Journal of biopharmaceutical statistics
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Multiregional clinical trials provide the potential to make safe and effective medical products simultaneously available to patients globally. As regulatory decisions are always made in a local context, this poses huge regulatory challenges. In this article we propose two conditional decision rules that can be used for medical product approval by local regulatory agencies based on the results of a multiregional clinical trial. We also illustrate sample size planning for such trials.
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Multiregional clinical trials including Japanese subjects are playing a key role in new drug development in Japan. In addition to the consideration of differences in intrinsic and extrinsic ethnic factors, deciding the sample size of Japanese subjects is an important issue when a multiregional clinical trial is intended to be used for Japanese submission. Accumulated experience suggests that there are several points to consider, such as the basic principles described in the guidance document, drug development strategy, trial phase, and disease background. The difficulty of interpreting the results of Japanese trials should also be considered.
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The main purpose of a Phase I trial of a new antitumor agent is to determine the appropriate dosing regimen and characterize the safety profile of a new molecular or monoclonal antibody. Phase II cancer clinical trials are conducted to assess the efficacy of a new anticancer therapy and to determine whether it has sufficient activity against a specific type of tumor to warrant further development. In this paper, commonly used statistical designs, based on either frequentist approaches or Bayesian methods, for Phase I and Phase II cancer clinical trials are reviewed and discussed. Future directions of designing more efficient trial are explored.
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The last 10 years have seen considerable interest in clinical trial designs that allow the seamless combination of Phases II and III in a single clinical trial. Such designs bring together the selection of the most promising of a number of treatments, as usually performed in a Phase II clinical trial, with the rigorous analysis and control of type I error rates required for a Phase III clinical trial. ⋯ This paper reviews methods based on the group-sequential methodology for monitoring of sequential clinical trials. The main focus of the paper will be a description of the methodology, including the setting in which short-term data are used for decision making at an early interim analysis.
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Handling missing data is an important consideration in the analysis of data from all kinds of medical device studies. Missing data in medical device studies can arise for all the reasons one might expect in pharmaceutical clinical trials. In addition, they occur by design, in nonrandomized device studies, and in evaluations of diagnostic tests. ⋯ Many types of missing data that can occur with diagnostic test evaluations are surveyed. Careful planning and conduct are recommended to minimize missing data. Although difficult, the prespecification of all missing data analysis strategies is encouraged before any data are collected.