Book section · January 1, 2022
For rare disease drug development, one of the major challenges is that there are only limited subjects available for clinical trials. FDA (2019), however, indicated that the Agency does not have intention to create a statutory standard for rare diseases dr ...
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Book section · January 1, 2022
The goal of the 21st century cures act is to decrease the administrative burdens, encourage innovation and enhance America's healthcare field. Along this line, the 21st century cures act is designed to help accelerate medical product development and bring ...
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Book section · January 1, 2022
Biosimilar assessment has received much attention since the Biologics Price Competition and Innovation (BPCI) Act passed by the United States (US) Congress in 2009. For assessment of biosimilar products, the US Food and Drug Administration (FDA) recommends ...
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Book section · January 1, 2018
When an innovative (brand-name) drug is going off patent protection, pharmaceutical or generic companies may file an abbreviated new drug application for generic approval. As indicated by the U.S. Food and Drug Administration (FDA), an approved generic dru ...
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Book section · January 1, 2018
Current regulation for generic approval is based on the assessment of average bioequivalence. As indicated by the United States Food and Drug Administration (FDA), an approved generic drug can be used as a substitute for the innovative drug. The FDA does n ...
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Book section · January 1, 2018
In recent years, the use of complementary and alternative medicine including botanical drug products and traditional Chinese (herbal) medicine (TCM) in humans for treating critical and/or life-threatening diseases has received much attention. In pharmaceut ...
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Book section · January 1, 2018
Regulatory inspection of clinical trial is necessary in order to (1) assess compliance with statutory requirements and regulatory requirement governing the conduct of clinical trials and (2) verify the accuracy and reliability of clinical trial data submit ...
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Book section · January 1, 2018
In clinical trials, a typical approach for the evaluation of safety and efficacy of a test treatment under investigation is to first test for the null hypothesis of no treatment difference in efficacy based on clinical data collected under a valid trial de ...
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Book section · January 1, 2018
In clinical development of a test treatment under investigation, clinical trials are often conducted for the evaluation of safety and efficacy of the test treatment. To provide an accurate and reliable assessment of the test treatment under study, adequate ...
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Book section · January 1, 2018
For assessment of biosimilarity for biosimilar products, the United States (US) Food and Drug Administration (FDA) proposed a stepwise approach for providing the totality of the evidence of similarity between a proposed biosimilar product and a US-licensed ...
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Book section · January 1, 2018
In recent years, microdosing approach has received much attention in pharmaceutical research and development. The concept of microdosing approach focuses on safety signal detection, which is primary for exploratory purpose (FDA, 2006; ICH, 2009). Burt (201 ...
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Book section · January 1, 2018
In recent years, the assessment of biosimilarity between a proposed biosimilar product and an innovative biological product has attracted much attention since the passage of the Biologics Price Competition and Innovation Act in 2009. In this article, we pr ...
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Book section · January 1, 2018
The objective of sample size calculation is to select an appropriate sample size so that not only the Type I error probability can be controlled under the specified level when the null hypothesis is true, but also to assure sufficient power for detection o ...
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Book section · January 1, 2018
The purpose of good statistics practice is not only to minimize bias but also to minimize variability that may occur before, during, and after the conduct of the studies. This entry discusses the role of statistics in drug development and their importance ...
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Book section · January 1, 2018
This entry evaluates the generalizability of clinical results observed from a clinical trial by means of a sensitivity analysis with respect to changes in mean and standard deviation of the primary clinical endpoints of the study. ...
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Book section · January 1, 2018
This entry reviews three approaches to reproducibility probability and provides examples and applications for this clinical research tool. ...
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Book section · January 1, 2018
In pharmaceutical/clinical development, commonly considered two-stage seamless adaptive designs include a two-stage phase I/II or phase II/III adaptive trial that combines one phase IIb study for dose finding or treatment selection and one phase III study ...
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Book section · January 1, 2018
In biopharmaceutical studies, diagnostic tests are routinely used to screen for, diagnose, grade, and monitor the progression of diseases. To validate and evaluate the performance of a test, it is often compared with a reference standard that reflects the ...
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Book section · January 1, 2018
This entry discusses calibration for obtaining analytical results and its statistical validity and also summarizes statistical methods for assessment of performance characteristics for assay validation. ...
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Book section · January 1, 2018
The development of biosimilar products provides a more affordable alternative to general patient population, compared to the brand-name products. However, the availability of more and more biosimilar products in the marketplace also raises a critical issue ...
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Book section · January 1, 2018
Missing values in studies are commonly encountered. An item nonrespondent refers to a subject who fails to answer some (not all) of the items. This entry is focused on the approaches clinical researchers can take in dealing with item nonrespondents, lookin ...
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Book section · January 1, 2018
This entry summarizes the most commonly used imputation methods and investigates their statistical properties, and also discusses recent developments. ...
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Book section · January 1, 2018
This entry details the bootstrap approach to statistical analysis by providing several examples of this method to test its validity and applications. ...
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Book section · January 1, 2018
Blinding is an approach used in clinical trials meant to eliminate bias by blocking the identity of treatments. This entry focuses on different types of clinical trial blinding and discusses the importance of this practice in obtaining honest results. ...
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Book section · January 1, 2018
A pharmaceutical development process consists of non-clinical (e.g., assay and process validation and stability testing), pre-clinical (e.g., animal and bioavailability bioequivalence studies), and clinical (e.g., phases 1–3 clinical trials) development. I ...
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Book section · January 1, 2018
The purpose of an adaptive design is not only to efficiently identify clinical benefits of the test treatment under investigation, but also to increase the probability of success in the drug development process. One of the commonly considered adaptive desi ...
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Book section · January 1, 2018
In practice, the shelf-life of a frozen drug product is usually determined based on a two-phase stability study. This entry examines statistical models and procedures for two-phase stability analysis and presents an example concerning the establishment of ...
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Book section · January 1, 2018
The aim of this entry is not only to provide a comprehensive summarization of the issues that are commonly encountered when applying/implementing the adaptive design methods in clinical research but also to include recent development such as the role of th ...
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Book section · January 1, 2018
A botanical drug product is often recognized as a traditional Chinese (herbal) medicine (TCM). The use of TCM in humans for treating various diseases has a history of a few thousand years, although not much convincing scientific evidence (documentations) r ...
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Book section · January 1, 2018
Randomization plays an important role in the conduct of clinical trials. This entry discusses several models and methods of clinical trial randomization and reviews the statistical effects randomization has on clinical trials as well as examples of when ra ...
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Book section · January 1, 2018
Slope Approach for Assessment of Dose Proportionality/Linearity Under a Crossover Design In this entry, we consider tests for assessment of dose proportionality/linearity under a general crossover design based on the slope approach idea. ...
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Book section · January 1, 2018
When the patent of a biological drug expires, alternative, biosimilar products are often developed. They are expected to have highly similar clinical effects with the original drug. Still, even after the approval of the biosimilarity of two drug products, ...
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Book section · January 1, 2018
It is widely recognized that, as opposed to in vivo, in vitro methods are less variable, easier to control, and more likely to detect differences between products if they exist. This entry details several analysis methods for in vitro bioequivalence testin ...
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Book section · January 1, 2018
With more and more generics becoming available in the marketplace, the safety/efficacy concerns may arise as the result of interchangeably use of approved generics. However, bioequivalence assessment for regulatory approval among generics of the innovative ...
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Book section · January 1, 2018
Translational Medicine: Concepts, Statistical Methods, and Related Issues This entry focuses on statistical methods commonly employed in translational medicine, which is a multi-disciplinary entity that bridges basic scientific research with clinical devel ...
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Book section · January 1, 2018
The purpose of this entry is not only to introduce Consortium for Globalization of Chinese medicine, but also to provide some basic considerations regarding practical issues that are commonly encountered when conducting a traditional Chinese medicine clini ...
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Book section · January 1, 2018
This entry describes the study design and bioequivalence criteria of particle size distribution for both nonprofile and profile analysis, and offers some statistical issues as well as simulated results in an example study for further illustration. ...
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Book section · January 1, 2018
This entry is focused on the analysis of the last observations, which are defined as observations from the last time point for patients who completed the study and the last observations prior to the dropout for patients who did not complete the study. ...
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Book section · January 1, 2018
In most clinical trials comparing a test drug and a control treatment effect is usually established by comparing mean response change from baseline of some primary study endpoints assuming that their corresponding variabilities are comparable. This entry g ...
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Book section · January 1, 2018
In recent years, multiregional clinical trials (MRCTs) that conduct clinical trials simultaneously in Asia-Pacific region, Europe and the United States have become very popular for global pharmaceutical development. The purpose of MRCTs is to shorten the t ...
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Book section · January 1, 2018
The primary objective of this entry is to use real data sets to demonstrate the application of testing methods and provide numerical results from some of these tests. ...
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Book section · January 1, 2018
This entry will review the issues surrounding biosimilars, including manufacturing, quality control, clinical efficacy, side effects (safety), and immunogenicity. In addition, it will also attempt to address the question regarding how regulatory agencies a ...
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Book section · January 1, 2018
When the bioequivalence (BE) of a generic product to a reference drug is stated, their interchangeability is generally assumed. This implies that the drug products can be readily switched and substituted. However, it is important to distinguish between the ...
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Book section · January 1, 2018
This entry outlines the limitation of average bioequivalence for the assessment of drug interchangeability, reviews the decision rules, and statistical methods for evaluation of individual bioequivalence, and provides a comprehensive review of FDA guidelin ...
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Book section · January 1, 2018
This article focuses on logistic regression process for model building, its validation, and its generalizability in case–control studies. The process includes determination of associations between potential risk factors and clinical outcomes, identificatio ...
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Book section · January 1, 2018
The International Conference on Harmonization (ICH) was organized to provide an opportunity for important initiatives to be developed by regulatory authorities, as well as to provide an opportunity for industry associations to promote international harmoni ...
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Book section · January 1, 2017
When a biological drug patent expires, alternative biosimilar products are developed. The development of biosimilar products is complicated and involves numerous considerations and steps. The assessment of biosimilarity and interchangeability is also compl ...
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Book section · January 1, 2007
In clinical research, in addition to comparing mean responses between treatment groups, it is also of interest to compare variabilities of responses between treatment groups. In practice, it is a concern that (1) larger variability may result in a worse sa ...
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Book section · January 1, 2007
In this article, the focus will be on sample size calculation based on a continuous study endpoint for comparing means (i.e., treatment effects) under some study designs. These designs include parallel designs, crossover designs, titration designs, and enr ...
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Book section · January 1, 2007
In practice, the objective of sample size calculation is to select the minimum sample size in such a way that the desired power can be obtained for detection of a clinically meaningful difference at the prespecified significance level. Therefore, the selec ...
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Book section · January 1, 2007
This article discusses three commonly employed testing procedures: the exponential model, Cox's proportional hazard model, and the log-rank test. The sample size formula for testing equality, superiority, and equivalence are discussed for each method. ...
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Book section · January 1, 2006
The median effective dose (MED) is the median of the tolerance distribution of the dose levels for a stimulus that generates, on average, predefined responses in 50% of experimental units. The median effective dose is usually denoted as ED[[inf]]50[[/inf]] ...
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Book section · January 1, 2006
A brief history of regulatory development using bioavailability and bioequivalence studies for approving generic drug products is provided. Concepts of drug exchangeability and switchability are illustrated and their relationship with average bioequivalenc ...
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Book section · January 1, 2006
The concept and definitions of minimum therapeutic effective dose (MTED) and therapeutic window of a drug are presented. Design and analysis for estimating MTED are overviewed. Design issues such as inclusion of a placebo concurrent control, selection of d ...
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