Hello, everyone. Welcome to COVID-19 and Clinical Registries. Both the chat and Q&A features will be available throughout the session, so please ask questions, make comments, and stay engaged. Thank you for joining us today and for attending this session. Now I'll turn it over to Bill, our moderator, to introduce today's panelists. Well, good afternoon, everyone, or I guess it's still late morning on the West Coast. We really do appreciate your joining us for what I think is going to be a terrific discussion, and my thanks to our panelists who I'll introduce as we go along. In Chinese, the symbol for crisis has two characters. One is a character for danger, and the second is a character for opportunity. I think what we're going to be discussing today is, quite frankly, the opportunities that COVID has presented, particularly relative to the use of registries. I'm very pleased to have, as I say, our distinguished group of panelists, and I'd like first to introduce Dr. Nancy Dreyer. In addition to her PhD, she has her Master's in Public Health and is the Chief Scientific Officer for IQVIA. So Nancy's going to lead us off, and she has to leave a little bit early, so we're going to do her question and answers at the end of her session, and then we'll proceed on to the rest of the program. Dr. Dreyer, please go ahead. Thanks very much, and hello, everybody. I'm delighted to be here and appreciate this opportunity to talk to you. I'm going to bring up my slides as we say more willingly. Okay. I'm assuming that you can see what I see, and I'll go dark so I don't eat up your bandwidth. Hi, everybody. By way of background, I'm a practicing epidemiologist. I've been at this for nearly, we'll just say more than 30 years. I have a deep, abiding respect and interest in patient registries and had the privilege of being called on by the U.S. Agency for Healthcare Research and Quality in collaboration with Centers for Medicare and Medicaid back in 2007 when they came to us and they said, you know, we're never going to have enough information on clinical trials on patients that are of interest to us, so we need to understand how to use these patient registries. So I was able to be a senior editor of a book that was published in 2007 and again in 2010, 14, and the fourth edition in 2020, which is a how-to book. It's actually a user's guide for registries of patient outcomes. Been very influential and also given me a great opportunity to stay in touch with the movers and the shakers in patient registries, and you certainly are in the right society and with the right people who understand the value of this. I wanted to take this time to share with you a little bit of some of the new approaches that we're using to patient registries. Specifically, I'm going to start out giving you a little bit of history, if you will, of how patient registries filled a need that people that turned out to be critically important. So let's go back in time. Okay, here we are. I don't know if anyone remembers this, because this was a pandemic threat that pretty much stayed contained to Southeast Asia, but it was about 2005, 2006, avian H5N1 influenza. Now, this was an attention-getter, because this disease, when you got the median time to death from first symptom to death was nine days. And the case fatality rate in Indonesia, for example, was over 80%. So you were likely to die. You were likely to die quickly. And the question was, if there were any effective treatments, could you even get them? So this, as you remember, we were busy culling chickens and worried about how to stop the spread of this flu that used birds as an intermediate host. So I had the privilege of having the opportunity or being asked, could we put together a global patient registry? Now, this was like ancient times in terms of technology. So imagine that this registry was all a paper-based endeavor. We actually, I like to think of it as shoe leather epidemiology, an old term, but it really applied here. I used my shoe leather or my airline miles, traveled all around the world to the major countries that were affected by avian influenza. And we appealed to whether it was the local health department or hospitals or physicians who had written up their cases and asked if we could use a standard case report form and abstract their records. The WHO, meanwhile, was interested in this and trying to put together a registry. But while they were laying the groundwork, and if you can imagine trying to organize ministries of health from 146 countries, you can understand how daunting that task was. Instead, I was able to just go out with a small team and we were able to assemble information on two-thirds of the world's known cases. The major focus was to find out if there was anything, any treatment or anything that enhanced your chance of survival. So remember, there was no time to do a clinical trial. There were no approved treatments. This study or this work was funded by Hoffman LaRoche. At that time, Tamiflu was relatively new, oseltamivir. It was approved for seasonal influenza. Nobody thought it was going to be any help, particularly for this disease. But the opportunity was to see if there was any treatment. It didn't matter whether it was Roche's product, but any treatment that could prolong survival. It was really an exciting venture. What we learned is Tamiflu was used widely. It was a relatively new antiviral at the time. If you used it according to the package insert, which is within 48 hours of first symptom, it quadrupled your chance of survival. So talk about a big effect, a big benefit. But then if anyone spent time in Southeast Asia, there are a lot of rural settings where you don't necessarily have access to medical care quickly. And Indonesia, for example, is a lot of islands where you can't necessarily get any medication on your island. So we did look at delayed initiation of treatment and found that even if you didn't get your start, your Tamiflu until five days after first symptom onset, or I guess it's six to eight days as shown on this slide, we nearly doubled, this nearly doubled your chance of survival. So this is an example right there, that second bullet point on the right. This was news. This was a huge finding because there were no treatments. It was a treatment that could be repurposed and it had a big benefit. We also were able, had the privilege of working with pediatricians from around the world. And we looked separately at the symptoms experienced by children and their prognosis and found very different prognosticators. Just for example, if there are any pediatricians in the audience, we found that children who had a runny nose, really that was one of their presenting symptoms, almost always survived. And some of my colleagues were thinking that perhaps they were just shedding the virus. I don't know who else picked it up, but it's an example. And you can see here, we have, we wrote up the case study, this as a case study in the Journal for Clinical Studies, just describes not just how we did it, but governance and working with the various societies. Talks about what worked and what didn't work, references right here. So fast forward, that's a nice story, looking at medical records, you know, in places where they weren't automated and everything was old-fashioned. Now I want to take you to the next milestone in my registry career. And this is, this is, I don't know, eight years ago or so. This is a project I did with the European Medicines Agency. And the question was pretty much, can you trust consumer reporting? So the EMA was looking for new ways to do pharmacovigilance. And they wondered, could you go right to the patient? Now I realize I'm talking to a bunch of clinicians, but bear with me, I'm going to show you what this is valuable. But the, what, so what we did is a demonstration project. And we picked pregnancy, because little is known, and women don't generally come for care in the first trimester of pregnancy. So, and especially if it's not their first baby. So they, we, they don't get counseling, and we don't know much about teratogenic factors early in pregnancy. So tremendous unmet need. So EMA said, let's, let's, we got this funded by the Innovative Medicines Initiative, or the European Commission. And in partnership with EMA, we did a test to see if we could recruit pregnant women, if they would tell us about their pregnancy and the various factors that might affect their unborn. And then in, we did this in four countries. You can see their flags there, UK, Denmark, Poland, and the Netherlands. In the, in Denmark, we were able to, with patient's permission, or participant's permission, we were able to link their responses with a national prescription register in the country where everybody's prescriptions were recorded. So we could validate whether people told us the truth and whether they were accurate reporters. So the objective was to find out, could they report things accurately? And it was a fascinating project. We found out, not surprisingly, that women took a lot of medications in pregnancy. They took a lot of non-prescription medications, which were not available in any record, like an electronic medical record or a prescription register. So already, if you're trying to understand teratogenic effects, non-prescription medications are certainly an important factor to study. We did find when you talked directly to to pregnant women, they were happy to share or willing to share information on things they may or may not have shared with their medical care provider. For example, they were happy to tell us about their marijuana, their cocaine, their alcohol, their tobacco use. So it did show that it was a valuable source of information. When we compared their self-reported prescription medications with the Danish National Registry, we had pretty good agreement on their prescriptions for chronic indications, not as good agreement on prescriptions intended for short-term use. Now, the question comes up is why is that? When we dug a little deeper, especially on the meds for short-term use, we found something that I bet will be no surprise to you, namely that people didn't always finish their meds and they often kept them around for a while. So if we looked farther back in their prescription registry, we found the antidepressants. We found a variety of drugs which or the codeine or something they took on a PRN basis. And we did also ask them how often they didn't fill prescriptions that their doctor ordered and the like. So it turned out to be a great source of information, except when it came to the birth outcomes. A woman could tell you if she had a baby with a rare health, very rare and serious defect, she could practically quote you the ICD code. But the bulk of the consumer reports we had were vague and not particularly useful. You know, the eyes don't look quite right, the nose is in the middle of the face or his head's kind of big. So things we couldn't interpret and it was a very strong lesson which I've carried with me about the value of clinical validation for outcomes of special interest. So it was a useful lesson and a useful proof point and a great exercise to do in collaboration with a regulator where it wasn't a question of doing something funded by a funder that had a vested interest in the outcome. So now we started out with 2006. We went up to about 2008-10. These were still early days of doing internet-based studies and you might be wondering what does this have to do with COVID. So let's now we're up to 2020. IQVIA on its own, I could say dine but it wasn't really a dine, but on its own expense decided to launch a direct-to-consumer COVID research program. Now you might be wondering why would we go to the communities when the big problems were how to save lives when people were hospitalized and of course you're right. But this is more than a story just the COVID that we're all experiencing is more than just a just a problem for those who are serious enough to be in hospital. We wanted to know why do some people get coronavirus but not get sick and why do some people only have mild conditions and what could we learn from studying that. So this CARE project, the COVID Active Research Experience, is now running in the United States and if you're good at geography you'll know that on the right I'm showing the map of the UK where we're also operating. We started our first wave of recruitment in the U.S. in April and recruiting in the UK in July and we're very excited to welcome the FDA as one of our official sponsors. There's an unusual feature of this registry in the U.S. that I wanted to draw your attention to in that sizable bullet on the bottom of the chart. Namely that in the United States we're able to use what they call a tokenization process to support linkage with other accessible real-world data that we have at IQVIA. Specifically we're able to link patient with their consent link patient respondents or participant respondents to outpatient pharmacy data to some ambulatory care data and some hospitalization data. And I just want to emphasize this. We can't link everybody. Right now we're linking about half of the people with data that we have but imagine when you're asked to tell to talk about the medications you take. You may not remember them all and for example this gives us a chance to have a validation subset if you will. So you know Jane Doe said she was taking antihypertensive let's see what she filled. So it's a nice way to reassure yourself about the accuracy and completeness of reporting of various events including consultation for medical care. Now in this in this political day and age this it's turning out that this registry is actually becoming even more important because it addresses one of the questions about who do you trust? And I'm sure I would trust just about everybody listening to this to this session but there's so much misinformation and it's hard for people to tell what to trust or not but there is a great deal of belief among consumers that we can trust each other. So the idea of person generated health data is continuing to grow in terms of the value that's ascribed to it and look at the kinds of data that we're trying to get out here. So remember the concept is people recorded the target population is people record recruited from the community based on exposure not test results. So if you live in a cloistered environment never get out this is not the registry for you. But if you have family members who get out or you're a health care worker or you go out and go grocery shopping or do your chores or go to an office these are the kinds of people we're trying to collect information. So the main thing we're studying is symptoms and symptom severity and changes over time. So that's the key outcome variable. And then this clover leaf is showing you the key things that we're looking at again in an effort to find out if there is any combination or any meds that are being repurposed for COVID that work and what makes you recover faster or be more resistant. So we've got the prescription meds the non-prescription meds we wanted at the encouragement with of FDA they said gee it'd be great if you got the OTC meds and the vitamins and the herbals. Maybe it's a combination of zinc and something else maybe it's vitamin D. We don't know but we're asking and we're asking questions in a way that consumers can ask can answer. We also understand that everything has to be taken in the context of people's underlying health conditions. Are they obese? Do they have a variety of conditions situations like that? We are asking if they've been tested for COVID and soon we'll be adding questions about the vaccine. So for those of you who like the details, here's a little bit of information. You can see we record them at baseline, we talk to them, and then we have follow-ups monthly every one week for the first month and then two weeks for months two through 12 because now we're going out into long COVID. So that's what we're doing. I think the value then of extending this to vaccines as imagined, we'll be able to compare people who get different vaccines, so you know if one is working better than the other or safer than the other. We'll have the background in the unvaccinated to understand symptom and symptom progression and we hope to be building a steady flow of events because we can't wait for the formal studies and the formal trials. And with that, let me stop. I'll leave you with my yin-yang. We need all these kinds of research tools and I'd be delighted to take questions or however you'd like to proceed. Thanks very much, Dr. Dry. That was just terrific. We do have a question actually that Greg has put in the chat and I don't know, Greg, if you want to just go ahead and ask it directly if you'll take yourself off mute. Sure, I'm happy to and thanks, Nancy, because that was really, really great and interesting to see. So the question is about you described the care registry program and linkage of that to prescription and other health care and counter information and I'm wondering is the limitation you described, is that the participant willingness to share or is that a technical feasibility of the ability to connect those elements? I don't know how much of a limitation is one versus the other. Yeah, I think it's large. So to participate in the care registry, you must consent to linkage. That's part of the participation. And then the linkage question is just there are a number of ways to link data. We could ask people to one by one download their EMR. Now we can. We haven't done that or haven't done that yet. Instead, we've taken the easiest, the low hanging fruit, if you will. And for those of you who know IQVIA, we are a big data company. So through various licenses we've had, we've started with that and started with that linkage. It's about, you know, we have about a 10% sample of the hospitalizations in the United States and various levels of details. You never can link as many as you want though. So we need partnerships and we need, you know, we did this all on our own. Now we're growing a little bit. So hopefully more linkages will be possible. Because we need that clinical validation. We need that clinical input. But we also need to know what on earth people are really doing at home. Great point. Deidre, there's one other in the Q&A box, I believe. Let's see. Yeah, this is from Dr. John Morris. It says, Dr. Jarre, do you think that the, quote, direct-to-consumer approach will be the dominant registry and a long-term follow-up engagement mode following COVID? I think it will. Because let's think about where we are today. I mean, who wants to go out of their house if you don't have to? I mean, I, you know, my husband's older than I am and he wants to stay home all the time. Nobody should go out, nobody should leave, and we shouldn't visit our children. And there, you know, people aren't getting the medical care they need or less and less of it. So, I think that it's, COVID is a great example during shutdowns and the consequences of trying to understand how people are feeling and how sick they are. Because many are reluctant to get medical care. And I think the long COVID that is now getting to be a concern is another a good example. Or the questions about if you've been hospitalized and survive a hospitalization, what is life like? So, we're hearing questions about, you know, what's my mental functioning if I've been on a ventilator for a month? Or I've had some heroic and successful medical care, but what does that mean for me afterwards? It's the, we can call them patients because that's what comes easy to tongue, but these people, whether or not they've ever been admitted to a medical care facility, they're going to have the answers. Or the information, certainly, yes. Well, thank you very much. I hope you can stay with this as best you can toward the end. Our next presenter is Dr. Pauline Goyle. And Dr. Goyle is the, in addition to his medical degree, also has a master's in health administration and is the associate executive director of quality for the American College of Emergency Physicians. And as he said earlier, has a background in ENT. Dr. Goyle, I'll leave to you whether you want to display your camera during your talk, but if we can bring up his slides. Good afternoon. Can you see my slides, please? Yes. Okay. Thanks for the kind introduction and what a great presentation from Nancy. So I'm Pauline Goyle. I'm associate executive director for quality at American College of Emergency Physicians. ASAP is a physician society with more than 40,000 emergency physicians who are members of ASAP. We are a 50 year old organization. We celebrated our 50th anniversary last year and our headquartered in Dallas, Texas. I also have my colleague, associate executive director, Dr. Sandy Schneider, who helped me with the content and slide. She is a practicing emergency physician. A little bit about ASAP and ASAP's response to COVID-19. So ASAP being the frontline for emergency care was very well impacted by COVID-19, especially in New York, New Jersey area. And ASAP was very quick and responsive in standing up a chat for our members. So out of our 40,000 members, we quickly had 5,000 members from 70 countries bring a lot of contribution into the chat room where we did sort of crowdsourcing to understand what was happening around the world. And we were learning about the various kinds of cases and conditions that were presenting into the emergency department, what treatment were being given in terms of all the tests that were done, what were the criteria for selection of patient for ICU care, for ventilator requirement, and various other trials that were going on in the various parts of the world. So using that crowdsourcing knowledge base, we quickly produced a field guide for COVID-19. Typically a field guide of this kind could take up to three years to build, but it was quickly put together in three weeks as version one. And then every month we refined and improved it as we learned more and more in terms of content. The field guide is more than 200 pages and it has been downloaded more than 100,000 times in past six months. So some of the important learning from our crowdsourcing was that early communication was probably the most important aspect in COVID-19. Communication not only within the teams that were supporting the patient, but then all the hospital infrastructure and administration needed to be on the same page. And then collection of knowledge and dissemination of knowledge in timely fashion to both medical community as well as field community, which is the patient and family members, was extremely important so that people could plan for use of protective equipment or PPE and they could also look into availability of various medical and non-medical supplies, etc. They would also learn what was working and what was not working. Also would learn about some of the medications that were tried initially, but were causing some side effects for not producing the intended outcomes that were desired in the beginning. So we stood up a COVID-19 website, which was constantly updated and the content was managed actively. We created a lot of education material through literature research and had various task forces working on several components. Some of them were working with FDA on the drug usage, use of PPE, as well as immunization. There were other task forces that were working with CDC on public health information collection, education build out and dissemination, such as how to handle your groceries, simple things, what should public do, whether we use mask or not use mask, what does social distancing mean, etc. Then there were other task forces that were working on physician and nurse education and kind of providing them a hotline 24-7 if they had any questions or if they needed guidance. There were other aspects of support that we build out. So ASAP reached out to various hotels because our emergency physicians were constantly exposed to COVID patients and it was not safe for them to go home, especially if they had another family member who had COVID risk condition. So ASAP worked with Marriott and Hilton to arrange a million room nights on volunteer basis and those were offered to emergency physicians and nurses so that instead of going home if they were exposed, they could go and stay in a hotel that would reduce their family risk. So those were the kind of peer support and industry support that we started to do. So as we went through COVID, it was important for us to understand the physician wellness aspect also. We quickly learned that physician burnout during COVID period was very, very high and that required special kind of reach out to various physicians and nurses and help them to how to take care of themselves. There were also financial burden that were being produced, especially in emergency medicine, because the biggest impact in emergency medicine was that routine patients stopped coming to emergency department for risk of COVID. So patients with chest pain, patient with trauma, patients with pregnancy complications would not show up in emergency department anymore. And there were 30 to 50% volume drop in emergency department, which created a lot of financial nightmare for various emergency medicine groups and physicians. And there were cash issues, etc. So ASAP worked with various financial institutions, banks, and consultants to put together financial survival guide, as well as various webinars for our physician population. We also created free counseling services for our emergency physician groups, how to manage and how to apply for various government and non-governmental aid that was available, help them completed their applications as well. So coming to registry, what role did our registry play during COVID? So ASAP has our clinical emergency data registry or CDER. CDER has been in the making for five years. As we learned from Nancy and others that it takes a generation to build a mature registry platform and make it fully operational and useful. So we are still in our early infancy with five-year history behind us. Though there has been some tremendous growth that has happened, as you will see on this slide, that in last five years, we have been able to accumulate 50 million patient visit records, which has data both from billing companies, as well as the EHR. These 50 million records represent 30 million unique patients. On year-by-year basis, we currently have 20 to 25 million records that are coming to our registry on an annual basis that represent around 13 million unique patients. If we look at the other parameters of our registry, we are currently connected to 700 hospitals across the nation and have captured 15% of the market. We have automated data interfaces with these 700 hospitals where we collect clinical data of everything that has happened in the emergency department from patient arrival to patient departure. Our goal is to double that number over the next three to five years. Around 300 or so hospitals are currently in implementation and another 300 or so are in various phases of negotiation and security analysis at this moment. So, we put together various projects to support COVID through our registry platform. One of the projects that we have started to work with CDC is to feed into their surveillance system. So, CDC has a National Syndromic Surveillance Program, and with that program, they collect data on a daily basis from various hospitals across the nation. The data is around syndromic surveillance, such as influenza-like illness, and if patients are coming with high fever or more painkillers are being prescribed, or more lab tests are being run for certain conditions, et cetera. But that data is very limited in terms of reach out to various hospitals and the various data elements that can be collected. So, we are currently partnering with CDC to augment their data set and provide them a more rich data set within seven days of the visit for various COVID-like or influenza-like conditions. We are also working with Yale University to look into various upper respiratory infection information. So, we did a baselining of our 50 million patient visits from 2019 to look into various symptoms, signs, and tests and results for upper respiratory infection, and we are doing a side-by-side comparison of those with our 2020 data as it becomes available, and we are putting together that comparative analysis to understand what has changed in the paradigm and presentation to emergency department. We were also recently selected to support one of the projects with the Office of National Coordinator, which is called Leading Edge Acceleration Project. This is a project in which ONC is looking to understand how are registry platforms being used for various standard methodology for data dissemination, data collection, and interoperability support. So, we will be working with ONC to understand the use of fast health information resources or FHIR interface, how can registries use FHIR interface both for data acquisition as well as data insight dissemination back to various hospitals and emergency physicians. We are partnered with Georgetown University as well as MedStar hospital chain out of Washington, D.C. for this particular project. So, what are some of the limitations of the data that we are collecting at this moment? So, one important component is our registry platform is a secondary data source. We do not have a real-time data collection methodology at this moment. Some of the hospitals do a nightly batch push, and we collect data once in 24 hours. Some of the hospitals want to do it over the weekend, and we get data once a week. Others want to do it once a month basis, so it comes once a month. We also have a registry connector tool, which has capability to do a real-time data collection, but because of various hospital security protocols, hospitals open up their IP window only for hours during non-peak time. So, we are kind of dependent upon various technology architecture, how data can be collected. So, that's a big limitation in data collection. The other piece, as I mentioned earlier, was there was a severe impact on the emergency department volume. Some of the states like New York and New Jersey, emergency department volume dropped 70, 80 percent in March, April, May timeframe. It has started to come. They are still down 30, 50 percent. It's not the same business anymore. That has really led to realignment of various workforce into the emergency department, and there have been severe financial impacts to emergency department and various other businesses associated with emergency care. There have been more demand in various hotspots. So, ASAP is also working on a volunteer methodology wherever there is more need for emergency care. How can we help our physicians move in those areas where demand is soaring and more critical care is needed? As we are seeing a new surge since last week, there are various cities, governments that have started to set up various triage rooms into tents outside the hospital and parking lots, et cetera, and the demand for emergency care is increasing. So, we are working on that and then tracking data also that is helping us to understand where is more demand. Some of the other barriers that we faced was the delay in reporting from various sites. Various clinicians were distracted due to COVID-19 priorities, and they didn't pay attention to submission of data in timely fashion. A lot of physician organizations wanted to do data validation and quality check before they would hit the submit button to us. So, those are the limitations on the hospital side also. The other driver for data submission was the MIPS reporting, and some of the physician practices are applying for hardship exemption to CMS, and they do not want to participate into the registry this year. Financial barriers are also causing participation to slow down or stop. So, where are some of the opportunities for future? So, in spite of all the delays and difficulties in data accumulation, we certainly have understanding, you know, what are some of the typical presentation in COVID-19, such as skin manifestation or loss of various smell and sensations that patients are coming with. We are also trying to understand what are the cyclical pattern of infection. Are patients coming back? Can COVID, same patient, get COVID second time or not. And we are also building various risk stratification tool as well as triage best practices and decision-making protocol, which patient goes home and what is the treatment protocol and discharge instruction, which patient should be admitted to ward and which patient should go to ICU and what are the indications for use of ventilator or not. So moving forward, where are we heading? So we are trying to change the framework of our registry based upon learning from COVID-19. Real-time data collection is very important. Standardization of data collection is extremely important. We are also learning a lot from CDC. What is their current data collection platform? What are the gaps and how can registry help to fill in that gap? We are also working on a national weather service data model which means how can we be kind of a weather service and provide a timely update to various hospital and to the community, where is surge happening and what do they need to do, how to prepare such as weatherman will tell you, take umbrella, it's going to rain today, but be prepared for a snow storm. How can we tell our public and community about that? So with that, I stop here and maybe we'll take questions in the end. Thank you and over to you, William. Thank you very much, Dr. Goyal. And let's go ahead and move on to our next presenter, Dr. Greg Martin. And Dr. Martin is a professor of medicine at Emory University School of Medicine and the executive associate division director in the division of pulmonary allergy, critical care and sleep medicine and is currently president-elect of the Society for Critical Care Medicine. So Dr. Martin, please proceed. Thank you very much, Bill. I certainly appreciate the opportunity to present today. Can you see my slides now? All right. So thank you, I appreciate the opportunity to talk. It's certainly my genuine pleasure to talk about the virus registry that the Society of Critical Care Medicine has been running. I'm grateful for the invitation from CMSS to talk at the annual meeting. As Bill said, I'm a pulmonary and critical care physician at Emory University, and I'm the president-elect for the Society of Critical Care Medicine. And like all of us here, I'm presenting this on behalf of many other people who are doing a lot of the hard work and making this work really well. So one of the things that I think everyone would probably recognize, but one of the questions that first came to us was why a registry? For instance, why when COVID-19 began, was it something for our society? And really, it comes down to the parts of our society that are impacted. So for instance, our members very quickly saw the type of care they were providing to be changed and morphed from the typical critical care, intensive care services, to things that often were involved with COVID-19, whether directly or indirectly impacted. But also our patients were certainly impacted by that. And we've heard today about both the pre-hospital, what happens to patients as they're coming into the hospitals, but also those patients who may experience long COVID, long haul symptoms, and those patients often are those who become more severely ill. So our patients with critical illness related to COVID-19 were an important component as well. And finally, because our mission is to deliver the highest quality care, understanding what's happening with COVID was an important component of that as well. Now, it's certainly the case, nothing new here about pandemics. We've seen pandemics for many thousands of years. Everyone would very rightly say that this one is different, that 3000 BC, we did not have the ability to collect data in real time and harmonize that and share that back. And that would even be true in 1918 and 1958. But it's increasingly difficult to make that argument. So we've seen pandemics and showing epidemics in more recent times, and increasingly as time goes by, we're getting better and better, as you've seen from others, to collect this kind of data, to even automate that kind of data collection. And the fact that we failed in the past really is not a good reason to allow us to continue failing. And in fact, this is really the core principle behind why SCCM has been successful in developing the virus registry, is because we have recognized and we have seen, and we've participated in caring for patients with prior major epidemics and pandemics. But in fact, some of them were fortunately very brief, like SARS-CoV-1 and the 2009 influenza epidemic, and others were more localized. MERS has continued to smolder in the Middle East, but has not been the worldwide pandemic. But it's given us the opportunity to learn about these things. In fact, harmonize, develop data definitions and other processes that work because of the ability to collect data and share it across institutions. And then Ebola actually taught us something different because Ebola largely was an epidemic or pandemic in a resource limited area. And it had taught us different things that we needed to think about. Now, all of that doesn't mean that it's easy. In fact, there are still several things that needed to happen. There's issues with how do you define things? A lot of that was evolving and still changing with COVID-19. The data points, the IRB regulations that may go along with the registry and sharing data, and even the legal agreements, things like data use agreements that become at least difficult, but maybe even contentious. So when we were beginning to stand this up, we realized that our prior experience and even our prior attempts to try and understand epidemics and pandemics that affected critically ill patients and critical care medicine were in fact the learning basis for what we're able to accomplish now. So when we move forward into 2020, we realized that those early failures actually were the foundation or the basis for doing things much better. And we had even started before the COVID-19 pandemic with developing what we call the Critical Care Data Dictionary or C2D2, meaning the ability to collect and harmonize data across institutions, across hospitals, and even across countries so that we could rapidly deploy collection methods and deploy data collection tools, case report forms, and other things. We also had begun to develop automated processes for data collection using harvesting methods and middleware for collecting data from electronic health record systems. And in fact, we had begun to develop the process of having sleeper nodes or sleeper institutions that would be able to activate if a epidemic or pandemic came along, or even a natural or man-made disaster came along, we could in fact activate those to do real-time data collection in the midst of a major disaster or an emergency. So a lot of that was the foundation for a virus, which is a cross-sectional registry. It's an observational study of largely, it's not just critical care, but adult and pediatric patients who require hospitalization with COVID-19. We define the starting point as January of 2020 in order to capture these patients. And if you scan the QR code or open up your phone to see that, it'll link you to more information about the registry itself. But what we really did is we were able to build on that foundation. For instance, the C2D2 Foundation, the sleeper nodes, the prior institutions that had been in place or been in smaller efforts to work together on projects, and allowed us from what you see at the bottom, starting in March 11th, within 20 days to move from conception to execution. So within 20 days, we had the IRB approvals, the protocol built, the data collection tools in place. And in fact, institutions were already inputting data. And within a week, particularly using social media and other sort of global strategies for capturing or advertising to investigators and institutions, we had over 170 sites who had expressed interest and were interested to share their data and begin putting their data into the systems. Now, if you look at the flow diagram for the virus COVID-19 registry, you'll see that a lot of these things work in parallel. And in fact, some of these things, like defining the data elements from C2D2, the IRB submissions, and even the data collection forms, which we used in REDCap, because that's a relatively universal system that can be used and is often either free or readily available as a secure tool for data collection. A lot of those things had been modeled or made available already. So we could build some of those things in parallel, but it moves us very quickly to get into the point of having data collection and even getting it into a database where we can do the data quality checks, the cleaning, and then ultimately, as I'll show you in a minute, how do we disseminate that information back out? So just to give you a sense of what we do collect, there's a number of things that we collect, particularly on days here at the beginning of someone's hospitalization with COVID-19. All of this information goes into REDCap, and it's all built on the International Severe Acute Respiratory and Emerging Infection Consortium, known as ISARIC. And that ISARIC forum is really a collaboration or consortium of networks around the world who have agreed to standardize their data collections and to help collect information on emerging infections or other critical illnesses. And by standardizing these things, again, using our systems and the ISARIC data forms, allowed us to very quickly stand these up and, in fact, be as harmonized as possible, not just in the US, but really globally. So this is the map of where we are now. There's over 290 sites active, both adult and pediatric, all around the world, spanning 30 countries. You can see that a lot of this is in North America, but it really represents globally almost every place, certainly every continent in the world. And then finally, the subject enrollment. What we see is I showed you that it began in March, but in fact, we have over 30,000 patients now. This shows you out here into October, we're getting up to about 29,000, but we now have over 30,000 patients globally into the registry. And increasingly, those leaps that you see can occur because we get more and more electronic transfer of data. One of the things that we've done to try and share this data back to people is we've created a dashboard, and this is available now. Anyone can go to sccmcovid19.org and actually see this. And it really shows up on the very simplest basis in three areas. The left side is who sought help, meaning the demographics and characteristics of the patients. What are the most common symptoms people had? What are the comorbidities that patients had? Other things that describe the people involved. That middle column is about the support that they received. What percentage of patients required respiratory support of some form? How many were mechanically ventilated? How many received dialysis, for instance, with acute kidney injury? And ultimately then in the right-hand column, what happened to them? How long did they stay in the hospital? How many patients died? What was their hospital discharge status? And we make all of that publicly available so that people can use it. But then increasingly in our dissemination strategy, it's not just the dashboard. It's also publications which we use for academic purposes and sharing with the lay public, but also then the other collaborative things that we've done, like for instance, with the American College of Radiology, with Point Click Care, with societies like the Infectious Disease Society of America, and then trying to increasingly link with the other registries, like the American Heart Association, and using things, some of the sources of support that we've received from, for instance, the Moore Foundation to help us to build those collaborations and share them even more beyond what we use in the critical care societies, but even out to other societies as well. So the current status of the virus COVID-19 registry is that we have the dashboard built. I would encourage all of you to take a look at that. The Cohort Explorer, which is the next step, is actually already in existence in a beta phase. So that tool exists and allows people to begin to look at what does the cohort actually look at, begin to build virtual cohorts. If you wanted to simply see the patients from one state, one region, those patients who are mechanically ventilated, those patients who are of a certain age group, those patients with certain comorbidities, we can begin to parse that out and develop virtual cohorts for comparison or study. We also have a number of ancillary studies that people have proposed and we're working through those. There's over 30 of them approved now that are moving forward. We have the collaborations that I mentioned. And finally, obviously the manuscripts, and there's several manuscripts already out or showing up in press. So there's a couple of things that we've certainly learned in this process. The collaboration is one thing. I mentioned the prior experience, particularly learning from prior efforts in working in pandemics, working in epidemics, and understanding the elements that need to be put in place really before things begin so that you can make those things work as quickly as possible. That means things like the IRB approvals, the data use agreements, other things that need to be in place, but even the networking, identifying sites and the elements of data harmonization that we've talked about. The other thing that we recognize is several challenges, which would not probably surprise people, but there are resource limitations, certainly within individual sites, but even within the societies and other things that you have to work within the constraints you have for doing the work you wanna do. There's always scope creep. So there's always the question of, well, can we add this? Can we do that? And those things often are very important to consider, but you have to draw some lines and decide where your money or your efforts are best spent. And then finally, political barriers to participation. And there are, even as a simple example, many, many registries out there. And that's one reason why we wanna harmonize or link those because we can easily make this more efficient and more valuable for everyone. So I certainly wanna recognize not just the work being done, but also the sources of support. I mentioned the Moore Foundation as one, but a lot of the work that's being done comes out of Mayo Clinic and also Boston University, who's helped build the dashboard. Inference, Lintech, and the American College of Radiology have been wonderful partners to get started. And PointClickCare has been helpful in identifying, de-identifying the data, particularly for some specific uses. So with that, I would encourage any of you to contact us, Dr. Rahul Kashyap and Dr. Vishakha Kumar are our co-investigative leads for the registry. And I would encourage you to contact either of them. And you're certainly welcome to contact me as well if you have questions. So thank you everyone. And I'll stop there and answer questions. Thanks very much, Craig. It was really terrific presentations all across the board. And we've got about five minutes for questions and answers. Let's see, I don't see any in the queue right now, but I may start us off. And maybe I'm not sure if Dr. Dreyer is still with us, but can you give me one example of how this real-time monitoring has led to feedback where there's been a change in clinical patient care? Whether it be early institution of mechanical ventilation or later institution, or those types of things. Because I think that as each of you have talked about, this kind of real-time assessment, hopefully we could get it to where we actually get applicable changes in care. Craig, maybe to you first. I'll be happy to start. And it's, I think what you mentioned, Bill, is really important because as we began, and I think everyone began, we recognized that COVID-19 was not just new, but really a big unknown. And we're now seeing improvements in mortality, improvements in the duration people are in the hospital, other outcomes that are important. And some of that is simply better understanding, better learning. So when we built the virus registry, we intentionally very quickly built that dashboard because we wanted to be able to share that information back to people as quickly as possible. Now that's not necessarily the hardcore science that helps you understand the inflammatory cascade or the effect of various details that are gonna really help drive, for instance, new therapies, but it begins to serve as the basis for understanding in your setting and what are you seeing? How are the things working? What are other people doing? And this is just one component of it. So for instance, SCCM, the society also has a lot of online resources, including the ability for people to pose those kinds of questions and even share their individual resources. If their hospital or institution has a protocol or a learning tool for this, a lot of that was posted on there too. And so all these to us were sort of the complimentary pieces to help people learn from each other. Terrific. Pawan, any examples from your work? Well, certainly we learned a lot through COVID. The most important piece was how to provide safe environment for the patient when they come to emergency department. Telemedicine played a huge role in emergency medicine, especially for triage purposes. And we had to really reconfigure our emergency department and create a clean room versus a COVID room and then have a social distancing arrangement within those rooms. The cleaning of various supplies and equipment was another key challenge that was brought in and the availability of PPE into the quick turnaround environment and how to reuse that. So those were some of the key learning. That's terrific. This being CMSS, how can specialty societies, and again, we at the American College of Radiology greatly appreciated our collaboration with Society of Critical Care Medicine, but how can specialty societies best enable this? We're clearly not out of the woods on this. How can we best through the organization perhaps and bring this even to the next level? So let me start, maybe. Sorry, Dan. Sure. So it is about patient. So the patient is center of our universe and all of us are trying to serve patient, but patient goes through various gateways to get the care. They may come to outpatient clinic, but may need hospitalization. Over the weekend and nights when they do not have ambulatory care available, they may land up into emergency department, but that's a place where they get stabilization, but ultimately either they will go back to primary care or will get hospitalized. How do we have better transitions of care? How do we have better availability of information to the care provider? So it is about managing those complex workflows and sharing the knowledge about the patient, patient conditions and treatment effectiveness. That's where I think all of us have opportunity to collaborate better and share that knowledge and time with them. Terrific. And Greg, I'll give you the last word. I certainly agree with that. And it's, I mean, the patient is at the center of our universe as well as where our goal is to deliver the high quality care. So as I think about it, one of the things that we've seen across medical specialties is that, you know, you take it as an example patient who comes in, is admitted with COVID-19, maybe has a history of kidney disease or cancer. That patient is gonna go through a pre-hospital environment like in the emergency department, and they may be hospitalized on the ward, they may end up in the ICU and they may end up with long haul symptoms or other things that require care after hospitalization. But each of those transitions are an important element of the specialties of care, right? So we've got EMS, emergency medicine, hospital medicine, intensive care, critical care medicine, and all these other specialties like cardiology, oncology, nephrology that may be involved. And as we see it, particularly from the registry perspective, those patients end up in multiple registries. So if we're trying to understand what happens to an individual patient and the sequence of care and their outcomes, being able to link these registries can be incredibly valuable because then we have a much better understanding of the longitudinal aspects of care that are going on for each person. Well, thank you very much. And I hope all of you in the listening audience will join me in thanking Drs. Dreyer, Goyal and Martin for just a terrific session. My thanks to all of you. We now have a 15 minute break and I hope all of you will join us at the 3.30 plenary session. So thanks and everybody have a good afternoon. Thanks everyone. Thank you.

clinical registries

COVID-19

patient care

data collection

public health emergencies

global patient registries

real-time monitoring

data harmonization

collaboration

clinical decision-making