25928 Federal Register / Vol. 65, No. 87 / Thursday, May 4, 2000 / Notices

The survey instrument is short and

poses minimal burden on the time of

respondents. Estimates of time required

to complete the survey during the pilot

phase range from 7 to 20 minutes. The

annual hour burden calculation assumes

each survey will last 15 minutes,

therefore the total of annualized hourly

costs to participants is estimated to be

$30,040.

John M. Eisenbert,

Director.

[FR Doc. 00–10983 Filed 5–3–00; 8:45 am]

BILLING CODE 4160–90–M

DEPARTMENT OF HEALTH AND

HUMAN SERVICES

Centers for Disease Control And

Prevention

[60Day–00–36]

Proposed Data Collections Submitted

for Public Comment and

Recommendations

In compliance with the requirement

of section 3506 (c)(2)(A) of the

Paperwork Reduction Act of 1995, the

Centers for Disease Control and

Prevention is providing opportunity for

public comment on proposed data

collection projects. To request more

information on the proposed projects or

to obtain a copy of the data collection

plans and instruments, call the CDC

Reports Clearance Officer on (404) 639–

7090.

Comments are invited on: (a) Whether

the proposed collection of information

is necessary for the proper performance

of the functions of the agency, including

whether the information shall have

practical utility; (b) the accuracy of the

agency’s estimate of the burden of the

proposed collection of information; (c)

ways to enhance the quality, utility, and

clarity of the information to be

collected; and (d) ways to minimize the

burden of the collection of information

on respondents, including through the

use of automated collection techniques

for other forms of information

technology. Send comments to Seleda

Perryman, CDC Assistant Reports

Clearance Officer, 1600 Clifton Road,

MS–D24, Atlanta, GA 30333. Written

comments should be received within 60

days of this notice.

Proposed Projects

Youth Risk Behavior Survey—(0920–

0258)—Renewal—National Center for

Chronic Disease Prevention and Health

Promotion (NCCDPHP). The proposed

project is the 2001 national schoolbased Youth Risk Behavior Survey. The

purpose of this request is to renew OMB

clearance to continue an ongoing

biennial survey among high school

students attending regular public,

private, and Catholic schools in grades

9–12. The survey assesses priority heath

risk behaviors related to the major

preventable causes of mortality,

morbidity, and social problems among

both youth and adults in the U.S. OMB

clearance for the 1999 survey expired

January 2000 (OMB No. 0920–0258,

expiration 01/00). Data on the health

risk behaviors of adolescents is the

focus of approximately 40 national

health objectives in Healthy People

2010. The Youth Risk Behavior Survey

provides data to measure at least 10 of

these health objectives and 3 of the 10

Leading Health Indicators. In addition,

the Youth Risk Behavior Survey can

identify racial and ethnic disparities in

health risk behaviors. No other national

source of data measures as many of the

2010 objectives that address behaviors

of adolescents. The data also will have

significant implications for policy and

program development for school health

programs nationwide.

The total estimated cost to student

respondents is $47,250, which is

calculated in terms of their time spent

in responding to the survey and is based

on an assumed minimum wage of $5.25/

hour for the 1999–2000 school year. The

total estimated cost to school

administrators is $5,882 which is

calculated in terms of their time spent

in recruitment and is based on an

assumed average hourly rate of $34.

Thus, the total costs to respondents,

based on the costs of their time, are

$53,132.

Respondents Number of

respondents

Number of

responses

per respondent

Burden per

response

(in hours)

Total burden hours.

High school students ....................................................................................................... 12,000 1 0.75 9,000

School administrators ...................................................................................................... 345 1 0.50 173

Total .......................................................................................................................... 12,345 9,173

Dated: April 28, 2000.

Charles W. Gollmar,

Acting Associate Director for Policy Planning

and Evaluation, Centers for Disease Control

and Prevention.

[FR Doc. 00–11095 Filed 5–3–00; 8:45 am]

BILLING CODE 4163–18–P

DEPARTMENT OF HEALTH AND

HUMAN SERVICES

Centers for Disease Control and

Prevention

Notice of Intent; Genetic Testing Under

the Clinical Laboratory Improvement

Amendments

SUMMARY: The Centers for Disease

Control and Prevention (CDC) acts as a

scientific advisor to the Health Care

Financing Administration (HCFA) in

development of requirements for

clinical laboratories under the Clinical

Laboratory Improvement Amendments

(CLIA). The CDC is issuing this notice

to advise the public that the Department

of Health and Human Services (HHS)

will be preparing a Notice of Proposed

Rule Making (NPRM) to revise the CLIA

regulations applicable to laboratories

performing human genetic testing.

Before issuing the NPRM, comments are

being solicited on the recommendations

of the Clinical Laboratory Improvement

Advisory Committee (CLIAC) to change

current CLIA requirements to

specifically recognize a genetic testing

specialty. This new speciality area will

address unique testing issues in the preanalytic, analytic, and post-analytic

phases of testing that could affect the

accuracy and reliability of test results,

and related issues such as informed

consent, confidentiality, counseling,

and the clinical appropriateness of a

genetic test. To ensure that a full range

of issues relating to this proposed action

are addressed and potential impacts are

identified, comments and suggestions

are invited from all interested parties.

Comments or questions regarding this

proposed action should be directed to

CDC at the address below.

The Department has also established

a Secretary’s Advisory Committee on

Genetic Testing (SACGT) to advise the

Department on the medical, scientific,

ethical, legal, and social issues raised by

the development and use of genetic

Federal Register / Vol. 65, No. 87 / Thursday, May 4, 2000 / Notices 25929

testing. The SACGT is currently

addressing, in consultation with the

public, broad questions related to the

adequacy of oversight of genetic testing.

If, after public consultation and

analysis, SACGT finds that further

oversight measures are warranted, it

will recommend options for such

oversight. The public comment for the

SACGT issues is being conducted

separately (See the December 1, 1999

Federal Register, 64 FR 67273). The

reason for independent solicitations is

that the SACGT is addressing more

general aspects of genetic testing, such

as the criteria that should be used to

assess the benefits and risks of genetic

tests. That purpose differs from this

solicitation that deals specifically with

the application of CLIA to genetic

laboratory testing. The two requests for

public comments thus solicit

complementary information: the SACGT

comments will guide development of

recommendations to the Secretary on

policy and oversight issues, whereas

comments on the CLIAC

recommendations will guide

development of appropriate genetic

testing laboratory requirements for

revision of the CLIA regulations.

DATES: Written comments received by

July 3, 2000, will be incorporated into

the record.

ADDRESSES: Send comments to D. Joe

Boone, Ph.D., Assistant Director for

Science, Division of Laboratory

Systems, Public Health Practice Program

Office, Centers for Disease Control and

Prevention, 4770 Buford Highway., N.E.,

Mailstop G25, Atlanta, Georgia 30341, at

telephone (770) 488–8080.

SUPPLEMENTARY INFORMATION:

Background

A. Human Genetic Testing

Human genetic testing involves the

analysis of chromosomes,

dioxyribonucleic acids (DNA),

ribonucleic acids (RNA), and genes and

gene products (e.g. proteins and

enzymes) to detect heritable or acquired

disease-related disorders or conditions.

Federal and private-sector human

genome projects will soon decipher the

structure for the 100,000 to 140,000

genes residing on the 23 pairs of human

chromosomes. It is expected that along

with this definition of structure will

come associations between the

variations in gene structure and a

variety of conditions and diseases. Once

associations have been delineated, the

use of genetic testing is expected to

expand significantly to determine

whether an individual has a condition

or disease or might develop a condition

or disease in the future.

Human genetic testing is expected to

lead to a whole new era in health care.

Some tests may determine not only

whether an individual has a particular

disease or condition, but also may

determine their risk of developing a

disease or condition in the future.

However, along with the tremendous

potential for improving health and

preventing disease, genetic testing can

also do great harm if errors occur in: (1)

The selection of an appropriate test, (2)

the performance of the test, (3) the

interpretation of the tests results, or (4)

the clinical application of the test

results. False-positive or false-negative

results can be especially troublesome

when the test is being used to predict

future risk of disease in an individual

without any current symptoms of

disease.

The process of performing a genetic

test can be broken into three distinct

phases: (1) The pre-analytic phase,

which encompasses such events as

determining which genetic test, if any,

is appropriate to answer the clinical

question being asked and collecting an

appropriate sample and transporting it

to the test site; (2) the analytical phase,

which involves steps taken to perform

the analysis and analyze the results; and

(3) the post-analytic phase, which

includes reporting and interpretation of

the results. It is important to recognize

that the laboratory may need to be

involved in carrying out or assisting

with all three phases of testing and that

errors can occur either within the

laboratory or at the interface between

the laboratory and the care provider.

In the pre-analytic phase, one recent

study found that 20 percent of

adenomatous polyposis coli (APC)

genetic tests were ordered for

inappropriate indications and 19

percent of patients received genetic

counseling before testing occurred

(Giardiello FM, et al. The use and

interpretation of commercial APC gene

testing for familial adenomatous

polyposis. N Engl J Med 1997;336:823–

827). Another recent survey of 245

molecular genetic testing laboratories

found that 55 percent of the laboratories

did not require informed consent prior

to testing and 31 percent did not have

a written policy on confidentiality

(McGovern MM, et al. Quality assurance

in molecular genetic testing laboratories.

JAMA 1999;835–840). This same study

found what the authors considered to be

substandard laboratory practice, which

could lead to adverse clinical outcomes,

in 15 percent of the laboratories. In the

post-analytic phase of testing, the

Giardiello study reported that 31

percent of the cases were misinterpreted

by the physician. The McGovern study

found that 30 percent of laboratories did

not provide access to genetic

counseling.

These and other studies point to the

need for improvements in laboratory

practice and better coordination

between the care provider, laboratory,

genetic counselor, and the patient to

ensure quality in genetic testing. The

HHS has sought the advice of experts in

laboratory medicine and genetic testing

to help identify places in the testing

process where testing problems are most

likely to occur, and to determine what

modifications to current CLIA

regulations could provide greater

assurance of accurate and reliable

testing. Issues for which the laboratory

might provide additional assistance to

the laboratory user such as informed

consent, counseling, and protecting

confidentiality were also considered.

The recommendations below were

developed during a series of public

meetings of the Clinical Laboratory

Improvement Advisory Committee

(CLIAC).

B. Current Roles of Government and

Professional Organizations in Genetic

Testing

In considering whether to create a

genetic specialty under CLIA and

whether to include the provisions

recommended by the CLIAC, it is

important to understand the current

roles of government and professional

organizations in genetic testing, and to

note that no single agency or

organization is likely to be able to

address all of the issues raised by

genetic testing.

Genetic tests are currently regulated at

the Federal level through three

mechanisms: (1) The Clinical Laboratory

Improvement Amendments (CLIA); (2)

the Federal Food, Drug, and Cosmetic

Act; and (3) during investigational

phases of test development, under

applicable regulations for the Protection

of Human Subjects (45 CFR 46, 21 CFR

50, and 21 CFR 56). In addition, some

States regulate and private-sector

organizations monitor genetic testing

laboratories.

On October 31, 1988, Public Law 100–

578, Clinical Laboratory Improvement

Amendments of 1988 (CLIA), Section

353 of the Public Health Service Act, (42

U.S.C. 263a) was enacted. On February

28, 1992 (57 FR 7002), HHS published

a final rule applicable to all laboratories

that examine human specimens to

provide information for the diagnosis,

prevention, or treatment of any disease

or impairment of, or assessment of the

health of, human beings. (Note:

Facilities that only perform testing for

forensic purposes and research

25930 Federal Register / Vol. 65, No. 87 / Thursday, May 4, 2000 / Notices

laboratories that test human specimens

but do not report patient specific results

are exempt from the CLIA regulations.)

Under CLIA, laboratories are required

to meet specific requirements before

they can become CLIA-certified.

Regulated tests are categorized

according to their level of complexity:

waived, moderate, and high complexity,

with the regulatory requirements

increasing in stringency with the

complexity of the tests performed.

Under CLIA, the Health Care Financing

Administration (HCFA) in partnership

with CDC develops standards for

laboratory certification. The advice of

the HHS Clinical Laboratory

Improvement Advisory Committee

(CLIAC) may also be sought.

Laboratories performing non-waived

tests receive on-site inspections

conducted by HCFA or by designated

organizations or State-operated CLIA

programs.

Overall monitoring includes a

comprehensive evaluation of the

laboratory’s operating environment,

personnel, proficiency testing, quality

control, and quality assurance.

Laboratory directors are required to take

specific actions to establish a

comprehensive ongoing quality

assurance program, which ensures that

the performance of all steps in the

testing process is accurate. Although

laboratories under CLIA are responsible

for all aspects of the testing process

(from specimen collection through

specimen analysis and reporting of the

results), CLIA oversight emphasizes

intralaboratory processes as opposed to

the clinical uses of test results.

All laboratory testing devices, kits and

their components are subject to FDA

oversight under the Federal Food, Drug,

and Cosmetic Act. Testing devices and

tests that are packaged and sold as kits

to multiple laboratories require

premarket approval or clearance by the

FDA. This premarket review involves an

analysis of the device’s accuracy as well

as its analytical sensitivity and

specificity. Premarket review is

performed based on data submitted to

FDA’s scientific reviewers. In addition,

for devices for which the link between

clinical performance and analytical

performance has not been well

established, FDA requires additional

analyses to determine the test’s clinical

characteristics, or its clinical sensitivity

and specificity. In some cases, FDA

requires that the predictive value of the

test be analyzed.

The majority of new genetic tests are

being developed by laboratories for their

own use, that is, in-house tests. The

FDA established a measure of regulation

of in-house tests by instituting controls

over the active ingredients (analytespecific reagents) used by laboratories to

perform tests. This regulation subjects

reagent manufacturers to certain general

controls, such as good manufacturing

practices; however, with few

exceptions, the current regulatory

process does not require a premarket

review of these reagents. The regulation

requires that the sale of reagents be only

to laboratories capable of performing

high-complexity tests and requires that

certain information accompany both the

reagents and the test results. The labels

for the reagents must also state that

‘‘analytical and performance

characteristics are not established.’’

Also, the test results must identify the

laboratory that developed the test and

its performance characteristics and must

include a statement that the test ‘‘has

not been cleared or approved by the

U.S. FDA.’’ In addition, the regulation

prohibits direct marketing of in-house

developed tests to consumers.

Human subjects participating in the

research phase of development of a

genetic test are under the protection of

human research subjects regulations

administered by the National Institutes

of Health (NIH) and the FDA. NIH

oversees the protection of human

research subjects in HHS-funded

research, while the FDA oversees the

protection of human research subjects in

trials of investigational (unapproved)

devices, drugs, or biologics being

developed for eventual commercial use.

Fundamental requirements of these

regulations are that experimental

protocols involving human subjects be

reviewed by an organization’s

Institutional Review Board (IRB) to

assure the safety of the subjects and that

risks do not outweigh potential benefits.

Some State agencies may monitor

laboratories performing genetic testing,

including licensure of personnel and

facilities. In some instances, the State

Public Health Laboratory and Stateoperated CLIA program are responsible

for quality assurance activities. A few

States, such as New York, have

promulgated regulations that go beyond

the requirements of CLIA. States also

administer newborn screening programs

and provide other genetic services

through maternal and child health

programs.

Private-sector organizations, in

partnership with HCFA and CDC may

also develop laboratory and clinical

guidelines and standards. A number of

organizations are involved in helping to

assure the quality of laboratory practices

and in developing clinical practice

guidelines to ensure the appropriate use

of genetic tests. These organizations

include the College of American

Pathologists (CAP), which develops

standards for its membership and

establishes and operates proficiency

testing programs; the NCCLS (formerly

called the National Committee on

Clinical Laboratory Standards), which

develops consensus recommendations

for the standardization of test

methodologies; and the American

College of Medical Genetics (ACMG),

which develops guidelines for the use of

particular tests and test methodologies

and works with the CAP to provide

proficiency tests for certain genetic

tests. Other organizations, such as the

American Academy of Pediatrics,

American College of Obstetrics and

Gynecology, American Society of

Human Genetics, and National Society

of Genetic Counselors, are also involved

in the development of guidelines and

recommendations regarding the

appropriate use of genetic tests.

Presently, no federal agency has

specifically addressed other aspects of

oversight that are critical to the

appropriate use of a genetic test,

including the clinical validity and

clinical utility of a given test. Also not

addressed are other important issues

such as informed consent and genetic

counseling.

C. Proposed Changes to CLIA Laboratory

Regulations

Currently, CLIA has very specific

requirements for certification of

laboratories in areas such as cytology,

microbiology, and clinical cytogenetics;

a specialty category of genetics does not

currently exist even though genetic

testing is covered under the general

provisions of CLIA. If a genetics

specialty category is created, genetic

testing will need to be defined (see

definitions under question 1).

Recommendations of Clinical

Laboratory Improvement Advisory

Committee (CLIAC)

On September 11, 1997, January 29,

1998, May 28–29, 1998, September 17–

18, 1998, and September 22–23, 1999

the CLIAC met to develop

recommendations on how the CLIA

regulation might be modified to address

genetic testing. Summary accounts of

the meetings at which these

recommendations were developed can

be found at the CDC website at http://

www.phppo.cdc.gov/dls/cliac/

default.asp. The CLIAC’s deliberations

provide definitions for laboratories

performing genetic testing; address

issues in the pre-analytic, analytic, and

post-analytic phases of testing; and

describe how a laboratory’s

responsibilities and those of the care

Federal Register / Vol. 65, No. 87 / Thursday, May 4, 2000 / Notices 25931

provider, genetics counselor, and

individual being tested are related.

While these recommendations were

developed by experts in the field of

genetics and laboratory aspects of

genetic testing, we are interested in

determining the impact of imposing the

specific requirements recommended by

CLIAC on the wide spectrum services

offered by the nation’s 170,000 clinical

laboratories. We are interested in

determining which, if any, of these

recommendations might prove

problematic to low volume laboratories,

which may be the only source of a

specific genetic test. Finally, we are

interested in receiving comments about

whether implementing these

recommendations would increase,

decrease, or have no effect on the

quality of, access to, or cost of genetic

testing services.

Please note that genetic testing

laboratories are already subject to the

current personnel, quality assurance,

quality control, and patient test

management provisions of CLIA (42

CFR Part 493). Also note that the

recommendations have been divided

into topics which apply globally to all

phases of genetic testing, and those

specific to the pre-analytic, analytic,

and post-analytic phases of testing.

While this Notice of Intent requests

comments on a range of laboratory

issues related to potential regulation of

genetic testing recommended by the

CLIAC, the Department has not yet

determined whether the scope of CLIA

will allow regulation of all of these

issues.

CLIA Questions on Which Comment Is

Being Solicited

The CLIAC has made

recommendations on the issues listed

below. We are interested in receiving

comments on the following questions

which arise when considering the

adoption of these recommendations

under the regulatory provisions of CLIA.

General Requirements

Note: These issues apply to more than one

phase of the testing process.

1. Are the Following Definitions for

Categories of Genetic Testing To Be

Covered Under a New CLIA Specialty of

Genetics Appropriate (or Too Broad or

Too Restrictive)?

A. Current CLIA Requirement: A

specialty of genetic testing has not been

defined under CLIA. However, CLIA

already applies to genetic testing since

it regulates any laboratory that examines

human specimens to provide

information for diagnosis, prevention, or

treatment of any disease or impairment

of, or assessment of the health of,

human beings.

B. CLIAC Recommendation: The

CLIAC suggested that the following

definitions for the specialty of genetic

testing be adopted.

Molecular genetic and cytogenetic

test—An analysis performed on human

DNA, RNA, and chromosomes to detect

heritable or acquired disease-related

genotypes, mutations, phenotypes, or

karyotypes for clinical purposes. Such

purposes would include predicting risk

of disease, identifying carriers, and

establishing prenatal or clinical

diagnoses or prognoses in individuals,

families, or populations.

Biochemical genetic test—The

analysis of human proteins and certain

metabolites, which is predominantly

used to detect inborn errors of

metabolism, heritable genotypes, or

mutations for clinical purposes. Such

purposes would include predicting risk

of disease, identifying carriers, and

establishing prenatal or clinical

diagnoses or prognoses in individuals,

families, or populations. [Tests that are

used primarily for other purposes, but

may contribute to diagnosing a genetic

disease (e.g. blood smear, certain serum

chemistries), would not be covered by

this definition.]

C. Issue: A genetic speciality will be

linked to specific personnel

qualifications and responsibility

requirements, as well as proficiency

testing and quality control provisions

(see other recommendations which

could also be implemented under the

specialty). Therefore, inclusion or

exclusion from the specialty could alter

a laboratory’s staffing plans,

reimbursements, and overall costs.

2. What Is the Role of a Laboratory

Director in Documenting the Clinical

Validity of a Genetic Test Their

Laboratory Plans To Offer? If There is a

Role, How Should the Laboratory

Director’s Documentation of the Clinical

Validity of a Genetic Test Be Monitored?

A. Current CLIA Requirement: Under

493.1407 Standard; Laboratory director

responsibilities, (e) the laboratory

director must ensure that testing

systems developed and used for each of

the tests performed in the laboratory

provide quality laboratory services for

all aspects of test performance, which

includes the pre-analytic, analytic, and

post-analytic phases of testing, ensure

that the test methodologies selected

have the capability of providing the

quality of results required for patient

care, and ensure that verification

procedures used are adequate. Under

493.1213 Standard; establishment and

verification of method performance

specifications, prior to reporting patient

test results the laboratory must verify or

establish for each method, the

performance specifications for:

accuracy; precision; analytical

sensitivity and specificity, if applicable;

the reportable range of patient test

results; the reference range; and any

other applicable performance

characteristics.

B. CLIAC Recommendation: Although

the CLIAC considered the scope of the

current laboratory director

responsibilities to be adequate, they

were concerned about how to monitor

the laboratory director’s documentation

of the clinical validity for the tests

performed. The CLIAC recommended

adding specific requirements for

analytical and clinical validation of tests

(see question 7 below).

C. Issue: Although there are specific

requirements for analytic validation, no

specific requirements for clinical

validation have been included under

CLIA. Clinical validation of all tests,

such as cholesterol, has been assumed

to have been documented before tests

are offered. Concerns about requiring

specific documentation of the clinical

validity of genetic tests have been

expressed, with some expressing the

view that establishing the clinical

validity and documenting it for the tests

offered are outside of the laboratory’s

purview.

3. Who Should Be Authorized To Order

a Genetic Test?

A. Current CLIA Requirement: Under

493.1105 Standard; Test requisition—

the laboratory must perform tests only at

the written or electronic request of an

authorized person.

Note: Under 493.2 Definitions—An

authorized person means an individual

authorized under State law to order tests or

receive results, or both.

B. CLIAC Concern: The CLIAC raised

the issue that some States provide no

guidance on this issue.

C. Issue: Is genetic testing sufficiently

different from other types of laboratory

testing to warrant a new Federal

requirement to define who is authorized

to order a genetic test?

4. Should the Laboratory Be Required

to Document That Informed Consent

Has Been Obtained by an Authorized

Person From the Person Being Tested

Before Performing Certain Genetic Tests

or Types of Tests (Screening, Diagnostic,

Carrier, Presymptomatic,

Susceptibility)?

A. Current CLIA Requirement: CLIA,

at present, does not specifically require

a laboratory to document that an

informed consent has been obtained by

25932 Federal Register / Vol. 65, No. 87 / Thursday, May 4, 2000 / Notices

an authorized person before testing is

performed.

B. CLIAC Recommendation: The

CLIAC recommended the following

guidance on this issue.

• Because of the sensitive nature of

certain genetic tests, the laboratory must

have assurance that the ‘‘authorized’’

person has obtained informed consent.

• At the request of the ‘‘authorized’’

person, the laboratory shall assist in

developing appropriate informed

consent for the particular test, including

the limitations and consequences of the

test results.

Note: The National Bioethics Advisory

Commission in its August 1999 report on

‘‘Research Involving Human Biological

Materials: Ethical Issues and Policy

Guidance’’ provides guidance to research

laboratories, which are exempt from CLIA if

they do not report patient specific results.

These recommendations do not apply to

clinical interventions, quality control, or

teaching, but only to ‘‘a systematic

investigation designed to develop or

contribute to generalizable knowledge.’’

C. Issue: Imposition of this

requirement on laboratories could serve

to protect patients from inappropriate

testing, but increases the laboratory

burden of documentation and could also

delay obtaining genetic testing results.

Are the CLIA regulations an appropriate

place for regulating informed consent

related to genetic testing? Also, how do

current State medical consent laws

factor into this?

5. Should Additional Processes Be in

Place to Enhance the Confidentiality of

Certain Genetic Test Information and

Results?

A. Current CLIA Requirement: Under

493.1109 Standard; Test report, (a)—the

laboratory must have adequate systems

in place to report results in a timely,

accurate, reliable, and confidential

manner, and, ensure patient

confidentiality throughout those parts of

the testing process that are under the

laboratory’s control.

B. CLIAC recommendation: The

CLIAC recommended the following

guidance on this issue.

• Due to the sensitive nature of

certain genetic test results, the

laboratory must have a policy in place

to protect the confidentiality of test

result reporting.

• All requests for additional tests

must follow confidentiality and

informed consent requirements (see

above).

Note: HHS under the Health Insurance and

Portability and Accountability Act (HIPAA)

published in the Federal Register on

November 3, 1999 a proposed rule Standards

for Privacy of Individually Identifiable

Health Information. This rule applies to

individually-identifiable health information

that has been electronically transmitted or

maintained. The NPRM is accessible at

(http://www.aspe.hhs.gov/admnsimp/).

C. Potential implication of the CLIAC

issue: This would not impose an

additional requirement on laboratories,

but would clarify that a policy must be

in place for the genetic specialty. Is

being this explicit for genetic testing

necessary?

6. Assuming That a Genetic Specialty

Under CLIA Is Defined and Recognized,

Should a Laboratory Covered Under

This Specialty Be Required To Provide

Genetic Counseling to Their Clients

(Including Medical Care Providers and

Patients), for the Tests They Offer?

A. Current CLIA Requirement: Under

493.1419/493.1457 Standard; Clinical

Consultant responsibilities—

laboratories are required to have a

qualified clinical consultant to provide

consultation regarding the

appropriateness of the testing ordered

and interpretation of test results. The

consultant must be available to provide

consultation and to assist in ensuring

that appropriate tests are ordered to

meet clinical expectations, and ensure

that reports of test results include

pertinent information required for

specific patient interpretation, and that

matters related to the quality of test

results are communicated.

B. CLIAC Recommendation: The

CLIAC recommended that the

qualifications and responsibilities of the

clinical consultant be expanded to

assure that someone associated with the

laboratory be capable of providing

genetic counseling to the laboratory’s

clients (care providers, patients,

individuals, etc.).

Clinical Consultant—Be an M.D.,

D.O., and have two years experience in

genetic testing.; or hold a Ph.D. in a

relevant discipline, be Board certified,

and have two years experience in

genetic testing; or hold an MS in

Genetic Counseling, be Board certified,

and have two years experience in

genetic testing (prospective).

Clinical Consultant—For genetic

testing, require that the Clinical

Consultant assist clients in ordering

appropriate tests to meet clinical needs.

C. Issues: Will there be a sufficient

number of qualified clinical consultants

available and is the experience

mentioned necessary for all types of

genetic tests? Will care providers

request/accept assistance in ordering

genetic tests? What should the role of

the laboratory be in counseling

providers and/or patients. Does it

extend to family members?

Requirements Related to Specific Phases

of the Testing Process

These issues apply to one phase of the

testing process.

7. Should the Following Requirements

Be Added Under a Specialty of Genetics

to CLIA To Address Unique Aspects of

Laboratory Responsibility for Genetic

Testing?

Pre-Analytic Phase

Obtaining Clinical Information on the

Test Requisition and the Ordering of

Additional Tests

A. Current CLIA Requirement: Under

493.1419/493.1457; Standard; Clinical

Consultant responsibilities—

laboratories are required to have a

qualified clinical consultant to provide

consultation regarding the

appropriateness of the testing ordered

and interpretation of test results. The

consultant must be available to provide

consultation and to assist in ensuring

that appropriate tests are ordered to

meet clinical expectations, and ensure

that reports of test results include

pertinent information required for

specific patient interpretation, and that

matters related to the quality of test

results are communicated. Also under

493.1105, Standard; Test Requisition,

(f)—the laboratory must assure that the

requisition or test authorization

includes any additional information

relevant and necessary to a specific test

to assure accurate and timely testing

and reporting.

B. CLIAC recommendation: Test

Requisition and ordering additional

tests:

• Appropriate clinical information to

ensure accurate and reliable genetic

testing must be provided with the test

request.

Note: In some instances very explicit

information may be required to decide which

test method to use and to appropriately

interpret the results. Such information would

include all that is relevant and necessary to

ensure accurate and timely testing,

interpretation and reporting of results and

elements to ensure proper identification of

the subject being tested. Relevant information

for a genetic test may include date of birth,

gender, ethnicity, and/or family history)

• When deemed necessary, the

laboratory shall assist those ordering

tests by suggesting follow-up tests,

when appropriate, to expedite the

function of obtaining relevant clinical

information.

Re-Use of Tested Specimens.

• When patient identifiers are not

removed from the specimens, informed

consent must be obtained prior to re-use

of previously tested specimens for

quality control (QC) and quality

assurance (QA) purposes.

Federal Register / Vol. 65, No. 87 / Thursday, May 4, 2000 / Notices 25933

• When the laboratory intends to reuse previously tested specimens

without patient identifiers for QC and

QA, it must have a procedure that

permits patients with a personal

objection to other uses of their specimen

to be able to elect not to have their

specimen used for these purposes.

• The use of a retained sample does

not require informed consent if all

identifiers are removed and the patient

has had an opportunity to decline being

tested.

C. Issue. The laboratory may require

additional patient information in order

to make decisions about which specific

tests or additional tests would be most

useful to provide the needed clinical

information. However, this information

may be difficult to obtain in every

instance. With respect to additional

testing, coverage or payment for testing

may be an issue. The conditions under

which testing specimen may be re-used

for quality control is generally accepted

as good laboratory practice, but not

explicitly provided for under current

requirements.

Analytic Phase

Personnel Qualifications

A. Current CLIA Requirement: Under

Subpart M—Personnel for High

Complexity Testing:

Laboratory Director—Be an M.D. or

D.O. or DPM with certification in

clinical and/or anatomic pathology; or

be a Ph.D. and be certified by a board

approved by HHS; or be an M.D. or D.O.

and have two years directing or

supervising high complexity testing; or

hold a doctorate degree in a chemical,

physical, biological, or clinical

laboratory science, be certified, and

have two years of supervisory

experience in high complexity testing;

or be grandfathered.

Technical Supervisor—Although no

genetic specialty currently exists, the

following technical supervisor

requirements apply to the specialty of

cytogenetics.—Be an M.D., D.O. or DPM

with four years of training or experience

in genetics, two of which have been in

clinical cytogenetics; of Ph.D. with four

years of training or experience in

genetics, two of which have been in

clinical cytogenetics.

General Supervisor—Be qualified as a

laboratory director or technical

supervisor; or be an M.D., D.O., DPM, or

have a Doctorate, Masters or

Baccalaureate degree in a chemical,

physical, biological or clinical

laboratory science, and have one year

training or experience in high

complexity testing; or have an Associate

degree, or equivalent, in a chemical,

physical, biological or clinical

laboratory science and have two years

training or experience in high

complexity testing; or be grandfathered.

Clinical Consultant—Be qualified as a

laboratory director or be an M.D., D.O.,

DPM and licensed to practice medicine

in the State in which the laboratory is

located.

B. CLIAC recommendation: To the

current requirements listed above, add

the following:

Laboratory Director—Be an M.D. or

D.O. or DPM with certification in

clinical and/or anatomic pathology; or

be an M.D., D.O., or Ph.D. and be

certified in medical genetics by a board

approved by HHS; or be an M.D. or D.O.

and have two years directing or

supervising high complexity testing; or

hold a doctorate degree in a chemical,

physical, biological, or clinical

laboratory science, be certified, and

have two years of supervisory

experience in high complexity testing;

or be grandfathered

If a genetic specialty is developed, the

CLIAC recommended the following

personnel qualifications.

Technical Supervisor—Be an M.D. or

D.O. with certification in clinical and/

or anatomic pathology plus two years

sub-specialty training in genetics and

have two years supervisory experience

in high complexity genetic testing, or

have four years supervisory experience

in high complexity genetic testing in the

relevant subspecialty; or be an M.D.,

D.O. or Ph.D. and be certified in the

appropriate medical genetics specialty

and have two years experience directing

or supervising high complexity genetic

testing in the relevant subspecialty; or

hold a doctorate degree in a chemical,

physical, biological, or clinical

laboratory science, and have four years

of training or supervisory experience in

high complexity genetic testing in the

relevant subspecialty; or be

grandfathered.

General Supervisor—Be qualified as a

laboratory director or technical

supervisor; or be an M.D., D.O., hold a

Doctorate or Masters degree in a

chemical, physical, biological or clinical

laboratory science, and have two years

experience in high complexity genetic

testing; or hold a Baccalaureate degree

in a chemical, physical, biological or

clinical laboratory science and have

three years experience in high

complexity genetic testing; or be

grandfathered.

Clinical Consultant—Be an M.D.,

D.O., and have two years experience in

genetic testing.; or hold a Ph.D. in a

relevant discipline, be Board certified,

and have two years experience in

genetic testing; or hold an MS in

Genetic Counseling, be Board certified,

and have two years experience in

genetic testing (prospective).

C. Issue: Could assure higher quality

in genetic testing, but could restrict who

could serve in these personnel

categories. The extent of the impact is

dependent upon the tests included in

the definition of the genetic specialty.

Personnel Responsibilities

A. Current CLIA Requirements: See

Subpart M of 42 CFR Part 493.

B. CLIAC Recommendations. To the

current requirements, add the following:

Technical Supervisor—The Technical

Supervisor (in addition to the

Laboratory Director and Clinical

Consultant currently required under

CLIA) must ensure that reports include

pertinent information required for

clinical interpretation that is meaningful

to a non-geneticist health care provider.

Clinical Consultant—For genetic

testing, require that the Clinical

Consultant assist clients in ordering

appropriate tests to meet clinical needs.

C. Issue: Could assure higher quality

in genetic testing, but could be difficult

for all laboratories to acquire the

personnel with the skills needed.

Quality Control and Patient Test

Management

A. Current CLIA Requirement. Under

493.1105 Standard; Test requisition and

493.1107 Standard; Test records a

laboratory must ensure that the

requisition or test records include

patient’s name or unique identifier and

laboratory number; date of collection

and receipt in the laboratory. Under

493.1213 Standard; establishment and

verification of method performance

specifications, prior to reporting patient

test results the laboratory must verify or

establish for each method, the

performance specifications for:

accuracy; precision; analytical

sensitivity and specificity, if applicable;

the reportable range of patient test

results; the reference range; and any

other applicable performance

characteristics.

B. CLIAC Recommendation. The

CLIAC recommended that the following

new provisions be added:

Quality Control/Contamination

• A specimen should be stabilized

until the clinical information for

accurate testing is available.

• The laboratory must be designed to

minimize contamination.

• Amplification procedures which are

not in wholly closed systems must have

separation between preparative and

post-amplification steps.

• Work processes must minimize risk

of mixing samples, and risk of

25934 Federal Register / Vol. 65, No. 87 / Thursday, May 4, 2000 / Notices

contamination of equipment, reagents,

and/or supplies.

• RNA work areas must be separated

from DNA work areas.

Specimen Integrity

• Requirements to ensure

identification of the subject being

testing include: date of birth; gender;

ethnicity; patient or family number;

specimen source; time of collection; and

name of person obtaining sample

Validation of Tests

Analytic validation:

• Laboratories must verify or

establish reproducibility for each

method within and between runs, and

between technologists.

• Methodology must be appropriate

for conditions being evaluated.

• Quality control parameters must be

applicable.

• Reagents must be validated.

Clinical Validation: Laboratories must

consider the following clinical

parameters for test validation:

• A positive confirmatory test must

have a defined positive predictive value

which can be communicated to the care

giver.

• Where the disease prevalence is

more frequent than 1/10,000, the

validity must be documented in at least

10 positive probands (including cell

lines or DNA/RNA) prior to offering the

test.

• Predictive value should be defined

in terms of ethnic populations, when

applicable

C. Issue: These recommendations are

based on what the CLIAC considers to

be good laboratory practice in genetic

testing. They represent extensions to

existing requirements to specifically

address some of the unique aspects of

genetic testing. Are these sufficiently

comprehensive, adequate, or are they

not needed?

Proficiency Testing (PT)

A. Current CLIA Requirement: Under

493.801 Condition; Enrollment and

testing of samples—a laboratory must

enroll in an approved proficiency

testing program for each specialty for

which it seeks certification. Currently,

no PT requirement exists, because there

is no genetic specialty, therefore the

following PT requirement applies.

Under 493.1703 Standard; Comparison

of test results—when a laboratory

performs tests for which PT is

unavailable, the laboratory must have a

system for verifying the accuracy and

reliability of its test results at least twice

a year.

B. CLIAC Recommendation: The

CLIAC recommended including the

following new provision:

• When an approved PT program

does not exist for the test, the

regulations should require alternatives

(to be performed three times per year,

on five specimens per event). Examples

include: Split samples sent to another

laboratory; blinded test samples; test

samples in duplicate by separate

technologists, in a blinded manner; and

other equivalent approaches

C. Issue: Requiring PT would provide

a basis for evaluating the accuracy of

genetic testing.

Post-Analytic Phase

Special Reporting Requirements

A. Current CLIA Requirement: Under

493.1109 Standard; Test report—a

laboratory must, upon request, make

available to clients a list of test methods

and information that may affect the

interpretation of test results, such as

interferences.

B. CLIAC Recommendation:

Laboratory reports must include the

following, as applicable, as they relate

to the interpretation of the test result:

—Interpretation.

—Comments.

—Recommendations for further

testing or clinical consultation.

—Summary of the test method and its

limitations.

• When individual interpretation of

the test result is required, the signature

of the Director or designee must appear

on the report.

• A means to quickly contact the

Laboratory Director/Technical

Supervisor, in addition to address, must

be indicated on the report.

• Any reference to family members in

a test report must utilize standardized

pedigree nomenclature or numeric

indicators, instead of individual names.

• Specific requirements for reporting

molecular genetic testing include:

—A list of the mutant alleles tested.

—The rate detection of the panel.

— A revised assessment of likelihood

based on test results, as applicable.

—Important clinical implications for

other family members should be

provided, as applicable.

—Variables that affect test

interpretation (e.g. ethnicity) must be

specified in the report, and limitations

of the testing must be defined.

C. Issue: Requiring laboratories to

provide this information could increase

the accuracy of interpretation of genetic

testing reports, but may increase the

laboratories’ burden.

Record/Specimen Retention

A. Current CLIA Requirement: Under

493.1109 Standard; Test report—the

laboratory must retain the original or an

exact duplicate of each test report for a

period of at least two years after the date

of reporting.

B. CLIAC Recommendation:

• Copies of patient reports of genetic

testing shall be retrievable for a

minimum of 10 years, or longer if

required by State law. Electronic reports

are acceptable.

• The laboratory must have a policy

defining specimen retention policies.

C. Issue: Maintaining reports for a

longer period of time may be beneficial

but this could be burdensome.

Dated: April 27, 2000.

Jeffrey Koplan,

Director, Centers for Disease Control and

Prevention.

[FR Doc. 00–11093 Filed 5–3–00; 8:45 am]

BILLING CODE 4163–18–P

DEPARTMENT OF HEALTH AND

HUMAN SERVICES

Centers for Disease Control and

Prevention

[Program Announcement 00107]

Population-Based Surveillance of

Autism Spectrum Disorders and Other

Developmental Disabilities; Notice of

Availability of Funds

A. Purpose

The Centers for Disease Control and

Prevention (CDC) announces the

availability of fiscal year (FY) 2000

funds for a cooperative agreement

program for Population-Based

Surveillance of Autism Spectrum

Disorders and other Developmental

Disabilities. CDC is committed to

achieving the health promotion and

disease prevention objectives of

‘‘Healthy People 2010.’’ This

announcement is related to the focus

area of Maternal, Infant and Child

Health. http://www.health.gov/

healthypeople.

The purpose of the program is to:

Enhance an existing system or develop

and implement a new system to

undertake a multiple source

surveillance methodology, from existing

data records, for determining the

prevalence of autism and other

developmental disabilities, such as

mental retardation, cerebral palsy, and

vision and hearing impairments, in 3–10

year-old children within a

geographically-defined area

(combination of States, Statewide, or

regions within a State).

B. Eligible Applicants

Assistance will be provided only to

the health departments of States or their