Clinical trials

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Jane: Hello, and welcome to the MS Plus podcast. My name is Jane, and I am an MS certified nurse.

Have you ever heard about clinical trials? Do you know how they're run and what it means to participate? The whole concept can seem a bit puzzling. So we've decided to enlist an expert. We are thrilled to be joined by Dr. Therese Burke A.M. to discuss all things clinical trials. Dr. Therese is a registered nurse and Multiple Sclerosis certified nurse who has decades of experience in immunology clinical trial nursing, and as an MS clinic nurse.

Therese has completed a PhD in exploring the lived experience of people with relapsing remitting MS. She's currently working at MS Australia as a clinical platform coordinator and is also a senior research fellow of the University of Notre Dame Australia. On January 26th of this year, Therese was recognised for her significant service to MS research and nursing by being made a member of the Order of Australia AM)

Here is my chat with Therese.

Therese, what are clinical trials?

Therese: Clinical trials are really a tool that we use to answer the question, Does this work, or is this better than something else?

Now I think most people associate this with clinical drug trials and looking at drug development and new drugs, and in which case that's entirely true. We need to compare the new drug against what's already available or against no treatment, just so that we can answer that question, Is this better?

But there's all different types of clinical trials, not just drug trials. So there might be trials for a new diagnostic procedure, or a new test, or a new way of doing things, but the same principle applies. It's our tool to find out, is this better?

Jane: So how did they then differ from other research in the MS space?

Therese: I look at it like this, Jane, that research is really the big umbrella where we're looking at new things that can involve clinical drug trials, that can involve surveys, it can involve questionnaires, it's really the broader umbrella of finding out more about something, and in this case, we are looking at medicine and we're looking at MS in particular. So clinical trials come under that umbrella of research as one of the tools that we can use and that's usually how I like to look at it. Research is much broader, and then clinical trials are one of the tools under research that we can use to look at how something works.

Jane: And how have clinical trials helped us so far in the MS space?

Therese: Well, because we live in Australia, I'm really proud to say that, because of clinical trials, we now have the 13 or 14 drugs that we currently have in Australia to treat relapsing remitting MS.

And I say that proudly, because Australia's one of the only countries in the world that has access to these drugs first line, once the diagnosis of MS is made, and they've come about because very brave souls have put their hand up to say, I want to be involved, I want to take part, I want to see if this new treatment is better for me, or for other people.

Jane: I've heard about different phases talked about in regard to clinical trials like phase 1, 2, 3, and four. What does all of that mean?

Therese: Yes, that can be a bit scary for people to understand, but really it just refers to the stage of development of that particular clinical trial. So, we talk about things being preclinical and that's all of the research that goes into, for example, a drug or a molecule where it's tested in animals and in other ways or in the laboratory, and they're getting it ready to test in humans, and then we go into the four different phases.

So, phase one is the very early first in human studies, usually a very small group of people, what they call healthy volunteers, where they're just trying to work out what the dose might be, what the side effects might be, but in a very small group of people until they get more information, and then it just progresses through phases two, three, and four.

So, phase two, they start to use it in the particular disease. So for us, a phase two study would be possibly the first studies in people living with MS, but still quite smallish numbers, up to around a hundred and they're still looking at how it works and looking at safety, and how effective the drug is.

And then by the time it gets into phase three studies, that's where most of the studies in MS in Australia are placed, and that's where we have thousands of people. And the criteria for getting into that study is opened up a bit so it represents more like real life, not completely, but more like it, and it's usually thousands of people at that stage, and they're really looking for long-term effects as well. So that may be over a couple of years.

And then we have phase four, and that's still a really important phase that happens after the drugs marketed and a lot of people don't realise that some of those drugs still remain in phase four, where we still keep keeping an eye out for any other new side effects that might happen, or side effects that might happen in the long term.

So, I think it's good for people to realise that it doesn't always stop when a drug's marketed. There's continuing research just to make sure that everything's remaining okay.

Jane: And then in terms of how the clinical trials are organised, or what type of clinical trials they are, there's lots of terms that we hear about, so can I ask you some words and you explain to us what they mean?

Therese: Yes, it's almost like it's a separate language, but yes, they can be easily explained.

Jane: Perfect. So tell us about placebo.

Therese: So placebo is probably the simplest one to explain, and that's when it's a dummy drug, so a pretend drug. So, for instance, in a clinical trial, we might be comparing the new drug that we're really interested in seeing how that works in humans, and then some people in the trial will be allocated a placebo. So that means they won't be receiving any drug at all. It will just be what we call a sugar pill or a sham treatment.

If it was a physio study, it would be not getting the treatment that's being asked for, and in some studies that aren't drug trials, you might have two groups and one might get the treatment first while the other gets the pretend treatment, and then they might swap them over. So that way it's a lot more fair. Placebo is just our way of saying no treatment comparison group.

Jane: And then there's also something called blinding or double blind. Can you tell us what that means?

Therese: Really important for people to understand what this means. So, being blinded means that you don't know which drug, or which dose, or whether it is drug, in fact, or placebo, for the duration of the study, so, we'll find that most studies taking place in Australia will have some blinding.

So single blinding means that the patient or the person involved in the study, the participant, is not aware of what they're taking, but their doctor or healthcare team may be. And in some studies that's absolutely essential, but a lot of them are also double blinded, which means the participant is not aware of what they're taking and neither is the doctor or the healthcare team.

Obviously that's an ideal scenario because you don't want any bias to be brought into how people are assessed in a trial. We want to see what's going to happen naturally.

Jane: Okay. And then what about double dummy? What does that mean?

Therese: Oh, this is a funny one. It's a bit more complicated, but essentially double dummy is like double placebo, so dummy meaning not the real treatment, and we use this in very specific studies and for people with MS the best way to explain it will be around taking a tablet or taking an infusion because they're two very common methods of taking medication for people with MS. So obviously if both groups were taking a tablet, you could disguise that in a capsule and nobody would know.

But obviously if you're doing an infusion for someone and they're going into a hospital and having a cannula inserted, or a drip and having a treatment, we can't disguise that. So what double dummy means is that the group that are allocated to having the oral tablet will get the real oral tablet and the infusion will be a placebo, or a dummy infusion and the opposite for the other group.

So the other group will be getting the real infusion and then a dummy tablet. So it means it's hidden as to what the treatment, is and obviously that's a very complicated one, but that has happened in Australia because obviously now a lot of our treatments are infusion and that's the way that we were able to test them using a double dummy clinical trial.

Jane: And then what about randomised? What does that mean?

Therese: So when we are doing a study, we need to be certain that we're not bringing in our own biases with how we assess what's going on, and that might be assessing for instance, in MS, it might be disability scale. For example, the EDSS, which some people will be familiar with, which is the disability scale that we use to determine the step of ambulation that someone with MS has. And often we use that in clinical trials.

So, we don't want to pick and choose who gets which treatment because that's not fair. It's not fair for the participant, and it's not fair for the results of the study. So being randomized means it's up to random chance what treatments you get.

Jane: And before we move on, I think it's interesting to discuss the idea of bias or any kind of conflicts.

And so what we're saying is the purpose of this is that I can't walk in and say, ‘Therese, I know I'm your favourite patient, so with that clinical trial, can I have the active drug, can you put me in the active group?” And then you say, “yes, Jane, I can”. And then when you see me, you say, “look, I really need you to report your side effects because you are actually in the active group. So we really need to know what's going on.”

That's why, isn't it? Because we are trying to take out any kind of input that's going to skew the data from what's actually true.

Therese: Yes, that's right Jane. I'm smiling as you were talking about that scenario because I've been in that situation before where people have actually come to me with that, or we might have been in clinic, and this was particularly before we had the modern day treatments, so I'm going back a dozen years or so to when we didn't have any oral treatments or any infusion treatments and, in taking injections all the time was quite difficult for people.

And so they really wanted to be part of those early studies, particularly with some of the new tablet formulations for MS, and often I would hear, I really want to take part, but only if I get the tablet. It's heartbreaking as a healthcare professional because you really want them to have the best chance to get that too, but at the end of the day, Jane, it's just not good science. We need this clinical trial to be robust, we need it to deliver the true results, and the only way that we can do that is to go in with a randomized and unbiased fashion, and that can be hard, and I have had people that have been assigned to the treatment that they didn't want. But mostly people do go through with that because sometimes, not all the time, but sometimes there might be a little carrot for them at the end.

After a certain period of time, they may be able to switch over to the study drug. So sometimes that's made it more helpful for people to do that. But generally speaking, people just accept it, and move on knowing that if any time something goes wrong or they're not comfortable, or the treatment isn't working for them, that there's still the possibility to withdraw from the clinical trial, you're not signing up forever.

Jane: And I imagine there's a lot of staff involved in running trials. So how is it funded?

Therese: Yes, it's a really expensive process, and that's why we have to make sure that when we do trials, we do do them properly and we do adhere to the rules.

So there's different ways that that clinical trials can be funded. Obviously, one of the most common is through the pharmaceutical industry. So a pharmaceutical company might develop a molecule through that preclinical stage, up to phase one first studying humans. And then, they're responsible for the ensuring, phases of the trial take place.

And, not only take place, but take place in reputable organisations, and there's a lot of monitoring that goes on to protect that. So that's one way that studies are funded which most people would be aware of. But there's other ways that clinical trials can be funded because, as we've already discussed, it doesn't have to be a drug, it could be a physiotherapy treatment or a mindfulness methods.

So in those sorts of studies, often grants from the government, and people may have heard of the NHMRC, the National Health and Research Council of Australia. They have a lot of grants in medicine and even MS Australia gives out a certain amount of money each year for researchers that have peer reviewed research and they can contribute, towards the funding and sometimes institutions or universities.

If a clinician, or a neurologist is doing a clinical trial through their own university or hospital, there may be funding from the university for that too. So lots of variation in funding, but one thing is common, Jane, from what you've said, and that is that it's a very expensive process.

Jane: And I'm sure that makes the stakes quite high as well in terms of making sure that everything's strictly adhered to. As a nurse that has worked in clinical trials to raise, were you quite strictly bound by, the eligibility criteria and the ways that things should be done?

Therese: Absolutely. You just can't go off that Jane. And sometimes that can be immensely disappointing for patients and participants. They might really want to go into a study and there might be certain tests that have to happen before they're allowed into the study just to make sure that they're in that group that we're after, that we were talking about previously.

And sometimes those test results don't go the way that the participant would like, and they may not be able to take part, and that can be heartbreaking. But a more heartbreaking scenario is to put them into the study and then for that not to be right and to have to withdraw them, that's even a more heartbreaking, scenario.

So our best bet is to do it properly from the beginning and, usually patients, if it's well explained to them before they start, they know what they're up against and they should have that expectation that things may not go their way, but they'll still receive the same clinical care as they normally would have, and they're not going to be cast to the side.

So extremely important to follow that criteria.

Jane: And I want to quickly jump back you talked about peer reviewed. We hear a lot about the term, like a journal article that's peer reviewed. What does that actually mean?

Therese: Being peer reviewed means that experts in that particular field who review the study. They look particularly at the methodology, how the study was conducted. They look at the results, they make sure that everything ticks every scientific box, of which it's a very long list, to ensure that everything is above board and, meets a certain standard, and these are standards that just can't be broken in medicine and science. We just cannot run that risk. So if a study is peer reviewed, it means that people have independently looked at it, assessed it, and agreed that it's in keeping with what our standard guidelines and rules are.

Jane: Thank you for explaining that because we hear that a lot, I think, in the news and especially after COVID, lots of people talking about peer reviewed articles in terms of clinical trials being offered. If I was in a clinic and a clinical trial was offered to me, do I have to say yes, you have to participate when they're offered to you?

Therese: Absolutely not. In clinical trials is such a great option for people, Jane, because particularly when we are dealing with diseases without a cure and MS is one of those diseases, so we don't have a cure. So we are always still on the lookout for the holy grail. And so clinical trial should always be on the table for everybody living with an incurable illness so that they have the opportunity to see what else is out there and what avenues are available to them.

Because as we also know in MS, not every drug works for everybody. It's highly individual what the response is, so we need to know that it's an option now by saying that it doesn't mean that a clinical trial is right for everybody. As I've already talked about we have very strict eligibility criteria to who can be included and who's excluded from a study.

And we've explained why that's needed, it might even be something you're interested in, but you always have the right to refuse because there are a lot of things to consider with participating in a clinical trial and being right for the participant is number one on that list. And that can be hard because, particularly if you're in a clinic or you're seeing a neurologist or an MS nurse, or another healthcare practitioner for your MS care, you develop relationships with them. And then sometimes if it's presented to you to be involved in a clinical trial, your immediate response might be, yes, I like these people, I don't want to let them down.

But that's often not the right reason to take part. There still has to be a really good level of confidence from the participant that this is the right thing for them. And sometimes that's a really difficult thing, and I think we're going to talk about a little bit later ways that that can be handled.

Jane: So how can you make sure that you are making an informed decision? Because we are very begun informed, consent informed decision making, but as you said, it might feel a bit overwhelming if your doctor or nurse is suggesting a clinical trial and they're providing you with paperwork that explains it, but it might feel like it's all happening a little bit quickly.

How do you make sure you're making an informed decision?

Therese: This is absolutely critical, Jane. This isn't just something little on the side. This is the whole crux of, really good clinical trials, is making sure that the participant has a really, really solid idea about what's expected of them to participate in the clinical trial and what they should expect from the clinical trial themselves.

Absolutely critical. So my recommendation is, if a trial's presented to you, that you need time. I don't think being presented with a lengthy information sheet in a clinic setting and being asked to sign on the spot is a good way of doing that.

In Australia, we have a national statement that's released by the NHMRC that governs all the way that ethics committees and research should be performed , in Australia, and they have a whole section devoted to informed consent. And part of that is that the participant really knows what's going to happen and not just a tick box or, you understand what's happening, don't you, sort of scenario. That's absolutely not what we're talking about. We're talking about a participant that's able to recite back to you exactly what's expected of them and have the opportunity to ask questions.

And there should be copious questions. It shouldn't be a, read the sheet and have no questions. There must be things that people don't understand from those forms. As I said, they can be very lengthy, very wordy, difficult to understand. So it's important that you have the opportunity to talk to your research team about any questions you have.

And my personal opinion is that you need to walk away from the clinic to do that. And you should have the opportunity to talk to significant others about it as well. And there might be people in your family, it might be trusted friends, it might be your GP. but just to have that opportunity to make sure all your questions are answered, that you have a really solid understanding of what's being asked of you, and that you have the opportunity to run it by ours and have those discussions because in the long run, if you are really prepared, things are going to go so much better for you and for the clinical trial.

Jane: Absolutely. And so , one question would be risks. So you're going to have questions about what the risks are and that should be explained to you, right?

Therese: Absolutely. So the participant information sheet will always outline that, that's a requirement of having ethics approval in Australia from the national statement. So there should be a really good outline about what the potential risks are and, what the known risks are because, depending on what phase of that study, like we talked about before, whether it's very early phase one, or whether it's a later study phase three, there will be some knowledge around what would be expected as a side effect or a risk.

But then there's also the potential risks that haven't occurred yet that might potentially happen with a particular drug just based on what we know about it. So, that's an area that people really need to concentrate on and make sure that they have a really good handle on what the potential risks to them are.

And we've been talking about clinical drug trials, but as I mentioned, there's also non-drug trials in the physiotherapy world, the psychological world, where it might not be a physical risk, it might be a mental health risk. So those sorts of things need to be really well understood before any procedures take part in the study.

Jane: And then what about benefits? That should be explained as well, I'm guessing in terms of what the individual might gain, if the hospital gains anything. What the data is useful for. Discuss what the benefits could be.

Therese: Yes, and the benefits is a really important part for people living with MS because, you want to know as a participant what could happen to you that might be a good outcome from this clinical trial as well.

That can be just as important as looking at the risks and that might be a personal benefit. So it might be that you do much better because you're on a better drug or a better therapy and, so personally, that might be helping with your symptoms or your long-term MS management.

But there also could be other benefits to you, and it could be that usually in a clinical trial there would be more visits than in normal standard care for MS and you might have more contact with the neurologist, or the MS nurse, or other healthcare practitioner involved and that could be a real benefit. For some people, other people like the fact that they have a closer eye kept on them because obviously in a clinical trial we do a lot more assessments, a lot more surveys, a lot more tests. So we are keeping an ultra-close eye on people and for some people that's the pure benefit.

And we have others who aren't even interested in benefits for themselves, Jane, at all. That's the furthest thing from their mind. But they're really interested in the benefits to the wider MS community. And these are the people that sometimes do a study because they're concerned about their own children, or they're concerned about loved ones or even the broader MS community as a whole. They're the real people that are there for altruism. They just want to make things better for people living with MS, as a whole.

So there's a whole range of benefit, and for those people it can be a real mental health benefit and they feel like they're giving back. So we have that whole gamut of what the potential benefits could be, not just the obvious ones.

Jane: And then what about the lifestyle impact of all of this? Because you mentioned that there could be more visits, so I'm sure all trials are different, but roughly, what could it look like in terms of the impact for someone's lifestyle, and their life?

Therese: You're right, there is a huge difference because you can have a very complicated early phase study with lots and lots of, visits, particularly at the beginning. And there might be lots of blood tests trying to work out how the drug works in the bloodstream, and that could continue for some time, but there could be other studies that are very light on in visits. There might be a very big study visit at the beginning and end, and it might be a bit lighter in the middle. One thing's for certain that you need to look at your own lifestyle and look at what's being asked of you in the study.

And most clinical trials these days would have a table within that information sheet that clearly outlines how long you need to be there for what's being asked of you, and how often and, you need to have a really good think about, is that something I can fit into my life with work and family and social and with any of the symptoms that I'm living with, with MS and how that's going to work.

So, we ask people to do that right at the beginning before any paperwork is signed so that we know that they go into it with the expectations of what's going to, because we want it to work for them as well. If you're absolutely ultra busy, having to come to a hospital or a clinic for an extra 12 visits a year is probably not going to work. So we need to balance that for.

Jane: And what about the worry and the fear of the unknown, because we talked about blinding, and placebo, and risks, and you are being tested on. So tell me about how people work through that and how they can talk to their health professionals about that.

Therese: A really good way of doing that is just going back to basics with what's being asked of you, how early on in the phases this is, obviously we've heard the phrase ‘guinea pigs’ before. I don't like using it, but I think I'm going to say it, in the olden days, a long time ago, that was possibly the case, particularly when you are looking at phase one studies, which are first in humans. There is a real element of risk that's not present in later phase studies. So, for those people that can be particularly trying and they have to think through a lot.

On that front, about what they're prepared to do. and then for later phase studies, the risks, they're not not there because sometimes we do find out things after a long period of time or when we open up to a lot more people. We find the really rare risks because then you're testing in thousands, instead of in dozens.

So things might come up, so people need to take that step back and work out what they can live with for good mental health, because we want people to have a good experience in trials day. We don't want it to be something that is a source of constant fear. As a clinical trial coordinator working for many years, I did see that from time to time, and that's an awful way to live.

There's enough living with the burden of MS as it is, without adding more on top of that. So we want to err on that. It's a comfortable level of risk for somebody to deal with.

Jane: So, Therese, do people ever get paid or, are there any financial incentives that people might want to participate for?

Therese: I'd prefer to look at it as helpful incentives to participation. Now in Australia we have very strict guidelines about what's allowed through the national statement, which then filters down to ethics committees. So when clinical trials are presented to ethics committees in Australia, they look at each trial specifically to see what the incentives might be, and being paid to be in a study is not one of them in Australia. Other countries can be used, but in Australia we have very strict guidance around that. but we also need to support people financially to be able to participate. So, the way that it'll often work in a clinical trial is that participants might receive a travel allowance which will cover their transport to and from the hospital accommodation if they're traveling from regional areas.

A really common one, which is a problem at many metropolitan hospitals is hospital parking because that means that participants have to outlay money to participate. But that's something that can often be covered by the clinical trial site. Either free parking or that parking might be reimbursed.

And sometimes in early phase studies there might be, or in non-drug studies, there might be things like, a movie voucher or just something of a small monetary value that might be given in some cases, but all of it needs to be approved by an ethics committee before that can happened. So you've got that reassurance that it's reasonable, and it's following the proper guidelines.

Jane: And what are some of the barriers for people to participate in clinical trials?

Therese: I think there's a lot of barriers, Jane. There's a lot of barriers in general. And then I think when we are looking at MS, there's certain barriers that are not specific to MS or unique because it might be to other diseases which incur disability.

But there's certainly things on top of the normal things. So, distance, and the time asked of people to be involved in a study are probably the two big ones. But then when we are looking at people with MS, we have symptoms like fatigue, which we don't need to be explaining to people with MS, is just such a profound part of everyday life and often curtails what people are able to do.

So when you're looking at a clinical trial which might have quite a lot of visits earlier, and the visits might be long visits with a lot of procedures, or tests being done that can really take a toll on people with MS, and it might deter them from wanting to take part in a study that in other ways would be very good for them and something they'd like to take part in.

So always ask the clinical trial staff if arrangements can be made for, and it may or may not be possible, but if arrangements can be made just to change things or have breaks between tests, something as simple as knowing if you're going for clinical trial visits, that there's a disabled toilet nearby can be hugely important. Just to have that knowledge and know that you're being taken care of.

So we have those sort of barriers, and sometimes we also have just social barriers that can impact on people, Jane, they may just not be going to a centre that offers trials and they might not have the ability to know how to find out about clinical trials.

So we're going to talk about some of those things later. but those sorts of barriers can get in the way to participation, but also awareness. A lot of the things that we've talked about today, is hopefully demystifying some of those things about clinical trials so that people can look at it with a different lens now and not be too fearful or frightened that that's a whole area that they just don't want to be involved in.

Jane: And then in terms of eligibility, I'm sure there are differences between trials, but are there some general things that might be quite common? Like for example, saying the age group might be 18 to 65 years old, or certain, previous health issues that might be ruled out.

I'm just thinking for some people might they find that because of a certain factor in their health or their age, for example, that they're not eligible for a number of trials.

Therese: This is a real personal passion of mine, because in years gone by, particularly in the last 10 to 15 years, there's been a lot of studies in Australia for people with relapsing remitting MS and often quite early relapsing remitting MS, so that automatically excluded a lot of people in older age groups, and in people who'd already gained disability and, I used to see it a lot in clinic and it would break my heart because we didn't have anything to offer these people. But what I can tell you now is things are changing a little and there's a big international push for progressive MS.

So people who have started to gain disability, they may have had relapsing remitting MS and now are in secondary progressive MS phase, or people who have primary progressive MS, there’s a big push for trials to really get into new treatments and looking at repurposed drugs and giving progressive MS exactly what it deserves.

And so I'm really happy to report that probably in the near future. Can't put a date on that but, coming soon, we're going to have more trials hopefully brought to Australia that, particularly on those older age groups and people that have gained a bit more disability, so that they also have equal chance of having a change to their life, that could be brought about by a new or different drug.

Jane: Absolutely. And you touched on extra visits. Do people have their standard MS appointments, maybe six-monthly MRIs at a urologist appointment, and on top of that clinical trial visits, does it all happen at the same time, or does your clinical trial participation kind of happen instead of your normal MRIs and your normal reviews?

Therese: That's such a great question. It's such a great question because I think that's a great unknown, right? So people, sometimes if they've got excellent clinical care that they're really happy with, they're a bit tentative about putting their hand up for a trial because they're just not sure what's going to happen.

So usually what happens is you'll have your normal, what we call standard of care, MS care, which is what you would normally go through. And that's usually based around the drugs that you're on, or the drugs that you're not on, how your MS is progressing, and you might have either six monthly or yearly visits, and you may have an MRI annually each year, or more often if you're on certain drugs and you progress along, but then you add the clinical trial on top of. Right?

And so, it may be in the same centre that you're receiving your normal MS care, or it may be you're still receiving your normal MS care and you're having your trial care in another centre with another doctor, and it's usually layered on top. And the reason for that is, remember before we were talking about blinding so, if you're in a clinical trial, and nobody knows if you're even on a therapy, or if you're on the placebo therapy, if you were in that trial for four years, the people involved in the clinical trial looking after you don't know the results of your MRI, they don’t know the results of your blood tests.

So they're going off to be analysed. So we still need to know how you're going. So often you'll have both. So you'll have your normal standard of care, and then laid on top of that will be clinical trial progress and that might be different tests with different doctors at different times.

Jane: So it is a few extra visits.

Therese: Quite likely, quite likely, if you're at the same centre though, that impact might not be as great because they're still getting to see you and doing your disability schools and things like that as you go along. So it may not be as great, but there should be a double layer at some point.

Jane: Definitely. If somebody is already taking a medication, say they're already on a disease modifying therapy to treat their MS, how does it work then, if they want to go on a clinical trial? Does it mean you have to stop your other medications and supplements? What happens with your medications?

Therese: Also a great question, and there's a lot of variability here, Jane, but just as a general rule, for some clinical trials you can stay on your normal treatment and the clinical trial will be an add-on, and that's okay for some studies remembering that we are getting all similar people into that study.

So everybody will be at that same starting point of already being on a treatment and then having an addition to that treatment. And some of our new trials coming through that are looking at remyelination and neuroprotection might be an add-on therapy to an existing disease modifying therapy.

So everyone's coming in on the same boat, if you like, but some other studies, particularly if their early phase studies might require people to come off certain medications and have what we call a washout, where they might have a period of one. Not on drug. and obviously that is not ideal for everybody and everybody you know, is at a different spot with their MS. So that would be something that the clinician, the neurologist would look at really carefully, before advising on that. And often, clinicians might be offered a clinical trial and they might say no on the basis that the people that they're looking after it might not be good for them or it's not in keeping with how we do things in Australia, remembering, as I mentioned before, that in Australia, we have such a wide range of medications that are available in subsidized, which is very different to some countries that don't have any access or very poor access to any treatments at all. So, there is that variation. Some people will stay on their drugs and it will be an add-on, and some people will need to wash out certain drugs at certain times.

Jane: We've talked about how sometimes the clinical trial might be done by the person's current neurologist, but there are other times where it's at a different neurologist or a different centre.

If that's the case, can you ask your current can you ask your current neurologist, Hey, I heard of this trial, I saw of this trial. What do you think? Do you need to get their opinion? Do they have to agree with you participating?

Therese: It would be really good to talk to your current neurologist and find out what they think about the study, particularly as they're looking after your normal MS care they would always want to be involved in that decision, Jane, because it's going to impact on your future care.

So, in an ideal situation with what you've described, you would have really great communication and honesty between the participant and their current neurologist, and then also with the clinical trial neurologist, if that was a different site and a different person, that you would have a ring of communication where everybody's on the same page.

There would be a letter after every visit to each other, phone calls, if necessary, if something changes, particularly as there might be side effects involved. And so you need to be able to report them to both parties. So the key to that situation is, yes, it can happen, it's definitely possible, but there has to be great communication and honesty between the participant in the trial, the current neurologist, and the trial neurologist.

And that's usually the nurses looking after the studies, or the study coordinators are usually really good with that because they're aware that that can be a potential problem, or an issue. So they usually ensure that everybody's in the loop, if you like, and that everyone's on the same page.

Jane: In terms of the clinical trials, how long does it go for when someone participates? Are we talking a couple of months, or could it be a couple of years for someone's direct participation in their section of a clinical trial?

Therese: The answer is huge variability. Some studies only go for a very short period of time, so it might be a very early phase study that might just be working out the dose of a drug. So that might go for a shorter period of time, which might be months, and other studies we're up into year 11 and year 12 because you've continued to follow people over time and often that will evolve into a new study, which might be just a once-a-year visit just to gain more information about a drug, I'm thinking, especially if the care MS one and care MS two studies in Australia, that involved a certain new drug and they just went on for a long period of time because there was the potential for long-term side effects and we wanted to really capture those and know exactly what was happening. So, it can be years and years, but usually, I want to say around two, three years might be the most common sort of timeframe, but as I mentioned, it can be much sooner and much later.

But, that doesn't mean that you sign up forever. I just want to make that really clear. It's all completely voluntary. So you might start out in a trial and then it might not suit you at year two or year three or year four, or you may have had enough, or you might be moving on or something else might be coming up.

You can always pull out of a study. So always a good idea if you're thinking that way, to talk to the trial staff, talk it over with them and see what they think. but it's always voluntary at every stage.

Jane: And what are some of the common myths of clinical trials, common myths might be that doctors get bonuses if they get extra people in, or people might think, look, if I say no, my doctor's going to be stroppy with me, and they won't be keen on me anymore.

Therese: They're the ones that I was thinking of too, Jane.

It's just that fear of the unknown, isn't it? It's like, if I go ahead and do this, there's lots in it that makes me happy, but I don't know what's happening the other end. So there are costs involved in a trial like we were talking about before, and doctors and study coordinators are paid for their participation in this study.

But it's within a budget that's approved by ethics and governance of a hospital, so particularly the governance area. So you can be reassured that they're not getting extra kickbacks, they're not getting free trips, they're not getting dinners out and all of that. That just does not happen within the framework of clinical trials in Australia.

We have really strict guidelines and rules that come through Medicine Australia. So it's not that sort of scenario. And also that it's all about being a guinea pig. As I mentioned before, there's different phases and we have different sorts of information available at different stages.

So, people can be quite more reassured that, particularly in the later phase studies that we already have accumulating evidence that might give us more information, and I think probably the third one that came about most often for me which is that if you sign up, you are in it for forever and a day.

That's just not true. Everybody involved in this study, it's very clear in our Australian guidelines, has the ability to withdraw for any reason at any time, and they should still receive the same standard of care afterwards. Meaning that there should be no penalty to someone if they decide to withdraw from a study.

And I think people might worry about that because I think that's something I would worry about, that if I say no or I want to pull out that they're not going to like me anymore, they're not going to provide help, they're not going to be there if I need them in a relapse. But we do have very strict guidelines to prevent that happening in Australia.

Jane: Well, that's wonderful to know that even though there's a purpose of the clinical trial, that they're going to help your wellbeing at heart. That if you need to, it's okay to call up and say, look, Theresa, I'm really sorry, I just can't continue that. You are not going to say, “Well, we can't have that. So strap up and let's sort yourself out and come back when you're feeling better.”

That's not going to happen, is it? Yes.

Therese: So, and that's a really important point because that means that the informed consent might be there in the beginning, but that informed consent should be there for the whole duration of the trial. So if things become known, it might become necessary to reconsent patients.

For instance, if a new side effect was identified, that should be relayed to all of the clinicians and they should relay that to all the clinical trial participants. And there might be further discussion about whether you still want to take part knowing this now, and that should be revisited all the time.

And certainly I think it's good practice at every visit just to confirm that the participant or the patient is happy to continue. And if there's any new questions that they've got.

Jane: So, Therese, for people listening, if they want to find out more about clinical trials, especially in the MS space or how to get involved, where can they go?

Therese: So MS Australia has a clinical trials network website and page, you can go into that by state to find out what clinical trials, not just clinical trials, but all research, what research is happening around you.

You can also search by type of MS, whether it's relapsing remitting MS, clinically isolated syndrome, secondary progressive, primary progressive, and you can see all of the different studies there. They're all listed with contact people that you can give a call or an email to find out more information, also bearing in mind that just because you express an interest in a study that doesn't obligate you to take part in it, and the clinicians and the clinical trial staff are very aware of that, sometimes it's just information gathering for you as a participant or a patient and you just like to ask more.

Just because you ask a question doesn't mean that they're putting you in the study next Monday. You still need to have all of those normal discussions, so don't be fearful if it's something you're interested in, but you just want more information to put your hand up and seek that out.

Jane: And what's coming up next in clinical trials?

Therese: This is quite a recent, addition to the landscape of clinical trials in Australia, and it's one that I'm particularly really excited about because I'm originally from a country town before I moved to the big smoke, and I think

we all know that there's people that are living in, particularly rural and remote areas and also some regional areas, who don't have the same access as everybody else now. That's been noted in Australia for some time, and there's a new program that's been launched later this year called Tele Trials Australia, and that program is funded by the government to try and get access to everybody, no matter where they live in the country. and that might involve being linked in with a major metropolitan centre, but being able to have some of your study assessments at a place that's a lot closer to home.

So that means that people can be involved from those regional areas. And I think that's a really exciting move forward because, as I said before, just to have the availability of clinical trials when you're living with a disease with no cure is just an important thing to have on the table and gives you hope for the future as well.

So we don't want those people living in the regional areas, rural and remote, to feel like they're not cared for, they're not part of the picture, they're just as important, and these are the first steps towards involvement for those people, which is really exciting.

Jane: Thank you so much, Therese. That was wonderful. And I have learned so much more about clinical trials.

I think what we're hoping people take away is the main message is it is voluntary. If you want to participate, you can, but you don't have to take some time to learn about what's involved. And, also that there's lots of rules and safeguards in place to make it as safe and ethical as possible.

Therese: That's exactly right. So we are very lucky in Australia, we've got very strict guidelines, and rules and they need to be adhered to, and they're monitored very closely. So you can have that reassurance that, as much as possible, it's being looked at from every angle to ensure it's appropriate and safe and ethical for this process to happen, but also equally to know that you are in charge too. That you're in charge of whether you'd like to participate or not participate, but to have that chance, for some people it's a really important part of looking after themselves, to be able to give back. And clinical trials and research can be a really important part of that, for some people living with MS.

Jane: Amazing. Thank you so much for joining us, Therese. Thank you.

Therese: Oh, it's been my pleasure. Thanks Jane.

Jane: Thanks again to Therese for joining us and helping us understand a little bit more about clinical trials. You can head to the website, mstrials.org.au to have a look at the Clinical Trials Network and as discussed in the podcast.

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