Related papers: Extent of Safety Database in Pediatric Drug Develo…
Development of effective treatments in pediatric population poses unique scientific and ethical challenges in addition to the small population. In this regard, both the U.S. and E.U. regulations suggest a complementary strategy, pediatric…
Among many efforts to facilitate timely access to safe and effective medicines to children, increased attention has been given to extrapolation. Loosely, it is the leveraging of conclusions or available data from adults or older age groups…
In preclinical investigations, e.g. in in vitro, in vivo and in silico studies, the pharmacokinetic, pharmacodynamic and toxicological characteristics of a drug are evaluated before advancing to first-in-man trial. Usually, each study is…
Throughout the different phases of a drug development program, randomized trials are used to establish the tolerability, safety, and efficacy of a candidate drug. At each stage one aims to optimize the design of future studies by…
Meta-analysis is a powerful tool for assessing drug safety by combining treatment-related toxicological findings across multiple studies, as clinical trials are typically underpowered for detecting adverse drug effects. However, incomplete…
The analysis of adverse events (AEs) is a key component in the assessment of a drug's safety profile. Inappropriate analysis methods may result in misleading conclusions about a therapy's safety and consequently its benefit-risk ratio. The…
Algorithmic recommendations and decisions have become ubiquitous in today's society. Many of these data-driven policies, especially in the realm of public policy, are based on known, deterministic rules to ensure their transparency and…
Background: Assessment of long-term survival for health technology assessment often necessitates extrapolation beyond the duration of a clinical trial. Without robust methods and external data, extrapolations are unreliable. Flexible…
The development of a new diagnostic test ideally follows a sequence of stages which, amongst other aims, evaluate technical performance. This includes an analytical validity study, a diagnostic accuracy study and an interventional clinical…
This paper addresses the problem of children's online safety in the context of the growing digital landscape. With a surge in the use of digital technology among children, there has been an increase in online safety harms, risks and…
Phase I dose-finding trials are increasingly challenging as the relationship between efficacy and toxicity of new compounds (or combination of them) becomes more complex. Despite this, most commonly used methods in practice focus on…
There is growing interest in Bayesian clinical trial designs with informative prior distributions, e.g. for extrapolation of adult data to pediatrics, or use of external controls. While the classical type I error is commonly used to…
Phase I dose-escalation trials must be guided by a safety model in order to avoid exposing patients to unacceptably high risk of toxicities. Traditionally, these trials are based on one type of schedule. In more recent practice, however,…
We assess the accuracy of Bayesian polynomial extrapolations from small parameter values, x, to large values of x. We consider a set of polynomials of fixed order, intended as a proxy for a fixed-order effective field theory (EFT)…
Phase I oncology trials aim to identify a safe dose - often the maximum tolerated dose (MTD) - for subsequent studies. Conventional designs focus on population-level toxicity modeling, with recent attention on leveraging pharmacokinetic…
The increasing prevalence of rich sources of data and the availability of electronic medical record databases and electronic registries opens tremendous opportunities for enhancing medical research. For example, controlled trials are…
There are several steps to confirming the safety and efficacy of a new medicine. A sequence of trials, each with its own objectives, is usually required. Quantitative risk metrics can be useful for informing decisions about whether a…
The primary goal of drug safety researchers and regulators is to promptly identify adverse drug reactions. Doing so may in turn prevent or reduce the harm to patients and ultimately improve public health. Evaluating and monitoring drug…
Adverse drug events (ADEs) are unexpected incidents caused by the administration of a drug or medication. To identify and extract these events, we require information about not just the drug itself but attributes describing the drug (e.g.,…
Phase I clinical trials are designed to test the safety (non-toxicity) of drugs and find the maximum tolerated dose (MTD). This task becomes significantly more challenging when multiple-drug dose-combinations (DC) are involved, due to the…