1、临床观察性研究中的若干方法学问题和实例分享Min Yao, MD, MPHClinical ScientistBoston University Medical CenterDepartment of SurgeryBoston, MA13917765296内容临床观察性研究: 真实世界(real world)研究观察性研究中控制混淆因子的基本方法概述举例：多因素相关回归举例：倾向性得分配对法临床事件风险预测研究卫生经济学研究 Science tells us what we can do; Guidelines tells we should do; Observational study
2、tells what we are actually doing临床医学研究的分类临床研究实验性研究Experimental studies观察性研究Observational studies临床试验 横断面研究 队列研究 病例对照研究观察性研究的定义与目的定义不对研究对象施加任何外部干预而获得的事实材料的研究方法。record as it is目的 了解在真实世界(real world) 或者现实条件下疾病原因、发病机理、分布、发生、诊断、治疗、预后等等。临床观察性研究的三种常用方法病例-对照研究(case-control study)队列研究(cohort study)横断面/现况研究(c
3、ross-sectional study)观察性临床研究的类型病例-对照研究(Case-Control Study)肺癌非患者吸烟非吸烟时间观察性临床研究的类型队列研究(Cohort Study)肺癌非患者吸烟非吸烟时间观察性临床研究的类型横断面研究(Cross Sectional Study) 流行病调查/普查(survey)时间时间点时间点混杂因素的控制方法Control for Confounding1、随机化Randomization2、限制Restriction3、配对Matching4、分层Stratification 5、多元回归分析法Multiple Regression或者上
4、述数个方法的联合应用混杂因素的控制方法可用在研究设计和数据统计阶段研究设计数据统计研究实行随机化配对分层限制配对分层限制多元分析回归偏离真实结果的数据混淆因素有偏倚的结论混杂因素的控制方法之一多元回归分析法一个医学事件的发生往往是多个因素（变量）共同作用的结果：如果以血压为例，在我们评价某个抗高血压药物对血压的影响，必须同时考虑病人的年龄、性别、饮食、运动、是否有糖尿病史、同时服用的其他药物等等诸多因素影响。多元回归g2102g7616法是研究多个g19647g7530变量g1147间的g11560g1218g1485g17286g1955g13099以g2554g1973在g16372g55
5、63性的g13583g16849学方法。g17994g17911一g13099列g3901g7538的g7072学运g12743，g6685g12138g2612个变量g1086事件的g1955g13099。多元回归统计方法的选择条件 方法Continue连续性指标血压下降，减少体重，胆固醇降低Multiple linear regression多元线性模型Dichotomous,二分类指标有效率、治愈率、死亡率Multiple logistic regression多元Logistic回归模型Time-to-even 生存时间开始治疗至事件发生(死亡)的时间Cox proportional
6、hazards modelCOX比例风险模型A Pragmatic Retrospective Cohort Study Evaluating Clinical Outcomes in High Risk Patients with Chronic Lower Extremity Ulcers Treated with Negative Pressure Wound TherapyMin Yao, Matteo Fabbi, Hisae Hayashi, Nanjin Park, Khaled Attala, Michael A French and Vickie R. DriverPrese
7、nter: Min Yao MD, MPHClinical Research ScientistLimb Preservation and Wound CareDepartment of SurgeryBoston University Medical Center Boston, MA 02118 NPWT is used in the treatment of chronic, acute, sub-acute, traumatic, wounds with different etiology: diabetic, peripheral arterial disease, pressur
8、e, surgical and burn Mechanisms of action for NPWT Providing a moist, closed wound healing environment Drawing wound edges together Removing infectious materials and fluids Reducing edema Promoting tissue perfusion and formation, which Prepare wound bed for closure by secondary intention. Background
9、Negative Pressure Wound Therapy (NPWT)Portal UnitObjectives1. To evaluate efficacy of Negative Pressure Wound Therapy (NPWT) on wound healing in patients with chronic lower extremity ulcers and multiple co-morbidities across a real world continuum of care settings.2. To determine the effectiveness o
10、f early advanced care for patients treated with and without NPWTStudy Design This is a retrospective cohort study Subjects were divided into two groups based on exposure to NPWT: Treatment group: Wounds treated with NPWT Control group: Wounds not treated with NPWT Two groups are matched on wound siz
11、e and surgical incision and drainage (I/D)Study DesignInclusion/Exclusion Criteria Lower extremity ulcers with and without NPWT were included in this study (2002-2010). Patients with following conditions were excluded from the study: HIV positive Active malignancy with chemotherapy Less than 18 year
12、s old More than 80 years old Traumatic wounds due to motor vehicle accidents Burn ulcers Sickle cell disease On steroidData Source Boston University Medical Center Electronic Medical Record (EMR) Data Retrieved from Boston Medical Center Electronic Data Warehouse for the period of 2002 to 2010. Data
13、 Capture Electronic data capture by database query Demographics Diagnostic code (ICD-9) Inpatient and outpatient procedures (CPT code) Hospitalizations (room and board) Clinic visits (room and board Meds Lab Manual data capture by chart review History of ulcer Start date/end date of index ulcers Siz
14、e and grade of index ulcers Duration of NWPT application History of amputation .Clinic Data Capture and ConversionElectronic Data CollectionRoom and BoardMedICD-9/CPTLabRadiologyMicrosoft AccessSASManual Data Capture by Chart ReviewUlcer onsetUlcer start date and end dateSize and gradeDuration of NW
15、PTStatistical AnalysisTable1-Patient CharacteristicsIs wound healing only affected by Negative Pressure Wound Technology (NPWT) or not ? Age BMI Diabetes Chronic Kidney Disease Chronic Liver Disease Peripheral vascular disease Anemia Hypoalbuminemia Infection Duration of ulcers Stage of Ulcers Histo
16、ry of AmputationUnadjusted HR * (95% CI) Adjusted HR* (95% CI)All ulcers 2.25 (1.73-3.96) 2.63 (1.87-3.70)Diabetic ulcersWagner 1-2 1.85 (1.26-2.69) 2.73 (1.61-4.62)Wagner 3-4 2.54 (1.77-3.65) 2.74 (1.78-4.21)Type of UlcersDiabetic ulcers 2.38 (1.75-3.23) 3.26 (2.21-4.83)Arterial ulcers 2.33 (1.57-3
17、.48) 2.27 (1.56-3.78)Venous ulcers 4.90 (1.72-13.59) 6.31 (1.49-26.6)Pressure ulcers 2.19 (1.03-4.66) 1.72 (0.43-6.95)Initiation of NWPT after ulcer onset (month)Unadjusted HR (95% CI)Adjusted HR (95% CI) P value0-3 3.11 (1.58-6.12) 3.38 (1.68-6.82) 0.014-12 1.83 (0.82-4.06) 2.18 (0.94-5.07) 0.0712 + 1.0 (reference) 1.0 (reference) .Long Rank testP0.01ConclusionNPWT is effective in accelerating wound healing in patients with multiple co-morbidities and complicated non healing lower extremity ulcers Early NPWT application may yield more wound healing benefits
