How Much Would You Give to Save a Dying Bird? Patient Advocacy and Biomedical Research

       挽救一只垂危的“鸟”，你能做点什么呢？病人的努力VS医学研究

    In 1994, Frank McCormack, a pulmonologist interested in innate immunity, arrived at his new job at the University of Cincinnati to find a letter on his desk. It was from Sue Byrnes, a music teacher whose 22-year-old daughter Andrea had been diagnosed with lymphangioleiomyomatosis (LAM), a slowly progressive cystic lung disease that affects about 5 in 1 million women worldwide. Andrea, an avid soccer player, had undergone five operations for a knee injury but remained sidelined. When she began to have intractable abdominal pain, she was told she had irritable bowel syndrome caused by emotional stress. On her seventh visit to the emergency department, she was found to have retroperitoneal bleeding and a 21-cm mass on her kidney — an angiomyolipoma, which the Byrneses later learned was associated with LAM. Chest pain and shortness of breath soon ensued, and Andrea was again told that her symptoms were psychological. Then, during a flight, her lung collapsed. A tension pneumothorax developed, and she arrived at a Denver hospital without a pulse.

     在1994年，一个对自然免疫感兴趣的名叫Frank McCormack 的胸腔科医生来到他的新工作地──辛辛那提大学，他发现办公桌上有封信。这封信来自于一位叫Sue Byrnes的音乐老师，Sue Byrnes有个22岁的女儿叫Andrea，Andrea被诊断为LAM病，该病是一种慢性的肺囊肿病，危及到全世界百万分之五的妇女。Andrea曾经是一名痴迷的足球运动员，由于膝盖受伤而经历过五次手术，已经退役。当她患有顽固性的腹痛时，医生告诉她，她是得了由精神压力导致的过敏性肠道综合症。在第七住院的时候，她被查出后腹膜出血，肾部有个21厘米的肿块（血管肌脂瘤），后来 Byrne夫妇才知道这与LAM有关。随之而来的是胸部疼痛和呼吸短促，然而Andrea又一次被告知，这种症状是由于心理因素造成的。在一次飞行中，她的肺衰竭，在她被送到Denver医院时已经几乎没有了心跳，

     Though the doctors in Denver noted cystlike lesions in Andrea's lungs and suspected LAM, her scans were sent elsewhere for confirmation. While they awaited the results, the Byrneses read a research article that suggested that most women with LAM died 5 to 8 years after the diagnosis was made. When they received confirmation of Andrea's diagnosis by mail, they had to tell their daughter themselves what they had learned about the disease. Andrea asked endless questions for which they had no answers. But Sue told her, “I'm going to do something about this. I promise you, I will change all this.” Andrea replied, “Mom, you're my best hope.”McCormack, who had been highly recommended by the Denver doctors, knew the therapeutic options for Andrea were limited. He was confronted with the agony of telling a patient, “I'm sorry, but there's not much I can do for you.” Having to impart such a hopeless prognosis is sufficiently untenable that many physicians avoid it by offering the patient therapies of unproven benefit.

    虽然 Denver医院的医生在Andrea的肺部发现到囊肿状的病变，并怀疑是LAM，她的片子还是被送到其它地方待以确诊。在他们等待结果的时候，他们看到一篇研究的文章，文章上说：大部分人在确诊后的5至8年死亡。当他们收到 Andrea的确诊邮件的时候，Byrne夫妇必须告诉女儿，他们对该病的了解。 Andrea问了一个又一个问题，而Byrne夫妇都不知如何回答。但是妈妈告诉她：“我将为该病做点事情，我保证将会带来些改变。” “您是我最大的希望” Andrea回应道。Denver医院的医生为他们极力推荐McCormack医生，然而McCormack医生明白，目前的治疗手段还是有限的。McCormack医生面临着困惑：是不是要告知病人没有太好的治疗方法。为了避免告知病人无治的诊断，医生经常是进行一些未被证实有效的“治疗”。

  McCormack took a different approach. He suggested that Sue, who had already begun writing letters to community groups and patients with LAM, enlist pulmonologists around the country to convince the National Institutes of Health to create a LAM registry. Later on, he recommended that she start a foundation, and though he urged her to seek a more renowned pulmonologist to be its scientific director, she refused. “Dr. McCormack had shown heart, compassion, and commitment,” she recalls. “That was good enough for me.” McCormack and Byrnes have worked together on foundation matters nearly every day since.

    McCormack医生另辟蹊径：鉴于Sue已经开始给全国的LAM群体和个人写信， McCormack医生建议她号召全国的胸腔科医生说服卫生部门建立一个LAM登记处。后来 McCormack医生建议她成立一个基金会。尽管 McCormack医生强烈要求她找一个更有威望的胸腔科医生来担任科研主任，Sue并没有同意，她说：“ McCormack医生所表现出的爱心、同情心、责任心让我深受感动”。从那时起，他们就携手料理基金会的事务。

In the wake of the 1989 Exxon Valdez oil spill, participants in a psychology experiment were asked how much they would pay for nets to save birds from drowning in ponds of crude oil. Three groups were each given the hypothetical opportunity to save a specific number of birds: 2000, 20,000, or 200,000. Despite the differences in the number of birds assigned to each group, the average contributions the participants proposed to rescue them were remarkably similar: $80, $78, and $88, respectively. “What the participants reacted to,” writes Daniel Kahneman, “was a prototype — the awful image of a helpless bird drowning, its feathers soaked in thick oil. The almost complete neglect of quantity in such emotional contexts has been confirmed many times.”1

     在埃克森·瓦尔迪兹号溢油事故发生后不久，人们做了一个心理实验。参与者要回答一个问题：为了救在残酷的油水快被淹死的海鸟，你愿意出多少钱来买网。参与者被分成三个组，每组都给以一个假设要营救海鸟的具体数量：分别是2000,20000和200000。尽管每组被分配的数量并不相同，每组所出钱的平均数竟出奇地相似，分别是80美元，78美元和88美元。 Daniel Kahneman写道：“参与者关注的是无助的海鸟的翅膀浸泡在厚厚的油中而即将淹死的可怕情景。在这样的情景中，人们几乎彻底忘却了数量，这种现象已经多次被证实。

This psychological disconnect between the impassioned impulse to save a life in danger and the dispassion required when scientific data must be quantified helps clarify the evolving relationship between patient advocacy and biomedical research. Rebecca Dresser, a bioethicist and expert on this topic, recognizes the richness patient advocates bring to clinical research, particularly in emphasizing outcomes that matter to patients and in identifying patients who are willing to participate in trials. Moreover, advocacy offers an opportunity for purpose and hope in desperate circumstances. But does it offer false hope?

上面试验中表明：挽救生命的主观能动性与具体数据之间并不相关（主观能动性的重要性所在）。因此我们也能理解，病人的自我宣传将促进医学的研究。Rebecca Dresser是这方面的专家，她指出病人的宣传将会带来医学研究的丰硕成果，她们在宣传中强调研究成果对病人的意义，并且鼓励病人参加试验。此外，病人的宣传带来了机会和希望。然而病人的宣传也会产生不利因素吗？

Dresser points to the persistent notion that “all we have to do is throw money at illness and we'll find a cure.” There remains a pervasive misunderstanding about the slow pace of clinical research and its frequent failure to deliver. She recalls the actor Christopher Reeve's pleas for funding of embryonic stem-cell research, fostering a mistaken belief that dollars for stem cells would immediately result in paralyzed patients being able to get up out of their wheelchairs.

Dresser表明她的坚定信念：“我们所要做的就是在研究上投入，然后找到治疗的方法”。对于医学研究的缓慢进展和研究试验不断的失败，人们总是持有误解。她回忆起演员克里斯托夫·里夫为了胎儿干细胞而筹集资金，带给人们一种错误的信念：只要为研究投入资金就会使瘫痪的病人从轮椅中站起来。
   This impulse to raise money to find a cure, however misguided, has roots in historical triumphs. Around 1948, Sidney Farber was a struggling pathologist seeking to cure childhood leukemia. Thwarted in his attempts to advance testing of his already successful antifolate agents, he had an insight more relevant to human nature than to cell division: cancer needed a poster child (see Part 2 of the documentary video “Getting Better: 200 Years of Medicine”). Enter Farber's patient “Jimmy,” a 12-year-old Boston Braves fan. One night, Jimmy was featured on a nationally broadcast radio show, and as he was quizzed about Braves trivia, the baseball team's players paraded into his hospital room. Listeners were told that if $20,000 were donated, Jimmy would get a television to watch the Braves play. Thus was born the Jimmy Fund, which not only has raised more than $750 million to date, but also established what remains a unifying principle of advocacy efforts: in order to generate funding and awareness, every disease must have a face.

这种为了寻找治疗方法而筹集资金的举措，虽然被误解，但是有成功的先例。大约在1948年，病理学家Sidney Farber仍在为寻求儿童白血病的治疗方案而努力。在他研制的抗叶酸药剂的后期试验中，他失败了。他更加意识到人性比细胞分离的研究更重要：癌症需要一个“海报儿童”去宣传。(详细请看纪录片的第二部分“越来越好：医学的200年”）。点击Farber的病人“Jimmy”，Jimmy是一个12岁的孩子，他是棒球运动员Boston Braves的球迷。一天晚上，Jimmy被安排做一个全国性的广播节目的专访，当他在被问及对Boston Braves的了解时，棒球队的队员游行到他的病房。听众们听到一则消息：如果能募捐到20000美元，Jimmy将会有电视看Boston Braves的球赛。于是Jimmy基金就诞生了，迄今为止，它不仅筹集到七亿五千万的资金，而且还建立了一个统一的宣传原则：为了征集资金和引起人们的注意，每种疾病都需要“露一露脸”。

In 1992, my aunt, a 41-year-old attorney and compassionate spitfire, elected to undergo high-dose chemotherapy with autologous bone marrow transplantation (HDC-ABMT) — a last-ditch measure for treating her widely metastatic breast cancer. HDC-ABMT was an experimental therapy that had been tested with modest success in phase 2 trials. Phase 3 testing hadn't been completed, but because HDC-ABMT constituted a more intense version of a treatment already approved by the Food and Drug Administration (FDA), it fell outside the purview of the usual approval process. My aunt had three young children, and HDC-ABMT seemed to be her only hope.

在1992年，我有一个41岁的姑姑，她是个成功的律师，她进行了自体骨髓移植，她患有乳癌，并已经转移，对此骨髓移植是最后一招。自体骨髓移植当时还处于试验阶段，在第二期试验收到了比较好的效果。第三期的实验还没有完成，但由于食品和药物管理局同意进行大面积的治疗试验，这种方法的进展似乎超越了正常程序。我的姑姑有三个孩子，自体骨髓移植对她来说也许是最后一丝希望。

By then, AIDS activism had changed the very nature of patient advocacy. Physicians' willingness to prescribe HDC-ABMT off label permitted its decade-long use. But patient advocates were profoundly influential in making the investigational treatment accessible and appealing. As Siddhartha Mukherjee explains, “AIDS activism had transformed” the idea that experimental treatment was appropriately “unavailable for general public use.”2 Activists insisted that an investigational agent was not “a hothouse flower meant to be cultivated only in the rarefied greenhouses of academic medicine, but rather a public resource merely waiting in the warming antechamber of science while doctors finished clinical trials that would, in the end, prove the effica  cy of said drugs or procedures anyway.”2

       在那时，艾滋病激进主义者已经改变了病人的宣传方式。医生们愿意“无标签”使用自体骨髓移植的方法，使得其能够长期被使用。同时病人的宣传也产生了巨大的影响力，加快了临床的实验进展。正如Siddhartha Mukherjee所说：“艾滋病激进主义者改变了以往的看法即实验性的治疗方法不能大面积铺开。”激进主义者坚定地认为：“温室条件的花不一定非要在绝对的温室环境下才能被培育。正如药品一样，只要对于有把握在最终试验取得成功的，有需要的患者在前期就可以使用。

   In the case of AIDS, militant activism proved lifesaving. Progress in treating patients with HIV infection and AIDS depended as much on impassioned advocacy as on understanding retroviruses (see Part 3 of the documentary video “Getting Better: 200 Years of Medicine”). When men were dying in agonizing and unprecedented ways, unable to obtain drugs that showed promise in clinical trials, protestors demanded that approval of antiretroviral therapy be expedited. As famously noted by Larry Kramer, founder of the AIDS Coalition to Unleash Power (ACT UP), “Double-blind studies were not created with terminal illness in mind.”2

    在艾滋病的例子中，激进主义是为了救命。 对于免疫缺陷病研究的进展不仅取决于对逆转录酶病毒的认识，也取决于对该病的宣传。（请看纪录片的第三部分）。当人们因为病痛濒临死亡而又没有药物可用，病人会要求进行抗逆转录病毒治疗。艾滋病志愿者组织的发起人Larry Kramer曾经说：“双盲的研究不一定要到病情的晚期才进行”。

By 1992, regulatory burdens were relaxed, and the FDA initiated the Accelerated Approval Program, allowing drugs for life-threatening and otherwise untreatable diseases to be approved on the basis of surrogate end points. Thousands of patients who would otherwise have died began receiving effective treatment.

到1992年，食品和药物管理局放宽了监控并启动了快捷审批计划。基于替代终点（对病情的综合评估），一些用于致命性和无法根治疾病的药品得到批准。千千万万的病人得到有效的治疗，不然的话，他们就失去了生命。

Although such leniency was a coup for AIDS activists, the same impulse backfired in the case of HDC-ABMT, in which patient advocates focused on insurers that refused to cover this experimental therapy. The advocates urged women to take their cause to the courts. Stories of young women dying at the hands of faceless, profit-driven insurance companies were captivating, and the impulse to “save the dying bird” often prevailed. In one case, a federal judge noted, “To require that the plaintiff or other plan members wait until somebody chooses to present statistical proof . . . that would satisfy all the experts means that plan members would be doomed to receive medical procedures that are not state of the art.”3 Hamstrung, insurers agreed to cover the cost of HDC-ABMT, which averaged around $80,000. As a result, over the course of a decade, some 41,000 women opted to undergo the therapy, with about 9 out of 10 women choosing to receive the treatment outside a clinical trial.4

   这种政策性的放宽对于艾滋病激进主义者来说是一个很大的改变，然而在自体骨髓移植的案例中却适得其反。他们的病人把宣传的重心放在了保险公司，而保险公司不同意进行试验。他们把保险公司告上了法庭。好多年轻的妇女死于无耻的贪财的保险公司手中，这样的结果令人吃惊，但挽救生命的宣传者还是最终获胜。一个联邦法官如是说：“如果叫病人们等到试验结果出来时才采取治疗措施，尽管专家们会这么认为，但这样的做法是不明智的”。迫于无理，保险公司同意承担承担自体骨髓移植的费用，大约要80000美元每例。在接下来的十年中，大约41000名妇女参加了治疗，其中百分之九十的人都选择不参加临床试验。

  After undergoing HDC-ABMT, my aunt spent 41 days in the hospital, wracked by infection and misery, and then died. The treatment was covered by her insurers but probably shouldn't have been. After years of painfully slow trial enrollment, investigators finally reached some scientific truth: Among women with metastatic breast cancer, HDC-ABMT causes more harm than good.5

在进行了自体骨髓移植之后，我的姑姑在医院住了41天，饱受感染和疼痛的折磨，然后去世了。治疗费用是由她的保险公司支付的。在接下来缓慢的试验中，研究者最终发现：对于乳癌转移的患者来讲，自体骨髓移植弊大于利。

People tend to magnify the risks posed by emotionally salient events and to underestimate the risks posed by more common events — part of a phenomenon called the “availability cascade.” For example, although the risk of dying of asthma is nearly 20 times that of dying in a tornado, people consistently believe that tornadoes are the more likely killers.1,6 The cascade occurs when the media latch onto an emotionally charged event and ignite the public imagination so that not only the event but the fact that people care about it becomes a story — and a political issue.

人们倾向于放大重大事件引起的风险，而低估普通事件造成的风险，这种经验主义的现象称作“有效性错觉”。比如说：虽然哮喘病的致命性危害是龙卷风致命性危害的20倍，但是人们还是坚定地认为龙卷风的危害性更大。当媒体报道了伤感的事件，这样的错觉就产生了，报道激起了人们的想象力，从而不仅是事件本身，人们的对该事件的关注也都变成一个政治话题。

   Consider the withdrawal of approval of Avastin (bevacizumab) for women with end-stage breast cancer or the outcry against the recommendation by the U.S. Preventive Services Task Force that mammography screening for women under 50 years of age be done less frequently. The mind sees the faces of women who insist that Avastin or mammography saved their lives rather than the countless others who were harmed by these interventions. I believe that the same cycle of emotional availability and media coverage trapped insurers into paying for HDC-ABMT for women with metastatic breast cancer.

  来看看这些例子：不论是撤回许可安维汀（贝伐珠单抗注射液）用于晚期乳癌，还是抗议美国预防医学工作组不允许乳房X线多次用于50岁以下的妇女，人们只是关注了安维汀和乳房X线救了她们命的人们，而不关注还有更多人因为治疗的介入而产生的危害。我认为同样是情感因素和媒体的报道，迫使保险公司为自体骨髓移植买单。

  The challenge inherent in the evolving relationship between patient advocates and biomedical research lies in this psychological netherworld where emotions and numbers intersect. It is the advocate's job to give a disease emotional salience, to put a face to the illness and make people care. But it's the physician-scientist's job to generate data, analyze the data to permit reasoned risk–benefit assessments, and communicate those judgments to the public. Both roles are critical, but what happens when they merge? As Dresser notes, “Patient advocacy organizations that once let scientists determine the research agenda now decide for themselves what leads are most promising and award funds to researchers willing to pursue those leads. . . . A new breed of patient advocate sits at the table with scientists and policymakers, setting research agendas, planning studies, and considering how study results should affect clinical practice.”7

    病人的宣传与医学研究两者关系的挑战在于大众情感与病人数量之间的协调与否。宣传者让疾病被认同、被关注。医学研究者通过实验数据评估疾病并向人们报告他们的结论。宣传者与研究者的角色都很重要，如果他们之间能够很好地合作，情况会怎么样呢？正如Dresser所说：“以往宣传组织是让研究者来决定研究的计划，现在宣传组织与研究者一起讨论后来决定研究的计划，然后筹集资金给愿意承担的研究者来进行研究。一个新的组织是与研究者一起坐下来讨论，制定研究计划，预测研究效应。

The newest stage of this evolution is apparent in the Patient-Centered Outcomes Research Institute (PCORI), which will oversee comparative-effectiveness research. As Ellen Sigal, a patient advocate and PCORI board member, notes, patients have long been “symbolically at the table” but “only in a check-the-box sort of way.” PCORI's very mission is to fund research that matters to patients. Says Sigal, “The information that patients value may differ from the information that trials typically seek. Patients can remind researchers of the importance of quality of life or side effects of chemotherapy. Patients can also remind researchers, `I would never enroll in a trial like that.'”

  正如一个叫病人至上研究成果评价所，这个组织评估研究成果的相对效应。这个组织的理事会成员Ellen Sigal指出：“以往病人只是象征性的坐在讨论桌旁，如今该组织有权利决定哪些有研究价值然后再资助。研究者的研究有时不是病人的需求所在，病人可以提醒研究者生活质量的重要性以及化疗的副作用，病人也可以自愿决定参不参加试验”。

But what kinds of trials should patients enroll in? Here, the ethical challenge of trial design can collide with the passions of advocates — with unknown consequences. Sigal's organization, Friends of Cancer Research, for instance, recently worked with Congress and the FDA to add a clause to drug regulations allowing certain drugs that show promise in phase 1 testing to be granted a “breakthrough” designation. Drug sponsors would collaborate with the FDA early on, aiming to shorten the time to approval and minimize the number of patients assigned to receive comparatively ineffective control regimens.

   然而病人会参加什么样的试验呢？伦理的挑战在于实验计划与宣传者情感的碰撞，这种碰撞带来的结果并不明了。正如Sigal所在的癌症研究联谊会，他们最近与国会和食品药品监督局一道在药品的管理中增加了一个条款，该条款允许一些在试验期第一阶段表明有望的药物在政策上更加灵活。药品赞助商与食品药品监督局携手，缩短药品的审批时间，尽量减少使用相对无效对照药物的人数。

Vemurafenib, for example, a BRAF inhibitor recently approved for treating melanoma, showed tremendous promise in phase 1 and phase 2 trials, but this drug consequently created profound distress during phase 3 testing when some patients who could clearly benefit were instead receiving a control drug known to be ineffective. Was continued ineffective treatment really necessary when a new therapy was producing responses in 50% of patients?

例如一种叫vemurafenib的分子抑制剂，它最近被批准用来治疗黑素瘤。在第一和第二试验阶段，它便显出可喜的前景，然而在第三阶段却遇到了很大的障碍，本来可以受益的人们在使用了对照药物后发现效果消失。如果一种方法在50%的病人中表现出效果，还有必要一定要用控制药物吗？

But controls exist for a reason. Will the breakthrough designation foster successful scientific advances, as with AIDS, or tragically uncontrolled experimentation, as with HDC-ABMT? Of course we should pay attention to what matters to patients. But robust clinical trials must continue. As Dresser emphasizes, “Research is not treatment.”

   但是控制药物的运用是有其道理的。药物管理政策的灵活是会推进医学的发展如艾滋病，还是会导致悲惨的不用控制药物的实验如小细胞肺癌大剂量化疗自体骨髓移植？当然了，我们应该关注病人的切身利益。同时坚定的临床试验还是要继续。正如Dresser所说：“研究并不是治疗”。

   Sue Byrnes has never conflated the two. Research remains the LAM Foundation's core mission, though patients remain critically involved in the process. During an annual meeting, researchers share their insights into the disease with patients, who in turn offer testimonials about living with LAM. This model, says McCormack, has fostered a collaborative, informed spirit that has driven progress against LAM.

 Sue Byrnes从来没有混淆研究与治疗之间的区别。研究工作依然是LAM基金会的核心使命，病人在此过程中起到了关键性的作用。在一次年度会议上，研究者跟病人分享他们对病情的认识，同时病人向研究者汇报她们的生活状况。 McCormack说，这种模式体现了一种合作的、相互知情的精神，从而加快了攻克LAM的进程。

Indeed, since Byrnes began her efforts, the research environment and treatment paradigm for LAM have been transformed. In 1994, there was no LAM registry; today, the LAM Foundation has identified 1800 patients throughout several countries. Funding for LAM research, which was nonexistent at the time of Andrea's diagnosis, surpassed $40 million from federal and other sources, plus more than $10 million from the LAM Foundation, in 2011. Most important, young women with LAM need no longer be told that nothing can be done about their disease. Last year, McCormack and colleagues published the results of the first randomized, controlled trial for LAM, which showed the efficacy of sirolimus in preserving pulmonary function and improving quality of life.8

 事实上， 自从Byrnes开始她的尝试，LAM的研究环境和治疗模式有所改变。1994年时还没有LAM的登记机构，如今LAM基金会已经登记了来自于多个国家的1800名患者。在Andrea被确诊的时候，LAM还没有基金，在2011年LAM的资助已经超过4000万美元，这些钱来自于政府以及其它渠道其中1000万来自于LAM基金会。更重要的是，年轻的女性LAM患者们，不再被告知医学对该病束手无策。去年 McCormack和他的同事公布了第一个随机的、控制的LAM研究结果。结果表明：雷帕霉素可以保护肺功能还能提高生活质量。

McCormack acknowledges that the trial would have been impossible without the 15 years of research preceding it, plus some serendipity: one fortuitous event was the finding that the genes that cause tuberous sclerosis also encode a protein, the deficiency of which activates the cell-growth pathway in the lungs of patients with LAM. Coincidentally, sirolimus, which specifically targets that pathway, had just been approved by the FDA. But most critical was that impulse to save the metaphorical drowning bird.

McCormack认为：如果没有前15年的研究和一些意外的发现，这种试验是不可能的。其中一个意外发现就是：导致结节性硬化的基因也对蛋白进行编码，这种基因的缺失会激活LAM病人肺部的细胞生长路径。巧的是，刚被食品药品监督局批准的雷帕霉素就是抗击这种路径生长的。最有意义的还应该是这样药能够挽救垂危的生命。

As McCormack notes, “What LAM has taught me about medicine and health systems pales in comparison to what LAM has taught me about human nature.” He emphasizes physicians' tremendous volunteerism: “I can't recall a single physician investigator we called who said no. They are primarily motivated by wanting to have something to offer their patient.”

McCormack指出：“LAM教给我人性的知识远远胜过医学的知识，医生的志愿工作也起到了极大的作用，我们需要人手的时候，不管叫到哪个医生，没有一个拒绝的，医生们都很想为病人做点事情。”

And as pointed out by Alan Barker, a pulmonologist at Oregon Health and Science University and an investigator in the sirolimus trial, physicians' altruistic impulse was matched by that of patients: “The women who participated in the trial made enormous sacrifices. They travelled great distances. They were given no guarantees on anything.”

“Put yourself in their shoes,” McCormack says. “Half of normal lung function remaining, declining by 10% year after year, and signing up with the 50% chance that lung function would drop by another 20% on placebo while the promising drug being tested is available with a prescription from any doctor and a trip to the pharmacy.” But hearing these numbers did not temper the patients' desire to help; they knew their participation remained essential to the scientific process.

   俄勒冈健康与科学大学的胸腔科医生Alan Barker是雷帕霉素试验的研究员，他指出：“参与试验的妇女们做出了巨大的牺牲, 她们需要长途旅行，而且没有资金赞助”。 McCormack说：“我们也要替这些参与者试验的病人想想，她们的肺功能只有正常人的一半，而且每年以10%的速度下降，在试验阶段，用了无效对照剂后肺功能又会下降20%，这样的试验后，该药才会被批准为处方药，药厂才会生产。”虽然有这样的影响，病人们还是义无返顾地参与，他们深知他们的参与对于研究的进程至关重要。

      We are thus left with a paradox: although the altruistic impulse may make our minds less receptive to data, it is this very impulse that allows us to generate data in the first place. But if emotional responses are insensitive to numbers, numbers are equally insensitive to the human psyche. Establishing any drug's safety and efficacy depends on an acceptable benefit–risk ratio, but the values assigned to the variables that we include in those ratios will always be a matter of debate. How can we quantify the agony of facing an untreatable disease? Can we measure the harms we inflict because we can't bear to tell patients they have no options? Can we assign a numerical value to hope? For those aspects of disease that elude our measurement, we will forever depend on the insights and passions of our patients.

     于是我们得出了一个似是而非的结论：尽管这种无私的行为使得我们面对数据结果不那么敏感，然而正是她们无私的参与才得出了数据结果。但是如果人们在情感上对于数据不敏感，同样的心里也不会关注。能否生产出安全的有效的药物取决于接受范围内的利弊比率，但是与比率相关的变量所占的分量一直是有争论的。我怎么能衡量面对无治病的痛苦吗？我们能估量出当我们告诉病人无法治疗时而带给她们的伤害吗？我们能给出药物前景一个定量的价值吗？这些方面使得我们不能精确地评估这些变量，我们将会更关注病人的感受。

来源：新英格兰医学杂志 New England Journal of Medicine

翻译志愿者：王亮