相关论文: A time-to-event three-outcome design for randomize…

Immunotherapies have revolutionized cancer treatment. Unlike chemotherapies, immune agents often take longer time to show benefit, and the complex and unique mechanism of action of these agents renders the use of multiple endpoints more…

In oncology, phase II or multiple expansion cohort trials are crucial for clinical development plans. This is because they aid in identifying potent agents with sufficient activity to continue development and confirm the proof of concept.…

Pathologic complete response (pCR) is a common primary endpoint for a phase II trial or even accelerated approval of neoadjuvant cancer therapy. If granted, a two-arm confirmatory trial is often required to demonstrate the efficacy with a…

When planning an oncology clinical trial, the usual approach is to assume proportional hazards and even an exponential distribution for time-to-event endpoints. Often, besides the gold-standard endpoint overall survival (OS),…

In many phase II trials in solid tumours, patients are assessed using endpoints based on the Response Evaluation Criteria in Solid Tumours (RECIST) scale. Often, analyses are based on the response rate. This is the proportion of patients…

Mid-study design modifications are becoming increasingly accepted in confirmatory clinical trials, so long as appropriate methods are applied such that error rates are controlled. It is therefore unfortunate that the important case of…

Biomarker-guided designs are increasingly used to evaluate personalized treatments based on patients' biomarker status in Phase II and III clinical trials. With adaptive enrichment, these designs can improve the efficiency of evaluating the…

The use of drug combinations in clinical trials is increasingly common during the last years since a more favorable therapeutic response may be obtained by combining drugs. In phase I clinical trials, most of the existing methodology…

Purpose: Two-stage single-arm trial designs are commonly used in phase II oncology to infer treatment effects for a binary primary outcome (e.g., tumour response). It is imperative that such studies be designed, analysed, and reported…

We propose a two-stage design for a clinical trial with an early stopping rule for safety. We use different criteria to assess early stopping and efficacy. The early stopping rule is based on a criteria that can be determined more quickly…

Recently there has been much work on early phase cancer designs that incorporate both toxicity and efficacy data, called Phase I-II designs because they combine elements of both phases. However, they do not explicitly address the Phase II…

It is crucial to design Phase II cancer clinical trials that balance the efficiency of treatment selection with clinical practicality. Sargent and Goldberg proposed a frequentist design that allow decision-making even when the primary…

When a novel treatment has successfully passed phase I, different options to design subsequent phase II trials are available. One approach is a single-arm trial, comparing the response rate in the intervention group against a fixed…

Time-to-event endpoints are central to evaluate treatment efficacy across many disease areas. Many trial protocols include interim analyses within group-sequential designs that control type I error via spending functions or boundary…

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…

In single-arm phase II oncology trials, the most popular choice of design is Simon's two-stage design, which allows early stopping at one interim analysis. However, the expected trial sample size can be reduced further by allowing…

2-in-1 design (Chen et al. 2018) is becoming popular in oncology drug development, with the flexibility of using different endpoints at different decision time. Based on the observed interim data, sponsors choose either to seamlessly…

The analysis of multiple time-to-event outcomes in a randomised controlled clinical trial can be accomplished with exisiting methods. However, depending on the characteristics of the disease under investigation and the circumstances in…

Likelihood methods for measuring statistical evidence obey the likelihood principle while maintaining bounded and well-controlled frequency properties. These methods lend themselves to sequential study designs because they measure the…

In oncology, phase II studies are crucial for clinical development plans as such studies identify potent agents with sufficient activity to continue development in the subsequent phase III trials. Traditionally, phase II studies are…