasets through the NHLBI BioData Catalyst® (BDC) ecosystem, focusing on the challenges and successes of harmonizing these datasets for broader research use. Our findings highlight the importance of establishing standardized data formats, adopting common data elements and creating and maintaining robust data governance structures that address common challenges (i.e., data privacy and data-sharing limitations resulting from informed consent). These efforts resulted in a set of comprehensive and interoperable datasets from 5 clinical trials and 13 cohort studies that will enable downstream reuse in analyses and collaborations. The principles and strategies outlined, derived through experience with consortia data, can lay the groundwork for advancing collaborative and efficient data sharing.

There has been substantial recent renewed interest and investment to assess the therapeutic potential of psychedelic compounds in addiction disorders. This editorial discusses the available evidence from randomised trials and future research directions in the field, together with potential implications for patients, professionals and the wider addiction treatment system.

Vaccines have revolutionised the field of medicine, eradicating and controlling many diseases. Recent pandemic vaccine successes have highlighted the accelerated pace of vaccine development and deployment. Leveraging this momentum, attention has shifted to cancer vaccines and personalised cancer vaccines, aimed at targeting individual tumour-specific abnormalities. The UK, now regarded for its vaccine capabilities, is an ideal nation for pioneering cancer vaccine trials. This article convened experts to share insights and approaches to navigate the challenges of cancer vaccine development with personalised or precision cancer vaccines, as well as fixed vaccines. Emphasising partnership and proactive strategies, this article outlines the ambition to harness national and local system capabilities in the UK; to work in collaboration with potential pharmaceutic partners; and to seize the opportunity to deliver the pace for rapid advances in cancer vaccine technology.

Extant literature reveals how patients of marginalized social identities, socioeconomic status (SES), and medical experiences – especially patients of color and older adults – are underrepresented in cancer clinical trials (CCTs). Emerging evidence increasingly indicates CCT underrepresentation among patients of lower SES or rural origin, sexual and gender minorities, and patients with comorbid disability. This review applies an intersectional perspective to characterizing CCT representativeness across race and ethnicity, age, sexual and gender identity, SES, and disability. Four databases were systematically queried for articles addressing CCT participation inequities across these marginalizing indicators, using the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. One hundred one articles were included in a qualitative evaluation of CCT representativeness within each target population in the context of their intersectional impacts on participation. Findings corroborate strong evidence of CCT underrepresentation among patients of color, older age, lower SES, rural origin, and comorbid disabling conditions while highlighting systemic limitations in data available to characterize representativeness. Results emphasize how observed inequities interactively manifest through the compounding effects of minoritized social identity, inequitable economic conditions, and marginalizing medical experiences. Recommendations are discussed to more accurately quantify CCT participation inequities across underserved cancer populations and understand their underpinning mechanisms.