Thomas Jaki

A Fast, Flexible Simulation Framework for Bayesian Adaptive Designs—The R Package BATSS

Dominique‐Laurent Couturier, Rainer Puhr, Stephane Heritier, Thomas Jaki et autres

ABSTRACT The use of Bayesian adaptive designs for randomised controlled trials has been hindered by the lack of software readily available to statisticians. We have developed a new software package (Bayesian Adaptive Trials Simulator Software— BATSS ) for the statistical software R, …

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Adaptive versus fixed designs in confirmatory clinical trials: centering the choice on ethics

Stef Baas, Lukas Pin, David S. Robertson, Frank Bretz et autres

BACKGROUND: Because confirmatory clinical trials are costly, large-scale endeavors, the choice of their design carries significant weight. While the current methodological landscape offers tools to address residual pre-trial uncertainty through prespecified adaptations to design elements, design choices remain frequently constrained by prevailing …

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Optimal Weighted Tests for Replication Studies and the ‘Two‐Trials Rule’ With Multiple Hypotheses

David S. Robertson, Thomas Jaki

ABSTRACT 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 formalized by the “two‐trials” rule, where two pivotal studies are required …

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Introducing precision-weighted bias as a performance measure to inform the inclusion of adaptive designs in meta-analysis

羅浩雲 Martin Law, D Robertson, Sofía S. Villar, Tim P. Morris et autres

We propose a novel, intuitive measure of statistical performance: precision-weighted bias. Precision-weighted bias is defined as the unconditional bias of an estimator weighted by the degree of information (precision) it contains. Current guidelines, such as GRADE and CONSORT, often view the potential …

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Extension and Application of the Partial Continual Reassessment Method to a Phase-IIa Dose-Finding Tuberculosis Trial with a Continuous Endpoint

Alessandra Serra, Thomas Jaki, Pavel Mozgunov

Novel regimens for treating Tuberculosis (TB) are currently under clinical evaluation. Often, these consist of regimens of multiple novel agents that are compared to a standard regimen. Selecting a minimum efficacious dose of a regimen can be challenging, as dosing of two …

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An evaluation of designs for Phase I/IIa dose-finding studies in Tuberculosis

Alessandra Serra, Pavel Mozgunov, P. Scott Phillips, Thomas Jaki

Early development of tuberculosis (TB) treatments often separates dose-finding in healthy volunteers (Phase I) and safety and early activity in patients (Phase IIa). The BTZ-043 study (NCT04044001) is a recent study that combined these two objectives in patients in a single study. …

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Operationalizing Allocation Probability Tests: Practical Guidance on Optimized Implementation for Power and Robustness

Stina Zetterstrom, David S. Robertson, Thomas Jaki, Sofía S. Villar

Recently, a new testing approach for response-adaptive clinical trials was proposed based on the allocation probabilities (AP) rather than the outcome data. While original work on the AP test focused on binary and normal endpoints and demonstrated that significant efficiency gains are …

A randomized controlled Phase I de-escalation trial of molnupiravir and nirmatrelvir/ritonavir combination for mild-moderate SARS-CoV-2 infection

Saye Khoo, Richard FitzGerald, Christopher John Edwards, Shazaad S. Y. Ahmad et autres

OBJECTIVES: The AGILE CST-8 (NCT04746183) Phase I de-escalation trial evaluated the safety and tolerability of combination molnupiravir and nirmatrelvir/ritonavir for mild-moderate COVID-19. METHODS: Adult outpatients with SARS-CoV-2 infection within 5 days of symptoms were randomly assigned 2:1 to receive molnupiravir [starting at …

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The RECOVERY Trial:

Lily Ding, Thomas Jaki, Jingjing Ye

Robust Bayesian Sequential Borrowing for Multi-Population Clinical Programmes

Erik Hermansson, Lynn Dunsire, David J. Svensson, Thomas Jaki

We introduce Robust Bayesian Sequential Borrowing (RBSB), a framework for extrapolating evidence across adjacent subgroups in multi-population clinical programmes where studies are conducted in sequence and populations are ordered by clinical proximity. Conventional approaches weight all historical sources uniformly or exclude distant …

Modern Clinical Trials: Seamless Designs and Master Protocols

Abigail Burdon, Thomas Jaki, Xijin Chen, Pavel Mozgunov et autres

BACKGROUND: Drug development is often inefficient, costly and lengthy, yet it is essential for evaluating the safety and efficacy of new interventions. Compared with other disease areas, this is particularly true for Phase II/III cancer clinical trials where many drug candidates fail …

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Optimal Dose and Safety of Intravenous Favipiravir in Hospitalized Patients With COVID ‐19: A Dose‐Escalating, Randomized Controlled Phase Ib Study

Tim Rowland, Richard FitzGerald, Elizabeth Challenger, Laura A. Dickinson et autres

AGILE (NCT04746183) is a Phase Ib/IIa platform, evaluating candidates to treat COVID-19. Candidate Specific Trial 6 evaluated the safety and optimal dose of a novel intravenous formulation of favipiravir in a dose-escalating, open-label, randomized, controlled, Bayesian adaptive Phase Ib trial. Hospitalized adults …

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