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An Improved Approach for Confirmatory Phase III Population Pharmacokinetic Analysis
Author(s) -
Hu Chuanpu,
Zhou Ghui
Publication year - 2008
Publication title -
the journal of clinical pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.92
H-Index - 116
eISSN - 1552-4604
pISSN - 0091-2700
DOI - 10.1177/0091270008318670
Subject(s) - ambiguity , robustness (evolution) , covariate , computer science , population , exploratory analysis , dosing , econometrics , contrast (vision) , medicine , machine learning , mathematics , data science , artificial intelligence , pharmacology , biochemistry , chemistry , environmental health , gene , programming language
In contrast to the traditional extensive exploratory approach, the authors propose a confirmatory approach to phase III population pharmacokinetics for regulatory submissions. In their approach, they recommend a prespecified primary analysis based on phase I/II data and phase III study design. Their approach also incorporates several specific sensitivity analyses to evaluate the robustness of the conclusions. According to statistical rationale, this approach eliminates certain biases that may occur in the estimated covariate effects, thereby precluding potentially unnecessary dosing adjustments and allowing for more accurate assessments of ambiguity in the results. Because exploration is vastly reduced, the analysis time is also substantially shortened. The proposed analyses are relatively easy to implement, although careful and prospective planning is required. Applications of the approach are provided, including 2 phase III analyses for regulatory submissions. Differences between the proposed approach and the commonly used extensive exploratory analyses submitted to regulatory agencies were small and consistent with practical expectations.