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Abstract Trans-arterial chemoembolization (TACE) is an important yet variably effective treatment for management of hepatic malignancies. Lack of response can be in part due to inability to assess treatment adequacy in real-time. Gold-standard contrast enhanced computed tomography and magnetic resonance imaging, although effective, suffer from treatment-induced artifacts that prevent early treatment evaluation. Non-contrast ultrasound is a potential solution but has historically been ineffective at detecting treatment response. Here, we propose non-contrast ultrasound with recent perfusion-focused advancements as a tool for immediate evaluation of TACE. We demonstrate initial feasibility in an 11-subject pilot study. Treatment-induced changes in tumor perfusion are detected best when combining adaptive demodulation (AD) and singular value decomposition (SVD) techniques. Using a 0.5 s (300-sample) ensemble size, AD + SVD resulted in a 7.42 dB median decrease in tumor power after TACE compared to only a 0.06 dB median decrease with conventional methods.
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Sample size re‐estimation in Phase 2 dose‐finding: Conditional power versus Bayesian predictive power
Abstract Unblinded sample size re‐estimation (SSR) is often planned in a clinical trial when there is large uncertainty about the true treatment effect. For Proof‐of Concept (PoC) in a Phase II dose finding study, contrast test can be adopted to leverage information from all treatment groups. In this article, we propose two‐stage SSR designs using frequentist conditional power (CP) and Bayesian predictive power (PP) for both single and multiple contrast tests. The Bayesian SSR can be implemented under a wide range of prior settings to incorporate different prior knowledge. Taking the adaptivity into account, all type I errors of final analysis in this paper are rigorously protected. Simulation studies are carried out to demonstrate the advantages of unblinded SSR in multi‐arm trials.
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- Award ID(s):
- 2210371
- PAR ID:
- 10401115
- Publisher / Repository:
- Wiley Blackwell (John Wiley & Sons)
- Date Published:
- Journal Name:
- Pharmaceutical Statistics
- Volume:
- 22
- Issue:
- 2
- ISSN:
- 1539-1604
- Page Range / eLocation ID:
- p. 349-364
- Format(s):
- Medium: X
- Sponsoring Org:
- National Science Foundation
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