Introduction and Overview of Rome IV – Dr. Douglas A. Drossman

please symposium agenda I assume you all have your packets we’ll start I’ll be giving an introduction and overview of the Rome foundation and the Rome for process and then we’ll have the working team reports which will be moderated by Robin Spiller we’ll have a brief break and then we’ll go into the support committee reports then the sponsor presentations and then at the end we’ll have an open forum for discussion I think it’s remarkable to have so many pharmaceutical companies together working together and I look forward to how the meeting goes so let me just tell you something and I apologize to the to the Rome for members because it’s the same pretty much the same talk I gave yesterday but by necessity we have to do it for the sponsors our mission is to improve the lives of people with functional GI disorders the focus is on the people with functional GI disorders we do this in three ways to promote the recognition and legitimization of the field to develop a scientific understanding of their pathophysiological mechanisms and to optimize clinical management this is probably the busiest slide we have just to give you an idea of what the Rome Foundation has done we developed the first classification system in 1990 we established the research utility and legitimize IBS and functional GI disorders to clinicians if you go back in many ways disorders that were of a functional GI nature were not not valued as much we promote a biopsychosocial model meaning that we’re looking at the integration of mind gut interactions and research and patient care we did develop the and validated the questionnaires to identify research populations and in 1993 20 years ago we published the first national epidemiologic study and what you’ll hear is that we’re now involved in global evaluation by Rome – these criteria were adapted by pharmaceuticals and regulatory agencies so if you’re doing a study in IBS or constipation or dyspepsia often this is going to be the the inclusion criteria what what you see here and what happens at our advisory board is we have a forum for interaction among industry and regulatory agencies and this involves the Japanese regulatory agency I believe is here today the EMA and the FDA we started in the last few years with rome 3 to start translating questionnaires and so we have become a global presence as I’ll show you and we’ll be moving forward further translations with Rome for hopefully concurrent with the Rome for publication we established annual research awards and we will now begin to increment them and we have international symposium the organization is a non-profit international organization 501c3 it has a president and board the members are selected similar to the National Academy or the Institute of Medicine that the board will determine areas of need or interest or value and then we select people based on a criterion system we have an Advisory Council that includes industry regulatory NIH and iff Gd we do have an associate’s program where people can join and we’re currently over 500 we have our system of committees and working teams and we have our administrative staff go on to the next slide this is the the the board is shown up here we have administration group the liaison committee which I’ll show you involves our global outreach public relations and support services which will be the web the book and so on and then our committee structure is down here there are six some support committees that you’ll hear from five working the clinical algorithms committee which is going to be revised and the Rome 4 committees which was launched yesterday at orientation as well as 19 pharmaceutical pharmaceutical sponsors this is our administrative staff just so that you’ll recognize them when Kelly it is our executive director Cecile Rooker’s director of marketing Michele is our administrator who handles the

scientific committee work Claudia Rojas has just come on about six months ago and is our Latino representative who will be involved in the booth and other Latin American programs and then we have our web site tech design we have a very effective medical illustrator which you’ll see the product in the next few years and we have a trade show monitor now Nik Sartorius who is the president of w-h-o wrote about the night icd-10 that was about to start he said a classification is a way of seeing the world at a point in time there was no doubt that scientific progress and experience with the use of these guidelines will ultimately require their revision and update and I think this is an important point when Rome first started coming out there was a lot of anxiety that things were gonna be etched in stone and it won’t change and it would stall progress well I think it couldn’t be further from the truth because what the whole process is one is evaluation and modification if needed if criteria are going to change the idea is to maintain the criteria but there is clear if there is clear evidence that a criteria needs to change that has to be provided before it’s accepted and occurs this is just the rationale for symptom criteria and you have to understand when the Rome committee’s their own working team started 20 years ago the concept was we need to find a better research instrument or physiologic instrument to define these conditions but as we learned that that’s one part of a larger picture which is the symptoms that patients bring to symptoms are defined by multiple factors as things have evolved in over the 20 years and so by having a symptom based diagnosis you have the ability to identify groups and to understand their physiologic determinants most importantly symptoms are what patients bring to doctors patients don’t bring to doctors that they have a physiologic disturbance or biochemical abnormality there is epidemiologic support that has bred true the strongest being IBS in terms of its three symptoms based on factor analysis population studies and clinical studies and this obviously has treatment implications and what I’ll show you later is that as we start to look at profiling these patients in a sense of looking at the dimensionality of their illness not just whether they have a diagnosis or not we can have very valuable treatment implications and this provides diagnostic standards it was actually modeled after the psychiatric classification and this is helpful for as you know for clinical trials and clinical care the limitations or qualifications is that the criteria are not fully evidence-based we really began this process by a Delphi approach when there was no science to define these conditions we brought experts together from around the world but as time has gone on we’ve what we’ve done is we’ve incorporated the evidence now one of the things we don’t do is that we don’t rely on evidence-based data let me put it this way we don’t rely on meta analyses to find clinical meaning we use a combination of looking at the evidence and then looking at that in the proper clinical context by people who’ve worked in this area and any changes that we’re doing are going to need validation we also recognize that the criteria done for research are not sufficient for clinical practice we can subgroup cap patients into categories and look at physiologic features but that needs to be translated into clinical management we recognize the fact and there’s been some recent concern that do we need to have these anatomic distinctions are there similarities and what goes on in the mid gut in the inner rectal area or the the upper the dyspeptic area and so we’re trying to look at ways to to undertake that for Rome for and to develop some clear ideas of distinctions that are clinically relevant so we need to identify meaningful subgroups diagnostic groups we want groups based on physiologic features that might be targeted for example to a particular drug we want to look at biomarkers and we will modify the criteria to fit new knowledge the concept of the biopsychosocial model is really nothing

new it’s just that there is a brain got access there are certain patients who might have only physiologic disturbances but when you get for example into chronic painful conditions you have interaction between this and there’s brain imaging to support that and we’ll be moving into demonstrating that in the papers not to mention that there could be genetic polymorphisms or environmental factors CAD which can amplify or modify this leading to the clinical outcomes that we see how have we done Rome one began around here the article started in 90 92 93 and the bromb one book was here and rome 2 came out about here and then rome 3 came out here and you can see there’s an incremental rise primarily where they’re using these big criteria and this is about one sixth of the articles that of pub been published on for example irritable bowel syndrome we we don’t want to take credit but we value the our participation in the rise in in in research going on in these areas we really began around 1988 with the Rome the first committee in Rome and if you’re wondering why it’s called the Rome foundation it’s because Aldo tore Sallee and also Enrico Karate re who’s here really had the idea of setting up working teams which were committees to solve clinical problems that did not have the evidence and so the Delphi method began here the first one was a first author was grant Thompson who did the paper on diagnostic criteria for IBS that then moved into 1990 when a full classification occurred and then the rest is history beginning with the rome 1 book the rome 2 book and then there was a supplement in gut rome 3 was in 2006 and then a supplement in gastroenterology and then we’ve also developed a primary care book clinical algorithms and a computer based imaging program round four will be scheduled to come out in 2016 fully ten years after rome 3 the computer-based learning program will be the basis for images that will be present in the book and online we do have a website which is a repository of information you can pick up the questionnaires for research the diagnostic criteria the publications for rome 3 this was the most recent thing is the communication skills workshop which is online if you’re interested in under ‘king in doctor/patient communications we have an annual newsletter and i suspect it’ll be out there grant Thompson wrote a primary care book but we’re taking this further by having a full committee as you’ll hear that we’ll be addressing where primary care doctors see these conditions I want to remind you that every year this is the sixth year we have an AGA Institute Rome Foundation lectureship we try to stay ahead of the game in terms of what’s important and this year it’s going to be on the role of food sensitivities and microbiota and functional GI disorders with two well recognised speakers in the area Kevin Whalen and Sheila crow and they’ll be speaking on Sunday morning from 8:00 to 9:30 room 109 a as I mentioned we did the communication skills workshop if you’re interested you could see it either at the AG a website where you can get CME credit or you can go to the Rome foundation website one of our new features is the Rome update so a dtw we will have an evaluation of the abstracts this will then be just adjudicated by committee is to to have the top abstracts and that’ll be presented in a video news format this was what was done last year and that will be online for CME credit the clinical algorithms is something we began in 2010 four years after the rome 3 process of publication and it came out of the criticism that the patients don’t come to you with diagnostic criteria they don’t say I have functional vomiting or irritable bowel syndrome they come with symptoms so the algorithms as you can see begin with a series of about 15 symptoms diarrhea abdominal pain nausea vomiting and so on and takes you through the diagnostic pathway coming to a diagnosis

so these algorithms as shown here they become we use standard decision-making we have a case report and annotated references with the each algorithm and then this leads to precise final diagnosis so it’s a diagnostic tool that could be helpful for primary care doctors medical students healthcare extenders and the like and it may reduce clinical costs by making an effort not to overdo diagnose six studies we now have translations in four languages and that’s going to be one of our features for Rome for is that these algorithms will be updated and available in the chapters I do want to thank our pharmaceutical sponsors anyone who’s here has a star next to their name that means that you’re going to be hopefully involved with the evaluation of the documents and providing feedback we have a total of 19 full sponsors 20 pharmaceutical companies we are engaged in collaborative efforts with the FDA and regulatory agencies Lin Chang is the Rome representative on the FDA C path committee we have had involvement with the various regulatory agencies they participate in the endpoints and outcomes and the IBS global conferences and we’re now talking about every two years in Milwaukee having something else like that that is of a involves regulatory aspects we do work closely with the IFF GD we we have collaborative meetings as I mentioned and we have a shared philosophy for patient care I want to introduce one other new committee that just formed which is the Rome am a pediatric committee the EMA came to us asking can we help them develop guidelines for pediatric functional GI disorders so we set up a subcommittee with Yan tock who was on the Rome Board Yan Tama now who’s with the EMA in pediatrics and Miguel SAP’s who’s in the child adolescent committee Rome the Rome committee and this cus subcommittee will be interacting with the design of treatment trial which Brennan’s Spiegel chairs and the pediatric child adolescent with Carlo dilorenzo chairs and they’ll make recommendations both to the Rome committees as well as to the EMA and then this will be reviewed by the committee for medicinal products for human use of the EMA and then hopefully there’ll be a combined set of recommendations for a design of pediatric functional GI disorders now I want to talk a little bit about the Global Initiative is ami here I’m ISA Berber okay you’ll be talking more on this is that right all right okay I’ll go quickly the International Liaison Committee which Dan do a trois co-chairs has been a committee that is an outreach to our global organizations they consult with their own foundation they’ll EA’s with other organizations Omni will tell you more about the translation project and the international committees which we have now several to try to not only bring our own information to these these areas but to learn from them in order to modify our criteria to make it truly a integrative culture of cross-cultural recommendations this is the International Liaison Committee representing the Middle East Eastern Europe Western Europe China Japan and Latin America this committee meets regularly and makes recommendations to us we’ve translated the rome 3 book into four languages and our algorithms also into four languages I imagine that in your packet you might have if you don’t have the algorithms we can have them available for you this all began with our 2011 meeting in Milwaukee and you can go online at the Rome foundation and see the actually hear and see the presentations one of our newest initiative is the China initiative where the hospital at Beijing set up a wing for teaching it’s a combined Rome Foundation North American educational foundation to teach functional GI disorders to gastroenterology in China I mentioned about the associates program the associates

program is a way for people to actually join because the nature of the committee is to select members this will allow people as you can see of a more international nature of a very international nature to come in to have discounts to be in given invitations and this involves a variety of individuals and anybody in a medical field including pharmaceuticals can be associates so that’s the overview and I think we have a very busy schedule so what I’m gonna do now is to give you a little bit about Rome for and then we’ll go into the presentations so you’ll understand what our what our goals are going to be the editorial board consists of five associate editors a managing editor administration and we have other staff as well involved we will be publishing the book online and in in printed version in 2016 and we’re fortunate to have this like Rome 3 as a special issue of Gastroenterology now why do we want to do Rome 4 people always say why do you keep reinventing well science has changed if you think about what’s happened since 2006 there’s much more involvement in the microenvironment microflora brain gut interactions more recently food and diet there’s constant discussion about the best research study design endpoints and outcomes and we’re also talking about new treatment options that didn’t exist in at that time we’re also feeling that we can move from consensus base to evidence-based diagnostic and treatment recommendations we also can I think dispel the functional organic dichotomy the idea of low-grade mucosal immune dysfunction some of the work being done in brain imaging is in many ways Organa fiying functional GI disorders just like there are organic disorders that could be functionalized you can see the concept of IBD IBS and so on we need to start to look at this within a multinational context and we’ve made considerable efforts to bring that information in and we also need to reach primary care what’s new for round four is that we’re going to what we’ve done right now we’re at the midpoint of the process where a series of committees by design have prospectively acquired new data to meet the needs of the field which will then be discussed today at the symposium we have expanded our chapters into areas that we think are very important to consider we’re updating the algorithms we’re going to have concurrent release of translations and you’ll hear more about that later online access this is going to be an online book the online book is going to open the door to have virtually unlimited information in terms of images graphic graphic images and so on now you might wonder how the committees were selected we have a set of criteria for the chairs and committee members based on academic accomplishment in their area of illness of an international nature there has to be some diversity in terms of the institutions and diversity issues as shown here in terms of discipline we have a multidisciplinary group of basic scientists clinician clinical gastroenterologist epidemiologist psychologists psychiatrists and the like and we also foster a group working in groups so the editorial board proposed names to the chairs and co-chairs once they were selected and there were some conditions like if a previous chair or co-chair was on it we wanted them to be on the committee as a member to help with the process and then we were looking at areas that we think were new or diversity issues one thing a Rome does have a network of associations of understanding in the countries who are the important people involved in those areas and then we suggested the members and endorsed them in 2012 so with this collaboration the chairs and coaches actually selected the committee we made recommendations they brought it back to us we endorsed it and then invitations went out in October there were a couple of conference calls that were set up and the meeting was now and now for the next two years the committee’s will be developing their chapters what are some of the challenges we want to address well I think we have to understand the overlap across conditions of conditions like PDS and

EPS and gastroparesis where does bloating and distension fit in with these disorders there are the really distinct syndromes or are they so involved with other conditions that they might be important to consider in their evaluation or criteria the whole concept of IBS see and constipation and now oh I see needs to be thought about primarily by the bowel committee then there’s the Co Association of bowel and pelvic floor conditions what about pain and discomfort in diagnostic criteria we’ve tended to acknowledge that both can be used for criteria other companies have shown that there might be distinct disc differences what is the physiologic load that is necessary in understanding conditions like functional heartburn is it nerd or do you have to have evidence of lack of pH or impedance what are the postprandial symptoms how do they relate to the IBS how two biomarkers fit in are there cross-cultural differences and then what is the role of the CNS on symptom severity and reporting so these are this is a variety of challenges we’re looking to undertake the support committees there are a series of committees as I’ve mentioned that are in place now you will hear from these committees questionnaire and validation systematic review is the committee that’s going to be providing the evidence for the committee and meta-analyses primary-care you’ll be hearing about that today too in terms of two roles one is how do primary care doctors understand these disorders and and then secondly how would we quotes translate this to a area of relevancy for primary care this will be a publication and then later a book for primary care some of you have heard may have heard this already but we are looking to develop guidelines to subset patients into clinically meaningful groups and if the way to think about this is that the wrong criteria is a categorical diagnosis you either have it or you don’t what we’re looking to do is to add dimensionality to that so that we can look at the essentially the continuum of patients with a condition say irritable bowel or dyspepsia and look at treatment as it may be affected by those subsets so we’re going to be profiling these patients with modifiers and then this will be in used online in the diagnostic chapters so here is a profile as it’s set up where the categorical diagnosis is the Rome criteria as it exists now that will continue to be the same with its aim there’s a priorities of how it gets published as a criterion what we then have is a class of clinical modifiers and this may have relevance for treatment it definitely does when you look at IBS CDM if you look at Rome three well everybody talks about IBS C and ibs-d it’s not in the criteria it’s merely a table that recommends a way of subsetting it so now when a patient an individual patient is profiled they’ll have a diagnosis and they’ll have a categorization is post infectious etiology going to be something that might involve different treatments than the lifelong history we also have a patient designated impact based on a question that we that can be asked where they can rate it as none mild moderate severe we know that in the more severe cases a functional bowel with pain there may be comorbidities that are preventing normal regulatory activities occurring from the brain to the gut and then there will be severity and physiologic features and continents as an example where there might be so much severity it might require different treatments than if it’s milder the working teams have published the guidelines for brain imaging in 2009 outcomes and endpoints in 2009 guidelines for severity 2011 and the role of intestinal intestinal flora 2013 and in addition to that the food and diet has just come out this month the food and diet is shown here there are a series of five articles in the american journal gastroenterology and I believe we may have copies for you and also we have the sorry we have the Asian working team which has been doing surveys to try to understand

how people in Asia are reporting these symptoms there are distinct differences the role of bloating for example is more commonly used in Asia one of the other important areas is that we’re endoscopic evaluation is much less expensive and the risk of cancer is higher there’s a distinction in the diagnostic approach where the the Asians might more likely do treat a test and then treat whereas we might do treat first you’ll hear more from AMI on the international cross-cultural research so we will have a chapter structure that includes for the criteria chapters of which there are five each condition we’ll have a diagnostic entity’s definition epidemiology the criteria any justification for change in the criteria pathophysiology clinical evaluation the multi-dimensional profile which I just mentioned will be actually part of the online version and as a separate book and treatment and recommendations for future research the content area chapters that are not diagnostic chapters will main pretty much maintain the same structure and there may be new chapter formats that are created the online features I want to mention that this is going to really open the area for for investigation for searching the book because you can download the full book or by selected chapters it’s also available as rental so or online a per search so if a medical student sees a case that he or she wants to evaluate for rounds the next day they can go online and pay for the search itself the computer-based learning and algorithms and the images will all be online as well so you could click on a condition such as dyspepsia you can then go to the algorithm or multidimensional case examples we also will be bundling this with a printed book there will be discounts actually any room for sponsor will have free access to the online publication so the deliverables I think we’ve talked about they’ll be a Rome for book now it’s going to be a three volume set the ebook and we are working on iPad applications and updating these they’re also going to have a pediatric book in a primary care book here’s the timetable I think you’ve seen this slide before we are right here in the middle of the process and then we’ll have annual updates for you in 2015 you will be getting manuscripts pre-publication for comments from the scientific the the research people in your in your organizations and then it’ll come out as a journal supplement and book the quality control it’s a very interesting collaboration we have with sponsors because we have to have the sponsors a part of yet apart from the process to avoid any perception of undue influence we have instituted the Institute of Medicine guidelines for interactions with conflict of interest there is a confidentiality statement and let me mention if the sponsors if you’ve not had a chance to sign your own confidentiality if you go out to the front during the break please sign it just saying that this information can be contained within your committee but not outside of that or outside of members there’s a peer review process which is just like any other publication and there will be an embargo on information until final editing and publication the last slide is just to show you the benefits of sponsorship we can skip the special certificate though you will get one but you provide feedback in preliminary on preliminary manuscripts you will receive a summary of the meta analyses done you will have free access to the questionnaires in criteria we now have instituted a copyright and licensing policy for studies which could cost ten to thirty thousand dollars as a sponsor you know that’s waived and you’ll get some bells and whistles all right thank you