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Genetic Counseling and Cystic Fibrosis Carrier Screening: Results of a Survey

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Title:
Genetic Counseling and Cystic Fibrosis Carrier Screening: Results of a Survey
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Background paper
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United States. Congress. Office of Technology Assessment.
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U.S. Congress. Office of Technology Assessment
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English
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53 p. : ill. ; 28 cm.

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Subjects / Keywords:
Health surveys -- United States ( LCSH )
Genetic disorders -- United States ( LCSH )
Cystic fibrosis gene -- United States ( LCSH )
Cystic fibrosis -- United States -- Genetic aspects ( LCSH )
Genetic counseling -- United States ( LCSH )
Genetic screening -- United States ( LCSH )
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federal government publication ( marcgt )

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General Note:
This paper presents results from a 1991 OTA survey of 431 genetic counselors and nurse geneticists. It was conducted to better understand the environment in which the average genetic counselor or nurse in genetics works, to describe the infrastructure and tools available to these professionals, to assess the state of practice in the provision of cystic fibrosis (CF) carrier screening, and to evaluate their attitudes regarding CF carrier screening.

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University of North Texas
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University of North Texas
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This item is a work of the U.S. federal government and not subject to copyright pursuant to 17 U.S.C. §105.
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Y 3.T 22/2:2 G 28/6 ( sudocs )

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IUF:
University of Florida
OTA:
Office of Technology Assessment

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Genetic Counseling and Cystic Fibrosis Carrier Screening: Results of a Survey October 1992 OTA-BP-BA-97 NTIS order #PB93-101764

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Recommended Citation: U.S. Congress, Office of Technology Assessment, Genetic Counseling and Cystic Fibrosis Carrier Screening: Results of a Survey--Background Paper, OTA-BP-BA-97 (Washington, DC: U.S. Government Printing Office, September 1992). For sale by the U.S. Government Printing Office Superintendent of Documentts, Mail Stop: SSOP, Washington. DC 20402-9328 ISBN 0-16-0380936

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Foreword For years, experts have theorized about the consequences of increased knowledge of human genetics. In the early 1990s, development of a DNA-based test to identify carriers of cystic fibrosis (CF) moved the debate from the theoretical to the practical. The CF carrier assay is but one of many tests to come that will place genetic counselors and nurses working in genetics at the front line on the issues raised by assimilation of DNA tests into clinical practice. This OTA Background Paper presents results from a 1991 OTA survey of 431 genetic counselors and nurse geneticists. It was conducted to better understand the environment in which the average genetic counselor or nurse in genetics works, to describe the infrastructure and tools available to these professionals, to assess the state of practice in the provision of CF carrier screening, and to evaluate their attitudes regarding CF carrier screening. The survey supports OTAs August 1992 assessment Cystic Fibrosis and DNA Tests: Implications of Carrier Screening; the full assessment was requested by the House Committee on Science, Space, and Technology, the House Committee on Energy and Commerce, and Representative David R. Obey. The survey data collected by OTA reflect the tensions and concerns surrounding the widespread implementation of CF carrier screening. Those who currently oppose routine carrier screening for CF raise concerns about the sensitivity of the test, the numbers of individuals that would be potentially screened and the subsequent effect on the clinical genetics infrastructure--and the possibilities of stigma, discrimin ation, and poor quality in services. Those who think CF carrier screening should be widely available believe the information provided by the test increases patient autonomy and lowers uncertainty regarding reproductive futures. OTA was assisted in preparing the survey instrument and Background Paper by a panel of advisors, contractors, workshop participants, and reviewers selected for their expertise and diverse points of view. We gratefully acknowledge the contribution of each of these individuals. OTA, however, remains solely responsible for the contents of this Background Paper. /y/ &# J6i9-JOHN H. GIBBONS Director Ill

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Cystic Fibrosis and DNA Tests: Implications of Carrier Screening Advisory Panel Jessica G. Davis, Panel Chair Co-Director, Division of Human Genetics New York Hospital Cornell University Medical College New York, NY Arthur L. Beaudet Professor Howard Hughes Medical Institute Baylor College of Medicine Houston, TX Debra L. Collins Genetic Counselor University of Kansas Medical Center Kansas City, KS Beth A. Fine Genetic Counselor/Clinical Instructor Northwestern University Medical School Chicago, IL Lynn D. Fleisher Attorney Sidley & Austin Chicago, IL Clark C. Havighurst William Neal Reynolds Professor of Law Duke University School of Law Durham, NC John Z. Jacoby, III Clinical Assistant The Cystic Fibrosis Center St. Vincents Hospital and Medical Center New York, NY Angle Khachadour General Counsel Hastings College of the Law San Francisco, CA Katherine W. Klinger Vice President, Science Integrated Genetics Framin gham, MA Arthur Lifson Vice President CIGNA Companies Hartford, CT Robert F. Murray, Jr. Professor Department of Pediatrics and Child Health Howard University School of Medicine Washington, DC Mark V. Pauly Executive Director Leonard Davis Institute of Health Economics University of Pennsylvania Philadelphia, PA Susan Poling Parent Silver Spring, MD Thomas K. Reed, Jr. chairman Vivigen, Inc. Santa Fe, NM Philip R. Reilly President Shriver Center for Mental Retardation, Inc. Waltharn, MA Joseph D. Schulman Director Genetics & IVF Institute Fairfax, VA NOTE: OTA is grateful for the valuable assistance and thoughtful critiques provided by the advisory panel members. The panel does not, however, necessarily approve, disapprove, or endorse this report. OTA assumes full responsibility for the report and the accuracy of its contents. iv

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Genetic Counseling and Cystic Fibrosis Carrier Screening: Results of a Survey OTA Project Staff Roger C. Herdman, Assistant Director, OTA Health and Life Sciences Division Michael Gough, Biological Applications Program Manager Robyn Y. Nishimi, Project Director Kathi E. Hanna, Study Director Ellen L. Goode, Research Analyst Margaret A. Anderson, Analyst l and Contractor Sheryl M. Winston, Research Analyst Administrative Staff Ccile Parker, Office Administrator Linda Rayford-Journiette, PC Specialist Jene Lewis, Administrative Secretary Contractors Gary B. Ellis, Editor, Silver Spring, MD John M. Boyle, Schulman, Ronca & Bucuvalas, Inc., Silver Spring, MD Ferdinand J. Chabot, Newton, IA Bob Jones, IV, Arlington, VA Ann C.M. Smith, Reston, VA 1 Through December 1991

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Contents Page Chapter 1. Introduction and Background ... .oo***. ... ee. .oo. ... ... *.oo. o.. ..oo. o*0**0o 1 WHAT IS CYSTIC FIBROSIS? . . . . . . . . . . . . . . 2 THE CYSTIC FIBROSIS GENE . . . . . . . . . . . . . 2 CYSTIC FIBROSIS MUTATION ANALYSIS . . . . . . . . . . 2 CONTROVERSY ABOUT CYSTIC FIBROSIS CARRIER SCREENING . . . . 3 SCOPE AND ORGANIZATION OF THIS BACKGROUND PAPER . . . . . 4 CHAPTER 1 REFERENCES . . . . . . . . . . . . . . 4 Chapter 2. Providers, Clientele, and Genetic Services ... ... ... ... ... ... ... ... ... .. *...0 5 THE SURVEY POPULATION . . . . . . . . . . . . . 5 Genetic Counselors . . . . . . . . . . . . . . . . 5 Nurses in Genetics . . . . . . . . . . . . . . . . 6 Demographic Profile of Survey Respondents . . . . . . . . . . 7 WORK ENVIRONMENTS . . . . . . . . . . . . . . 7 GENETICS CLIENTELE . . . . . . . . . . . . . . . 9 FEES AND THIRD-PARTY COVERAGE . . . . . . . . . . . 11 Fees for Genetic Services . . . . . . . . . . . . . . . 11 Third-Party Coverage . . . . . . . . . . . . . . . . 12 SUMMARY . . . . . . . . . . . . . . . . . . 14 CHAPTER 2 REFERENCES . . . . . . . . . . . . . . 15 Chapter 3. Cystic Fibrosis Carrier Screening: Policies and Practices . . . . 17 POLICIES AND PRACTICES, SUMMER 1991 . . . . . . . . . . 17 Policies on Cystic Fibrosis Carrier Screening . . . . . . . . . . 17 Criteria for Cystic Fibrosis Carrier Screening . . . . . . . . . . 19 Practices Regarding DNA-Based Cystic Fibrosis Carrier Tests . . . . . . 19 PREFERRED STRATEGIES AND PROTOCOLS . . . . . . . . . 21 Who Should Provide Cystic Fibrosis Carrier Screening? . . . . . . . 22 Who Should Pay for Cystic Fibrosis Carrier Screening? . . . . . . . . 23 Strategies for Screening Various Populations . . . . . . . . . . 23 PROFESSIONAL CAPACITY . . . . . . . . . . . . . . 26 ISSUES TO BE ADDRESSED BEFORE IMPLEMENTATION . . . . . . 27 SUMMARY . . . . . . . . . . . . . . . . . . 28 CHAPTER 3 REFERENCES . . . . . . . . . . . . . . 28 Chapter 4. Summary . . . . . . . . . . . . . . . . 31 Appendix A. Survey Method ... .me. . . . . . . . . . . . . . 35 Appendix B. Survey Instrument ... ..oo. ..** . . . . . . . . . . 36 Appendix C. Acronyms and Glossary . . . . . . . . . . . . 48 Figures 1-1. Inheritance of Cystic Fibrosis . . . . . . . . . . . . . 1 1-2. Cystic Fibrosis Mutation Test Results at 85 Percent Sensitivity . . . . . . 3 2-1. Geographic Distribution of Survey Respondents . . . . . . 6 2-2. primary Service Areas of Respondents . . . . . . . . . . . 8 . . . 2-3. Average Hours Spent Per Week on Public Education . . . . . . . . 8 2-4. Racial/Ethnic Background of Clinical Genetics Clientele . . . . . . . 9 2-5. Age Distribution of Genetics Clientele . . . . . . . . . . . 9 2-6. Frequency of Patients Seen by Major Areas of Clinical Practice . . . . . 10 2-7. Number of Cystic Fibrosis Patients or Families Seen in Genetics Units in 1990 . . 11

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2-8. Health Care Coverage for Genetics Clientele . . . . . . . . . . 12 2-9. General Types of Health Care Coverage for Genetics Clientele . . . . . . 12 2-10. Third-Party Reimbursement for General Genetic Counseling and Counseling Specifically for Cystic Fibrosis . . . . . . . . . . . . . 13 3-1. Opinions on Optimal Rate of Detection . . . . . . . . . . . 19 3-2. Frequency of Requests for Cystic Fibrosis Carrier Screening/Testing, January-June1991 . . . . . . . . . . . . . . . . 20 3-3. Comparison of Requests for Cystic Fibrosis Carrier Screening/TestingBetween January-June 1991 and Past 2 Years . . . . . . . . . . . . 20 3-4. Opinions Regarding Genetic Counseling of Individuals with a Positive Family History . . . . . . . . . . . . . . . . . 21 3-5. Opinions Regarding Genetic Counseling of Individuals with a Negative Family History . . . . . . . . . . . . . . . . . 21 3-6. Opinions Regarding the Need for Informed Consent Prior to Cystic Fibrosis Carrier Screening . . . . . . . . . . . . . . . . 22 3-7. Opinions Regarding the Use of Educational Materials as aSource of Information About Cystic Fibrosis Carrier Screening . . . . . . . . . . . 22 3-8. Extent to Which Various Groups Should Be Involved with Cystic Fibrosis Pretest Education . . . . . . . . . . . . . . . . 24 3-9. Opinions Regarding the Need for More Genetic Counselors . . . . . . 27 Tables l-1. A Priori Carrier Risks for Cystic Fibrosis . . . . . . . . . . 1 2-1. Geographic Concentration of Survey Respondents . . . . . . . . 7 2-2. Primary Work Setting . . . . . . . . . . . . . . . 7 2-3. Average Weekly Schedule of Genetic Counselor or Nurse in Genetics . . . . 8 2-4. Formats for Genetic Counseling . . . . . . . . . . . . . 8 2-5. Most Common Diseases for Which Carrier Screening/Testing Is Offered . . . 11 2-6. Average Fees and Knowledge of Fees for Genetic Services . . . . . . . 11 2-7. Fees for General Counseling . . . . . . . . . . . . . 12 2-8. Difficulties in Obtaining or Retaining Health Insurance After Genetic Tests . . . 13 2-9. Case Descriptions of Genetic Testing and Health Insurance Problems . . . . 14 3-l. A Priori Carrier Risks for Cystic Fibrosis . . . . . . . . . . 18 3-2. Sources of Information About New Advances in Human Genetics . . . . . 18 3-3. Likelihood of Introducing the Topic of DNA Testing for Cystic Fibrosis . . . 18 3-4. Specific Policies Regarding DNA Testing for Cystic Fibrosis . . . . . . 18 3-5. Minimal Criteria for Cystic Fibrosis Carrier Screening Protocol . . . . . 19 3-6. Types of Genetic Analyses Provided for Cystic Fibrosis Screening Testing . . . 20 3-7. Cystic Fibrosis Mutations Routinely Analyzed . . . . . . . . . . 20 3-8. Preferred Organizations for Implementation of Voluntary Cystic Fibrosis Carrier Screening . . . . . . . . . . . . . . . . 23 3-9. Preferred Sites for Cystic Fibrosis Carrier Screening Programs . . . . . . 23 3-10. Who Should Pay for Cystic Fibrosis Carrier Screening? . . . . . . . 26 3-n. Target Populations for Cystic Fibrosis Carrier Screening. . . . . . . 26 3-12. Frequency of Patients Seen by Major Areas of Clinical Practice . . . . . 26 3-13. Time Required for Genetic Counseling for Various Conditions . . . . . 27 3-14. Strategies for Implementation of Widespread Cystic Fibrosis Carrier Screening . . 27 3-15. Issues that Need to be Addressed by Pilot Programs in Cystic Fibrosis Carrier Screening . . . . . . . . . . . . . . . . 28 vii

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Chapter 1Introduction and BackgroundCystic fibrosis (CF) is the most common, life-shortening, recessive genetic disorder affecting Cau-casians of European descent. From 1,700 to 2,000 babies with CF are born annually in the United States. The diagnosis of an infant with CF often reveals the first and only clue that the genetic trait exists in the family. Parents of a child with CF are, by definition,obligate CF carriers. They have no symptoms of CF,but with each pregnancy are at 1 in 4 risk of havinga child with CF and 1 in 2 risk of having a child whois a carrier (figure l-l). Such couples are sometimes referred to as carrier couples, or couples who are positive/positive (+/+). If a couple is positive/negative (+/-)the father is a carrier, but the motheris not, or vice versatheir offspring can be CF carriers, but cannot have CF. Couples are not at risk of having a child with CF if only one or neither partner is a carrier. Four of five individuals with CF are born to families with no previous history of the illness. Beyond the approximately 30,000 Americans whoFigure I-lInheritance of Cystic FibrosisoCarrier parentsohave CF, as many as 8 million individuals could be CF carriers. With no knowledge of a family history of CF, American Caucasians have about a 1 in 25 risk of being a CF carrier. The risk of carrier status increases when an individual in a family is diag-nosed with CF, with risks calculated by relationshipto the affected individual (table l-l). Prior to 1989, the absence or presence of CF in ones family, as well as ethnic and racial background, were the only indicators available to determine risk of carrier status. In 1989, however, scientists identified the most common change, or mutation, in the genetic material-deoxyribonucleic acid (DNA)-that causes CF. Following this discov-ery came tests to detect mutations in the specific areaof DNAthe CF gene-that is responsible for thedisease.The Office of Technology Assessment (OTA)report Cystic Fibrosis and DNA Tests: Implicationsof Carrier Screening (1) focuses on using these DNA tests to screen and identify CF carriers amongthe general population before they have a child with CF. This background paper, conducted in support ofthe OTA assessment, reports the results of an OTA survey of 431 members of either the National Society of Genetic Counselors (NSGC) or theInternational Society of Nurses in Genetics (ISONG).Conducted in summer 1991, the survey was designed to evaluate genetic counseling attitudes andpractices regarding widespread CF carrier screening, a prospect that has been viewed with mixed feelings.Table l-lA Priori Carrier Risks for Cystic Fibrosis25% 25%.chance50%chance unaffectedchance affected noncarrier unaffectedcarrierSOURCE: Office of Technology Assessmentp 1992.Negative family historyCaucasian. . . . . .1 in 25 (4%)African American. . . . 1 in 60 to 65 (1.5 to 1.7%) Asian American . . . . 1 in 150 (0.79.)Hispanic American. . . . 1 in 40 to 50 (2 to 2.5%) Positive family historyParent of child with CF. . . .1 in 1 (1OO%)Sibling with CF. . . . 2 in 3 (67%)Aunt or uncle with CFa. . . 1 in 3 (33%)First cousin with CF. . . .1 in 4 (25%)Niece/nephew with CFa. . . 1 in 2 (50%)a Consanguineous. SOURCE: Office of Technology Assessment, 1992.

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2 l Genetic Counseling and Cystic Fibrosis Carrier Screening: Results of a Survey Consensus exists that individuals who have relatives with CF should be told about the availability of CF carrier tests; the disagreement is whether everyone should be informed about the assays, since 80 percent of babies with CF are born to couples with no previous family history of the condition. Concern about the scientific, legal, economic, ethical, and social implications of the prospect that large numbers of people might be screened for their CF carrier status led the House Committee on Science, Space, and Technology, the House Committee on Energy and Commerce, and Representative David R. Obey to request the OTA assessment. WHAT IS CYSTIC FIBROSIS? CF is not a new disease. First described in 17th century folklore, medical literature has long documented that CF compromises many functions throughout the body--chiefly the respiratory, gastrointestinal, and reproductive systems and the sweat glands. Many affected babies are not immediately diagnosed as having CF Although the disease is always present at birth in affected individuals, the onset of recognizable clinical symptoms varies widely. Physicians diagnose CF using a combination of clinical criteria and diagnostic laboratory tests. Although an assay called the sweat test remains the primary diagnostic test for CF DNA mutation analysis can diagnose more than 70 percent of cases. CF exerts its greatest toll on the respiratory and digestive systems, and the severity of respiratory problems often determines the quality of life and survival. There is no cure for CF Treatment focuses on managing the respiratory and digestive symptoms to maintain a stable condition and lengthen lifespan. Because of CFs varied progression, the regimen and level of therapy depends on the individual. Most therapy involves home treatment (e.g., chest physical therapy to clear mucus from the lungs), outpatient care at one of more than 110 clinics devoted specifically to CF health care, and occasional hospital stays. Today, physicians can look to an ever-expanding array of new pharmaceutical options to manage the care of CF patients; on the horizon are hopes for gene therapy. Over the last half-century, treatment of CF has evolved so that an illness nearly always fatal in early childhood is now one where life expectancy into adulthood is common. Fifty years ago, most infants born with CF died in the frost 2 years of life. In 1990, median survival was 28 years--i.e., of the individuals born with CF in 1962, half were alive in 1990. THE CYSTIC FIBROSIS GENE CF is a genetic illness transmitted from parents to their children via genetic directions stored in DNA. In humans, these directions, including those responsible for CF are stored among genes arrayed on 46 structures called chromosomes. The gene responsible for CF lies on chromosome 7 and results in a product called the cystic fibrosis transmembrane conductance regulator (CFTR). In most people with CF a three-base pair deletion in both of their CF alleles results in a faulty CFTR, which leads to CF pathology. This three-base pair mutation occurs at position number 508 in the CFTR and is abbreviated as delta F508 (AF508). More than 170 additional mutations in the CF gene also lead to faulty CFTRs. Individuals with CF have two of the same, or two different, mutations. CF carriers have only one mutation; their second CF allele produces normal CFTR. About 70 percent of CF carriers have the AF508 mutation. l International studies demonstrate ethnic and regional variation in the frequency distribution of this mutation; as expected, the multicultural nature of the United States reflects this variation. Most of the other 170+ mutations appear in a small fraction of individuals or families, although a few occur at a frequency as great as 1 to 3 percent. Some symptoms (or their lack of severity) correlate with particular mutations. Digestive difficulties from pancreatic insufficiency, for example, generally associate with AF508. CYSTIC FIBROSIS MUTATION ANALYSIS With localization of the CF gene, AF508, and other CF mutations, it is now possible to directly analyze DNA from any individual for the presence 1 Quoted mu~tion fiquencies for AF508 and other CFmutations always depend on racial and ethnic background. Throughout this background Paper, OTA presents current expert estimates of appropriate ranges of detection frequencies or sometimes uses a specitlc figure with qualification (e.g., about 90 percent; approximately95 percent). OTA adopts such language to avoid restating each time that afkquency depends on racial and ethnic background, not to underemphasize the importance in the distriioution variation of CF mutations. In some cases-made clear within the text-a speeitlc frequency is chosen for illustrative or hypothetical purposes.

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Chapter 1--Introduction and Background l 3of CF mutations. Using todays technologies, CF mutation analysis is usually a one-time test that caninform an individual whether he or she carries any ofthe CF mutations for which tests are conducted. Carrier screening for CF (or CF carrier screening) refers to performing CF mutation analysis on DNAfrom an individual who has no family history of CFCurrent technology, however, can leave ambiguity, but not because the tests per se are imprecise. Properly performed, DNA-based tests for CF mutations are accurate and specific-meaning if the mutation (or another CF mutation) is presentin the individuals genome and an assay is performed to search for that mutation, the test will detect it more than 99 percent of the time, absent laboratory error. Instead, ambiguity stems from the intrinsic nature of the cause of the disease: Besides more than 170 mutations in the CF gene alsocause CF In the United States, about 1 in 25 Caucasians carries one CF mutation. Current assays use plus 6 to 12 other CF mutations andidentify about 85 percent of CF carriers (in Ashkena-zic Jews, identifies about 95 percent of carriers). Thus, using means 10 to 15 percent of actual carriers go undetected. In other words, since tests to detect 170+ mutations areimpractical, a negative test result does not guaranteethat a person is not a carrier. Using DF508+6-12 means that some couples receive test results that indicate one partner is a carrier and one is not, when in fact the negative partner carries one of the rare CF mutations that is not assayed. Thus, while most couples whose test results are +/are at zero risk of having a child with CF some couples with a +/test result actually are couples whose genetic status is +/+ (but goesundetected) and who are at 1 in 4 risk of a child with CF for each pregnancy. Couples with a +/test result,then, might misunderstand that their reduced risk ofbearing a child with CF is not zero risk (figure 1-2).CONTROVERSY ABOUT CYSTIC FIBROSIS CARRIER SCREENINGProspects of routine CF carrier screening polarizepeople. No mandatory genetic screening programsof adult populations exist in the United States. OTA has found it highly unlikely that CF carrier screeningwill set a precedent in this regard (l). People agreethat persons with a family history of CF should havethe opportunity to avail themselves of CF mutation analysis, yet controversy swirls around using the same tests in the general population.Figure 1-2Cystic Fibrosis Mutation Test Results at 85 Percent Sensitivity100,000couples Run CF mutation test (85% sensitivity)TEST RESULTSSome of these couples are a different type, but go undetected Some of these couples 1,152 (No risk.) 4 are a different type, (1 in 4 risk with each pregnancy. Remaining but go undetected -/couples are at no risk.) 116 (1 in 4 risk with each pregnancy. (1 in 4 risk with each pregnancy. Remaining For first pregnancy for 100,000 couples, 29 CF-affected fetuses detectable, +/couples are at no risk.) 11 missed.)SOURCE: Office of Technology Assessment, 1992.

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4 l Genetic Counseling and Cystic Fibrosis Carrier Screening: Results of a Survey Proponents of a measured approach to CF carrier screening express concern about several issues that might be raised if use of CF carrier tests becomes routine. Invariably, discussions about CF carrier screening raise concerns about the use of genetic information by insurance companies (2) and become linked broader social concerns about health care reform in the United States. Related to this are concerns about commercialization of genetic research, i.e., that market pressures will drive widespread use of tests before the potential for discrimination or stigmatization by other individuals or institutions (e.g., employers and insurers) is assessed. Also expressed are questions about the adequacy of quality assurance for DNA diagnostic facilities, personnel, and the tests themselves. Others also wonder whether the current number of genetic specialists can handle a swell of CF carrier screening cases, let alone cases from tests for other genetic conditions expected to arise from the Human Genome Project. Finally, the extraordinary tensions in the United States about abortion affect discussions about CF carrier testing and screening. Those who advocate CF carrier tests for use beyond affected families are equally concerned about these issues. They assert, however, that individuals should be routinely informed about the assays so they can decide for themselves whether to be voluntarily screened. Proponents of providing such information believe that failing to inform patients now about the availability of CF carrier assays denies people the opportunity to make personal choices about their reproductive futures, either prospectively-e. g., by avoiding conception, choosing to adopt, or using artificial insemination by donor-or by using prenatal testing to determine whether a fetus is affected. SCOPE AND ORGANIZATION OF THIS BACKGROUND PAPER One of the tasks of genetic specialists is to provide the educational and counseling services necessary to successful implementation of new technologies. Increasingly, genetic counselors and nurses working in genetics will be at the front line on the issues raised by DNA technologies assimilation into practice. The OTA survey was conducted to better understand the environment in which the average genetic counselor or nurse in genetics works, to describe the infrastructure and tools available to these professionals, to assess the state of practice in the provision of CF carrier screening, and to evaluate their attitudes regarding CF carrier screening. The results of the survey are reported in chapters 2 and 3. A summary appears in chapter 4. A description of the survey methodology is in appendix A, and the survey instrument is reproduced in appendix B. CHAPTER 1 REFERENCES 1. 2. U.S. Congress, Office of Technology Assessment, Cystic Fibrosis and DNA Tests: Implications of Carrier Screening, OTA-BA-532 (Washington, DC: U.S. Government Printing Office, August 1992). U.S. Congress, Office of Technology Assessment, Genetic Tests and Health Insurance+Results of a Survey, OTA-BP-BA-98 (Washington, DC: U.S. Government Printing Office, October 1992).

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Chapter 2 Providers, Clientele, and Genetic Services The purpose of the OTA survey was to evaluate the extent to which genetic counselors and nurses in genetics are routinely offering carrier screening for cystic fibrosis CF to their clientele, to assess their attitudes and beliefs about the appropriateness of such screening, and to obtain a sense of the environment in which they work. While members of the National Society of Genetic Counselors (NSGC) and the International Society of Nurses in Genetics (ISONG) are by no means the only health professionals providing genetic counseling, they comprise a professional segment devoted explicitly to that end. Physicians, social workers, public health workers, and research scientists also provide genetic services. Those groups were not included in this survey. To better understand the setting in which routine carrier screening for CF might take place, OTA gathered data regarding not only counselors attitudes and practices regarding CF carrier screening (ch. 3), but also the settings in which they work, the numbers and types of clients they serve, clinical practices, work routines, fees charged, and thirdparty payment options available to their clientele. Understanding the environment in which CF carrier screening takes place was a critical part of the analysis reported in Cystic Fibrosis and DNA Tests: Implications of Carrier Screening (10). THE SURVEY POPULATION Of the 703 members of the NSGC who received questionnaires, 351-or 50 percentresponded. Of the 110 members of ISONG who received the questionnaire, 80-or 73 percentresponded. Thus, 80 percent of the respondent group are members of NSGC and 20 percent are members of ISONG. l As preliminary analysis revealed no significant difference in question response between the two populations, all data were combined for the final analysis. The combined response rate is 53 percent. Genetic Counselors The master s-level genetic counselor is a relatively new addition to the health care system. In 1971, 10 graduates of the first such program entered the workforce; in 1979, the NSGC was incorporated as a professional organization. Today, there are approximately 1,000 master s-level genetic counselors practicing in the United States. Master s-level genetic counselors receive specialized multidisciplinary training and experience to prepare them for counseling related to a wide variety of genetic disorders and birth defects. They are typically graduates from a 2-year masters degree program, during which time they receive didactic course work in the principles and application of human genetics, clinical and medical genetics, genetic laboratory methods, and interviewing and counseling. Genetic counselors are also trained in social, ethical, legal, and cultural issues relating to genetic diseases, principles of public health and health care delivery systems, and education for the lay and professional community (12). Over the past 20 years, master s-level graduate programs in genetic counseling have increased to 15, and combined, they produce approximately 75 graduates each year (7). At the time of the OTA survey, there were 703 genetic counselors who were full members of NSGC (associate, student, and foreign members were not surveyed). Of all respondents to the survey, 70 percent had a masters degree in genetic counseling. An additional 10 percent held a masters degree in another area, and 8 percent had a Ph.D. Genetic counselors receive a minimum of 400 hours of supervised clinical trainin gin at least three clinical settings, including a general genetics clinic, a prenatal diagnosis clinic, and a speciality disease clinic. Until 1992, graduates were eligible to sit for the certification examination in genetic counseling by the American Board of Medical Genetics (ABMG), but continuing certification of these individuals by this body is uncertain. In the past, counselors were required to submit their credentials and a logbook of 50 cases obtained in a clinically accredited training 1 ne5e re5pome rate5 are ~ical of other mail surveys reported in the literature (1,6). One review found response rates for a two wave swey (fiti mailing and one followup) ranged from 37 to 58.4 percent (6). OTAs aggregate response rate clearly falls within this range, as does the response rate of the genetic counselors; the response rate of the nurses in genetics exceeds it.

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6 l Genetic Counseling and Cystic Fibrosis Carrier Screening: Results of a SurveyFigure 2-l-Geographic Distribution of Survey Respondentsa IDSD 22NE 5KS (I) (2) NM 1OK4 NH 3 (1) ME \7i-AR v 1-x HI 2 (<1) (1)(<1)PR 1 (<1) of respondents from a State is listed, with the percentage the number represents in parentheses.SOURCE: Office of Technology Assessment, 1992.site before taking the exam (7). Most surveyrespondents survey were board certified (65 percent)or board eligible (19 percent).Nurses in GeneticsThere are nearly 2 million registered professional nurses in the United States, many involved inmaternal and child health nursing. These profession-als provide a unique potential to contribute to the effective delivery of genetic services. Efforts areunder way to encourage the incorporation of clinicalgenetics into the curricula of schools of nursing at both the graduate and undergraduate level (4). The need for better genetics education in nursing stemsfrom the recognition that genetics generally has beenwithin the realm of tertiary care; thus, genetics specialists are not always in the position to screen every individual needing genetics referral (4). That is, individuals in need of genetic services must firstbe identified by the primary health care professiona1,and in some settings-such as community, occupational, or school health-nurses are the only link with the health care system (3). Thus, nurses can assist in the identification, education and counseling, and followup of patients (2,4). Though nurses can be a valuable part of genetics services, to date they are a largely untapped resource (3). Opportunities for clinical genetics experience in nursing programs vary. Genetics is generally a part of the nursing school curriculum, but variabilityexists among programs (3). Four of the 200 universi-ties in the United States that offer graduate degrees

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Chapter 2-Providers, Clientele, and Genetic Services l 7in nursing have established programs providing amaster s-level genetics major (3). A small number ofnurses, particularly those in maternal and child health nursing, have focused on genetics in order to sit for the genetic counseling examination given by the American Board of Medical Genetics (ABMG) (3,5). There are over 100 nurses employed in genetics who also belong to ISONG and thereforereceived OTAs questionnaire. It is likely that many more nurses deliver genetic services but are uniden-tifiable through current databases. Of the total survey respondents,12 percent reported having either an R.N. or B.S.N. degree. Nurses might also have a masters degree or Ph.D. and could be included in the 80 percent of respondents who reported having a masters degree or the 8 percent who reported having a Ph.D.Demographic Profile of Survey RespondentsThe typical individual working as a genetic counselor or nurse in genetics is likely to be female (92 percent), in her mid-30s (mean age of 37), Caucasian (96 percent; 2 percent are Hispanic, 1 percent African American, 1 percent Asian American), and married (70 percent). On average, she islikely to have been in practice for 6 to 7 years, havingreceived her degree in 1985. Eight-seven percent ofthese individuals speak only English; 5 percent alsospeak Spanish, and 8 percent speak English and a language other than Spanish. Respondents represented every State except Ar-kansas, Louisiana, Kentucky, Mississippi, Montana, and Nevada (figure 2-1). There is a heavy concentra-tion of counselors in five States, with 43 percent of respondents located in California, Illinois, NewJersey, New York, and Pennsylvania, and 23 percentlocated in three northeastern States, New Jersey, New York, and Pennsylvania (table 2-l). California had the highest representation at 15 percent. These data are consistent with those collected and biannually reported by the NSGC (8). Hence, OTAs survey respondent pool is representative of the NSGC membership and no sample weighting wasnecessary.WORK ENVIRONMENTSThe majority of respondents (83 percent) are currently engaged in providing genetic counseling. Seventeen percent work in an environment where they are not encountering direct patient contact, perhaps serving as administrators, educators, orTable 2-l-Geographic Concentration ofSurvey RespondentsState Number (percent) California . . . . . . 63(1 5) New York . . . . . . 47(1 1) Pennsylvania . . . . . .25( 6)New Jersey . . . . . .24( 6)Illinois. . . . . . . .19( 5)Total . . . . . . 178 (43)SOURCE: Office of Technology Assessment, 1992.Table 2-2Primary Work SettingNumber (percent)University medical center. . . .151 (36) Private hospital or medical facility . .150(36)Public health department. . . .22( 5)Health maintenance organization. . .15( 4)College or university . . . .14( 3)Private group practice . . . .11 (3)Free-standing clinic . . . . .10( 2)Commercial laboratory . . . .9 (2)Other . . . . . . . .31 (7)SOURCE: Office of Technology Assessment, 1992.researchers. The primary work settings for all respondents are presented in table 2-2. Most counselors and nurses are employed in a university medical center (36 percent) or a private hospital ormedical facility (36 percent). The remainder work ina variety of settings, such as public health departments, health maintenance organizations, collegesor universities, private group practices, free standingclinics, or commercial laboratories. Again, thesedata are consistent with the data collected by NSGCon a biennial basis for its professional status survey(8).Centers of expertise in clinical genetics tend to belocated at large urban medical centers, often with a teaching mission. The work location and setting of the survey population reflect that tendency. Respondents are most likely to work in a metropolitanor urban setting (58 percent) (figure 2-2). Counselorsand nurses in genetics are less likely to be found working in rural settings. Counselors tend to work with M.D. geneticists, Ph.D. geneticists, other ge-netic counselors, and a variety of support staff. Mostrural centers are unable to support this level of professional personnel and often rely on regional service areas. Five percent of respondents reported working in a regional genetics area.Respondents spend nearly two-thirds (65 percent)of their work weekabout 26 hours per week-on patient activities, whether direct patient contact

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8 l Genetic Counseling and Cystic Fibrosis Carrier Screening: Results of a SurveyFigure 2-2Primary Service Areas of RespondentsMetropolitan/Urban 8?40SOURCE: Office of Technology Assessment, 1992.Suburban (e.g., intake or counseling) or indirect (e.g., written communication, scheduling, and management of referrals) (table 2-3). An additional day is spent onadministrative procedures. This leaves little time forother activities such as educating other health professionals or the general public. On average,counselors and nurses in genetics spend little time onpublic education. Fifty percent report spending no time on this activity, while 26 percent report spending, on average, an hour a week on public education (figure 2-3). Individual counseling sessions are time and labor intensive and are the primary format for delivering genetic information (table 2-4). Respondents report that they seldom if ever rely on group counseling (67 percent) or videotape with counseling (76 percent). On average, each genetic counselor and nurse ingenetics saw 482 patients in 1990. Averages do not,however, speak to the great variability among practices. Responses ranged from 10 to 2,300 clients. Counselors and nurses providing prenatalTable 2-3-Average Weekly Schedule of Genetic Counselor or Nurse in GeneticsFigure 2-3Average Hours Spent Per Weekon Public Education I50504 II26 ---10I --3. . .. .. .. .. .. .. .. .. . . . o 2 3 4 5 Numbers of hours per weekSOURCE: Office of Technology Assessment, 1992.diagnosis and followup for elevated maternal serumalpha-fetoprotein (MSAFP) screening tend to havemore clients.In routine genetic counseling, the genetics spe-cialist elicits the reasons for testing or screening anddiscusses the implications of possible outcomes. The counselor prepares the individual for bothpositive and negative test results. A genetic counsel-ing session is also the time to discuss risk reduction strategies, irrelevant, and the nature and severity of the disorder for which the test is being done. One task of the genetics professional is to communicate risks to the client-a job not easily performed. Themore complex the information, or the more emotion-ally laden, the more time might be required. Surveyrespondents estimate that the time needed to conduct routine prenatal counseling is 1 hour. Counseling forTable 2-4-Formats for Genetic CounselingActivity Hours per week Predominant response (%) Direct patient contact . . . . . .15indirect patient activities. . . . . .11Administration/management . . . .7Educating health professionals . . . .3Research . . . . . . . .2Educating the general public. . . . .1Marketing/business . . . . . .1individual counseling sessions Almost always (84) Group counseling . . . Seldom if ever (67) Videotape alone . . . Seldom if ever (98) Videotape with counseling . Seldom if ever (76) Written educational materials. .Very often(24)Slide-tape . . . . Seldom if ever (88) Interactive computer. . . Seldom if ever (97)SOURCE: Office of Technology Assessment, 1992. SOURCE: Office of Technology Assessment, 1992.

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Chapter 2-Providers, Clientele, and Genetic Services l 9newly diagnosed genetic disorders in newborns, children, or adults takes more time and more visits. Carrier testing for families with a positive familyhistory for CF was estimated to take, on average, twovisits involving more than 1 hour each. Counseling for CF carrier screening, with no family history,however, was estimated to take one visit of less thanan hour. The need for sufficient and appropriate pretest education and post-test counseling is discussed in depth in the full OTA report (10).GENETICS CLIENTELEGenetic counselors and nurses in genetics work ina variety of settings and often the setting in which they work dictates the types of clients they encounter. For example, working in a department of obstetrics and gynecology is likely to mean that themajority of ones clients are pregnant or undergoing family planning prior to pregnancy. Employment in a department of pediatrics or a childrens hospitalmeans that most clients are likely to be children andtheir families. Some counselors work in specialty clinics, such as cranio-facial clinics or sickle cell screening centers. Thus, their clientele are morelikely to be adult or African American, respectively. The OTA survey results are reported in the aggregateand fail to illustrate that some practitioners work inspecialized settings, often with one type of clientele.The majority of individuals seen by genetic counselors and nurses in genetics are Caucasian (70 percent) (figure 2-4). Respondents report an ethnic and racial breakdown that is reflective of nationalpopulation averages. For example, approximately 15percent of genetics clientele are reported as AfricanAmerican; this minority group represents 12 percentof the U.S. population. These data do not provide information, however, about equitable allocation ofgenetic services locally or regionally. African Amer-icans or Asian Americans might find genetic services accessible in one city or one region but not in another. Genetics services in cities with large minority populations might be more likely to hirehealth care providers with language or cultural skillssuitable to certain populations. Ninety-two percent of genetics clientele are English speaking. As mentioned earlier, 13 percent of genetic counselors and nurses reported fluency in alanguage other than English, but no effort was madeby OTA to correlate provider fluency with clienteleneeds.Figure 2-4Racial/Ethnic Background of Clinical Genetics ClienteleAfrican American 1 15%surname10%Asian American 4% Native American 1 %SOURCE: Office of Technology Assessment, 1992,A variety of age groups are seen, but adults ofreproductive age comprise 70 percent of the average clinic clientele. The second largest group of individ-uals seen are children (11 percent). Infants and neonates collectively comprise 14 percent of genetics clientele (figure 2-5).Most of the adults of reproductive age are seen forprenatal diagnosis (figure 2-6), most likely for advanced maternal age. Prenatal genetics patients were reported as being seen very often or almost always by nearly two-thirds of respondents (figure 2-6). Clearly, prenatal diagnosis is a primary reason for individuals to have contact with the clinical genetics setting. Respondents also reported thatFigure 2-5Age Distribution of Genetics ClienteleNeonatal7%Infants ildren1% Adolescents4% Adults of postreproductive age reproductive age SOURCE: Office of Technology Assessment,1992.297-911 0 92 2

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10 l Genetic Counseling and Cystic Fibrosis Carrier Screening: Results of a Survey . \ \,\, \,\, o. , . \ , ,. , . . . , .,,,.,.,,,,,,,,,,,,,.,,,.,.,., /, / .., . . ,. f.*.,.,.,.,.0 . . . . . . I I 0 00 000 000 I ,,.,.,.,,,,,,,,,,,,,.,,, .,,,.,,,,,,,,,.,.,.,.,.,., .,,,.,,,.,.,.,.,,,.,,,.,.,.,.,,,,,.,.,.,.,.,.,,,.,.,.,,,,, ,,,,.,.,.,.,.,.,,,.,.,.,.,.,., . . . ,,,,.,,,.,.,.,.,.,,,,,,,.,.,.,,,.,.,.,,,.,...,.,.,.,,,,,,,,,. ,.,.,.,.,.,,,,,.,.,,..,.,, ,,.,,,,,,,,,,..,.,.,., ,,,,,,,,,,.........,.,,.,,, .,.,.,,,,,.,.,.,.,..,,,,.,.,. I 00 00o110 0 0 0 0 , , , , -. . . . . . . # , # , , , , , ,. . . . . , , , , , , ,. . . ?,/,/, ./, ?..,/,?,/,/ , , , , , , , ,. . . ., , , , , , , , . . . . . . . ,. . . . . ,

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Chapter 2-Providers, Clientele, and Genetic Services l 11pregnant women receiving followup counseling for abnormal MSAFP results often (27 percent) or very often (31 percent) are apart of their clientele (figure 2-6). Individuals seeking carrier screening for avariety of genetic disorders, such as those describedin table 2-5, seldom (22 percent) or sometimes (50 percent) comprise the clientele in genetics clinics (figure 2-6). Cystic fibrosis was reported mostfrequently as the disease for which carrier screeningor testing is offered (table 2-5), and a majority ofrespondents (62 percent) report they have seen morethan 100 clients for CF-related reasons in 1990(figure 2-7).FEES AND THIRD-PARTY COVERAGEHow expensive are genetic services and will insurers pay for them? How do third-party payers decide what is medically indicated and, therefore, should be covered? Many of these issues are addressed in the full OTA report (10) as well as theBackground Paper, Genetic Tests and Health Insur-ance-Results of a Survey (11). In this survey of genetic counselors and nurses, OTA obtained information about the fees charged by providers for avariety of genetic services, including those related toCF and their experiences with third-party coverage. Costs of services and the availability of third-partycoverage will be crucial to the rate and magnitude atwhich services will be used. This is particularly relevant to the debate about CF carrier screening as the procedure is relatively new, is counter to most insurers policies against paying for screening, and could involve potentially large numbers of people.For many years, genetic counselors have faced the problem that few third-party insurers will reimbursefor counseling services unless performed by aphysician. The costs of counseling are reimbursed asTable 2-5-Most Common Diseases for Which CarrierScreening/Testing Is Offered1.2.3.4. 5. 6. 7. 8.(Ranked by frequency of response)Cystic fibrosisTay Sachs disease Sickle cell anemiaDuchenne muscular dystrophyThalassemia HemophiliaHemoglobinopathiesFragile X syndromeSOURCE: Office of Technology Assessment, 1992.Figure 2-7Number of Cystic Fibrosis Patients or Families Seen in Genetics Units in 1990I6260 50 40 30 2010 0-10 11-20 21-30 31-40 41-5091-100 +100Number of patientsSOURCE: Office of Technology Assessment, 1992.general medical consultation fees or absorbed as partof costs on research grants (9).Fees for Genetic ServicesGenetic counseling can be provided alone or in conjunction with diagnostic procedures. Most survey respondents work in large university or private medical centers where billing departments are often quite separate and distinct from the various clinical departments. Fees are coded and processed independently. This might explain why a majority of respondents did not know whether certain genetic services were reimbursable and, in some cases, did not even know the fee schedule for basic genetic services (table 2-6). For those who knew the fee schedule for genetic services, general genetic counseling averaged $80 per session. The range was $0Table 2-6-Average Fees and Knowledge of Fees for Genetic ServicesPercent respondents uncertain ServiceFeeof feeGeneral genetic counseling . . .$80 45Genetic counseling for CF with apositive family history . . . .$112 54Genetic counseling for CF with a negative family history. . . .$105 68Routine metabolic screen . . .$157 70Routine cytogenetic analysis. . . .$425 50DNA analysis for CF . . . .$235 66SOURCE: Office of Technology Assessment, 1992.

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12 l Genetic Counseling and Cystic Fibrosis Carrier Screening: Results of a SurveyTable 2-7Fees for General CounselingFeePercent response $0 to 50.. . . . . . . . .$51 to loo . . . . . . . 31 $101 to 150 . . . . . . . 25$151 to 200 . . . . . . . .2$201 to 250 . . . . . . . .7$251 to 300. . . . . . . .$301 to 350 . . . . . . . 38SOURCE:Office of TechnologyAssessmentj 1992.to $350 (table 2-7). The fee for genetic counseling for individuals with a family history of CF was not significantly different from the fee that would be charged to individuals requesting the same services with a negative history for CF($112 versus $105). In the summ er of 1991, the average fee for DNAanalysis for CF was $235 although spring 1992 datacollected separately by OTA found an average cost of $170 per sample.Third-Party CoverageRespondents reported that most of their clients arecovered by some type of health insurance. Two percent said that their patients seldom if ever have health care coverage, whereas 63 percent reportedthat their clients very often or always have coverage(figure 2-8). Commercial insurance, health maintenance organizations, or managed care programs comprise over half of the coverage (figure 2-9). Medicaid (21 percent) and Blue Cross/Blue Shield plans (17 percent) also cover genetics clients. Four percent of clients have no insurance and 3 percentare indigent.With regard to coverage of genetic counseling services accompanying DNA-based tests to deter-mine CF carrier status, respondents reported a higherlikelihood of coverage if there is a family history of CF than if there is no family history (figure 2-10). This result was confirmed by OTAs survey of health insurers, which found health insurers rarely reimburse individuals for CF carrier tests in the absence of a family history (11). OTA attempted to ascertain whether individuals who avail themselves of genetic tests subsequently have difficulty obtaining or retaining health insurance. The survey asked for reported occurrences for genetic tests, generally, not just carrier tests for CF or other disorders.2 OTA asked:Figure 2-8-Health Care Coverage for Genetics Clientele40330 Seldom if ever Sometimes Often Very often Always or almost alwaysSOURCE: Office of Technology Assessment, 1992.Figure 2-9-General Types of Health Care Coverage for Genetics ClienteleI Commercial Medicaid HMO or 17%managed care 22ASOURCE: Office of Technology Assessment, 1992.Have any of your patients experienced difficultiesin obtaining or retaining health insurance coverage as a result of genetic testing? If yes, please providedetails.Approximately four-fifths (347) of the 431 respondents to OTAs inquiry currently perform genetic counseling. Fifty respondents (14 percent) reported they had clients who had experienced difficulties obtaining or retaining health care coverof OTA asked respondents to speculate about accepting applicants with certain genetic (11).

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Chapter 2-Providers, Clientele, and Genetic Services 13Figure 2-10-Third-Part y Reimbursement for General Genetic Counseling and Counseling Specifically for Cystic Fibrosis302725 16 2019Seldom Sometimes OftenVery oftenAlmostif ever coveredcovered covered alwayscoveredcovered General genetic With no family With familycounselinghistory of CF history of CFSOURCE: Office of Technology Assessment, 1992.age as a result of genetic testing (table 2-8). Because some respondents described more than one case, the number of affirmative answers understates the actualnumber of cases. Examin ation of the qualitativeresponses, some of which are presented in table 2-9,reveals affirmative responses represent, at minimum, 68 individual cases. (Where the term patients was used with specifics not described, a single event was recorded.)It is important to emphasize that most of the casesrevealed through the OTA survey do not involve recessive disorders and carrier screening for condi-tions like CF And while one assumption might have been that health care coverage for CF carriers wouldnot be an issue because the individuals have no symptoms of the disorder, OTAs survey of health insurers reveals that a few respondents would require a waiting period or deny coverage for CFcarriers (10,1 1).Test results for some conditions where positive results led to reported difficulties-such as forHuntington disease, adult polycystic kidney disease,and Marfan syndrome-were cited by more than one respondent. In addition to affirmative answers, several respondents reported that although they had no direct experience with a patients difficulty inTable 2-8-Difficulties in Obtaining or Retaining Health Insurance After Genetic TestsQuestion: Have any of your patients experienced difficulties in obtaining or retaining health insurance coverage as aresult of genetic testing? Number (percent)No . . . . . . .28181Yes . . . . . .5014No answer . . . . .165SOURCE: Office of Technology Assessment, 1992.obtaining or retaining health care coverage, they hadclients who feared their coverage would be dropped if they requested payment for tests from insurers. One respondent commented that greater than 80 percent of her clients who test for Huntington disease self-pay. Similarly, others with no direct experience said they often advise patients not to request reimbursement for a test so that an insurer would not learn that testing had occurred. One counselor offered the information that a patient had refused testing for adult polycystic kidney disease because of concern over health insurance. Anotherrespondent reported that a patient with a CF-affectedchild had been dropped by one insurance companyand would not consider prenatal testing in the future for fear her current insurer would not cover the childshould she decide to continue the pregnancy. The data collected through this question permitneither extrapolation about the total number of casesthat have occurred in the United States nor speculation about any trends. OTA also did not attempt to ascertain whether patients had challenged-or were challenging-insurers rulings. Thus, OTA cannot determine whether some of the disputes reported in table 2-9 were resolved fully in favor of the consumer because the initial judgment was deemed improper or illegal. Some cases, for example, reported a fetus or newborn had tested positive andthe policy cancelled. In all 50 States and the District of Columbia, insurers must cover (or offer the optionto include) a newborn child if a valid insurance contract for the parent exists. However, whether theinsurance company can deny specific benefits for thenewborn by evoking the preexisting conditionclause generally contained in all insurance contracts is unclear.In presenting table 2-9, OTA does not judge the validity-positively or negatively-of the claim. Some cases might have been settled in favor of the individual. Others might have been cases where an

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14 l Genetic Counseling and Cystic Fibrosis Carrier Screening: Results of a Survey Table 2-9-Case Descriptions of Genetic Testing and Health Insurance Problems a Positive test for adult polycystic kidney disease resulted in canceled policy or increased rate for company of newly diagnosed individual. Positive test for Huntington disease resulted in canceled policy or being denied coverage through a health maintenance organization. Positive test for neurofibromatosis resulted in canceled policy. Positive test for Marfan syndrome resulted in canceled policy. Positive test for Down syndrome resulted in canceled policy or increased rate. Positive test for alpha-1 -antitrypsin defined as preexisting condition; therapy related to rendition not covered. Positive test for Fabry disease resulted in canceled policy. Woman with balanced translocation excluded from future maternity coverage. Positive Fragile X carrier status and subsequent job change resulted in no coverage. After prenatal diagnosis of hemophilia-affected fetus, coverage denied due to preexisting condition clause. Denied coverage or encountered difficulty retaining coverage after birth of infant with phenylketonuria. Woman diagnosed with Turners syndrome denied coverage for cardiac status based on karyotype. Normal electrocardiogram failed to satisfy company. Family with previous Meckel-Gruber fetus denied coverage in subsequent applications despite using prenatal diagnosis and therapeutic abortion. Mother tested positive as carrier for severe hemophilia. Prenatal diagnosis revealed affected boy; not revered as preexisting rendition when pregnancy carried to term. After a test revealed that a woman was a balanced translocation carrier, she was initially denied coverage under spouses insurance because of risk of unbalanced conception. Subsequently overturned. Woman without prior knowledge that she was an obligate carrier for X-linked adrenoleukodystrophy found out she was a carrier. She had two sons, both of whom were healthy, but each at 50 percent risk. Testing was done so they could be put on an experimental diet to prevent problems that can arise from midto late childhood or early adulthood. One boy tested positive. The familys private pay policy (Blue Cross/Blue Shield) is attempting to disqualify the family for failing to report the family history under preexisting conditions. After birth of child with CF unable to insure unaffected siblings or themselves. alggl OTA survey of genetic counselors and nurses in genetics. Not all cases, or multiple cases involving same disorder, listed. SOURCE: Office of Technology Assessment, 1992. applicant attempted to select against an insurer by misrepresenting his or her health history, which would have been resolved against the individual. In 1991, at least 50 genetic counselors or nurses in clinical practice knew of at least 68 actual incidents where their own patients reported difficulties with health insurance due to genetic tests. OTA estimates, based on the average number of patients directly counseled, that genetic counselors and nurses responding to the survey collectively saw about 110,600 individuals in 1990. However, OTA did not advise respondents to limit descriptions of clients insurance difficulty to 1990. Thus, it is unlikely that all reported cases occurred in 1990; assuming all cases occurred in 1990 means the 68 cases represent 0.06 percent of patients seen by respondents. Critics question whether the data-especially the qualitative descriptionsmerely represent more anecdotal stories that unfairly present one side of the story and for which no response can be developed. Skeptics point out that some of the cases might fall into the gray area of whether exclusion or increased rates resulted because an adverse medical condition was revealed through a diagnostic test that just happened to be genetic. The border between what conditions are genetic or not is blurred, however, and will become increasingly diffuse. Because geneticbased predictive testing promises to have a profound impact on clinical medicine-and because access to medical care is inextricably linked to private health insurance in this country-these cases underscore certain policy dilemmas arising from the increased availability of genetic assays. SUMMARY Although genetic counselors and nurses in genetics work in a variety of settings, they are concentrated in metropolitan medical centers on the West coast or Northeast region. States with a large proportion of rural residents are less likely to be served. The clientele served, in the aggregate, tend to be representative of the national averages for majority and minority groups, although no effort was made by OTA to match racial and ethnic data with regions, cities, or localities. Most genetic counselors have a masters degree and are either certified or eligible for professional

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Chapter 2-Providers, Clientele, and Genetic Services l 15 certification. They spend most of their work week seeing or talking with clients. Less time is spent on administration and research, and even less on professional and public education. Seventy percent of the genetics clientele is comprised of adults of reproductive age suggesting the strong influence of prenatal diagnosis as a primary genetics service. Respondents report that their counseling services are frequently not covered by third parties, even when medically indicated. OTAs survey reports consumers can experience difficulties in obtaining or retaining health care coverage after genetic tests. Because genetic-based predictive testing promises to have a profound impact on clinical medicine-and because access to medical care is inextricably linked to private health insurance in this country-these cases underscore certain policy dilemmas arising from the increased availability of genetic assays. 4. 5. 6. 7. 8. 9. 10. 1. 2. 3. CHAPTER 2 REFERENCES Boyle, J.M., Schulman, Ronca & Bucuvalas, Inc., Silver Spring, MD, personal communications July 11 1991, August 1992. Fibison, W.J., The Nursing Role in the Delivery of Genetic Services, Issues in Health Care of Women 4:1-15, 1983. 12. Forsman, I., Education of Nurses in Genetics, American Journal of Human Genetics 43;552-558, 1988. Jones, S.L., Decision Making in Clinical Genetics: Ethical Implications for Perinatal Practice, JournuZ of Perinatal and Neonatal Nursing 1:11-23, 1988. Jones, S.L., Genetics & IVF Institute, Fairfax, VA, personal communication, December 1991. Kanuck, L., and Berenson, C., Mail Surveys and Response Rates: A Literature Review, Journal of Marketing Research 12;440-454, 1975. National Society of Genetic Counselors, Wallingford, PA, personal communication, June 1991. National Society of Genetic Counselors, Report to Membership: 1992 Professional Status Survey, Perspectives in Genetic Counseling, newsletter of the National Society of Genetic Counselors, Inc., summer 1992. U.S. Congress, Office of Technology Assessment, Cystic Fibrosis, Genetic Screening, and Insurance, transcript of workshop proceedings, Feb. 1, 1991. U.S. Congress, Office of Technology Assessment, Cystic Fibrosis and DNA Tests: Implications of Carrier Screening, OTA-BA-532 (Washington, DC: U.S. Government Printing Office, August 1992). U.S. Congress, Office of Twhnology Assessment, Genetic Tests and Health Insurance+tesults of a Survey, OTA-BP-BA-98 (Washington, DC: U.S. Government Printing OffIce, October 1992). Walker, A. P., Scott, J.A., Biesecker, B. B., et al., Report of the 1989 Asilomar Meeting on Education in Genetic Counseling, American Journal ofHuman Genetics 46:1223-1230, 1990.

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Chapter 3 Cystic Fibrosis Carrier Screening: Policies and Practices Prospects of routine cystic fibrosis CF carrier screening polarize people. Everyone agrees that persons with a family history of CF should have the opportunity to avail themselves of CF mutation analysis, yet controversy swirls around using the same test in the general population. This polarization is illustrated in the written comments of two survey participants. NO to widespread screening! Must be close to 100 percent detection for all CF mutations before it can even be considered. Lets go with screening! I cant believe we are not halfday through a pilot program by mid 1991. As described in the full OTA report (18), proponents of a measured approach to CF carrier screening express concern about several issues that might be raised if CF carrier screening becomes routine, such as the use of genetic information by insurance companies to set rates or deny coverage, and concerns that market pressures will drive widespread use of tests before the potential for discrimination or stigmatization by other individuals or institutions is assessed. Also expressed are questions about the adequacy of quality assurance for DNA diagnostic facilities, personnel, and the tests themselves. Still others also wonder whether the current number of health care professionals in genetics can handle a swell of CF carrier screening cases, let alone cases of other genetic conditions arising from increased knowledge from the Human Genome Project. Finally, the extraordinary tensions in the United States about abortion affect discussions about CF carrier testing and screening. In s ummer 1991, OTA asked genetic counselors and nurses in genetics to provide data regarding their experiences concerning CF carrier screening as a means to judge the validity of these concerns. The questionnaire was designed to gather data on the frequency of DNA analysis for CF carrier status and trends over time, clinic policies regarding CF carrier screening, counseling and clinical practices regarding CF carrier testing and screening, and sources influencing the development of, and policies and procedures related to, CF mutation analysis. Survey participants were also asked their opinions about who should conduct carrier screening, in what settings, and on what target population(s). Respondents were encouraged to rank the most important issues to be addressed before embarking on a large-scale screening program. The data in this chapter are specific to CF carrier screening. Data regarding third-party reimbursement for DNA-based tests are presented in chapter 2, along with general demographic data concerning the survey respondents and their clientele and clinical settings. POLICIES AND PRACTICES, SUMMER 1991 Survey participants were asked to consider three issues. First, what is their opinion or the policy of their institution about the appropriateness of CF carrier screening at this time? Second, what are the current logistics of providing DNA-based tests for CF carrier status-i.e., once a decision had been made to offer CF mutation analysis, which mutations are analyzed, and how are those individuals to be tested identified or contacted? Third, survey participants were asked to estimate whether requests for DNA-based tests for CF had changed since the tests development in 1989. Policies on Cystic Fibrosis Carrier Screening Currently, it is standard practice to offer CF carrier tests to individuals who have a positive family history of CF (6,16,18). An unaffected sibling of an individual with CF has a 2 in 3 likelihood of being a CF carrier. A consanguineous uncle or aunt of an individual with CF has a 1 in 2 likelihood of being a carrier. A first cousin of an individual with CF has a 1 in 4 likelihood of being a carrier (table 3-l). As of the s ummer of 1991, most genetic counselors and nurses in genetics did not offer unsolicited CF mutation assays to individuals with a negative family history. A large majority of survey respondents use medical journals and other professional sources to obtain information regarding new advances in human genetics (table 3-2), and the American Society of Human Genetics (ASHG) and the National Institutes of Health (NIH) published policy documents in 1990 discouraging CF carrier

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18 l Genetic Counseling and Cystic Fibrosis Carrier Screening: Results of a Survey Table 3-lA Priori Carrier Risks for Cystic Fibrosis Negative family history Caucasian. . . . . 1 in 25 (4%) African American . . . 1 in 60 to 65 (1.5 to 1.7%) Asian American. . . . 1 in 150 (0.7%) Hispanic American. . . . 1 in 46 (2.2%) Positive family history Parent of child with CF . . 1 in 1 (100%) Sibling with CF . . . 2 in 3 (67%) Aunt or uncle with CF a . . 1 in 3 (33%) First cousin with CF . . . 1 in 4 (25%) Niece/nephew with CF . . 1 in 2 (50%) a Consanguineous. SOURCE: Office of Technology Assessment, 1992. Table 3-2-Sources of Information About New Advances in Human Genetics Percent Human genetics indicating yes Medical journals . . . . . 96 Professional colleagues . . . . 94 National inferences . . . . 83 American Society of Human Genetics . 82 National Society of Genetic Counselors 80 State or regional conferences . . 71 Grand rounds . . . . . . 44 Lay press . . . . . . . 37 Continuing education courses . . 35 Literature from biotechnology companies or commercial firms. . . . . 35 Other . . . . . . . . 8 SOURCE: Office of Technology Assessment, 1992. screening (6,16). 1 Seventy-six percent of respondents stated that they were familiar with the 1990 ASHG statement. Thirty-five percent were familiar with the NIH statement. OTAs survey of genetic counselors and nurses revealed that 53 percent of respondents believe that CF carrier tests should only be offered to individuals with a positive family history of CF and not to those with a negative family history. Twenty-one percent felt that CF carrier tests should be offered to individuals with no family history. The most frequently cited reasons for making tests available to individuals regardless of family history were to reduce anxiety or increase patient autonomy. In the words of one counselor, DNA screening is a personal issue, different in every case. What one person or family feels may be quite different from that of another person or family in any given genetic disorder with any given family history. Twenty-six percent of respondents were uncertain as to whether they should provide CF carrier screening where family history is negative. When asked about their likelihood of introducing the topic of CF carrier tests during a counseling session, 82 percent of respondents stated that they would seldom, if ever, do so to all patients or families (table 3-3). Seventy-three percent would seldom, if ever, discuss it with pregnant women seeking prenatal diagnosis unless there was a family history of CF in which case, 90 percent would almost always bring it up during counseling. When asked whether their institution or clinic had a specific policy regarding CF carrier screening, 33 percent of genetic counselors and nurses responded in the affirmative. Of those responses, 70 percent stated that it is the policy of their clinic or organization to offer CF carrier tests only to those with a positive family history (table 3-4). The overall lack of policies for CF carrier screening apparently stems from the fact that, in general, explicit and official policies for clinical practices were not routine at the majority of facilities. When asked whether their group or unit had Table 3-3-Likelihood of Introducing the Topic of DNA Testing for Cystic Fibrosis Predominant Patient population response (Percent) All patients/families. . . Seldom if ever (82) Pregnant women seeking prenatal diagnosis . . . . Seldom if ever (73) Coupies/individuals with a family history of CF . . . Almost always (90) Caucasian coupies/individuals with a negative history of CF Seldom if ever (65) individuals/famiiies who inquire about CF . . . . Almost always (80) Selected coupies/individuals . Seldom if ever (72) SOURCE: Office of Technology Assessment, 1992. Table 3-4-Specific Policies Regarding DNA Testing for Cystic Fibrosis Policy Percent Offer to all regardless of family history . . . 14 Offer only to those with a positive family history . 70 Provide to those with no family history upon request if informed consent is obtained . . . . 16 SOURCE: Office of Technology Assessment, 1992, 1 III 1992, ASHGS lead~ship issued a revised swtenlent that CF mutation analysis is not recommended fOr th05e without a ftily hiStOv of m, but it has not yet ken published (1,18).

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Chapter Cystic Fibrosis Carrier Screening: Policies and Practices 19official policies and procedures for other issues in genetics, 21 percent reported they have policies regarding DNA storage, 42 percent have policies in place concerning prenatal diagnosis for sex selection, 37 percent have policies regarding cases of nonpaternity, and 28 percent adhere to policies regarding confidentiality and Huntington diseasetesting.Criteria for Cystic Fibrosis Carrier ScreeningSixty-five percent of survey participants felt strongly that there is an optimum rate of detection that should be reached before they would feel comfortable offering CF carrier screening, as compared to 14 percent who felt there is not and 21 percent who were uncertain. Of those who felt there is an optimum rate of detection, nearly half (46 percent) said that 95 percent test sensitivity should be required before proceeding with widespreadscreening. Twenty-five percent believe test sensitivity should be even higher, with 4 percent stating thatit should be 100 percent (figure 3-l). However, survey respondents ranked the availability of adequate counseling and an adequatesystem of referral for individuals who test positive asslightly more important criteria for CF carrierscreening than test sensitivity (table 3-5). Guaranteeof informed consent also was mentioned as necessary for implementation of large-scale CF carrierscreening.Perhaps the point on which there was greatest consensus among the respondents is on the issue of autonomy and choice in screening. There are no mandatory genetic screening programs of adult populations in the United States. Ninety-nine per-cent of survey participants responded that CF carrier screening should be voluntary and never mandatory.Practices Regarding DNA-Based Cystic Fibrosis Carrier TestsWhen asked about the frequency of requests for DNA testing or screening for CF carrier status during the 6-month period from January to June1991, most respondents reported occasional requests (figure 3-2). When asked to compare this time periodwith the previous 2 years, nearly half indicated a small increase in the number of requests and a quarter noted a large increase in requests (figure 3-3). The survey did not distinguish whether the requests were carrier tests for individuals known toFigure 3-lOpinions on Optimal Rate of Detection60,I4675% 80% 85% 90% 95% 97% 98% 99% 100% Optimal test sensitivitySOURCE: Office of Technology Assessment, 1992.Table 3-5-Minimal Criteria for Cystic Fibrosis Carrier Screening ProtocolQuestion: What do you feel should be the minimum criteria for CFcarrier screening protocol)? CriteriaPercentaProvision of adequate counseling . . . . 40 Adequate system of referral in place . . . 37 Improved test sensitivity. . . . . . 35 Guarantee of informed consent . . . . 32 Availability of educational materials. . . . 18 Only offer to families with a positive history of CF 15 Must be voluntary. . . . . . . 14 Reasonable cost or payment . . . . 12 Protection of confidentiality . . . . . 12 not add to 100; respondents could reply with answers.SOURCE: Office of Technology Assessment, 1992.be at risk by virtue of family history or carrierscreens for individuals with no known family historyof CF Although 55 percent of survey participants responded that a CF treatment center exists at their institution, 86 percent reported that they do not provide genetic counseling through that facility. Several respondents noted that this is the choice of the CF treatment provider, not necessarily the genetics unit. Because OTA did not survey CF treatment centers, it is not known to what extent CF families are informed of, offered, or request carrier testing. The data do show, however, that most families who have a child with CF are not routinely

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20 l Genetic Counseling and Cystic Fibrosis Carrier Screening: Results of a SurveyFigure 3-2Frequency of Requests for Cystic Fibrosis Carrier Screening/Testing, January-June 199160.5(-) -48 I100 Never Occasionally Very frequently Rarely FrequentlySOURCE: Office of Technology Assessment, 1992.Figure 3-3-Comparison of Requests for cystic FibrosisCarrier Screening/Testing Between January-June 1991and Past 2 Years46 A large decrease No change A small decrease A small increaseincreaseSOURCE: Office of Technology Assessment, 1992.seen in genetics service settings, and few counselorshave routine contact with CF families. Encouraging known carriers to notify consanguineous relatives (e.g., siblings and first cousins) provides economic and pragmatic benefits because it can detect a larger percentage of at-risk couples(18); testing those known to be at higher risk becauseof family history is more effective than screening those with unknown risk. In reality, complex psychological factors enter when family members of individuals with CF contemplate screening, and it cannot be assumed that all will want to be tested. For this type of carrier identification to work, those providing health care and counseling to CF families will have to actively participate in referrals of relatives to genetics centers, an uncommon practice, according to OTAs data. Fewer than 10 percent of respondents reported contacting previously identified CF families with whom they had had contact about the availability of CF mutationanalysis.For those respondents whose institutions are engaged in CF carrier testing or screening, direct DNA mutation analysis is the most common approach (table 3-6). In the recent past, the sensitivityof the carrier test was limited to the DF508 mutation.All respondents involved in analyzing CF carrierstatus assay for the DF508 mutation. But roughly 74percent indicated that they also test for at least oneother mutation, most commonly four others, G551D,R553X, G542X, and N1303K (table 3-7). At thetime the survey was done, the mutation that accountsfor 60 percent of CF mutations in Jewish persons ofTable 3-6Types of Genetic Analyses Provided forCystic Fibrosis Screening/TestingProcedure Percent responseDirect mutation analysis. . . . .67Prenatal DNA analysis. . . . . .63DNA linkage analysis . . . . .61DNA haplotyping . . . . . .56 Staging of studies . . . . . .37DNA banking . . . . . . .31Fetal intestinal enzyme analysis . . 28SOURCE: Office of Technology Assessment, 1992.Table 3-7-Cystic Fibrosis MutationsRoutinely AnalyzedMutation Percent responseDF508 . . . . . . . .100 G551D . . . . . . . .77R553X . . . . . . . 76G542X . . . . . . . .71N1303K . . . . . . . .70 Other . . . . . . . . 79SOURCE: Office of Technology Assessment, 1992.

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Chapter 3-Cystic Fibrosis Carrier Screening: Policies and Practices l 21Central and Eastern European descent (Ashkenazic Jews), W1282X, had not been found.2Respondents report an almost even split betweencommercial and university-based laboratories as thefacility performing their CF mutation assays (45 percent and 48 percent, respectively). Most centers send the sample offsite (76 percent), frequently to a laboratory greater than 150 miles away. Finally, although the need for professional and public education was cited as critical for theimplementation of widespread carrier screening, fewgenetic counselors and nurses in genetics reported spending professional time engaged in either activity. For those respondents who do, an average of 3 hours per week devoted to educating health profes-sionals and 1 hour per week on educating the general public was reported (ch. 2). For CF carrier screening,specifically, 8 percent of genetic counselors and nurses had developed, or were in the process of developing, educational materials relevant to DNA tests for CF mutation.PREFERRED STRATEGIES AND PROTOCOLSThe importance of informed consent, careful presentation of counseling, and confidentiality have long been recognized as essential components of genetic testing and screening (9). Respondents strongly agreed that genetic counseling shouldprecede DNA tests for CF carrier status regardless offamily history (figures 3-4 and 3-5). Geneticists,perhaps more than any other medical specialty, haveadvocated a nondirective approach to counseling and have a strong commitment to patient autonomy (3). Further, a history of concern exists about thedelivery of genetic information by health profession-als used to a more directive approach (7). This concern has been played out in the debate over maternal serum alpha-fetoprotein (MSAFP) screening and is a factor in the reluctance of the clinical genetics community to rush toward widespread screening for any disease (18). For example, as part of the debates surrounding MSAFP and CF carrier screening, concern has been voiced about informed consentin particular, that tests would be available to primary care practitioners who might incorporateFigure 3-4-Opinions Regarding Genetic Counseling of Individuals with a Positive Family History100 1I93 0 Strongly agree Undecided Strongly Agree Disagreedisagree Genetic counseling should precede DNA testing for CF when there is a positive family history.SOURCE: Office of Technology Assessment, 1992.Figure 3-5-Opinions Regarding Genetic Counselingof Individuals with a Negative Family History6050c 40308 20lo-0 84I 18 Strongly agree Undecided strongly Agree Disagreedisagree Genetic counseling should precede DNA testing for CF when there is a negative family history.SOURCE: Office of Technology Assessment, 1992. test sensitivity was 75 to 85 depending on race and most Commercial laboratories e DF508 and 6 to 12 additional mutations, and taken together these mutations comprise 85 to 90 percent of CF mutations in U.S.Caucasians (95 percent in Jews).297-911 0 92 3

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22 l Genetic Counseling and Cystic Fibrosis Carrier Screening: Results of a Surveythe assay into their practice without considering theinformed consent requirements usually adhered to ingenetics practices. Seventy-nine percent strongly agree that informed consent prior to CF carrier screening is a necessity (figure 3-6). In addition to informed consent, prescreening education for clients is imperative. Information regarding an individuals a priori risk, types of testsavailable, and uncertainties in risk assessment basedon screening results are important for potential screenees to understand. When asked if educational materials can provide adequate information aboutCF carrier screening, 44 percent disagreed or stronglydisagreed with that concept (figure 3-7).Who Should Provide Cystic Fibrosis Carrier Screening?Concern about the complex nature of some genetic information and the need in some cases for post-test counseling leads many human genetics professionals to advocate restricting CF carrier screening primarily to the human genetics community. Pretest education, felt many respondents, can be offered by a wide range of professionals (figure 3-8), but organizing CF carrier screening should beprovided by genetic specialists (table 3-8). Nearly 82Figure 3-6Opinions Regarding the Need for Informed Consent Prior to Cystic Fibrosis Carrier Screening 7913 Strongly agree Undecided strongly Agree DisagreedisagreeInformed consent prior to CF carrier screening is a necessity.SOURCE: Office of Technology Assessment, 1992.Figure 3-7-Opinions Regarding the Use of Educational Materials as a Source of Information About Cystic Fibrosis Carrier Screening 30 15 Io 7 28I Strongly agree Undecided Agree DisagreedisagreeEducational materials (culturally sensitive and understandable) can provide adequate information about CF carrier screening.SOURCE: Office of Technology Assessment, 1992.percent of the respondents surveyed by OTA said thehuman genetics community should be the primary organizer of CF carrier screening programs (table 3-8). Also mentioned were State or local healthdepartments (59 percent) and primary caregivers (27percent). Over 89 percent believed CF populationscreening should be provided in genetics centers, but59 percent thought CF carrier screening could alsobe provided in the primary care setting or organized,community-wide programs (53 percent) (table 3-9). Concern about the sometimes difficult nature of communicating risk information regarding CF even for experienced genetic centershas led somein the clinical genetics community to caution againstrapid movement to routine CF carrier screening (2). In the words of one respondent:Counseling should not be left to hurried family practitioners or OBs [obstetrician/gynecologists], who routinely spend less than 15 minutes with eachpatient.As noted in chapter 2, most counselors and nursesspend little to no time on professional education or general public education in schools and communities. Thus, the majority of people will rely on their primary care provider for preliminary, if not most,

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Chapter 3-Cystic Fibrosis Carrier Screening: Policies and Practices l 23 Table 3-8Preferred Organizations for lmplementation of Voluntary Cystic Fibrosis Carrier Screening Organization Yes No a (percent) Human genetics community . . 82 15 State or local health department. . 59 39 Voluntary health organizations . . 30 67 Primary caregivers . . . . 27 71 Medical societies . . . . 17 81 Federal Government . . . . 15 82 as per~nt gave no res~nse SOURCE: Office of Technology Assessment, 1992. Table 3-9-Preferred Sites for Cystic Fibrosis Carrier Screening Programs Site Yes No a (percent) Genetics centers . . . . 89 7 Primary care setting . . . . 59 37 Community-wide . . . . . 53 43 Public health department. . . . 48 49 Public schools . . . . . 14 83 Workplace . . . . . . 9 87 =qs per~nt gave no response SOURCE: Office of Technology Assessment, 1992. genetic information (18), and many survey respondents said primary care providers and public health departments should play an active role in educating the public about DNA tests for CF carrier status (figure 3-8). Health care provider and communitywide genetics education will become increasingly important, as will the interaction of genetic specialists with other health professionals and the public. Who Should Pay for Cystic Fibrosis Carrier Screening? When asked who should pay for screening, 80 percent of respondents ranked third parties as the primary source of payment (table 3-10). Self pay was ranked second, and employers ranked last. Additionally, some participants noted that if screening ever became mandatory, as in many State newborn screening programs, the State or Federal Government should be responsible for payment. Strategies for Screening Various Populations Two key considerations in deciding how routine CF carrier screening is best implemented are the clinical settings in which it will take place and the target populations. Delineation of a target group (or groups) determines other elements such as location, educational approach and tools, time, format, types of counseling, facilities, and publicity. The NIH statement on CF carrier screening emphasized the importance of preconceptional screening (16). Most pilot projects in the United Kingdom are directed at preconceptional populations (18). One program in Canada targets high school students (11). Newborn Screening Numerous newborn screening programs exist for genetic disorders such as sickle cell anemia and phenylketonuria. These are programs intended to screen for the presence of disease, although some can also detect the carrier status of the newborn. Using the immunoreactive trypsin assay, Wisconsin has performed statewide neonatal screening for CF disease since 1985, and primary care physicians have been cooperative in referring screened patients to designated CF centers for followup (14). But even newborn screening for CF disease is not without controversy. Evidence of heightened anxiety and disrupted maternal-infant bonding have been reported in cases of false-positive diagnoses (4). For at least two reasons, many believe that newborn screening is an inappropriate and inefficient mechanism for carrier detection. First, newborns determined to be carriers must be tracked through their reproductive years to ensure they are aware of their carrier status. Second, detection of newborn carriers might unnecessarily raise the anxiety level of parents. Thus, newborn screening for CF carrier status is not generally viewed as acceptable (15). This survey revealed that 33 percent of genetic counselors and nurses in genetics believed the newborn population would be an appropriate target group for widespread CF carrier screening (table 3-11). Adolescent Preconceptional Screening Some geneticists advocate carrier screening at the high-school level (11). A recent nationwide survey of American attitudes about, and knowledge of, genetic tests showed better knowledge and more positive attitudes in younger populations (17). Studies of pregnant women known to be carriers of a hemoglobinopathy gene have shown that age is a predictor of postcounseling knowledge-younger women (and adolescents as young as 12 years old) are more likely to understand genetic information (13). While not routinely done in the United States,

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24 Genetic Counseling and Cystic Fibrosis Carrier Screening: Results of a SurveYFigure 3-8-Extent to Which Various Groups Should Be Involved with Cystic Fibrosis Pretest EducationPrimary care providers35, I3130+I I252015lo5(-JJ--100200122Little toSome Moderate GreatAll orno extent extentextent extent almostallGenetic counselors770.2180.54 Little toSome Moderate GreatAll orno extent extentextent extent almostallNursesI 33 30 26 Little toSome Moderate Great orno extent extentextentextent almostallPublic health departments 3530-2828 0L20 0Little toSome Moderate GreatAll orno extent extentextent extent almostallGenetics programs 0.240 30 &o 1073Little toSome Moderate GreatAll orno extent extentextentextent almostallFamily planning clinics2626 0 Little toSome Moderate GreatAll orno extent extentextentextent almostall

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Chapter 3-Cystic Fibrosis Carrier Screening: Policies and Practices l 25Voluntary support groups oJII Little toSome Moderate GreatAll orno extent extentextentextent almostallLay press 40 c o 30 20 oLittle toSome Moderate GreatAll orno extent extentextent extent almostallSOURCE: Office of Technology Assessment, 1992.high-school screening programs have been conducted in Montreal, Canada for some time. For any disease where screening is done in childhood or adolescence, however, the benefits of such screening, including savings in resources or anxiety, must be balanced against the potential problems, such as the possibility that an adolescent will be falsely assigned to a low-risk group because of poor test sensitivity (thereby obviating further screening), or the possibility of psychosocial harm to the child as a result of identified carrier status (9). Adolescents were not considered an appropriatetarget by the genetic counselors and nurses surveyedSchools 36Little toSome Moderate GreatAll orno extent extentextent extent almostallTelevision o 36Little toSome Moderate GreatAll orno extent extentextent extent almostallby OTA (table 3-11). Less than one-fifth felt individuals ages 13 to 18 years should be screened; only 6 percent responded that children ages 2 through 12 years should be screened. AdultsPreconceptional or Prenatal? One debate surrounding CF carrier screening focuses on whether the goals are best accomplished by targeting preconceptional adults or pregnantwomen. These approaches are not necessarily mutu-ally exclusive. Many believe, however, that thereceipt of troubling information during pregnancy isnot desirable, and that it would be better for

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26 l Genetic Counseling and Cystic Fibrosis Carrier Screening: Results of a Survey Table 3-10-Who Should Pay for Cystic Fibrosis Carrier Screening? Table 3-1 2Frequency of Patients Seen by Major Areas of Clinical Practice Rank order Area Predominant response 1. Third parties 2. Self pay 3. State, city, or county 4. Federal Government 5. Employers SOURCE: Office of Technology Assessment, 1992. Table 3-1 lTarget Populations for Cystic Fibrosis Carrier Screening Population Yes No a (percent) Adults in reproductive years. . . 88 8 Prenatal . . . . . . 75 22 Pregnant women or couples . . 66 31 Newborns . . . . . . 33 63 Children ages 13 to 18 . . . 19 78 Children ages 2 to 12 . . . 6 91 Adults in post reproductive years. . 3 94 a3 per~nt had no response in each cate90rY. SOURCE: Office of Technology Assessment, 1992. individuals to know their risks before getting pregnant (12). Others argue that individuals not facing a pregnancy are not motivated to seek or use information on their carrier status, but will wait until they are either plannin g a family or starting a family before viewing such information as useful (5). CF carrier screening offered as part of primary health care rather than prenatal care is likely to encourage preconceptional CF carrier screening. For most individuals, however, the first real opportunity for carrier screening takes place postconception (8). In the future, the primary responsibility for providing CF carrier screening might reside with the obstetrician, as has happened with MSAFP screening. Sixty-six percent of respondents to OTAs survey identified pregnant women or couples as the appropriate target population for CF carrier screening, yet 88 percent more generally identified adults in their reproductive years as the appropriate target group (table 3-11). While most respondents state that the ideal target population for carrier screening is the preconceptional adult, in reality, the first target population is likely to be the prenatal population because it has been the traditional entry point into genetic services for many people and comprises the largest population served by genetics centers (table 3-12). Prenatal genetics. . . . . Pediatric genetics . . . . Adult genetics . . . . . Teratogen exposure . . . . Reproductive loss . . . . Specialty disease(s) clinics . . Newborn screening . . . . MSAFP screening followup. . . Carrier screening . . . . Very often Sometimes Sometimes Sometimes Sometimes Sometimes Seldom if ever Often Sometimes SOURCE: Office of Technology Assessment, 1992. PROFESSIONAL CAPACITY Another issue in considering widespread carrier screening for CF is whether there are enough adequately trained health professionals to handle the volume of tests. One study estimated that a minimumof651,000 counseling hours would be required annually if the maximum estimate of 6 to 8 million preconceptional couples are screened for CF carrier status (19). Considering the current number of practicing genetic counselors in the United States today, this translates to 17 weeks per year from each genetic counselor to serve solely CF-related clients. On the other hand, another estimate suggests the supply of genetic specialists could absorb routine carrier screening for CF sickle cell anemia, hemophilia, and Duchenne muscular dystrophy, assuming that obstetricians or other primary care physicians perform the screening on pregnant women, with referral of those with positive results to genetics professionals (10). The counselors and nurses surveyed by OTA estimate pretest counseling time for CF carrier status would range from about 45 minutes to over 1 hour, depending on family history (table 3-13). It is unclear to what extent increased demand for CF carrier screening would strain the current system. Current estimates undercount the number of health care professionals who practice genetic counseling and assume that counseling would always be provided in a clinical genetics setting by board-certified or board-eligible counselors. Such estimates also ignore the role that aggressive public education can play in improving pretest knowledge. Improvements in public education could result in dramatically less time required in formal counseling, as could reliance on health professionals not formally trained in genetics.

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Chapter 3-Cystic Fibrosis Carrier Screening: Policies and Practices l 27Table 3-1 3-Time Required for Genetic Counseling for Various Conditions Figure 3-9Opinions Regarding the Need for More Genetic CounselorsTimeNumber Condition(minutes/visit) visitsPrenatal counseling for advancedmaternal age . . . . . 54Positive family history for neural tubedefects . . . . . . 57 Elevated MSAFP screen . . . 55Couple with newly diagnosed (Tri21)Down syndrome child . . . 78Couple with 14/21 translocation Downsyndrome child . . . . 73Carrier testing for Duchenne musculardystrophy . . . . . 75Newly diagnosed case ofneurofibromatosis . . 70 Newly diagnosed CF family. . . 59Carrier testing for CF with a positivefamily history . . . . . 70Carrier testing for CF with a negativefamily history. . . . . . 44SOURCE: Office of Technology Assessment, 1992.1 12 2 2 2221Two-thirds of respondents strongly agreed that aneed for more genetic counselors exists (figure 3-9).A few respondents raised the possibility of training single-genecounselors to assist in the increased workload, although others expressed concern about this prospect, as taking a family history can reveal other genetic conditions that might not be detected by an individual trained to handle one genetic disorder (18). Still other respondents mentioned the need for more professional education of health care providers who might be in the position of adminis-tering such tests, and many survey participants notedthat all groups of health care providers should be involved after appropriate training and education. Noted one genetic counselor, Once screening is close to 100 percent sensitive, doctors and nurses could easily be trained to provide the necessary counseling. When asked what strategies would be considered to alleviate the projected increase in workload should widespread CF carrier screening occur, 55percent gave either no response or reported that theyhad not yet developed any. Of those who had considered or developed strategies, 40 percent said they would plan professional education activities toeducate other health professionals, 21 percent would develop videotapes for patient education, 15 percentsaid they would conduct public education, and 14 30-25 20lo-0 Strongly agree Undecided Agree Disagreedisagree A need for more genetic counselors exists.SOURCE: Office of Technology Assessment, 1992.Table 3-14-Strategies for Implementation of Widespread Cystic Fibrosis Carrier ScreeningQuestion:What strategies have you considered implementing if widespread screening for CF becomes a reality?aStrategyPercentPlan professional education activities . . . 40Develop videotapes for patient education . . . 21Conduct public education . . . . . . 15Arrange for group counseling sessions . . . 14 Administrative changes in clinics to handle patient load. 13a237 of the 43 I respondents gave no response.SOURCE: Office of Technology Assessment, 1992.percent reported they would arrange for group counseling sessions (table 3-14).ISSUES TO BE ADDRESSEDBEFORE IMPLEMENTATIONWhen OTA undertook this survey, privately funded pilot projects were under way, but federally funded pilot studies to evaluate CF mutation analysis in the general population had not yet begun, although NIH had begun a grant competition forsuch projects (18).3 Thus, OTA asked survey respond1991, a research initiative on clinical assessments of alternative approaches to genetic counseling related to CF mutation analysis (18).

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28 l Genetic Counseling a&Cystic Fibrosis Carrier Screening: Results of a Survey Table 3-15-Issues that Need to be Addressed by Pilot Programs in Cystic Fibrosis Carrier Screening Rank order 1. Access to genetic counseling 2. Education of the public 3. Payment/cost 4. Sensitivity of the test 5. Protection of confidentiality 6. Quality control and assurance 7. Identification of a target group 8. Availability of reproductive options SOURCE: Office of Technology Assessment, 1992. ents what issues they viewed as important before widespread screening is embraced. Specifically, survey participants were asked at the conclusion of the questionnaire to list by priority the important issues to be addressed by pilot studies in CF carrier screening. Interestingly, the sensitivity of the test, which was often cited as the reason not to proceed with screening, was ranked fourth (table 3-15). Access to genetic counseling was listed as the most important issue to be addressed. But with vast geographic inequities in availability of genetic services it is not clear how access could be considered as anything other than a variable in following pretest and post-test consumer behavior. Education of the public was ranked as second in level of importance for evaluation by pilot programs. Payment and cost issues were ranked third. SUMMARY A majority (53 percent) of genetic counselors and nurses in genetics do not offer unsolicited CF carrier screening. They are also unlikely to be providing genetic counseling and DNA tests to families followed in CF clinics and have not yet made efforts to contact CF families seen previously to offer carrier testing to family members. Those who advocate CF carrier tests for use beyond affected families argue that individuals should be routinely informed about the assays so they can decide for themselves whether to be voluntarily screened. This population was a minority (21 percent) of respondents. If carrier screening is to become routine, 99 percent of respondents believe it should be voluntary, and a majority prefer it be offered to preconceptional adults. Given the clientele found in most clinical genetics settings, it is likely that CF carrier screening will be offered as part of family planning or reproductive health, and the medical specialty most likely to offer the test will be obstetrics. This perceived tension over the technologys control likely contributes to the opinions of some in the clinical genetics community that widespread CF carrier screening is premature until greater genetics education of professionals is in place. With regard to CF carrier screening, concern exists that layers of uncertainty will inhibit informed consent, adequate pretest education, and post-test counseling and that, ultimately, more harm than good might be done. Yet respondents recognize the critical role that could be played in pretest education by other health care professionals and some indicated that should the momentum toward CF carrier screening accelerate, they would make efforts to increase their public and professional education activities. 1. 2. 3. 4. 5. 6. 7. 8. 9. 10. CHAPTER 3 REFERENCES American Society of Human Genetics, Statement of the American Society of Human Genetics on Cystic Fibrosis Carrier Screening, personal communication, June 1992. Biesecker, L., Bowles-Biesecker, B., Collins, F., et al., General Population Screening for Cystic Fibrosis Is Premature, American Journal of Human Genetics 50:438-439, 1992. Botk.in, J.R., Prenatal Screening: Professional Standards and the Limits of Parental Choice, Obstetrics and Gynecology 75:875-880, 1990. Bowling, F., Cleghorn, G., Chester, A., et al., Neonatal Screening for Cystic Fibrosis, Archives of Disease in Childhood 63:196-198, 1988. Brock, D.J., Cystic Fibrosis, Antenatal and Neonatal Screening, N.J. Wald (cd.) (New York, NY: Oxford University Press, 1984). Caskey, C.ll, Kaback, M.M., and Beaudet, A.L., The American Society of Human Genetics Statement on Cystic Fibrosis, American Journal of Human Genetics 46:393, 1990. Clarke, A., Is Non-Directive Genetic Counseling Possible?, Lancet 338:998-1001, 1991. Elias, S. E., Annas, G.J., and Simpson, J. L., Carrier Screening for Cystic Fibrosis: Implications for Obstetrics and Gynecologic Practice, American Journal of Obstetrics and Gynecology 164;1077-1083, 1991. Harper, P. S., and Clarke, A., Viewpoint: Should we Test Children for Adult Genetic Diseases?, Lancet 335:1205-1206, 1990. Holtzman, N. A., Proceed With Caution: Predicting Genetic Risks in the Recombinant DNA Era (Balti-

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Chapter 3-Cystic Fibrosis Carrier Screening: Policies and Practices l 29 11. 12. 13. 14. 15. more, MD: The Johns Hopkins University Press, 1989). Kaplan, F., Clew, C., and Scriver, C.R., Cystic Fibrosis Carrier Screening by DNA Analysis: A Pilot Study of Attitudes Among Participants, American Journul of Human Genetics 49:240-243, 1991. Lipkin, M., Fisher, L., Rowley, P.T, et al., Genetic Counseling of Asymptomatic Carriers in a Primary Care Setting, Annals of Internal Medicine 105:115123, 1986. Imader, S., Sutera, C. J., Walden, M., et al., Prenatal Screening for Hemoglobinopathies. II. Evaluation of Counseling, American Journal of Human Genetics 48:447451, 1991. Mischler, E., Farrell, P., Bruns, T., et al., Progress Report: Neonatal Screening for Cystic Fibrosis in Wisconsin, Wisconsin Medical Journal 88:14-18, 1989. Modell, B., Cystic Fibrosis Screening and Community Genetics, Journal of Medical Genetics 27:475479, 1990. 16. 17. 18. 19. National Institutes of Health, Workshop on Population Screening for the Cystic Fibrosis Gene, Statement From the National Institutes of Health Workshop on Population Screening for the Cystic Fibrosis Gene, New England Journal of Medicine 323:7071, 1990. Singer, E., Public Attitudes Toward Genetic Testing, in Population Research and Policy Review 10:235-255, 1991. U.S. Congress, Office of Twhnology Assessment, Cystic Fibrosis and DNA Tests: Implications of Carrier Screening, OTA-BA-532 (Washington, DC: U.S. Government Printing Office, August 1992). Wilfond, B.S., and Fost, N., The Cystic Fibrosis Gene: Medical and Social Implications for Heterozygote Detection, Journal of the American Medical Association 263:2777-2783, 1990.

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Chapter 4 Summary For years, experts theorized about confronting the potential consequences of increased knowledge of human genetics. In the early 1990s, the cystic fibrosis CF mutation test moved the debate from the theoretical to the practical. OTA concludes that the value of the CF carrier testis the information it provides. No one can estimate in common terms what it means to an individual to possess information about his or her genetic status, especially when the value concerns reproductive decisionmaking. On a larger scale, the potential for widespread CF carrier screening raises legal, ethical, economic, and political considerations. This survey of genetic counselors and nurses working in genetics, conducted in the summer of 1991, reflects the tensions and concerns surrounding dissemination of CF mutation analysis. The survey was conducted to better understand the environment in which the average genetic counselor or nurse in genetics works, to describe the infrastructure and tools available to these professionals, to assess the state of practice in the provision of CF carrier screening, and to evaluate their attitudes regarding CF carrier screening. In s ummer 1991, most genetic counselors and nurses in genetics did not offer unsolicited CF carrier screening and expressed concerns about access to health insurance, quality control, public education, dis crimination, stigmatization, and the adequacy of trained personnel as reasons why they did not. They are also unlikely to be providing genetic counseling and DNA tests to families followed in CF clinics and have not yet made efforts to contact CF families seen previously to offer carrier testing to family members, although agreement exists that such individuals should be offered CF mutation analysis. Reasons why survey respondents do not offer CF mutation analysis are varied, but professional guidelines exert some influence. The 1990 policy statement of the American Society of Human Genetics (ASHG) stated that CF carrier screening is NOT yet the standard of care, and a majority of survey respondents were aware of that statement. Several stated that it alone was the reason for their refusal to offer CF carrier screening. In mid-1992, after extended discussion, ASHGs leadership approved a revised statement that CF mutation analysis is not recommended for those without a family history of CF Some argue that the subtle change in language of the new statement reflects an evolution of debate within the society-that some believe CF carrier screening may now be offered to individuals without a family history of CF although it might not be the standard of care. Others argue that ASHGs position is unchanged. The effect of the new statement remains to be seen. Concern about test sensitivity was another barrier that respondents said should be addressed before routine CF carrier screening. Two-thirds of participants felt that an optimum frequency of detection should be reached before they would feel comfortable offering CF carrier screening to the general population, although nearly a quarter of respondents were uncertain about whether an optimum was necessary. Of those who felt there is an optimal frequency of detection, nearly half felt that 95 percent test sensitivity should be required before proceeding with widespread CF carrier screening. Twenty-five percent believed test sensitivity should be greater than 95 percent, with 4 percent stating that it should be 100 percent. At the time this survey was conducted, test sensitivity was approximately 80 percent. It has increased to 85 to 90 percent as of summer 1992, so opinions might have changed. Two other factors ranked slightly more important than test sensitivity as criteria to consider before implementing routine CF carrier screening: the availability of adequate counseling and an adequate system of referral for individuals who test positive. Genetic counseling can be labor intensive. Survey respondents indicated that they spend most of their work week seeing or talking with clients; patient loads are frequently heavy. Respondents said that, given the potentially complex or emotional nature of some genetic information, professionals trained in human genetics are essential to insure high quality care and informed consent. Guarantee of informed consent also was mentioned as necessary for implementation of large-scale carrier screening. Those who advocate CF carrier tests for use beyond affected families are no less concerned about

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32 l Genetic Counseling and Cystic Fibrosis Carrier Screening: Results of a Survey informed consent and quality of services. Proponents argue that the tests are sensitive enough for current use and that individuals should be routinely informed about the assays so they can decide for themselves whether to be voluntarily screened. These voices believe that failing to inform patients now about the availability of CF carrier assays denies people the opportunity to make personal choices about their reproductive futures. In this survey population, however, advocates of routine CF carrier screening were in the minority. Perhaps the point on which there was greatest consensus among respondents is on the issue of autonomy and choice in screening. There are no mandatory genetic screening programs of adult populations in the United States. Ninety-nine percent of survey participants responded that CF carrier screening should be voluntary and never mandatory. Given the existing tensions surrounding CF mutation analysis in the general population, who should serve as gatekeeper of this new technology? Survey respondents strongly believe that CF carrier screening should be organized by and provided by the human genetics community. This assumes, however, that large numbers of Americans will learn of their CF carrier status through interaction with the genetic services system. Based on the client populations reported in this survey, routine CF carrier screening will likely integrate into medicine in the reproductive context first. The prenatal population has been the traditional entry point into genetic services for many people; OTAs survey found 70 percent of the genetics clientele are adults of reproductive age, reinforcing the notion of prenatal diagnosis as an entry point for primary genetics service. Preconceptional individuals are the ideal population for CF carrier screening, according to survey respondents, but for most individuals the first real opportunity for carrier screening takes place postconception. Thus, despite survey respondents desire that information about the availability of assays such as CF mutation analysis should come from genetic specialists, the primary responsibility for providing CF carrier screening is likely to reside with obstetricians, at least initially, and especially if reimbursement for CF mutation analysis and its attendant counseling become part of routine obstetric care. Such a scenario would mirror that which has occurred with maternal serum alpha-fetoprotein screening to detect fetuses with neural tube or abdominal wall defects or Down syndrome-a prospect that concerns some, but not others. OTAs survey of genetic counselors and nurses also reports some consumers experience difficulties in obtaining or retaining health care coverage after genetic tests, though the large majority were not for carrier status, but were for genetic illness. Nevertheless, because genetic-based predictive testing promises to have a profound impact on clinical medicineand because access to medical care is inextricably linked to private health insurance in this country such cases underscore certain policy dilemmas arising from the increased availability of genetic assays. Critics of widespread CF carrier screening question whether the present genetic counseling system in the United States can handle the swell of cases if CF carrier screening becomes routine. Currently, about 1,000 master s-level genetic counselors practice in the United States, and an additional 100 nurses in genetics provide similar services. OTAs survey of genetic counselors and nurses in genetics indicates that respondents believe routine CF carrier screening will strain the present genetic services delivery system. Respondents estimated that, on average, 1 hour would be needed to obtain a three-generational family history and to discuss CF carrier screening and genetic risks. Skeptics of a personnel shortage assert that counseling about CF carrier assays is likely to take place in the general obstetric/prenatal context, however, and believe 1 hour exaggerates the amount of time that suffices for all prenatal tests, let alone only CF carrier screening. Furthermore, counseling related to CF carrier screening is likely to extend beyond genetics professionals to include other physicians and allied health professionals. For example, an unknown number of social workers, psychologists, and other public health professionals perform genetic counseling, often to minority and underserved populations. ultimately, the issue of adequate services and professional capacity could turn on the extent to which patients receive genetic services through specialized clinical settings, as they largely do now, versus access through primary care, community health, and public health settings. Overall, OTA cannot conclude whether increased numbers of genetic specialists are necessary, but clearly in-

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Chapter Summary .33 creased genetics education for all health care professionals is desirable. Routine carrier screening for CF-and tests yet to be developed for other genetic conditions-will require adequate training and education of individuals in the broader health care delivery system. Some survey respondents recognize the critical role other health care professionals will play in pretest education and indicated that should the momentum toward CF carrier screening accelerate, they would make efforts to increase their public and professional education activities. Although genetic counselors and nurses in genetics work in a variety of settings, they are concentrated in metropolitan medical centers on the West coast or in the Northeast. States with large rural populations are less likely to be served. The clientele served, in the aggregate, tend to be representative of the national averages for racial and ethnic populations, although no effort was made by OTA to match racial and ethnic data with regions, cities, or localities. This diversity presents great opportunity in terms of professional and public education, yet few counselors report an emphasis on these activities in their weekly routine because patient services comprise two-thirds of their time. One of the tasks of genetic specialists, however, is to provide the educational and counseling services necessary to successful implementation of new technologies. Diagnostic tools, such as DNA tests, can provide powerful information. Increasingly, genetic counselors and nurses working in genetics will be at the front line on the issues raised by assimilating DNA technologies into clinical practice.

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Appendix A Survey Method Data for this survey were collected from 431 survey questionnaires mailed to 813 individuals in June and July of 1991. The sample was drawn from the membership list of the National Society of Genetic Counselors (NSGC) and the mailing list of the International Society of Nurses in Genetics (ISONG). Only full members (excluding student, associate, and foreign memberships) of the NSGC were surveyed. The initial mailing list provided by ISONG was screened to remove individuals who were not practicing nurses from the sample (e.g., journalists, vendors). Questionnaires were not numerically or otherwise coded, and hence were completely anonymous. Respondents were asked to return their questionnaire in a post-paid envelope provided by OTA. Approximately 2 weeks after the initial mailing, a followup letter was sent to all survey respondents. The second wave improved the response rate by about 15 percent. The content of the instruments was identical for the two populations, but the questionnaires were reproduced on different colored stock for easier tracking. Preliminary analysis revealed no significant difference in question response between the NSGC and ISONG samples, and so all data were combined into one set for the final analyses. Surveys returned after September 30, 1991 were not included in the final data analyses. A statistical software package was used to provide frequency distributions and cross-tabulations of the data. No weighting was done of the sample, as OTA believes that the sample closely represents the entire population.

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Appendix B Survey Instrument As part of the 1992 assessment Cystic Fibrosis and DNA Tests: Implications of Carrier Screening, OTA surveyed the summer 1991 memberships of the International Society of Nurses in Genetics and the National Society of Genetic Counselors. The items for the two questionnaires were identical, and the following is a reproduction of the survey instrument. -36--

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Appendix B-Survey Instrument 37 Office of Technology Assessment United States Congress Washington, D.C. 20510-8025 SURVEY OF GENETIC COUNSELING ATTITUDES AND PRACTICES REGARDING CYSTIC FIBROSIS SCREENING Genetic Counselor Demographics 1. 2. 3. 4. 5. 6. 7. 8. 9. 10. Sex: a. female Age: years b. male Race: a. Asian d. b. Black c. Caucasian f Marital status: a. married b. widowed d. Hispanic Native American Other: never married divorced/separated In what State do you work? State a. ZIP code b. Degrees held: a. MA/MS Genetic counseling b. RN/BSN c. MSN d. MPH MSW Ph. D.: M.D. J.D. i. currently in degree program: (type) Year granted: How many years of clinical practice as a genetic counselor do you have? Certification status (American Board of Medical Genetics) a. Board certified (CIRCLE Year): 1982, 1984, 1987, 1990 b. Board eligible not necessary for position d: none Are you fluent in any language other than English? a. no b. yes, I speak English and (specify other): Present employment status: a. full time b. part time: hours/week c. not working

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38 l Genetic Counseling and Cystic Fibrosis Carrier Screening: Results of a Survey 11. Which best describes your work setting(s)? Designate a primary (1) and secondary (2) setting, if applicable. a. b. :: ; 9. h. i. j. ~ k. L m. n. o. p. q. private hospital/medical facility university medical center free standing clinic Health Maintenance Organization (HMO) private group practice solo private practice private industry (specify type): State laboratory (specify type): regional laboratory (specify type): commercial laboratory Public Health department (State, county, or city) State government agency Federal government agency voluntary health organization educational institution (K-12) higher educational institution (undergraduate or graduate) other: 12. On average, how many hours a week are you involved in: a. b. d: f g. h. i. direct patient contact (counseling patients) indirect patient activities (review of literature or records, coordinating referrals) performing administrative/managerial tasks educating health professionals, medical students, GC trainees educating the general public, schools, undergraduates performing laboratory work research marketing/business other: 13. What sources of information about new advances in the field of human genetics do you rely on? (check all that apply) a. b. d: f g. : h. i. j. k. professional colleagues medical journals grand rounds State or regional conferences national conferences American Society of Human Genetics National Society of Genetic Counselors continuing education courses literature from biotechnology/commercial firms lay press other: 14. In your current position, how frequently were you asked about DNA testing/screening for CF during the 6-month period from January June, 1991? Please consider this in the context of your total clinical practice. a. never b. rarely occasionally d: frequently e. very frequently

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Appendix B-Survey Instrument .39 15. If you were asked about DNA testing/screening for CF please estimate the number of requests per month (January June, 1991)? (per month) 16. Compared to 2 years ago, would you say the number of requests made between January June, 1991 represents: a. a large decrease b. a small decrease no change d: a small increase e. a large increase 17. If you noted an increase, when did you note this? (month/year) 18. In your current position are you engaged in providing genetic counseling? a. If NO, skip the CLINICAL PRACTICE QUESTIONS and GO TO QUESTION #46 THE NEXT SERIES OF QUESTIONS ARE TO BE ANSWERED BY THOSE INDIVIDUALS WHO CURRENTLY PROVIDE GENETIC COUNSELING SERVICES (All others please skip to question #46.) 19. Which best describes the primary service area in which you work? rural suburban metropolitan/urban statewide regional (more than one State) national other: 20 Current level of staffing (including yourself) in your counseling unit/program (please indicate number). a. b. c. d. e. f. # M.D. geneticists Ph.D. geneticists M.D./Ph.D. geneticists genetic counselors secretaries other:

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40 l Genetic Counseling and Cystic Fibrosis Carrier Screening: Results of a Surve Y 21. Indicate the frequency of patients seen by you for each major area of clinical practice. 1 =seldom if ever; 2=sometimes; 3=often (i.e., majority); 4=very often; 5=all or almost all 22. 23. 24. a. b. d: f g. ~ h. i. prenatal genetics pediatric genetics adult genetics teratogen exposure reproductive loss specialty disease(s) newborn screening clinics (please specify): MSAFP screening follow-up carrier screening (specify disease): Does your institution participate in collecting the CORN data set? a. yes b. no c. dont know For each of the following categories, indicate the number (or best estimate) of genetics clients/patients served in 1990, either DIRECTLY (i.e., counselor to client relationship; one-on-one genetic counseling) or INDIRECTLY (i.e., involvement such as consultant to primary care physician regarding a patient, telephone consultation). TYPE OF PATlENT CONTACT Direct Indirect Total All patients seen in 1990 a. by your unit: b. by you individually: CF patients/families seen in 1990 c. by your institution: d. by you individually: With respect to your clinical practice, estimate the percent (%) of your patients who are: A. RACE/ETHNICITY Percent (%) a. Asian/Pacific Islander b. Black c. Caucasian d. Native American e. Spanish surname f. unable to estimate B. AGE DISTRIBUTION 9. h. i. j. k. 1. m. neonatal infants children adolescents adults reproductive age adults post reproductive age unable to estimate

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Appendix B-Survey Instrument l 41 24. (cont.) With respect to your clinical practice, estimate the percent (%) of your patients who are: C. LANGUAGE Percent (%) n. English speaking o. Non-English speaking p. unable to estimate 25. Do your patients have health care coverage? a. seldom if ever (0-15% of patients seen) b. sometimes (about 16-50% of patients) often (about 51 -74A of patients) d: very often (about 75-69% of patients) e. always or almost always (90-100% of patients) 26. Please estimate the percent of patients by category of coverage. Coveraqe Category Percent(%. a. commercial insurance b. Blue Cross/Blue Shield c. HMO or managed care plan d. Medicaid e. Medicare f. CHAMPUS g. self pay h. no insurance i. indigent j. unknown 27. For individuals with insurance coverage, what has been your experience with reimbursement of fees for service in each of the following areas? Also, please indicate the average fee amount charged for each service. 1 =seldom if ever covered; 2 =sometimes covered; 3 = often covered; 4 very often covered; 5=almost a/ways covered; 6=uncertain a. b. c. d. e. f. general genetic counseling: Fee $ genetic counseling for cystic fibrosis with positive family history: Fee $ genetic counseling for cystic fibrosis with negative family history: Fee $ routine metabolic screen: Fee $ routine cytogenetic analysis: Fee $ DNA analysis for cystic fibrosis: Fee $

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42 l Genetic Counseling and Cystic Fibrosis Carrier Screening: Results of a Survey 28. Have you had any experience with a patients insurance claims for DNA testing being rejected? a. no experience b. yes. Please provide details: 29. Have any of your patients experienced difficulties in obtaining or retaining health insurance coverage as a result of genetic testing? a. no experience b. yes. Please provide details: 30 Consider the following reasons for referral for genetic counseling. Please estimate to the best of your ability, the average NUMBER of patients you see per month, total amount of direct COUNSELOR TIME spent (in minutes), and the average number of VISITS needed to provide genetic counseling to individuals and/or families for each of the following scenarios. (Answer for cases appropriate to your practice.) a. b. c. d. e. f. g h. i. j + prenatal counseling for advanced maternal age positive family history for neural tube defects concerns for current pregnancy Elevated MSAFP screen Couple with newly diagnosed (Tri 21) Downs Syndrome child Couple with 14/21 translocation Downs Syndrome child Carrier testing for DMD Newly diagnosed case of neurofibromatosis Newly diagnosed CF family Carrier testing for CF with a positive family history Carrier testing for CF with a negative family history AVG # visits 31. If you have not been involved with counseling for CF based on your experience, how much direct counselor time (minutes) would you estimate would be needed to: a. obtain 3 generational family pedigree: (minutes) b. discuss carrier testing and recurrence risks: (minutes) 32. How would this estimate compare to the direct patient time spent with your typical patient load? a. more time b. less time c. about the same

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Appendix B-Survey Instrument 43 33. 34. 35. How frequently do you use each of the following formats to provide genetic counseling? 1 =seldom if ever; 2=sometimes; 3=often; 4=very often; 5=almost always a. individual counseling session(s) b. group counseling videotape alone d: videotape with counseling written educational materials f slide-tape g. interactive computer Where is the closest CF treatment center to your institution? a. at my institution b. less than or equal to 50 miles greater than 50 miles d: not aware of one Do you personally provide genetic counseling through the CF treatment center in your area? a. no b. If yes, please provide the following information for 1990. 1) total # new patients seen by the CF center 2) total # return patients seen by the CF center 3) # referrals for genetic counseling 4) # requests for information on DNA testing 5) # undergoing actual DNA testing individuals families 36. Do you or your group/unit have a specific policy regarding DNA testing for CF a. no, we do not. b. yes; if yes, what is it? 37. Are individuals/families seeking DNA testing for CF asked to sign an informed consent? a. no b. yes 38. Do you or your group/unit have official policies and procedures for other issues in genetics? (check all that apply) a. DNA storage b. prenatal diagnosis for sex selection non-paternity d: confidentiality and Huntingtons disease testing e. other:

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44 l Genetic Counseling and Cystic Fibrosis Carrier Screening: Results of a Survey 39. For each of the following patient groups, indicate how often, if at all, you introduce the topic of DNA testing for CF 1=seldom if ever; 2=sometimes; 3=often; 4=very often; 5=almost always a. all patients\families b. pregnant women seeking prenatal diagnosis couples/individuals with a positive family history for CF d: Caucasian couples/individuals with negative family history for CF f. individual/families who inquire about CF e. selected couples/individuals; how selected: 40 Have you made an effort to contact old genetics families as appropriate regarding the availability of CF testing? a. yes, by (check all that apply): 1) telephone 2) letters/mass mailing 3) at future visits 4) other: b. no, because (check all that apply): 1) not enough time; too busy 2) no mechanism for rapid chart retrieval 3) requires chart by chart analysis 4) plan to do so in future, as time permits 5) other: 41. During the last 12 months: a. Have you referred any patients for DNA testing for CF 1) no 2) yes: how many individuals: # samples b. Have you=referred any patients/families for DNA testing for other disorders? 1) no 2j yes: how many individuals: # samples If yes,for which conditions: 42. At your institution, is DNA testing for CF a. performed at onsite/inhouse lab b. sent offsite to lab less than or equal to 50 miles away c. sent offsite to lab between 50 miles and 150 miles away d. sent offsite to lab greater than 150 miles away 43. Type of laboratory used for CF testing: a. private/commercial b. private hospital university hospital d: regional laboratory e. other:

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Appendix B-Survey Instrument 45 44. 45. 46. 47. 48. 49. 50. 51. 52. If you are-or have been-involved with CF testing, does the laboratory you use provide (check all that apply): a. b. d: f g. direct mutation analysis DNA linkage analysis DNA haplotyping staging of studies depending on case prenatal DNA analysis fetal intestinal enzyme analysis DNA banking For direct mutation analysis of CF what mutations does the laboratory you use include? (Please list or give number): THE FOLLOWING QUESTIONS ARE TO BE ANSWERED BY ALL RESPONDENTS Are you familiar with the following statements concerning CF screening published by: a. 1990 ASHG ad hoc CF Screening Committee: no yes b. 1990 NIH panel: no yes if yes to either one of the above how have you incorporated this into clinical practice? At this time do you think it is appropriate to provide CF screening in cases where family history is negative? a. no b. yes c. uncertain if yes, why? Do you feel there is a optimum rate of detection at which widespread CF carrier screening should proceed? a. yes, specify: % rate of detection b. n o c. no opinion Are you familiar with the NSGC brochure Genetic Testing for Cystic Fibrosis: A Handbook for Professionals? a. no b. yes Have you developed any educational materials relevant to DNA testing specifically for CF a. no b. yes (Please send a copy.) Have you been tested for CF carrier status? a. no b. yes If you have been tested for CF carrier status, why were you tested? a. research subject b. wanted to know positive family history d: family planning e. other:

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46 l Genetic Counseling and Cystic Fibrosis Carrier Screening: Results of a Survey 53. How was your test covered? a. by my insurance b. professional courtesy c. self pay d. research subject 54. To what extent, if at all, should each of the following groups be involved with educating the public about DNA testing for CF if it becomes standard practice? a. b. d: f g. h. j k. 1=to little or no extent; 2=to some extent; 3=to a moderate extent; 4=to a great extent; 5=to a very great extent; 6=no opinion primary care providers public health departments genetic counselors genetics programs nurses family planning clinics voluntary support groups schools lay press television other: 55. If widespread CF carrier screening begins, it should be: a. mandatory b. voluntary 56. If widespread CF carrier screening begins, what target populations should be screened? (check all that apply) a. b. c. d. e. f. g. prenatal newborns children ages 2-12 children ages 13-18 adults in reproductive years adults post reproductive years pregnant women or couples 57. If CF carrier screening is voluntary, who should organize the screening programs? (check all that apply) a. voluntary health organizations b. State or local health department Federal Government d: medical societies the human genetics community f primary care givers g. : others (specify): 58. If CF carrier screening is mandatory, who should organize the screening programs? (check all that apply) a. b. c. d. f g. voluntary health organizations State or local health department Federal Government medical societies the human genetics community primary care givers others (specify):

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Appendix B-Survey Instrument l 47 59. 60. 61. 62. 63. Where should CF population screening programs be provided? (check all that apply) a. in public schools b. in public health departments in organized, community-wide programs d: in the primary care setting i.e., physicians in genetic centers/programs f in the workplace g. other (specify): Who should pay for screening? (Please rank, but be realistic.) a. b. c. d. f self pay by patient third party payment employers State/city or county Federal government other (specify): Do you agree or disagree with the following statements? 1=strongly agree; 2=agree; 3=undecided; 4=disagree; 5=strongly disagree) a. genetic counseling should precede DNA testing for CF when there is a positive family history. b. genetic counseling should precede DNA testing for CF when there is a negative family history. c. educational materials (culturally sensitive and understandable) can provide adequate information about CF screening. d. a need for more genetic counselors exists. e. informed consent prior to CF screening is a necessity. In your opinion, what are the important issues that need to be addressed by pilot programs in CF screening? List in order of priority: 1. 2. 3. 4. What strategies have you considered implementing if widespread screening for CF becomes a reality? 64. What do you feel the minimum criteria for CF carrier screening should be (protocol)? Thank YOU very much for your cooperation in answering our Questions! On the back of this survey, please feel free to give us as any other options, concerns, or suggestions that you feel our questions did not address. These comments will be anonymous, but may be incorporated in our report to Congress.

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Appendix C Acronyms and Glossary Acronyms -/negative CF carrier/negative CF carrier (couple) +/positive CF carrier/negative CF carrier (couple) +/+ positive CF carrier/positive CF carrier (couple) ABMG American Board of Medical Genetics ASHG American Society of Human Genetics BC/BS Blue Cross and Blue Shield CF -cystic fibrosis -cystic fibrosis transmembrane conductance regulator DF508 -delta F508 (most prevalent CF mutation) DF508#i12-delta F508 plus 6 to 12 additional CF DNA G542X G551D Em40 ISONG MSAFP N1303K NSGC OTA R553X W1282X mutations -deoxyribonucleic acid a CF mutation a CF mutation health maintenance organization International Society of Nurses in Genetics maternal serum alpha-fetoprotein a CF mutation National Institutes of Health (NIH) National Society of Genetic Counselors -Office of Technology Assessment a CF mutation a CF mutation Glossary of Terms Allele: Alternative form of a genetic locus (e.g., at a locus for eye color there might be alleles resulting in blue or brown eyes); alleles are inherited separately from each parent. beta~-thalassemia: An autosomal recessive disorder affecting the red blood cells, resulting in anemia, infections, growth retardation, and other complications. ~-thalassemia predominantly occurs among individuals of Mediterranean, Middle Eastern, Asian Indian, Chinese, Southeast Asian, and African descent. Buccal: Relating to the inside of the cheek. A buccal swab collects cells that can be analyzed for CF mutations. Carrier: An individual apparently normal, but possessing a single copy of a recessive gene obscured by a dominant allele; a heterozygote. Chest physical therapy (chest PT): A cornerstone of CF therapy that moves the mucus blocking major air passages out of the lungs. A specific form of chest PT is bronchial drainage during which an individual claps on the chest or back of the patient who is usually lying on a table. Chromosome: A threadlike structure that carries genetic information arranged in a linear sequence. In humans, it consists of a complex of nucleic acids and proteins. Confidentiality: A fundamental component of the health care provider-patient relationship in which the professional has the duty to keep private all that is disclosed by the patient. Consanguineous: Related by blood or origin, rather than by marriage. Cystic fibrosis CF A life-shortening, autosomal recessive disorder affecting the respiratory, gastrointestinal, reproductive, and skeletal systems, as well as the sweat glands. CF is caused by mutations in the CF gene that affect the CF gene product, cystic fibrosis transmembrane conductance regulator (CFTR). Individuals with CF possess two mutant CF genes. Cystic fibrosis carrier: An individual who possesses one CF mutation and one normal CF gene. CF carriers manifest no symptoms of the disorder. See carrier. Cystic fibrosis carrier screening: The performance of tests on persons for whom no family history of CF exists to determine whether they have one aberrant CF gene and one normal CF gene. See cystic fibrosis screening. Cystic fibrosis screening: The performance of tests to diagnose the presence or absence of the actual disorder, in the absence of medical indications of the disease or a family history of CF This type of diagnostic screening usually involves newborns, but rarely for CF except in Colorado and Wisconsin. See cystic fibrosis carrier screening. Cystic fibrosis transmembrane conductance regulator (CFTR): The CF gene product, which regulates chloride (Cl-) conductance and might be a Cl ion channel, the structure that governs Cl entry and exit in the cell. CFTR produced by a mutant CF gene is frequently impaired, resulting in the medical manifestations of CF in affected individuals. DF508: A three base pair deletion in the CF gene that results in a faulty CF gene product (i.e., a flawed CFTR). This mutation results in the deletion of one amino acid, phenylalamine, at position number 508 in CFTR. DF508 is the most common mutant allele among the greater than 170 identified in the CF gene. Deoxyribonucleic acid (DNA): The molecule that encodes genetic information. DNA is a double-stranded helix held together by weak bonds between base pairs of nucleotides. 48

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Appendix C-Acronyms and Glossary l 49 Discrimination: Differential treatment or favor with a prejudiced outlook or action. Dominant: An allele that exerts its phenotypic effect when present either in homozygous or heterozygous form. DNA: See deoxyribonucleic acid. DNA analysis: A direct examination of the genetic material, DNA, to reveal whether a individual has mutation(s) for CF or other disorders. DNA probe: Short segment of DNA labeled with a radioactive or other chemical tag and then used to detect the presence of a particular DNA sequence through hybridization to its complementary sequence. Gene: The fundamental physical and functional unit of heredity. A gene is an ordered sequence of nucleotide base pairs to which a specific product or function can be assigned. Gene therapy: The deliberate administration of genetic material into the cells of a patient with the intent of correcting a specific genetic defect. Genetic counseling: A clinical service involving educational, informational, and psychosocial elements to provide an individual (and sometimes his or her family) with information about heritable conditions. Genetic counseling is performed by genetics specialists, including physicians, Ph.D. clinical geneticists, genetic counselors, nurses, and social workers. Genetic screening: The analysis of samples from asymptomatic individuals with no family history of a disorder, groups of such individuals, or populations. Genetic testing: The use of specific assays to determine the genetic status of individuals already suspected to be at high risk (e.g., family history or symptoms) for a particular inherited condition. Genetics: The study of the patterns of inheritance of Specific traits. Genome: AU the genetic material in the chromosomes of a particular organism; its size is generally given as its total number of base pairs. The human genome is 3.3 billion base pairs. Heterozygote: A heterozygous individual, such as a CF carrier. Heterozygous: Having two different alleles at a particular locus. Homozygote: A homozygous individual. Homozygous: Having the same alleles at a particular locus. Immunoreactive trypsin (IRT) test: An assay that measures levels of pancreatic trypsin, a digestive enzyme. As a protocol for newborn CF screening, a drop of blood is isolated on a card, dried, and chemically analyzed to detect elevated levels of the enzyme. It is not intended to be a diagnostic test. Mutation: Changes in the composition of DNA. Nucleotide: The unit of DNA consisting of one of four basesadenine, guanine, cytosine, or thymineattached to a phosphate-sugar group. The sugar group is deoxyribose in DNA. In RNA, the sugar group is ribose, and the base uracil substitutes for thymine. Probe: A short segment of DNA tagged with a reporter molecule, such as radioactive phosphorus ( 32 P), used to detect the presence of that particular complementary DNA sequence. Protein: A biological molecule whose structure is determined by the sequence of nucleotides in DNA. Proteins are required for the structure, function, and regulation of cells, tissues, and organs in the body. Recessive: An allele that exerts its phenotypic effect only when present in homozygous form, otherwise being masked by the dominant allele. Sensitivity: The ability of a test to identify correctly those who have a disease. Sickle cell anemia: An autosoma1 recessive disorder affecting red blood cell flow through the circulatory system, causing complications in numerous organ systems. Sickle cell anemia predominantly occurs in individuals of African descent. Sickle cell trait: The heterozygous state of sickle cell anemia; sickle cell carrier status. Single-gene disorder: Hereditary disorder caused by a single gene (e.g., cystic fibrosis, Tay-Sachs disease, sickle cell anemia). Specificity: The ability of a test to identify correctly those who do not have the characteristic which is being tested. Stigmatization: Branding, marking, or discrediting because of a particular characteristic. Sweat test: An assay used to confirm CF that measures levels of sodium Na + ) and chloride (Cl-) ions. These ions appear in high concentrations in patients with CF Sweating is induced by running a low electric current through a pilocarpine-soaked gauze pad on the individuals arm or back. The amounts of Na + and Clin the sweat can then be determined to confirm or question a diagnosis of CF Tay-Sachs disease: A lethal autosomal recessive disorder affecting the central nervous system which results in mental retardation and early death. Tay-Sachs disease predominantly occurs among Jews of Eastern and Central European descent and populations in the United States and Canada descended from French Canadian ancestors.


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