KERCasts

Reducing the burden of research to participants

December 02, 2020 KER Unit
KERCasts
Reducing the burden of research to participants
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KERCasts
Reducing the burden of research to participants
Dec 02, 2020
KER Unit

In this KER Cast installment, Dr. Victor Montori is joined by Dr. Isabelle Boutron, professor of epidemiology at the Université de Paris and head of the INSERM-METHODS team within the Centre of Research in Epidemiology and Statistics (CRESS). Dr. Boutron discusses her clinical and research background, including her experience as a post-doctoral scholar at Oxford; her interest in reducing waste in research design, conduct, and reporting; and the absolute necessity of clinical research that interrogates the world from the perspective of the patient.

Show Notes Transcript

In this KER Cast installment, Dr. Victor Montori is joined by Dr. Isabelle Boutron, professor of epidemiology at the Université de Paris and head of the INSERM-METHODS team within the Centre of Research in Epidemiology and Statistics (CRESS). Dr. Boutron discusses her clinical and research background, including her experience as a post-doctoral scholar at Oxford; her interest in reducing waste in research design, conduct, and reporting; and the absolute necessity of clinical research that interrogates the world from the perspective of the patient.

Victor Montori:

Good morning, it's time to start the KERcast. Brought to you by the Knowledge and Evaluation Research unit at Mayo Clinic. I am Victor Montori from the KERunit and today we are in for a treat. We are delighted to have Isabelle Boutron today as our guest of our KERcast. Isabelle is a professor of epidemiology at the University of Paris. She heads the methods team at INSERM, which is a Epidemiology and Statistics Research Center, CRESS at INSERM, which is, in my opinion, one of the top two or top three clinical epidemiology centers in the world. She is also the director of Cochrane France, and he's extremely active in the areas of bias and the reporting of clinical trials. Isabelle, what a pleasure to have you. Welcome to the KERcast.

Isabelle Boutron:

Thank you very much Victor. I'm delighted to be here. Sorry, I'm from home in my son's bedroom, but I'm doing my best.

Victor Montori:

That is that is phenomenal. We're just so happy to have you. Isabelle one of the ways we start this conversation is to talk about the journey, you know, how people have come to be, who they are and where they are and how they're doing things, and oftentimes is helpful for some of the younger people listening to know, you know, is this something that was designed, you know, this is the path you set up to do? Or to what extent this is the result of good luck and fortune. So, so how does one become Isabelle Boutron?

Isabelle Boutron:

Well, it wasn't planned at all. And it was really the results of good luck. And I think meeting the right people and being able to grab the opportunity when they occur. So I was, you know, a normal medical student with no plan, I was becoming willing to become a rheumatologist, I was thinking of having working in a private setting. And at the end of my studies I was, yeah, after three and almost four years of my, of my studies, I had the opportunity to do a Master. And I had the opportunity to do this Master, supervised by Philippe Ravaud became after that my mentor in the field of clinical epidemiology. And I just sort of realized that's where I wanted to be and where I wanted to go. And so I sort of move completely to clinical epidemiology. As you know, stop everything I was doing and start again, as a Master's student, stopped working to do PhD student didn't know where I was, where I was going, but just enjoying what I was doing. And then opportunity appeared progressively because I was enjoying what I was doing. So the work went quite well. And then some opportunity just arose but it was just not planned at all. And I think it's just, you suddenly you meet some people and you realize that's where you need to go and just don't think and just go there. That's my advice.

Victor Montori:

Yeah. Yeah. Well, it, it was, sounds like it was particularly lucky to have had in that first Master's experience the opportunity to find something that really caught your imagination. And also, you know, a phenomenal mentor like Philippe, right I mean, that that was the, that was a...But you were not you were not satisfied with just, with just that, you ended, you ended up going to Oxford.

Isabelle Boutron:

Oh, yeah. So that that was more planned. I sort of I had in my to do lists, you know, I did a to do list and in my to do list, I wanted to go abroad. I wanted to work to have the experience abroad because it's an experience I had when I was younger, and I really enjoyed it. And so I went to Oxford, after my PhD and again, I was very lucky because first it was Oxford, which is pretty nice.

Victor Montori:

Sounds like a really nice place yeah.

Isabelle Boutron:

And second, and mainly I was working with Doug Altman Professor Doug Altman who is professor of statistics and is a phenomenon researcher who did a lot, particularly for improving the reporting of research, improving the quality of research, moving toward responsible research. So for me, it has been a fantastic experience to be, to be in Oxford. It was both a research experience and a family experience. Because I was there with all my family.

Victor Montori:

You said that you had the experience of going abroad at a younger age. Where did you go?

Isabelle Boutron:

So actually, my dad did a postdoc, and just send me to his cousin because he didn't want me with him. And I've got some cousins who were in the States in California. And I spent six months when I was 11. Went to school, I couldn't speak a word on English at the beginning and just went to school. And that was fantastic experience.

Victor Montori:

Phenomenal, so then, then you moved your family to Oxford, and to embed yourself in the English culture.

Isabelle Boutron:

Exactly. So that was our goal. So we had some rules, you can't go back to France for one year, and you need to have the perfect English life. So children went to school, and we participated in all of the very British life, with a British Christmas. And so that was our British experience.

Victor Montori:

What, what was the most, what was the most British thing that you ended up doing?

Isabelle Boutron:

We went to the church, because there was sort of, well, I think Christmas for me was very, it's very different in England then in France. So having the proper British dinner, my mum came to Oxford to do Christmas with us. So that was a phenomenal experience. And we did some painting, we tried everything, we tried everything I can tell you all the weekends, we were trying everything.

Victor Montori:

That is a wonderful adventure. Dog Altman was quite the character wasn't he? I saw him for the first time in Rome in 2000. He was a scary character, because he had big hair, and big eyebrows. He looked like the devil and, and then you approached him. And he was a sweetheart, you know, he was an extremely generous person.

Isabelle Boutron:

Yeah, he was fantastic, very kind and very busy, of course, but he always had time for you. So you could go in his office. And it was just chatting, chatting about research for one hour, which is incredible. I mean, it's a fantastic experience. So you had this desk, with papers all over the desk, and you discuss research and suddenly he'd say, oh, I've got very nice paper on this topic. And you just look in all the paper all the times and find you a fantastic paper. So yeah, it was, it was a fantastic experience working with him. And we also, I also had to learn to work, because as still, it doesn't look but there are some differences in culture between the way we communicate in France and the way you communicate in, in Britain, in France, we are quite direct, you know, if you've got something to say you just say it, which could be a bit moody in, in England, so I had to learn to be much more not so direct. So So, in, in Doug Altman's team there was Sally Hopewell and so she was my mentor. So she taught me how to write English emails, how to, yeah, ask for in a good way to communicate in a good way and not to be so straightforward.

Victor Montori:

So Sally was your cultural, your what would be your your translator, your cultural translator/interpreter.

Isabelle Boutron:

Exactly. And then she came to France and so I became her French teacher say how to write French...

Victor Montori:

Did she become more direct?

Isabelle Boutron:

She became much more direct, yeah. We had that type of, we had that type of conversation where she was, you know, talking for five minutes and at the end, I was just Sally just tell me what you want.

Victor Montori:

Which one do you prefer? Do you prefer the more direct approach or the the more what would be less direct

Isabelle Boutron:

I am comfortable with most direct approach? approach.

Victor Montori:

You reverted to your French Ways.

Isabelle Boutron:

Yeah, absolutely. Yeah,

Victor Montori:

That is, that is, that is great. You mentioned that Doug Altman was interested in responsible research you want to tell us, tell us a little bit more about what that means.

Isabelle Boutron:

So it's it's he worked a lot on the bad quality of research actually he worked a lot showing that we had a lot of waste in the research we were conducting and he participated in a lot of papers related to that, and the waste rules at different levels. First, when you set up the research questions, where you're going to focus on on the wrong research questions, and this is because, for example, you're going to use the wrong comparator. And there is a very nice paper that Philippe did on this topic, where he looked at all registered randomized control trials in the field of Rheumatology of Rheumatoid arthritis, and he showed that a lot of the trials, compare the new treatment to placebo. And this is not ethical, because there's some active treatment, and you should compare the new treatment to an active treatment. And so that's an important waste in research. Another important waste in research was the wrong, choosing the wrong outcome focusing on an outcome that is not relevant for patients, not clinically important. And that's also an important waste in research. And, of course, all the waste related to bad methods, and not reporting the results of research, or not being transparent in reporting the results. So that was, yeah, a lot what he did and, and I got really interested andreally hooked by the topic.

Victor Montori:

Do you think that the the reason people end up pursuing this wasteful research? Is it because they they don't know how to ask those questions? Or is, is there something corrupting the way they're thinking about the questions? You know, is there something that is, that is affecting their choice? For instance, I, you know, we published a paper on spin where we suggested that the choice of a wrong competitor had to do with the need to show that the new one was was better, and that had commercial implications and so forth. But what's your take? What, why does, why does this wasteful research happen?

Isabelle Boutron:

I think it's mixed, I think, I don't think at least I would say for academic researcher, I don't think an academic researcher, you know, wakes up saying, thinking, I'm going to do bad research to have a publication? I don't think so. I think, I really think they want to do research, they want to do good research. But I think there's an educational issue where they are stuck in that topic. I mean, very often they work in, in fundamental research, and they want to apply it to more applied research. And so what's interesting them, for their research for their knowledge, what they really are interested in is very often surrogate markers. And they completely forget the patient. So I think there's a mixed of that. And of course, the need to have publication. And so the need to have publication, which is sort of you're not very conscious of it, while you're conscious of it. But you don't probably don't realize how much it influence the way you do research. And, and I think that the need of publications, make them do a quick research, and not and not so good research. So I think, yeah, I'm sort of Doug Altman used to say, I'm not a black and white man, I'm a grey man. And because you know, it's not right or wrong. And I think it's, it's it's quite a mix of different issue. And sometimes when you tell the researcher: Well, this is not interesting to patients, they're not aware of it, they're not aware of the fact that the research they are doing is wasting research.

Victor Montori:

Yeah, the, you're very generous. Yeah.

Isabelle Boutron:

I knew you would say that, I think I think it's a bit of both. I don't Yeah. But I think it's not completely. Now when you try to convince them that it's bad research. They're not very open to the discussion.

Victor Montori:

I can imagine that, yeah, I we've, in our group we've discussed, you know, where questions come from and, and we try to distinguish questions that come from a knowledge gap versus a question that comes from a practice gap. And in general, find it more compelling and perhaps more useful to produce research that tries to address a problem in practice. Then the next step in knowledge, I think, which is what one of the reasons you pointed out is this, people are enamored with their fundamental research, trying to bring it to the bedside and doing so still looking at mechanistic outcomes rather than, than clinical outcomes.

Isabelle Boutron:

I'm working...sorry...

Victor Montori:

No, no I was just going to ask you, it sounds like in your, in your journey there's been a lot of joy and in the work that you've done and working with great people, and one, a member of our audience is asking us if you think that, that what has guided this path of enjoying your work? Has it been working with the right people or pursuing the important questions?

Isabelle Boutron:

I think it's both. I think it's both. I mean, it's working with the right people, because Philippe Ravaud got lots of different ideas and so he is, very enthusiastic and very much pushing you also, I mean, giving you opportunity. So that was working with the right people. But definitely the questions that were tackled within his team and within my team now, we're really, I mean, the fact that you answer important question that you look at research differently, that I really like the idea of trying to criticize what we are doing on the, you know, everyday by this with no questioning, and I think, you know, stepping back and saying, Oh, is this? Is this a good way of doing it? And should we question what we're doing sometimes? I think it's it's very stimulating, because suddenly you step back and you realize, Oh, yes, it's all that bad. There is a huge amount of improvement that is possible.

Victor Montori:

It takes a particular personality to enjoy that aha moment where you realize, Hmm, maybe I was not thinking about it right. And then now in the discussion all of the sudden it becomes clear to you. And when that happens it is an incredible pleasure, isn't it?

Isabelle Boutron:

Yeah, yeah, definitely. Yeah, definitely.

Victor Montori:

If you think about a value, something that has been pushing your career forward, what what do you think has been that primary value that has been pushing you forward?

Isabelle Boutron:

So I think for me, there's two, not one but two important things that pushes me first, I need to enjoy what I'm doing. So for me, enjoying the work I'm doing is really important. And I think when I was practicing, as a medical doctor, I was really enjoying what I was doing, because I was, you know, I loved discussing, discussing with patients and taking time with patients. At the end of my study, the times with patients were getting shorter and shorter. So I was not so much enjoying what I was doing anymore, but and then when I started doing research, I was really enjoying what I was doing, and particularly collaborating with people and moving things forward. And I think the other thing is that I need to feel that it's useful. I need to think that the work I'm doing has, yeah, will be useful in one way to, to improve something. And so I think I need to have the impression that it could have an impact. Otherwise, it doesn't. Sometimes, if you try to think too much of it you're not sure about it. But But yeah, for me, it's something that is important ...

Victor Montori:

It has to be fun, and it has to be useful. Now fun, fun, seems to me, it's it's intrinsic, you sort of know when you're having fun, but useful is going to be always the judgment of someone else. How do you how do you realize that something that you're doing is useful? Is that something that you you learn from your team? Or do you have other ways of getting to that conclusion?

Isabelle Boutron:

Well, it's probably wishful thinking, you know, you think well, possibly could be useful. But it's, it's, I think, for me, it's important to think, well, possibly that could be useful. Yeah. And, and, and, again, if you, if you think if you step back and you think about very critically, it's not very easy to see, well, is it really useful or not? Like, you never know, I mean, it's sort of impossible to know, but at least you have the impression that it's trying to go in a good direction, I would say,

Victor Montori:

You know, we torture ourselves sometimes looking at the things that we've done, and, you know, you, you know, on good day, you say ah yeah, this was good work, and then you're maybe, but only my mother has read it and maybe it is not so good, but and then but then somebody discovers your paper, cites it, or brings it up at a conference or you see it, somebody brings it up on Twitter. So sometimes, the oddest papers, have a second life, you know, in somebody discovers them and they become helpful, and so those those are good moments aren't they?

Isabelle Boutron:

Yeah, yeah, definitely...

Victor Montori:

In our unit, we have these three values, patient centeredness, integrity, and generosity. And I like to ask our guests, if any of these ring particularly strongly in their soul, and which of these, you know, does it for you?

Isabelle Boutron:

So I think two are important for me, again, two sorry. But probably when I think of my journey, at different time points, so probably, integrity was the first I was focusing on. And because that's what I tackled in my research, and, and, and worked a lot on this topic and was more, having more and more understanding about it. And then, and I think it's probably, thanks to the work, particularly you did, and some other people did to highlight more of the importance to be much more focused on patients that I sort of, but I must say, because I thought back to that, about this, and I must say, it was not at the beginning. If I want to be honest, it was not at the beginning, I was not so much into at least, I was not realizing how important it was. And it's more in the second step, where I really realized that if you want to do good research, you can't do it from the point of view of the researcher, you need to look to move to the point of view of the patients. And if you don't do that, you won't do good research. And so I think progressively, this is how I moved to, to, to patient centered research, it's really realizing that, to integrity was important, but it's not enough to do good research.

Victor Montori:

So let's let's do both sides of that. Let's start with the integrity bit, the integrity focus. So you've done, you know, important work in trying to identify what makes research and research reporting, how the conduct and reporting of research enhances the value of the validity of that research, which eventually translates into more impact to patients, but downstream. What's been your favorite in that work? Is there a particular part of that work focused on research and research reporting that has a special place in your heart?

Isabelle Boutron:

Yeah, well, I think it's probably the one I did with Doug Altman, during my postdoc where we worked on spin. And, and so because I, during this postdoc, I, you know, came with several ideas at the beginning, first idea, oh Yes, it's interesting, but think again, then second idea well, it's interesting, but think again. And so we had several meeting where, you know, I worked a lot for the meeting, and then had to think again, and then I came with the idea with, on spin. And, and he said, Oh, I think it's not doable, but let's do it. And so we move that forward. And and that was Yeah, really, really exciting.

Victor Montori:

And the work was exciting. What about the impact of that work?

Isabelle Boutron:

I think it worked. It had some impact because it was presented, So it was for me, it was a, I had to present it at the peer review Congress, which is a very impressive Congress. And I was, you know, I, I think I had, I think 10 minutes to talk. And I think I must have practiced for hours and hours for this 10 minutes. I was so stressed. But but it went well and the people were quite positive about it, and it was published in JAMA. And then people try to reproduce it and worked on the concept. So I think that was, yeah, quite a nice one. Yeah.

Victor Montori:

Yeah. I was trying to remember Isabelle when we met in person the first time and it was at a meeting that you had organized to try to come up with better reporting for non pharmacologic studies. And as far as I know, I was brought in because PJ Devereaux couldn't make it because he was working on blinding and that sort of thing. And I was helping out and that sort of thing, but it was it was the first time I was in a room with all the heroes of clinical epidemiology that you have brought in together to Paris and I remember we had a very nice dinner at the bottom of the pyramid and the Louvre, which was spectacular. But I think that was the first time I met you. And it was just quite impressive group of people you brought into to develop those standards, it must have been quite fun to put that together.

Isabelle Boutron:

Yeah, so it was, well, at that time I was a PhD student, it was mainly organized by Philippe Ravaud. But actually what we did, I think we did not know personally, most of the people in the room, we just did PubMed, and took the, pick the people where, you know, we like the papers. And so you did a wonderful paper on blinding. And that was really, really interested and say, we were delighted to have you. And there was all these people. And there are a few, quite a lot of people were, after the meeting, you know, the meeting, you've got the scientific part, and then you have the social part. And Philippe organized the social part in a wonderful way. And so it was really an opportunity to create links with people where you just knew the papers, but not the person. And we had very strong collaborations with a lot of the people in the room. Actually, that was a great experience. Yeah.

Victor Montori:

Yeah. I mean, the people in that room were also quite, you know, there's a lot of common values. There were a lot of common values.

Isabelle Boutron:

Yeah, yeah, exactly. Yeah.

Victor Montori:

That makes it fun. Um, let's talk about the other side, when, when you went to the, if this was a, if this was Star Wars, you know, you went to the from the dark side to the light side, you know, when you turned from a research perspective, researchers perspective to a patient's perspective. What is what is that research like these days? What is your patient focused research like these days?

Isabelle Boutron:

So I think I would because I've been thinking about about it. And I think that you did a presentation. So I think you did a presentation at EvidenceLive in Oxford. Philippe went to this presentation, and told us, you need to look at the video. And so we all looked at the video. And it's and you were talking about burden of treatments. And that's where some people in the team really started working on, on the burden of treatment and move we already had, I mean, we were already focusing more on, on patient centered research. But this was really sort of a switch. And I have one of my colleagues worked a lot on the burden of treatment, such as Viet-Thi Tran, and he collaborated with you. And then I had some people I knew did participate in clinical research, and told me that experience and I was just appalled. I mean, it was they had a very terrible experience and appalling experience. And so I thought, well, perhaps there is minimally disruptive medicine. But you could have also a burden for research for the patients. And you could try to improve research and reduce this burden for patients. And so that's how we try it started by doing a systematic review on qualitative studies. And we found very interesting results.

Victor Montori:

This is the challenge of, for potential research participants to participate in clinical research and the burden that that participation would have on them, in addition to the fact that if they're participating probably they have a condition, a condition that is being managed, self managed, treated, so it's incremental to the burden of treatment for their condition you said that that this was triggered, in part by some appalling experiences without going into those what have you heard and what did you learn from the qualitative review that opened your eyes to the experience of participants who conduct the research.

Isabelle Boutron:

So from the from the systematic review, you could see how stressful it could be for patients when they learned that the treatment will be randomized. So what they will get will be randomized and I think that's for a lot of patient is extremely stressful. And with the fear to get the wrong treatment. And and to lose chance because you get the wrong treatment. And all the, how painful it was for them, the ways the research were organized, where they were losing so much times just trying to find a way to get parking way to, waiting in the waiting room just to see research trial was going to collect data and, and, and also one point that, a rule then that I think is also really important and that came back from the the experience is that when, for example, the treatment does not work and the patient withdrew from the study, it can be extremely difficult for the patient, because they were in, in a specific environment, they knew people were taking care of them, they had some hope of a treatment that might work. And suddenly we tell them well it doesn't work, bye, bye, you go back to usual care. And that can be extremely, extremely difficult. And I think most researcher don't realize what it is to be a patient. And I think there's also a wrong feeling, a wrong understanding from researcher, when I discuss with my colleagues, they think that because I keep asking them, well, if you, if you would be participating in this, in this trial, would you come at all the visits, and they always answers, but I don't have the condition and I won't be so much willing to participate in a trial. And so and I think that's really this wrong impression from the researcher, that if you have the conditions, you're ready to do anything. And, and you've got time to do anything. And I think that's where we really need to train investigators and people doing trials. And for them to really go on the I have the other, you know, vision of what it is to participate in trials and to do only trial they would be happy to do, to participate in.

Victor Montori:

Yeah, it's an extension of the, some of the behaviors that patients have observed in I mean, let me put a parenthesis here. So this, this description that you've given us, is it mostly in cancer trials, or is in a range of trials?

Isabelle Boutron:

I think it's what my experience was in cancer trials, but I think it could be in any trials.

Victor Montori:

Yeah, it's interesting, because I've noticed that in clinical practice, some cancer doctors, some of them who participate actively in clinical trials, you know, they they implement protocols, and they bring patients into studies, that when when patients are not, when the treatment is not working for the patient in the first line treatment, and they try a second line treatment, then they try the third and the fourth and the fifth and the sixth and the seventh line treatment. And you know, the patient's well being, you know, the attention to their quality of life, the palliative care approaches, those sort of things, get pushed aside because we are on this track of trying to beat the cancer. And I wonder if it's the same mindset, that is, that is coming from clinical practice to the clinical trial, or from the clinical trial to clinical practice, where if the goal is to beat cancer, what else could be more important than that? So you know, we just assumed that you as a, as a participant, are willing to do everything andanything. Do you have that impression?

Isabelle Boutron:

I do. But I think it's not only related to cancer, I think it's true in all severe disease, because I had exactly the same type of experience for very rare and very severe rheumatologic disease, where I mean, the patients are ready, they will be ready to do to do anything, because it's a severe disease, and and completely forgetting that, so while you could, yeah, you need to you need to change your mindset. I think that's really important. And I think there's, for me, it's a lot of training. And, yeah, I think it's a lot of training, I think a...

Victor Montori:

A lot of training in what?

Isabelle Boutron:

I think in the training of medical students, in the training of investigators, in the training of medical doctors who wants to do clinical research, we need to, for them to really change of mindset. And I think it will be both good for the patients who will have a different experience, but also good for the research because they will do better research.

Victor Montori:

Yeah, yeah. It's, it seems at a core level, almost like a failure of empathy, or an excessive amount of empathy with future patients. Because that's the other thing is that you sometimes commit to a particularly difficult protocol, because you're trying to improve the value and validity of the research you're doing now. So you can benefit future patients. And maybe you have too much of a commitment to the future patient and too little of a commitment to your participants.

Isabelle Boutron:

Yeah, yeah.

Victor Montori:

Yeah. The, one of the, one of the, one of the angles, of course, that you've described is the stress of being randomized to the wrong thing and then you went to the other end, which is At the end of the study, either because the randomly allocated intervention didn't work or the study finished, that people exit the study protocol, exit the study team, exit the study relationships that might have carried a patient over a period of time. There is a, you're the head of Cochrane, France, there's a Cochrane Review that is often used to justify inviting patients into clinical trials, that indicates that on average, patients that participate in clinical trials get better care than patients who do not participate in a clinical trial. It sounds like that, that was a very superficial review, given the discussion we're having now.

Isabelle Boutron:

Um, yeah, that's is significant question. I think they might have sort of a I mean, they have more follow up more visit, and so that they might have sort of a more treatment and be better taken care of on some part, but it doesn't mean that their quality of life during this, this period will be much better, and whether the long term effect would be much better. So I think, I mean, when we did the systematic review on qualitative study, we also had some patients, highlighting, the good experience they had when doing research. And very often these patients, although highlighted the difficulty when the study ends, because all the context of the study, because probably the team was good and was emphatic and took away care, when the study suddenly finished, and they go back, that's where they, they had, they had the difficulties. So it's not black and white again, but it's not, it's more, I think we can definitely do much better. I think we probably went through just like look at the number of visits, where you ask the patient to come to the hospital, while probably could be done from home completing questionnaire, the number of questionnaire you ask them to, to fulfill, which is just, you know, impressive. I think all these could be, could definitely be simplified and and make the burden for patients much, much lower.

Victor Montori:

What is your impression about the value of having patients as co-investigators in the study process from the design, from identifying the question, designing those, those study procedures, perhaps even designing the coming off the study process and so forth? What, have you had experience with that? What is your sense of

Isabelle Boutron:

So I had experience with that, and it it? worked very well. And my sense of that is, I think it's important to do it, but I don't know how to do it well, if you want. And I think there's a lot of sort of statement, there must be what we call patient and public involvement. And it's even a box to tick. For example, in the UK, to get some funding, you'd need to tick the box patient and public involvement. And I think a lot of investigators just put the name of patients, we have the patient center, because man one, and that's done. And then you have some patients group that become professional of patient and public involvement. So I, Is this the right patients to involve and to help designing the study? I don't know. It should be, should it be very often it's a small number of patients that is involved with a lot of physicians. So do they really have a voice? I'm not sure. Or sometimes you could have the opposite with where patient would have a very, very strong voice. And, and perhaps not. I mean, I, I must, I think it's important to do but I think we need to work on how we do it. And I'm not sure having just one or two patients. I mean, in a way it's comfortable or Yes, we did involve some patients your comfortable. I did I did the right thing, but I'm not sure we really know how we should do it. And I think we definitely need to work on what is best way to involve patients. And my feeling is that it should be a lot of patients that are involved to help constructing a study and not limited number of patient that might have high knowledge in methodology, but will have a specific point of view and might not represent the point of view of all the patients. And I think what we need and probably the point of view that the patient we'd have in one setting might be completely different if he lives one hour from the hospital or if he lives two hours from the hospital. According to a job, according to I mean, there's lots of, it's not one patients, it's lots of lots of different people with a huge diversity of value of what is important for them. And, and I think, yeah, we need to find good ways to involve patients.

Victor Montori:

I think having the angle of the burden of participation is an angle that makes the, adds to the richness of that involvement. Because, like you, I've been involved in situations where the patient's voice is brought in to tick a box like you, like you say, or where we're just asking for general impressions, you know, what do you think of our questionnaire? What do you think of our procedure? You know, but I think the angle of how, how easy or difficult or whether you think there'll be some friction or some pain points or some, what additional care will people need, as they go through this that is not in our protocol, and perhaps even not paid by the study, and so forth. These may become really practical questions and your your, your proposal that we don't have just a few patients, but we have a large number of people that represent, are similar to the patients that we are going to be enrolling seems quite interesting. I don't know the situation in France about this. As you know, I have my suspicions, but I don't know it, is in relation to the notion of diversity and inclusion. There is a I think a very welcome development in terms of having a more more diverse workforce in clinical practice a more diverse workforce in research, and, and certainly more diverse and set of participants in clinical research so that we have greater confidence that our results apply more broadly, as we come up with them. The issue of burden of participation in research seems to me will be one that will interact quite strongly with factors that contribute to the discrimination of people in general in society, but also discriminate against them in their ability to participate in care, and their ability to participate in research. Have you, have you gotten into, into that space what have you, what what insights have you developed?

Isabelle Boutron:

We didn't go in, well, we tried to explore what would be the willingness of patients in terms, for example of organization of research. So we did sort of a survey where patients, we use protocol, industry protocols of randomized controlled trials, and we created a vignette describing the protocols and proposed to the patients different organization of, so they could sign the consent form from home or sign it at the hospital, they could come at all the visit at hospitals, some at hospital, some at home, or all from home. And at the end of the study, and what we could see that there was a huge diversity. And so there's not one type of organizations that would, would please most of the patients. And so I think we definitely need to think of the way we do research to be much more flexible. That's my point of view. And it's quite a good, you know, it's a huge change in the way people organize research, because they don't like flexibility in research, you hate, it needs to be completely organized. And I think we can make it organized but also lose some flexibility. And what we will lose by the flexibility, we might gain it on another aspect where patients might be both more willing to stay in the study might be more willing to participate in to study. And we showed in this with this vignette, that if you organize the study, according to the preference of patients, you have much more patient who would accept to participate, would be happy to participate. So So I think it's Yeah, it's a big change in the way, but I think the diversity of the, of the patients and and we need this diversity in trials because otherwise we're going just to include all with the same patient living next to the hospital. In this specific setting. I think this diversity will bring a lot to the trials and and will be very useful.

Victor Montori:

If you go beyond biological diversity and you start looking at social factors you know, country of origin, ethnicity, cultural differences, even gender? Have you, have you, have you interacted with, with the, with the efforts to try to improve that that form of diversity as well.

Isabelle Boutron:

Not I would say not, not so much. I think we always try to discuss it with the investigators, particularly currently you know in France we are a bit behind. But currently, we're fighting on age because they tend to exclude the more age patients. So we tried to stop exclusion criteria that have no sense that excluding patient because they, again, I think it's because they are in a very in a specific context, I mean, they imagine the trials related to their own research, and forget that it's, it's very applied research. And, and so they're going to add a huge number of exclusion criteria for the patient. And so we try to fight a little bit on that when we plan the trials.

Victor Montori:

We've gone a little bit through, you know, the integrity and the quality of research talked a little bit about the patient perspective, and how taking that in might make clinical research better. When I was introducing you, at the top of of our talk of our conversation, I mentioned a number of administrative positions. And I wonder, I wonder about that, is, in your you know, you seem to enjoy research quite a bit, or are taking these administrative positions a curse, a bad thing or natural evolution, something that people should be jumping at the opportunity to do? Or something you have to do because you're, you're a team player? What's your, what's your sense about this, this apaprent the evolution towards taking positions in administration?

Isabelle Boutron:

Well, I must say, the life when I was a PhD student and postdoc student was, you know, the most wonderful time I mean, if you have in the audience, if people are PhD or postdoc, just, you know, grab it and, you know enjoy, afterwards, of course, you have new responsibility. I still, I mean, you learn a lot with this responsibility, and you enjoy part of it, not all of it. I think, for example, having the responsibility of other researcher trying to help them during their career, supervising them is really, yeah, enjoyable. I mean, it's very, very interesting. And having the interaction with junior researchers is really interesting and rewarding. So my, my strategy on that was to do it, the latest possible, to take all these responsibility, but now I've got no choice. And I can't, I can't push them anymore. So I just have to take them. But because that's part of what you say a team player, you need to at one point you need to your, your part. But yes, my strategy was really to push it. And I was quite lucky because I was able to push it to quite, quite, for a while, and not and I'm not taking responsibility I don't want to do. So for some of them, which unless people tell me, well, there's no choice, we need someone to do it, I would do it. But if there's some responsibility that might be rewarding in terms of title and in terms of position within the university, but but I knew that it would mean stopping a lot of research I'm enjoying. I will try not to take it as much as possible. Yeah. So that's more my strategy about that.

Victor Montori:

So now that you have those, those the opportunity of those responsibilities. What are you doing with it? Are you doing something crazy? Something, something unusual with it? Are you trying to create a different, different set of environments or other things are you, do you have a particular mission that you're after?

Isabelle Boutron:

So it depends on responsibility. Currently the research team, it is still Philippe Ravaud there so it's, it's a bit different? Cochrane, I'm trying to, to find my way to to understand the system, it's a huge system. And then to try to move forward the project or ideas or way way of doing that, I think could be different as, for example, for Cochrane in the context of COVID. We did the platform, where we identify all randomized control trials, collect data, put the analyses online as soon as they are done, so every week we redo the analysis and we give it to them. And that's very unusual. I mean, that's not Cochrane classical way of doing and so we try to push, but they were quite open and I think and so we try to push the other way of doing it.

Victor Montori:

Cochrane has a relatively new area on sustainable, sustainable medicine, that has caught my attention, because it seems like an extension of not only doing sustainable research, in other words, research that is useful, that is not wasteful, that answer questions that matter and do so in ways that don't waste patients time, energy or attention, right, and so more of a kinder form of research for patients more minimally disruptive. And are you involved in that effort at all? Or have you, has it come under your, your, your your purview?

Isabelle Boutron:

I don't think so. No.

Victor Montori:

Yeah, it's a it's a field, it is a Cochrane field on sustainable, sustainable medicine.

Isabelle Boutron:

Okay,

Victor Montori:

It seems, it seems like it might be a potential point of interaction with this work.

Isabelle Boutron:

Yeah absolutely.

Victor Montori:

Yeah, COVID has changed everything, right. It's, it's interesting, because the last time we saw each other in person, it was just right after the the Notre Dame had, you know, had that fire and, and everything was closed the the, your office, which is right next door, had residues of the, of the smoke, come on the plants in the beautiful garden there. And, and, you know, I remember the pictures, Viet sent me some pictures from the window, and you can see the fires, you know, and, and you couldn't imagine a bigger disaster in such a such a jewel, architectural jewel, and such a symbol of Paris, and then COVID hit, you know, it's like, oh, you don't think it could be worse, oh, here's worse, right? And how has, how has the dynamic dynamic changes brought about by COVID, in terms of, for instance, the ability to interact more broadly, electronically, how has that change the way the, one the way your team is working, but also the way you're imagining the future of research to be.

Isabelle Boutron:

So it changed completely the way we are working within the team, because we were locked down in March, and we are currently still locked down. So still working from home. And so it's only online interactions, I must say, for the team its, I think it's, it's problematic, because it's very difficult. And, and so I'm looking forward to have a new face to face meeting where I mean the interactions much easier, you can you can interact much easily, and you can see the face and see you know the body language of the people much easily. So for me, the work from home and through video is not the optimal way of doing research, it works very well for, for a lot of things and you, you, you gain a lot of time, that's for sure. But there's also a lot of interaction, which is, you know, the, the not the, the interaction that happens, but was not planned. And this interaction in research that happens but not was not planned is really important. And it's really when you have lunch, take a coffee when you go outside and discuss and, and it's that and that's for me it's really a difficulty for, currently for research.

Victor Montori:

Yeah, our team has been apart also since, since March. And we, we meet every, every morning for a few minutes to check in. And when things were relaxing a little bit, we've we had a small group come together outside with a fire, you know, in the middle so we have those, but there, I think we're all hungry for the same moments that you're describing, being in the same room and it you know, maybe maybe it's just more fun, maybe it is just the more, more of the serendipity more of the chance discussion that can emerge. I think it affects creativity. I think it affects the range of ideas and the, and the extent to which you can listen to each other without taking turns. And you know, this, the reason is the personal interaction. So it's a bit sad, that in addition to all the deaths and the difficulties with In the illness and so forth, the isolation, the separation and, and the cost this will have on on people's careers is significant. Having been with your group in person, it's a wonderful chemistry that you have. And I'm sure, I'm sure they all miss it tremendously to be in the room with you.

Isabelle Boutron:

Yeah, it's, it's, it's really a difficulty. But so hopefully we'll come back a little bit with mask and...

Victor Montori:

Vaccines. Yeah, hopefully, that will happen soon. Um, we're getting to the end of our time. And, and one of the things that I think it's always interesting, when, when we talk to, in talking with you and talking withother people like you in this series has been to ask people, what's next? What's coming? What was the big next adventure? For Isabelle Boutron? What's next for you?

Isabelle Boutron:

I don't know, I mean, more, more responsibilities, I think. So I need to think how I'm going to take over these responsibilities. And, and hopefully, maintain sufficient time for research. I think currently, I'm quite, very much involved in, into Cochrane and to meta research and research on research. And so I think that's where I really want to continue investing particularly in, in meta research and continue this, you know, self criticism, but I like what I like in meta research is that you criticize what is been done, but you criticize also what you're doing yourself, otherwise it's a bit too easy. So so I think that's, for me, it's, it's, it's what I'm going to plan doing. And my goal is really to try to, to still have time to collaborate on research project, to work with people like you and internationally and, and to continue enjoying really the research we're doing. That's my goal.

Victor Montori:

Yeah, well, if, if life is, is teaching us anything is that you have to leave a little bit of room for that surprise opportunity that comes up. Because sometimes they come with a lot of fun and, and that's, I am glad, very glad that that you found the paper on PubMed that led you to invite me that first time to Paris.

Isabelle Boutron:

It was great to have you, yeah.

Victor Montori:

Very glad that Philippe brought the video and, and help us come together to work with Viet for instance on the burden of treatment questionnaire, all that work and, and work with you on research reporting and minimally disruptive research and, you know, the collaboration within our group has been very good and a lot of fun, the hallmark of working with you, and, and I am so, so happy that someone with your commitment to integrity to research and, and collaborative research and fun, helpful, useful, useful research is in a position of leadership and in a capacity to shape how the next generation of researchers are going to move us forward. So Isabelle it has been a wonderful pleasure chatting with you today, helping others learn what I know of you and, and to hear from you how you see the world which is absolutely wonderful. Thank you very much for coming to the KERcast.

Isabelle Boutron:

Well, thank you so much for this invitation. It's been a pleasure discussing with you and, and hopefully we will have other collaborations soon.

Victor Montori:

Looking forward to those and thanks everyone for joining us today. We hope to see you next week in the, in the KERcast from, from the KERunit at Mayo Clinic. Until next time, and please take care.