Ep 44: Fatigue and how to help patients, including insights from the LIFT trial

In this podcast, Jess Little, specialist MSK physiotherapist, talks to Professor Neil Basu, academic Rheumatologist and Professor Lorna Paul, professor of allied health science about fatigue and particularly what we can do to help patients. It covers everything from the importance to patients of considering fatigue to interventions including the role of personalised exercise plans and cognitive behavioural approaches. 

To read more about the LIFT trial  https://www.thelancet.com/journals/lanrhe/article/piis2665-9913(22)00156-4/fulltext

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Transcript

 Jessica Little   
 Hello and thank you for joining this Talking Rheumatology Spotlight Podcast focusing on the LIFT trial. I'm Jess little, a national clinical lead physiotherapist and member of the Digital Learning Board for the British Society of Rheumatology. Today, I'm excited and delighted to say that I'm joined by two leading experts in the field, both who are authors involved in the LIFT trial study group. We're going to be talking about the LIFT group what research has brought so far and what this means for us in a practical sense as clinicians impacting our patients care. So firstly welcome and thank you to Lorna Paul and Neil Basu for joining us. Lorna, if I can get you to go first and give us a little bit of an introduction to yourself and your background, please.
Paul, Lorna   1:10
 Hi, my name's Lorna Paul. I'm a physiotherapist by background and my current role is Professor of Allied Health Science at Glasgow Caledonian University and within the LIFT trial I was responsible with a colleague, Stuart Grey from University of Glasgow and leading the PEP arm and that was the personal exercise programme arm.
Jessica Little   1:33
 Thank you, Lorna and Neil can get you to do a bit of an introduction.
Neil Basu   1:38
 Thank you. So I'm an academic rheumatologist up at the University of Glasgow.
 I lead a number of research programmes, but one which is closest to my heart is understanding the biology of fatigue, which is a pervasive problem for many of the patients that I see in my rheumatology clinics.
 I've been thinking deeply about fatigue for many, many years, and in fact in my previous role at the University of Aberdeen, that's where we, together of many colleagues, compiled, compiled this LIFT trial, the lessening impact of fatigue, fatigue, trial in rheumatology. It feels like a long, long time ago, doesn't it, Lorna, that, that this all started, but these clinical trials take a while to come to fruition.
Jessica Little   2:27
 Thank you, both fascinating to hear about both your careers and your involvement so far. So I think, Neil, that that's a good a good intro to probably the next bit we want to go on to and think about was how did we get there with the LIFT trial. You know, what brought you there and what was it trying to address or look at?
Neil Basu   2:48
 Well, patients for decades have been telling us clinicians of the importance of fatigue, and quite rightly, they've been very frustrated and felt ignored because I think there's been a great disconnect between what they've been seeing and what the priorities have been of the biomedical community generally. So I think patient power has pushed this up the agenda and when I was a boy, when I did my PhD, my a long, long time ago the first steps really, after being totally compelled by this and my clinics and being able to not answer the questions of my patients, was how do we raise the profile of this amongst the clinical community and my approach at that stage was through good old epidemiology where we are essentially quantifying what our patients are telling us, whether it's the levels of fatigue, severities of fatigue in the population and crucially, the impact of fatigue on patients, quality of life, their ability to work, their their day-to-day. So we did those studies and in doing so really raised hopefully the importance of this to the policy makers, to the funders, to provide that evidence to underpin what the patients have been telling us for a while.
 So eventually we've caught up and my interest, as I said up front, was to try and better understand the mechanisms of this symptom, hopefully to develop new interventions but in the meantime, because all this research takes a while, there's clearly uncontroversial interventions, non pharmacological interventions which exist already, and yet as a clinician it's not something that I can easily prescribe, and it and it is that implementation challenge which is what inspired the lift trial I would suggest.
Jessica Little   5:01
 And I think I think you're right there is that implementation issue, isn't there like getting that understanding and getting that evidence to start to impact and do things. Lorna where did we get to next with LIFT, how did we get to practically implementing it and doing the study, what did that involve?
Paul, Lorna   5:26
 So as Neil said, it's a, it's a big team when you run a study like this. So we have everything from statisticians, health economists obviously the academics. Probably the key people involved were the patient partners and we did a lot of work with the patient partners to help co produce the interventions that we were going to deliver as part of lift and but we can summarise what lift was about, but basically we had three arms to the trial so we had usual carec we had the arm that I was responsible for which was the personalised exercise programme, and we had cognitive behavioural approaches to managing fatigue, so we developed those 3 strands in collaboration with people that had the conditions and I think one of the novel things about lift was it's not condition specific, so it's not specifically about rheumatology or specifically about AxSpA, but it was really about the inflammatory rheumatology conditions together and because with the idea that fatigue is fatigue and we could unpick it and the stats later if there was a difference between the different pathologies but actually we were managing fatigue, we weren't managing the clinical condition if you like. So I think you know that was a real sort of novel aspect and I think a real way forward and we now look at some of the other conditions that we would we can group things together, we don't have to do everything condition specific.
Jessica Little   6:59
 Neil, do what you come in?
Neil Basu   7:02
 Yeah, no, I just want to emphasise that and then from a service perspective
 when, when you're just trying to help various different patients with various different disorders, we for the first time wanted to make life easier for the clinical departments.
 Fatigue is relevant for rare diseases such as vasculitis, fatigue is relevant for common diseases such as rheumatoid arthritis. We're never going to have a fatigue specific programme for each of these different diseases, no, no department can do that. But all the previous studies that had been done in this space, of which there are quite a few, they've all been biassed towards the commoner conditions such as rheumatoid arthritis and so we really wanted to demonstrate the more generic concept as, as Lorna has emphasised, the transferability of these interventions across a typical general rheumatology clinic.
Jessica Little   7:59
 Yeah, definitely. And as you say, like the impact of that fatigue is fatigue independent of condition almost.
 And with the PEP arm so that the exercise arm and the CBA arm was there any crossover what clinicians were delivering these types of interventions and the trial were those physiotherapists or mental health practitioners or?
Paul, Lorna   8:30
 From the PEP side, the intervention was delivered by physiotherapists. The idea was originally would really have preferred sort of band 7 specialist rheumatology physios and when we got to deliver the trial reality, that wasn't possible all the time and so we had people who were generally band 6 and above, so they were fairly experienced clinical staff delivering the PEP intervention and was based on the patient's personal goals, so it was very much geared towards what the patient wanted to do. It was delivered over 8 sessions, the first sessions face to face, but the majority of the intervention was delivered remotely, which again opens up, you know, great opportunities, particularly when in Scotland and I'm sure other parts of the UK and around the world where we have rural populations and people working and with caring responsibilities and all the rest of it, so delivered remotely. Remember this was pre COVID so clinicians weren't as used to delivering remote interventions at that point, so most of the sessions were delivered across the phone. I think if we were doing it now, I think clinicians would have been happier on near me attend anywhere type platforms but at that time most were delivered over the phone and the interventions themselves had sort of three different components there was an assessment component there was an exercise component and there was a sort of homework part, so it was based on behaviour change and the idea was to improve people's physical activity and exercise towards the national physical activity guidelines but to do that really gradually so we weren't just jumping in, you know, saying you've got to do 30 minutes a week so we were building that up, but not just
 the number of minutes if you like, of physical activity, but because we were interested in increasing people's physical conditions so some of our patients are deconditioned. We had to get that physical activity at a particular intensity so it wasn't just going for a walk, but actually you had to get your heart rate up so you had to walk that walk that bit faster and actually, we had some patients who were really physically active and we had to reduce their physical activity or encourage them to reduce their physical activity, I should say but taking you know, doing that at a higher intensity to get the benefits of the programme, and I can only speak for Pep the CBA was delivered, Neil, will probably correct me here, by psychologists and did we have occupational therapists as well?
Neil Basu   11:16
 So the key theme around the CBA arm was recognising that there isn't that much clinical psychology support and most rheumatology departments unlike physiotherapy, which I appreciate also, there's a shortage of physiotherapists and rheumatology departments, but there is a significant shortage of psychology, again, a more pragmatic implementation perspective was can we supervise the team, the MDT of the rheumatology department deliver this and that might be occupational therapist, it might be a physiotherapist it might be a specialist nurse. I think most of our colleagues ultimately were specialist rheumatology nurses, people of no previous background at all, in delivering psychological interventions, but with the right training and the right support, we wanted to test whether they could be up skilled enough for pragmatic way again to be able to deliver the intervention.
Jessica Little   12:19
 I think that's exciting, isn't it? As one of these clinicians within the MDT to be able to have that shared skill and often when you have patients, you know you're frustrated. if that's an area that you can't touch on and support in so that seems like a like a really nice progression for clinicians within that.
 From a clinician hat on for myself when patients were coming into the trial
 when this type of intervention was delivered, how did the patients become stratified into whatever group they were going into? So how was it practically for a clinician? How could I work that out? What did the trial find out to help with that?
Neil Basu   13:08
 So we were very keen to make sure this mirrored a typical NHS service so if I put myself in my clinic like I have this afternoon and a patient comes to me reporting significant fatigue, my knee jerk reaction, and probably the correct reaction is OK, am I treating the underlying disease correctly first? So i.e is there lots of active inflammation going on and I've got a ton of cool tools now to be able to offer that to patients and variably are very successful. So that's probably not the time point to be able to introduce these interventions because treating the inflammation can in some patients reduce their fatigue so that's why we intentionally focused in on patients who were otherwise considered stable by their local clinical team or on stable medications, there wasn't any room to modulate the fatigue further through peripheral inflammatory targeting but yet they were still disabled by their fatigue. So this was the group that we wanted to target and this is a rather sizable group. I mean, this dominates like half our clinics so this is not a small niche, but nonetheless, this was the group that we wanted to identify make sure there weren't any other medical explanations for their fatigue, such as significant anaemia, chronic renal impairment, thyroid dysfunction so and we screened out these other reversible causes of fatigue, then it was this group that we would then go on to randomise to either receive the PEP, the cognitive behavioural approach or standard care which in most UK centres is the versus arthritis educational booklet which we all hand out. I would want to emphasise, we have mentioned it yet and I apologise that this whole trial is funded by versus arthritis so very grateful to them and actually their booklet that is still considered standard of care. There's some nice evidence that this is a really positive intervention for patients to our comparator here in the trial was a positive intervention rather than a placebo.
Jessica Little   15:28
 Fantastic. So suppose that's a good time to kind of talk about what were the outcomes for these patients. So once they were randomised into these groups, was there a discernible difference? Could we see patients responding better in one area than not, or was that that blended approach a good approach step?
Neil Basu   15:51
So and it took at least a couple of years, pandemic slowed things down a wee bit, we ended up recruiting about 370 patients or so if you're randomised to these three arms, those receiving the acts of interventions of CBA, PEP have up to between 6 to 8 interventions, it varied from individual to individual. It was very much determined between the therapist and individual how much they would require but essentially up to about six months of therapy.
 My most clinical trials such as this have their primary endpoint right after the intervention is completed. Now we didn't think again that was that useful because we all know from the past that patients always feel good after receiving some contact. The key thing for us is that if six months down the track after they've had no interaction at all with their therapist they're still benefiting then we've done something that's been important for that patient. So our primary endpoint came at a year, so that's six months after they'd had any contact at all. Of course, the therapist educated the individuals to maintain the skills that they had evolved during the sessions, but there was no further booster sessions as such after that so our prime endpoints that year were two there were fatigue severity but our patients, our patient partners in the group really inspired us to also include fatigue impact as a secondary primary outcome, IE how does the fatigue affect their day-to-day and that is recognised to be just as important as the level of severity. So there were two primary endpoints and we had numerous other secondary outcomes looking at other dimensions of quality of life the headline results were that both the cognitive behavioural approach and the PEP, provided both statistical and clinical improvements in fatigue severity and fatigue impact at a year, so we're delighted that these effects had been maintained despite the lack of intervention. And as I wanted to emphasise again, these were clinically important impacts and not just a P value of less than .05 which we often get attracted by.
Jessica Little   18:35
 Amazing and as for some of the patients that were in that trial, has there been any longer term anecdotal feedback or any formal feedback that's come from them after that year to see if they're still utilising the tools and the skills that they've learned?
Neil Basu   18:55
 I have the privilege of still seeing a lot of these patients who were recruited when I was in Aberdeen in clinic, I still go up to Aberdeen once a month to do a clinic and
 it's a real, real great, great news story to hear that some people have maintained that and felt that it's transformed their lives. Now, that's not scientific, this is after quality to quality, to perspective, from the physician interaction, we don't have that longer follow up data, but I think my sense is that for at least a subgroup they've really engaged, they've kept and maintained these skills and to their benefit.
Jessica Little   19:41
 Which is amazing and I suppose that takes me to my next thought process or questions as around the longer term for the lift group and what that looks like as are there plans to do any further look at things or look at longer term impact in a more formal way?
Neil Basu   20:02
 Well, our primary objective and motivation has always been to try and implement this into the NHS and so that the second phase after reporting the headline efficacy data and I should also emphasise safety data, this was entirely safe, there were no serious adverse events reported for any of the arms, we of course live in a very difficult financial climate in the NHS and so the health economic analysis was really critical and we made sure that that was done robustly up front and we adhered to essentially the same sort of rules and approaches that one would engage with if you were testing a pharmacological drug and we well, not we, more erudite colleagues in the health economic space did some robust analysis for us and ultimately reported that the PEP, the exercise intervention was cost effective for NHS tarrifs, so if it was a drug, it would go through NICE, I mean, we quantified the PEP Lorna to be around £550 or so let's put that into context, Jessica, I mean, the cost of some of the targeted therapies, all of the targeted therapies, we use are substantially more than that and yet we don't really have difficulties in accessing most of these drugs or as yet still we are challenged in trying to access good physiotherapy or good specialist nursing so that's why we've very much in the next phase of around PEP whilst I want to emphasise that the CBA was effective as well. It turned out not to be cost effective, so I think it does have a role and we want to promote that but in terms of our primary objective integrating into NHS, we have to follow the NHS rules and so in the first instance, we're prioritizing how do we get implementation of the PEP
 and Lorna and I have spent a lot of times sort of lobbying, speaking to Parliament
 Policy makers, trying to get the word out. Very pleased to hear and consistently positive feedback, I mean, this is not controversial, nobody's questioning the science here, nobody's questioning the importance. It's just a bit of a jungle at the moment the NHS and to navigate that requires persistence but Lorna and I are still here persistent as always and we have the subjective and we hope that many of the listeners in the podcast will show interest in your respective regions and
 we'd be very happy to support going forward and working out local solutions.
Jessica Little   23:18
 OK. And I think that's key, isn't it? It's the clinicians, the people that are listening to this podcast and often it's just getting that first start and how you initiate that conversation or how you engage or where's the right place to refer to, to get this kind of expertise. Do either of you have any practical hot tips for clinicians who feel they want to learn a bit more about this or want to start implementing more of this within their service where they could go for more information, Lorna.
Paul, Lorna   23:55
 I can sort of speak from perspective of the PEP arm, I mean, I think the first thing to say is nothing that we delivered was rocket science. It was very much day-to-day bread and butter therapy. So you know, you don't need any specialist skills or equipment or whatever it was, you know, it was very much day-to-day what we would, what we would you know say was bread and butter. And I think what the challenges are is, as Neil's alluded to, are the challenges around funding in the NHS and this was not just given somebody a leaflet, but you actually have to put a bit of resource into to it but we do have the manuals, we're happy to share resources that we've that we've got. I think one of the key things is the training, although I'm saying it's not rocket science. I think certainly from our qualitative work in the trial, both the patients and the therapists brought up the importance of training and how that helped with their confidence in terms of delivering it, particularly at that point, you know over the telephone so I think for us to develop you know, as we've talked about a train the trainer type approach and so that people would do a bit of training and to understand the structure of it and the reason why we're doing it, we would put that sort of training programme together, but the resources are all there to be used and I think probably we're in a better position now than we were when we started pre COVID because we're all much better at delivering interventions remotely. I'm not sure the NHS are quite know how to deliver digital interventions, I think that's the challenge because we can, you could have, you know, one or two therapists in a in a hub delivering to a kind of large geographical area. It doesn't need to be everything with an individual, you know, hospitals or even trusts but there isn't really a model to roll that out but certainly as Neil said, we've got the evidence, it's the big question now is how do we implement it? And we're absolutely open to any ideas, thoughts, interests that that people have got.
Jessica Little   26:08
 Yeah and I think it's, it's an exciting time. It's almost like a really timely space that this research came out and because if you think what's happened in the last five years and particularly COVID and the acceleration of digital and virtual remote healthcare, it's a really exciting, fast-paced developing area where it almost gives, as you say, a lot more accessibility to this type of support and care that that maybe wasn't easy for patients in rural areas or busy, busy lives to come and do 8 face to face sessions, as its a lot to fit into to someone's life when life's going on round about it so yeah, it's very exciting.
 Thank you both very much for joining us today that was really interesting. I'm sure we'll have more coming up in the future around particularly the exercise and the PEP arm of this trial, which will be good but yeah, thank you both for today.
Paul, Lorna   27:13
 Thank you.
Neil Basu   27:15
 Thanks, Jessica.