Summary of 11th Meeting
September 17-18, 2007
Washington, DC

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The Secretary’s Advisory Committee on Heritable Disorders and Genetic Diseases in Newborns and Children was convened for its 11th meeting at 9:05 a.m. on Monday, Sept. 17, 2007, at the Ronald Reagan Building and International Trade Center in Washington, D.C. The meeting was adjourned at 1:58 p.m. on Tuesday, Sept. 18, 2007. In accordance with the provisions of Public Law 92-463, the meeting was open for public comments on Sept. 17, 2007.

 CONTENTS
I. WELCOME, OPENING REMARKS
II. EVIDENCE-BASED REVIEWS OF CONDITIONS NOMINATED FOR THE UNIFORM NEWBORN SCREENING PANEL
III. COMMITTEE BUSINESS—DISCUSSION OF THE NOMINATION AND EVALUATION PROCESS FOR CANDIDATE CONDITIONS ON THE UNIFORM NEWBORN SCREENING PANEL
A. Fine-Tuning the Nomination Form
B. Process for Handling Nominations
C. Inviting an FDA Representative to the January 2008 Meeting to Discuss Access to Data
IV. SACGHS TASK FORCE ON OVERSIGHT OF GENETIC TESTING
V. UPDATES FROM FEDERAL AGENCIES
A. Agency for Health Care Research and Quality (AHRQ)
B. Centers for Disease Control and Prevention (CDC)
C. Health Resources and Services Administration (HRSA)
D. National Institutes of Health (NIH)
VI. PUBLIC COMMENT SESSION
VII. COMMITTEE BUSINESS—SUBCOMMITTEE REPORTS & DISCUSSION
A. Laboratory Standards & Procedures Subcommittee Report
B. Education & Training Subcommittee Report
C. Followup & Treatment Subcommittee Report
VIII. FEDERAL LEGISLATION: AN UPDATE
IX. COMMITTEE BUSINESS—PLANNING THE COMMITTEE’S NEW RESEARCH WORKGROUP
X. GENETIC ALLIANCE
XI. GENETIC ALLIANCE PROJECTS RELATED TO CONSUMER PERSPECTIVES ON NEWBORN SCREENING
XII. HHS SECRETARY’S PERSONALIZED HEALTHCARE INITIATIVE
XIII. COMMITTEE BUSINESS
APPENDIX A: WRITTEN PUBLIC COMMENTS

I. WELCOME, OPENING REMARKS

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

Agenda for the Meeting. Dr. Howell opened the meeting by welcoming participants and saying that he hoped that the Advisory Committee would finalize the nomination process adding conditions to the uniform newborn screening panel. Dr. Howell then gave a brief overview of the agenda:

• Status of the process for nominating/evaluating candidate conditions for inclusion on the uniform newborn screening panel. Dr. James Perrin, the chair of the new external Evidence Review Group (ERG) that will be involved in reviewing evidence for conditions nominated to the uniform newborn screening panel, and Dr. Nancy Green would present minor changes to the nomination form and gave an update on progress regarding the ERG.
  
  
• Secretary’s Advisory Committee on Genetics, Health, and Society (SACGHS)—Task Force on Genetic Testing. Dr. Ferreira-Gonzalez, the chair of the SACGHS Task Force on the Oversight of Genetic Testing, would give a report on its work.
  
  
• Update from Federal agencies involved in newborn screening. Ex officio members of the Committee from the Agency for Healthcare Research and Quality (AHRQ), Centers for Disease Control and Prevention (CDC), Health Resources and Services Administration (HRSA), and National Institutes of Health (NIH) would give updates on their agencies’ activities related to newborn screening.
  
  
• Subcommittee meetings and reports. The Advisory Committee’s Laboratory Standards & Procedures Subcommittee, Education & Training Subcommittee, and Followup & Treatment Subcommittee would meet on Monday, Sept. 17, 2007, and give reports to the full Committee on Tuesday, Sept. 18, 2007. All of the subcommittee meetings would be open to the public.
  
  
• Federal legislative update. Cindy Pellegrini from the American Academy of Pediatrics (AAP) would update the Advisory Committee on Federal legislative developments.
  
  
• Report from the Advisory Committee’s new Research Workgroup. Dr. Michael Watson, the chair of the Advisory Committee’s soon-to-be established Workgroup on (Infant, Childhood, and Adolescent Genetics and Screening) Research would give his first report.
  
  
• Genetic Alliance. Ms. Terry would report to the Advisory Committee on the recent activities and programs of the Genetic Alliance.
  
  
• Four Genetic Alliance projects on consumer perspectives in newborn screening. Ms. Terry would describe the Genetic Alliance’s four HRSA-funded projects related to consumer perspectives on newborn screening.
  
  
• Report on the Personalized Healthcare Initiative. Dr. Gregory Downing would give an update on the Personalized Healthcare Initiative in the Office of the Secretary of Health and Human Services (HHS).

Finally, Dr. Howell explained that to allow time for the Committee to discuss the nomination process, Dr. Susan Berry would not give her scheduled presentation on the Inborn Errors of Metabolism Information System of the Region 4 Genetics Collaborative. The Advisory Committee will invite her to give her presentation at another meeting.

Two Nominations for Adding Conditions to the Uniform Newborn Screening Panel. Dr. Howell announced that HRSA had received two nominations for adding conditions to the uniform newborn screening panel: (1) one for Krabbe disease from Micki Gartzke, representing the Hunter’s Hope Foundation; and (2) one for severe combined immunodeficiency (SCID) from Dr. Jennifer Puck, representing the SCID Newborn Screening Working Group; Immune Deficiency Foundation; and Jeffrey Modell Foundation. These nomination packages were provided to the Committee for informational purposes only.

Approval of Minutes. The minutes from the May 17-18th, 2007, meeting of the Advisory Committee on Heritable Disorders and Genetic Diseases in Newborns and Children [Tab #5 in the materials distributed to Advisory Committee members] were approved.

Letter & Certificates of Appreciation. Dr. Howell presented certificates of appreciation from the HHS Secretary to the following Advisory Committee members whose 4-year terms are ending in September 2007: Dr. Amy Brower, chair of the Laboratory Standards & Procedures Subcommittee; Dr. James Newton; Dr. Greg Hawkins, chair of Education & Training Subcommittee; and Dr. Peter Coggins. Dr. van Dyck then presented Dr. Howell with a certificate of appreciation from the HHS Secretary and thanked him for his leadership, vision, and contributions as the Advisory Committee’s chair since the Committee’s inception.

New Committee Members and Liaisons. Dr. Howell welcomed two new nonvoting organizational liaison representatives to the Advisory Committee: Dr. Timothy Geleske from the American Academy of Pediatrics (AAP) and Dr. Alan Fleischman from the March of Dimes. He also welcomed two new nonvoting organizations and their organizational liaison representatives to the Advisory Committee: Dr. Michael Watson from the American College of Medical Genetics (ACMG) and Dr. Barbara Burton from the Society for Inherited Metabolic Disorders (SIMD).

Committee Business. Dr. Howell referred Advisory Committee members to several materials included under TAB #17 of the materials in their notebooks and said that they would be discussed on the second day of the meeting: (1) an article about the recent increase in the incidence of congenital hypothyroidism in New York State by Katherine Harris and Kenneth Pass; (2) information about a U.S. patent involved in newborn screening; (3) the Advisory Committee’s standard operating procedures ("ACHDGDNC: Policies and Procedures for Operation and the Development of Recommendations for Screening Newborns and Children for Heritable Disorders and for the Heritable Disorders Program”); and (4) the calendar for the Advisory Committee’s 2008 meetings.

II. EVIDENCE-BASED REVIEWS OF CONDITIONS NOMINATED FOR THE UNIFORM NEWBORN SCREENING PANEL

James Perrin, M.D., FAAP
Professor of Pediatrics, Harvard Medical School
Director, MassGeneral Hospital Center for Child and Adolescent Health Policy
Director, MCHB Evidence Review Group, Systems of Care for Children and Youth with Special Care Needs

Nancy S. Green, M.D.
Division of Pediatric Hematology
Associate Dean for Clinical Research Operations
Columbia University Medical Center

Dr. Perrin, who chairs the Advisory Committee’s external Evidence Review Group (ERG) that will review evidence on conditions nominated for inclusion on the uniform newborn screening panel, described progress since the June meeting of the Advisory Committee on plans for the ERG. In recent months, Dr. Perrin and his colleagues have worked on developing draft definitions of terms used on the nomination form, developing a draft template for the ERG’s evidence reviews, and begun planning how to perform evidence reviews on nominated conditions. The plans are still very preliminary and have to be approved by the Advisory Committee. Nevertheless, the ERG is eager to get started and hopes to get an assignment soon, so that it can perform its first evidence review for the Advisory Committee’s meeting in May 2008.

Background on the Nomination Process. Dr. Perrin reminded Advisory Committee members that the process Advisory Committee members approved for nominating and reviewing conditions nominated for inclusion on the newborn screening panel involves three steps:

• Step #1: Nomination form submitted by proponent(s) of adding a condition
  
  
• Step #2: Federal administrative review of the nomination form
  
  
• Step #3: Review by the Secretary’s Advisory Committee on Heritable Disorders and Genetic Diseases in Newborns and Children
  
  
  1. Advisory Committee review
     
     
  2. Evidence-based review by an external ERG (but no recommendations)
     
     
  3. Advisory Committee review and decision

The role of the external ERG is to review and report on the evidence relevant to the Advisory Committee in making recommendations about which conditions to add or remove from the uniform newborn screening panel recommended by ACMG. The ERG will not itself make recommendations to the Advisory Committee.

Composition of the ERG. Dr. Perrin proposed that the ERG be based in Boston at the MassGeneral Hospital Center for Child and Adolescent Health Policy. He further proposed that the core staff of the ERG include in addition to himself Project Director Diane Romm, Ph.D. (epidemiology/methods); Trish Mullaley, R.N. (consumer); Lisa Prosser, Ph.D. (cost/benefit analysis); Marsha Browning, M.D., M.P.H. (genetics); Ellen Lipstein, M.D. (health services research fellow); Alex Kemper, M.D., M.P.H. (methods and screening); and Nancy Green, M.D. (consultant).

To give the ERG broader national representation and review, Dr. Perrin proposed that the ERG have its own external advisory group. Possible members include Ned Calonge, M.D. (a health officer at the Colorado State Health Department), Robert Davis, M.D., M.P.H. (a health services researcher at the Center for Health Research, Kaiser Southeast), Celia Kay, M.D., Ph.D. (a geneticist at the University of Colorado who represents the American Academy of Pediatrics (AAP) on the group), and Ed McCabe (a geneticist and chair of the UCLA Department of Pediatrics). The ERG would appreciate thoughts from the Advisory Committee about whether there should there be other types of people or other people among this group.

Dr. Perrin said that he expects the ERG will be further assisted by members of the Advisory Committee, as well as by individuals with ad hoc expertise for specific disorders. The procedures of the ERG will be very transparent so that people can understand what the procedures and processes are in the development of evidence. The ERG has a clear understanding of the importance of dealing with problems of conflicts of interest.

Draft Definitions of Terms on the Nomination Form. Dr. Perrin and his colleagues proposed draft definitions of several key terms (mostly from the nomination form) and asked for comments from Advisory Committee members on these definitions. The definitions were included under TAB #6 in the materials distributed to Advisory Committee members prior to the meeting.

• Severity of disease: (a) morbidity, disability, mortality; (b) burden of illness (family perspective); (c) vulnerability to morbidity, disability, mortality.
  
  
• Urgency: How soon after birth treatment needs to be initiated to be effective (to prevent complications or irreversible damage). Spectrum from life threatening to immediate to priority.
  
  
• Efficacy: (a) benefit: extent of prevention of mortality, morbidity, disability; (b) what are the treatment issues that may limit child or family acceptance or adherence?
  
  
• Risks of screening: (a) false positives, carrier detection, phenotypes with no or little morbidity; detection or suggestion of other disorders; (b) association—how strong is the reported relationship between a test result and a disease?
  
  
• Risks of treatment: Potential medical or other ill effects from treatment.
  
  
• Acceptability (invasiveness): (a) what tests/procedures are required; (b) how acceptable are these tests; (c) primary newborn screening and confirmatory testing.
  
  
• Availability: What is the availability of the (confirmatory) test in clinical practice?

After obtaining comments on these definitions from Advisory Committee members, the ERG will put the definitions out for public comment, so that the definitions can be revised and finalized prior to the Advisory Committee’s next meeting in January 2008.

Draft Template for Evidence Reviews. Dr. Perrin and his colleagues proposed a template for the ERG to use in performing evidence reviews of conditions nominated for inclusion on the uniform newborn screening panel. That template, “Draft Template for Evidence Reviews,” dated Sept. 17, 2007, was included under TAB #6 in the materials distributed to Advisory Committee members in advance of the meeting.

The components of the proposed evidence review template for the ERG are as follows:

1. Background
   
   
   • Information on the condition (prevalence, genetics, natural history, different forms of the condition)
     
     
   • Rationale for current review of the condition
     
     
2. Methods of review
   
   
   • Data sources: The ERG will limit studies to human studies only; will exclude case reports; will describe in reviews exactly how it obtained and evaluated data.
     
     
   • Decision model: The ERG will have a decision model that leads to evidence questions in each review.
     
     
   • Data abstraction: The ERG will describe actual methods of data abstraction and any new analyses it may do.
     
     
   • Focus groups of experts (investigators and families): To answer questions that cannot be answered via evidence review of either published data or available data from either principal investigators, the ERG will put together focus groups of experts to the ERG estimate severity and burden.
     
     
   • Screening and diagnostic testing. The ERG will describe in detail what is known about screening and diagnostic testing for the condition. It will define risks of screening such as false positives, carrier detection, phenotypes with little or no morbidity, and in some cases, the detection or suggestion of other disorders. It will also define risks of diagnostic testing.
     
     
   • Treatment. The ERG will describe in detail what it can determine from the evidence about the risks and benefits of treatment, and the applicability of treatment to specific condition groups, early versus late onset, etc.
     
     
3. Evidence review questions. The ERG will address questions about the natural history of the condition, including the variations of the condition, the differences between genotype and phenotype; what is known about prevalence of the condition and prevalence of subgroups; what is known about burden and severity of the condition; what is known about methods of screening and diagnosis; what is known about treatment effectiveness and variations; and to a degree what is known about costs of screening and treatment.
   
   
4. Lack of information. The ERG will indicate where data are absent, what the level of uncertainty is, and what new information or studies would be most critical to help the Committee make decisions about the condition.
   
   
5. Presentation of results. The ERG will present what evidence it can gather in summary and table form for the Advisory Committee to review in making its recommendations to the Secretary. The ERG will not make recommendations. The responsibility for making recommendations to the HHS Secretary about a particular condition will rest solely with the Advisory Committee.

Dr. Alex Kemper has written a paper on pitfalls in developing evidence in newborn screening in which he used Pompe disease as a prototype model. The ERG plans to share Dr. Kemper’s paper with the Advisory Committee and to seek publication of the paper. In addition, Dr. Nancy Green, who chaired the Advisory Committee's workgroup on the criteria that were included in the nomination form, reported that she, Dr. Marie Mann from HRSA, Dr. Howell, and Dr. Lloyd-Puryear have a paper in press in Genetics and Medicine about the nomination process.

Questions & Comments

Advisory Committee members made several comments regarding the ERG’s draft definitions of terms from the nomination form for evidence reviews:

• Page 1 of the nomination form: Condition, severity of disease: (a) morbidity, disability, mortality; (b) burden of illness (family perspective); (c) vulnerability to morbidity, disability, mortality. Dr. Boyle, noting that the terms “burden of illness” and “vulnerability” were rather vague, asked whether the ERG intended to make them crisper. Dr. Perrin said the ERG would welcome help in this area. Dr. Telfair, Dr. Boyle, and Ms. Terry suggested that the ERG consider defining these terms with reference to quality of life scales developed specifically for children with chronic conditions. Dr. Howell suggested that Dr. Boyle and Dr. Dougherty assist the ERG in specifying these terms.
  
  
• Page 2 of the nomination form: Treatment, Efficacy (Benefits): (a) benefit: extent of prevention of mortality, morbidity, disability; (b) what are the treatment issues that may limit child or family acceptance or adherence? Dr. Perrin asked for the Advisory Committee’s help in identifying treatment issues that may limit child and family acceptance or adherence. Dr. Dougherty said that she thought such topics did not belong in a discussion of efficacy, which is an applicable term when using a treatment in a clinical trial, and would instead belong in a discussion of effectiveness, which is the applicable term when using a treatment with normal people in normal, everyday situations. Dr. Perrin disagreed, stating that if no one will accept treatment in a randomized clinical trial, there is a problem. He added, however, that perhaps the ERG and Advisory Committee might want to consider adding the term “effectiveness” of treatment to the nomination form and evaluation process.

Advisory Committee members made several additional comments related to the ERG’s criteria and process:

• Criteria for the quality of evidence reviewed. Dr. Dougherty, noting that the ERG’s work is going to be groundbreaking, emphasized that it is very important for the ERG have criteria for the quality of evidence it reviews. Dr. Perrin replied that the ERG will use standard measures of quality when it can but that such measures will be difficult to use in the case of (a) focus groups used to estimate burden of illness and severity, which raise issues of bias; and (b) data from unpublished sources or case reports. In the latter instances, however, the ERG will be able to put limits around the confidence levels.
  
  
• Capturing benefits of treatment. Dr. Howell asked how the ERG would capture benefits of for conditions like Fragile X, which don’t have traditional treatments but for which screening and early detection might confer benefits from early intervention or counseling. Dr. Perrin said if early intervention improves outcomes, the ERG would include that as benefit of treatment. Dr. Howell asked whether the ERG would consider benefits for parents in terms of having other children. Dr. Perrin said one member of the ERG, Dr. Lisa Prosser, has worked on that problem, and the ERG believes it will be able to address that benefit to a degree; however, the available literature on that benefit to parents is more generic than condition specific.
  
  
• Presenting evidence from focus groups. Dr. Howell asked how the ERG would present evidence from focus groups to the Advisory Committee. Dr. Perrin said the ERG would probably negotiate that with principal investigators. In general, the ERG would provide a summary table rather than very specific tables on evidence.
  
  
• Dealing with conflicts of interest. Dr. Howell asked how the ERG would deal with the fact that many conditions detected via newborn screening are rare conditions, and most experts will have tremendous conflicts of interest. Dr. Perrin stated that the ERG would focus on the evidence that experts have to support their positions. He noted that the ERG may encounter bias when it uses experts to define burden, so it has to be especially careful and thoughtful in that area. The ERG will be very open about where the data it uses come from and will state recognized conflicts of interest. Dr. Howell underscored the importance of stating recognized conflicts of interest so they would be above the board. Dr. Green added that some questions related to conflicts of interest would probably have to come to the full Advisory Committee for additional deliberation.
  
  
• Mechanism for assessing bias in evidence reviews. Dr. Boyle suggested that the ERG develop some sort of mechanism for assessing and making bias explicit in its deliberations. Dr. Perrin agreed that this was a good suggestion. He noted that the Institute of Medicine, for example, has a bias statement for new committees in which people need to explain what their positions are, what their experience has been in a particular area, what statements they've made publicly about a particular piece of work, etc. The ERG could consider developing its own mechanism.
  
  
• Readiness for the ERG to begin its deliberations. Noting that HRSA had received two nominations for adding conditions to the uniform newborn screening panel—one for Krabbe disease and one for severe combined immunodeficiency (SCID)—Dr. Howell asked whether the ERG was ready to proceed with evaluating evidence. Dr. Perrin replied that the ERG would like to start with one condition first, and then take on another condition a couple of months later. Dr. Howell stated that he was eager to move forward as quickly as possible, but the evidence review is so critical—and in fact, groundbreaking—that it really has to be very carefully done.

III. COMMITTEE BUSINESS—DISCUSSION OF THE NOMINATION AND EVALUATION PROCESS FOR CANDIDATE CONDITIONS ON THE UNIFORM NEWBORN SCREENING PANEL

A. Fine-Tuning the Nomination Form

The Advisory Committee considered two changes to the form it has approved for nominating conditions to be added to the uniform newborn screening panel.

Adherence. The first change considered by the Advisory Committee was on page 2 of the nomination form in the “Treatment” section—namely, changing the word “compliance” in the definition of “Efficacy (Benefits)” to “adherence.” Dr. Green explained that the nomination form formerly said "Treatment limitations, such as difficulty with acceptance or compliance," and noted that that term compliance was value-laden and therefore not appropriate in this context. She and Dr. Perrin and their colleagues believed what the nomination group had intended was a more neutral term of such as "adherence" or “acceptance” and recommended using one of these terms.

The Advisory Committee accepted this recommendation and voted unanimously to approve the following motion:

• MOTION #1: On the nomination form for adding conditions to the uniform newborn screening panel, the Advisory Committee approves changing the word “compliance” to “adherence” on page 2 under the “Treatment” category in the definition of “Efficacy (Benefits).”

Effectiveness. The second change considered was also on page 2 of the nomination form in the “Treatment” section. Several members of the Advisory Committee underscored the importance of considering effectiveness in the ERG’s evaluation of the evidence on conditions nominated for inclusion on the uniform newborn screening panel. Dr. Boyle explained that the “efficacy” of an intervention is the gold standard—a measure of how something works under ideal conditions of use such as a clinical trial; the “effectiveness” of an intervention is a measure of how something works in a real-world setting such as a newborn screening program.

Dr. Dougherty recommended adding a new line for “Effectiveness.” Dr. Lloyd-Puryear explained that because the nomination form had already been approved by the Advisory Committee and released to the public, the Committee would have to make a proposal to change the nomination form and then formally vote on that proposal if it wanted to change the form.

Dr. Green instead suggested just adding the word “Effectiveness” in parentheses after “Efficacy.” She explained that the distinction between effectiveness and efficacy is not generally known to the public, so adding a separate box for “effectiveness’ might be confusing to nominators. To address that concern, Dr. Dougherty suggested changing the title of the “Efficacy” box to “Treatment Effectiveness” and then letting the ERG determine whether the studies cited were efficacy studies or effectiveness studies. Dr. Green recommended leaving the nomination form as it was and asking the ERG to address effectiveness in its evidence review document. Dr. Brower agreed with Dr. Green, and Dr. Dougherty stated that she was comfortable with having effectiveness dealt with in the ERG’s evidence review.

Finally, Dr. Howell stated that it was the sense of the Committee that the nomination form would not be changed with respect to “Efficacy (Benefits)”and that effectiveness would be addressed in the ERG’s evidence review.

• DECISION #1: The external Evidence Review Group (ERG), in reviewing the evidence for conditions nominated for the uniform newborn screening panel, will consider and report on evidence pertaining to the effectiveness of treatment, as well as to the efficacy of treatment.

Ms. Terry volunteered to help HRSA address technical issues for Mac users in submitting nomination forms. Dr. Lloyd-Puryear said she would welcome her help.

B. Process for Handling Nominations

Dr. Howell initiated discussion of how the Advisory Committee should proceed with the two nominations of conditions to be added to the uniform newborn screening panel that had already been received: one for Krabbe disease and one for severe combined immunodeficiency (SCID). Copies of these two nominations were provided to members of the Advisory Committee at the meeting.

Dr. Green suggested that the Advisory Committee advise the ERG on which of the two nominations should be considered first to ensure a robust test of the ERG’s process and interaction between the ERG and the Advisory Committee. Because disorders for which there have been no pilot studies would be unlikely to traverse the entire review process, she recommended that the Committee pick a disorder for which there have been pilot studies.

Dr. Watson, on the other hand, noted that Krabbe and SCID are enormously different conditions and are likely to draw out very different issues and recommended that the Advisory Committee ask the ERG to perform evidence reviews for both conditions to evaluate its processes. Dr. Howell agreed, stressing the importance of getting the Advisory Committee to process nominations as quickly as possible. Otherwise conditions will rapidly be going before the public and be screened for widely before the Advisory Committee has had a chance to even look at them.

Dr. Lloyd-Puryear pointed out that in the process Advisory Committee members approved for nominating and reviewing conditions nominated for inclusion on the newborn screening panel, HRSA is supposed to perform the initial review of nomination forms. She noted that HRSA had not set up its own system of review yet and asked what criteria HRSA should use in deciding to send nominations forms ahead and how to prioritize the nominations received. Dr. Howell explained that HRSA’s role is simply to confirm that the nomination form is ready to go forward, not to do a scientific or priority-setting or qualitative review.

Dr. Howell pointed out that the Advisory Committee had not yet given formal approval to the ERG proposal presented by Dr. Perrin. Dr. Green stated that what Dr. Perrin had presented to the Committee at this meeting was very, very preliminary and that he would submit a more formal proposal. His presentation today had not even been reviewed by the ERG’s own advisory group.

Ms. Terry asked whether it was correct to tell potential nominators of conditions for inclusion on the uniform newborn screening panel to use the nomination form previously approved by the Advisory Committee even though there were going to be iterative changes to the form. She also asked what the timeline for considering conditions nominated would be, given that the ERG’s process has not yet been approved. Several Committee members noted that it was important to build trust with the nominators by framing out when the process for reviews is going to be in place.

Dr. Green responded to Ms. Terry that groups with nominations of conditions they would like to see added to the uniform newborn screening panel should go ahead and submit the nominations. She added that Dr. Perrin would like to consider one condition before the Advisory Committee’s next meeting in January 2008, but he is reluctant to set a timeline for evidence reviews, in part because the timeline is likely to vary by condition.

Dr. van Dyck and Dr. Alexander said that, much as they would like the Advisory Committee to move forward on reviewing nominations for adding conditions to the uniform newborn screening panel, it was not ready to do so for two reasons. First, HRSA had not established its own process for reviewing performing administrative reviews (not scientific or priority-setting or qualitative reviews) before sending nominations on to the Advisory Committee. Second, the Advisory Committee had not yet approved Dr. Perrin’s proposal for the ERG and its process for reviewing the evidence.

To address the first issue, Dr. Alexander suggested that the Advisory Committee ask HRSA to develop its procedures for processing nominations; that the Advisory Committee consider the nominations for Krabbe and SCID as have been given to the Committee for informational purposes only and that the Committee ask HRSA to process the nominations and then formally submit them to the Committee as soon as possible. That way the Committee might be able to make a recommendation about how to move ahead with the Krabbe and SCIC nominations at its next meeting in January 2008.

To address the second issue, Dr. Alexander recommended that the Advisory Committee ask Drs. Perrin and Green to move expeditiously to incorporate revisions and turn their draft ERG proposal into a final report and submit the final report to HRSA to distribute to the Committee members. He also recommended asking HRSA to schedule a conference call prior to January 2008 for the Advisory Committee to review and modify or accept the revised ERG proposal. Finally, he recommended that HRSA move expeditiously to establish the ERG and get it in place once the ERG proposal is approved by the full Committee.

Dr. Howell and other Committee members accepted Dr. Alexander’s suggestions.

• DECISION #2: HRSA will move expeditiously to develop mechanisms for administrative review of nominations, so that it can process the nominations for Krabbe disease and SCID and any other nominations that come in.
  
  
• DECISION #3: Dr. Perrin and Dr. Green will submit a revised final document regarding the ERG and evidence-based review processes to HRSA as soon as possible. HRSA will distribute the document to Advisory Committee members and schedule a conference call with Committee members, so they can approve or modify the plan prior to the Advisory Committee’s January 2008 meeting. Once the plan has been approved, HRSA will move expeditiously to establish the ERG.

Another recommendation from Dr. Alexander and Dr. Boyle was that Dr. Howell appoint a subcommittee of the Advisory Committee to (1) determine whether nominations were ready for evidence-based review; and (2) develop criteria for prioritizing nominations, so that the full Advisory Committee could consider which nominations to send to the ERG at its upcoming meeting in January 2008. Dr. Howell agreed with this suggestion and asked Advisory Committee members to let him know if they would serve on the subcommittee. Dr. Lloyd-Puryear urged Committee members who were leaving the Committee but who had not yet been replaced to stay involved in the process until their replacements had been named.

• DECISION #4: Dr. Howell will appoint a Nomination Review and Prioritization workgroup of the Advisory Committee (1) to review nomination forms processed by HRSA to determine the nominations’ readiness for referral to the ERG; and (2) to develop criteria regarding the prioritization (if any) of the Krabbe disease, SCID, and other nominations received from HRSA. The workgroup will report to the Advisory Committee at the Committee’s next meeting in January 2008.

Ms. Terry proposed giving the Krabbe and SCID nominations to Dr. Perrin and his colleagues immediately, so that they could use them to fine tune the ERG’s own processes while they were waiting for the nominations to be formally assigned to them for evidence-based review. Dr. Watson noted that both Krabbe and SCID were quite different from Pompe disease, which was used initially to develop the ERG’s processes, so it would be useful for the ERG to have the nominations for the purpose Ms. Terry set forth.

• DECISION #5: The nominations for Krabbe and SCID will be given to Dr. Perrin prior to being referred to the ERG formally, so that he and his colleagues can use them to fine tune the ERG’s own processes.
  C. Inviting an FDA Representative to the January 2008 Meeting to Discuss Access to Data

Dr. Green explained that one reason Dr. Perrin is reluctant to set a timeline for evidence-based reviews by the ERG, apart from the fact that the timeline will vary by condition, is that the process for getting unpublished data from the Food and Drug Administration (FDA) is uncertain. She asked the Advisory Committee to discuss how to hasten getting such data in order to expedite the ERG’s evidence review process.

Speaking as FDA’s representative to the Committee, Dr. Hausman explained that many people have raised this issue over the past 20 to 30 years. He said there are different rules depending on which FDA center is involved, but any data that come in to FDA about drugs, foods, or biologics are proprietary, and FDA is limited in its capacity to share certain types of information. Dr. Hausman said that there was no way he could promise access to any data, but he would be happy to facilitate communications between the Advisory Committee and the policy people at FDA who could address questions on this topic.

Dr. Howell accepted Dr. Hausman’s offer, saying he would like to have the appropriate FDA representative make a presentation to the Advisory Committee at its upcoming meeting in January 2008.

• DECISION #6: With Dr. Hausman’s assistance, an FDA policy person who can address issues related to gaining access to FDA data on newborn screening tests will be identified and asked to make a presentation to the Advisory Committee at its meeting in January 2008.

IV. SACGHS TASK FORCE ON OVERSIGHT OF GENETIC TESTING

Andrea Ferreira-Gonzalez, Ph.D.
Professor of Pathology
Director of Molecular Diagnostics Laboratory
Virginia Commonwealth University

Dr. Ferreira-Gonzalez reported on the newly created the Task Force on Oversight of Genetic Testing of the Secretary’s Advisory Committee on Genetics, Health, and Society (SACGHS). Dr. Ferreira-Gonzales is the chair of the task force, which was created in response to a mandate from the HHS Secretary in March 2007.

The HHS Secretary’s overarching mandate for SACGHS is “to explore, analyze, and deliberate on the broad range of human health and societal issues raised by the development and use, as well as potential misuse, of genetic technologies” and “to make recommendations to the Secretary of HHS and other departments upon request.” The scope of SACGHS includes the integration of genetic technologies into health care and public health; clinical, ethical, legal and societal implications