• 지식경영연구
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• 제21권3호
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• pp.105-121
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• 2020

신약 개발과 관련하여 글로벌 판매망이 구축되지 않은 국내 바이오텍에게 가장 필요한 것은 신약의 기술이전과 관련된 의사 결정이다. 각 임상 단계별 성공 확률이 다르고, 어느 임상 단계에서 기술이전 계약을 하느냐에 따라서 총 계약금액과 로열티가 달라지게 된다. 이런 기술이전 계약의 특징과 바이오텍의 취약한 재무 구조 등으로 인하여, 바이오텍이 빅파마에게 기술 이전을 하는 시기를 정하는 것은 매우 중요한 의사 결정 문제가 된다. 이 연구에서는 '신약의 기술이전 최적시기 결정 문제'라는 연구모형을 제시하고, 의사결정트리 방법론으로 결과를 도출하였다. 사례 연구로, first-in-class 신약을 대상으로 FDA 글로벌 임상을 진행하고 있는 국내 바이오텍에 적용해 보았다. 타겟 질환의 시장 크기와 예상 시장 침투율은 알려져 있다고 가정하였을 때, 임상 1상이나 2상 이후에 기술이전을 하는 것이 이익을 최대화할 수 있는 대안임을 알 수 있었다. 본 연구는 제약 분야 문제에 경영과학 방법론을 사용할 수 있는 개념적인 틀을 제시하여 신약 기술이전에 대한 지식 및 연구의 기반이 될 수 있을 것으로 기대된다.

• 응용통계연구
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• 제15권2호
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• pp.323-336
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• 2002

최근에 1상 임상실험 에서 사용되는 continual reassessment method (CRM)에 대한 연구가 활발히 이루어지고 있다. 본 논문에서는 세 명의 환자를 하나의 환자 군으로 삼아 동일한 용량을 투여하는 수정된 CRM에 대한 연구를 실행하였다. 지금까지 CRM에 대한연구는 대부분 시뮬레이션에 의존하여 왔지만, 본 논문에서는 모든 가능한 경우를 고려하는 방법(complete enumeration)을 사용하였다. 이 새로운 방법은 시뮬레이션을 대체할 유용한 방법이라 사료된다. 이 새로운 방법을 이용하여, 용량독성곡선이 logistic함수, hyperbolic tangent 함수, power 함수일 때, 수정된 CRM에서 결정한 최대허용용량에서의 독성 확률이 목표 독성 확률로 잘 수렴함을 보였다. 하지만, 실험 전에 용량들을 적절히 선택하지 못하면, 최대허용용량에서의 독성 확률이 목표 독성 확률과 상당한 차이를 낼 수도 있음을 발견하였다.

• Journal of Gastric Cancer
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• 제21권4호
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• pp.418-425
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• 2021

Purpose: We designed a new regimen by combining intraperitoneal (IP) paclitaxel (PTX) with systemic S-1 plus oxaliplatin (SOX) for the treatment of advanced gastric cancer with peritoneal metastasis. This dose-escalation study aimed to determine the maximum tolerated dose (MTD) and recommended dose (RD) of IP PTX administered weekly to patients. Materials and Methods: Eight cycles of IP PTX plus SOX regimen were administered to the patients. S-1 was administered orally twice daily at a dose of 80 mg/m²/day for 14 consecutive days, followed by 7 days of rest. Intravenous oxaliplatin was administered at a fixed dose of 100 mg/m² on day 1, while IP PTX was administered on days 1 and 8. The initial dose of IP PTX was 40 mg/m², and the dose escalation was set in units of 20 mg/m² up to 80 mg/m². Dose-limiting toxicities (DLTs) were defined as grade 3 non-hematologic toxicities, grade 4 leukopenia, grade 3 febrile neutropenia, and grade 3 thrombocytopenia. Results: Nine patients were included in the study. No DLTs were observed in any of the enrolled patients. Therefore, the MTD was not reached, and the RD of IP PTX was determined to be 80 mg/m². Four patients (44%) showed a decreased peritoneal cancer index score on second-look laparoscopic examination. Conclusions: The present study determined the dose for further clinical trials of IP PTX to be 80 mg/m², when combined with a systemic SOX regimen.

• BMB Reports
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• 제36권1호
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• pp.110-119
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• 2003

The acetylation state of histone is reversibly regulated by histone acetyltransferase (HAT) and deacetylase (HDAC). An imbalance of this reaction leads to an aberrant behavior of the cells in morphology, cell cycle, differentiation, and carcinogenesis. Recently, these key enzymes in the gene expression were cloned. They revealed a broad use of this modification, not only in histone, but also other proteins that involved transcription, nuclear transport, and cytoskeleton. These results suggest that HAT/HDAC takes charge of multiple-functions in the cell, not just the gene expression. HDAC is especially known to play an important role in carcinogenesis. The enzyme has been considered a target molecule for cancer therapy. The inhibition of HDAC activity by a specific inhibitor induces growth arrest, differentiation, and apoptosis of transformed or several cancer cells. Some of these inhibitors are in a clinical trial at phase I or phase II. The discovery and development of specific HDAC inhibitors are helpful for cancer therapy, and decipher the molecular mode of action for HDAC.

• 구강회복응용과학지
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• 제28권1호
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• pp.15-25
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• 2012

치주치료에 있어 교합치료의 타당성은 오래전부터 연구되어오고 있으나 아직도 논란이 많은 부분이다. 그 중에서도, 교합삭제를 이용한 수동적 정출(passive eruption)의 치료 효과에 대한 연구는 아직 보고된 바가 많지 않다. 본 연구의 목표는 교합삭제를 이용한 수동적 정출이 치주부착수준, 치주낭깊이 등의 치주임상지표들에 미치는 효과를 평가하는 것이다. 본 연구는 부산대학교 치과병원 치주과에서 중등도 치주염으로 치료받은 환자 중, 연구대상조건을 만족하는 16명의 환자, 40개의 치아를 대상으로 하였다. 연구 시작 단계에서 임의로 분류한 실험군과 대조군 치아 모두 임상적, 방사선적 검사를 시행하였다. 치석제거술과 치근활택술, 구강 위생 교육을 포함한 초기치료를 시행하고 4주 후 임상적, 방사선적 검사를 재실시하였다. 이 때 실험군은 교합면 삭제를 이용한 수동적 정출을 시행하고 대조군은 아무런 처치를 하지 않았다. 그 후 6개월 이후 임상적, 방사선적 검사를 재실시하였다. 그 결과 1)연구시작 단계와 비교 시, 초기치료에 의해 임상지표를 통한 치주조직의 염증상태가 개선되었으며, 2)실험군에서 치주낭깊이, 치아동요도, 치조골 소실 감소와 각화치은 폭경 증가가 더 큰 것으로 나타났다 (p<0.05). 이 결과로 볼 때, 초기치료와 함께 교합조정을 이용한 수동적 정출술이 치주치료에 도움을 줄 수 있을 것으로 사료된다.

• 수면정신생리
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• 제6권1호
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• pp.46-51
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• 1999

목 적 : 광치료는 계절성 기분장애, 약간의 비계절성 주요 우울장애 및 월경전우울증 등의 치료에 이용되고 있다. 저자들은 일중주기리듬의 장애가 병인론으로 제시되고 있는 월경전 불쾌기분 장애에 대한 광치료 효과를 평가하기 위하여 광치료의 임상시도를 하였다. 방 법 : DSM-IV의 월경전 불쾌기분장애 진단기준에 충족되는 4명의 환자에서 광박스(light box,Apolo bright lite III)를 이용한 저녁 광치료(6:30-8:00pm) 시도하였다. 결 과 : 연구대상은 광치료 후, 그 정도에는 차이가 있으나, 월경전기 증상과 더불어 우울기분과 불안이 감소하는 변화를 보였다. 본 연구는 임상시도로 연구대상이 적고, 위약 효과의 통제가 없으며, 증상 평가 방법에 있어 어려움 등 한계가 있으나, 이러한 변화는 특히 비정형 우울증상이 있는 환자에서 두드러졌으며, 신체증상보다는 심리증상에 보다 효과적인 결과를 보였다. 결 론 : 광치료는 월경전불쾌기분 장애 환자의 약물학적 치료에 대안적 방법으로 볼 수 있겠다. 향후 보다 많은 수의 환자를 대상으로, 위약대조 교차연구(아침, 저녁 광치료)가 필요할 것으로 사료된다.

• Journal of mucopolysaccharidosis and rare diseases
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• 제3권2호
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• pp.41-43
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• 2017

Prader-Willi syndrome (PWS) is a genetic disorder that is considered, especially on child, to cause poor feeding, hypotonia, failure to thrive, developmental delay and hypogonadism which is known to affect between 1 in 10,000 and 30,000 people. The children with PWS are viewed as affected by growth hormone (GH) insufficiency, although the exact mechanisms of GH deficiency are not fully understood. However, the benefits of GH treatment in children with PWS are well established. Myers, et al. (2006), Grugni, et al. (2016) indicated its positive effects on linear growth, body composition, motor function, respiratory function and psychomotor development. Despite of its effectiveness and advantages had been well known and proven in many other studies, there is only one recombinant GH product that is approved for PWS in Korea, $Genotropin^{(R)}$, till now. A phase III clinical study of GH treatment with $Eutropin^{TM}$, in 34 Korean PWS children is in progress, which is expected to have comparable effects and safety profile with the active control by assessing auxological changes such as height standard deviation score, body composition changes such as lean body mass and percent body fat, motor and cognitive development using Bayley scale, and safety profiles.

• Journal of Gastric Cancer
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• 제17권2호
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• pp.132-144
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• 2017

Purpose: To identify baseline prognostic factors for survival in patients with disease progression, during or after chemotherapy for the treatment of advanced gastric or gastroesophageal junction (GEJ) cancer. Materials and Methods: We pooled data from patients randomized between 2009 and 2012 in 2 phase III, global double-blind studies of ramucirumab for the treatment of advanced gastric or GEJ adenocarcinoma following disease progression on first-line platinum- and/or fluoropyrimidine-containing therapy (REGARD and RAINBOW). Forty-one key baseline clinical and laboratory factors common in both studies were examined. Model building started with covariate screening using univariate Cox models (significance level=0.05). A stepwise multivariable Cox model identified the final prognostic factors (entry+exit significance level=0.01). Cox models were stratified by treatment and geographic region. The process was repeated to identify baseline prognostic quality of life (QoL) parameters. Results: Of 1,020 randomized patients, 953 (93%) patients without any missing covariates were included in the analysis. We identified 12 independent prognostic factors of poor survival: 1) peritoneal metastases; 2) Eastern Cooperative Oncology Group (ECOG) performance score 1; 3) the presence of a primary tumor; 4) time to progression since prior therapy <6 months; 5) poor/unknown tumor differentiation; abnormally low blood levels of 6) albumin, 7) sodium, and/or 8) lymphocytes; and abnormally high blood levels of 9) neutrophils, 10) aspartate aminotransferase (AST), 11) alkaline phosphatase (ALP), and/or 12) lactate dehydrogenase (LDH). Factors were used to devise a 4-tier prognostic index (median overall survival [OS] by risk [months]: high=3.4, moderate=6.4, medium=9.9, and low=14.5; Harrell's C-index=0.66; 95% confidence interval [CI], 0.64-0.68). Addition of QoL to the model identified patient-reported appetite loss as an independent prognostic factor. Conclusions: The identified prognostic factors and the reported prognostic index may help clinical decision-making, patient stratification, and planning of future clinical studies.

• 여성건강간호학회지
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• 제7권1호
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• pp.67-79
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• 2001

This study was designed to verify the effect of Doula-type-delivery nursing care on plasma $\beta$-endorphin, serum cortisol, related to delivery stress during labor, and postpartum anxiety of primipara by a quasi experiment(nonequivalent control group pretest-posttest design), from December, 1999 to August, 2000. The subjects of this experiment consisted of sixty eight primipara, with single gestation, full term, uncomplicated pregnancies, thirty three for the experimental group and thirty five for the control group. Their mean age was 26.1 years for the experimental group and 25.5 years for the control group. Their mean gestation period was 39.7 weeks for the experimental group and 40.1 weeks for the control group. As treatment, Doula-type-delivery nursing care was given for the experimental group. Data assessed plasma $\beta$-endorphin, serum cortisol during labor, and anxiety during postpartum. Plasma $\beta$-endorphin, serum cortisol were measured in the latent phase before treatment(pre-test) and the transition phase after treatment(posttest). Also, anxiety was measured in the latent phase before treatment(pre-test) and 24 hours postpartum after treatment(posttest). Data was analyzed by t-test, $x^2$-test, Repeated measures ANOVA with SAS Program. The results of this study were as follows; 1. Plasma $\beta$-endorphin was significantly elevated in the experimental group who were cared for with Doula-type-delivery nursing care during labor(P=.0463). 2. No significant group effects were found, but significant time effects were found for serum cortisol. 3. The postpartum anxiety of the experimental group was significantly lower than the control group(P=.0110). In conclusion, these findings indicate that Doula-type-delivery nursing care during labor could be effective in increasing maternal plasma $\beta$-endorphin and decreasing postpartum anxiety. Doula-type-delivery nursing care during labor could be applied as an effective nursing treatment for primipara.

• 대한기관윤리심의기구협의회지
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• 제2권1호
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• pp.23-31
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• 2020

Purpose: To obtain opinions from Korean Institutional Review Board (IRB) members' self-evaluation on ability to conduct fairness review of clinical trial protocol with presence of conflict of interest and from investigators and IRB members on financial conflict of interest through surveying. Methods: IRB members and researchers in 9 different hospitals were asked to answer survey questions via email. Results: Responders were 115 personnel (IRB Chair/vice 18, medical member 30, non-medical member 28, and researcher 39) from 9 centers. Compared to IRB medical members, IRB chair/vice respondents scored higher with statistically significance on 10 point scale (8.44±1.381 vs. 7.30±1.685, p=0.005) when asked to self-evaluate fairness reviewing a protocol proposed by an investigator from the same department and a protocol from the company that supports the scientific committee of responders. When reviewing a protocol proposed by a hospital director, non-medical members scored statistically significantly higher than medical-members (7.47±1.76 vs. 8.07±2.70, p=0.034). When asked about the limitation of labor fee for principal investigator on phase 3 Human clinical trials of the Investigational new drug, while the responses range was wide, 60% answered that labor cost of principal investigator should be less than 30% of total budget for clinical trials with a budget of 100 million won. 51.3% answered that there is no need to disclose the labor cost of the principal investigator in the consent form. Since every investigator can be influenced unconsciously by conflict of interest, the answer that 'responder agrees that there is need for management' was the most chosen answer (IRB member 61.8%, investigator 64.1%, multiple answers allowed). Conclusion: Considering scores on questions of fairness by IRB members were between 7.23-8.56 on scale of 0 to 10 point when IRB members were asked about reviewing a clinical trial protocol, it cannot be said with absolute certainty that there is no issue regarding fairness in the review process. Therefore, there should be more ways to safeguard fairness for these issues. There is a need that the disclosure amount of honorarium from sponsor should be lower than 100 million Korean won. Considering the results of the survey in which respondents expressed their thoughts, it is likely that more education on the concept of conflict of interest is needed.