• 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.

• Journal of Advanced Marine Engineering and Technology
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• 제36권6호
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• pp.774-779
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• 2012

MILD(Moderate and Intense Low Oxygen Dilution) 연소는 연소 가스의 재순환을 이용하여 고온 형성을 최대한 억제하고 질소산화물의 발생을 저감하는 동시에 연소로의 내부 온도 균일화를 통한 열 이용 효율을 향상시킬 수 있는 연소기술이다. 본 연구에서는 원추형 연소로에서 연료 유량은 고정하고 공기 유량으로 당량비(${\Phi}$)를 조절하고 배기가스를 측정하여 MILD 연소특성을 도출하였다.

• 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 Korean Neurosurgical Society
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• 제65권2호
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• pp.315-324
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• 2022

Objective : The aim of this study was to verify the equivalence and effectiveness of the tablet-administered Korean Repeatable Battery for the Assessment of Neuropsychological Status (K-RBANS) for the prevention and early detection of dementia. Methods : Data from 88 psychiatry and neurology patient samples were examined to evaluate the equivalence between tablet and paper administrations of the K-RBANS using a non-randomly equivalent group design. We calculated the prediction scores of the tablet-administered K-RBANS based on demographics and covariate-test scores for focal tests using norm samples and tested format effects. In addition, we compared the receiver operating characteristic curves to confirm the effectiveness of the K-RBANS for preventing and detecting dementia. Results : In the analysis of raw scores, line orientation showed a significant difference (t=-2.94, p<0.001), and subtests showed small to large effect sizes (0.04-0.86) between paper- and tablet-administered K-RBANS. To investigate the format effect, we compared the predicted scaled scores of the tablet sample to the scaled scores of the norm sample. Consequently, a small effect size (d≤0.20) was observed in most of the subtests, except word list and story recall, which showed a medium effect size (d=0.21), while picture naming and subtests of delayed memory showed significant differences in the one-sample t-test. In addition, the area under the curve of the total scale index (TSI) (0.827; 95% confidence interval, 0.738-0.916) was higher than that of the five indices, ranging from 0.688 to 0.820. The sensitivity and specificity of TSI were 80% and 76%, respectively. Conclusion : The overall results of this study suggest that the tablet-administered K-RBANS showed significant equivalence to the norm sample, although some subtests showed format effects, and it may be used as a valid tool for the brief screening of patients with neuropsychological disorders in Korea.

• Communications for Statistical Applications and Methods
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• 제22권6호
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• pp.605-613
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• 2015

A three-arm parallel design has been proposed to assess the biosimilarity between a biological product and a reference product using relative distance (Kang and Chow, 2013). The three-arm parallel design consists of two arms for the reference product and one arm for the biosimilar product. This paper extended the three-arm parallel design to a (k + 1)-arm parallel design composed of k (${\geq}3$) arms for the reference product and one arm for the biosimilar product. A new relative distance was defined based on Euclidean distance; consequently, a corresponding test procedure was developed based on asymptotic distribution. Type I error rates and powers were investigated both theoretically and empirically.

• 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.

• The Korean Journal of Pain
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• 제34권3호
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• pp.339-345
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• 2021

Background: Ultrasound-guided caudal epidural injection (CEI) is limited in that it cannot confirm drug distribution at the target site without fluoroscopy. We hypothesized that visualization of solution flow through the inter-laminar space of the lumbosacral spine using color Doppler ultrasound alone would allow for confirmation of drug distribution. Therefore, we aimed to prospectively evaluate the usefulness of this method by comparing the color Doppler image in the paramedian sagittal oblique view of the lumbosacral spine (LS-PSOV) with the distribution of the contrast medium observed during fluoroscopy. Methods: Sixty-five patients received a 10-mL CEI of solution containing contrast medium under ultrasound guidance. During injection, flow was observed in the LSPSOV using color Doppler ultrasonography, following which it was confirmed using fluoroscopy. The presence of contrast image at L5-S1 on fluoroscopy was defined as "successful CEI." We then calculated prediction accuracy for successful CEI using color Doppler ultrasonography in the LS-PSOV. We also investigated the correlation between the distribution levels measured via color Doppler and fluoroscopy. Results: Prediction accuracy with color Doppler ultrasonography was 96.9%. The sensitivity, specificity, positive predictive value, and negative predictive value were 96.7%, 100%, 100%, and 60.0%, respectively. In 52 of 65 patients (80%), the highest level at which contrast image was observed was the same for both color Doppler ultrasonography and fluoroscopy. Conclusions: Our findings demonstrate that color Doppler ultrasonography in the LS-PSOV is a new method for determining whether a drug solution reaches the lumbosacral region (i.e., the main target level) without the need for fluoroscopy.

• 한국양식학회지
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• 제17권2호
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• pp.122-127
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• 2004

On protein equivalence base, fishmeal (FM) was replaced by lysine cell mass (LCM) in selected different diets in Korean rockfish, Sebastes schlegeli (Hilgendorf) Eight experimental diets were formulated to contain 100% FM (LC $M_{0}$), 90% FM+10% LCM (LC $M_{10}$),80% FM+20% LCM (LC $M_{20}$), 70% FM+30% LCM (LC $M_{30}$), 60% FM+40% LCM (LC $M_{40}$ ), 70% FH+30% LCM+lysine (LC $M_{+Lys}$), 60% FM+40% LCM+lysine (LC $M_{40+Lys}$), and 50% FM+50% LCM+lysine (LC $M_{50+Lys}$). Experimental individuals of the fish (12.6 g) were randomly fed on one of the experimental diets. After 6 weeks of feeding trial, weight gain (WG) and feed efficiency (FE) of fish fed LC $M_{0}$ diet was significantly (P〈0.05) higher than those of fish fed LC $M_{20}$, LC $M_{30}$, LC $M_{40}$ , LC $M_{30+Lys}$, LC $M_{40+Lys}$, and LC $M_{50+Lys}$ diets, however, there was no significant difference in WG of fish fed LC $M_{0}$ and LC $M_{10}$ diets. Supplementation of lysine has no effect on WG. There was no significant difference in condition factor (CF) of fish fed LC $M_{0}$, LC $M_{10}$ and LC $M_{20}$ diets. Hemoglobin (Hb) of fish fed LC $M_{0}$, LC $M_{10}$, LC $M_{20}$, LC $M_{30}$, LC $M_{40}$ , LC $M_{30+Lys}$, and LC $M_{40+Lys}$, diets were not significantly different from each other. No significant differences were observed in hematocrit (PCV) and hepatosomatic index (HSI) among all dietary treatments. Apparent digestibility of dry matter (ADM) and protein (ADP) of diets significantly decreased with increase in dietary LCM level, though there was no difference in ADM and ADP between LC $M_{0}$ and LC $M_{10}$. These results indicate that LCM could replace up to 10% of fishmeal in Korean rockfish diets.ish diets.iets.ish diets.s.ish diets.

• 한국심리학회지:학교
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• 제9권3호
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• pp.485-503
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• 2012

본 연구의 목적은 학업수행과 성취결과에 주요한 예측변인 중 하나인 학업참여(academic engagement)를 측정하는 UWES-S(Utrecht Work Engagement Scale-Student)(Schaufeli et al., 2002a; 2002b) 척도를 타당화 하고, 학업참여와 학업동기 및 학업 만족도 간의 구조적인 관계를 파악하는 것이다. 본 연구의 타당화 표본은 우리나라 대학생들로써, 예비검사 285명, 본검사 366명으로 구성되었고, 그 절차는 다음과 같다. 첫째, UWES-S의 17개 문항에 대한 기술통계치 검토 및 척도의 요인구조 탐색을 위한 탐색적 요인분석을 실시하였다. 둘째, 문항의 심리측정학적 특성을 검토하기 위하여 등급반응모형에 기반한 문항 특성치를 추정하였다. 셋째, 척도의 내적타당도를 검증하기 위해 확인적 요인분석이 실시되었으며, 외적 타당도 확보를 위해서는 학업동기 및 학업만족 변인을 포함한 구조방정식 모형이 활용되었다. 이에 따른 연구결과는 다음과 같다. 첫째, 예비검사의 자료를 활용한 기술통계치 검토 및 탐색적 요인분석 결과 3요인 구조가 지지되었으며, 4개의 문항이 제거된 최종 13개 문항이 제안되었다. 둘째, 등급반응모형에 의해서 추정된 문항 특성치들을 검토한 결과, 최종 문항의 양호도는 수용 가능한 수준이었고, 또한 학업참여 척도의 3요인 모형(열정, 헌신, 몰두)은 자료에 잘 부합하는 것으로 나타났다. 또한 외적타당도 검증 결과, 학업참여는 학업동기와 학업만족을 부분매개 하는 것으로 나타났다. 마지막으로 본 연구에서 타당화 된 대학생용 UWES-S와 기존에 타당화 된 고등학생용 UWES-S(추헌택, 손원숙, 2011)와의 차이점을 논의하고, 표본별 학업참여 구인의 동등성 검증의 필요성 및 추후 척도 타당화 연구를 위한 제언을 포함하였다.