AMERICAN ACADEMY OF PEDIATRICS IMPROVING THE AVAILABILITY OF PEDIATRIC DEVICES Washington, D.C. Monday, June 28, 2004 2 1 PARTICIPANTS: 2 JON S. ABRAMSON, M.D. 3 JOANNE R. LESS, PH.D. 4 BRAM D. ZUCKERMAN, M.D. 5 SUSAN MEADOWS, M.S. 6 LYNNE RICE 7 MARLENE HAFFNER, M.D. 8 ROSEMARY ROBERTS, M.D. 9 TERRIE L. CRESCENDI 10 KHODAYAR RAIS-BAHRAMI, M.D. 11 ROBERT M. CAMPBELL, JR., M.D. 12 LOU QUATRANO 13 ANDRE A. MUELENAER, JR., M.D. 14 ALFRED L. WICKS 15 JOHN H. GREINWALD, M.D. 16 ROBERT H. O'HOLLA 17 PATRICIA B. SHRADER, Esquire 18 TOM CONNAUGHTON 19 TODD ENGLANDER 20 MARIBETH SAYRE, M.D. 21 SUSAN ALPERT, M.D. 22 KATHY JENKINS, M.D. BETA REPORTING (202) 638-2400 1-800-522-2382 (703) 684-2382 3 1 PARTICIPANTS (CONT'D): 2 MURRAY M. LUMPKIN, M.D. 3 ELAINE VINING 4 JEANNE IRELAND 5 DIANE DORMAN 6 STEVEN GROSSMAN 7 ELIZABETH JACOBSON 8 TARN FEDERICI 9 BENJAMIN H. WALLFISCH 10 MARILYN J. FIELD 11 ANN LANGLEY 12 LISA KAESER 13 SARAH LINDEFOYT, M.D. 14 15 16 17 * * * * * 18 19 20 21 22 BETA REPORTING (202) 638-2400 1-800-522-2382 (703) 684-2382 4 1 P R O C E E D I N G S 2 (8:57 a.m.) 3 DR. ABRAMSON: We'll start out by 4 just everybody introducing themselves, 5 talking about what their affiliation is; if 6 they want to say a sentence or two and what 7 their interest is. 8 I'll start out. I'm John 9 Abramson. I'm Chair of the Department of 10 Pediatrics at Wake Forest and I just am the 11 past head of the Committee on Infectious 12 Disease Redbook where issues of both drugs 13 and devices come up repeatedly and we asked 14 the Academy to think about both. Initially, 15 they took on the issue of drugs and now 16 we're about to take on the issue of devices, 17 and also I'll also talk about a little bit 18 the issue of tests; lab tests, those kind of 19 things. 20 Mac, do you want to go around? 21 DR. LUMPKIN: Sure. Hi. Good 22 morning, everybody. I'm Mac Lumpkin. I am BETA REPORTING (202) 638-2400 1-800-522-2382 (703) 684-2382 5 1 the Acting Deputy Commission at FDA for 2 International and Special Programs. My 3 background is pediatric infectious diseases 4 and I'm here with a fairly large delegation 5 from FDA and people who will introduce 6 themselves as we get around to that part of 7 the table. 8 DR. JENKINS: I'm Kathy Jenkins. 9 I'm a pediatric cardiologist at the 10 Children's Hospital in Boston and I've been 11 involved with sponsoring pediatric device 12 trials for a number of years through my 13 hospital. 14 DR. ALPERT: I'm Susan Alpert. 15 I'm a chief quality and regulatory officer 16 at Medtronic in Minneapolis, and I used to 17 be with FDA. I'm also a pediatrician, 18 pediatric-infectious disease, two careers 19 ago. 20 DR. SAYRE: I'm Maribeth Sayre. 21 I'm with Masimo Corporation. We make pulse 22 oximeters and are based in Irvine, BETA REPORTING (202) 638-2400 1-800-522-2382 (703) 684-2382 6 1 California, and I'm a neonatologist by 2 training. 3 MR. ENGLANDER: My name is Todd 4 Englander. I'm a retail sales manager for 5 Cook Critical Care, one of the companies and 6 this is my first meeting. 7 MR. CONNAUGHTON: I'm Tom 8 Connaughton, Vice President of Legislative 9 Affairs 컴컴 pediatrics product, 10 particularly for critical care, and I'm 11 happy to be here. 12 MS. SHRADER: Good morning. I'm 13 Pat Shrader, with 컴컴 Dickinson & Company. 14 I'm Vice President for Public Policy and 15 Regulatory Affairs. For those of you who 16 are not familiar, we make a lot of low-risk 17 devices, but encounter, I think some of the 18 same issues, with devices for the pediatric 19 population that some of the other companies 20 do. 21 MR. O'HOLLA: Good morning. I'm 22 Bob O'Holla, Vice President of Regulatory BETA REPORTING (202) 638-2400 1-800-522-2382 (703) 684-2382 7 1 Affairs for the Device Businesses, within 2 Johnson & Johnson, and going back to our 3 history, we care about babies, and so we're 4 very interested in defining the topic here 5 this morning so we have a clear direction 6 forward. 7 MR. WICKS: Good morning. I'm Al 8 Wicks. I'm a professor of mechanical 9 engineering, Virginia Tech. My area is 10 instrumentation signal processing. We have 11 a strong relationship with Wake Forest now 12 and 컴컴 Biomedical, where we try to 13 integrate the activities in the chemical 14 engineer department with medical needs and I 15 have an interest in that area. 16 DR. MUELENAER: I'm Andy 17 Muelenaer. I'm from the 컴컴 Biomedical 18 Institute, but I'm also a practicing 19 pediatric pulmonologist in critical care and 20 I went in the military, did neonatology 21 also. I'm the medical director for the 컴컴 22 Biomedical Institute, which is a partnership BETA REPORTING (202) 638-2400 1-800-522-2382 (703) 684-2382 8 1 between an integrated health system, the 2 University of Virginia, and Virginia Tech, 3 and I've worked with Al on projects. 4 My reason for being here is I'm 5 involved in technology transfer from the 6 universities and the development of medical 7 devices. I'm also an inventor and I also 8 own my own small company. So I have several 9 perspectives today. 10 MR. QUATRANO: My name's Louis 11 Quatrano. I'm with the National Institutes 12 of Child Health and Community Development, 13 and in particular, the National Center for 14 Medical Rehabilitation Research and involved 15 in supporting device development and so 16 forth as the program 컴컴. 17 MR. CAMPBELL: I'm Bob Campbell, a 18 pediatric orthopedist at the University of 19 Texas outside San Antonio. I'm very 20 interested in 컴컴 surgical devices; I 21 helped developed one, and I'm on the 22 National Organization of Rare Disorders BETA REPORTING (202) 638-2400 1-800-522-2382 (703) 684-2382 9 1 Medical Advisory Committee. 2 DR. RAIS-BAHRAMI: Good morning. 3 I'm Rais-Bahrami Khodayar. I'm a 4 neonatologist at Children's National Medical 5 Center at the George Washington School of 6 Medicine. 7 MS. ROBERTS: I'm Rosemary 8 Roberts. I am from the Center from Drugs. 9 I am the Deputy Director of the Office of 10 Counterterrorism and Pediatric Drug Czar. 11 (?) 12 (Laughter) 13 DR. LUMPKIN: Also known as bombs 14 and babies. 15 (Laughter) 16 DR. HAFFNER: Hi. I'm Marlene 17 Haffner. I'm the I think sole internist in 18 the group here, so I'm delighted that you 19 allow me to be here. I have, for the last 20 almost 18 years, been responsible for the 21 FDA's Office of Orphan Products Development, 22 just finding ways to develop particularly BETA REPORTING (202) 638-2400 1-800-522-2382 (703) 684-2382 10 1 drugs, but also devices for folks with rare 2 diseases. We have long targeted pediatrics, 3 so we're really pleased to see emphasis from 4 the device arena coming here and we worked 5 closely with Dr. Campbell in the development 6 of his device. So I'm delighted to be here. 7 I have one other thing to say and 8 that is that -- and I think I can say this 9 in a pediatric group -- I have a bit of ADD 10 and so I do needlepoint during meetings. 11 It's the only way I can concentrate, 12 otherwise, I'm not here. So I hope I don't 13 bother you. 14 (Laughter) 15 MS. RICE: I'm Lynn Rice. I'm 16 with the Center for Devices and Radiological 17 컴컴. I'm also Director of the Office of 18 Communication, Education and Radiation 19 Programs and so we're here to work on how we 20 can put the education piece as well as 21 working on the report to Congress. 22 MS. MEADOWS: I'm Susan Meadows. BETA REPORTING (202) 638-2400 1-800-522-2382 (703) 684-2382 11 1 I work with Lynn in the Office of 2 Communication, Education and Radiation 3 programs. I'm an advisor in that office and 4 I work in the area of constituent relations 5 and human factors. Our role here is to 6 coordinate the development of the report 7 back to Congress. 8 DR. ZUCKERMAN: Good morning. I'm 9 Bram Zuckerman. I'm the Director, FDA 10 Division of Cardiovascular Devices, so I'm 11 here as a representative of one of the 12 pre-market divisions that regulates medical 13 devices. We're currently responsible for 14 the pre-market review of cardiovascular 15 devices, cardiothoracic surgery devices, and 16 peripheral vascular devices that are used to 17 treat arterial disease. I'm an adult 18 cardiologist by background. 19 MS. LESS: I'm Joanne Less from 20 the Center from Devices and 컴컴 Help. 21 Normally, I work in investigational and 22 humanitarian devices. I've been on detail BETA REPORTING (202) 638-2400 1-800-522-2382 (703) 684-2382 12 1 for the last year and a half directing the 2 implementation of MDUFMA, the Medical Device 3 User Fee Modernization Act, of which this 4 report is so-called the technical amendment. 5 Thank you. 6 DR. LINDEFOYT: I'm Sarah 7 Lindefoyt. I also work at FDA in the Office 8 of Work and Products Development. I'm a 9 family physician and I direct 컴컴 device 10 program in our office, which is part of 11 Joanne's program to develop devices for 12 conditions that affect 컴컴. 13 MS. VINING: I'm Elaine Vining. 14 I'm with the American Academy of Pediatrics 15 and I want to welcome everybody and thank 16 you for the long trips you've taken and give 17 you a couple of housekeeping items while I 18 have the floor. 19 (Laughter) 20 MS. VINING: One is please help 21 yourself to coffee and breakfast across the 22 way. Lunch will be served there as well. BETA REPORTING (202) 638-2400 1-800-522-2382 (703) 684-2382 13 1 The ladies' room and men's room require a 2 key, which you get at the front desk here. 3 The men's room is on this side through our 4 glass doors. The women have to go across 5 the elevator banks and then you'll find the 6 restrooms there and please speak up. This 7 is going to be recorded. We have a 8 transcriber here, but also there is an 9 individual from the FDA on the phone and it 10 will be helpful for him to hear the 11 conversation as well and yourselves as well 12 because the air-conditioning gets a little 13 bit loud here, and if it's hot or cold or if 14 it's comfortable, please let us know and 15 we'll try to do whatever we can. 16 Thank you. 17 MS. IRELAND: I'm Jeanne Ireland 18 with the Elizabeth Glaser Pediatric AIDS 19 Foundation for 컴컴 Public Policy. We're 20 thrilled to be co-hosting the meeting and 21 want to thank AAP for putting together a 22 lovely meeting, as always, and it's just BETA REPORTING (202) 638-2400 1-800-522-2382 (703) 684-2382 14 1 wonderful to see everybody from so many 2 different areas all in the same room. 3 MS. DORMAN: I'm Diane Dorman, 4 National Organization for Rare Disorders; 5 Vice President for Public Policy, and I'd 6 like to mirror Jeanne's comments. Welcome, 7 everyone. 8 Thank you. 9 MS. JACOBSON: I'm Liz Jacobson. 10 I'm Executive 컴컴 and Regulatory Affairs at 11 컴컴, which is the largest trade association 12 of medical device manufacturers in the 13 world. Our manufacturers make about 90 14 percent of the dollar value of the devices 15 that are sold in this country and our 16 members range from small companies to very 17 large companies and about 70 percent of our 18 members are small companies. So this is a 19 very exciting meeting and 컴컴. 20 MS. FEDERICI: I'm Tara Federici, 21 컴컴 Vice President of 컴컴 Regulatory 22 Affairs 컴컴. BETA REPORTING (202) 638-2400 1-800-522-2382 (703) 684-2382 15 1 MR. WALLFISCH: I'm Ben Wallfisch 2 with the Medical Device Manufacturers 3 Association. In general, we 컴컴 to talk 4 about access to the 컴컴. 5 MS. KAESER: I'm Lisa Kaeser. I'm 6 the 컴컴 Director at the National Institute 7 of Child Health and Human Development. 8 MS. FIELD: I'm Marilyn Field at 9 the Institute of Medicine, National Academy 10 of Sciences and we're in the process of 11 undertaking a legislatively requested study 12 of post-market surveillance and pediatric 13 medical devices on the study for 컴컴. 14 MS. KELLY: I'm Claire Kelly. I'm 15 the Associate Director of Public Policy at 16 the National Association of Children's 17 Hospital and we're also 컴컴. 18 DR. ABRAMSON: Thank you. This 19 is -- oh; I'm sorry. I didn't mean to. 20 SPEAKER: I was blocking his view 21 here. 22 MS. BUTTERFIELD: I'm Christian BETA REPORTING (202) 638-2400 1-800-522-2382 (703) 684-2382 16 1 Butterfield. I'm here at the Academy of 2 Pediatrics and I'm also representing the 3 Pediatrics Academic Society, APS SPR, 컴컴, 4 and also the Society for 컴컴. 5 MS. ROSENFELD: Hi. I'm Taren 6 Rosenfeld. (?) I'm actually here with the 7 Academy of Pediatrics. 8 MS. MATTHEWS: I'm Katie Matthews. 9 I'm here also with the Academy and I'm here 10 if you need anything. 11 (Laughter) 12 DR. ABRAMSON: Anybody else I 13 missed? 14 SPEAKER: On the phone. 15 DR. ABRAMSON: Oh; on the phone. 16 I'm sorry. Yes. Can the person on the 17 phone introduce themselves? 18 MR. RUDOLPH: Yes; Paul Rudolph. 19 I'm with the FDA, Office of the 20 Commissioner, Office of Policy. 21 DR. ABRAMSON: Thank you. When we 22 took on the issue of drugs, we did this in a BETA REPORTING (202) 638-2400 1-800-522-2382 (703) 684-2382 17 1 collaborative manner with companies, the 2 FDA, and others, and I think came out with a 3 set of rules and regulations that markedly 4 improve our ability to use drugs that are 5 safe and efficaciously for children; the 6 same thing here. That's exactly what we 7 want to do. We want to work 8 collaboratively. We're having to spend 9 time, about four years ago, getting into 10 this with Susan Alpert, when she was at the 11 FDA, I came to realize that it's a very 12 different beast, but still the aim, the 13 final aim, is to create devices and tests 14 that can be used with children safely and 15 efficaciously. 16 The goal of the meeting is to 17 generate some consensus around action steps 18 that stakeholders can independently or 19 collaboratively build on or institute to 20 improve the availability of pediatric 21 devices. It's to also encourage 22 participation, but need to limit the length BETA REPORTING (202) 638-2400 1-800-522-2382 (703) 684-2382 18 1 of responses, so I will at times ask you to 2 speak and please do so, but I am going to 3 have to limit so that we can get through 4 this in a day so that we don't take on any 5 one particular device or issue to any large 6 extent. 7 As groups, we're going to talk 8 largely about issues, not get weighed down 9 on the specifics, and how do we turn the 10 specific successes that we've had with 11 devices into a broader solution for children 12 and I want to encourage creative ideas and 13 solutions. The Dammer Act, the regulations 14 and legislation that goes with it were 15 creative. They were a new way of doing 16 things and I think very good. 17 Mac, do you want to say anything 18 and then we'll get on to a few of the 19 presentations and then we'll open up to 20 discussion. 21 DR. LUMPKIN: Yes. Thanks, Jon. 22 I feel very good sitting next to Jon here. BETA REPORTING (202) 638-2400 1-800-522-2382 (703) 684-2382 19 1 As some of you might know, Jon was a 2 resident when I was a medical student at 3 Wake Forest, so we've been side by side 4 before. It goes back than either of us care 5 to remember. 6 I would like to take this 7 opportunity, on behalf of the senior 8 political and senior career leadership at 9 FDA and all of my colleagues who are here to 10 thank all of you for being here today and 11 especially one more time to be able to say 12 publicly a great deal of thanks to Elaine 13 and the American Academy and the Glaser 14 Foundation and NORD and others who clearly 15 were the catalyst and the instrument that 16 made the situation occur with 17 pharmaceuticals that did occur over the past 18 seven or eight years of struggle to get us 19 to the position that Jon was just talking 20 about. 21 I mean, there was clearly no other 22 group, other than AAP, that was as tenacious BETA REPORTING (202) 638-2400 1-800-522-2382 (703) 684-2382 20 1 and as committed to seeing that particular 2 effort be taken forward, through all the ups 3 and the downs and two pieces of legislation 4 and court cases and all kinds of things that 5 we had to go through. I mean, every time it 6 seemed very bleak or that this was going to 7 be taken off course, Elaine would rally the 8 forces of good and once again it would come 9 forward. 10 So Elaine again, thank you for 11 what you did then and thank you very much 12 for what we're trying to do here and your 13 role and the role of all your colleagues 14 here in trying to make it happen when it 15 comes to devices. 16 I think when we were looking at 17 the pharmaceutical situation and trying to 18 figure out how could we make that a better 19 situation for children, not only in our 20 country, but ultimately to spill over to 21 children around the world, there were really 22 two fundamental principles that I think all BETA REPORTING (202) 638-2400 1-800-522-2382 (703) 684-2382 21 1 of us were unwilling to give on, and one was 2 the reality that children are not just 3 little adults, and because of that, that 4 makes a difference and no one is better than 5 pediatricians and caregivers of children to 6 know what those differences are and to try 7 to make the laws and the regulations and 8 public policy recognize those differences. 9 The second was that children are 10 not second-class citizens and if there are 11 scientific standards for safety and efficacy 12 for adults, there has to be a good 13 explanation if we don't use those same 14 standards in children as to why we are not 15 using those same standards; that indeed 16 children are not second- class citizens. 17 They should be our first among equal 18 citizens, and if we're going to be 19 responsible for them as adults, they deserve 20 the best from a scientific perspective that 21 we can get. 22 So I think, you know, those two BETA REPORTING (202) 638-2400 1-800-522-2382 (703) 684-2382 22 1 principles served us very, very well as we 2 went forward, looking at how, as Jon said, 3 very collaboratively try to figure out what 4 we could do to make the pharmaceutical world 5 better for children. 6 I think that's why we're here 7 today. As people have already said, we have 8 a very tight deadline from the FDA to 9 produce a report to Congress that will 10 hopefully be the foundation for a public 11 policy debate on how this country can go 12 forward in the world of devices and in order 13 to put that report together, we need to 14 identify what barriers exist today to 15 getting well-studied, well-developed, 16 well-manufactured, well- understood products 17 or devices available to our children. 18 There might be regulatory 19 barriers. There might be clinical barriers. 20 There might be ethical barriers. There 21 might be legal barriers. There might be 22 economic barriers. These were all barriers BETA REPORTING (202) 638-2400 1-800-522-2382 (703) 684-2382 23 1 that existed as far as the pharmaceutical 2 situation was concerned and they were all 3 ones that we had to identify and deal with 4 and many of which we continue to deal with 5 as we go forward. 6 So I think our goal here today is 7 to try to identify those barriers and also 8 to begin to put forward solutions to getting 9 us beyond those barriers and I know I and my 10 colleagues very much look forward to hearing 11 your perspectives on this so we can go 12 forward with this initiative. 13 Unfortunately, I'm going to have 14 to leave at ten this morning to go to a 15 meeting at the Department, but unless things 16 change, I should be back after lunch and I 17 plan to be here all afternoon to hear the 18 afternoon discussion. 19 So I do look forward to this 20 meeting. Again, thank you all for being 21 here and again thanks, Elaine, for 22 everything. Thank you. BETA REPORTING (202) 638-2400 1-800-522-2382 (703) 684-2382 24 1 DR. ABRAMSON: I'm going to give 2 the first presentation. I promise you I'll 3 be done by 9:30 with mine. 4 I was at the Institute of Medicine 5 last week and I think the Institute of 6 Medicine heard a lot of information and a 7 very vibrant discussion of things that 8 pediatricians in various specialties need to 9 get better devices and I think they heard 10 from epidemiologists and others the 11 scientific problems in trying to get those 12 regulations and things that are necessary to 13 do these studies underway and find out what 14 the safety issues are. I'm even going to 15 try to highlight a few issues for you. 16 (Discussion off the record) 17 DR. ABRAMSON: While we're 18 waiting, let me make a few points. We're 19 going to concentrate on devices, but there 20 are issues also surrounding tests. A good 21 example of this, from my standpoint, is that 22 for many, many years, there were rapid 컴컴 BETA REPORTING (202) 638-2400 1-800-522-2382 (703) 684-2382 25 1 tests on cerebral spinal fluids that were 2 available that were being used and these 3 tests are neither sensitive or specific 4 enough to be useful, but they will be used 5 to make decisions and I think really to 6 adverse outcomes in children, some of them 7 not being treated inappropriately; some of 8 them being treated 컴컴. 9 So there are a whole lot of issues 10 that surround the issue of testing that 11 we're not going to get to today; maybe 12 another day. 13 So these are the new 컴컴 14 technologies. These are considered -- I 15 think we should make the point that there's 16 an ethical responsibility to assure that we 17 have safe and effective devices for use in 18 children for the various diseases that they 19 have. 20 Next slide. These are the number 21 of new devices. These are not what I'm 22 going to call "me-too devices," which I'll BETA REPORTING (202) 638-2400 1-800-522-2382 (703) 684-2382 26 1 show you in the next slide, but these are a 2 number of new devices that have been 3 approved by the FDA since 1993. 4 Next slide. These are a number of 5 what I would call "me-too devices," so you 6 have an 컴컴 and now you have an improvement 7 or alleged improved in an 컴컴 monitor and 8 those do not require the same degree of 9 safety and efficacy testing that the new 10 devices do. 11 Next slide. These are some of the 12 things that are here coming out predicted in 13 the next five years and as you can see, if 14 they work, they're going to be remarkable 15 improvements in our ability to take care of 16 patients. So there's a lot of promise out 17 there in the world of devices. 18 Next. So there are steps towards 19 컴컴 pediatric device needs that 2001 컴컴 20 the protection of pediatric 컴컴 research 21 studies were extended. In 2002, there were 22 medical device user fees, 컴컴 Act of 2002. BETA REPORTING (202) 638-2400 1-800-522-2382 (703) 684-2382 27 1 So 컴컴 the Dammer Act, and they include 2 provisions for the 컴컴 to conduct a study 3 and report back to Congress by October 2006 4 on 컴컴 surveillance of pediatric medical 5 devices. 6 Next. 컴컴 updated and now the 7 FDA has a report due to Congress by 8 October 1, 2004, on various availability of 9 devices intended for the treatment and 10 diagnosis of diseases that affect children, 11 and then the Federal Registry Notice 12 requesting public comment on 컴컴 13 availability. 14 Next. So the points that many of 15 you 컴컴 not overall, you know, is that 16 infants and children suffer from many of the 17 same diseases and conditions as adults, 18 similar to adults. The pediatric population 19 need devices that 컴컴 long and prudent 20 life, 컴컴, establish effective and 컴컴 21 safety, will shorten hospital stays, reduce 22 basic procedures, and to me, there's a BETA REPORTING (202) 638-2400 1-800-522-2382 (703) 684-2382 28 1 burgeoning world of in-home devices, 2 ventilators being used at home. 3 We experienced extreme frustration 4 during the past decade, trying to get any 5 child who needs a long-term ventilator out 6 of your hospital and what was created 7 because these institutions or hospitals that 8 specialize in this don't exist and the 9 reimbursement's inadequate is these patients 10 go home. They go home on home ventilators. 11 They go home without any power supply 12 back-up except for batteries. 13 There are pumps that we use in 14 homes to deliver drugs. There are many 15 reports of 컴컴 drugs being given too fast 16 to 컴컴. These are all problems that have 17 been created and I think this is a 18 particular area that people have not paid 19 attention to. 20 Next. There are diseases and 21 conditions that are unique to children and 22 there are adult diseases and conditions that BETA REPORTING (202) 638-2400 1-800-522-2382 (703) 684-2382 29 1 occur in children for which children 컴컴. 2 So there's a whole category of 3 devices that you just can't shorten the 4 length of the decatheter and fix the problem 5 for the child. 6 Next. There are dynamic growth in 7 potential devices that impact growth; 8 potential migration of titanium devices when 9 they're used in plastic surgery and they 10 sort of don't stay in the same position as 11 they would in an adult who's not growing. 12 There are differences in 컴컴 13 sizes. The biochemistry of a child is 14 different from adults and I'll try to give 15 you a few examples of these. 16 There's an active lifestyle of 17 infants, children and adolescents that 18 markedly affect devices. For instance, if 19 you go close to a playground where there are 20 particular types of plastic, it can 21 deprogram a Cochlear implant. This was 22 something I was unaware of prior to the BETA REPORTING (202) 638-2400 1-800-522-2382 (703) 684-2382 30 1 컴컴. 2 There are infections triggered by 3 pediatric-specific considerations. In other 4 words, urine contamination of a catheter in 5 the stomach and groin area of a baby who 6 wears diapers. That's not a problem, 7 particularly in adults, but it is a problem 8 in children. 9 Next. The impact of devices on 10 organ growth for infants and children, again 11 another example is undersized heart valves 12 used in children. We have to keep replacing 13 these. Is there not a way that we can come 14 up with that would allow the device to grow 15 as the child grows? 16 The impact of long-term device 17 implementation of children, the absorption 18 rate of 컴컴 cranial/facial devices, the 19 leaking of the gastrostomy tubes; those are 20 all just some of the examples that we really 21 don't know the long-term effect of. 22 Now, I sit there day and day BETA REPORTING (202) 638-2400 1-800-522-2382 (703) 684-2382 31 1 fighting the issue of giving 25 micrograms 2 of mercury and influenza vaccines. These, 3 to me, are much more long-term and much more 4 reasonable issues; efficacy and/or adverse 5 컴컴 in children may not be predicted from 6 the adult experience and there are many 7 examples of that, such as 컴컴 of 컴컴. So 8 no one can really predict it going in. 9 Next. There is a lack of 10 pediatric-specific information about a 11 device and diagnostic test. You know, the 12 Pharmaceutical Act, you only had to make one 13 point to get everybody's attention: At the 14 point where we 컴컴 for drug studies, 15 specifically for children. We were able to 16 tell people that 80 percent of the drugs 17 they were using at that time would be used 18 for an indication and/or age for which the 19 FDA did not approve. We don't even know 20 that in the 컴컴. We have no clue. We have 21 very little denominated 컴컴. 22 Lack of appropriate pediatric BETA REPORTING (202) 638-2400 1-800-522-2382 (703) 684-2382 32 1 devices may require more and basic treatment 2 whereas physicians' hospital staff have 3 gerry- rigged devices to make them work for 4 children. You have no idea how 컴컴 those 5 work, and again I want to bring home the 6 safety and efficacy of home devices. 7 Next. I'll stick to my own area 8 because I want to make several points for a 9 minute. There are lots of shunts, lines and 10 catheters. We accept high infection rates 11 now. We don't even know what the 컴컴 are, 12 but we all know that they're fairly high 13 because we're dealing with them every single 14 day, but we don't have denominated data. 15 So I think it is not okay to 16 accept them. We need to be able to create 17 catheters and lines that resist the 18 adherence of these bacteria to the lines and 19 make the rates of infection much lower. 20 VP shunts are a great example. I 21 can't tell you how many VP shunts I've seen 22 fail because either the shunt is no longer BETA REPORTING (202) 638-2400 1-800-522-2382 (703) 684-2382 33 1 worker or they get infected, and once they 2 get infected, boy, it's hard to treat them 3 with 컴컴 and often you don't even have to 4 replace the shunt. 5 Now, I've seen kids who no longer 6 have the ability to put them into their 7 ventricular perineum and you have to put 8 them into the heart and that's a huge 9 problem because those hearts later on get 10 all sorts of problems with the shunt being 11 in there. 12 Next. So we've talked about the 13 high rate of infection. 14 We've talked about the need for 15 better design, so the design issue; this is 16 not an issue that, per se, says that isn't 17 safe and effective. These lines are 18 effective, but they're not safe. They are 19 not safe at all. 20 Next. There are issues around 21 critical care and cardiology that 22 Dr. Jenkins may talk about. Left BETA REPORTING (202) 638-2400 1-800-522-2382 (703) 684-2382 34 1 ventricular cyst devices, we do not have 2 these for children less than five years of 3 age. That's a big problem. 4 Next. The ones for five to 5 seventeen are under protocol, is my 6 understanding, is under research protocol. 7 컴컴 infants and children less than five 8 years of age who have critical failure of 9 their ventricle have to be supported on 컴컴 10 extra corporeal membrane oxygenation until 11 they can be transported. 12 These systemizers are a much 13 better way of bridging that gap. All right. 14 There are these available 컴컴 that can 15 support pediatric patients in small infants. 16 They're in Germany. They ought to be in the 17 United States or at least we ought to know 18 that they're not safe and effective and 19 we're not going to 컴컴. 20 Next. So mere partnership among 21 all the stakeholders to improve the 22 availability of devices in neonates, BETA REPORTING (202) 638-2400 1-800-522-2382 (703) 684-2382 35 1 infants, children, and adolescents, I think 2 will create many more devices and more 3 opportunity for business if we can work 4 together and come up with ways of creating 5 the devices, but making sure they're safe 6 and effective. 7 We need tracking and reporting 8 mechanisms. The IOM heard a ton about this. 9 We have essentially no numerated 10 data and no 컴컴. Eight or ten clinicians 11 there were told that there are mechanisms 12 for reporting failures; none of the 13 commissions knew these, knew how to do 14 these. Where we do know how to do them for 15 drugs and vaccines. Expansion of 컴컴 16 systems to encourage development of devices. 17 Next. I'm going to move out of 18 the way here and, Joanne, you will talk 19 about the FDA's -- 20 MS. LESS: I have to go behind 21 you? 22 (Laughter) BETA REPORTING (202) 638-2400 1-800-522-2382 (703) 684-2382 36 1 MS. LESS: Can we do it sitting? 2 DR. ABRAMSON: Say it again. 3 MS. LESS: Is there a reason, when 4 we talk, not to do it sitting? 5 DR. ABRAMSON: No. 6 MS. LESS: Before I get started, 7 again I wanted to thank the American Academy 8 of Pediatrics and the other 컴컴 -- Diane 9 and Jeannie -- for all of your help in 10 pulling this meeting together. FDA, 11 obviously, couldn't do it, as quickly as 12 they did, and we really appreciate you 13 taking this on and doing it for us. 14 When Wayne and Jeannie and Diane 15 and I were talking about the agenda, one of 16 the things that we thought we should spend a 17 few minutes on is FDA's regulations. We 18 have three basic mechanisms to get 컴컴 19 devices to market, and we thought it was 20 important that everybody start on the same 21 page and understand the difference between 22 a 510(k) and an HDE, not, you know, to kill BETA REPORTING (202) 638-2400 1-800-522-2382 (703) 684-2382 37 1 you with it, but at least to give you some 2 basic information on that. 3 The first process that we have -- 4 and this is for the lower risk devices -- is 5 what we call a 510(k) and it's called that 6 because that's the section of the law that 7 it comes from. These are basically Class II 8 devices and unlike the patent process, a 9 company's goal here is to say that you're 10 just like something else that's already been 11 approved for marketing. 12 So you don't want to say yours is 13 unique or different. You want to say you're 14 just like something else that's out there 15 and most of these go through without 16 clinical data. There's usually marketing 17 that's just based on description 18 information, some performance testing, bench 19 testing, bio comparability, but only 20 about 10 to 15 percent actually include 21 clinical data and we see about 4,000 of 22 these per year. So it's our biggest BETA REPORTING (202) 638-2400 1-800-522-2382 (703) 684-2382 38 1 program. 2 The device we have here -- it took 3 me forever to figure out what it was and I 4 finally had to go ask somebody; I borrowed 5 this picture from someone. It's actually a 6 palm-held device for ECG. So it's one of 7 our newer things and it's kind of neat and 8 it did go through the 510(k) process. So it 9 goes to show that it's not just old 10 technology being found equivalent to old 11 technology. There's a lot of advances that 12 go through in the 510(k) process. 13 Premarket approval process is 14 reserved for our higher- risk devices; life 15 sustaining, life supporting, substantial 16 importance in treating disease. In this 17 process, the company needs to establish 18 reasonable assurance of safety and 19 effectiveness. That doesn't mean it has to 20 be absolutely safe and effective, but 21 reasonable assurance. 22 For these types of applications, BETA REPORTING (202) 638-2400 1-800-522-2382 (703) 684-2382 39 1 we see bench, animal, human data, and it's 2 important to find out that although all of 3 our PMAs do have clinical data in them, 4 they're not all randomized in full trials. 5 A lot of times we have historical data, 6 literature, crossover signs, patient 컴컴 7 their own control. 8 About 40 percent of the time we do 9 require post- approval studies. That really 10 depends on whether there's some unanswered 11 questions that we still feel that the 12 company needs to address in a post-market. 13 They should not be safety and effectiveness 14 related. It's usually long-term or a 15 specific question maybe that our advisory 16 panel 컴컴, and we see about 50 of these a 17 year. So it's a much smaller program, but 18 the bigger the device is, the higher the 19 risk. 20 Now I'm going to talk about the 21 HDE program, since this is the focus of so 22 much of their current discussion down on the BETA REPORTING (202) 638-2400 1-800-522-2382 (703) 684-2382 40 1 Hill. In 1990, with SMBA 90, Congress added 2 the humanitarian device exemption provision 3 to our statute and that was aimed at devices 4 that are supposed to be treating or 5 diagnosing diseases of which there's less 6 than 4,000 patients in the U.S. per year. 7 God only knows where the 4,000 came from. 8 It started as 8,000, if you look in the 9 legislative history, but when it was passed, 10 it was changed to 4,000. So there isn't 11 really a lot of discussion on where 12 the 8,000 came from or why it got cut 13 to 4,000. 14 For these devices, the idea was 15 that the company could not do a 컴컴 16 clinical trial to support safety and 17 effectiveness or reasonable terms of safety 18 and effectiveness and so because of that, 19 Congress added this provision to say that 20 the device could be exempt from 21 effectiveness as long as there's no other 22 alternative device out there and the company BETA REPORTING (202) 638-2400 1-800-522-2382 (703) 684-2382 41 1 would not otherwise bother to bring the 2 device to market. There was not enough of a 3 financial incentive to do that. 4 At the bottom, I have a couple of 5 the ones that we approved. The first one 6 over here is a cultured skin substitute for 7 컴컴 deformities. We have two heart valves 8 that have gone through; one Medtronic and 9 one from 컴컴, and again, these were aimed 10 at pediatric subjects for which there's a 11 higher rate of calcification to the heart 12 value is specially treated and try to slow 13 down that calcification rate. The last one 14 is the LVAD, that we just approved in 15 February for pediatrics from 5 to 16. 16 The approval threshold for an HDE 17 is completely different than what you see 18 for an PMA. Unlike a PMA, where you're 19 trying to show reasonable assurance of 20 safety and effectiveness, this is basically 21 what the statute says. It's a long 컴컴 22 threshold. The device will not expose BETA REPORTING (202) 638-2400 1-800-522-2382 (703) 684-2382 42 1 patients to an unreasonable or significant 2 risk of illness or injury. The probable 3 benefit outweighs the risk of illness or 4 injury, taking into account the probable 5 risks and benefits of alternative devices or 6 other treatments. 7 So unlike PMA, where a company 8 needs to show that their antibodies has 9 reasonable assurance and safety and 10 effectiveness, this is more of a comparison 11 where we're looking at the safety, we're 12 looking at probable benefit, but we're also 13 taking into account what else is on the 14 market for that patient population, and 15 that's the critical piece, because all of 16 these come in. There's almost nothing else 17 out there. We don't have a lot of data, but 18 when you look to see what the course of the 19 disease and what's going to happen to that 20 subject without the device, that's what 21 helps you make the decision. 22 For an HDE, the statute requires BETA REPORTING (202) 638-2400 1-800-522-2382 (703) 684-2382 43 1 IRB approval. Congress thought that even 2 though it's an improved device and 컴컴 3 marketing that the IRB should be involved, 4 it makes it complicated for the IRBs because 5 there's no protocol and there's also no 6 informed consent requirement under the 7 statute. So it's tough for the IRBs. 8 They're not exactly sure what they're 9 supposed to be looking at since we already 10 made that 컴컴. For an HDE, you can't make 11 a profit and you can recover your cost, just 12 like for an IDE. You can recoup your cost 13 of research development and your 컴컴 14 distribution. 15 So an HDE is sort of like a cross 16 between an IDE and a PMA as far as the 17 approval. The threshold is more like an 18 IDE, except 컴컴 approval. You can't make a 19 profit, but it is marketing 컴컴). 20 We only get about five or ten of 21 these per year. It's a fairly new program. 22 We didn't have any regulations until the mid BETA REPORTING (202) 638-2400 1-800-522-2382 (703) 684-2382 44 1 to late nineties; 1996, so we only get about 2 five per year. So it does sort of seem like 3 a new program to us. 4 It's a two-step process. We work 5 with Marlene Haffner's group and the Office 6 of Products Development makes these 7 decisions for us as to whether or not 8 there's less than 4,000 patients in the U.S. 9 per year, with that 컴컴. 10 Well, when we wrote the 11 regulation, what we wanted to do was make 12 sure the companies didn't waste their time 13 putting together an HDE that wouldn't either 14 meet the 4,000 threshold or wouldn't meet 15 our threshold for approval, and so we 16 divided up into two steps, and so the first 17 piece is to go to the Office of Orphan 18 Products Development. They make the 19 decision whether or not there's less 20 than 4,000 subjects in the U.S. from here. 21 If they meet that threshold, then they can 22 submit their HDE to us and the HDE BETA REPORTING (202) 638-2400 1-800-522-2382 (703) 684-2382 45 1 application looks like an PMA. It's 2 actually formatted just like that as far as 3 contents go, but it's different, since there 4 is no requirement for clinical trial, it's 5 mostly bench testing, animal testing, 컴컴 6 and some clinical experience. 7 I think we were at 컴컴' process, 8 the bottom of the statistics slide, HD 9 process and approvals. So far we've 10 approved 34 HDEs; 6 of these were 11 pediatrics, including the LVAD, a couple of 12 heart valves, water simulator. That's an 13 urgent stimulator 컴컴 for children with 14 spinobifida and also the 컴컴 stems. That 15 was originally the 컴컴 came from the 16 co-group and it came in as a PMA. We 17 concerted it over to an THE when the 18 regulation went into effect. It went to 19 panel as a PMA. The panel thought it was a 20 very promising device, but they didn't think 21 there was enough data to show reasonable 22 signs of safety effectiveness that we BETA REPORTING (202) 638-2400 1-800-522-2382 (703) 684-2382 46 1 converted it to an HDE. 2 We have 18 HDEs that we've 3 approved for both a coronary graft for 4 patients undergoing cabbage that don't have 5 enough 컴컴. Two finger joints, the 컴컴 6 and MCP and also from a descending aortal 7 section. 8 Then we have ten 컴컴 for both; 9 the gastric simulator. Medtronic 컴컴 10 nauseam, vomiting, due to gastric 컴컴. 11 That was actually again under IV for a very 12 long time, slow enrollment. A lot of 컴컴 13 requests. We actually had 컴컴 requests 14 that went to President Clinton asking that 15 that device be made available. 16 The company was about to give up. 17 They didn't think that they could do the 18 trial to support the PMA and then 컴컴 come 19 under the agency provision, and then one 20 that I mentioned 컴컴. 21 Now I have my slide with the 22 little 컴컴 patients and they move. You BETA REPORTING (202) 638-2400 1-800-522-2382 (703) 684-2382 47 1 can't see those. 2 (Laughter) 3 DR. ABRAMSON: We'll wait. 4 MS. LESS: It's worth waiting for, 5 let me tell you. 6 DR. ABRAMSON: We'll need to see 7 that. Why can't we use adult devices in 8 children? I think Dr. Abramson was talking 9 about this; Dr. Lumpkin, and all of you are 10 familiar with these reasons. 11 I wanted to give you an example 12 though. If you look at that list, the 13 disease or condition may be limited to 14 children the sizes of the device, the growth 15 of the patient, hormonal influences, 16 activity level of the children and the 17 maturity level of the patient. 18 The deep brain simulator that we 19 recently improved under the HD process pulls 20 in almost all of those. The deep brain 21 simulator was for chronic, intractable 22 primary dystonia, a little neurosimulator BETA REPORTING (202) 638-2400 1-800-522-2382 (703) 684-2382 48 1 that gets implanted 컴컴 in the abdomen, the 2 컴컴 up through the back of the neck into 3 the brain. 4 Well, in children, it makes it 5 more difficult because if you have two 6 neurosimulators, you can get crossed talked. 7 You don't have to worry about the size of 8 the neurosimulators, where you're implanting 9 it, whether or not you get some erosion 10 through the chest wall. As the child grows, 11 you don't have to worry about the 컴컴, 12 whether or not they need to have extensions 13 or lengthening; whether they're going to 14 migrate due to the activity level of the 15 child, and also that in simulators, usually 16 컴컴 under general anesthesia as opposed to 17 sedation for adults. So there's a lot of 18 different risks and a lot of different 19 things to think about just in that one 20 device. 21 The next one. Why do we need to 22 get the clinical data? Again, we've talked BETA REPORTING (202) 638-2400 1-800-522-2382 (703) 684-2382 49 1 about this a little bit already. Ensure the 2 device is properly designed. There is a 3 tendency, when a device comes in, that's 4 already approved for an adult indication, if 5 it's going to be changed or used in the 6 pediatric population, we say, well, we know 7 a lot about it, you know. It's really not 8 all that different. It's pretty similar. 9 Maybe if we can just get a little bit of 10 data, but if we have actual pediatric 11 clinical data, we can make sure that it is 12 properly designed if there are some unknown 13 risks that were not taken into account. 14 We want to also want to ensure the 15 safety and effectiveness is demonstrated, 16 again, that it's not presumed that we don't 17 just think that it's going to work okay 18 because you know it looks like it from the 19 adult data; that we get an accurate risk and 20 adverse event assessment. We've been 21 surprised by some adverse events when the 22 device goes into clinical trials, 컴컴 that BETA REPORTING (202) 638-2400 1-800-522-2382 (703) 684-2382 50 1 you don't necessarily think about, and if 2 you know what these risks and adverse events 3 are, you can address them through the 4 labeling. So hopefully even if there are 5 some events out there, you can mitigate the 6 risks through proper labeling. 7 The last thing I wanted to mention 8 under age appropriate instructions or use, 9 not just that you get the data so that you 10 know whether it's appropriate for infants or 11 pre- adolescents or whatever sub-population 12 you're indicating the device for, but also 13 if there's human factors issues; if the 14 advice is actually going to be used by the 15 child, that you make sure that you write the 16 instructions for use so that the child can 17 understand them. 18 When do we ask for pediatric 19 clinical data? There is no hard and fast 20 rule. We look at the device. We look at 21 the indications for use, and we look to see 22 whether obviously if the device is indicated BETA REPORTING (202) 638-2400 1-800-522-2382 (703) 684-2382 51 1 for children, do we have any adult data and 2 if we do, is it relevant or is it sufficient 3 in the case of the fetal bladder 컴컴, 4 obviously we weren't going to have any adult 5 data. We did use data though from a lung 6 study where that 컴컴 had been used to drain 7 fluid in the lung and we decided that 컴컴 8 could drain fluid in the lung that that 9 supported, then you could also drain urine. 10 So although it wasn't adult pediatric, it 11 was sort of a different type of study that 12 was done. 13 But we do look first to see 14 whether or not we can use the adult data. 15 Under the Food and Drug Modernization Act 16 of 1997, we were charged with making sure 17 that we look at the least 컴컴 for a company 18 to demonstrate effectiveness to get advice 19 on the market and we would consider this to 20 be part of that to look to see what data we 21 already have, whether we really do need to 22 have clinical data, whether we can 컴컴, and BETA REPORTING (202) 638-2400 1-800-522-2382 (703) 684-2382 52 1 a lot of times if a device is being 2 modified, that's what we can use. 3 In the case of the LVAD that we 4 approved in February, we had the old data. 5 The device was modified. There were two 6 basic modifications to go into the pediatric 7 population. One had to do with an 컴컴 of 8 the tubing coming off the LVAD, the other 9 with the diameter of the tubing, and main 10 concerns we had with that were the flow and 11 turbulence and so we could use some basic 12 animal testing to address that. 13 We also had some clinical 14 experience from Europe, and then we asked 15 for a post-approval study to make sure that 16 we do exactly what was going on and that we 17 had all of our bases covered. 18 The last is approval methods for 19 pediatrics. What we saw with the brain 20 stimulator was the level of stimulation for 21 pediatrics 컴컴 slightly different than what 22 you would expect for an adult. BETA REPORTING (202) 638-2400 1-800-522-2382 (703) 684-2382 53 1 When you look at marketing the 2 pediatric devices, they basically fall in 3 three categories. The first one is the 4 easiest: That adult device, you can use in 5 adults, you can use in pediatrics. There's 6 no special issues. These tend to be the 7 lower risk devices, the ones that 8 컴컴 510(k). Syringes, wound dressings, 9 컴컴, and 컴컴, manual surgical instruments, 10 monitoring and imaging devices. We don't 11 usually have clinical data to support those 12 and those are 컴컴 that are easier ones to 13 컴컴. 14 The second category are devices 15 that are limited to pediatric use: The 16 infant heel warmer and newborn hearing 17 screener -- those both in 510(k). I just 18 wanted to mention for the infant heel 19 warmer, that device is actually exempt 20 from 510(k), meaning a company can go to 21 market without coming into the agency if 22 it's for adults. If it's for infants, they BETA REPORTING (202) 638-2400 1-800-522-2382 (703) 684-2382 54 1 do have to 컴컴 submit a 510(k) to us, but 2 all we're really looking at is this 컴컴 3 device to make -- it's basically a heat 4 pack. You crumble it up and it generates 5 heat and we we're just looking at this 6 excellent device and making sure it gets to 7 the right temperature, doesn't get too hot, 8 doesn't stay there too long. 9 The fetal bladder stent went 10 through an HDE and we did have 컴컴 on that 11 and the occluder for PDA. Again, that went 12 through a PMA process so we did have a 13 clinical trial for that. 14 We tried to use bench and animal 15 testing as much as we can to answer at least 16 the basic safety and effectiveness questions 17 and then reserve the clinical data for 18 specific either risk questions or things 19 that the panel might raise. 20 Then we have sort of the adult 21 devices that get sized down or modified for 22 pediatrics and again this can be more BETA REPORTING (202) 638-2400 1-800-522-2382 (703) 684-2382 55 1 difficult because you have the adult device 2 out there and the tendency is to say well, 3 it's probably okay for pediatrics. We'll 4 get a little bit of data to make sure that 5 everything's okay, but how much is that 6 little data? Is it five or ten patients? 7 Is it a hundred patients? Sometimes it's 8 hard to decide how much you actually need to 9 identify 컴컴 make sure that you have a good 10 risk assessment for the device. 11 We have lots of examples of the 12 heart valves. Not only are they a different 13 size, like I mentioned, they're treated 14 differently to reduce the calcification 15 rates in pediatrics. We have orthopedic 16 implants, Cochlear implants, so you have 17 different issues with the Cochlear implant 18 that's for a 컴컴 the risk of a child versus 19 an adult, and the ventricular devices again; 20 there's different in 컴컴 rates, questions 21 that we have to be sure that we take into 22 account. BETA REPORTING (202) 638-2400 1-800-522-2382 (703) 684-2382 56 1 Again, mostly we've tried to start 2 with the bench and animal testing to address 3 these special issues and then turn to 4 clinical data when we need it. 5 I put up here a list of the 6 difficulties that we see in collecting 7 pediatrics clinical data and this isn't 8 necessarily everything obviously and it's 9 not -- it might not even be accurate -- but 10 this is what we're hearing from clinicians 11 and from 컴컴. 12 First, that doing a clinical trial 13 in children is unethical and we actually 14 have one clinical trial now that the IRB had 15 a difficult time reviewing and bumped it up 16 to FDA, and so there's one example and way 17 where the IRB thought it was unethical to do 18 the trial. 19 We also hear that there's problems 20 in enrollment by the prevalence of a disease 21 or condition, reluctance of the parents. 22 They don't want to put their child in a BETA REPORTING (202) 638-2400 1-800-522-2382 (703) 684-2382 57 1 clinical trial either because of the risks 2 or the inconvenience or just not knowing 3 enough about the device. 4 Same thing from clinical 5 investigators and IRBs; these are a little 6 bit reluctant to enroll children in clinical 7 trials, and a lot of that has to do with the 8 additional testing. They don't want to 9 expose their kids to whatever additional 10 things might go into the clinical trial that 11 they were getting 컴컴. Ensuring protocol 12 compliance can be much more difficult with 13 children, and lastly, the limited financial 14 incentive for industry. If the patient 15 population is small, the cost of the trial 16 is large, you have to use multiple sites to 17 get enough patients in a trial, it's going 18 to cost the company a lot more to do it and 19 maybe they won't bother; they'll just stick 20 with the adults. 21 The last thing that I wanted to 22 mention is if you don't have a pediatric BETA REPORTING (202) 638-2400 1-800-522-2382 (703) 684-2382 58 1 device available, what are the options for 2 an investigator or a physician 컴컴? 3 The first obviously would be to 4 use the device off label, and rather than 5 컴컴 different indications, I should have 6 also included devices that are labeled for 7 adult- patient populations, but then are 8 used in pediatrics. 9 So it's either adult devices that 10 are completely different indications, which 11 we do see a lot, or if it's a different 12 patient population by age, and under our 13 law, under Section 906 of the practice of 14 medicine, physicians are free to use an 15 approved device in any way they want and FDA 16 is not supposed to limit that or interfere 17 with that practice. 18 The only thing that we can do is 19 look at the company and make sure that 20 they're not promoting or advertising for 21 that 컴컴 indication. We see a lot of 22 emergency and compassionate use. Under BETA REPORTING (202) 638-2400 1-800-522-2382 (703) 684-2382 59 1 emergency use, the physician makes the 2 decision that as the best alternative for 3 his or her patient, under compassionate use, 4 they have to 컴컴 FDA and we make that 5 decision based on what we know about the 6 device, and again we're talking about 7 investigational devices or devices that are 8 being imported from overseas. 9 So we don't necessarily know a lot 10 about that device. We have some basic 11 information on it, the 컴컴, sometimes we'll 12 ask you for some testing. We might know 13 that it's on the market in Europe or it's 14 been CE marked, but it's not like a full- 15 blown kind of 컴컴 know a lot about that 16 device, so it's hard to make that decision 17 컴컴 compassionate 컴컴. So usually we'll 18 try to make that decision within a couple of 19 days. Emergency use of 컴컴 within minutes 20 or hours, so it's a tough decision to make 21 without much information. 22 The last is custom devices. We've BETA REPORTING (202) 638-2400 1-800-522-2382 (703) 684-2382 60 1 had some cases -- we had one recently -- 2 where an infant was involved in a car 3 accident and the physician went to a company 4 and said could you make a stabilizer for the 5 컴컴. So the company made it and it was 6 shipped out and the physician used it. 7 So there are these mechanisms 8 available, but there's not improved 9 pediatric device, but I would argue that 10 they're for the short term or they're good 11 for case-by-case, but it's certainly not 12 going to 컴컴 see on a larger scale. 13 Our challenge today: To encourage 14 the government 컴컴 new pediatric devices 15 without increasing the risk to pediatric 16 subjects. We don't necessarily want to 17 lower the threshold to get more pediatric 18 devices out there, just so that we have them 19 available. If we don't really know what the 20 risk profile is, we've done nothing more but 21 get 컴컴 out there that don't actually help 22 the subject, but our patients at risk. BETA REPORTING (202) 638-2400 1-800-522-2382 (703) 684-2382 61 1 Unduly increasing the burden on 2 컴컴 for FDA and 컴컴 proven for adults and 3 so trying to do all of this, I think is 4 going to be a challenge and we really 5 appreciate all the help that you can give us 6 since we have such a short time frame to 7 pull it all together. 8 (Laughter) 9 MS. LESS: Thank you. 10 DR. ALPERT: As you already heard, 11 many medical device companies already 12 address issues that are important in the 13 development and availability of pediatric 14 devices or devices for the pediatric 15 population; in fact, in a lot. As Joanne 16 pointed out, particularly for certain types 17 of devices, and that includes some of the 18 lower risk devices, it's a foregoing 19 conclusion, at the beginning of device 20 development, that is going to be for all 21 ages and all sizes and all groups of 22 patients and that development takes place, BETA REPORTING (202) 638-2400 1-800-522-2382 (703) 684-2382 62 1 making sure that all of the patients who are 2 in need of certain therapy are bracketed. 3 That doesn't mean that there 4 aren't challenges, and I'm going to talk a 5 little bit about them, but I wanted to make 6 a couple of introductory remarks, I think, 7 before I actually start the formal 8 presentation. One is to emphasize, as 9 Joanne pointed out, about four to five 10 thousand medical devices a year go through a 11 process called the 510(k) process, premarket 12 notification, and if you're not familiar, it 13 sounds like gee, those devices have no 14 understanding or there's no understanding of 15 the safety and effectiveness of those 16 devices, so why are they going to market and 17 that's been talked about in the press over 18 the last couple of years. 19 In reality, those devices may be 20 different and are compared on the basis of 21 their design in engineering, but their 22 safety and effectiveness is related to the BETA REPORTING (202) 638-2400 1-800-522-2382 (703) 684-2382 63 1 safety and effectiveness of the earlier 2 devices. So it's an assumption and a 3 movement of safety and effectiveness data 4 from one device to another. I didn't want 5 anybody to walk out of the room thinking 6 that there are 4,000 devices a year and 7 there's no information about whether they're 8 safe or effective because there is. It just 9 happens to be linked to an earlier device 10 and in many cases, those devices that go 11 through that process are actually linked to 12 an earlier device by the same company. So 13 we're talking about changes, modifications, 14 and improvements, and that's important to 15 understand about the device industry. 16 When it comes to existing 17 technologies, this is an evolutionary 18 process. Devices, engineers -- and there 19 are about three engineers in the room and 20 you will know and for those who don't know, 21 engineers don't leave anything alone. So as 22 things are evolved, by the time they get to BETA REPORTING (202) 638-2400 1-800-522-2382 (703) 684-2382 64 1 market, somebody's already been making 2 changes, making improvements, trying to make 3 it better, easier to use, less expensive, 4 and to address new diseases and new 5 conditions. So this is an evolving process. 6 When it comes to brand-new 7 technologies, most really revolutionary, 8 really novel technologies in the medical 9 device arena, come from work between someone 10 who's in need of the product. Someone who's 11 identified a specific new need and maybe an 12 engineer, maybe a big company, but it really 13 comes -- but the novel devices generally 14 come from someone's idea, from working with 15 someone who's in need. 16 So I think this particular group 17 getting together, where we have a lot of 18 people from different areas of pediatrics, 19 who can talk about needs is going to be 20 extremely helpful for the discussion. 21 I put a question mark after 22 barriers because I don't think that they're BETA REPORTING (202) 638-2400 1-800-522-2382 (703) 684-2382 65 1 really barriers. I think they're challenges 2 and they're challenges for all of us who are 3 physicians in neat- looking and in need of 4 certain kinds of devices, challenges for 5 industry to come up with the technologies 6 and the appropriate way of developing those 7 technologies and challenges for the 8 regulators as well to figure out how do we 9 do this while we don't increase the burden 10 so much that there's no one who can, in 11 fact, manufacture and -- design and 12 manufacture -- devices for special needs 13 populations, and I think of pediatrics as a 14 special need, although for many diseases, 15 it's really not so different, and also not 16 inordinately increasing the burdens that are 17 in place and the true barriers to putting 18 something in the market that would prevent 19 them being available even once they're 20 developed and manufactured. 21 I know we're not going to talk 22 about it today, but Jon did mention BETA REPORTING (202) 638-2400 1-800-522-2382 (703) 684-2382 66 1 reimbursement and I want to make sure that 2 we don't lose that thought that there is -- 3 there are the issues of design and 4 development of products through the issues 5 of the regulatory market entry and then 6 there are issues about reimbursement and 7 those also impact the availability of these 8 technologies. So if we increase the cost of 9 development being then too high and 10 reimbursement's a problem, we're not going 11 to have them available for the populations 12 as well. 13 So I just wanted to keep in mind 14 that these are challenges and they're 15 broader than just specifically identifying 16 what device is needed and who might develop 17 it. 18 These have already been talked 19 about. Identification of needs. I'm going 20 to come back to that in a moment. Research 21 needs for pediatric uses. I think Joanne 22 pointed out a lot of the issues that face us BETA REPORTING (202) 638-2400 1-800-522-2382 (703) 684-2382 67 1 as companies when it comes to developing 2 devices for use in the pediatric population. 3 I'll come back to that, and then the 4 development issues, which I want to spend a 5 little bit of time on so that we both have a 6 common understanding of some of the 7 challenges that are in place for companies 8 in developing devices for the pediatric 9 population. 10 Again, this ground has already 11 been gone over. There are issues about 12 products already in the market being used in 13 adults. Difference of size, which usually 14 comes to mind first, but is not the big 15 issue. The issue of performance, which 16 comes up much more often in the pediatric 17 population. The number of times that that 18 fluid is cycled, the rates at which pumps 19 and pacemakers still work; all those things 20 that challenge in terms of actual 21 performance measures and then risks, and 22 Joanne talked about those already. BETA REPORTING (202) 638-2400 1-800-522-2382 (703) 684-2382 68 1 If products are unavailable, 2 there's a real question about how do we get 3 that communication? How do we get the 4 communication from the population -- 5 clinical population -- and the physician 6 population, well enough recognized and the 7 industry population so that there is an 8 understanding of what the needs are, who's 9 in need, which pediatric population, which 10 age? 11 You already heard it's not about 12 adults in pediatrics, as all of you know. 13 It's about adults and newborns, infants, 14 small children, older children, adolescents. 15 There's lots of ways with breaking down the 16 pediatric population and the need to 17 understand where is this product in need, 18 what age group, what specific disease groups 19 and therefore what will be needed to get 20 into that population. 21 The next slide, please. I want to 22 spend most of my time right here, on this BETA REPORTING (202) 638-2400 1-800-522-2382 (703) 684-2382 69 1 slide, and that is because this points out 2 some of the challenges -- again, not 3 barriers -- but challenges to developing 4 devices in the pediatric population. One is 5 designed. 6 The infants for design development 7 really come best to us as industry from the 8 clinical population, from the clinical user, 9 from you, from the physicians. In 10 understanding what this population at need 11 is -- as I said, which of the pediatric 12 populations is in need; what are the special 13 issues for that population? What are the 14 special changes? What are the unique things 15 that happen to children as they grow and 16 mature that are important to understand and 17 design because it's not about size? It's 18 really about overall design, and going 19 back -- if you have already have a product 20 in market -- going back to develop that 21 device for pediatrics frequently means a new 22 device developed; a really new development BETA REPORTING (202) 638-2400 1-800-522-2382 (703) 684-2382 70 1 process, and that development process needs 2 a lot of information from the use of a 3 potential user community. 4 Another issue is materials. There 5 are materials that are perfectly safe for 6 use in adults that may not be as safe for 7 use in children and, therefore, for those of 8 us developing those devices, we need to go 9 back and do the materials testing. New 10 materials testing can be a four- or 11 five-year process. We're talking about long 12 lead times and understanding the needs for 13 materials to be tested, but that the bench 14 and lots of animal testing and some of that 15 animal testing is long-term testing in order 16 to be sure that the materials are 17 appropriate for pediatrics. 18 Again, when you go back, even if 19 you have a product in the market, never mind 20 the brand-new product, sometimes, as is 21 pointed out, the older product may be more 22 difficult because you're going to have to BETA REPORTING (202) 638-2400 1-800-522-2382 (703) 684-2382 71 1 reevaluate materials and change them and 2 that could change all device design. 3 On bench testing, bench testing is 4 done on the actual product most often so you 5 have to get through a lot of testing before 6 you can get to actually doing bench work, 7 but bench testing in the medical device 8 arena is extremely useful. It addresses not 9 only the performance of the device, but many 10 issues that are focused on safety and 11 effectiveness can, in fact, be evaluated at 12 the bench in engineering testing for medical 13 devices, and I'm emphasizing that because 14 it's not only about clinical testing. 15 Clinical testing in medical 16 devices pretty much is the confirmation that 17 you got it right and that you do understand 18 the issues of safety and effectiveness well 19 enough, but it's not from scratch because 20 bench testing -- and then the animal testing 21 that's done -- can get you significantly 22 down the road on the issues of safety and BETA REPORTING (202) 638-2400 1-800-522-2382 (703) 684-2382 72 1 effectiveness when you're talking about a 2 medical device. 3 Again, the devices are designed to 4 address a specific need, so they're created, 5 designed, developed, and built to meet those 6 specific needs. Therefore, knowing what the 7 end goal is allows the development of 8 testing and evaluation at the bench and then 9 in animals that is very specific to the 10 issues of safety effectiveness for the 11 product so that by the time you get to any 12 needed clinicals, it's really confirmation 13 testing and not putting something in and 14 saying you're not really sure how this 15 works, what it's going to do. It's really 16 quite a different process when we talk about 17 medical devices. 18 Animal testing has some challenges 19 in it as well. I think Joanne mentioned a 20 little bit about what's needed for doing 21 testing for medical devices if you are going 22 to be using them in infants or are you going BETA REPORTING (202) 638-2400 1-800-522-2382 (703) 684-2382 73 1 to be using them in small children? 2 Frequently that testing, there will be a 3 need for testing in appropriate aged animal 4 populations. 5 Again, it's a challenge to do 6 that, to design devices that you can 7 actually test in that way because animals 8 are not the same size obviously as the 9 populations we're trying to address 10 clinically. 11 So a lot of assumptions need to be 12 made in order for animal testing to be 13 appropriate. It really is a challenge for 14 the medical device developer. 15 When these are insufficient, when 16 design materials testing, bench testing and 17 animal testing don't get you all of the 18 information you need and when you've figured 19 out what you don't know and what needs 20 confirmation, you go into human clinicals. 21 A lot can be gained from doing 22 human clinicals and non- pediatric BETA REPORTING (202) 638-2400 1-800-522-2382 (703) 684-2382 74 1 populations where it's appropriate to have a 2 device used in an adult population. There 3 are situations where if a disease obviously 4 is only one condition, is only in the 5 pediatric population, there's no option, all 6 of the testing needs to be done or whatever 7 clinical testing needs to be done must be 8 done in the pediatric population, but for 9 many devices, the clinical information 10 developed in testing and use in an adult 11 population is extremely useful and very 12 informative for the use of pediatrics. 13 Again, pediatric clinical testing 14 isn't starting from scratch. We need to be 15 sure that we are more open to understanding 16 what can in fact be understood and used from 17 adult testing and what small amounts of 18 information might need confirmation, 19 particularly on issues of a particular 20 safety concern, an issue in pediatrics that 21 has to do with growth and maturing of the 22 pediatric patient versus the adult patient, BETA REPORTING (202) 638-2400 1-800-522-2382 (703) 684-2382 75 1 but a tremendous amount of safety and 2 effective information can, in fact, come 3 from the adult experience. So where and 4 when needed are really critical challenges 5 as well as questions for the medical device 6 developer. 7 Then an area of manufacturing, 8 when we talk about the manufacturing of 9 devices that are different from what is 10 already being manufactured, what we're 11 talking about has a couple of aspects. One 12 is when you manufacture devices, obviously 13 you have to develop the equipment that can 14 manufacture the device you're talking about, 15 although in the device industry, a lot of 16 work is done by operators, by humans. A lot 17 of people do a lot of handwork in the 18 development of medical devices. 19 There's still a lot of equipment 20 that's used and, therefore, moving from the 21 manufacture of a device for adults to a 22 different size or a different capacity, BETA REPORTING (202) 638-2400 1-800-522-2382 (703) 684-2382 76 1 different rate capacity, different engines, 2 different software, all of that, 3 manufacturing needs to be changed. So 4 that's a big area for us and understanding 5 what we're going to need to do for medical 6 devices. 7 There are shelf life issues. That 8 has to do with what's the size of the 9 population and how much of the device will 10 be used. It has to do with how we rate our 11 manufacturing, how we make sure that devices 12 of all of the different sizes can be 13 available appropriately in time, not just in 14 design and in development and through FDA, 15 but also continue to make them available 16 appropriately in the pediatric population 17 where you've had a range of different sizes 18 and performance issues across the pediatric 19 population, so that has to do with how we 20 manufacture and then there are times when 21 creating particular devices for the 22 pediatric population is going to have BETA REPORTING (202) 638-2400 1-800-522-2382 (703) 684-2382 77 1 challenges in manufacturing that don't exist 2 for the adult device. A lot of that may be 3 related to size. Some of it may be related 4 to use. 5 Again, I just want to point out 6 that the issues of developing a device for a 7 specific population in need, in particular 8 the pediatric population where there are 9 issues of size, development, change over 10 time, pose real significant challenges to 11 the manufacturing community. 12 Next slide. So what do we need? 13 Talking about barriers and challenges; we 14 have some from the device industry side and 15 I wanted to take on two. One is what we 16 need from the clinical community and then 17 I'm going to talk a little about what we 18 need from the regulatory community. 19 As I said, one of the issues that 20 comes up most often in devices and the way 21 in which most devices are developed is by 22 good communication between the use -- the BETA REPORTING (202) 638-2400 1-800-522-2382 (703) 684-2382 78 1 potential user -- and the individuals 2 designing -- trying to design -- the product 3 and therefore the input, design input, from 4 the clinical community is a critical need. 5 One of the things that I found 6 though from when I was at the FDA and 컴컴 7 industry is that although we'll know some of 8 the things, some of the needs, some of the 9 products, I am unaware of a good compendium 10 that identifies a good listing or website or 11 anyplace to go to find out what the critical 12 needs are for pediatric devices. Where are 13 the gaps, and that's got to come from the 14 clinical community. 15 We need the specialty societies 16 and practicing pediatrics in all areas of 17 pediatrics to identify the areas where there 18 are needs because without that gap, without 19 understanding what those gaps are and where 20 the needs are, it's really not possible for 21 us as manufactures to understand where we 22 need to go, understand where the critical BETA REPORTING (202) 638-2400 1-800-522-2382 (703) 684-2382 79 1 issues are, and understand how to move our 2 processes. 3 As I already pointed out, those 4 processes need lead time, so we need to have 5 an understanding from the community where 6 the real needs are, where the critical 7 issues are so that we can address them and 8 figure out do we have technologies already 9 available that need some modification to 10 work in pediatrics and where are the places 11 where really new development needs to take 12 place in order to meet pediatric needs. We 13 don't know what all those needs are. 14 As was already pointed out, many 15 companies already address pediatric needs 16 when they're making devices. The LVAD are 17 now down to five years old. Pacemakers go 18 all the way to infancy. All different types 19 of direct delivery devices are available for 20 all ages. There's lots of places where that 21 work is already being done. So we need to 22 understand better where are the gaps, where BETA REPORTING (202) 638-2400 1-800-522-2382 (703) 684-2382 80 1 are the leads so that we can address them. 2 I want to put in one comment, 3 although I know Pat will take this up later, 4 and that has to do with the development of 5 diagnostics. Most diagnostics do go 6 through -- come to market -- through 7 the 510(k) process that Joanne described; 8 the free market notification process, but 9 let me assure you that those 510(k)s contain 10 clinical data, but they're not new clinical 11 studies. 12 510(k)s on the diagnostic side 13 contain large numbers -- large amounts -- of 14 data that was developed with samples already 15 available to the manufacture and samples 16 from all different populations so that the 17 availability of testing -- I think one of 18 the issues that we'll face, and I'll let Pat 19 speak to the issues in diagnostics -- but 20 one of the issues is what are norms? In 21 order to understand the sensitivity and 22 specificity of a diagnostic test, you need BETA REPORTING (202) 638-2400 1-800-522-2382 (703) 684-2382 81 1 to understand what the norms are in that 2 population. Again, a place where we need 3 information, input, and cooperation from the 4 clinical community. 5 We also need the clinical 6 community to participate as we move forward 7 in helping us understand testing, in 8 participating in the appropriate trials and 9 data-gathering, whether they are pre-market 10 or post-market. We need a lot of 11 cooperation from the clinical community in 12 order to get the information and this is not 13 a one-size fits all, well, we're just 컴컴. 14 There are some real issues here about what's 15 the right kind of data to capture, how is 16 that data collected, how is it brought 17 forward, and whose data is it. 18 So we have a lot of issues where 19 we're going to need help from the clinical 20 community to take a leadership role in 21 defining what's needed and then moving on 22 and developing the bridge that will be BETA REPORTING (202) 638-2400 1-800-522-2382 (703) 684-2382 82 1 participants in whatever human testing is 2 needed and in capturing information 3 post-market. 4 Next slide. What we need from the 5 regulators -- Joanne talked about some of 6 these, but I'm going to reemphasize them. 7 One of the challenges here that I already 8 talked about, Joanne talked about, and Jon 9 mentioned it as well, is understanding what 10 amount of data is needed to move products 11 into use of pediatrics. If products are 12 already available for other populations -- 13 for the adult population maybe; for the 14 elderly population, which is not -- for 15 those not in devices who may not be aware -- 16 our devices also have to be evaluated in the 17 elderly frequently because they 18 physiologically are also not like people 19 between the ages of 18 and perhaps 컴컴. So 20 we do need to understand from the regulator 21 and need the regulator to understand how 22 current data can be used and the amounts of BETA REPORTING (202) 638-2400 1-800-522-2382 (703) 684-2382 83 1 current data that are already available that 2 can, in fact, be used to help move products 3 into the market specifically for pediatrics. 4 Reasonable requirements for 5 sufficient data development 컴컴 pediatrics. 6 Joanne talked about it a little as well and 7 from an industry perspective, one of the 8 critical needs from the regulator is 9 advanced understanding of what is going to 10 be necessary to put a product into the 11 market. 12 I already spoke several times 13 about the fact that device companies need 14 long lead times to do this development. If 15 we get through development and FDA has 16 changed the requirements, we're set back. 17 We're set back, we can't move our products 18 forward and we can't get them. So we need 19 to be sure that the regulator identifies 20 what the real data needs are, what's going 21 to be expected so we can move products 22 efficiently into the markets. BETA REPORTING (202) 638-2400 1-800-522-2382 (703) 684-2382 84 1 DR. ABRAMSON: You've been hooked. 2 DR. ALPERT: Is that the hook? 3 (Laughter) 4 DR. ABRAMSON: Yes. 5 DR. ALPERT: The next point, which 6 is almost visible, I think is the most 7 critical. As we go through this process 8 together, we need to be sure that we are not 9 creating additional barriers that are going 10 to prevent rather than promote the 11 development of devices for pediatrics. This 12 is a real challenge. 13 There are many things that sound 14 simple; they sound simple on their face. 15 Well, let's require certain kinds of 16 communications from companies about their 17 devices. They sound simple, but they create 18 barriers that may, in fact, not only prevent 19 new devices from being developed, but may, 20 in fact, have the unanticipated effect of 21 removing devices from available to 22 pediatricians that are already in the BETA REPORTING (202) 638-2400 1-800-522-2382 (703) 684-2382 85 1 market. 2 So I'm putting a caution on the 3 table that we don't in this process create 4 new barriers that are going to adversely 5 impact what is currently in the market and 6 adversely impact the capacity to have new 7 products in the market. 8 Let me look and see what was at 9 the bottom of that slide, and then pathways 10 to market with clear expectations. 11 There are different requirements 12 for different types of medical devices, and 13 as Joanne pointed out, there are three 14 major -- actually four major -- ways in 15 which medical devices can move into the 16 market through the regulatory process. One 17 of the things that we need from FDA is clear 18 understanding of which devices will qualify 19 for HDE, which devices can be developed 20 through pediatrics and still go through the 21 pre-market notification of the 510(k) 22 process. BETA REPORTING (202) 638-2400 1-800-522-2382 (703) 684-2382 86 1 What specific devices might need 2 pre-market approval; PMA devices? Which can 3 be done as supplements which are changes to 4 currently available products that can go 5 through a more abbreviated process. 6 We need very clear pathways from 7 the regulators. So we need the information 8 from them as to what's going to be needed in 9 the pathway as well. The regulatory 10 mechanisms that will be available and 11 perhaps we might need new mechanisms to make 12 these devices more readily available in a 13 faster way in the marketplace. 14 So, in summary, there are lots of 15 challenges for the medical device 16 manufacture, designer and manufacturer, 17 based on the needs of the pediatric 18 population and the specific physiology of 19 pediatrics. These are not trivial and they 20 take time, energy, and obviously money to 21 make these developments so that the products 22 will be available, but before we can BETA REPORTING (202) 638-2400 1-800-522-2382 (703) 684-2382 87 1 initiate those development programs, we need 2 information about where the gaps are and 3 what the real needs are for the pediatric 4 population and we need the regulators to be 5 clear as to what the pathways and what their 6 needs will be so we can move pediatric 7 devices more readily into the market. 8 Again, a final reminder: Many, 9 many, many medical device companies already 10 have products in the market for the 11 pediatric population. Many are interested 12 and are working on developing new products 13 and many more could come in if they knew 14 what the gaps and needs were. 15 I look forward to the discussion. 16 I'm pleased to see people from all different 17 aspects of the pediatric needs in the room 18 together and I hope that we can come up with 19 an approach that will work for all of us. 20 Thanks. 21 MR. ABRAMSON: Susan, thank you. 22 I'm going to ask everybody to come back BETA REPORTING (202) 638-2400 1-800-522-2382 (703) 684-2382 88 1 at 10:30; take a break, come back at 10:30. 2 We'll start the discussion, the whole rest 3 of the day will be open discussion through 4 our sets of questions and I very much look 5 forward to the input. 6 Thank you. 7 (Discussion off the record) 8 DR. ABRAMSON: 컴컴 which we'll 9 get to before lunch and the others we'll get 10 to later on, but what we want to end up 11 today is potentially one or more proposals 12 that might pull all of these problems that 13 have been highlighted for you today; how we 14 might work together better and a lot of us 15 have been thinking about this for a while 16 and we'll come to discuss this later on. 17 So this morning, what I hope to do 18 is to take on the following questions: What 19 are the unmet medical device needs across 20 the pediatric population? Is the need for 21 pediatric medical devices concentrated in 22 certain medical specialties? Is there a way BETA REPORTING (202) 638-2400 1-800-522-2382 (703) 684-2382 89 1 to prioritize the kind of devices needed for 2 the pediatric population and how does the 3 lack of availability of appropriate devices 4 impact 컴컴? 5 Those are further declining 6 problem questions. You'll see it's 7 inevitable that we won't cleanly answer all 8 questions though. We'll move back and forth 9 between these four questions. In the 10 afternoon, we're going to talk about how to 11 put this problem together with a workable 12 solution. 13 So let's take on the issue of what 14 of the unmet medical device needs across 15 pediatric population and a subset 컴컴 occur 16 컴컴 condition of pediatric specific and 17 those that affect both children and adults. 18 So does anybody want to answer any 19 of those questions? 20 (No response) 21 DR. ABRAMSON: All right; then I 22 will start them off. BETA REPORTING (202) 638-2400 1-800-522-2382 (703) 684-2382 90 1 (Laughter) 2 SPEAKER: I think you need to 컴컴 3 those questions. 4 DR. ABRAMSON: We need medical 5 devices that can actually allow us not to 6 use 컴컴, and a good example of one that's 7 been created already is the 컴컴. So we do 8 a lot less blood 컴컴, but we're still 9 having to get electrolytes. We're still 10 having to go in after the vein to get that. 11 This is probably an issue I'm sure 12 that also adults would like. 13 SPEAKER: Excuse me. We really 14 can't hear back here. I don't know if you 15 can speak up or not. 16 DR. ABRAMSON: Sure; I'll try to 17 speak up. So the question we're on is what 18 are the unmet medical device needs across 19 pediatric populations? I've started off 20 with one that I think is fairly obvious and 21 fairly simple and that is the ability to 22 monitor more things without having to BETA REPORTING (202) 638-2400 1-800-522-2382 (703) 684-2382 91 1 actually stick a vein to draw blood. We've 2 had pulse ox's for a good piece of time. I 3 know people have tried to create CLQ 4 equivalents, and not successfully. 5 I know no one who has created 컴컴 6 we can measure sodium potassium; those kinds 7 of things, and I think the glucose one, 8 though there are a couple of devices that 9 have been created to do that, do not 10 specifically measure the exact glucose 11 there. When you compare, you know, somebody 12 to draw blood and say its one/a hundred and 13 you look at the sensor and say -- the 14 sensors are better at looking at, you know, 15 gross changes than they are what is the 16 specific number. 17 So I'll throw out