Clinical trial simulation

OBJECTIVES: The aim of this study was to update previously estimated public health impact and cost effectiveness of recombinant zoster vaccine (RZV) for the prevention of herpes zoster (HZ) in Canadians aged ≥50 years using longer-term RZV efficacy and waning data and real-world coverage and completion. METHODS: A multicohort Markov model was used to conduct a cost-utility analysis comparing RZV with no HZ vaccination among Canadians aged ≥50 years...

The utilization of biodegradable magnesium (Mg) alloys in the fabrication of temporary non-vascular stents is an innovative trend in biomedical engineering. However, the heterogeneous degradation profiles of these biomaterials, together with potential bacterial colonization that could precipitate infectious or stenotic complications, are critical obstacles precluding their widespread clinical application. In pursuit of overcoming these limitations, this study applies the principles of biomimicry, particularly the hydrophobic and anti-fouling characteristics of lotus leaves, to pioneer the creation of nanocomposite coatings...

A ready-to-use (RTU) long-acting injectable (LAI) formulation of aripiprazole monohydrate for administration once every 2 months, available in 960 mg (Ari 2MRTU 960) or 720 mg doses, has been developed for the treatment of schizophrenia or bipolar I disorder. A previously developed and validated population pharmacokinetic model for characterizing aripiprazole plasma concentrations following administration of oral aripiprazole or aripiprazole once-monthly (AOM) intramuscular injection was expanded to include the RTU LAI formulation of aripiprazole (Ari RTU LAI)...

AIMS: Prednisolone is the cornerstone of treatment for idiopathic nephrotic syndrome in children, but is associated with marked side-effects. Therapeutic drug monitoring using saliva would be a patient-friendly option to monitor prednisolone treatment. To assess the feasibility of saliva monitoring, we described the pharmacokinetics (PK) of unbound prednisolone in plasma and saliva of children with first onset steroid-sensitive nephrotic syndrome (SSNS). METHODS: Children (age 2-16 years) with SSNS participating in a randomized, placebo-controlled trial with levamisole were treated with an 18-week tapering schedule of prednisolone...

Simulated daylight photodynamic therapy is a relatively new and potentially less painful alternative to conventional red light photodynamic therapy for actinic keratosis. Qualitative research exploring patient experiences of pain and skin reactions during these treatments is scarce. To address this, semi-structured interviews were conducted of 10 patients aged 60-81 years with symmetrically distributed actinic keratoses 4 weeks after split-face treatment with conventional red light photodynamic therapy and simulated daylight photodynamic therapy...

Primary membranous nephropathy (PMN) is the most common cause for adult nephrotic syndrome. Rituximab has demonstrated promising clinical efficacy by random controlled trials and the off-label use is widely adopted in PMN. However, the standard dosage is borrowed from B cell lymphoma treatment with far more antigens and is oversaturated for PMN treatment, accompanied with additional safety risk and unnecessary medical cost. More than 15% serious adverse events were observed under standard dosage and low dose therapies were explored recently...

BACKGROUND: Dental restorations play a crucial role in preserving the structural integrity and function of posterior teeth. However, wear resistance remains a significant concern for these restorations. MATERIALS AND METHODS: In this RCT, 120 participants with posterior tooth restoration needs were randomly assigned to two groups. Group A received conventional composite restorations, while Group B received NanoFilled Composite restorations. The restorations were placed according to standardized protocols...

OBJECTIVES: ORIENT-16, a phase III clinical trial conducted at 62 hospitals in China, reported that add-on sintilimab (Sin) to chemotherapy (Chemo) had favorable efficacy ( p  < 0.05) for patients with advanced HER2-negative gastric or gastroesophageal junction cancer (GC/GEJC). This study aimed to evaluate the cost-utility of the Sin+Chemo based on results of ORIENT-16 from the perspective of Chinese healthcare payers. METHODS: A three-state partitioned survival model was developed to simulate the 10-year life expectancy and total healthcare costs for patients with advanced HER2-negative GC/GEJC...

Enrolling patients to the standard of care (SOC) arm in randomized clinical trials, especially for rare diseases, can be very challenging due to the lack of resources, restricted patient population availability, and ethical considerations. As the therapeutic effect for the SOC is often well documented in historical trials, we propose a Bayesian platform trial design with hybrid control based on the multisource exchangeability modelling (MEM) framework to harness historical control data. The MEM approach provides a computationally efficient method to formally evaluate the exchangeability of study outcomes between different data sources and allows us to make better informed data borrowing decisions based on the exchangeability between historical and concurrent data...

Covariate analysis in population pharmacokinetics is key for adjusting doses for patients. The main objective of this work was to compare the adequacy of various modeling approaches on covariate clinical relevance decision-making. The full model, stepwise covariate model (SCM) and SCM+ PsN algorithms were compared in a clinical trial simulation of a 383-patient population pharmacokinetic study mixing rich and sparse designs. A one-compartment model with first-order absorption was used. A base model including a body weight effect on CL/F and V/F and a covariate model including 4 additional covariates-parameters relationships were simulated...

Traditional vaccine efficacy trials usually use fixed designs and often require large sample sizes. Recruiting a large number of subjects can make the trial expensive, long, and difficult to conduct. A possible approach to reduce the sample size and speed up the development is to use historical controls. In this paper, we extend the robust mixture prior (RMP) approach (a well established approach for Bayesian dynamic borrowing of historical controls) to adjust for covariates. The adjustment is done using classical methods from causal inference: inverse probability of treatment weighting, G-computation and double-robust estimation...

BACKGROUND: Handovers during medical emergencies are challenging due to time-critical, dynamic and oftentimes unorderly and distracting situations. We evaluated the effect of distraction-reduced clinical surroundings during handover on (1) the recall of handover information, (2) the recall of information from the surroundings and (3) self-reported workload in a simulated in-hospital cardiac arrest scenario. METHODS: In a parallel group design, emergency team leaders were randomly assigned to receive a structured handover of a cardio-pulmonary resuscitation (CPR) either inside the room ("inside group") right next to the ongoing CPR or in front of the room ("outside group") with no audio-visual distractions from the ongoing CPR...

BACKGROUND: The escalating prevalence of cesarean delivery globally poses significant health impacts on mothers and newborns. Despite this trend, the underlying reasons for increased cesarean delivery rates, which have risen to 36.3% in Portugal as of 2020, remain unclear. This study delves into these issues within the Portuguese health care context, where national efforts are underway to reduce cesarean delivery occurrences. OBJECTIVE: This paper aims to introduce a machine learning, algorithm-based support system designed to assist clinical teams in identifying potentially unnecessary cesarean deliveries...

Randomized clinical trials (RCTs) are essential to guide medical practice; however, their generalizability to a given population is often uncertain. We developed a statistically informed Generative Adversarial Network (GAN) model, RCT-Twin-GAN, that leverages relationships between covariates and outcomes and generates a digital twin of an RCT (RCT-Twin) conditioned on covariate distributions from a second patient population. We used RCT-Twin-GAN to reproduce treatment effect outcomes of the Systolic Blood Pressure Intervention Trial (SPRINT) and the Action to Control Cardiovascular Risk in Diabetes (ACCORD) Blood Pressure Trial, which tested the same intervention but had different treatment effect results...

Background: Cluster randomized trials (CRTs) are randomized trials where randomization takes place at an administrative level (e.g., hospitals, clinics, or schools) rather than at the individual level. When the number of available clusters is small, researchers may not be able to rely on simple randomization to achieve balance on cluster-level covariates across treatment conditions. If these cluster-level covariates are predictive of the outcome, covariate imbalance may distort treatment effects, threaten internal validity, lead to a loss of power, and increase the variability of treatment effects...

Starting from drug discovery, through research and development, to clinical trials and FDA approval, artificial intelligence (AI) plays a vital role in planning, developing, assessing modelling, and optimization of product attributes. In recent decades, machine-learning algorithms integrated into artificial neural networks, neuro-fuzzy logic and decision trees have been applied to tremendous domains related to drug formulation development. Optimized formulations were transformed from lab to market based on optimized properties derived from AI Technologies...

Ethnopharmacological relevance: Pelvic inflammatory disease (PID) is a frequently occurring gynecological disorder mainly caused by the inflammation of a woman's upper genital tract. Generally, antibiotics are used for treating PID, but prolonged use poses potential risks of gut bacterial imbalance, bacterial resistance, super bacteria production, and associated adverse reactions. Traditional Chinese medicine (TCM) has shown unique advantages in various ailments and has received widespread clinical research attention...

BACKGROUND: Virtual simulation-based education for healthcare professionals has emerged as a strategy for dealing with infectious disease disasters, particularly when training at clinical sites is restricted due to the risk of infection and a lack of personal protective equipment. This research evaluated a virtual simulation-based education program intended to increase nurses' perceived competence in providing psychological support to patients affected by infectious disease disasters...

PURPOSE: The health and economic consequences of artificial intelligence (AI) systems for mechanically ventilated intensive care unit patients often remain unstudied. Early health technology assessments (HTA) can examine the potential impact of AI systems by using available data and simulations. Therefore, we developed a generic health-economic model suitable for early HTA of AI systems for mechanically ventilated patients. MATERIALS AND METHODS: Our generic health-economic model simulates mechanically ventilated patients from their hospitalisation until their death...

ETHNOPHARMACOLOGICAL RELEVANCE: Major Depressive Disorder (MDD) emerges as a complex psychosomatic condition, notable for its considerable suicidality and mortality rates. Increasing evidence suggests the efficacy of Chinese herbal medicine in mitigating depression symptoms and offsetting the adverse effects associated with conventional Western therapeutics. Notably, clinical trials have revealed the adjunctive antidepressant potential of Kaiyu Zhishen Decoction (KZD) alongside Western medication...