Related papers: A straightforward meta-analysis approach for oncol…
Although there is an extensive statistical literature showing the disadvantages of discretizing continuous variables, categorization is a common practice in clinical research which results in substantial loss of information. A large…
Recently, the strategy for dose optimization in oncology has shifted to conduct Phase 2 randomized controlled trials with multiple doses. Optimal biologic dose selection from Phase 1 trial data to determine candidate doses for Phase 2…
Multi-cancer early detection (MCED) tests offer to screen for multiple types of cancer with a single blood sample. Despite their promising diagnostic performance, evidence regarding their population benefit is not yet available. Expecting…
Meta-analysis is a systematic approach for understanding a phenomenon by analyzing the results of many previously published experimental studies. It is central to deriving conclusions about the summary effect of treatments and interventions…
Chemotherapy is one of the primary modalities of cancer treatment. Chemotherapy drug administration is a complex problem that often requires expensive clinical trials to evaluate potential regimens. One way to alleviate this burden and…
In early-phase cancer clinical trials, the limited availability of data presents significant challenges in developing a framework to efficiently quantify treatment effectiveness. To address this, we propose a novel utility-based Bayesian…
Treatment of cancer has rapidly evolved over time in quite dramatic ways, for example from chemotherapies, targeted therapies to immunotherapies and chimeric antigen receptor T-cells. Nonetheless, the basic design of early phase I trials in…
During drug development, evidence can emerge to suggest a treatment is more effective in a specific patient subgroup. Whilst early trials may be conducted in biomarker-mixed populations, later trials are more likely to enrol…
In this paper, a methodology is proposed that enables to analyze the sensitivity of the outcome of a therapy to unavoidable high dispersion of the patient specific parameters on one hand and to the choice of the parameters that define the…
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…
In a Phase II dose-finding study with a placebo control, a new drug with several dose levels is compared with a placebo to test for the effectiveness of the new drug. The main focus of such studies often lies in the characterization of the…
Random-effects meta-analyses are used to combine evidence of treatment effects from multiple studies. Since treatment effects may vary across trials due to differences in study characteristics, heterogeneity in treatment effects between…
Designing modern oncology trials requires synthesizing evidence from prior studies to inform hypothesis generation and sample size determination. Trial designs based on incomplete or imprecise summaries can lead to misspecified hypotheses…
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…
Adaptive Phase 2/3 designs hold great promise in contemporary oncology drug development, especially when limited data from Phase 1 dose-finding is insufficient for identifying an optimal dose. However, there is a general concern about…
[See paper for full abstract] Meta-analysis is a crucial tool for answering scientific questions. It is usually conducted on a relatively small amount of ``trusted'' data -- ideally from randomized, controlled trials -- which allow causal…
For many years Phase I and Phase II clinical trials were conducted separately, but there was a recent shift to combine these Phases. While a variety of Phase~I/II model-based designs for cytotoxic agents were proposed in the literature,…
Decision-making in personalized medicine such as cancer therapy or critical care must often make choices for dosage combinations, i.e., multiple continuous treatments. Existing work for this task has modeled the effect of multiple…
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…
Phase I dose-escalation trials constitute the first step in investigating the safety of potentially promising drugs in humans. Conventional methods for phase I dose-escalation trials are based on a single treatment schedule only. More…