NNEWBORN SSCREENING:: TTOWARD A UUNIFORM SSCREENING PPANEL AND SSYSTEM 1 Newborn Screening Steering Committee Jose Cordero, MD, MPH Michele A. Lloyd-Puryear, MD, PhD Centers for Disease Control and Prevention Maternal and Child Health Bureau Health Resources and Services Administration Health Resources and Services Administration E. Steven Edwards, MD Marie Y. Mann, MD, MPH (Project Officer) Past President Maternal and Child Health Bureau American Academy of Pediatrics Health Resources and Services Administration R. Rodney Howell, MD Tricia Mullaley American College of Medical Genetics Genetic Alliance University of Miami School of Medicine Peter van Dyck, MD, MPH Jennifer L. Howse, PhD Maternal and Child Health Bureau President Health Resources and Services Administration March of Dimes Birth Defects Organization Michael S. Watson, PhD (Project Director) American College of Medical Genetics Newborn Screening Expert Group R. Rodney Howell, MD (Chair) Fernando Guerra, MD, MPH American College of Medical Genetics San Antonio Metropolitan Health District University of Miami School of Medicine W. Harry Hannon, PhD (ex officio) William Becker, DO Centers for Disease Control and Prevention Association of Public Health Laboratories Ohio State Department of Health James Hanson, MD (ex officio) Ohio State University National Institute of Child Health and Human Development Coleen Boyle, PhD (ex officio) National Institutes of Health Centers for Disease Control and Prevention Cecilia Larson, MD George C. Cunningham, MD, MPH New England Newborn Screening Program Genetics Disease Branch California Department of Health Services Michele A. Lloyd-Puryear, MD, PhD (ex officio) Maternal and Child Health Bureau Michael R. DeBaun, MD, MPH Health Resources and Services Administration Washington University School of Medicine Marie Y. Mann, MD, MPH (ex officio) (Project Stephen M. Downs, MD Officer) Indiana University School of Medicine Maternal and Child Health Bureau Health Resources and Services Administration Edward Goldman, JD University of Michigan Hospitals Scott McLean, MD, LTC, MC (ex officio) and Health System United States Army Stephen I. Goodman, MD Gurvaneet Randhawa, MD, MPH (ex officio) University of Colorado Health Sciences Center Agency for Healthcare Research and Quality 2 Piero Rinaldo, MD, PhD Bradford Therrell, PhD Mayo Clinic College of Medicine National Newborn Screening and Genetics Resource Center Derek Robertson, MBA, JD University of Texas Health Science Center Healthcare Consultant/Family Representative at San Antonio Mark Rothstein, JD Thomas Tonniges, MD University of Louisville American Academy of Pediatrics Robert D. Steiner, MD Wanda Yazzie, RN, MPH Oregon Health & Science University New Mexico Department of Health Sonia Suter, MS, JD Michael S. Watson, PhD (Project Director) George Washington University Law School American College of Medical Genetics Newborn Screening Conditions and Criteria Work Group Piero Rinaldo, MD, PhD (Chair) Kenneth Pass, PhD Mayo Clinic College of Medicine New York State Department of Health Association of Public Health Laboratories Donald Bailey, PhD (Family Representative) University of North Carolina at Chapel Hill Jennifer M. Puck, MD National Human Genome Research Institute Celia I. Kaye, PhD, MD National Institutes of Health University of Texas Health Science Center at San Antonio Bradford Therrell, PhD National Newborn Screening Alex R. Kemper, MD, MPH and Genetics Resource Center University of Michigan Health System University of Texas Health Science Center at San Antonio Michele A. Lloyd-Puryear, MD, PhD Maternal and Child Health Bureau Michael S. Watson, PhD (Project Director) Health Resources and Services Administration American College of Medical Genetics Marie Y. Mann, MD, MPH (Project Officer) Maternal and Child Health Bureau Health Resources and Services Administration Newborn Screening External Review Group Franklin Desposito, MD Arnold Strauss, MD University of Medicine and Dentistry of New Vanderbilt University School of Medicine Jersey Tracy Trotter, MD Gary Hoffman Private pediatric practice, California Wisconsin State Laboratory of Hygiene Anne M. Willey, PhD, JD Kathy Stagni Association of Public Health Laboratories Organic Acidemia Association New York State Department of Health 3 Newborn Screening Diagnosis and Follow-up Work Group Harvey L. Levy, MD (Chair) Danielle Laraque, MD Children’s Hospital Boston Mt. Sinai School of Medicine Harvard Medical School Kelly R. Leight, JD (Family Representative) James R. Eckman, MD CARES Foundation Emory University School of Medicine Derek Robertson, MBA, JD Michele A. Lloyd-Puryear, MD, PhD Healthcare Consultant/Family Representative Maternal and Child Health Bureau Health Resources and Services Administration Bradford Therrell, PhD National Newborn Screening Fred Lorey, PhD and Genetics Resource Center California Department of Health Services University of Texas Health Science Center at San Antonio Marie Y. Mann, MD, MPH (Project Officer) Maternal and Child Health Bureau Michael S. Watson, PhD (Project Director) Health Resources and Services Administration American College of Medical Genetics Deborah L. Marsden, MBBS Barbara Yawn, MD Children’s Hospital Boston American Academy of Family Physicians Harvard Medical School Julie Miller, BS Nebraska Department of Health Newborn Screening HIPAA Work Group Edward B. Goldman, JD (Chair) Lynn D. Fleisher, PhD, JD University of Michigan Hospitals Sidley, Austin, Brown and Wood and Health System Mark Rothstein, JD Coleen Boyle, PhD University of Louisville Centers for Disease Control and Prevention Health Resources and Services Administration Sonia Suter, MS, JD George Washington University Law School Beverly Dozier Centers for Disease Control and Prevention Health Resources and Services Administration 4 TABLE OF CONTENTS ABSTRACT ....................................................................................................................................7 INTRODUCTION.........................................................................................................................12 SECTION I: DEVELOPING A UNIFORM SCREENING PANEL.............................................14 A. Background.......................................................................................................................14 B. Methods Used for Assessing Conditions...........................................................................25 C. Results...............................................................................................................................49 D. Discussion.........................................................................................................................54 E. Summary ...........................................................................................................................76 SECTION II: THE NEWBORN SCREENING SYSTEM: PROGRAM EVALUATION, COST- EFFECTIVENESS, INFORMATION NEEDS, AND FUTURE NEEDS.......................78 A. The Newborn Screening System........................................................................................78 B. Program Evaluation..........................................................................................................89 C. Cost-Effectiveness Analysis ..............................................................................................94 D. Information Gaps and a Research Agenda ......................................................................95 E. Future Needs.....................................................................................................................98 F. Summary .........................................................................................................................100 REFERENCES............................................................................................................................102 FIGURES, APPENDICES AND BOX FIGURES Figure 1: Raw Data For Mcad Deficiency (16 Of 90 Total Respondents)..................................109 Figure 2: Raw Data For Pku (16 Of 120 Total Respondents).....................................................110 Figures 3a – 3e: Side-By-Side Comparison Of Mcad And Pku for the Criteria Used................111 Figure 4: Final Scores (Sum Of Mean Scores) For All Conditions ............................................116 Figure 5: Survey Scores Sorted By Testing Platforms................................................................117 Figure 6: Scores By Test Availability (Test/No Test).................................................................118 Figure 7: Scores For All Conditions Distinguished By Screening Panel Category....................119 Figure 8: Distribution Of Conditions Into Screening Panel Categories......................................119 Figure 9: Survey Scores Sorted By Testing Platforms................................................................121 Figure 10: National State Quality Assurance And Oversight For Newborn Screening Program Components.....................................................................................................................122 5 APPENDICES Appendix 1: Newborn Screening Fact Sheet Validation & Fact Sheets .....................................123 Appendix 2: Condition Evaluation Tool .....................................................................................308 Appendix 3: Condition ACT(ion) Sheets....................................................................................309 Appendix 4: Program