Clinical trials are a vital component of translational science, providing crucial information on the efficacy and safety of new interventions and forming the basis for regulatory approval and/or clinical adoption. At the same time, they are complex to design, conduct, monitor, and report successfully. Concerns over the last two decades about the quality of the design and the lack of completion and reporting of clinical trials, characterized as a lack of “informativeness,” highlighted by the experience during the COVID-19 pandemic, have led to several initiatives to address the serious shortcomings of the United States clinical research enterprise.

Against this background, we detail the policies, procedures, and programs that we have developed in The Rockefeller University Center for Clinical and Translational Science (CCTS), supported by a Clinical and Translational Science Award (CTSA) program grant since 2006, to support the development, conduct, and reporting of informative clinical studies.

We have focused on building a data-driven infrastructure to both assist individual investigators and bring translational science to each element of the clinical investigation process, with the goal of both generating new knowledge and accelerating the uptake of that knowledge into practice.

Adolescent-onset schizophrenia (AOS) is associated with cognitive impairment and poor clinical outcome. Cognitive dysfunction is thought to reflect functional dysconnectivity between the frontal cortex and the striatum, Previous work [1] has shown frontostriatal dysconnectivity in large WM tracts explain core cognitive deficits, with processing speed, which is affected by alterations in WM connectivity, being an intermediary variable.

To undertake a follow-up MRI study using whole-brain structural connectomics to track topological changes in the follow-up (1st episode versus follow-up), in order to characterize the early stages (evolution of the first two years) of the disorder.

A follow-up study of 25 AOS subjects and 25 age and sex-matched healthy subjects.

Network theory will be applied to identify topological alterations in structural networks, including frontostriatal white matter (WM) tracts in relation to cognition and outcome measures.

The authors have not supplied their declaration of competing interest.

Patients with suspected opioid overdose frequently require naloxone treatment. Despite recommendations to observe such patients for 4 to 24 hours after naloxone, earlier discharge is becoming more common. This prospective, observational study of patients with presumed opioid overdose examines the safety of early disposition decisions and the accuracy of outcome prediction by physicians 1 hour after the administration of naloxone.

The study was carried out at St. Paul’s Hospital, an inner city teaching centre that cares for most of the injection drug users in Vancouver, BC. Patients were formally assessed 1 hour after receiving naloxone for presumed opioid overdose. Demographics, medical history and physical examination were documented on specific data forms, and physicians recorded their comfort with early discharge. Patients were followed up, and those who required a critical intervention or suffered a pre-defined adverse event (AE) within 24 hours of their 1-hour assessment were identified.

Of 573 patients, 48% were discharged in less than 2 hours, 23% in 2–4 hours and 29% in >4 hours. 94 patients who were held in the emergency department (ED) or admitted required a critical intervention, including supplemental oxygen for hypoxia (74), repeat naloxone (52), antibiotics administered intravenously (IV) (14), assisted ventilations (13), fluid bolus for hypotension (12), charcoal for associated life-threatening overdose (6), IV inotropic agents (2), antiarrhythmics for sustained tachycardia >130 beats/min (1), and administration of bicarbonate for arterial [HCO3] <5 or venous CO2 <5 (1). Physicians predicted adverse events with 94% sensitivity and 59% specificity. No discharged patients suffered a serious AE within 24 hours of ED discharge.

Emergency physicians can clinically identify patients at risk of deterioration after naloxone reversal of suspected opioid overdose. Prolonged observation or hospital admission is not usually required. Selective early discharge of patients with presumed opioid overdose is feasible and appears safe. A clinical prediction rule may be useful in identifying patients eligible for early discharge.