1報(bào)告地點(diǎn)：萬芳醫(yī)院報(bào)告時(shí)間：2009/11/6報(bào) 告 者：和信醫(yī)院 李建勳 藥師指導(dǎo)藥師：2 Assess：了解臨床的需求（Clinical Problem）Ask：發(fā)現(xiàn)問題的所在（Question）Acquire：找尋最好的資料（Best Evidence）Appraise：分析資料（Validity,Importance）Apply：應(yīng)用在病人身上（Patient）3Mr.Cheng is a 60 year old male patient.He was diagnosed as hepatitis B and C virus infection related hepatocellular carcinoma(HCC)on 2003.He has received radiotherapy during 2003/1/243/6,transarterial chemoembolization(TACE)during 2006/3/42007/12/4,computer tomography-guided radiofrequency ablation(RFA)on 2008/8/5.In 2009 April,abdominal sonography showed that HCC progress to retroperitoneal lymph nodes,which is suspected extrahepatic seeding tumor between abdominal wall and right lobe liver.At that time,the lab data showed elevated alpha-fetoprotein(AFP)93.46 ng/mL.At that time,the doctor considered sorafenib 400mg PO BID for this patient.Is sorafenib effective for this patient?4 Assess：了解臨床的需求（Clinical Problem）Ask：發(fā)現(xiàn)問題的所在（Question）Acquire：找尋最好的資料（Best Evidence）Appraise：分析資料（Validity,Importance）Apply：應(yīng)用在病人身上（Patient）5 背景問題（Background Questions）：對(duì)疾病的基本認(rèn)識(shí) 5W1H：Who,Where,What,When,How,Why 疾病的某一面向 前景問題（Foreground Questions）：對(duì)病人的特定問題 處理某疾病病人的特定問題 每個(gè)病人有不同的特性：年齡、性別、伴隨疾病與疾病嚴(yán)重程度等6 肝癌是全球排名第五位的癌癥，每年約有五十萬至一百萬的新病例。肝癌更是死亡率第三位的癌癥，全球每年約有六十萬人死於肝癌。全球肝癌的盛行率有地理分佈的差異，低盛行區(qū)如北美和中美洲等，其盛行率約每10萬人口3-4 人；而亞太地區(qū)屬於肝癌高盛行區(qū)，盛行率高達(dá)每10萬人口30-40 人。西元 2000 年全球肝癌患者，亞洲地區(qū)高達(dá)44 萬人，而北美地區(qū)只有1萬 2仟人，全球肝癌患者約 75%集中於亞洲地區(qū)。肝癌為臺(tái)灣 10 大癌癥發(fā)生率的第二位，每10萬人口發(fā)生率男性約 26人、女性約8人，男女比例約 3:1。林志陵,高嘉宏.肝癌的流行病學(xué).中華癌醫(yī)會(huì)誌.2008;24(5):277-2817 Liver cirrhosis Hepatitis B Virus Hepatitis C Virus Alcohol Cigarette smoking Betel nut Afaltoxin Obesity Fatty liver Non-alcohol steatohepatitis(NASH)Diabetes Hereditary tyrosinemia Hepatic porphyria Genetic hemochromatosis 1 antitrypsin deficiency林志陵,高嘉宏.肝癌的流行病學(xué).中華癌醫(yī)會(huì)誌.2008;24(5):277-2818 Common Symptoms Abdominal pain Weight loss Weakness Fullness and anorexia Abdominal Swelling Jaundice Vomiting Common Physical Sign Hepatomegaly Hepatic bruit Ascites Splenomegaly Jaundice Wasting FeverDeVita VT,et al.Devita,Hellman&Rosenbergs Cancer:Principles&Practice of Oncology,8th Edition9 Radiology X-ray Sonography Computed tomography(CT)Magnetic resonance imaging(MRI)Biopsy Alpha-fetoprotein(AFP)SerologyDeVita VT,et al.Devita,Hellman&Rosenbergs Cancer:Principles&Practice of Oncology,8th Edition10 Surgery Partial hepatectomy Liver transplantation Local Ablative Therapy Cryosurgery Microwave ablation Ethanol injection Acetic acid injection Radiofrequecy ablation(RFA)Regional Therapy(hepatic artery transcatheter treatments)Transarterial chemotherapy Transarterial embolization(TAE)Transarterial chemoembolization(TACE)Transarterial radiotherapy90Y microspheres131I lipiodol Conformal external-beam radiation therapy Systemic TherapyDeVita VT,et al.Devita,Hellman&Rosenbergs Cancer:Principles&Practice of Oncology,8th Edition111.除了腫瘤侵犯程度外，需考慮肝臟存留機(jī)能2.病理報(bào)告取得不易，臨床分期應(yīng)用廣泛3.依應(yīng)用目的區(qū)分預(yù)後的預(yù)測(cè)與治療方法的選擇12 Prognosis TNM Okuda CLIP(Cancer of the Liver Italian Program)JIS(Japanese Integrated Score)Treatment BCLC(Barcelona Clinic Liver Cancer)13盧勝男,顏毅豪,林芷蕓等.肝細(xì)胞癌之臨床分期.中華癌醫(yī)會(huì)誌.2008;24(5):295-3031415CLIP:Cancer of the Liver Italian Program16JIS:Japanese Integrated Score17BCLC:Barcelona Clinic Liver CancerBruix J and Sherman M.Hepatology 2005;42(5):1208-123618Kudo M.Oncology 2007;72(supp1):2-15JSH:Japan Society of Hepatology;TAI:transcatheter arterial infusion chemotherapy，也稱作hepatic arterial infusion(HAI)19 背景問題（Background Questions）：對(duì)疾病的基本認(rèn)識(shí) 5W1H：Who,Where,What,When,How,Why 疾病的某一面向 前景問題（Foreground Questions）：對(duì)病人的特定問題 處理某疾病病人的特定問題 每個(gè)病人有不同的特性：年齡、性別、伴隨疾病與疾病嚴(yán)重程度等20One-sentenced Question（請(qǐng)用一句話表達(dá)你的問題）As to advanced HCC patient,can sorafenib improve survival?Patient or Problem（描述病患、疾病或病徵的型態(tài)）Hepatocellular carcinomaIntervention or Investigation（包括治療、檢驗(yàn)、或預(yù)後因子）SorafenibComparison（通常用於比較目前的治療或診斷）PlaceboOutcome（對(duì)病患有意義的臨床結(jié)果）SurvivalType of Question Therapy Diagnosis Prognosis Harm Others_Type of Study Design Meta-analysis RCT Cohort Studies Case Control Studies Case Series Case Reports21 Assess：了解臨床的需求（Clinical Problem）Ask：發(fā)現(xiàn)問題的所在（Question）Acquire：找尋最好的資料（Best Evidence）Appraise：分析資料（Validity,Importance）Apply：應(yīng)用在病人身上（Patient）2223搜尋策略：Systems Summary Synopses Synthesis Studies關(guān)鍵字Primary or MeSH Term同義字1同義字2PHepatocellular carcinomaORORANDISorafenibORORANDCPlaceboORORANDOSurvivalORORAND搜尋結(jié)果 174 articles:limit to clinical trials(by reviewer)1.Llovet JM,Ricci S,Mazzaferro V,et al.N Engl J Med 2008;359(4):378-90(Phase III Trial)2.Cheng AL,Kang YK,Chen Z,et al.Lancet Oncol 2009;10(1):25-34(Phase III Trial)3.Abou-Alfa GK,Schwart L,Ricci S,et al.J Clin Oncol 2006;24:4293-4300(Phase II Trial)4.Stumberg D,Clark JW,Awada A,et al.The Oncologist 2007;12:426-437(Phase I Trial)5.Furuse J,Ishii H,Nakachi K,et al.Cancer Sci 2008;99:159-165(Phase I Trial)6.Worns MA,Weinmann A,Pfingst K,et al.J Clin Gastroenterol 2009;43:489-495(Small sample size,regardless of liver function,and negative results)7.11 articles shows the efficacy of combination with other systemic chemotherapy 資料來源：UpToDate Cochrane Library ACPJP Pubmed _關(guān)鍵性結(jié)論24 Assess：了解臨床的需求（Clinical Problem）Ask：發(fā)現(xiàn)問題的所在（Question）Acquire：找尋最好的資料（Best Evidence）Appraise：分析資料（Validity,Importance）Apply：應(yīng)用在病人身上（Patient）25N Engl J Med 2008;359:378-90Llovet JM,Ricci S,Mazzaferro V,Hilgard P,Gane E,et al.26Study Design:Randomized,double-blinded,placebo-controlled trialStudy Place:121 centers in 21 countries in Europe,North America,South America,and AustraliaIntervention:sorafenib 400mg BID or placeboInclusion Criteria:1.Advanced HCC,confirmed by pathological analysis2.ECOG performance status of 2 or less3.Child-Pugh liver function class A4.Adequate hematological(PLT,Hb),hepatic(Alb,Bil-T,GOT,GPT),and renal function(sCr)Exclusion Criteria:1.Previously received molecularly targeted therapy or systemic treatment27 The Primary Outcome Overall Survival Time to Symptomatic Progression:FHSI84,ECOG progress to 4,or death The Secondary Outcome Time to Radiological Progression:by RECIST The Disease-control Rate:CR+PR+SD SafetyFHSI8 Questionnaire：用以評(píng)估HCC病人癥狀的嚴(yán)重程度CR:complete response;PR:partial response;SD:stable disease28902 Patients were screened300 were excluded 244 had protocol exclusion criteria 24 withdrew consent 15 had an adverse event 11 died 6 were lost to folloe-up602 underwent randomization299 were assigned to receive sorafenib(intention-to-treat population)303 were assigned to receive placebo(intention-to-treat population)1 had an adverse event1 had a protocol violation1 had a protocol violation297 received sorafenib(safety population)302 received placebo(safety population)226 Discontinued sorfenib 86 had an adverse event 61 had radiologic and symptomatic progression 28 withdrew consent 3 died 1 had ECOG score of 4 47 had other reason242 Discontinued placebo 90 had an adverse event 62 had radiologic and symptomatic progression 25 withdrew consent 7 died 6 had ECOG score of 4 52 had other reason71 included in the ongoing study60 included in the ongoing studyLlovet JM,et al.New Engl J Med 2008;359:378-90 29VariableSorafenib(N=299)Placebo(N=303)Sorafenib(N=299)Placebo(N=303)Age yr64.9 11.266.3 10.2 Lung67(22)58(19)Sex no(%)Macroscopic vascular invasion,extrahepatic spread,or both Male260(87)264(87)Absent90(30)91(30)Female39(13)39(13)Present209(70)212(70)Region no(%)Child-Pugh class no(%)Europe and Australia263(88)263(87)A284(95)297(98)North America27(9)29(10)B14(5)6(2)Central and South America9(3)11(4)Biochemical analysisCause of disease no(%)Albumin g/dL Hepatitis C only87(29)82(27)Median3.94.0 Alcohol only79(26)80(26)Range2.7-5.32.5-5.1 Hepatitis B only56(19)55(18)Total bilirubin mg/dL Unknown49(16)56(19)Median0.70.7 Other28(9)29(10)Range0.1-16.40.2-6.1ECOG performance status no(%)Alpha-fetoprotein ng/mL o161(54)164(54)Median44.399.0 1114(38)117(39)Range0-208 x 1040-5 x 105 224(8)22(7)Previous therapy no(%)BCLC stage no(%)Surgical resection57(19)62(20)B(intermediate)54(18)51(17)Locoregional therapy C(advanced)244(82)252(83)transarterial chemoembolization86(29)90(30)Macroscopic vascular invasion no(%)108(36)123(41)percutaneous ethanol injection28(9)20(7)Extrahepatic spread no(%)159(53)150(50)radiofrequency ablation17(6)12(4)Lymph nodes89(30)65(21)radiotherapy13(4)15(5)301.本篇研究病人分配是否隨機(jī)？是 隨機(jī)分配是否對(duì)研究人員保密？是2.本篇研究隨機(jī)分配後的病人是否都被納入分析？是3.在接受治療當(dāng)中，病人與醫(yī)療人員是否雙盲？是4.除了要比較的治療外，兩組病人是否都被同等對(duì)待？是5.一開始分配的兩組條件是否相同？是31OutcomeSorafenib(N=299)Placebo(N=303)Hazard ratio(95%CI)P valueOverall survival(mo)0.69(0.55-0.87)0.001 Median10.77.9 95%CI9.413.36.89.11-yr survival rate(%)44330.009Time to symptomatic progression(mo)1.08(0.88-1.31)0.77 Median4.14.9 95%CI3.5-4.84.2-6.3Time to radiologic progression(mo)0.58(0.45 0.74)0.001 Median5.52.8 95%CI4.1-6.92.7-3.9Level of response(%)Complete00NA Partial210.05 Stable disease71670.17Disease-control rate(%)43320.002Llovet JM,et al.New Engl J Med 2008;359:378-90 32Llovet JM,et al.New Engl J Med 2008;359:378-90 331.最重要的副作用：Grade 3/4 Hand-foot Skin ReactionControl event rateExperimental event rateRelative risk increaseAbsolute risk increaseNumber needed to harmCEREERRRI=(EER-CER)/CERARI=EER-CERNNH=1/ARI0/302=0%8/297=2.693602%2.693602%37ARI:以sorafenib治療100人，會(huì)增加約3人三/四級(jí)手足癥候群的機(jī)會(huì)。NNH:每治療37位病人，會(huì)有1人會(huì)發(fā)生三/四級(jí)手足癥候群。NNT(Number Need to Treat)or NNH(Number Need to Harm):在一段實(shí)驗(yàn)期間內(nèi)，使一位病人達(dá)到實(shí)驗(yàn)組治療之有益結(jié)果（或不良反應(yīng)）所需治療的病人數(shù)目。341.最重要的副作用：Grade 3/4 diarrheaControl event rateExperimental event rateRelative risk IncreaseAbsolute risk increaseNumber needed to harmCEREERRRI=(EER-CER)/CERARI=EER-CERNNH=1/ARI2/302=0.662251%8/297=2.693602%3.0632632.028649%49ARI:以sorafenib治療100人，會(huì)增加2人三/四級(jí)腹瀉的機(jī)會(huì)。NNH:每治療49位病人，會(huì)有1人會(huì)發(fā)生三/四級(jí)腹瀉。NNT(Number Need to Treat)or NNH(Number Need to Harm):在一段實(shí)驗(yàn)期間內(nèi)，使一位病人達(dá)到實(shí)驗(yàn)組治療之有益結(jié)果（或不良反應(yīng)）所需治療的病人數(shù)目。35Lancet Oncol 2009;10:25-34Cheng AL,Kang YK,Chen ZD,Tsao CJ,Qin SK,et al.36271 Patients were screened45 Not randomized 3 had an adverse event 4 withdrew 1 lost to follow-up 37 protocol exclusion criteria226 underwent randomization150 were assigned to receive sorafenib(intention-to-treat population)76 were assigned to receive placebo(intention-to-treat population)1 excluded due to adverse event1 had a protocol violation149 received sorafenib(safety population)75 received placebo(safety population)129 Discontinued sorfenib 69 had disease progresson 22 had adverse events 23 withdrew consent 12 died 2 lost to follow-up 1 non-compliant to treatment72 Discontinued placebo 48 had disease progression 7 had adverse events 11 withdrew consent 2 died 3 lost to follow-up 1 protocol violation20 included in the ongoing study3 included in the ongoing studyCheng AL,et al.Lancet Oncol 2009;10:25-34 37381.本篇研究病人分配是否隨機(jī)？是 隨機(jī)分配是否對(duì)研究人員保密？是2.本篇研究隨機(jī)分配後的病人是否都被納入分析？是3.在接受治療當(dāng)中，病人與醫(yī)療人員是否雙盲？是4.除了要比較的治療外，兩組病人是否都被同等對(duì)待？是5.一開始分配的兩組條件是否相同？是39OutcomeSorafenib(N=299)Placebo(N=303)Hazard ratio(95%CI)P valueOverall survival(mo)0.69(0.55-0.87)0.001 Median1077.9 95%CI9.413.36.89.11-yr survival rate(%)44330.009Time to symptomatic progression(mo)1.08(0.88-1.31)0.77 Median4.14.9 95%CI3.5-4.84.2-6.3Time to radiologic progression(mo)0.58(0.45 0.74)COX-2 inhibitor 列舉同義字 Conventional conventional OR traditional 避免使用縮寫 CVD cardiovascular diseases 使用明確詞彙 Cardiovascular risk cardiovascular diseases AND risk 調(diào)整廣狹義詞 Cardiovascular diseases myocardial infarction69ArticlesQueriesTranslationTranslationDatabaseStandard(MeSH)authoruserCyclo-oxygenase-2 selective inhibitors and nonsteroidal anti-inflammatory drugs:balancing gastrointestinal and cardio-vascular risk.BMC Musculoskelet Disord 2007 Aug 3;8:73.Cardiovascular disease AND risk1.Cardiovascular disease/chemically induced*2.Risk 1.Cardiovascular disease2.Risk 70 單字 或 片語 Cardiovascular diseases OR cardiovascular diseases 切截字 Therap*:therapy,therapeutic,therapeutics 同義字（用MeSH可避免大部分的困擾）單複數(shù)：inhibitor/inhibitors；英美拼法：edema/oedema；全名縮寫：cardiovascular disease/CVD；同義異形字：carotid ultrasonography/carotid ultrasound/carotid Doppler 廣狹義詞 Cardiovascular disease myocardial infarction711.彈性組合檢索：P+I+C+O2.透過Detail檢驗(yàn)是否選用MeSH term3.透過Display:Citation線索修正關(guān)鍵字4.限定條件：Limit(年齡、性別、人類、研究設(shè)計(jì))3.滾出更多文章：Related Articles7273Llovet JM,et al.Sorafenib in Advanced Hepatocellular Carcinoma.New Engl J Med 2008;359:378-90 研究設(shè)計(jì)研究設(shè)計(jì)人人/動(dòng)物、年齡、性別動(dòng)物、年齡、性別74 選用MeSH term（並避免雙引號(hào)、切截字元）COX-2 selective inhibitor COX-2 inhibitor 列舉同義字 Conventional conventional OR traditional 避免使用縮寫 CVD cardiovascular diseases 使用明確詞彙 Cardiovascular risk cardiovascular diseases AND risk 調(diào)整廣狹義詞 Cardiovascular diseases myocardial infarction75 單字 或 片語 Cardiovascular diseases OR cardiovascular diseases 切截字 Therap*:therapy,therapeutic,therapeutics 同義字（用MeSH可避免大部分的困擾）單複數(shù)：inhibitor/inhibitors；英美拼法：edema/oedema；全名縮寫：cardiovascular disease/CVD；同義異形字：carotid ultrasonography/carotid ultrasound/carotid Doppler 廣狹義詞 Cardiovascular disease myocardial infarction76 選用MeSH term（並避免雙引號(hào)、切截字元）COX-2 selective inhibitor COX-2 inhibitor 列舉同義字 Conventional conventional OR traditional 避免使用縮寫 CVD cardiovascular diseases 使用明確詞彙 Cardiovascular risk cardiovascular diseases AND risk 調(diào)整廣狹義詞 Cardiovascular diseases myocardial infarction771.彈性組合檢索：P+I+C+O2.透過Detail檢驗(yàn)是否選用MeSH term3.透過Display:Citation線索修正關(guān)鍵字4.限定條件：Limit(年齡、性別、人類、研究設(shè)計(jì))3.滾出更多文章：Related Articles78彈性組合檢索79謹(jǐn)慎：使用謹(jǐn)慎：使用limits後，後，in process、supplied by publisher、非、非Medline的的文獻(xiàn)將被排除，因?yàn)榇藱C(jī)制是針對(duì)已被文獻(xiàn)將被排除，因?yàn)榇藱C(jī)制是針對(duì)已被Medline做過索引程序的書目所設(shè)計(jì)做過索引程序的書目所設(shè)計(jì)8081Llovet JM,et al.Sorafenib in Advanced Hepatocellular Carcinoma.New Engl J Med 2008;359:378-90 研究設(shè)計(jì)研究設(shè)計(jì)人人/動(dòng)物、年齡、性別動(dòng)物、年齡、性別82 Validity 可信度 Importance 重要性 Practicability 應(yīng)用性83Internal Validity:Is there a causal relationship between two variables?Criteria to establishing a cause-effect relationship:1.Temporal Precedence:the cause must happen before the effect.2.Co-variation:If X then Y,and if not X then not Y.Or a dose-response relationship:if more of the X then more of Y,and if less of X then less of Y.3.Without other Plausible Explanations:the problem with the“third variable”or“missing variable”.Other variable(s)causes the outcome.It is important but not always possible to“rule out”plausible explanations.841.本篇研究病人分配是否隨機(jī)？隨機(jī)分配是否對(duì)研究人員保密？2.在接受治療當(dāng)中，病人與醫(yī)療人員是否雙盲？3.除了要比較的治療外，兩組病人是否都被同等對(duì)待？4.一開始分配的兩組條件是否相同？5.本篇研究隨機(jī)分配後的病人是否都被納入分析？85Montori VM and Guyatt GH.CMAJ 2001;165(10):1339-1341866.病人是否追蹤時(shí)間夠長且完整？所有研究對(duì)象追蹤的時(shí)間是否夠久來觀察到測(cè)量結(jié)果的發(fā)生？失去追蹤比率 20%，嚴(yán)重影響實(shí)驗(yàn)結(jié)果，通常結(jié)果不被接受。假定一實(shí)驗(yàn)有100人，4人死亡，如果有20人失去追蹤，出死亡率=4/80=5%如果失蹤的20人皆存活，4/100=4%如果失蹤的20人皆死亡，24/100=24%87 Validity 可信度 Importance 重要性 Practicability 應(yīng)用性88 本篇文獻(xiàn)研究的結(jié)果在臨床上重要嗎？強(qiáng)度：本實(shí)驗(yàn)是否有效或有害 有效：RRR:relative risk reduction ARR:absolute risk reduction NNT:number need to treat 有害：RR:relative risk OR:odd ratio 效度：本實(shí)驗(yàn)是否準(zhǔn)確？95%confidence interval(95%CI)89 Validity 可信度 Importance 重要性 Practicability 應(yīng)用性90如何將本文獻(xiàn)資料應(yīng)用在我們的病人身上？1.該治療方式在我們醫(yī)療系統(tǒng)是否可行？2.該研究結(jié)論是否可應(yīng)用在我們的患者？3.我們的患者透過該治療可能得到的好處與傷害（benefits and harms）？4.我們患者的價(jià)值觀及對(duì)結(jié)果的期待？911.目前Sorafenib(Nexavar)在本院為臨採品項(xiàng)，無健保價(jià)，病人需自費(fèi)購買，自費(fèi)價(jià)為一錠1387元，一天5547元。2.本研究結(jié)論應(yīng)用在此病人時(shí)可能的限制為：1.SHARP Trial收納的研究對(duì)象為歐洲與美國的病人，發(fā)生HCC的原因以HCV與alcohol為主，而此病人為HBV-related HCC，研究結(jié)果可能不適用。2.SHARP Trial的研究結(jié)果應(yīng)用於亞洲國家人種時(shí)，會(huì)有基因上的差異，可能不適用。3.依據(jù)SHARP Trial的研究結(jié)果，我們預(yù)期此病人透過治療存活時(shí)間可延長2.8個(gè)月，但發(fā)生Grade 3/4的手足癥候群、腹瀉的NNH分別為37和49。92931.1972年英國臨床流行病學(xué)者Archie Cochrane提出實(shí)證醫(yī)學(xué)的概念。強(qiáng)調(diào)Randomized controlled trials 的重要性，並認(rèn)為所有醫(yī)療行為都應(yīng)有嚴(yán)謹(jǐn)研究及證實(shí)為有效的根據(jù)，才能將醫(yī)療資源做最有效的運(yùn)用。2.在近代，實(shí)証醫(yī)學(xué)這個(gè)名詞於1992年由加拿大McMaster大學(xué)的Gordon Guyatt博士正式提出，隨後引起國際醫(yī)學(xué)界廣泛關(guān)注。結(jié)合網(wǎng)路並強(qiáng)調(diào)以隨機(jī)對(duì)照實(shí)驗(yàn)結(jié)果改進(jìn)各種醫(yī)療計(jì)劃，David L.Sackett於1993年成立Cochrane Collaboration 和 Cochrane Library。94SUNY Downstate EBM Tutorial http:/library.downstate.edu/EBM2/research.htm95SUNY Downstate EBM Tutorial http:/library.downstate.edu/EBM2/research.htm96SUNY Downstate EBM Tutorial http:/library.downstate.edu/EBM2/research.htm97SUNY Downstate EBM Tutorial http:/library.downstate.edu/EBM2/research.htm98SUNY Downstate EBM Tutorial http:/library.downstate.edu/EBM2/research.htm991001.這個(gè)治療是否可行？是病患可否負(fù)擔(dān)？可2.這個(gè)治療對(duì)你的病人有幫助嗎？有3.評(píng)估我們的患者透過該治療可能得到的好處與傷害。1)估計(jì)本國此疾病的發(fā)生率（PEER,patients expected event rate）PEER=16.2%估計(jì)方法 PEER=論文中的CER1012)根據(jù)疾病的發(fā)生率（PEER），計(jì)算本治療在國內(nèi)的NNT、NNH。PEER method，假設(shè)RRR，RRI不受地區(qū)影響改變。NNT=1/(PEER x RRR)=1/(0.162 x 0.13)=47.48NNH=1/(PEER x RRI)=1/(0.07 x 0.142)=100.603)根據(jù)個(gè)人經(jīng)驗(yàn)粗估本疾病治療好處及副作用的危險(xiǎn)性是論文中的 f 倍ft=1 NNTpatient=NNTreported/ft=47.48fh=1 NNHpateint=NNHreported/fh=100.601024)根據(jù)病人的期望，比較患者接受此治療的好處與壞處。Sdisease（得到疾病的嚴(yán)重度）=0.1Sharm（進(jìn)行治療的副作用）=0.9S(severity factor)=Sharm/Sdisease=95)患者接受此治療得到的利害比（LHH,likelihood of being helped or harmed）原始LHH=ARR:ARI=(1/NNT):(1/NNH)=2.12Adjusted LHH=(1/NNT)x ft x S:(1/NNH)x fh =19.08103 Definition:the best available approximation to the truth or falsity of a given proposition,inference,or conclusion.Typology of validity Conclusion Validity(statistical conclusion validity):Is there a relationship between the two variables?The confidence we have on the conclusions we reach about relationships in our data(i.e.there is a significant correlation between two variables.)It concerns only whether such a relationship exists,but not whether such a relationship is a causal one.Internal Validity:Assuming that there is a relationship in this study,is the relationship a causal one?External Validity:Assuming that there is a causal relationship between the constructs of the cause and the effect,can it be generalized to other persons,places or times.104 Typology of Validity(continued)Content Validity is evaluated by showing how well the content of the test samples the class of situations or subject matter about which conclusions are to be drawn.Criterion-related Validity is evaluated by comparing the test scores with one or more external variables(called criteria)considered to provide a direct measure of the characteristic or behavior in question.Predictive validity indicates the extent to which an individuals future level on the criterion is predicated from prior test performance.Concurrent Validity indicates the extent to which the test scores estimate an individuals present standing on the criterion.Construct Validity is evaluated by investigating what qualities a test measures,that is,by determining the degree to which certain explanatory concepts or constructs account for performance on the test.1051.生存時(shí)間是指從某個(gè)標(biāo)準(zhǔn)時(shí)間（如發(fā)病、確診、開始治療或手術(shù)的時(shí)間）算起至死亡為止的存活時(shí)間。2.廣義的生存時(shí)間為研究開始至事件發(fā)生的時(shí)間。3.生存研究的資料可分為完全資料（complete data）或截尾資料（censored data）。4.因某種原因未能觀察到研究對(duì)象明確的研究結(jié)果，則不能確定該研究對(duì)象的確切生存時(shí)間，這類資料稱為截尾資料（censored data）。5.雖然截尾資料提供的訊息是不完全的，但它告訴我們此研究對(duì)象歷經(jīng)了一段時(shí)間仍然存活。1061.Is the number of censoring small enough?(226+242)/(299+303)=77.74%2.Is the reason of censoring associated to the primary event?Adverse events,radiologic and symptomatic progression,withdrew consent,died of other reason,ECOG score of 4,and other reason107108背景問題Background Questions前景問題Foreground Questions經(jīng)驗(yàn)的累積謝謝觀看/歡迎下載BY FAITH I MEAN A VISION OF GOOD ONE CHERISHES AND THE ENTHUSIASM THAT PUSHES ONE TO SEEK ITS FULFILLMENT REGARDLESS OF OBSTACLES.BY FAITH I BY FAITH