Summary of Fifth Meeting
July 21-22, 2005
Washington DC

• Printer-friendly Summary

The Secretary’s Advisory Committee on Heritable Disorders and Genetic Diseases in Newborns and Children was convened for its fifth meeting at 9:05 a.m. on Thursday, July 21, 2005, in the Rotunda Ballroom at the Ronald Reagan Building and International Trade Center in Washington, D.C. The meeting was adjourned at 2:50 p.m. on Friday, July 22, 2005. In accordance with the provisions of Public Law 92-463, the meeting was open for public comments from 1 p.m. to 2:00 p.m. on Friday, July 22, 2005.

Committee Members Present:

R. Rodney Howell, M.D.
Committee Chairperson
Professor
Department of Pediatrics
The University of Miami School of Medicine
P.O. Box 016820
Miami, FL  33101

Duane Alexander, M.D.*
National Institutes of Health
Director
National Institute of Child Health and Human Development
31 Center Drive, Room 2A03
Mail Stop Code 2425
Bethesda, MD  20892-2425

William J. Becker, D.O., M.P.H.
Medical Director
Bureau of Public Health Laboratories
Ohio Department of Public Health
1571 Perry Street, P.O. Box 2568
Columbus, OH  43216-2568

Coleen Boyle, Ph.D., M.S.*
Centers for Disease Control and Prevention
Associate Director
Science and Public Health Team
National Center on Birth Defects and Developmental Disabilities
1600 Clifton Road, Mail Stop E87
Atlanta, GA  30333

Amy Brower, Ph.D.
Medical Informatics and Genetics
Executive Director
Third Wave Molecular Diagnostics
502 South Rosa Road

Peter B. Coggins, Ph.D.
PerkinElmer
Senior Vice President
PerkinElmer Life and Analytical Sciences
President
549 Albany Street
Boston, MA  02118

Denise Dougherty, Ph.D.*
Agency for Healthcare Research and Quality
Senior Advisor, Child Health
540 Gaither Road
Rockville, MD  20850

E. Stephen Edwards, M.D., F.A.A.P.
2700 Conover Court
Raleigh, NC  27612-2919

Gregory A. Hawkins, Ph.D.
Wake Forest University School of Medicine
Assistant Professor
Department of Internal Medicine
Center for Human Genomics
Medical Center Boulevard
Winston-Salem, NC  27157-1054

Piero Rinaldo, M.D., Ph.D.
Mayo Clinic College of Medicine
Professor of Laboratory Medicine
Department of Laboratory Medicine and Pathology
Chair, Division of Laboratory Genetics
Mayo Clinic Rochester
200 1st Street, S.W.
Rochester, MN  55905

Derek Robertson, J.D., M.B.A.
Powers, Pyles, Sutter & Verville, PC
Attorney-at-Law
1875 I Street, N.W., 12th Floor
Washington, D.C. 20006-5409

Joseph Telfair, Dr.P.H., M.S.W., M.P.H. *
Secretary's Advisory Committee on Genetics, Health, and Society
Department of Maternal and Child Health
School of Public Health
University of Alabama at Birmingham
1665 University Boulevard, Room 320
Birmingham, AL  35294-0022

Peter C. van Dyck, M.D., M.P.H., M.S.*
Health Resources and Services Administration
Associate Administrator
Maternal and Child Health Bureau
U.S. Department of Health and Human Services
Parklawn Building
5600 Fishers Lane, Room 18-05
Rockville, MD  20857

Executive Secretary

Michele A. Lloyd-Puryear, M.D., Ph.D.
Health Resources and Services Administration
Chief, Genetic Services Branch
Maternal and Child Health Bureau
U.S. Department of Health and Human Services
Parklawn Building
5600 Fishers Lane, Room 18A-19
Rockville, MD  20857

CONTENTS

I. WELCOME, OPENING REMARKS

II. COMMITTEE BUSINESS—THE AMERICAN COLLEGE of MEDICAL GENETICS (ACMG) NEWBORN SCREENING REPORT AND PUBLIC COMMENTS

A. Update on the Status of the ACMG Report
B. Committee Discussion of the ACMG Report and Public Comments

III. STATUS OF THE STATES—UPDATE ON NEWBORN SCREENING  PROGRAMS

IV. THE ROLE OF EVIDENCE AND OTHER FACTORS IN DECISIONMAKING

A. Evidence, Politics, and Technological Change
B. Making Policy When Evidence Is Meager and in Dispute
C. Incorporating Evidence-Based Expert Opinion Into the Decisionmaking Process

V. COMMITTEE BUSINESS—THE PROCESS FOR MODIFYING THE UNIFORM NEWBORN SCREENING PANEL AND SUBCOMMITTEES’ CHARGES

A. Process for Modifying the ACMG Uniform Newborn Screening Panel
B. Proposed Charges for the Committee’s Three Subcommittees

VI. AMERICAN COLLEGE OF OBSTETRICIANS AND GYNECOLOGISTS (ACOG)—NEWBORN SCREENING OPINION

VII. COMMITTEE BUSINESS—SUBCOMMITTEE REPORTS

A. Education & Training Subcommittee Report
B. Followup & Treatment Subcommittee Report
C. Laboratory Standards & Procedures Subcommittee Report

VIII. PUBLIC COMMENT SESSION

IX. COMMITTEE BUSINESS—CALENDAR, NONVOTING REPRESENTATIVES, LETTER TO HHS SECRETARY ABOUT THE ACMG REPORT

APPENDIX A:  WRITTEN PUBLIC COMMENTS

I. WELCOME, OPENING REMARKS

Rodney Howell, M.D.
Chair, Secretary’s Advisory Committee on Heritable Disorders and Genetic Diseases in Newborns and Children
Professor of Pediatrics
University of Miami School of Medicine

Steven Smith
Senior Advisor to HRSA Administrator Betty James Duke, Ph.D.
Health Resources and Services Administration (HRSA)
U.S. Department of Health and Human Services (HHS)

Dr. Howell welcomed everyone to the fifth meeting of the Advisory Committee on Heritable Disorders and Genetic Diseases in Newborns and Children and introduced Mr. Steven Smith, who was speaking in place of HRSA Administrator Dr. Betty Duke, who was unable to be present. Mr. Smith, he noted, is a senior advisor to Dr. Duke and assists in all aspects of the agency's management, including budget oversight, policy development and program administration. From 1980 to 2001, he worked at the Administration for Children and Families.

Mr. Smith brought greetings from Dr. Duke and thanked the Committee for providing a great public service to DHHS and the Nation. He expressed particular thanks to Dr. Howell for serving as chair and Dr. van Dyck and Dr. Lloyd-Puryear, who have kept Dr. Duke and the Secretary of Health and Human Services well informed about what the Committee has been doing.

He noted that HHS has more than 200 advisory committees, and HRSA alone has 16 advisory committees. The Secretary’s Advisory Committee on Heritable Disorders and Genetic Diseases in Newborns and Children is one of the preeminent committees. HRSA needs the experience, good judgment, and advice of the Committee.  Newborn screening is an area where science has advanced, and public policy has to keep up with it.

Mr. Smith said he  knew the Committee would be considering public comments on the American College of Medical Genetics (ACMG) report, Newborn Screening: Toward a Uniform Screening Panel and System. HRSA looks forward to the Committee’s review of the comments and to advising us. HRSA would consider that the recommendations would be good if they   (1) improve access to services, especially to the underserved, the most vulnerable populations; (2) ensure that services are high quality (science);  and (3) make services culturally competent (e.g., health literacy considered in giving information to parents who have to make treatment decisions).

Dr. Howell thanked Mr. Smith and noted that there was a busy agenda for the 2-day meeting, so questions from the audience would be permitted only during the official public comment period:

• Update and Committee discussion of the ACMG report on newborn screening. Dr. van Dyck would begin with an update on the status of the ACMG report Newborn Screening: Toward a Uniform Screening Panel and System. The Secretary of Health and Human Services is awaiting the Committee’s comments and recommendations on the ACMG report so the Committee would be spending a considerable amount of time on that.
• Update on the status  of the states with respect to newborn screening by Dr. Bradford Therrell, Director of the National Newborn Screening and Genetic Resource Center (NNSGRC).
• Presentations on the role of evidence and other factors in public policy decisionmaking. As a followup to the Committee’s earlier discussions about the role of evidence and other factors in decisionmaking, several outside experts would make presentations related to this topic.
• Presentation by the American College of Obstetricians and Gynecologists (ACOG) on newborn screening.
• Discussion of the Committee’s three subcommittees’ charges. The Committee would discuss the charges of the Education & Training Subcommittee, the Followup & Treatment Subcommittee, and the Laboratory Standards & Procedures Subcommittee. Dr. Howell noted the Committee would defer further discussion of the subcommittees’ charges until after the presentations on the  decision-making process.
• Subcommittee meetings and reports. Concurrent meetings of the Committee’s three subcommittees would be held on Friday, July 22, 2005, and would be open to public participation. Subsequently, the subcommittees would report on their plans and activities to date.
• Public comments. Members of the public would be given an opportunity to make statements to the Committee.

Approval of Minutes. The first item of business, Dr. Howell said, was the approval of the minutes from the previous meeting of the Committee held April 21-22, 2005. Dr. Boyle moved to approve the minutes, and the Committee unanimously voted to approve them.

Committee Correspondence. Dr. Howell drew Committee members’ attention to two letters in the materials they received prior to the meeting. One was a letter he recently sent to HHS Secretary Michael Leavitt on behalf of the Committee. The Committee had not yet reviewed the final report at its January 13-14, 2005 meeting, Dr. Howell’s letter said, but had unanimously recommended the following with respect to the disposition of the draft ACMG report: (1) that the final ACMG report to HRSA be sent to the Secretary of Health and Human Services under Chairman Howell’s signature on behalf of the Committee; (2) that the final ACMG report be released into the public domain as soon as possible for review and comment; (3) that the Committee review, report, and make comments on the report as a Committee during the public comment period; and (4) that the Committee provide advice to the Secretary on the public comments received by the Secretary.

Dr. Howell also drew attention to a letter written to him by Dr. Howse, President,  March of Dimes on July 8, 2005. Her letter raised questions about the proposed charges for the Laboratory Standards & Procedures Subcommittee. Dr. Howse said that she did not think that decisions about adding new conditions to the uniform panel should reside in any specific subcommittee. Dr. Howell asked Dr. Brower to briefly discuss proposed modifications to the charge of the Laboratory Standards & Procedures Subcommittee she chairs. Dr. Brower did this. Dr. Howell postponed  the Committee’s discussion of subcommittee charges until the afternoon of the first day of the meeting.

II. COMMITTEE BUSINESS—THE ACMG NEWBORN SCREENING REPORT AND PUBLIC COMMENTS

A. Update on the Status of the ACMG Report

Peter van Dyck, M.D., M.P.H.
Associate Administrator
Maternal and Child Health Bureau
Health Resources and Services Administration (HRSA)

Dr. van Dyck reported on the status of the ACMG report Newborn Screening: Toward a Uniform Screening Panel and System. In all, there were 187 public comments, including 155 submitted by the May 8, 2005, deadline and 32 submitted after the deadline. As the Committee had requested in April, Dr. Lloyd-Puryear sent each Committee member a set of the public comments, along with an alphabetized list of the individuals and organizations who commented on the report, about 6 weeks ago, so that Committee members would be able to review the comments and discuss them at this meeting.

The U.S. Department of Health and Human Services (HHS) has begun its internal review of the ACMG report and public comments with Federal agencies that are affected or have programmatic responsibilities related to newborn screening. HRSA, the agency with primary responsibility, will take all the information it has gathered related to newborn screening and will review that information and send its recommendations to the Secretary. The plan is to move as expeditiously as possible, but the time frame will be months. The mechanism, by which the recommendation to the Secretary will emerge, Dr. van Dyck explained, is still being worked out, but HRSA will probably draft  a report, and then have Federal agencies comment. HRSA will share the outcome with the Committee once it has HHS clearance.

B. Committee Discussion of the ACMG Report and Public Comments

Rodney Howell, M.D.
Chair, Secretary’s Advisory Committee on Heritable Disorders
and Genetic Diseases in Newborns and Children
Professor of Pediatrics
University of Miami School of Medicine

Dr. Howell said he thought the public comments on the ACMG newborn screening report were extremely thoughtful. The vast majority said the report was very good some were focused on newborn screening for immunodeficiencies etc; and a small number of comments not supportive. Dr. Howell said he believed it would be helpful to discuss the issues raised in that seem call Committee action improve process making recommendations related screening. members agreed this was good approach. Boyle added perhaps should also consider which might specific Committee’s three subcommittees.

Issues Raised in Public Comments on the ACMG Report That Call for Committee Action to Improve the Process. Dr. Howell then proposed the following as a preliminary list of areas that he thought the Committee should take on as its task to move the report forward and asked Committee members for their comments:

1. The need to consider newborn screening for immunodeficiency disorders
2. Cutting edge technologies for newborn screening—their development and validation, method of implementation, etc.
3. The need for a broad approach to long-term follow-up, data collection and analysis, methods of diagnostic confirmation and presumptive tests
4. How to get findings from newborn screening back to the medical home and how to facilitate affected individuals back into adult care
5. The need to develop much better treatment for disorders identified via newborn screening
6. The need to evaluate health systems and perform outcomes research to ensure better functioning of the newborn screening system and related health systems
7. The need to educate families, professionals, and the public about newborn screening and related issues
8. The need for new and better screening technologies to include timing of screening; spectrum of diseases; ethical, legal and social issues; privacy issues; the sharing of patient data; other areas, storing of samples, etc.
9. Public policy decisionmaking related to newborn screening

Dr. Howell asked Committee members for comments on the following recommendations that the Committee might make:

10. There should be a uniform panel of newborn screening tests that all states should do. Having variation among stae screening programs is scientifically unsound, as well as deadly for babies of families in certain states.
11. States must retain strong oversight over newborn screening programs. Newborn screening is a public health issue, and regardless of whether the screening is done commercially or in a state lab, states must have oversight over screening programs to make sure that they are consistent.
12. There should be a national quality assurance program for newborn screening.

Dr. Telfair recommended adding the following two items to Dr. Howell’s list: 

13. Access to health care—the need to look at health systems in terms of access from the consumer's perspective 
14.  Literacy—the need to translate information into an understandable way for the general public

Dr. Dougherty  stated another item:  15. Issues raised by  the state health departments or the Association of State and Territorial Health Officials (ASTHO) and the labs about financing for screening and cost-effectiveness analysis.

Dr. Howell noted that copies of recent, ASTHO Issue Report, Financing State Newborn Screening Systems in an Era of Change, had been distributed to Committee members. Dr. Becker said he did not think that state officials felt the report was compelling enough to be considered a blueprint for national policy—and he suggested that Committee needs to engage state health officials as important partners in advancing newborn screening and the adoption of the uniform panel.

Dr. Edwards suggested assigning each of the 15 or so topics in the list of proposed topics to one of the Committee’s subcommittees, to a working group, or to the Advisory Committee as a whole. Dr. Howell said he thought working through the list would be an agenda item for years but agreed that the Committee might assign topics to subcommittees.

Inviting a Nonvoting Representative of ASTHO to Participate in the Deliberations of the Committee. Dr. Becker suggested that perhaps the Committee should consider ASTHO Executive Director Dr. George Hardy’s request in September 2004 that a policy level person from the states be added to the Committee. Dr. van Dyck noted the Committee’s charter specifies how many members are allowed, and the Committee membership is full right now. People can propose additional Committee members when people turn over, but decisions about who becomes a member rest with the Secretary of Health and Human Services.

Dr. Howell asked Dr. van Dyck to comment on how the Committee might involve state health officials. Dr. van Dyck said there are at least two ways that state health officials might be involved: (1) Committee members could propose to Dr. Howell state health officers who would be appropriate to serve on the subcommittees; and (2) subcommittees could hear from state health officers in the deliberations of the Committee. In response to a question from Dr. Boyle about whether state health officials could be liaison members of the Committee, Dr. Lloyd-Puryear explained that state health officials could be “nonvoting representatives, appointed by specific organizations. They can be part of the Committee’s deliberations and the organization must cover the representative’s travel and other costs.

Several Committee members agreed that it made sense to ask ASTHO to send a nonvoting representative to the Committee. Dr. Rinaldo suggested that other organizations also might be invited to send a nonvoting representative. Dr. Alexander replied there might be others the Committee wants to invite, but that shouldn’t interfere with the Committee’s action on ASTHO. Dr. Howell agreed that state health departments are such a critical aspect of newborn screening that beginning with ASTHO seems like a good idea. Dr. Becker made the following motion, and the Committee passed it unanimously:   

MOTION #1: The Committee recommends that the Association of State and Territorial Health Officials (ASTHO) be invited to send a nonvoting representative to participate in the Committee’s deliberations.

Dr. Edwards suggested that each subcommittee consider other organizations that should have nonvoting representatives at the Committee and recommend them to the Committee. Dr. Howell agreed to this.

Drafting a Letter to the HHS SecretaryRegarding the ACMG Newborn Screening Report and Public Comments on the Report. Dr. van Dyck reminded the Committee that it still needs to send a letter to the Secretary in which it makes a formal statement about approving the ACMG report and commenting on the public comments on the report. Dr. Howell agreed and indicated that he would like to have the Committee discuss what points should be in the letter to the Secretary so that a letter could be drafted by him and Dr. Lloyd-Puryear, then circulated to Committee members for their review.

Dr. Howell explained that his intention was to draft a letter saying the Committee had read all the public comments on the ACMG report, and having read them, would recommend that the Committee focus in several identified areas to respond to these comments and for future direction for the Committee. Dr. Telfair remarked that it would be helpful in putting the letter together to agree on the key content areas. Dr. Howell and other Committee members agreed.

Several Committee members made additional suggestions for the letter. Dr. Alexander stated that most of the public comments on the ACMG report were positive and clearly endorsed a uniform newborn screening panel that should be done in all states. The concerns raised in the public comments, he said, fell into two broad categories:

• Concerns about the process for identifying conditions  to be included on the ACMG uniform newborn screening panel, given that there is limited evidence and the need to come to some kind of decision. Despite the criticisms of the process, most people did not quarrel with the outcome. The presentations to the Committee on making decisions with limited information will help the Committee be in a better position to respond to these criticisms.
• Concerns about the consequences of implementing the uniform newborn screening panel. One area of concern that needs to be addressed above and beyond what is in the ACMG report is the need to ensure that a process for doing followup (confirmation of diagnosis, counseling, and care) is in place before massively expanding newborn screening. Other areas of concern that need to be addressed pertain to physician preparation, parental education, and ensuring that funding is in place to provide equitable access to newborn screening.

Perhaps, Dr. Alexander suggested, the Committee could assure the Secretary that these issues need to be addressed above and beyond what   is in the report and that the Committee intends to address them. Dr. Boyle  agreed, stating that she thought that the Committee’s letter to the Secretary should be fairly general and state that the Committee is using what it learned from the public comments to help it evaluate its decision-making processes and future agenda.

Dr. Becker replied that the Committee would probably move past the report before HHS completes its internal process, but as part of the process  it must attend to a few routine activities,  the public comments.

Mr. Robertson recommended that the Committee’s letter advise the Secretary about how the Committee believes public comments related to things such as the issue of scientific validation and process affect the report, saying something like: “The Committee recognizes these issues, but we do not think it detracts from the core ACMG newborn screening report, so we still recommend the report.”  He reminded the Committee that the ACMG report was not its (the Committee’s) report.

There was  a long discussion of what the letter to the Secretary should say. Some Committee members agreed that  most of the public comments on the ACMG report sent to HHS were favorable with respect to the report and supportive of a uniform newborn screening panel.” Dr. Rinaldo said he thought most of the negative comments missed the point that the main focus of the ACMG expert panel was to articulate general principles and develop a uniform newborn screening panel. Dr. Hawkins and Dr. Becker agreed. Dr. Dougherty expressed some concerns about the evidence base underlying the recommendations that the ACMG uniform panel be adopted by every state.

Dr. van Dyck agreed with Mr. Robertson, saying the Committee ought to consider how the public comments affect the Committee’s overall opinion of the report and its recommendations. Dr. Rinaldo said that rather than looking at the comments one by one, the Committee should assess whether the criticisms change the core conclusions about the uniform panel. Dr. Brower suggested that the letter say that the public comments do not change the 29 conditions and secondary conditions based on these comments, but do change how we act in the future. Dr. Dougherty agreed - the letter could say that the Committee has heard these concerns and has taken several steps to improve things (e.g., inviting a representative from ASTHO and whatever the Committee decides to do following the presentations on making policy decisions when evidence is meager).

Dr. Howell agreed to this plan. He noted, however, that the letter should say that the Committee is going to support the ACMG report and will be working on some of the concerns raised in the public comments in its future work.

Dr. van Dyck emphasized that the Committee had to make some recommendation to enable Dr. Lloyd-Puryear and HRSA staff to draft the letter and distribute it to the Committee for further input. He added that the letter should highlight no more than five or six issues. There were several suggestions about what these issues should be. Dr. Becker said he thought that the Committee’s list of subcommittees identified the primary issues. Dr. Edwards suggested highlighting as one point issues not addressed in the ACMG report. The Committee then made a list of these areas, which included the following: 

• Concerns about the methodology used by the expert panel (to be listed first) 
• Management issues:  partnering with the medical home, transitioning into adult care, new and better treatments 
• Financing issues, including the cost of newborn screening expansion and treatment
• Cutting-edge technologies: their development, validation, and implementation of new technologies and new applications of existing technologies and new areas of clinical utilization
• Approach to long-term followup and data collection and analysis
• Methods of diagnosis and confirmation of presumptive diagnosis
• Need for evaluation of health systems and outcomes research, improvement of  newborn screening and related health care systems
• Education for families, professionals, and the general public
• Research: better and new screening technologies, incidence and spectrum of diseases, ethical and legal issues
• Privacy issues:  sharing of patient data, consent and refusal, storage of samples, etc.
• State policy-setting processes
• Quality assurance
• Public health oversight
• Whether the newborn screening will be mandated or just be a recommendation

Dr. Robertson recommended that the Committee say that the public comments do not take away from the report’s central findings or recommendations. Dr. Howell agreed. Dr. Van Dyke said that during lunch, the staff would make a separate list of the issues raised by Dr. Howell  

Dr. Howell said the Committee would return to discuss its letter to the Secretary of Health and Human Services about the ACMG report and public comments on the report after it had heard the presentations from experts on the role of evidence and other factors in decisionmaking.  

Dr. Therrell gave an update on newborn screening activities in the states, referring to   two handouts. The first of  the handouts was a two-page “U.S. National Screening Status Report—Updated 7/12/05” (which indicates the status of  each state in terms of screening for  the  core 29 conditions and the  secondary conditions identified in the ACMG newborn screening report.

The second handout of  maps and graphs presented by Dr. Therrell showed growth in the number of states screening for specific conditions from May 2004 to June 2005. Considering what is universally available, either by mandate or universal option,  currently six is the lowest number of disorders screened  by New Hampshire, although several other states are close to that number in their screening panel. Some states have screening for 10 to 19 disorders universally available. The lower numbers of screened conditions seem to be in the Mountain States and in the South. Two states have screening for 23 to 25 disorders universally available. Four more states screen for 26. Five more do 27. Thirteen more do 28. Nine other states do 29 disorders, but only 2 of them actually mandate all 29 conditions recommended by the ACMG expert group. In the maps and graphs, screening for MCADD (medium chain acyl-CoA dehydrogenase deficiency) is used as an indicator of 12-14 other disorders screened by tandem mass spectrometry (MS/MS).

A graph of the percentage of newborns screened for various conditions in the United States as of June 2005 indicated that the percentage of newborns screened for all 29 conditions in the ACMG uniform panel is at least 60 percent, with the exception of the percentage screened for cystic fibrosis (now 33 percent).

NNSGRC asked states whether they had changes in their newborn screening programs in the past 6 months they wanted to report. Dr. Therrell stated their responses:

• California began mandated screening for all 15 MS/MS conditions and CAH (congenital adrenal hyperplasia) on July 11,  2005. It does not screen for biotinidase or cystic fibrosis and also has no legislative mandate for hearing screening.
• Colorado has mandated the full scan of MS/MS disorders and expects the screening to be implemented in spring of 2006.
• Connecticut added 13 more MS/MS conditions in January 2005, so it currently screens for the full panel. This state also is screening for  cystic fibrosis, but it is not mandated.
• On January 3, Georgia added MCADD, PKU (phenylketonuria), HCY (homocystinuria), MSUD (maple syrup urine disease), and (TYR) tyrosinema and changed over to MS/MS. In late June, the state changed its rules to say that a sample is valid after 24 hours instead of 48 hours. Georgia is one of five states still without a fee but is  developing a  fee structure.
• Iowa began screening for cystic fibrosis in mid-July, I It is now the second state to mandate all 29 conditions in the ACMG-recommended uniform panel. The lab has courier service and is operating 24/7.  It uses its fees to support  various services and expects an increase in 2006..
• Kentucky is adding disorders in a stepwise fashion. It mandated the addition of CAH, biotinidase, cystic fibrosis, and the full scan MS/MS in March 2005, is adding CH (congenital hyperthyroidism) in August,  and MCADD in September. Kentucky has not yet mandated cystic fibrosis or (BIO) biotinidase deficiency.
• Michigan universally is piloting 11 additional conditions detected by MS/MS, so it has expanded its newborn screening panel to include 29 conditions as a pilot. It is working towards a fee increase to pay for the comprehensive program and services, and for cystic fibrosis.
• Minnesota has mandated screening newborns for cystic fibrosis, and  anticipates  start-up by Spring 2006. It is moving to a new laboratory facility in October 2005.
• Missouri added 20 disorders after a 5-month pilot of MS/MS plus BIO. In August, the $25 fee will increase to $50. The state’s pilot of screening for BIO will begin late this year, and a cystic fibrosis pilot  in 2006.
• Nebraska is one of 3 or 4 states that has a law which mandates screening without an option for dissent, and there have been challenges to that law, which the state continues to win.   One lawsuit is over the right to dissent from newborn screening. The state supreme court recently ruled that the state has the right not to offer dissent. Another lawsuit  filed in Federal court on grounds of religious discrimination has now been dropped. Nebraska expects to add screening for cystic fibrosis and CAH in January 2006. It is doing expanded screening by MS/MS as a free option, and 95 percent of the people are accepting that option.
• New Hampshire is the state with the least number of mandated disorders. An advisory committee recommended expanding the newborn screening panel to include disorders such as CAH, MCADD, BIO, Sickle Cell Disease and cystic fibrosis, but the state legislature did not approve it.  A new law gives the commissioner and the advisory committee more power.  If it is signed  the advisory committee will move forward and expand the program by next year.
• New Jersey currently does not mandate screening for 13 conditions detected through MS/MS but screens for them anyway as part of the differential diagnosis. It has a new law which requires that the state inform the parents about testing that is not mandated by the state and where the testing is available. The state has also changed its rules to say that a heelstick filter paper sample is valid after 24 hours instead of 48 hours.
• North Dakota is adding cystic fibrosis early in the fall and increasing its fee from $36 to $44.  It follows the lead of Iowa NBS lab where the samples are sent
• Oklahoma added CAH and cystic fibrosis to its screening panel in February 2005.
• Rhode Island, though currently screening only for MCADD and amino acid disorders, is trying to expand to the 29 core conditions listed in the ACMG uniform panel by July 2006. They have an active program that looks at all  newborns by day 6 to see who has been screened and who hasn't been, and then they track those babies without a screen  to try to get them back in.
• South Dakota, which previously mandated screening for only three disorders, has expanded its rules to include a previously universal pilot for CAH, BIO, and Sickle Cell Disesea  and the  MS/MS full scan. It sends MS samples to Texas,  cystic fibrosis samples to Massachusetts, and a private laboratory provides the rest of the testing in-state.  
• The Texas legislature finally has agreed to allow start-up funds for the expansion of newborn screening. The extent of the expansion will be determined in part by the fee structure. The current fee  is $19.50 a sample, and they have authority to raise  it to $36 a sample after they  respond to a written review (October 2005)  of its program by  NNSGRC and perform an in-depth cost analysis by March 2006.  When these conditions have been satisfied by the commissioner and the Texas Medical Association, Texas can expand the state’s program,  which is anticipated by October of 2006.
• Utah has begun a  full scan MS/MS pilot using the local private laboratory, ARUP. It  has a fee of $31, authority to go to $35, but  will raise that figure to $65. Utah expects to be doing the full 29 conditions and secondary targets, CAH and BIO by January 2006.  cystic fibrosis is not included.
• Virginia now screens for MCADD and the basic amino acid disorders, but is  not screening for cystic fibrosis or doing expanded MS/MS. The Virginia Board of Health mandated screening to include the full ACMG uniform panel and the anticipated start is March 2006.
• Washington State’s cystic fibrosis NBS advisory committee will recommend r cystic fibrosis to the Board of Health in October.

Questions and Comments

Following Dr. Therrell’s presentation, Committee members posed a number of questions. Dr. Edwards asked whether the changes in screening were occurring in response to the ACMG report or the March of Dimes recommendations or some other recommendations, or whether they just happened spontaneously even before the ACMG report was released. Dr. Therrell said that the ACMG report and the March of Dimes report card had definitely contributed. States were waiting for the ACMG report, which was released in March 2005. Dr. Rinaldo said he suspects that the acceleration began around 2002, when the ACMG/HRSA panel began to be developed.

Dr. Brower asked whether hearing screening, which is in a different database, should be brought into one central database. Dr. Therrell said that makes sense to him and that he had advocated for that. The problem is that the programs inside the state health department are often set up in two different silos, so the states report their hearing data to Centers for Disease Control and Prevention (CDC) and report their metabolic data to NNSGRC. Between 15 and 20 states actually collect their hearing data on the newborn screening metabolic form. Dr. Howell added that a per similar issue might arise in the case of congenital heart disease or Wilson's disease, where the time frame is not in the usual 24 to 48 hours.

Mr. Robertson asked about what the District of Columbia was doing. Dr. Therrell reported that it was screening for 10 disorders. D.C. has a contract with a private laboratory which offers expanded testing through the hospitals, so the testing is sort of at the option of the parents. D.C. does not have a fee for newborn screening; payment comes from government funds (Jill - This is incorrect. Payment has been turned over to the hospitals.  Also all hospitals are not offering supplemental screening.) Dr. Therrell said that he had heard that physicians  may not know that their states do certain tests. Dr. Howell closed the session by commenting that the Education & Training Subcommittee has as much or more work to do with professionals as with the public.

IV. THE ROLE OF EVIDENCE AND OTHER FACTORS IN DECISIONMAKING

Dr. Howell opened this session by welcoming three speakers invited to give presentations to the Committee about various aspects of the question of how to make decisions on the basis of evidence and other factors—particularly when evidence is limited, as it is in the case of newborn screening because of the rarity of the conditions.

A. Evidence, Politics, and Technological Change

Bhaven Sampat, M.D.
International Center for Health Outcomes and Innovation Research (INCHOIR)
Columbia University 

Dr. Sampat gave a presentation on the interplay between evidence and politics in managing technological change in medicine. His presentation was based on work done by his colleagues at Columbia University, Annetine C. Gelijns, Ph.D., and Alan J. Moskowitz, M.D.

Dr. Sampat remarked, it’s a fascinating time to explore the interface between evidence and politics for 3 interrelated reasons:  1) policymakers feel an increasing  imperative to manage the health and economic aspects of technological change, and many find it frustrating and elusive; 2) decisions on how to handle the explosive filed of medical innovation translate quite directly into regulatory and reimbursement decisions- who gets what medical care and on what terms; and 3) these sometimes arcane analytical issues often  make their way quickly and directly onto the radar screens of public opinion.  Basically interpretation and application of analytic findings varies considerable across nations.  For example, coronary artery bypass (CABG) and tonsillectomies procedures are supported by lots of evidence, but there are different adoption decisions in as indicated by different  rates across advanced industrialized countries. These variations aren’t explained by differences in disease prevalence alone.  Other factors such as professional uncertainty, economics, and social cultural value judgments also play a role.  Empirical analyses do not provide off-the shelf policy decisions, or at least rarely do.According to Dr. Sampat, industrialized nations are facing many challenges that stem from the remarkable medical progress over the past 50 years or so. Managing innovation is a formidable task. Decisions to adopt innovations are always made in context of considerable uncertainty about indications, populations, risks, effectiveness, and those sorts of things. Costly new technologies raise important economic questions and also trigger questions about whether a particular technology is the best way to spend our scarce health care dollars.  Most industrialized nations use supply-side mechanisms – for example, public planning  and regulatory tools to distribute or limit the supply of medial technologies.  On the demand side, some countries, like the United Kingdom, use global or regional budgets, whereas countries like the United States and Germany employ instead coverage and reimbursement decisions made by insurers to control the uses of technology.  Although better empirical evidence about the costs and consequences of medical technologies can make policy decisions sharper and better grounded, translating analysis into policy is itself a highly difficult process. Three underexamined challenges make transforming evidence into policy difficult: 

• Challenges inherent in the dynamics of technological change. Many areas of medicine are characterized by extremely high rates of innovation. Furthermore, after new technologies are introduced into practice, the medical profession shapes and expands their application, as the case of CABG illustrates. Only 4 percent of patients who were treated with CABG today would have met the eligibility criteria of the trials that determined the surgery’s initial value. Even cost-saving technologies can increase expenditures if they expand the size of target market. In addition, totally new and often unexpected indications of use are sometimes found, as in the case of alpha blockers. First introduced for hypertension, alpha blockers were found 20 years later to be an important agent in the treatment of benign prostate hyperplasia. The dynamics of technological change makes the questions and evidence base change, a situation that argue for ongoing assessments. Randomized clinical trials (RCTs) conducted in specialized centers with well-defined populations are used to permit hypothesis testing, but even if well conducted, RCTs have limits (e.g., short time horizon, questions about generalizability, costly to conduct). Consequently, regulatory decisions are made in a context of uncertainty—a situation that argues for postmarketing studies with observational studies and practical RCTs. Funding for postmarketing studies is limited, though, so considerable uncertainty will always remain about the value of many evolving technologies.
• Challenges in using analytical policy tools. Although regulatory decisions rely heavily on quantitative data, the acceptability of particular risk-benefit tradeoffs depends on value judgments. To illustrate, the heart failure drug Flosequinan was approved because it improves quality of life, but later was withdrawn because it was found to reduce survival; yet when the issue was presented to heart failure patients with very debilitating disease, 40 percent responded that they would accept a slightly higher risk of death to achieve a better quality of life. Similar issues arise in budgetary and reimbursement decisions where payers and advisory bodies, such as the advisory committees for Medicare and Medicaid, struggle with making tradeoffs between costs and benefits. These decisions increasingly are grounded in what's known as cost-effectiveness analysis—a technique for comparing the relative value of various clinical strategies typically in terms of quality-adjusted life years (QALYs) or the cost of an intervention per quality-adjusted life year saved. Cost-effectiveness analyses can encourage purchase of good value for money, but there are variations in how the evidence is operationalized (e.g., should cost-effectiveness ratios be used as strict thresholds or not?), as well as other challenges associated with the use of this technique (e.g., such analyses may not take into account whether the technology is established or emerging and whether the cost-effectiveness ratio is static or evolving).
• The challenge of inherently political factors, especially those dealing with the preferences of stakeholders, helps shape the translation of evidence into policy decisions. Even if there is enough evidence to do cost-effectiveness analyses, policymakers still must wrestle with conflicts of values and interests. Cost-effectiveness analyses, for example, may be insensitive to such important qualitative considerations, such as equity and distributive justice. For this reason, it is important that policymakers consider how to integrate qualitative considerations (e.g., the preferences of stakeholders) into priority-setting.

In sum, Dr. Sampat said, the difficulties in translating evidence into policy manifest themselves in a range of ways, including in the evolving applications of technologies, questions about the interpretation and extrapolation of evidence, and a wide variety of value judgments. He and his colleagues believe that these uncertainties and questions about the evidence base argue for a continued evaluation of technologies both in the pre- and postmarketing settings. They also believe that the existence of a variety of value judgments also raises the question of institutional innovation, in particular the question of how policymakers, and society, should integrate myriad stakeholders into priority-setting.

Questions & Comments       

Dr. Howell noted that in discussions of screening newborns for rare diseases, one of the issues that has surfaced is that such diseases are rare by definition, but once they are defined and once a treatment is available, all persons who appear with that are immediately treated. Thus, the need for developing a system for following all these children as a "postmarketing" type strategy is going to be a very critical issue, because we are going to be learning more about the conditions over time.

B. Making Policy When Evidence Is Meager and in Dispute

David Atkins, M.D., M