Clinical Research Design and Biostatistical Methods

Purpose: To proceed effectively with clinical research requires an understanding of the fundamental principles of study design and biostatistical methods. In this article, we identified and summarized basic clinical research designs and some of the key biostatistical methods that have been commonly used in clinical research. Materials and Methods: In an observational study, cross-sectional, case- control and Cohort designs were illustrated and compared. In a clinical trial study, parallel group design and cross-over designs were described according to their characteristics. Also, the biostatistical methods for their usages classified and summarized. Results: Understanding and evaluating research design are part of the process researchers must use to determine both the quality and usefulness of their research. Adequate applications to biostatistical methods are need; i.e., descriptive statistics, Student´s t-test, ANOVA, nonparametrics, categorical data analysis, correlation and regression, and survival analysis. Conclusions: Research findings are used by clinical researcher to guide their practice and reduce their uncertainty in clinical decision making. However, to understand how to interpret research results, it is important to be able to understand basic statistical concepts and types of study design. Clinicians should also appropriately choose the biostatistical methods to suit their purposes.ope

(A) study for statistical epidemic model using MCMC

의학전산통계학 협동과정/박사[한글]전염병에 대한 통계학적 접근은 최근들어 SEIR 모형이 기본적인 모형으로 많이 사용되며, 이 모형들은 S(susceptible), E(exposed), I(infectious), R(recovered or removed)의 상태로 나뉘어 있는 개체들에 대한 모집단의 기본 모형을 이용해 연구자가 원하는 모수들을 추정하는 접근 방법에 따라 여러 가지 변형된 모형이 제시되어 왔다. 누락되거나 관찰하지 못한 잠복기와 감염기, 관찰되지 않은 변수 등, 누락 자료를 다수 포함할 수 밖에 없는 전염병 자료에서 나타날 수 있는 특성이 모수의 추정을 어렵게 하는 경향이 있기 때문에, 근래에 모수들을 좀 더 수월하게 추정하기 위해서 마코브 체인 몬테 카를로(Markov chain Monte Carlo, MCMC)를 이용한 접근법이 많이 사용되고 있다.본 연구에서는 MCMC를 근간으로 한 접근법에서 실제로 얻을 수 있는 자료에 좀 더 근접한 모형을 만들기 위해, 시간의 흐름을 이산형으로 정의하고, 모형에 사용되는 변수의 결측치 및 통제 효과에 대해서도 추정을 할 수 있는 방법을 개발하였다.모형의 타당성을 위해 임의 자료를 통한 시뮬레이션으로 모수를 추정하였으며, 이 후 실제 전염병 자료를 이용하여 기존의 연구에 도출된 추정치의 결과와 비교하였다. 기존의 연구와 결과를 비교하면, 표준편차는 커지는 결과를 얻었는데, 이는 결측치가 포함되고 이항분포를 사용하였기 때문이다. 그러나 모수의 추정치는 전체적으로 실제값에 더 가까워져 좋은 결과를 얻었다고 할 수 있으며, 이를 통해 시간의 이산형을 고려하고, 누락된 자료를 함께 모수 추정에 사용하였던 모형이 전염병 예측 모형의 사용에 적합함을 알 수 있었다. [영문]Stochastic compartmental models are widely used in the statistical analysis of epidemic diseases. These models consider populations of individuals as being partitioned in disjoint subsets(SEIR : susceptible, exposed, infectious and removed(or recovered)) and represent the transitions of individuals between compartment as stochastic processes.In order to capture the stochastic nature of the transitions between the compartmental populations in such a model we specify appropriate conditional binomial distributions. In addition, a relatively simple temporally varying transmission rate function is introduced that allows for the effect of control interventions. This study develops Markov chain Monte Carlo methods for inference that are used to explore the posterior distribution of the parameters. The algorithm is further extended to integrate numerically over state variables of the model, which are unobserved. This provides a realistic stochastic model that can be used by epidemiologists to study the dynamics of the disease and the effect of control interventions.ope

Linkage analysis of quantitative trait loci using structural equation model.

의학전산통계학협동과정 의학통계학전공/석사[한글] 본 논문에서는 양적 형질 유전자의 연관성 분석을 위해 구조방정식 모형을 적용시켜, 서로 다른 염색체 상의 유전자들 및 다양한 환경적 요인과 여러 가지 형질간의 관계를 복합적으로 규명하기 위한 방법을 제시하였다. 이를 위해서 형제쌍 자료를 이용했을 때와 개인자료를 적용시켰을 때, 각각의 모형을 제시하였고 이에 대한 타당성을 확보하였다.본 연구에서는 한국의 심혈관 질환을 연구하기 위해 실제로 조사된 자료를 이용하였는데, 유전자는 CETP와 APOE, 환경적 요인은 흡연과 음주, 그리고 양적 형질은 LDL과 BMI, APO-AI를 사용하였다.ACE 유전 모형을 응용해서 구축한 구조방정식 모형을 실재 자료에 적용해 봄으로써 기존의 연구에서 밝혀졌던 CETP와 APO-AI의 연관성을 증명할 수 있었으며, APOE와 CETP가 BMI와도 의미 있는 연관성을 보이는 것을 확인했다. 또한 환경적 영향력이 LDL과 BMI에 많은 영향력을 나타냄으로써 유전적인 것 이외의 효과에 대한 연관성도 규명할 수 있었으며, 이를 통해 구조방정식 모형을 이용해 연관성 분석을 시행할 수 있음을 밝혔다. [영문] In this thesis, I applied the structural equation model for the quantitative trait loci, and presented the approach that search out the complex relationships between the genes on the different chromosome and several trait. For this approach, I structured each model using sib-pairs and individual data set.In this study, I used CETP(chromosome no.16) and APOE(chromosome no.19) on the markers, smoking and drinking on the environmental effects and LDL, BMI and APO-AI on the quantitative traits which in the real research data set for studying the cardiovascular disease in South Korea.Structural equation model from this study, applied the ACE genetic model that is the result of obtaining real data set, found out the estimation between two markers(APOE and CETP) and BMI, including the relationships between APOE and LDL, and CETP and APO-AI.Furthermore it estimated the environmental effects that defined smoking and drinking.From the results, structural equation model can use the one possible approach for the QTL linkage analysis.ope

이러닝 베스트 강좌 인터뷰

서울대학교에 새로운 교수학습관리시스템 e-TL을 도입하여 운영해온 지도 반 학기가 지났다. 이에 e-TL을 활발하게 사용하고 있는 강의를 선정하여 교수님들의 강의노하우에 대해 이야기를 나눠보는 기회를 가졌다

Serotonin-related gene pathways associated with undifferentiated somatoform disorder

It has been suggested that serotonergic hypofunction and serotonergic pathway genes underlie the somatic symptoms of somatoform disorders. We examined a variety of serotonin-related gene polymorphisms to determine whether undifferentiated somatoform disorder is associated with specific serotonin-related gene pathways. Serotonin-related polymorphic markers were assessed using single nucleotide polymorphism (SNP) genotyping. One hundred and two patients with undifferentiated somatoform disorder and 133 healthy subjects were enrolled. The genotype and allele frequencies of tryptophan hydroxylase (TPH)1 A218C, TPH2 rs1386494, serotonin receptor 2A-T102C (5-HTR 2A-T102C), 5-HTR 2A-G1438A and serotonin transporter (5HTTLPR) gene were compared between the groups. The Hamilton Rating Scale for Depression and the somatization subscale of the Symptom Checklist-90-Revised (SCL-90-R) were used for psychological assessment. Patients with undifferentiated somatoform disorder had higher frequencies of the TPH1 C allele than healthy controls (p=0.02) but the difference was not significant after Bonferroni correction. The frequency of TPH1 genotype also did not differ significantly between the patients and the healthy controls, nor did TPH2 rs1386494, 5-HTR 2A-T102C, 5-HTR 2A-G1438A or 5HTTLPR allele and genotype frequencies differ significantly between the two groups. These findings suggest that a variety of serotonin-related gene pathways are unlikely to be definite genetic risk factors for undifferentiated somatoform disorder. Therefore, the pathogenesis of the disorder may be related to epigenetic factors, including psychosocial and cultural factors. Nonetheless, future studies need to include a larger sample of subjects and polymorphisms of more serotonin-related gene variants.ope

Prevalence Estimation of Cataract based on a Screening Test

Purpose: To estimate the prevalence of cataracts based on screening test results and statistical estimation methods. Methods: Between June 1994 and September 2005, 85,505 persons aged 20 years and older were screened at a health promotion center for a general health care screen. We assumed that all subjects had complete screening results; however some subjects had an unknown disease status. A 2×3 table form could be generated from this data set. To estimate cataract prevalence, we used a maximum likelihood estimation method to reconstruct a 2×2 table including probabilities for each cell. Results: The overall estimated cataract prevalence was 13.98% (95% confidence intervals, 13.75% to 14.21%). We estimated the prevalence of cataracts to be 15.29% in men (95% confidence intervals, 14.95% to 15.63%) and 12.97% in women (95% confidence intervals, 12.65% to 13.29%). In addition, we found that the cataract prevalence distinctly increased in people aged 60 years or older. Conclusions: We found that these estimated cataract prevalences were not considerably different from study results obtained in other countries. Therefore, our method may be considered to be appropriate for estimating prevalence. Our results indicate that cataract prevalence in our study population increases with age and highlight the need for early detection and early interventions.ope

Sebum output as a factor contributing to the size of facial pores

BACKGROUND: Many endogenous and exogenous factors are known to cause enlarged pilosebaceous pores. Such factors include sex, genetic predisposition, ageing, chronic ultraviolet light exposure, comedogenic xenobiotics, acne and seborrhoea. This study was an attempt to determine the factors related to enlarged pores. OBJECTIVES: To assess the relationship of sebum output, age, sex, hormonal factors and severity of acne with pore size. METHODS: A prospective, randomized, controlled study was designed. A total of 60 volunteers, 30 males and 30 females, were recruited for this study. Magnified images of pores were taken using a dermoscopic video camera and measured using an image analysis program. The sebum output level was measured with a Sebumeter. RESULTS: Using multiple linear regression analysis, increased pore size was significantly associated with increased sebum output level, sex and age. Among the variables, sebum output level correlated most with the pore size followed by male sex. In comparing male and female participants, males had higher correlation between the sebum output level and the pore size (male: r = 0.47, female: r = 0.38). Thus, additional factors seem to influence pore size in females. Pore size was significantly increased during the ovulation phase (P = 0.008), but severity of acne was not significantly associated with the pore size. CONCLUSIONS: Enlarged pore sizes are associated with increased sebum output level, age and male sex. In female patients, additional hormonal factors, such as those of the menstrual cycle, affect the pore size.ope

The relation between anger management style, mood and somatic symptoms in anxiety disorders and somatoform disorders

The objective of this study was to examine the relationship between anger management style, depression, anxiety and somatic symptoms in anxiety disorder and somatoform disorder patients. The subjects comprised 71 patients with anxiety disorders and 47 with somatoform disorders. The level of anger expression or anger suppression was assessed by the Anger Expression Scale, the severity of anxiety and depression by the Symptom Checklist-90-Revised (SCL-90-R) anxiety and depression subscales, and the severity of somatic symptoms by the Somatization Rating Scale and the SCL-90-R somatization subscale. The results of path analyses showed that anger suppression had only an indirect effect on somatic symptoms through depression and anxiety in each of the disorders. In addition, only anxiety had a direct effect on somatic symptoms in anxiety disorder patients, whereas both anxiety and depression had direct effects on somatic symptoms in somatoform disorder patients. However, the anxiety disorder group showed a significant negative correlation between anger expression and anger suppression in the path from anger-out to anger-in to depression to anxiety to somatic symptoms, unlike the somatoform disorder group. The results suggest that anger suppression, but not anger expression, is associated with mood, i.e. depression and anxiety, and somatic symptoms characterize anxiety disorder and somatoform disorder patients. Anxiety is likely to be an important source of somatic symptoms in anxiety disorders, whereas both anxiety and depression are likely to be important sources of somatic symptoms in somatoform disorders. In addition, anger suppression preceded by inhibited anger expression is associated with anxiety and somatic symptoms in anxiety disorders.ope

Correlation between traumatic events and posttraumatic stress disorder among North Korean defectors in South Korea

The number of North Korean defectors entering South Korea has been increasing rapidly since 1994. Two hundred North Korean defectors in South Korea were studied to identify their experiences of traumatic events in North Korea and during defection, and the correlation with Posttraumatic Stress Disorder (PTSD). Researchers conducted face-to-face interviews and assisted defectors in performing a self-report assessment of this survey. The study questionnaire consisted of demographic characteristics, the Traumatic Experiences Scale for North Korean Defectors, and the PTSD part of the Structured Clinical Interview for DSM-III-R Korean version. Prevalence rate of PTSD in defectors was 29.5%, with a higher rate for women. In factor analysis, the 25 items of traumatic events experienced in North Korea were divided into three factors: Physical Trauma, Political-Ideological Trauma, and Family-Related Trauma. In addition, the 19 items of traumatic events during defection were grouped into four factors: Physical Trauma, Detection and Capture-Related Trauma, Family-Related Trauma, and Betrayal-Related Trauma. In multifactorial logistic regression analysis, Family-Related Trauma in North Korea had a significant odds ratio.restrictio

Regression Methods for Overdispersed Dichotomous Response Data

In neuropsychiatrical research, many problems of statistical inference concern the relationship between the PTSD and traumatic experiences. The logistic model is widely used for modeling a relationship between the covariate and the magnitude of the PTSD. A common complication in the logistic model for dichotomous response data is overdispersion. In this study, two different methods for analyzing dichotomous response data are illustrated and compared. One method is the logistic regression approach, where the numbers of dichotomous responses are predicted by the logistic function of covariates. The other one is the overdispersed logistic regression approach, where the overdispersion is measured by a scale parameter in the variance function of the dichotomous response. In dichotomous response model, when reponses are overdispersed, the overdispersed logistic regression produces more appropriate standard errors of the regression coefficients and the 95% confidence intervals of odds ratios. Therefore, in neuropsychiatrical research, it is recommended to examine the overdispersion problems for their data set before applying the logistic regression model.ope