Administering drug at a dose lower than that used in pivotal clinical trials, known as fractional dosing, can stretch scarce resources. Implementing fractional dosing with confidence requires understanding a drug's dose-response relationship. Clinical trials aimed at describing dose-response in scarce, efficacious drugs risk underdosing, leading dose-finding trials to not be pursued despite their obvious potential benefit. We developed a new set of response-adaptive randomized dose-finding trials and demonstrate, in a series of simulated trials across diverse dose-response curves, these designs' efficiency in identifying the minimum dose that achieves satisfactory efficacy. Compared to conventional designs, these trials have higher probabilities of identifying lower doses while reducing the risks of both population- and subject-level underdosing. We strongly recommend that, upon demonstration of a drug's efficacy, pandemic drug development swiftly proceeds with response-adaptive dose-finding trials. This unified strategy ensures that scarce effective drugs produce maximum social benefits.
Download full-text PDF |
Source |
|---|---|
| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC10615276 | PMC |
| http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0287511 | PLOS |
Publication Analysis
Top Keywords
Similar Publications
Quantitative evaluation of accumulated and planned dose deviations in patients undergoing gated and non-gated lung stereotactic body radiation therapy patients: a retrospective analysis.
Transl Lung Cancer Res
December 2024
Department of Radiation Oncology, Tongji University Affiliated Shanghai Pulmonary Hospital, Shanghai, China.
Background: Stereotactic body radiation therapy (SBRT) is crucial for treating early-stage inoperable non-small cell lung cancer (NSCLC) due to its precision and high-dose delivery. This study aimed to investigate the dosimetric deviations in gated (GR) versus non-gated radiotherapy (NGR), analyzing the impact of tumor location, target volume, and tumor motion range on dose distribution accuracy.
Methods: Sixty patients treated with either gated (n=30) or non-gated (n=30) SBRT for early-stage NSCLC were retrospectively analyzed.
Background: In settings with low pneumococcal conjugate vaccine (PCV) coverage, multi-age cohort mass campaigns could increase population immunity, and fractional dosing could increase affordability. We aimed to evaluate the effect of mass campaigns on nasopharyngeal pneumococcal carriage of Pneumosil (PCV10) in children aged 1-9 years in Niger.
Methods: In this three-arm, open-label, cluster-randomised trial, 63 clusters of one to four villages in Niger were randomly assigned (3:3:1) using block randomisation to receive campaigns consisting of a single full dose of a 10-valent PCV (Pneumosil), a single one-fifth dose of Pneumosil, or no campaign.
Mass doses of fractional pneumococcal vaccine in humanitarian settings.
Lancet Infect Dis
January 2025
Every Breath Counts Coalition, New York, NY, USA.
Impact of Pediatric Posterior Fossa Tumor Treatments on Working Memory Tracts Using Resting-State fMRI and Tractography.
J Neuroimaging
January 2025
Toulouse NeuroImaging Center (ToNIC), INSERM, University of Toulouse Paul Sabatier, Toulouse, France.
Background And Purpose: Working memory, a primary cognitive domain, is often impaired in pediatric brain tumor survivors, affecting their attention and processing speed. This study investigated the long-term effects of treatments, including surgery, radiotherapy (RT), and chemotherapy (CT), on working memory tracts in children with posterior fossa tumors (PFTs) using resting-state functional MRI (rs-fMRI) and diffusion MRI tractography.
Methods: This study included 16 medulloblastoma (MB) survivors treated with postoperative RT and CT, 14 pilocytic astrocytoma (PA) survivors treated with surgery alone, and 16 healthy controls from the Imaging Memory after Pediatric Cancer in children, adolescents, and young adults study (NCT04324450).
The role of a vaccine booster for a fractional order model of the dynamic of COVID-19: a case study in Thailand.
Sci Rep
January 2025
Department of Applied Basic Subjects, Thatphanom College, Nakhon Phanom University, Nakhon Phanom, 48000, Thailand.
This article addresses the critical need for understanding the dynamics of COVID-19 transmission and the role of booster vaccinations in managing the pandemic. Despite widespread vaccination efforts, the emergence of new variants and the waning of immunity over time necessitate more effective strategies. A fractional-order mathematical model using Caputo-Fabrizio derivatives was developed to analyze the impact of booster doses, symptomatic and asymptomatic infections, and quarantine measures.
View Article and Find Full Text PDFWant AI Summaries of new PubMed Abstracts delivered to your In-box?
Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!