Accelerating evidence generation: Addressing critical challenges and charting a path forward.

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.

The All of Us Research Program is an opportunity to enhance the diversity of US biomedical research.

The All of Us Research Program has prioritized the enrollment of people from backgrounds historically underrepresented in medical research to bring precision medicine to the full diversity of the US population and to improve health outcomes for all.

A framework for assessing clinical trial site readiness.

Clinical trial processes are unnecessarily inefficient and costly, slowing the translation of medical discoveries into treatments for people living with disease. To reduce redundancies and inefficiencies, a group of clinical trial experts developed a framework for clinical trial site readiness based on existing trial site qualifications from sponsors. The site readiness practices are encompassed within six domains: research team, infrastructure, study management, data collection and management, quality oversight, and ethics and safety.

The NIH-led research response to COVID-19.

Investment, collaboration, and coordination have been key.

Advancing translational science education.

In this communication, the authors offer considerations for how the scientific community can capitalize on decades of translational science advances and experiential knowledge to develop new education opportunities for a diverse and highly skilled translational science workforce. Continued advancement of the field of translational science will require new education approaches that distill key concepts in translational science from past and ongoing research initiatives and teach this foundational knowledge to current and future translational scientists. These key concepts include generalizable scientific and operational principles to guide translational science, as well as evidence-informed practices.

The IDeaS initiative: pilot study to assess the impact of rare diseases on patients and healthcare systems.

Background: Rare diseases (RD) are a diverse collection of more than 7-10,000 different disorders, most of which affect a small number of people per disease. Because of their rarity and fragmentation of patients across thousands of different disorders, the medical needs of RD patients are not well recognized or quantified in healthcare systems (HCS).

Methodology: We performed a pilot IDeaS study, where we attempted to quantify the number of RD patients and the direct medical costs of 14 representative RD within 4 different HCS databases and performed a preliminary analysis of the diagnostic journey for selected RD patients.

The National COVID Cohort Collaborative (N3C): Rationale, design, infrastructure, and deployment.

Objective: Coronavirus disease 2019 (COVID-19) poses societal challenges that require expeditious data and knowledge sharing. Though organizational clinical data are abundant, these are largely inaccessible to outside researchers. Statistical, machine learning, and causal analyses are most successful with large-scale data beyond what is available in any given organization.

Diversity and inclusion for the All of Us research program: A scoping review.

The All of Us Research Program (All of Us) is a national effort to accelerate health research by exploring the relationship between lifestyle, environment, and genetics. It is set to become one of the largest research efforts in U.S.

The "All of Us" Research Program.

Knowledge gained from observational cohort studies has dramatically advanced the prevention and treatment of diseases. Many of these cohorts, however, are small, lack diversity, or do not provide comprehensive phenotype data. The All of Us Research Program plans to enroll a diverse group of at least 1 million persons in the United States in order to accelerate biomedical research and improve health.

Development of the Initial Surveys for the All of Us Research Program.

Background: The All of Us Research Program is building a national longitudinal cohort and collecting data from multiple information sources (e.g., biospecimens, electronic health records, and mobile/wearable technologies) to advance precision medicine.

Correction: A collaborative translational research framework for evaluating and implementing the appropriate use of human genome sequencing to improve health.

[This corrects the article DOI: 10.1371/journal.pmed.

A collaborative translational research framework for evaluating and implementing the appropriate use of human genome sequencing to improve health.

In a Policy Forum, Muin Khoury and colleagues discuss research on the clinical application of genome sequencing data.

Neuroepigenomics: Resources, Obstacles, and Opportunities.

Long-lived post-mitotic cells, such as the majority of human neurons, must respond effectively to ongoing changes in neuronal stimulation or microenvironmental cues through transcriptional and epigenomic regulation of gene expression. The role of epigenomic regulation in neuronal function is of fundamental interest to the neuroscience community, as these types of studies have transformed our understanding of gene regulation in post-mitotic cells. This perspective article highlights many of the resources available to researchers interested in neuroepigenomic investigations and discusses some of the current obstacles and opportunities in neuroepigenomics.

Community resources and technologies developed through the NIH Roadmap Epigenomics Program.

This chapter describes resources and technologies generated by the NIH Roadmap Epigenomics Program that may be useful to epigenomics researchers investigating a variety of diseases including cancer. Highlights include reference epigenome maps for a wide variety of human cells and tissues, the development of new technologies for epigenetic assays and imaging, the identification of novel epigenetic modifications, and an improved understanding of the role of epigenetic processes in a diversity of human diseases. We also discuss future needs in this area including exploration of epigenomic variation between individuals, single-cell epigenomics, environmental epigenomics, exploration of the use of surrogate tissues, and improved technologies for epigenome manipulation.

Data use under the NIH GWAS data sharing policy and future directions.

Unlabelled: In 2007, the US National Institutes of Health (NIH) introduced the Genome-Wide Association Studies (GWAS) Policy and the database of Genotypes and Phenotypes (dbGaP) to facilitate 'controlled' access to GWAS data based on participants' informed consent. dbGaP has provided 2,221 investigators access to 304 studies, resulting in 924 publications and significant scientific advances. Following on this success, the 2014 Genomic Data Sharing Policy will extend the GWAS Policy to additional data types.

Cannabinoid receptor-2 and HIV-associated neurocognitive disorders.

Despite the wide spread use of highly active antiretroviral therapy (HAART), mild forms of HIV-associated neuro cognitive disorders (HAND) remain commonplace. HAART treated patients now show low levels of viremia and more subtle yet biologically important signs of brain macrophage and microglial activation. Adjunctive therapeutic strategies are required to eliminate HIV-1 infection and suppress immune activation and its associated neuroinflammation.

National Institute on Drug Abuse symposium report: drugs of abuse, dopamine, and HIV-associated neurocognitive disorders/HIV-associated dementia.

The National Institute on Drug Abuse organized a symposium on drugs of abuse, dopamine, and HIV-associated neurocognitive disorders (HAND)/HIV-associated dementia (HAD) in Rockville, Maryland, October 4, 2011. The purpose of this symposium was to evaluate the potential role of dopamine in the potentiation of HAND/HAD by drugs of abuse. A summary of the symposium has been presented in this report.

Do opioids activate latent HIV-1 by down-regulating anti-HIV microRNAs?

Researchers have recently demonstrated the presence of anti-HIV-1 microRNAs (miR-28, miR-125b, miR-150, miR-223, and miR-382) in monocytes, macrophages, and CD4+ T cells, which are the primary targets of HIV infection. These miRNAs appear to regulate the level of infectivity of HIV-1 in the target cells, and thus have an impact on HIV-1 latency. The levels of these miRNAs are significantly higher in resting CD4+ T cells than those in active CD4+ T cells, whereas HIV-1 infectivity is greater in active than in resting CD4+ T cells.