Implementation Science in Global Health with Patti Gravitt, PhD

• After receiving her Master's of Science in biology from the University of North Carolina, Gravitt moved into diagnostics technology with the Cetus Corporation to help advance the development of PCR technology.
• Working with epidemiologists at Cetus exposed her to the possibility of merging her background in molecular biology with epidemiological research in HPV, which led to her PhD in epidemiology at Johns Hopkins. 
• Cervical cancer is the number one cause of death from cancer in women in 37 different countries, many of which are in Africa.  Gravitt says the biggest barrier to reducing global disparities in cervical cancer is the affordability of currently available evidence-based prevention intervention. 
• HPV vaccines are highly effective. Recent studies show that 70 to 90 percent of all future cervical cancer cases can be eliminated if the vaccine is administered properly. 
• In high-income countries, cervical cancer numbers have been significantly reduced through administering screening for precancerous lesions and through HPV DNA testing. 
• In addition to cost issues, in many low-income countries there remains a cultural stigma around cervical cancer, as it’s often associated with being promiscuous or “unclean.” 
• Implementation science efforts to bridge this gap in care include the possibility of a simple yet effective low-cost test kit that women could administer to themselves. 
• Rather than her identity being anchored to her particular discipline, Gravitt has always been open to shifting her disciplinary focus, following HPV and cervical cancer research as it unfolds, hence her move to implementation science. 
• In her position at NCI, Gravitt celebrates that NCI has been one of the largest investors in the research that provides the tools and technologies making a difference in cervical cancer treatment and prevention everywhere in the world.
• Gravitt advocates for taking a systems based approach when looking at complex obstacles of global health, allowing for more comprehensive and sustainable solutions. She compares the systems of molecular biology to the systems of human behavior and infrastructure, urging an approach that takes advantage of how inherently adaptive such systems are.
• Within the programs she’s developing at CGH, Gravitt promotes a greater emphasis on embedded implementation research, where researchers prioritize a bidirectional learning process between those delivering and those receiving cancer interventions.
• Quoting Russell Ackoff, a seminal systems thinker, Gravitt offers advice to young global health professionals, urging them to consider that “the righter we do the wrong thing, the wronger we become.” In other words, one should be mindful of global health interventions that unknowingly cause harm, despite being labeled as “expertise” or best practices.

[00:00:00] Dr. Rob Murphy: Welcome to the Explore Global Health Podcast. I'm Dr. Rob Murphy, Executive Director of the Havey Institute for Global Health here at Northwestern University Feinberg School of Medicine. Today's guest, Dr. Patti Gravitt, has dedicated her career to Global Human Papillomavirus, HPV, and cervical cancer research and prevention, and most recently has shifted her focus to advocating for implementation science and systems approaches to tackle such global cancer health disparities. Her NIH funded research includes the study of cervical cancer prevention in Peru's Loreto region in the Amazon rainforest. She's trained as a molecular epidemiologist, implementation scientist, and currently is the Senior Advisor of Populations and System Sciences at the National Cancer Institute Center for Global Health. We are delighted to have her on the show today to talk about her career path in global health, her cervical cancer research, and how implementation science research can be applied through a systems thinking lens to achieve global health equity in cancer. Welcome, Patti.

[00:01:19] Dr. Patti Gravitt: Thank you, Rob. It's a pleasure to be here with you guys.

[00:01:22] Dr. Rob Murphy: Let's start with how you began your career. You received your Master's of Science in Biology from the University of North Carolina. And later completed your PhD in Epidemiology from Johns Hopkins University. Can you tell me about your early days and why you pursued biology and later epidemiology?

[00:01:39] Dr. Patti Gravitt: I came from a working class family, I'm the first person in my family to go to college at all, much less to get an advanced degree. And we grew up in a fairly small farming community in North Carolina. My father worked for the power company there. And so what he was seeing as I was getting ready to apply for colleges is that, you know, the engineers who came in were making, you know, more money than he'd ever made in his life, in their first job. So he thought, electrical engineering Patty, you're smart. You could do math well. You go, go, go do that. And UNC Charlotte was actually a really excellent school for electrical engineering in our state. I took the first kind of introductory class in electrical engineering and said, this is absolutely not for me. And so at some point after switching majors a couple of times, I said, okay, , whatever I'm taking this semester, that's the easiest for me to do well in, and I have to work the least hard at it, I'll do that. And that just turned out to be biology. So I continued on at UNCC to advance, you know, with a master's in science in general biology, but really focused on molecular biology. This was, between 1988 and 1990, and we were one of the first labs to actually do polymerase chain reaction at UNCC. So that's what kind of got me started into a love for molecular biology. And then I moved over to the diagnostic industry because I'm one of the few people who had experience in looking at PCR-based diagnostics. This was in the early nineties, and this is really where Cetus Corporation, who developed PCR was working with Roche Biomedical Laboratories at the time who are now LabCorp and transferring a lot of their diagnostic capabilities for HLA testing for Papillomavirus, which is the thing I worked on in graduate school as well, into diagnostics in the laboratory for clinical use. And so I worked and actually was invited to move to Cetus to help advance that work in the diagnostics industry. Stayed there for about seven years, working in industry, developing the molecular assays that we used to define the HPV was actually a cause of cervical cancer to differentiate which genotypes cause cervical cancer. And in doing that I worked with a lot of epidemiologists to try to really untangle the causal associations between HPV infection, which, you know, there are more than a hundred different HPV types. So which ones cause cancer and which ones are pretty ubiquitous and benign was an important research objective. And in doing that, I decided there's a real opportunity for people with a molecular biology expertise to move into epidemiology and kind of merge those two disciplines. So that's what I did when I moved to Johns Hopkins in what year was that? 1998 to pursue my PhD.

[00:04:08] Dr. Rob Murphy: Your interest in HPV and cervical cancer started really quite early. What inspired you to focus your research on cervical cancer, particularly in the global context?

[00:04:18] Dr. Patti Gravitt: Yeah, that's a really good question. And I think like most people, you really start thinking about your subject matter fairly opportunistically. So my master's thesis advisor was just starting to look at human papillomavirus. Again, this was in the era where we were still trying to define whether or not it was actually causally associated with cervical cancer. Then I grew really interested in it and the questions just kept building and emerging. It was something that felt really fortunate to have experienced of getting into a field just as it was growing. We had spent most of the eighties really believing that cervical cancer may be caused by other sexually transmitted infections like herpes viruses or chlamydia. And so it was really in the mid 1980s when Harald zur Hausen, who won the Nobel Prize for papillomavirus showed some pretty compelling evidence that most cervical cancer tumors had papillomavirus DNA in them. So, my work started with working on how to detect hPV DNA in human tissues. And then how to, you know, conduct the epidemiologic research to prove those causal associations, and then how to translate that evidence, into things that could help clinical practice. So I just kept working on that for many years. Then, you know, again, opportunity knocked and so one of my mentors at Johns Hopkins was Kirti Shaw, somebody who had been long involved in many of the seminal studies to prove that HPV was a causal factor in cervical cancer development. At the very end of my PhD, I worked with him on writing a grant to do some molecular epidemiologic studies in India. And so the grant ended up getting funded. I was fortunate enough to be offered a tenure track faculty position at Hopkins to pursue that work and develop my own research. So that's where I started working in India with the initial goal just to do the molecular epi work. But that was my initiation into global health.

[00:06:07] Dr. Rob Murphy: According to a recent report from the American Cancer Society, cervical cancer is the number one cause of death from cancer in women in 37 different countries, with 29 of those countries being in Sub-Saharan Africa and the rest in Central and South America. What are the biggest barriers to reducing this global disparity, and what kind of solutions do you propose?

[00:06:30] Dr. Patti Gravitt: I think the biggest barrier, to be honest, is the access to currently available evidence-based prevention intervention. So we have a really highly effective HPV prophylactic vaccine, which we've just over the past few years discovered that if you give one single dose between the ages of nine and 13, it will prevent at least 70 to 90% of all future opportunities for cervical cancer development. Scotland just came out with a paper which showed that since their vaccine introduction program, they have had zero cervical cancer cases now in Scotland among those who were vaccinated at the appropriate early age. So this is really a population phenomenon. Unfortunately, there are still certainly cost issues with making the vaccine available in some of the countries in Sub-Saharan Africa. Sometimes there are political will, so I think that, you know, we can rest assured though that with Gavi, with a lot of international UN agency partners, there's a lot of effort to meet and work with the political governance structures within these countries to see how we can get vaccines available. And for the lowest resource settings in Sub-Saharan Africa, that probably should be the absolute highest priority. And the second thing, and it's what I work on the most now, is we have prevented cervical cancer from being a number one cause, or even in the top 10 leading causes of cancer mortality in many high-income countries by effectively screening for precancerous lesions and treating them and preventing ongoing progression to invasion. And that's through our PAP screening programs, which have now been really improved upon with a much more sensitive test, which could be delivered less often. And that's HPV DNA testing as a good marker for people who are at risk for having pre-cancer. And then further diagnostics could identify those and treat them before they progress. Treatment being really simple, outpatient procedures. That again is a cost issue in many countries. It requires a lot of infrastructure across multiple sectors of the healthcare delivery system. You know, people are very willing in many global settings to talk about breast cancer, but there's still an incredible amount of stigma around saying you have cervical cancer because it's associated with being unclean. It's associated in many cultures with being promiscuous. And so there's a lot of education that we need to do around that too. But we're trying to use implementation science, implementation research methods as well as some of the foundational research that's been developed to show, for example, that women could get screened by simply taking a little q-tip type swab and doing a self vaginal sample just like they were putting a tampon in and out really quickly. And, screening could be as simple as that. Many of them are gonna test negative and don't need to do anything for five or 10 years. And those who test positive, we're trying to get them to primary health centers for immediate evaluation and treatment. But that still remains a real logistical challenge as well as a cost challenge.

[00:09:31] Dr. Rob Murphy: Throughout your career, you've had some incredibly interesting roles around the country and the world. Just as an example, from 2011 to 2013, you were Vice Dean of Research at Perdana University Graduate School of Medicine in Malaysia. What was that like?

[00:09:48] Dr. Patti Gravitt: That was such an important experience in my career, I think. This was something that the Prime Minister's office in Malaysia did in collaboration with Johns Hopkins School of Medicine actually. So that was the partner school. I was at the School of Public Health. It was the development of the first Graduate School of medicine in Malaysia. The only one in Southeast Asia, other than that, was the National University of Singapore's Graduate School of Medicine with Duke University. So the idea was to take the curriculum that Hopkins had developed and apply it in private University of Malaysia and we wanted to establish the same three legs of academic medicine that Hopkins espoused which would be clinical care, teaching and research. So when we were thinking about research opportunities, it turns out that the person who was appointed to be dean at this new university from Hopkins, he and his wife and I had been working on STI research for many years, right? So I just happened to see her in the hallway and said, you know what? I think you've got this great opportunity. Nobody in Southeast Asia does epidemiology. It's really a needed part of research to balance some of the more omics type basic science that's going on in that region. And she said, well, why don't you go talk to Charlie about it? So, Charlie Wiener and I spoke and he said, why don't you come out and be Vice Dean for research? And so that was really an interesting example. There were some politics involved at the end of the day, so we left. But really understanding how research is conducted, the way that it's valued in a different context has been really important too in translating how we try to build capacity for cancer research at the NCI because we do have to appreciate that the metrics for quality research, the competing priorities researchers have in different countries really is quite different from what we experience in the United States. So it takes a lot of understanding to really help to develop the cancer research workforce that we really need to be more impactful in reducing cancer burden across the world because it really is gonna have to derive from those people working in their own settings and prioritizing research according to their own needs.

[00:11:52] Dr. Rob Murphy: I think I wanna emphasize one thing you just said. These connections that you made that ended up being so important were personal interactions. And you know, it's something that we really miss nowadays because there's so much, just digital meetings, virtual meetings and everything, just bumping into someone in a hallway and getting this idea I mean, it really highlights the personal interactions that are necessary to move issues forward. I think that's just a great example.

[00:12:24] Dr. Patti Gravitt: I think it is. And I think that, you know, just having those, I would call them agendaless opportunities to engage with your peers being there in person and, and being able to ideate together to kind of just randomly express an interest, you never know where it's gonna go. I mean, I've always felt that I've stumbled into all these fantastic opportunities and learning experiences and I don't know that I was seeking them out, you know, it's just they, they presented themselves. So that's another thing to always say is you, you've gotta be open to being prepared when those doors open for you.

[00:12:55] Dr. Rob Murphy: Let's move up to 2021. You were brought on as the new deputy director for the Center for Global Health at the National Cancer Institute, where you were tapped to lead implementation science efforts and provide scientific and programmatic direction across research, training, partnership, and dissemination goals. Tell me about this shift from molecular epidemiology research to implementation science research and your position at the NIH.

[00:13:23] Dr. Patti Gravitt: It's a great question and I always say that, you know, some people really become very disciplinary. I think my identity as a scientist became really attached to papillomavirus research and cervical cancer research, and less on which disciplinary focus I was applying. I kind of kept learning new disciplinary focus as the science progressed in that general area. So it started with the molecular biology needs, then moving to the epidemiologic associations, and then I realized as I was trying to do molecular epi work in the field in many different countries. Again, it's the challenge of human behaviors and how you can give anybody a technology, but you can't make them use it, right? And so there has to be a lot of meeting people halfway and that became just such a fascinating challenge to me, learning from the behavioral scientists who are really a key part of implementation research, you know, and understanding some of the theories. And I just really like to learn new things over time. I get quite bored if I have to just apply the same thing over and over again for a different problem. So that's just been really fascinating. One of the reasons I was so enthusiastic to move to NCI is that NCI has been one of the largest investors in the research that gives us the tools and technologies to actually make a difference in cervical cancer burden everywhere in the world 'cause they really did prioritize, along with many other funders, that we need technologies that will work in the context that they're the most needed. And that includes Sub-Saharan African, many other parts of the world. And we've had those and that evidence is generated and yet still not being used. And so really implementation science is that science to kind of help us to understand how we can do that better.

[00:14:59] Dr. Rob Murphy: Many trainees and interested junior scientists and faculty say, you know, What should I specialize in? What classes I should take or degrees I should get? Like why don't you just tell us how your background in molecular epidemiology enhanced your past and current role at the NCI?

[00:15:20] Dr. Patti Gravitt: I can give you my retrospective analysis of that. The one thing is that what defined molecular biology to me is very similar to what defines implementation research to me, and that is incredible complexity of systems that do not behave in a linear and predictable fashion. So in molecular biology, an enzyme may be induced to be expressed under a variety of circumstances, and it's going to be regulated by a variety of different mechanisms, and you can't always predict which ones are going to be infect because it's gonna depend, kind of what I would say was, you know, the soup it's sitting in at the time. Right. That's the beauty. And, I think of natural systems, right? They've got redundancy built in. The problem is that we can't really learn what we need to learn from them if we just start taking them apart and studying them independently. And a lot of the recent advances in molecular biology and systems biology are making tremendous advances in that way. I view that what how I used to look at molecules and cells and organs and you know, hormonal communications and things like that, cellular signaling, when I was a molecular biologist, applies equally when I start understanding human situations and how people interact together in a system to deliver a service, to receive a service, to make something sustainable over time to interact with their political environments. And so the principles of those two things are very much about understanding complex systems and applying a systems thinking lens to how you not necessarily solve a problem for good, because complex systems are adaptive, but how you engage with them and understand them to keep improving them over time. And so if I had to give anybody some things that I think every scientist from every discipline would benefit, it's from learning a little bit more about critical systems thinking theory and just how, we can take a textbook and understand immunology, but you can't understand the system of the immune response without taking a system lens. And so systems thinking has really been the thing that I've learned over the past decade that has changed how I approach all of my work. And I am almost evangelical about it.

[00:17:26] Dr. Rob Murphy: The NCI is known for cutting edge research. What innovative approaches are being developed under your leadership that might help detect and treat cervical cancer compared to what the standard approach was before you arrived?

[00:17:39] Dr. Patti Gravitt: Well, again, I think that the approaches we're using to cervical cancer within the programs that I'm developing at CGH is acknowledging what you said at the very beginning of your question, that we've already done so much innovation. We have so many technical tools. So what we're trying to do is to bring in similar innovation and implementation research to ensure that those tools get used and implemented sustainably where they're needed, and learning from that so that we can help, you know, kind of spread those best practices across multiple countries and contexts. And one of the things that we're trying to do that's a bit innovative in the implementation science world. It is not novel, so please don't think that, but it is innovative I think in terms of how we might fund implementation science, is looking at embedded implementation research where we do a better job, and I think we're doing this in clinical trials and many other things is more community and practitioner engaged research, because we have as much to learn from the people who deliver and receive and have to engage in these cancer control interventions like cervical cancer screening and vaccination, as they have to learn from us who generated the efficacy evidence, and so really enabling the researchers to learn from the ground and that bidirectional learning of us helping to show novelty and innovation and how people could change and transform their health systems to improve the cervical cancer mortality outcomes. That's what we're really trying to model in terms of the cervical cancer space right right now.

[00:19:12] Dr. Rob Murphy: Looking toward the future, what collaborative global efforts, whether through research partnerships or public health initiatives, do you see as crucial to sustaining the progress against cervical cancer?

[00:19:23] Dr. Patti Gravitt: I do think what's crucial is to take a more pragmatic view of the acceptability of practitioners in using tools and technologies in a way that works for them. I also think cost. A lot of times what's coming out for us are really effective, but very expensive health interventions, and while they can reduce mortality, they end up not reducing mortality because of exorbitant costs to many of these situations. And remembering even in countries with high cervical cancer rates, they also have competing priorities of things that are, for example, really reducing life expectancy, really creating high, you know, infant childhood mortality. And of course, anybody who has to make the hard decisions of where I'm gonna prioritize limited resources. It's probably in protecting the kids and not the middle aged women. That to me is just it's an understandable and hard choice, but I do think that the more that we can push getting really low cost tools that are available to countries, what would be great if there was much more local manufacturing for those tools so that you also avoided all of the importation, taxation, customs costs, you know, lots of, lots of challenges there with supply chain. I think those are things that would really move the needle, in my opinion.

[00:20:41] Dr. Rob Murphy: I have one last question. And I ask this of all my interviewees. What advice do you have for young people listening who are just now embarking on a career in global health?

[00:20:53] Dr. Patti Gravitt: It's a fantastic career. I would encourage you to read. There is so much literature coming out of the global health experts and those are the global health experts living in non-high income countries who are really giving us all incredible advice of how we approach research from a more equitable collaborative stance. How we, you know, try to remove the colonial lens that tends to have driven our research efforts in global health for quite some time. I think those are really important things that I would encourage people to read and understand there's a lot of compelling literature from the perspective of people who are addressing the problems in their own countries that we can learn a lot from. And I think the second thing it's a quote from Russell Ackoff who's a seminal systems thinker, and I say it to everybody every chance I get, and particularly to students who are embarking in the academic rigor of learning a discipline. But just remembering when you get out into the real world, and it's very particularly true in global health, you can only learn so much from a book, and we have to really make sure that we're not doing the wrong thing right. Because as Russell Ackoff said, we're largely devoted to doing the wrong thing right. And the problem with that is the righter we do the wrong thing, the wronger we become. And the way that I translate that into global health is we can be using the methodologies and our disciplinary expertise in exactly the way it was taught to us. But if it's hitting the absolute wrong target. We could just tie the knots tighter and tighter together that are really creating the barriers. And so the very first thing in the global health space is to hear what the colleagues on the ground are saying and what they care about and what they're thinking. And take your expertise and meet them where they are to partner together to co-create how to make the next level of advancement. That to me would be my best advice.

[00:22:48] Dr. Rob Murphy: I learned so much about implementation science, and I think your perspective is sorely needed. And we can all incorporate implementation into all of our work.

[00:23:00] Dr. Patti Gravitt: Absolutely.

[00:23:01] Dr. Rob Murphy: Thank you very much, Patti.

[00:23:02] Dr. Patti Gravitt: It was my pleasure and thanks so much for the invitations.

[00:23:05] Dr. Rob Murphy: Follow us on Apple Podcasts or wherever you listen to podcasts, to hear the latest episodes and join our community that is dedicated to making a lasting positive impact on global health.