Genetic Counseling and Cystic Fibrosis

Carrier Screening: Results of a Survey

October 1992

OTA-BP-BA-97

NTIS order #PB93-101764
Recommended Citation:

U.S. Congress, Office of Technology Assessment, Genetic Counseling and Cystic Fibrosis

Carrier Screening: Results of a Survey--Background Paper, OTA-BP-BA-97 (Washington,

DC: U.S. Government Printing Office, September 1992).

For sale by the U.S. Government Printing Office

Superintendent of Documentts, Mail Stop: SSOP, Washington. DC 20402-9328

ISBN 0-16-038093- 6
Foreword

For years, experts have theorized about the consequences of increased knowledge of

human genetics. In the early 1990s, development of a DNA-based test to identify carriers of

cystic fibrosis (CF) moved the debate from the theoretical to the practical. The CF carrier assay

is but one of many tests to come that will place genetic counselors and nurses working in

genetics at the front line on the issues raised by assimilation of DNA tests into clinical practice.

This OTA Background Paper presents results from a 1991 OTA survey of 431 genetic

counselors and nurse geneticists. It was conducted to better understand the environment in

which the average genetic counselor or nurse in genetics works, to describe the infrastructure

and tools available to these professionals, to assess the state of practice in the provision of CF

carrier screening, and to evaluate their attitudes regarding CF carrier screening. The survey

supports OTA’s August 1992 assessment Cystic Fibrosis and DNA Tests: Implications of

Carrier Screening; the full assessment was requested by the House Committee on Science,

Space, and Technology, the House Committee on Energy and Commerce, and Representative

David R. Obey.

The survey data collected by OTA reflect the tensions and concerns surrounding the

widespread implementation of CF carrier screening. Those who currently oppose routine

carrier screening for CF raise concerns about the sensitivity of the test, the numbers of

individuals that would be potentially screened—and the subsequent effect on the clinical

genetics infrastructure--and the possibilities of stigma, discrimination, and poor quality in

services. Those who think CF carrier screening should be widely available believe the

information provided by the test increases patient autonomy and lowers uncertainty regarding

reproductive futures.

OTA was assisted in preparing the survey instrument and Background Paper by a panel

of advisors, contractors, workshop participants, and reviewers selected for their expertise and

diverse points of view. We gratefully acknowledge the contribution of each of these

individuals. OTA, however, remains solely responsible for the contents of this Background

Paper.

/y’/ &# J6’i9--

JOHN H. GIBBONS

Director

. . .

Ill
Cystic Fibrosis and DNA Tests: Implications of Carrier Screening

Advisory Panel

Jessica G. Davis, Panel Chair

Co-Director, Division of Human Genetics

New York Hospital

Cornell University Medical College

New York, NY

Arthur L. Beaudet

Professor

Howard Hughes Medical Institute

Baylor College of Medicine

Houston, TX

Debra L. Collins

Genetic Counselor

University of Kansas Medical Center

Kansas City, KS

Beth A. Fine

Genetic Counselor/Clinical Instructor

Northwestern University Medical School

Chicago, IL

Lynn D. Fleisher

Attorney

Sidley & Austin

Chicago, IL

Clark C. Havighurst

William Neal Reynolds Professor of Law

Duke University School of Law

Durham, NC

John Z. Jacoby, III

Clinical Assistant

The Cystic Fibrosis Center

St. Vincent’s Hospital and Medical Center

New York, NY

Angèle Khachadour

General Counsel

Hastings College of the Law

San Francisco, CA

Katherine W. Klinger

Vice President, Science

Integrated Genetics

Framingham, MA

Arthur Lifson

Vice President

CIGNA Companies

Hartford, CT

Robert F. Murray, Jr.

Professor

Department of Pediatrics and Child Health

Howard University School of Medicine

Washington, DC

Mark V. Pauly

Executive Director

Leonard Davis Institute of Health Economics

University of Pennsylvania

Philadelphia, PA

Susan Poling

Parent

Silver Spring, MD

Thomas K. Reed, Jr.

chairman

Vivigen, Inc.

Santa Fe, NM

Philip R. Reilly

President

Shriver Center for Mental Retardation, Inc.

Waltharn, MA

Joseph D. Schulman

Director

Genetics & IVF Institute

Fairfax, VA

NOTE: OTA is grateful for the valuable assistance and thoughtful critiques provided by the advisory panel members. The panel does

not, however, necessarily approve, disapprove, or endorse this report. OTA assumes full responsibility for the report and the

accuracy of its contents.

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

OTA Project Staff

Roger C. Herdman, Assistant Director, OTA Health and Life Sciences Division

Michael Gough, Biological Applications Program Manager

Robyn Y. Nishimi, Project Director

Kathi E. Hanna, Study Director

Ellen L. Goode, Research Analyst

Margaret A. Anderson, Analystl 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, MD

Ferdinand J. Chabot, Newton, IA

Bob Jones, IV, Arlington, VA

Ann 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 1

WHAT IS CYSTIC FIBROSIS? . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 2

THE CYSTIC FIBROSIS GENE . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 2

CYSTIC FIBROSIS MUTATION ANALYSIS . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 2

CONTROVERSY ABOUT CYSTIC FIBROSIS CARRIER SCREENING . . . . . . . . . . . . . . . . 3

SCOPE AND ORGANIZATION OF THIS BACKGROUND PAPER . . . . . . . . . . . . . . . . . . . . 4

CHAPTER 1 REFERENCES . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 4

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

THE SURVEY POPULATION . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 5

Genetic Counselors . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 5

Nurses in Genetics . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 6

Demographic Profile of Survey Respondents . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 7

WORK ENVIRONMENTS . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 7

GENETICS CLIENTELE . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 9

FEES AND THIRD-PARTY COVERAGE . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 11

Fees for Genetic Services . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .11

Third-Party Coverage . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .12

SUMMARY . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .14

CHAPTER 2 REFERENCES . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .15

Chapter 3. Cystic Fibrosis Carrier Screening: Policies and Practices . . . . . . . . . . . . . . . . . . . 17

POLICIES AND PRACTICES, SUMMER 1991 . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 17

Policies on Cystic Fibrosis Carrier Screening . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 17

Criteria for Cystic Fibrosis Carrier Screening . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 19

Practices Regarding DNA-Based Cystic Fibrosis Carrier Tests . . . . . . . . . . . . . . . . . . . . . . . . . 19

PREFERRED STRATEGIES AND PROTOCOLS . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 21

Who Should Provide Cystic Fibrosis Carrier Screening? . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 22

Who Should Pay for Cystic Fibrosis Carrier Screening? . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 23

Strategies for Screening Various Populations . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .23

PROFESSIONAL CAPACITY . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 26

ISSUES TO BE ADDRESSED BEFORE IMPLEMENTATION . . . . . . . . . . . . . . . . . . . . . . . . . 27

SUMMARY . . . . . . . . . . . . . . . . . . . . . . . . . .. . . . . . . . . . . . . . . . . . . . . . . . . . .. . . . . . . . . . . . . . . . . . . . . 28

CHAPTER 3 REFERENCES . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .28

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

Appendix A. Survey Method ... .me. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 35

Appendix B. Survey Instrument ... ..oo. ..** . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 36

Appendix C. Acronyms and Glossary . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 48

Figures

1-1. Inheritance of Cystic Fibrosis . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1

1-2. Cystic Fibrosis Mutation Test Results at 85 Percent Sensitivity . . . . . . . . . . . . . . . . . . . . . . . . 3

2-1. Geographic Distribution of Survey Respondents . . . . . . . . . . . . . . . . . . . . . . . . . . 6

2-2. primary Service Areas of Respondents . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 8

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

2-3. Average Hours Spent Per Week on Public Education . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 8

2-4. Racial/Ethnic Background of Clinical Genetics Clientele . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 9

2-5. Age Distribution of Genetics Clientele . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 9

2-6. Frequency of Patients Seen by Major Areas of Clinical Practice . . . . . . . . . . . . . . . . . . . . . . . 10

2-7. Number of Cystic Fibrosis Patients or Families Seen in Genetics Units in 1990 . . . . . . . . . 11
2-8. Health Care Coverage for Genetics Clientele . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 12

2-9. General Types of Health Care Coverage for Genetics Clientele . . . . . . . . . . . . . . . . . . . . . . . . 12

2-10. Third-Party Reimbursement for General Genetic Counseling and Counseling

Specifically for Cystic Fibrosis . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 13

3-1. Opinions on Optimal Rate of Detection . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 19

3-2. Frequency of Requests for Cystic Fibrosis Carrier Screening/Testing,

January-June1991 . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .20

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

January-June 1991 and Past 2 Years . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .20

3-4. Opinions Regarding Genetic Counseling of Individuals with a Positive

Family History . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 21

3-5. Opinions Regarding Genetic Counseling of Individuals with a Negative

Family History . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 21

3-6. Opinions Regarding the Need for Informed Consent Prior to Cystic Fibrosis

Carrier Screening . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 22

3-7. Opinions Regarding the Use of Educational Materials as aSource of Information

About Cystic Fibrosis Carrier Screening . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 22

3-8. Extent to Which Various Groups Should Be Involved with Cystic Fibrosis

Pretest Education . . . . . . . . . . . . . . . . . . . . . . . . . . . .. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .24

3-9. Opinions Regarding the Need for More Genetic Counselors . . . . . . . . . . . . . . . . . . . . . . . . . . . 27

Tables

l-1. A Priori Carrier Risks for Cystic Fibrosis . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1

2-1. Geographic Concentration of Survey Respondents . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 7

2-2. Primary Work Setting . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 7

2-3. Average Weekly Schedule of Genetic Counselor or Nurse in Genetics . . . . . . . . . . . . . . . . . 8

2-4. Formats for Genetic Counseling . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 8

2-5. Most Common Diseases for Which Carrier Screening/Testing Is Offered . . . . . . . . . . . . . . . 11

2-6. Average Fees and Knowledge of Fees for Genetic Services . . . . . . . . . . . . . . . . . . . . . . . . . . . . 11

2-7. Fees for General Counseling . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 12

2-8. Difficulties in Obtaining or Retaining Health Insurance After Genetic Tests . . . . . . . . . . . . 13

2-9. Case Descriptions of Genetic Testing and Health Insurance Problems . . . . . . . . . . . . . . . . . . 14

3-l. A Priori Carrier Risks for Cystic Fibrosis . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 18

3-2. Sources of Information About New Advances in Human Genetics . . . . . . . . . . . . . . . . . . . . . 18

3-3. Likelihood of Introducing the Topic of DNA Testing for Cystic Fibrosis . . . . . . . . . . . . . . . 18

3-4. Specific Policies Regarding DNA Testing for Cystic Fibrosis . . . . . . . . . . . . . . . . . . . . . . . . . 18

3-5. Minimal Criteria for Cystic Fibrosis Carrier Screening Protocol . . . . . . . . . . . . . . . . . . . . . . . 19

3-6. Types of Genetic Analyses Provided for Cystic Fibrosis Screening Testing . . . . . . . . . . . . . 20

3-7. Cystic Fibrosis Mutations Routinely Analyzed . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .20

3-8. Preferred Organizations for Implementation of Voluntary Cystic Fibrosis

Carrier Screening . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 23

3-9. Preferred Sites for Cystic Fibrosis Carrier Screening Programs . . . . . . . . . . . . . . . . . . . . . . . . 23

3-10. Who Should Pay for Cystic Fibrosis Carrier Screening? . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 26

3-n. Target Populations for Cystic Fibrosis Carrier Screening. . . . . . . . . . . . . . . . . . . . . . . . . . . . 26

3-12. Frequency of Patients Seen by Major Areas of Clinical Practice . . . . . . . . . . . . . . . . . . . . . . 26

3-13. Time Required for Genetic Counseling for Various Conditions . . . . . . . . . . . . . . . . . . . . . . . 27

3-14. Strategies for Implementation of Widespread Cystic Fibrosis Carrier Screening . . . . . . . . 27

3-15. Issues that Need to be Addressed by Pilot Programs in Cystic Fibrosis

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

vii
Chapter 1

Introduction and Background

Cystic fibrosis (CF) is the most common, lifeshortening, recessive genetic disorder affecting Caucasians of European descent. From 1,700 to 2,000

babies with CF are born annually in the United

States. The diagnosis of an infant with CF often

reveals the first and only clue that the genetic trait

exists in the family.

Parents of a child with CF are, by definition,

obligate CF carriers. They have no symptoms of CF,

but with each pregnancy are at 1 in 4 risk of having

a child with CF and 1 in 2 risk of having a child who

is a carrier (figure l-l). Such couples are sometimes

referred to as carrier couples, or couples who are

positive/positive (+/+). If a couple is positive/

negative (+/-)—the father is a carrier, but the mother

is not, or vice versa—their offspring can be CF

carriers, but cannot have CF. Couples are not at risk

of having a child with CF if only one or neither

partner is a carrier.

Four of five individuals with CF are born to

families with no previous history of the illness.

Beyond the approximately 30,000 Americans who

Figure I-l—Inheritance of Cystic Fibrosis

o Carrier parents o

have CF, as many as 8 million individuals could be

CF carriers. With no knowledge of a family history

of CF, American Caucasians have about a 1 in 25

risk of being a CF carrier. The risk of carrier status

increases when an individual in a family is diagnosed with CF, with risks calculated by relationship

to the affected individual (table l-l).

Prior to 1989, the absence or presence of CF in

one’s family, as well as ethnic and racial background, were the only indicators available to determine risk of carrier status. In 1989, however,

scientists identified the most common change, or

mutation, in the genetic material-deoxyribonucleic

acid (DNA)-that causes CF. Following this discovery came tests to detect mutations in the specific area

of DNA—the CF gene-that is responsible for the

disease.

The Office of Technology Assessment (OTA)

report Cystic Fibrosis and DNA Tests: Implications

of Carrier Screening (1) focuses on using these

DNA tests to screen and identify CF carriers among

the general population before they have a child with

CF. This background paper, conducted in support of

the OTA assessment, reports the results of an OTA

survey of 431 members of either the National

Society of Genetic Counselors (NSGC) or the

International Society of Nurses in Genetics (ISONG).

Conducted in summer 1991, the survey was designed to evaluate genetic counseling attitudes and

practices 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 affected

noncarrier unaffected

carrier

SOURCE: Office of Technology Assessmentp 1992.

Negative family history

Caucasian. . . . . . . . . . . . . . . . . . . . 1 in 25 (4%)

African American. . . . . . . . . . . . . . . 1 in 60 to 65 (1.5 to 1.7%)

Asian American . . . . . . . . . . . . . . . . 1 in 150 (0.79’.)

Hispanic American. . . . . . . . . . . . . 1 in 40 to 50 (2 to 2.5%)

Positive family history

Parent of child with CF. . . . . . . . . . 1 in 1 (1OO%)

Sibling with CF. . . . . . . . . . . . . . . . 2 in 3 (67%)

Aunt or uncle with CFa. . . . . . . . . . 1 in 3 (33%)

First cousin with CF. . . . . . . . . . . . . 1 in 4 (25%)

Niece/nephew with CFa. . . . . . . . . 1 in 2 (50%)

a Consanguineous.

SOURCE: Office of Technology Assessment, 1992.

–1–
2 ● Genetic Counseling and Cystic Fibrosis Carrier Screening: Results of a Survey

Consensus exists that individuals who have relatives with CF should be told about the availability of

CF carrier tests; the disagreement is whether

everyone should be informed about the assays, since

80 percent of babies with CF are born to couples

with no previous family history of the condition.

Concern about the scientific, legal, economic, ethical, and social implications of the prospect that large

numbers of people might be screened for their CF

carrier status led the House Committee on Science,

Space, and Technology, the House Committee on

Energy and Commerce, and Representative David

R. Obey to request the OTA assessment.

WHAT IS CYSTIC FIBROSIS?

CF is not a new disease. First described in 17th

century folklore, medical literature has long documented that CF compromises many functions throughout the body--chiefly the respiratory, gastrointestinal, and reproductive systems and the sweat glands.

Many affected babies are not immediately diagnosed as having CF Although the disease is always

present at birth in affected individuals, the onset of

recognizable clinical symptoms varies widely. Physicians diagnose CF using a combination of clinical

criteria and diagnostic laboratory tests. Although an

assay called the sweat test remains the primary

diagnostic test for CF DNA mutation analysis can

diagnose more than 70 percent of cases.

CF exerts its greatest toll on the respiratory and

digestive systems, and the severity of respiratory

problems often determines the quality of life and

survival. There is no cure for CF Treatment focuses

on managing the respiratory and digestive symptoms to maintain a stable condition and lengthen

lifespan. Because of CF’s varied progression, the

regimen and level of therapy depends on the

individual. Most therapy involves home treatment

(e.g., chest physical therapy to clear mucus from the

lungs), outpatient care at one of more than 110

clinics devoted specifically to CF health care, and

occasional hospital stays. Today, physicians can

look to an ever-expanding array of new pharmaceutical options to manage the care of CF patients; on

the horizon are hopes for gene therapy.

Over the last half-century, treatment of CF has

evolved so that an illness nearly always fatal in early

childhood is now one where life expectancy into

adulthood is common. Fifty years ago, most infants

born with CF died in the frost 2 years of life. In 1990,

median survival was 28 years--i.e., of the individuals born with CF in 1962, half were alive in 1990.

THE CYSTIC FIBROSIS GENE

CF is a genetic illness transmitted from parents to

their children via genetic directions stored in DNA.

In humans, these directions, including those responsible for CF are stored among genes arrayed on 46

structures called chromosomes. The gene responsible for CF lies on chromosome 7 and results in a

product called the cystic fibrosis transmembrane

conductance regulator (CFTR). In most people with

CF a three-base pair deletion in both of their CF

alleles results in a faulty CFTR, which leads to CF

pathology. This three-base pair mutation occurs at

position number 508 in the CFTR and is abbreviated

as delta F508 (AF508). More than 170 additional

mutations in the CF gene also lead to faulty CFTRs.

Individuals with CF have two of the same, or two

different, mutations. CF carriers have only one

mutation; their second CF allele produces normal

CFTR.

About 70 percent of CF carriers have the AF508

mutation. l International studies demonstrate ethnic

and regional variation in the frequency distribution

of this mutation; as expected, the multicultural

nature of the United States reflects this variation.

Most of the other 170+ mutations appear in a small

fraction of individuals or families, although a few

occur at a frequency as great as 1 to 3 percent. Some

symptoms (or their lack of severity) correlate with

particular mutations. Digestive difficulties from

pancreatic insufficiency, for example, generally

associate with AF508.

CYSTIC FIBROSIS

MUTATION ANALYSIS

With localization of the CF gene, AF508, and

other CF mutations, it is now possible to directly

analyze DNA from any individual for the presence

1 Quoted mu~tion fiquencies for AF508 and other CFmutations always depend on racial and ethnic background. Throughout this background Paper,

OTA presents current expert estimates of appropriate ranges of detection frequencies or sometimes uses a specitlc figure with qualification (e.g., about

90 percent; approximately95 percent). OTA adopts such language to avoid restating each time that afkquency depends on racial and ethnic background,

not to underemphasize the importance in the distriioution variation of CF mutations. In some cases-made clear within the text-a speeitlc frequency

is chosen for illustrative or hypothetical purposes.
Chapter 1--Introduction and Background ● 3

of CF mutations. Using today’s technologies, CF

mutation analysis is usually a one-time test that can

inform an individual whether he or she carries any of

the CF mutations for which tests are conducted.

Carrier screening for CF (or CF carrier screening)

refers to performing CF mutation analysis on DNA

from an individual who has no family history of CF

Current technology, however, can leave ambiguity, but not because the tests per se are imprecise.

Properly performed, DNA-based tests for CF mutations are accurate and specific-meaning if the

 mutation (or another CF mutation) is present

in the individual’s genome and an assay is performed to search for that mutation, the test will

detect it more than 99 percent of the time, absent

laboratory error. Instead, ambiguity stems from the

intrinsic nature of the cause of the disease: Besides

 more than 170 mutations in the CF gene also

cause CF

In the United States, about 1 in 25 Caucasians

carries one CF mutation. Current assays use 

plus 6 to 12 other CF mutations and

identify about 85 percent of CF carriers (in Ashkenazic Jews, identifies about 95 percent of

carriers). Thus, using means 10 to 15

percent of actual carriers go undetected. In other

words, since tests to detect 170+ mutations are

impractical, a negative test result does not guarantee

that a person is not a carrier.

Using DF508+6-12 means that some couples

receive test results that indicate one partner is a

carrier and one is not, when in fact the negative

partner carries one of the rare CF mutations that is

not assayed. Thus, while most couples whose test

results are +/- are at zero risk of having a child with

CF some couples with a +/- test result actually are

couples whose genetic status is +/+ (but goes

undetected) and who are at 1 in 4 risk of a child with

CF for each pregnancy. Couples with a +/- test result,

then, might misunderstand that their reduced risk of

bearing a child with CF is not zero risk (figure 1-2).

CONTROVERSY ABOUT CYSTIC

FIBROSIS CARRIER SCREENING

Prospects of routine CF carrier screening polarize

people. No mandatory genetic screening programs

of adult populations exist in the United States. OTA

has found it highly unlikely that CF carrier screening

will set a precedent in this regard (l). People agree

that persons with a family history of CF should have

the opportunity to avail themselves of CF mutation

analysis, yet controversy swirls around using the

same tests in the general population.

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

100,000

couples

Run CF mutation test

(85% sensitivity)

TEST RESULTS

Some of these couples

are a different type,

but go undetected

Some of these couples

1,152 

(No risk.)

4 

are a different type, (1 in 4 risk with each pregnancy. Remaining

but go undetected -/- couples are at no risk.)

116 

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

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

11 missed.)

SOURCE: Office of Technology Assessment, 1992.
4 ● Genetic Counseling and Cystic Fibrosis Carrier Screening: Results of a Survey

Proponents of a measured approach to CF carrier

screening express concern about several issues that

might be raised if use of CF carrier tests becomes

routine. Invariably, discussions about CF carrier

screening raise concerns about the use of genetic

information by insurance companies (2) and become

linked broader social concerns about health care

reform in the United States. Related to this are

concerns about commercialization of genetic research, i.e., that market pressures will drive widespread use of tests before the potential for discrimination or stigmatization by other individuals or

institutions (e.g., employers and insurers) is assessed. Also expressed are questions about the

adequacy of quality assurance for DNA diagnostic

facilities, personnel, and the tests themselves. Others

also wonder whether the current number of genetic

specialists can handle a swell of CF carrier screening

cases, let alone cases from tests for other genetic

conditions expected to arise from the Human

Genome Project. Finally, the extraordinary tensions

in the United States about abortion affect discussions about CF carrier testing and screening.

Those who advocate CF carrier tests for use

beyond affected families are equally concerned

about these issues. They assert, however, that

individuals should be routinely informed about the

assays so they can decide for themselves whether to

be voluntarily screened. Proponents of providing

such information believe that failing to inform

patients now about the availability of CF carrier

assays denies people the opportunity to make

personal choices about their reproductive futures,

either prospectively-e. g., by avoiding conception,

choosing to adopt, or using artificial insemination by

donor-or by using prenatal testing to determine

whether a fetus is affected.

SCOPE AND ORGANIZATION OF

THIS BACKGROUND PAPER

One of the tasks of genetic specialists is to provide

the educational and counseling services necessary to

successful implementation of new technologies.

Increasingly, genetic counselors and nurses working

in genetics will be at the front line on the issues

raised by DNA technologies’ assimilation into

practice.

The OTA survey was conducted to better understand the environment in which the average genetic

counselor or nurse in genetics works, to describe the

infrastructure and tools available to these professionals, to assess the state of practice in the provision

of CF carrier screening, and to evaluate their

attitudes regarding CF carrier screening. The results

of the survey are reported in chapters 2 and 3. A

summary appears in chapter 4. A description of the

survey methodology is in appendix A, and the

survey instrument is reproduced in appendix B.

CHAPTER 1 REFERENCES

1.

2.

U.S. Congress, Office of Technology Assessment,

Cystic Fibrosis and DNA Tests: Implications of

Carrier Screening, OTA-BA-532 (Washington, DC:

U.S. Government Printing Office, August 1992).

U.S. Congress, Office of Technology Assessment,

Genetic Tests and Health Insurance+Results of a

Survey, OTA-BP-BA-98 (Washington, DC: U.S. Government Printing Office, October 1992).
Chapter 2

Providers, Clientele, and Genetic Services

The purpose of the OTA survey was to evaluate

the extent to which genetic counselors and nurses in

genetics are routinely offering carrier screening for

cystic fibrosis CF to their clientele, to assess their

attitudes and beliefs about the appropriateness of

such screening, and to obtain a sense of the

environment in which they work. While members of

the National Society of Genetic Counselors (NSGC)

and the International Society of Nurses in Genetics

(ISONG) are by no means the only health professionals providing genetic counseling, they comprise

a professional segment devoted explicitly to that

end. Physicians, social workers, public health workers, and research scientists also provide genetic

services. Those groups were not included in this

survey.

To better understand the setting in which routine

carrier screening for CF might take place, OTA

gathered data regarding not only counselors’ attitudes and practices regarding CF carrier screening

(ch. 3), but also the settings in which they work, the

numbers and types of clients they serve, clinical

practices, work routines, fees charged, and thirdparty payment options available to their clientele.

Understanding the environment in which CF carrier

screening takes place was a critical part of the

analysis reported in Cystic Fibrosis and DNA Tests:

Implications of Carrier Screening (10).

THE SURVEY POPULATION

Of the 703 members of the NSGC who received

questionnaires, 351-or 50 percent—responded. Of

the 110 members of ISONG who received the

questionnaire, 80-or 73 percent—responded. Thus,

80 percent of the respondent group are members of

NSGC and 20 percent are members of ISONG.l

As preliminary analysis revealed no significant

difference in question response between the two

populations, all data were combined for the final

analysis. The combined response rate is 53 percent.

Genetic Counselors

The master’ s-level genetic counselor is a relatively new addition to the health care system. In

1971, 10 graduates of the first such program entered

the workforce; in 1979, the NSGC was incorporated

as a professional organization. Today, there are

approximately 1,000 master’ s-level genetic counselors practicing in the United States.

Master’ s-level genetic counselors receive specialized multidisciplinary training and experience to

prepare them for counseling related to a wide variety

of genetic disorders and birth defects. They are

typically graduates from a 2-year master’s degree

program, during which time they receive didactic

course work in the principles and application of

human genetics, clinical and medical genetics,

genetic laboratory methods, and interviewing and

counseling. Genetic counselors are also trained in

social, ethical, legal, and cultural issues relating to

genetic diseases, principles of public health and

health care delivery systems, and education for the

lay and professional community (12). Over the past

20 years, master’ s-level graduate programs in genetic counseling have increased to 15, and combined, they produce approximately 75 graduates

each year (7). At the time of the OTA survey, there

were 703 genetic counselors who were full members

of NSGC (associate, student, and foreign members

were not surveyed). Of all respondents to the survey,

70 percent had a master’s degree in genetic counseling. An additional 10 percent held a master’s degree

in another area, and 8 percent had a Ph.D.

Genetic counselors receive a minimum of 400

hours of supervised clinical trainingin at least three

clinical settings, including a general genetics clinic,

a prenatal diagnosis clinic, and a speciality disease

clinic. Until 1992, graduates were eligible to sit for

the certification examination in genetic counseling

by the American Board of Medical Genetics (ABMG),

but continuing certification of these individuals by

this body is uncertain. In the past, counselors were

required to submit their credentials and a logbook of

50 cases obtained in a clinically accredited training

1 ne5e re5pome rate5 are ~ical of other mail surveys reported in the literature (1,6). One review found response rates for a two wave swey(fiti

mailing and one followup) ranged from 37 to 58.4 percent (6). OTA’s aggregate response rate clearly falls within this range, as does the response rate

of the genetic counselors; the response rate of the nurses in genetics exceeds it.

–5–
6 ● Genetic Counseling and Cystic Fibrosis Carrier Screening: Results of a Survey

Figure 2-l-Geographic Distribution of Survey Respondentsa

ID SD

2 2

NE

5

KS

 (I)

(2)

NM 1 OK

4

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 survey

respondents survey were board certified (65 percent)

or board eligible (19 percent).

Nurses in Genetics

There are nearly 2 million registered professional

nurses in the United States, many involved in

maternal and child health nursing. These professionals provide a unique potential to contribute to the

effective delivery of genetic services. Efforts are

under way to encourage the incorporation of clinical

genetics into the curricula of schools of nursing at

both the graduate and undergraduate level (4). The

need for better genetics education in nursing stems

from the recognition that genetics generally has been

within the realm of tertiary care; thus, genetics

specialists are not always in the position to screen

every individual needing genetics referral (4). That

is, individuals in need of genetic services must first

be identified by the primary health care professiona1,

and in some settings-such as community, occupational, or school health-nurses are the only link

with the health care system (3). Thus, nurses can

assist in the identification, education and counseling, and followup of patients (2,4). Though nurses

can be a valuable part of genetics services, to date

they are a largely untapped resource (3).

Opportunities for clinical genetics experience in

nursing programs vary. Genetics is generally a part

of the nursing school curriculum, but variability

exists among programs (3). Four of the 200 universities in the United States that offer graduate degrees
Chapter 2-Providers, Clientele, and Genetic Services ● 7

in nursing have established programs providing a

master ’s-level genetics major (3). A small number of

nurses, particularly those in maternal and child

health nursing, have focused on genetics in order to

sit for the genetic counseling examination given by

the American Board of Medical Genetics (ABMG)

(3,5). There are over 100 nurses employed in

genetics who also belong to ISONG and therefore

received OTA’s questionnaire. It is likely that many

more nurses deliver genetic services but are unidentifiable through current databases. Of the total

survey respondents, 12 percent reported having

either an R.N. or B.S.N. degree. Nurses might also

have a master’s degree or Ph.D. and could be

included in the 80 percent of respondents who

reported having a master’s degree or the 8 percent

who reported having a Ph.D.

Demographic Profile of Survey Respondents

The typical individual working as a genetic

counselor or nurse in genetics is likely to be female

(92 percent), in her mid-30s (mean age of 37),

Caucasian (96 percent; 2 percent are Hispanic, 1

percent African American, 1 percent Asian American), and married (70 percent). On average, she is

likely to have been in practice for 6 to 7 years, having

received her degree in 1985. Eight-seven percent of

these individuals speak only English; 5 percent also

speak Spanish, and 8 percent speak English and a

language other than Spanish.

Respondents represented every State except Arkansas, Louisiana, Kentucky, Mississippi, Montana,

and Nevada (figure 2-1). There is a heavy concentration of counselors in five States, with 43 percent of

respondents located in California, Illinois, New

Jersey, New York, and Pennsylvania, and 23 percent

located in three northeastern States, New Jersey,

New York, and Pennsylvania (table 2-l). California

had the highest representation at 15 percent. These

data are consistent with those collected and biannually reported by the NSGC (8). Hence, OTA’s

survey respondent pool is representative of the

NSGC membership and no sample weighting was

necessary.

WORK ENVIRONMENTS

The majority of respondents (83 percent) are

currently engaged in providing genetic counseling.

Seventeen percent work in an environment where

they are not encountering direct patient contact,

perhaps serving as administrators, educators, or

Table 2-l-Geographic Concentration of

Survey 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)

SOURCE: Office of Technology Assessment, 1992.

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)

SOURCE: Office of Technology Assessment, 1992.

researchers. The primary work settings for all

respondents are presented in table 2-2. Most counselors and nurses are employed in a university

medical center (36 percent) or a private hospital or

medical facility (36 percent). The remainder work in

a variety of settings, such as public health departments, health maintenance organizations, colleges

or universities, private group practices, free standing

clinics, or commercial laboratories. Again, these

data are consistent with the data collected by NSGC

on a biennial basis for its professional status survey

(8).

Centers of expertise in clinical genetics tend to be

located at large urban medical centers, often with a

teaching mission. The work location and setting of

the survey population reflect that tendency. Respondents are most likely to work in a metropolitan

or urban setting (58 percent) (figure 2-2). Counselors

and nurses in genetics are less likely to be found

working in rural settings. Counselors tend to work

with M.D. geneticists, Ph.D. geneticists, other genetic counselors, and a variety of support staff. Most

rural centers are unable to support this level of

professional personnel and often rely on regional

service areas. Five percent of respondents reported

working in a regional genetics area.

Respondents spend nearly two-thirds (65 percent)

of their work week—about 26 hours per week-on

patient activities, whether direct patient contact
8 ● Genetic Counseling and Cystic Fibrosis Carrier Screening: Results of a Survey

Figure 2-2—Primary Service Areas of Respondents

Metropolitan/Urban

8?40

SOURCE: Office of Technology Assessment, 1992.

Suburban

(e.g., intake or counseling) or indirect (e.g., written

communication, scheduling, and management of

referrals) (table 2-3). An additional day is spent on

administrative procedures. This leaves little time for

other activities such as educating other health

professionals or the general public. On average,

counselors and nurses in genetics spend little time on

public education. Fifty percent report spending no

time on this activity, while 26 percent report

spending, on average, an hour a week on public

education (figure 2-3). Individual counseling sessions are time and labor intensive and are the

primary format for delivering genetic information

(table 2-4). Respondents report that they seldom if

ever rely on group counseling (67 percent) or

videotape with counseling (76 percent).

On average, each genetic counselor and nurse in

genetics saw 482 patients in 1990. Averages do not,

however, speak to the great variability among

practices. Responses ranged from 10 to 2,300

clients. Counselors and nurses providing prenatal

Table 2-3-Average Weekly Schedule of Genetic

Counselor or Nurse in Genetics

Figure 2-3—Average Hours Spent Per Week

on Public Education

I

50 504 

I

I

26

---- 10

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

 o 2 3 4 5 

Numbers of hours per week

SOURCE: Office of Technology Assessment, 1992.

diagnosis and followup for elevated maternal serum

alpha-fetoprotein (MSAFP) screening tend to have

more clients.

In routine genetic counseling, the genetics specialist elicits the reasons for testing or screening and

discusses the implications of possible outcomes.

The counselor prepares the individual for both

positive and negative test results. A genetic counseling session is also the time to discuss risk reduction

strategies, irrelevant, and the nature and severity of

the disorder for which the test is being done. One

task of the genetics professional is to communicate

risks to the client-a job not easily performed. The

more complex the information, or the more emotionally laden, the more time might be required. Survey

respondents estimate that the time needed to conduct

routine prenatal counseling is 1 hour. Counseling for

Table 2-4-Formats for Genetic Counseling

Activity Hours per week Predominant response (%)

Direct patient contact . . . . . . . . . . . . . . . . . . . . . . 15

indirect patient activities. . . . . . . . . . . . . . . . . . . 11

Administration/management . . . . . . . . . . . . . . . 7

Educating health professionals . . . . . . . . . . . . . 3

Research . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 2

Educating the general public. . . . . . . . . . . . . . . 1

Marketing/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.
Chapter 2-Providers, Clientele, and Genetic Services ● 9

newly diagnosed genetic disorders in newborns,

children, or adults takes more time and more visits.

Carrier testing for families with a positive family

history for CF was estimated to take, on average, two

visits involving more than 1 hour each. Counseling

for CF carrier screening, with no family history,

however, was estimated to take one visit of less than

an hour. The need for sufficient and appropriate

pretest education and post-test counseling is discussed in depth in the full OTA report (10).

GENETICS CLIENTELE

Genetic counselors and nurses in genetics work in

a variety of settings and often the setting in which

they work dictates the types of clients they encounter. For example, working in a department of

obstetrics and gynecology is likely to mean that the

majority of one’s clients are pregnant or undergoing

family planning prior to pregnancy. Employment in

a department of pediatrics or a children’s hospital

means that most clients are likely to be children and

their families. Some counselors work in specialty

clinics, such as cranio-facial clinics or sickle cell

screening centers. Thus, their clientele are more

likely to be adult or African American, respectively.

The OTA survey results are reported in the aggregate

and fail to illustrate that some practitioners work in

specialized settings, often with one type of clientele.

The majority of individuals seen by genetic

counselors and nurses in genetics are Caucasian (70

percent) (figure 2-4). Respondents report an ethnic

and racial breakdown that is reflective of national

population averages. For example, approximately 15

percent of genetics clientele are reported as African

American; this minority group represents 12 percent

of the U.S. population. These data do not provide

information, however, about equitable allocation of

genetic services locally or regionally. African Americans or Asian Americans might find genetic services accessible in one city or one region but not in

another. Genetics services in cities with large

minority populations might be more likely to hire

health care providers with language or cultural skills

suitable to certain populations.

Ninety-two percent of genetics clientele are English speaking. As mentioned earlier, 13 percent of

genetic counselors and nurses reported fluency in a

language other than English, but no effort was made

by OTA to correlate provider fluency with clientele

needs.

Figure 2-4—Racial/Ethnic Background of

Clinical 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 of

reproductive age comprise 70 percent of the average

clinic clientele. The second largest group of individuals seen are children (11 percent). Infants and

neonates collectively comprise 14 percent of genetics clientele (figure 2-5).

Most of the adults of reproductive age are seen for

prenatal diagnosis (figure 2-6), most likely for

advanced maternal age. Prenatal genetics patients

were reported as being seen very often or almost

always by nearly two-thirds of respondents (figure

2-6). Clearly, prenatal diagnosis is a primary reason

for individuals to have contact with the clinical

genetics setting. Respondents also reported that

Figure 2-5—Age Distribution of Genetics Clientele

Neonatal

7% Infants

ildren

1%

Adolescents

4%

‘Adults of post-

 reproductive age

reproductive age

SOURCE: Office of Technology Assessment, 1992.

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

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Chapter 2-Providers, Clientele, and Genetic Services ● 11

pregnant women receiving followup counseling for

abnormal MSAFP results often (27 percent) or very

often (31 percent) are apart of their clientele (figure

2-6). Individuals seeking carrier screening for a

variety of genetic disorders, such as those described

in table 2-5, seldom (22 percent) or sometimes (50

percent) comprise the clientele in genetics clinics

(figure 2-6). Cystic fibrosis was reported most

frequently as the disease for which carrier screening

or testing is offered (table 2-5), and a majority of

respondents (62 percent) report they have seen more

than 100 clients for CF-related reasons in 1990

(figure 2-7).

FEES AND THIRD-PARTY

COVERAGE

How expensive are genetic services and will

insurers pay for them? How do third-party payers

decide what is medically indicated and, therefore,

should be covered? Many of these issues are

addressed in the full OTA report (10) as well as the

Background Paper, Genetic Tests and Health Insurance-Results of a Survey (11). In this survey of

genetic counselors and nurses, OTA obtained information about the fees charged by providers for a

variety of genetic services, including those related to

CF and their experiences with third-party coverage.

Costs of services and the availability of third-party

coverage will be crucial to the rate and magnitude at

which services will be used. This is particularly

relevant to the debate about CF carrier screening as

the procedure is relatively new, is counter to most

insurers’ policies against paying for screening, and

could involve potentially large numbers of people.

For many years, genetic counselors have faced the

problem that few third-party insurers will reimburse

for counseling services unless performed by a

physician. The costs of counseling are reimbursed as

Table 2-5-Most Common Diseases for Which Carrier

Screening/Testing Is Offered

1.

2.

3.

4.

5.

6.

7.

8.

(Ranked by frequency of response)

Cystic fibrosis

Tay Sachs disease

Sickle cell anemia

Duchenne muscular dystrophy

Thalassemia

Hemophilia

Hemoglobinopathies

Fragile X syndrome

SOURCE: Office of Technology Assessment, 1992.

Figure 2-7—Number of Cystic Fibrosis Patients or

Families Seen in Genetics Units in 1990

I 62

60

 50

 40

 30

 20

10

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

Number of patients

SOURCE: Office of Technology Assessment, 1992.

general medical consultation fees or absorbed as part

of costs on research grants (9).

Fees for Genetic Services

Genetic counseling can be provided alone or in

conjunction with diagnostic procedures. Most survey respondents work in large university or private

medical centers where billing departments are often

quite separate and distinct from the various clinical

departments. Fees are coded and processed independently. This might explain why a majority of

respondents did not know whether certain genetic

services were reimbursable and, in some cases, did

not even know the fee schedule for basic genetic

services (table 2-6). For those who knew the fee

schedule for genetic services, general genetic counseling averaged $80 per session. The range was $0

Table 2-6-Average Fees and Knowledge of

Fees for Genetic Services

Percent

respondents

uncertain

Service Fee of fee

General genetic counseling . . . . . . . . . . . $80 45

Genetic counseling for CF with a

positive family history . . . . . . . . . . . . . . $112 54

Genetic counseling for CF with a

negative family history. . . . . . . . . . . . . $105 68

Routine metabolic screen . . . . . . . . . . . . $157 70

Routine cytogenetic analysis. . . . . . . . . . $425 50

DNA analysis for CF . . . . . . . . . . . . . . . . $235 66

SOURCE: Office of Technology Assessment, 1992.
12 ● Genetic Counseling and Cystic Fibrosis Carrier Screening: Results of a Survey

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 counseling

for individuals with a family history of CF was not

significantly different from the fee that would be

charged to individuals requesting the same services

with a negative history for CF($112 versus $105).

In the summer of 1991, the average fee for DNA

analysis for CF was $235 although spring 1992 data

collected separately by OTA found an average cost

of $170 per sample.

Third-Party Coverage

Respondents reported that most of their clients are

covered by some type of health insurance. Two

percent said that their patients seldom if ever have

health care coverage, whereas 63 percent reported

that their clients very often or always have coverage

(figure 2-8). Commercial insurance, health maintenance organizations, or managed care programs

comprise over half of the coverage (figure 2-9).

Medicaid (21 percent) and Blue Cross/Blue Shield

plans (17 percent) also cover genetics clients. Four

percent of clients have no insurance and 3 percent

are indigent.

With regard to coverage of genetic counseling

services accompanying DNA-based tests to determine CF carrier status, respondents reported a higher

likelihood of coverage if there is a family history of

CF than if there is no family history (figure 2-10).

This result was confirmed by OTA’s survey of

health insurers, which found health insurers rarely

reimburse individuals for CF carrier tests in the

absence of a family history (11).

OTA attempted to ascertain whether individuals

who avail themselves of genetic tests subsequently

have difficulty obtaining or retaining health insurance. The survey asked for reported occurrences for

genetic tests, generally, not just carrier tests for CF

or other disorders.2 OTA asked:

Figure 2-8-Health Care Coverage for

Genetics Clientele

40

33

0

 Seldom if ever Sometimes Often

 Very often Always or almost always

SOURCE: Office of Technology Assessment, 1992.

Figure 2-9-General Types of Health Care Coverage

for Genetics Clientele

I Commercial

Medicaid 

HMO or

 17% managed care 22°A

SOURCE: Office of Technology Assessment, 1992.

Have any of your patients experienced difficulties

in obtaining or retaining health insurance coverage

as a result of genetic testing? If yes, please provide

details.

Approximately four-fifths (347) of the 431 respondents to OTA’s inquiry currently perform

genetic counseling. Fifty respondents (14 percent)

reported they had clients who had experienced

difficulties 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 for

General Genetic Counseling and Counseling

Specifically for Cystic Fibrosis

30

27

25 

16

20 19

Seldom Sometimes Often Very often Almost

if ever covered covered covered always

covered covered

 General genetic With no family With family

counseling history of CF history of CF

SOURCE: Office of Technology Assessment, 1992.

age as a result of genetic testing (table 2-8). Because

some respondents described more than one case, the

number of affirmative answers understates the actual

number of cases. Examination of the qualitative

responses, some of which are presented in table 2-9,

reveals affirmative responses represent, at minimum, 68 individual cases. (Where the term ‘‘patients” was used with specifics not described, a

single event was recorded.)

It is important to emphasize that most of the cases

revealed through the OTA survey do not involve

recessive disorders and carrier screening for conditions like CF And while one assumption might have

been that health care coverage for CF carriers would

not be an issue because the individuals have no

symptoms of the disorder, OTA’s survey of health

insurers reveals that a few respondents would

require a waiting period or deny coverage for CF

carriers (10,1 1).

Test results for some conditions where positive

results led to reported difficulties-such as for

Huntington disease, adult polycystic kidney disease,

and Marfan syndrome-were cited by more than one

respondent. In addition to affirmative answers,

several respondents reported that although they had

no direct experience with a patient’s difficulty in

Table 2-8-Difficulties in Obtaining or Retaining

Health Insurance After Genetic Tests

Question: Have any of your patients experienced difficulties in

obtaining or retaining health insurance coverage as a

result of genetic testing?

Number (percent)

No . . . . . . . . . . . . . . . . . . . . . . . . . 281 81

Yes . . . . . . . . . . . . . . . . . . . . . . . . 50 14

No answer . . . . . . . . . . . . . . . . . . . 16 5

SOURCE: Office of Technology Assessment, 1992.

obtaining or retaining health care coverage, they had

clients who feared their coverage would be dropped

if they requested payment for tests from insurers.

One respondent commented that greater than 80

percent of her clients who test for Huntington

disease self-pay. Similarly, others with no direct

experience said they often advise patients not to

request reimbursement for a test so that an insurer

would not learn that testing had occurred. One

counselor offered the information that a patient had

refused testing for adult polycystic kidney disease

because of concern over health insurance. Another

respondent reported that a patient with a CF-affected

child had been dropped by one insurance company

and would not consider prenatal testing in the future

for fear her current insurer would not cover the child

should she decide to continue the pregnancy.

The data collected through this question permit

neither extrapolation about the total number of cases

that have occurred in the United States nor speculation about any trends. OTA also did not attempt to

ascertain whether patients had challenged-or were

challenging-insurers’ rulings. Thus, OTA cannot

determine whether some of the disputes reported in

table 2-9 were resolved fully in favor of the

consumer because the initial judgment was deemed

improper or illegal. Some cases, for example,

reported a fetus or newborn had tested positive and

the policy cancelled. In all 50 States and the District

of Columbia, insurers must cover (or offer the option

to include) a newborn child if a valid insurance

contract for the parent exists. However, whether the

insurance company can deny specific benefits for the

newborn by evoking the preexisting condition

clause generally contained in all insurance contracts

is unclear.

In presenting table 2-9, OTA does not judge the

validity-positively or negatively-of the claim.

Some cases might have been settled in favor of the

individual. Others might have been cases where an
14 ● Genetic Counseling and Cystic Fibrosis Carrier Screening: Results of a Survey

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 experimental

diet to prevent problems that can arise from mid- to late childhood or early adulthood. One boy tested positive. The family’s private

pay policy (Blue Cross/Blue Shield) is attempting to disqualify the family for failing to report the family history under preexisting

conditions.

After birth of child with CF unable to insure unaffected siblings or themselves.

alggl OTA survey of genetic counselors and nurses in genetics. Not all cases, or multiple cases involving same disorder, listed.

SOURCE: Office of Technology Assessment, 1992.

applicant attempted to select against an insurer by

misrepresenting his or her health history, which

would have been resolved against the individual.

In 1991, at least 50 genetic counselors or nurses

in clinical practice knew of at least 68 actual

incidents where their own patients reported difficulties with health insurance due to genetic tests. OTA

estimates, based on the average number of patients

directly counseled, that genetic counselors and

nurses responding to the survey collectively saw

about 110,600 individuals in 1990. However, OTA

did not advise respondents to limit descriptions of

clients’ insurance difficulty to 1990. Thus, it is

unlikely that all reported cases occurred in 1990;

assuming all cases occurred in 1990 means the 68

cases represent 0.06 percent of patients seen by

respondents.

Critics question whether the data-especially the

qualitative descriptions—merely represent more anecdotal stories that unfairly present one side of the

story and for which no response can be developed.

Skeptics point out that some of the cases might fall

into the gray area of whether exclusion or increased

rates resulted because an adverse medical condition

was revealed through a diagnostic test that just

happened to be genetic. The border between what

conditions are genetic or not is blurred, however, and

will become increasingly diffuse. Because geneticbased predictive testing promises to have a profound

impact on clinical medicine-and because access to

medical care is inextricably linked to private health

insurance in this country-these cases underscore

certain policy dilemmas arising from the increased

availability of genetic assays.

SUMMARY

Although genetic counselors and nurses in genetics work in a variety of settings, they are concentrated in metropolitan medical centers on the West

coast or Northeast region. States with a large

proportion of rural residents are less likely to be

served. The clientele served, in the aggregate, tend

to be representative of the national averages for

majority and minority groups, although no effort

was made by OTA to match racial and ethnic data

with regions, cities, or localities.

Most genetic counselors have a master’s degree

and are either certified or eligible for professional
Chapter 2-Providers, Clientele, and Genetic Services ● 15

certification. They spend most of their work week

seeing or talking with clients. Less time is spent on

administration and research, and even less on

professional and public education. Seventy percent

of the genetics clientele is comprised of adults of

reproductive age suggesting the strong influence of

prenatal diagnosis as a primary genetics service.

Respondents report that their counseling services are

frequently not covered by third parties, even when

“medically indicated.’

OTA’s survey reports consumers can experience

difficulties in obtaining or retaining health care

coverage after genetic tests. Because genetic-based

predictive testing promises to have a profound

impact on clinical medicine-and because access to

medical care is inextricably linked to private health

insurance in this country-these cases underscore

certain policy dilemmas arising from the increased

availability of genetic assays.

4.

5.

6.

7.

8.

9.

10.

1.

2.

3.

CHAPTER 2 REFERENCES

Boyle, J.M., Schulman, Ronca & Bucuvalas, Inc.,

Silver Spring, MD, personal communications July 11”

1991, August 1992.

Fibison, W.J., “The Nursing Role in the Delivery of

Genetic Services,” Issues in Health Care of Women

4:1-15, 1983. 12.

Forsman, I., “Education of Nurses in Genetics,”

American Journal of Human Genetics 43;552-558,

1988.

Jones, S.L., ‘‘Decision Making in Clinical Genetics:

Ethical Implications for Perinatal Practice,” JournuZ

of Perinatal and Neonatal Nursing 1:11-23, 1988.

Jones, S.L., Genetics & IVF Institute, Fairfax, VA,

personal communication, December 1991.

Kanuck, L., and Berenson, C., “Mail Surveys and

Response Rates: A Literature Review,” Journal of

Marketing Research 12;440-454, 1975.

National Society of Genetic Counselors, Wallingford,

PA, personal communication, June 1991.

National Society of Genetic Counselors, “Report to

Membership: 1992 Professional Status Survey,”

Perspectives in Genetic Counseling, newsletter of the

National Society of Genetic Counselors, Inc., summer 1992.

U.S. Congress, Office of Technology Assessment,

“Cystic Fibrosis, Genetic Screening, and Insurance,” transcript of workshop proceedings, Feb. 1,

1991.

U.S. Congress, Office of Technology Assessment,

Cystic Fibrosis and DNA Tests: Implications of

Carrier Screening, OTA-BA-532 (Washington, DC:

U.S. Government Printing Office, August 1992).

U.S. Congress, Office of Twhnology Assessment,

Genetic Tests and Health Insurance+tesults of a

Survey, OTA-BP-BA-98 (Washington, DC: U.S.

Government Printing OffIce, October 1992).

Walker, A. P., Scott, J.A., Biesecker, B. B., et al.,

“Report of the 1989 Asilomar Meeting on Education

in Genetic Counseling,’ American Journal ofHuman

Genetics 46:1223-1230, 1990.
Chapter 3

Cystic Fibrosis Carrier Screening: Policies and Practices

Prospects of routine cystic fibrosis CF carrier

screening polarize people. Everyone agrees that

persons with a family history of CF should have the

opportunity to avail themselves of CF mutation

analysis, yet controversy swirls around using the

same test in the general population. This polarization is illustrated in the written comments of two

survey participants.

NO to widespread screening! Must be close to 100

percent detection for all CF mutations before it can

even be considered.

Let’s go with screening! I can’t believe we are not

halfday through a pilot program by mid 1991.

As described in the full OTA report (18), proponents of a measured approach to CF carrier screening

express concern about several issues that might be

raised if CF carrier screening becomes routine, such

as the use of genetic information by insurance

companies to set rates or deny coverage, and

concerns that market pressures will drive widespread use of tests before the potential for discrimination or stigmatization by other individuals or

institutions is assessed. Also expressed are questions

about the adequacy of quality assurance for DNA

diagnostic facilities, personnel, and the tests themselves. Still others also wonder whether the current

number of health care professionals in genetics can

handle a swell of CF carrier screening cases, let

alone cases of other genetic conditions arising from

increased knowledge from the Human Genome

Project. Finally, the extraordinary tensions in the

United States about abortion affect discussions

about CF carrier testing and screening.

I n summer 1991, OTA asked genetic counselors

and nurses in genetics to provide data regarding their

experiences concerning CF carrier screening as a

means to judge the validity of these concerns. The

questionnaire was designed to gather data on the

frequency of DNA analysis for CF carrier status and

trends over time, clinic policies regarding CF carrier

screening, counseling and clinical practices regarding CF carrier testing and screening, and sources

influencing the development of, and policies and

procedures related to, CF mutation analysis. Survey

participants were also asked their opinions about

who should conduct carrier screening, in what

settings, and on what target population(s). Respondents were encouraged to rank the most important

issues to be addressed before embarking on a

large-scale screening program.

The data in this chapter are specific to CF carrier

screening. Data regarding third-party reimbursement for DNA-based tests are presented in chapter

2, along with general demographic data concerning

the survey respondents and their clientele and

clinical settings.

POLICIES AND PRACTICES,

SUMMER 1991

Survey participants were asked to consider three

issues. First, what is their opinion or the policy of

their institution about the appropriateness of CF

carrier screening at this time? Second, what are the

current logistics of providing DNA-based tests for

CF carrier status-i.e., once a decision had been

made to offer CF mutation analysis, which mutations are analyzed, and how are those individuals to

be tested identified or contacted? Third, survey

participants were asked to estimate whether requests

for DNA-based tests for CF had changed since the

tests’ development in 1989.

Policies on Cystic Fibrosis Carrier Screening

Currently, it is standard practice to offer CF

carrier tests to individuals who have a positive

family history of CF (6,16,18). An unaffected

sibling of an individual with CF has a 2 in 3

likelihood of being a CF carrier. A consanguineous

uncle or aunt of an individual with CF has a 1 in 2

likelihood of being a carrier. A first cousin of an

individual with CF has a 1 in 4 likelihood of being

a carrier (table 3-l).

As of the summer of 1991, most genetic counselors and nurses in genetics did not offer unsolicited

CF mutation assays to individuals with a negative

family history. A large majority of survey respondents use medical journals and other professional

sources to obtain information regarding new advances in human genetics (table 3-2), and the

American Society of Human Genetics (ASHG) and

the National Institutes of Health (NIH) published

policy documents in 1990 discouraging CF carrier

–17 -
18 ● Genetic Counseling and Cystic Fibrosis Carrier Screening: Results of a Survey

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

Negative family history

Caucasian. . . . . . . . . . . . . . . . . . . . 1 in 25 (4%)

African American . . . . . . . . . . . . . . . 1 in 60 to 65 (1.5 to 1.7%)

Asian American. . . . . . . . . . . . . . . . 1 in 150 (0.7%)

Hispanic American. . . . . . . . . . . . . 1 in 46 (2.2%)

Positive family history

Parent of child with CF . . . . . . . . . 1 in 1 (100%)

Sibling with CF . . . . . . . . . . . . . . . 2 in 3 (67%)

Aunt or uncle with CFa. . . . . . . . . . 1 in 3 (33%)

First cousin with CF . . . . . . . . . . . . 1 in 4 (25%)

Niece/nephew with CF . . . . . . . . 1 in 2 (50%)

a Consanguineous.

SOURCE: Office of Technology Assessment, 1992.

Table 3-2-Sources of Information About

New Advances in Human Genetics

Percent

Human genetics indicating yes

Medical journals . . . . . . . . . . . . . . . . . . . . . . . 96

Professional colleagues . . . . . . . . . . . . . . . . 94

National inferences . . . . . . . . . . . . . . . . . . . 83

American Society of Human Genetics . . . . . 82

National Society of Genetic Counselors . . . 80

State or regional conferences . . . . . . . . . . . 71

Grand rounds . . . . . . . . . . . . . . . . . . . . . . . . . 44

Lay press . . . . . . . . . . . . . . . . . . . . . . . . . . . . 37

Continuing education courses . . . . . . . . . . . 35

Literature from biotechnology companies

or commercial firms. . . . . . . . . . . . . . . . . . 35

Other . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 8

SOURCE: Office of Technology Assessment, 1992.

screening (6,16).1 Seventy-six percent of respondents stated that they were familiar with the 1990

ASHG statement. Thirty-five percent were familiar

with the NIH statement.

OTA’s survey of genetic counselors and nurses

revealed that 53 percent of respondents believe that

CF carrier tests should only be offered to individuals

with a positive family history of CF and not to those

with a negative family history. Twenty-one percent

felt that CF carrier tests should be offered to

individuals with no family history. The most frequently cited reasons for making tests available to

individuals regardless of family history were to

reduce anxiety or increase patient autonomy. In the

words of one counselor, ‘‘DNA screening is a

personal issue, different in every case. What one

person or family feels may be quite different from

that of another person or family in any given genetic

disorder with any given family history.’ Twenty-six

percent of respondents were uncertain as to whether

they should provide CF carrier screening where

family history is negative.

When asked about their likelihood of introducing

the topic of CF carrier tests during a counseling

session, 82 percent of respondents stated that they

would seldom, if ever, do so to all patients or

families (table 3-3). Seventy-three percent would

seldom, if ever, discuss it with pregnant women

seeking prenatal diagnosis unless there was a family

history of CF in which case, 90 percent would

almost always bring it up during counseling.

When asked whether their institution or clinic had

a specific policy regarding CF carrier screening, 33

percent of genetic counselors and nurses responded

in the affirmative. Of those responses, 70 percent

stated that it is the policy of their clinic or

organization to offer CF carrier tests only to those

with a positive family history (table 3-4).

The overall lack of policies for CF carrier

screening apparently stems from the fact that, in

general, explicit and official policies for clinical

practices were not routine at the majority of facilities. When asked whether their group or unit had

Table 3-3-Likelihood of Introducing the Topic of

DNA Testing for Cystic Fibrosis

Predominant

Patient population response (Percent)

All patients/families. . . . . . . . . . . . Seldom if ever (82)

Pregnant women seeking prenatal

diagnosis . . . . . . . . . . . . . . . . . . Seldom if ever (73)

Coupies/individuals with a family

history of CF . . . . . . . . . . . . . . Almost always (90)

Caucasian coupies/individuals

with a negative history of CF . Seldom if ever (65)

individuals/famiiies who inquire

about CF . . . . . . . . . . . . . . . . . . Almost always (80)

Selected coupies/individuals . . . . Seldom if ever (72)

SOURCE: Office of Technology Assessment, 1992.

Table 3-4-Specific Policies Regarding DNA Testing

for Cystic Fibrosis

Policy Percent

Offer to all regardless of family history . . . . . . . . . . . . . 14

Offer only to those with a positive family history . . . . . 70

Provide to those with no family history upon request

if informed consent is obtained . . . . . . . . . . . . . . . . . 16

SOURCE: Office of Technology Assessment, 1992,

1 III 1992, 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 in

genetics, 21 percent reported they have policies

regarding DNA storage, 42 percent have policies in

place concerning prenatal diagnosis for sex selection, 37 percent have policies regarding cases of

nonpaternity, and 28 percent adhere to policies

regarding confidentiality and Huntington disease

testing.

Criteria for Cystic Fibrosis Carrier Screening

Sixty-five percent of survey participants felt

strongly that there is an optimum rate of detection

that should be reached before they would feel

comfortable offering CF carrier screening, as compared to 14 percent who felt there is not and 21

percent who were uncertain. Of those who felt there

is an optimum rate of detection, nearly half (46

percent) said that 95 percent test sensitivity should

be required before proceeding with widespread

screening. Twenty-five percent believe test sensitivity should be even higher, with 4 percent stating that

it should be 100 percent (figure 3-l).

However, survey respondents ranked the availability of adequate counseling and an adequate

system of referral for individuals who test positive as

slightly more important criteria for CF carrier

screening than test sensitivity (table 3-5). Guarantee

of informed consent also was mentioned as necessary for implementation of large-scale CF carrier

screening.

Perhaps the point on which there was greatest

consensus among the respondents is on the issue of

autonomy and choice in screening. There are no

mandatory genetic screening programs of adult

populations in the United States. Ninety-nine percent of survey participants responded that CF carrier

screening should be voluntary and never mandatory.

Practices Regarding DNA-Based

Cystic Fibrosis Carrier Tests

When asked about the frequency of requests for

DNA testing or screening for CF carrier status

during the 6-month period from January to June

1991, most respondents reported occasional requests

(figure 3-2). When asked to compare this time period

with the previous 2 years, nearly half indicated a

small increase in the number of requests and a

quarter noted a large increase in requests (figure

3-3). The survey did not distinguish whether the

requests were carrier tests for individuals known to

Figure 3-l—Opinions on Optimal Rate of Detection

60,

I

46

75% 80% 85% 90% 95% 97% 98% 99% 100%

 Optimal test sensitivity

SOURCE: Office of Technology Assessment, 1992.

Table 3-5-Minimal Criteria for Cystic Fibrosis

Carrier Screening Protocol

Question: What do you feel should be the minimum criteria for CF

carrier screening protocol)?

Criteria Percent a

Provision of adequate counseling . . . . . . . . . . . . . . . . 40

Adequate system of referral in place . . . . . . . . . . . . . 37

Improved test sensitivity. . . . . . . . . , , . . . . . . . . . . . . 35

Guarantee of informed consent . . . . . . . . . . . . . . . . . 32

Availability of educational materials. . . . . . . . . . . . . . 18

Only offer to families with a positive history of CF 15

Must be voluntary. , . . . . . . . . . . . . . . . . . . . . . . . . . . . 14

Reasonable cost or payment . . . . . . . . . . . . . . . . . . . 12

Protection of confidentiality . . . . . . . . . . . . . . . . . . . . 12

 not add to 100; respondents could reply with 

answers.

SOURCE: Office of Technology Assessment, 1992.

be at risk by virtue of family history or carrier

screens for individuals with no known family history

of CF

Although 55 percent of survey participants responded that a CF treatment center exists at their

institution, 86 percent reported that they do not

provide genetic counseling through that facility.

Several respondents noted that this is the choice of

the CF treatment provider, not necessarily the

genetics unit. Because OTA did not survey CF

treatment centers, it is not known to what extent CF

families are informed of, offered, or request carrier

testing. The data do show, however, that most

families who have a child with CF are not routinely
20 ● Genetic Counseling and Cystic Fibrosis Carrier Screening: Results of a Survey

Figure 3-2—Frequency of Requests for Cystic Fibrosis

Carrier Screening/Testing, January-June 1991

60

.5(-) - 48

I

10

0

 Never Occasionally Very frequently

 Rarely Frequently

SOURCE: Office of Technology Assessment, 1992.

Figure 3-3-Comparison of Requests for cystic Fibrosis

Carrier Screening/Testing Between January-June 1991

and Past 2 Years

46

 A large decrease No change

 A small decrease A small increase increase

SOURCE: Office of Technology Assessment, 1992.

seen in genetics service settings, and few counselors

have routine contact with CF families.

Encouraging known carriers to notify consanguineous relatives (e.g., siblings and first cousins)

provides economic and pragmatic benefits because

it can detect a larger percentage of at-risk couples

(18); testing those known to be at higher risk because

of family history is more effective than screening

those with unknown risk. In reality, complex psychological factors enter when family members of

individuals with CF contemplate screening, and it

cannot be assumed that all will want to be tested.

For this type of carrier identification to work,

those providing health care and counseling to CF

families will have to actively participate in referrals

of relatives to genetics centers, an uncommon

practice, according to OTA’s data. Fewer than 10

percent of respondents reported contacting previously identified CF families with whom they had

had contact about the availability of CF mutation

analysis.

For those respondents whose institutions are

engaged in CF carrier testing or screening, direct

DNA mutation analysis is the most common approach (table 3-6). In the recent past, the sensitivity

of the carrier test was limited to the DF508 mutation.

All respondents involved in analyzing CF carrier

status assay for the DF508 mutation. But roughly 74

percent indicated that they also test for at least one

other mutation, most commonly four others, G551D,

R553X, G542X, and N1303K (table 3-7). At the

time the survey was done, the mutation that accounts

for 60 percent of CF mutations in Jewish persons of

Table 3-6—Types of Genetic Analyses Provided for

Cystic Fibrosis Screening/Testing

Procedure Percent response

Direct mutation analysis. . . . . . . . . . . . . . . . 67

Prenatal DNA analysis. . . . . . . . . . . . . . . . . . 63

DNA linkage analysis . . . . . . . . . . . . . . . . . . . 61

DNA haplotyping . . . . . . . . . . . . . . . . . . . . . . 56

Staging of studies . . . . . . . . . . . . . . . . . . . . . 37

DNA banking . . . . . . . . . . . . . . . . . . . . . . . . . 31

Fetal intestinal enzyme analysis . . . . . . . . . . 28

SOURCE: Office of Technology Assessment, 1992.

Table 3-7-Cystic Fibrosis Mutations

Routinely Analyzed

Mutation Percent response

DF508 . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 100

G551D . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 77

R553X . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 76

G542X . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 71

N1303K . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 70

Other . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 79

SOURCE: Office of Technology Assessment, 1992.
Chapter 3-Cystic Fibrosis Carrier Screening: Policies and Practices ● 21

Central and Eastern European descent (Ashkenazic

Jews), W1282X, had not been found.2

Respondents report an almost even split between

commercial and university-based laboratories as the

facility performing their CF mutation assays (45

percent and 48 percent, respectively). Most centers

send the sample offsite (76 percent), frequently to a

laboratory greater than 150 miles away.

Finally, although the need for professional and

public education was cited as critical for the

implementation of widespread carrier screening, few

genetic counselors and nurses in genetics reported

spending professional time engaged in either activity. For those respondents who do, an average of 3

hours per week devoted to educating health professionals and 1 hour per week on educating the general

public was reported (ch. 2). For CF carrier screening,

specifically, 8 percent of genetic counselors and

nurses had developed, or were in the process of

developing, educational materials relevant to DNA

tests for CF mutation.

PREFERRED STRATEGIES

AND PROTOCOLS

The importance of informed consent, careful

presentation of counseling, and confidentiality have

long been recognized as essential components of

genetic testing and screening (9). Respondents

strongly agreed that genetic counseling should

precede DNA tests for CF carrier status regardless of

family history (figures 3-4 and 3-5). Geneticists,

perhaps more than any other medical specialty, have

advocated a nondirective approach to counseling

and have a strong commitment to patient autonomy

(3). Further, a history of concern exists about the

delivery of genetic information by health professionals used to a more directive approach (7). This

concern has been played out in the debate over

maternal serum alpha-fetoprotein (MSAFP) screening and is a factor in the reluctance of the clinical

genetics community to rush toward widespread

screening for any disease (18). For example, as part

of the debates surrounding MSAFP and CF carrier

screening, concern has been voiced about informed

consent—in particular, that tests would be available

to primary care practitioners who might incorporate

Figure 3-4-Opinions Regarding Genetic Counseling

of Individuals with a Positive Family History

100

1

I

93

0

 Strongly agree Undecided Strongly

 Agree Disagree disagree

Genetic counseling should precede DNA testing for CF

when there is a positive family history.

SOURCE: Office of Technology Assessment, 1992.

Figure 3-5-Opinions Regarding Genetic Counseling

of Individuals with a Negative Family History

60-

 50-

c

 40-

 30-

8

 20-

lo0

84

I

 18

 Strongly agree Undecided strongly

_ Agree Disagree disagree

Genetic counseling should precede DNA testing for CF

when there is a negative family history.

SOURCE: Office of Technology Assessment, 1992.

 test sensitivity was 75 to 85 depending on race and most Commercial 

laboratories e DF508 and 6 to 12 additional mutations, and taken together these mutations comprise 85 to 90 percent of CF mutations in U.S.

Caucasians (95 percent in Jews).

297-911 0 - 92 - 3
22 ● Genetic Counseling and Cystic Fibrosis Carrier Screening: Results of a Survey

the assay into their practice without considering the

informed consent requirements usually adhered to in

genetics practices. Seventy-nine percent strongly

agree that informed consent prior to CF carrier

screening is a necessity (figure 3-6).

In addition to informed consent, prescreening

education for clients is imperative. Information

regarding an individual’s a priori risk, types of tests

available, and uncertainties in risk assessment based

on screening results are important for potential

screenees to understand. When asked if educational

materials can provide adequate information about

CF carrier screening, 44 percent disagreed or strongly

disagreed with that concept (figure 3-7).

Who Should Provide Cystic Fibrosis

Carrier Screening?

Concern about the complex nature of some

genetic information and the need in some cases for

post-test counseling leads many human genetics

professionals to advocate restricting CF carrier

screening primarily to the human genetics community. Pretest education, felt many respondents, can

be offered by a wide range of professionals (figure

3-8), but organizing CF carrier screening should be

provided by genetic specialists (table 3-8). Nearly 82

Figure 3-6—Opinions Regarding the Need for

Informed Consent Prior to Cystic Fibrosis

Carrier Screening

79

13

 Strongly agree Undecided strongly

 Agree Disagree disagree

Informed consent prior to CF carrier screening is a necessity.

SOURCE: Office of Technology Assessment, 1992.

Figure 3-7-Opinions Regarding the Use of

Educational Materials as a Source of Information

About Cystic Fibrosis Carrier Screening

30

 15

I

o

7

28 I

 Strongly agree Undecided

 Agree Disagree disagree

Educational materials (culturally sensitive and understandable)

can provide adequate information about CF carrier screening.

SOURCE: Office of Technology Assessment, 1992.

percent of the respondents surveyed by OTA said the

human genetics community should be the primary

organizer of CF carrier screening programs (table

3-8). Also mentioned were State or local health

departments (59 percent) and primary caregivers (27

percent). Over 89 percent believed CF population

screening should be provided in genetics centers, but

59 percent thought CF carrier screening could also

be provided in the primary care setting or organized,

community-wide programs (53 percent) (table 3-9).

Concern about the sometimes difficult nature of

communicating risk information regarding CF

even for experienced genetic centers—has led some

in the clinical genetics community to caution against

rapid movement to routine CF carrier screening (2).

In the words of one respondent:

Counseling should not be left to hurried family

practitioners or OB’s [obstetrician/gynecologists],

who routinely spend less than 15 minutes with each

patient.

As noted in chapter 2, most counselors and nurses

spend little to no time on professional education or

general public education in schools and communities. Thus, the majority of people will rely on their

primary care provider for preliminary, if not most,
Chapter 3-Cystic Fibrosis Carrier Screening: Policies and Practices ● 23

Table 3-8—Preferred Organizations for lmplementation

of Voluntary Cystic Fibrosis Carrier Screening

Organization Yes Noa

(percent)

Human genetics community . . . . . . . . . . 82 15

State or local health department. . . . . . . 59 39

Voluntary health organizations . . . . . . . . 30 67

Primary caregivers . . . . . . . . . . . . . . . . . . 27 71

Medical societies . . . . . . . . . . . . . . . . . . . 17 81

Federal Government . . . . . . . . . . . . . . . . 15 82

as per~nt gave no res~nse

SOURCE: Office of Technology Assessment, 1992.

Table 3-9-Preferred Sites for Cystic Fibrosis

Carrier Screening Programs

Site Yes Noa

(percent)

Genetics centers . . . . . . . . . . . . . . . . . . . 89 7

Primary care setting . . . . . . . . . . . . . . . . . 59 37

Community-wide . . . . . . . . . . . . . . . . . . . . 53 43

Public health department. . . . . . . . . . . . . 48 49

Public schools . . . . . . . . . . . . . . . . . . . . . 14 83

Workplace . . . . . . . . . . . . . . . . . . . . . . . . 9 87

=qs per~nt gave no response

SOURCE: Office of Technology Assessment, 1992.

genetic information (18), and many survey respondents said primary care providers and public health

departments should play an active role in educating

the public about DNA tests for CF carrier status

(figure 3-8). Health care provider and communitywide genetics education will become increasingly

important, as will the interaction of genetic specialists with other health professionals and the public.

Who Should Pay for Cystic Fibrosis

Carrier Screening?

When asked who should pay for screening, 80

percent of respondents ranked third parties as the

primary source of payment (table 3-10). Self pay was

ranked second, and employers ranked last. Additionally, some participants noted that if screening ever

became mandatory, as in many State newborn

screening programs, the State or Federal Government should be responsible for payment.

Strategies for Screening Various Populations

Two key considerations in deciding how routine

CF carrier screening is best implemented are the

clinical settings in which it will take place and the

target populations. Delineation of a target group (or

groups) determines other elements such as location,

educational approach and tools, time, format, types

of counseling, facilities, and publicity.

The NIH statement on CF carrier screening

emphasized the importance of preconceptional screening (16). Most pilot projects in the United Kingdom

are directed at preconceptional populations (18).

One program in Canada targets high school students

(11).

Newborn Screening

Numerous newborn screening programs exist for

genetic disorders such as sickle cell anemia and

phenylketonuria. These are programs intended to

screen for the presence of disease, although some

can also detect the carrier status of the newborn.

Using the immunoreactive trypsin assay, Wisconsin

has performed statewide neonatal screening for CF

disease since 1985, and primary care physicians

have been cooperative in referring screened patients

to designated CF centers for followup (14). But even

newborn screening for CF disease is not without

controversy. Evidence of heightened anxiety and

disrupted maternal-infant bonding have been reported in cases of false-positive diagnoses (4).

For at least two reasons, many believe that

newborn screening is an inappropriate and inefficient mechanism for carrier detection. First, newborns determined to be carriers must be tracked

through their reproductive years to ensure they are

aware of their carrier status. Second, detection of

newborn carriers might unnecessarily raise the

anxiety level of parents. Thus, newborn screening

for CF carrier status is not generally viewed as

acceptable (15). This survey revealed that 33 percent

of genetic counselors and nurses in genetics believed

the newborn population would be an appropriate

target group for widespread CF carrier screening

(table 3-11).

Adolescent Preconceptional Screening

Some geneticists advocate carrier screening at the

high-school level (11). A recent nationwide survey

of American attitudes about, and knowledge of,

genetic tests showed better knowledge and more

positive attitudes in younger populations (17).

Studies of pregnant women known to be carriers of

a hemoglobinopathy gene have shown that age is a

predictor of postcounseling knowledge-younger

women (and adolescents as young as 12 years old)

are more likely to understand genetic information

(13). While not routinely done in the United States,
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 providers

35,

I 31

30+I

I

25-

20-

15-

lo5 -

(-JJ--

100

20

01

22

Little to Some Moderate Great All or

no extent extent extent extent almost

all

Genetic counselors

77

0.2

18

0.5 4

Little to Some Moderate Great All or

no extent extent extent extent almost

all

Nurses

I

33

 30

26

Little to Some Moderate Great or

no extent extent extent extent almost

all

Public health departments

35

30- 28 28

0L

20

0

Little to Some Moderate Great All or

no extent extent extent extent almost

all

Genetics programs

0.2

40

 30

& o

 10

73

Little to Some Moderate Great All or

no extent extent extent extent almost

all

Family planning clinics

26 26

0

Little to Some Moderate Great All or

no extent extent extent extent almost

all
Chapter 3-Cystic Fibrosis Carrier Screening: Policies and Practices ● 25

Voluntary support groups

oJI

I

Little to Some Moderate Great All or

no extent extent extent extent almost

all

Lay press

40

c

o

 30

 20

o

Little to Some Moderate Great All or

no extent extent extent extent almost

all

SOURCE: Office of Technology Assessment, 1992.

high-school screening programs have been conducted in Montreal, Canada for some time. For any

disease where screening is done in childhood or

adolescence, however, the benefits of such screening, including savings in resources or anxiety, must

be balanced against the potential problems, such as

the possibility that an adolescent will be falsely

assigned to a low-risk group because of poor test

sensitivity (thereby obviating further screening), or

the possibility of psychosocial harm to the child as

a result of identified carrier status (9).

Adolescents were not considered an appropriate

target by the genetic counselors and nurses surveyed

Schools

36

Little to Some Moderate Great All or

no extent extent extent extent almost

all

Television

o

36

Little to Some Moderate Great All or

no extent extent extent extent almost

all

by OTA (table 3-11). Less than one-fifth felt

individuals ages 13 to 18 years should be screened;

only 6 percent responded that children ages 2

through 12 years should be screened.

Adults—Preconceptional or Prenatal?

One debate surrounding CF carrier screening

focuses on whether the goals are best accomplished

by targeting preconceptional adults or pregnant

women. These approaches are not necessarily mutually exclusive. Many believe, however, that the

receipt of troubling information during pregnancy is

not desirable, and that it would be better for
26 ● Genetic Counseling and Cystic Fibrosis Carrier Screening: Results of a Survey

Table 3-10-Who Should Pay for Cystic Fibrosis

Carrier Screening?

Table 3-1 2—Frequency of Patients Seen

by Major Areas of Clinical Practice

Rank order Area Predominant response

1. Third parties

2. Self pay

3. State, city, or county

4. Federal Government

5. Employers

SOURCE: Office of Technology Assessment, 1992.

Table 3-1 l—Target Populations for Cystic Fibrosis

Carrier Screening

Population Yes Noa

(percent)

Adults in reproductive years. . . . . . . . . . 88 8

Prenatal . . . . . . . . . . . . . . . . . . . . . . . . . . 75 22

Pregnant women or “couples” . . . . . . . . 66 31

Newborns . . . . . . . . . . . . . . . . . . . . . . . . . 33 63

Children ages 13 to 18 . . . . . . . . . . . . . . 19 78

Children ages 2 to 12 . . . . . . . . . . . . . . . 6 91

Adults in post reproductive years. . . . . . 3 94

a3 per~nt had no response in each cate90rY.

SOURCE: Office of Technology Assessment, 1992.

individuals to know their risks before getting pregnant (12). Others argue that individuals not facing a

pregnancy are not motivated to seek or use information on their carrier status, but will wait until they are

either planning a family or starting a family before

viewing such information as useful (5).

CF carrier screening offered as part of primary

health care rather than prenatal care is likely to

encourage preconceptional CF carrier screening. For

most individuals, however, the first real opportunity

for carrier screening takes place postconception (8).

In the future, the primary responsibility for providing CF carrier screening might reside with the

obstetrician, as has happened with MSAFP screening. Sixty-six percent of respondents to OTA’s

survey identified pregnant women or couples as the

appropriate target population for CF carrier screening, yet 88 percent more generally identified adults

in their reproductive years as the appropriate target

group (table 3-11). While most respondents state

that the ideal target population for carrier screening

is the preconceptional adult, in reality, the first target

population is likely to be the prenatal population

because it has been the traditional entry point into

genetic services for many people and comprises the

largest population served by genetics centers (table

3-12).

Prenatal genetics. . . . . . . . . . . . . . . . . . .

Pediatric genetics . . . . . . . . . . . . . . . . . .

Adult genetics . . . . . . . . . . . . . . . . . . . . .

Teratogen exposure . . . . . . . . . . . . . . . . .

Reproductive loss . . . . . . . . . . . . . . . . . .

Specialty disease(s) clinics . . . . . . . . . . .

Newborn screening . . . . . . . . . . . . . . . . .

MSAFP screening followup. . . . . . . . . . .

Carrier screening . . . . . . . . . . . . . . . . . . .

Very often

Sometimes

Sometimes

Sometimes

Sometimes

Sometimes

Seldom if ever

Often

Sometimes

SOURCE: Office of Technology Assessment, 1992.

PROFESSIONAL CAPACITY

Another issue in considering widespread carrier

screening for CF is whether there are enough

adequately trained health professionals to handle the

volume of tests. One study estimated that a minimumof651,000 counseling hours would be required

annually if the maximum estimate of 6 to 8 million

preconceptional couples are screened for CF carrier

status (19). Considering the current number of

practicing genetic counselors in the United States

today, this translates to 17 weeks per year from each

genetic counselor to serve solely CF-related clients.

On the other hand, another estimate suggests the

supply of genetic specialists could absorb routine

carrier screening for CF sickle cell anemia, hemophilia, and Duchenne muscular dystrophy, assuming

that obstetricians or other primary care physicians

perform the screening on pregnant women, with

referral of those with positive results to genetics

professionals (10).

The counselors and nurses surveyed by OTA

estimate pretest counseling time for CF carrier status

would range from about 45 minutes to over 1 hour,

depending on family history (table 3-13). It is

unclear to what extent increased demand for CF

carrier screening would strain the current system.

Current estimates undercount the number of health

care professionals who practice genetic counseling

and assume that counseling would always be provided in a clinical genetics setting by board-certified

or board-eligible counselors. Such estimates also

ignore the role that aggressive public education can

play in improving pretest knowledge. Improvements

in public education could result in dramatically less

time required in formal counseling, as could reliance

on health professionals not formally trained in

genetics.
Chapter 3-Cystic Fibrosis Carrier Screening: Policies and Practices ● 27

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

Various Conditions

Figure 3-9—Opinions Regarding the Need for

More Genetic Counselors

Time Number

Condition (minutes/visit) visits

Prenatal counseling for advanced

maternal age . . . . . . . . . . . . . . . . . . . . 54

Positive family history for neural tube

defects . . . . . . . . . . . . . . . . . . . . . . . . . 57

Elevated MSAFP screen . . . . . . . . . . . . . 55

Couple with newly diagnosed (Tri21)

Down syndrome child . . . . . . . . . . . . . 78

Couple with 14/21 translocation Down

syndrome child . . . . . . . . . . . . . . . . . . . 73

Carrier testing for Duchenne muscular

dystrophy . . . . . . . . . . . . . . . . . . . . . . . 75

Newly diagnosed case of

neurofibromatosis . . . . . . . , . . . . . 70

Newly diagnosed CF family. . . . . . . . . . . 59

Carrier testing for CF with a positive

family history . . . . . . . . . . . . . . . . . . . . . 70

Carrier testing for CF with a negative

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

SOURCE: Office of Technology Assessment, 1992.

1

1

2

2

2

2

2

2

1

Two-thirds of respondents strongly agreed that a

need for more genetic counselors exists (figure 3-9).

A few respondents raised the possibility of training

‘‘single-gene’ counselors to assist in the increased

workload, although others expressed concern about

this prospect, as taking a family history can reveal

other genetic conditions that might not be detected

by an individual trained to handle one genetic

disorder (18). Still other respondents mentioned the

need for more professional education of health care

providers who might be in the position of administering such tests, and many survey participants noted

that all groups of health care providers should be

involved after appropriate training and education.

Noted one genetic counselor, “Once screening is

close to 100 percent sensitive, doctors and nurses

could easily be trained to provide the necessary

counseling.

When asked what strategies would be considered

to alleviate the projected increase in workload

should widespread CF carrier screening occur, 55

percent gave either no response or reported that they

had not yet developed any. Of those who had

considered or developed strategies, 40 percent said

they would plan professional education activities to

educate other health professionals, 21 percent would

develop videotapes for patient education, 15 percent

said they would conduct public education, and 14

 30- 25

20-

lo0

 Strongly agree Undecided

 Agree Disagree disagree

A need for more genetic counselors exists.

SOURCE: Office of Technology Assessment, 1992.

Table 3-14-Strategies for Implementation of

Widespread Cystic Fibrosis Carrier Screening

Question:What strategies have you considered implementing if

widespread screening for CF becomes a reality?a

Strategy Percent

Plan professional education activities . . . . . . . . . . . . . . . 40

Develop videotapes for patient education . . . . . . . . . . . . 21

Conduct public education . . . . . . . . . . . . . . . . . . . . . . . . . 15

Arrange for group counseling sessions . . . . . . . . . . . . . . 14

Administrative changes in clinics to handle patient load. . 13

a237 of the 43 I respondents gave no response.

SOURCE: Office of Technology Assessment, 1992.

percent reported they would arrange for group

counseling sessions (table 3-14).

ISSUES TO BE ADDRESSED

BEFORE IMPLEMENTATION

When OTA undertook this survey, privately

funded pilot projects were under way, but federally

funded pilot studies to evaluate CF mutation analysis in the general population had not yet begun,

although NIH had begun a grant competition for

such 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 by

Pilot Programs in Cystic Fibrosis Carrier Screening

Rank order

1. Access to genetic counseling

2. Education of the public

3. Payment/cost

4. Sensitivity of the test

5. Protection of confidentiality

6. Quality control and assurance

7. Identification of a target group

8. Availability of reproductive options

SOURCE: Office of Technology Assessment, 1992.

ents what issues they viewed as important before

widespread screening is embraced. Specifically,

survey participants were asked at the conclusion of

the questionnaire to list by priority the important

issues to be addressed by pilot studies in CF carrier

screening.

Interestingly, the sensitivity of the test, which was

often cited as the reason not to proceed with

screening, was ranked fourth (table 3-15). Access to

genetic counseling was listed as the most important

issue to be addressed. But with vast geographic

inequities in availability of genetic services it is not

clear how access could be considered as anything

other than a variable in following pretest and

post-test consumer behavior. Education of the public

was ranked as second in level of importance for

evaluation by pilot programs. Payment and cost

issues were ranked third.

SUMMARY

A majority (53 percent) of genetic counselors and

nurses in genetics do not offer unsolicited CF carrier

screening. They are also unlikely to be providing

genetic counseling and DNA tests to families

followed in CF clinics and have not yet made efforts

to contact CF families seen previously to offer

carrier testing to family members. Those who

advocate CF carrier tests for use beyond affected

families argue that individuals should be routinely

informed about the assays so they can decide for

themselves whether to be voluntarily screened. This

population was a minority (21 percent) of respondents.

If carrier screening is to become routine, 99

percent of respondents believe it should be voluntary, and a majority prefer it be offered to preconceptional adults. Given the clientele found in most

clinical genetics settings, it is likely that CF carrier

screening will be offered as part of family planning

or reproductive health, and the medical specialty

most likely to offer the test will be obstetrics. This

perceived tension over the technology’s control

likely contributes to the opinions of some in the

clinical genetics community that widespread CF

carrier screening is premature until greater genetics

education of professionals is in place. With regard to

CF carrier screening, concern exists that layers of

uncertainty will inhibit informed consent, adequate

pretest education, and post-test counseling and that,

ultimately, more harm than good might be done. Yet

respondents recognize the critical role that could be

played in pretest education by other health care

professionals and some indicated that should the

momentum toward CF carrier screening accelerate,

they would make efforts to increase their public and

professional education activities.

1.

2.

3.

4.

5.

6.

7.

8.

9.

10.

CHAPTER 3 REFERENCES

American Society of Human Genetics, “Statement of

the American Society of Human Genetics on Cystic

Fibrosis Carrier Screening,” personal communication, June 1992.

Biesecker, L., Bowles-Biesecker, B., Collins, F., et

al., “General Population Screening for Cystic Fibrosis Is Premature,” American Journal of Human

Genetics 50:438-439, 1992.

Botk.in, J.R., “Prenatal Screening: Professional Standards and the Limits of Parental Choice,” Obstetrics

and Gynecology 75:875-880, 1990.

Bowling, F., Cleghorn, G., Chester, A., et al.,

“Neonatal Screening for Cystic Fibrosis,” Archives

of Disease in Childhood 63:196-198, 1988.

Brock, D.J., “Cystic Fibrosis,” Antenatal and Neonatal Screening, N.J. Wald (cd.) (New York, NY:

Oxford University Press, 1984).

Caskey, C.’ll, Kaback, M.M., and Beaudet, A.L.,

“T’he American Society of Human Genetics Statement on Cystic Fibrosis,” American Journal of

Human Genetics 46:393, 1990.

Clarke, A., “Is Non-Directive Genetic Counseling

Possible?,” Lancet 338:998-1001, 1991.

Elias, S. E., Annas, G.J., and Simpson, J. L., “Carrier

Screening for Cystic Fibrosis: Implications for Obstetrics and Gynecologic Practice,” American Journal of Obstetrics and Gynecology 164;1077-1083,

1991.

Harper, P. S., and Clarke, A., ‘Viewpoint: Should we

Test Children for ‘Adult’ Genetic Diseases?,” Lancet 335:1205-1206, 1990.

Holtzman, N. A., Proceed With Caution: Predicting

Genetic Risks in the Recombinant DNA Era (Balti-
Chapter 3-Cystic Fibrosis Carrier Screening: Policies and Practices ● 29

11.

12.

13.

14.

15.

more, MD: The Johns Hopkins University Press,

1989).

Kaplan, F., Clew, C., and Scriver, C.R., “Cystic

Fibrosis Carrier Screening by DNA Analysis: A Pilot

Study of Attitudes Among Participants,” American

Journul of Human Genetics 49:240-243, 1991.

Lipkin, M., Fisher, L., Rowley, P.T, et al., “Genetic

Counseling of Asymptomatic Carriers in a Primary

Care Setting,” Annals of Internal Medicine 105:115-

123, 1986.

Imader, S., Sutera, C. J., Walden, M., et al., “Prenatal

Screening for Hemoglobinopathies. II. Evaluation of

Counseling,” American Journal of Human Genetics

48:447451, 1991.

Mischler, E., Farrell, P., Bruns, T., et al., “Progress

Report: Neonatal Screening for Cystic Fibrosis in

Wisconsin,” Wisconsin Medical Journal 88:14-18,

1989.

Modell, B., “Cystic Fibrosis Screening and Community Genetics, “ Journal of Medical Genetics 27:475-

479, 1990.

16.

17.

18.

19.

National Institutes of Health, Workshop on Population Screening for the Cystic Fibrosis Gene, “Statement From the National Institutes of Health Workshop on Population Screening for the Cystic Fibrosis

Gene,” New England Journal of Medicine 323:70-

71, 1990.

Singer, E., “Public Attitudes Toward Genetic Testing, ” in Population Research and Policy Review

10:235-255, 1991.

U.S. Congress, Office of Twhnology Assessment,

Cystic Fibrosis and DNA Tests: Implications of

Carrier Screening, OTA-BA-532 (Washington, DC:

U.S. Government Printing Office, August 1992).

Wilfond, B.S., and Fost, N., “The Cystic Fibrosis

Gene: Medical and Social Implications for Heterozygote Detection,” Journal of the American Medical

Association 263:2777-2783, 1990.
Chapter 4

Summary

For years, experts theorized about confronting the

potential consequences of increased knowledge of

human genetics. In the early 1990s, the cystic

fibrosis CF mutation test moved the debate from

the theoretical to the practical. OTA concludes that

the value of the CF carrier testis the information it

provides. No one can estimate in common terms

what it means to an individual to possess information about his or her genetic status, especially when

the value concerns reproductive decisionmaking. On

a larger scale, the potential for widespread CF carrier

screening raises legal, ethical, economic, and political considerations.

This survey of genetic counselors and nurses

working in genetics, conducted in the summer of

1991, reflects the tensions and concerns surrounding

dissemination of CF mutation analysis. The survey

was conducted to better understand the environment

in which the average genetic counselor or nurse in

genetics works, to describe the infrastructure and

tools available to these professionals, to assess the

state of practice in the provision of CF carrier

screening, and to evaluate their attitudes regarding

CF carrier screening.

I n summer 1991, most genetic counselors and

nurses in genetics did not offer unsolicited CF

carrier screening and expressed concerns about

access to health insurance, quality control, public

education, discrimination, stigmatization, and the

adequacy of trained personnel as reasons why they

did not. They are also unlikely to be providing

genetic counseling and DNA tests to families

followed in CF clinics and have not yet made efforts

to contact CF families seen previously to offer

carrier testing to family members, although agreement exists that such individuals should be offered

CF mutation analysis.

Reasons why survey respondents do not offer CF

mutation analysis are varied, but professional guidelines exert some influence. The 1990 policy statement of the American Society of Human Genetics

(ASHG) stated that CF carrier screening is “NOT

yet the standard of care,” and a majority of survey

respondents were aware of that statement. Several

stated that it alone was the reason for their refusal to

offer CF carrier screening. In mid-1992, after

extended discussion, ASHG’s leadership approved

a revised statement that CF mutation analysis ‘is not

recommended’ for those without a family history of

CF Some argue that the subtle change in language

of the new statement reflects an evolution of debate

within the society-that some believe CF carrier

screening may now be offered to individuals without

a family history of CF although it might not be the

“standard of care. ” Others argue that ASHG’s

position is unchanged. The effect of the new

statement remains to be seen.

Concern about test sensitivity was another barrier

that respondents said should be addressed before

routine CF carrier screening. Two-thirds of participants felt that an optimum frequency of detection

should be reached before they would feel comfortable offering CF carrier screening to the general

population, although nearly a quarter of respondents

were uncertain about whether an optimum was

necessary. Of those who felt there is an optimal

frequency of detection, nearly half felt that 95

percent test sensitivity should be required before

proceeding with widespread CF carrier screening.

Twenty-five percent believed test sensitivity should

be greater than 95 percent, with 4 percent stating that

it should be 100 percent. At the time this survey was

conducted, test sensitivity was approximately 80

percent. It has increased to 85 to 90 percent as of

summer 1992, so opinions might have changed.

Two other factors ranked slightly more important

than test sensitivity as criteria to consider before

implementing routine CF carrier screening: the

availability of adequate counseling and an adequate

system of referral for individuals who test positive.

Genetic counseling can be labor intensive. Survey

respondents indicated that they spend most of their

work week seeing or talking with clients; patient

loads are frequently heavy. Respondents said that,

given the potentially complex or emotional nature of

some genetic information, professionals trained in

human genetics are essential to insure high quality

care and informed consent. Guarantee of informed

consent also was mentioned as necessary for implementation of large-scale carrier screening.

Those who advocate CF carrier tests for use

beyond affected families are no less concerned about

–31–
32 ● Genetic Counseling and Cystic Fibrosis Carrier Screening: Results of a Survey

informed consent and quality of services. Proponents argue that the tests are sensitive enough for

current use and that individuals should be routinely

informed about the assays so they can decide for

themselves whether to be voluntarily screened.

These voices believe that failing to inform patients

now about the availability of CF carrier assays

denies people the opportunity to make personal

choices about their reproductive futures. In this

survey population, however, advocates of routine

CF carrier screening were in the minority.

Perhaps the point on which there was greatest

consensus among respondents is on the issue of

autonomy and choice in screening. There are no

mandatory genetic screening programs of adult

populations in the United States. Ninety-nine percent of survey participants responded that CF carrier

screening should be voluntary and never mandatory.

Given the existing tensions surrounding CF mutation analysis in the general population, who should

serve as gatekeeper of this new technology? Survey

respondents strongly believe that CF carrier screening should be organized by and provided by the

human genetics community. This assumes, however, that large numbers of Americans will learn of

their CF carrier status through interaction with the

genetic services system.

Based on the client populations reported in this

survey, routine CF carrier screening will likely

integrate into medicine in the reproductive context

first. The prenatal population has been the traditional

entry point into genetic services for many people;

OTA’s survey found 70 percent of the genetics

clientele are adults of reproductive age, reinforcing

the notion of prenatal diagnosis as an entry point for

primary genetics service.

Preconceptional individuals are the ideal population for CF carrier screening, according to survey

respondents, but for most individuals the first real

opportunity for carrier screening takes place postconception. Thus, despite survey respondents’ desire that information about the availability of assays

such as CF mutation analysis should come from

genetic specialists, the primary responsibility for

providing CF carrier screening is likely to reside

with obstetricians, at least initially, and especially if

reimbursement for CF mutation analysis and its

attendant counseling become part of routine obstetric care. Such a scenario would mirror that which has

occurred with maternal serum alpha-fetoprotein

screening to detect fetuses with neural tube or

abdominal wall defects or Down syndrome-a

prospect that concerns some, but not others.

OTA’s survey of genetic counselors and nurses

also reports some consumers experience difficulties

in obtaining or retaining health care coverage after

genetic tests, though the large majority were not for

carrier status, but were for genetic illness. Nevertheless, because genetic-based predictive testing promises to have a profound impact on clinical medicineand because access to medical care is inextricably

linked to private health insurance in this country—

such cases underscore certain policy dilemmas

arising from the increased availability of genetic

assays.

Critics of widespread CF carrier screening question whether the present genetic counseling system

in the United States can handle the swell of cases if

CF carrier screening becomes routine. Currently,

about 1,000 master’ s-level genetic counselors practice in the United States, and an additional 100

nurses in genetics provide similar services. OTA’s

survey of genetic counselors and nurses in genetics

indicates that respondents believe routine CF carrier

screening will strain the present genetic services

delivery system. Respondents estimated that, on

average, 1 hour would be needed to obtain a

three-generational family history and to discuss CF

carrier screening and genetic risks.

Skeptics of a personnel shortage assert that

counseling about CF carrier assays is likely to take

place in the general obstetric/prenatal context, however, and believe 1 hour exaggerates the amount of

time that suffices for all prenatal tests, let alone only

CF carrier screening. Furthermore, counseling related to CF carrier screening is likely to extend

beyond genetics professionals to include other

physicians and allied health professionals. For

example, an unknown number of social workers,

psychologists, and other public health professionals

perform genetic counseling, often to minority and

underserved populations.

ultimately, the issue of adequate services and

professional capacity could turn on the extent to

which patients receive genetic services through

specialized clinical settings, as they largely do now,

versus access through primary care, community

health, and public health settings. Overall, OTA

cannot conclude whether increased numbers of

genetic specialists are necessary, but clearly in-
Chapter Summary .33

creased genetics education for all health care professionals is desirable. Routine carrier screening for

CF-and tests yet to be developed for other genetic

conditions-will require adequate training and education of individuals in the broader health care

delivery system. Some survey respondents recognize the critical role other health care professionals

will play in pretest education and indicated that

should the momentum toward CF carrier screening

accelerate, they would make efforts to increase their

public and professional education activities.

Although genetic counselors and nurses in genetics work in a variety of settings, they are concentrated in metropolitan medical centers on the West

coast or in the Northeast. States with large rural

populations are less likely to be served. The clientele

served, in the aggregate, tend to be representative of

the national averages for racial and ethnic populations, although no effort was made by OTA to match

racial and ethnic data with regions, cities, or

localities. This diversity presents great opportunity

in terms of professional and public education, yet

few counselors report an emphasis on these activities in their weekly routine because patient services

comprise two-thirds of their time.

One of the tasks of genetic specialists, however,

is to provide the educational and counseling services

necessary to successful implementation of new

technologies. Diagnostic tools, such as DNA tests,

can provide powerful information. Increasingly,

genetic counselors and nurses working in genetics

will be at the front line on the issues raised by

assimilating DNA technologies into clinical practice.
Appendix A

Survey Method

Data for this survey were collected from 431 survey

questionnaires mailed to 813 individuals in June and July

of 1991. The sample was drawn from the membership list

of the National Society of Genetic Counselors (NSGC)

and the mailing list of the International Society of Nurses

in Genetics (ISONG). Only full members (excluding

student, associate, and foreign memberships) of the

NSGC were surveyed. The initial mailing list provided by

ISONG was screened to remove individuals who were not

practicing nurses from the sample (e.g., journalists,

vendors).

Questionnaires were not numerically or otherwise

coded, and hence were completely anonymous. Respondents were asked to return their questionnaire in a

post-paid envelope provided by OTA. Approximately 2

weeks after the initial mailing, a followup letter was sent

to all survey respondents. The second wave improved the

response rate by about 15 percent.

The content of the instruments was identical for the two

populations, but the questionnaires were reproduced on

different colored stock for easier tracking. Preliminary

analysis revealed no significant difference in question

response between the NSGC and ISONG samples, and so

all data were combined into one set for the final analyses.

Surveys returned after September 30, 1991 were not

included in the final data analyses. A statistical software

package was used to provide frequency distributions and

cross-tabulations of the data. No weighting was done of

the sample, as OTA believes that the sample closely

represents the entire population.

–35–
Appendix B

Survey Instrument

As part of the 1992 assessment Cystic Fibrosis and DNA Tests: Implications of Carrier Screening, OTA surveyed

the summer 1991 memberships of the International Society of Nurses in Genetics and the National Society of Genetic

Counselors. The items for the two questionnaires were identical, and the following is a reproduction of the survey

instrument.

-36--
Appendix B-Survey Instrument 37

Office of Technology Assessment

United States Congress

Washington, D.C. 20510-8025

SURVEY OF GENETIC COUNSELING ATTITUDES AND PRACTICES

REGARDING CYSTIC FIBROSIS SCREENING

Genetic Counselor Demographics

1.

2.

3.

4.

5.

6.

7.

8.

9.

10.

Sex: a. female

Age: years

b. male

Race: a. Asian d.

b. — Black

c. — Caucasian f“ —

Marital status:

a. married

b. — widowed d. —

Hispanic

Native American

Other:

never married

divorced/separated

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

Degrees held:

a. MA/MS - Genetic counseling

b. — RN/BSN

c. — MSN

d. — MPH

MSW

Ph. D.:

M.D.

J.D.

i. —

currently in degree program: (type)

Year granted:

How many years of clinical practice as a genetic counselor do you have?

Certification status (American Board of Medical Genetics)

a. Board certified (CIRCLE Year): 1982, 1984, 1987, 1990

b. — Board eligible

not necessary for position

d: none

Are you fluent in any language other than English?

a. no b. yes, I speak English and (specify other):

Present employment status:

a. full time

b. part time: hours/week

c. — not working
38 ● Genetic Counseling and Cystic Fibrosis Carrier Screening: Results of a Survey

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

applicable.

a.

b. —

:: —

;“ —9. —

h.

i.

j. ~

k.

L —

m.

n. —

o.

p. —

q. —

private hospital/medical facility

university medical center

free standing clinic

Health Maintenance Organization (HMO)

private group practice

solo private practice

private industry (specify type):

State laboratory (specify type):

regional laboratory (specify type):

commercial laboratory

Public Health department (State, county, or city)

State government agency

Federal government agency

voluntary health organization

educational institution (K-12)

higher educational institution (undergraduate or graduate)

other:

12. On average, how many hours a week are you involved in:

a.

b.

d:

f“

g.

h.

i.

direct patient contact (counseling patients)

indirect patient activities (review of literature or records, coordinating referrals)

performing administrative/managerial tasks

educating health professionals, medical students, GC trainees

educating the general public, schools, undergraduates

performing laboratory work

research

marketing/business

other:

13. What sources of information about new advances in the field of human genetics do you rely on?

(check all that apply)

a.

b. —

d: —

f“ —

g. :

h.

i. —

j. —

k.

professional colleagues

medical journals

grand rounds

State or regional conferences

national conferences

American Society of Human Genetics

National Society of Genetic Counselors

continuing education courses

literature from biotechnology/commercial firms

lay press

other:

14. In your current position, how frequently were you asked about DNA testing/screening for CF

during the 6-month period from January - June, 1991? Please consider this in the context of your

total clinical practice.

a. never

b. —

rarely

occasionally

d: frequently

e. —

very frequently
Appendix B-Survey Instrument .39

15. If you were asked about DNA testing/screening for CF please estimate the number of requests per

month (January - June, 1991)? (per month)

16. Compared to 2 years ago, would you say the number of requests made between January - June,

1991 represents:

a. a large decrease

b. —a small decrease

no change

d: —a small increase

e. —a large increase

17. If you noted an increase, when did you note this? (month/year)

18. In your current position are you engaged in providing genetic counseling?

a.

If NO, skip the CLINICAL PRACTICE QUESTIONS and GO TO QUESTION #46

THE NEXT SERIES OF QUESTIONS ARE TO BE ANSWERED BY THOSE

INDIVIDUALS WHO CURRENTLY PROVIDE GENETIC COUNSELING SERVICES

(All others please skip to question #46.)

19. Which best describes the primary service area in which you work?

rural

suburban

metropolitan/urban

statewide

regional (more than one State)

national

other:

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

number).

a.

b.

c.

d.

e.

f.

#

M.D. geneticists

Ph.D. geneticists

M.D./Ph.D. geneticists

genetic counselors

secretaries

other:
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 genetics

pediatric genetics

adult genetics

teratogen exposure

reproductive loss

specialty disease(s)

newborn screening

clinics (please specify):

MSAFP screening follow-up

carrier screening (specify disease):

Does your institution participate in collecting the CORN data set?

a. yes b. no c. don’t know

For each of the following categories, indicate the number (or best estimate) of genetics

clients/patients served in 1990, either DIRECTLY (i.e., counselor to client relationship; one-on-one

genetic counseling) or INDIRECTLY (i.e., involvement such as consultant to primary care physician

regarding a patient, telephone consultation).

TYPE OF PATlENT CONTACT

Direct Indirect Total

All patients seen in 1990

a. by your unit:

b. by you individually:

CF patients/families seen in 1990

c. by your institution:

d. by you individually:

With respect to your clinical practice, estimate the percent (%) of your patients who are:

A. RACE/ETHNICITY Percent (%)

a. Asian/Pacific Islander

b. Black

c. Caucasian

d. Native American

e. Spanish surname

f. unable to estimate

B. AGE DISTRIBUTION

9.

h.

i.

j.

k.

1.

m.

neonatal

infants

children

adolescents

adults - reproductive age

adults - post reproductive age

unable to estimate
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 of

fees for service in each of the following areas? Also, please indicate the average fee amount

charged for each service.

1 =seldom if ever covered; 2 =sometimes covered; 3 = often covered;

4 very often covered; 5=almost a/ways covered; 6=uncertain

a.

b.

c.

d.

e.

f. —

general genetic counseling: Fee $

genetic counseling for cystic fibrosis with positive family history: Fee $

genetic counseling for cystic fibrosis with negative family history: Fee $

routine metabolic screen: Fee $

routine cytogenetic analysis: Fee $

DNA analysis for cystic fibrosis: Fee $
42 ● Genetic Counseling and Cystic Fibrosis Carrier Screening: Results of a Survey

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 insurance

coverage 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 of

your ability, the average NUMBER of patients you see per month, total amount of direct

COUNSELOR TIME spent (in minutes), and the average number of VISITS needed to provide

genetic counseling to individuals and/or families for each of the following scenarios. (Answer for

cases appropriate to your practice.)

a.

b.

c.

d.

e.

f.

g

h.

i.

j+

prenatal counseling for advanced maternal age

positive family history for neural tube defects

concerns for current pregnancy

Elevated MSAFP screen .

Couple with newly diagnosed

(Tri 21) Down’s Syndrome child

Couple with 14/21 translocation

Down’s Syndrome child

Carrier testing for DMD

Newly diagnosed case of neurofibromatosis

Newly diagnosed CF family

Carrier testing for CF

with a positive family history

Carrier testing for CF

with a negative family history

AVG

# visits

31. If you have not been involved with counseling for CF based on your experience, how much direct

counselor time (minutes) would you estimate would be needed to:

a. obtain 3 generational family pedigree: (minutes)

b. discuss carrier testing and recurrence risks: (minutes)

32. How would this estimate compare to the direct patient time spent with your typical

patient load?

a. more time b. less time c. about the same
Appendix B-Survey Instrument . 43

33.

34.

35.

How frequently do you use each of the following formats to provide genetic counseling?

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

a. individual counseling session(s)

b. —group counseling

videotape alone

d: —

videotape with counseling

written educational materials

f“ —

slide-tape

g. interactive computer

Where is the closest CF treatment center to your institution?

a. at my institution

b. —

less than or equal to 50 miles

greater than 50 miles

d: —not aware of one

Do you personally provide genetic counseling through the CF treatment center in your area?

a. no b.

If yes, please provide the following information for 1990.

1) total # new patients seen by the CF center

2) total # return patients seen by the CF center

3) # referrals for genetic counseling

4) # requests for information on DNA testing

5) # undergoing actual DNA testing individuals families

36. Do you or your group/unit have a specific policy regarding DNA testing for CF

a. no, we do not. b. yes; if yes, what is it?

37. Are individuals/families seeking DNA testing for CF asked to sign an informed consent?

a. no b. yes

38. Do you or your group/unit have official policies and procedures for other issues in genetics?

(check all that apply)

a. DNA storage

b. —

prenatal diagnosis for sex selection

non-paternity

d: —confidentiality and Huntington’s disease testing

e. —other:
44 ● Genetic Counseling and Cystic Fibrosis Carrier Screening: Results of a Survey

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

DNA testing for CF

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

a. all patients\families

b. —

pregnant women seeking prenatal diagnosis

couples/individuals with a positive family history for CF

d: — Caucasian couples/individuals with negative family history for CF

f. —

individual/families who inquire about CF

e. —

selected couples/individuals; how selected:

4 0 . Have you made an effort to contact old genetics families as appropriate regarding the availability of CF

testing?

a. yes, by (check all that apply):

1) telephone

2) —

letters/mass mailing

3) —at future visits

4) —

other:

b. no, because (check all that apply):

1) not enough time; too busy

2) —no mechanism for rapid chart retrieval

3) —

requires chart by chart analysis

4) —

plan to do so in future, as time permits

5) —other:

41. During the last 12 months:

a. Have you referred any patients for DNA testing for CF

1) no

2) —

yes: how many individuals: # samples

b. Have you=referred any patients/families for DNA testing for other disorders?

1) no

2j —yes: how many individuals: # samples

If yes,for which conditions:

42. At your institution, is DNA testing for CF

a. performed at onsite/inhouse lab

b. —sent offsite to lab less than or equal to 50 miles away.

c. —sent offsite to lab between 50 miles and 150 miles away

d. sent offsite to lab greater than 150 miles away

43. Type of laboratory used for CF testing:

a. private/commercial

b. — private hospital

university hospital

d: —

regional laboratory

e. —

other:
Appendix B-Survey Instrument . 45

44.

45.

46.

47.

48.

49.

50.

51.

52.

If you are-or have been-involved with CF testing, does the laboratory you use provide

(check all that apply):

a.

b. —

d: —

f“ —

g. 

direct mutation analysis

DNA linkage analysis

DNA haplotyping

staging of studies depending on case

prenatal DNA analysis

fetal intestinal enzyme analysis

DNA banking

For direct mutation analysis of CF what mutations does the laboratory you use include? (Please list or

give number):

THE FOLLOWING QUESTIONS ARE TO BE ANSWERED BY ALL RESPONDENTS

Are you familiar with the following statements concerning CF screening published by:

a. 1990 ASHG ad hoc CF Screening Committee: no — yes

b. 1990 NIH panel: no yes —

if yes to either one of the above how have you incorporated this into clinical practice?

At this time do you think it is appropriate to provide CF screening in cases where family history is

negative?

a. no b. yes c. uncertain

if yes, why?

Do you feel there is a optimum rate of detection at which widespread CF carrier screening should

proceed?

a. yes, specify: % rate of detection

b. — n o

c. — no opinion

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

Professionals”?

a. no b. yes

Have you developed any educational materials relevant to DNA testing specifically for CF

a. no b. yes (Please send a copy.)

Have you been tested for CF carrier status?

a. no b. yes

If you have been tested for CF carrier status, why were you tested?

a. research subject

b. — wanted to know

positive family history

d: —

family planning

e. —

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

53. How was your test covered?

a. by my insurance

b. — professional courtesy

c. —

self pay

d. —

research subject

54. To what extent, if at all, should each of the following groups be involved with educating the public about

DNA testing for CF if it becomes standard practice?

a.

b.

d:

f

g.

h.

j

k.

1=to little or no extent; 2=to some extent; 3=to a moderate extent;

4=to a great extent; 5=to a very great extent; 6=no opinion

primary care providers

public health departments

genetic counselors

genetics programs

nurses

family planning clinics

voluntary support groups

schools

lay press

television

other:

55. If widespread CF carrier screening begins, it should be:

a. mandatory b. voluntary

56. If widespread CF carrier screening begins, what target populations should be screened? (check all that

apply)

a.

b.

c.

d.

e. —

f.

g. —

prenatal

newborns

children ages 2-12

children ages 13-18

adults in reproductive years

adults post reproductive years

pregnant women or “couples”

57. If CF carrier screening is voluntary, who should organize the screening programs? (check all that apply)

a. voluntary health organizations

b. — State or local health department

Federal Government

d: — medical societies

the human genetics community

f“ — primary care givers

g. : others (specify):

58. If CF carrier screening is mandatory, who should organize the screening programs? (check all that apply)

a.

b.

c. —

d.

f“

g. —

voluntary health organizations

State or local health department

Federal Government

medical societies

the human genetics community

primary care givers

others (specify):
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 schools

b. —in public health departments

in organized, community-wide programs

d: —

in the primary care setting i.e., physicians

in genetic centers/programs

f“ —in the workplace

g. —

— other (specify):

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

a.

b. —

c.

d. —

f“ —

self pay by patient

third party payment

employers

State/city or county

Federal government

other (specify):

Do you agree or disagree with the following statements?

1=strongly agree; 2=agree; 3=undecided; 4=disagree; 5=strongly disagree)

a. genetic counseling should precede DNA testing for CF when there is a positive family history.

b. —genetic counseling should precede DNA testing for CF when there is a negative family history.

c. —educational materials (culturally sensitive and understandable) can provide adequate

information about CF screening.

d. a need for more genetic counselors exists.

e. —

informed consent prior to CF screening is a necessity.

In your opinion, what are the important issues that need to be addressed by pilot programs in CF

screening? List in order of priority:

1.

2.

3.

4.

What strategies have you considered implementing if widespread screening for CF becomes a reality?

64. What do you feel the minimum criteria for CF carrier screening should be (protocol)?

Thank YOU very much for your cooperation in answering our Questions! On the back of this survey, please feel

free to give us as any other options, concerns, or suggestions that you feel our questions did not address. These

comments will be anonymous, but may be incorporated in our report to Congress.
Appendix C

Acronyms and Glossary

Acronyms

-/- —negative CF carrier/negative CF carrier

(couple)

+/- —positive CF carrier/negative CF carrier

(couple)

+/+ —positive CF carrier/positive CF carrier

(couple)

ABMG —American Board of Medical Genetics

ASHG —American Society of Human Genetics

BC/BS —Blue Cross and Blue Shield

CF -cystic fibrosis

-cystic fibrosis transmembrane

conductance regulator

DF508 -delta F508 (most prevalent CF mutation)

DF508#i12-delta F508 plus 6 to 12 additional CF

DNA

G542X

G551D

Em40

ISONG

MSAFP

N1303K

NSGC

OTA

R553X

W1282X

mutations

-deoxyribonucleic acid

—a CF mutation

—a CF mutation

—health maintenance organization

—International Society of Nurses in

Genetics

—maternal serum alpha-fetoprotein

—a CF mutation

—National Institutes of Health (NIH)

—National Society of Genetic Counselors

-Office of Technology Assessment

—a CF mutation

—a CF mutation

Glossary of Terms

Allele: Alternative form of a genetic locus (e.g., at a locus

for eye color there might be alleles resulting in blue or

brown eyes); alleles are inherited separately from each

parent.

beta~-thalassemia: An autosomal recessive disorder affecting the red blood cells, resulting in anemia, infections,

growth retardation, and other complications.

~-thalassemia predominantly occurs among individuals of Mediterranean, Middle Eastern, Asian Indian,

Chinese, Southeast Asian, and African descent.

Buccal: Relating to the inside of the cheek. A buccal swab

collects cells that can be analyzed for CF mutations.

Carrier: An individual apparently normal, but possessing a single copy of a recessive gene obscured by a

dominant allele; a heterozygote.

Chest physical therapy (chest PT): A cornerstone of CF

therapy that moves the mucus blocking major air

passages out of the lungs. A specific form of chest PT

is bronchial drainage during which an individual claps

on the chest or back of the patient who is usually lying

on a table.

Chromosome: A threadlike structure that carries genetic

information arranged in a linear sequence. In humans,

it consists of a complex of nucleic acids and proteins.

Confidentiality: A fundamental component of the health

care provider-patient relationship in which the professional has the duty to keep private all that is disclosed

by the patient.

Consanguineous: Related by blood or origin, rather than

by marriage.

Cystic fibrosis CF A life-shortening, autosomal recessive disorder affecting the respiratory, gastrointestinal,

reproductive, and skeletal systems, as well as the sweat

glands. CF is caused by mutations in the CF gene that

affect the CF gene product, cystic fibrosis transmembrane conductance regulator (CFTR). Individuals with

CF possess two mutant CF genes.

Cystic fibrosis carrier: An individual who possesses one

CF mutation and one normal CF gene. CF carriers

manifest no symptoms of the disorder. See carrier.

Cystic fibrosis carrier screening: The performance of

tests on persons for whom no family history of CF

exists to determine whether they have one aberrant CF

gene and one normal CF gene. See cystic fibrosis

screening.

Cystic fibrosis screening: The performance of tests to

diagnose the presence or absence of the actual disorder,

in the absence of medical indications of the disease or

a family history of CF This type of diagnostic

screening usually involves newborns, but rarely for

CF except in Colorado and Wisconsin. See cystic

fibrosis carrier screening.

Cystic fibrosis transmembrane conductance regulator

(CFTR): The CF gene product, which regulates

chloride (Cl-) conductance and might be a Cl- ion

channel, the structure that governs Cl- entry and exit in

the cell. CFTR produced by a mutant CF gene is

frequently impaired, resulting in the medical manifestations of CF in affected individuals.

DF508: A three base pair deletion in the CF gene that

results in a faulty CF gene product (i.e., a flawed

CFTR). This mutation results in the deletion of one

amino acid, phenylalamine, at position number 508 in

CFTR. DF508 is the most common mutant allele

among the greater than 170 identified in the CF gene.

Deoxyribonucleic acid (DNA): The molecule that encodes genetic information. DNA is a double-stranded

helix held together by weak bonds between base pairs

of nucleotides.

4 8 –
Appendix C-Acronyms and Glossary ● 49

Discrimination: Differential treatment or favor with a

prejudiced outlook or action.

Dominant: An allele that exerts its phenotypic effect

when present either in homozygous or heterozygous

form.

DNA: See deoxyribonucleic acid.

DNA analysis: A direct examination of the genetic

material, DNA, to reveal whether a individual has

mutation(s) for CF or other disorders.

DNA probe: Short segment of DNA labeled with a

radioactive or other chemical tag and then used to

detect the presence of a particular DNA sequence

through hybridization to its complementary sequence.

Gene: The fundamental physical and functional unit of

heredity. A gene is an ordered sequence of nucleotide

base pairs to which a specific product or function can

be assigned.

Gene therapy: The deliberate administration of genetic

material into the cells of a patient with the intent of

correcting a specific genetic defect.

Genetic counseling: A clinical service involving educational, informational, and psychosocial elements to

provide an individual (and sometimes his or her

family) with information about heritable conditions.

Genetic counseling is performed by genetics specialists, including physicians, Ph.D. clinical geneticists,

genetic counselors, nurses, and social workers.

Genetic screening: The analysis of samples from asymptomatic individuals with no family history of a

disorder, groups of such individuals, or populations.

Genetic testing: The use of specific assays to determine

the genetic status of individuals already suspected to

be at high risk (e.g., family history or symptoms) for

a particular inherited condition.

Genetics: The study of the patterns of inheritance of

Specific traits.

Genome: AU the genetic material in the chromosomes of

a particular organism; its size is generally given as its

total number of base pairs. The human genome is 3.3

billion base pairs.

Heterozygote: A heterozygous individual, such as a CF

carrier.

Heterozygous: Having two different alleles at a particular

locus.

Homozygote: A homozygous individual.

Homozygous: Having the same alleles at a particular

locus.

Immunoreactive trypsin (IRT) test: An assay that

measures levels of pancreatic trypsin, a digestive

enzyme. As a protocol for newborn CF screening, a

drop of blood is isolated on a card, dried, and

chemically analyzed to detect elevated levels of the

enzyme. It is not intended to be a diagnostic test.

Mutation: Changes in the composition of DNA.

Nucleotide: The unit of DNA consisting of one of four

bases—adenine, guanine, cytosine, or thymineattached to a phosphate-sugar group. The sugar group

is deoxyribose in DNA. In RNA, the sugar group is

ribose, and the base uracil substitutes for thymine.

Probe: A short segment of DNA tagged with a reporter

molecule, such as radioactive phosphorus (32P), used

to detect the presence of that particular complementary

DNA sequence.

Protein: A biological molecule whose structure is

determined by the sequence of nucleotides in DNA.

Proteins are required for the structure, function, and

regulation of cells, tissues, and organs in the body.

Recessive: An allele that exerts its phenotypic effect only

when present in homozygous form, otherwise being

masked by the dominant allele.

Sensitivity: The ability of a test to identify correctly those

who have a disease.

Sickle cell anemia: An autosoma1 recessive disorder

affecting red blood cell flow through the circulatory

system, causing complications in numerous organ

systems. Sickle cell anemia predominantly occurs in

individuals of African descent.

Sickle cell trait: The heterozygous state of sickle cell

anemia; sickle cell carrier status.

Single-gene disorder: Hereditary disorder caused by a

single gene (e.g., cystic fibrosis, Tay-Sachs disease,

sickle cell anemia).

Specificity: The ability of a test to identify correctly those

who do not have the characteristic which is being

tested.

Stigmatization: Branding, marking, or discrediting because of a particular characteristic.

Sweat test: An assay used to confirm CF that measures

levels of sodium Na+

) and chloride (Cl-) ions. These

ions appear in high concentrations in patients with CF

Sweating is induced by running a low electric current

through a pilocarpine-soaked gauze pad on the individual’s arm or back. The amounts of Na+ and Cl- in the

sweat can then be determined to confirm or question a

diagnosis of CF

Tay-Sachs disease: A lethal autosomal recessive disorder affecting the central nervous system which results

in mental retardation and early death. Tay-Sachs

disease predominantly occurs among Jews of Eastern

and Central European descent and populations in the

United States and Canada descended from French

Canadian ancestors.