• The Korean Journal of Applied Statistics
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• v.24 no.3
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• pp.495-503
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• 2011

When a patent of an innovative (brand-name) small-molecule drug expires, generic copies of the innovative drug may be marketed if their therapeutic equivalence to the innovative drug has been shown. The small-molecule drugs are considered therapeutically equivalent and can be used interchangeably if two drugs are shown to be pharmaceutically equivalent with identical active substance and bioequivalent with comparable pharmacokinetics in a crossover clinical trial. However, the therapeutic equivalence paradigm cannot be applied to biosimilars since the active ingredients of biosimilars are huge molecules with complex and heterogeneous structures, and these molecules are difficult to replicate in every detail. The European Medicine Agency(EMEA) has introduced a regulatory biosimilar pathway which mandates clinical trials to show therapeutic equivalence. In this paper, we discuss statistical considerations in the design and analysis of biosimilar cancer clinical trials.

• Communications for Statistical Applications and Methods
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• v.22 no.4
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• pp.389-399
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• 2015

It is important not to overcalculate sample sizes for clinical trials due to economic, ethical, and scientific reasons. Kang and Kim (2014) investigated the accuracy of a well-known sample size calculation formula based on the approximate power for continuous endpoints in equivalence trials, which has been widely used for Development of Biosimilar Products. They concluded that this formula is overly conservative and that sample size should be calculated based on an exact power. This paper extends these results to binary endpoints for three popular metrics: the risk difference, the log of the relative risk, and the log of the odds ratio. We conclude that the sample size formulae based on the approximate power for binary endpoints in equivalence trials are overly conservative. In many cases, sample sizes to achieve 80% power based on approximate powers have 90% exact power. We propose that sample size should be computed numerically based on the exact power.

• Magazine of the Korea Institute for Structural Maintenance and Inspection
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• v.18 no.1
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• pp.63-68
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• 2014

• Korean Journal of Clinical Pharmacy
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• v.27 no.2
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• pp.105-112
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• 2017

Background: Generic medications are approved on the basis of bioequivalence with brand medications in healthy volunteers rather than the target population, there remains a substantial uncertainty regarding their clinical effectiveness and safety. The object of this paper is to compare the clinical equivalence of generic statin drugs in patients. Methods: Literature published before September 2016, which is indexed in PubMed, EMBASE, RISS, comparing generic to brand products in statins. Outcomes included blood lipid level, proportion of days covered (adherence), hospitalization and mortality. Results: 511 citations were screened, of which 11 studies met eligibility criteria (6 randomized clinical trials, 5 observational studies). Generic atorvastatin was clinical equivalent with brand drugs in blood lipid level (3 RCTs) and generic simvastatin was also clinical equivalent with brand drugs (2 RCTs). 2 of 3 studies reported no significant difference in proportion of days covered except 1 study which reported generic statin significantly enhance proportion of days covered (p<0.001). Hospitalization was no significant difference in all studies (p>0.05). 1 study reported that all cause of mortality was significantly low in generic drugs (p<0.0001). Conclusion: Published data on comparing clinical efficacy of generic and brand statins were insufficient in both quantity and quality. This systematic review suggests that additional studies on clinical equivalence and safety of generic medications in patients would be needed.

• Journal of Plant Biotechnology
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• v.47 no.4
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• pp.261-272
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• 2020

Approvals for cultivation and import of genetically modified (GM) crops have dramatically increased around the world. Comparative compositional studies are an important aspect of safety assessments of products from GM crops and are based on substantial equivalence. Compositional analyses focus on determining similarities and differences between the compositions of the GM crops and their conventional counterparts, and thereby assessing the compositional equivalence of GM crops and their conventional comparators. The analytes, such as major constituents, key nutrients, and antinutrients, are generally determined on a crop-specific basis according to the OECD consensus document. The use of standard methods throughout the processes, such as selection of comparators, field trials, analytical methods, and statistical data analysis, is crucial. In this study, we showed the general framework of compositional studies. Literature for compositional studies of GM crops conducted abroad and in Korea was reviewed to obtain information about analytes, conventional counterparts, cultivation year, location, and statistical methods. The studies conducted abroad assessed for commercial release of GM crops such as soybean, maize, and cotton, while domestic studies were mainly performed for research in rice. In addition, we suggested a guidance for conventional comparators and field trials applicable to the domestic situation.

• Journal of the Korean Society of Combustion
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• v.13 no.3
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• pp.1-8
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• 2008

A flame stability diagram in a partially premixed flame is typically expressed using the axis coordinates of heat input rate and equivalence ratio. These diagrams are inadequate for identifying changes in combustion conditions and flame stability when a reference fuel is substituted with other fuels under identical operating conditions. This study proposes a new type of diagram and validates it experimentally. In this new diagram, the axis coordinates are air flow rate and Wobbe fuel flow rate, defined as the fuel flow rate multiplied by the square root of the relative density. The diagram was validated in trials using various fuels, including $CH_4$, $C_{3}H_{8}$, and LFG-$C_{3}H_{8}$ mixed fuels, in a domestic gas-range and an gas interchangeability test burner. The results of these trials show that the new diagram can provide information useful for assessing gas interchangeability of combustion conditions and flame stability when one fuel is substituted with another under identical operating conditions.

• Communications for Statistical Applications and Methods
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• v.27 no.1
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• pp.1-14
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• 2020

Investigations of biosimilarity between reference drugs and test drugs required statistical tests; in addition, statistical tests to evaluate biosimilarity have been recently proposed. Ordinal outcome data has been observed in research; however, appropriate statistical tests to deal with ordinal endpoints for biosimilar have not yet been proposed. This paper extends existing design for ordinal endpoints. Using measure of nominal-ordinal association and relative distances between drugs are defined so that testing procedures are developed. Through simulation studies, we investigate type I error rate and power to show the performance of our suggested method. Furthermore, a comparison between the statistical tests and other designs is proviede to show significance of ordinal endpoints.

• The Korean Journal of Applied Statistics
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• v.25 no.1
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• pp.125-138
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• 2012

Recent assessments of the biosimilarity of biologic products have received considerable global attention. A clinical trial should be conducted to assess the biosimilarity of a biosimilar product and a innovator biological product. In this paper we will describe several methods for the implementation of clinical trials and statistical analysis, a real international case and related international guidelines.

• Journal of the Korean Association of Oral and Maxillofacial Surgeons
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• v.48 no.6
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• pp.331-341
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• 2022

This systematic review evaluates current evidence regarding the feasibility of using needleless jet injection instead of a conventional local anesthetic needle. EBSCO, ProQuest, PubMed, and Scopus databases were used to identify relevant literature published in English from 2005 to 2020. Ten studies were selected. Five of them were randomized clinical trials, 3 case-control studies, and 2 equivalence trials. Using the Critical Appraisal Skills Program checklist, 6 studies scored between 67% and 100%, and 4 studies scored between 34% and 66%. According to Jadad's scale, 2 studies were considered strong, and 8 studies were considered moderate in quality. The results of the 10 studies showed differences in patient preference for needleless jet injection. Needleless injection technique has been found to be particularly useful in uncooperative patients with anxiety and needle phobia. Needleless jet injection is not technique sensitive. However, with needleless jet anesthesia, most treatments require additional anesthesia. Conventional needle anesthesia is less costly, has a longer duration of action, and has better pain control during dental extraction. Needleless jet anesthesia has been shown to be moderately accepted by patients with a fear of needles, has a faster onset of action, and is an efficient alternative to conventional infiltration anesthesia technique.

• Communications for Statistical Applications and Methods
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• v.19 no.1
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• pp.47-55
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• 2012

The newly revised bioequivalence guideline of Korea allows the add-on test since July 1, 2008 when the initial bioequivalence trial fails to show the equivalence of two drugs. The statistical model of the add-on test and its two stage testing procedures are discussed. Some statistical points of consistency test in the add-on test are considered and the issue on the sample size of add-on test is discussed. Some reasonable alternative like Japan's guideline for bioequivalence studies is recommended to secure the proper use of an add-on study through some simulation studies.