Case study: Various methods for an unblinded sample size re-estimation in a bioequivalence study

Objective: New technique was adopted and validated to estimate pivotal sample size from the pilot study data and to establish bioequivalence (BE) of highly variable drugs (HVD), paroxetine, a novel controlled release (CR) matrix tablets utilized ghatti Gum as a rate controlling membrane, in human subject under fed conditions by reference scale design. Methods: Bootstrapping technique was adopted to calculate the pivotal sample size from pilot study data for HVD paroxetine. The reliability and validation of the method were tested in a semi replicate three sequence (RRT, RTR, and TRR where T stand for test drug and R stand for reference drug) cross-over BE study in 24 healthy subjects under fed conditions. Results: The ratio of the pharmacokinetic (PK) metric obtained from the bootstrapping technique after log transformation was 1.04 for Cmax, 1.23 for AUCT, and 1.21 for AUCI with corresponding power of the study which was greater than 80% from pilot study data simulation. The ratio of the PK metric obtained from the reference scaling design in the present study was 1.00 for Cmax, 1.21 for AUCT, and 1.17 for AUCI. The upper limit of the Cmax, AUCT, and AUCI at 95% confidence limit was −0.143, −0.136, and −0.17, respectively. Conclusion: The test paroxetine CR formulation was bioequivalent with reference drug under fed conditions. The technique used for estimation of the sample size in the pivotal study was found reliable, and bootstrapping technique plays an important role in calculating sample size where intrasubject variability was immaterial.

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A Comparison of Virtual Condition Cylinder Evaluation Methods in Coordinate Metrology

Volume 1: 34th Design Automation Conference, Parts A and B ◽

10.1115/detc2008-49798 ◽

2008 ◽

Cited By ~ 1

Author(s):

Steven Turek ◽

Sam Anand

Keyword(s):

Sample Size ◽

Geometric Analysis ◽

Sampled Data ◽

Material Condition ◽

Novel Approach ◽

Real World Applications ◽

Coordinate Metrology ◽

Normal Method ◽

Geometric Relationship

When a cylindrical datum feature is specified at maximum material condition (MMC) or least material condition (LMC) a unique circumstance arises: a virtual condition (VC) cylindrical boundary must be defined [1]. The geometric relationship between a cylindrical point cloud obtained from inspection equipment and a VC cylinder has not been specifically addressed in previous research. In this research, novel approaches to this geometric analysis are presented, analyzed, and validated. Two of the proposed methods are new interpretations of established methods applied to this unique geometric circumstance: least squares and the maximum inscribing cylinder (MIC) or minimum circumscribing cylinder (MCC). The third method, the Hull Normal method, is a novel approach specifically developed to address the VC cylinder problem. Each of the proposed methods utilizes a different amount of sampled data, leading to various levels of sensitivity to sample size and error. The three methods were applied to different cylindrical forms, utilizing various sampling techniques and sample sizes. Trends across sample size were analyzed to assess the variation in axial orientation when compared to the true geometric form, and a relevant case study explores the applicability of these methods in real world applications.

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Physiologically Based Dissolution Testing in a Drug Development Process—a Case Study of a Successful Application in a Bioequivalence Study of Trazodone ER Formulations Under Fed Conditions

AAPS PharmSciTech ◽

10.1208/s12249-020-01662-8 ◽

2020 ◽

Vol 21 (5) ◽

Author(s):

Dorota Danielak ◽

Bartłomiej Milanowski ◽

Krzysztof Wentowski ◽

Maria Nogowska ◽

Michał Kątny ◽

...

Keyword(s):

Drug Development ◽

Development Process ◽

Bioequivalence Study ◽

Drug Development Process ◽

Dissolution Testing ◽

Physiologically Based

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The rise and decline of TQM in the NHS

The TQM Journal ◽

10.1108/tqm-01-2012-0002 ◽

2014 ◽

Vol 26 (5) ◽

pp. 499-509 ◽

Cited By ~ 2

Author(s):

Uche Nwabueze

Keyword(s):

Quality Management ◽

Sample Size ◽

Practical Implication ◽

Real Life ◽

Leadership Role ◽

Future Research ◽

Rapid Decline ◽

Total Quality ◽

Content Type

Purpose – The purpose of this paper is to delineate the factors responsible for the decline of total quality management (TQM) in the National Health Service (NHS). It is suggested that if these factors were initially identified and eliminated prior to implementation, the decline of TQM as a strategy for improving the provision and delivery of quality patient care could have been prevented. Design/methodology/approach – The case study approach was chosen because it is the preferred method when “how” or “what” questions are being posed. It is applicable as is evident in this paper where the researcher has little control over events and when the focus is on a contemporary phenomenon within some real-life context. The case study enables the researcher to give an accurate rendition of actual events; it contributes uniquely to the knowledge of individual, organisational, social, and political phenomena. The semi-structured face-to-face interview constituted the main data collection technique of the research. Interviews were held with 23 quality management managers in the British NHS. The central focus of the interview was on “what” factors contributed to the rapid decline of TQM in the NHS. The respondents were chosen because they were directly involved with the implementation of TQM. They were in the vintage position to offer a full insight into the TQM initiative. The analysis of the case is based on Yin's analytic technique of explanation building. Findings – The decline of TQM in the NHS could have been prevented if top executives in hospitals had adopted the sequential steps to quality improvement: In the authors opinion, to land a man on the moon needed a belief in the possibility and breakthrough in the attitudes that viewed space travel as pure science fiction as opposed to a practical reality, and so it should have been with TQM in the NHS. However, the attitude of many NHS managers was that TQM was all right for “other institutions” because “they need it” whereas in the NHS, “we don’t”. This negative attitude should have been overcome if TQM was to be accepted as a corporate, all encompassing philosophy. Research limitations/implications – The limitation of the research may be the sample size of the respondents, which was limited to 23 quality managers that had hands-on experience and the leadership role to lead and implement TQM in the NHS. Future research may consider a broader sample size. It may also be considered for new research to use surveys to identify a broader set of reasons why TQM declined in the NHS. Practical implications – This paper is the first constructive insight to determine reasons for the decline of TQM in the NHS from the individuals who had the sole responsibility for implementation. Any other, group would have amounted to hearsay. Therefore, to constructively delineate the reasons for failure, it was pertinent to learn from the quality managers directly and to ensure that the reasons was representative of their experiences with TQM. The practical implication is to prepare future managers about how to avoid failure. Originality/value – The paper clearly suggests the systematic process required for effective implementation of TQM in a healthcare setting by identifying factors that must be avoided to ensure the successful and sustainable implementation of TQM.

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