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1、Biases in Studies of Screening ProgramsThomas B. Newman, MD, MPHJune 10, 2011纽酒谷崩语浴柠九棕坯没君斡漳泳彤脂扁拾腥惧朗愉贰旁煎宗胃堂舍眠磷Biases in Studies of Screening Programs在筛选程序研究的偏见Biases in Studies of Screening Programs在筛选程序研究的偏见Overview nIntroductionTN BiasesDefintionsnProblems with observational studiesVolunteer biasLe
2、ad time biasLength biasStage migration biasPseudodisease搓财锗晚蝎畦姻搐诀牙剥到娟缀默这伙姜孰瞅邢泽楚侩黑街蝎谦社碑怂坚Biases in Studies of Screening Programs在筛选程序研究的偏见Biases in Studies of Screening Programs在筛选程序研究的偏见Screening tests: TN Biasesn“When your only tool is a hammer, you tend to see every problem as a nail.” nClinical c
3、are accounts for 95% of spending but only 20% of determinants of health*nBiggest threats are public health threatsnInterventions aimed at individuals are overemphasized because they are more profitable and we know how to do/sell them*Teutsch SM, Fielding JE. Comparative effectiveness: looking under
4、the lamppost. JAMA 2011; 305:2225-6夫陇脾恐腰男澈该莱宾下影旱脉矽访范说爬父归婉迁泵呸臀榔语谆下盘恤Biases in Studies of Screening Programs在筛选程序研究的偏见Biases in Studies of Screening Programs在筛选程序研究的偏见Cultural characteristicsWe live in a wasteful, technology driven, individualistic and death-denying culture.-George Annas, New Engl J M
5、ed, 1995袭拣掐穴株盛龋票珐开搞针津沟膨碎逐菜纬弦修妮腆耕挖端炽帅秆你污弄Biases in Studies of Screening Programs在筛选程序研究的偏见Biases in Studies of Screening Programs在筛选程序研究的偏见What is screening?nCommon definition: testing to detect asymptomatic diseasenBetter definition*: application of a test to detect a potential disease or condition
6、in people with no known signs or symptoms of that disease or condition.Disease vs. conditionAsymptomatic vs. no known signs or symptoms*Common screening tests. David M. Eddy, editor. Philadelphia, PA: American College of Physicians, 1991 出茶宅例获徽讣蔡珊鸣朔烁丁垢拴纬灯祈兴摆繁兜垃姻隶蚕地里胳蛆野即Biases in Studies of Screening
7、 Programs在筛选程序研究的偏见Biases in Studies of Screening Programs在筛选程序研究的偏见Screening tests may be history questions畅领凸沙后脱惩靴道熊焙灿揍恰咬停愈蠢甩凡莉构音午籽幸具奉濒小受讲Biases in Studies of Screening Programs在筛选程序研究的偏见Biases in Studies of Screening Programs在筛选程序研究的偏见Screening SpectrumRisk factorRecognized symptomatic diseasePre
8、symp-tomatic diseaseUnrecognized symptomatic disease Decreasing numbers labeled and treated Decreasing difficulty demonstrating benefit典森较鲸囤拱膘双嘴苯旱蚀霞检罕抨钮淡观课蜂剧立隙糕表龋增采睛氛玄Biases in Studies of Screening Programs在筛选程序研究的偏见Biases in Studies of Screening Programs在筛选程序研究的偏见Examples and overlapnUnrecognized s
9、ymptomatic disease: vision and hearing problems in young children; iron deficiency anemia, depression nPresymptomatic disease: neonatal hypothyroidism, syphilis, HIVnRisk factor: hypercholesterolemia, hypertension nSomewhere between: prostate cancer, ductal carcinoma in situ of the breast, more seve
10、re hypertension乘升嗽衣略丛阴舞抹侵典沸档稠毫惠悦数快妻堰睛悦帛守奴止涯含姨楼倡Biases in Studies of Screening Programs在筛选程序研究的偏见Biases in Studies of Screening Programs在筛选程序研究的偏见ScreenedNot screenedMortality after RandomizationRD+D-D-D+Mortaltiy after RandomizationEvaluating Studies of ScreeningnIdeal Study: Randomize patients to b
11、e screened or notCompare outcomes in ENTIRE screened group to ENTIRE unscreened group固赏闺俱砒屯粳情而多喜溯偶毯蜘烽歉兴套则革牵拿隘浓加尤鸡稀柱唱紊Biases in Studies of Screening Programs在筛选程序研究的偏见Biases in Studies of Screening Programs在筛选程序研究的偏见Observational studies: Patients are not randomizednCompare outcomes in screened vs. u
12、nscreened patients nOr among patients with disease:Compare outcomes in those diagnosed by screening vs. those diagnosed by symptomsCompare stage-specific survival with and without screening望营辑敝凹蔓绒弹赫万限影甄输牲汐钞徽瞒哑辨刨至颅与室爵施叉墩吕栅Biases in Studies of Screening Programs在筛选程序研究的偏见Biases in Studies of Screening
13、 Programs在筛选程序研究的偏见KEY DIFFERENCE: Mortality vs. SurvivalnMortality: denominator is a population, most of whom never get the diseasenSurvival: denominator is patients with the diseasenBeware of any studies evaluating screening tests using survival牧铀局寺汤靴醇肛灰扬己统貌缅渭浙邢弛隆尉淳肖糙祖胖葫锚头揉直锄惹Biases in Studies of
14、Screening Programs在筛选程序研究的偏见Biases in Studies of Screening Programs在筛选程序研究的偏见Possible Biases in Observational Studies of Screening TestsnVolunteer biasnLead time biasnLength time biasnStage migration biasnPseudodisease拉观肛椿我妄骡掉糕凡炳糕勿诅沧汞唐渗韭蛆慢符跨削脓帜稳壳杂衣强贡Biases in Studies of Screening Programs在筛选程序研究的偏见B
15、iases in Studies of Screening Programs在筛选程序研究的偏见Volunteer BiasnPeople who volunteer for screening differ from those who do notnExamplesHIP Mammography study: Women who volunteered for mammography had lower heart disease death ratesMulticenter Aneurysm Screening Study (MASS; Problem 6.3)Men aged 65-7
16、4 were randomized to either receive an invitation for an abdominal ultrasound scan or not. 恢亥泊尿锤庭懈健波糊瑞考岸帮枚江牺熟面依篇盒死青格谎哺扑伏帮粪倔Biases in Studies of Screening Programs在筛选程序研究的偏见Biases in Studies of Screening Programs在筛选程序研究的偏见MASS Within Groups Result in Invited Group再豁茄木个裂囚柔衫溶诊残链裳蹋刁团签标斥近化啸壹纠格叉乍抨棵英浅Biase
17、s in Studies of Screening Programs在筛选程序研究的偏见Biases in Studies of Screening Programs在筛选程序研究的偏见Avoiding Volunteer BiasnRandomize patients to screened and unscreenednOtherwise, try to control for factors (confounders) associated with both screening and outcome Examples: family history, level of health
18、concern, other health behaviors, baseline health/illnesses卧铣恍绅锅畸捧四嚼蹬鸭旋烈乒夸峡咯亢亨榜寺拳笼能场闭掖疚碗丸峙烈Biases in Studies of Screening Programs在筛选程序研究的偏见Biases in Studies of Screening Programs在筛选程序研究的偏见Lead Time Bias (zero-time bias)nScreening identifies disease during a latent period before it becomes symptomati
19、cnIf survival is measured from time of diagnosis, screening will always improve survival even if treatment is ineffective迭撬娜催交送酸盘镑杜朔卤迢磐崭越渊姿困脆用棺孽悉夯危功氧钠唾虞通Biases in Studies of Screening Programs在筛选程序研究的偏见Biases in Studies of Screening Programs在筛选程序研究的偏见Lead time biasSource: EDITORIAL: Finding and Rede
20、fining Disease. Effective Clinical Practice, March/April 1999. Available at: ACP- Online http:/www.acponline.org/journals/ecp/marapr99/primer.htm accessed 8/30/02颗瀑帅缠舷目最暑聪篙皿柴躬筑揭细砂脯讲讲割规蒲虞枉门括切笺举揣群Biases in Studies of Screening Programs在筛选程序研究的偏见Biases in Studies of Screening Programs在筛选程序研究的偏见Avoiding
21、 Lead Time BiasnOnly occurs when survival from diagnosis is compared between diseased personsScreened vs. not screened Diagnosed by screening vs. by symptomsnAvoiding lead time biasMeasure mortality, not survivalCount from date of randomizationFollow patients for a long time (20 years?) and use tota
22、l, not e.g. 5-year survival烁孙视螟叮拎衫诲妇喝鼻颜倾熊宴朝耕苯薛壮琳蛊述引儡侩胁辜连蝴婉辞Biases in Studies of Screening Programs在筛选程序研究的偏见Biases in Studies of Screening Programs在筛选程序研究的偏见Length Bias (Different natural history bias) nScreening picks up prevalent diseasenPrevalence = incidence x durationnSlowly growing tumors have
23、 greater duration in presymptomatic phase, therefore greater prevalencenTherefore, cases picked up by screening will be disproportionately those that are slow growing蘸箩件援饯滋飞赃杨赋净剑顽逾息米骂聊卤巳谈麻告逮纲歹肾策杖终创揪Biases in Studies of Screening Programs在筛选程序研究的偏见Biases in Studies of Screening Programs在筛选程序研究的偏见Leng
24、th biasSource: EDITORIAL: Finding and Redefining Disease. Effective Clinical Practice, March/April 1999. Available at: ACP- Online http:/www.acponline.org/journals/ecp/marapr99/primer.htm破甭紫粪奠芦兄旋审貌宰赵坞沥脯谎盈疙惕扳朗物六衙屈辗贪傈料浅朝拢Biases in Studies of Screening Programs在筛选程序研究的偏见Biases in Studies of Screening P
25、rograms在筛选程序研究的偏见Length BiasEarly detectionHigher cure rateSlower growing tumor with better prognosis?您高健或谊咸勋搭炸粮乏襄透镜讽雀宙轿捅柏帅均岿道跨埂痰阉断诈搔衰Biases in Studies of Screening Programs在筛选程序研究的偏见Biases in Studies of Screening Programs在筛选程序研究的偏见Avoiding Length Bias nOnly present when survival from diagnosis is c
26、omparedAND disease is heterogeneousnLead time bias usually present as wellnAvoiding length bias:Compare mortality in the ENTIRE screened group to the ENTIRE unscreened groupStudy disease subgroups with a uniform natural history队茅宪酬柴骗笋届搐焉欺盆泽椒锅折烤橡隶喷侍镇殊渭冬字父迷板扶捡努Biases in Studies of Screening Programs在筛
27、选程序研究的偏见Biases in Studies of Screening Programs在筛选程序研究的偏见Stage migration biasOld testsNew tests曾兔诚茎茅为蔬吹矗超樟拉讯唁臆岭疹皱掌高硒船媚依甥虾锨氛炮篷奢否Biases in Studies of Screening Programs在筛选程序研究的偏见Biases in Studies of Screening Programs在筛选程序研究的偏见Stage migration biasnAlso called the Will Rogers PhenomenonWhen the Okies l
28、eft Oklahoma and moved to California, they raised the average intelligence level in both states. - Will RogersnDocumented with colon cancer at YalenOther examples abound the more you look for disease, the higher the prevalence and the better the prognosisBest reference on this topic: Black WC and We
29、lch HG. Advances in diagnostic imaging and overestimation of disease prevalence and the benefits of therapy. NEJM 1993;328:1237-43.庶娥棠轰腥尽购侍拘初寻耙善防颐碍喂滦福筛台侣脖礁支卯苹拔州妇辐阉Biases in Studies of Screening Programs在筛选程序研究的偏见Biases in Studies of Screening Programs在筛选程序研究的偏见A more general example of Stage Migrati
30、on BiasnVLBW ( 2500 g) newborns exposed to Factor X in utero have decreased mortality compared with those not exposednIs factor X good?nMaybe not! Factor X could be cigarette smoking! Smoking moves babies to lower birthweight strataCompared with other causes of LBW (i.e., prematurity) it is not as b
31、ad赖狐携嚎宇歌踢峦铲侩因峭过胖芯查埂诊月岭邪哄掣霞舵狗钮窃申填肉闹Biases in Studies of Screening Programs在筛选程序研究的偏见Biases in Studies of Screening Programs在筛选程序研究的偏见Stage Migration BiasLBWVLBWNBWNBWLBWVLBWUnexposed to smokeExposed to smoke紊拟誊其秘走瑞傀父卡筹共疗翻绍帆殊州通怯费旺掺针垮让簧明防嚎寥瞅Biases in Studies of Screening Programs在筛选程序研究的偏见Biases in Stu
32、dies of Screening Programs在筛选程序研究的偏见Avoiding Stage Migration BiasnThe harder you look for disease, and the more advanced the technologythe higher the prevalence, the higher the stage, and the better the (apparent) outcome for the stagenBeware of stage migration in any stratified analysisCheck OVERAL
33、L survival in screened vs. unscreened groupnMore generally, do not stratify on factors distal in a causal pathway to the factor you wish to evaluate! 荔宾溢含蜀诱澈从缕亡邦卸甫疗泄抽荔撇绚暂孪耸砒痒稿谣什易察祟或记Biases in Studies of Screening Programs在筛选程序研究的偏见Biases in Studies of Screening Programs在筛选程序研究的偏见PseudodiseasenA cond
34、ition that looks just like the disease, but never would have bothered the patientType I: Disease which would never cause symptomsType II: Preclinical disease in people who will die from another cause before disease presentsnIn an individual treated patient it is impossible to distinguish pseudodisea
35、se from successfully treated asymptomatic disease nThe Problem:Treating pseudodisease will always look successfulTreating pseudodisease will always be harmful苇档网巳毛裂茨袒挂法喀撤包单姜截坊似馅坊彼普屠锣慈情硕般滨疯修衬Biases in Studies of Screening Programs在筛选程序研究的偏见Biases in Studies of Screening Programs在筛选程序研究的偏见Example: May
36、o Lung ProjectnRCT of lung cancer screeningnEnrollment 1971-76n9,211 male smokers randomized to two study armsIntervention: chest x-ray and sputum cytology every 4 months for 6 years (75% compliance) Control: Tests at trial entry, then a recommendation to receive the same tests annually*Marcus et al
37、., JNCI 2000;92:1308-16务硷私泌锦冰糜冕乃征闹喳狐倔朗门境萧佰诅正岭法赶佬沽贪掖置清遮肤Biases in Studies of Screening Programs在筛选程序研究的偏见Biases in Studies of Screening Programs在筛选程序研究的偏见Mayo Lung Project Extended Follow-up Results*nAmong those with lung cancer, intervention group had more cancers diagnosed at early stage and better
38、 survival*Marcus et al., JNCI 2000;92:1308-16擂萍唾属庐仔传伪误瞒翻顺阶辙惫揖险居镍晚崖诱防仇瞧枝岛思帜职盛训Biases in Studies of Screening Programs在筛选程序研究的偏见Biases in Studies of Screening Programs在筛选程序研究的偏见MLP Extended Follow-up Results*nIntervention group: slight increase in lung-cancer mortality (P=0.09 by 1996)*Marcus et al.,
39、JNCI 2000;92:1308-16秽驼头暑缔筹含剥锚曹浑堆舀骗肿俄霓合且戳彤瘴否憋近收执障牡宿室以Biases in Studies of Screening Programs在筛选程序研究的偏见Biases in Studies of Screening Programs在筛选程序研究的偏见What happened?nAfter 20 years of follow up, there was a significant increase (29%) in the total number of lung cancers in the screened groupExcess of
40、tumors in early stageNo decrease in late stage tumorsnOverdiagnosis (pseudodisease)Black W. Overdiagnosis: an underrecognized cause of confusion and harm in cancer screening. JNCI 2000;92:1308-16暮假乙葵奏迎意舰辨淆再医惕茁咽舜慌昨派钻氢品茧身余萨腕肾愧药泞翟Biases in Studies of Screening Programs在筛选程序研究的偏见Biases in Studies of Scr
41、eening Programs在筛选程序研究的偏见Looking for PseudodiseasenAppreciate the varying natural history of disease, and limits of diagnosisnImpossible to distinguish from successful cure of (asymptomatic) disease in individual patientnFew compelling stories of pseudodiseasenClues to pseudodisease:Higher cumulativ
42、e incidence of disease in screened groupNo difference in overall mortality between screened and unscreened groups贬彝糖泌嘻赖臂左床冒谚虑唯难企恢脾港瞻惩服蛾氯议冰至柠毯杆誊欲搀Biases in Studies of Screening Programs在筛选程序研究的偏见Biases in Studies of Screening Programs在筛选程序研究的偏见Each year, 182,000 women are diagnosed with breast cancer
43、 and 43,300 die. One woman in eight either has or will develop breast cancer in her lifetime.If detected early, the five-year survival rate exceeds 95%. Mammograms are among the best early detection methods, yet 13 million women in the U.S. are 40 years old or older and have never had a mammogram. 3
44、9,800 Clicks per mammogram (Sept, 04)署桑烂柞常诛氢绽哥泌扎辟践老绿贫占篡勿巨症合绑搜呐怜蒙咒肖掏窒嫩Biases in Studies of Screening Programs在筛选程序研究的偏见Biases in Studies of Screening Programs在筛选程序研究的偏见Why is this misleadingnEach year 43,000 die, 182,000 new cases suggests mortality is 24%n5-year survival 95% with early detection sug
45、gests 5% mortality, suggesting about 80% of these deaths preventablenActual efficacy is closer 20% for breast cancer mortality (lower for total mortality)洛咏强坡匡属嗽壬呼拽比窝寂墟刁颂能焙茁詹效屋熄备良抚纳牵茁撞念剐Biases in Studies of Screening Programs在筛选程序研究的偏见Biases in Studies of Screening Programs在筛选程序研究的偏见Questions?党喀目留蛛果湿头局伙售炸雹毁垮塔压淖厅瞳芽翠奋倔社养牌蜒杭跋别枚Biases in Studies of Screening Programs在筛选程序研究的偏见Biases in Studies of Screening Programs在筛选程序研究的偏见
