循證治療-2011課件

1、循證臨床實(shí)踐之治療篇新疆醫(yī)科大學(xué)第一附屬醫(yī)院循證醫(yī)學(xué)研究所羅坤循證臨床實(shí)踐(5A)提出問(wèn)題（asking question）證據(jù)檢索（acquiring evidence）評(píng)價(jià)證據(jù) （appraising evidence）應(yīng)用證據(jù) （appling evidence）后效評(píng)價(jià) （after assessment）證據(jù)的特點(diǎn)等級(jí)之分：對(duì)象之分：社區(qū)醫(yī)生、專(zhuān)科醫(yī)生、病人類(lèi)別之分：病因?qū)W、診斷、治療、預(yù)后?證據(jù)等級(jí)金字塔(The Evidence Pyramid)評(píng)價(jià)證據(jù) （appraising evidence）真實(shí)性重要性臨床實(shí)用性Background Randomized trials of

2、 surgery for epilepsy have not been conducted, because of the difficulties involved in designing and implementing feasible studies. The lack of data supporting the therapeutic usefulness of surgery precludes making strong recommendations for patients with epilepsy. We conducted a randomized, control

3、led trial to assess the efficacy and safety of surgery for temporal-lobe epilepsy. 癲癇的外科治療的隨機(jī)對(duì)照研究在設(shè)計(jì)和實(shí)施上很困難，對(duì)癲癇的病人是否手術(shù)無(wú)據(jù)可依，因此設(shè)計(jì)此項(xiàng)研究來(lái)評(píng)價(jià)手術(shù)的有效性和安全性。研究結(jié)果是否可靠 ARE THE RESULTS OF THIS INDIVIDUAL STUDY VALID? 1.Was the assignment of patients to treatment randomized? 分組是否隨機(jī)？ Until recently, it was believed

4、that hormone replacement therapy (HRT) could decrease the risk of coronary artery disease (CAD) in post-menopausal women with a history of established CAD. This belief was based on data from several observational studies which found that women who used HRT had a decreased risk of the disease. Clinic

5、ians and patients were subsequently surprised by the results of a randomized trial of women with established CAD, which found that the risk of CAD was not reduced with HRT! And, even more recently, the Womens Health Initiative study found that HRT was not effective in the primary prevention of CAD e

6、ither. 直到現(xiàn)在，人們還認(rèn)為有冠心病史的絕經(jīng)后婦女用激素替代療法（HRT）可以減少風(fēng)險(xiǎn)。根據(jù)源于一些觀察性研究。但是，隨機(jī)對(duì)照研究卻發(fā)現(xiàn)激素替代療法（HRT）不能減少其風(fēng)險(xiǎn)。最近，有研究表明，激素替代療法（HRT）作為一級(jí)預(yù)防也無(wú)效。Randomization balances the treatment groups for prognostic factors, even if we dont yet know enough about the target disorder to know what they all are. 隨機(jī)化可以將已知和未知的影響因素均勻分布到兩組中去。S

7、tampfer MJ, Colditz GA. Estrogen replacement therapy and coronary heart disease: a quantitative assessment of the epidemiologic evidence. Prev Med 1991; 20: 4763.Hulley S, Grady D, Bush T, etal. Randomized trial of estrogen plus progestin for secondary prevention of coronary heart disease in postmen

8、opausal women. JAMA 1998; 280: 60513.Rossouw JE, Anderson G, Prentice RL, etal. Risks and benefits of estrogen and progestin in healthy postmenopausal women: principal results from the Womens Health Initiative randomized controlled trial. JAMA 2002; 288: 3213.方法80例顳葉癲癇的病人隨機(jī)分為兩組手術(shù)組：40例 手術(shù)+抗癲癇藥物治療對(duì)照組：

9、40例 抗癲癇藥物治療結(jié)果評(píng)價(jià)由不知道研究的兩位資深癲癇專(zhuān)家來(lái)評(píng)價(jià)隨機(jī)隱藏試驗(yàn)設(shè)計(jì)階段病人序列號(hào)123.n隨機(jī)號(hào)xxxxxxxxxxxx分組號(hào):試驗(yàn)實(shí)施階段1、實(shí)施干預(yù)2、觀察指標(biāo)3、收集資料4、分析資料5、統(tǒng)計(jì)處理Randomization and InterventionsAfter stratification according to the presence or absence of generalized motor seizures, patients were randomly assigned to surgical or medical treatment. The ra

10、ndom assignments were prepared outside the study center and delivered in sealed, opaque, sequentially numbered envelopes. 內(nèi)含有隨機(jī)隱藏4.Was follow-up of patients sufficiently long and complete? 隨訪(fǎng)是否完全并且時(shí)間足夠長(zhǎng)？ Ideally, wed like to see that no patients were lost to follow-up because these patients may have

11、 had outcomes that would affect the conclusions of the study. If, for example, patients receiving the experimental treatment dropped out because of adverse outcomes, their absence from the analysis would lead to an over-estimation of the efficacy of the treatment. 理想的話(huà)，最好不要有失訪(fǎng)或脫落，因?yàn)樵谑гL(fǎng)的病人中可能有事件發(fā)生，這將

12、影響研究結(jié)果。例如：試驗(yàn)組的病人因不良事件而脫落，這就會(huì)使治療效果被高估。Worst Case Analysis: 最差結(jié)果分析： Take all patients who were lost to follow-up, assign them the worst case outcome (assume that everyone lost from the group whose remaining members fared better had a bad outcome, and that everyone lost from the group whose remaining m

13、embers fared worse had a good outcome). 假定所有失訪(fǎng)的病人都是結(jié)果相反的病人。比如：本組病人效果良好，則將本組失訪(fǎng)的病人當(dāng)作結(jié)果不良來(lái)處理；如果本組病人效果差，則將本組失訪(fǎng)的病人當(dāng)作結(jié)果良好來(lái)處理。(It would be unusual for a trial to withstand a worst case analysis if it lost more than 20% of itspatients) （如果失訪(fǎng)超過(guò)20%，很少有臨床試驗(yàn)?zāi)芙?jīng)受住最差結(jié)果分析的考驗(yàn)）5.Were all patients analyzed in the grou

14、ps to which they were randomized? 是否所有的病人都在自己的隨機(jī)分配組中進(jìn)行分析？Intention-to-treat Analysis:治療意向分析： To preserve the value of randomization, we should demand an “intention-to-treat analysis” whereby all patients are analyzed in the groups to which they were initially assigned, regardless of whether they rec

15、eived their assigned treatment. It is important that we not only look for the term “intention-to-treat analysis” in the methods but also look at the results to ensure that this analysis was actually done. 為了確保隨機(jī)化的功效，不論病人是否接受相應(yīng)的治療，所有的病人都必須在自己的隨機(jī)分配組中進(jìn)行分析。我們?cè)诜治鑫恼聲r(shí)，不僅要看有無(wú)“治療意向分析”的字樣，還要仔細(xì)觀察是否確實(shí)正確地實(shí)施了。The

16、 absolute benefit ofsurgery in terms of the rate of freedom from seizures was large (50 percentage points for seizures impairingawareness and 35 percentage points for all seizures) and precise (confidence intervals were narrow). Our intention-to-treat analysis yielded a rate of freedom from seizures

17、 impairing awareness in the surgical group of 58 percent. Although this rate is lower than that found in studies assessing the cumulative freedom from seizures from the time of surgery (69 percent in one study and 63 percent in another. the rate of freedom from seizures among the 36 patients who act

18、ually underwent surgery was 64 percent6.Were patients, clinicians, and study personnel kept blind to treatment? 治療是否盲病人、醫(yī)師和研究者？ Blinding is necessary to avoid patients reporting of symptoms or their adherence to treatment being affected by hunches about whether the treatment is effective. Similarly,

19、 blinding prevents the report or interpretation of symptoms from being affected by the clinicians or outcomes assessors suspicions about the effectiveness of the study intervention. When patients and clinicians cant be kept blind (such as in surgical trials), often it is possible to have other, blin

20、ded clinicians assess clinical records (purged of any mention of treatment) or to use objective outcome measurements. 盲病人是為了避免病人知情后對(duì)癥狀感知的影響以及對(duì)隨機(jī)化的順從。同理，盲醫(yī)師和研究者是為了避免他們知情后對(duì)癥狀報(bào)告和解釋的影響。 當(dāng)病人和醫(yī)師都無(wú)法盲時(shí)（如外科手術(shù)），則盲獨(dú)立評(píng)價(jià)者或采用客觀指標(biāo)評(píng)價(jià)。7. Were groups treated equally, apart from the experimental therapy? 除干預(yù)措施外，是否其他的治

21、療都一樣？ Blinding of patients, clinicians and study personnel can prevent them from adding any additional treatments (or “co-interventions”), apart from the experimental treatment, to just one of the groups. 盲病人、醫(yī)師和研究者就可以防止某組有意或無(wú)意接受額外治療。There were no crossovers from the medical group to the surgical gr

22、oupARE THE VALID RESULTS OF THIS INDIVIDUAL STUDY IMPORTANT?研究結(jié)果是否重要？ The relative risk reduction (RRR) (relative benefit increase or relative risk increase) calculated as (|CER EER|/CER). In this example, the RRR is (5.7% 4.3%)/5.7% (i.e. 25%), and we can say that statin therapy decreased the risk

23、of stroke by 25% relative to those who received placebo. 相對(duì)風(fēng)險(xiǎn)減少（ relative risk reduction，RRR) 是治療研究最常用的指標(biāo)，根據(jù)研究的不同，也可以稱(chēng)為相對(duì)益處增加（ relative benefit increase ）或相對(duì)風(fēng)險(xiǎn)增加（ relative risk increase），計(jì)算方法是： |CER EER|/CER 本例中，RRR (5.7% 4.3%)/5.7% 25%。換句話(huà)說(shuō)就是：與對(duì)照組相比，他汀治療組中風(fēng)的風(fēng)險(xiǎn)減少了25%。 The RRR doesnt reflect the risk

24、 of the event without therapy (the CER, or baseline risk), and therefore cannot discriminate huge treatment effects from small ones. Absolute risk reduction (ARR) (or the risk difference)(absolute benefit increase or absolute risk increase) and it preserves the baseline risk. The inverse of the ARR

25、(1/ARR) is a whole number and has the useful property of telling us the number of patients that we need to treat (NNT) with the experimental therapy for the duration of the trial in order to prevent one additional bad outcome. 絕對(duì)風(fēng)險(xiǎn)減少(absolute risk reduction，ARR) 或稱(chēng)風(fēng)險(xiǎn)差(risk difference)，根據(jù)研究的不同，也可以稱(chēng)為絕

26、對(duì)益處增加(absolute benefit increase ）或絕對(duì)風(fēng)險(xiǎn)增加（ absolute risk increase) 。 絕對(duì)風(fēng)險(xiǎn)減少的倒數(shù)1/ARR，我們稱(chēng)之為NNT（number needed to treat），也就是需要治療多少病人可以防止一例不良事件。 We can describe the adverse effects of therapy in an analogous fashion, as the number needed to cause harm to one more patient (NNH) from the therapy. The NNH is

27、 calculated as 1/ARI. In the statin study, 0.03% of the control group experienced rhabdomyolysis compared with 0.05% of patients who experienced this in the group that received a statin. This absolute risk increase of |0.03% 0.05%|=0.02% generates an NNH over 5 years of 5000. This means that wed nee

28、d to treat 5000 patients with a statin for 5 years to cause one additional patient to have rhabdomyolysis. 我們也可以用同樣的方法描述不良事件，用絕對(duì)風(fēng)險(xiǎn)增加的倒數(shù)1/ARI算出NNH（number needed to harm），也就是需要治療多少病人可以發(fā)生一例不良事件。在本例研究中，對(duì)照組有0.03%的病人發(fā)生橫紋肌溶解，而治療組有0.05%。則，絕對(duì)風(fēng)險(xiǎn)增加是|0.03% 0.05%|=0.02% ，NNH=5000，也就是5000人治療5年才有1例出現(xiàn)橫紋肌溶解。2.How pr

29、ecise is this estimate of the treatment effect? 治療效果的估計(jì)有多精確？ NNTs are estimates of the truth and we should specify the limits within which we can confidently state that the true NNT lies. If we want to specify the limits within which the true NNT lies 95% of the time, its called specifying the “95%

30、confidence interval” (95% CI). The confidence interval provides the range of values that are likely to include the true risk and quantifies the uncertainty in measurement. NNT是客觀事實(shí)的估算值，我們必須界定一個(gè)范圍并在一定程度上肯定真實(shí)值是在這個(gè)范圍內(nèi)。如果我們界定一個(gè)范圍，真實(shí)值在95%的時(shí)間內(nèi)都處在這個(gè)范圍中，我們稱(chēng)之為“95%可信區(qū)間”（95% confidence interval，95% CI）?？尚艆^(qū)間是一個(gè)

31、數(shù)值范圍，真實(shí)值就在這個(gè)范圍內(nèi)。可信區(qū)間量化了測(cè)量的不確定性。KaplanMeier Event-free Survival Curves Comparing the Cumulative Percentages of Patientsin the Two Groups Who Were Free of Seizures Impairing Awareness (Complex Partial or Generalized Seizures) (Panel A) and Free of All Seizures (Including Auras) (Panel B). In both analyses, more patients in the surgical group were free of seizures (P0.001 by the log-rank test). Follow-up began 1 day after surgery in the surgical group and 25 days after randomization in themedical group. Monthly Rates of