• Title, Summary, Keyword: MTD

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Maximum Tolerated Dose Estimate by Curve Fitting in Phase I Clinical Trial (제1상 임상시험에서 곡선적합을 이용한 MTD 추정법)

  • Heo, Eun-Ha;Kim, Dong-Jae
    • Communications for Statistical Applications and Methods
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    • v.18 no.2
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    • pp.179-187
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    • 2011
  • The purpose of a Phase I clinical trial is to estimate the maximum tolerated dose, MTD, of a new drug. In this paper, the MTD estimation method is suggested by curve fitting the dose-toxicity data to an S-shaped curve. The suggested MTD estimation method is compared with established MTD estimation procedures using a Monte Carlo simulation study.

Maximum tolerated dose estimation using continual reassessment method in Phase I Clinical Trial (연속재평가방법에 가속화 단계를 적용한 MTD 추정법)

  • Kwon, Dohee;Kim, Dongjae
    • The Korean Journal of Applied Statistics
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    • v.32 no.5
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    • pp.741-752
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    • 2019
  • The purpose of a Phase I Clinical Trial is to determine the maximum tolerated dose (MTD). MTD is important because it affects subsequent clinical trials; however, the existing method has a problem due to an inadequate dose allocated to patients. In this paper, an MTD estimation method is proposed to complement the problems of the existing MTD estimation method. The suggested method applies the initial acceleration step to the modified continual reassessment method. Monte Carlo Simulation Study is adapted to compare a suggested MTD estimation method with the standard design and the modified continual reassessment method.

Estimation of Maximal Tolerated Dose in Sequential Phase I Clinical Trials

  • Park, In-Hye;Song, Hae-Hiang
    • Communications for Statistical Applications and Methods
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    • v.6 no.2
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    • pp.543-564
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    • 1999
  • The principal aim of a sequential phase I clinical trial in which the toxicity reponses of a group of patient(s) determine the dose level of the next patient(s) group is to estimate the maximal tolerated dose(MTD) of a new drug, In this paper we compared with a simulation study the performance of the MTD estimates that are determined by a stopping rule in a design and also those that are determined by analyzing the data after a clinical trial is terminated. To the latter belong the mean median mode and maximum likelihood estimates. For the Standard Methods the stopping rule MTD is quite inefficient but the median MTD has a best efficiency and is robust with respect to the three different toxicity curves. The problem of non-convergence of MLE MTD is severe. A more improved MTD estimate is produced by combining the advantages of the various MTD estimates and its efficiency is better than the single median MTD estimate especially for the toxicity curve of an unlucky choice of dose levels. The simulation results suggest that simple types of phase I designs can be combined with relatively standard analytic techniques to provide a more efficient MTD estimate.

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Clinical Utility of Amplified Mycobacterium Tuberculosis Direct Test in the Diagnosis of Pulmonary Tuberculosis (폐결핵 잔단에서 Amplified Mycobacterium Tuberculosis Direct Test의 임상적 유용성)

  • Park, Sam-Seok;Kwak, Kyung-Rok;Hwang, Ji-Yun;Yun, Sang-Myeong;Ryue, Chi-Chan;Chang, Chul-Hun;Lee, Min-Gi;Park, Sun-Gue
    • Tuberculosis and Respiratory Diseases
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    • v.47 no.6
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    • pp.747-756
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    • 1999
  • Background: Acid-fast stain and cultures for diagnosis of pulmonary tuberculosis are primary and essential method, but have their limitation : low sensitivity and time consuming. The objective of this study is comparison of amplified Mycobacterium tuberculosis direct test(MTD) by the conventional AFB smears and cultures in the detection of Mycobacterium tuberculosis in respiratory specimens. Methods: During the period between November, 1997 and May, 1998 a total of 267 respiratory specimens (sputum 173, bronchial washing 94) from 187 patients suspected pulmonary tuberculosis were subjected to AFB smears, cultures and MID test. MID is based on nucleic acid amplification. We compared the MID with 3% Ogawa culture method. In positive AFB smear and negative MID specimen, positive culture identification between nontuberculous mycobacterium and M.tuberculosis was assesed by using Accuprobe M.tuberculosis complex probe. In negative AFB smear and negative AFB culture, MTD results are assessed by clinical follow-up. Results : 1) Compared with culture in sputum and bronchial fluid specimens, sensitivity and specificity of MTD in positive AFB smear is 79.7% and 20.0%, sensitivity and specificity of MTD in negative AFB smear specimens is 75.0% and 79.7%. 2) Discrepant analysis is assessed by clinical follow-up and other specimen results beyond study. Culture negative but MTD positive specimens were proved to be true positive and gave MTD sensitivity 79.2%, specificity of 84.4%, positive predictive value 80.5% and negative predictive value 83.2%. 3) 14 out of 31 specimens in negative AFB smear, negative AFB culture and positive MTD showed pulmonary tuberculosis diagnosed on clinical follow-up and sensitivity is 45.2%. 4) 2 out of 13 specimens in positive AFB smear, positive AFB culture and negative MID diagnosed as non tuberculous mycobacterium by Accuprobe culture. Conclusion: This study suggested that MID in respiratory specimens is simple and rapid diagnostic method, but considered adjuvant method rather than replace the conventional AFB smear and culture.

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Two-Stage Maximum Tolerated Dose Estimation by Stopping Rule in a Phase I Clinical Trial (제1상 임상시험에서 Stopping Rule을 이용한 두 단계 MTD 추정법)

  • Lee, Na-Mi;Kim, Dong-Jae
    • Communications for Statistical Applications and Methods
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    • v.19 no.1
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    • pp.57-64
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    • 2012
  • Phase I clinical trials determine the maximum tolerated dose(MTD) of a new drug. In this paper, we proposed a two-stage MTD estimation method by a Stopping rule in a phase I clinical trial. The suggested MTD estimation method is compared to the standard design(SM3) and the continual reassessment method(CRM) using a Monte Carlo simulation study.

A Study on Moving Target Defense Issue and Certification Requirements (Moving Target Defense 이슈 및 평가인증 요구사항에 대한 연구)

  • Moon, Seo Yeon;Kim, Jae Woong;Park, Jong Hyuk
    • Proceedings of the Korea Information Processing Society Conference
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    • pp.158-161
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    • 2018
  • 2011년 미국에서 최초로 소개된 후 기존 보안 기술과 다른 새로운 정보시스템 보호 기술로 Moving Target Defense(MTD)가 활발히 연구 되고 있다. MTD는 시스템의 구성 요소들을 뷸규칙적이고 동적으로 변화시켜 공격표면(Attack surface)을 줄임으로써 외부 공격에 대한 보안성을 높인다. 주로 시스템 정보를 수집 및 분석하여 공격하는 보안 위협들에 효과적이며 특히 지능형 지속 보안 위협(Advanced Persistent Threat), 킬 체인(Kill-Chain) 보안에 뛰어난 성능을 기대할 수 있다. 최근 MTD 시스템 구현 및 개발로 상용화가 시작되었으나 MTD 활용을 통해 어느 정도의 보안성 및 효율성을 가지는지에 대한 성능 평가인증, 시험지침 등이 표준화 되어있지 않아 기준이 모호한 실정이다. 본 논문에서는 이러한 최근 MTD 이슈에 대해 살펴보고 MTD와 연관 되어있는 각 분야에 어떤 평가인증 요구사항들이 있는지 분석한다. 이를 통해 MTD에 어떠한 평가인증 요구사항이 있는지 도출하여 앞으로 MTD 평가인증 표준화 참고 및 활용에 기여 할 수 있을 것으로 전망한다.

Maximum Tolerated Dose Estimation with Dose De-Escalation Design in a Phase I Clinical Trials (제 1상 임상시험에서 용량 감량을 허용하는 MTD 추정법)

  • Jang, Eunah;Kim, Dongjae
    • The Korean Journal of Applied Statistics
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    • v.27 no.7
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    • pp.1115-1123
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    • 2014
  • The main purpose of phase I clinical trials is to estimate the Maximum Tolerated Dose (MTD), which minimizes side effect and assures safety of a new drug by evaluating the toxicity at each dose-level. The conventional MTD estimation methods is Standard method (Storer, 1989; Korn et al., 1994), Accelerated Titration Designs (Simon et al., 1997) and DM method (Dixon and Mood, 1948) etc. In this paper, MTD estimation method with de-escalation is suggested phase I clinical trials. The proposed MTD estimation method is compared to Accelerated Titration Designs, SM3 without de-escalation method and SM3 with de-escalation method using a Monte Carlo simulation.

Development of Dermal Transduction Epidermal Growth Factor (EGF) Using A Skin Penetrating Functional Peptide (피부투과 기능성 펩타이드를 이용한 경피투과성 상피세포성장인자의 개발)

  • Kang, Jin Sun;La, Ha Na;Bak, Sun Uk;Eom, Hyo Jung;Lee, Byung Kyu;Shin, Hee Je
    • Journal of the Society of Cosmetic Scientists of Korea
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    • v.45 no.2
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    • pp.175-184
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    • 2019
  • The epidermal growth factor (EGF) has a intrinsic function of inducing growth and proliferation of cells through interacting with cell membrane receptors in human epidermis and dermis layer. These functions of EGF are used as a main ingredient for wound healing medicines and anti-aging cosmetics. As a cosmetic ingredient, the EGF has a problem in exhibiting its natural efficacy due to the lack of the ability to penetrate through the stratum corneum, which is known as the skin barrier. In this study, a recombinant human epidermal growth factor ($MTD_{151}-EGF$) fused with the macromolecule transduction domain $(MTD)_{151}$ with the skin penetration ability was developed to improve the skin penetration efficiency of the EGF. Expression of $MTD_{151}-EGF$ was performed in E. coli transformed with a vector encoding the $MTD_{151}-EGF$ gene and then purified. The purified $MTD_{151}-EGF$ was evaluated using cell proliferation assay, cytotoxicity test and skin penetration test by franz diffusion cell assay and artificial skin. Cell proliferation activity of $MTD_{151}-EGF$ purified to high purity of 99% or above was equivalent to the EGF or better, and cytotoxicity was not observed. In addition, the $MTD_{151}-EGF$ showed an excellent penetration efficiency compared to the EGF in the skin penetration test with EGF and $MTD_{151}-EGF$ labeled by FITC in an artificial skin penetration model. Based on the quantitative analysis of the penetrating substance using franz diffusion cell assay, the amount of penetration was about 16 times more than that of EGF. These results can be regarded as an effective alternative to improve the existing physical transdermal penetration method related to the use of various active ingredients for cosmetics.

A Study on the Measurement of Texture Depth of Pavement Using Portable Laser Profiler (Portable Laser Profiler를 이용한 도로 포장의 노면조직 깊이 측정 방법 연구)

  • Hong, Seong Jae;Hyun, Tak Jib;Kim, Hyung Bae;Kwon, Oh Sun;Lee, Seung Woo
    • International Journal of Highway Engineering
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    • v.14 no.6
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    • pp.45-55
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    • 2012
  • PURPOSES : Skid resistance and noise of roads highly depend on the characteristics of pavement texture. Therefore, estimation of texture characteristics may give useful information for the skid resistance and noise of road. Generally, Sand Patch Test is performed in order to estimate MTD(Mean Texture Depth). However, it is time-consuming and needs traffic control. This study aimed to investigate the effectiveness of measurement texture depth using the Portable Laser Profiler that give the MPD(Mean Profile Depth). METHODS : MTD and MPD were collected on the number of expressway sections including Central Inland Test Road sections in Korea. Statistical analysis are performed to establish the relationship between MTD data based on Sand Patch Test and MPD data obtained by the Portable Laser Profiler. RESULTS : Linear relationship MPD and MTD is observed for both of asphalt pavement and concrete pavement such as R-square of 0.51 to 0.58. CONCLUSIONS : Even though, the test method and definition of MPD and MTD are different. EMTD(Estimated Mean Texture Depth) can be obtained by using the correlationship between MPD with MTD.

Correlation Between Tumorigenic Doses and the Maximum Tolerated Dose of Carcinogens (발암물질의 발암용량과 최대내성용량의 상관관계)

  • 이병무;김근종
    • Environmental Mutagens and Carcinogens
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    • v.19 no.2
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    • pp.108-111
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    • 1999
  • Correlation between the tumorigenic dose (TD) and the maximum tolerated dose (MTD) was examined to search for the most relevant TD values related to the MTD. Using benzo(a)pyrene (B(a)P) 2-yr bioassay data, correlation coefficients between values of $TD_{1-}$50/ and the MTD were estimated from linearized or non-linearlized dose-response curves. The highest correlation coefficients (0.9966-1.0000) were obtained from T $D_{1-}$10/ in linearized dose-response curves while the highest (0.9966-1.0000) were estimated from $TD _{5-}$10/ in non-linearized dose-response eurves. These data suggest that TDs-lo were more closely related to the MTD than the ,$TD_{5-}$10/ in B(a)P 2-yr bioassay and that in lieu of the $TD_{50}$ they could be efficiently applicable to risk assessment and management.ent.

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