How Are Prescription Drugs Approved in Canada?

　　When a pharmaceutical company has a new drug.it applies to Health Canada for a licence to sell it.Based on information the company provides,including the results of clinical trials,the drug is either approved or the application is rejected.

　　Is There a Difference in the Way Drugs Are Approved for Children and Adults?

　　Normally.drugs are tested in adults first.Dr.Denis Daneman.a clinical investigator at The Hospital for Sick Children in Toronto,says,“we have to be remarkably careful because children are physiologically different than adults and are seen by physicians as a highly vulnerable group.”

　　What Happens Once a Drug Is Approved?

　　“Once approved,” explains Daneman.“it's available on the market and doctors can prescribe it for any indication they'd like to.” Even if it has not been tested specifically in children.he says.“physicians may start to use it either in small trials or what we call off-label (use of a prescription drug to treat a condition for which the drug has not been approved) in children.”

　　How Common Is Off-label Use?

　　Dr.Michael Rieder. director of the Adverse Drug Reaction Clinic at the Children's Hospital of Western Ontario,says,“drugs commonly used in children，such as antibiotcs and asthma drugs,are tested in children.” But,he says,“there is a misconception that children take only those drugs.We did a study looking at a million kids in Canada over a year.It turns out they used l,400 different drugs,of which 60 percent have not been tested,or approved for use in children.”

　　If a Drug Is Safe in Adults,Why Do You Need to Test It in children?

　　Health Canada's Dr.Siddika Mithani says.“children are not small adults.”Their physiology is different.That goes for adolescents.too.Dr.Eric Wookltorton.an Ottawa-based family physician who writes a column on adverse events for the Canadian Medical Association Journal,says,“Depo Provera is an injectable birth-control product used by women of all ages.No one thought to test it in adolescents until recently.Teenagers are laying down bone density and this drug decreased bone density.”

　　Are Older Drugs Safer?

　　“If I were to use a medication off-label that's been around for some time,I'd be less concerned about it.” advises Dr.Peter Nieman.a Calgary pediatrician.“But if you use a medication that's being promoted as che best thing since sliced bread,and you know it's fairly new and are using it off-label,you are a bit nervous.”

　　How Many Side Effects Are Reported?

　　In 2004 Health Canada received 10,238 reports of adverse reactions in people of all ages.The number of reports has been increasing since 1999,when just under 6,000 were sent in.However.Dr.Bruce Carleton.of the pharmaceutical outcomes program at the Children's and Women's Health Centre of British Columbia，says,“95 percent of negative reactions are never reported.”Wooltorton explains:“how do you track the more minor,long-term side effects,the ones where kids are a little bit stunted in growth or they are having learning problems in school.There's no regulation and no financial incentive to report anything at all.”

　　Should We Be More Careful with Some Drugs?

　　Dr.Jack Uetrecht,a Canada Research Chair in adverse drug reactions,advises extra caution with drugs that affect the central nervous system.“The effects and long-term outcomes of giving these types of drugs aren't totally understood. Make sure the appropriate tests are given to make as clear a diagnosis as possible.and that the appropriate treatment is given based on that diagnosis.Talking to the patient for a few minutes and prescribing a drug would not be the best method.If there is a severe clinical problem and a clear clinical benefit,then the benefit is worth the risk.”

　　Can Side Fffects Be Prevented?

　　If your child has had a reaction to a drug in the past,an allergist can advise if she is still allergic.and if so,what could be used instead.Genome Canada is funding an $8.4-million research project that may help prevent side effects in the future.led by Carleton and geneticist Michael Hayden,director of the Centre for Molecular Medicine and Therapeutics.It is looking for genetic markers that would signal if a child was at risk for an adverse reaction.“There are genetic differences in the way a lot of physiological processes happen in the human body,”says Carleton.“It makes sense that those differences would affect the way we process drugs.Therefore,understanding when that situation exists would help us to construct better guidelines.”

　　What Should You Ask About Your Child's Prescription?

　　First,be sure it is really necessary,says Wooltorton.“A lot of children don't always need prescriptions for a lot of things.Ear infections are an example of when antibiotics are sometimes,but not always,necessary.But there is a tendency in our society to want our kids to be like us.We want to get back to work.We want them to get back to school.We want a quick fix.But‘how wi11 we know the drug is working?'A child with asthma,for example,is usually given a couple of medications.One will be to open the airways.He should feel better after the First dose.If he doesn't,we have a problem.The other medication is used to reduce inflammation.This will decrease the number of acute breathless episodes,but it takes time to have an effect.”Find out how long your physician has been using the drug,says Rieder,and what the experience has been like.Your doctor may know quite a lot about the drug, even if it is being used off-label.

　　What Should Parents Watch Out for?

　　Dr.Michael Kramcr,of the Canadian Institutes of Health Research,says you should contact your physician“if your child is very sleepy or is agitated and unable to sleep.You should also be concerned about any rashes that cause blistering or hivcs.”When you pick up a medication at the drugstore,it often comes with a list of potential side effecfs.Maura MacPhee,who teaches in the School of Nursing at the University of British Columbia,says,“this is generic information.Before leaving the physician's office,make sure you know what side effects are the ones you need to worry about with your child.”

　　How Safe Is the System?

　　In the last 25 to 30 years,we have seen significant advances in the treatment of childhood leukemia.“When I was training 30 years ago,”says Daneman,“childhood leukemia had an 80-percent mortality rate;now the survival rate is better than 80 percent.”Another important development:More drugs are being tested now in children.Daneman says:“if you look at the number of studies that go on,there are many more in the last five to eight years than there were 20 0r 30 years ago.”

　　練習題

　　1.Which of the following is requested by Health Canada before it permits a drug to be sold?

　　A) The aize and the weight of the drug.

　　B) The suggested price of the drug.

　　C) The results of clinical trials of the drug.

　　D) The production budget of the drug.

　　2.Who is seen by Dr.Denis Daneman as a highly vulnerable group?

　　A) Pregnant women. B) Children.

　　C) Elderly people over 70. D) Middle-aged men.

　　3.How many kinds of drugs are now used by children off-label?

　　A) 840. B) 60. C) 1400. D) 560.

　　4.Depo Provera is a drug that can result in adolescents'_____________.

　　A) stomach upset B) low blood pressure

　　C} high cholesterol D) decreased bone density

　　5.Some minor and long-term side effects were not reported due to______________.

　　A) patients' ignorance B) lack of financial incentive

　　C) doctor's irresponsibility D) shortage of health workers

　　6.Dr.Jack Uetrecht is most concerned about drugs' side effect on________________.

　　A) the nervous system B) the digestive system

　　C) the respiratory system D) the skeleton system

　　7.Dr.Jack Uetrecht suggests that an accurate diagnosis is the basis of________________.

　　A) appropriate treatment B) prescribing a new drug

　　C) avoidance of side effects D) feasible medical tests

　　8.The project funded by Genome Canada hopes to prevent adverse reactionsafter identifying relevant______________.

　　9.If a child with asthma suffers acute breathless episodes,he should take medicine to________________.

　　10.When buying a medicine in a drugstore or getting it from a physician,parents need to watch out for its__________________.

　　答案詳解

　　1.[C][定位]根據題干中大寫的專有名詞Health Canada查找到第1個小標題How Are Prescription Drugs Approved in Canada?部分的第2句。

　　解析：原文該句中的including...后的內容與選項C相同，因此本題答案為選項C。

　　2.[B][定位]根據題干中的人名Dr.Denis Daneman查找到第2個小標題Is There a Difference in the Way Drugs Are Approved for Children and Adults?部分的第2句。

　　解析：原文該句中的children...are seen... as a highly vulnerable group明確表明本題應選B。

　　3.[A][定位]根據題干中的off-label以及選項是的數字查找到第4個小標題How Common Is Off-label Use?部分的末句。

　　解析：本題答案需經過簡單的計算才能得出，根據原文該段末句提及的1400種藥有60%屬于off-label可以算出本題答案應為選項A。選項B和C雖然在原文提及，但不符合題意，選項D在原文沒有直接提及，也不符合題意。

　　4.[D][定位]根據題干中的藥名Dcpo Provera查找到第5個小標題If a Drug Is Safe in Adults,Why Do You Need to Test It in Children?部分的末句。

　　解析：原文該句末的this drug指的是該段倒數第3句提到的Depo Provera，末句指出Depo Provera會“decreased bone density”，顯然，本題答案應為選項D。

　　5.[B][定位]根據題干中的minor and long-term查找到第7個小標題How Many Side Effects Are Reported?部分的最后三句。

　　解析：原文該段倒數第3句描述了如題干所述的現象，末句解釋了原因，選項B是末句提到的兩個原因之一，為本題答案。

　　6.[A][定位]根據題干中的人名Dr.Jack Uetrecht查找到第8個小標題Should We Be More Careful with Some Drugs?部分的首句。

　　解析：原文該句表明Dr.Jack Uetrecht建議對于影響中樞神經系統的藥物要格外謹慎，可見“神經系統”(nervous system)是他所關注的領域，因此本題應選A。

　　7.[A][定位]根據題干中的人名Dr.ack Uetrecht和the basis of查找到第8個小標題Should We Be More Careful with Some Drugs?部分的第3句。

　　解析：原文中的is...based on...與題目中的is the basis of...意思相反，這兩個詞組的主語和賓語位置也相反，本題答案應在原文is based on...前作主語，選項A與此處主語相同，由此可見，選項A正確。

　　8.[genetic markers]

　　[定位]根據題干中的大寫專有名詞Genome Canada查找到第9個小標題Can Side Effects Be Prevented?部分的第3句。

　　解析：空白處應為名詞成分，作identifying的賓語。原文該部分第2、3句表明這個計劃要做兩件事：prevent side effects和look for genetic markers，題止提到了第一件事.而identifying和原文中的looking for功能相同，由此可見，looking for的賓語就是本題答案。

　　9.[reduce inflammation]

　　[定位]根據題干中的a child with asthma和acute breathless episodes查找到第10個小標題What Should You Ask About Your Child's Prescription?部分的倒數第3、4句。

　　解析：to表明空白處應為動詞不定式成分。原文該段提到了哮喘的兩種情況，本題提到的是第2種情況，倒數第4句指出這種情況可以通過吃藥“消炎”來減輕癥狀，因此本題答案應為“消炎”，即倒數第4句提到的reduce inflammation。

　　10.[(potential)side effects]

　　[定位]根據題干中的watch out for查找到第11個小標題What Should Parents Watch Out for?部分的最后三句。

　　解析：空白處應為名詞成分，作for的賓語。原文這三句都是為了解答本部分小標題提出的問題，表明父母要注意的就是藥品的副作用，因此side effects就是本題答案。

　　參考譯文

　　兒童處方藥有多安全?

　　最近出現了大量有關兒童和青少年處方藥的新聞報道。加拿大衛生部已經對患者和醫生都信賴的一些藥品發出警告，并且從市場上撤銷了另外幾種藥。到底是怎么回事?父母們應該了解這些復雜而令人費解的問題。

　　在加拿大處方藥是怎樣被核準的?

　　當一家制藥公司生產了一種新藥，就會向加拿大衛生部申請銷售該新藥的許可證。[l]衛生部根據公司所提供的信息，包括臨床實驗結果，要么批準這種藥品要么駁回銷售許可申請。

　　兒童藥物和成人藥物在審批方面有什么不同?

　　一般來說，藥品首先要在成人中進行試驗。[2]多倫多兒童醫院的臨床研究員Denis Daneman醫生說，“我們必須非常謹慎，因為兒童的生理特點不同于成年人，醫生把兒童看做是非常容易受到傷害的群體。”

　　一旦藥品被批準會怎樣?

　　Daneman醫生解釋說，“藥品一經批準就可以在市場上銷售，而醫生可以根據病人的病情把該藥品開進自己的處方。”他說，“即使這種藥并沒有針對兒童進行專門的試驗，醫生也會在給兒童治病過程中開始小范圍地嘗試使用，或者作為一種我們所稱之為非標識藥使用(把一種處方藥應用到沒有得到許可的使用范圍)。”

　　非標識藥的使用有多普遍?

　　西安大略兒童醫院藥品不良反應門診部主任，Michael Rieder醫生說，“給兒童治療時普遍使用的藥物，如抗生素、哮喘藥，都會在兒童當中進行試驗。但是，人們有一種誤解，認為兒童只使用這些藥品。我們進行了一項長達一年時間的研究，在加拿大觀察了1OO萬名兒童，結果表明：[3]他們服用了1400種不同的藥品，其中60%的藥品，要么就是沒有經過針對兒童的臨床實驗，要么就是沒有得到準許用于治療兒童疾病。”

　　如果一種藥品對成年人是安全的，為什么還要在兒童中進行試驗呢?

　　加拿走衛生部醫生Siddika Mithani說：“兒童不是小大人。”他們的生理機能是不同的。青少年也是如此。Eric Wooltorton醫生是一名渥太華市的家庭醫生，他負責《加拿大醫療協會》雜志不良反應事件專欄。他說，“甲孕酮是一種用于所有年齡婦女的注射節育產品。直到最近，人們才針對青少年就這種藥物進行測試。[4]青少年的骨質密度正在下降，而這又正是一種降低骨質密度的藥物。”

　　藥物使用越久越安全嗎?

　　卡爾加里兒科醫師Peter Nieman認為：“如果我使用一種已經被使用過一段時間的非標識藥物的話，我不會太擔心。但是如果你使用的是一種被宣傳為出現切片面包以來最好的東西，而你知道它是一種新藥，把它當作非標識藥物使用，那么你就會感到有點緊張。”

　　有多少副作用被報道?

　　2004年，加拿大衛生部收到不同年齡階段出現藥品不良反應的報道10238例，報道的數目自1999年以來一直在增加，而當時只有不到6000例。然而，美國哥倫比亞兒童和婦女健康中心制藥規劃部門的Bruce Carleton醫生說，有95%的不良反應從未被報道過。Wooltorton解釋說：“你很難追蹤那些更不引人注意的長期的副作用，這些副作用的表現是，孩子長得矮小，或者在校有學習困難。[5]根本沒有規定也沒有財政機制來保障對這些副作用的報道。”

　　對于某些藥品我們應該更加謹慎嗎?

　　[6]加拿大藥物不良反應研究部主任，Jack Uetrecht醫生建議，對于影響中樞神經系統的藥物要格外謹慎。“人們還沒有完全理解使用這類藥物所帶來的副作用及及其長期后果。[7]一定要確保進行恰當的試驗，來使診斷盡可能地明確，而正確治療必然以明確的診斷為依據。與患者交談幾分鐘就開處方不是最佳的方法。如果是一個嚴重的健康問題，而且可以獲得臨床治療效果，那么這個治療效果才是值得冒險的。”

　　副作用可以預防嗎?

　　如果你的孩子過去對某種藥物有過敏反應，過敏癥專科醫師可能會建議檢查現在是否仍然過敏，如果是的話，醫生會建議使用什么替代藥物。[8]加拿大基因研究組織正投資一項840萬美元的研究項目，該項目也許可以在將來有助于預防副作用。它是由Carleton和分子醫學和治療學中心主任，遺傳學者Michael Hayden主持。該項目正在研究當一個孩子有出現不良反應的風險時，會有什么樣的遺傳標記表現出來。Carleton說，“人體的很多生理過程是存在基因差異的。那些差異會影響我們用藥的方法，這一點很重要。所以，了解什么時候會出現這些基因差異有助于我們更好地確立指導方案。”

　　對于你孩子的處方你應該了解什么?

　　Wooltorton說，“首先，得確定處方藥的確是有必要才用。就很多疾病，多數的孩子并不總是需要藥方。耳部感染就是一個很好的例子，耳部感染有時候需要抗生素，但并非總是必不可少的。在我們的社會.人們都傾向于希望孩子們像我們大人一樣。我們必須回去上班，我們也希望孩子們回到學校，我們希望問題得到快速解決。但‘我們又怎么知道藥物是否正在起作用呢?’例如，一個患有哮喘病的兒童通常會被要求服幾種藥。其中一種藥會使他的氣管擴張。服了第一劑后，他應該感覺呼吸順暢一些。如果他并沒有感覺好些，就說明我們用錯藥了。[9]另一種藥用于消炎，是為了減少急性呼吸堵塞癥狀出現的頻率，但需要一定的時間才能見效。”Rieder說，要了解你的醫生用這種藥用了多長時間，有什么樣的臨床療效。或許你的醫生非常了解這種藥。盡管這是一種非標識藥。

　　家長應慎防什么?

　　加拿大衛生研究協會的Michael Kramer醫生說，“如果你的孩子嗜睡。或表現急躁不安，無法入睡，你就應該跟醫生聯系。你還應該小心引起高燒或假膜性喉頭炎的皮疹。”[10]在藥店買的藥通常容易帶來一系列潛在的副作用。英國哥倫比亞大學護理學院的老師Maura MacPhee說，“這是一般常識。在離開醫生的辦公室之前，一定要問明白這些用藥對你的孩子會有哪些副作用。”

　　這種機制有多安全?

　　在過去的25到30年里，我們已經看到了兒童白血病治療方面的長足進步。Daneman說：“30年前我讀醫的時候，兒童白血病的死亡率達到80%;而現在治愈率超過了80%。”另外一個重要的進步是：現在更多的藥物要在兒童身上做實驗。Daneman還說：“如果你看看正在進行的研究項目的數量，就會發現最近5至8年的研究數量大大超過20年或30年以前。”