Document Detail

A sensitivity analysis of the modified chi-square ratio statistic for equivalence testing of aerodynamic particle size distribution.
MedLine Citation:
PMID:  23344791     Owner:  NLM     Status:  MEDLINE    
Demonstration of equivalence in aerodynamic particle size distribution (APSD) is one key component for establishing bioequivalence of orally inhaled drug products. We previously proposed a modified version of the Chi-square ratio statistic (mCSRS) for APSD equivalence testing and demonstrated that the median of the distribution of the mCSRS (MmCSRS) is a robust metric when test (T) and reference (R) cascade impactor (CI) profiles are identical. Here, we systematically evaluate the behavior of the MmCSRS when T and R CI profiles differ from each other in their mean deposition and variability on a single and multiple sites. All CI profiles were generated by Monte-Carlo simulations based upon modified actual CI data. Twenty thousand sets of 30 T and 30 R CI profiles were simulated for each scenario, and the behavior of the MmCSRS was correlated to metrics that characterize the difference between T and R product in mean deposition and variability. The two key findings were, first, that the MmCSRS is more sensitive to difference between T and R CI profiles on high deposition sites, and second, that a cut-off value for APSD equivalence testing based on the MmCSRS needs to be scaled on the variability of the R product. The former is considered as beneficial for equivalence testing of CI profiles as it decreases the likelihood of failing identical CI profiles by chance, in part, due to increasing analytical variability associated with lower deposition sites. The latter is expected to be important for consistently being able to discriminate equivalent from inequivalent CI profiles.
Benjamin Weber; Sau L Lee; Robert Lionberger; Bing V Li; Yi Tsong; Guenther Hochhaus
Publication Detail:
Type:  Journal Article     Date:  2013-01-24
Journal Detail:
Title:  The AAPS journal     Volume:  15     ISSN:  1550-7416     ISO Abbreviation:  AAPS J     Publication Date:  2013 Apr 
Date Detail:
Created Date:  2013-04-05     Completed Date:  2013-10-22     Revised Date:  2014-01-26    
Medline Journal Info:
Nlm Unique ID:  101223209     Medline TA:  AAPS J     Country:  United States    
Other Details:
Languages:  eng     Pagination:  465-76     Citation Subset:  IM    
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MeSH Terms
Administration, Inhalation
Chemistry, Pharmaceutical
Chi-Square Distribution
Computer Simulation
Linear Models
Models, Statistical*
Monte Carlo Method
Particle Size
Technology, Pharmaceutical / methods*
Therapeutic Equivalency
Reg. No./Substance:

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine

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