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There is a recognized unmet need for clinical trials to provide evidence-informed care for infants, children and adolescents. This Special Communication outlines the capacity of 3 distinct trial design strategies, sequential, parallel, and a unified adult-pediatric bayesian adaptive design, to incorporate children into clinical trials and transform this current state of evidence inequity. A unified adult-pediatric whole-of-life clinical trial is demonstrated through the Staphylococcus aureus Network Adaptive Platform (SNAP) trial.
Regular intramuscular benzathine penicillin G injections have been the cornerstone of rheumatic heart disease (RHD) secondary prophylaxis since the 1950s. As the pharmacological correlate of protection remains unknown, it is difficult to recommend changes to this established regimen. Determining the minimum effective penicillin exposure required to prevent Streptococcus pyogenes infection will accelerate development of new long-acting penicillins for RHD prevention as well as inform opportunities to improve existing regimens. The CHIPS trial will address this knowledge gap by directly testing protection afforded by different steady state plasma concentrations of penicillin in an established model of experimental human S. pyogenes pharyngitis.
Prioritisation of clinical trials ensures that the research conducted meets the needs of stakeholders, makes the best use of resources and avoids duplication. The aim of this review was to identify and critically appraise approaches to research prioritisation applicable to clinical trials, to inform best practice guidelines for clinical trial networks and funders.
Antimicrobials are the most commonly prescribed drug class in children. Overuse through inappropriate prescribing is a key driver of antimicrobial resistance and is recognized as one of the top 10 threats to global health by the World Health Organization.
Pulmonary exacerbations are associated with increased morbidity and mortality in people with cystic fibrosis (CF). There is no consensus about which outcomes should be evaluated in studies of pulmonary exacerbations or how these outcomes should be measured.
Staphylococcus aureus bloodstream (SAB) infection is a common and severe infectious disease, with a 90-day mortality of 15%-30%. Despite this, <3000 people have been randomized into clinical trials of treatments for SAB infection.
The in-vivo plasma concentration of penicillin needed to prevent Streptococcus pyogenes pharyngitis, recurrent acute rheumatic fever, and progressive rheumatic heart disease is not known. We used a human challenge model to assess the minimum penicillin concentration required to prevent streptococcal pharyngitis.
BK polyomavirus (BKPyV) is a common opportunistic infection in kidney transplant recipients, typically reactivating in the context of immunosuppression. Although asymptomatic in immunocompetent individuals, reactivation in transplant recipients can cause BKPyV-associated nephropathy (BKPyVAN), a leading cause of graft dysfunction and loss. BKPyV viremia affects approximately 10%-15% of transplant recipients, and once BKPyVAN is established, the risk of graft failure can exceed 50%.
Clinical trial designs are typically narrowly focused on error control in hypothesis testing, but this approach is inadequate in many contexts, particularly when a decision maker intends to, or must, consider multiple relevant clinical and health economic outcomes under uncertainty. Value-of-information (VoI) metrics can be used to estimate the monetary value of data collection to the decision maker.
Pulmonary exacerbations pose a significant clinical burden on people with cystic fibrosis (pwCF). Whether management of exacerbations should change in the context of modulator therapy is unclear. We describe the characteristics, treatment and lung function outcomes of pulmonary exacerbations requiring intravenous antibiotic therapy (PERITs) in a contemporary Australian cohort of pwCF, in an era of rapidly broadening access to modulator therapy.