#362 - 50 Studies Every Neonatologist Should Know

Hello friends 👋

What if you could hold in your hands a roadmap to the most influential studies that have shaped modern neonatology? In this special episode of The Incubator Podcast, Ben and Daphna sit down with Dr. John Zupancic, Dr. Susanna Hay, and Dr. Roger Soll to discuss the release of their new book, 50 Studies Every Neonatologist Should Know. Together with their co-editors Dr. Barbara Schmidt and Dr. Haresh Kirpalani, the team has distilled decades of neonatal research into an accessible, thoughtfully structured volume designed to guide clinicians, trainees, and educators.

The conversation explores the motivation behind the book, the editorial process of selecting just 50 landmark trials from thousands, and the importance of revisiting historical studies to understand how evidence has evolved over time. From the groundbreaking DART trial to the early work of pioneers like Bill Silverman, the authors emphasize not only the science but also the stories, challenges, and human insights that lie behind each study.

Whether you are a seasoned neonatologist or just beginning your training, this episode provides a behind-the-scenes look at a project that brings clarity and context to evidence-based practice.

📖 Get your copy of the book here: https://amzn.to/4nVTqcq

Link to episode on youtube: https://youtu.be/DzbtGYY0N6M

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The transcript of today's episode can be found below 👇

Welcome back to The Incubator Podcast. Today’s episode is a special one. We’re joined by Dr. John Zupancic, Dr. Susanna Hay, and Dr. Roger Soll to talk about their brand new book, 50 Studies Every Neonatologist Should Know. This book takes us through the landmark trials that shaped our field—studies that changed practice, inspired debate, and continue to influence how we care for babies today.

In this conversation, we explore how the editors selected the studies, the history and stories behind them, and why reflecting on the past is just as important as keeping up with the latest research.

And here’s something exciting—our guests will also be joining us at the upcoming Delphi Neonatal Innovation Conference in Fort Lauderdale, where they’ll be signing copies of their book. Delphi is happening January 26–28, 2026, and it’s not just a conference—it’s an experience. You’ll hear world-class talks, engage in innovative workshops, and connect with colleagues in unique and inspiring ways.

👉 Register now at www.delphiconference.org, and don’t forget to use the code INCUBATOR for 10% off your registration

Ben Courchia

Hello everybody. Welcome back to the Incubator Podcast. We are back today for a special interview on the Incubator Podcast. We're joined by three esteemed neonatologists. We have the pleasure of having on the podcast today, Dr. John Zupancic, Dr. Susanne Hay:, and Dr. Roger Soll. John, Susanne, Roger, welcome to the podcast.

For the people who may not be familiar with our guests, Dr. John Zupancic is Associate Chief of Neonatology at Beth Israel Deaconess Medical Center and an Associate Professor of Pediatrics at Harvard Med School. He also directs the EPOCH program (Exploring Pathways to Optimize Child Health), which leads clinical research in neonatology at his institution.

Dr. Roger Soll is the H. Wallace Professor of Neonatology at the University of Vermont and Vice President of the Vermont Oxford Network, where he directs network clinical trials and follow-up. He's also coordinating editor of the Cochrane Neonatal Library.

And Dr. Susanne Hay is a clinical neonatologist at Beth Israel Deaconess Medical Center and Boston Children's Hospital. You are also an instructor in pediatrics at Harvard Med School.

I'm thrilled to have them on the show today. And we have the pleasure of having you on to discuss the release of a brand-new book called 50 Studies Every Neonatologist Should Know. It is published by Oxford University Press. It's a phenomenal book. It's a book that Daphna and I have been talking about for some time and a book that needed to be written. And we're so excited to finally have it in print and have a copy.

I guess it’s important to mention that this book is a collection of summaries of important research papers published in the field of neonatology. It is edited by our three guests, but you were also joined by Dr. Barbara Schmidt and Dr. Harish Kirpalani. And it's already amazing that we got you three on the call, so I can't even imagine if we had to coordinate schedules for five possible guests.

John, I wanted to start with you. What was the "why" behind this book? I think people should know that it's part of a larger series aimed at helping clinicians identify the most impactful research in their field. And this book is specifically designed for the neonatology community. Can you tell us what motivated you to bring this to neonatology specifically? Was there a moment, maybe as a trainee or even as an educator, where you realized that there was a real need for a resource like this?

John Zupancic

Yes, thank you, Ben. That's a really important question because even beyond the content of the book, the question highlights something that we think is one of the big remaining challenges in evidence-based practice and medicine now, which is this idea of knowledge dissemination and knowledge translation. There are people doing great trials, but trying to get those into the hands of clinicians in a digested way, in a way that helps them to make decisions at the bedside, is really important and it's really challenging. There are 200 to 400 randomized trials, just randomized trials, published annually. And we're pretty good at getting through those, thanks in large part to the new technologies, thanks to your podcast, for example, where you're able to go through six or eight per week and put them on the table for people. Thanks to EBNEO and other platforms that have figured out a way to use social media to get information out. But even with all of that –our faculty and fellows have three journal clubs a month, some with waffles and some with lunch – we still cannot get through everything we need to in the contemporary trials. So we continue to try to do that with new work that's being produced.

But years ago, another nuance came up with this realization that if you're practicing at the time a trial is released, you hear about it through one of these mechanisms. You go to a scientific conference and hear about the challenges that were faced or the innovations that the trial brought online. You remember that as you're incorporating the intervention that the trial looked at into your practice. But it's really hard to do that going backwards.

So when we say, as we do almost every week, "I'm going to put this baby on the DART protocol," how many new practitioners necessarily know that that trial was stopped early? That it was only based on 70 babies? That the well-meaning information that came out from our directives from the American Academy of Pediatrics and the Canadian Pediatric Society actually slowed down or made much more challenging recruitment to that trial? Or if we're thinking about the generalizability of therapeutic hypothermia, if you weren't here when HELIX was released, you might not know that. So how do we ensure that people understand the strength of evidence for current practice that is based on studies that happened before?

How many of those studies are there? Well, between 2003 and 2022, there are 5,600 randomized trials. The possibility of surfacing that is just impossible for any particular set of trials. You might see them in guidelines, but you'd have to read the footnotes.

That was part of this issue of going backwards and looking at studies. The second thing is a little more kind of romantic, I guess. It hits this idea that when neonatology started, it was a blank slate. Somebody had to establish this whole new field of evidence, at the bench and at the bedside, with human studies. And so this incredibly rich history deserves to be brought up. There's a great deal of learning that can happen around how people attacked those questions.

At about the same time that we were starting to think about this, I was giving a talk and mentioned Mary Ellen Avery's name. And there were blank faces. It was early career folks. I asked, "How many people have heard of Mel Avery?" Less than 10% of the room put up their hands. I thought, that's too bad. These people were really extraordinary individuals. How do we get them the recognition? How do we use them as role models in absentia?

Sorry — it's referred to as verbose, and that might apply to me.

So we started this thing called the 52 in 52 RCT challenge about 10 years ago. It was a Twitter campaign where we released one trial publication a week with a couple of little notes and sometimes a link to something historical about the impact that it had. It was a little contest: if people read all 52, they got a Starbucks card. The fellowship program that had all of its fellows reading all 52 got a pizza party. That ended up being Duke, by the way.

There was a little bit of conversation in social media about these various trials. But then it evaporates, and we started thinking, how can we make this more permanent?

Ben Courchia

Thank you for that. Roger, I wanted to ask you a little bit about something that John just mentioned. When trials do come out, we tend to pay a lot of attention to them in the moment, and we rarely do the work of going back and seeing the place that a trial maybe holds along the neonatology timeline. I think this book is so good for that. We can go back to a trial like John mentioned - the DART trial from Lex Doyle - and see where the evidence stands now, 10 or 20 years down the road. What was the evidence like, and how do we put it in context of other papers?

Can you tell us a little bit about the importance of doing that, to look at data in real time, but also retrospectively review the level of evidence that has influenced practice?

Roger Soll

Ben, it’s a great question. One of the joys of doing this project was, as John alluded to, going back historically. There are studies that span 70 years of neonatology included in this book, and some of them are truly seminal trials that sent us down the whole road of doing this type of evidence-based medicine. I don’t think our colleagues are aware of the contributions of people like Bill Silverman. What we do on a daily basis relates back to work that he’s done. The humidity or heat that we use in incubators dates right back to Bill, but so do the fundamental questions about how do we know what we know? It was fantastic. There are studies in this book that predate any involvement I had in medicine, from my childhood. There are studies that John and Susanne may think are archaic that I remember well from when they were introduced as a fellow and influenced my practice.

At the bedside now, it's just all there. Like, yeah, we screen at six weeks for ROP. We do this. But not understanding that basic issue. These were mostly the building blocks. We didn’t take a lot of the follow-up studies you're referring to, Ben, but you're right - there's a rich matrix of studies. Certainly our work at Cochrane tries to explore that. We chose studies that were paradigms, either the first or the breakthrough, that led to that whole building of the evidence. If you looked at the studies chronologically, the methodologies have changed a lot. The expectations around methodologies, the sophistication of outcome measures, and the analyses really are quite dynamic. So I think there’s a lot that people learn about the whole landscape of trials from the book.

Ben Courchia

Thank you. Susanne, I wanted to maybe ask you a little bit about the structure of the book, because in a way it reads almost like a spoken narrative. And as a podcaster, I loved the pacing of the book. I’m wondering if that was intentional in making it feel like a conversation. For people who haven’t seen the inside of the book: each chapter focuses on a specific study and it’s structured in a very consistent manner asking, "What is the research question? Why was the study done?" It has the years, the location, the number of patients. It goes through the results. There’s a commentary, a section on criticisms and limitations. I thought that section was very interesting. And as a podcaster, I loved the last section: the conversation with the trialist, where, when available, you went back to the first author and asked some questions. Can you tell us a little bit, from an educational standpoint - because I feel like this book is so valuable for trainees and early-career neonatologists - what was the thought process behind structuring the book in this manner?

Susanne Hay

Yeah, absolutely. So when we started, we got kind of the rough template of the 50 Studies series from Oxford, and essentially, they let us use that as guidance. So we got to play with it. And I think one of the biggest additions we did was this interview section that you mentioned. It came quite quickly to our team when we began discussing all these different studies and what we wanted to represent, because there’s so much more of a conversation around these studies, as we’ve been talking about, than just their printed form and analysis. These studies continue and there’s more dialogue around them. We wanted to give the trialists, when available, the opportunity to answer some of these questions that keep coming up, and give us more detail around the publication, other thoughts they had, and thoughts for the future of their research. It’s easily one of our favorite sections, and it really enriched the product, I think, for us.

Ben Courchia

Yeah, I think that, as we were mentioning earlier, specifically in the DART trial, when Lex Doyle mentions that basically it was hard to complete the study because everybody was steroid-dependent. I mean, that is such an insight that you don’t really get from the paper. But you get this sort of perspective from the first author years down the road. It’s so interesting to see that while we’re trying to study, the field may move faster than science would dictate. And I think that’s so cool to even know about that.

Roger Soll

If I can interject - Susanne was great about getting pithy comments at the end, but there was a lot of conversation around it among the editorial team, among Barb and Harish and the three of us. Also not to be forgotten: individual sections were written by the current trialists, mid-career and some late-career folks who have a unique perspective in the 21st century about trials. And they weighed in. So we had lots of opinions going. And kudos to Susanne for distilling it down to: "Okay, what’s the gem here after all of this discussion?" I think she did a beautiful job with that.

Susanne Hay

That’s true. We were always up against the word count. Each of these chapters was so rich because not only did we have this interview section from the trialists, we also had this incredible dream team of contributing authors - who were, in their own rights, experts in these fields - who would then comment on it and talk about all the different research going on, how they thought it could be strengthened, how it should be interpreted. Editing was one of the hardest jobs, trying to cut this down and make this into a book that you can carry around.

Ben Courchia

Yeah. As you know, sometimes you buy these movies on DVD and you can get the editor’s cut or the director’s cut. I would love to have all the unedited stuff and see where everybody’s comments were. It would be very cool to know.

Roger, I wanted to go back because you did mention Dr. Bill Silverman, and I think this is such an important point. One of the legacies that Dr. Silverman left the community is that questions should be asked for our babies, and questions should be investigated in a very rigorous manner. I think that if we are so attached to following randomized controlled trial approaches to clinical questions in neonatology, it is in great part thanks to him. I would highly recommend everybody reads his book Where’s the Evidence? I mean, it’s just a must.

That being said, in the introduction to the book, you do mention that RCTs, while scientifically rigorous, have inherent limitations. We’ve seen over the years the introduction of other modalities in terms of studying clinical questions, whether these are observational studies or other forms of trials. And the book does not really limit itself to a specific trial type. Can you tell us a little bit about how we welcome a more diverse form of trial design, and how do we tease out the trials that are done well and answer questions in a valuable way?

Roger Soll

In no way is this book trying to say that all those other sources of evidence are irrelevant to our practice. If anything, we’re trying to reclaim the birthright of RCTs in this very rich environment now of evidence, all of which contributes to our practice.

To the specifics of your question - trials have sort of peaked. Whether it’s a COVID phenomenon, or whether it’s an energy and funding phenomenon, they have steadily increased over the past two decades, but they’re sort of peaking in number. And I think we need to see more trials, and we need to see more innovative trials. Some of the issues that really represent the current state of trials include: the use of cluster trials (understanding that when we want to look at complex interventions, the institution and center is probably the major site) and the platform trial (where we can build multiple trials about our practices and generate evidence at a faster pace). One criticism of all the trials in 50 Studies is that almost every trial is underpowered. I’m not sure we sent that message out. We could have written it in every chapter…and then you would be interviewing us, Ben, saying, “That was one boring book!” So I think if anything, we see it as a need to continue this effort in the 21st century. And you’re right, we don’t really go into the fact that perhaps we need to think of even different approaches to the randomized trial to make this a really valid and important contribution. I’d be very curious what John and Susanne have to say.

John Zupancic

Yeah, I wholeheartedly agree. This is a little bit like a photo album, and you don’t know what trials are going to look like even immediately after we wrapped up the proofs. There was much more talk about PLATIPUS (Platform for Adaptive Trial in Perinatal UnitS), platform trials coming on board, and other trial designs. So this idea of moving the field forward on a base that was innovative in its day (there’s a lot of innovation described in those 50 studies) but moving it forward is so important.

I think it comes back to this issue that you had brought up earlier about conversations. We see the actual studies that are fairly succinct in their publication and the word limits are very strict. But the conversation around them tends to happen in the back rooms. There's ten or fifteen minutes at the scientific conferences, and then there aren’t a lot of places where you can talk about where this should go, where is this going, other than in the hallways of those conferences.

So I think trying to facilitate that. In the old days, there were a lot more letters to the editor, for example, saying, “This would’ve been great as a cluster trial. Maybe we should do that.” I completely agree with you, Roger. I think we need to figure out a way of pushing for that kind of innovation in methodology. And I’m not sure where that push is necessarily going to happen, but it deserves thinking.

Roger Soll

One of the interesting things we could have added is what was left out of the trials. So, I mean, for example, you look at the cooling trials and they are fantastic, but they're a very strict population treated in a very strict window. And we are still struggling with what we should do with the child who has mild hypoxic ischemic encephalopathy. And I think we probably do know more about duration and depth now because of the NIH work. But trials are stereotypic and specific. And we could have written reams about all the unanswered questions that deserve further trials. A separate book.

Susanne Hay

We kept talking about what's our next spin-off, all the different things we could have done, all the different kind of other trials we might want to look into. So certainly a fun idea for a spin-off, thinking about different ways to approach topics and how to interpret these trials that are so much newer to a lot of us.

Ben Courchia

My next question for you guys is related to something that Roger brought up in terms of understanding the timeline of studies. First of all, I was shocked sometimes to see how some studies were completed in an efficient manner. I believe that some of the studies, four years done from initiation to publication, it's very impressive. Some others almost a decade. What does that say about the importance of understanding how long it took for a study to go from inception to completion? Can you guys talk a little bit more about that? I'm going to let John take this one and then we'll go around.

John Zupancic

I think you summarized what we took away about efficiency of trial design. In order to answer more questions, we have to have more efficient trials. And the idea that because of the constraints of sometimes regulatory oversight, sometimes funding, sometimes it's our conception of trials that the person with the good idea doesn't necessarily have a patient population, so they're trying to get as many patients enrolled in answering a question as possible, but it just takes years and years and years. Or COVID - although interestingly, one of the most efficient trials or trial ideas came out of COVID, which was the adult platform trial in the UK. That was an incredible contribution, I think, methodologically and obviously in terms of the questions it answered because of necessity. But I would argue that it isn't just COVID that's the necessity. It's the issue that you brought up, that if we ask a question, it takes 10 years to answer it. That's putting a lot of babies potentially at risk of either a therapy that isn't good or a therapy that should be in practice and isn't yet. The piece after it is also really important. Once you have a trial that has shown something, in order to get it into guidelines for professional societies, that can sometimes take three, four, five years to get it put out by the AAP, for example. So I think going back to this idea of platform trials, it's a way of improving efficiency and improving the timeline. I think there are other ways to do that, but it's got to be addressed.

Ben Courchia

Yeah. And there's some chapters where it doesn't mention the trial begin date. And then it'd get me wondering, like, I'm wondering how long that took. When did they begin exactly? Susanne, do you have any thoughts on trial periods and how long and how short some of them?

Susanne Hay

Absolutely, so I think it was fun when we were putting the book together to see kind of within these sections how the timeline worked out between some studies. You'd see like one study really struggling with equipoise, having to kind of change the way they're doing it, and then another study doing a randomized trial several years later. So different approaches and how we actually can answer a question for our field was fascinating to watch. And also I think in the discussion section these trials are so difficult to run. I think we were very purposefully critical, largely just to talk about how we can trust these studies, how we can interpret them, but also pointing out that it's all in the real world. So every study is going to have some limitations and how hard these teams are all working to minimize that.

John Zupancic

You know, coming back to that issue of recruitment that you brought up, Susanne, I also wonder how a climate of trust or distrust in the scientific process might start to work in here. Roger will know the answer to this, but I think Bill Silverman was the person who said, for every baby, a trial, and for every trial, a baby. And I think that there was a period of time where that seemed to be becoming the accepted mode and I do worry going forward if it's going to be more difficult rather than less to get consent for this process. I don't know the solution.

Ben Courchia

Trust is at an all-time low. So I wouldn't be surprised if recruitment required more effort and more time. Roger, do you have any thoughts on that?

Roger Soll

I agree with John. I mean, I wish that we were like the pediatric oncology group where literally the vast majority of patients are seen in the context of the next trial. The trials build on themselves and answer nuanced questions. They don't just say this worked. Now they want to know which dose and when and can we minimize the dose, et cetera. So the idea that somehow, probably through cluster designs, every baby can be involved. One thought I had, and this is far from a criticism of the book, I don't know if there's one shred of evidence in the book that helps us understand how to manage the 22-24 week gestation baby. Okay, I mean that's just the nature of the timeline you were alluding to, Ben. In this historical perspective, we have huge gaps. And we need to address that as we move forward. I think John was alluding to, it's going to have to be a more innovative approach that involves whole populations and engages families and laypeople in the process and embracing that we cannot move forward further without their assistance and their input. So yeah.

Ben Courchia

So along those lines, it's something you mentioned before. One other thing that stood out to me is sometimes for certain papers, how far back these studies go. And it doesn't seem like you guys set a limit on the search function of your studies by date. Going back, for example, in the hematology section on the study for vitamin K, we're looking at a study that was done in the mid-60s. And that's pretty bold, especially in an area where a lot of us now are saying, the population was so different at that time, and the tools that we had available were very different. My question is, how did you assess the value of these very early trials? And were there any concerns that maybe the care context, the technology, even the diagnostic definitions might have changed? And are there any enduring lessons that those early efforts actually provide and still remain to today?

Roger Soll

Well, vitamin K is a great example because it does belong. Term babies are still term babies. Breastfeeding is still breastfeeding. And vitamin K deficiency still exists. And in fact, it looked at clinical outcomes, not surrogates and biochemical outcomes. It's a beauty and great for people to know how Sutherland did that historically. So love that it's there. On the other hand, if we looked at CPAP studies, the earliest ones are in big babies, 34-week gestation babies, no steroids, little experience from nursing staff. What can you glean from that in today's practice? So we tried to pick studies, if they were historical, that either methodologically changed our approach (some of the Silverman studies) or ones that were so tried and true that we do it every day in our practice, and we don't necessarily know where that came from. But you're right, it's a challenge. And people would argue that maybe the most recent evidence is the only trustworthy evidence for our babies.

Susanne Hay

I remember the vitamin K chapter specifically, Anna Curley commenting on this is some interesting language used in this manuscript because it was just so old. But I think that was one of the challenges in our books, finding kind of which study to represent. But we'd always comfort ourselves with the related study section. So we try to pull that study into kind of how it is relevant currently to our field and whether studies kind of build off of that and went further with this information. So it was certainly hard to not include some of the more current studies on topics, but we tried to find kind of what we felt was the biggest seminal piece in many cases.

Ben Courchia

John, I'm curious to get your thoughts on this subject and also maybe expand a little bit on that question. Do you think that we're too quick to discard the past? I mean, the scientific method has been rigorously followed for many, many years, and our predecessors have sometimes addressed the question in a very rigorous manner. Should we not be discarding old data the way we are currently doing it, which I think is quite aggressive?

John Zupancic

That's interesting because as Susanne and Roger were talking and as I was listening to your question, I was thinking one of the issues there is that we included studies, as they alluded to, that broke new ground. But the issue comes up like either it broke new ground and just established something and it's unlikely to change, but sometimes you're dealing with a different population of patients. And the question comes up not so much about discarding the information from the past, but when do we ask the question again? And not even necessarily with any nuance to it or tweaking to it, but just same question, different era. For example, BPD is a completely different beast compared to 1989 when Roger was starting his surfactant trials.

So I think the short answer is that there's no simple rule about when to discard the past. I think we must be aware of what our evidence is based on. And that translates practically into always, in any guideline, having the certainty of evidence assessed. Every recommendation has a certainty of evidence attached to it from whatever kind of study is done (trial or not) and we understand, based on the footnote, when that information was done. Is it directly relevant to our patients? Is it indirect because it's old? And then somebody thinks about when to re-ask a question. And then importantly, the funding must be there to re-ask that question. Because I think sometimes people say, well, this isn't innovative. It was something that was established in 1992, do we really need to go back and see who needs surfactant these days?

Roger Soll

Yeah, surfactant is a good example on that though, John, because we did the first trials in the eighties, but the trials comparing our approaches of aggressive prophylactic care versus later treatment of established disease were done in the ‘90’s. There was very low rates of antenatal steroids, very little use of CPAP. Those studies had a very strong effect on decreasing mortality and pneumothorax. When repeated by Vermont Oxford Network and by the NICHD in a more current population, in fact, the opposite effect is seen. So it's not a trivial question. We have to think about where, like milk cartons, studies have expired and need to be discarded. But you have to think carefully, because there's a lot of resources, as you noted, John. It's a very costly process to say: when do we need to ask this again? And do we have equipoise to ask it again?

Ben Courchia

So one of the questions I wanted to ask you, because I was trying to understand the process of putting this book together. I'm assuming then that you guys pick 50 studies that are going to enter the book. And once the writing process begins, do you have someone checking that no more studies are coming out that might actually trump the ones that you currently are working on? Because it sounds like a terrifying process where you're finishing one and then something else comes up. So I guess my question is: in a way, this book does capture a moment in time. I'm curious to get your thoughts on that. Is there any tension knowing this? And maybe is the book format something that is even scary to approach, especially as the book goes to print? This landscape continues to evolve at a very fast pace, as you guys mentioned earlier. So I'm just curious to get your thoughts on that.

Susanne Hay

It was a fun race. This book ended up taking us quite a while to put together because every chapter went through every editor. We really wanted each chapter to be meaningful and well-written and thoughtful and fully represent these trials. In the background, we were getting these magnificent studies published all the time. And to go back to just selecting the studies - it took us, I think, at least six months to wean down to 50 studies. We tried to do it as objectively as possible, doing huge searches on number of citations. Studies had to be in high-level journals. We have our own database that JZ and I are working on. So just finding the biggest trials there and looking through all of them. Just getting that alone, we were seeing trials come up.

During the whole process, the nice thing is we cover a pretty broad scope in our book. So whenever this happened, we tried to make it an associated reference to still keep a nod to where things are current and keep our data as relevant as possible to the clinicians reading our book. But yeah, we weren't able to add chapters after that, despite the temptation.

John Zupancic

I would just echo what Roger said about how much work Susanne put into that part of it. And also to say, you mentioned that Harish Kirpalani and Barbara Schmidt were on the editorial team for this. And as you're seeing in this interview, there are lots of different opinions and perspectives.

When we add in the expertise and immense experience of Harish and Barbara, you can imagine that the selection of studies, and the entertainment of new studies that should maybe trump another one as you said,  was a very active discussion. As it would be if you put any five clinicians into a room and said: what do you want to talk about for Journal Club?

Ben Courchia

I feel like we all have studies that we truly love. Like there are some papers that you're like, I live and die by this paper. And I can't imagine strong neonatologists coming into a room and then allowing certain studies to be put under the microscope. So I'm just wondering if we could go around the room in the last few minutes we have together and you could tell us a little bit about, of all the studies present in the book, the one that you favor the most? Why is that? And maybe the study that was left out of the book that you really wish made it into the book?

Roger Soll

Well, I'll start with a beloved study while these guys think. I love the original CRYO trial. It came out during my fellowship. ROP was a disease that, if found, had no specific treatment and it was just heartbreaking that we could do so little for it. My mentor, Jerry Lucy and obviously Bill Silverman before, were so involved in this breakthrough therapy. And then, the innovation of randomizing eyes! Moving forward with that just struck me as so clever and thoughtful, that they wanted, whatever the results were, at least one eye to get the best treatment.

Ben Courchia

Can you clarify this for people, because I know what you're talking about. What does that mean, “randomizing the eye”?

Roger Soll

If you met criteria, if one eye was worse, that's the eye that got treated if you were randomized to treatment. If they were similar, you got randomized to left eye or right eye. So it was just so thoughtful about what are the consequences downstream. We have equipoise. We don't know if this will work. And it was thoughtful and clever. And of course, because it worked and changed our practice and changed what we could share with families; this has always been very close to my heart. So Dale Phelps, her crew who did that, I've always had great admiration for.

Susanne Hay

I'll jump with the next study that really captivated me. I'm also probably biased because I had such a fun interview with Dr. Bartlett, but I absolutely loved the randomized play-the-winner ECMO trial. I thought the setting in which he performed it and the thoughtfulness of finding this very unusual design at the time to try to test this potentially life-saving therapy (where equipoise was rapidly being lost) and try to actually generate some data around it was fascinating.

Roger Soll

Bartlett was the most unbelievable interview, about all the other things he did as well. But here's a surgeon who came up with this adaptive design because he kept getting the criticism that the observational work he had done didn't convince anyone. And then interestingly, such a powerful therapy - what is it, Suzanne, only 11 or 12 patients wound up in the study? - and it's poo-poo’ed in a way. He clearly showed that it works. It doesn’t show safety with 12 patients, but he showed that it works.

Susanne Hay

He was such a great thinker and example of collaboration too, because he talked about the scathing reviews he got after this because it's such a small study and quite the statement. And then he went on to do another study with one of his sharpest critics of that, to try to work together. It was just such an amazing story.

Ben Courchia

I like how he described it as “crazy and outrageous” — I believe that's what he said in the commentary about the technique. That sounds pretty wild. John, what was your favorite article in the book?

John Zupancic

Yeah, I mean, it's like choosing children, I suppose.

Ben Courchia

Well, you've already narrowed it down to 50 studies and now I'm asking you an even bigger question, to give me the one.

John Zupancic

It's fair enough. I think the one that has always stood out to me because of its intellectual integrity regarding the idea of a trial was also from the surgeons, who are sometimes criticized for not being as committed as they should be to trials, it was the MOMS trial of in utero meningomyelocele repair. And the reason I chose that is that they decided as a community basically to stop using a therapy until they, unless it was in a trial design. And I think that that was really an impressive thing to do. If you think about how often the proverbial horse gets out of the barn with therapies, for which we have very low certainty of evidence before that evidence accumulates, here was a group who said, we're going to make sure we do this study and it's going to be what it is, but at least we'll have better guidance about whether this is the right thing to do at the end of it. So I really liked that commitment and it stood out.

Ben Courchia

And there was a lot at stake with that particular intervention. I think that the balance between outcomes and prematurity is something that was definitely in the balance. My favorite trial will remain the skin-to-skin from Columbia. I'm just so enamored by the simplicity of the intervention and the effect.

I guess that we are close to the end. My next question is going to be, when is the second edition coming out? Susanne is laughing. Go ahead, Susanne.

Susanne Hay

My gosh, this project was just such a joy, I think, for the entire team to get together and write. We are itching to figure out the next project, and we are tickled to see all these new studies coming out with the hope of writing another edition. So we're certainly hoping to do something. I don't think we've settled on what the next move is yet.

Roger Soll

I enjoyed this process and being invited in on this process by John and Susanne so much. And it'll be interesting. We need to think about what the next angle is that will serve the community's interests.

John Zupancic

One of the things that I think would be interesting in going backwards is to think about non-randomized trials. But the trouble there is that there are 100,000 of those, probably. But understanding what the pathway was from establishing the link between surfactant and RDS in premature babies through to having a therapy available only 20 years later or so, that would be very interesting too. Extending the question-asking before you get to the human experimentation part would be.

Susanne Hay

We have so many different angles. Also, our book ended up getting picked up by some parents too. We got some feedback later as well, which was fun and exciting. I mean, largely it is targeted toward clinicians, but it was also something where you sense there's some need for that too. So we’ve played a little bit with thinking about how we can bring some of this to parents.

Ben Courchia

Yeah, I think it's going to be, in my opinion, the next frontier for neonatology. And it's already been well investigated, but the role that parents will play both in study design, study process, and then analysis is key. I'm just curious, what kind of feedback did parents give you on the book? That must have been terrifying.

Susanne Hay

They actually loved it. One of the ones that contacted me was a historian, so he really enjoyed going through and seeing how things had come about, which was fun. I mean, I don't think they were looking as much at the trial design aspects, but yeah.

Ben Courchia

As for trainees, can you imagine if a parent read the book and comes into rounds prepared? This is a terrifying proposition.

Roger Soll

Maybe it's a job for AI, guys. Feed the book in and have them print our chapters out in readable forms at a 10th grade level.

Ben Courchia

It's a very interesting point you're making, Roger. This is a subject we're going to address at the upcoming Delphi conference: talking a little bit about the use AI can have not just in helping clinicians with decision-making, but maybe helping the relationship between clinicians and parents. I think you're right on the money. There are tremendous opportunities, in my opinion, that could be explored.

John Zupancic

Can I just make one more point before we go? I think we were about to wrap up, but I wanted to make sure to underline something that Roger said at the very beginning, which was that we edited this, and we've been talking a lot about the discussions that we had. But each chapter was actually written and the hard work was actually done by a group of really impressive individuals who were willing to wade in and put their thoughts on paper and who are, as Roger said, in many cases, trialists or data synthesis people on their own. I just wanted to really thank them and make sure it was understood that all we were doing was corralling their ideas into a book.

Ben Courchia

I picked up the book at some random times of the day or night, and sometimes I even got fooled. I'm like, did that person write that? Oh no, he's not the PI, he is the editor of this particular section. But the list is too long to go through, it includes Nick Embleton, Sarah DeMauro, Souvik Mitra, Brian King...there's a long, long list of contributors. I don't exactly know how you got such a high-quality group of people together and to collaborate, but it is very impressive. Prakesh Shah, Ravi Patel - I mean, it's a long, long list. It’s important to mention this before we wrap up.

Susanne, John, Roger, thank you so much for being on the show and sharing this short hour with us. The book is called 50 Studies Every Neonatologist Should Know. You can grab a copy on Amazon. You can get it in Kindle format, you can get it in hard copy. We'll put some links in the description. Congratulations. And we're looking forward to the next edition.

John Zupancic

Thank you so much for having us.