Statistics in clinical Trials : Meta Analysis in Clinical Trials

남정모 ( Chung Mo Nam ) 한국보건정보통계학회 (구 한국보건통계학회) 2007 보건정보통계학회 추계학술대회 Vol.2007 No.-

이중구간중도절단된 생존자료의 생존함수 비교를 위한 검정: 한국인 암 예방연구 중 당뇨병에의 응용

지선하,남정모,김진흠,Jee, Sun-Ha,Nam, Chung-Mo,Kim, Jin-Heum 한국통계학회 2009 응용통계연구 Vol.22 No.3

이중구간중도절단된 자료의 생존함수를 비교하기 위한 두 검정법을 소개하고 한국인 암 예방연구 (Jee 등, 2005) 자료에 적용하여 당뇨병 잠복시간의 분포를 성별과 연령에 따라 비교하였다. Kim 등 (2006)의 검정법을 이중구간중도절단된 자료로 확장한 검정법은 위험집합의 크기에만 의존하는 가중값을 사용하기 때문에 대용량 자료의 분석에서 Sun (2006)의 검정법보다 계산 시간을 대폭 줄일 수 있으며, 이산형 생존자료뿐만 아니라 연속형 생존자료에도 적용가능한 장점이 있다. 당뇨병의 잠복시간이 성별에 따라 매우 유의하게 달랐으며 여자의 잠복시간이 남자보다 긴 것으로 나타났다. 4개 연령그룹 간 당뇨병의 잠복시간도 성별에 관계 없이 매우 유의하게 달랐으며 여자의 경우가 남자의 경우보다 그 차이가 훨씬 더 유의했다. 한편, 소표본 모의실험을 통해 제안한 검정법과 Sun (2006)의 검정법의 검정력을 비교하였으며 제안한 검정법의 검정력이 Sun (2006)의 검정법보다 더 좋은 것으로 나타났다. Two tests were introduced for comparing several survival functions with doubly interval-censored data and illustrated with data surveyed by Korean Cancer Prevention Study (Jee et al., 2005). The test which extended Kim et al. (2006)'s test to the doubly interval-censored data has an advantage over Sun (2006)'s test in terms of saving computation time because the proposed test only depends on the size of risk set, and also the proposed test is applicable to continuous failure time data as well as discrete failure time data unlike Sun's test. Comparing male with female groups on the incubation time of diabetes was highly different and the survival of female group was longer than that of male one. Regardless of gender, the difference in survival functions of four age groups was highly significant with p-value of less than 0.001. This trend was more remarkable for female group than for male one. Simulation results showed that the significance level of both tests was well controlled and the proposed test was better than Sun's test in terms of power.

일배체형에 기초한 고혈압과 ACE 유전자의 연관성 분석

김진흠,남정모,강대룡,서일,Kim Jinheum,Nam Chung Mo,Kang Dae Ryong,Suh Il 한국통계학회 2005 응용통계연구 Vol.18 No.2

In this study we investigate the association between the haplotype block of 4 SNPs in ACE genes and hypertension with a case-control dataset of size of 277 and 40 families data collected from Kangwha studies. To this end we perform a haplotype-based case-control association study and a haplotype-based TDT study. We do the same analysis with tag-SNPs that can identify the haplotype block. Through a cladogram analysis we make the evolution-tree of haplotypes and then classify the haplotypes into a few clades by collecting haplotypes exposed to the disease to the same extent. We also discuss the association between these clades and hypertension. 본 연구에서는 강화연구(서일, 2004)를 통해 수집된 277명의 환자-대조군 자료와 40개의 가계 자료를 이용하여 ACE(angiotensin-I converting enzyme) 유전자 내에 있는 4개의 단일염기다형성(single nucleotide polymorphism; SNP)으로 이루어진 일배체형(haplotype)과 고혈압의 관련성을 알아보고자 한다. 이를 위해 일배체형에 기초한 환자-대조군의 우도비 검정과 가계 자료의 TDT(transmission/disequilibrium test) 연구를 수행하고자 한다. 또한 이 일배체형을 동정(identification)할 수 있는 tag-SNPs에 기초하여 동일한 연구를 하고자 하며, Seltman 등(2003)이 제안한 분기도(cladogram) 분석 방법을 써서 일배체형의 진화 과정에서 가깝게 위치하고 질병 발생 위험이 비슷한 클레이드(clade)를 찾아내고 이 클레이드와 고혈압의 연관성을 살펴보고자 한다.

혈압의 역학적 연구와 지속성(tracking)에 대한 통계학적 분석

서일,남정모,강형곤,Suh, Il,Nam, Chung-Mo,Kang, Hyung-Gon 한국통계학회 1993 응용통계연구 Vol.6 No.2

이 연구는 혈압에 대한 역학적인 연구의 특성 및 중요성을 소개하고 우리나라 아동의 혈압에 지속성 현상이 있는가를 밝히고자 하였다. 지속송에 대한 통계적 분석방법으로서 상관분석, 성장곡선 모형을 이용한 McMahan의 방법, 그리고 Blomqvist가 제안한 방법등을 우리나라 일부지역에서 6년간 추적관찰된 아동혈압자료에 적용하여 그 결과들을 비교 분석하였다. 측정오차를 교정한 상관분석은 계산이 용이하다는 장점이 있으나 추정된 상관계수 행렬이 시간의 차(lag-difference)에 따라 단조함수가 되지 않을 수 있으며 이런 경우 지속성에 대한 해석상의 어려움이 있다. McMahan 모형은 지속성을 역학적인 관점에서 타당성이 이다고 생각되는 상대 순위의 유지도란 개념으로 정의하고 또한 전체자료에 대한 공분산구조를 모형에 반영하여 요약된 지속성에 대한 지표를 계산할 수 있는 장점이 있으나, 계산이 복잡하고 성장곡선모수의 치수를 결정하는데 따른 어려움이 있다. Blomqvist 모형은 지속성을 초기 시점에서의 측정값과 전체 시계열자료에서의 변화율간의 선형적인 관계로부터 정의하고 이 경우 발생할 수 있는 평균으로서의 회귀에 대한 영향을 수학적으로 교정하였다는 장점이 있으나, 추정값이 양수가 아닌 경우 역학적인 관점에서의 해석상의 문제점이 존재한다. This study introduced speical characteristics of an epidemiologic study on blood pressure and compared several statistical methods for evaluating the tracking phenomenon of blood pressure for Korean children. While correlation coefficients adjusted for measurement error are commonly used for the evaluation of tracking, it is hard to interpretate the results when correlation functions for lag-difference are not monotonous. McMahan defined a tracking as maintenance of relative rank over time and calculated tracking index usng growth curve model. The tracking index in McMahan's model is complicate to calculate, and it is hard to determine the degree of growth curve parameter. Blomqvist showed the relationship between the rate of change and the initial value. This concept could be extended for the evaluation of tracking. However, it is not so easy to interpretate the estimates in his model when those are non-positive.

과천시민의 고혈압 인지, 치료, 조절과의 관련요인

최연희,남정모,주미현,문기태,심지선,김현창,서일,Choi, Youn-Hee,Nam, Chung-Mo,Joo, Mi-Hyun,Moon, Ki-Tae,Shim, Jee-Seon,Kim, Hyeon-Chang,Suh, Il 대한예방의학회 2003 예방의학회지 Vol.36 No.3

Objectives : To identify the factors related to awareness, treatment, and control of hypertension in a Gwacheen population. Methods : This study surveyed 1,176 Gwacheon residents older than 40 years, and measured blood pressure using a standardized guideline in 1999. The study subjects were 473 adults (175 males, 295 females) with hypertension defined as a systolic blood pressure $\geq$140 mmHg, diastolic blood pressure $\geq$90 mmHg or reported treatment with antihypertensive medication. Information on awareness, treatment, and control of hypertension, and sociodemographic and health-related factors .was collected through person-to-person interviews with a structured questionnaire. Results : Overall, 252 (53.3%) of hypertensive subjects were aware of their condition, of whom as many as 193 (76.6%) were being treated, and 81 (42.0%) had their blood pressure controlled at the recommended level (<140/90 mmHg). However, of the 473 subjects found to have hypertension, only 40.8% were being treated, and 17.1% were under control. There were no significant differences in the proportions of awareness, treatment, and control of hypertension. In multiple logistic regression models, awareness of hypertension was positively associated with age and family history of hypertension in females. Control of hypertension was also positively associated with haying a partner and marital status in females.. Conclusion : These findings demonstrate that much greater efforts on improving awareness, treatment, and control of hypertension are needed, even in urban community settings, considering related factors such as a9e, family history, and marital status. However, these factors should be further investigated for their causal relationship.

초경시기와 아동기 및 청소년기의 신체성장의 변화 : 강화연구

김창수,남정모,김덕희,김현창,이강희,지선하,서일,Kim, Chang-Soo,Nam, Chung-Mo,Kim, Duck-Hi,Kim, Hyun-Chang,Lee, Kang-Hee,Jee, Sun-Ha,Suh, Il 대한예방의학회 2000 예방의학회지 Vol.33 No.4

Objectives : To assess height, weight and body mass index from childhood to adolescence according to the age at menarche and hence to study the influence of childhood growth on the menarche age. Methods : $\lceil$The Kangwha Study$\rfloor$was a community-based prospective cohort study which included the entire population of 219 female first graders in Kangwha county in 1986. Among the 219 girls, 119 girls who had received complete follow up checks during the study period$(1986\sim1997)$, were included in this study, except one for whom menarche age information was unavailable. The remaining 118 girls were divided into three groups according to the timing of menarche : early(<25 percentile), intermediate and late($\geq75$ percentile) maturers. Results : The average age at menarche was 12.7 years . early 11.3 years, intermediate 12.6 years and late 13.7 years. The early maturers were taller and heavier between $6\sim8$ years. But, the mean weight and body mass index at the menarche age did not differ statistically among the three groups. The weight and body mass index of the early maturers were consistently higher than those of the late maturers over the entire period of the study. Conclusions : Critical body weight and body mass index must be attained for menstruation to be attained and the age at menarche is largely determined by the childhood growth. In addition, it seems that childhood growth and age at menarche are associated with adolescent weight and body mass index.

청소년기 비만지표와 초기 성인기 경동맥 내중막 두께와의 관련성: Kangwha Study

이유정,남정모,김현창,허남욱,서일,Lee, Yoo-Jung,Nam, Chung-Mo,Kim, Hyeon-Chang,Hur, Nam-Wook,Suh, Il 대한예방의학회 2008 예방의학회지 Vol.41 No.2

Objectives : The aim of this study is to investigate the association between obesity indices(body mass index, weight, waist-hip ratio and waist circumference) in adolescents and the carotid intima-media thickness (C-IMT) in early adulthood. We also wanted to identify the best predictor for C-IMT among these obesity indices. Methods : This study used community-based prospective cohort study, known as the Kangwha Study, and the data we used were from subjects who were 16-years old in 1996 (defined as "adolescence") and 25 years-old in 2005 (defined as "early adulthood"). The 256 subjects (113 men and 143 women) who were used for analysis participated in both follow-ups, and they underwent B-mode ultrasonography of the carotid arteries at the early adulthood follow-up. Obesity indices were defined as the body mass index, weight, waist-hip ratio and waist circumference. The C-IMT was defined as the mean of the maximal IMT of each common carotid artery. The C-IMT and obesity indices associations were evaluated via multivariable regression, logistic regression and the receiver-operator characteristic curve analyses. Results : In men, all the obesity indices in adolescence were showed to have statistically significant positive association with C-IMT in early adulthood. However, no such relationship was showed in women. On multiple regression and logistic regression analysis, the waist-hip ratio showed the biggest relationship with the C-IMT among the 4 obesity indices. However, there were no statistical significant differences and no best predictor was found. For the women, the obesity incidences and C-IMT showed no relationships. Conclusions : This study suggested that obesity in adolescence was related to an increase C-IMT in healthy young Korean men.

흡연과 음주가 남성 암 사망에 미치는 영향: 강화 코호트 연구

이상규,남정모,이상욱,오희철,Lee, Sang-Gyu,Nam, Chung-Mo,Yi, Sang-Wook,Ohrr, Hee-Chul 대한예방의학회 2002 예방의학회지 Vol.35 No.2

Objective : To examine the relationship between cigarette smoking, alcohol and cancer mortality in men in the Kangwha cohort after 12 years and 10 months of follow up. Methods : The subjects consisted of 2,681 men in the Kangwha cohort aged over 55 in 1985. Number of deaths and the time to death front all cancers and other cause were measured and the data for the smoking and drinking habits were obtained from the baseline survey data in 1985. All subjects were categorized into four groups according to their smoking habits: non-smokers, ex-smokers, mode(ate-smokers (1-19 cigarettes per day), heavy-smokers ($\geq$20 cigarettes per day). In addition, they were also categorized according to their drinking habits: non-drinkers, light-drinkers ($\leq$1 drink per week), moderate-drinkers (<3 drinks per day), heavy-drinkers ($\geq$3 drinks per day). The cancer specific death rates were calculated according to their smoking and drinking status. The adjusted risk ratio for all cancer deaths according to their smoking and drinking status were estimated using the Cox's proportional hazard regression model. Results : Using nonsmokers as the reference category, the adjusted risk ratio for all cancer deaths were 1.573(95% CI=1.003-2.468) for heavy-smokers. For lung cancer deaths, the adjusted risk ratios were 3.540(95% CI=1.251-10.018) for moderate-smoker and 4.114(95% CI=1.275-13.271) for heavy-smokers. Compared to non-drinkers, the adjusted risk ratio for stomach cancer was 2.204(95% CI=1.114-4.361) for light-drinkers. Conclusion : Smoking is the most significant risk factor for cancer deaths particularly lung cancer.

농약사용과 사망률과의 관계에 대한 코호트연구

오희철,남정모,이선희,Oh, Hee-Chul,Nam, Chung-Mo,Lee, Sun-Hee 대한예방의학회 1991 예방의학회지 Vol.24 No.3

The purpose of this study is to examine the relationship between pesticide use and mortality, and cancer mortality which are recognized as health hazards of pesticides. Data were analyzed from a cohort of 6,066 people aged fifty-five or over and who have been residing in the main island of Kangwha county. Death certificates, computerized citizenship registers searches, and household interview survey lead to get more than ninety-seven percents follow-up rate for the first five year observation period. Important findings are as follows : 1. Age specific mortality rates of pesticide users are significantly lower than those of pesticides nonusers. The SMR of male is 0.80, and 0.58 for females respectively probably due to healthy worker effects. But, age specific cancer mortality rates are significantly higher than those of pesticide nonusers (SMR=1.59) in males. This finding is not observed in females (SMR=0.85), however. 2. Logistic regression analyses showed that self-reported health status, drinking, and smoking histories in male are significantly associated with total mortality rate. The histories of pesticide use are also calculated to be highly associated with cancer mortality as in univariate analyses in males. In female, self-reported health status, age of first delivery are found to be significantly related to total mortality rate. Only drinking history is calculated to be associated with cancer mortalities in females. Data from further observation of 'Kangwha cohort' and indepth analyses of these are highly expected.

Sodium(Na)과 Potassium(K) 섭취가 청소년의 혈압변화에 미치는 영향

서일,남정모,이강희,지선하,김석일,김규상,김춘배,Suh, Il,Nam, Chung-Mo,Lee, Kang-Hee,Jee, Sun-Ha,Kim, Suk-Il,Kim, Gyu-Sang,Kim, Chun-Bae 대한예방의학회 1998 Journal of Preventive Medicine and Public Health Vol.31 No.3

In order to investigate the effect of the urinary excretion of sodium and potassium on the change on blood pressure over 3 years, 668 adolescents aged 13 years living in Kangwha area were investigated in a longitudinal follow-up study. Two measurements were taken on each blood pressure (diastolic, systolic) and the average of the two readings was used in the analysis. Sodium and potassium intake were estimated by the determination of those electrolytes in 24hr urine. The mixed model regression analysis was used to identify the effect of urinary sodium and potassium on the change of blood pressure after controlling for BMI of each age. On simple bivariate analysis no relationship was found between urinary sodium excretion and systolic or diastolic blood pressure among both male and female, however, a significant positive association between urinary potassium excretion and systolic blood pressure among male. The results of mixed regression analysis showed that the body mass index (BMI) were more influential that urinary electrolytes among this study subjects. It suggested that risk factors observed from the adults, may not be identical with that of the growing aged population. After control of the BMI and age, significant association between sodium and diastolic BP among male, and association between potassium and systolic BP among female, were found. In summary, the results indicate that growth has been more influential than dietary factor on blood pressure for growing aged population.