Research on nutraceutical and dietary interventions in psychiatry has grown substantially, but progress is hindered by methodological inconsistencies and limited reporting standards. To address this, the International Society for Nutritional Psychiatry Research presents the first guidelines on clinical trial design, conduct, and reporting for future clinical trials in this area. Recommendations were developed using a Delphi process including eighteen researchers with considerable clinical trial expertise and experience in either methodology, nutraceutical, or dietary interventions in psychiatry. These guidelines provide forty-nine recommendations for clinical trial design and outcomes, five for trial reporting, and seven for future research priorities. The recommendations included in these guidelines are designed to inform both nutraceutical and dietary clinical trial interventions in Nutritional Psychiatry. Common themes include an emphasis on the importance of a multidisciplinary research team and integration of co-design processes into the conduct and design of clinical research, methods to improve transparency and replicability of trial outcomes, and measures to address common biases in nutrition trials. Furthermore, we provide recommendations for future research including examining a greater variety of nutraceutical and dietary interventions, scalable delivery models, effectiveness and implementation studies, and the need to investigate these interventions in the prevention and management of less studied psychiatric conditions (e.g. schizophrenia and bipolar disorder). Recommendations included within these guidelines are intended to improve the rigor and clinical relevance of ongoing and future clinical trials in Nutritional Psychiatry.

‘Each has shaped the other.’1

Evidence abounds on the salience of attachment to early development and beyond. In 2018, Adshead distilled the relevance of 20 years of attachment theory to psychiatric practice.2 We argue research funders must move one step further: develop the evidence around perinatal attachment-informed interventions.

Efficient evidence generation to assess the clinical and economic impact of medical therapies is critical amid rising healthcare costs and aging populations. However, drug development and clinical trials remain far too expensive and inefficient for all stakeholders. On October 25–26, 2023, the Duke Clinical Research Institute brought together leaders from academia, industry, government agencies, patient advocacy, and nonprofit organizations to explore how different entities and influencers in drug development and healthcare can realign incentive structures to efficiently accelerate evidence generation that addresses the highest public health needs. Prominent themes surfaced, including competing research priorities and incentives, inadequate representation of patient population in clinical trials, opportunities to better leverage existing technology and infrastructure in trial design, and a need for heightened transparency and accountability in research practices. The group determined that together these elements contribute to an inefficient and costly clinical research enterprise, amplifying disparities in population health and sustaining gaps in evidence that impede advancements in equitable healthcare delivery and outcomes. The goal of addressing the identified challenges is to ultimately make clinical trials faster, more inclusive, and more efficient across diverse communities and settings.

The Accelerating COVID-19 Therapeutic Interventions and Vaccines (ACTIV) Cross-Trial Statistics Group gathered lessons learned from statisticians responsible for the design and analysis of the 11 ACTIV therapeutic master protocols to inform contemporary trial design as well as preparation for a future pandemic. The ACTIV master protocols were designed to rapidly assess what treatments might save lives, keep people out of the hospital, and help them feel better faster. Study teams initially worked without knowledge of the natural history of disease and thus without key information for design decisions. Moreover, the science of platform trial design was in its infancy. Here, we discuss the statistical design choices made and the adaptations forced by the changing pandemic context. Lessons around critical aspects of trial design are summarized, and recommendations are made for the organization of master protocols in the future.

Underrepresentation of people from racial and ethnic minoritized groups in clinical trials threatens external validity of clinical and translational science, diminishes uptake of innovations into practice, and restricts access to the potential benefits of participation. Despite efforts to increase diversity in clinical trials, children and adults from Latino backgrounds remain underrepresented. Quality improvement concepts, strategies, and tools demonstrate promise in enhancing recruitment and enrollment in clinical trials. To demonstrate this promise, we draw upon our team’s experience conducting a randomized clinical trial that tests three behavioral interventions designed to promote equity in language and social-emotional skill acquisition among Latino parent–infant dyads from under-resourced communities. The recruitment activities took place during the COVID-19 pandemic, which intensified the need for responsive strategies and procedures. We used the Model for Improvement to achieve our recruitment goals. Across study stages, we engaged strategies such as (1) intentional team formation, (2) participatory approaches to setting goals, monitoring achievement, selecting change strategies, and (3) small iterative tests that informed additional efforts. These strategies helped our team overcome several barriers. These strategies may help other researchers apply quality improvement tools to increase participation in clinical and translational research among people from minoritized groups.

Meta-analyses traditionally compare the difference in means between groups for one or more outcomes of interest. However, they do not compare the spread of data (variability), which could mean that important effects and/or subgroups are missed. To address this, methods to compare variability meta-analytically have recently been developed, making it timely to review them and consider their strengths, weaknesses, and implementation. Using published data from trials in major depression, we demonstrate how the spread of data can impact both overall effect size and the frequency of extreme observations within studies, with potentially important implications for conclusions of meta-analyses, such as the clinical significance of findings. We then describe two methods for assessing group differences in variability meta-analytically: the variance ratio (VR) and coefficient of variation ratio (CVR). We consider the reporting and interpretation of these measures and how they differ from the assessment of heterogeneity between studies. We propose general benchmarks as a guideline for interpreting VR and CVR effects as small, medium, or large. Finally, we discuss some important limitations and practical considerations of VR and CVR and consider the value of integrating variability measures into meta-analyses.

There is increasing recognition of the crucial need for robust community engagement in health research and clinical trials. Despite this awareness, challenges persist in bridging the gap between researchers and communities. Much of the current discourse focuses on addressing issues such as cultural humility and equitable partnerships. To expand this conversation, we conducted community engagement studios, following the model by Joosten et al. We wanted to gather perspectives on research involvement across New Mexico. This process and resultant findings offer valuable insights into effective community engagement practices and advance clinical and translational science by amplifying community voices and needs.

While tension-type headache (TTH) is the most common primary headache disorder, its effect according to sex, race and ethnicity remains unclear. We investigated disparities in sex, racial and ethnic representation in TTH clinical trials with comparison to global disease burdens. In this cross-sectional analysis, TTH clinical trials had female overrepresentation and racial and ethnic minority underrepresentation, which may affect understanding of the impact of TTH on different populations and personalized treatment development. Trial enrollment that is diverse and reflective of global disease burdens is crucial for improving study generalizability, understanding of diverse clinical presentations, and ensuring healthcare equity.

In this issue, Zakout discusses European Union (EU) legal provisions for inclusion of patients of all types in clinical trials.1 Shee highlights the unfortunate failure to include adequate numbers of older adults and adults with disabilities in clinical trials of anti-cancer agents. We agree with her argument that this is an ethical issue as well as a scientific and clinical issue.

Conducting clinical trials is often complex and involves many individuals from a variety of services, each with a specific role in ensuring its successful implementation. Although an experienced clinical trialist may anticipate many of the challenges, others may be unexpected and detrimental to the successful completion of a study. We describe the use of simulation during preparation for initiation of a randomized clinical trial of a new preparation of antiseizure medication in neonates with seizures. The process of identification of stakeholders and roles, scenario development, and identification of challenges are described. Lessons learned included the potential benefits of simulation exercises, simulation challenges, and challenges associated with the study itself. We posit that going through the steps of a study, rather than merely reading them from a manual of procedures, will help identify potential barriers, complexities, and contingencies that are not readily apparent and may result in fewer protocol deviations and violations.

Correction of dietary calcium and protein undernutrition using milk, yoghurt, and cheese in older adults in aged care homes is associated with reduced fractures and falls(1). As these foods contain potentially atherogenic fats, we aimed to determine whether these dietary changes adversely affect serum lipid profiles. Sixty aged care homes in Australia were randomised to intervention (n = 30 milk, yoghurt, and cheese enriched menu) or control (n = 30 regular menu) for 2 years. A sample of 159 intervention and 86 control residents (median age 87.8 years) had dietary intakes recorded using plate waste analysis and fasting serum lipids measured at baseline and 12 months. Diagnosis of cardiovascular disease and use of relevant medications were determined from medical records. Data were analysed using mixed effects linear regression model adjusting for clustering (aged care home) and other confounders. Intervention increased daily dairy servings from 1.9 ± 1.0 to 3.5 ± 1.4 (p<0.001) while controls continued daily intakes of £ 2 servings daily (1.7 ± 1.0 to 2.0 ± 1.0 (p<0.05). No group differences were observed for serum total cholesterol/high-density lipoprotein-C (TC/HDL-C) ratio, Apoprotein B/Apoprotein A (ApoB/ApoA) ratio, low-density lipoprotein-C (LDL-C), non-HDL-C, or triglycerides (TGs) at baseline and 12 months. Among older adults in aged care homes, correcting insufficiency in the daily intake of calcium and protein using milk, yoghurt and cheese does not alter serum lipid levels, suggesting that this is a suitable intervention for reducing the risk of falls and fractures.

The survey investigates COVID-19 information source trust levels and Vietnamese Americans’ willingness to participate in clinical trials. An analysis of 212 completed surveys revealed that trust in coronavirus disease 2019 (COVID-19) clinical trial information from university hospitals and drug companies was associated with willingness to participate in clinical trials. Trust in COVID-19 information from federal governments and state governments was also associated with willingness to participate in clinical trials. However, trust in local health facilities was linked to trial participation reluctance. The results suggest that Vietnamese Americans’ participation in clinical trials can be increased by identifying and using trusted sources of information.

Evidence shows that talking with patients about psychotic experiences can be beneficial. The key question is therefore: which psychological methods can help patients most? This editorial presents ten principles for the design and development of effective psychological treatments. These principles are perceptible characteristics of successful interventions.

The case of clinical trials for convalescent plasma during COVID-19 illustrates important lessons for realizing public sector approaches to biomedical research and development. These lessons, centering on mission, transparency, and spillover effects, can be translated to wider efforts to develop a “public option” for clinical trials.

Interventional clinical studies of convalescent plasma to treat COVID-19 were predominantly funded and led by public sector actors, including blood services operators. We aimed to analyze the processes of clinical studies of convalescent plasma to understand alternatives to pharmaceutical industry biopharmaceutical research and development, particularly where public sector actors play a dominant role. We conducted a qualitative, critical case study of purposively sampled prominent and impactful clinical studies of convalescent plasma during 2020-2021.