Comparison of Proportions Part II Instructor: 李奕慧 yihwei@mail.tcu.edu.tw 1 Lecture Overview Study designs in epidemiology Measures of study effect for 2 categorical variables 1. Risk difference 2. Relative risk 3. Odds ratio McNemar’s test for Matched-pair study 2 Epidemiologic Study Design Analytical studies Intervention studies Clinical trials Observational studies Cross-sectional studies Cohort studies Case-control studies 3 Measures of Study Effect For cohort and cross-sectional studies only RD p1 p2 risk difference RR p1 / p2 risk ratio/relative risk For any type of study p1 / q1 OR p2 / q2 odds ratio 4 Risk difference (RD, p1-p2) 戴安全帽 頭部 合計 受傷 是 否 是 12 62 74 否 88 38 126 合計 100 100 200 第一組:意外發生時機車騎士沒有戴安全帽 p1:第一組母體比例 第一組樣本 n1=100, pˆ 1 (頭部受傷比例)=0.62 第二組:意外發生時機車騎士有戴安全帽 p2: 第二組母體比例 第二組樣本:n2=100, pˆ 2 =0.12 5 建構 p1-p2 的信賴區間(confidence interval, CI) ( pˆ 1 pˆ 2 ) Z / 2 pˆ 1 (1 pˆ 1 ) pˆ 2 (1 pˆ 2 ) n1 n2 where pˆ 1 pˆ 2 0 . 5 , Z 0 .025 1 . 96 0.62x0.38 0.12x0.88 0.0584 100 100 0.5 1.96x0.0584 = (0.386, 0.614) 沒戴安全帽頭部受傷的機率, 較有戴安全帽者高出 39%~61%,戴安全帽的機 車騎士,在車禍發生時,可 以減少39%~61%的頭部受 傷的機會。 6 檢定 H0:p1-p2=0 versus Ha:p1-p20 Z ˆ1 p ˆ 2 ) ( p1 p2 ) (p ˆ1 (1 p ˆ1 ) p n1 ˆ 2 (1 p ˆ2 ) p n2 Z = 0.5/0.058 =8.56, P-value < 0.001 Reject H0, there are significant differences in the population proportions between the two groups. 7 2 sample proportion test.xls 8 Example for Clinical trial and Risk Difference BMJ 2006;333;11939 比較Intervention group與Control group病人 住院3天後的死亡率(death after day 3) 每一個病人皆觀察其死亡(=1)或存活(=0)情形 Intervention group:5/132 (5%)的人住院3天後死 亡 Control group: 8/133 (8%)的人住院3天後死亡 兩組住院3天後死亡率的差異(control-intervention) 為 2% (point estimate), 95%CI:(-3% to 8%),表 示兩組母體死亡率差異的範圍介於-3%~8%, Intervention不會影響病人的死亡率。 10 Cohort study / Clinical trial Disease + Exposed (Intervention) Disease - Study population Disease + Non-exposed (Control) Disease - 11 Cohort Data 2 x 2 table ill not ill Exposed a b Unexposed c d Incidence in exposed (p1) = a/(a+b) Incidence in non-exposed(p2) = c/(c+d) 12 Effect measures in cohort studies Hypothesis Is the incidence among exposed higher than among unexposed Absolute measures Risk difference (RD) Relative measures Relative P1 P2 risk/Risk Ratio (RR) P1 P2 13 Foodborne Outbreak in a Wedding, Dublin Ate ham Did not eat ham ill not ill Incidence 49 49 98 50% 4 6 10 40% 53 55 108 Risk difference 0.5 - 0.4 = 0.1 (10%) Relative risk 0.5 / 0.4 = 1.25 14 RR與OR的意義 RR=1 RR>1 RR<1 ln(RR)=0 ln(RR)>0 ln(RR)<0 沒有相關 危險因子 保護因子 15 Relative risk RR = 1.25 RR = 1.13 RR = 13 RR= 0.8 25 % increase in risk 13 % increase in risk 13 fold increase 20% of risk reduction 16 Example for Relative Risk A Randomized Trial of Aspirin on the Risk of Embolic Events in Patients With Infective Endocarditis JACC, 2003;42(5):775–80 17 aspirin * bleeding Crosstabulation Bleeding ((果) Yes(=1) No(=2) Total Count 17 42 59 Aspirin Yes(=1) % within aspirin 28.8% 71.2% 100.0% (因) No(=2) Count 8 47 55 % within aspirin 14.5% 85.5% 100.0% Total Count 25 89 114 % within aspirin 21.9% 78.1% 100.0% Pearson Chi-Square Continuity Correctionb Likelihood Ratio Fisher's Exact Test Linear-by-Linear Association N of Valid Cases Chi-Square Tests Asymp. Sig. Exact Sig. (2- Exact Sig. (1(2-sided) sided) sided) Value df a 3.385 1 .066 2.603 1 .107 3.455 1 .063 .074 .053 3.355 1 .067 114 a. 0 cells (.0%) have expected count less than 5. The minimum expected count is 12.06. b. Computed only for a 2x2 table Aspirin.sav 18 Risk Estimate 95% Confidence Interval Odds Ratio for aspirin (yes / no) For cohort bleeding = yes For cohort bleeding = no N of Valid Cases Value 2.378 Lower .931 Upper 6.074 1.981 .930 4.218 .833 .685 1.013 114 OR = (17/42)/(8/47) = 2.38 RR = (17/59)/(8/55) =1.98 Aspirin.sav 19 Case-control (Retrospective) Exposed Cases Non-exposed Study Population Exposed Controls Non-exposed 20 Odds ratio in Case-control and Cohort study 有子宮頸癌 CASE 150 無子宮頸癌 Control 50 Total Nonsmoker 150 250 400 Total 300 300 600 Smoker 200 OR for smoking =(150/150)/(50/250) = 5 OR for cervical cancer = (150/50)/(150/250) = 5 不管是針對暴露因子,或疾病的odds ratio都相等, odds ratio不會因為研究設計而有所改變。 21 Relative Risk and Odds ratio P( Disease | exposed) {1 P( Disease | exposed)} OR P( Disease | un exposed) {1 P( Disease | un exposed)} (cohortstudy) P(exposed | Case) /{1 P( Disease | Case)} P(exposed | Control) /{1 P(exposed | Control)} (case controlstudy) P( Disease | exposed) RR P( Disease | un exposed) 當疾病發生的機率很低時,OR RR 22 smoking * Cervical_cancer Crosstabulation smoking Total Yes (=1) Count % within Cervical_cancer Cervical_cancer Yes (=1) No(=2) 150 50 50.0% 16.7% No (=2) Count % within Cervical_cancer 150 250 50.0% 83.3% Count % within Cervical_cancer Total 200 33.3% 400 66.7% 300 300 600 100.0% 100.0% 100.0% Risk Estimate Odds Ratio for smoking (yes / no) Value 5.000 For cohort Cervical_cancer = yes 2.000 For cohort Cervical_cancer = no .400 N of Valid Cases 600 95% Confidence Interval Lower Upper 3.424 7.302 1.722 .311 2.323 .515 Cervical cancer2.sav 23 Matched Pair Study Design Journal of Stroke and Cerebrovascular Diseases, 2005: pp 174-178 24 SBP control (<=140 mmHg) status before and after stroke admission Before After Control Not 合計 Control 20 (67%) 10 30 (47%) Not 14 (41%) 20 34 合計 34 (53%) 30 64 H0: Pbefore=Pafter (中風前SBP控制的比例=中風後SBP控制的比例) Ha: PbeforePafter Stroke.sav 25 Paired categorical data, McNemar test Before After Number of pts Controlled Controlled 20 Not controlled Not controlled 20 Not Controlled Controlled 14 Controlled Not controlled 試問住院前後血壓控制情形有改善嗎? 10 26 Chi-Square Tests Asymp. Sig. Exact Sig. Exact Sig. Value df (2-sided) (2-sided) (1-sided) Pearson Chi-Square Fisher's Exact Test McNemar Test N of Valid Cases 4.158a 1 .041 .049 .036 .541c 64 a. 0 cells (.0%) have expected count less than 5. The minimum expected count is 14.06. b. Computed only for a 2x2 table c. Binomial distribution used. 應該使用McNemar檢定的結果, 而非一般的Chi-square檢定結果。 27 Thank you! 28