统计在医学上的应用

1、统计在医学上的应用The application of statistics in medicine西医在上个世纪对人类的最大贡献就是发现了抗生素。Western medicine in the largest contribution to the human is the discovery of antibiotics. 抗生素是治疗所有细菌性疾病的最佳武器，但是在治疗肺结核时却遇到了点小麻烦。肺结核史称“白色瘟疫”，是一种很厉害的传染病。人类虽然早在1885年就分离出结核杆菌，但很长一段时间内医生们拿它毫无办法，病人只有寄希望于自己的免疫系统足够坚强。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. 最先被发现对肺结核有效的抗生素是链霉素。可是，和青霉素不同的是，使用链霉素的肺结核病人的病情经常会反复，医生们一直搞不懂到底是为什么。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. 揭开谜底的是一个名叫布拉德福德希尔(Bradford Hill)的生物统计学家。此人出生于英国的一个医生世家，小时候立志要子承父业，却因第一次世界大战的缘故被迫加入空军。服役期间他得了肺结核，幸运的是他的免疫系统足够坚强，侥幸逃过一劫。不过他元气大伤，当医生的幻想破灭了，只好改行学习经济学，并因此而获得了大量的统计学知识。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. 希尔的恩师格林伍德是个非常聪明的学者，他认为现代医学必须运用统计学的方法才能保证治疗的准确性。要知道，当时的西方医学骨子里和中医一样，仍然属于“经验医学”，医生们更愿意相信自己多年临床积累的经验，而不是客观的科学实验。格林伍德则不然，他本人精通统计学，非常推崇1935年出版的一本名为怎样设计科学实验的教科书。这本书的作者运用统计

7、学原理，提出了一整套设计科学实验的方法和原则。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，格林伍德从伦敦卫生学校首席教授的职位上退休，他推荐希尔做为自己的接班人。就这样，一个没有受过科班训练的统计学家当上了医学院的教授。次年希尔被邀请加入了肺结核试验委员会，这个委员会的主要任务就是检验链霉素到底能不能治疗肺结核。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，青霉素刚被用于临床时根本不会有人想到要去检验它的有效性，因为病人服药后几天内就见效，临床效果好得惊人。可是肺结核杆菌外表有一层厚厚的黏膜，链霉素不容易接触到它，因此病人往往需要连续注射几个月链霉素才能见效。即使如此，当时的英国医学界仍然认为没必要进行什么科学检验，只要多找几个病人，观察一下疗效就可以了。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. 做为一个外行，希尔不信邪，他坚持必须先进行一次科学试验来验证链霉素的有效性。正好当时英国刚刚从二战中走出来，国库空虚，买不起那么多链霉素大量供应给医院，专家们只好同意先进行一次小规模临床试验，并请希尔来设计试验方案

14、。希尔找来108名患者充当“试验品”，其中54人服药，52人做为对照。但究竟谁服药谁对照，完全是随机选取的，就连主治医生也不知道谁是谁，这个方法是希尔对现代医学所做的最大的贡献，他认为医生的主观印象会影响试验的准确性，必须随机取样，并用统计学的方法对结果进行分析。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，服药的病人中有28人病情明显好转，对照组却有14人死亡，显示链霉素确实有效。假如事情到此结束的话，希尔的贡献也许就不值一提了。可是，3年后，服药组有32人死亡，对照组则死了35人，两者几乎不存在统计意义上的差别。这一惊人的结果让医生们得出结论：链霉素确实有效，但是一段时间后细菌会产生抗药性。假如当初没采用希尔的建议，那么医生们决不会那么快就得出这个结论。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，解决办法自然很快就想出来了，那就是在使用链霉素的同时。再让病人服用另一种药物。这个药很

20、快就找到了，这就是“对-氨基水杨酸”(PAS)。这种药单独使用时疗效并不高，但医生们希望两种药结合使用能对付细菌的抗药性，理由很简单：假如病菌对每种药物的抗药性产生几率都是1，那么同时产生两种抗药性的几率就是1/10000。试验结果验证了这一理论的正确性，链霉素+PAS的方法使结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%. 后来又有几种新药被发现，医生们又按照希尔的方法进行了几次试验，证明3种药物合用的疗效比两种药物还要好很多。如果

23、三种药物持续用上2年的话，结核病的治愈率几乎可以达到100。人类终于宣布攻克了“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". 希尔采用的这一方法叫做“随机对照试验”(Randomised Controlled Trial)，这种方法很快就成为医学研究领域的标准试验方法，目前所有已知的西药必须经过这种方法的检验才能上市。从此，西医从经验医学时期进入了实证医学的时代。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，希尔的故事还远未结束。1947年，英国医学研究委员会又给希尔布置了一个新的任务：找出肺癌和吸烟之间的关系。那一年英国的肺癌死亡率比25年前提高了15倍，这个数字引起了广泛的关注。大家都想找出其中的原因，有人说这是因为工业化造成的空气污染，还有人说这是由于新式柏油马路散发的有毒气体，只有少数医生怀疑是吸烟造成的。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. 众所周知，两次世界大战造就了大批吸烟者，据统计，英国当时有超过90的成年男子都是香烟的瘾君子。正是因为吸烟人数实在太多，希尔犯了难。他不可能去统计得肺癌的人当中抽烟的有多少，不抽烟的有多少，因为他几乎找不到不吸烟的人。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. 怎么办呢?希尔想出了一个变通的办法。首先，他做了个合乎情理的假设：如果吸烟确实能引起肺癌，那么吸烟越多的人得肺癌的几率就越大。其次，他认为必须排除其它的致癌因素，比如空气污染，初次吸烟年龄，居住环境等等。换句话说，他必须找出一群人，其它方面都比较相似，只有吸烟的量不同。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，他从伦敦的医院里找出了649个肺癌病人，以及同样数量的情况相似的其它病人。然后他雇佣了一批富有经验的调查人员，挨个询问病人的吸烟史，把结果做成了一个统计表。结果显示，肺癌病人中有99.7的人吸烟，其它病人则有95.8是瘾君子。这两个数字当然说明不了什么问题，可当他把病人按照吸烟数量的多少分成不同的组之后，情况发生了变化。有4.9的肺癌病人每天吸50支烟以上，而只有2.0的其它病人每天吸这么多烟。也就是说，吸烟越多的人患肺癌的几率就越大。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，希尔把这个实验结果发表在英国医学杂志上，首次科学地证明了吸烟和肺癌的对应关系。但是这个结果相当微妙，不懂统计学的人很难理解其中的重大意义。为了进一步说明这个问题，希尔又设计了一个全新的实验。他给6万名英国医生发了封调查表，请求他们把自己的生活习惯和吸烟史详细记录下来寄还给他。之所以选择医生做为调查对象，是因为希尔相信医生们

36、对自己生活状况的描述能力肯定比普通老百姓更精确，也更诚实。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4万名医生寄回了调查表。希尔把他们按照吸烟数量进行了分类，并要求他们(或者他们的家属)及时汇报自己的健康状况。2年半后，有789名医生因病去世，其中只有36人死于肺癌。但是当他把医生们的吸烟量和发病率联系起来后，发现只有肺癌的死亡率和吸烟量有对应的关系，其余疾病都和吸烟量没有任何关联。比如，每天吸25克烟草的人的肺癌死亡率比每天吸1克烟草的人多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，大约有2万名当初接受调查的英国医生去世了，其中有883名医生死于肺癌。如果把他们的吸烟数量和肺癌发病率联系起来的话，就可以得出一个惊人的结论：每天吸25根烟以上的人得肺癌的几率比不吸烟的人多25倍!后来其它一些类似的研究也都得出了相似的

42、结论。现在，吸烟和肺癌的关系已经是家喻户晓了，发达国家的烟民数量正在逐年下降，其肺癌的发病率也呈现出下降的趋势。那些因为戒烟而免于肺癌的人真应该感谢希尔当初所做的贡献。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. 希尔使用的第一种方法叫做“对照研究”(Case ControlStudy)，第二种方法叫做“定群研究”(Cohort Study)。这两种方法是目前群体医学研究领域最常用的两种生物统计学方法，我们所熟悉的大部分关于健康的忠告都应该经过这两