genetic counseling and cystic fibrosis carrier screening: results of a survey

Genetic Counseling and Cystic FibrosisCarrier Screening: Results of a Survey

October 1992

OTA-BP-BA-97NTIS order #PB93-101764

Recommended Citation:U.S. Congress, Office of Technology Assessment, Genetic Counseling and Cystic FibrosisCarrier Screening: Results of a Survey--Background Paper, OTA-BP-BA-97 (Washington,DC: U.S. Government Printing Office, September 1992).

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Foreword

For years, experts have theorized about the consequences of increased knowledge ofhuman genetics. In the early 1990s, development of a DNA-based test to identify carriers ofcystic fibrosis (CF) moved the debate from the theoretical to the practical. The CF carrier assayis but one of many tests to come that will place genetic counselors and nurses working ingenetics 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 geneticcounselors and nurse geneticists. It was conducted to better understand the environment inwhich the average genetic counselor or nurse in genetics works, to describe the infrastructureand tools available to these professionals, to assess the state of practice in the provision of CFcarrier screening, and to evaluate their attitudes regarding CF carrier screening. The surveysupports OTA’s August 1992 assessment Cystic Fibrosis and DNA Tests: Implications ofCarrier Screening; the full assessment was requested by the House Committee on Science,Space, and Technology, the House Committee on Energy and Commerce, and RepresentativeDavid R. Obey.

The survey data collected by OTA reflect the tensions and concerns surrounding thewidespread implementation of CF carrier screening. Those who currently oppose routinecarrier screening for CF raise concerns about the sensitivity of the test, the numbers ofindividuals that would be potentially screened—and the subsequent effect on the clinicalgenetics infrastructure--and the possibilities of stigma, discrimination, and poor quality inservices. Those who think CF carrier screening should be widely available believe theinformation provided by the test increases patient autonomy and lowers uncertainty regardingreproductive futures.

OTA was assisted in preparing the survey instrument and Background Paper by a panelof advisors, contractors, workshop participants, and reviewers selected for their expertise anddiverse points of view. We gratefully acknowledge the contribution of each of theseindividuals. OTA, however, remains solely responsible for the contents of this BackgroundPaper.

/y’/&# J6’i9--JOHN H. GIBBONSDirector

. . .Ill

Cystic Fibrosis and DNA Tests: Implications of Carrier ScreeningAdvisory Panel

Jessica G. Davis, Panel ChairCo-Director, Division of Human Genetics

New York HospitalCornell University Medical College

New York, NY

Arthur L. BeaudetProfessorHoward Hughes Medical InstituteBaylor College of MedicineHouston, TX

Debra L. CollinsGenetic CounselorUniversity of Kansas Medical CenterKansas City, KS

Beth A. FineGenetic Counselor/Clinical InstructorNorthwestern University Medical SchoolChicago, IL

Lynn D. FleisherAttorneySidley & AustinChicago, IL

Clark C. HavighurstWilliam Neal Reynolds Professor of LawDuke University School of LawDurham, NC

John Z. Jacoby, IIIClinical AssistantThe Cystic Fibrosis CenterSt. Vincent’s Hospital and Medical CenterNew York, NY

Angèle KhachadourGeneral CounselHastings College of the LawSan Francisco, CA

Katherine W. KlingerVice President, ScienceIntegrated GeneticsFramingham, MA

Arthur LifsonVice PresidentCIGNA CompaniesHartford, CT

Robert F. Murray, Jr.ProfessorDepartment of Pediatrics and Child HealthHoward University School of MedicineWashington, DC

Mark V. PaulyExecutive DirectorLeonard Davis Institute of Health EconomicsUniversity of PennsylvaniaPhiladelphia, PA

Susan PolingParentSilver Spring, MD

Thomas K. Reed, Jr.chairmanVivigen, Inc.Santa Fe, NM

Philip R. ReillyPresidentShriver Center for Mental Retardation, Inc.Waltharn, MA

Joseph D. SchulmanDirectorGenetics & IVF InstituteFairfax, VA

NOTE: OTA is grateful for the valuable assistance and thoughtful critiques provided by the advisory panel members. The panel doesnot, however, necessarily approve, disapprove, or endorse this report. OTA assumes full responsibility for the report and theaccuracy of its contents.

iv

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

Cécile 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, MDFerdinand J. Chabot, Newton, IA

Bob Jones, IV, Arlington, VAAnn C.M. Smith, Reston, VA

1 Through December 1991

Contents

Page

Chapter 1. Introduction and Background ... .oo***. ... ee. .oo. ... ... *.oo. o.. ..oo. o*0**0o 1WHAT IS CYSTIC FIBROSIS? . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 2THE CYSTIC FIBROSIS GENE . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 2CYSTIC FIBROSIS MUTATION ANALYSIS . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 2CONTROVERSY ABOUT CYSTIC FIBROSIS CARRIER SCREENING . . . . . . . . . . . . . . . . 3SCOPE AND ORGANIZATION OF THIS BACKGROUND PAPER . . . . . . . . . . . . . . . . . . . . 4CHAPTER 1 REFERENCES . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 4

Chapter 2. Providers, Clientele, and Genetic Services ... ... ... ... ... ... ... ... ... .. *...0 5THE SURVEY POPULATION . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 5

Genetic Counselors . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 5Nurses in Genetics . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 6Demographic Profile of Survey Respondents . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 7

WORK ENVIRONMENTS . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 7GENETICS CLIENTELE . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 9FEES AND THIRD-PARTY COVERAGE . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 11

Fees for Genetic Services . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .11Third-Party Coverage . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .12

SUMMARY . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .14CHAPTER 2 REFERENCES . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .15

Chapter 3. Cystic Fibrosis Carrier Screening: Policies and Practices . . . . . . . . . . . . . . . . . . . 17POLICIES AND PRACTICES, SUMMER 1991 . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 17

Policies on Cystic Fibrosis Carrier Screening . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 17Criteria for Cystic Fibrosis Carrier Screening . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 19Practices Regarding DNA-Based Cystic Fibrosis Carrier Tests . . . . . . . . . . . . . . . . . . . . . . . . . 19

PREFERRED STRATEGIES AND PROTOCOLS . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 21Who Should Provide Cystic Fibrosis Carrier Screening? . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 22Who Should Pay for Cystic Fibrosis Carrier Screening? . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 23Strategies for Screening Various Populations . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .23

PROFESSIONAL CAPACITY . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 26ISSUES TO BE ADDRESSED BEFORE IMPLEMENTATION . . . . . . . . . . . . . . . . . . . . . . . . . 27SUMMARY . . . . . . . . . . . . . . . . . . . . . . . . . .. . . . . . . . . . . . . . . . . . . . . . . . . . .. . . . . . . . . . . . . . . . . . . . . 28CHAPTER 3 REFERENCES . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .28

Chapter 4. Summary . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 31

Appendix A. Survey Method ... .me. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 35Appendix B. Survey Instrument ... ..oo. ..** . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 36Appendix C. Acronyms and Glossary . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 48

Figures

1-1. Inheritance of Cystic Fibrosis . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 11-2. Cystic Fibrosis Mutation Test Results at 85 Percent Sensitivity . . . . . . . . . . . . . . . . . . . . . . . . 32-1. Geographic Distribution of Survey Respondents . . . . . . . . . . . . . . . . . . . . . . . . . . 62-2. primary Service Areas of Respondents . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 8

. . . . . . . . . . . .

2-3. Average Hours Spent Per Week on Public Education . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 82-4. Racial/Ethnic Background of Clinical Genetics Clientele . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 92-5. Age Distribution of Genetics Clientele . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 92-6. Frequency of Patients Seen by Major Areas of Clinical Practice . . . . . . . . . . . . . . . . . . . . . . . 102-7. Number of Cystic Fibrosis Patients or Families Seen in Genetics Units in 1990 . . . . . . . . . 11

2-8. Health Care Coverage for Genetics Clientele . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 122-9. General Types of Health Care Coverage for Genetics Clientele . . . . . . . . . . . . . . . . . . . . . . . . 122-10. Third-Party Reimbursement for General Genetic Counseling and Counseling

Specifically for Cystic Fibrosis . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 133-1. Opinions on Optimal Rate of Detection . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 193-2. Frequency of Requests for Cystic Fibrosis Carrier Screening/Testing,

January-June1991 . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .203-3. Comparison of Requests for Cystic Fibrosis Carrier Screening/TestingBetween

January-June 1991 and Past 2 Years . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .203-4. Opinions Regarding Genetic Counseling of Individuals with a Positive

Family History . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 213-5. Opinions Regarding Genetic Counseling of Individuals with a Negative

Family History . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 213-6. Opinions Regarding the Need for Informed Consent Prior to Cystic Fibrosis

Carrier Screening . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 223-7. Opinions Regarding the Use of Educational Materials as aSource of Information

About Cystic Fibrosis Carrier Screening . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 223-8. Extent to Which Various Groups Should Be Involved with Cystic Fibrosis

Pretest Education . . . . . . . . . . . . . . . . . . . . . . . . . . . .. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .243-9. Opinions Regarding the Need for More Genetic Counselors . . . . . . . . . . . . . . . . . . . . . . . . . . . 27

Tables

l-1. A Priori Carrier Risks for Cystic Fibrosis . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 12-1. Geographic Concentration of Survey Respondents . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 72-2. Primary Work Setting . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 72-3. Average Weekly Schedule of Genetic Counselor or Nurse in Genetics . . . . . . . . . . . . . . . . . 82-4. Formats for Genetic Counseling . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 82-5. Most Common Diseases for Which Carrier Screening/Testing Is Offered . . . . . . . . . . . . . . . 112-6. Average Fees and Knowledge of Fees for Genetic Services . . . . . . . . . . . . . . . . . . . . . . . . . . . . 112-7. Fees for General Counseling . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 122-8. Difficulties in Obtaining or Retaining Health Insurance After Genetic Tests . . . . . . . . . . . . 132-9. Case Descriptions of Genetic Testing and Health Insurance Problems . . . . . . . . . . . . . . . . . . 143-l. A Priori Carrier Risks for Cystic Fibrosis . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 183-2. Sources of Information About New Advances in Human Genetics . . . . . . . . . . . . . . . . . . . . . 183-3. Likelihood of Introducing the Topic of DNA Testing for Cystic Fibrosis . . . . . . . . . . . . . . . 183-4. Specific Policies Regarding DNA Testing for Cystic Fibrosis . . . . . . . . . . . . . . . . . . . . . . . . . 183-5. Minimal Criteria for Cystic Fibrosis Carrier Screening Protocol . . . . . . . . . . . . . . . . . . . . . . . 193-6. Types of Genetic Analyses Provided for Cystic Fibrosis Screening Testing . . . . . . . . . . . . . 203-7. Cystic Fibrosis Mutations Routinely Analyzed . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .203-8. Preferred Organizations for Implementation of Voluntary Cystic Fibrosis

Carrier Screening . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 233-9. Preferred Sites for Cystic Fibrosis Carrier Screening Programs . . . . . . . . . . . . . . . . . . . . . . . . 233-10. Who Should Pay for Cystic Fibrosis Carrier Screening? . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 263-n. Target Populations for Cystic Fibrosis Carrier Screening. . . . . . . . . . . . . . . . . . . . . . . . . . . . 263-12. Frequency of Patients Seen by Major Areas of Clinical Practice . . . . . . . . . . . . . . . . . . . . . . 263-13. Time Required for Genetic Counseling for Various Conditions . . . . . . . . . . . . . . . . . . . . . . . 273-14. Strategies for Implementation of Widespread Cystic Fibrosis Carrier Screening . . . . . . . . 273-15. Issues that Need to be Addressed by Pilot Programs in Cystic Fibrosis

Carrier Screening . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 28

vii

Chapter 1

Introduction and Background

Cystic fibrosis (CF) is the most common, life-shortening, recessive genetic disorder affecting Cau-casians of European descent. From 1,700 to 2,000babies with CF are born annually in the UnitedStates. The diagnosis of an infant with CF oftenreveals the first and only clue that the genetic traitexists 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 sometimesreferred to as carrier couples, or couples who arepositive/positive (+/+). If a couple is positive/negative (+/-)—the father is a carrier, but the motheris not, or vice versa—their offspring can be CFcarriers, but cannot have CF. Couples are not at riskof having a child with CF if only one or neitherpartner is a carrier.

Four of five individuals with CF are born tofamilies with no previous history of the illness.Beyond the approximately 30,000 Americans who

Figure I-l—Inheritance of Cystic Fibrosis

o Carrier parents o

have CF, as many as 8 million individuals could beCF carriers. With no knowledge of a family historyof CF, American Caucasians have about a 1 in 25risk of being a CF carrier. The risk of carrier statusincreases 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 inone’s family, as well as ethnic and racial back-ground, were the only indicators available to deter-mine risk of carrier status. In 1989, however,scientists identified the most common change, ormutation, in the genetic material-deoxyribonucleicacid (DNA)-that causes CF. Following this discov-ery came tests to detect mutations in the specific areaof DNA—the 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 theseDNA tests to screen and identify CF carriers amongthe general population before they have a child withCF. This background paper, conducted in support ofthe OTA assessment, reports the results of an OTAsurvey of 431 members of either the NationalSociety of Genetic Counselors (NSGC) or theInternational Society of Nurses in Genetics (ISONG).Conducted in summer 1991, the survey was de-signed to evaluate genetic counseling attitudes andpractices regarding widespread CF carrier screening,a prospect that has been viewed with mixed feelings.

Table l-l—A Priori Carrier Risks for Cystic Fibrosis

25% 25%.chance 50% chance

unaffected chance affectednoncarrier unaffected

carrier

SOURCE: Office of Technology Assessment p 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 CF a. . . . . . . . . . 1 in 3 (33%)First cousin with CF. . . . . . . . . . . . . 1 in 4 (25%)Niece/nephew with CF a. . . . . . . . . 1 in 2 (50%)

a Consanguineous.

SOURCE: Office of Technology Assessment, 1992.

–1–

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

Consensus exists that individuals who have rela-tives with CF should be told about the availability ofCF carrier tests; the disagreement is whethereveryone should be informed about the assays, since80 percent of babies with CF are born to coupleswith no previous family history of the condition.Concern about the scientific, legal, economic, ethi-cal, and social implications of the prospect that largenumbers of people might be screened for their CFcarrier status led the House Committee on Science,Space, and Technology, the House Committee onEnergy and Commerce, and Representative DavidR. 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 docu-mented that CF compromises many functions through-out the body--chiefly the respiratory, gastrointesti-nal, and reproductive systems and the sweat glands.

Many affected babies are not immediately diag-nosed as having CF Although the disease is alwayspresent at birth in affected individuals, the onset ofrecognizable clinical symptoms varies widely. Phy-sicians diagnose CF using a combination of clinicalcriteria and diagnostic laboratory tests. Although anassay called the sweat test remains the primarydiagnostic test for CF DNA mutation analysis candiagnose more than 70 percent of cases.

CF exerts its greatest toll on the respiratory anddigestive systems, and the severity of respiratoryproblems often determines the quality of life andsurvival. There is no cure for CF Treatment focuseson managing the respiratory and digestive symp-toms to maintain a stable condition and lengthenlifespan. Because of CF’s varied progression, theregimen and level of therapy depends on theindividual. Most therapy involves home treatment(e.g., chest physical therapy to clear mucus from thelungs), outpatient care at one of more than 110clinics devoted specifically to CF health care, andoccasional hospital stays. Today, physicians canlook to an ever-expanding array of new pharmaceu-tical options to manage the care of CF patients; onthe horizon are hopes for gene therapy.

Over the last half-century, treatment of CF hasevolved so that an illness nearly always fatal in earlychildhood is now one where life expectancy intoadulthood is common. Fifty years ago, most infantsborn with CF died in the frost 2 years of life. In 1990,median survival was 28 years--i.e., of the individu-als born with CF in 1962, half were alive in 1990.

THE CYSTIC FIBROSIS GENECF is a genetic illness transmitted from parents to

their children via genetic directions stored in DNA.In humans, these directions, including those respon-sible for CF are stored among genes arrayed on 46structures called chromosomes. The gene responsi-ble for CF lies on chromosome 7 and results in aproduct called the cystic fibrosis transmembraneconductance regulator (CFTR). In most people withCF a three-base pair deletion in both of their CFalleles results in a faulty CFTR, which leads to CFpathology. This three-base pair mutation occurs atposition number 508 in the CFTR and is abbreviatedas delta F508 (AF508). More than 170 additionalmutations in the CF gene also lead to faulty CFTRs.Individuals with CF have two of the same, or twodifferent, mutations. CF carriers have only onemutation; their second CF allele produces normalCFTR.

About 70 percent of CF carriers have the AF508mutation. l International studies demonstrate ethnicand regional variation in the frequency distributionof this mutation; as expected, the multiculturalnature of the United States reflects this variation.Most of the other 170+ mutations appear in a smallfraction of individuals or families, although a fewoccur at a frequency as great as 1 to 3 percent. Somesymptoms (or their lack of severity) correlate withparticular mutations. Digestive difficulties frompancreatic insufficiency, for example, generallyassociate with AF508.

CYSTIC FIBROSISMUTATION ANALYSIS

With localization of the CF gene, AF508, andother CF mutations, it is now possible to directlyanalyze 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., about90 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 frequencyis chosen for illustrative or hypothetical purposes.

Chapter 1--Introduction and Background ● 3

of CF mutations. Using today’s technologies, CFmutation 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 CF

Current technology, however, can leave ambigu-ity, but not because the tests per se are imprecise.Properly performed, DNA-based tests for CF muta-tions are accurate and specific-meaning if the

mutation (or another CF mutation) is presentin the individual’s genome and an assay is per-formed to search for that mutation, the test willdetect it more than 99 percent of the time, absentlaboratory error. Instead, ambiguity stems from theintrinsic 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 Caucasianscarries 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 ofcarriers). Thus, using means 10 to 15percent of actual carriers go undetected. In otherwords, since tests to detect 170+ mutations are

impractical, a negative test result does not guaranteethat a person is not a carrier.

Using DF508+6-12 means that some couplesreceive test results that indicate one partner is acarrier and one is not, when in fact the negativepartner carries one of the rare CF mutations that isnot assayed. Thus, while most couples whose testresults are +/- are at zero risk of having a child withCF some couples with a +/- test result actually arecouples whose genetic status is +/+ (but goesundetected) and who are at 1 in 4 risk of a child withCF 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 CYSTICFIBROSIS CARRIER SCREENING

Prospects of routine CF carrier screening polarizepeople. No mandatory genetic screening programsof adult populations exist in the United States. OTAhas 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 mutationanalysis, yet controversy swirls around using thesame tests in the general population.

Figure 1-2—Cystic Fibrosis Mutation Test Results at 85 Percent Sensitivity

100,000couples

Run CF mutation test(85% sensitivity)

TEST RESULTS

Some of these couplesare 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. Remainingbut go undetected -/- couples are at no risk.)

116

(1 in 4 risk with each pregnancy. (1 in 4 risk with each pregnancy. RemainingFor first pregnancy for 100,000 couples,

29 CF-affected fetuses detectable,+/- couples are at no risk.)

11 missed.)



Proponents of a measured approach to CF carrierscreening express concern about several issues thatmight be raised if use of CF carrier tests becomesroutine. Invariably, discussions about CF carrierscreening raise concerns about the use of geneticinformation by insurance companies (2) and becomelinked broader social concerns about health carereform in the United States. Related to this areconcerns about commercialization of genetic re-search, i.e., that market pressures will drive wide-spread use of tests before the potential for discrimi-nation or stigmatization by other individuals orinstitutions (e.g., employers and insurers) is as-sessed. Also expressed are questions about theadequacy of quality assurance for DNA diagnosticfacilities, personnel, and the tests themselves. Othersalso wonder whether the current number of geneticspecialists can handle a swell of CF carrier screeningcases, let alone cases from tests for other geneticconditions expected to arise from the HumanGenome Project. Finally, the extraordinary tensionsin the United States about abortion affect discus-sions about CF carrier testing and screening.

Those who advocate CF carrier tests for usebeyond affected families are equally concernedabout these issues. They assert, however, thatindividuals should be routinely informed about theassays so they can decide for themselves whether tobe voluntarily screened. Proponents of providingsuch information believe that failing to informpatients now about the availability of CF carrierassays denies people the opportunity to makepersonal 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 determinewhether a fetus is affected.

SCOPE AND ORGANIZATION OFTHIS BACKGROUND PAPER

One of the tasks of genetic specialists is to providethe educational and counseling services necessary tosuccessful implementation of new technologies.Increasingly, genetic counselors and nurses workingin genetics will be at the front line on the issuesraised by DNA technologies’ assimilation intopractice.

The OTA survey was conducted to better under-stand the environment in which the average geneticcounselor or nurse in genetics works, to describe theinfrastructure and tools available to these profes-sionals, to assess the state of practice in the provisionof CF carrier screening, and to evaluate theirattitudes regarding CF carrier screening. The resultsof the survey are reported in chapters 2 and 3. Asummary appears in chapter 4. A description of thesurvey methodology is in appendix A, and thesurvey instrument is reproduced in appendix B.

CHAPTER 1 REFERENCES1.

2.

U.S. Congress, Office of Technology Assessment,Cystic Fibrosis and DNA Tests: Implications ofCarrier 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 aSurvey, OTA-BP-BA-98 (Washington, DC: U.S. Gov-ernment Printing Office, October 1992).

Chapter 2

Providers, Clientele, and Genetic Services

The purpose of the OTA survey was to evaluatethe extent to which genetic counselors and nurses ingenetics are routinely offering carrier screening forcystic fibrosis CF to their clientele, to assess theirattitudes and beliefs about the appropriateness ofsuch screening, and to obtain a sense of theenvironment in which they work. While members ofthe National Society of Genetic Counselors (NSGC)and the International Society of Nurses in Genetics(ISONG) are by no means the only health profes-sionals providing genetic counseling, they comprisea professional segment devoted explicitly to thatend. Physicians, social workers, public health work-ers, and research scientists also provide geneticservices. Those groups were not included in thissurvey.

To better understand the setting in which routinecarrier screening for CF might take place, OTAgathered data regarding not only counselors’ atti-tudes and practices regarding CF carrier screening(ch. 3), but also the settings in which they work, thenumbers and types of clients they serve, clinicalpractices, work routines, fees charged, and third-party payment options available to their clientele.Understanding the environment in which CF carrierscreening takes place was a critical part of theanalysis reported in Cystic Fibrosis and DNA Tests:Implications of Carrier Screening (10).

THE SURVEY POPULATION

Of the 703 members of the NSGC who receivedquestionnaires, 351-or 50 percent—responded. Ofthe 110 members of ISONG who received thequestionnaire, 80-or 73 percent—responded. Thus,80 percent of the respondent group are members ofNSGC and 20 percent are members of ISONG.l

As preliminary analysis revealed no significantdifference in question response between the twopopulations, all data were combined for the finalanalysis. The combined response rate is 53 percent.

Genetic Counselors

The master’ s-level genetic counselor is a rela-tively new addition to the health care system. In1971, 10 graduates of the first such program enteredthe workforce; in 1979, the NSGC was incorporatedas a professional organization. Today, there areapproximately 1,000 master’ s-level genetic counsel-ors practicing in the United States.

Master’ s-level genetic counselors receive special-ized multidisciplinary training and experience toprepare them for counseling related to a wide varietyof genetic disorders and birth defects. They aretypically graduates from a 2-year master’s degreeprogram, during which time they receive didacticcourse work in the principles and application ofhuman genetics, clinical and medical genetics,genetic laboratory methods, and interviewing andcounseling. Genetic counselors are also trained insocial, ethical, legal, and cultural issues relating togenetic diseases, principles of public health andhealth care delivery systems, and education for thelay and professional community (12). Over the past20 years, master’ s-level graduate programs in ge-netic counseling have increased to 15, and com-bined, they produce approximately 75 graduateseach year (7). At the time of the OTA survey, therewere 703 genetic counselors who were full membersof NSGC (associate, student, and foreign memberswere not surveyed). Of all respondents to the survey,70 percent had a master’s degree in genetic counsel-ing. An additional 10 percent held a master’s degreein another area, and 8 percent had a Ph.D.

Genetic counselors receive a minimum of 400hours of supervised clinical trainingin at least threeclinical settings, including a general genetics clinic,a prenatal diagnosis clinic, and a speciality diseaseclinic. Until 1992, graduates were eligible to sit forthe certification examination in genetic counselingby the American Board of Medical Genetics (ABMG),but continuing certification of these individuals bythis body is uncertain. In the past, counselors wererequired to submit their credentials and a logbook of50 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). OTA’s aggregate response rate clearly falls within this range, as does the response rateof the genetic counselors; the response rate of the nurses in genetics exceeds it.

–5–


Figure 2-l-Geographic Distribution of Survey Respondents a

ID SD2 2

NE5

KS

(I)

(2)

NM 1 OK4

NH 3 (1) ME

\ 7

‘i--

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 Genetics

There are nearly 2 million registered professionalnurses in the United States, many involved inmaternal and child health nursing. These profession-als provide a unique potential to contribute to theeffective delivery of genetic services. Efforts areunder way to encourage the incorporation of clinicalgenetics into the curricula of schools of nursing atboth the graduate and undergraduate level (4). Theneed 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 screenevery individual needing genetics referral (4). Thatis, individuals in need of genetic services must firstbe identified by the primary health care professiona1,and in some settings-such as community, occupa-tional, or school health-nurses are the only linkwith the health care system (3). Thus, nurses canassist in the identification, education and counsel-ing, and followup of patients (2,4). Though nursescan be a valuable part of genetics services, to datethey are a largely untapped resource (3).

Opportunities for clinical genetics experience innursing programs vary. Genetics is generally a partof the nursing school curriculum, but variabilityexists among programs (3). Four of the 200 universi-ties in the United States that offer graduate degrees

Chapter 2-Providers, Clientele, and Genetic Services ● 7

in nursing have established programs providing amaster ’s-level genetics major (3). A small number ofnurses, particularly those in maternal and childhealth nursing, have focused on genetics in order tosit for the genetic counseling examination given bythe American Board of Medical Genetics (ABMG)(3,5). There are over 100 nurses employed ingenetics who also belong to ISONG and thereforereceived OTA’s questionnaire. It is likely that manymore nurses deliver genetic services but are uniden-tifiable through current databases. Of the totalsurvey respondents, 12 percent reported havingeither an R.N. or B.S.N. degree. Nurses might alsohave a master’s degree or Ph.D. and could beincluded in the 80 percent of respondents whoreported having a master’s degree or the 8 percentwho reported having a Ph.D.

Demographic Profile of Survey Respondents

The typical individual working as a geneticcounselor 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, 1percent African American, 1 percent Asian Ameri-can), 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 alanguage 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 ofrespondents 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). Californiahad the highest representation at 15 percent. Thesedata are consistent with those collected and biannu-ally reported by the NSGC (8). Hence, OTA’ssurvey respondent pool is representative of theNSGC 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 wherethey are not encountering direct patient contact,perhaps serving as administrators, educators, or

Table 2-l-Geographic Concentration ofSurvey Respondents

State Number (percent)

California . . . . . . . . . . . . . . . . . . . . . . . . . 63(1 5)New York . . . . . . . . . . . . . . . . . . . . . . . . . 47(1 1)Pennsylvania . . . . . . . . . . . . . . . . . . . . . . 25( 6)New Jersey . . . . . . . . . . . . . . . . . . . . . . . . 24( 6)Illinois . . . . . . . . . . . . . . . . . . . . . . . . . . . . 19( 5)

Total . . . . . . . . . . . . . . . . . . . . . . . . . . . 178 (43)


Table 2-2—Primary Work Setting

Number (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)


researchers. The primary work settings for allrespondents are presented in table 2-2. Most coun-selors and nurses are employed in a universitymedical center (36 percent) or a private hospital ormedical facility (36 percent). The remainder work ina variety of settings, such as public health depart-ments, 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 ateaching mission. The work location and setting ofthe survey population reflect that tendency. Re-spondents are most likely to work in a metropolitanor urban setting (58 percent) (figure 2-2). Counselorsand nurses in genetics are less likely to be foundworking in rural settings. Counselors tend to workwith M.D. geneticists, Ph.D. geneticists, other ge-netic counselors, and a variety of support staff. Mostrural centers are unable to support this level ofprofessional personnel and often rely on regionalservice areas. Five percent of respondents reportedworking in a regional genetics area.

Respondents spend nearly two-thirds (65 percent)of their work week—about 26 hours per week-onpatient activities, whether direct patient contact


Figure 2-2—Primary Service Areas of Respondents

Metropolitan/Urban

8?40


Suburban

(e.g., intake or counseling) or indirect (e.g., writtencommunication, scheduling, and management ofreferrals) (table 2-3). An additional day is spent onadministrative procedures. This leaves little time forother activities such as educating other healthprofessionals or the general public. On average,counselors and nurses in genetics spend little time onpublic education. Fifty percent report spending notime on this activity, while 26 percent reportspending, on average, an hour a week on publiceducation (figure 2-3). Individual counseling ses-sions are time and labor intensive and are theprimary format for delivering genetic information(table 2-4). Respondents report that they seldom ifever rely on group counseling (67 percent) orvideotape 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 amongpractices. Responses ranged from 10 to 2,300clients. Counselors and nurses providing prenatal

Table 2-3-Average Weekly Schedule of GeneticCounselor or Nurse in Genetics

Figure 2-3—Average Hours Spent Per Weekon Public Education

I

50504

I

I

26

- - - - 10

I --- 3. . . . . . . ... .. .. .. .. .. .. .. . . . . . . . . . . . . . . .

o 2 3 4 5

Numbers of hours per week


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 reductionstrategies, irrelevant, and the nature and severity ofthe disorder for which the test is being done. Onetask of the genetics professional is to communicaterisks 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 conductroutine prenatal counseling is 1 hour. Counseling for

Table 2-4-Formats for Genetic Counseling

Activity Hours per week Predominant response (%)

Direct patient contact . . . . . . . . . . . . . . . . . . . . . . 15indirect patient activities. . . . . . . . . . . . . . . . . . . 11Administration/management . . . . . . . . . . . . . . . 7Educating health professionals . . . . . . . . . . . . . 3Research . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 2Educating the general public. . . . . . . . . . . . . . . 1Marketing/business . . . . . . . . . . . . . . . . . . . . . . 1

individual 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.


newly 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. Counselingfor CF carrier screening, with no family history,however, was estimated to take one visit of less thanan hour. The need for sufficient and appropriatepretest education and post-test counseling is dis-cussed in depth in the full OTA report (10).

GENETICS CLIENTELEGenetic counselors and nurses in genetics work in

a variety of settings and often the setting in whichthey work dictates the types of clients they encoun-ter. For example, working in a department ofobstetrics and gynecology is likely to mean that themajority of one’s clients are pregnant or undergoingfamily planning prior to pregnancy. Employment ina department of pediatrics or a children’s hospitalmeans that most clients are likely to be children andtheir families. Some counselors work in specialtyclinics, such as cranio-facial clinics or sickle cellscreening 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 geneticcounselors and nurses in genetics are Caucasian (70percent) (figure 2-4). Respondents report an ethnicand 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 provideinformation, however, about equitable allocation ofgenetic services locally or regionally. African Amer-icans or Asian Americans might find genetic serv-ices accessible in one city or one region but not inanother. Genetics services in cities with largeminority populations might be more likely to hirehealth care providers with language or cultural skillssuitable to certain populations.

Ninety-two percent of genetics clientele are Eng-lish speaking. As mentioned earlier, 13 percent ofgenetic counselors and nurses reported fluency in alanguage other than English, but no effort was madeby OTA to correlate provider fluency with clienteleneeds.

Figure 2-4—Racial/Ethnic Background ofClinical Genetics Clientele

African American 1 15%

surname 10%

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 averageclinic clientele. The second largest group of individ-uals seen are children (11 percent). Infants andneonates collectively comprise 14 percent of genet-ics clientele (figure 2-5).

Most of the adults of reproductive age are seen forprenatal diagnosis (figure 2-6), most likely foradvanced maternal age. Prenatal genetics patientswere reported as being seen very often or almostalways by nearly two-thirds of respondents (figure2-6). Clearly, prenatal diagnosis is a primary reasonfor individuals to have contact with the clinicalgenetics setting. Respondents also reported that

Figure 2-5—Age Distribution of Genetics Clientele

Neonatal7% Infants

ildren1%

Adolescents4%

‘Adults of post- reproductive age

reproductive age


2 9 7 - 9 1 1 0 - 92 - 2


. . . . \ , \,\, \,\,

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, , , , , , , , , , , , , , , , , , , -. . . . . . . . . . . . . . . . . . . . . . . . . . . . # , , , , , , # , , , , , , , , , , , , , , , , , , , , , ,. . . . . . . . . , . . . . . . . . . . . , , , , , , , , , , , , , , , , , , , , . , , , , ,. . . . . . . . . . , ?,/,/, ./, ?..,/,?,/,/ , , , , , , , , , , , , , , , , , , , , , , , , , , , , ,. . . . . . . . . ., . . , , , , , , , , , , , , , , , , , , , , , , , , , , , , , ,. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . ,. . . . . . . . . . . . . . . . . . ,


pregnant women receiving followup counseling forabnormal MSAFP results often (27 percent) or veryoften (31 percent) are apart of their clientele (figure2-6). Individuals seeking carrier screening for avariety of genetic disorders, such as those describedin table 2-5, seldom (22 percent) or sometimes (50percent) 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-PARTYCOVERAGE

How expensive are genetic services and willinsurers pay for them? How do third-party payersdecide what is medically indicated and, therefore,should be covered? Many of these issues areaddressed 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 ofgenetic counselors and nurses, OTA obtained infor-mation 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 particularlyrelevant to the debate about CF carrier screening asthe procedure is relatively new, is counter to mostinsurers’ policies against paying for screening, andcould involve potentially large numbers of people.

For many years, genetic counselors have faced theproblem that few third-party insurers will reimbursefor counseling services unless performed by aphysician. The costs of counseling are reimbursed as

Table 2-5-Most Common Diseases for Which CarrierScreening/Testing Is Offered

1.2.3.4.5.6.7.8.

(Ranked by frequency of response)Cystic fibrosisTay Sachs diseaseSickle cell anemiaDuchenne muscular dystrophyThalassemiaHemophiliaHemoglobinopathiesFragile X syndrome


Figure 2-7—Number of Cystic Fibrosis Patients orFamilies Seen in Genetics Units in 1990

I 6260

50

40

30

20

10

0-10 11-20 21-30 31-40 41-5091-100 +100

Number of patients


general medical consultation fees or absorbed as partof costs on research grants (9).

Fees for Genetic Services

Genetic counseling can be provided alone or inconjunction with diagnostic procedures. Most sur-vey respondents work in large university or privatemedical centers where billing departments are oftenquite separate and distinct from the various clinicaldepartments. Fees are coded and processed inde-pendently. This might explain why a majority ofrespondents did not know whether certain geneticservices were reimbursable and, in some cases, didnot even know the fee schedule for basic geneticservices (table 2-6). For those who knew the feeschedule for genetic services, general genetic coun-seling averaged $80 per session. The range was $0

Table 2-6-Average Fees and Knowledge ofFees for Genetic Services

Percentrespondents

uncertainService Fee of fee

General genetic counseling . . . . . . . . . . . $80 45Genetic counseling for CF with a

positive 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 66



Table 2-7—Fees for General Counseling

Fee Percent 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 . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 38

SOURCE:Office of TechnologyAssessmentj 1992.

to $350 (table 2-7). The fee for genetic counselingfor individuals with a family history of CF was notsignificantly different from the fee that would becharged to individuals requesting the same serviceswith a negative history for CF($112 versus $105).In the summer of 1991, the average fee for DNAanalysis for CF was $235 although spring 1992 datacollected separately by OTA found an average costof $170 per sample.

Third-Party Coverage

Respondents reported that most of their clients arecovered by some type of health insurance. Twopercent said that their patients seldom if ever havehealth care coverage, whereas 63 percent reportedthat their clients very often or always have coverage(figure 2-8). Commercial insurance, health mainte-nance organizations, or managed care programscomprise over half of the coverage (figure 2-9).Medicaid (21 percent) and Blue Cross/Blue Shieldplans (17 percent) also cover genetics clients. Fourpercent of clients have no insurance and 3 percentare indigent.

With regard to coverage of genetic counselingservices accompanying DNA-based tests to deter-mine CF carrier status, respondents reported a higherlikelihood of coverage if there is a family history ofCF than if there is no family history (figure 2-10).This result was confirmed by OTA’s survey ofhealth insurers, which found health insurers rarelyreimburse individuals for CF carrier tests in theabsence of a family history (11).

OTA attempted to ascertain whether individualswho avail themselves of genetic tests subsequentlyhave difficulty obtaining or retaining health insur-ance. The survey asked for reported occurrences forgenetic tests, generally, not just carrier tests for CFor other disorders.2 OTA asked:

Figure 2-8-Health Care Coverage forGenetics Clientele

40

33

0

Seldom if ever Sometimes Often

Very often Always or almost always


Figure 2-9-General Types of Health Care Coveragefor Genetics Clientele

I Commercial

Medicaid

HMO or 17% managed care 22°A


Have any of your patients experienced difficultiesin obtaining or retaining health insurance coverageas a result of genetic testing? If yes, please providedetails.

Approximately four-fifths (347) of the 431 re-spondents to OTA’s inquiry currently performgenetic counseling. Fifty respondents (14 percent)reported they had clients who had experienceddifficulties obtaining or retaining health care cover-

of OTA asked respondents to speculate about accepting applicants with certain genetic (11).

Chapter 2-Providers, Clientele, and Genetic Services . 13

Figure 2-10-Third-Part y Reimbursement forGeneral Genetic Counseling and Counseling

Specifically for Cystic Fibrosis

3027

25

16

20

19

Seldom Sometimes Often Very often Almostif ever covered covered covered always

covered covered

General genetic With no family With familycounseling history of CF history of CF


age as a result of genetic testing (table 2-8). Becausesome respondents described more than one case, thenumber of affirmative answers understates the actualnumber of cases. Examination of the qualitativeresponses, some of which are presented in table 2-9,reveals affirmative responses represent, at mini-mum, 68 individual cases. (Where the term ‘‘pa-tients” was used with specifics not described, asingle event was recorded.)

It is important to emphasize that most of the casesrevealed through the OTA survey do not involverecessive disorders and carrier screening for condi-tions like CF And while one assumption might havebeen that health care coverage for CF carriers wouldnot be an issue because the individuals have nosymptoms of the disorder, OTA’s survey of healthinsurers reveals that a few respondents wouldrequire a waiting period or deny coverage for CFcarriers (10,1 1).

Test results for some conditions where positiveresults led to reported difficulties-such as forHuntington disease, adult polycystic kidney disease,and Marfan syndrome-were cited by more than onerespondent. In addition to affirmative answers,several respondents reported that although they hadno direct experience with a patient’s difficulty in

Table 2-8-Difficulties in Obtaining or RetainingHealth Insurance After Genetic Tests

Question: Have any of your patients experienced difficulties inobtaining or retaining health insurance coverage as aresult of genetic testing?

Number (percent)

No . . . . . . . . . . . . . . . . . . . . . . . . . 281 81Yes . . . . . . . . . . . . . . . . . . . . . . . . 50 14No answer . . . . . . . . . . . . . . . . . . . 16 5


obtaining or retaining health care coverage, they hadclients who feared their coverage would be droppedif they requested payment for tests from insurers.One respondent commented that greater than 80percent of her clients who test for Huntingtondisease self-pay. Similarly, others with no directexperience said they often advise patients not torequest reimbursement for a test so that an insurerwould not learn that testing had occurred. Onecounselor offered the information that a patient hadrefused testing for adult polycystic kidney diseasebecause 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 futurefor 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 specula-tion about any trends. OTA also did not attempt toascertain whether patients had challenged-or werechallenging-insurers’ rulings. Thus, OTA cannotdetermine whether some of the disputes reported intable 2-9 were resolved fully in favor of theconsumer because the initial judgment was deemedimproper or illegal. Some cases, for example,reported a fetus or newborn had tested positive andthe policy cancelled. In all 50 States and the Districtof Columbia, insurers must cover (or offer the optionto include) a newborn child if a valid insurancecontract for the parent exists. However, whether theinsurance company can deny specific benefits for thenewborn by evoking the preexisting conditionclause generally contained in all insurance contractsis unclear.

In presenting table 2-9, OTA does not judge thevalidity-positively or negatively-of the claim.Some cases might have been settled in favor of theindividual. Others might have been cases where an


Table 2-9-Case Descriptions of Genetic Testing and Health Insurance Problemsa

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 Turner’s 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 spouse’s 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 experimentaldiet to prevent problems that can arise from mid- to late childhood or early adulthood. One boy tested positive. The family’s privatepay policy (Blue Cross/Blue Shield) is attempting to disqualify the family for failing to report the family history under preexistingconditions.

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.


applicant attempted to select against an insurer bymisrepresenting his or her health history, whichwould have been resolved against the individual.

In 1991, at least 50 genetic counselors or nursesin clinical practice knew of at least 68 actualincidents where their own patients reported difficul-ties with health insurance due to genetic tests. OTAestimates, based on the average number of patientsdirectly counseled, that genetic counselors andnurses responding to the survey collectively sawabout 110,600 individuals in 1990. However, OTAdid not advise respondents to limit descriptions ofclients’ insurance difficulty to 1990. Thus, it isunlikely that all reported cases occurred in 1990;assuming all cases occurred in 1990 means the 68cases represent 0.06 percent of patients seen byrespondents.

Critics question whether the data-especially thequalitative descriptions—merely represent more an-ecdotal stories that unfairly present one side of thestory and for which no response can be developed.Skeptics point out that some of the cases might fallinto the gray area of whether exclusion or increasedrates resulted because an adverse medical condition

was revealed through a diagnostic test that justhappened to be genetic. The border between whatconditions are genetic or not is blurred, however, andwill become increasingly diffuse. Because genetic-based predictive testing promises to have a profoundimpact on clinical medicine-and because access tomedical care is inextricably linked to private healthinsurance in this country-these cases underscorecertain policy dilemmas arising from the increasedavailability of genetic assays.

SUMMARYAlthough genetic counselors and nurses in genet-

ics work in a variety of settings, they are concen-trated in metropolitan medical centers on the Westcoast or Northeast region. States with a largeproportion of rural residents are less likely to beserved. The clientele served, in the aggregate, tendto be representative of the national averages formajority and minority groups, although no effortwas made by OTA to match racial and ethnic datawith regions, cities, or localities.

Most genetic counselors have a master’s degreeand are either certified or eligible for professional


certification. They spend most of their work weekseeing or talking with clients. Less time is spent onadministration and research, and even less onprofessional and public education. Seventy percentof the genetics clientele is comprised of adults ofreproductive age suggesting the strong influence ofprenatal diagnosis as a primary genetics service.Respondents report that their counseling services arefrequently not covered by third parties, even when“medically indicated.’

OTA’s survey reports consumers can experiencedifficulties in obtaining or retaining health carecoverage after genetic tests. Because genetic-basedpredictive testing promises to have a profoundimpact on clinical medicine-and because access tomedical care is inextricably linked to private healthinsurance in this country-these cases underscorecertain policy dilemmas arising from the increasedavailability of genetic assays.

4.

5.

6.

7.

8.

9.

10.

1.

2.

3.

CHAPTER 2 REFERENCESBoyle, 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 ofGenetic Services,” Issues in Health Care of Women4:1-15, 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,” JournuZof 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 andResponse Rates: A Literature Review,” Journal ofMarketing Research 12;440-454, 1975.National Society of Genetic Counselors, Wallingford,PA, personal communication, June 1991.National Society of Genetic Counselors, “Report toMembership: 1992 Professional Status Survey,”Perspectives in Genetic Counseling, newsletter of theNational Society of Genetic Counselors, Inc., sum-mer 1992.U.S. Congress, Office of Technology Assessment,“Cystic Fibrosis, Genetic Screening, and Insur-ance,” transcript of workshop proceedings, Feb. 1,1991.U.S. Congress, Office of Technology Assessment,Cystic Fibrosis and DNA Tests: Implications ofCarrier 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 aSurvey, 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 Educationin Genetic Counseling,’ American Journal ofHumanGenetics 46:1223-1230, 1990.

Chapter 3

Cystic Fibrosis Carrier Screening: Policies and Practices

Prospects of routine cystic fibrosis CF carrierscreening polarize people. Everyone agrees thatpersons with a family history of CF should have theopportunity to avail themselves of CF mutationanalysis, yet controversy swirls around using thesame test in the general population. This polariza-tion is illustrated in the written comments of twosurvey participants.

NO to widespread screening! Must be close to 100percent detection for all CF mutations before it caneven be considered.Let’s go with screening! I can’t believe we are nothalfday through a pilot program by mid 1991.

As described in the full OTA report (18), propo-nents of a measured approach to CF carrier screeningexpress concern about several issues that might beraised if CF carrier screening becomes routine, suchas the use of genetic information by insurancecompanies to set rates or deny coverage, andconcerns that market pressures will drive wide-spread use of tests before the potential for discrimi-nation or stigmatization by other individuals orinstitutions is assessed. Also expressed are questionsabout the adequacy of quality assurance for DNAdiagnostic facilities, personnel, and the tests them-selves. Still others also wonder whether the currentnumber of health care professionals in genetics canhandle a swell of CF carrier screening cases, letalone cases of other genetic conditions arising fromincreased knowledge from the Human GenomeProject. Finally, the extraordinary tensions in theUnited States about abortion affect discussionsabout CF carrier testing and screening.

I n summer 1991, OTA asked genetic counselorsand nurses in genetics to provide data regarding theirexperiences concerning CF carrier screening as ameans to judge the validity of these concerns. Thequestionnaire was designed to gather data on thefrequency of DNA analysis for CF carrier status andtrends over time, clinic policies regarding CF carrierscreening, counseling and clinical practices regard-ing CF carrier testing and screening, and sourcesinfluencing the development of, and policies andprocedures related to, CF mutation analysis. Surveyparticipants were also asked their opinions aboutwho should conduct carrier screening, in what

settings, and on what target population(s). Respond-ents were encouraged to rank the most importantissues to be addressed before embarking on alarge-scale screening program.

The data in this chapter are specific to CF carrierscreening. Data regarding third-party reimburse-ment for DNA-based tests are presented in chapter2, along with general demographic data concerningthe survey respondents and their clientele andclinical settings.

POLICIES AND PRACTICES,SUMMER 1991

Survey participants were asked to consider threeissues. First, what is their opinion or the policy oftheir institution about the appropriateness of CFcarrier screening at this time? Second, what are thecurrent logistics of providing DNA-based tests forCF carrier status-i.e., once a decision had beenmade to offer CF mutation analysis, which muta-tions are analyzed, and how are those individuals tobe tested identified or contacted? Third, surveyparticipants were asked to estimate whether requestsfor DNA-based tests for CF had changed since thetests’ development in 1989.

Policies on Cystic Fibrosis Carrier Screening

Currently, it is standard practice to offer CFcarrier tests to individuals who have a positivefamily history of CF (6,16,18). An unaffectedsibling of an individual with CF has a 2 in 3likelihood of being a CF carrier. A consanguineousuncle or aunt of an individual with CF has a 1 in 2likelihood of being a carrier. A first cousin of anindividual with CF has a 1 in 4 likelihood of beinga carrier (table 3-l).

As of the summer of 1991, most genetic counsel-ors and nurses in genetics did not offer unsolicitedCF mutation assays to individuals with a negativefamily history. A large majority of survey respond-ents use medical journals and other professionalsources to obtain information regarding new ad-vances in human genetics (table 3-2), and theAmerican Society of Human Genetics (ASHG) andthe National Institutes of Health (NIH) publishedpolicy documents in 1990 discouraging CF carrier

–17 -


Table 3-l—A Priori Carrier Risks for Cystic Fibrosis

Negative family historyCaucasian. . . . . . . . . . . . . . . . . . . . 1 in 25 (4%)African American . . . . . . . . . . . . . . . 1 in 60 to 65 (1.5 to 1.7%)Asian American. . . . . . . . . . . . . . . . 1 in 150 (0.7%)Hispanic American. . . . . . . . . . . . . 1 in 46 (2.2%)

Positive family historyParent of child with CF . . . . . . . . . 1 in 1 (100%)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 CF . . . . . . . . 1 in 2 (50%)

a Consanguineous.


Table 3-2-Sources of Information AboutNew Advances in Human Genetics

PercentHuman genetics indicating yes

Medical journals . . . . . . . . . . . . . . . . . . . . . . . 96Professional colleagues . . . . . . . . . . . . . . . . 94National inferences . . . . . . . . . . . . . . . . . . . 83American Society of Human Genetics . . . . . 82National Society of Genetic Counselors . . . 80State or regional conferences . . . . . . . . . . . 71Grand rounds . . . . . . . . . . . . . . . . . . . . . . . . . 44Lay press . . . . . . . . . . . . . . . . . . . . . . . . . . . . 37Continuing education courses . . . . . . . . . . . 35Literature from biotechnology companies

or commercial firms. . . . . . . . . . . . . . . . . . 35Other . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 8SOURCE: Office of Technology Assessment, 1992.

screening (6,16).1 Seventy-six percent of respond-ents stated that they were familiar with the 1990ASHG statement. Thirty-five percent were familiarwith the NIH statement.

OTA’s survey of genetic counselors and nursesrevealed that 53 percent of respondents believe thatCF carrier tests should only be offered to individualswith a positive family history of CF and not to thosewith a negative family history. Twenty-one percentfelt that CF carrier tests should be offered toindividuals with no family history. The most fre-quently cited reasons for making tests available toindividuals regardless of family history were toreduce anxiety or increase patient autonomy. In thewords of one counselor, ‘‘DNA screening is apersonal issue, different in every case. What oneperson or family feels may be quite different fromthat of another person or family in any given geneticdisorder with any given family history.’ Twenty-six

percent of respondents were uncertain as to whetherthey should provide CF carrier screening wherefamily history is negative.

When asked about their likelihood of introducingthe topic of CF carrier tests during a counselingsession, 82 percent of respondents stated that theywould seldom, if ever, do so to all patients orfamilies (table 3-3). Seventy-three percent wouldseldom, if ever, discuss it with pregnant womenseeking prenatal diagnosis unless there was a familyhistory of CF in which case, 90 percent wouldalmost always bring it up during counseling.

When asked whether their institution or clinic hada specific policy regarding CF carrier screening, 33percent of genetic counselors and nurses respondedin the affirmative. Of those responses, 70 percentstated that it is the policy of their clinic ororganization to offer CF carrier tests only to thosewith a positive family history (table 3-4).

The overall lack of policies for CF carrierscreening apparently stems from the fact that, ingeneral, explicit and official policies for clinicalpractices were not routine at the majority of facili-ties. When asked whether their group or unit had

Table 3-3-Likelihood of Introducing the Topic ofDNA Testing for Cystic Fibrosis

PredominantPatient 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)


Table 3-4-Specific Policies Regarding DNA Testingfor Cystic Fibrosis

Policy Percent

Offer to all regardless of family history . . . . . . . . . . . . . 14Offer only to those with a positive family history . . . . . 70Provide to those with no family history upon request

if informed consent is obtained . . . . . . . . . . . . . . . . . 16SOURCE: Office of Technology Assessment, 1992,

1 III 1992, ASHG’S 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).

Chapter Cystic Fibrosis Carrier Screening: Policies and Practices . 19

official policies and procedures for other issues ingenetics, 21 percent reported they have policiesregarding DNA storage, 42 percent have policies inplace concerning prenatal diagnosis for sex selec-tion, 37 percent have policies regarding cases ofnonpaternity, and 28 percent adhere to policiesregarding confidentiality and Huntington diseasetesting.

Criteria for Cystic Fibrosis Carrier Screening

Sixty-five percent of survey participants feltstrongly that there is an optimum rate of detectionthat should be reached before they would feelcomfortable offering CF carrier screening, as com-pared to 14 percent who felt there is not and 21percent who were uncertain. Of those who felt thereis an optimum rate of detection, nearly half (46percent) said that 95 percent test sensitivity shouldbe required before proceeding with widespreadscreening. Twenty-five percent believe test sensitiv-ity should be even higher, with 4 percent stating thatit should be 100 percent (figure 3-l).

However, survey respondents ranked the avail-ability 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 neces-sary for implementation of large-scale CF carrierscreening.

Perhaps the point on which there was greatestconsensus among the respondents is on the issue ofautonomy and choice in screening. There are nomandatory genetic screening programs of adultpopulations in the United States. Ninety-nine per-cent of survey participants responded that CF carrierscreening should be voluntary and never mandatory.

Practices Regarding DNA-BasedCystic Fibrosis Carrier Tests

When asked about the frequency of requests forDNA testing or screening for CF carrier statusduring 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 asmall increase in the number of requests and aquarter noted a large increase in requests (figure3-3). The survey did not distinguish whether therequests were carrier tests for individuals known to

Figure 3-l—Opinions on Optimal Rate of Detection

6 0 ,

I46

75% 80% 85% 90% 95% 97% 98% 99% 1 0 0 %

Optimal test sensitivity


Table 3-5-Minimal Criteria for Cystic FibrosisCarrier Screening Protocol

Question: What do you feel should be the minimum criteria for CFcarrier screening protocol)?

Criteria Percent a

Provision of adequate counseling . . . . . . . . . . . . . . . . 40Adequate system of referral in place . . . . . . . . . . . . . 37Improved test sensitivity. . . . . . . . . , , . . . . . . . . . . . . 35Guarantee of informed consent . . . . . . . . . . . . . . . . . 32Availability of educational materials. . . . . . . . . . . . . . 18Only offer to families with a positive history of CF 15Must be voluntary. , . . . . . . . . . . . . . . . . . . . . . . . . . . . 14Reasonable cost or payment . . . . . . . . . . . . . . . . . . . 12Protection of confidentiality . . . . . . . . . . . . . . . . . . . . 12

not add to 100; respondents could reply with answers.


be at risk by virtue of family history or carrierscreens for individuals with no known family historyof CF

Although 55 percent of survey participants re-sponded that a CF treatment center exists at theirinstitution, 86 percent reported that they do notprovide genetic counseling through that facility.Several respondents noted that this is the choice ofthe CF treatment provider, not necessarily thegenetics unit. Because OTA did not survey CFtreatment centers, it is not known to what extent CFfamilies are informed of, offered, or request carriertesting. The data do show, however, that mostfamilies who have a child with CF are not routinely


Figure 3-2—Frequency of Requests for Cystic FibrosisCarrier Screening/Testing, January-June 1991

60

.5(-) - 48I

10

0

Never Occasionally Very frequently

Rarely Frequently


Figure 3-3-Comparison of Requests for cystic FibrosisCarrier Screening/Testing Between January-June 1991

and Past 2 Years

46

A large decrease No change

A small decrease A small increase increase


seen in genetics service settings, and few counselorshave routine contact with CF families.

Encouraging known carriers to notify consan-guineous relatives (e.g., siblings and first cousins)provides economic and pragmatic benefits becauseit 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 screeningthose with unknown risk. In reality, complex psy-chological factors enter when family members ofindividuals with CF contemplate screening, and itcannot be assumed that all will want to be tested.

For this type of carrier identification to work,those providing health care and counseling to CFfamilies will have to actively participate in referralsof relatives to genetics centers, an uncommonpractice, according to OTA’s data. Fewer than 10percent of respondents reported contacting previ-ously identified CF families with whom they hadhad contact about the availability of CF mutationanalysis.

For those respondents whose institutions areengaged in CF carrier testing or screening, directDNA mutation analysis is the most common ap-proach (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 of

Table 3-6—Types of Genetic Analyses Provided forCystic Fibrosis Screening/Testing

Procedure Percent response

Direct mutation analysis. . . . . . . . . . . . . . . . 67Prenatal DNA analysis. . . . . . . . . . . . . . . . . . 63DNA linkage analysis . . . . . . . . . . . . . . . . . . . 61DNA haplotyping . . . . . . . . . . . . . . . . . . . . . . 56Staging of studies . . . . . . . . . . . . . . . . . . . . . 37DNA banking . . . . . . . . . . . . . . . . . . . . . . . . . 31Fetal intestinal enzyme analysis . . . . . . . . . . 28


Table 3-7-Cystic Fibrosis MutationsRoutinely Analyzed

Mutation Percent response

DF508 . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 100G551D . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 77R553X . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 76G542X . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 71N1303K . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 70Other . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 79SOURCE: Office of Technology Assessment, 1992.

Chapter 3-Cystic Fibrosis Carrier Screening: Policies and Practices ● 21

Central and Eastern European descent (AshkenazicJews), W1282X, had not been found.2

Respondents report an almost even split betweencommercial and university-based laboratories as thefacility performing their CF mutation assays (45percent and 48 percent, respectively). Most centerssend the sample offsite (76 percent), frequently to alaboratory greater than 150 miles away.

Finally, although the need for professional andpublic education was cited as critical for theimplementation of widespread carrier screening, fewgenetic counselors and nurses in genetics reportedspending professional time engaged in either activ-ity. For those respondents who do, an average of 3hours per week devoted to educating health profes-sionals and 1 hour per week on educating the generalpublic was reported (ch. 2). For CF carrier screening,specifically, 8 percent of genetic counselors andnurses had developed, or were in the process ofdeveloping, educational materials relevant to DNAtests for CF mutation.

PREFERRED STRATEGIESAND PROTOCOLS

The importance of informed consent, carefulpresentation of counseling, and confidentiality havelong been recognized as essential components ofgenetic testing and screening (9). Respondentsstrongly 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 counselingand 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). Thisconcern has been played out in the debate overmaternal serum alpha-fetoprotein (MSAFP) screen-ing and is a factor in the reluctance of the clinicalgenetics community to rush toward widespreadscreening for any disease (18). For example, as partof the debates surrounding MSAFP and CF carrierscreening, concern has been voiced about informedconsent—in particular, that tests would be availableto primary care practitioners who might incorporate

Figure 3-4-Opinions Regarding Genetic Counselingof Individuals with a Positive Family History

1001

I93

0

Strongly agree Undecided Strongly

Agree Disagree disagree

Genetic counseling should precede DNA testing for CFwhen there is a positive family history.


Figure 3-5-Opinions Regarding Genetic Counselingof Individuals with a Negative Family History

60-

5 0 -c

4 0 -

30-8

2 0 -

l o -

0

84

I 18

Strongly agree Undecided strongly

_ A g r e e Disagree disagree

Genetic counseling should precede DNA testing for CFwhen there is a negative family history.


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


the assay into their practice without considering theinformed consent requirements usually adhered to ingenetics practices. Seventy-nine percent stronglyagree that informed consent prior to CF carrierscreening is a necessity (figure 3-6).

In addition to informed consent, prescreeningeducation for clients is imperative. Informationregarding an individual’s a priori risk, types of testsavailable, and uncertainties in risk assessment basedon screening results are important for potentialscreenees to understand. When asked if educationalmaterials can provide adequate information aboutCF carrier screening, 44 percent disagreed or stronglydisagreed with that concept (figure 3-7).

Who Should Provide Cystic FibrosisCarrier Screening?

Concern about the complex nature of somegenetic information and the need in some cases forpost-test counseling leads many human geneticsprofessionals to advocate restricting CF carrierscreening primarily to the human genetics commu-nity. Pretest education, felt many respondents, canbe offered by a wide range of professionals (figure3-8), but organizing CF carrier screening should beprovided by genetic specialists (table 3-8). Nearly 82

Figure 3-6—Opinions Regarding the Need forInformed Consent Prior to Cystic Fibrosis

Carrier Screening

79

13

Strongly agree Undecided strongly


Informed consent prior to CF carrier screening is a necessity.


Figure 3-7-Opinions Regarding the Use ofEducational Materials as a Source of Information

About Cystic Fibrosis Carrier Screening

30

15

I

o

7

28 I

Strongly agree Undecided


Educational materials (culturally sensitive and understandable)can provide adequate information about CF carrier screening.


percent of the respondents surveyed by OTA said thehuman genetics community should be the primaryorganizer of CF carrier screening programs (table3-8). 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 ofcommunicating risk information regarding CFeven for experienced genetic centers—has 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 familypractitioners or OB’s [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 orgeneral public education in schools and communi-ties. Thus, the majority of people will rely on theirprimary care provider for preliminary, if not most,


Table 3-8—Preferred Organizations for lmplementationof Voluntary Cystic Fibrosis Carrier Screening

Organization Yes Noa

(percent)Human genetics community . . . . . . . . . . 82 15State or local health department. . . . . . . 59 39Voluntary health organizations . . . . . . . . 30 67Primary caregivers . . . . . . . . . . . . . . . . . . 27 71Medical societies . . . . . . . . . . . . . . . . . . . 17 81Federal Government . . . . . . . . . . . . . . . . 15 82as per~nt gave no res~nse


Table 3-9-Preferred Sites for Cystic FibrosisCarrier Screening Programs

Site Yes Noa

(percent)Genetics centers . . . . . . . . . . . . . . . . . . . 89 7Primary care setting . . . . . . . . . . . . . . . . . 59 37Community-wide . . . . . . . . . . . . . . . . . . . . 53 43Public health department. . . . . . . . . . . . . 48 49Public schools . . . . . . . . . . . . . . . . . . . . . 14 83Workplace . . . . . . . . . . . . . . . . . . . . . . . . 9 87=qs per~nt gave no response


genetic information (18), and many survey respond-ents said primary care providers and public healthdepartments should play an active role in educatingthe public about DNA tests for CF carrier status(figure 3-8). Health care provider and community-wide genetics education will become increasinglyimportant, as will the interaction of genetic special-ists with other health professionals and the public.

Who Should Pay for Cystic FibrosisCarrier Screening?

When asked who should pay for screening, 80percent of respondents ranked third parties as theprimary source of payment (table 3-10). Self pay wasranked second, and employers ranked last. Addition-ally, some participants noted that if screening everbecame mandatory, as in many State newbornscreening programs, the State or Federal Govern-ment should be responsible for payment.

Strategies for Screening Various Populations

Two key considerations in deciding how routineCF carrier screening is best implemented are theclinical settings in which it will take place and thetarget populations. Delineation of a target group (orgroups) determines other elements such as location,

educational approach and tools, time, format, typesof counseling, facilities, and publicity.

The NIH statement on CF carrier screeningemphasized the importance of preconceptional screen-ing (16). Most pilot projects in the United Kingdomare directed at preconceptional populations (18).One program in Canada targets high school students(11).

Newborn Screening

Numerous newborn screening programs exist forgenetic disorders such as sickle cell anemia andphenylketonuria. These are programs intended toscreen for the presence of disease, although somecan also detect the carrier status of the newborn.Using the immunoreactive trypsin assay, Wisconsinhas performed statewide neonatal screening for CFdisease since 1985, and primary care physicianshave been cooperative in referring screened patientsto designated CF centers for followup (14). But evennewborn screening for CF disease is not withoutcontroversy. Evidence of heightened anxiety anddisrupted maternal-infant bonding have been re-ported in cases of false-positive diagnoses (4).

For at least two reasons, many believe thatnewborn screening is an inappropriate and ineffi-cient mechanism for carrier detection. First, new-borns determined to be carriers must be trackedthrough their reproductive years to ensure they areaware of their carrier status. Second, detection ofnewborn carriers might unnecessarily raise theanxiety level of parents. Thus, newborn screeningfor CF carrier status is not generally viewed asacceptable (15). This survey revealed that 33 percentof genetic counselors and nurses in genetics believedthe newborn population would be an appropriatetarget group for widespread CF carrier screening(table 3-11).

Adolescent Preconceptional Screening

Some geneticists advocate carrier screening at thehigh-school level (11). A recent nationwide surveyof American attitudes about, and knowledge of,genetic tests showed better knowledge and morepositive attitudes in younger populations (17).Studies of pregnant women known to be carriers ofa hemoglobinopathy gene have shown that age is apredictor of postcounseling knowledge-youngerwomen (and adolescents as young as 12 years old)are more likely to understand genetic information(13). While not routinely done in the United States,

24 . Genetic Counseling and Cystic Fibrosis Carrier Screening: Results of a SurveY

Figure 3-8-Extent to Which Various Groups Should Be Involved with Cystic Fibrosis Pretest Education

Primary care providers3 5 ,

I 3130+

II

25-

20-

15-

l o -

5 -

(-JJ--

100

20

0 1

22

Little to Some Moderate Great All orno extent extent extent extent almost

all

Genetic counselors

77

0.2

18

0.54


all

Nurses

I

33

3026

Little to Some Moderate Great orno extent extent extent extent almost

all

Public health departments35

30- 28 28

0L

20

0


all

Genetics programs

0.2

40

30

& o

10

73


all

Family planning clinics

26 26

0Little to Some Moderate Great All or

no extent extent extent extent almostall


Voluntary support groups

o J -

II


all

Lay press

40

co 30

20

oLittle to Some Moderate Great All or

no extent extent extent extent almostall


high-school screening programs have been con-ducted in Montreal, Canada for some time. For anydisease where screening is done in childhood oradolescence, however, the benefits of such screen-ing, including savings in resources or anxiety, mustbe balanced against the potential problems, such asthe possibility that an adolescent will be falselyassigned to a low-risk group because of poor testsensitivity (thereby obviating further screening), orthe possibility of psychosocial harm to the child asa result of identified carrier status (9).

Adolescents were not considered an appropriatetarget by the genetic counselors and nurses surveyed

Schools

36


all

Television

o

36


all

by OTA (table 3-11). Less than one-fifth feltindividuals ages 13 to 18 years should be screened;only 6 percent responded that children ages 2through 12 years should be screened.

Adults—Preconceptional or Prenatal?

One debate surrounding CF carrier screeningfocuses on whether the goals are best accomplishedby 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


Table 3-10-Who Should Pay for Cystic FibrosisCarrier Screening?

Table 3-1 2—Frequency of Patients Seenby Major Areas of Clinical Practice

Rank order Area Predominant response

1. Third parties2. Self pay3. State, city, or county4. Federal Government5. Employers


Table 3-1 l—Target Populations for Cystic FibrosisCarrier Screening

Population Yes Noa

(percent)Adults in reproductive years. . . . . . . . . . 88 8Prenatal . . . . . . . . . . . . . . . . . . . . . . . . . . 75 22Pregnant women or “couples” . . . . . . . . 66 31Newborns . . . . . . . . . . . . . . . . . . . . . . . . . 33 63Children ages 13 to 18 . . . . . . . . . . . . . . 19 78Children ages 2 to 12 . . . . . . . . . . . . . . . 6 91Adults in post reproductive years. . . . . . 3 94a3 per~nt had no response in each cate90rY.


individuals to know their risks before getting preg-nant (12). Others argue that individuals not facing apregnancy are not motivated to seek or use informa-tion on their carrier status, but will wait until they areeither planning a family or starting a family beforeviewing such information as useful (5).

CF carrier screening offered as part of primaryhealth care rather than prenatal care is likely toencourage preconceptional CF carrier screening. Formost individuals, however, the first real opportunityfor carrier screening takes place postconception (8).In the future, the primary responsibility for provid-ing CF carrier screening might reside with theobstetrician, as has happened with MSAFP screen-ing. Sixty-six percent of respondents to OTA’ssurvey identified pregnant women or couples as theappropriate target population for CF carrier screen-ing, yet 88 percent more generally identified adultsin their reproductive years as the appropriate targetgroup (table 3-11). While most respondents statethat the ideal target population for carrier screeningis the preconceptional adult, in reality, the first targetpopulation is likely to be the prenatal populationbecause it has been the traditional entry point intogenetic services for many people and comprises thelargest population served by genetics centers (table3-12).

Prenatal genetics. . . . . . . . . . . . . . . . . . .Pediatric genetics . . . . . . . . . . . . . . . . . .Adult genetics . . . . . . . . . . . . . . . . . . . . .Teratogen exposure . . . . . . . . . . . . . . . . .Reproductive loss . . . . . . . . . . . . . . . . . .Specialty disease(s) clinics . . . . . . . . . . .Newborn screening . . . . . . . . . . . . . . . . .MSAFP screening followup. . . . . . . . . . .Carrier screening . . . . . . . . . . . . . . . . . . .

Very oftenSometimesSometimesSometimesSometimesSometimesSeldom if everOftenSometimes


PROFESSIONAL CAPACITY

Another issue in considering widespread carrierscreening for CF is whether there are enoughadequately trained health professionals to handle thevolume of tests. One study estimated that a minim-umof651,000 counseling hours would be requiredannually if the maximum estimate of 6 to 8 millionpreconceptional couples are screened for CF carrierstatus (19). Considering the current number ofpracticing genetic counselors in the United Statestoday, this translates to 17 weeks per year from eachgenetic counselor to serve solely CF-related clients.On the other hand, another estimate suggests thesupply of genetic specialists could absorb routinecarrier screening for CF sickle cell anemia, hemo-philia, and Duchenne muscular dystrophy, assumingthat obstetricians or other primary care physiciansperform the screening on pregnant women, withreferral of those with positive results to geneticsprofessionals (10).

The counselors and nurses surveyed by OTAestimate pretest counseling time for CF carrier statuswould range from about 45 minutes to over 1 hour,depending on family history (table 3-13). It isunclear to what extent increased demand for CFcarrier screening would strain the current system.Current estimates undercount the number of healthcare professionals who practice genetic counselingand assume that counseling would always be pro-vided in a clinical genetics setting by board-certifiedor board-eligible counselors. Such estimates alsoignore the role that aggressive public education canplay in improving pretest knowledge. Improvementsin public education could result in dramatically lesstime required in formal counseling, as could relianceon health professionals not formally trained ingenetics.


Table 3-1 3-Time Required for Genetic Counseling forVarious Conditions

Figure 3-9—Opinions Regarding the Need forMore Genetic Counselors

Time NumberCondition (minutes/visit) visits

Prenatal counseling for advancedmaternal age . . . . . . . . . . . . . . . . . . . . 54

Positive family history for neural tubedefects . . . . . . . . . . . . . . . . . . . . . . . . . 57

Elevated MSAFP screen . . . . . . . . . . . . . 55Couple with newly diagnosed (Tri21)

Down syndrome child . . . . . . . . . . . . . 78Couple with 14/21 translocation Down

syndrome child . . . . . . . . . . . . . . . . . . . 73Carrier testing for Duchenne muscular

dystrophy . . . . . . . . . . . . . . . . . . . . . . . 75Newly diagnosed case of

neurofibromatosis . . . . . . . , . . . . . 70Newly diagnosed CF family. . . . . . . . . . . 59Carrier testing for CF with a positive

family history . . . . . . . . . . . . . . . . . . . . . 70Carrier testing for CF with a negative

family history. . . . . . . . . . . . . . . . . . . . . 44


11

2

2

2

22

2

1

Two-thirds of respondents strongly agreed that aneed for more genetic counselors exists (figure 3-9).A few respondents raised the possibility of training‘‘single-gene’ counselors to assist in the increasedworkload, although others expressed concern aboutthis prospect, as taking a family history can revealother genetic conditions that might not be detectedby an individual trained to handle one geneticdisorder (18). Still other respondents mentioned theneed for more professional education of health careproviders who might be in the position of adminis-tering such tests, and many survey participants notedthat all groups of health care providers should beinvolved after appropriate training and education.Noted one genetic counselor, “Once screening isclose to 100 percent sensitive, doctors and nursescould easily be trained to provide the necessarycounseling.

When asked what strategies would be consideredto alleviate the projected increase in workloadshould widespread CF carrier screening occur, 55percent gave either no response or reported that theyhad not yet developed any. Of those who hadconsidered or developed strategies, 40 percent saidthey would plan professional education activities toeducate other health professionals, 21 percent woulddevelop videotapes for patient education, 15 percentsaid they would conduct public education, and 14

3 0 - 25

2 0 -

lo-

0

Strongly agree Undecided


A need for more genetic counselors exists.


Table 3-14-Strategies for Implementation ofWidespread Cystic Fibrosis Carrier Screening

Question:What strategies have you considered implementing ifwidespread screening for CF becomes a reality? a

Strategy Percent

Plan professional education activities . . . . . . . . . . . . . . . 40Develop videotapes for patient education . . . . . . . . . . . . 21Conduct public education . . . . . . . . . . . . . . . . . . . . . . . . . 15Arrange for group counseling sessions . . . . . . . . . . . . . . 14Administrative 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 groupcounseling sessions (table 3-14).

ISSUES TO BE ADDRESSEDBEFORE IMPLEMENTATION

When OTA undertook this survey, privatelyfunded pilot projects were under way, but federallyfunded pilot studies to evaluate CF mutation analy-sis in the general population had not yet begun,although NIH had begun a grant competition forsuch projects (18).3 Thus, OTA asked survey respond-

1991, a research initiative on clinical assessments of alternative approaches to genetic counseling related to CF mutation analysis (18).

28 ● Genetic Counseling a&Cystic Fibrosis Carrier Screening: Results of a Survey

Table 3-15-Issues that Need to be Addressed byPilot Programs in Cystic Fibrosis Carrier Screening

Rank order

1. Access to genetic counseling2. Education of the public3. Payment/cost4. Sensitivity of the test5. Protection of confidentiality6. Quality control and assurance7. Identification of a target group8. Availability of reproductive options


ents what issues they viewed as important beforewidespread screening is embraced. Specifically,survey participants were asked at the conclusion ofthe questionnaire to list by priority the importantissues to be addressed by pilot studies in CF carrierscreening.

Interestingly, the sensitivity of the test, which wasoften cited as the reason not to proceed withscreening, was ranked fourth (table 3-15). Access togenetic counseling was listed as the most importantissue to be addressed. But with vast geographicinequities in availability of genetic services it is notclear how access could be considered as anythingother than a variable in following pretest andpost-test consumer behavior. Education of the publicwas ranked as second in level of importance forevaluation by pilot programs. Payment and costissues were ranked third.

SUMMARYA majority (53 percent) of genetic counselors and

nurses in genetics do not offer unsolicited CF carrierscreening. They are also unlikely to be providinggenetic counseling and DNA tests to familiesfollowed in CF clinics and have not yet made effortsto contact CF families seen previously to offercarrier testing to family members. Those whoadvocate CF carrier tests for use beyond affectedfamilies argue that individuals should be routinelyinformed about the assays so they can decide forthemselves whether to be voluntarily screened. Thispopulation was a minority (21 percent) of respond-ents.

If carrier screening is to become routine, 99percent of respondents believe it should be volun-tary, and a majority prefer it be offered to preconcep-tional adults. Given the clientele found in mostclinical genetics settings, it is likely that CF carrier

screening will be offered as part of family planningor reproductive health, and the medical specialtymost likely to offer the test will be obstetrics. Thisperceived tension over the technology’s controllikely contributes to the opinions of some in theclinical genetics community that widespread CFcarrier screening is premature until greater geneticseducation of professionals is in place. With regard toCF carrier screening, concern exists that layers ofuncertainty will inhibit informed consent, adequatepretest education, and post-test counseling and that,ultimately, more harm than good might be done. Yetrespondents recognize the critical role that could beplayed in pretest education by other health careprofessionals and some indicated that should themomentum toward CF carrier screening accelerate,they would make efforts to increase their public andprofessional education activities.

1.

2.

3.

4.

5.

6.

7.

8.

9.

10.

CHAPTER 3 REFERENCESAmerican Society of Human Genetics, “Statement ofthe American Society of Human Genetics on CysticFibrosis Carrier Screening,” personal communica-tion, June 1992.Biesecker, L., Bowles-Biesecker, B., Collins, F., etal., “General Population Screening for Cystic Fibro-sis Is Premature,” American Journal of HumanGenetics 50:438-439, 1992.Botk.in, J.R., “Prenatal Screening: Professional Stand-ards and the Limits of Parental Choice,” Obstetricsand Gynecology 75:875-880, 1990.Bowling, F., Cleghorn, G., Chester, A., et al.,“Neonatal Screening for Cystic Fibrosis,” Archivesof Disease in Childhood 63:196-198, 1988.Brock, D.J., “Cystic Fibrosis,” Antenatal and Neo-natal Screening, N.J. Wald (cd.) (New York, NY:Oxford University Press, 1984).Caskey, C.’ll, Kaback, M.M., and Beaudet, A.L.,“T’he American Society of Human Genetics State-ment on Cystic Fibrosis,” American Journal ofHuman Genetics 46:393, 1990.Clarke, A., “Is Non-Directive Genetic CounselingPossible?,” Lancet 338:998-1001, 1991.Elias, S. E., Annas, G.J., and Simpson, J. L., “CarrierScreening for Cystic Fibrosis: Implications for Ob-stetrics and Gynecologic Practice,” American Jour-nal of Obstetrics and Gynecology 164;1077-1083,1991.Harper, P. S., and Clarke, A., ‘Viewpoint: Should weTest Children for ‘Adult’ Genetic Diseases?,” Lan-cet 335:1205-1206, 1990.Holtzman, N. A., Proceed With Caution: PredictingGenetic Risks in the Recombinant DNA Era (Balti-


11.

12.

13.

14.

15.

more, MD: The Johns Hopkins University Press,1989).Kaplan, F., Clew, C., and Scriver, C.R., “CysticFibrosis Carrier Screening by DNA Analysis: A PilotStudy of Attitudes Among Participants,” AmericanJournul of Human Genetics 49:240-243, 1991.Lipkin, M., Fisher, L., Rowley, P.T, et al., “GeneticCounseling of Asymptomatic Carriers in a PrimaryCare Setting,” Annals of Internal Medicine 105:115-123, 1986.Imader, S., Sutera, C. J., Walden, M., et al., “PrenatalScreening for Hemoglobinopathies. II. Evaluation ofCounseling,” American Journal of Human Genetics48:447451, 1991.Mischler, E., Farrell, P., Bruns, T., et al., “ProgressReport: Neonatal Screening for Cystic Fibrosis inWisconsin,” Wisconsin Medical Journal 88:14-18,1989.Modell, B., “Cystic Fibrosis Screening and Commun-ity Genetics, “ Journal of Medical Genetics 27:475-479, 1990.

16.

17.

18.

19.

National Institutes of Health, Workshop on Popula-tion Screening for the Cystic Fibrosis Gene, “State-ment From the National Institutes of Health Work-shop on Population Screening for the Cystic FibrosisGene,” New England Journal of Medicine 323:70-71, 1990.

Singer, E., “Public Attitudes Toward Genetic Test-ing, ” in Population Research and Policy Review10:235-255, 1991.

U.S. Congress, Office of Twhnology Assessment,Cystic Fibrosis and DNA Tests: Implications ofCarrier Screening, OTA-BA-532 (Washington, DC:U.S. Government Printing Office, August 1992).

Wilfond, B.S., and Fost, N., “The Cystic FibrosisGene: Medical and Social Implications for Heterozy-gote Detection,” Journal of the American MedicalAssociation 263:2777-2783, 1990.

Chapter 4

Summary

For years, experts theorized about confronting thepotential consequences of increased knowledge ofhuman genetics. In the early 1990s, the cysticfibrosis CF mutation test moved the debate fromthe theoretical to the practical. OTA concludes thatthe value of the CF carrier testis the information itprovides. No one can estimate in common termswhat it means to an individual to possess informa-tion about his or her genetic status, especially whenthe value concerns reproductive decisionmaking. Ona larger scale, the potential for widespread CF carrierscreening raises legal, ethical, economic, and politi-cal considerations.

This survey of genetic counselors and nursesworking in genetics, conducted in the summer of1991, reflects the tensions and concerns surroundingdissemination of CF mutation analysis. The surveywas conducted to better understand the environmentin which the average genetic counselor or nurse ingenetics works, to describe the infrastructure andtools available to these professionals, to assess thestate of practice in the provision of CF carrierscreening, and to evaluate their attitudes regardingCF carrier screening.

I n summer 1991, most genetic counselors andnurses in genetics did not offer unsolicited CFcarrier screening and expressed concerns aboutaccess to health insurance, quality control, publiceducation, discrimination, stigmatization, and theadequacy of trained personnel as reasons why theydid not. They are also unlikely to be providinggenetic counseling and DNA tests to familiesfollowed in CF clinics and have not yet made effortsto contact CF families seen previously to offercarrier testing to family members, although agree-ment exists that such individuals should be offeredCF mutation analysis.

Reasons why survey respondents do not offer CFmutation analysis are varied, but professional guide-lines exert some influence. The 1990 policy state-ment of the American Society of Human Genetics(ASHG) stated that CF carrier screening is “NOTyet the standard of care,” and a majority of survey

respondents were aware of that statement. Severalstated that it alone was the reason for their refusal tooffer CF carrier screening. In mid-1992, after

extended discussion, ASHG’s leadership approveda revised statement that CF mutation analysis ‘is notrecommended’ for those without a family history ofCF Some argue that the subtle change in languageof the new statement reflects an evolution of debatewithin the society-that some believe CF carrierscreening may now be offered to individuals withouta family history of CF although it might not be the“standard of care. ” Others argue that ASHG’sposition is unchanged. The effect of the newstatement remains to be seen.

Concern about test sensitivity was another barrierthat respondents said should be addressed beforeroutine CF carrier screening. Two-thirds of partici-pants felt that an optimum frequency of detectionshould be reached before they would feel comforta-ble offering CF carrier screening to the generalpopulation, although nearly a quarter of respondentswere uncertain about whether an optimum wasnecessary. Of those who felt there is an optimalfrequency of detection, nearly half felt that 95percent test sensitivity should be required beforeproceeding with widespread CF carrier screening.Twenty-five percent believed test sensitivity shouldbe greater than 95 percent, with 4 percent stating thatit should be 100 percent. At the time this survey wasconducted, test sensitivity was approximately 80percent. It has increased to 85 to 90 percent as ofsummer 1992, so opinions might have changed.

Two other factors ranked slightly more importantthan test sensitivity as criteria to consider beforeimplementing routine CF carrier screening: theavailability of adequate counseling and an adequatesystem of referral for individuals who test positive.Genetic counseling can be labor intensive. Surveyrespondents indicated that they spend most of theirwork week seeing or talking with clients; patientloads are frequently heavy. Respondents said that,given the potentially complex or emotional nature ofsome genetic information, professionals trained inhuman genetics are essential to insure high qualitycare and informed consent. Guarantee of informedconsent also was mentioned as necessary for imple-mentation of large-scale carrier screening.

Those who advocate CF carrier tests for usebeyond affected families are no less concerned about

–31–


informed consent and quality of services. Propo-nents argue that the tests are sensitive enough forcurrent use and that individuals should be routinelyinformed about the assays so they can decide forthemselves whether to be voluntarily screened.These voices believe that failing to inform patientsnow about the availability of CF carrier assaysdenies people the opportunity to make personalchoices about their reproductive futures. In thissurvey population, however, advocates of routineCF carrier screening were in the minority.

Perhaps the point on which there was greatestconsensus among respondents is on the issue ofautonomy and choice in screening. There are nomandatory genetic screening programs of adultpopulations in the United States. Ninety-nine per-cent of survey participants responded that CF carrierscreening should be voluntary and never mandatory.

Given the existing tensions surrounding CF muta-tion analysis in the general population, who shouldserve as gatekeeper of this new technology? Surveyrespondents strongly believe that CF carrier screen-ing should be organized by and provided by thehuman genetics community. This assumes, how-ever, that large numbers of Americans will learn oftheir CF carrier status through interaction with thegenetic services system.

Based on the client populations reported in thissurvey, routine CF carrier screening will likelyintegrate into medicine in the reproductive contextfirst. The prenatal population has been the traditionalentry point into genetic services for many people;OTA’s survey found 70 percent of the geneticsclientele are adults of reproductive age, reinforcingthe notion of prenatal diagnosis as an entry point forprimary genetics service.

Preconceptional individuals are the ideal popula-tion for CF carrier screening, according to surveyrespondents, but for most individuals the first realopportunity for carrier screening takes place post-conception. Thus, despite survey respondents’ de-sire that information about the availability of assayssuch as CF mutation analysis should come fromgenetic specialists, the primary responsibility forproviding CF carrier screening is likely to residewith obstetricians, at least initially, and especially ifreimbursement for CF mutation analysis and itsattendant counseling become part of routine obstet-ric care. Such a scenario would mirror that which hasoccurred with maternal serum alpha-fetoprotein

screening to detect fetuses with neural tube orabdominal wall defects or Down syndrome-aprospect that concerns some, but not others.

OTA’s survey of genetic counselors and nursesalso reports some consumers experience difficultiesin obtaining or retaining health care coverage aftergenetic tests, though the large majority were not forcarrier status, but were for genetic illness. Neverthe-less, because genetic-based predictive testing prom-ises to have a profound impact on clinical medicine-and because access to medical care is inextricablylinked to private health insurance in this country—such cases underscore certain policy dilemmasarising from the increased availability of geneticassays.

Critics of widespread CF carrier screening ques-tion whether the present genetic counseling systemin the United States can handle the swell of cases ifCF carrier screening becomes routine. Currently,about 1,000 master’ s-level genetic counselors prac-tice in the United States, and an additional 100nurses in genetics provide similar services. OTA’ssurvey of genetic counselors and nurses in geneticsindicates that respondents believe routine CF carrierscreening will strain the present genetic servicesdelivery system. Respondents estimated that, onaverage, 1 hour would be needed to obtain athree-generational family history and to discuss CFcarrier screening and genetic risks.

Skeptics of a personnel shortage assert thatcounseling about CF carrier assays is likely to takeplace in the general obstetric/prenatal context, how-ever, and believe 1 hour exaggerates the amount oftime that suffices for all prenatal tests, let alone onlyCF carrier screening. Furthermore, counseling re-lated to CF carrier screening is likely to extendbeyond genetics professionals to include otherphysicians and allied health professionals. Forexample, an unknown number of social workers,psychologists, and other public health professionalsperform genetic counseling, often to minority andunderserved populations.

ultimately, the issue of adequate services andprofessional capacity could turn on the extent towhich patients receive genetic services throughspecialized clinical settings, as they largely do now,versus access through primary care, communityhealth, and public health settings. Overall, OTAcannot conclude whether increased numbers ofgenetic specialists are necessary, but clearly in-

Chapter Summary .33

creased genetics education for all health care profes-sionals is desirable. Routine carrier screening forCF-and tests yet to be developed for other geneticconditions-will require adequate training and edu-cation of individuals in the broader health caredelivery system. Some survey respondents recog-nize the critical role other health care professionalswill play in pretest education and indicated thatshould the momentum toward CF carrier screeningaccelerate, they would make efforts to increase theirpublic and professional education activities.

Although genetic counselors and nurses in genet-ics work in a variety of settings, they are concen-trated in metropolitan medical centers on the Westcoast or in the Northeast. States with large ruralpopulations are less likely to be served. The clienteleserved, in the aggregate, tend to be representative of

the national averages for racial and ethnic popula-tions, although no effort was made by OTA to matchracial and ethnic data with regions, cities, orlocalities. This diversity presents great opportunityin terms of professional and public education, yetfew counselors report an emphasis on these activi-ties in their weekly routine because patient servicescomprise two-thirds of their time.

One of the tasks of genetic specialists, however,is to provide the educational and counseling servicesnecessary to successful implementation of newtechnologies. Diagnostic tools, such as DNA tests,can provide powerful information. Increasingly,genetic counselors and nurses working in geneticswill be at the front line on the issues raised byassimilating DNA technologies into clinical prac-tice.

Appendix A

Survey Method

Data for this survey were collected from 431 surveyquestionnaires mailed to 813 individuals in June and Julyof 1991. The sample was drawn from the membership listof the National Society of Genetic Counselors (NSGC)and the mailing list of the International Society of Nursesin Genetics (ISONG). Only full members (excludingstudent, associate, and foreign memberships) of theNSGC were surveyed. The initial mailing list provided byISONG was screened to remove individuals who were notpracticing nurses from the sample (e.g., journalists,vendors).

Questionnaires were not numerically or otherwisecoded, and hence were completely anonymous. Respon-dents were asked to return their questionnaire in apost-paid envelope provided by OTA. Approximately 2weeks after the initial mailing, a followup letter was sent

to all survey respondents. The second wave improved theresponse rate by about 15 percent.

The content of the instruments was identical for the twopopulations, but the questionnaires were reproduced ondifferent colored stock for easier tracking. Preliminaryanalysis revealed no significant difference in questionresponse between the NSGC and ISONG samples, and soall data were combined into one set for the final analyses.

Surveys returned after September 30, 1991 were notincluded in the final data analyses. A statistical softwarepackage was used to provide frequency distributions andcross-tabulations of the data. No weighting was done ofthe sample, as OTA believes that the sample closelyrepresents the entire population.

–35–

Appendix B

Survey Instrument

As part of the 1992 assessment Cystic Fibrosis and DNA Tests: Implications of Carrier Screening, OTA surveyedthe summer 1991 memberships of the International Society of Nurses in Genetics and the National Society of GeneticCounselors. The items for the two questionnaires were identical, and the following is a reproduction of the surveyinstrument.

-36--

Appendix B-Survey Instrument 37

Office of Technology AssessmentUnited States Congress

Washington, D.C. 20510-8025

SURVEY OF GENETIC COUNSELING ATTITUDES AND PRACTICESREGARDING 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 . — Blackc . — Caucasian f “ —

Marital status:a. marriedb . — widowed d. —

HispanicNative AmericanOther:

never marrieddivorced/separated

In what State do you work? State a. ZIP code b.

Degrees held:a. MA/MS - Genetic counselingb . — RN/BSNc . — MSNd . — MPH

MSWPh. 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, 1990b . — Board eligible

not necessary for positiond: 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 timeb. part time: hours/weekc . — not working


11. Which best describes your work setting(s)? Designate a primary (1) and secondary (2) setting, ifapplicable.

a.b . —

:: —

;“ —9. —h.i.j . ~k.L —

m.n . —

o.p . —q. —

private hospital/medical facilityuniversity medical centerfree standing clinicHealth Maintenance Organization (HMO)private group practicesolo private practiceprivate industry (specify type):State laboratory (specify type):regional laboratory (specify type):commercial laboratoryPublic Health department (State, county, or city)State government agencyFederal government agencyvoluntary health organizationeducational 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 taskseducating health professionals, medical students, GC traineeseducating the general public, schools, undergraduatesperforming laboratory workresearchmarketing/businessother:

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 colleaguesmedical journalsgrand roundsState or regional conferencesnational conferencesAmerican Society of Human GeneticsNational Society of Genetic Counselorscontinuing education coursesliterature from biotechnology/commercial firmslay pressother:

14. In your current position, how frequently were you asked about DNA testing/screening for CFduring the 6-month period from January - June, 1991? Please consider this in the context of yourtotal clinical practice.

a. neverb . — rarely

occasionallyd: frequentlye . — very frequently

Appendix B-Survey Instrument .39

15. If you were asked about DNA testing/screening for CF please estimate the number of requests permonth (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 decreaseb . — a small decrease

no changed : — a small increasee . — 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 THOSEINDIVIDUALS 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?ruralsuburbanmetropolitan/urbanstatewideregional (more than one State)nationalother:

2 0 . Current level of staffing (including yourself) in your counseling unit/program (please indicatenumber).

a.

b.

c.

d.

e.

f.

#

M.D. geneticists

Ph.D. geneticists

M.D./Ph.D. geneticists

genetic counselors

secretaries

other:

40 ● Genetic Counseling and Cystic Fibrosis Carrier Screening: Results of a SurveY

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 geneticspediatric geneticsadult geneticsteratogen exposurereproductive lossspecialty disease(s)newborn screening

clinics (please specify):

MSAFP screening follow-upcarrier screening (specify disease):

Does your institution participate in collecting the CORN data set?a. yes b. no c. don’t know

For each of the following categories, indicate the number (or best estimate) of geneticsclients/patients served in 1990, either DIRECTLY (i.e., counselor to client relationship; one-on-onegenetic counseling) or INDIRECTLY (i.e., involvement such as consultant to primary care physicianregarding a patient, telephone consultation).

TYPE OF PATlENT CONTACT

Direct Indirect TotalAll patients seen in 1990

a. by your unit:

b. by you individually:

CF patients/families seen in 1990c. 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

Appendix B-Survey Instrument ● 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 -74°A 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 offees for service in each of the following areas? Also, please indicate the average fee amountcharged 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 $


28. Have you had any experience with a patient’s 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 insurancecoverage as a result of genetic testing?

a. no experience b. yes. Please provide details:

3 0 . Consider the following reasons for referral for genetic counseling. Please estimate to the best ofyour ability, the average NUMBER of patients you see per month, total amount of directCOUNSELOR TIME spent (in minutes), and the average number of VISITS needed to providegenetic counseling to individuals and/or families for each of the following scenarios. (Answer forcases 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 defectsconcerns for current pregnancy

Elevated MSAFP screen .

Couple with newly diagnosed(Tri 21) Down’s Syndrome child

Couple with 14/21 translocationDown’s Syndrome child

Carrier testing for DMD

Newly diagnosed case of neurofibromatosis

Newly diagnosed CF family

Carrier testing for CFwith a positive family history

Carrier testing for CFwith a negative family history

AVG# visits

31. If you have not been involved with counseling for CF based on your experience, how much directcounselor 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 typicalpatient load?a. more time b. less time c. about the same

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 aloned : — videotape with counseling

written educational materialsf “ — slide-tapeg . interactive computer

Where is the closest CF treatment center to your institution?a. at my institutionb . — less than or equal to 50 miles

greater than 50 milesd : — 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 CFa. 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 storageb . — prenatal diagnosis for sex selection

non-paternityd : — confidentiality and Huntington’s disease testinge . — other:


39. For each of the following patient groups, indicate how often, if at all, you introduce the topic ofDNA testing for CF

1=seldom if ever; 2=sometimes; 3=often; 4=very often; 5=almost always

a. all patients\familiesb . — pregnant women seeking prenatal diagnosis

couples/individuals with a positive family history for CFd : — Caucasian couples/individuals with negative family history for CFf . — individual/families who inquire about CFe . — selected couples/individuals; how selected:

4 0 . Have you made an effort to contact old genetics families as appropriate regarding the availability of CFtesting?a. yes, by (check all that apply):

1) telephone2 ) — letters/mass mailing3 ) — at future visits4 ) — other:

b. no, because (check all that apply):1) not enough time; too busy2 ) — no mechanism for rapid chart retrieval3 ) — requires chart by chart analysis4 ) — plan to do so in future, as time permits5 ) — other:

41. During the last 12 months:a. Have you referred any patients for DNA testing for CF

1) no2 ) — yes: how many individuals: # samples

b. Have you=referred any patients/families for DNA testing for other disorders?1) no2 j — yes: how many individuals: # samplesIf yes,for which conditions:

42. At your institution, is DNA testing for CFa. performed at onsite/inhouse labb . — sent offsite to lab less than or equal to 50 miles away.c . — sent offsite to lab between 50 miles and 150 miles awayd. sent offsite to lab greater than 150 miles away

43. Type of laboratory used for CF testing:a. private/commercialb . — private hospital

university hospitald : — regional laboratorye . — other:

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 analysisDNA linkage analysisDNA haplotypingstaging of studies depending on caseprenatal DNA analysisfetal intestinal enzyme analysisDNA banking

For direct mutation analysis of CF what mutations does the laboratory you use include? (Please list orgive 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 — yesb. 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 isnegative?

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 shouldproceed?

a. yes, specify: % rate of detectionb . — n oc . — no opinion

Are you familiar with the NSGC brochure “Genetic Testing for Cystic Fibrosis: A Handbook forProfessionals”?

a. no b. yes

Have you developed any educational materials relevant to DNA testing specifically for CFa. 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 subjectb . — wanted to know

positive family historyd : — family planninge . — other:


53. How was your test covered?a. by my insuranceb . — professional courtesyc . — self payd . — research subject

54. To what extent, if at all, should each of the following groups be involved with educating the public aboutDNA testing for CF if it becomes standard practice?

a.b.

d:

fg.h.

jk.

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 providerspublic health departmentsgenetic counselorsgenetics programsnursesfamily planning clinicsvoluntary support groupsschoolslay presstelevisionother:

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 thatapply)

a.b.c.d.e . —

f.g . —

prenatalnewbornschildren ages 2-12children ages 13-18adults in reproductive yearsadults post reproductive yearspregnant women or “couples”

57. If CF carrier screening is voluntary, who should organize the screening programs? (check all that apply)a. voluntary health organizationsb . — State or local health department

Federal Governmentd : — medical societies

the human genetics communityf “ — primary care giversg . : 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 organizationsState or local health departmentFederal Governmentmedical societiesthe human genetics communityprimary care giversothers (specify):

Appendix B-Survey Instrument ● 47

59.

60.

61.

62.

63.

Where should CF population screening programs be provided? (check all that apply)a. in public schoolsb . — in public health departments

in organized, community-wide programsd : — in the primary care setting i.e., physicians

in genetic centers/programsf “ — in the workplaceg . —

— other (specify):

Who should pay for screening? (Please rank, but be realistic.)a.b . —

c.d . —

f “ —

self pay by patientthird party paymentemployersState/city or countyFederal governmentother (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 CFscreening? 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 feelfree to give us as any other options, concerns, or suggestions that you feel our questions did not address. Thesecomments will be anonymous, but may be incorporated in our report to Congress.

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 GeneticsASHG —American Society of Human GeneticsBC/BS —Blue Cross and Blue ShieldCF -cystic fibrosis

-cystic fibrosis transmembraneconductance regulator

DF508 -delta F508 (most prevalent CF mutation)DF508#i12-delta F508 plus 6 to 12 additional CF

DNAG542XG551DEm40ISONG

MSAFPN1303K

NSGCOTAR553XW1282X

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 locusfor eye color there might be alleles resulting in blue orbrown eyes); alleles are inherited separately from eachparent.

beta~-thalassemia: An autosomal recessive disorder affect-ing the red blood cells, resulting in anemia, infections,growth retardation, and other complications.~-thalassemia predominantly occurs among individu-als of Mediterranean, Middle Eastern, Asian Indian,Chinese, Southeast Asian, and African descent.

Buccal: Relating to the inside of the cheek. A buccal swabcollects cells that can be analyzed for CF mutations.

Carrier: An individual apparently normal, but possess-ing a single copy of a recessive gene obscured by adominant allele; a heterozygote.

Chest physical therapy (chest PT): A cornerstone of CFtherapy that moves the mucus blocking major airpassages out of the lungs. A specific form of chest PTis bronchial drainage during which an individual claps

on the chest or back of the patient who is usually lyingon a table.

Chromosome: A threadlike structure that carries geneticinformation arranged in a linear sequence. In humans,it consists of a complex of nucleic acids and proteins.

Confidentiality: A fundamental component of the healthcare provider-patient relationship in which the profes-sional has the duty to keep private all that is disclosedby the patient.

Consanguineous: Related by blood or origin, rather thanby marriage.

Cystic fibrosis CF A life-shortening, autosomal reces-sive disorder affecting the respiratory, gastrointestinal,reproductive, and skeletal systems, as well as the sweatglands. CF is caused by mutations in the CF gene thataffect the CF gene product, cystic fibrosis transmem-brane conductance regulator (CFTR). Individuals withCF possess two mutant CF genes.

Cystic fibrosis carrier: An individual who possesses oneCF mutation and one normal CF gene. CF carriersmanifest no symptoms of the disorder. See carrier.

Cystic fibrosis carrier screening: The performance oftests on persons for whom no family history of CFexists to determine whether they have one aberrant CFgene and one normal CF gene. See cystic fibrosisscreening.

Cystic fibrosis screening: The performance of tests todiagnose the presence or absence of the actual disorder,in the absence of medical indications of the disease ora family history of CF This type of diagnosticscreening usually involves newborns, but rarely forCF except in Colorado and Wisconsin. See cysticfibrosis carrier screening.

Cystic fibrosis transmembrane conductance regulator(CFTR): The CF gene product, which regulateschloride (Cl-) conductance and might be a Cl- ionchannel, the structure that governs Cl- entry and exit inthe cell. CFTR produced by a mutant CF gene isfrequently impaired, resulting in the medical manifes-tations of CF in affected individuals.

DF508: A three base pair deletion in the CF gene thatresults in a faulty CF gene product (i.e., a flawedCFTR). This mutation results in the deletion of oneamino acid, phenylalamine, at position number 508 inCFTR. DF508 is the most common mutant alleleamong the greater than 170 identified in the CF gene.

Deoxyribonucleic acid (DNA): The molecule that en-codes genetic information. DNA is a double-strandedhelix held together by weak bonds between base pairsof nucleotides.

4 8 –

Appendix C-Acronyms and Glossary ● 49

Discrimination: Differential treatment or favor with aprejudiced outlook or action.

Dominant: An allele that exerts its phenotypic effectwhen present either in homozygous or heterozygousform.

DNA: See deoxyribonucleic acid.DNA analysis: A direct examination of the genetic

material, DNA, to reveal whether a individual hasmutation(s) for CF or other disorders.

DNA probe: Short segment of DNA labeled with aradioactive or other chemical tag and then used todetect the presence of a particular DNA sequencethrough hybridization to its complementary sequence.

Gene: The fundamental physical and functional unit ofheredity. A gene is an ordered sequence of nucleotidebase pairs to which a specific product or function canbe assigned.

Gene therapy: The deliberate administration of geneticmaterial into the cells of a patient with the intent ofcorrecting a specific genetic defect.

Genetic counseling: A clinical service involving educa-tional, informational, and psychosocial elements toprovide an individual (and sometimes his or herfamily) with information about heritable conditions.Genetic counseling is performed by genetics special-ists, including physicians, Ph.D. clinical geneticists,genetic counselors, nurses, and social workers.

Genetic screening: The analysis of samples from asymp-tomatic individuals with no family history of adisorder, groups of such individuals, or populations.

Genetic testing: The use of specific assays to determinethe genetic status of individuals already suspected tobe at high risk (e.g., family history or symptoms) fora particular inherited condition.

Genetics: The study of the patterns of inheritance ofSpecific traits.

Genome: AU the genetic material in the chromosomes ofa particular organism; its size is generally given as itstotal number of base pairs. The human genome is 3.3billion base pairs.

Heterozygote: A heterozygous individual, such as a CFcarrier.

Heterozygous: Having two different alleles at a particularlocus.

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 digestiveenzyme. As a protocol for newborn CF screening, adrop of blood is isolated on a card, dried, and

chemically analyzed to detect elevated levels of theenzyme. 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

bases—adenine, guanine, cytosine, or thymine-attached to a phosphate-sugar group. The sugar groupis deoxyribose in DNA. In RNA, the sugar group isribose, and the base uracil substitutes for thymine.

Probe: A short segment of DNA tagged with a reportermolecule, such as radioactive phosphorus (32P), usedto detect the presence of that particular complementaryDNA sequence.

Protein: A biological molecule whose structure isdetermined by the sequence of nucleotides in DNA.Proteins are required for the structure, function, andregulation of cells, tissues, and organs in the body.

Recessive: An allele that exerts its phenotypic effect onlywhen present in homozygous form, otherwise beingmasked by the dominant allele.

Sensitivity: The ability of a test to identify correctly thosewho have a disease.

Sickle cell anemia: An autosoma1 recessive disorderaffecting red blood cell flow through the circulatorysystem, causing complications in numerous organsystems. Sickle cell anemia predominantly occurs inindividuals of African descent.

Sickle cell trait: The heterozygous state of sickle cellanemia; sickle cell carrier status.

Single-gene disorder: Hereditary disorder caused by asingle gene (e.g., cystic fibrosis, Tay-Sachs disease,sickle cell anemia).

Specificity: The ability of a test to identify correctly thosewho do not have the characteristic which is beingtested.

Stigmatization: Branding, marking, or discrediting be-cause of a particular characteristic.

Sweat test: An assay used to confirm CF that measureslevels of sodium Na+) and chloride (Cl-) ions. Theseions appear in high concentrations in patients with CFSweating is induced by running a low electric currentthrough a pilocarpine-soaked gauze pad on the individ-ual’s arm or back. The amounts of Na+ and Cl- in thesweat can then be determined to confirm or question adiagnosis of CF

Tay-Sachs disease: A lethal autosomal recessive disor-der affecting the central nervous system which resultsin mental retardation and early death. Tay-Sachsdisease predominantly occurs among Jews of Easternand Central European descent and populations in theUnited States and Canada descended from FrenchCanadian ancestors.

genetic counseling and cystic fibrosis carrier screening: results of a survey

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