Dr. Mary-Ann Etiebet: Saving Mothers' Lives

Harlan Krumholz: Welcome to Health & Veritas. I’m Harlan Krumholz.

Howard Forman: And I’m Howie Forman. We are physicians and professors at Yale University, and we’re trying to get closer to the truth about health and healthcare.

Harlan Krumholz: So Howie, what’s something in the health news that got your attention?

Howard Forman: So we have three colleagues here—Jordan Peccia, Alessandro Zulli, and Ed Kaplan—who work together with others to show that you can use wastewater, which is basically sewage, to predict the amount of SARS-CoV-2, the virus that causes COVID, in the community, and they’ve proven this several different ways. It’s been a very reliable, predictive way of knowing which way the outbreak is going. And even though we’re in a very favorable time right now, with a waning outbreak, it’s just as important, if not more important, to see if there are changes in various communities, particularly in the state of Connecticut.

They’ve published several papers on this and proven it’s a relatively inexpensive source of very valuable information. And I recently discovered that this ended in Connecticut, the actual ongoing work as opposed to the research, and was really pleased to find that that our colleague and neighbor, Jonathan Rothberg, stepped up to refund this effort. And it just is a reminder to me that you can do all the great research, develop novel means, but you also have to make things sustainable. And our usual public health funding mechanisms, which are always going to be somewhat limited, may allow something as valuable as this to fall through the cracks. And I’m just thankful, again, to Jonathan Rothberg and these scholars for allowing this to continue so that we can continue to track throughout the state.

Harlan Krumholz: It’s not a glamorous job, but it was really clever and has worked really well. And it’s nice to see that Jonathan’s supporting it going forward.

Howard Forman: Agreed. So what’s on your mind this week?

Harlan Krumholz: Well, in the health news side, I just wanted to highlight an article that had me thinking, that came out recently in The New England Journal of Medicine. It was about looking at people who were depressed, had depressive symptoms and had been treated and now consider themselves well enough to come off of those medications. And there’s a lot of controversy about these antidepressants. It turns out in this country—this is from the UK, but in UK too—we use them quite often. And a lot of the population is on them. This is a burning question: Can you ever come off them? Do you need to stay on them? And how does it work? And so they took a large number of practices and studied some people over about a year and randomized them to people who, if you felt well enough and you were no longer having depressive symptoms could just stop, and other people, they had them continue. I thought what was interesting was the way that they expressed the results of this trial. And I just want to point out that this is some of the difficulty in communications of studies.

So they said, among patients in primary care practices who felt well enough to discontinue antidepressant therapy, those who were assigned to stop their medication had a higher risk of relapse, by a year later, than those who continued. Okay. So you hear that and you say, “Okay, wow. Yeah, you really can’t stop them, because the people who stopped taking the antidepressants had a higher risk of the depressive symptoms coming back.” And that sounds like, “Whoa, everybody should keep taking the meds,” but if you dig into the results. and by the way, this is New England Journal of Medicine, been vetted, gone through peer review. This is the message. And so many doctors will just read the conclusion because there’s just so much to keep up on these days. I mean, you just can’t possibly dig in, but if you dig into this, it’s interesting.

If you say that at a year, the relapse occurred in almost about 40% in the maintenance group, the group that continued to take it. And in 56% of the people who quit. So there’s two things here that really occur to me, as I read it. One, 44% of the people who stopped, did fine. They were able to get off the meds. I would be celebrating that, like if you stopped, 44% were, hey, a year later, good. That seems to me to be like, worth a try. Right?

And the other thing was, even the people who continued to take the medication, four in 10 had a relapse. So, that’s also telling us these aren’t the greatest drugs in the world. I mean, the difference here is between 40% and 56%, which really means that the benefit of taking the meds. I would’ve framed this result in an entirely different way, which is that continuing on the meds was disappointing. The meds aren’t that effective. Four in 10 end up getting relapsed; depression’s a tough disease. And second of all, if you tried getting off them, about four in 10 were able to stay off.

Howard Forman: Yeah. No. And it goes back to our discussion a couple of weeks ago with Dr. Erica Spatz about shared decision-making and how this is the type of information that a good physician can present to a patient in the way that you did, to allow them to have input into a decision about whether to stop or continue on a drug that may or may not have side effects for that patient. So these are all important factors to consider, but it starts off with the physician actually understanding some fairly simple numbers. This isn’t higher math, these are simple numbers, but framing it in a way that a patient can understand.

Harlan Krumholz: That’s right. That’s exactly right.

Howard Forman: So I’m really delighted today that we get to have Dr. Mary-Ann Etiebet as our guest. I have been fortunate to know her for well over two decades, having met her first when she was a medical student here, but in fact, she was a Yale undergrad before that. She was a medical student. She was a business school student here in our second cohort of MD/MBA students. And then she went on to do clinical internal medicine, followed by an infectious disease fellowship in New York, followed by a faculty position at the University of Maryland, where she spent I think half of her time with a PEPFAR [President’s Emergency Plan for AIDS Relief] grant in sub-Saharan Africa, both investigating as well as hoping to intervene and reduce maternal-fetal transmission of AIDS, which is to say that her entire career has been committed at this point to the challenges that are faced by women and childbirth and maternal-fetal transmission.

And so she had a few other roles in between, but when she had the opportunity a few years ago to take on a global health role in health equity at Merck for Mothers, I was really overjoyed to hear about her passion for that and how neatly it fit into her career. So I just want to welcome Mary-Ann, let her say a couple of words about that work that she’s doing now, and then turn it over to you, Harlan, for a question.

Mary-Ann Etiebet: Thank you so much, Howie, for that wonderful introduction. It’s so great to be back, even if it’s just virtually at Yale. And Harlan, it’s great to see you after so many years. I can’t wait for the conversation. What I would like to say is that my passion for addressing these global health challenges that occur similarly, both here in the United States and outside, really started at Yale and all of the different opportunities Yale afforded its students to really dig deep into the issues but also to be part of the solution. And that solution mindset, that thinking about what’s the next frontier, how can we think about new ways of solving for these problems, how can we bring research tools to them, all of that was incubated at Yale. And I’m just now really excited to be able to put it even more into practice and to think about how to create new norms across different sectors, whether it be academia, public sector, the NGO community, or now at Merck in the private sector to help advance health equity.

Harlan Krumholz: Yeah. The audience should know I’m a great admirer of you, Mary-Ann, and actually in preparation for this podcast, the more I was reading about the things that you were doing, it got me very excited. And you’re really the best of what comes out of Yale, which is a sense of a deep commitment to try to make society better, not just to contribute, not just to advance in a field, not just to get titles, but actually to make tangible differences in people’s lives. In this area that you focused on, first of all, why do we in the U.S. do so poorly, and why does this problem seem so intractable? I mean, you are making progress trying to make a difference, but gosh, we think of ourselves as being exceptional in so many ways in this country. And yet our exceptionality in this area is really in the negative direction. How do you conceptualize the problem?

Mary-Ann Etiebet: Yeah. Thank you for that question, Harlan. And I think I’d like to try and answer it two ways, one, through the experience with Merck for Mothers, because I think that gives you a very specific window into what’s happening in the health equity space and how, at least through that initiative, we have worked to try and help close the gap. But you mentioned the term exceptionalism and I think that’s exactly the crux of it. When we think about exceptionalism, I think we have set our sights on the best and just focused on that without thinking about who are we actually offering the best to, and who is the best available too? What we need to do is actually focus on, are we able to bring that exceptionalism to everybody? Is it inclusive exceptionalism?

And when we asked that question, we actually have found at Merck for Mothers, which was created back in 2011, for part of the audience who may not know about the program, but back in 2011 at Merck, which is also known as MSD outside of the U.S. and Canada, committed $500 million to helping end preventable maternal deaths. And I think as we have experienced the first 10 years of the initiative, we found that sometimes inadvertently we’ve actually been part of the problem of exacerbating these inequities we see in maternal health outcomes because we think perhaps a rising tide lifts all boats, or if we focus on the most technology-advanced solutions—and we know in academia we’re guilty of trying to figure out what the best next intervention is—whereas we can really focus on what do we know works and how do we make sure that it works for everybody.

So that’s one of the lessons we’ve learned at Merck for Mothers, that in order to address health inequities, we really need to focus on getting the measurement right in terms of understanding if we’re reaching everybody. But the other area I’d like to talk to both of you about is, how do we create more inclusive processes around understanding if what we’re doing works. Because—

Harlan Krumholz: Well, let me just ask you one quick question. How do moms die? Because in this country, I think when people are pregnant, that’s the last thing on their mind, that I might not survive this pregnancy, at least in the circles that we’re in. Right? And yet for some populations, this is not rare and it happens. So how do people die in pregnancy? I mean, how does it happen?

Mary-Ann Etiebet: Yeah. And the answer to that really does depend on where you are dying. And unfortunately it also depends on oftentimes the color of your skin. In the United States, we know that the top drivers of maternal mortality oftentimes have to do with cardiovascular risk factors or comorbidities. But we also know that, for example, postpartum hemorrhage is also a top contributor of maternal mortality. I think the key thing for people to understand is that at least 60% of these deaths are preventable. And when you dig into those deaths, you understand that there are at least three to four contributing causes to the death. And those contributing causes don’t just lie around the medical interventions or clinical factors. Oftentimes they lie in the community, in the lack of coordination across care teams, in the lack of communication across care teams, or in the lack of having access to services. So it really is multifactorial, and we’ve realized, based on those investigations, that the solutions also have to be multifactorial. They can’t just be limited to medical care and solutions in the hospital.

Harlan Krumholz: Well, let me just ask one more, and then I’ll let you go, Howie. Sorry. We usually like to go back and forth, but I’m so interested in this. And also, I think sometimes, again, for the audience, maternal mortality is a sanitization of this concept that moms are dying. Moms are dying, and they’re dying at rates that is unconscionable and preventable. These are people dying. Since you’ve studied it, I just want to understand, are these people who are sick and then they give birth and then some complication occurs? Or is this most often a surprise, which is people who’ve been neglected through pregnancies, they come in late, they’ve got an issue, and then catastrophic events occur? I mean, I’m trying to just characterize this for people listening, because these are individual tragedies of just immense, immense consequence.

Mary-Ann Etiebet: I’ll share a personal story. And I think from that, you’ll really see that one, it is a tragedy, and two, it is definitely a surprise. It’s a unexpected surprise to catastrophes.

Harlan Krumholz: Catastrophes. Yeah.

Mary-Ann Etiebet: I think where the surprise happens is in those healthy moms who are entering their pregnancy journey, kind of filled with a sense of expectation and joy. My husband’s sister-in-law, that happened to her about 30 years ago now. She walked into a Brooklyn hospital but didn’t walk out. And when my husband asked me, “What happened? What could we have done? We had no idea.” It’s just heartbreaking to have seen all the different potential missed opportunities for things to have happened.

I’ll share the personal story with you. This was her second pregnancy. She had about, I think a three-year-old girl at the time. My husband oftentimes was roped into babysitting duties when she had to go for her clinic appointments. This was one such clinic appointment she was going to, and he was babysitting her elder daughter and got the call that she should go into the hospital. Didn’t know why. He had been asking over her health because he had noticed that she was puffed up. She didn’t look the same. She had gained a lot of weight in her face, in her legs. When he asked her questions about, “Is everything all right?,” from her perspective she said, "Yes. Doctor checked me out. Nothing for me to do." But for those of you who may be seeing where this story is going, she had undiagnosed preeclampsia.

Harlan Krumholz: And just for the audience, preeclampsia is—

Mary-Ann Etiebet: Thank you, Harlan. So preeclampsia is a condition where you have raised blood pressure during pregnancy that can cause some complications in different organs and can lead to irreversible damage in your kidneys, can lead to seizures. And by the time she walked into the hospital, it had gotten to the stage where she was seizing. And unfortunately, they were not able to manage it, and she died. And again and again, he asked the question, “Why didn’t we know sooner? Why didn’t we bring her to medical attention sooner?” And so these are some of the things that have informed the work that Merck for Mothers is doing.

Recently we’ve partnered with the CDC on something called the Hear Her campaign, which is about informing everybody, pregnant women, new moms, their partners, their families, their caregivers, what some of the warning signs of complications to pregnancy and childbirth are so that they recognize them. They can seek the appropriate medical attention. And then most importantly, those teams are activated to respond. Because one of the things we need to make sure that the audience knows is if you’re a Black woman in the United States, you are two to three times more likely to die to preventable causes of pregnancy and childbirth. In New York City, in Brooklyn, it’s eight to 12 times more likely if you are a Black woman. My sister-in-law’s daughter, who right now is of child-bearing age, she is actually more likely to die than her mother was. So this, as you said, is unconscionable tragedy. And what we are hearing from our collaborators is that many in the health system are not listening to Black and brown women when they say something is not right.

Howard Forman: You talked about some of the vast discrepancies and outcomes that we see between Black women and White women in America. And also about the fact that we are worse than a lot of emerging economies. Within our peer nations, we’re not even in their peer group in many ways. And with emerging economies, economies that have vastly lower resources, we perform worse in this area. What are the types of interventions that you have been supporting? And can you tell us some success stories, either domestically or globally, that speak to why this is not just a problem but a problem that we can address and fix?

Mary-Ann Etiebet: Great question. There are definitely success stories out there. I think the challenge is how do we scale and replicate them? Outside of the U.S., there is a lot of work to do to increase the standard of care that’s given and increase quality of care that’s given. There’s also a lot of work to do to make sure that women are giving birth with skilled birth attendants or in quality facilities. And so that’s a lot of the work that Merck for Mothers supports outside of the U.S.

And just to give you one example, in a partnership called Saving Mothers, Giving Life, which we entered into with many different U.S. government agencies, that a health-system-strengthening approach to increasing quality across and saturating quality across districts actually saw more than a 40% decrease in maternal mortality rates during those interventions. I think the interesting finding there, and that is something where I think it’s actually very related to what we’re experiencing during COVID, again, it wasn’t just one change that made the difference. It was a whole array of interventions that supported women, from increased awareness and education, getting them to facilities and supporting quality care while they were at facilities. And for many of us, whether we work in the health system or we just experience healthcare, I think we understand just how complex and complicated it can be because there are so many different touchpoints. And so that type of investment in health systems is critical if we are to see improvements and, as Harlan so aptly said, our mothers not to die during pregnancy and childbirth.

Harlan Krumholz: So I’m just thinking that there are likely lots of interventions, community level, government level, local, federal, but how much do you think of this is because of the actual cost of care to individuals? People are either uninsured or underinsured. And so there’s a reluctance to seek care because it will cause financial toxicity. It will cause them to have to expend resources they just don’t have, [that] they need or rent and food. And then if you combine that with a lack of trust in a system, like uncertainty about whether people are really interested in what’s important in your life, I mean, is that what you think is at the crux of this, or is it structural racism? And then are there pieces to this system that are just set up against folks, people of color, in ways that people who don’t have to face those challenges have difficulty imagining? I mean, where do you think it is?

Mary-Ann Etiebet: So Harlan, it really is all of the above, and I can’t overestimate this enough because we have to address all of these factors. You mentioned access to care and insurance and financial hardship. We know that many of these deaths actually happen after women have given birth, after they’ve gone back home when they’re in their communities, often when, for example, their Medicaid coverage, which in many places now ends about six weeks after delivery, after that six-weeks point. And so because of that, they don’t have anyone to call if they are experiencing symptoms, or you’re right, they don’t want to go to the emergency room because of the potential financial hit, or they don’t have anyone to take care of their other children while they go and seek medical attention.

So that is definitely a factor and something that we need to fix, but it is also all of the above because when you look at the data and you control for income, education, zip code, financial coverage, you still see differences between races in not just deaths but also in adverse events. So there is a huge element of structural and systemic racism that is affecting this in the United States. Some studies show probably about 50%; it’s driving about 50% of the difference.

The other thing you mentioned around what we also call the social determinants of health, those non-health factors that are driving poorer health outcomes. We see that in our community partnerships when folks don’t have housing, or there are not hospitals or facilities close by or that are easily accessible through transport. So it really is all of the above, and that’s why it has to be a whole-of-society approach to the solutions. It’s not just any one sector’s responsibility. I also like to flip that and think about it from a more optimistic perspective, because it means we all have a role that we can play, and we can all make a difference because there’s so many things driving this phenomenon.

Howard Forman: One of the challenges of the last two years, I think, during the COVID pandemic is that we uncovered this really vast array of disparities in health and health outcomes based on race and other factors. So it’s an easy topic to talk about right now, everybody in healthcare talks about health equity, but I’m curious to know, how do we sustain that momentum and how do we take the work that you are doing in this specific area and draw more attention to the broader field of health equity and both identify the challenges and respond to them? What are your thoughts on that?

Mary-Ann Etiebet: That’s exactly what our team is tasked with right now. How can we take the lessons that we have learned, the information around some of the impact and successes that we’ve had in the maternal health space, how can we now take that into other areas that our company is working in, whether it be oncology, infectious disease, and others? What I will say is that in order for us to sustain this momentum, we need mechanisms in place to hold us accountable. And we need the data to be able to understand if we are actually making a difference, if we’re actually moving the needle. If we don’t have those accountability tools, I do believe—or I do fear—that in six months, in 12 months, the world would’ve moved on to its next crisis and have forgotten the still critically important work that we have to do around health equity.

Howard Forman: I just want to thank you once again for being the consummate educator, scholar, and leader that you are and also to point out for our listeners how not just gracious but generous you are with your time in mentoring students and junior physicians that are out there. You are a true leader, and we are just so proud to have played some small part in your career development. So thanks for joining us.

Harlan Krumholz: So just last thing, Mary-Ann—your prediction. How long till we fix this problem?

Mary-Ann Etiebet: Well, if our team has anything to do about it, 2030 is the finish line we and the rest of the world have set for ourselves with the sustainable development goal. And we’re working full steam ahead.

Harlan Krumholz: Good. Within a decade.

Mary-Ann Etiebet: Yes.

Harlan Krumholz: Good.

Howard Forman: Thank you.

Harlan Krumholz: Okay. Thank you.

Mary-Ann Etiebet: Thank you.

Howard Forman: Harlan, what’s one thing that inspires you or keeps you up at night?

Harlan Krumholz: Yeah. I think this goes more in the theme of keeping me up at night, it’s something that’s been occupying my thoughts lately. We are so proud of the Affordable Care Act, Obamacare, it seems like it’s here to stay. Thank goodness. But yet, you and I have talked a lot about its need for improvement and expansion and how it was really just a first step in a progression that’s necessary in order to really raise our healthcare system to a level that many others have already achieved, let alone beyond that.

I think one of the things that we often forget is that there are still many, many Americans who are uninsured. Now we know underinsurance, people who don’t have adequate insurance, continues to be a problem, but they’re almost close to 10% of the population, 28 million people, 30 million people, something like that, who actually don’t have insurance in this country. And for them, it continues to be a constant threat if they don’t feel well, they’ve got a problem, and I spent last weekend in a clinic that we run at Yale for people who are uninsured, working with medical students, it’s a remarkable clinic, the HAVEN Clinic. The medical students did just this fantastic job. And we as attendings come in and do our best to help, but they really run this and provide so many support, education, social work, assistance, pharmacy assistance, and so forth. But we ran into a situation where there were people with diabetes who were on a medication that can reduce their risk, known to reduce the risk of death and complications by about 20, 25%. And we ran out. And none of those people in the clinic could afford it. It’s an expensive medication. It’s about over a thousand dollars a month. And so we had to start taking people off of that medication because they simply couldn’t afford it. In the United States, we have the means by which we could help people be healthier—clear med with strong evidence. And yet we had to take it off, and so I’ve been just thinking a lot about, shouldn’t we in this country be identifying the essential medications, the medications that we know have the strongest evidence and provide the greatest benefit and make sure that there’s no one in our country who can’t have the benefit of them? I mean, for example, we have a drug that can cure hepatitis C. And yet we know that there are people in this country who simply can’t afford it, don’t have access to it. And we have colleagues who have written about this in the prison system where you get free healthcare, but there are people who don’t want to get access to those meds, because they’re too expensive. So I think this is something that has to be solved, and it will be a continuing source of inequity, actually growing disparity if we don’t, as new meds come out, they provide greater benefits, and yet there’s populations that just can’t have access to them.

Howard Forman: No, it’s a great narrative there. First, I just want to comment on that. The Commonwealth Fund did a nice brief on this a couple years back just pointing out that the underinsured grew by just about as much is the uninsured shrank after the ACA was implemented, which is not to say the ACA wasn’t successful, but to your point, we just still have a lot more work to do. And access is the end point. It’s not just about saying you have health insurance; it’s making sure that you could actually access the healthcare system. And I want to also just thank you for staffing that clinic. I’ve been a peripheral helper in that clinic for 15 years as a faculty advisor and coordinating the radiology piece for it. Those students do amazing work. It is a large group of individuals that provide really high-quality care, supported and mentored by people like you. So thank you very much.

Harlan Krumholz: It’s really all about the students. So thank you, Howie, but really my contribution’s so modest compared to theirs and so many other attendings also involved. So how about you, what’s on your mind lately? Anything keeping you up or actually delighting you lately?

Howard Forman: No, I really was delighted. I don’t know. There was a very funny video that came out right after Halloween that showed a 14-year-old boy taking two Reese’s Pieces out of the bucket and was just so excited by it and so happy by it. And it just reminded me that things are much, much closer to normal now than they were just a year ago. The Macy’s Thanksgiving Day Parade is going to be back to its usual self. We have full classrooms. Plans for Christmas are back. So even as we still worry about COVID and we make future plans, I think it’s just great to acknowledge how far we’ve come and how much benefit these vaccines and other non-pharmaceutical interventions have helped us in getting to this point. And so I just am feeling really good about these things today.

Harlan Krumholz: No, I’m so glad you hit a bright note. Yeah. We still have work to do with vaccinations, boosters, kids. There’s lots coming out and things to do, but it’s nice to see as I watch sports and I see, compared to a year ago, things are very different. We can just hope they continue on a similar trajectory.

You’ve been listening to Health & Veritas with Harlan Krumholz and Howie Forman.

Howard Forman: So how did we do? To give us your feedback or to keep the conversation going, you can find us on Twitter.

Harlan Krumholz: I’m at H-M-K-Y-A-L-E, H-M-K-Yale.

Howard Forman: And I’m at The Howie. That’s @ T-H-E-H-O-W-I-E.

Harlan Krumholz: Health & Veritas is produced with the Yale School of Management. Thanks to our researcher, Sherrie Wang, and to our producer, Blake Eskin of Noun & Verb Rodeo. Talk to you soon, Howie.

Howard Forman: Thanks a lot, Harlan. Talk to you soon.