Related papers: Random-effects meta-analysis of phase I dose-findi…
Background: Phase I trials desire to identify the maximum tolerated dose (MTD) early and proceed quickly to an expansion cohort or phase II trial for efficacy. We propose an early completion method based on multiple dosages to accelerate…
Drug combination trials are increasingly common nowadays in clinical research. However, very few methods have been developed to consider toxicity attributions in the dose escalation process. We are motivated by a trial in which the…
Phase I dose-finding trials in oncology seek to find the maximum tolerated dose (MTD) of a drug under a specific schedule. Evaluating drug-schedules aims at improving treatment safety while maintaining efficacy. However, while we can…
Early phase, personalized dose-finding trials for combination therapies seek to identify patient-specific optimal biological dose (OBD) combinations, which are defined as safe dose combinations which maximize therapeutic benefit for a…
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,…
The conventional more-is-better dose selection paradigm, which targets the maximum tolerated dose (MTD), is not suitable for the development of targeted therapies and immunotherapies as the efficacy of these novel therapies may not increase…
Nowadays, more and more clinical trials choose combinational agents as the intervention to achieve better therapeutic responses. However, dose-finding for combinational agents is much more complicated than single agent as the full order of…
This paper proposes a novel criterion for the allocation of patients in Phase~I dose-escalation clinical trials aiming to find the maximum tolerated dose (MTD). Conventionally, using a model-based approach the next patient is allocated to…
Aims: Combinations of treatments can offer additional benefit over the treatments individually. However, trials of these combinations are lower priority than the development of novel therapies, which can restrict funding, timelines and…
Some patients benefit from a treatment while others may do so less or do not benefit at all. We have previously developed a two-stage network meta-regression prediction model that synthesized randomized trials and evaluates how treatment…
To investigate intervention effects on rare events, meta-analysis techniques are commonly applied in order to assess the accumulated evidence. When it comes to adverse effects in clinical trials, these are often most adequately handled…
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…
Individualized treatment decisions can improve health outcomes, but using data to make these decisions in a reliable, precise, and generalizable way is challenging with a single dataset. Leveraging multiple randomized controlled trials…
Phase Ib/II oncology trials, despite their small sample sizes, aim to provide information for optimal internal company decision-making concerning novel drug development. Hybrid controls (a combination of the current control arm and controls…
Dose-finding trials for oncology studies are traditionally designed to assess safety in the early stages of drug development. With the rise of molecularly targeted therapies and immuno-oncology compounds, biomarker-driven approaches have…
Novel dose-finding designs, using estimation to assign the best estimated maximum- tolerated-dose (MTD) at each point in the experiment, most commonly via Bayesian techniques, have recently entered large-scale implementation in Phase I…
According to Davey et al. (2011) with a total of 22,453 meta-analyses from the January 2008 Issue of the Cochrane Database of Systematic Reviews, the median number of studies included in each meta-analysis is only three. In other words,…
Combination of several anti-cancer treatments has typically been presumed to have enhanced drug activity. Motivated by a real clinical trial, this paper considers phase I-II dose finding designs for dual-agent combinations, where one main…
An early phase clinical trial is the first step in evaluating the effects in humans of a potential new anti-disease agent or combination of agents. Usually called "phase I" or "phase I/II" trials, these experiments typically have the…
Random effects meta-analysis is widely used for synthesizing studies under the assumption that underlying effects come from a normal distribution. However, under certain conditions the use of alternative distributions might be more…