Related papers: A multistate model for early decision making in on…
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),…
Overall survival (OS) is the gold standard for assessing patient benefit and cost-effectiveness of new cancer drugs. However, it is often difficult to use OS as the primary endpoint in randomized clinical trials (RCTs) for patients with…
As cancer patient survival improves, late effects from treatment are becoming the next clinical challenge. Chemotherapy and radiotherapy, for example, potentially increase the risk of both morbidity and mortality from second malignancies…
An unprecedented number of new cancer targets are in development, and most are being developed in combination therapies. Early oncology development is strategically challenged in choosing the best combinations to move forward to late stage…
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.…
The development of targeted therapies, which benefit only a subgroup of patients treated for a given type of cancer, has been extremely attractive to many investigators. Adaptive seamless phase II/III designs in oncology clinical trials…
Purpose: PFS is often used as a surrogate endpoint for OS in metastatic breast cancer studies. We have evaluated the association of treatment effect on PFS with significant HR$_{OS}$ (and how this association is affected by other factors)…
Progression free survival (PFS) and tumour response (TR) have been investigated as surrogate endpoints for overall survival (OS) in advanced colorectal cancer (aCRC), however their validity has been shown to be suboptimal. In recent years,…
In oncology clinical trials, characterizing the long-term overall survival (OS) benefit for an experimental drug or treatment regimen (experimental group) is often unobservable if some patients in the control group switch to drugs in the…
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…
Clinical trials often collect data on multiple outcomes, such as overall survival (OS), progression-free survival (PFS), and response to treatment (RT). In most cases, however, study designs only use primary outcome data for interim and…
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…
In this work, we investigate the population dynamics of tumor cells under therapeutic pressure. Although drug treatment initially induces a reduction in tumor burden, treatment failure frequently occurs over time due to the emergence of…
In assessing Overall Survival (OS) in oncology studies, it is essential for the efficacy measure to be Logic-respecting, for otherwise patients may be incorrectly targeted. This paper explains, while Time Ratio (TR) is Logic-respecting,…
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…
Indolent cancers are characterized by long overall survival (OS) times. Therefore, powering a clinical trial to provide definitive assessment of the effects of an experimental intervention on OS in a reasonable timeframe is generally…
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…
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…
In oncological clinical trials, overall survival (OS) is the gold-standard endpoint, but long follow-up and treatment switching can delay or dilute detectable effects. Progression-free survival (PFS) often provides earlier evidence and is…
Traditional health authority approval for oncology drugs is based on a clinical benefit endpoint, or a valid surrogate. In 1992 the FDA created the Accelerated Approval pathway to allow for earlier approval of therapies in serious…