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A Bioequivalence Test by the Direct Comparison of Concentration-versus-Time Curves Using Local Polynomial Smoothers.

ABSTRACT: In order to test if two chemically or pharmaceutically equivalent products have the same efficacy and/or toxicity, a bioequivalence (BE) study is conducted. The 80%/125% rule is the most commonly used criteria for BE and states that BE cannot be claimed unless the 90% CIs for the ratio of selected pharmacokinetics (PK) parameters of the tested to the reference drug are within 0.8 to 1.25. Considering that estimates of these PK parameters are derived from the concentration-versus-time curves, a direct comparison between these curves motivates an alternative and more flexible approach to test BE. Here, we propose to frame the BE test in terms of an equivalence of concentration-versus-time curves which are constructed using local polynomial smoother (LPS). A metric is presented to quantify the distance between the curves and its 90% CIs are calculated via bootstrapping. Then, we applied the proposed procedures to data from an animal study and found that BE between a generic drug and its brand name cannot be concluded, which was consistent with the results by applying the 80%/125% rule. However, the proposed procedure has the advantage of testing only on a single metric, instead of all PK parameters.

SUBMITTER: Tian S

PROVIDER: S-EPMC5165228 | biostudies-literature | 2016

REPOSITORIES: biostudies-literature

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A Bioequivalence Test by the Direct Comparison of Concentration-versus-Time Curves Using Local Polynomial Smoothers.

Tian Suyan S Chang Howard H HH Orange Dana D Gu Jingkai J Suárez-Fariñas Mayte M

Computational and mathematical methods in medicine 20161205

In order to test if two chemically or pharmaceutically equivalent products have the same efficacy and/or toxicity, a bioequivalence (BE) study is conducted. The 80%/125% rule is the most commonly used criteria for BE and states that BE cannot be claimed unless the 90% CIs for the ratio of selected pharmacokinetics (PK) parameters of the tested to the reference drug are within 0.8 to 1.25. Considering that estimates of these PK parameters are derived from the concentration-versus-time curves, a d ...[more]

PMID: 28050196

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Project description:This paper contributes to the environmental literature by (i) demonstrating that the estimated coefficients and the statistical significance of the non-leading terms in quadratic, cubic, and quartic logarithmic environmental Kuznets curve (EKC) specifications are arbitrary and should therefore not be used to choose the preferred specification and (ii) detailing a proposed general-to-specific type methodology for choosing the appropriate specifications when attempting to estimate higher-order polynomials such as cubic and quartic logarithmic EKC relationships. Testing for the existence and shape of the well-known EKC phenomenon is a hot topic in the environmental economics literature. The conventional approach widely employs quadratic and cubic specifications and more recently also the quartic specification, where the variables are in logarithmic form. However, it is important that researchers understand whether the estimated EKC coefficients, turning points, and elasticities are statistically acceptable, economically interpretable, and comparable. In addition, it is vital that researchers have a clear structured non-arbitrary methodology for determining the preferred specification and hence shape of the estimated EKC. We therefore show mathematically and empirically the arbitrary nature of estimated non-leading coefficients in quadratic, cubic, and quartic logarithmic EKC specifications, being dependent upon the units of measurement chosen for the independent variables (e.g. dependent upon a rescaling of the variables such as moving from $m to $bn). Consequently, the practice followed in many previously papers, whereby the estimates of the non-leading terms are used in the decision to choose the preferred specification of an estimated EKC relationship, is incorrect and should not be followed since it potentially could lead to misleading conclusions. Instead, it should be based upon the sign and statistical significance of the estimated coefficients of the leading terms, the location of turning point(s), and the sign and statistical significance of the estimated elasticities. Furthermore, we suggest that researchers should follow a proposed general-to-specific type methodology for choosing the appropriate order of polynomials when attempting to estimate higher-order polynomial logarithmic EKCs.

Dataset Information

A Bioequivalence Test by the Direct Comparison of Concentration-versus-Time Curves Using Local Polynomial Smoothers.

Publications

A Bioequivalence Test by the Direct Comparison of Concentration-versus-Time Curves Using Local Polynomial Smoothers.

Similar Datasets

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