 Thank you. I also appreciate the opportunity to to come here and participate in this meeting Just as a bit of background my my interest in this area stems back to 1984 when I mentioned to dr. Shear that I was thinking of doing a PhD and he encouraged me to to talk to a guy by named a Steven Spielberg and The rest is kind of history My interest has run the the gamut from Replacing hepatic microzones in the the Spielberg lymphocyte assay with purified p-450s Through to looking at anti p-450 antibodies and anti convulsant hypersensitivity To the current interest in improving the information that is available for these reactions and other Adverse drug reactions in a pediatric setting So I'll start off first of all by saying that there is no current initiative analogous to the drug-induced liver injury network addressing severe cutaneous adverse drug reactions in the the US There's a group called the Institute for safe medication practices that periodically reviews This type of information that's been reported to the FDA adverse event reporting system As a Canadian about to become an American citizen, I thought I would include the Canadian initiative in this area and And and What led me to what leads me to the the topics I'm really going to discuss is the fact that One of the many many times dr. Carlton who heads up the the Canadian initiative will bemoan the fact that he needs to Renew the funding for the infrastructure of his network every five years to keep it alive And I think the current experience with the drug-induced liver injury network shows that the survival of many many of these Networks is dependent upon grant funding And so what we tried to do at our institution is to build a program that is perceived to have value to the Institution so that the collection of adverse drug reaction related information Can be paid for out of the operations of the hospital, but also feed research initiatives And so the first thing I'm going to do is just show this This text that I've pulled out of the report by the Institute for safe medication practices in January of last year showing the the types of The drugs that have been associated with severe skin reactions in fares and you can see at the top of the list is Lomotrogene Followed by ibuprofen and then co-trimoxazol. So this is certainly in in fitting with a number of the other international initiatives this is a map of the 51st state that shows all of the sites. Oh Oh So that actually that wasn't one of the tests one of the questions on the citizenship exam Yeah, yeah, I said poor I said Puerto Rico. Yeah, right okay So the the the blue circles are on this map represent the initial What used to be called the GATC? Network and then when they renewed their funding they had to have a slightly different focus or else They couldn't get funded and so that became the Canadian pharmacogenomics network for drug safety and they added adult sites in the in the red, but this is a nationwide initiative that has standardized data capture and provides data most of their work to date has been on things like cisplatin ototoxicity and Adriamison cardiotoxicity, but they've also replicated the the results the associations between 3101 and 1502 for carbamazepine hypersensitivity in children now We have participated in the international the ISAC the international severe events consortium as have other American institutions But and one of the challenges that we found was that there was an awful lot of work related to re-entering The data from the way that we collect it into whatever platform is being used to collect data for Whatever organization is doing the study Now it is worth noting that one of the mandates for joint commission accreditation is ADR reporting But prior to this initiative it was done very poorly at our institutions we would only have on average 10 to 12 adverse events that were reported to our pharmacy and therapeutics committee every quarter and While we believe that we provide a high quality of care for our patients We doubt that that means that we only have 10 or 12 adverse events every three months and So this led us to consider development of some Systems that would allow us ultimately to Implement preemptive interventions in the event that we were able to identify children who were at high risk for a severe Event we also wanted a system so we wanted to improve the quality of information That's in the electronic medical record itself But we also wanted it to have it there in a form that it could be easily extracted to participate in Different research initiatives and at our institution we call this the pharmacogenomics of pediatric drug safety there are papids program Now the papids program the research program is falls under another larger umbrella that we call Goldilocks For genomic and ontogeny linked dose individualization and clinical optimization for kids And it's the concept of finding the right drug or the dose that is not too big not too small Just right for children for those of you who forget the story of Goldilocks and three bears but this is all part of a Program of our pediatric clinical pharmacology program that is designed to improve the use of medications in kids And so the program is currently led by a clinical pharmacology trained pediatric infectious disease specialists who also heads up our antibiotic stewardship program and who has an interest in Coat remox is all hypersensitivity as well in the past year with a full-time dedicated clinical pharmacist and other ancillary personnel Fact that so the program is run out of the division of clinical pharmacology, which is a division in the Department of Pediatrics We rely on some assistance from the Department of Pharmacy as well but we had eight hundred and three unique ADRs that were entered into this system in the past year and Although the the clinical pharmacist in our program was responsible for about half of those there were more than 20 other health care practitioners in the institution who contributed to the reporting and so what we've attempted to do is to Standardize and get the data into the electronic medical record in a form that can be extract extractable as As defined fields and I have to thank he's not here So he won't be publicly embarrassed, but I have to thank dr. Dan Rodin from Vanderbilt who five years ago Visited our institution when we were considering Developing a Vanderbilt type Repository and de-identified electronic medical record system and he encouraged us at that time to do to work on Getting data into the electronic medical record in a form that made it much easier to extract and so we took that advice and the next few slides with whatever time I have available is going to show you the way that this the data are collected and I will say that The platform that we use for the research side of the operation is discover e. It's the same platform that the international Severe events consortium severe adverse events consortium used for their data capture And it was facilitated by having in Kansas City Cernar Corporation We also use the Cernar EMR, but here is Some of the information that goes into the electronic medical records and general information list of drugs With a field for other And then an initial type now this is until this time everything went into the electronic medical record as an allergy and You may not be able to see on in this panel here, but we now break this We call them adverse reactions and we break it up into allergy hypersensitivity Side effect unknown religious pressure preference precaution newly reported newly documented And then a final type Also, there is classification for severity Which is intended to provide the practitioners with advice as to whether the same drug or drug class Should it could be given a gain or avoided? We also have we don't like rash although rash is one of the words that triggers Us to get involved the other thing is that on the banner bar Because we know that clinicians themselves are not interested in going through this process They don't have the time we now have on the banner bar a button that anybody who suspects An adverse reaction of occurring they hit that button and it triggers our group into action to to initiate the documentation so here are all of the descriptions of rash that we like people to tick off when present Where it's located And then we capture information related to to medications and Then the suspicious drugs and then the neuronal algorithm is included in the EMR But we are also having people go through we also go through the liver pool algorithm so that we can do some comparative work as well Finally how is it treated and Here's an example of of nausea and vomiting to Amoxicillin that was reported as an allergy but is recoded as a side effect so you know we can give amoxicillin a gain and Then these are just some screen captures from the discovery database that the trigger for the research project is an average drug reaction of medium severity or greater and Again Similar data fields So just to just to finish up there is no current a national initiative our goal is to can To hopefully convince healthcare systems through maybe a system that can be adopted by others that ADR surveillance programs do have value to the institution and data collection and Fine phenotype detail should be a part of regular practice. We need to standardize nomenclature and Having the infrastructure already in place would allow research funding to go more to the research or the science than to Infrastructure that needs to be resustained on a regular basis. So I'll just close by acknowledging the slides from the CPNDS from Bruce Carleton Jennifer Lowry is a clinical pharmacology and clinical toxicology trained General pediatrician who did all the heavy lifting to get this system in place in our institution Jane Goldman is the ID specialist who now heads it up the other individuals help Help with the data collection and also the content of the data I'm indebted to David Kaufman and Alan Mitchell at the Sloan Epidemiology Center Because a lot of the content was adapted from their Earlier involvement in and this type of work. So, thank you Thank you very much We have a few minutes for questions related to this presentation before going into a general discussion So this is a very nice initiative How do you then use this to convince health care system that there's value and how do you define the value here? That's so difficult. I find if you don't do health economic study to show the value of predictive testing or so Yes. Yeah, the the value demonstrating the value is Collecting objective evidence of the value is is Some what difficult our institution kind of gets it so they don't need to be convinced but getting other institutions to To say well, we're not going to do this until you can demonstrate to us that it's cost effective I don't know One of the ways that we've been considering is that hospital charges The bulk of the hospital charges tend to occur in the first Two days two to three days of a hospitalization and then the you know the revenue if you will drops down after that And so we're wondering if one way that we can do it is to show demonstrate that we're lengthening hospital stays Hopefully by fewer Atrogenic events and maybe that'll be cost effective and this is definitely something that we struggle with we are fortunate to be in an institution who Values a culture of safety and is willing to see whether this will pay off Mark if I can just add to that Mark Williams a geisinger We've spent a lot of time thinking about this and I would just add two things one is in this realm One of the levers that you can really pry on pretty hard as patient safety That's a big issue for all health care systems because they're being scrutinized about patient safety So avoidable events using this type of information Provides an opportunity where you may not have to make as much of a cost case As you would in other cases and in particular we're not talking about this in this meeting But if you think about sip 2d6 and opioids which are high Visibility in terms of patient safety that's something that some institutions have been able to use to get that implemented the second thing is we use the term cost effectiveness, but Healthcare systems aren't interested in cost effectiveness it in the sense of how we usually use the term Which is sort of a societal perspective cost effectiveness that doesn't mean anything to them what Steve is actually describing It's not cost effectiveness, but it's really a business case For that and you can use economic tools for this But you have to model it from the perspective of the health care delivery system so that it's relevant And we've actually published several papers on how to how to do this But once you can actually Explain to them in the context of what it means Related to the business case then you can really move this forward and the first one is always the hardest And if you're successful with that then it's a little bit easier going forward That's a very interesting this this would be only hospitalized children or how do you capture? Children on the outside who have an adverse reaction and are not hospitalized say That's a that's a very interesting question. So once we started doing this we realized that There were still a lot of adverse drug reactions that we were missing and mostly these were the Children that were coming into the urgent care or emergency department with a Chief complaint of an adverse drug reaction where the ED made a diagnosis of an adverse drug reaction But it never got entered into the system right and so now hard to follow to yeah, and so now Like most of the initiatives at our institution. It takes a committed clinician to get involved and It turned out that one of the urgent care docs came to Dr. Goldman and saying, you know, here's this Situation we knew it was happening because we do monitor by ICD-9 codes and so now we have an urgent care physician who is going through She's gone through the first nine months 202 cases For for 2014 to get the documentation in the system. I doubt that we are capturing Everything right now. We don't have it in our outpatient clinics But we hope to capture everything once we have the committed faculty members so much I'm so impressed by The system you put in place. I wish we could implement it nationally and as I talked yesterday I have five thousand signatures here of this petition from people from all over the United States in Naples, Italy saying my child died of this and it went unreported to every single drug out there and You know, if there's any way we can help to try to get awareness out there and Get a system in place to make it safer for the consumer. We'd be more than willing to help Thank you, so I just to add to that I would say that The system that I showed you is not hard-coded into Cerner the this exists as power forms that are on top and and You know, there really isn't I don't know enough about the medical informatics to know But certainly the content that's being captured can be put into other forms. And of course discovery is a web-based Application that will We just wanted to be able to reduce the amount of effort in for those Consented Patients the amount of effort that we would have to redo getting the data into the the database And so we try to pull as many fields directly from the EMR as we can to populate the discovery database It's wanted to follow up with this idea of leveraging such Information for public health. So one question is do you have a system in place where you can take these? These reports essentially and send them to the FDA as a as an FDA report because frankly you could have the Potential for an interface not just for research Where you pull data but and and patient management when issues come up to deal with in real time But also to report publicly the FDA and we're very interested in getting such kinds of high quality information So that's a very interesting comment a few years ago at another meeting here in in Washington Diane Murphy came up and and wanted us to consider Making a pediatric Designing a pediatric med watch form because there's lots of information that pediatric pediatricians are interested in That aren't included in the current med watch form and so we pursued that and and and then we were we were told Well, not to bother because there was no way at the FDA to to change the The information that was being collected so I I Can't answer the question exactly, but I believe that we are manually entering or submitting some of the more serious ones to To fairs, but I'd have to go back and check with Our folks it would be nice to automate it It should be automatable, but it would also be important to include information that pediatrics pediatricians find relevant like Vaccination history and we can talk offline about this, but there are ways to do this relatively expeditiously as an attachment So that you don't really have to spend too much time fooling around with the computer And I do have another contact yet We can talk about that after I have another contact at the FDA who was interested in this as well if you had decision support built into the information that's in your Allergy and ADR information and I think it's greatly organized it because it's such an allergy Boxes there's such a waste basket of irrelevant information and distractors that lead to bad patient care And and I wondered if you had decision support That you've actually, you know actually followed up on for instance if someone actually is labeled as having an ADR To a moxicillin if a child is labeled as having an ADR to a moxicillin do Clinicians really act on that in a way that they will actually give that because you know what what usually happens is a Moxicillin is in the allergy box, but it clearly states the a side effect that is not an allergy But people will still avoid giving it So have you actually followed up to see if actually your organization of information makes a difference or do you actually? have actual active pharmacist involvement and reconciliation of information as patients are Followed up in your system So there are there are a couple of dimensions to that questions so in terms of the the allergy business we do make referrals The the adverse drug reaction group does make referrals to allergy when there is a suspicion of an allergic mechanism being involved in terms of the Information that's available. I don't know if I would describe it as a formal decision support per se but under the final severity in the in the EMR These are the categories and if you can't read them The final severity is unknown then we have life-threatening delayed discharge permanent disability, which are severe But down here are is information that could be useful in terms of you know, the the Drug should be stopped I Think I think we have the there I didn't include it for time But there are recommendations in the EMR as to whether the drug or the same class of drug can be Considered safely in the future. We don't know How well at least I don't know how well that's being followed I don't know if the folks have have chased up on some of that Actually going back to the cost effectiveness. We were actually considering looking at the use of this Rithromycin increasing with the with the number of Beta-lactam related allergies that were in the system that were not allergies But I don't know the results of that either the short answer is that that we are trying to provide guidance, but it's not a formal decision-support thing at this at this stage Yeah, I had question just a logistics So you have a staff person at the hospital who gets contacted every time this box is checked Is that what am I understanding? Yes, we do it's a clinical so the one the one position that's that is supported solely for this pro program and the Is a clinical pharmacist who is in our division of clinical pharmacology? We also as part of our clinical pharmacology program. We have a sort of a personalized medicine consult service individual pediatric individualized pediatric therapeutics consult service some of the people who are affiliated with that service also and Inter-data and it's being extended now where if if a button is triggered in a Particular unit and there is a clinical pharmacist in that unit They are now starting to what we are training them to to collect the information. It's You know the program is expanding expanding when you We get more buy-in and we get people actually Interested and and committed to this as as a value to the institution So they're mostly pharmacy trained and that's the training of the people involved in this right. We have pharmacists Physicians and I believe a couple of people who have entered reports have been nurses as well So I think at this point we're going to open the Floor for general discussion. Thank you very much, Dr. Litter