• Communications for Statistical Applications and Methods
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• 제19권6호
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• pp.877-884
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• 2012

Phase I trials determine the maximum tolerated dose(MTD) and the recommended dose(RD) for subsequent Phase II trials. In this paper, a MTD estimation method applied to a biased coin design is proposed for Phase I Clinical Trials. The suggested MTD estimation method is compared to the SM3 method and the NM method (Lee and Kim, 2012) using a Monte Carlo simulation study.

• Communications for Statistical Applications and Methods
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• 제26권2호
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• pp.163-173
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• 2019

Simon's two-stage designs are frequently used in phase II single-arm trials for efficacy studies. A concern of safety studies is too many patients who experience an adverse event. We show that Simon's two-stage designs for efficacy studies can be similarly used to design a two-stage safety study by modifying some of the design parameters. Given the type I and II error rates and the proportion of adverse events experienced in the first stage cohort, we prescribe a procedure whether to terminate the trial or proceed with a stage 2 trial by recruiting additional patients. We study the relationship between a two-stage design with a safety endpoint and an efficacy endpoint as well as use simulation studies to ascertain their properties. We provide a real-life application and a free R package gen2stage to facilitate direct use of two-stage designs in a safety study.

• Journal of Acupuncture Research
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• 제15권2호
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• pp.183-198
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• 1998

This study was done in order to present clinical trial method for safety of herb-acupuncture. The results were summerized as follow: In case of western medicine, clinical trial divides into four phase 1. Phase I: Investigate safety and drug movement for health people. 2. The first phase II: Investigate safety, effectiveness for the limited patient. The late phase II: Investigate propriety of an applicable disease, the way to use and dose. 3. Phase III: Through the comparative, public trial, investigate a final, applicable disease and side effect. 4. Phase IV: After NDA, investigate safety and effectiveness for the wide patients. In case of herb-acupuncture, we have to investigate the following for safety and effectiveness 1. Drug dose: Decide with 1/2 or 1/3 of oral dosage or a basis of animal's of maximum dosage or a ratio of man and animal. 2. Toxicity: Examine blood, urine, liver function, EKG, after herb-acupuncture during acertain period of time. 3. Regional response: Estimate response of swelling, redness, pruritus. etc 4. Treatment effectiveness: After exactly diagnosis, estimate effectiveness with a objective guide post.

• 한국발생생물학회:학술대회논문집
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• 한국발생생물학회 2009년도 특별 Symposium
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• pp.43-45
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• 2009

• 대한예방의학회:학술대회논문집
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• 대한예방의학회 2002년도 제54차 추계 학술대회 연제집
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• pp.192-193
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• 2002

• Journal of Acupuncture Research
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• 제25권2호
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• pp.227-242
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• 2008

Objectives : To compare the efficacy of local acupoint with distal acupuncture at relieving pain and improving function in knee osteoarthritis. Designs : A randomized, single-blinded, crossover clinical trial. Settings : One outpatient clinic(department of acupuncture & moxibustion) located in academic teaching hospital, South Korea. Patients : 17 patients with osteoarthritis of the knee(mean age 62.76[$SD{\pm}4.37$] years). Interventions : The trial had 4 stages : baseline(2weeks), phase I and II(each 2weeks), washout period(2weeks). Patients were randomly assigned to either group A or group B. Group A received acupuncture at local acupoints during phase I, then acupuncture at distal acupoints in phase II. Group B received the treatments in reverse order. In each phase, the patients were treated with acupuncture for 6 times. Measurements : The primary outcome was subjective pain as measured by a 100mm visual analogue scale(VAS) ranging from 0(no pain) to 10(worst pain ever). Secondary outcomes were changes in the Western Ontario and McMaster Universities Osteoarthritis Index(WOMAC) total and pain scores. Measurements were obtained at baseline, 1st day of phase I and II, and 2 days after last treatment of phase I and II. Results : The 17 participants in 2 groups were well matched for age, sex, target knees, baseline VAS score, WOMAC pain score and WOMAC score. Participants in local acupoint group experienced greater improvement than distal acupoint group at 2 days after last treatment in WOMAC total score(mean difference, -10.65[95% CI, -20.56 to -0.74] ; P=0.036) but not in VAS(mean difference, -12.41[95% CI, -29.56 to 4.73] P=0.15) and WOMAC pain score(mean difference, -1.82[95% CI, -3.98 to 0.33] ; P=0.094). Conclusions : Local acupoints are more effective than distal acupoints at relieving pain and improving function in knee osteoarthritis.

• Asian-Australasian Journal of Animal Sciences
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• 제14권10호
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• pp.1419-1424
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• 2001

Previous research in our laboratory has demonstrated the importance of lactose in phase I and II pig starter diets. Two experiments were conducted to evaluate the use of a carbohydrate by-product (food by-products) as a replacement for lactose. In Exp. I, 120 weaned pigs ($14{\pm}2d$ and 5.65kg) were allotted in a randomized complete block design (RCBD) to 10 replications with four pigs per pen. This experiment evaluated three carbohydrate sources (lactose, carbohydrate by-product, and 50-50 blend of the carbohydrate by-product and lactose). The carbohydrate sources were added at 26% in the phase I diets and 15% in the phase II diets. Phase I diets contained 7.5% spray dried plasma protein (SDP). The phase I diets were fed from d 0 to 14 and the phase II diets from d 15 to 28. There were no significant differences between carbohydrate sources on pig performance in phase I. However, during phase II pigs fed the diet with lactose had an improved gain/feed ratio (G/F) (p=0.06) compared to pigs fed the carbohydrate by-product. For the entire 28 d trial ADG, ADFI and G/F were similar for the 50-50 blend and those fed lactose. Total replacement of lactose with the carbohydrate byproduct resulted in a reduced G/F (p=0.09). Exp. 2 used 100 weaned pigs ($17{\pm}2d$ and 4.75kg) with five replications with five pigs per pen. This experiment evaluated four carbohydrate treatments (lactose, carbohydrate by-products, 50-50 blend, and corn). All phase I diets contained 3.5% SDP with the carbohydrate sources included at 15%, and were fed d 0 to 14. The phase II diets contained 7.5% of the carbohydrate sources and were fed d 15 to 27. A common phase III diet was fed d 28 to 42. During all phases pigs fed com tended to have a lower ADG than pigs fed the other carbohydrate sources with the 50-50 blend resulting in the highest ADG. The results of both experiments suggest that this carbohydrate by-product can replace at least 50% of the lactose in phase I and phase II pig starter diets.

• Asian-Australasian Journal of Animal Sciences
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• 제18권3호
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• pp.384-389
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• 2005

These experiments were conducted to evaluate the feeding value of rice protein concentrate (RPC) in weaning pigs. In expt. I, a 5-week feeding trial was conducted with 126 pigs (L${\times}$Y${\times}$D; 21 d-old; 5.32${\pm}$0.34 kg). Treatments were spray-dried plasma protein (SDPP; control), soy protein concentrate (SPC) and RPC (phase 1), and dried porcine soluble (DPS; control), SPC and RPC (phase 2). An ileal digestibility trial was also conducted to compare digestibility of amino acids in the tested protein sources. In expt. II, 160 weaning pigs (L${\times}$Y${\times}$D; 21 d-old; 5.65${\pm}$0.35 kg) were used in a 5-week feeding trial to determine the optimal inclusion level of RPC in the diet. Treatments were control (9% SPC), and three levels of RPC instead of SPC in the diets (3, 6 and 9%). During phase 1, pigs fed SDPP showed better (p<0.05) ADG and FCR compared with those fed SPC or RPC, while there was no difference in ADFI among treatments. During phase 2, however, pigs fed DPS showed lower (p<0.05) ADG than those fed SPC or RPC. During the total period, there were no significant differences in ADG, ADFI and FCR among treatments. The apparent ileal digestibilities of his, lys, phe, thr and met were not different among the tested protein sources. The apparent ileal digestibilities of arg, ile, leu and val were lower (p<0.05) in RPC than SDPP. The true ileal digestibilities of arg and leu were lower (p<0.05) in RPC than SDPP and SPC. However, that of met was higher (p<0.05) in RPC than SDPP. In expt. II, there were no significant differences in ADG and FCR when SPC was substituted with RPC up to 9% during the total period. In conclusion, based on our experimental results, RPC would replace SPC in the complex prestarter diet, which is somewhat cheaper than SPC.

• Journal of Gastric Cancer
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• 제8권2호
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• pp.57-64
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• 2008

현재 국소 위암에서 유일한 완치적 치료법은 수술적 절제이나 적절한 수술적 치료에도 불구하고 상당 수의 환자들이 재발을 경험한다. 이에 다학제적 병용 치료 전략에 대해 많은 관심이 있어왔고 특히 최근에는 암의 병기 감소, 근치적 절제률의 증가, 미세 원격전이의 조기 치료 등의 가능성을 가지는 수술 전 선행항암화학요법에 대한 관심이 증대되고 있다. 최근의 3상 임상 연구인 MAGIC trial은 수술 전후 항암화학요법이, 수술 단독에 비해, 병리학적 병기를 감소시키며 국소 재발과 원격 전이를 감소시켜 생존율을 향상시킴을 보고하였고 또 다른 3상 연구인 FNLCC 94012/FFCD 9703 trial 역시, 수술 전후 항암화학요법이 근치적 절제율과 생존율을 향상시킴을 보고하였다. 두 연구는 수술 전후 항암화학요법에 대한 것이지만 수술 후 보조항암화학요법의 불량한 치료 순응도에 비추어 볼 때 치료성적의 향상은 주로 수술 전 선행항암화학요법에 기인하는 것으로 생각된다. 상기 연구들이 이루어진 서양과 달리 광범위(D2) 림프절 절제술을 표준적 치료로 시행하고 있는 한국의 현실에서 이들 연구결과를 그대로 적용하기에는 어려움이 있으나 한국에서 이루어진, 국소 진행성 위암 환자를 대상으로 한 몇 가지 임상 연구 역시 선행항암화학요법을 통한 근치적 절제률의 증가 및 병기 감소 효과를 시사하였다. 이러한 고무적인 치료 성적에 근거하여 향후 수술 전 또는 수술 전후 항암화학요법이 국소 위암에서 표준적인 치료 전략으로 자리잡을 수 있을 지 결론을 짓기 위해서는 대규모 임상 연구가 시행되어야 할 것이다.

• 응용통계연구
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• 제32권1호
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• pp.1-13
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• 2019

최근에 제안된 심리스(seamless) 제 2상/제 3상 임상시험 디자인은 기존의 임상시험 디자인들과 비교하여 피험자수를 줄일 수 있을 뿐만 아니라 임상 개발 시간을 단축시킬 수 있다는 장점을 가지고 있어 임상시험연구자들의 많은 관심을 끌고 있다. 또한 제 3상 시험을 단독으로 진행 하였을 때보다 더 높은 검정력을 가질 수 있으므로 임상시험에서 매우 효율적이라 말할 수 있다. 본 논문에서는 제 2상에서 최고효과 용량군을 선정하기 위한 여러 가지 다중가설 검정방법들을 제시하고 제 2상에서 최고효과 용량군을 선정한 후에 제 2상과 제 3상을 결합하는 여러 가지 유의확률 결합검정방법들을 제시하였다. 또한 모의실험을 통해서 심리스 제 2상/제 3상 임상설계가 적용되었을 때 여러 가지 방법들을 비교함으로써, 제 2상/제 3상 표본의 크기 조합이나 분산의 크기가 다른 여러 가지 상황에서 가장 적절한 방법을 선택하는 가이드라인을 제시하고자 한다.