Oby: From the campus of Harvard Medical School, this is ThinkResearch, a podcast devoted to the stories behind clinical research. I'm Oby.

Brendan: And I'm Brendan, and we are your hosts. ThinkResearch is brought to you by Harvard Catalyst, Harvard University's clinical and translational science center.

Oby: And by NCATS, the National Center for Advancing Translational Sciences.

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As a pandemic hit Boston and shut down labs and research across our community, patient safety remain the top priority. In a dermatology clinical trial studying a painfully debilitating skin condition called hidradenitis suppurativa, essential work had to go on without compromising the integrity of the research.

Dr. Alexa Kimball led this research team at Beth Israel Deaconess Medical Center in her clinical role, while also leading the hospital through the COVID-19 pandemic as CEO of Harvard Medical Faculty Physicians. On this episode, Dr. Kimball tells the story of using her experience as a clinician while also managing the logistical and managerial component of the hospital during this time. Dr. Alexa Kimball is a professor of dermatology at Harvard Medical School and the president and CEO of Harvard Medical Faculty Physicians at Beth Israel Deaconess Medical Center. Hi, Dr. Kimball. Welcome to the show.

Alexa Kimball: Thanks very much for having me.

Oby: You're a professor of dermatology and a clinical researcher. One of the areas you study is a disease called hidradenitis suppurativa. Can you tell us about this condition?

Alexa Kimball: Yes. Thanks. I study a disease called hidradenitis suppurativa. It has a name that's very challenging to pronounce, so I will just refer to it as HS as we proceed. But just for a moment, why it's called that-- hidradenitis refers to certain types of sweat glands, and suppurativa refers essentially to pus. And as I describe the disease briefly, you'll understand why the name really fits.

It's actually a more common disease than people anticipate. We now think it's about 1% of the population, and affects primarily young women, probably 20 to 30 in age-- 30 years and age, generally. And the way I describe it most of the time is like Crohn's disease of the skin. These patients are afflicted by abscesses, and boils, and [inaudible] [? of ?] [? tunneling ?] skin that has a lot of pus and drainage.

And it's primarily in the armpits and the groin, but can affect areas like the buttocks, under the breast-- in some cases, even around the face. So it is a debilitating disease, both because of the pain, and the odor, and all the other aspects of dressing changes and things that people have to do to try to disguise it, or that people tend to do to try to disguise it.

Oby: Tell us about how you encountered your first patient with this condition.

Alexa Kimball: Well, in dermatology training, we often would see the most severe cases, and so I would have told you 20 years ago that the only people were affected were really severe. They had scarring, and again, all of this drainage and all of this disfigurement from it. And then, around 2006, I was referred a patient who had had surgery.

And the surgeries can be quite extensive in order to take out all the areas that are involved, and they were-- the wounds there weren't healing as they had hoped, and so they wanted my opinion. And it was just truly a random encounter, in the sense that the surgeon hadn't picked me particularly, the patient hadn't picked me particularly, but I was the dermatologist who showed up.

And all of a sudden, I had this aha moment where everything that I had been studying in psoriasis, another very common skin disease, needed to be studied in this disease. And all the questions that we needed to ask were the same. The answers were going to be really different, but the questions were the same.

And from that moment, I just had this burning framework to try to solve and understand this disease much more profoundly. And then a couple of good things happened, one of which happened around the same [? time. ?] [? because ?] I had studied how to develop scoring systems and [? outcomes, ?] a colleague of mine in industry asked me to help design a scoring system to potentially put a therapy into a clinical trial. And so that was the perfect moment to say, how do we measure this? How do we think about it? What's the biology, and how do we really advanced the therapies for patients?

Oby: So you have a number of clinical trials open right now. Could you tell us of some-- the different approaches you're looking at to improve treatment of HS?

Alexa Kimball: Well, we're still, actually, I would say in the beginning of our journey of understanding with precision what causes HS. Clearly, the microbiome plays a role, given where it distributes in the body, which is-- tends to be the folds. There is clearly an inflammatory response and a wound healing response that goes awry and [? is mis-programmed. ?]

But what I think, scientifically, is so interesting is that this is going to be not a bench to bedside discovery. It's going to be a bedside to bench. And some of it we're not going to figure out till we actually tried therapies in patients and see what happens. So most of the studies that we currently have ongoing have to do with changing the immune response in the skin and, again, taking from other successes in skin diseases, using IL-23 inhibition, IL-17 inhibition, JAK inhibitors-- which have more of a pan-inhibitory profile-- and then some very early experimental medications that do things like block CD40 immunology-- so lots of excitement, and we're trying out a lot of stuff.

Oby: Yeah. So when the pandemic hit and research had to be stopped, what were some of the challenges you faced to keep patients safe?

Alexa Kimball: So as a investigator in clinical trials, and as I train a lot of people, the first thing that I do when they come is I sit them down and say, here is our hierarchy of thinking. It is always about the patient and the patient safety first. So you, as a clinician or investigator, need to evaluate what to do in an unusual circumstance to aid that patient.

Then the next thing you really have to think about is, what do I need to do to preserve study integrity? Because if we don't get good data and we don't preserve how the study is done, patients will have participated without there being an answer that they contributed to. And so you have a responsibility to the study in that regard.

And then there are a lot of clear regulatory things that you need to work through that are really designed to serve both of those needs. But really, if you have those two principles in mind, [? it'll ?] [? be ?] most of the way. So we were told that we needed to evaluate our studies, decide what was essential to continue, figure out who could be converted to telehealth, figure out how we were going to do measurements, how were we going to get patients their medications, and how were we going to manage this through it. So it was a lot of challenging considerations, but that was the framework we used.

Oby: Could we step back a second? I wanted to unpack a little bit the-- when you were talking about some of the treatments that you're trying from either other successful trials or things you've done in clinic. And you were talking about blocking some certain markers or-- can you explain a little bit more about that and what that means, what that does? I was just curious, as you were talking about and talking about the different markers, what they are, and what they do, and what you're blocking.

Alexa Kimball: Sure. So when you unpack what causes many skin diseases, just being part of this paradigm, you have some sort of insult, injury, or something that your skin is reacting to. Your skin [inaudible] incredibly robust immunologic system, because it's really your first line of defense.

But in the-- its attempts to protect you, it sometimes over-responds or misresponds. And you could see why there would be a lot of even evolutionary pressure to design systems that were protective against skin diseases, particularly when there were no real therapies [inaudible]. And so there seemed to be a couple of very important pathways in the skin that we really determined in the course of developing medications for psoriasis, and that includes interleukin 17 pathway and interleukin 23.

And so these two cytokines are incredibly important in driving the skin's immune response, [? and ?] [? seem ?] to be highly specific to the skin and gut-- more so than, say, TNF-alpha inhibition, which is a more general immune cytokine sort of engine. And so when we're trying medications like this out, what we're trying to do is essentially calm down the immune response that is ongoing, allow for the wound healing program to reset by getting the inflammation to calm down, and essentially revert back to a more normalized approach to whatever the insult and injury might be.

Oby: So your work has been affected by the pandemic not only as a researcher, but as the CEO of Harvard Medical Faculty Physicians at Beth Israel. How did your experience as a clinician inform your decision making around the pandemic as CEO?

Alexa Kimball: So as CEO of Harvard Medical Faculty Physicians at Beth Israel Deaconess Medical Center, we employ about 750 physicians and a couple other providers as well. And so with the abrupt shutdown of some clinical care, but the incredible needs in other areas-- particularly the ICU, infectious disease, and the emergency department-- we were managing an incredibly fluid situation in terms of planning and logistics.

I do continue to see patients and do research, and I think those two things that I do really helped me be better at my job in terms of understanding what physicians are encountering, what the patients are experiencing, and how to find ways to make the systems work better for people. And I think one of my big takeaways from this experience in terms of the empathy that you need for the experience is that everyone went through this in a really different way under very different circumstances.

And you couldn't anticipate or understand them all, but everybody was hurting, or grieving, or trying their best, and dealing with all sorts of unpredictable things. And that, I think, was something that was very core from my experience as a clinician and as a researcher as well.

Oby: What kind of processes were put in place in the hospital to manage the influx of patients and the research demand on them?

Alexa Kimball: Well, in the research area, we had to figure out which patients and studies were really essential. And for my patients with HS, who have scarring, disfiguring, potentially infected areas that can sometimes require hospitalization, it really was a risk benefit analysis about, what did it mean to continue in the study versus not being on medications at all, and what monitoring could we safely do?

Fortunately, with telehealth connections, there was a lot of work we could do remotely, but it's almost impossible to do a good assessment of disease activity by telehealth. You can kind of get a sense from pictures and video, for sure, but to do a really quality score was almost impossible. So that said, we wanted to make sure we were doing the best for them.

So the patients who were on studies that we felt in our judgment were appropriate to continue, given the other options for them, we continued. We stopped putting new patients onto studies until we had a better sense of where we were, but we were able to get them through it and be able to really come out here on the other side, I think, with a good outcome for them and for the study overall.

The other thing that happened is that we had a huge number of inquiries that came in around doing COVID-related studies [inaudible] interest from all sorts of different sources for-- everything from prevention to ICU treatment. And these were really important to do, and to do well, because obviously, the whole world is watching and waiting for us to figure out better approaches for managing this disease.

So it was a moment where my background and clinical research, again, came in handy, both-- I had queries come in, and I knew where to send them, but also in thinking through, how many studies could we really do? How did we keep the burden on the teams to a reasonable level? How did we make sure that we had enough patients in each of those studies? So these were all really important questions as we chose which ones we wanted to participate in.

Oby: What are some of your takeaways from earlier this year?

Alexa Kimball: The first is I work at an incredible place with incredible people. The teams just dug in, rallied, thought creatively, worked their tails off, and committed in all sorts of selfless ways to getting us through this and saving a lot of people. This was incredibly challenging, but the resiliency and the power of the mission here was what really kept everybody going, and people were remarkable.

So that was a great story. I think the second is, as a manager and as a leader, I really had to switch gears to think about a different type of management style in order to see us through a crisis. I've been through a few smaller crises before, so I had a little bit of practice generically, but this required really a wholesale different approach to, how do you organize teams, communication, processes in order to make the moves we had to make in a really dynamic way in an uncertain time? And I'm starting deliberately to go back to my more typical management thinking [inaudible] really did require a totally different approach for a period of time.

Oby: Right.

Alexa Kimball: Reflecting back, one of the huge advantages we had in Boston was really the breadth and depth of our medical community. We also had a little bit more time than New York did, because we were a little bit behind the wave. And I think those two things together allowed us to prepare incredibly well, and so it never felt as chaotic here as it sounds like it may have been in New York.

So a few things-- one is we had a robust research community completely ready to receive these new ideas, queries, studies, and investigation. We also had a research community of clinicians who were able to change their day-to-day activities and help us with the clinical needs that we had in a way that you might not find in other parts of the country.

And people did this. They put their research labs on low burner, and they dedicated themselves to this effort, and that was an incredible help for us. And then lastly, as we think about the ecosystem in Boston, we have all these incredible universities outside of direct delivery of medical care.

And we were able to use the innovation around town to help us get swabs, to help us make masks, to help us figure out how to sterilize things. We really capitalized on the entire intellectual capital here in Boston and that incredible goodwill to solve a lot of problems, particularly early in the epidemic.

Oby: I have a question more so about the future, and even thinking about going into the fall and the winter, and maybe resorts about-- you've learned so much during this time, and you've been talking about the different managerial style you employ. Do you think that is something that will need to be employed again? What do you see happening even in your research, as we as we move forward from here? I know that's a bit of a nebulous question, because we don't really know what's next, but--

Alexa Kimball: So it is daunting to think about managing this again, for sure. And I think there's two scenarios that we need to be thoughtful and start to plan for as potential. One is, in the scenario where we truly have another huge surge, what do we need to think about? Well, the first is this is not going to happen over a 48-hour period. There is some notice as you see cases and numbers go up, so we will have some time.

And I think, because of what we learned, we can be much more precise about what needs to be shut down, and when, and how we move into other areas for ICU care or other things. Remember, we pretty much doubled our ICU space outside of normal space to accommodate. So we know how to do that now, and we know what physicians we need, and we know what teams we need, so we'll be better at it.

And so I think, between the warning, the testing, and the experience, we'll be able to be much more surgical, as it were, in terms of how we ramp up, ramp down, and what we need to close. So that part's good. The other thing we have to think about is, as we enter the fall, people are inside more. Obviously, bringing people back to school at the universities and in elementary schools is really unknown.

And so thinking a lot about the multiple scenarios within that one that we need to manage is going to be really critical, because you can imagine not just a huge surge, but you could have just a substantial increase in cases that's truly persistent and a more constant way throughout winter and spring. And that requires a different type of call on the resources, more like we would see maybe in a really bad influenza season-- certainly need to think and plan carefully around it, but might feel different than a surge.

As I think about the therapies that we need in order to manage all of this, obviously, a vaccine would be incredible, but if we could even come up with a medication that mitigated it [inaudible] early in the [inaudible] so that we could treat broader populations, that would also be a game-changer.

Oby: Mm-hmm.

Alexa Kimball: And so I think-- and this has been the approach-- but we clearly need to be firing on all cylinders, because one solution's probably not going to be enough. We'll need several in order to get us through this. That said, we took a very bad hand and got through it here in Boston about as well as we could have, and I'm really proud of the work that we did, and really grateful to everyone who contributed.

Nothing makes me happier than being allowed to get back to doing some research and [inaudible] the regular clinical setting. It's both really good to see the patients and good to feel that sense of normal interaction, albeit under some slightly different circumstances. I think getting reopened in general is complicated. There's just tons of logistics, both in clinical care and in research, but they're all doable.

It just takes a lot of planning to figure out what you need, who should come in, how do you contact them, how do you reschedule-- all of those types of things. And I think the main part we don't really know yet is how patients are going to feel about coming back. Already, we've seen a lot of people come back, and I would say, in my practice, of all different levels of intensity of their illness.

But we just don't know how people are going to feel about coming back into research or coming back in for things that maybe they don't view as important. And so we'll have to continue to communicate with them how important these things are and how-- the precautions that we have taken in every environment to really protect people-- both our staff and our patients as well.

Oby: Well, Dr. Kimball, thank you so much for being with us and having this conversation. It's been a pleasure.

Alexa Kimball: Thanks very much for including me.

Brendan: Thank you for listening. If you've enjoyed this podcast, please rate us on iTunes and help us spread the word about the amazing research taking place across the Harvard community.

Oby: To learn more about the guests on this episode, visit our website, catalyst.harvard.edu/thinkresearch.