Howell, R. Rodney

English

Case Western Reserve University School of Law

Health Matrix: The Journal of Law-MedicineVolume 19 | Issue 12009Systems to Determine Treatment Effectiveness inNewborn ScreeningR. Rodney HowellFollow this and additional works at: https://scholarlycommons.law.case.edu/healthmatrixPart of the Health Law and Policy CommonsThis Article is brought to you for free and open access by the Student Journals at Case Western Reserve University School of Law Scholarly Commons.It has been accepted for inclusion in Health Matrix: The Journal of Law-Medicine by an authorized administrator of Case Western Reserve UniversitySchool of Law Scholarly Commons.Recommended CitationR. Rodney Howell, Systems to Determine Treatment Effectiveness in Newborn Screening, 19 Health Matrix 155 (2009)Available at: https://scholarlycommons.law.case.edu/healthmatrix/vol19/iss1/8SYSTEMS TO DETERMINETREATMENT EFFECTIVENESS INNEWBORN SCREENINGR. Rodney Howell, MD.tDR. HOWELL: Max, thank you, very much. It's my pleasure tobe here today to talk about newborn screening with this distinguishedgroup of LC researchers and clinicians.This afternoon, what I'm going to do is to spend the time I havetalking with you about some systems that are in place and that arebeing put in place nationally, to decide, whether or not, indeed, condi-tions are treatable in the newborn screening panel. And I'll go throughsome of the rationale behind that as we proceed.These first comments are well known to all of you. Newbornscreening has been around for a long time. I think, fundamentally,however, once a serious but apparently treatable condition has beenidentified, it has been felt that controlled studies in those conditionswould be not ethically sound. And this has resulted in the fact thatthey are extraordinarily meager studies in outcomes and, particularly,in peer-reviewed journals. The amount of information on these rareconditions has continued to be meager. And the result is that in veryfew of the conditions do we have, really, what we would considerperfect information about the effective treatment in the long-term out-comes.This has been discussed extensively and this panel is very muchaware about the American College of Medical Genetics panel thatcame up with the recommended uniform panel. This has been widelydiscussed. This group, as you know, recommended a core panel of 29conditions. The secondary targets were a number of 25. We couldspend a month talking about this and I'll be glad to discuss it withanybody in private. There are a few conditions that are excluded anda considerable number of conditions that were not on the panel be-cause there was no test available.I might point out this report has not only been groundbreaking asfar as changing the practice of newborn screening in the United States,t Professor of Pediatrics, Miller School of Medicine, University of Miami,Florida.HEALTH MATRIXit has, arguably, been one of the most discussed documents, of, cer-tainly, my lifetime. And many folks in this room, as I sit around look-ing, have written highly critical documents about this. I can see twowithout changing my eye. What I might point out is that there were29 put on primary conditions and 25 secondary targets. But I willinclude one article from a scientific journal that is Nature Geneticsand I have quoted this in view of the company present today. NatureGenetics said in 2007, "perhaps we can learn from one of the mostimpressive recent exercises in evidence-based medicine, namely theAmerican College of Medical Genetics Systematic Prioritization ofGenes for Newborn Screening." I will not further comment aboutthat.Now, what are some of the challenges that we have to deal with inthe area of newborn screening? Number one, there are enormous ex-pansions of potential targets and that's just been emphasized in Don'srecent presentation. Poor understanding of the clinical significance,scalability, affordability, invariability of complexes of policy, but wecome down to the bottom line again, of striking lack of publishedpeer-reviewed articles. And I might point out there were more than100 people that worked on the ACMG report that you've seen here fora couple of years. And it was the people whose careers have beendevoted to this, but families were involved. There were legal people,ethicists, et cetera. The basic fact was is that there was not a lot ofconcrete, long-term information about many of these conditions andeveryone was very much aware of that.What are some of things that are going on that I think will impactour information about the conditions that are on the panel? I'd like todiscuss, briefly, the recent collaborative screening and genetics col-laborative groups around the country. Many of you are very familiarwith this in that the HRSA has established this group of folks, whosegoals were to address mal-distribution of genetic resources, promotegenetics, promote translation of genetic medicine in the public healthand healthcare services, cooperate in studies to establish best labora-tory practices and the appropriate cut-off phase. I'm going to spend agood bit if time with that in the later panel. But also to work withnational groups to effect, to evaluate treatment outcomes and long-term follow-up. There are seven of these regional collaborativegroups and one national coordinating center that is operated withHRSA.This is the map for those of you - many of you work within theseand you're very familiar with these, but basically, you have the UnitedStates, divided up into seven regions. The great value of this, asidefrom the sharing of information and so forth, is that these groups areclosely involved with the state health departments in all of the regions[Vol. 19:1552009] TREATMENT EFFECTIVENESS IN NEWBORN SCREENING 157and they have contact with the folks who are collecting the patientsand the information and so they provide an extraordinarily good op-portunity to do a large number of things and there are many thingsgoing on.The groups are encouraged to establish cooperative programs.Region 4 is one region that is currently working very, very hard in aninternational collaboration. It has actually, expanded beyond theseven regions and now has people from all over the world to look atcut-offs and false positives. And the other regions around the countryare developing individual projects. But the reason I go into this sys-tem is that the next part of my discussion is going to be discussing arecently announced NIH program that will be dealing and will be builton top of the original collaborative programs. I might point out thatJeff Botkin today asked about the action sheets that are handed outthrough the regional collaborative networks to address one of the keyproblems with newborn screening. As this group is intimately aware,the conditions, individually, are rare, and it would be unrealistic toexpect any practitioner to be aware of all of these conditions. Thetypical situation that happens is that on Friday afternoon - it'd be aday like this - about this time of day on a rainy Friday afternoon, youget a call in your office that you have a child that has just beenscreened positive in the state health department with the condition thatyou, literally, have never heard of. That is the paradigm that we dealwith.I might point out, these ACT sheets are designed to be availableonline and they, actually, are online and they have been developed forall the core and secondary targets. They are really designed to pro-vide immediate point of learning, education and so forth. And theyalso are currently included in the American Academy of Pediatrics'plan at the newborn clinical report in their task force.Let me just show you one of these. Many of you are familiar withthese, but this happens to be the one for thyroid disorders. And it,basically, provides a differential diagnosis. It tells you exactly whatto do, immediately. It has some comments about the diagnosticevaluation and it then has some additional information you can clickon and go there. We have not yet talked about the genetic home ref-erence, and I am not going to talk about that today, but the NationalLibrary of Medicine, working with the parts of the NIH, has on itsGenetic Home Reference site all of the conditions that are included inthe panel and it's done for parents. And so, it is a very nice source for,really, highly vetted information. I might point out that certain stateshave their own ACT sheets that are customized for their specific pro-gram. But it is also intended that these national Act sheets will alsobe customized for the local site.HEALTH MA TRIXThe thing I would like to talk about next is the fact that NICHDhas recognized that there is a very meager amount of informationabout these conditions and so, fundamentally, one that they havefunded a variety of programs that I have listed here about innovativetechnologies and strategies. One of the things that they are currentlyinvolved in is to set up a NICHD newborn screening translationalresearch network. There is some background information about theneed, et cetera and NICHD proposes to establish this network, and itis far beyond a proposal at this time in that the contract for the coordi-nating center of this network will be awarded in the current federalfiscal year. So, it will be awarded before October of this year. Theseare the kinds of things that this network is expected to do. Numberone, it is planned to develop a virtual repository for residual driedblood spots, as appropriately stored by the states, that they would de-velop and oversee laboratory and practice standard guidelines andwork with the laboratories for the clinical diagnosis included in thepanel so there would be specific discussions about diagnostic confir-mation; that they would develop policies and recommendations aboutinformed consent that might be appropriate for newborn screening.We are all aware of the fact that informed consent documents must bedeveloped at the institutional level, but we are also aware of the factthat national collaborative groups such as the Children's Oncologygroup make a great deal of progress by having a nationally vetted in-formed consent that applies - that then can be worked on at the insti-tution locally.Fundamentally, the long-term plan is that this network would pro-vide a mechanism by which research can be initiated and there can belong-term follow-up of patients with rare conditions, et cetera, as aresearch effort. This is a five year proposal for the coordinating cen-ter and, as times goes along, it will have additional activities to coor-dinate between other state and federal estimates and develop standardprotocols and research. It will also be working on a data-sharing pol-icy so that there can be nationally acquired data on the various andsundry children who are being diagnosed and how they will be fol-lowed-up in some of the research protocols. This is, in general, whatit would look like: the translation research coordinating center in thecenter, but working with various and sundry grants, and coordinatingmany activities. There will be a steering committee and this will beclosely tied to the states' newborn screening programs.Let me comment just briefly in my final remarks about the advi-sory committee on heritable disorders and genetic diseases in new-bors and children and the law that was just signed last week hasshortened the name, mercifully. That committee has been just re-newed for another five years. Fundamentally, this is a broadly based[Vol. 19:1552009] TREATMENT EFFECTIVENESS IN NEWBORN SCREENING 159committee that provides recommendations to the Secretary of Healthand Human Services about the appropriate application of universalscreening, newborn tests, technologies, policies, guidelines and pro-grams. Now, many of you are aware of this committee and many ofyou have been involved with the committee, but it has medical, tech-nical and scientific people. It has a broad group of public membersand representatives from the federal agencies, such as the March ofDimes and other professional groups who have relevance to newbornscreening.The committee is currently looking at new nominations for new-born screening and the nomination process, as outlined here, is to be avery broad process where anybody can make nominations. It wouldbe streamlined; it would be transparent and there are consistent crite-ria. And the main areas for consideration by the group will be thecondition, the test and the treatment. This is the form that is on theweb site of HRSA and it is a very simple form, I might point out. Ittakes a lot of time to fill it out properly, but basically, there is infor-mation about the condition, the incidence, the timing of onset andseverity, the test, such as the screening test to be used and the modal-ity of screening, validity, confirmation and the risk of false positiveand carrier detections and things of that nature, the treatment, modal-ity, urgency, efficacy, availability, risk and then the references.This nomination then comes to the committee. But one thing thatrecently has changed, and that we think that will be a very big issue, isthat once this report comes to the advisory committee, if the advisorycommittee thinks that yes, this looks like a perfectly reasonable pro-posal, it then will go to a totally external evidence-based committee.And that committee is operating under a contract with HRSA, but it istotally independent from the advisory committee and it is headed by agroup of distinguished folks at Harvard who are involved in evidence-basis research and is headed by Dr. Jim Perrin. And that group willdo a formal review of the evidence about these rare conditions. And Imight point out that formal evidence review in these rare conditionsjust has not been done before and they have really spent a lot of timethinking about it. They have identified some issues that we are awareof, the lack of randomized trials, they are rare. There is limited in-formation on the cost. They are concerned about access to the evi-dence; the published evidence is meager, as you know. There areunpublished results that they will look at. They are going to try to getas much as possible FDA data, such as when you introduce a newtherapy, such as Myozyme, where you have an approved drug; theFDA will have those data. And they are going to use proprietary data,when possible. They will review the thing just to be sure that theform is filled out and so forth.HEALTH MATRIXAnd I might point out, as of this moment, the Maternal and ChildHealth Bureau has already received five nominations for conditions,as I have shown here. Two have been seen sufficiently by the com-mittee to send to the evidence group and so forth. And those two thathave been seen by the committee and sent out for evidence review, isPompe disease and Severe Combined Immune Deficiency (SCID).Those are the two conditions that have gotten to that point.The evidence review is going to publish all of their material, butthey will have a clear conflict of interest policy. That is a very inter-esting issue, because most of the people that recommend conditions ofthis nature are heavily conflicted because they have either been in-volved in research or they have families with the condition. And it isa very small community. They recognize that; they want to have thatclearly stated.Let me zip through some of the things. They are going to reviewthe natural history, including variations in phenotype, the prevalence,impact and severity, methods of screening and diagnosis and things ofthat nature; the feasibility and acceptability of screening. They aregoing to look at the benefits of treatment, screening positive individu-als otherwise diagnosed persons. Harms or risks involved in thescreening, diagnosis and treatment and the cost.They are publishing their search methods, such as the time frameand the search engines that they have used. They are going to usepeer-reviewed English literature, English only. Gray literature, theyare going to review. They are going to exclude case reports. I thinkthat this will be an interesting problem, because so much of the mate-rial in here tends to be individual or small numbers of the cases. Theyare going to review consensus statements, but not for abstraction.They are going to, once they have finished with all the data abstrac-tion and quality assessments and so forth, and analyze the raw datathat they have. They are then going to have focus groups that willdiscuss their findings and they will make the input public, whichwould include families and investigators.And severity estimates are particularly important. For example,for those of us who have been taking care of your children for a longtime, we tend to think that, well, you know that, the diet, the PKU is avery straight forward treatment. Families do not think so. It is a bigdeal; it is very complicated. And so severity will clearly have a verydifferent view depending on whether or you're living with it or at adistance.Finally, once this evidence review, it will come back to the advi-sory committee. All the decisions will be made by the advisory com-mittee and some of the possible recommendations from the advisorycommittee will be that this is recommended for universal screening,[Vol. 19:1552009] TREATMENT EFFECTIVENESS IN NEWBORN SCREENING 161that there should be some targeted screening done, or some pilot stud-ies done. They will identify studies that will be done and, hopefully,that will feed back to the NIH who will say, if there are studies thatneed to be done, these should be proposals that are sent out as RFAsand so forth.No recommendation is listed here as an outcome, which I think isan unfortunate turn, because I think if you do not make any recom-mendation that tends to be a recommendation of sorts. And you canrecommend against newborn screening.But anyway, I think that one of the - I will close with this. Thatis, I will comment briefly about public law, 110-204, that was signedon April 24th by President Bush and the working document was theNewborn Screening Saves Lives Act. That legislation authorizes 58and a half million dollars to improve, expand, coordinate and evaluatefederal research, education, programmatic activities. It is intended tohelp the state and local health agencies to provide screening, counsel-ing, healthcare services, state laboratories, parents, families, and fundnew technologies and follow-up treatment. So we will be very inter-ested to see what happens with that.I think that it was widely felt that there was not a chance thatwould get through the Senate. It was further confirmed that there wasnot a chance that it would get through the House. And thirdly, it wasfelt there was not a chance the President would sign it. And all threeof those happened. And I might point out, almost exclusively, be-cause of very active parent and advocate procedures. Now the samepeople that told me all those three things, there is not a chance thatany money will be appropriated, but we will have to see.Thank you very much. (Applause).(Presentation concluded.)

Systems to Determine Treatment Effectiveness in Newborn Screening

https://scholarlycommons.law.case.edu/cgi/viewcontent.cgi?article=1180&amp;context=healthmatrix

Systems to Determine Treatment Effectiveness in Newborn Screening

Abstract

Similar works

Full text

Available Versions

Case Western Reserve University School of Law