Talking Clinical Trials: Participant's experience and perspective

Colm: 0:12

Hello to you, and welcome back to the Dementia Podcast. As always, I'm your host, Colm Cunningham, and it's great to have you with us. In this episode, we're going to be talking to people who've participated in clinical trials for treatment related to their symptoms of dementia. With my guest today, we'll be exploring not only the clinical, but the personal and practical elements of these trials, sharing their experiences along the way. So why are we doing this? Well, three years ago, I heard about a conference speaker who had dementia who was on a clinical trial, and I was appalled to hear that the way that trial was paused was by email, I wouldn't expect that for anybody but particularly for somebody with dementia. So I thought it was important to talk about best practice and to hear from some people who are directly involved, albeit in the Australian context. We will in our show notes, of course, help you understand where to link to clinical trials in your country. Before we go ahead I must apologize that we're in lockdown here in a few states in Australia, so it has had an impact on us not being able to have our usual studio setup. So apologies a little bit for the audio. We will at the end of podcast include some show notes about glossary of terms because we do get a wee bit research in some of the conversations. For example, we talk about efficious when we're talking really about effectiveness. We also talk about placebos, but I'm glad my first guest and colleague is Professor Steve McFarlane. Steve is our head of clinical services, and leads our clinical trials. So firstly, Steve, when we're talking about clinical trials in relation to dementia, are we talking about medications that are going to help all types of dementia or specific ones?

Steve MacFarlane: 1:59

We're mainly talking about Alzheimer's disease Colm, because although there are over 100 different types of dementia, and many of them are very rare, Alzheimer's accounts for about 70% of all cases. So most research funding has gone into developing drugs that are Alzheimer specific. Having said that there are now a number of other trials coming through looking at the less common types of dementia.

Colm: 2:22

And do you expect that these trials will cure Alzheimer's or manage some of what you experience when you have Alzheimer's?

Steve MacFarlane: 2:31

I think the latter really. I mean, one of the unfortunate things about Alzheimer's is that we know that the pathology that proteins in the brain that cause the disease appear up to 20 years before people develop symptoms. And the implication of that is by the time you've developed the very first symptoms of Alzheimer's disease, a lot of brain cells have already been severely damaged or in fact, are dead. And we're not going to be able to bring those brain cells back to life. So I think the most of what we can expect from a highly successful medication would be to arrest the progression of the disease. But a more realistic goal is probably simply to slow its progression down.

Colm: 3:11

So if we were looking at what a treatment will look like in the next two decades, what do you hope that trials like the ones you're involved in will change in experience people with dementia have?

Steve MacFarlane: 3:21

Well, we've seen some progress come through very recently Colm, there was a new drug approved in the US for the treatment of Alzheimer's disease for the first time in over 20 years earlier this year. And I think we'll see more variations on the theme of that drug. It's a class of drug called monoclonal antibodies. But going forward, I think the field of Alzheimer's treatment will increasingly replicate what we see in cancer treatment, that it's not a one drug does the whole thing type approach. But I think we'll be seeing combination therapies, as different classes of drugs show different areas of effectiveness in Alzheimer's. So we'll be using a lot more combinations than single drugs. It's the way I think the future is going to pan out there.

Colm: 4:02

So we will be talking to john about his experience of being actually on a trial. One of the things that sometimes comes up is am I on the real drug or on the placebo? Could you tell us a little bit about what is a placebo? And what does it mean in the context of dementia drug trials?

Steve MacFarlane: 4:18

Okay, a placebo is an inactive substance, you might have heard them referred to as sugar pills. And if the study medication has been given in a pill form, there will be another pill that's made up to look and taste exactly like the real pill, which contains an inactive substance that won't have any effect on the disease. And the reason it's important to use a placebo arm in trials like this is if you've got a group of people who seem to be benefiting from a drug, you have to be able to compare them to a comparable group of people who aren't getting an active treatment so that you can be sure that the benefits that we're seeing are in fact due to the drug and not just due to something called the placebo effect, where the We'll think they're getting a drug so tend to report themselves as being better than if they weren't known to be on any substance. So placebos really important. Most trials nowadays will have a placebo controlled phase for a year, possibly up to two years. But because these trials are very big, and they can take a couple of years to recruit 1000s of patients, they'll usually offer what's called an open label extension phase, the people who finish the trial first, they get to then be guaranteed to receive the study drug for an indefinite period until the results of the placebo control trial are over. So there is a net benefit to patients being guaranteed to receive the study drug at some point in all of these trials, but the placebo controlled phase can vary from anything between 12 weeks to a couple of years.

Colm: 5:52

Steve, my last question is we're obviously going to be talking to somebody about what it's important from their point of view by being on a trial. You've worked in this area for a long time, are there any things that have become more important to you in the way people with dementia and their relatives who are supporting them are treated during trials that you're involved in?

Steve MacFarlane: 6:10

Sure. And one of the interesting things when you're looking at clinical trial, participants, comas, even if you look at the group who received the active drug, and the group who received placebo, the placebo treated treated group actually do better than people who don't participate in clinical trials at all, which is really interesting. And I think the probable explanation for that is even just being involved in a trial means that you get close, regular expert follow up by people who are familiar with the disease under consideration, and you possibly get better quality, and certainly more frequent follow up than if you were just under the care of a medical specialist or a GP. So there are benefits for participation, whether you're on study or not. And one of the things I'm sure you'll hear from Maree and our guests later today is that they do feel valued, valued and part of a treatment team and looking after trial participants and their carers is one of the things that helps keep them engaged and stop dropping out of the study during the course of a treatment period that can last for two or three years. So if you take care of your trial participants, they tend to do better for longer, regardless of whether they're on placebo, and to not drop out of the trial. So it's a great thing for patients and their carers to be involved with

Colm: 7:28

Steve, thanks so much for helping us understand as we start this conversation, some of the important issues. I'll see you very soon on dementia podcast,

Steve MacFarlane: 7:36

It's always a pleasure, Colm. Thanks.

Colm: 7:37

And now I am pleased to introduce our guests from Melbourne in Australia. Maree Mastwyk is the manager at our clinical trials team who works with Steve and it's fantastic to have her extensive experience reflected in the discussions we're going to have next. But with her, we will have John. John's a person living with dementia, who is currently on a clinical trial with us. And along with him, Tricia his partner. And together they're going to share their personal experience. So thank you all for joining us on this important topic. Tricia, what led you and john to be involved?

Tricia: 8:14

When we heard about the diagnosis, which we all suspected would be the case, because John's mother had Alzheimer's around the same age as John and i had been noticing for the past few years. So we were prepared for the diagnosis. And so with that preparation of thinking about that, we'd also decided to look up and see what else was possibly available, even though we had heard there was no treatment. So thinking of it as a hereditary diagnosis or illness, or disease and thinking of the children and I think they were also thinking ahead when I say children, adults in their 40s we thought let's see what other what's happening with trials we then spoke to the neurologist about we were keen looking towards the future. And he suggested HammondCare. Plus there would be others that HammondCare with anavex. So as a group, and we suggested to John and we were all in agreement so that we'd go ahead,

Colm: 9:38

Maree I imagine there's a number of stages before people like John and Trisha get involved in clinical trials.

Maree Mastwyk: 9:45

Well clinical trials are an opportunity to trial a medication that may be efficacious in a particular condition if there is existing standards treatment that's often used as a comparator against a new potential drug. But in Alzheimer's disease, as Tricia said, there is no cure for Alzheimer's disease. So we still have to compare potential treatments for Alzheimer's against placebo, to see if the treatment improves the situation that the person would otherwise go through really, clinical trials go through quite a long process, there's 10 to 15 years in the lab, if there is some indication of efficacy, then they will have a phase one study where it's given to healthy volunteers, usually young people that are paid for the experience to test it for safety. And that's done in small numbers. Then in phase two, they will give it to people with the disease under study. And that will again be a small study, to continue to safety work, but also to look at efficacy. So it's a proof of concept study. And then phase three, there will be two large studies of 1500 people or more looking at safety tolerability still that always continues and efficacy.

Colm: 11:12

Maree, can I ask you in terms of the point at which John and Tricia would find themselves coming for their first conversation. What are the important steps that you in the team said I turned sure that on our first day of having a conversation with you, you're all ready for them? I imagine you have a number of processes to support them.

Maree Mastwyk: 11:32

We start off with a telephone call. And we encourage people to come and meet us before they start. And I think Trisha did that in the UK many late hours. Yes, she came by herself, but that not with John John was at that stage trusting Tricia's judgment. And we had a chat about the clinical trial and what was involved. So what is involved is at the first visit, we go through a consent form. And usually people have the opportunity always people have the opportunity read the consent form before they come for the screening visit and have their questions read. Then the doctor goes through the consent form with the participant and the study partner. All Alzheimer's disease studies have a study partner. And that process usually takes 30 or 40 minutes. Once we have consent, we go through eligibility criteria. And that usually starts with cognitive assessments. Because the the drug may be looking for people with mild Alzheimer's or mild cognitive impairment, then we make sure that the regardless so physically on the study, so they have a full gamut of physical tests, the study continues for six months, two years. However long efficacy content is done at intervals. And safety assessment is done at every visit. And we will put any changes in cognates or adverse events to make sure that the patient is healthy and safe. During participations.

Colm: 13:09

JOHN, I would love to understand what's important to you as a participant.

John: 13:13

Yeah, I did want to see if there was any material that I could read, to come to an understanding of what the process would be. And I think mostly that was not so much in mostly conversation. As taught, things would be conducted. I think there are probably occasions where I haven't attended. I don't, I don't have any knowledge of those. I have heard from time to time just listen to in science programs on radio, that they are achieving some results from this process. But I haven't really had that confirmed to me a personal basis.

Colm: 14:02

Tricia, I realize that you are an important support here to ensure that John gets to all the appointments and gets the information he needs to make informed decisions about being part of this. What's been important for you. And indeed, what do you think's important for anybody else thinking of us being a support to somebody taking part in a trial?

Tricia: 14:22

Well, one of the first things is Maree suggested or not suggested, she said, I, I came along by myself, I really want you to, for me, I will really want to know who people are. I want to know the environment. I want to know what I'm coming into. I want to feel like it's friendly, and that people can respond in a very human way that is in my life generally. Otherwise, I find I lose interest. So I chatted to Maree. I probably came in and just said what was on my mind, Maree responded really well in a very sort of friendly and listening way. And so I understood the environment to a certain extent. And after that, I got to meet the team especially well, Steve, but I have to say, Paul, who has been main contact has been incredible. I mean, I couldn't. I couldn't hope for anyone better than Paul. His humour, his life his spirit. And I think that for me, also has given me just a feeling like we can belong to the team for as long as possible. It's that normality and humanity that keeps us going. And through that, I can. Well I know John has responded, well, it's, and I think people who perhaps are a little bit shyer than me, may feel it, but can't won't express it. But I think underlying it all, is that contact,

Colm: 16:14

So consistency, relationships, knowing the environment, and it's, it's striking, you said earlier in the conversation that but you're part of the team, you're not a subject of the team, you're a part of it. That's a really powerful message. Can I ask you both, because as Maree said, quite rightly, the important steps to ensure that a trial is being run well, and that we're ensuring that you're safe, supported, and all the right pre getting involved, tests are done. That's a lot of work. I'm wondering what advice from both your point of view John and Tricia, as you would give to anybody thinking of taking part in a trial,

John: 16:53

I would recommend that they engage in it, or inquire about it and find out if it works for them, I understand that there are no treatments out there. And I understand that there are treatments which come about and come evolving out of a process such as this experiment, give me the opportunity to be involved in, in, in something that's possibly going to lead to clearer insight, so possibly going to lead to some form of treatment. I could only recommend that they go ahead.

Colm: 17:28

And Tricia, clearly, you have indicated that your personality would also say that the checking out would also have happened regardless, because that's the way you're wired. But for somebody who isn't wired like you, have you've got some advice for them,

Tricia: 17:41

Well, I would always just say to anybody is to trust their instincts, I would say it intuitive, instinctive feel no matter what personality because as human beings, we all find our way to something, and we all make our own decisions. So I would never say, absolutely do it, I would just say trust your feelings. And at any time you feel overwhelmed by the process, then you can stop it. You can end it. And that's what the team, also says we can, we can end at any point, like the team, if they come across something that's not right, within the trial, my understanding is they can see it, we'll accept that. And vice versa. So it's a very, I don't think it's a personality thing. I think it's just a trust within yourself, and what the capacities of yourself to continue, because that's what's important for the partner, as well as the person with the disease.

Colm: 18:48

Maree, is there any more that you would add to that in terms of how the team need to think about this? Because obviously, occasionally, there may be changes in the protocol or the process as you're going along. And so any tips that you would suggest for people listening?

Maree Mastwyk: 19:01

Well, certainly, we revise our practices regularly, we listen to what people say and make changes as we think necessary on a day to day basis. So as as and when they occur.

Colm: 19:19

Any final thoughts Maree?

Maree Mastwyk: 19:21

people need hope. And I think clinical trials do give people some hope. There's also as Trish hit on the support, there's regular review and support, at all visits. You don't have to wait for those six monthly reviews with specialists which are coming in here more frequently. And you have somebody on speed dial, and we can always do unscheduled visits if there's a problem.

Colm: 19:46

John, Maree earlier talked about hope. What does that mean for you?

John: 19:51

Hope is that the treatment has some benign effect on the treated and I thought I assume that's kind of what we're all looking at six, whatever that is, I assume I presume that is your process?

Colm: 20:14

Absolutely. Absolutely. computers. Yeah,

Tricia: 20:16

I have found by being we, and we've both been open to all our friends. So once the diagnosis happened, and we received that, then that openness and to be able to talk about the trial, and to include all friends, and close neighbors, to know what's happening, has been an amazing experience. And I think that, Maree spoke about this which I'm just following on that openness and kindness, will it through the openness, the kindness comes, and an understanding, and then you hear of other people's stories, and then people will open up and talk about, oh, my mother had that. And I will ask, Well, how did they feel, and that caring between people and the honesty of what's happening in your own household? Is it just ripples out? It's like, just an incredible experience. And the other thing that was important to us, for our family, and I think this is still what's going to happen, the end of the trial, and I think people should know this. But for us here anyway, I believe John will be given the drug, real drug for perhaps up to two years. I'm not absolutely clear. But I think that's what it is. Now. So we have altruism on one hand, but also very practical and pragmatic. And how, as a family, and we're looking towards that, that that will give John an opportunity. So as well as the wider community, we're looking at supporting John, and perhaps it could help.

Colm: 22:11

Well, it has really helped to have you share your thoughts today, because it's a real privilege to be able to hear from somebody living with dementia and their carer who at the end of the day, are the reason why we exist in our roles. We've done a lot of work to ensure that this space was right and safe and that you were in in control of the messages today. But at the end it I realize it's also very personal. So I cannot thank you enough for people listening across the world that you've been willing to share your stories. Thank you, all three of you for taking part today.

Tricia: 22:47

Thank you, thanks for the opportunity Colm.

Colm: 22:50

It was so wonderful to get to talk to Maree and to John and Tricia. As always in our show notes we'll have important links that may help and inform your thinking. And please as always, don't hesitate to give us your feedback through Hello@dementiacenter.com. We welcome your thoughts and ideas on this and future episodes. thank you as always for listening and bye for now.