• Communications for Statistical Applications and Methods
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• v.19 no.6
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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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• v.26 no.2
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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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• v.15 no.2
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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.

• Proceedings of the Korean Society of Developmental Biology Conference
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• 2009.02a
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• pp.43-45
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• 2009

• 대한예방의학회:학술대회논문집
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• 2002.10a
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• pp.192-193
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• 2002

• Journal of Acupuncture Research
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• v.25 no.2
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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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• v.14 no.10
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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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• v.18 no.3
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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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• v.8 no.2
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• pp.57-64
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• 2008

In gastric cancer, the only potentially curative treatment is surgery that attempts to achieve curative (R0) resection. However, despite the use of curative resection, a recurrence develops in a high percentage of patients, especially in cases of serosa and/or lymph node involvement. As a strategy to improve the survival of the patients with resectable advanced gastric cancer, neoadjuvant chemotherapy has been evaluated in several phase II trials and a few phase III trials. The results of these trials have confirmed the feasibility and safety of this approach with no apparent increase in surgical complications. Recently, the findings of a large phase III randomized trial (MAGIC trial) have indicated that compared to the use of surgery alone, perioperative chemotherapy, using both a neoadjuvant and adjuvant strategy, decreased the number of T and N stage cancers and improved survival. The results of another recent phase III trial (FNLCC 94012/FFCD 9703) also showed that compared to the use of surgery alone, perioperative chemotherapy improved the R0 resection rate and survival. In both trials, the improved outcomes may be attributed to the use of neoadjuvant chemotherapy because of poor compliance with adjuvant chemotherapy. These results cannot be directly translated to clinical practice in Korea due to differences in surgical techniques and outcomes. However, the findings of a few small phase II and III trials performed in patients with locally advanced gastric cancer in Korea have also suggested that neoadjuvant chemotherapy would result in the improvement of the R0 resection rate and down-staging of the disease. More effective chemotherapy regimens are needed in future large randomized trials to determine the subset of patients that will benefit from neoadjuvant chemotherapy and to determine the extent of benefit.

• The Korean Journal of Applied Statistics
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• v.32 no.1
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• pp.1-13
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• 2019

An adaptive seamless Phase II/III clinical trial design enables a reduction in the sample size (in comparison to a conventional design) that also shortens the clinical development time. It is also very effective in clinical trials since it can have higher statistical power than Phase III alone. In this study, we use extensive simulation studies to compare several multiple hypothesis testing methods that can help select the best doses in a Phase II study along with several methods to combine p-values of the Phase II and Phase III study.