U.S. DEPARTMENT OF HEALTH AND HUMAN SERVICES
HEALTH RESOURCES AND SERVICES ADMINISTRATION
MATERNAL AND CHILD HEALTH BUREAU

ADVISORY COMMITTEE ON HERITABLE DISORDERS AND
GENETIC DISEASES IN NEWBORNS AND CHILDREN
VOLUME II
Printer-friendly Volume II
Friday, October 21, 2005
ll:14 a.m.

Rotunda Room
Ronald Reagan Building and
International Trade Center
1300 Pennsylvania Avenue, N.W.
Washington, D.C.

PARTICIPANTS

R. RODNEY HOWELL, M.D., Chairperson
MICHELE A. LLOYD-PURYEAR, M.D., Ph.D.,
Executive Secretary

MEMBERS:

WILLIAM J. BECKER, D.O., M.P.H.
AMY BROWER, Ph.D.
PIERO RINALDO, M.D., Ph.D.

LIAISON MEMBERS:

JOSEPH TELFAIR, Dr.P.H., M.S.W., M.P.H.

EX-OFFICIO MEMBERS:

COLEEN BOYLE, Ph.D., M.S.
DENISE DOUGHERTY, Ph.D.

ORGANIZATION REPRESENTATIVES:

NORMAN B. KAHN, JR., M.D.,
American Academy of Family Physicians

C O N T E N T S

PAGE

Opening Remarks and Welcome

R. Rodney Howell, M.D. 3

Follow-Up and Treatment:

Coleen Boyle, Ph.D. 5
Chair, Follow-up and Treatment Subcommittee

Committee Business - Subcommittee Reports

Education and Training:

William J. Becker, D.O., M.P.H. 23
Education and Training Subcommittee

Questions from the Committee 33

Laboratory Standards and Procedures:

Amy Brower, Ph.D. 33
Chair, Laboratory Standards and Procedures
Subcommittee

Public Comments:

John Adams 37
Jana Monaco 45
Micki Gartzke 52
Barbara Trainor 60
Cynthia Joyce 65

Committee Business: 73

P R O C E E D I N G S

[11:14 a.m.]

DR. HOWELL: Ladies and gentlemen, let's all find a seat and we'll resume the General Committee Meeting today, having had very busy subcommittees earlier today, and we have reports from three subcommittees. The Chair of the first subcommittee seems to be absent at this time--Dr. Becker--but here he comes. And the first report that we're going to have is from Bill, who's going to talk about the meeting of his Education and Subcommittee meeting. Bill?

DR. BECKER: Actually, Rod, they need to change the computer out from my presentation.

DR. HOWELL: Okay.

DR. BECKER: While that's happening, would it be more expedient to go to one of the other subcommittees?

DR. HOWELL: Well, it would be fine with me. Coleen, could you--are you ready to go?

DR. BOYLE: Sure, I'd be happy to.

DR. HOWELL: Okay. Well, we'll switch and ask Dr. Boyle to then do the Follow-up and Treatment while we're modifying the computer system here.

DR. BOYLE: Okay. Follow-up and Treatment

DR. BOYLE: Well, we had invited guests to our subcommittee this morning--Tim Huff, who is in Sunean (ph) Albany, who has been doing--I don't know if he's still in the audience here--oh, there he is, hi, Tim. He has been involved with Brad Therrell on a project to assess long-term follow-up from state newborn screening programs. I have actually done sort of a two-face project; one was a specific questionnaire to try to highlight some of the issues in terms of barriers to long-term follow-up, and then that was followed up. And in the process of conducting a more of a qualitative-related research project to expand on what he learned from the initial phase, I think what he presented to us was very helpful in terms of trying to identify some of the challenges with long-term follow-up. Some of the, perhaps grayness around the areas of defining what short-term--the responsibilities for short-term follow-up and long-term follow-up, and many of the impediments that state health departments face, I think in terms of we had a very lively discussion following his presentation in terms of perhaps some of the policy implications from his work. And, obviously, his work is evolving and ongoing, and we will continue to involve him in our subcommittee's deliberations. But in terms of some of the policy implications, I thought some of the things that he pointed out as well as others pointed out were very important. I wanted to highlight those. And these are to try to identify and reconcile contradictions that appear to exist between, essentially, the theory of long-term follow-up and what is actually happening in reality. And that is can we ensure access to a medical home be accomplished through long-term follow-up, sort of trying to help prioritize; key areas that we feel, as a committee, might--may be important and to make some kind of recommendations, policy recommendations, in terms of their feasibility, and then also, to try and establish realistic benchmarks for performance for long-term follow-up and to really engage, obviously, the newborn screening programs and other vested parties in terms of trying to understand a little bit more about what would be realistic in terms of benchmarks. And maybe we as a--I guess my preliminary thoughts in thinking through this morning's discussion is that might be something that we as a committee can begin to--at least as a subcommittee--we can come back to you are a recommendation that we think that should be developed and that might be very helpful in terms of assuring quality and equity of care across state programs.

The rest of our morning, actually, was spent on we have broken down as a subcommittee maybe a little too finely, but we have a number of work groups going around the issues that we have been charged with. And I actually was going to ask the leaders of those work groups to just say a few comments about what their work group has been working on and perhaps some of the next steps that they anticipate. I'm going to turn first to my left to Denise, who's been kind of overseeing the work of the work group that's looking at health care systems integration.

DR. DOUGHERTY: Thank you. It's actually health systems integration, since it includes public health and health care delivery, which is very important for newborn screening, but, yeah, those words do get complicated.

What I did for the group was pull together a partial preliminary draft of some issues, putting the newborn screening follow-up issues in a context of, one, the rest of the health care system and its challenges about being integrated and then going to the children with special health care needs and their challenges in being integrated, and then flowing down to the elements of short-term and long-term follow-up that have been identified in pieces of literature such as the ACMG report and the challenges that are faced in trying to, when states can't 100 percent implement those elements, and also pull together out of the literature some models of better care coordination like the chronic care model and the innovative care for chronic illness model, and the EHDI model that was mentioned--everybody wasn't here--on early hearing detection and intervention model for follow-up.

So we still have a lot of work to do, but we agreed to--people thought that this was a fairly good start, and we could work with this document, this draft document. They had some wonderful suggestions about how to improve it, and also volunteer to look at the electronic version and fill in more of the elements of the short and long-term follow-up--because they're not all in this chart that I developed--and also fill in some of the barriers to achieving those goals of short-term and long-term follow-up.

So--and we also agreed that we should have this looked at by somebody from the state newborn screening program perspective, because there's nobody like that on our group, and they would know more about they the elements and the barriers, so we're going to have that. George and Fan and Julie, we'll ask them to take a look at this, too.

So I think what we agreed to was that we were going to try and complete a document that identified the elements and the barriers or challenges, and that would be an interim document. So people are to follow-ups, or people are to have their comments to me and suggestions and elements and so forth by mid-November, and our subgroup will have a call, a conference call, in early January to finalize the document, or hopefully finalize or at least have another discussion about the document on barriers. And as a next step we would go on to charge two, which is identify some recommendations to overcome those barriers. So, and that's when we really need to pull in the IT, and the financing group, and the parent group and so forth.

So that's where we are. We also talked about adding a couple of consultants to our group, so I had need to talk to our Chair about that. Thank you. Any questions.

DR. HOWELL: Denise, what are you going to do with this document when it's done?

DR. DOUGHERTY: Well, we're not sure, but I mean what we have decided is, like Coleen said, we have broken into these four different subgroups. What we need to do at some point is bring everything together in order to make recommendations. So I think ultimately the decision--I was asking this question yesterday--what do we do after we do all this work? I think we're supposed to give a report to the entire Advisory Committee from the entire subcommittee.

DR. BOYLE: I think what we're trying to do is work towards specific recommendations, and, as I mentioned before, some of those recommendations might be that we've identified the barriers, we've identified potentially some recommendations for overcoming those barriers. There may be something, specifically, that needs to be developed that this larger committee would vote on in terms of perhaps going forward with a white paper on, you know, specific processes and benchmarks to assure short and long-term follow-up related issues. Like I'm just using this as an example, but I guess that's where I'm trying to move the group towards to have something tangible at the end that could be related to sort of policy that might help with achieving measurable milestones for short and long-term follow-up. Brad--where's Brad? Brad was sort of overseeing a work group on thinking about financing-related issues.

DR. THERRELL: We're not quote as well organized in terms of our thought process. This group is Dr. Cunningham, Dr. van Dyck and I, and we sort of asked for some guidance about where we should go with financing. Are we talking about follow-up in treatment, or are we talking about bigger financing issues? And so we sort of took it in a more global context, and we're looking for some guidance on this.

But financing sort of permeates everything, and so, you know, fee structures are there in the states. In most states there are still five places that don't charge a fee, but then they have other financing issues; but those who do charge a fee, we felt like there were a lot of questions about that fee structure: How is it formulated; where does it go; what does it pay for? You know, does it go into a special fund, and are our states allowed to use those funds for treatment and follow-up issues and so on?

So there were so many questions about that and so many different policies around the country related to that that we thought one of the best things that might happen from all this is to have some sort of a national meeting to talk about financing issues and bring forward those people who have successful parts of financing strategies to talk about their successes and how they got there, and how those models might be applied to other state programs. And somebody asked me, "Well, how do we identify those?" And I think the answer to that is when--my experience is--when you ask a state, do you have a good system of such and so, they don't tell you they do unless they're willing to back it up because they know the next question I'm going to ask is: Give me examples of how that works, and can we examine that further?

So I think we could find models, and we could bring people together to discuss these sorts of things if we wanted to go that way. But there are, you know, questions about CPT codes on a national level and how financing is tied to CPT codes, and whether there should be one CPT code that everything, or whether there has to be a variable CPT code because the states are variable in the laboratory services that they offer, questions about who pays for confirmatory and monitoring laboratory testing, and how do we make sure that everybody has access to those kinds of services, questions about how Title 5 and Medicaid are related in terms of relationships within the states that are apparently required by law but may not be in place, and states may not be utilizing that to the best of their ability.

So there are a number of different issues, and I guess what we're looking for right now is sort of should we be limited to looking at in follow-up treatment only, or do you want to look at financing as a bigger issue; do you want to talk about in terms of having sort of a national meeting of state representatives to talk about best models or where do we go from here?

DR. BOYLE: Questions for Brad? Thank you, Brad. Jill, do you want to try and address that, either at the microphone or the table, whichever works for you? And Jill is overseeing a group on the impact on families and caregivers.

MS. LEVY-FISCH: Okay, I prepared a report which I will send to the full committee. I contacted various advocacy groups. There were about six or seven to see what we could do to address the needs of the families and what they view as barriers to their treatment and follow-up for their children. I would just like to say I got a good number of responses. I'm still looking to hear from the sickle cell community; I didn't get one single response, and I know there are needs in that area so I'm hoping that that's something we can address.

One of the main issues that families are facing are issues concerning formula coverage for medical formulas. We need to provide national direction for formula coverage for all the disorders. As things stand now, many of the insurance plans are very disease-specific as to what they cover such as formulas for PKU, but the other disorders that require formulas, if they're not specifically specified, then the families are having extreme difficulty getting coverage.

We also need to address money for low protein foods. These disorders that require a low protein diet, they're available only by mail order, and they're extremely costly and the parents are having a difficult time providing the financial need for that.

Also formula coverage after children age out and are over 18 is an issue that was brought to my attention. Some families have indicated they're not receiving their screening results in a timely manner, which is something that needs to be addressed under short-term follow-up. Many have waited over a week and then received a positive result. And due to these delays some babies have died and others have suffered a crisis, and I've had several reports of hospitals batching their tests, which also delays access to diagnosis.

Many families have also had issues with early intervention programs. They feel it's a great program but extremely difficult for them to put into place. The whole process is not very individualized, and many service coordinators do not get as involved as they should or the parents will bike (ph). In turn, families have been denied crucial services such as feeding therapy because the coordinators did not know the proper way to secure these services for the child. When children are diagnosed at a later age, the families feel they do not have the same access to services as the young child or an infant.

Families expressed a great desire for a medical home. Right now most families are coordinating the wrong services and specialists for their child, and they feel extremely burdened and overwhelmed. Pediatricians are really leaving everything in the hands of the families, and some families stated they're so tired and overwhelmed that it becomes harder to care enough to be more assertive.

Clinical staff and physicians as well as parents need to be educated as to the purpose, results, and importance of newborn screening tests. Some hospitals are forgetting to do the screening prior to the baby being discharged from the hospital. Just to give you one example, one family happened to see a newborn screening brochure on a table as they were being discharged with their new baby, and the screening tests had never been done. The parents asked for their baby to be screened, and this baby turned out to have glycosemia, and this really could have been a disaster.

Families are also desperate for respite care, and that came through loud and clear. They're spending endless days or weeks in the hospital when their children are ill, and then coming home and managing that care on a daily basis they're feeling exhausted, and I hear many times feelings of isolation. There is a severe lack, as we know, of specialists to care for these children. More training is needed for those who are treating children with these disorders. There should be internship programs funded to train doctors and nurses to treat the children who are identified through newborn screening. We really need to figure out a way to draw them in and train them.

When a child is first identified with a newborn screening, the doctor they generally see first is the pediatrician, and the pediatricians do not have enough knowledge of these disorders as to how to treat them and, in turn, do not have the information necessary for families. These families are spending countless hours looking on the internet and making phone calls trying to find information when their time could be certainly better spent.

Many insurance plans do not pay for specialists that families need to see out of state, and, due to the shortage of specialists, many families do travel all over the country to seek proper care for their child. Medicaid reimbursement, it's indicated that the reimbursement for home nursing care is extremely poor and getting quality care is an issue. Many families rely heavily on home nursing care, and when their home care nurses are sick or on vacation, there are many instances where the families are unable to get a replacement.

Families need access to affordable testing to rule out disorders in other family members, and attention must be paid to the older children with disorders sa they transition into adulthood which would fall under long-term follow-up. Most if not all of the metabolic specialists seem to be pediatric specialists. Older patients do not feel comfortable visiting pediatric clinics for treatment. One possibility is maybe to have the pediatric specialists have an adult clinic in an adult setting to see these children as they get older.

The issues the older patients face are much different than the infants. The older children are having a hard time sticking to their special diets when they're with their peers, and certainly those with feeding tubes have issues that need to be addressed. Families would also like access to social workers, not just for their child but for themselves given that the disorders affect the entire family and not just the affected child.

I will update this as I get more responses from families, but this is what I've been able to get right now, and if anyone has any questions?

DR. HOWELL: Thank you very much, Jill.

MS. LEVY-FISCH: Okay.

DR. BOYLE: Thanks, Jill. We also have had a lively discussion on our phone calls as to whether or not there really should be two different committees because, obviously, a lot of the issues that Jill is uncovering through her work really do impact on the issues of health systems integration. So right now we've kept them as separate work groups because I guess feel like it's very important to really highlight the impact on families and caregivers, but maybe through time that we sort of integrate those two groups. And just lastly, our last group is on information systems, and I've done a little bit of work in contacting Alan Hinman trying to address some of the IT integration issues in terms of major barriers and arrive at some recommendations. And I met with Debby, actually, during our work group time, and she has offered very kindly to help assist me as well as Alan if I continue to use him as a consultant to again arrive at some recommendations in this area.

DR. HOWELL: Questions of Coleen about her committee? It sounds like you had a busy morning. We'll move on. We're running a touch behind time, but apparently Bill is going to address us from the remote side over there. Is that correct?

DR. BECKER: Hello. Yeah, this is a testimony to the incompatibility between Mackintosh and PC. Education and Training

DR. BECKER: I'll try to go fairly quickly. We also are not compatible--oh, it's nice to see the audience. It's also Quicken is not--the Mac equipment is not compatible with the LCD projector, so, unfortunately, I'm unable to project all these. Obviously, we met this morning. There have been some membership changes in the subcommittee. Dr. House's term on the Secretary's Advisory Committee concluded on September 30th, and Dr. House asked me to be the Chair and I agreed. I don't know what I was thinking, but anyway Dr. Hawkins continues to serve on the committee. Dr. Edwards is also a member of the committee--of the subcommittee representing AAP, although he was unable to be here today. And Anne Gramiak stepped in to give a presentation on AAP's activities. Dr. Tony Gregg from ACOG is also a member, but as you all probably know, he's not been able to join us at this meeting. Dr. Norman Kahn from the American Academy of Family Physicians is also a member of the subcommittee, and my point for mentioning all those particular persons is they represent association partners that we feel are essential for the task at hand, education and training. We do have a couple of additional potential positions to be filled from the newborn screening program. I have a nominee from California; also from a newborn screening birth facility from Ohio, and then we still have a couple of open positions that we need to fill in the not too distant future. Subcommittee reviewed the approved charges, and we have no suggestions to make to those at this particular time. Dr. Kahn updated us on AAFP educational activities. They, as had been reported here previously, have a program called Annual Clinical Focus which this year is devoted to genomics. It's a series of eight programs. Newborn screening is one of those programs, and it is up on the web right now, www.AFP.org. There were 19 participating organizations that contributed to this program. It is designed for providers, but it's likely that it could be used with newborn screening program staff as well as birthing centers staff as well, and we're going to take a look at that. In fact, one of my assignments to the subcommittee is that we will review this program and make comments on it about its utility in, particularly, these other groups in the near future. Anne Gramiak from the American Academy of Pediatrics updated us on their work. The newborn screening parent and provider materials that they'd been working on are just infinitely close to being released, anticipated in early November '05. This, as many of you will recall, is the work--it's a combination of association work, Maternal Child Health Bureau, Louisiana state, Dr. Terry Davis, who's spoken before us, as well as the partner associations that I've been mentioning. AAP, at Dr. Edwards' request, has devised an evaluation process for these materials. It will be in the form of a survey, and this was something requested at our last face-to-face meeting back in July. AAP is also working on sort of their policy statement. It's in the form of what they call a clinical report on newborn screening in the medical home, and those policy statements, obviously, will be forthcoming. Other association reports that we received this morning--ACOG, obviously, wasn't able to participate because of Tony's absence--I did hear from Julia Ingleston from NICHD. We had heard from her in July about a consortium, really, of federal agencies that are developing newborn screening materials, and while Julia emailed me prior to this meeting and said she didn't have anything to report new at this time, we do anticipate at least some of their matrix development to be ready for review by the next Secretary's Advisory Committee meeting. Other business, some of the other avenues that we were considering particularly revolved around the concept that perhaps we might need to broaden our consideration of how to distribute printed resources to the general public, and we engaged in a conversation about some ideas of groups where to go. And I can certainly provide you details of that, but I'm going to shorten the conversation down just a bit. Other groups that we particularly mentioned--and I think these are interesting to consider providing newborn screening education for the illiterate, the disabled, deaf or blind persons who might need newborn screening information, those are something that we're going to consider. A very novel idea came up and consider asking Google about the order of information that is provided when you type into their search engine "newborn screening." In other words, is it possible for us to consider what the order of--you know, I'm going to guess that maybe, you know, most people when they use that particular search engine, they click on the first two or three links that come up. And it may be that we can devise a way to guide them to more generic resources or resources that we think are appropriate. One of the things that I would like to put on the table for committee discussion is--maybe this afternoon after we finish the subcommittee reports--is the concept of a general announcement in the form of perhaps a public service announcement, or PSA, that might come from the Secretary's Advisory Committee for parents and providers. Our subcommittee felt that the message to parents ought to be about the general importance of newborn screening whereas the message to providers would be about the importance of emerging national recommendations for newborn screening that--and this message could perhaps be taken through the association partners or perhaps and/or the March of Dimes. Obviously, this particular suggestion for committee consideration is pending HHS Secretary's approval of our recommendation, but if we feel that that is something that may be imminent, it may be helpful for us to consider a general announcement, you know, to be proactive in forming a PSA or several PSAs in the time that we're waiting for the Secretary to take some action. And then finally, one of the bigger, a couple of ideas, training needs--remember, we're the Education and Training Subcommittee--and this will be an ongoing discussion. Obviously, we could all list, I think, who needs training from state programs, laboratorians, providers, residents, health care workers, et cetera. And there's obviously some overlaps here with the other subcommittees' work. Another novel idea that came out and something we want to put out for the committee's consumption and consideration is consider approaching or establishing, or whatever it needs, a national spokesperson for newborn screening. There clearly are people who would have high visibility, and I can think of a couple people who have even testified to our own committee at some earlier meetings who might be interested and/or willing. And then finally, one of the issues that seems apparent to us is that we're going to need to coordinate the information that's being developed so that there's some uniformity in the messages. Our action steps in most of this I think is basically for Rod and Michele, I think, is we do intend to establish more regular conference calls. I have given them the assignment, as mentioned earlier, to review the AAFP newborn screening program. We will review the HRSA LSU prepared materials when they become available. We would like to invite Donna Williams to the next Secretary's Advisory Committee as a consultant to give her presentation to our subcommittee, most of whom were not present a couple meetings ago and so did not receive, you know, the presentation that she made. So we'd like to bring her back, basically. And that is, in a nutshell, what was a very animated discussion and a very delightful group. Thank you.

DR. HOWELL: Thank you very much, Bill. Are there questions of Dr. Becker?

DR. KAHN: Well, this is not a question, I hope that this is just additive. For those who are interested in going to the web to see this newborn screening program--sometimes websites can be hard to navigate--if you go to AAFP.org right on the home page center column toward the bottom, there are three words: Annual Clinical Focus. Click on that, and when you get to that next page, Pictunomics (ph), and it's in there. And that way, with two clicks you can get to it, and otherwise you'll get lost on the home page. And while I have the microphone, I just want to thank three people without whom this program would not have happened, and that's Michele Puryear and Jim Hanson, and then Jean Johnson from the National Hemogenal Research Institute.

DR. HOWELL: Thank you very much for that comment. Any additional comments of what happens when you click Google on newborn screening? I've never done that. DR. : The National Newborn Screenings and Genetic Resource Center.

DR. HOWELL: Brad's program comes up. We answered that question, okay? Yes, Joe, okay. Joseph?

DR. TELFAIR: Yesterday the question on--I understand, Bill, that materialwise that you're dealing both materialwise in terms of the education side and the training side--what, as a committee, have you considered related to cultural and linguistic competency issues? I know that you have some of the information you mentioned directly through literacy, and I applaud the group for thinking of groups, both low or no literacy, but I'm also wondering about sort of cultural issues as well. Thank you.

DR. BECKER: First of all, the material being developed by the HRSA--the MCHB LSU are both in English and in Spanish, as well in the newborn screening program person that we have invited and tentatively needs to be approved from California, California has one of the largest cadre of multilinguistic newborn screening information that I'm aware of. Brad may be aware of some others, but those are the ones that I'm aware of, and so we feel like we're working towards, you know, including multiple ethnic areas into our conversations.

DR. HOWELL: Other comments for Bill? Thank you very much and so forth. We'll zip along now to the third subcommittee report, and Dr. Amy Brower will talk about the Laboratory Standards and Procedures Subcommittee, which was a very packed agenda this morning.

DR. BROWER: Great. Well, I'll try to keep us on target and get out for lunch on time. Laboratory Standards and Procedures

DR. BROWER: We met today, our Laboratory Subcommittee, and we really focused on our two charges related to the laboratory procedures and infrastructure services. We want to, as our first priority, focus on the harmonization of operational lab procedures. Our ultimate interest is to find all true cases with no false negatives and with the minimum number of false positives. An example of the work that we'll be doing is defining better cutoffs by looking at disease range instead of the normal general population. We'll be working to compile the experience of multiple laboratories and working with the APHL. The outcome of our efforts, our goal, is to be able to develop guidelines or techniques to offset cutoffs, and we'll present our findings to the committee as a whole for consideration. This is going to require our subcommittee working with the APHL, with state laboratories, and with industries, and we also want to especially capitalize on all the great efforts that are going on in the regional collaboratives, and we'll report all that back to the committee. Specifically, we have formed a working group to work on one of our first priorities for the short term, which is really to design a study to assess the utility of the routine second spot, and we'll have a working group that will address the design of that study, and they'll be working to define the indicators and the criteria for that study. And that's it.

DR. HOWELL: Questions or comments about Amy's two key issues that will focus, one of which involves really looking perhaps at a grant type activity that would support the study on the famous second spot? (No response.)

DR. HOWELL: Hearing no comments, you were so brisk we actually finished a bit early but not much, and so we're going to adjourn for lunch, and again the lunch in the Concourse Level is for the committee members and subcommittee and ex-officio members, and we welcome everybody there. We resume promptly at 1 o'clock for the Comments and wind up the Committee Business. Thank you very much. (Whereupon, at 11:55 a.m., the meeting recessed, to reconvene at 1:00 p.m., this same day.)

A F T E R N O O N S E S S I O N [1:00 p.m.]

DR. HOWELL: Ladies and gentlemen, let's find our seats and resume our afternoon session so we can conclude our activities on time. We're pleased to have a distinguished panel of public commentators today, and, as usual, we greatly appreciate and welcome these comments, and they're extremely useful as the committee deliberates directions, et cetera. The first person on my list is John Adams, who's the Treasurer of the Canadian Organization for Rare Diseases. Mr. Adams-- Public Comments MR. ADAMS: Mr. Chairman--

DR. HOWELL: You're ahead of the game, I--

MR. ADAMS: At one point in my presentation, Mr. Chairman, I've got to use who I know, Professor Therrell's slides from yesterday just to make a point. But thank you very much for a fellow named John Adams. It's nice to be back in Washington. This is the third time I've had the opportunity to attend meetings of this, the open sessions of this open advisory committee, which I greatly appreciate. I am, for those of you who don't know me, I am the PKU Dad for Toronto, Canada, and like almost all parents, my wife and I knew nothing about rare disorders and PK, including PKU, until our son was born 18 years ago and detected. So I'm very, very thankful that many years ago a whole bunch of total strangers set up a universal public health newborn screening, a universal newborn screening system in order to protect my baby and all the other babies as far as it's gone.

I'm brand new as Treasurer of the Canadian Organization of Rare Disorders, or CORD. We have adopted a policy on newborn screening that court urges all Canadian Provinces and Territories to implement as soon as possible comprehensive and inclusive newborn screening within each jurisdiction at the highest prevailing international standards. So keep going at what you're doing. Keep moving those yardsticks, please.

Thank you. I'm sad to report from the Canadian, and adding a little bit of international perspective here today, that no Canadian medical organization has yet seen fit to take a public position on the topic of newborn screening, not the Canadian College of Medical Genetics, not the Canadian Pediatric Society, not the Canadian College of Family Physicians, not the Garad Association (ph), which is the trade association of metabolic professionals and, actually, CORD, I think, is the first organization at the national level or the provincial level to take a position. So we do have a little bit of a gap here.

And just to give you a little perspective, there are some parallels and some differences between the U.S. federal state situation and the Canadian federal provincial one, but I do want to say we have no national strategy, and we have no national process in Canada for addressing the issues of newborn screening. We have no federal activities and no federal funding for newborn screening, not one penny.

All right, the word "screening" does not appear in any fashion in the Canada Health Act, and we have no--for example, we have no office of rare disorders at the Canadian equivalent of the NIH. We have no policy on orphan drugs at the Canadian equivalent of the FDA. We have no definition what is a rare disorder at the federal or the provincial levels. So we have some work to do, and I look to best practices in other jurisdictions, including the United States for some guidance in this respect.

I do say--I'm going to say this twice today in two contexts--but in this respect of rare disorders, Canada operates like a Third World country. I did not invent that phrase, I will attribute it to an independent officer of the anterior government later on. All right. All right, so that's the quick view, and we have some similar issues I wanted to--I just want to use this map for a second to do a quick visualization of the comparison of 13 different jurisdictions across Canada. They range from Saskatchewan screening babies for a total of 29 conditions, and Quebec screening 90 percent of its babies for a total of 28 conditions, to the bottom of the list, my home province of Ontario, which today still screens for a total of three conditions, PKU, CH, and hearing, although we are making some progress. And I want to tell you a little about that, and I want to say to this committee, to HRSA, and to some of the particular participants, I want to say my personal word of thanks for being resources and being sources of information and inspiration in terms of the applicacy that we need so badly in our country to try to pull up our socks.

In a word, there are most of the provinces in Canada would fall well within the bottom category here in Brad's classification of fewer than 10. Matter of fact, today there are only two provinces, all right, and that's what I want to say. We are making progress, though. The Province of Ontario, my home province, is the largest province in terms of population of screening for fee. We have got to the point of an expansion to seven conditions from three. That didn't last too many cycles. We got to the point of 21 conditions, all metabolic; that didn't last the first 24-hour news cycle when it was announced in the first week of September because we still--that expansion still omitted such disorders as the cycle cell diseases, which was completely unacceptable in today's kind of society, and it also missed the endocrine disorders such as congenital adrenal hyperplasia. Last, on September the 28th, the government of Ontario made an announcement they intend to take Ontario from worst to first. We're waiting for a definition and articulation of what is meant by first. The plan is to have tandem mass-based and other expanded screening up by the 1st of March, and, frankly, I'm pushing for as much of the ACMG full panel as endorsed by this advisory committee to your Secretary as possible. I'm also pushing because we are so far behind, and it will take some time to develop the domestic lab and other capabilities. I am pushing for a quick start that we should swallow our pride as proud Ontarians, and we should buy on a transition basis. We should be prepared to buy the service from outside of Ontario.

So the difference between even the announcement that there are babies being born every week who are at risk of premature death or permanent life-long disability as a result of the gap between three conditions and whatever the Ontario screening panel is going to end up to be. So if you hear me ranting and raving just a little bit about the need for a quick start, I hope to use Ontario as a demonstration project for other jurisdictions who want to do quick starts as a ways and means, as we're not the early adopters, we're late adopters, but perhaps we can apply some of the lessons for to speed up the pace of implementation of change.

So with that, and the other thing I will bring, the Ontario ombudsman, the have an independent officer of the Ontario legislature called the ombudsman, and he wrote a report that was issued in the last week of September. It does have the double helix, and it does have the letters of the helix in the proper order, and it does say--talked about the right to be impatient. And I think that I share that sense of impatience with many other parents and other lay advocates.

So I hope that you will continue to do your hard work, and I hope that you will continue to keep an eye in terms of the role model that you are serving as an open advisory process for others. There was a meeting of the Ontario Advisory Committee on Wednesday afternoon of this week. For the first time they did invite in an endocrinologist and hematologist for the first time there. I look forward to the day when I an report to you on a future occasion that the meetings are open and that they have invited in parent and lay advocates. Thank you very much for your time and attention. (Applause.)

DR. HOWELL: Thank you very much, John. We'll move ahead to Jana Monaco, who is a parent and board member of the Organic Acidemia Association.

MS. MONACO: Okay, good afternoon. I thank you again for the continued opportunity to offer my comment to you in support of the process of expanding newborn screening, and I have to commend you for your efforts to move the process along. Yes, I am on the Board of Directors of the Organic Acidemia Association and speak for all of us, and the parent of two children with isovaleric acidemia. And I have to say that I can attest to all the Jill Fisch said earlier as a parent and my concerns. As I sat and thought about what I wanted to comment, I monitored my son's seizure last night and thought about how Steven will turn eight years old next week, but he will not celebrate in a conventional way like most children his age. That is because if you view him from an evidence-based approach and highlight a few points, Steven meets the criteria but as a result of not being screened at birth. A test was available, but he didn't get it. Treatment was available, but it came a little too late. As for the burden of the disease, we don't have time to completely review the result of the severe brain damage to a child and the family. As for cost-effectiveness, we have that one covered, too. The evidence-based criteria is the same with our daughter Caroline, except the outcome is far different, and we would like to see more cases like hers, so I ask you to be cautious and not get too caught up with the evidence base but keep in mind the facts that are not measured in quantitative means. Does this make me a person with a conflict of interests? I certainly hope not. Rather, I hope that I am viewed as an expert and important stakeholder in this process. I cringed yesterday at the slightest suggestion of David Adkins' presentation that some parents could possibly be too biased when it comes to the evaluation process of adding disorders to the list, or that anyone could be somewhat biased. If this were true and I were only interested in IVA, I would not be here any longer since ours is on the primary target list. When reviewing this process, I would like to think that Dr. Watson would be consulted given the fact that he and the ACMG produced the scorecard and the list of criteria. He and his staff are trained experts that were originally chosen to complete this task and can provide valuable insight and answer many questions that people may have regarding the scorecarding criteria for adding the disorders to the list. This leads me to the addition of new members to the committee. Careful consideration is given when doing so, and the newest representatives on board can certainly contribute to the committee from their area of knowledge and how it relates to newborn screening. Nancy Green recommended a few potential new additions yesterday, and when thinking about the team of specialists that care for our children with these disorders, it would only make sense to include their involvement if they express an interest. One of her suggestions, neurology is one of those areas of consideration. These disorders, no doubt, can be neurologically involved. There are children like Steven who have a great deal of neurological involvement, hence making that specialty one of the key team players in his overall health care or medical home. In our organization we have several children with neurological issues with their disorders along with others who have these neurological concerns but no diagnosis yet; and yet their neurological status plays a key role in helping to make that diagnosis. Gastroenterology is another specialty that could be considered if they were interested. We have a large number of children dependent on G tubes, or NG tubes, along with various other GI issues. It only makes sense to utilize people who have direct involvement and a certain level of knowledge with managing these disorders. As we move along in the process of expanding newborn screening, much emphasis is shifted to the subcommittee's work and their charges. I think it is imperative to stay linked with the regional collaboratives and what they are focusing on. I will maintain my position in working with the education work group for our region. We have discussed the idea of databases before, though it has quite quiet this time on that topic. I think it is imperative to maintain a methodology of tracking newly diagnosed cases and track the management and care of current cases. It is the most logical way to document vital information to further understand the primary targeted disorders and develop a better understanding about the secondary targeted disorders and those awaiting their place on the list. I see this as a vital piece to help in the process of adding condition to the uniform panel. This should be a key objective in the follow-up subcommittee because medicine builds on itself, and we have to find a way to continue that growth. There have been concerns expressed about privacy issues, yet I have come to learn there are a lot of misconceptions out there regarding HIPA that impede a good, thorough documentation of information. Each of the family organizations has their own rudimentary database, and this is an example of OAA, so with the long list of names of potential people. Recently, we celebrated in OAA with one of our adult cases of the birth of her new baby, and through lots of follow-up and care--I wanted to bring a picture and share the family--everything went well due to good follow-up and collaboration with her metabolic folks and her OB-GYN. So in conclusion, I would like to thank you for your continued efforts developing this uniform panel and newborn screening program and for respecting the role of the parent. As we saw yesterday when looking at the state maps, we are making progress in this area, but we must continue to help get it to that uniform status. Thank you. (Applause.)

DR. HOWELL: Thank you very much, Jana. I failed to ask if there were any key questions after John's talk, but let's see if there are questions of Jana before she leaves.

DR. RINALDO: No.

DR. HOWELL: Still here?

MS. MONACO: Yes, I'm here.

DR. HOWELL: Oh, no, no, for John, I'm sorry. Well, why don't we go ahead and do a question for John, if--he's gone so you're out of luck. Okay, I'm pleased to now recognize Ms. Micki Gartzke, who is presenting on behalf of Kelly Leight, who is Executive Director of the CARES Foundation, Incorporated, which is the Congenital Adrenal Hyperplasia Research, Education and Support. You can sit there right at the head of the table, if you like.

MS. GARTZKE: Yes.

DR. HOWELL: Push the button in any way, Ms. Gartzke.

MS. GARTZKE: Thank you, Dr. Howell. "Dear Michele: "I am writing to you today in the hopes that you will bring up an important issue at the meeting of the Secretary's Committee on Newborn Screening and Genetics later this week. We are concerned about a problem that has arisen lately with newborn screening. "We have seen that some of the suppliers of newborn screening equipment and supplies have apparent monopolies on the provision of certain types of supplies and equipment. When these manufacturers of technology assays or other materials and equipment have quality control problems, shortages or the likes, the states are left in a difficult situation with nowhere else to turn. They may be required to revaluate and reset cutoffs based upon different lots of assays, or can be left in a bind when technology has quality issues or there are manufacturing shortages. These problems can overwhelm state newborn screening programs that run on limited resources anyways. "In addition, this can lead to harm to families and children through false positives/negatives and delays in diagnosis. False positives in particular can be very damaging as they can lead easily to skepticism on the part of the health care community. Unfortunately, we have seen situations where children have been screened positive, but the primary care providers assume it is a false positive and delay telling the parents or ordering follow-up tests with appropriate treatment. "We hope that the committee will consider this issue and perhaps come up with ways to alleviate these kind of problems. "Kelly Leight, Executive Director of CARES Foundation."

DR. HOWELL: Thank you very much, Micki.

MS. GARTZKE: Thank you.

DR. HOWELL: I think that one of the comments I would make is that at Amy's committee this morning one of the key areas in the Laboratory Subcommittee was focusing on some quality issues, some harmonization issues, and one of the major areas under discussion there was the issue of identifying all children and at the same time minimizing false positives. Amy, would you like to comment about that, because it is specifically relevant to the comment here.

DR. BROWER: I think it was a very important issue and one that the Laboratory Subcommittee is going to tackle right away. We know that through the working group we feel like we can get a good handle on steps to take initially and make some real impact in the near future.

DR. HOWELL: Further questions of Micki? Thank you very much. Micki also represents the Hunters' Hope Foundation, but she's wearing a different hat today and so forth. Next we have two people listed. I think we're going to have a double duo here, but we have Cynthia Joyce, who is Executive Director of the Spinal Muscular Atrophy Foundation, and Barbara Trainor from the Families With Spinal Muscular Atrophy, who are here to present. Ladies?

MS. JOYCE: Thank you, Dr. Howell, and members of the committee for giving us this opportunity to talk. SMA is relatively new to this committee, I think, and as we've learned about it, courtesy of the NICHD and other activities in Washington, we've been really impressed with your progress and we'd like to applaud it. Barbara and I are here today for with a very special request to the committee, and that is that you consider adding Spinal Muscular Atrophy to the uniform panel--or to this panel--for uniform screening efforts. Our point is that the biology of SMA is very compelling. It is one of the most common of the autosomal genetic recessive--autosomal recessive genetic diseases. The birth rate ranges from on in 6,000 to one in 10,000 infants born each year, and the carrier frequency for this disease is quite high with a range of one in 35 to one in 50 adults. SMA is caused by a loss of function mutation in the SMN (ph) gene that results in motor neuron death, muscle atrophy, and severe to catastrophic loss of function. At least 60 percent of children born every year with SMA present with the most catastrophic phenotype of this disease and generally die before reaching two years of age. So, as you can imagine, it's very devastating to families. But special and sensitive diagnostic testing has been available fear many years. It is often implemented only as the last resort in the diagnostic process. Consequently, infants and children are subject to stressful, often painful and inappropriate tests that only delay preventive care. Early diagnosis will enable the development and implementation of treatment plans that can reduce morbidity and save lives. We hope that you will support the addition of SMAS to the Uniform Newborns Screening Panel to help prevent the needless suffering of infants and children, to help the professional and lay community advance standards of care, and to support the use emerging new treatment paradigms. We believe that SMA meets the principles and criterias established by the committee thus far, and strongly encourage the committee to review this disease state for including into the panel as a primary target for the following reasons, specifically: First of all, the mutation causing SMA is detectable by blood sample testing immediately on birth when symptoms are rarely visible. Secondly, the test is sensitive and definitive in over 95 percent of the cases. Without this test, the differential diagnosis of SMA can be a circular exercise, as I've mentioned already, and can be a painful process and an expensive process for both the families and the health care system. This adds needless time and expense to the care process. The genetic tests for SMA are not cost-prohibitive at this time, but we recognizes that the current testing procedures could be modified and adapted for a more cost-effective manner, and the community is actively working with NICHD to make that happen. Thirdly, the detection, the early detection, will ensure that children suffering from this disease will receive the benefits of effective management, including respiratory care, preventive physical therapy, and nutritional support. These care strategies actually do prevent morbidity and save lives, and they're important to implement early when people are not in any emerging situation. Lastly, early detection will enable clinical trials of agents that may save motor neurons and preserve function for these children. Evidence from prenatally identified children indicates that motor neuron loss in SMA occurs after birth, suggesting that a neonatal treatment window is not only possible but actually may be essential for this disease. We can assure you that the SMA professional community is well organized to provide care and poised to help advance newborn screening efforts in these areas. Primary treatment centers are most often MDA clinics, and there's over 100 of them supported around the country right now, as you probably already know. We hope, in fact, that specific treatments--specific treatments not palliative care treatments--for SMA are on the horizon, and there are a number of clinical trials underway right now throughout the world, two of which are being conduct in the United States right now. It's essential that newborn screening be widely available at the time that any new treatment option is shown to be effective in order to help children as quickly as possible and prevent further disability. In conclusion, by virtually all means and all measures, SMA falls well within the criteria established by the committee for the development of screening panel. It's important to note that early diagnosis will foster disease management to reduce the burden of illness now and will help support the clinical evaluation of emerging new treatment options designed to protect and save motor neurons in the future, and we hope you'll agree with us that this investment is well worth the cost. So I'd like to turn it over to Barbara for a first-hand, a first-person discussion of what this might mean. Thank you.

MS. TRAINOR: Dr. Howell, and members of the committee, thank you for the opportunity to appear before you today. My name is Barbara Trainor, and I am a board member of Families With Spinal Muscular Atrophy and founder of the Chesapeake chapter, one of 25 chapters throughout the country. I am also a mother of three children, including my daughter Erin Marie, who lost her life at only five and a half months of age almost 13 years ago to spinal muscular atrophy. I am humbled to be here representing millions of parents who have had children affected by SMA. All new parents make the assumptions that the healthy baby they bring home from the hospital will be with them forever. Sadly, this is not always the case. Because SMA is a recessive disorder, there is rarely any indication throughout family history that a child might be at risk for SMA. Having already given birth to one healthy daughter, I expected nothing less of our second child, Erin. At Erin's birth, there was not a single indication when we brought her home from the hospital that there was anything wrong. Yet less than four weeks this otherwise alert baby began to show signs of deteriorating movement. Her deterioration was swift and painful. At the time of Erin's diagnosis parents with children diagnosed with SMA had no hope, which makes the devastation, the feelings of helplessness that much more intense. Yet today hope exists in the form of newborn screening. The technology exists to begin screening for SMA immediately, which would allow us to identify children soon after birth. The test is cost-effective and results are available in a timely fashion with a very high rate of accuracy. As a mother, I would have welcomed this important information and begun planning for the care of my child. With a specific treatment for SMA, even though it does not exist currently, it is true that care plans and supportive care make an important difference to families affected by SMA. Furthermore, as Cynthia had mentioned, phase two clinical trials are underway around the world. It is ironic to me that newborn screening for SMA is not indicated because a cure does not exist. Yet the development of a cure depends heavily on screening newborns in order to identify SMA-afflicted children who might participate in clinical trials. Universal screening for SMA is an integral component in the development of a cure. It is my sincere wish that one day children born with SMA will be identified soon after birth and can begin treatment immediately to protect their motor neurons and stave off the degeneration that can lead to death. While the march toward the cure will not bring back Erin, it can prevent other parents from experiencing the excruciating pain of losing a child. My hope today is that in the future we can give new parents of children diagnosed with SMA the hope that newborn screening can provide. I thank the committee for your graciousness and willingness to listen to me. If you have any questions, I'm more than happy to answer any. (Applause.)

DR. HOWELL: Are there questions of Ms. Joyce or Ms. Trainor? Bill?

DR. BECKER: Yes, thanks. Ms. Joyce, I am generally aware that there is a pilot project. In addition to the clinical trials that you referred to in this country, there's a pilot project that's either been proposed--I think it's maybe with HRSA moneys--to assess the applicability of the newborn screening for sort of high-volume type work, which is something that would be needed for a massive screening project. Are you aware of that, of those grants? Because we were contacted--

MS. JOYCE: Yeah.

DR. BECKER: --we were contacted in Ohio about the possibility, because we have a Pediatric Neurology Center at our Children's Hospital--about the possibility of doing some work with them. We had to turn them down because we're working on Duchenne muscular dystrophy right now, but I know that there's a project out there going on.

DR. HOWELL: Let me comment about that in that it's a public information but NICHD has recently funded a major grant to Dr. Pryor to look at the development and refinement of the test appropriate for the newborn screening. And again, Dr. Pryor is in your state, but it really was predicated on the fact that there are these clinical trials out there, and the newborn screening test had not been at the level that would be required for public use but NICHD has come to the table in a big-time way for that, which is very timely, et cetera.

MS. JOYCE: And thanks for the heads-up about the clinic availability, because we'll make sure that Dr. Pryor knows that there's other clinics interested I participating.

DR. BECKER: Actually, I know Dr. Pryor. He's at Ohio State University, and my other hat--not the state of Ohio--and he's the one that contacted us about development of a multiplex assay, and we have provided him some samples. We just can't do the work ourselves right this second, so we are working with him.

DR. HOWELL: Thank you. Thank you very much, Ms. Joyce, Ms. Trainor, et cetera. Our next person is Dr. Carol Greene from the Society of Inherited Metabolic Disorders. Dr. Greene.

DR. GREENE: Thank you. I am Carol Greene, a physician-geneticist and a board member of the Society of Inherited Metabolic Disorders, speaking on behalf of the Society. SAD appreciates very much the ongoing activities of this committee and looks forward to ongoing improvements in the quality of newborn screening that will result from your input. As you consider next steps in your activities, both in your goals and the strategies to achieve goals, SID would like to make two points today. First, in keeping with the membership pool that we have previously presented here, the SID continues to emphasize the need to address long-term issues in your work. It has been pointed out by various members of the committee yesterday that newborn screening is a system, and newborn screening is not just a test. A critical part of the newborn screening system after screening and diagnosis is long-term care, without which there is no point in screening. The effect of Katrina on interruption of care has been mentioned here. SID points out that as important as it is to develop strategies to protect patients in the phase of the disaster, Katrina just highlights, albeit on a massive scale, what health care providers and patients and families face every day in every state. And here I'll add as an aside, not part of my prepared remarks, that we heard that very eloquently just a little bit ago from Jill Fisch. It is routine to struggle with access to needed health care, either because of lack of specialty providers in an area, or because of funding constraints with access to essential therapies, or to necessary monitoring tests. We hope this committee will address these issues and also address the need for ongoing data collection on outcomes to continually improve the system as a whole. Second--and again as an aside, not part of my prepared remarks--I very much appreciate the work of the subcommittee which I'm privileged to be on which is looking at exactly those issues. Thank you. Second, we urge continued efforts--and I think we just heard a little bit about this also this morning--on issues of quality in the testing component of the newborn screen. We appreciate the problems of false positive screens. SID members who are part of newborn screen laboratories interact with the primary are providers, who need to send repeat screens on the babies with borderline or gray zone results and to track and match results. And those who, like myself, are clinicians are directly involved with health care providers and families when newborn screening gives an initial critical result or a repeat screen is positive. Some of the current controversies in newborn screening may be at least partly driven by variability and experience at both levels. In some states and for some tests there is a very high level of false positive screens while in others the experience is less burdensome. I have personally experienced some years ago, with a change in state lab galactosemia screening, a level of positive of positive newborn screens for that condition that seriously taxed our care delivery system. Conversely, right now in Maryland, while I cannot speak to the rate of repeat screens required for borderline or gray zone tests, when I receive a call as a clinician for a positive newborn screen from tandem mass specs, since that technique was added in our state, we have at least nine babies with confirmed biochemical abnormalities. Three have classic disease and one has a B-12 deficient mother--of course, that's a quick cure--and that's out of approximately 12 referrals. So we have only three definite false positives. Colleagues in other states are seeing a much higher level of referral for false positives. The newborn screen isn't just a test, but the system succeeds or fails beginning with the quality of the initial test, and we depend on the best possible balance of sensitivity and specificity to avoid both failures in case finding, and on the other end risk of overwhelming families and the system with false positive results that could be avoided by appropriate quality management. And as always, the SID is ready and eager to work with this committee in any way we can help to achieve our mutual goals.

DR. HOWELL: Thank you very much, Carol. Are there comments for Dr. Greene? (Applause.) I'm aware there's a comment area coming out in one of your clinical journals about the importance of false positives soon which will be quite consistent with your discussion here, because that's a critical area, clinically, and can overwhelm the system, et cetera. Thank you very much. Our next person is Dr. Andrea Gropman from the Child Neurology Society. Dr. Gropman?

DR. GROPMAN: Thank you, Dr. Howell, and the committee members. It's been a privilege to participate in the open meeting and also to be able to give my comments here today. I appreciate that. I wear two hats. Yes, I'm a child neurologist and I'm also trained as a clinical geneticist. Today I'm coming on behalf of the Child Neurology Society. There are a thousand child neurologists in the United States, 500 of whom are also members of the Child Neurology Subcommittee of the American Academy of Pediatrics. On behalf of the child neurologists I can say that as a group we wholeheartedly support your efforts in the implementation and follow-up and strategies related to the newborn screening. In that vein we are also accustomed to some of the difficulties that this group is struggling with in terms of management of individuals with complex health care needs as we face some of these similar issues. I cannot emphasize some of the comments that have been raised by the parents because we, also, as sensitive to those issues. The reason I am here today is basically to make a plea on behalf of child neurologists and also the other subspecialists who are not here, but probably should be considered as important partners in this process, especially with regard to the ultimate integration of health services. I speak on behalf of child neurologists, endocrinologists, and also hematologists--one could also extend this to infectious disease specialists-to consider us as potential consultants or liaisons in this process as we try to move forward. I think, particularly for child neurology, this may be a pertinent point to make if disorders such as Duchenne muscular dystrophy for which there are pilot studies looking at the feasibility of including this in the newborn screen, and also other disorders such as SMA are considered to be added to the panel of newborn screening. So to keep the comments brief, in summary, we appreciate the efforts you're doing, and we consider ourselves supporters and hope to be considered as partners in this process, as well as our other colleagues who would also probably feel similarly. Thank you.

DR. HOWELL: Thank you very much, Dr. Gropman. (Applause.) Are there questions? (No response.) Thank you very much. The expertise of your group is obviously greatly appreciated. And our final commentator this afternoon is Claudine Tiffault, who is a project evaluator from the Sickle Cell Disease Association of America. There seems to be considerable surprise on the part of--(Laughter). Maybe you signed up for dinner last night. (Laughter.) And there was a piece of carbon paper under it, or something. (Laughter.) Having been called upon, would you like to say anything? I mean you've had adequate time to prepare your remarks. (Laughter.)

MS. TIFFAULT: I would have definitely prepared something if I knew I was going to be speaking. But just thank you for the wonderful work you guys are doing in behalf of Sickle Cell Disease. We're glad to be involved, even at the table with Dr. Telfair and just be witness to what's going on. You guys are doing fabulous work and just continue. Thank you.

DR. HOWELL: Thank you very much. (Applause.) Committee Business

DR. HOWELL: That's the end of our public commentators. We are through with that, we are--everybody was succinct with their wisdom this afternoon, and so we come into the final thing on our agenda which is entitled "Committee Business." And let's do a few real housekeeping duties before we get into the discussions, in the event that we have a long discussion. The meetings for the future are under Tab 13, and let's look at those and get those settled. And there are several options that are listed here. And these areas that are highlighted, I am told by Michele, are the dates that have been responded to by those who have responded as being a reasonable time. And so if we look at, more globally, at the event, could I suggest as a talking point that we consider the 23rd and 24th of February for the next meeting? Any comments about that?

DR. TELFAIR: I just--I'm sorry. MS. : We used your calendar, didn't we?

DR. HOWELL: Denise's calendar is in the mix? MS. : Yes.

DR. HOWELL: Your calendar is on the OD (?). Excuse me, Joseph.

DR. TELFAIR: No, it's okay. Thank you very much.

DR. HOWELL: I'm sorry.

DR. TELFAIR: Dr. Howell, I was just wondering, not everyone's here, and I didn't know, or is this adequate to actually get feedback on the dates?

DR. HOWELL: I think so, but let me tell you two things: Number one, everyone has had an email request to please fill in the dates that they found acceptable, and they're all here and so forth, and so that we have some options here, and I think we should go ahead and decide on the thing, because we can't do anything to bring our absent members back. DR. TELFAIR: I'm not in dis--okay, that's an astute obser--no, anyway, I'm not in disagreement with that. I'm just wondering because of a quorum, if you needed a quorum. But, okay.

DR. HOWELL: We do have a quorum. Our core model is just, as I said, is the 23rd--we have two things: One is these are the dates that came back as open on the committee members and so forth, and I'm just suggesting we basically have several options, but I was looking at 23rd and 24th. Does that seem sensible to the gathered group? I see nods up and down. What about the 22nd and 23rd of June, if we kind of go toward the end of the time? And toward the end of October? October 30th and the 31st? Oh, well, we seem to have a crisis in information here. Here comes the person that knows. Kerry is going to tell us, apparently the dates that we are selecting are the dates that were not available. Is that right? We're going to have to take your sage advice because we should have known that you knew what you were talking about, but in view of the fact that the dates we have selected are the dates that nobody's available, that we will have to go back, and we'll depend on Michele to come back and come up with some dates. And we'll just decide this online for the thing. And if you don't respond about the dates, that would be an issue because Kerry has clarified. For those of you that don't know, the person that you get emails from all the time and so forth is Kerry Diener who just came up and so forth. Okay, you have a question?

DR. RINALDO: Yes. It's Thursday, Friday for the month of, you know, something that has to be that way, or can be--

DR. LLOYD-PURYEAR: Does it have to be, as opposed to Monday, Tuesday? Or Wednesday, Thursday? It can be any--

DR. RINALDO: No, you know, sometime earlier in the week better than the end, but--

DR. HOWELL: Is there any generic comment about is there a time--in general, is there a time of the week that is preferred?

DR. BROWER: Tuesday and Wednesday. Tuesday and Wednesday, or Wednesday, Thursday.

DR. HOWELL: Any comment about Amy's comment. Amy feels it would be better to have days kind of within the week rather than spanning the weekend and so forth. Is there any comment about that? Obviously, you have to be available.

DR. RINALDO: Actually, my inclination was the opposite. I would rather travel on the weekend because, like for me--like this trip really caused a loss of a working day just to get here, and I would prefer to travel on the weekend, but that's just my--

DR. HOWELL: You're talking about, since we end on the-- DR. RINALDO: Coming in on Sunday, ending the meeting Monday and Tuesday.

DR. HOWELL: Which would mean you could leave on Tuesday afternoon and get back, and you basically, you're talking about reducing the time away by a day is what you're saying. If it were earlier in the week, you could travel at the end of the meeting and so forth.

DR. RINALDO: Exactly.

DR. HOWELL: Any comment about that? Amy is, obviously, she's a middle-of-the-week person there. Any other comments? Joe?

DR. TELFAIR: Any--most--a lot of days--and I realize this may be just for myself--but I think some of us who have other responsibilities, it's actually more stable the way it had been to do this other, like teaching, like other group work, like family, you know, et cetera, it's easier, that way of doing that, structurally, was--worked out much better. That's my two cents, but I'm a liaison to the group, so--

DR. HOWELL: Well, we appreciate your two cents.

DR. TELFAIR: Yeah, I understand. Thank you, sir.

DR. HOWELL: Bill?

DR. BECKER: Rod, I agree with Piero's comment. It, doing the meetings on a Monday, Tuesday would alleviate a little bit of a time away concern if you have to make requests for that particular time. On the other hand, I think what's most important and maybe what, part of what, Joseph was mentioning is whatever we do, let's continue to be consistent with it. It's easier to schedule if it's always on Thursday, Friday, or if it's always on Monday and Tuesday, of it it's always on Tuesday and Wednesday.

DR. HOWELL: If it's good with the committee, then we will recirculate this to be certain, because the calendars may have changed, and we'll come up with some days. Can we do that, Michele?

DR. LLOYD-PURYEAR: Um-hmm. I'll do it on Monday.

DR. HOWELL: Outstanding, and so forth. Now, the other thing that I'd like to bring up before we get into what I would call committee business, and that is that we had discussed the fact that we're expecting people will send notes to us about people that they've--or groups that would be appropriate liaison to the committee. And we will develop, as Peter suggested, some systematic way of looking at that about the value and all the other things and so forth. There are two groups that have been before this committee for some time that I would like to bring up again, because we've been discussing them during the past year. One is a person from the military, who has very specific newborn screening issues, and the other that's been under considerable discussion is FDA because of their active involvement in so many things we do. And I'd like to have a discussion of those, and then we will look, then, at a variety of important other groups and people that might need to be added in the future. Can we have a comment about those two groups as far as--these are suggestions for liaison appointments to the committee.

DR. TELFAIR: I can just make a comment because of the other committee that I sit on, and both of those groups, you know, are--or representatives from both of those agencies, the veterans, Department of Veteran Affairs, and the FDA, I sit on those committees, and there's a substantive amount of information and work that's being done on both of those ends related to issues of newborn screening, particularly issues of genetics and newborn screening genomics. So I would really strongly endorse for consideration of those groups, representatives from those groups, working with that and, specifically, their offices within those agencies that focus on these types of issues. So I would strongly encourage that because I think they would bring a lot to this committee.

DR. HOWELL: Would anyone else like to comment about that? The military has been actively involved with the development of the original guidelines that came through and so forth, and they had a lot to say and a lot to add and a lot of specific issues to bring to the table. And certainly I would support that. Peter? Peter's not here. Piero, can you comment?

DR. RINALDO: I'm in support. I believe that the military has jurisdiction over something like 60,000 babies born to active-duty personnel every year, which is larger than probably the average state. So I think they do have a significant stake when it comes to newborn screening issue, and I think they should be involved.

DR. HOWELL: Coleen? It would appear that there's general agreement. We've had some head-noddings and some vocal, but Denise has something to say.

DR. DOUGHERTY: I just want some clarification. When we invite an organization to come as a liaison, do they pay for themselves to come to the meeting? It's all--

DR. HOWELL: Yes.

DR. DOUGHERTY: --it's all on them?

DR. HOWELL: Yes.

DR. DOUGHERTY: Okay, thank you.

DR. HOWELL: That's correct. So that, well, it would seem to me that having heard some specific comments and so forth that we'll proceed, then, to invite the Department of Defense, either the military and the FDA, and then we will proceed as we move along to have other liaisons that will bring certain expertise and wisdom to this committee. What other things would you like to discuss at this point, ladies and gentlemen, and the area? Lauren?

MS. RASKIN-RAMOS: In a different topic, just an announcement that you can cross out the "To Be Determined" under ASTHO in your member roster now that I'm pleased to announce that Dr. Chris Koss (ph), who is the Pediatric Director from the New York Department of Health, has agreed to represent us still on this committee, and I'm sorry we couldn't get the approvals through for him to be here this week, but we're excited to be more engaged in the future.

DR. HOWELL: Thank you very much. That will be an important addition and so forth, et cetera. Other items of business that someone would like to bring up? Michele, are there some things that we need to bring up?

DR. LLOYD-PURYEAR: The February agenda.

DR. HOWELL: Comments about the February agenda? We will be developing the February agenda over time, but it would be a good time to weigh in on some specific areas of interest that you would have discussed, or people you would like to bring. Denise?

DR. DOUGHERTY: I think it would be good for our committee, especially our subcommittee, to hear from some of the regional collaboratives, probably useful for the rest of the other people, too. Bill whispered in my ear, "Yes."

DR. BECKER: Well, I agree with that, and it may be through the Coordinating Center, through ACMG.

DR. HOWELL: That would certainly be a logical place, I would think. Prior to the meeting here, I had spoken to Michele about the fact that I think that they--what that group is doing has a potential of value in newborn screening, and I think that we would certainly like to have some important input in it about what they're doing.

DR. DOUGHERTY: I think for hearing from the Coordinating Center, and Jill also--Fisch--she has a set of slides--but hearing from some of the collaborators themselves I think would also be helpful to get the kind of front line experience.

DR. HOWELL: Right, it seems to me that there might be some virtue in having a duo or more of some core things and so forth, but every time we discuss this group, there seems to be something else that could be really integrated with their efforts that could be important, et cetera. What other things should we hear about next time? Joseph?

DR. TELFAIR: Yeah, I just have a suggestion for, being someone that's a liaison from a similar committee and in for liaisons, I know it's important because the other committees that I sit on, we do have like a brief update, if any at all of formal liaisons about their work as it relates to this committee. So I think that in the spirit of engagement, you know, to sort of improve the engagement, and maybe if there was maybe like a five-minute, if they have that much information about what they're doing, in relationship that this committee might be interested in, just an update, just a few words or whatever, you know, as a point of engagement I think would be good, if that happened at this committee.

DR. HOWELL: That's an interesting idea, to bring a little bit of commentary on that. For example, for the National Advisory Council's NIH, obviously, have liaisons representing a certain thing, and they do two things. One of the things they do--and you'll be sad you brought this up--is that they prepare a written document for each meeting that describes some of the key things that you've been doing so that it becomes a part of this book. And then you can have an opportunity to comment. And I think those written documents are very valuable and so forth. But I like that idea. Oh, the other area that--excuse me, let me comment about one thing before I forget it--and the thing is, is that the other group that's doing some important things that we need to hear about, and also perhaps been there, activities to fit in with some of the things we would like to do is the Office of Rare Diseases at the National Institutes of Health, that is funding--they have funded a group of centers of excellence in rare diseases. And I think--this is a personal viewpoint--is that it would be key that, for example, if a person with hyperammonemia is discovered in Montana, that they are able to plug into the Center of Excellence in Urea Cycle Defects that happens to be here in Washington and get plugged into the therapeutic things and what they're doing, and all that sort of thing. But I would hope that we might have an opportunity to have Dr. Groft and his people come in about some of the movements in the Office of Rare Disease. Does that seem--everybody seems to think that's--

DR. RINALDO: This might require some discussion, but, you know, yesterday we had a lot of I think very productive discussions, and one of the things that emerged both in the discussion of the evidence-based process and also in potential revision to the criteria, was a concept of harm caused by newborn screening. At the same time, we all had been hearing or seeing comments made by people who claim significant harm caused by newborn screening. I would like to have them come here and tell us about the harm, and so that we can put all these things at least through the test of evidence and see what is true, what is missing, what is just and true.

DR. HOWELL: One of the things that I'm aware of is that there is a project underway that's just beginning from an expert pediatric historian, a person who's formally trained in history to do analytic things in history, and the specific project is to examine adverse effects that are recognized and reported from newborn screening. And that, I think--

DR. RINALDO: And I would like something more.

DR. HOWELL: Well, this is going to be a fairly detailed report.

DR. RINALDO: Okay.

DR. HOWELL: You would like to have some of the folks talk about adverse effects to come here and defend their position.

DR. RINALDO: Yes.

DR. HOWELL: I don't think they will come.

DR. RINALDO: I really would like to see that happen. And if they don't come, that, I will think, we'll be entitled to infer from their lack of participation what is the evidence behind their claims.

DR. HOWELL: Bill?

DR. BECKER: Another topic.

DR. HOWELL: Let's put that topic to bed, since it may recur. Michele? Peter? I have no problem at all with asking--

DR. LLOYD-PURYEAR: Are you talking about Norm Kahn? I'm just asking--(Laughter.)

DR. RINALDO: Can we start?

DR. HOWELL: You know, I think the thing is about the issue of adverse effects. I think that if--I think some of us have been in newborn screening longer than most people have been alive, and we're aware of some issues that have come up with treatment. I mean we didn't just get off the boat with people that didn't understand DIAS (ph), and it did what were really not smart things to do. And there were some significant problems that developed occasionally, and a fair number of transient problems. We're fully aware of that. But I think that we're not aware, at least--and I've talked with people like Selma Sniderman, who preceded me, and she's still very much alive. She's the only one that fit that category, and she is unaware of, except for a handful of people, but the thing is that if there are, indeed, significant adverse effects out there, we certainly should know about them. And I mean if there is information to bring to this group that we could benefit for, I'm all for it and so forth. And we can certainly ask.

DR. RINALDO: My point is if you look at the recent scientific and nonscientific articles, we're talking about Nature magazine, New England Journal of Medicine, we're not talking about minor--minor venues, there has been strong claims of, you know, of really the unintended consequences or of the screening. And I think, you know, people may agree or disagree. I just would like to see the evidence used by the people who made those comments to say that, you know, what is the magnitude of the harm caused by screening. That's--now, how to achieve this goal, I'd gladly leave it to you and to--

DR. LLOYD-PURYEAR: Along that line, the criteria work group that was set up, are you--you're supposed to be reporting in February, too, right?

DR. DOUGHERTY: Right. We met, the five of us, last night, and there's a list of just buckets of criteria that are being--we're now circulating so everybody can look at it. And then we'll have a conference call. So we'll need some help with setting that up from you.

DR. HOWELL: Bill, excuse me, you had another comment? The bottom line, we will see about the possibility of getting someone to come, and we know who to get to come.

DR. RINALDO: Make sure to put a lot of time for questions.

DR. BECKER: Rod, one of the groups that our subcommittee did not identify in our charges but probably ends up being an important group across the entire committee are the policymakers. And now we have representation from ASTHO, but there's another group of policymakers that might benefit from interaction with the committee, the full committee, and we might benefit from hearing a presentation from them about their group, and that's the NCSL, National Conference of State Legislators. And I'm aware that there is someone present here at the meeting today, and we don't have to put that person on the spot right this second, but maybe for the February meeting, since that's really what the agenda issue is right now, is to ask for a presentation from NCSL because they are probably a major stakeholder. We thought of this as another group, not necessarily in our charge, but eventually we'll need to consider education for that group of people as we move forward with expanded newborn screening.

DR. HOWELL: Coleen? VOICE: (Off mike.)

DR. HOWELL: We'll ask Michele to be in contact with you at least. Thank you very much. Coleen?

DR. BOYLE: Yeah, I guess for February, I was thinking that as a full committee we needed to move along on the process. And I know that the process of nomination and evaluation of new candidate conditions and, actually, sort of revaluation of existing conditions are on the panel, and I'm not quite sure how to move that process along. I know we're talking about the actual criteria on this small group of five, but I feel like there are other things that we need to be thinking about in terms of flushing that out further. So somehow that process needs to be moved along. I'm not quite sure how to move it along, but I think we need to give some thought to that as well.

DR. HOWELL: Did you have some specific areas you want to focus on? I mean the criteria, certainly, is one key underpinning for that, et cetera.

DR. BOYLE: Well, I'm assuming that perhaps between now and February HRSA will make some decisions in terms of how the expert review group, how that whole concept will be managed in terms of the actual reviews of the scientific and other literature in terms of evaluating tests, new tests or new conditions that are proposed. But again, I feel like there's a whole system in place, as we heard about the example of ACIP yesterday, and we also heard a lot from David Atkins. I feel like there's some--there needs to be some really deliberative thought given to the process that we had that you folks outlined in terms of that, at least the framework for it. I don't know who's going to be thinking about that. I don't feel like it's a done deal. I know we have a skeleton of a process. Now, how do we put the sort of the little flesh on the bones of that process.

DR. LLOYD-PURYEAR: Do you want Piero to redo the flow diagram and send that out again for thinking, for looking at?

DR. BOYLE: Yeah, and maybe between now and February we can think about what needs to be done in a deliberative way.

DR. LLOYD-PURYEAR: Well, the work group, I mean from my notes what I have is that your work group is supposed to be figuring out three sets of criteria. One set would be the nomination form; one set is on what basis for accepts or rejects; and the one set is the evaluation by what we were calling the evidence-based work groups. So that's a key piece that we can't even--we can't--I mean we can--Peter's already told you what we're leaning towards.

DR. BOYLE: No, no, no. I know that. DR. LLOYD-PURYEAR: Your piece is a core part of that, of presenting it to a group.

DR. HOWELL: Piero has something today, but it would be--it would seem to me that once we come up with these valuative forms, shall we call them, for folks to use and so forth, and once the HRSA group has considered the evidence-based thing and so forth, probably one of the first things that is going to happen is to actually have a trial balloon that--a specific recommendation using those criteria and having it go through the system. And probably that'll be the time when we see areas that probably need fine tuning and so forth. Maybe I'm wrong on that.

DR. BOYLE: and I don't know if we want to take a new condition, or we want to take, you know, new conditions that are on the new panel, and maybe one that has considerable evidence and one that doesn't, and see how it works with conditions that are already part of the panel. Something like that.

DR. RINALDO: I don't see that we--well, personally, we prefer to--just look at SMA, you know. That was not even on the radar screen throughout the process, not to the point of being included in 84 conditions. And now we're already talking about really what appears to be immunity implementation. You know, I believe that the uniform plan still are a relatively young product, and I would let it, you know, be for the time being and see how it works, and then look at the evidence. I would work on new conditions, and at the same time my comment would be that, as we discussed yesterday, I think it is quite valuable and to look at those criteria and expand them. I really hope it will--and that could be relatively easy, looking after the least that Denise provided to some of us earlier--if we can look at those and see how those can be incremental criteria. I really hope that--at least I would really think it wouldn't be the best use of our time if we start now going and revisiting the other criteria. So to eliminate talk, let's, if this is a sort of a change of pace and is no longer an issue comparing to the past, let's sought (ph) some criteria quickly. And then, so in February I agree. I think a test drive is really what we all like to see, and I would do it with something that is new and not one of the existing conditions. That would be my preference.

DR. HOWELL: Let's consider these issues and so forth, et cetera. I think that--but I think the key thing is to look again at the diagram. Let's look at the criteria as they are evolving from the committee that you all are actively involved with and so forth and see what we can do. My own personal preference would also be to look at something new, but there may be virtue in looking both ways. My impression is that there are a handful of conditions that are out there that have considerable evidence underlying them at this point and so forth, and it'll be interesting to look at some of those. I think it would be a good experience and so forth, and again it would also serve the virtue of moving head, which is always good. What other things do we need to discuss before we depart on this Friday afternoon before the rain stops? Anybody have any other comments? Joseph?

DR. TELFAIR: Actually, just that--it's not a comment, it's just a thank you to the persons who came and helped, were supportive to the subcommittees. Their input was very valuable, so I just actually want to thank those persons publicly.

DR. HOWELL: Well, I think I would, on behalf of the committee, would also like to underline that, because the subcommittees were extremely productive this time, and I think of very concrete things are underway. And so we should be able to move this thing ahead, et cetera. Any other comments? (No response.)

DR. HOWELL: Thank you very much. Have a nice weekend and we'll see you in February at a date to be determined, hopefully not on the days that no one can come. (Whereupon, at 2:08 p.m. the meeting concluded.)