Parkinson's Clinical Trials: Red Flags, Safety, and What to Consider

《帕金森症播客》由戴维斯·芬尼基金会出品，为您带来帕金森症患者、照护者以及专业人士的真实故事、宝贵经验和专业见解。

The Parkinson's Podcast is brought to you by the Davis Phinney Foundation and brings you the stories, wisdom, and expertise of people living with Parkinson's, care partners, and Parkinson's professionals.

在本期《帕金森症播客》中，克里斯·克鲁格与多伦多大学的临床研究团队对话，深入探讨临床试验的运作方式、参与者如何获得更好的试验体验，以及为什么团队协作对试验至关重要且效果更好。

In this episode of the Parkinson's podcast, Chris Krueger talks with a clinical research team from University of Toronto about how the clinical trial process works, how participants can have the best experience in a trial, and why a team approach to trials is necessary and good.

在本期节目中，您将听到阿方索医生的分享。

In this episode, you'll hear from Dr.

阿方索·法萨诺医生，

Alfonso Fasano, Dr.

阿图罗·阿本德斯·科罗纳医生，萨拉·纳格德卢，一位拥有生物医学工程背景的临床研究协调员，以及杨宇妍护士，她在多伦多大学支持临床试验工作。

Arturo Abundes Corona, Sara Naghdlou, a clinical research coordinator with a background in biomedical engineering, and Yu-Yan Poon, a registered nurse who supports trials at the University of Toronto.

正如团队所强调的开放与包容精神，他们邀请克里斯直接称呼他们的名字。

In keeping with the open and welcoming spirit the team describes, they invited Chris to use their first names.

本期节目由BlueRock生物治疗公司赞助。

This episode is sponsored by BlueRock Therapeutics.

你好，阿方索。

Hi, Alfonso.

你能跟听众简单介绍一下你的背景，以及你是怎么参与到帕金森病研究中的吗？

Can you tell the audience a little bit about your background and how you came to be involved in Parkinson's research?

当然可以。

Yes.

谢谢你们邀请我。

First of all, thanks for having me.

能来这儿我很荣幸。

It's a pleasure.

我决定当神经科医生，是因为当学生时，我对脑深部刺激技术特别着迷。

And, yeah, I I decided to, become a neurologist because I was fascinated when I was a student by deep brain stimulation.

那时候DBS还处于早期阶段，我第一次看到患者接受治疗时，简直震惊了。

The back then, it was early days that DBS was used, and it was mind blowing when I saw the first patient.

我当时还是医学生。

I was a medical student.

所以从一开始，我就决定投身神经科，专门研究脑深部刺激。

So I I knew already to start in neurology, I wanted to do deep brain stimulation.

由于深部脑刺激主要用于帕金森病，所以帕金森病自然就成了我关注的重点。

And because deep brain stimulation is largely used in Parkinson's disease, automatically Parkinson's disease became the disease of interest.

于是，我就在这里了。

So and now here I am.

很好。

Great.

我注意到你的名字经常出现在各种临床试验报告里，你参与了大量研究，既协助推进试验，也担任过很多研究的负责人。

And so as I I've seen your name in a lot of different trial reports, and you participate in a lot of studies, in terms of, you know, helping to run the studies and being a PI on a lot of a lot of research.

为什么这必不可少呢？

Why why is that necessary?

为什么临床试验这么重要？

Why are clinical trials necessary?

当然。

Absolutely.

我们今天做这个播客，正是出于这个原因——遗憾的是，公众对临床试验的作用以及科学如何进步，讨论得还不够多。

This the real reason we are doing this podcast today because it's, unfortunately, discussed enough with the big public, what's the role of trials and how science moves forward.

结果就是，我们在新冠疫情期间看到了这种情况——很多人把责任推给医疗界，觉得他们不够快，或者对疫苗的使用充满疑虑、担忧，甚至牵扯到医学研究的伦理问题。

And the net result of this, we've seen it during the COVID pandemic where a lot of people were actually, blaming the medical community, you to be fast enough or if there are, there were use of, let's say, vaccines, they were seen with a lot of reluctancy and a lot of concerns and a lot of issues that tapped into ethical aspects of doing research.

所以我们必须清楚地解释科学是如何进步的。

So it is absolutely crucial that we explain how science moves forward.

科学的进步本来就是缓慢的，而且必须如此，因为有些研究活动可能对患者的健康构成风险。

And science moves forward slowly and has to because some of these activities can be dangerous to patients' health.

临床试验目前是科学方法验证某种疗法是否有效且安全的唯一途径，而这归根结底才是我们真正想要的。

Clinical trials are basically the the way at the moment the scientific method works to prove that something works and is safe, which is at the end of the day what we want.

我们可以详细讨论试验是怎么设计的，但简单来说，我们的目标就是证明某种疗法既安全又有效，而且要在最符合伦理的前提下，尽可能快地完成验证——当然，正如我所说，科学自有它的节奏。

We can go into the details of how trials, are are are designed, but in a nutshell, our goal is to prove that something is safe and effective, and we are trying to prove this in the most ethical way and the fastest possible way even though, as I said, science takes its own time.

所以我总是提醒我的病人：当某种疗法听起来太完美，号称能治所有病，而且完全没有任何研究依据就推到你面前时，一定要保持警惕，别轻易相信。

And that's why I always tell my patients to be careful and skeptical when something is seen as too good, when it fixes everything and when it's brought to them absolutely without studies.

不幸的是，有时候背后是商业利益在驱动，甚至存在真正的骗局，尤其是在网上。

Unfortunately, sometimes there are commercial interests and there are real scams, especially online.

这也是为什么大家必须了解科学是如何推进的，这样才能避免自己陷入不必要的风险。

And and that's the other reason people need to know how science moves forward so that they are not exposing themselves to risks.

是的

Yeah.

谢谢你给出的全面介绍。

Thanks for thanks for the big picture overview.

在这期播客里，我们想聊聊临床试验的背景。

And I think one of the things we wanna do on this podcast episode, in this conversation is talk about the background of clinical trials.

同时我们也想谈谈试验是怎么实际开展的，还有那些热情支持这项工作的人，以及他们对帕金森病群体的广泛影响。

But we also wanna talk about how they actually run and and the the fact that there's a lot of people who are really passionately supporting this work and, and how that influences the Parkinson's community more generally.

不过在那之前，我们先继续花几分钟，把重点放在这个总体概述上，你介意吗？

But right now, we're just gonna stay focused for a couple more minutes on on the sort of overview pieces, if you don't mind.

你能简单说说临床试验有哪些类型，以及各个阶段是怎么划分的吗？

Can you just say a little bit about what types of trials there are, and what what about phases of trial?

大家应该了解哪些关于试验类型和阶段的信息？

What should people know about types of trial and phase of trial?

当然可以。

Absolutely.

我来给你做个概括。

I'll I'll give you an overview.

你别插太多话，因为听众很快就会明白，临床试验离不了一个庞大的团队。

Try not to talk too much because as, the listeners will understand soon, clinical trials are not possible without a big team of people.

实际上，我的工作范围很有限。

And, actually, my job is quite limited.

我做的事情很少。

I I do very little.

作为主要研究者，我或许会领功，

And and, yes, as a PI, I might take credit.

但说实话，我之所以能领功，是因为万一出问题，我也得担责任。

In reality, the credit comes from the fact that I take also responsibility if something goes wrong.

不过，我本人其实并不亲自操办这些试验。

But, absolutely, I'm not really running the trials myself.

我们相信，你很快就会听到那些真正推动试验的团队成员的声音。

I we doubt that the the team, the people that you the listeners will listen, from very soon.

我刚才说的这些，其实都做不到。

None of what I'm saying is possible.

所以我会尽量简短一点。

So I'll try to be, short here.

回到你刚才的问题，我们有哪些类型的临床试验。

Back to your question, what type of clinical clinical trials we have.

简单来说，这些试验可以分为两大类。

So, in in a in nutshell, we can divide these trials in two big categories.

一种是观察性研究，我们只是长期跟踪某种疾病或疾病中的某种现象。

We can have observational, studies where we simply follow, say, a disease or a particular phenomenon within a disease over time.

其中一些长期跟踪的，我们称之为纵向研究。

And some of these are when we follow them over time, they're called longitudinal.

有时候只是某个时间点的快照，这种叫横断面研究。

Sometimes it's just a snapshot, and this is what we call it the we call these studies cross sectional.

有时候，也是最容易做的，就是回顾过去发生过什么、做过什么，这叫回顾性研究。

Sometimes, and these are the easiest to do, we look back on what's happened, happened, what's been done, and we call this retrospective studies.

显然，在这种情况下，最好的观察性研究是纵向研究，因为我们可以说：从现在开始。

Obviously, the best studies in this context, the observational ones, are the longitudinal ones because we say, okay.

我们会持续追踪所有帕金森病患者，看看他们什么时候会出现不自主运动——这只是帕金森可能引发的一个问题例子。

From now on, we follow all people suffering from Parkinson's disease because we wanna see when they develop dyskinesias, just to mention a problem that Parkinson's can cause.

因为是纵向研究，我们会以严谨且标准化的方式密切跟进这些患者。

So because it's longitudinal, we are following these people closely and in a very thorough and standardized fashion.

这类研究能提供更丰富的信息。

So these are the type of studies that give us more information.

典型的这类研究还包括对疾病发病率或患病率的调查。

Typical studies like these are also studies that are looking at the incidence or prevalence of a disease.

也就是说，我们想知道某种问题有多普遍，尤其是发病率，我们要统计每年新出现多少例。

So how common a certain problem is, in particular for incidents, we want to know how many new cases per year of a particular problem we see.

但我猜大家最关心的还是另一类试验，也就是干预性研究。

But I guess the biggest interest goes for another type of trials, which are the interventional ones.

我刚才讲了观察性研究，现在我们来谈谈干预性研究。

So I told you about the observational, but, now we talk about the interventionals.

而干预性研究，顾名思义，就是在测试某种干预措施。

And interventionals, as the name says, are testing an intervention.

这可能是某种药物。

This can be a medication.

也可能是生活方式的调整。

It can be a lifestyle change.

或者是康复训练方法。

It can be a rehabilitation, technique.

又或者是外科手术治疗。

It can be a surgical treatment.

在这类试验中，通常至少要是前瞻性的，我们会实施某种干预。

And so in these trials, which are typically, they need to be at least prospective, we do an intervention.

我们会先评估患者在干预前的状态，干预后立即再评估，之后还会持续跟踪，看看这种干预的效果能持续多久。

So we assess the patient before the intervention, right after the intervention, and then over time, also to see for how long that particular intervention has an effect.

所以，这就是临床试验的两大主要类型。

And so these are the two big groups of of of trials.

你还提到了阶段这个话题。

You also mentioned the the topic of phases.

这更多是个专业术语，但大家有必要了解。

This is more of a a technical term, but people need to know about it.

一般来说，研究分为四个阶段。

Typically, there are four phases of research.

第一阶段、第二阶段、第三阶段，还有第四阶段，这都很清楚。

Phase one, two, and three, and four, obviously.

第一阶段是人体第一次接触某种药物之类的治疗手段的时候。

Phase one is this is the very beginning of when a human body is exposed to, let's say, a medication.

第一阶段通常只涉及很少的受试者，往往是健康志愿者，没有患病，自愿接受治疗。

Typically, phase one are done on a very few subjects, often normal subjects or subjects without the disease, volunteering to receive the treatment.

第二阶段就是把这种干预措施应用到更多患者身上了。

Phase two is when this particular intervention is now given to patients, a bigger group.

第二阶段试验的主要目的，是评估这种干预措施是否足够安全，可以进入第三阶段。

Usually phase two trials have the goal of discussing and determining whether that particular intervention is safe enough to move to phase three.

到了第三阶段，参与的人数就更多了。

And in phase three, we have a bigger group.

通常这时候是多中心研究，参与者会进入所谓的随机对照试验。

Usually, these are multicenter studies where people at this point are entering what we call a randomized controlled trial.

所谓随机，就是一部分人接受治疗，另一部分人不接受，具体谁分到哪一组，我们不能自己决定。

Randomized means that a group of people get the treatment, the other group doesn't, and we cannot decide who gets it and who doesn't.

所以我们会让电脑随机分配，决定谁接受实际治疗，谁不接受。

So we really randomly, let usually a computer decide who is, receiving the active treatment versus not.

我解释一下为什么叫‘对照’——就是说有一组人不接受实际治疗，而是接受安慰剂或另一种干预手段。

And when I say, so I explain why randomized, controlled means that we have a group that is not getting it, but is getting a placebo or another intervention.

这就是‘对照’的意思。

This is what we mean when we say controlled.

如果试验成功，就会进入第四阶段，这时药物或其他疗法会提供给更大规模的人群。

And then if successful, successful, they they enter enter phase phase four four where where the medication is usually given or medication or something else is given to a larger group of people.

这时候就不再采用盲法了。

It's not blinded anymore.

这实际上是更大规模的人群，随访时间更长，通常是一年。

It's really a larger cohort of of people followed for longer, usually a year.

这些研究主要是为了深入评估疗效，同时从安全性角度发现那些在小规模受试者中看不到的潜在问题。

And these are meant to really explore the efficacy, but also safety wise to detect potential concerning, problems that are not visible, when you only select, and enroll few patients.

因为一些罕见的不良反应，只有在纳入越来越多的人之后才会显现出来。

Because some rare events, you don't see them until you start, enrolling more and more people.

有时候，即使到了第四期也还是发现不了。

And sometimes you don't see them even in phase four.

你得等到药物获批上市、广泛使用后，才可能遇到其他情况。

You need to wait until the medication is approved and commercialized when something else happened.

比如帕金森病里有一种药叫托卡朋，一期到四期试验都表现很好，上市后也很有效，但后来有少数患者出现了肝衰竭这种罕见事件。

For example, in Parkinson's, there was a great drug called Tolcapone, very effective phase one, two, three, and four, all good, was commercialized, very effective for Parkinson's, but then a rare event happened and happened in a few patients that is, liver failure.

所以那时所有与这种药物使用相关的流程都必须重新调整。

And so this is when the, everything had to be, changed, every all the procedure related to the use of this medication had to change.

从某种意义上说，药物即使上市了，也依然处在持续的试验阶段。

So in a way, a medication is always in a trial phase even when it's finally commercialized.

为了总结一下这部分讨论，我想问问你，这些年来你看到临床试验有哪些变化？在帕金森病的临床试验设计和方法上，哪些改变是最积极的？

Just to round out this part of this conversation, I wonder if you can say how have you seen trials change over the years and, you know, what changes have been most positive in the way trials are run and and and approaches that are being taken to clinical trials in Parkinson's?

哪些变化带来的好处最大？

What changes have been most beneficial?

确实如此。

Yeah.

这是个非常好的问题。

This is a great question.

我想提到两点。

I wanna mention two things.

第一点是，我们逐渐意识到，患者真正关心的并不是震颤减轻了多少，或者做UPDRS量表测试时手指活动是否更灵活。

The first one is that we realize that what care what patients care is not if they can have less tremor necessarily or can move better their fingers when once we do the, UPDRS, which is the classic scales we use for Parkinson's.

他们更在意的是生活质量能不能提升。

They wanna have a better quality of life.

因此，很多试验的首要评估指标已经发生了转变，不再只关注疾病带来的运动症状，而是转向了功能、残疾程度和生活质量这些更贴近患者实际体验的指标。

So that's why there's been a shift in the primary endpoints in many trial where the trial has focused on scales measuring functioning, disability, quality of life, rather than the actual motor problem that comes from the disease.

这是一个很大的变化，主要是由深部脑刺激的研究推动的。我们知道深部脑刺激非常有效，但患者却并不满意。

That's been a big change that was largely driven by the studies in deep brain stimulation where we knew that deep brain stimulation was very effective and yet patients weren't happy.

这也让我们意识到，有时候这些干预措施会导致言语问题。

And this is why why we realized that sometimes these these interventions cause speech problems.

这些问题比减少震颤更重要，因为沟通对人类来说至关重要。

They are more important than having less tremor because communication is key to humans.

我还可以举出更多例子。

And I can I can give you many more examples?

另外一点是，这些年我们逐渐意识到，有些干预措施表面上看似乎能改变疾病进程。

The other thing that we changed over over the years is recognizing that some interventions, they look like they are disease modifying.

但实际上它们之所以有效，是因为产生了症状缓解的作用。

They're actually, helping because they have a symptomatic effect.

也就是说，我们当初测试这种药物时，是希望它能延缓疾病进展，结果也确实看到了效果。

Meaning that we test the medication thinking that the medication makes the disease slow down, and we see that.

之所以看到效果，是因为这种药物对帕金森病的症状有积极的改善作用。

We see that because that medication has a positive effect against the symptoms of Parkinson's.

所以我们只是在掩盖病情的进展。

So we're just masking the progression.

这么说吧，通过这些试验过程，一个明显的变化是，参与试验的人开始更加关注帕金森病患者的真实体验，而不再只盯着最初设计或选定的那些指标。

And it sounds like one of the ways to summarize that is it sounds like maybe through the trial process, we've one of the things that's changed is people have people involved in the process have started to pay more attention to the actual experience of the the the people with Parkinson's that are participating in these trials rather than just looking at the outcomes that were initially approached or designed for the trial or chosen for the trial.

没错。

Correct.

明白了。

Okay.

那我现在最后问你一个问题。

So maybe last question I'll ask you at this point.

如果有人在考虑参加临床试验，应该注意哪些警示信号？又该怎么判断某个试验是否适合自己？

What red flags should people watch out for if they're considering a trial, and and how should somebody evaluate if a trial is a good fit for them?

这是个非常好的问题，非常实际。

That's a very good question because it's very practical.

首先，临床试验的设计和审批都经过了伦理委员会的审核。

So first things first, clinical trials are designed and they're approved by ethical review boards.

伦理审查委员会的目标是确保所提出的方案是合理的，安全性足够，并且方案中有明确用通俗语言向患者描述的注意事项。

And the goal of the ethical review board is to make sure that what's proposed is plausible, is safe enough that if there are notes that are clearly described in lay language to patients in the protocol.

但简单来说，第一步就是仔细阅读方案，然后是知情同意书。另外很重要的一点是，如果有不清楚的地方，一定要提问。

But the starting point, just to give you an answer in a few words, is to read carefully the protocol, then from consent, and if to ask and and is the other important point is to ask questions if something is not clear.

对。

Yeah.

我想补充一点，提问的对象不一定仅限于参与试验的人员。

And I guess I would add one little note there, which is that asking questions doesn't have to be limited to the people involved in the trial.

其实，我想说这么一件事。

In fact, well, I'll I'll say this.

我自己就患有帕金森病，也参加过一些研究项目。

I I happen to live with Parkinson's myself, and I participated in some research.

每次遇到这种情况，我都会去问别人，甚至去问我的全科医生，而不是直接问我自己的运动障碍专科医生，我会问：

And I always went to other people, to my to my primary care doctor even, not even to my my own movement disorder specialist and said, hey.

这适合我吗？

Does this sound right for me?

有时候我问了别人，结果他们说不行，但我还是参加了试验。因为我跟其他人聊过，这其实是我整个过程的一部分，我觉得特别重要。

And, you know, sometimes I got no when I ended up participating in the trial anyway because I've I talked to other people and, you know, but that's that was just it was part of my process, and I think it's was an important part of my process.

对。

Yeah.

这确实有道理，但我们也得承认，尤其是新疗法刚出来的时候，相关信息本来就少，有些东西听起来可能挺奇怪的。

It is a valid point, but, also, we need to acknowledge that sometimes, especially when it's new, you know, new interventions, there's not much knowledge out there, and few things might sound strange.

对不懂行的人来说，征求别人意见是合理的，但同时也要明白，这很可能正是你最终决定参与的原因。

And to someone who's not in the field, it makes sense to ask opinion, but also that needs to be taken into account that that's probably the reason why you eventually decide to be part of this right anyways.

还有一种信息来源是网上，但网上也可能是个坑。

There is another type of, information that you can gather online, and online can be a trap.

其实真正值得信赖的网站没几个。

So there are very few websites where people need to go to.

但如果你对生物学有一定了解，或者你咨询的人懂行，就可以去临床试验官网（clinicaltrial.gov），那里收录了所有临床试验的信息。

But if you have a good understanding of biology or the person you're asking to ask, they can go on clinicaltrial.gov, which is a website that collects all the clinical trials.

如果你被邀请参加某个临床试验，但在那个官网查不到相关信息，那就得留个心眼了。

If you're asked to be in a clinical trials and you don't find your clinical trials on that portal where these trials are typically recorded, that's suspicious.

还有其他数据库。

There are other databases.

最常用的是那个美国的数据库。

Is the most used one because it's the American one.

但这说明，如果你在网上查信息，还有其他独立渠道可以验证你听到的内容。

But this is to say that they're also independent way to validate what you're told if you go online.

另一个很好的信息来源是PubMed，我管它叫医生们的谷歌，你只要输入某种分子、疗法或者疾病，就能看到相关研究进展。

Another great source of information is PubMed, which is what I call the Google or doctors, where you can type a molecule or intervention, a disease, and you can see what's being done.

有时候病人会来找我，说他们想接受某种治疗。

Sometimes patients come to me and say, I wanna do this treatment.

那些都是我听过的最离奇的疗法。

They're the most exotic things I ever heard.

而且价格特别贵。

Very expensive.

是的。

Yeah.

人家跟我说这是实验性的，听起来还挺酷的，因为是实验性的。

And I'm being told it's experimental, and it sounds like it's cool when it's experimental.

但事实上，这些人根本就是在被骗，人家只是要他们掏钱来买这些所谓的治疗。

But in reality, all that these people are are receiving is a scam, is they're getting asked for money to be receiving these things.

有时候当着他们的面，因为我也不清楚所有临床试验，我就上网查给他们看，要是我遇到这种情况我会怎么做。

And sometimes in front of them, because I don't know all the trials, I go online and I show them what I will do if I were them.

所以我教他们该用哪些资源，结果我一在PubMed上搜这个疗法，连一篇相关论文都找不到。

So I teach them what resources to use, and it happens that I type that intervention on biomed, and there's not even a single paper on that.

这样一来，我就有底气告诉他们：别理这些人。

And so that gives me the confidence to say, you know, stay away from these people.

他们纯粹就是在骗你。

They're just scamming you.

还有很重要的一点：参加临床试验或者接受实验性治疗，本来就不该花钱。

The other important thing is that people are not supposed to pay to be in in clinical trials or in or receiving experimental treatments.

所以只要有人开口要钱，那就是明显的危险信号。

So if someone asks for money, that's a super red flag.

阿图罗，谢谢你今天抽出时间跟我聊聊。

Arturo, thanks for taking the time to to speak with me today.

能不能先跟我们讲讲，你在帕金森病和帕金森研究方面的背景？

And just wondering if you can start by telling your us a little bit about your background in Parkinson's and Parkinson's research.

当然可以。

Of course.

非常感谢邀请我参加这个系列访谈。

Thank you so so much for the invitation to this, series.

我觉得这样的对话特别重要，不只是和医生，也要和这里的整个团队交流。

I think it's quite important to have these conversations with not only doctors, but also the the whole team here.

我的背景是，在我的祖国墨西哥接受神经科培训，那时我真正爱上了运动障碍和神经退行性疾病，因为从临床检查的角度看，它们既有趣又极具挑战性。

So, my background is that I trained as a neurology a neurologist in my home country in Mexico, where I developed a real passion for movement disorders and neurodegenerative conditions because it was, in my eyes, the most interesting in terms of physical examination and also quite challenging.

但很早我就意识到两件事。

But early on, I actually realized two things.

第一，我们在解决这些问题、真正有效治疗患者方面，还差得很远。

First, that, we were quite far away from really solving these issues and really treating people effectively in many of these cases.

但与此同时，我也意识到，如果我们能积极倡导某些临床需求，真正为患者发声，就能产生非常积极的影响。

At But the same time, I also realized that, we could have a very positive impact if we, advocated for particular clinical needs and we really hurt our patients.

这让我对帕金森病和其他运动障碍产生了浓厚的兴趣。

So that made me really get a very important interesting to Parkinson's and other movement disorders.

这些年来，我围绕几个子课题做了研究，比如帕金森病中的社会健康决定因素——我觉得这个方向特别有意思，尤其是在拉丁美洲，那里的社会差距很大，人们的生活方式和对疾病的应对方式差异非常明显。

And over the years, since I've done research on several subtopics, let's call them, for example, social health determinants in Parkinson's disease, which I found quite interesting, particularly in Latin America where we have, a lot of divide in in terms of, how people live and how people, interact with their own diseases.

谢谢你的分享。

Thanks for the background.

我之所以想和多伦多团队的每一位成员聊聊，是因为我参加前两项临床试验时，被诊所里这么多专业人员深深打动了。

So one of the reasons I wanted to talk with with all of the team at Toronto in Toronto, all of your your team, is that when I participated in in the first two trials I participated in, one was observational and one was testing a possibly neuroprotective new treatment, I was so surprised and impressed by the fact that there was there were so many knowledgeable people in the clinic.

有一次，我照常去就诊，发现平时一直为我看诊的医生不在，换成了另一位医生。

And in fact, at one point, went in and the the person I had been seeing the physician that had been there every other time wasn't there, there was a different physician.

我当时还挺意外的。

And I was like, oh, well, that was a surprise.

但后来发现这反而是好事，因为我有更多机会和另一位医生交流，听到不同的看法。

But it turned out that was great for me because I got more time to talk to somebody else and hear their perspective.

所以我想问问，你能描述一下开展一项临床试验需要哪些条件吗？涉及哪些不同角色？这对帕金森病患者来说又有什么实际价值？

So I think, you know, I guess I wanted to ask you if you could describe what it takes to run a trial, the different roles that are involved, and and what the what value that brings to the to the experience for people with Parkinson's?

当然可以。

Of course.

当然可以。

Of course.

不是的。

No.

我觉得这是个非常关键的问题，因为很多人以为研究是某个机构单独完成的，但实际上，临床试验恰恰最能体现团队协作的重要性。

I think this is a a fundamental question because sometimes, the the general idea is that there's this entity that creates research in that soul, but, really, it's certainly a team effort, and running a clinical trial is the biggest example of this.

这需要一群有专业知识、充满热情的人，他们提出正确的问题，验证有意义的假设，更重要的是，确保参与者安全、得到妥善照顾，并且所有研究目标都真正以改善患者群体的生活为目的。

So it takes knowledgeable passionate people who ask the right questions, who test the correct hypothesis or meaningful hypothesis, but most importantly, who make sure also that the participants are safe and well cared for and the that the objectives of the research or the science that is, being tested is with with the intention of really helping a population.

归根结底，我们的终极目标是推动科学进步，提升帕金森病患者的生活质量。

So, in in the end, the ultimate goal is to advance science and improve quality of life for people living with Parkinson's disease.

这绝不仅仅靠一位医生就能做到。

And this does take more than just a doctor.

这确实需要科学家，但也需要其他以不同方式接触帕金森病患者的人。

It does take scientists, but also other people who may interact with people living with Parkinson's in different ways.

比如研究协调员、护士等等。

This includes research coordinators, nurses, etcetera.

由于临床试验涉及的是人，因此天然包含许多伦理考量。

And because trials involve human beings, this intrinsically has several ethical considerations.

所以团队的多样性也很重要，因为不同背景的人能带来不同视角，有助于化解可能出现的伦理问题。

So that diversity in the team also is quite important because that helps to dissipate these ethical issues or challenges that may come, because everyone has a different perspective on on this issue.

而这也正是为什么团队既需要多样化，又需要高度专业化的原因。

And, yeah, that's his that's, I think, the reason why the team should be so diverse and specialized at the same time.

我可以具体谈谈这个团队里各个角色的分工。

And, I can talk about, the different, you know, participants in this whole team, of course.

对。

Yeah.

如果你不介意的话，能简单介绍一下其中几个主要角色吗？

If you don't mind, can you just run down a couple of the the different roles?

我知道随着节目继续，我们还会再聊到这些角色，不过你能不能先简单介绍一下都有哪些关键职位？

And and I know that we'll we'll speak about these again in as the podcast progresses, but maybe you can just give a quick overview of what the what the different seats are, so to speak.

当然可以。

Yes.

当然可以。

Yes.

没问题。

Of course.

这个团队的构成有几个不同层面。

So there are several levels of this.

比如，有资助方，他们通常提供资金，让研究得以开展。

So for example, we have the sponsors who usually provide funding that makes the study possible.

还有主要研究者，以及其他子研究者，他们负责推动研究进展，回答核心的科学问题，或者设计严谨的实验方案来解决这些问题。

We have a principal investigator who and other sub investigators that basically drive the study forward and maybe answer the big scientific questions in hand or or try to prepare protocols that really will address this in a scientific, a very sound manner.

另外还有护士。

We also have nurses.

比如，这里就有于燕，她就是一个很好的例子。

We have Yu-Yan here, for example, who is an excellent example on this.

但这个团队成员的适应能力非常强。

But this this part of the team is incredibly versatile.

他们可以承担研究者的角色。

So they they can act as investigators.

也能担任评估员或护理人员。

They can act as raters, as caregivers.

基本上，他们是把整个团队串联起来的关键。

And, basically, they are kind of the glue that holds everything together.

他们还负责后续跟进，确保参与者整体体验良好。

They also handle follow ups and make sure participants have overall a positive experience.

他们同时也是参与者与临床团队、协调员之间的沟通桥梁。

And they can also be these conduits between participants and the clinical team and also the coordinators as well.

所以这是一个非常灵活的岗位。

So quite a versatile position.

我们还有团队协调员，也就是研究协调员，依我看，这是最具有挑战性的角色之一，因为他们不仅要懂背后的科学，还得确保项目持续推进。

Then we also have the team coordinator, the research coordinators per se, who, in my opinion, is one of the toughest roles because this involves not only knowing the science behind the things, but also basically they keep the project moving on.

他们要处理很多事，比如招募患者——这本身就很困难，总是充满挑战。

So they handle a series of things, for example, recruitment of patients who which, intrinsically, it's quite challenging always.

他们还要负责伦理委员会的审查、方案的修改，这些都必须做好，确保研究真正回答关键问题。

They also handle ethics committee reviews, amendments to the protocols that most must be done to ensure that the protocol, you know, answers the correct questions.

当然，还有患者照护和后勤安排。

And, of course, patient care and logistics as well.

这工作就像是科学家、临床人员和社工的结合体。

So it's it's a mixture between a scientist, some somewhat a clinician, but also kind of a social work situation there.

所以这个角色其实非常有意思。

So it's quite an interesting position to be in.

然后还有IRB，也就是机构审查委员会。

And then we have the IRB, which stands for Institutional Review Boards.

这个我们可以再深入聊，但它至关重要。

We can talk about this more in-depth, but this is fundamental.

如果没有IRB的批准，根本就谈不上研究。

There is no research if there is no IRB approvals, basically.

这是因为，正如我之前说的，我们在人体上测试药物或干预措施时，必须考虑内在的伦理问题。

And this is because, as I told you before, the intrinsic ethical considerations that have to be done when we test drugs or interventions in people.

所以，伦理委员会确保所有环节都符合最高的伦理标准，保护参与者免受伤害或不当做法的影响。

So the disease committee basically ensures that everything meets the highest ethical standards and protects participants from harm or from maybe practices that are not correct.

最后，我还想提一下，除了研究团队之外，参与者自己的医疗团队也很重要。

And finally, I also need to mention that maybe outside of the research team, we also have the participant's own care team.

这可能包括家人、朋友，以及通常负责照顾这位患者的主治医生。

And this may include family, friends, the primary physician that takes care of this patient usually.

这一点也很关键，必须纳入这个体系，因为这是成功不可或缺的支持。

And this is important to also kind of include in this list because that is a support that is essential for success.

它能提供安心感。

It it can give reassurance.

它还能客观地评估结果或某些事件的发生情况。

It can give also an objective measurement of outcomes or of, for example, events.

所以，为患者建立一个专属的支持网络非常重要。

So it's very important to to involve a network of support particular to the patient.

是的。

Yeah.

我待会儿会问你关于安全的问题，顺便分享一段我的经历，说明为什么我的医疗团队很重要——这正好是个很好的例子。

I had a I'm gonna ask you about safety in a second, and I'll share an experience that I had that relates to why my care team was important why a care team is important, and it'll be an example of my care team being important.

但我参加的某项研究中曾出现过一次不良反应。

But I had an adverse event occur in one of the studies I I participated in.

虽然不算严重，但他们立刻暂停了我的参与，只为确保我的安全。

It was relatively minor, but it put the brakes were immediately thrown on my participation in the trial because they wanted to make sure that I was safe.

我当时就想，好吧。

And I was like, okay.

这其实非常好。

Well, that's really great.

我很感激。

I appreciate that.

另一方面，他们也不希望成为唯一评估我经历的人，我也不希望只有他们来评估我这次不良事件的体验。

On the other hand, they also didn't wanna be the only people evaluating my and I didn't want them to be the only people evaluating my experience of this adverse event.

所以，我的全科医生最终成了我的参考对象，他们也鼓励我回去找他，他参与了评估那些决定不良事件性质的检测结果。

So my my in my primary care doctor ended up being a source of reference for me, and and they encouraged that too so that I went back to my primary care doctor, and he was involved in evaluating the test results that determine the nature of the adverse event.

但你再跟我多讲讲临床试验中的安全问题吧。

But tell me more about safety in clinical trials.

一个人该怎么评估自己对风险的承受能力，以及试验的安全性，确保两者相符呢？

So how can a person evaluate their risk tolerance and the safety profile of a trial and make sure they're in alignment?

当然。

Of course.

当然。

Of course.

我觉得这也是一个非常重要、非常关键的问题。

I think this is also a very, very important question.

首先，我们必须确保研究问题能够回应患者或参与者的实际需求。

So first of all, we need to make sure that, the patient's or the participant's needs is addressed by the research question.

比如，如果你根本没有运动障碍的问题，却去参加一个研究运动障碍的项目，那根本说不通。

So it it makes no sense to, for example, enroll in a project that is studying dyskinesias if you maybe don't have that issue.

这是第一点。

And that's first.

你得真正符合研究的要求。

So you need to really be the good fit.

因此，我们设定了纳入标准，也设定了排除标准。

And because of this, we have criteria that make people be included in a research protocol, but also exclusion criteria.

在正式开展研究之前，通常会有几次筛查访视，主要是判断你是否符合纳入条件，或者是否属于被排除的情况——也就是说，你可能并不适合这项研究。

So there are several visits that can be done before the actual research starts, but we can more or less screen for either inclusion criteria that might propel a patient's participation or exclusion criteria that may actually say, you know what, you might not be the best fit for this study in particular.

再回到伦理委员会，这一点非常重要。

And again, going back to the IRB, this is very important.

我认为，伦理委员会在保障研究安全方面，是最关键的把关者。

And I think the IRB might be the the most, important, let's say, actor in the safety, part of the research.

伦理委员会承担着多重职责，确保这些匹配条件真正落实到位。

The IRB has several roles in into these that guarantee that this alignment is in place.

他们会用放大镜一样细致地审查研究方案。

They review the research protocols very, very miniscule, like, with with a with a magnifying glass, I would say.

主要是为了评估潜在的风险和收益，确保研究符合最高的伦理标准。

And, basically, this is to assess potential risks, benefits, and to ensure that the research is adhering to the most important or highest standards of ethics.

他们还会做风险与收益的分析，因为即使我们知道某种治疗通常是安全的，参与者仍可能出现不良反应，但这些反应必须在可接受范围内。

They also do a risk benefit assessment analysis so that because, you know, even if we know that the treatment might be safe as you as your experience with the side effect that you gather adverse events, everyone can have an adverse event and but it has to be acceptable.

风险绝不能超过参与这项研究可能带来的收益。

It cannot be a risk that overcomes the benefits of this potential participation.

那样就完全违背伦理了。

That wouldn't be ethical at all.

我们必须设定一个界限：虽然可能会有一些不良反应，但绝不能危及参与者的安全。

So there has to be a limit where we can say, okay, there might be some adverse events, but it cannot go for something that really endangers the participant.

他们也会做这种风险评估。

They also do that risk analysis.

更重要的是，他们还会进行持续的监督。

And more importantly, they also, perform ongoing monitoring.

所以在研究的不同阶段，他们可能会要求提供初步的信息。

So in different stages of the research, they might ask for preliminary information.

他们可能会和研究团队的几位成员开会，这样我们可以把这些事情都讨论清楚。

They they might have meetings with the several members of the research team, therefore, we can address these these these things.

所有这些都是为了严格遵守非常精确的伦理和行为准则。

All of this is to be very clearly adhere to very precise standards of ethics and conduct.

Sara，谢谢你来到这里。

Sara, thank you for being here.

能跟我讲讲你的背景吗？还有研究协调员在临床试验中的角色，以及你是怎么进入这个行业的？

And can you tell me about your background and and the role of a coordinator in research trials, how you came to find yourself in this work?

非常感谢邀请我。

Thank you very much for having me.

我在UHN的运动障碍诊所担任临床协调员，和Fasano医生以及我们的临床研究团队一起工作。

I work as a research coordinator, clinical research coordinator at the Movement Sorters Clinic at UHN with Dr.

Fasano医生和我们的临床研究团队。

Fasano and our clinical research team.

我在这个岗位上已经干了将近四年。

I've been in this role for the past almost four years.

简单说一下我的工作内容，临床研究协调员就像是连接患者、医生、护士和研究团队的枢纽。

And just to explain a little bit about my role, the role of clinical research coordinator, it generally sits in the middle of everything between patients, physicians, nurses, research staff.

我就在中间，全程参与。

I'm there.

从患者第一次接触研究，到最终的随访，我都全程跟进。

I'm right right in the middle of all of them, and I am basically from someone's very first contact with the study to their final follow-up.

我帮他们理解并完成各项流程。

I help them navigate the the procedures.

包括讲解知情同意书、解答疑问、说明所有程序、安排就诊时间、发送提醒，确保他们在整个过程中不迷茫、有支持——我觉得最后这一点最重要。

This includes going over the consent form, answering their questions, explaining all of the procedures, scheduling visits, sending them reminders, making sure they feel not confused and supported along the way, which I think the last part is the most important part.

是的。

Yeah.

这就是我的主要工作。

So that that's basically my role.

根据我参与研究的经历，我发现协调员就像是我所有事情的核心，我做的每一件事都围绕着这个人展开。

So when I in my experience of participating in research, I found the the coordinator was kinda like the linchpin for everything I did, and I everything I was doing was pivoting around this person.

他们让我感觉特别被欢迎。

I felt so welcomed by them.

这些年来，我接触过好几位做这个角色的人，但每次都是同样的感受。

And in fact, were multiple people that I've worked with in that role over the years, and it's always the same story.

他们总是那个热情接待我的人，帮我安排日程、解释所有流程，以及处理我需要做的每一件事。

They're they're there's like they're the welcoming face that gets me to where I need to go next and scheduling and and and all the procedures and all the things I needed to do.

关于帕金森病研究中协调员的角色，还有没有什么其他人应该了解的吗？

Is there anything else somebody should know about the the role of a coordinator in in research for Parkinson's?

是的。

Yeah.

正如你刚才非常贴切地说的，当你参与临床试验时，研究协调员会成为你主要的联络人，更重要的是，他们会成为你的支持者。

So as as you very beautifully mentioned, the the research coordinator when when you, participate in a trial, the research coordinator becomes your main point of contact, and most importantly, your advocate.

如果有什么地方让你觉得不对劲，随时找我们就行。

So if something doesn't feel right, you reach out to us.

如果感觉哪里不对劲，身体不舒服，一定要主动联系我们。

If something feels off, you don't feel well, you definitely reach out to us.

如果生活突然忙起来，没时间了，也别犹豫，直接找我们。

If life gets complicated, let's say you don't have time, you reach out to us.

所以，请信任你的研究协调员，他们是你参与临床试验时的坚定支持者。

So rely on your research coordinator, and, again, they're they're your advocate when it comes to participating in clinical trials.

谢谢你的分享。

Thanks for that.

对，我完全同意。

And, yeah, I I would agree.

我的经历就是这样。

That was my experience.

我确实很依赖他们，这不仅对我自己有利，对整个试验的结果也有帮助——因为有人支持，参与者才更愿意坚持下去，而我接触过的协调员都做到了这一点。

I did rely on them, and it was always to my advantage and I think to the trial's advantage too to in terms of the outcomes were met because people can stay when they have a supportive presence for them, and that's what I found in the coordinators I've worked with.

这意味着，当你参与研究时，他们会一直和你保持联系。

So one thing about that means that you're touching base with people all the time when they're participating in research.

因为你接触的人这么多，我觉得你一定观察到一些参与者的态度和心态，正是这些让他们在临床试验中的体验特别好。

Because you see so many people, I think you have an an insight or or access to an answer to the question, what attitudes and mindsets have you seen from participants that have contributed to the best experience?

在临床试验里，谁的状态最积极？

Who's happiest in a clinical trial?

那些体验良好的人，通常是怎么做的？

What approaches are common for those folks who have positive experiences?

反过来，哪些做法会让临床试验的体验变差？

And then the flip side is what approaches to clinical trials maybe lead to not so good experiences?

我觉得在临床试验中体验最好的参与者，通常都抱着开放和好奇的心态参与进来。

So I think the participants who seem to have the best experience, in clinical trials, usually, they come in open minded and curious.

他们清楚临床试验不等于 guaranteed 的治疗，所以态度非常务实。

They understand that clinical trials are not treatments are are not guaranteed treatments, and they approach it very realistically.

而且他们普遍不把自己当成实验对象或研究对象。

And I think a very common mindset that they have, they they see themselves not as subjects or research subjects.

他们把自己看作研究的合作伙伴，是参与者——我觉得这种心态特别美好，也特别重要。

They see themselves as partners in research, as participants, which I think it's a very beautiful and very important mindset to have.

我觉得那些人参与研究和临床试验时，通常不会觉得太不知所措或太困惑。

And I feel like those people usually feel less overwhelmed and less confused when participating in research and clinical trials.

相反，我觉得最难的情况是，有人参加试验时，却期待一件本质上充满不确定性的事情给出明确答案。

On the flip side, I think one of the hardest situations is when somebody joins a trial and they expect certainty from something that in nature is uncertain.

当一个人抱着‘这一定能治好我’的希望，一旦结果不如预期，情绪上的打击往往会非常大。

When the hope is this is gonna fix me, for sure, the emotional impact can be very heavy when the outcome is not what what they expected originally.

所以我认为，正如你提到的，参与临床试验时，心态才是最关键的。

So I think that that the mindset, as you also mentioned, is the most important thing when participating in clinical trials.

是的。

Yeah.

谢谢你分享这些。

Thanks for that.

我觉得对于很多帕金森病患者来说，情况特别复杂——当你长期受病痛折磨，又没有有效的治疗手段，突然听说有个临床试验，就会想：也许这个能解决我的问题，可实际上又没有别的办法了。

I think it's, it's tricky when you're living with a condition like Parkinson's for many people when there's you don't have a good option and you think this you hear about a trial and you're like, well, then maybe that would help this problem I have, and and and there's no treatment that's really helping you.

所以这真的特别复杂，我很感谢你指出，如果带着‘这个试验一定能帮我’的心态去参加，确实会带来很大困扰。

You so it's just gonna be so complicated, and I appreciate you acknowledging that that can be a that can present if you enter a trial with the attitude that this is gonna help me.

你可能会被分到安慰剂，具体还要看试验的设计，这点大家得清楚。

Well, you could get a placebo and potentially depending on the trial, and that so people need to know that.

我同意。

I I agree.

这很重要。

It's important.

如果有人在考虑参与研究，你还有什么建议吗？

What other advice do you have for somebody if they're thinking about participating in research?

除了心态之外，还有什么方法能让人在试验中更容易感到满意呢？

How can somebody, for example, give themselves the best chance of being happy in a in a trial besides their approach?

关于这一点，你还有别的想说的吗？

Is there anything else you have to say about that?

我明白了，医生。

I see Doctor.

法萨诺也提到过，有什么问题尽管问，想问多少就问多少。

Fasano also mentioned that as well, but ask a lot of questions as many as you want, as many as you can.

请仔细阅读知情同意书，每一个字都要看清楚。

Read the consent form very, very carefully.

如果可能的话，建议你带一个人陪你一起读知情同意书，边读边提问。

If you are able to, if you would like to bring somebody with yourself to read the consent form with you, and again, ask questions.

请始终记住，你有权利慢慢考虑、随时改变主意，或者直接拒绝。

And just always keep in mind that you have the right to take your time, to change your mind, to say no.

即使你签了知情同意书，也要明白，知情同意不只是签个字就完事了。

And even if you sign the consent form, let's say, it's important to know that informed consent is not just a form that you sign when done.

我总是反复跟我的病人说，知情同意是一个持续沟通的过程。

I always, always make sure to tell this to my patients that informed consent is an ongoing conversation.

参与者随时都有权提问、暂停、终止参与或退出，研究人员和协调员会保障这项权利。

So participants always have the right to ask questions, to pause, to stop, to step back, and the coordinators research coordinators help protect that right.

宇燕，谢谢你今天和我聊这些。

Yu-Yan, thank you for talking with me today.

我想了解一下，你能简单说说你的背景吗？包括你整体的经历，以及你和帕金森病和相关研究的关系。

And, I wonder, can you just share a little bit about your background in in, generally and then also in relation to Parkinson's disease and and Parkinson's research?

谢谢你邀请我，克里斯。

Thank you for having me, Chris.

我在运动障碍门诊当护士已经二十多年了。

So I have been a nurse in the movement disorder clinic for a little over twenty years.

在此之前，我一直在重症监护室工作。

Before that, I was a nurse working at the intensive care unit.

我后来参与到帕金森病的研究，是因为那时候深部脑刺激的临床试验即将结束——我这么说有点暴露年纪了。

So how I came about to become involved in Parkinson's disease research is at that time, the deep brain stimulation clinical trial, I'm dating myself now, was coming to an end.

那是很多年前的事了。

It was many, many years ago.

由于这些患者长期受帕金森病困扰，病情复杂，需要大量的支持资源。

And then because of the complexity nature of this group of patient who have been struggling with Parkinson's for a long time, they require a lot of resources.

我刚被聘为门诊护士时，主要就是帮助那些刚结束临床试验的患者，协助他们管理病情，以及如何在社区里更好地生活。

So when I was first hired as just a clinic nurse is to help those group of patient who is finishing the clinical trial and help them manage their disease and also how to live their life productively in the community.

我当初就是这么被录用的——作为门诊护士，协助完成深部脑刺激的临床试验。

So that was how I was hired, helping finishing the deep brain stimulation clinical trial as a clinic nurse.