• 응용통계연구
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• 제24권3호
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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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• 제22권4호
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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.

• 한국구조물진단유지관리공학회지
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• 제18권1호
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• pp.63-68
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• 2014

• 한국임상약학회지
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• 제27권2호
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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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• 제47권4호
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• pp.261-272
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• 2020

전세계적으로 유전자변형(GM)작물의 재배와 수입에 대한 승인이 급격히 증가하고 있다. 영양성분 비교평가는 실질적 동등성에 기반하여 GM작물의 안전성 평가에서 중요한 역할을 담당하고 있다. 영양성분 비교평가는 GM작물과 대조작물 사이의 성분함량에서 차이와 유사성을, 그리고 GM작물과 상업품종간의 성분함량의 동등성을 결정하는데 중점을 두고 있다. 분석항목은 일반성분, 주요 영양성분과 항영양소 등이며 일반적으로 OECD 합의문에서 작물별로 제안하고 있는 항목들을 포함한다. 영양성분 비교평가를 위해서는 비교군의 선정, 포장 시험, 분석방법, 데이터 통계 처리 등의 전 과정에 걸쳐 표준화된 방법을 이용하는 것이 중요하다. 본 연구에서는 코덱스와 유럽식품안전청의 식품용 GM작물의 영양성분 비교평가를 위한 가이드라인을 소개하였다. 그리고 국내외의 GM작물 영양성분 비교평가 연구 논문들에 나타난 분석항목과 대조작물, 참조군 품종, 재배연도, 재배지역, 통계방법 등을 검토하였다. 해외의 경우 대두와 옥수수, 면화 GM작물에서 여러 나라 수출을 위한 규제기관의 가이드라인에 따른 연구가 많았다. 반면 국내의 경우는 GM작물 실험연구적 측면에서 비교평가 진행되었으며 주로 GM벼에서의 연구가 많았다. 마지막으로 국내에서 GM작물의 영양성분 비교평가 연구 수행에 적용할 수 있는 참조군 선정과 포장재배에 대한 가이드를 제시하였다.

• 한국연소학회지
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• 제13권3호
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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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• 제27권1호
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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.

• 응용통계연구
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• 제25권1호
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• pp.125-138
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• 2012

최근 들어 바이오시밀러에 대한 국내외 관심이 매우 증가하고 있다. 바이오시밀러가 오리지널 생물의약품과 효능과 안전성이 유사함을 보이기 위해서는 최종적으로 임상시험을 수행하여야 한다. 본 논문에서는 이러한 임상시험의 수행과 통계적 분석에 필요한 여러 방법들과 외국의 사례 그리고 관련된 가이드라인들을 살펴볼 것이다.

• Journal of the Korean Association of Oral and Maxillofacial Surgeons
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• 제48권6호
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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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• 제19권1호
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• pp.47-55
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• 2012

식품의약품안전청에서는 제제간의 생물학적 동등성의 입증이 실패했을 경우 추가시험을 허용하는 시험 기준을 2008년 7월부터 시행하고 있다. 생물학적 동등성 시험의 추가시험규정은 원시험에서의 동등성 평가가 불충분한 시험 예수 때문에 실패했을 때 별도의 재시험 시험계획서를 제출하지 않고 피험자수를 증가시켜 다시 시험하여 제제간의 동등성을 평가할 수 있는 근거를 마련한 점에 긍정적이다. 하지만 최근 추가시험의 규정에 따라 군당 12명 이상의 피험자를 사용했을 경우 오히려 추가시험의 일관성 검정 규정을 만족하지 못하여 추가시험이 실패되는 경우가 자주 발생하고 있어 추가시험규정에 대한 불만이 고조되고 있다. 본 연구에서는 이러한 상황이 발생되는 통계적 원인을 살펴보고 현 기준을 일본 규정처럼 조금 더 일반화하게 되면 추가시험을 더 폭넓게 사용할 수 있는 것을 제안하고자 한다.