Can the Concept Be Proven?
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Can the Concept Be Proven? Ying‑Ying Zhang1 · Naitee Ting2 Received: 7 September 2018 / Revised: 16 June 2019 / Accepted: 10 August 2020 © International Chinese Statistical Association 2020
Abstract During clinical development of new medicinal products, phase II is one of the most important stages. The first phase II trial is typically a Proof of Concept (PoC) study with limited sample size. To reduce the bias, one needs to discount the phase II estimate of the treatment effect. Under some mild conditions, the estimated assurances are increasing functions of the per group number of patients and the scaled observed treatment effect of the phase II trial for the three cases (no, additive, and multiplicative bias adjustment); and for multiplicative bias adjustment, the estimated assurance is an increasing function of the retention factor. The theoretical assurances are increasing functions of the per group number of patients of the phase II trial and the scaled true treatment effect of the phase III trial. The numerical simulations illustrate the above theoretical results. After obtaining the results of the phase II trial, it is still difficult for the project team (and the company) to make the Go/No Go decision. Finally, in addition to the investment and the statistical points of view, the Go/ No Go decision is also affected by many other factors. Keywords Phase II/III clinical trials · Proof of Concept · Launch criterion · Assurance · Go/No Go decision
Electronic supplementary material The online version of this article (https://doi.org/10.1007/s1256 1-020-09290-3) contains supplementary material, which is available to authorized users. * Naitee Ting naitee.ting@boehringer‑ingelheim.com Ying‑Ying Zhang [email protected]; [email protected] https://zhangyingying319.wordpress.com 1
Department of Statistics and Actuarial Science, College of Mathematics and Statistics, Chongqing University, Chongqing, China
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Department of Biostatistics and Data Sciences, Boehringer Ingelheim Pharmaceuticals, Inc., Ridgefield, CT, USA
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Statistics in Biosciences
1 Introduction For medicinal products discovered and developed to treat chronic diseases, most of the phase I clinical trials recruit normal healthy volunteers and, as a result, the disease improvement cannot be observed in phase I. Under this situation, study results cannot be used to assess product efficacy [11]. In phase I oncology trials, although cancer patients are recruited to help study the maximally tolerable dose (MTD), these patients may or may not be with the tumor type for which the drug is developed for. Also, the sample sizes used for phase I oncology trials are not large enough for the study of product efficacy. Therefore, in most of product development programs, phase II is the first time the product efficacy can be observed and evaluated. Under this circumstance, it is especially important that the product efficacy be established from the first phase II clinical trial. The most commonly used study design for a fi
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