統(tǒng)計(jì)在醫(yī)學(xué)上的應(yīng)用

1、統(tǒng)計(jì)在醫(yī)學(xué)上的應(yīng)用The application of statistics in medicine西醫(yī)在上個(gè)世紀(jì)對人類的最大貢獻(xiàn)就是發(fā)現(xiàn)了抗生素。Western medicine in the largest contribution to the human is the discovery of antibiotics. 抗生素是治療所有細(xì)菌性疾病的最佳武器，但是在治療肺結(jié)核時(shí)卻遇到了點(diǎn)小麻煩。肺結(jié)核史稱“白色瘟疫”，是一種很厲害的傳染病。人類雖然早在1885年就分離出結(jié)核桿菌，但很長一段時(shí)間內(nèi)醫(yī)生們拿它毫無辦法，病人只有寄希望于自己的免疫系統(tǒng)足夠堅(jiān)強(qiáng)。Antibiotics is th

2、e best weapon to treat bacterial diseases all, but when they met a little trouble in the treatment of tuberculosis. History of tuberculosis called "white plague", is a kind of very severe infections. Human although isolated mycobacterium tuberculosis as early as 1885, but the doctors take

3、it for a long time there is no way, the patient only hope that your immune system strong enough. 最先被發(fā)現(xiàn)對肺結(jié)核有效的抗生素是鏈霉素?？墒牵颓嗝顾夭煌氖牵褂面溍顾氐姆谓Y(jié)核病人的病情經(jīng)常會(huì)反復(fù)，醫(yī)生們一直搞不懂到底是為什么。The first was found for tuberculosis is effective antibiotics streptomycin. But, unlike the penicillin, using streptomycin tuberculosis

4、patients often repeated, doctors have been don't understand why. 揭開謎底的是一個(gè)名叫布拉德福德希爾(Bradford Hill)的生物統(tǒng)計(jì)學(xué)家。此人出生于英國的一個(gè)醫(yī)生世家，小時(shí)候立志要子承父業(yè)，卻因第一次世界大戰(zhàn)的緣故被迫加入空軍。服役期間他得了肺結(jié)核，幸運(yùn)的是他的免疫系統(tǒng)足夠堅(jiān)強(qiáng)，僥幸逃過一劫。不過他元?dú)獯髠?，?dāng)醫(yī)生的幻想破滅了，只好改行學(xué)習(xí)經(jīng)濟(jì)學(xué)，并因此而獲得了大量的統(tǒng)計(jì)學(xué)知識(shí)。To unravel the was a man named Bradford Hill biostatistician (Bradfor

5、d Hill). This person was born in a doctor's family in Britain, as a child to follow them, but because of the first world war was forced to join the air force. Service during the period he had tuberculosis, fortunately his immune system will be strong enough to get off the hook. He broadcast near

6、ly eviscerated, however, when the doctor disillusion, had to rerouted to study economics, and acquired a lot of statistical knowledge. 希爾的恩師格林伍德是個(gè)非常聰明的學(xué)者，他認(rèn)為現(xiàn)代醫(yī)學(xué)必須運(yùn)用統(tǒng)計(jì)學(xué)的方法才能保證治療的準(zhǔn)確性。要知道，當(dāng)時(shí)的西方醫(yī)學(xué)骨子里和中醫(yī)一樣，仍然屬于“經(jīng)驗(yàn)醫(yī)學(xué)”，醫(yī)生們更愿意相信自己多年臨床積累的經(jīng)驗(yàn)，而不是客觀的科學(xué)實(shí)驗(yàn)。格林伍德則不然，他本人精通統(tǒng)計(jì)學(xué)，非常推崇1935年出版的一本名為怎樣設(shè)計(jì)科學(xué)實(shí)驗(yàn)的教科書。這本書的作者運(yùn)用統(tǒng)計(jì)

7、學(xué)原理，提出了一整套設(shè)計(jì)科學(xué)實(shí)驗(yàn)的方法和原則。Hill's teacher greenwood is a very clever scholar, he thinks that modern medicine has to use statistical methods to ensure the accuracy of the treatment. Want to know, just like Chinese medicine, western medicine at that time his bones are still belong to "experience&

8、quot; of medicine, doctors are more willing to believe in yourself for many years clinical experience, rather than an objective scientific experiments. Greenwood, otherwise, he is proficient in statistics, in 1935 published a book called "how to design scientific experiment textbooks. The autho

9、r of the book using the statistics theory, put forward a set of methods and principles of design science experiments. 1945年，格林伍德從倫敦衛(wèi)生學(xué)校首席教授的職位上退休，他推薦希爾做為自己的接班人。就這樣，一個(gè)沒有受過科班訓(xùn)練的統(tǒng)計(jì)學(xué)家當(dāng)上了醫(yī)學(xué)院的教授。次年希爾被邀請加入了肺結(jié)核試驗(yàn)委員會(huì)，這個(gè)委員會(huì)的主要任務(wù)就是檢驗(yàn)鏈霉素到底能不能治療肺結(jié)核。In 1945, greenwood retired from the position of chief, a profess

10、or at the London school of hygiene and he recommended hill as his successor. In this way, one had no regular training on the statistical property of the medical school professor. Hill was invited to join the tuberculosis test board the following year, the main task of this committee is inspection st

11、reptomycin can cure tuberculosis. 要知道，青霉素剛被用于臨床時(shí)根本不會(huì)有人想到要去檢驗(yàn)它的有效性，因?yàn)椴∪朔幒髱滋靸?nèi)就見效，臨床效果好得驚人?？墒欠谓Y(jié)核桿菌外表有一層厚厚的黏膜，鏈霉素不容易接觸到它，因此病人往往需要連續(xù)注射幾個(gè)月鏈霉素才能見效。即使如此，當(dāng)時(shí)的英國醫(yī)學(xué)界仍然認(rèn)為沒必要進(jìn)行什么科學(xué)檢驗(yàn)，只要多找?guī)讉€(gè)病人，觀察一下療效就可以了。Just want to know, penicillin was used for clinical purposes won't someone think of going to test the effe

12、ctiveness of it because medication within days after the effective, clinical effect is good. But have a thick layer of mucous membrane tuberculosis bacillus appearance, streptomycin is not easy to come into contact with it, so the patient often require continuous injection of streptomycin to work a

13、few months. Even so, the then British scientific inspection of the medical profession still think don't need to, as long as find a few more patients, and observe the curative effect is ok. 做為一個(gè)外行，希爾不信邪，他堅(jiān)持必須先進(jìn)行一次科學(xué)試驗(yàn)來驗(yàn)證鏈霉素的有效性。正好當(dāng)時(shí)英國剛剛從二戰(zhàn)中走出來，國庫空虛，買不起那么多鏈霉素大量供應(yīng)給醫(yī)院，專家們只好同意先進(jìn)行一次小規(guī)模臨床試驗(yàn)，并請希爾來設(shè)計(jì)試驗(yàn)方案

14、。希爾找來108名患者充當(dāng)“試驗(yàn)品”，其中54人服藥，52人做為對照。但究竟誰服藥誰對照，完全是隨機(jī)選取的，就連主治醫(yī)生也不知道誰是誰，這個(gè)方法是希爾對現(xiàn)代醫(yī)學(xué)所做的最大的貢獻(xiàn)，他認(rèn)為醫(yī)生的主觀印象會(huì)影響試驗(yàn)的準(zhǔn)確性，必須隨機(jī)取樣，并用統(tǒng)計(jì)學(xué)的方法對結(jié)果進(jìn)行分析。As a layman, hill's spirit, he insisted that must first be a scientific experiment was carried out to verify the effectiveness of streptomycin. Britain had just wal

15、ked out of the world war ii, empty coffers, can't afford so much streptomycin plenty of supplies for hospitals, experts had to agree to a small clinical trials, and hill to design test plan, please. Hill to 108 patients as "experiment", among them 54 people, 52 people as control. But w

16、ho medicine who control, completely is randomly selected, even doctors don't know who is who, this method is hill did to modern medicine's greatest contribution, he think that the doctor's subjective impression will affect the accuracy of test, must be random sampling, and statistical me

17、thods to analyze the results. 半年后，服藥的病人中有28人病情明顯好轉(zhuǎn)，對照組卻有14人死亡，顯示鏈霉素確實(shí)有效。假如事情到此結(jié)束的話，希爾的貢獻(xiàn)也許就不值一提了。可是，3年后，服藥組有32人死亡，對照組則死了35人，兩者幾乎不存在統(tǒng)計(jì)意義上的差別。這一驚人的結(jié)果讓醫(yī)生們得出結(jié)論：鏈霉素確實(shí)有效，但是一段時(shí)間后細(xì)菌會(huì)產(chǎn)生抗藥性。假如當(dāng)初沒采用希爾的建議，那么醫(yī)生們決不會(huì)那么快就得出這個(gè)結(jié)論。Of patients after six months, there are 28 people condition improved markedly, the contr

18、ol group there are 14 people are dead, according to streptomycin really works. If things to this end, hill's contribution may be insignificant. Three years later, however, medication group has 32 people were killed and the control group died 35 people, almost there is no statistical significance

19、 difference. This surprising result let doctors concluded that streptomycin really effective, but the bacteria will develop resistance after period of time. If did not adopt hill's advice, so the doctors never reached this conclusion so quickly. 一旦找出原因，解決辦法自然很快就想出來了，那就是在使用鏈霉素的同時(shí)。再讓病人服用另一種藥物。這個(gè)藥很

20、快就找到了，這就是“對-氨基水楊酸”(PAS)。這種藥單獨(dú)使用時(shí)療效并不高，但醫(yī)生們希望兩種藥結(jié)合使用能對付細(xì)菌的抗藥性，理由很簡單：假如病菌對每種藥物的抗藥性產(chǎn)生幾率都是1，那么同時(shí)產(chǎn)生兩種抗藥性的幾率就是1/10000。試驗(yàn)結(jié)果驗(yàn)證了這一理論的正確性，鏈霉素+PAS的方法使結(jié)核病人的存活率上升到了80。Once find out the reason and solution naturally want to come out soon, that is at the same time of using streptomycin. Let patients taking another

21、 drug. This medicine will soon find it, that is "to - aminosalicylic acid (PAS). This medicine curative effect is low when used alone, but doctors hope that two kinds of drugs used in combination can deal with bacterial resistance, the reason is simple: if germs, drug-resistant strains of each

22、occurrence probability is 1%, then at the same time produce two kinds of drug resistance rate is 1/10000. Experimental results validate the correctness of the theory, method of streptomycin + PAS that TB patients survival rate increased to 80%. 后來又有幾種新藥被發(fā)現(xiàn)，醫(yī)生們又按照希爾的方法進(jìn)行了幾次試驗(yàn)，證明3種藥物合用的療效比兩種藥物還要好很多。如果

23、三種藥物持續(xù)用上2年的話，結(jié)核病的治愈率幾乎可以達(dá)到100。人類終于宣布攻克了“白色瘟疫”。Then there are several kinds of new drugs were found, doctors and several tests have been carried out according to hill's approach, to prove the curative effect of three kinds of medicines a lot better than the two drugs. If the three drugs for last

24、2 years, the cure rate of TB can reach almost 100%. Human finally announced to overcome the "white plague". 希爾采用的這一方法叫做“隨機(jī)對照試驗(yàn)”(Randomised Controlled Trial)，這種方法很快就成為醫(yī)學(xué)研究領(lǐng)域的標(biāo)準(zhǔn)試驗(yàn)方法，目前所有已知的西藥必須經(jīng)過這種方法的檢驗(yàn)才能上市。從此，西醫(yī)從經(jīng)驗(yàn)醫(yī)學(xué)時(shí)期進(jìn)入了實(shí)證醫(yī)學(xué)的時(shí)代。Hill, using a method called "randomized Controlled trials

25、 (Randomised Controlled trials), this approach quickly became a standard test method in the field of medical research, at present all the known western medicine must pass through the inspection of this method to the listed. Since then, western medicine from experience period has entered the era of e

26、vidence-based medicine. 至此，希爾的故事還遠(yuǎn)未結(jié)束。1947年，英國醫(yī)學(xué)研究委員會(huì)又給希爾布置了一個(gè)新的任務(wù)：找出肺癌和吸煙之間的關(guān)系。那一年英國的肺癌死亡率比25年前提高了15倍，這個(gè)數(shù)字引起了廣泛的關(guān)注。大家都想找出其中的原因，有人說這是因?yàn)楣I(yè)化造成的空氣污染，還有人說這是由于新式柏油馬路散發(fā)的有毒氣體，只有少數(shù)醫(yī)生懷疑是吸煙造成的。At this point, hill's story is far from over. In 1947, the British medical research council again gave hill a new

27、 task: find out the relationship between smoking and lung cancer. That year Britain's lung cancer mortality is 15 times higher than 25 years ago, that figure has caused wide attention. Everyone want to find out the reason, someone says this is because industrialization caused by air pollution, o

28、thers say it is because of the new asphalt is sending out poisonous gases, only a handful of doctors suspected to be caused by smoking. 眾所周知，兩次世界大戰(zhàn)造就了大批吸煙者，據(jù)統(tǒng)計(jì)，英國當(dāng)時(shí)有超過90的成年男子都是香煙的癮君子。正是因?yàn)槲鼰熑藬?shù)實(shí)在太多，希爾犯了難。他不可能去統(tǒng)計(jì)得肺癌的人當(dāng)中抽煙的有多少，不抽煙的有多少，因?yàn)樗麕缀跽也坏讲晃鼰煹娜?。As is known to all, the two world wars has produced a l

29、arge number of smokers, according to statistics, the UK was more than 90% of the adult male addicts are cigarettes. Because of too much smoking, hill made difficult. He won't be able to get lung cancer statistics of smoke, how many, how many don't smoke, because he almost couldn't find a

30、 people who don't smoke. 怎么辦呢?希爾想出了一個(gè)變通的辦法。首先，他做了個(gè)合乎情理的假設(shè)：如果吸煙確實(shí)能引起肺癌，那么吸煙越多的人得肺癌的幾率就越大。其次，他認(rèn)為必須排除其它的致癌因素，比如空氣污染，初次吸煙年齡，居住環(huán)境等等。換句話說，他必須找出一群人，其它方面都比較相似，只有吸煙的量不同。How to do? Hill came up with an alternative solution. First of all, he made a reasonable assumption: if smoking can cause lung cancer, s

31、o the more people smoking, the greater the risk of lung cancer. Second, he think must rule out other carcinogenic factors, such as air pollution, smoking age for the first time, living environment and so on. In other words, he must find a group of people, other aspects are similar, only the amount o

32、f smoking is different. 1948年，他從倫敦的醫(yī)院里找出了649個(gè)肺癌病人，以及同樣數(shù)量的情況相似的其它病人。然后他雇傭了一批富有經(jīng)驗(yàn)的調(diào)查人員，挨個(gè)詢問病人的吸煙史，把結(jié)果做成了一個(gè)統(tǒng)計(jì)表。結(jié)果顯示，肺癌病人中有99.7的人吸煙，其它病人則有95.8是癮君子。這兩個(gè)數(shù)字當(dāng)然說明不了什么問題，可當(dāng)他把病人按照吸煙數(shù)量的多少分成不同的組之后，情況發(fā)生了變化。有4.9的肺癌病人每天吸50支煙以上，而只有2.0的其它病人每天吸這么多煙。也就是說，吸煙越多的人患肺癌的幾率就越大。In 1948, he was from the hospital in London found

33、649 lung cancer patients, and the same number of similar to that of other patients. Then he hired a group of experienced researchers, each about the patient's smoking history, the results make a TAB. Results showed that lung cancer patients, 99.7% of people smoking, other patient 95.8% are drug

34、addicts. Doesn't mean all the Numbers, of course, what is the problem, but when he put the patients into different groups according to how much the number of smoking, the situation has changed. 4.9% of lung cancer patients smoke fifty cigarettes a day or more, while only 2.0% of the patients wit

35、h other suction smoke so much every day. That is to say, the more people smoking, the greater the chance of developing lung cancer. 1950年，希爾把這個(gè)實(shí)驗(yàn)結(jié)果發(fā)表在英國醫(yī)學(xué)雜志上，首次科學(xué)地證明了吸煙和肺癌的對應(yīng)關(guān)系。但是這個(gè)結(jié)果相當(dāng)微妙，不懂統(tǒng)計(jì)學(xué)的人很難理解其中的重大意義。為了進(jìn)一步說明這個(gè)問題，希爾又設(shè)計(jì)了一個(gè)全新的實(shí)驗(yàn)。他給6萬名英國醫(yī)生發(fā)了封調(diào)查表，請求他們把自己的生活習(xí)慣和吸煙史詳細(xì)記錄下來寄還給他。之所以選擇醫(yī)生做為調(diào)查對象，是因?yàn)橄栂嘈裴t(yī)生們

36、對自己生活狀況的描述能力肯定比普通老百姓更精確，也更誠實(shí)。The hill, in 1950, the experimental results published in the British medical journal, for the first time scientifically proved the corresponding relationship between smoking and lung cancer. But the result is quite delicate, do not know the statistics it is difficult to

37、understand the significance of them. To further illustrate the problem, hill and design a new experiment. He sent 60000 British doctors questionnaire, ask them to put their own lifestyle and smoking history details down and send it back to him. Choose doctor as investigation object, because hill bel

38、ieve doctors ability to descriptions of their living conditions must be more accurate than ordinary people, and more honest. 有4萬名醫(yī)生寄回了調(diào)查表。希爾把他們按照吸煙數(shù)量進(jìn)行了分類，并要求他們(或者他們的家屬)及時(shí)匯報(bào)自己的健康狀況。2年半后，有789名醫(yī)生因病去世，其中只有36人死于肺癌。但是當(dāng)他把醫(yī)生們的吸煙量和發(fā)病率聯(lián)系起來后，發(fā)現(xiàn)只有肺癌的死亡率和吸煙量有對應(yīng)的關(guān)系，其余疾病都和吸煙量沒有任何關(guān)聯(lián)。比如，每天吸25克煙草的人的肺癌死亡率比每天吸1克煙草的人多2

39、倍以上，而其它疾病的死亡率前者只比后者多20。There are 40000 doctors sent back the questionnaire. Hill put them according to the number of smoking are classified, and demanded that they (or their relatives) in a timely manner to report their health. After two and a half years, there are 789 doctors due to illness, died o

40、nly 36 people died of lung cancer. But when he put the smoking and the incidence of doctors, found that only the mortality of lung cancer and smoking have a corresponding relation, the rest of the disease is associated with smoking doesn't have any. Every day 25 grams of tobacco, for example, th

41、e lung cancer death rates than smoking every day people more than 2 times more than 1 gram of tobacco, and other disease mortality of the former only 20% more than the latter. 1993年，大約有2萬名當(dāng)初接受調(diào)查的英國醫(yī)生去世了，其中有883名醫(yī)生死于肺癌。如果把他們的吸煙數(shù)量和肺癌發(fā)病率聯(lián)系起來的話，就可以得出一個(gè)驚人的結(jié)論：每天吸25根煙以上的人得肺癌的幾率比不吸煙的人多25倍!后來其它一些類似的研究也都得出了相似的

42、結(jié)論?，F(xiàn)在，吸煙和肺癌的關(guān)系已經(jīng)是家喻戶曉了，發(fā)達(dá)國家的煙民數(shù)量正在逐年下降，其肺癌的發(fā)病率也呈現(xiàn)出下降的趨勢。那些因?yàn)榻錈煻庥诜伟┑娜苏鎽?yīng)該感謝希爾當(dāng)初所做的貢獻(xiàn)。In 1993, about 1993 had surveyed the British doctor died, of which 883 doctors death from lung cancer. If their number and incidence of lung cancer linked to smoking, you can get a surprising conclusion: suck people

43、over 25 cigarettes a day risk of lung cancer than non-smokers more than 25 times! Later some other similar studies have found similar results. Now, the relationship between smoking and lung cancer, it was already a household name, the number of smokers in developed countries are falling year by year, the incidence of lung cancer also present a downward trend. Those from lung cancer because of smoking the contribution which really should thank hill at the beginning. 希爾使用的第一種方法叫做“對照研究”(Case ControlStudy)，第二種方法叫做“定群研究”(Cohort Study)。這兩種方法是目前群體醫(yī)學(xué)研究領(lǐng)域最常用的兩種生物統(tǒng)計(jì)學(xué)方法，我們所熟悉的大部分關(guān)于健康的忠告都應(yīng)該經(jīng)過這兩