Conflict in South Asia, and simplifying GRADE.
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Welcome to the Medicine and Science Podcast from the BMJ. I'm Cameron Abassi, Editor-in-Chief.

In this episode, Gordon Guyatt, who is one of the founders of a system called GRADE, a structured way of assessing the quality of evidence in systematic reviews and clinical practice guidelines. Gordon thinks that process has become too complicated and he's now championing something called Core GRADE.

In deciding when, for instance, you have some studies that we would consider low risk of bias and some studies that are consistent with high risk of bias, we put together what we believe is a more congruent approach than was available previously. Recent escalations in the ever-simmering tensions between India and Pakistan brought us closer to conflict.

Conflict between two nuclear powers.

For a long time, doctors have campaigned for nuclear disarmament, and I'm joined online today by Chris Zielinski, who is president of the World Association of Medical Editors, and he's co-authored an editorial alongside me and other journal editors and academics about why nuclear war is a medical and health issue and we need to have disarmament. Thanks for joining us, Chris.

Also, to talk about the impact that the militarisation of South Asia is having on the populations of particularly India and Pakistan, I'm joined by Sanjay Nagral, a surgeon from Mumbai. Hi, Sanjay.

Hi, Kamran. And Zulfi Karbuta from the Institute for Global Health and Development at the Aga Khan University. Welcome, Zulfi. So just to be clear, Sanjay is in India and Zulfi is from Pakistan and they are co-chairs of our South Asian editorial board. But first, I'm going to turn to Chris. Chris, this editorial we've published last week

is a call for action around nuclear disarmament. Can you tell us a little more?

Yes, Cameron, thanks. It's a peculiar editorial in the sense that it's being published by over 100 journals around the world, the same editorial. And it aims to encourage countries which are attending the next World Health Assembly, which is starting this week, to renew WHO's mandate to report on nuclear war and health.

It's a mandate that WHO had for years since its reports in 1983 and 1987, but it's a mandate that lapsed in 2020.

So WHO's last report on the subject is almost 40 years old. And a resolution to this effect, that it should pick up its mandate again, has been drafted. And it's on the agenda of this upcoming World Health Assembly.

I have to say that nuclear risk is not just a question of concern about bombs going off, which of course is the principal concern, but it also includes the whole process of creating, testing, storing all the other allied activities associated with nuclear bomb development, each of which has some health benefits.

and consequences. Okay, so what you're saying is that what we'd like WHO to do is to document the extent of those risks and do that on an ongoing basis. Why is it important to document the

The worst case, of course, is that we blow the world to smithereens. But short of that, if any nation deploys nuclear weapons, damage will be local, and that local

It might be a very large local, but there will be a center where the bomb exploded and there'll be a decreasing impact with distance from the center. There'll be health consequences, therefore, a gradient of health consequences there.

caused by any nuclear explosions. And as I mentioned before, it's not just the actual explosions that we have to concern ourselves with, but the growing arsenals, the storage of nuclear weapons. Sorry, Chris, hang on a sec. So you're saying, but you say growing arsenals, but the arsenals have reduced, haven't they, over...

over years? They may be a smaller number. It's very difficult to compare these things because the power of the weapons is not uniform. But the numbers of weapons may be fewer, but the number is growing all the same. Fewer than in the past, I mean. Yeah. But growing. Why do you think the situation...

It's starting to deteriorate again. Chris, I mean, what we're arguing for clearly is that there's a pause on that proliferation. And we're also arguing that there should be no first use and then we want disarmament. But things are heading in the opposite direction. Yes. What are the reasons for that?

Well, I mean, as you said, disarmament is currently in reverse, and there are also extensive nuclear modernizations underway, as it's called. So the reasons must be...

a general tension in in in the world there's uh uh a nuclear armed russia israel engaged in active wars as well as as as uh as russia uh and as we've seen recently a bit of saber rattling and we'll hear more about this i'm sure later in this podcast between uh

India and Pakistan. It seems to be the next thing that everyone wants to talk about as soon as there's a tension. Okay, well let's talk about it now with Zulfi and Sanjay. I mean the saber rattling turned into something pretty serious. And one of the issues that we are all trying to kind of combat, and I'll go to Zulfi first on this, is that

We want countries to disarm, but because of what's happening, some people in those countries in particular, and perhaps other countries, will feel vindicated that they've got nuclear weapons. Is that a fair summary, Zulfi?

Yeah, I mean, I think there is some truth to that, Kamran, of course. And just to build on some of these previous points, you know, we had called at the time when both India and Pakistan did their first nuclear tests and became overt nuclear powers. Over 20 years ago, we had called for restraint and we had called for the

The fact that, you know, you will very soon beyond capacity, declared capacity, get into an arms race where you would see nuclear weaponization, development of delivery systems, and then more and more sophisticated nuclear devices under the

the notion that you could perhaps sometimes use this without having to use them in megatonnage. So increasingly what we have seen in the region, both from India and Pakistan, is the development of fairly sophisticated nuclear weaponry with things that could be called tactical nuclear weapons that you could use, you know, in the battlefield, so to say. And I think that's pretty dangerous, but you can also imagine how over the last few years

In particular, when people have witnessed what has happened to states that either gave up their nuclear capacity voluntarily, and Ukraine as is an example, mutually assured destruction is a deterrence to things that can impact on independence, autonomy, and sovereignty. And we've seen that example. So therefore, there is a very close nexus between overall conflict, peace,

and nuclear capability. So I will hold judgment on that, Kamran, but you're absolutely right in saying that while we have conflict in the world, and while we have issues that relate to big powers exerting their military superiority in a manner that decimates populations, that also threatens the existence of states,

the argument for people not going for nuclear capability becomes weaker and weaker. Yeah. So, Sanjay, I mean, when it comes to argument during this conflict, and I think a lot of the time, the rhetoric we hear is all about being more aggressive from the media, from politicians. It's generally inflammatory.

And you don't hear many voices, which I would describe as voices of reason, trying to calm things down, to de-escalate, to limit conflict. It's almost as if there's an orchestrated attempt to inflame the situation. Do you think that's an accurate way to describe what's happened and what's been happening?

Right, Kamran. So I'm just going to begin on a slightly personal note. So, you know, in mid-April, I was in Srinagar in Kashmir for a medical meeting. And we had a great meeting and I decided like thousands of tourists from India to spend some time. It's tulip season, so beautiful gardens full of tulips and flowers.

I returned actually just two days before the incident in Belgaum. And so I can imagine that as an immediate response to what happened there, something very sad. There was a lot of anger, angst amongst ordinary people. But of course, what happened later is I

I think coming together of history, coming together of how media works, there's geopolitics, right? And I think now the fog of war is lifting. And therefore, I think this is the time for now voices to start looking at the whole issue a little more with some sobriety.

Look at its impact on South Asia, on India, where we are, on the economy, on our state of development. So I think

these voices will now slowly come out. I think we've passed through a phase where emotions were running very high. And you're absolutely right that modern media has the capacity to use almost everything for TRPs. Yeah. Sanjeev, can I just build on that? I mean, when Zulfi talked about, you know,

a longstanding view of trying to bring people together. I mean, we've, we've at the BMJ and both of you have been involved at this involved with this various points and, and, you know, Zulfi throughout, um, is that, you know, we've made the argument that by focusing on health and wellbeing and inequalities, um,

we can bring people together. We have more in common. We're facing similar challenges by focusing on these issues. That's a way of bringing the populations together. We've always made those arguments and we repeatedly made them at various points. We even made them a few weeks ago when Sanjay, you and I were together at our South Asia Awards in Delhi. Do you think that's still a reasonable argument to make?

Zulfi to begin with and then Sanjay. Absolutely. I mean, I think there is much more that unites us than divides us. And as you've heard me say several times, there are many problems of the region that no one state can solve alone. I mean, so the region is...

currently torn asunder by politics and by this confrontation, which at times in the bigger picture is meaningless for the simple reason that our

human development indicators, or indicators related to poverty alleviation, or indicators related to health, and as I've just mentioned, climate and environment, are amongst the worst in the world. We may have a spat between India and Pakistan on who owns what water, but neither countries are water secure. So we need to do so much together in terms of the benefit, growth, and development of our people that

absolutely any diversion in terms of conflict or threats of conflict is basically usurping that fundamental human right to development in the region. And at some stage, people have to step back and say, what matters in the bigger picture? I think we need to ensure

that there are people-to-people contacts, professional-to-professional contacts when we step out of the boundaries of our region. And there are now so many meetings that take place between India, Pakistan, Bangladesh, and others in neutral territories. And in neutral places, like I was mentioning, this World Congress of Pediatrics just last week

People rub shoulders with each other, talk the same language, sit down and talk about common problems without the animosity, without the bluster and jingoism that you see on social media. So sanity has to prevail and people have to start discussing the real issues on the ground. And the real issues on the ground need to have civic society engagement, track to diplomacy, a

a whole movement towards rapprochement, which takes us away from this absolute brinksmanship, which one day could lead to disaster. Sanjay, what's your take on this?

Yeah, so I think, you know, a large part of what Dr. Bhattacharya has said is well known and it's part of history. And he's absolutely right that there are many people in both countries which do not have a sense of the history, the joint history of the region.

But I think, you know, we have for years together talked about peace and we have various initiatives. There were even people to people contacts. I think now the challenge for us is really to...

connect with our ordinary people who over the years, because of their own stresses, own economic difficulties, are easy prey for propaganda. So I think we have to create a counter-narrative. It's not easy in the region, but I don't think we have a choice. So when you say we haven't got a choice, of course, we agree with you. I mean, I certainly do. And I'm sure the others do.

do as well. It's how we do that because if there was one feature that stood out, you know, very prominent, there were several, but one of the most prominent was the extent of misinformation and disinformation that

during this whole recent conflict. And in trying to follow what was going on, I think a lot of it was trying to make sense of, well, do I trust this source? Is it genuine? Is what they're saying based on any facts whatsoever? And it was quite an effort to do that and to disentangle disinformation, misinformation from what was really happening.

How do we, I mean, it seems an impossible conundrum almost. Things have got so bad. It seems very difficult to pull it back to where we need it to be.

I mean, absolutely. I think one of the very obvious challenges we saw this time around is getting accurate information. And this is when we actually have an explosion of the internet where independent voices, independent information should ideally be available. But

But we really saw very little of that. Of course, there were individuals, I think, in both countries who put out more credible information. I think it's a part of the modern warfare strategy. I think it's becoming all over the world, disinformation and becoming part of strategy. Well, it's always been part of war and conflict, hasn't it? Misinformation, disinformation, propaganda,

It's just the way that it's used now is mind boggling. I think the tools are getting easier. I think the ability to impact on people is getting easier. You know, you have the mobile phone with everybody. You have reels, you have social media. So I think it's getting easier in that sense. Zulfi?

Well, I think it's a process of evolution. If you think people don't have disinformation in the developed world and North America for that matter, I mean, forget it. There's plenty of disinformation here. But I think it's a process of evolution and eventually,

people do learn how to go to reliable sites and how to go to reliable sources of information. I'm always amazed in rural Pakistan as to how many people tune to the BBC. I mean, we ask them, why do you tune to BBC Pashto service or Urdu service? They say, because they want to get the real news, right? So I think this too will write, but what we need now is, Kamran, I think is to use the benefit of some of the

growth in technology and communication that has happened certainly post-COVID. So in peaceful times in recent months over the last year, there have been many webinars where Pakistani professionals and Indian professionals have come together on health-related issues. I can certainly speak for my discipline of child health, where I've seen under the guise of South Asia Pediatric Association, a number of joint webinars

I think we need civic society voices to now begin to stand up and to have debates, discussions, discourse, which is not based on, as I said, jingoism or chest thumping, and also sensible voices to reignite the track to diplomacy in the region, which was such an important part of moving forward. There is, as Sanjay said, no alternative but to have peace.

in the subcontinent, in the region, between nations for development. There is no way out. So on the pages of the BMJ, which, you know, unfortunately, ordinary people don't read in South Asia. You should recommend it to them as well as the BBC. But some people do sensibly. And these are the kind of platforms that we should use to raise our voices.

Yeah. Okay. Listen, I mean, what you've said, I mean, clearly we all wish that to happen. The question is, how do we make it happen? And I just want you to reflect on that for a moment. I'll come back to both of you in terms of practical suggestions, mechanisms for changing the narrative, for changing the discourse, changing just the whole environment that we seem to be stuck in, this sort of doom loop that leads us to disaster. Yeah.

I sort of bring Chris back in. And Chris, when you're looking on, we've made this statement about nuclear disarmament. There's a motion that's going to go to the World Health Assembly within a few days. We seem to be talking about in an idealistic way, which is far removed from the direction of travel.

when it comes to the leaders, the media and large segments of the population that we're trying to persuade that the current path we're on is the wrong one? Just to recall that at WHO, I'm going to focus on the World Health Assembly here, when it considered the previous reports in 1983 and 1987 on the effects of nuclear war on health and health services,

The assembly concluded unanimously that nuclear weapons constitute the greatest imminent threat to the health and welfare of humankind. So it's clear that authoritative and current evidence is a crucial basis for good governance and policy. You can't avoid that, and yet the mandate of WHO to provide such evidence

evaporated about five years ago. So I think the solution, and it's a partial one, is to revive this mandate for WHO to provide authoritative evidence because this is the most acute existential risk to human and planetary health. So Zulfi and Sanjay, look, South Asia, 2 billion people

crammed into 5% or so of the world's landmass. I mean, even a non-nuclear conflict would be disastrous. What are the steps? What can we do to change the narrative, change the discourse, change the direction of political travel and get health back on the being top of the agenda? Sophie?

I think a necessary first step is to get people-to-people contact going, to have greater discussion and discourse on practical steps that need to be taken in terms of focusing on issues of social development, determinants, education, investment in health and health systems. How do we do that?

I think for the moment, the practical reality is that it will have to be done virtually, and thankfully that is possible, and it's the kind of thing that we should be organizing webinars, virtual conferences, debates, discussion, discourse, without having the shrill voices take over that discussion. But I also think they should not mute the shrill voices, but have them come and talk about the arguments as to why this should not be done.

Second, I think, Kamran, we need to find a way of building the political groundswell of support. And that does not necessarily need to only start at the top. It can start with a meeting of minds of the willing people.

And there is now a system of governance and government in both India, Pakistan and Bangladesh that has local governments, that has subnational, in a devolved system, provinces who may be willing to speak to these issues without necessarily engaging the ministers of government.

of foreign affairs and others. And the third, I think you will find, and I have in my experience also, that some of the biggest proponents and supporters of peace are also those who guard the borders of the nations to also get our armed forces to talk to each other in terms of what needs to be done to, you know, protect

kind of disengage and also reduce the amount of tension and the risk of an accidental exchange, which is a reality. So I think we start with those baby steps. And of course, we as professionals, Sanjay and I, who are both editors of the BMJ, you know, owe it to our readership to be talking about this and doing something practical.

Yeah, I mean, you've both done a lot on our editorial advisory boards. I mean, we're very grateful for you and the things you've written.

arguing for peace have always been very important. Sanjay, what can we do? Yeah, so again, I would go along with what Dr. Bhutta just said, but I think we'll have to wait it out a little. This is a time when emotions are charged. Everybody's angry and upset. I think when people go back to their lives, face the realities of life,

They're likely to be more receptive to what we are saying. Healthcare, especially people need to start identifying that as one of the central problems in their daily lives. Facing the barrage of day to day, people are traveling in extremely poor conditions, crammed into trains, crammed into buses. There's heat.

uh there is a pollution you know we we're almost beginning to internalize this as if you know it's it's our fate and i think we begin to question all this and when we we begin to question all this uh maybe we'll start seeing that that we may be wasting our energies in in in areas which we should not be and that for us as south asians uh

And as Indians, real modernity and development lies in enhancing our day-to-day lives. So I think that's the refocus that we need. Okay, listen, thank you all for your time today. It's a long road to get to where we want to, and we need to walk it together. Thank you so much. Thank you. GRADE is now used at the heart of evidence-based medicine to rate the reliability of research. And over that time, it's grown in extent and complexity.

Now, in the BMJ, one of the founders of GRADE, Gordon Guyatt, has launched with others something called CoreGRADE. And this is an attempt to get back to basics or at least focus people's efforts. Helen MacDonald, the BMJ's research integrity editor, spoke with Gordon to find out why we needed to make it simpler. Gordon, thank you so much for joining me today. Can you start by introducing yourself?

Gordon Guide, I'm a Distinguished Professor of Medicine and Health Research Methods at McMaster University in Canada. And you and a broad group of international colleagues are publishing a series of pieces in the VMJ under the banner of Core Grade. Can you tell us about Core Grade? What is it and why is it needed?

So about 20 years ago, launched in the BMJ was the great approach to rating certainty of evidence from systematic reviews and moving from evidence to recommendations and guidelines in health technology assessments.

Since that 2004 launch, GRADE has been extremely influential in the world of evidence-based medicine, the world of systematic reviews and guidelines. Very widely used, Cochrane Collaboration, major organizations in the United States, the leading textbooks, electronic textbooks that clinicians use, Dynamit and UpToDate, and many, many more.

So, a very influential system. However, over the years, things have gone swimmingly in many ways, but grade has become too complicated. And so, the recent writings take interesting advances, methodologic sophistication, but they have put ordinary grade users off to some extent.

In addition, the over 50 papers describing the GRADE approach from a methodologic point of view are now not well organized and very difficult to navigate. Where do you go for the latest? What is the latest in the guidance that the leaders in GRADE offer?

And the series on core grade attempts to, and I believe successfully, addresses that problem. And what it does is say, what are the essentials of using grade? When systematic reviewers and guideline developers and health technology assessment practitioners use grade, and they want to have one-stop shopping,

to say here is what you need and the essentials of using GRADE. That is what this seven-part series in the BMJ provides. It says when you are comparing intervention A to intervention B and deciding on its benefits, harms, and burdens that patients face,

This is what you need. You look at the evidence, process the evidence, and in the last paper in the series, move from evidence to recommendations. And what do you think were some of the most important aspects of laying out those essentials? What are the key messages?

Well, the key messages are at the process of looking at the evidence, examining the evidence, coming up with appropriate conclusions. In particular, the certainty of the evidence. How trustworthy is the evidence?

is inherently a complex process, but can be made, we believe, relatively simple. The key was to decide what was essential. And having used GRADE very, very intensively and extensively for a 20-year period, we felt our team were able to put together what we think are the essentials that make it as simple as possible, but not too simple.

Do you think there are any new approaches in there? Yes, there are new approaches in deciding when, for instance, you have some studies that we would consider

low risk of bias and some studies that are consistent with high risk of bias, we put together what we believe is a more congruent approach than was available previously. A big innovation that I really like is that we now have algorithms or flow charts for using GRADE which did not exist before. And we had one or

a reviewer who I was delighted to see Sherry Cates as a reviewer because we have a long relationship in advancing and teaching EBM and she made she said you need some folk charts or algorithms and that turned out to be a brilliant suggestion from a reviewer one of the it would be it's

It's the highlight of my life in terms of useful feedback from reviewers. And each now of the articles contains a flow chart to help people through. And I think that's a very nifty advance in my point of view.

I think aspects of grade and evidence-based medicine in general are often debated by the community. What do you anticipate might be the more controversial aspects of what you've set forward? Oh, gosh. I suppose that there could be, outside of the grade working group,

which was the unofficial organization that has produced much of the prior great guidance. I don't see, unless you still have people who...

controversies that relate to fundamentals in evidence-based medicine. So, for instance, the disagreements about the relative role of non-randomized studies and randomized studies will

be around forever as far as background. There will be groups like those dealing with rare diseases or public health who are reluctant to accept, who struggle, understandably in my view, with the standards of EBM and grade that say, if you really want to know what's going on and be confident about it, you better have randomized trials overwhelmingly.

discomfort with that, with accepting that. So that goes on in the background. It's not particular to grade and it's not particular to core grade, but that's a background. Aside from that, there may be disagreements within the grade expert community about

What is simple but not too simple? So we, and I would have said that if we erred at all, I hope we didn't, but if we erred at all, it would be on the side of avoiding what was too complex. And we set a standard, and the standard that we set is

There may be some guidance which is methodologically very sophisticated and elegant and take things forward from a methodologically rigorous. And if it isn't necessary to produce the best product,

If it isn't necessary to get you to an accurate assessment of the certainty of the evidence and a summary of the evidence and the appropriate recommendations, if it's not necessary to achieve that goal, it's not going to be part of court grade. That was the standard we set. And I'm very comfortable with that standard and think we did the right thing. But of course, one could argue in a particular case

aspect of methodologic sophistication, is it necessary to get to the right answer? So one might have arguments about that. So CoreGrade has just launched online and we'll see what people think about it over time. Within the team that's produced CoreGrade, have you got ambitions for your next step after this or does this feel like it's job done?

Well, we have what we think is a big idea that I am just introducing to my colleagues at the moment. Are you going to introduce it to us? This is really hot off the press. So what is needed now is a living document that

has as its center core grade. And core grade, I believe it will only need tweaks

in the immediate future. Who knows about a decade down the line? But science evolves and core grade will evolve. And what we don't want is the unfortunate situation that's happened now. So a new paper comes out and it says, okay, core grade, here's an improvement in core grade. Who's going to see it?

who is going to say, okay, there it is, all core grid users. So we need a platform that is a living core grid. And I hope to possibly, BMJ interested in helping to produce such a platform, but the platform will also be, there are,

Core grade is the essentials. But there are aspects of grade that do that we think, you know, when we produce these sophisticated methodologically rigorous advances, well, we don't think they're absolutely necessary, but they're nice. And more sophisticated grade users will want to use them. So we need guidance that one could think of it hangs off

So for instance, if you want to really understand fixed and random effects models, which, you know, coordinate, pick one, use it, use the basic. But if you really want to understand and use fixed and random effects models in the most sophisticated way, you need to know a bit more. It would be nice to have

a living document that has those sort of things hang off core grade. And possibly core grade just deals with comparison of intervention A versus intervention B. Well, we now have network meta-analysis. Can we have a core...

of grade for network meta-analysis. And can that be part of this living document? Well, you're looking at multiple treatments for the same situation. That's right. That's right. That's absolutely right. You've got absolutely right. And grade now deals with issues of prognosis.

hmm, that's not part of what we've done with the core, but maybe we could have a core for prognosis that could be part of this. And these may be published articles, but again, things evolve. I think we need a living grade, and that's the big idea for the future at the moment. Well, we shall talk more about that, no doubt. I hope so.

All of those core grade papers will be published in our research section on bmj.com. That's it for this episode. We'll be back in a fortnight with more medicine and science. Until then, I'm Cameron Abassi. Thanks for listening.

Bye.

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If you're not covered by insurance, get $80 off your first month with Talkspace when you go to Talkspace.com and enter promo code SPACE80. That's S-P-A-C-E-8-0. To match with a licensed therapist today, go to Talkspace.com and enter promo code SPACE80.