相关论文: Beyond the Two-Trials Rule

The two-trials rule in drug regulation requires statistically significant results from two pivotal trials to demonstrate efficacy. However, it is unclear how the effect estimates from both trials should be combined to quantify the drug…

Statistical methodology plays a crucial role in drug regulation. Decisions by the FDA or EMA are typically made based on multiple primary studies testing the same medical product, where the two-trials rule is the standard requirement,…

Statistical significance of both the original and the replication study is a commonly used criterion to assess replication attempts, also known as the two-trials rule in drug development. However, replication studies are sometimes conducted…

In clinical studies upon which decisions are based there are two types of errors that can be made: a type I error arises when the decision is taken to declare a positive outcome when the truth is in fact negative, and a type II error arises…

We study a statistical framework for replicability based on a recently proposed quantitative measure of replication success, the sceptical $p$-value. A recalibration is proposed to obtain exact overall Type-I error control if the effect is…

Background: Well-designed phase II trials must have acceptable error rates relative to a pre-specified success criterion, usually a statistically significant p-value. Such standard designs may not always suffice from a clinical perspective…

Conditional (European Medicines Agency) or accelerated (U.S. Food and Drug Administration) approval of drugs allow earlier access to promising new treatments that address unmet medical needs. Certain post-marketing requirements must…

Hybrid clinical trials, that borrow real-world data (RWD), are gaining interest, especially for rare diseases. They assume RWD and randomized control arm be exchangeable, but violations can bias results, inflate type I error, or reduce…

Replication studies are increasingly conducted to assess the credibility of scientific findings. Most of these replication attempts target studies with a superiority design, but there is a lack of methodology regarding the analysis of…

Practical employment of Bayesian trial designs is still rare. Even if accepted in principle, the regulators have commonly required that such designs be calibrated according to an upper bound for the frequentist type I error rate. This…

We introduce a new multiple type I error criterion for clinical trials with multiple populations. Such trials are of interest in precision medicine where the goal is to develop treatments that are targeted to specific sub-populations…

There are several steps to confirming the safety and efficacy of a new medicine. A sequence of trials, each with its own objectives, is usually required. Quantitative risk metrics can be useful for informing decisions about whether a…

Two-sample tests evaluate whether two samples are realizations of the same distribution (the null hypothesis) or two different distributions (the alternative hypothesis). We consider a new setting for this problem where sample features are…

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…

In a randomised clinical trial, when the result of the primary endpoint shows a significant benefit, the secondary endpoints are scrutinised to identify additional effects of the treatment. However, this approach entails a risk of…

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…

There is a growing interest in the implementation of platform trials, which provide the flexibility to incorporate new treatment arms during the trial and the ability to halt treatments early based on lack of benefit or observed…

FDA's Project Optimus initiative for oncology drug development emphasizes selecting a dose that optimizes both efficacy and safety. When an inferentially adaptive Phase 2/3 design with dose selection is implemented to comply with the…

When dealing with the problem of simultaneously testing a large number of null hypotheses, a natural testing strategy is to first reduce the number of tested hypotheses by some selection (screening or filtering) process, and then to…

Replication studies for scientific research are an important part of ensuring the reliability and integrity of experimental findings. In the context of clinical trials, the concept of replication has been formalised by the 'two-trials'…