Annual EMSC Grantee Meeting

Pediatric Emergency Care

Applied Research Network (PECARN) Update

June 20 – 22, 2006

NATHAN KUPPERMANN: Good morning, very nice to be here. And today I’m going to be talking about -- the title of the talk is actually Multi-center Research in Pediatric Emergency Care, but really what I’m going to talk to you all about is an update on the pediatric emergency care applied research network and as Dan mentioned, we are funded by EMSC, not only the four nodes of this network but our data center as well. So in brief, I’ll be speaking for about 25 minutes or so and the goals of this discussion, our first, briefly define and review PECARN for those of you who are not familiar with this network. We’ll give a brief history of PECARN, but I’m going to focus on ongoing research studies as well as upcoming studies and our goals for the near future.

So first, just by means of definition, what really is PECARN? PECARN is the first federally funded research network in EMSC in this country. It is funded through HRSA, MCHB and EMSC, with the purpose of developing an infrastructure that’s capable to overcome the inherent barriers for doing research in EMSC. And what PECARN provides is a number of things; first of all, it provides the infrastructure and leadership to do multi-center studies, both observational studies, as well as, randomized control trials. It supports research collaboration amongst EMSC researchers but equally important, it supports interactions amongst EMSC practitioners as well as researchers.

And finally, it encourages the translation of our research findings into the practitioner community. The structure of PECARN, which I’ll go over briefly, really there are four research nodes and a data coordinating center which we called CDMCC. For those of us who participate in PECARN we survive by our acronyms there are many of those but I won’t indulge you with all of them.

Our mission is pretty straightforward. The mission is to conduct high priority research into the prevention and management of acute illnesses and injuries in children of all ages.

Now why was PECARN needed and there actually are a number of reasons, but if I were to synthesize it down to four main reasons, will be as follows; first of all, there’s a low instance rate at pediatric emergency events. So to really study them you need to pool many large centers. There are large numbers of children that are required to attain not only the raw numbers but enough diversity to be representative of this nation as a whole. We needed an infrastructure to test the efficacy of treatments, as well as to test—to do studies on the transport and pre-hospital care of children in this country, and finally we needed a mechanism to study the process of translating our research findings into the treatment setting.

Just in brief, the history of how PECARN came to be. I sort of trace it back to the very early 90s where the Academy of Pediatrics had a collaborate research group that really was a blood, sweat, and tears operation. Completely non-funded voluntary and in the early and mid 90s actually did a fair amount of work and then in the late 90s we were asked, “How could we take this collaborate research network and take it to the next level?” Well, the answer is very simple, just give us some money and we can make it better, but in fact there was a series of partnership meetings between the APA-EMSC as well as our federal funding partners looking at the barriers to EMSC research and how to best overcome these.

These were in the late 90s and we looked at precedence for other collaborative research networks including other pediatric research networks such as the Vermont Neonatal Network, a highly successful network founded in the 80s, the Pediatric Oncology Network, as well as emergency medicine networks and there’s some successful models, the EMNet and the ID surveillance networks are just a couple of examples. Then HRSA/EMSC/MCHP sort of got together, thought about how best to do this and announced the RFP for PECARN in June of 2001. There was a competitive process and PECARN was created in September of 2001. We met for the first time in January of 2002 and that I think that was our sort of our sentinel event and so we are officially I think -- I call ourselves 4 and a half years old, marking that January ‘02 meeting.

So this, in brief, is the structure of PECARN. It consists of a big steering committee, 21 voting members. At the start of PECARN we were intensely democratic, and we’re still democratic but we wanted equal representation from the four nodes, so five members of each of these four nodes run the steering committee as well as the PI of the CDMCC, and again that’s our data center. So there’s a steering committee works closely with our data center. Mike Dean at Utah and Sally Jo Zuspan run that operation. We work obviously very closely with our funding partners: Dan Kavanaugh and Hae Young at HRSA/MCHP/EMSC and then we have four – we used to call them regional nodes except for my node, there was nothing regional about it so we actually changed it and then we called them research nodes. I organize one based at UC Davis. Jim Chamberlain organized one based in DC. Peter Dayan runs one of the nodes out of New York and Ron Maio out of Michigan and underneath these nodes we have several sub committees that really are charged to do the bulk of the nuts and bolts work in PECARN.

So each of those four nodes I show you consists of the following: there is a research node center and typically five to six hospital emergency department affiliates, and you see those bi-directional arrows, the node center really sends information this way but there’s bi-directional discussion on what research proposal to submit to PECARN and a lot of interactive and dynamic interchange between the participating hospitals in the research node center.

So this is the distribution of PECARN and we say we’re a national network but of course, in reality, we’re a conglomeration of the northeast lots of representation. Here, I am very lonely in the West Coast. The Utah data center and one of the centers the sites affecting Utah. Notice some big addresses, oh, we’re missing the Southeast, we could use some more money to include them. Oh, and I would say we could include some more of the West as well but that ‘s the distribution. The big blue stars are the research node centers and the big yellow star is our data center in Utah.

So what does the data center do, the data center, in fact, does quite a bit, they organize the network sites, they provide network leadership in conjunction with the steering committee. They’re very intimately involved with everything, in fact that we do, protocol development and study design, once a protocol is endorsed by the steering committee which I’ll discuss briefly, it then goes to the data center and they help develop it. They help with grant writing, hold grant writing workshops, they are involved in all the subcommittees, they do some training education, they help provide support in creation of manuals of operation for research studies, they provide study support and technical expertise -- all of our data is transmitted electronically. We have a virtual electronic space that is managed by the data center, they help with data collection analysis and they maintain our website. For those of you who are interested, the URL is listed there.

The steering committee works again closely in conjunction with the data center and our federal partners and it is the primary governing body in PECARN. As I mentioned, there’s equal membership from each of the nodes although once the grant competition ends, then we just become one big network and we’re not so aware of where each person is from, but when you compete for these grants, you compete as a node so that’s why this intense democracy in the network. As I’ve mentioned, equal membership as well as, representative from the data center, we are responsible as a governing body for reviewing and approving the scientific proposals in PECARN and my guess, if we were to look at it, we’ve endorsed about probably 30 percent of the research proposals that are submitted to us. We formulate and monitor policies and procedures that guide the research. We established and then revised the policies and by-laws for the network and we’ve also established sub-committees for carrying out the tasks of PECARN.

So this is a brief look at the different committees, again the Steering Committee, the Concept Protocol Review Sub-Committee PCRADS as we know it, a very important committee that is charged with doing the first screen of proposals that come our way. I want to mention, in brief that not t only do we accept proposals from within PECARN, but anybody in the country can submit a research proposal to us in PECARN and we will consider it, the same way we’d consider any proposal within PECARN, and if that study is endorsed by PECARN, that investigator and their center will be brought in to PECARN for purpose of conducting the study.

We have two such studies in PECARN currently. The Safety and Regulatory Affairs Sub-Committee, and Quality Assurance Sub-Committee, pretty self-explanatory. A more recent sub-committee was the Budget and Feasibility Sub-Committee, very important because as you all know, it’s exciting and all to get a grant but sometimes you get a grant that in fact, is relatively under funded for the scope of work that you are trying to do. So this Feasibility and Budget Committee really looks at our grant proposals to make sure that we are asking for the appropriate budget, making sure that we can actually do the study once we get the money. And finally, the Grant Writing Publication Sub-Committee, they establish guidelines for publications in PECARN. Arbitrate manuscript publication decisions and help with grant writing in PECARN.

The strengths and accomplishments of the network, as Dan mentioned, we have 21 sites we see; actually it’s about 900,000 children a year in all of our sites. There’s pretty wide geographic and hospital representation, that is children’s hospital, non-children, public, private, community and urban hospitals. We are very senior level expertise with regards to research, statistics, epidemiology, health services, et cetera.

And to date, this is what we -- our products, we have five published manuscripts, we have, I would say, probably another 10 to 15 under preparation. We have more than a dozen abstracts published, and these all really happened in the last two to three years because the first two years, we had to get the research network off the ground and in the last two years, we’re starting to see a lot of products and over the next year I anticipate many more publications from PECARN.

And I’m not sure why I put that slide in but -- by the way I was just telling Flora, just as a side note, I’m a scuba diver and I just have, like most of you, a pocket regular digital camera, I won’t even tell you the trade name because I don’t represent any camera company but online you can get underwater cases that just go around your simple pocket digital camera and it turns it into an underwater camera which is very nice. Okay a little plug there.

Okay. So, what I thought I’d do now is just briefly go over the ongoing research projects in PECARN. So our first study was called the PECARN Core Data Project. Once we we’re created we realized – until we get grant money to do because the funding that we got from EMSC, very generous funding built the infrastructure, but the charge was that we needed to go out and get money to do the research. Well, until you can get research money we had to do something, so we started a Core Data Project, in which we’re looking at the patients that we see in the network, again, funded through core funding and the objectives of that study are just to describe the PECARN population, to determine the availability and completeness of data that’s available through charts and electronic abstraction in PECARN, to test our ability to collect and transmit and manage data from all sites, to establish some benchmarking, and we did look at two specific issues regarding practice pattern variation for asthma and long bone fractures.

In this Core Data Project there were 25 hospitals, note that we now have 21 because the truth is -- is that if PECARN hospitals are not keeping up to the standards of PECARN they will leave PECARN and we’ll invite other hospitals in because we’re very rigorous about maintaining our quality that at annual ED census ranges from four to 86,000 all 25 hospitals are non-profit. I described the different types of hospitals, 17 of the 25 are Level One Trauma Centers and we have very diverse racial ethnic population. You can see about 48 percent African-American, 36 percent non-Hispanic Caucasian and 11 percent are Hispanic.

Our second study is the Effectiveness of Oral Dexamethasone for Acute Bronchiolitis. This was co-funded by EMSC and as well as HRSA/MCHB research program grant and the objectives to that study is to assess the effectiveness of oral dexasmethasone for moderate-to-severe bronchiolitis. It was a big randomized control trial; we finished data collection in April. We are cleaning and analyzing the data currently. This is an example of what we really want to do in PECARN that is when we take a controversial topic that’s very hard to study at a single site and do the definitive study on the topic so that we can then move on to the next important question.

The third study that we have ongoing is Therapeutic Hypothermia for Pediatric Cardio Pulmonary Arrest it’s a planning grant funded through the NIH. Which, the goals of which are to describe a cohort of pediatric patients after cardiac arrest from either outpatient or inpatient setting. We gather one year of pilot data looking at patient and event characteristics to really delineate factors that are associated with outcomes. To prepare for a large randomized control trial for therapeutic hypothermia in pediatric hypo cardio pulmonary arrest. 500 patients were enrolled. We’re analyzing the data now. There has been a subsequently submitted and funded NIH grant to prepare a manual of operations for the ultimate randomized control trial.

The fourth study is a study called the Childhood Head Trauma: Neuro-imaging Decision Rule, funded again by EMSC and MCHB research program and the goal of this study is to develop and validate a clinical decision rule for the use of neuro-imaging that identifies kids at high risk and low risk of brain injury after mild to moderate head trauma and the long term goal is really to create the evidence on which we can base appropriate decision making in terms of use of CT in the emergency department. The goal is to enroll 40,000 patients, and we’ve enrolled 37,000 we’ll be done in August with the data collection but then the real problem starts which is data cleaning of a database of 40,000 which we’re excited to do over the summer -- sort of excited to do.

The next study I want to mention is a study looking at Referral Patterns and Resource Utilization for Pediatric Emergency Department Patients Presenting with Mental Health Problems, as we know a crisis in this country and in very brief, this is a study to ascertain the sources of referral of patients to institutions with mental health issues and to really ascertain the organization and resource utilization in the care of these patients, and also look at variation in resource utilization by sight. This study is currently on, the data is being analyzed and the manuscript is about to be prepared.

Few more studies I want to mention Creating a Diagnosis Grouping System for Childhood ED Visits, funded through EMSC targeted issues grant. This is a study to develop a diagnostic grouping system using ICD-9 codes to describe childhood ED visits that is very parsimonious. As you know there are maybe 13,000 ICD-9 codes, many of which are very overlapping and the goal here was to create a very simple, easy to use severity and diagnosis classification system. The methods involve both Delphi and Nominal Group Consensus processes and the DGS as we called it, has 22 major groups and 73 subgroups compared to the 13,000 ICD-9 codes. It’s interesting to note that there are 48 ICD-9 codes that account for about 50 percent of all ED diagnoses. The data have been validated with both NHAMCS and state ED data sets and the next steps are to look at a severity scale based on the scoring system. Abstracts have been published on this study and manuscripts are in preparation.

We have a bioterrorism surveillance project that’s ongoing in PECARN. This is an example of a study from an investigator from outside the network. It’s funded through AHRQ and sponsored through Harvard Medical School. The goal is to develop and evaluate an information infrastructure for PECARN that creates an automated data stream of information to gather real time, clinical information from the EDs at PECARN for several reasons, one is for bioterrorism surveillance, but also for general public health surveillance and for clinical research and currently centers in PECARN are organizing the infrastructure to be able to participate in this surveillance project.

Another study funded by a Targeted Issues Grant is entitled, Predicting Cervical Spine Injury in Children, and the goal of this study is to identify a set of variables to separate children who are at negligible risk for a cervical spine injury from those that are non-negligible risk, and to test the criteria that identify these children in EMS system. It’s a case-control study, which has to be done for a very rare event phenomenon, but the ultimate goal of this study is really to refine spinal immobilization policies in the out-of-hospital systems.

As we know, many children after minor injuries, get thrown in a collar in the pre-hospital setting, they come in to the emergency department and they get irradiated like crazy and our goal is to try to find out which children really need to be immobilized in the first place out in the pre-hospital setting. Data collection is ongoing in this study. And the last study I want to tell about is Lorazepam for Status Pediatric Status Epilepticus funded through the NIH and this study – if I can move the slide – is funded in response to the FDA’s Best Pharmaceuticals for Children’s Act.

The ultimate objective is to obtain FDA labeling for Lorazepam for pediatric seizures and the study has two components, first is a pharmacokinetic study of Lorazepam in children with status epelepticus and this will lead to randomized control trial of Lorazepam versus Diazepam for status epelepticus for children. The pharmacokinetics study, I said it was complete in May, it’s actually be completed in June, right Jim? Back there, June it is. And then, soon afterwards we’ll be organizing the randomized control trial, which will be an exception from an informed-consent study. Just give me two more minutes I’ll be done.

Future studies that we have ongoing in PECARN. In PECARN, we always have a portfolio of ongoing stuff, grants that have been submitted and grants that are being prepared. It’s the only way to keep ourselves active and alive. We have two grants that have already been submitted. One is an abdominal trauma decisional grant submitted to NIH and the CDC. There is a grant on the safety of procedural sedation in the ED, which was recently submitted to the NIH. We are preparing an RCT of outpatient management of chronic asthma and that grant is under preparation.

We are currently developing a study looking at error reduction in the pediatric emergency department and we have two pre-hospital studies that are currently under development. One is the crash scene investigation, as well as a pre-hospital study looking at pain management of children in the pre-hospital setting.

And finally, we’re looking at studies to really test our ability to translate our research findings into practice. So our future goals are really to finalize and implement a formal research agenda to guide future research proposal development, to design and implement a plan to study and encourage the transfer of network findings into practice, and finally to collaborate more closely with EMSC practitioners to establish bi-directional exchange of information and collaboration. And with that I’m happy to take any questions. Anyone know this fish? It is huge group out of 4-foot grouper somewhere off the coast of Belice. Okay I’m happy to take any questions with that. Okay, thank you very much.