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The landscape of dose-finding designs for phase I clinical trials is rapidly shifting in the recent years, noticeably marked by the emergence of interval-based designs. We categorize them as the iDesigns and the IB-Designs. The iDesigns are…
The two-trials rule for drug approval requires "at least two adequate and well-controlled studies, each convincing on its own, to establish effectiveness". This is usually implemented by requiring two significant pivotal trials and is the…
Background: Experimental treatments pass through various stages of development. If a treatment passes through early phase experiments, the investigators may want to assess it in a late phase randomised controlled trial. An efficient way to…
A multi-arm multi-stage trial is a multi-arm trial which includes interim analyses - analysing the data at certain specified points, generally discontinuing treatments which are concluded to not work and proceeding with the remainder. It is…
There has been an increasing use of master protocols in oncology clinical trials because of its efficiency and flexibility to accelerate cancer drug development. Depending on the study objective and design, a master protocol trial can be a…
In phase I dose escalation studies for dual-agent combinations, at least one drug often has an established monotherapy dose. Consequently, substantial prior clinical safety data often exist for one or more monotherapies, allowing the study…
Individual participant data (IPD) meta-analyses of randomised trials are considered a reliable way to assess participant-level treatment effect modifiers but may not make the best use of the available data. Traditionally, effect modifiers…
Appropriate medication dosages in the intensive care unit (ICU) are critical for patient survival. Heparin, used to treat thrombosis and inhibit blood clotting in the ICU, requires careful administration due to its complexity and…
We propose a Bayesian optimal phase 2 design for jointly monitoring efficacy and toxicity, referred to as BOP2-TE, to improve the operating characteristics of the BOP2 design proposed by Zhou et al. (2017). BOP2-TE utilizes a…
The main objective of dose finding trials is to find an optimal dose amongst a candidate set for further research. The trial design in oncology proceeds in stages with a decision as to how to treat the next group of patients made at every…
Cross-study replicability is a powerful model evaluation criterion that emphasizes generalizability of predictions. When training cross-study replicable prediction models, it is critical to decide between merging and treating the studies…
Project Optimus, an initiative by the FDA's Oncology Center of Excellence, seeks to reform the dose-optimization and dose-selection paradigm in oncology. We propose a dose-optimization design that considers plateau efficacy profiles,…
During lab studies of text entry methods it is typical to observer very few errors in participants' typing - users tend to type very carefully in labs. This is a problem when investigating methods to support error awareness or correction as…
Warfarin dosing remains challenging due to narrow therapeutic index and highly individual variability. Incorrect warfarin dosing is associated with devastating adverse events. Remarkable efforts have been made to develop the machine…
The ICH E9(R1) addendum provides guidelines on accounting for intercurrent events in clinical trials using the estimands framework. However, there has been limited attention to the estimands framework for meta-analysis. Using treatment…
We consider a Bayesian framework based on "probability of decision" for dose-finding trial designs. The proposed PoD-BIN design evaluates the posterior predictive probabilities of up-and-down decisions. In PoD-BIN, multiple grades of…
In medical treatment and elsewhere, it has become standard to base treatment intensity (dosage) on evidence in randomized trials. Yet it has been rare to study how outcomes vary with dosage. In trials to obtain drug approval, the norm has…
An assurance calculation is a Bayesian alternative to a power calculation. One may be performed to aid the planning of a clinical trial, specifically setting the sample size or to support decisions about whether or not to perform a study.…
In October 2014, the US Drug Enforcement Agency (DEA) reclassified hydrocodone from Schedule III to Schedule II of the Controlled Substances Act, resulting in a prohibition on refills in the initial prescription. While this schedule change…
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,…