Spotlight on Research for Health: Translating evidence to policy

Generating scientific evidence is, although essential, just the first step. For clinical practice to be driven by evidence we must ensure that the knowledge is translated into policies that guide practice and are available for all. But how? The road from research to clinics is not a linear one, nor it is the same in every setting. Trials conducted in high-income countries can offer limited support to practice-changing in other contexts. So how do we go from evidence to implementation?

Taissa Vila, Editor-in-Chief at The Lancet Regional Health - Americas, speaks with Ana Claudia de Souza, a stroke neurologist and trialist at Hospital Moinhos de Vento in Brazil about translating evidence to clinical practice in low- and middle-income settings.

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Transcript

This transcript was automatically generated using speech recognition technology and may differ from the original audio. In citing or otherwise referring to the contents of this podcast, please ensure that you are quoting the recorded audio rather than this transcript.

Taissa: Hello and welcome to another episode of the Lancet Voice. I'm Thaisa Vila, the Editor in Chief of the Lancet Regional Health America as part of the Lancet Family of Journals. It's the 200 year anniversary for the Lancet, and as part of our celebrations, we're shining a light on multiple areas of health.

This podcast is focused on research for health, specifically the gap between knowledge and action and how we can ensure that evidence is used by policymakers in their decisions. Today we have a very special guest who's been involved in multiple areas of translation, this translational process. I have the pleasure to talk to Ana Cláudia de Souza, who is a Brazilian stroke neurologist And works in assistance to neurology patients, but also coordinating and managing clinical research projects at Hospital Muinhos de Vento in Porto Alegre in Brazil, where she is located.

Ana Cláudia, thank you very much for being with me today here. And I'll jump right in into our discussion. So I invited Ana Cláudia to this conversation because among many of her projects. She was involved in a landmark trial that represents quite nicely the idea of translating evidence to practice, and how this simple ask can have many different layers depending on the setting.

Anna is one of the medical scientists involved in the RESILIENT trial, which aimed to show that the feasibility of a well established procedure for stroke patients that had been only studied in high income settings. Ana, my first topic to you is, can you talk to us a little bit about the context in which the RESILIENT trial was designed and why it was such an important research question at that point?

Claudia: So thank you so much, Thaisa, for your invitation. And it's really a pleasure to have this opportunity to talk about the RESILIENT. The resilient trial was ideally built through through a group of neurologists, Dr. Raul Nogueira from the United States. He's one of the big heads that created the methodology of the trial.

And also here in Brazil. The, another principal investigator, Professor Sheila Martins, that is from the same city that I came. They built this study mainly because when they tried to incorporate this technology, the mechanical thrombectomy inside of our public health system, the government asked us, but it is very expensive and will it really work in the public health system?

Will it be feasible? And will it be cost effective to incorporate such a technology? They take into all those questions into the methodology. And the main objective of this trial was to prove that it could still benefit our population in our setting, because we know we have a lack of infrastructure.

And we know that mainly we don't have so many professionals that could perform those kind of procedures. And also we have another problem here in Brazil. The research is in that middle stage. So not all of the hospitals had good research centers well established. So they study was really challenging because we put a small and also a comprehensive stroke centers to to perform the study.

So it was a huge challenge that is started. With 20 hospitals and in the in the primary phase, what they did in those hospitals running phase. So Thank you. All the neurointerventionalists were training to perform the trial. Dr. Raul Nogueira came here in Brazil to teach all those doctors to perform the procedure.

Also Dr. Sheila Martins, she traveled all over states that participated to train them regarding the protocol and to stand with the right GCPs procedures to perform the trial. Dr. So it was a beautiful history because in that context, for example, in 2015, we had five main trials that proved the efficacy of mechanical thrombectomy in in a setting that is developed developed countries.

So the context is completely different. This procedure is is really important because one third of stroke patients, they have a severe type of stroke that we call large vascular occlusions. Only with a medication that is called intravenous alteplase, sometimes the clots cannot be dissolved. You must perform also a complementary procedure that is like a catheterism, but for the vessels of the brain.

The mechanical thrombectomy. They proved this benefit on 2015. And we know that here for the stroke treatment in our country, it took 17 years to approve one medication that is for all kind of types of ischemic stroke. It is called Alteplase. So it took 17 years to be incorporated. And we wanted.

This could not happen anymore. So because of this group of neurologists, they run and try to perform the resilient trial to understand the results and perform a cost effectiveness study to incorporate into our public health system. 

Taissa: 17 years, yeah. If we wait 17 years between every advance to Make it incorporate.

And you touched on a point that is very important and We can discuss this. It's generally, this is the bottleneck, what we call. You want to incorporate something in the lower and middle income countries, and you have several bottlenecks. But one, and a very important one, and you mentioned, is not having enough trained physicians or trained personnel all around, or having very specific hospitals where people should go to get that procedure, and that's not the case.

Visible. Having in the trial incorporated the training of others, that was part of your cost effective business study, I'm assuming, right? How do you see the acceptance of that and how challenging was that for a country as big as Brazil, I'm 

Claudia: thinking? Yeah, it was very challenging. Because the new interventionalists from all centers they had to be there on call 24 hours because of the resilient trial and they were there.

Not receiving to perform the procedures because it was a resident trial. It was with love for the patients. But when we assume this cost, for example we did for how much is a salary for a new interventionalist? How much time does the interventionalist spend in the angio suite and how much is the for example, to simulate how much does the procedure costs.

So we achieved, for example, in some hospitals that we had these numbers the hour of of a new interventionalist the total costs. Of other materials use it and the total cost of the hours that the patient is spending in Angio Suite, then we made, for example, an example that we applied for all centers for the, to simulate the cost of the total procedure with the devices updated and other costs.

Taissa: I assume that this is this was one of the most important parts of your study given that it was. It's almost a commissioned, as I understand trial from your government to say we won't implement this unless you show me it's relevant to, to our setting and it's doable in our setting. So this speaks a lot to cost effectiveness trials and parts of trials or specific trials.

And also to the importance of being careful in the translation of evidence from other settings. Another curiosity that I have is, we know it was a successful trial and we know that you showed the procedure was still feasible in your public health system. But, have you actually tried it?

identified any different outcomes compared to the other population that this has been studied before? 

Claudia: Yes. Unfortunately we found that our patients, they they had higher mortality rates because of the severity of their previous conditions. For example, hypertension, diabetes, they had this for a long time and the consequences of the, those chronic disease like heart failure past strokes.

So those patients, when they came to us they were really in a severe condition. And mainly if we can, for example, see the disparities of the results, but also And we can think about the reasons why, maybe because of the primary and secondary prevention that still is far from the ideal here in our country.

So this reflected in our outcomes. So our patients were in a more severe state and also they died more than compared to, to, to the other countries, but it was in the both arms. So it was not related to the procedure. And a very different result from what we saw in the developed countries. 

Taissa: This also speaks to what we were saying about the importance of the regulators asking you for this trial.

So it might be, we look at this and there's so much evidence around and can we just take this and incorporate, but the importance of having a contextualized research showing that this is still. I think that specific population. And I wonder if, how do you see this resonating around?

Did you see an impact after the trial in other countries in Latin America? Did you see this spread as being incorporated in other systems? 

Claudia: Yes, definitely. I think that, prove to prove that mechanical thrombectomy Really work it in an upper middle income country is an example for other countries that still don't have the mechanical thrombectomy implemented.

This is a really difficult balancing. We know that here in public health systems, we deal with constraints with funding constraints. So we have to try to allocate resources and we understand why they asked us. this kind of study. And here in Latin America, we have the same scenario.

So performing this and also showing that it's still, it is cost effective for a disease that is the first cause of mortality in our country was really an example. We have here in Latin America, lots of initiatives. to implement mechanical thrombectomy. For example, we have one that is the certification of stroke centers that is endorsed by the World Stroke Organization and also the Ibero American Society of Vascular Neurology.

that is helping to certify and to improve the treatment care in those hospitals. And also we have programs endorsed by the World Stroke Organization that, that is helping the countries. For example, we have in Colombia recently a course that new interventionists from United States are there to teach them how to perform the procedure.

And also we have other projects. I have one project that is analyzing the costs, the real costs of the ischemic stroke and their impact. And through this kind of study, we can see if the technologies could be cost effective. And after that, to be incorporated in those different kind of settings that we have here in Latin America.

Also, with this, the same initiative, for example, is being extended to Egypt, is being extended to India. So right now we are having a conference in India, a global stroke alliance with Southeast Asia countries to discuss about the, how to implement it. policies for a better stroke treatment and how to implement those evidence based treatments.

So it's a balance. Each country has its particularities. We have to be resilient. We have to adapt ourselves. So the name of the trial was really resilient and with any, it has a purpose. So all of the people involved were resilient to achieve the results into our public system. And right now this study is an example to translate it into practice and action for the stroke patients.

That's 

Taissa: wonderful. It's amazing to see it spreading like this. and in. Relatively short, shorter than 17 years for sure, and yeah, I have a point that you also touched, and I also, I know that we're just all this time saying that Brazilian was successful and example because we both know that it was eventually approved to be incorporated in the Brazilian public health system.

back in 2021. But I also know that this was not the end of the story. And it's actually pretty much almost the beginning of the story. Can you talk to us a little bit about what happens after you have the evidence and you go to them and say, okay, here's the evidence and it's contextualized. Now do it.

Claudia: Yeah. Now it's something that we call, for example, advocacy. We show with the results, we It's but we must address other kind of things. For example, how will be the funding released for those hospitals because a national policy for a national stroke plan should be rewritten and we must create codes for the hospitals to be reimbursed.

It's a long procedure to incorporate a new technology, it's still a long it's not reimbursed and still the funding was not released. Recently we had a meeting in, in, in Brasilia and representants from our National Stroke Society were there to talk about what is a stroke and our huge social and economic impact that we have here and the importance to incorporate the technology.

We achieved good results. Also, it was cost effective. Also we incorporated, but it's still, we don't have the funding. It's a procedure. So we are not just scientists. We have to adapt ourselves. We have to talk with different kinds of sponsors. We have to. Try to talk to the Ministry of Health to show our results and to show the importance of the disease.

So this is such a kind of implementing science of our evidences, of our results. It requires a lot of patience, a lot of resilience too, and now we expect that until the end of the year, we will have the results. This release, and then the hospitals that performed the mechanical thrombectomy for the resilient and also are certified could perform the procedure.

So it's still a long way until we can afford the treatment in the public health system for our patients. 

Taissa: It's tricky because if we think about scientists and doctors, we're not trained to do that part of the job, right? You get to the end of the trial and you think the evidence will still fit, but then you learn that you have to play multiple roles and learn new skills to talk to policymakers, talk to parliamentaries.

And the language that you need to use to convince them is different than the language that we use to convince scientists, right? It's tricky and It's a lot related to having the society involved. So you mentioned it as a implementation phase of this. And do you see the civil society and the patient societies playing an important part of this?

Have you had any experience working with patient societies on 

Claudia: phase? Definitely. It's very important. We have. Some patient societies here in Brazil for stroke patients and for example they really do the advocacy for the stroke patients. They help them, for example to facilitate access to rehabilitation.

That is another problem here in our country. And also they play a huge role. In, in, in participating, for example, in the stroke day in the 29th, October is the word stroke day. So during this week, all of vascular neurologists, stroke neurologists, and also the stroke associations, they participate together.

They, for example, they explain what is a stroke for the population. They go to the parks and they measure blood pressure. They talk to the patients, they evaluate the risk factors. They gave a lot of education lectures. To raise awareness of stroke. We are also in engaged on this.

We have, especially here, the the the efforts from the Brazilian stroke research network that is leading all the campaigns that happened all over the years. So definitely it's very important. To work in all levels of science and with education and primary prevention, secondary prevention, rehabilitation and acute phase, acute hospital phase.

So we. We have to balance it again and not forget any part of it. Yeah. 

Taissa: I feel 

Claudia: they 

Taissa: sometimes you gotta use speak to the heart and that's why sometimes they feel like the patient societies, they are really convincing for the policy makers because they seem more relatable than the scientists explaining why that procedure is so great.

So that's why. Having the interface of all levels is quite touching sometimes, and if that's what it takes. I have one point that I'm, I might have missed during our conversation, but we talked about many initiatives that are happening, and some of them are a result of the Resilient. But I also know that the trial itself gave birth To other little projects, do you want to talk to us about them and how they relate to our conversation today?

Claudia: Yes. We have the the continuum of the resilient trial. The the first is the resilient extent. That is mechanical thrombectomy for patients that came into the hospital over eight hours from symptom onset until 24 hours. So this is study. already is stopping for the first interim analysis to analyze the results if it's a benefit or not.

And also we have the the resilient extend IV that is testing another drug that is called tenecteplase in the extended window until nine hours. And we have Another trial that is the Resilient Direct TNK that is testing the TNK in the mechanical thrombectomy. The same centers and adding more centers that wanted to participate because of the great movement of the Resilient Trial are performing.

Mainly those two last trials because the resilient extent already reached our number, pre specified number for the first interim analysis. And it's possible that it will stop or not. Let's see. So it's really a good achievement for our stroke research team here in Brazil to keep continuing Those trials and the energy and 

Taissa: yeah, and this speaks to another point that's very important because although we've been focusing on this specific trial or this specific project that you are very related to, and this has a bigger impact.

That we can see in your previous message that is when one thing starts to work, it creates this chain of events. So you start showing to physicians in other departments and other researchers that it's possible. So they either want to participate in your next trial or you create this movement of growing the local research.

very much. Do you see this around you already? How 

Claudia: do you see this happening? No that's definitely we can see this and we have the Brazilian stroke network for the research that is is always growing. I can see their eyes. They are always trying to. Learn more and to participate.

They keep contacting us. Oh, now I have an ethics committee. How can I start here? Can we participate? So we send a feasibility for those centers and we evaluate and we work together. We train them if they are really willing to be there it has been a good experience. I think that it's growing and it's like you said it's possible it can be possible and we can achieve great results.

Not only for example, a positive result in a trial. But the power of this great network. So definitely it's good. So there 

Taissa: is one aspect of implementation that also plays an important role. And you may see this happening around as the cultural and acceptance of novelties from from the community and from the patients as well.

Is there any remarkable points around this that you've noticed about implementing something new and participating in the trial and talking to the patients about them being in the trial and, That part of the translation, 

Claudia: That's it that it's tricky because for example, when you are in in a emergency situation, for example, you are having a ischemic stroke and there is this acute phase trial mainly the acceptance is higher.

We train for example, the physicians that, that, that are evaluating the patients. to explain everything for the patient, but always to reassure the benefit, the potential benefit. Another tricky point is that we have to talk their language. So we have to adapt ourselves. We sometimes when you are starting research, you use the technical words and you don't engage your potential participant and you.

You just lost it, but you have to adapt your language. You have to explain all the procedures. And after that, mainly for the outpatient clinic phase trials, we have to have some strategies to retain those participants. We are trying to train everyone how to do this because it's not including Participant and not showing you, you have to adapt your language.

As you said, we have to improve our skills in different levels. No, absolutely. 

Taissa: I find the very, very important part is to reassure to the patient that being clear of the risks, but also be talking in their language, because in the end it's for their benefit that we're doing this. And it must be patient in the first place.

I find 

Claudia: it an encouraging skill. And we had a great acceptability of our patients because mainly it's a public health system and we were offering this, that they potentially could receive. A treatment that could change their lives. They were really, Oh, I want to participate.

So it's it, the acceptance was higher and even for the resilient X10IV and also the resilient direct TNK. The acceptability is not a problem, but always the communication issues could be a problem. You have explain things for the patients in their language, the benefit and the risks the benefits and the risks.

Taissa: I wonder if when you talk to other people that experience very different health systems situations where public health system is not universal like it is in Brazil. And if this is their main challenge, for example, in, in such implementations. 

Claudia: Yeah. Yeah. That it's always an enrichment for both parts, because if we understand each context, each reality, each cultural differences, the social disparities involved, And you try to really understand we can build better plans to address those problems, to create better national policies for the stroke patients.

And also when we are trying to here in, in India, we are performing the Global Stroke Alliance and it's not only a scientific conference. We are involving the ministers, we are involving the medical society, we are involving the stake, another stakeholders to work together, always together to implement all the evidence based strategies for stroke care.

So it's a group, it's a team work for performing this. Yes, it's a beautiful teamwork. 

Taissa: I think this is a very nice way to finish our talk and I'll thank you once again, Anna, for your participation and your amazing remarks. I learned a lot about Stroke Alliance and stroke care, and I hope you had a great time.

Gavin: Thanks so much for joining us for this episode of the Lancet Voice. This podcast will be marking the Lancet's 200th anniversary throughout 2023. by focusing on the spotlight with lots of different guest hosts from across the Lancet group. Remember to subscribe if you haven't already, and we'll see you back here soon.

Thanks so much for listening.