Federal Register / Vol. 62, No. 20 / Thursday, January 30, 1997 / Notices 4539

prevailing costs, which exist currently;

Frequency: Annually; Affected Public:

Not-for-profit institutions; Number of

Respondents: 11,300; Total Annual

Responses: 11,300; Total Annual Hours:

6385.

To obtain copies of the supporting

statement for the proposed paperwork

collections referenced above, or to

obtain the supporting statement and any

related forms, E-mail your request,

including your address and phone

number, to Paperwork@hcfa.gov, or call

the Reports Clearance Office on (410)

786–1326. Written comments and

recommendations for the proposed

information collections must be mailed

within 30 days of this notice directly to

the HCFA Paperwork Clearance Officer

designated at the following address:

OMB Human Resources and Housing

Branch, Attention: Allison Eydt, New

Executive Office Building, Room 10235,

Washington, DC 20503.

Dated: January 23, 1997.

Edwin J. Glatzel,

Director, Management Analysis and Planning

Staff, Office of Financial and Human

Resources, Health Care Financing

Administration.

[FR Doc. 97–2277 Filed 1–29–97; 8:45 am]

BILLING CODE 4120–03–P

Health Resources and Services

Administration

Program Announcement for a

Cooperative Agreement To Initiate an

Interdisciplinary Center for

Community-Based Learning

The Health Resources and Services

Administration (HRSA) announces the

awarding of a sole source cooperative

agreement to the Association of

Academic Health Centers to plan for

and implement an Interdisciplinary

Center for Community-Based Learning.

This activity will be supported under

the authority of Title III, Section 301, of

the Public Health Service Act. A

proposed three-year period of support

beginning in fiscal year 1997 is

anticipated with approximately

$100,000 per year.

The project will (1) strengthen and

institutionalize the academic health

centers commitment to interdisciplinary

community-based learning, particularly

in under served community settings, (2)

provide expertise to academic health

centers in regard to model

interdisciplinary community-based

curricula and training sites, and (3)

support an interdisciplinary network of

health care professionals working to

create and strengthen an

interdisciplinary community-based

curriculum.

The Association of Academic Health

Centers was chosen because it is the

recognized professional association

representing academic health centers,

with a mission that ‘‘seeks to explore

and study issues that relate to greater

coordination of health-related schools

and programs, both within and among

institutions, interdisciplinary and

multiprofessional concerns.’’

It also has previously established

relationships with several

multiprofessional groups and

associations which are actively

developing an agenda for

interdisciplinary community-based

learning and have ready access to

information regarding all

interdisciplinary community-based

training programs at academic health

centers in the country.

Federal Involvement

The Cooperative Agreement

mechanism is being used for this project

to allow for substantial Federal

programmatic involvement with the

planning, development, administration,

and evaluation of the Interdisciplinary

Center for Community-Based Learning.

Requests for Additional Information

Requests for additional information

regarding this sole source cooperative

agreement should be directed to: Sue

Hassmiller, Ph.D., R.N., Bureau of

Health Professions, Room 8–05, Health

Resources and Services Administration,

5600 Fishers Lane, Rockville, Maryland

20857, Telephone: (301)443–6700, Fax:

(301)443–2111, Email:

shassmiller@hrsa.dhhs.gov

Dated: January 23, 1997.

Ciro V. Sumaya,

Administrator.

[FR Doc. 97–2292 Filed 1–29–97; 8:45 am]

BILLING CODE 4160–15–P

National Institutes of Health

Proposed Recommendations of the

Task Force on Genetic Testing; Notice

of Meeting and Request for Comment

AGENCY: National Institutes of Health,

HHS.

ACTION: Notice.

SUMMARY: The Task Force on Genetic

Testing was created by the National

Institutes of Health (NIH)-Department of

Energy (DOE) Working Group on

Ethical, Legal, and Social Implications

of Human Genome Research to make

recommendations to ensure the

development of safe and effective

genetic tests, their delivery in

laboratories of assured quality, and their

appropriate use by health care providers

and consumers. The Task Force

reviewed genetic testing in the United

States, promulgated interim principles

consonant with its goals (‘‘Interim

Principles’’, available at http://

ww2.med.jhu.edu/tfgtelsi), and has

taken public comments into

consideration in revising them. Over the

past eight months the Task Force has

discussed policies to implement several

of its principles. It now submits

proposed recommendations for public

comment. These proposed

recommendations are available at http:/

/ww2.med.jhu.edu/tfgtelsi.

DATES: To assure consideration by the

Task Force, comments must be received

on or before March 10. The Task Force

will meet on March 17 from 8:00 a.m.

to recess and on March 18 from 8:00

a.m. to adjournment at approximately

12:00 noon. The meeting will take place

at the Doubletree Inn at the Colonnade,

4 West University Parkway, Baltimore,

Maryland, (410) 235–5400. Time

permitting, guests will have the

opportunity to speak on comments

already submitted, but no formal time is

being set aside. A final report, including

the principles and recommendations,

together with background information

and comments, will be issued shortly

after the meeting.

ADDRESSES: Written comments should

be sent to Neil A. Holtzman,

M.D.,M.P.H., Genetics and Public Policy

Studies, The Johns Hopkins Medical

Institutions, 550 N. Broadway, Suite

511, Baltimore MD, 21205–2004, faxed

to Dr. Holtzman at 410–955–0241, or emailed to tfgta@welchlink.welch.jhu.edu. Individuals

who plan to attend the March 17–18

meeting and need special assistance,

such as sign language interpretation or

other reasonable accommodations,

should contact Dr. Holtzman in advance

of the meeting.

Background

Scientific breakthroughs have greatly

accelerated the discovery of genes

which, when altered by mutation, result

in disease or in increased risk of

disease. When these mutations occur in

the germline (sperm or egg), they can be

passed from one generation to the next.

These basic research discoveries lead

readily to the development of tests for

inherited mutations. The number of

DNA-based genetic tests and the volume

of testing are increasing steadily. This

has been accomplished in part by the

work of the new biotechnology industry.
4540 Federal Register / Vol. 62, No. 20 / Thursday, January 30, 1997 / Notices

Aware of the potential for harm as

well as benefits, the National Center for

Human Genome Research (NCHGR/NIH)

set aside from its inception a portion of

its appropriation for consideration of

ethical, legal, and social implications of

human genome research. As part of its

joint program with NCHGR, the

Department of Energy (DOE) also set

aside a portion of its appropriation. This

initiative to anticipate problems in order

to maximize benefits and prevent or

minimize harm, of which the Task Force

on Genetic Testing is one activity, is

unprecedented in the development and

application of new biomedical

technologies. The principles and

recommendations of the Task Force

represent an attempt to build on

successes and prevent problems of the

past and present from continuing in the

future. Some past and present problems

will be described in the final report of

the Task Force.

For the most part, genetic testing in

the United States has developed

successfully, providing more options for

avoiding, preventing, and treating

inherited disorders. This success is

largely the result of testing being

undertaken in genetic centers or in

consultation with geneticists and

genetic counselors. In the next few

years, the use of genetic testing is likely

to expand rapidly while the number of

genetic specialists will remain

essentially unchanged. This means that

a greater burden for making genetic

testing decisions will fall on providers

who have had little formal training or

experience in genetics. The problems

they will encounter in providing genetic

tests are seldom encountered in other

areas of medicine.

• Much of medical practice and

medical testing is provided for people

who are already ill. Genetic testing will

increasingly be used to predict risks of

future disease in healthy people. Telling

healthy people about future risks can

heighten uncertainty and cause

psychological distress.

• For many other disorders,

interventions are available to cure,

prevent or ameliorate the condition.

This is not the situation for many

disorders for which genetic testing is

possible. Positive results of some tests

confront patients with difficult

reproductive decisions. These are

personal decisions that should not be

unduly influenced by providers or

society.

• Few other tests provide information

on the risk of future disease to healthy

relatives of the person being tested.

Providers have little guidance in

communicating genetic risks to relatives

and, simultaneously, keeping results

confidential.

• Differences in the frequency of

disease-related mutations among ethnic

groups can influence the

appropriateness of providing some

genetic tests, and heighten concern

about discrimination and stigmatization.

In addition, the predictions made by

genetic tests are not always certain and

often no independent test is available to

confirm the prediction. Test uncertainty

is not unique to genetic tests. However,

the psychological and physical effects of

testing are often greater for imperfect

genetic tests when no treatment is

available or when interventions of

unproven efficacy are life-long or

irreversible.

Key Principles

The Task Force enumerated

principles to address many of the

problems raised by predictive genetic

tests. Its proposed recommendations are

an effort to implement several of these

principles, highlighted below:

Validity and Utility of Genetic Tests

• Before a genetic test can be

generally accepted in clinical practice,

data must be collected to demonstrate

the benefits and risks that accrue from

both positive and negative results. The

primary responsibility for data

collection falls on test developers. For

many tests, however, data collection

must continue after tests are introduced

into practice.

• Protocols for the clinical validation

of genetic tests must receive the

approval of an institutional review

board (IRB). At present, IRBs have the

principal responsibility for the

protection of subjects participating in

validation studies. The Task Force is

concerned that current limitations of

IRBs might impair review of genetic

testing protocols.

Laboratory Quality and Certification

• A national accreditation program

for laboratories performing genetic tests,

which includes on-site inspection and

proficiency testing, is needed to

promote standardization across the

country. Although most laboratories

providing clinical laboratory tests are

certified under the Clinical Laboratory

Improvement Amendments (CLIA) of

1988, current regulations do not

adequately ensure the quality of genetic

testing. Professional organizations have

developed more appropriate quality

assessment of genetic tests than is

required under CLIA, but laboratories

performing genetic tests are not required

to use these voluntary accreditation

mechanisms.

Professional Competence in Genetics

• Health care professionals involved

in the provision of genetic tests should

be well-informed about their

implications, benefits and risks.

Students preparing for careers in health

care and current health care providers

themselves are not being taught enough

about human genetics and genetic

testing. Consequently, not all providers

in practice today may have adequate

competence to offer and interpret

genetic tests. Related problems are the

lack of standards for formal assessment

of new genetic testing technologies and

the limited impact of current efforts to

establish clinical guidelines for when

and how genetic tests should be offered.

Rare Genetic Diseases

• The development and maintenance

of tests for rare genetic diseases must be

encouraged. At a time when genetic

tests for common complex disorders are

increasing, tests for rare disorders may

be developed at a slower rate than in the

past. Some that have been available may

be more difficult or impossible to

obtain. Many physicians do not have

access to the best available information

and resources to identify and manage

rare diseases, or know where to turn for

help.

Informed Consent and Confidentiality

• Informed consent for a validation

study must be obtained whenever the

specimen can be linked to the subject

from whom it came. When specimen

identifiers are retained in either coded

or uncoded form, the opportunity exists

of being able to contact subjects even if

the intent of the original protocol is not

to do so.

• Health care providers must describe

the features of the genetic test, including

potential consequences, to potential test

recipients prior to the initiation of

predictive testing in clinical practice.

Individuals considering genetic testing

should be told the purposes of the test,

the chance it will give a correct

prediction, the implications of test

results and the options, and the benefits

and risks of the process. The

responsibility for providing information

to the individual lies with the referring

provider, not with the laboratory

performing the test.

• It is unacceptable to coerce or

intimidate individuals or families

regarding their decision about genetic

testing. Respect for personal autonomy

is paramount. People being offered

testing must understand that testing is

voluntary. Whatever decision they

make, their care should not be

jeopardized. Information on risks and
Federal Register / Vol. 62, No. 20 / Thursday, January 30, 1997 / Notices 4541

benefits must be presented fully and

objectively. A non-directive approach is

of the utmost importance when

reproductive decisions are a

consequence of testing or when the

safety and effectiveness of interventions

following a positive test result have not

been established. Obtaining written

informed consent helps to assure that

the person agrees to testing voluntarily.

• Results should be released only to

those individuals to whom the test

recipient has consented or subsequently

requested in writing. Means of

transmitting information should be

chosen to minimize the likelihood that

results will become available to

unauthorized persons or organizations.

Under no circumstances should results

be provided to any outside parties,

including employers, insurers,

government agencies, without the test

recipient’s written consent. Unless

potential test recipients can be assured

that the results will not fall into

unauthorized hands, some will refuse

testing for fear of losing insurance or

employment.

• Health care providers have an

obligation to the person being tested not

to inform other family members without

the permission of the person tested

except in extreme circumstances.

Disclosure by providers to other family

members is appropriate only when the

person tested refuses to communicate

information despite reasonable attempts

to persuade him or her to do so, and

when failure to give that information

has a high probability of resulting in

irreversible or fatal harm to the relative.

When test results have serious

implications for relatives, it is

incumbent on providers to explain to

people who are tested why they should

communicate the information to their

relatives.

Recommendations

A Genetics Advisory Committee

The Task Force joins the NIH–DOE

Joint Committee to Evaluate Ethical,

Legal, and Social Implications Program

of the Human Genome Project in

recommending that the Secretary of

Health and Human Services (HHS)

create, in the Office of the Secretary, a

federally chartered Advisory Committee

on Genetics and Public Policy (hereafter

the Advisory Committee) whose

members should include the

stakeholders in genetic testing. The

Secretary should establish formal

liaison between the Advisory

Committee and an already-established

HHS interagency group considering

policies of the Department relevant to

the development and provision of

genetic tests. In addition to assisting the

Advisory Committee, this interagency

group should develop coordinated and

consistent genetic testing policies in the

Department. The two committees whose

creation is recommended later in this

document, one to advise the Food and

Drug Administration (FDA) on assuring

the validity and utility of new genetic

tests, the other to advise the Clinical

Laboratory Improvement Advisory

Committee on assuring the quality of

laboratories performing genetic tests,

should report to the Advisory

Committee through the interagency

group.

Need for Interim Action

The Task Force recognizes that the

formation of the Advisory Committee

could take some time. It is also aware

that organizations have on occasion

developed and offered genetic tests

without always collecting data on test

validity and utility and without external

review. Consequently, the public is not

being adequately protected.

The Task Force recommends that the

Secretary of HHS use existing agencies

and policies to ensure that the public

will have adequate protection from

predictive genetic tests that have not

been adequately validated and whose

clinical utility has not been established.

It suggests two possibilities:

(1) FDA uses its acknowledged authority

under the Medical Device Amendments of

1976 (21 USC 321–392) to the Food, Drug,

and Cosmetic Act (21 USC 301–392), to

ensure that all organizations developing new,

predictive genetic tests submit protocols to

an institutional review board (IRB).

(2) The Health Care Financing

Administration (HCFA) establish policies

under Medicare and Medicaid to reimburse

for certain genetic tests (see below) only

when they are performed in laboratories that

can provide evidence that (a) the test has

been clinically validated (based on published

information or information provided by the

test developer) or that it is participating in a

systematic validation plan, and (b) they are

qualified to provide such tests (see below,

Laboratory Quality). Once HCFA adopts such

policies it is likely that other third-party

payers will quickly follow.

The Task Force makes a similar

recommendation to the Department of

Defense for reimbursement under the

Civilian Health and Medical Program

Uniform Services (CHAMPUS).

The need for stringent scrutiny of

certain predictive genetic tests. The

Task Force has sought to find ways to

identify tests that are more likely to

pose significant risks in their

developmental stage and when they

enter clinical practice. It recognizes that

existing resources for scrutinizing tests

are limited. Consequently, the Task

Force has attempted to identify

characteristics of tests and diseases that

raise the greatest concern and can be

used to prioritize tests for stringent

scrutiny. These characteristics include,

but are not necessarily limited to:

• A test’s potential for predicting

serious future disease in healthy people

(or their offspring). Even if a test

developer’s intended use of the test may

not be for predictive purposes, the

potential for such use, as is the case for

DNA-based genetic tests, increases the

level of scrutiny needed. The absence of

a confirmatory test heightens the

scrutiny a test needs.

• Test uncertainty. When only

healthy people with positive test results

will develop the disease and when all

people with positive results will

develop it, less scrutiny is needed than

when these conditions are not fulfilled.

• The safety and effectiveness of

clinical interventions in those with

positive test results of predictive tests.

Unless the safety and effectiveness of

clinical interventions for those with

positive test results have been

established, people who test positive

cannot be confident that interventions

will prevent the disease or improve its

outcome if it does occur.

Other characteristics that might play a

role in prioritizing are: the frequency of

occurrence of the disorder(s) detected

by the test under review, the use of the

test for population screening, whether

the disorder(s) detected occur more

frequently in some ethnic groups than

others, and whether the reliability of the

test under routine clinical laboratory

conditions has been established.

There are several junctures at which

these characteristics should be applied

to specific tests. The first occurs in the

review of protocols for investigating the

validity and utility of new tests.

Subjects participating in trials or pilot

programs to establish validity and

utility must be adequately protected,

particularly when they will be notified

of the results or simply when personal

identifiers will be retained with the

specimens. The protocol must have

sufficient scientific merit to justify the

participation of subjects. The

characteristics provided above could be

used by IRBs as a checklist to make sure

that the protocol addresses important

issues in test development. For instance,

if applicants fail to present data on test

uncertainty, they should be required to

supply that information or, if it is

unavailable, to collect the requisite data.

A grading system could be devised so

that protocols exceeding a certain score

would be designated as requiring

‘‘stringent scrutiny.’’ Alternatively, the

characteristics can be layered in an
4542 Federal Register / Vol. 62, No. 20 / Thursday, January 30, 1997 / Notices

algorithm or decision tree. (See Figure)

For instance, if a test has the potential

to predict future disease and there is no

confirmatory test, the next step in

deciding whether it needed stringent

scrutiny would be the extent of test

uncertainty. If this was unknown, data

collection would be needed. Once data

were collected, the next question is the

safety and effectiveness of interventions

in those with positive results. If the

benefit:risk ratio of intervention is high

and test uncertainty is low, the test

would not require close scrutiny. Even

if test uncertainty is low, close scrutiny

would be needed if the safety and

effectiveness of interventions had not

been established.

BILLING CODE 4140–01–P
Federal Register / Vol. 62, No. 20 / Thursday, January 30, 1997 / Notices 4543

BILLING CODE 4140–01–C
4544 Federal Register / Vol. 62, No. 20 / Thursday, January 30, 1997 / Notices

The second juncture occurs when a

test developer believes the test is

appropriate for clinical use. Review by

an organization independent of the

developer is needed to ensure that the

public will benefit from the test. The

Task Force is concerned that the

number of tests might overwhelm

external review processes and

needlessly delay the availability of tests

of potential benefit. To reduce the

likelihood of backlogs, the criteria

should be used to set priorities for

stringent scrutiny. Tests of low priority

would enter clinical practice without

scrutiny but could be considered again

at the third juncture.

The third juncture occurs when the

test is clinically available and there are

concerns that (1) it will not be used

when it is indicated, (2) it will be used

for inappropriate indication(s), or (3)

that more data on validity and utility are

needed. The same set of criteria can be

used to set priorities for post-marketing

surveillance requirements and

establishing guidelines for test use.

The Task Force recognizes that as

information and experience is gained,

the scrutiny a test needs is likely to

diminish. As further scientific and

technical advances occur, other criteria

may become more important and other

types of tests may then need stringent

scrutiny.

Assuring the Validity and Utility of New

Genetic Tests

The Task Force is concerned that the

high workload of IRBs, their variability

in community representation, in

evaluating protocols, and in expertise

germane to the review of genetic tests,

as well as the conflicts of interest that

can arise in local review, impairs

current review of genetic tests that

warrant stringent scrutiny. The Task

Force urges the Office of Protection of

Human Subjects from Research Risks,

with input from the proposed Advisory

Committee, to address these problems.

The Task Force is also concerned that

organizations that do not use federal

funds for the research and development

of genetic tests that will be marketed as

services may not seek outside review

from an independent IRB. The Task

Force is also concerned that data needed

after tests enter clinical practice may not

be collected.

The Task Force urges the proposed

Advisory Committee to recommend to

the Secretary the creation of a National

Genetics Board (NGB) whose goal would

be to assure the protection of human

subjects in the development of genetic

tests with the potential to predict future

disease. NGB members should be

broadly representative of stakeholders

in genetic testing, including but not

limited to test developers

(manufacturers and clinical

laboratories), consumers, professional

societies, health care providers, and

insurers. Some of its members must be

scientists capable of reviewing scientific

protocols. The Board should have its

own staff.

NGB would develop a checklist that

would enable local IRBs to identify

protocols that meet criteria for stringent

scrutiny. NGB would function along the

lines of one of the following models,

each of which each has advantages and

disadvantages. The Task Force did not

reach consensus on which model NGB

should follow. The Task Force is

especially interested in public

comments on the alternatives.

(1) NGB reviews all protocols

requiring stringent scrutiny. This

assures that expert assessment with

broad input will be consistently

obtained and conflicts of interest will be

minimized. However, if local IRBs also

review protocols before or after they are

sent to the NGB, funding or activation

of the protocols could be delayed. NGB

approval would be required before

federal funds are awarded. NGB should

also be available to review protocols

from commercial organizations

developing genetic tests without federal

funds.

(2) NGB has the discretion to choose

which protocols among those in need of

stringent scrutiny it will review. Those

protocols which NGB elects not to

review will be sent back to the local IRB

for review. Based on its selective

review, NGB will issue advisories to

local IRBs to assist them in the review

of similar protocols. Under this model,

the advantages of the first model are

reduced, but so is NGB’s work load;

local IRBs retain greater authority.

Delays are likely as protocols move

between local IRBs and NGB.

Under both model (1) and (2), local

IRBs could also request NGB review of

other genetic testing protocols. Based on

its available resources and backlog, NGB

could decide whether or not to review

these protocols. NGB could also assume

responsibility for the primary review for

the protection of human subjects of

multi-center and other collaborative

studies for the validation of genetic

tests.

(3) NGB focuses on generic policy

issues and sets general guidelines for

review. It is available for consultation

and advice, but has no mandatory

review function. Protocols that a local

IRB believes raises novel and

problematic issues could be sent to NGB

for analysis and comment. The

advantages and disadvantages of this

approach are similar to those described

for the second model; the likelihood of

consistent review is further reduced, but

as review is entirely the responsibility

of the local IRBs, delays are less likely.

Role of FDA. The Task Force

recognizes that developers of genetic

tests who do not rely on federal funds

are under no legal obligation to submit

protocols to the proposed NGB and have

not always obtained IRB approval for

validation protocols of tests they plan to

market as laboratory services. If tests

requiring stringent scrutiny were

regulated by FDA, even if they were to

be marketed as services, then under

existing regulations (21 CFR part 56),

protocols for clinical validation would

have to be submitted to an IRB

regardless of whether they came from

federally-funded organizations or not.

Although the FDA acknowledges its

authority under the Medical Device

Amendments to regulate genetic tests

marketed as services, it has chosen not

to do so. (Under the CLIA, clinical

laboratories must demonstrate analytical

validity of their tests but there is no

statutory or regulatory requirement for

them to establish the clinical validity or

utility of clinical laboratory tests.)

The Task Force recommends that

FDA:

(1) Establish a Genetics Advisory

Panel under the Medical Devices

Amendments (21 USC 321–392) which

would advise FDA on: (a) Strategies for

prioritizing genetic tests; (b) the

scientific, ethical, and social merits of

applications FDA receives for marketing

genetic tests; and (c) other matters

germane to genetic testing. In carrying

out its first function, this panel could

consult with the proposed NGB if it is

established, but it should not delay

formulating its strategies until that time.

(2) Adopt a strategy to prioritize

predictive genetic tests according to the

degree of scrutiny they need.

(3) Publicize the requirements it

develops for tests requiring stringent

scrutiny.

(4) Require that new genetic tests

meeting criteria for stringent scrutiny be

regulated under the Medical Device

Amendments (21 USC 321–392; 21 CFR

parts 200 et seq.) regardless of whether

their sponsor’s intention is to market

them as services or as kits.

Although a majority of the Task Force

supported all of these

recommendations, a consensus was not

reached on the fourth. The Task Force

is especially interested in public

comments on this recommendation.

Data collection. The data needed to

definitively establish the validity and

utility of a genetic test may take so long

to collect that if test developers could
Federal Register / Vol. 62, No. 20 / Thursday, January 30, 1997 / Notices 4545

not market their tests they would be

deterred from developing them. Data

collection is also a problem for rare

genetic diseases for which data from

several sources will have to be collected

to establish the validity and utility of

testing. Without a formal plan and

procedure for prospective data

collection, data will undoubtedly be lost

and the time to reach definitive

conclusions will be prolonged.

The Centers for Disease Control and

Prevention (CDC), in cooperation with

NCHGR, should expand the monitoring

of genetic disorders in order to provide

data on the validity of tests and post-test

interventions. It should establish

procedures for tracking healthy

individuals with positive test results, as

well as those diagnosed with inherited

disorders, to learn more about (1) test

validity, (2) the natural history of such

disorders, and the (3) safety and

effectiveness of interventions. The

collection of this data should be

undertaken in cooperation with local

providers and consultants in genetics

and other relevant specialties. At all

times the confidentiality of the data

collected must be protected.

For tests for which long periods of

data collection are needed, FDA should

grant conditional premarket clearance or

approval before all necessary data are

collected to make promising new

technologies available to the public and

enable test developers to obtain an

adequate return on their investment in

test development. Developers would be

responsible for continuing to collect

data as in the premarket phase and

make it available to FDA. When

sufficient data are collected, FDA will

decide whether or not to grant

unconditional approval. Conditional

premarket approval should be granted to

tests when FDA considers it likely that

the test will prove to make an important

contribution to the prevention or

management of the disorder. Under this

circumstance, third-party payers,

including government programs such as

Medicare, Medicaid, and CHAMPUS,

should reimburse for the test once it has

been conditionally approved. Managed

care organizations should also cover

tests given conditional approval.

Technology assessment. Many tests

currently on the market have not been

systematically validated nor subject to

external review. New tests that go

through these processes will be

modified under clinical conditions.

Technology assessment is important

to guide providers and consumers in the

use of genetic tests, but is unlikely to be

undertaken by existing technology

assessment agencies because genetic

tests do not entail huge expenditures of

health care dollars. NGB should serve as

a clearinghouse for technology

assessments of genetic tests that are

about to enter, or already are used in,

clinical practice. It could secure and

coordinate assessments of those

technologies it considers in need of

stringent scrutiny and coordinate

assessments to avoid unnecessary

duplication. NGB could also make

recommendations on appropriate use of

genetic tests with input from relevant

professional societies as well as

consumer groups.

Assuring Laboratory Quality

The Task Force is concerned about

the lack of Federal law or regulation

covering genetic tests except for

cytogenetic tests, limitations of existing

voluntary quality assurance and

proficiency testing programs,

inadequate assessment of the pre-and

post-analytic phases of testing, and the

absence of public information about

laboratories satisfactorily performing

genetic tests under existing voluntary

assessments.

CLIA has no standards specific to

genetic tests except for cytogenetics.

Currently New York State requires

certification of all laboratories

performing clinical genetic tests on state

residents. The College of American

Pathologists/American College of

Medical Genetics’’ (CAP/ACMG)

Molecular Pathology accreditation

program is also designed to assess

performance on the special problems of

genetic tests, placing greater emphasis

on the pre-and post-analytic phases of

testing than other programs. However,

CLIA-certified laboratories performing

genetic tests are not required to be

assessed by the CAP/ACMG program. If

they are not, genetic tests could be

accredited under CLIA without being

specifically assessed. Furthermore,

laboratories that participate in CAP/

ACMG’s Molecular Pathology program

do so voluntarily and not under CAP’s

regulatory (‘‘deemed’’) authority under

CLIA. (Under CLIA, HCFA has the

authority to grant deemed status

equivalence to an outside organization

that has a quality assurance and

proficiency testing survey program with

standards equal to or greater than

CLIA’s. CAP’s general proficiency

testing program has been ‘‘deemed’’

equivalent by HCFA.) As CLIA has not

established standards specifically for

genetic tests, it has no authority to

approve the CAP/ACMG Molecular

Pathology program.

Differences between state law and

Federal laws and regulations (and

among different nations), create

overlapping and often duplicative

requirements for laboratories. The Task

Force recommends that a national

accreditation program of quality

assurance and proficiency testing for

genetic tests equivalent to or more

stringent than those of New York State

and CAP/ACMG, should be established

under CLIA. This accreditation program

should include proficiency testing and

inspection of laboratories performing

genetic tests. Quality assurance

includes: (a) The skill and training of

laboratory staff; (b) evidence of

successful execution of the complex

techniques involved in genetic testing to

produce a correct and verifiable test

result; and (c) assessment of pre-testing

and post-analytic phases of testing.

Until such time as a national

accreditation program is established

under CLIA, the CAP/ACMG Molecular

Pathology program, expanded to

encompass all methods currently in use

in genetic testing, might itself serve as

the national program, and should be

accessible to any laboratory providing

clinical genetic testing. When a national

program is established the CAP/ACMG

Molecular Pathology program should

have deemed status.

The Task Force recommends the

establishment of a Genetics Advisory

Committee to the Clinical Laboratory

Improvement Advisory Committee

(CLIAC) to help address the deficiencies

of CLIA in assuring the quality of

genetic tests. The work of this genetics

committee should be reported to the

Advisory Committee on Genetics and

Public Policy through the interagency

group previously discussed. The work

of the proposed CLIAC advisory

committee should also be coordinated

with other HCFA programs, as well as

FDA, CDC, and other Federal agencies

involved setting genetic testing policies.

Pre-test education and post-test

counseling components of clinical

laboratory tests are critically important

parts of the laboratory test to physicians

who are not generally well informed

about genetic tests. Preanalytic

components include the information

about the test that laboratories make

available to providers and consumers

and the informed consent documents

and processes that laboratories may

require. Postanalytic components

include the information (interpretation)

given with the test result and counseling

services provided or arranged by

laboratories. In any quality assurance

program, closer scrutiny is needed of

pre-and post-test analytic components

of genetic testing than current

assessment programs provide. The Task

Force recommends that CAP/ACMG

seek advice and input from consumer

groups such as the Alliance of Genetic
4546 Federal Register / Vol. 62, No. 20 / Thursday, January 30, 1997 / Notices

Support Groups, as well as from the

National Society of Genetic Counselors

(NSGC), on standards for the quality of

pre-and post-analytic components of

genetic testing.

The Task Force recommends that

CAP/ACMG periodically publish, and

make available to the public, a list of

laboratories performing genetic tests

satisfactorily under its voluntary

program. The Task Force recognizes that

CAP is not currently required to

publish, and has not published, the

names of laboratories performing

satisfactorily in the CAP/ACMG

voluntary Molecular Pathology program.

Until such time as a program is

established under CLIA, publication

will enable providers and consumers to

select approved laboratories and will

also serve as an incentive for

laboratories to participate in the CAP/

ACMG quality assessment program.

This information should be

disseminated using the Internet and

other media accessible to consumers

and providers.

Managed care organizations and other

third-party payers should limit

reimbursement for genetic tests to the

laboratories on the published list of

those satisfactorily performing genetic

tests. Implementation of this

recommendation will be especially

important as more managed care

organizations move to restrict access to

laboratory services for their members to

a single contracted laboratory (which

may or may not be on the list of

qualified laboratories).

The Task Force recommends that

efforts should be made to harmonize

international laboratory standards to

assure the highest possible laboratory

quality for genetic tests. At present, no

mechanism exists to create international

standards of laboratory quality and

proficiency for genetic tests. Current

United States regulations require any

foreign laboratories performing clinical

laboratory tests on U.S. residents to hold

a CLIA certificate even if their nation’s

laboratory standards are more stringent

that those of CLIA (e.g., as is the case

with Canada).

Provider Competence

The Task Force wants to ensure that

non-geneticist providers adequately

appreciate many of the general issues

that should be considered and discussed

in offering, providing, and interpreting

predictive genetic tests. These issues

include: (1) Who should be offered a

specific test; (2) the benefits and risks of

each test; (3) the need for, and the

content of informed consent, and how

consent should be administered; (4) an

explanation of test results; and (5)

familiarity with genetic counseling

strategies and principles. A provider’s

need for knowledge is particularly keen

when tests are in transition from

research to clinical use and when

clinical utility is still under

investigation and there are no

established practice guidelines.

The Task Force endorses the recent

establishment of a National Coalition for

Health Professional Education in

Genetics by the American Medical

Association, the American Nurses

Association, and the NCHGR. The

Coalition should work in consultation

with its member organizations,

including non-genetics professional

societies, to encourage the development

of core curricula in genetics, with an

emphasis on having individual

professional organizations determine

their own needs in the design and

execution of the programs. It should

also encourage input by consumers in

the development of these curricula. The

Coalition should serve as a registry of,

and clearinghouse for, information

about various curricula and educational

programs, grants, and training pilot

programs in genetics education. By

providing educational resources, it

should encourage professional societies

to track the effectiveness of their

respective educational programs. The

Coalition should disseminate

information on available programs in

order to avoid inefficient duplication.

The Task Force strongly recommends

that board examinations used for

physician and specialty certification

increase both the quality and the

quantity of questions related to genetics.

This should further stimulate the

teaching of genetics to medical students,

as well as residents in many specialties.

The scores on these questions should

serve as feedback to improve curricula.

Ultimately, implementation of these

first two recommendations will improve

the provision of care. The remaining

recommendations are directed at shortterm needs.

For those specialties which both

require periodic passage of an

examination for recertification and

whose practitioners are likely to order

predictive genetic tests, examinations

for recertification should include

questions on medical genetics and

genetic testing, including predictive

testing.

Hospitals and managed care

organizations should use credentialing

and other mechanisms (such as prior

authorization) to limit the offering of

certain predictive genetic tests to

genetic health care professionals and

physicians who have demonstrated their

competence in dealing with the issues

enumerated above. Successful

completion of continuing education

courses could be required to

demonstrate competence. (The National

Coalition for Health Professional

Education in Genetics should be able to

provide information on available

programs for learning about the relevant

issues.)

Predictive genetic tests requiring

stringent scrutiny, as previously

described, should be among those for

which special credentials are needed.

As professional experience is gained

with tests for certain disorders, special

credentialing may no longer be required,

but other new genetic tests may take

their place. Third-party payers could

also establish policies that allow only

properly credentialed providers to be

reimbursed for their role in providing

tests.

The Task Force is of the opinion that

primary care providers and other nongeneticist specialists can and should be

involved in genetic testing. However,

they must first gain sufficient familiarity

with the issues involved. In some cases,

providers should work closely with

genetic health care professionals who

can serve as experienced repositories of

in-depth information about many

aspects of genetic testing. Several

laboratories already require this

collaboration. In this rapidly changing

field, providers should maintain their

knowledge of genetics throughout their

professional lives.

Credentialing bodies such as the Joint

Commission on Accreditation of

Healthcare Organizations (JCAHO) and

the National Committee for Quality

Assurance (NCQA) should assure that

hospitals and other health care

organizations develop continuous

quality improvement programs focusing

on genetic testing. Systematic and

periodic medical record review, with

feedback to providers, is one means of

assuring appropriate use of genetic tests.

Such review should assess the extent to

which providers’ records for frequentlyordered predictive genetic tests are in

accord with per-determined criteria.

These criteria should include, but not be

limited to, appropriate indications for

offering the test, offering the test when

it is indicated, and documentation of:

informed consent when appropriate, the

test result, information given to the

patient, and the patient’s response.

Mechanisms should be in place to

assure that review procedures will not

infringe on the confidentiality of the

medical records.

Except when time is of the essence,

such as with certain prenatal genetic

tests, obtaining informed consent and

actually performing the test should be
Federal Register / Vol. 62, No. 20 / Thursday, January 30, 1997 / Notices 4547

delayed several days after the test is

offered and information given to the

patient. This would give people

considering testing the opportunity to

absorb information about the test,

contemplate the implications of testing,

and discuss testing with others.

Rare Genetic Diseases

Physicians who encounter patients

with symptoms and signs of rare genetic

diseases should have access to the best

available information about rare genetic

diseases. This will enable them to

include such diseases in their

differential diagnosis, to know where to

turn for assistance in clinical and

laboratory diagnosis, and to find

laboratories that test for rare diseases.

The quality of laboratories providing

tests for rare diseases must be assured,

and a comprehensive system to collect

data on rare diseases must be

established. Although these are issues

that relate primarily to the diagnosis of

patients with symptoms and signs, they

have major implications for predictive

testing in asymptomatic relatives who

may be at risk of disease or who are

carriers of alleles for the disease and

whose future children may be at risk.

The Task Force is aware of a number

of efforts to address one or more of these

issues, including the availability of

disease-based databases on research

projects by the NIH Office of Rare

Diseases (ORD), on information for

consumers and providers by the

National Organization of Rare Disorders,

the Alliance of Genetic Support Groups

and its member organizations, and by

the American Academy of Pediatrics,

and on clinical laboratories providing

tests through the Helix National

Directory (available to providers only).

In addition, the Society for Inherited

Metabolic Disorders is compiling

information for providers on diagnostic

evaluations of rare disorders, and the

ACMG is developing databases on tests

that should be used for diagnosis of

specific disorders.

The Task Force recommends that NIH

give ORD a mandate to coordinate these

public and private efforts to improve

awareness of rare genetic diseases. Such

coordination is important to avoid

unnecessary duplication, to use

expertise most efficiently and to address

the concerns of the various groups. ORD

could serve as a gateway for provider

and public inquiries about these

disorders.

In cooperation with other

organizations, and on a regular basis,

ORD should identify laboratories worldwide that perform tests for rare genetic

diseases, the methodology employed,

and whether the tests they provide are

in the investigational stage, or are being

used for clinical diagnosis and decision

making. Laboratories should notify ORD

about impending cessation of their

testing so that provisions for a transition

to other laboratories can be made.

ORD should also be responsible for

assuring that tests for rare genetic

diseases, which have been demonstrated

to be safe and effective, continue to be

available if and when their developers

leave the field, and no other laboratory

is prepared to offer the test, and/or the

methodology is too complex to be

readily adopted by other laboratories.

The Task Force urges that additional

funds be appropriated for ORD to

undertake this expanded role.

In accordance with current law, the

Task Force is of the opinion that any

laboratory performing any genetic test

on which clinical diagnostic and/or

management decisions are made should

be certified under CLIA. If specimens

must be sent to a non-CLIA licensed

research facility, the referring physician

must be made aware of the investigative

nature of the test.

The Task Force recognizes that the

current CLIA certification process may

place a heavy burden on some

laboratories doing small numbers of

diagnostic tests for rare diseases. Several

laboratories currently performing these

tests are primarily engaged in research,

with the tests stemming from their

research efforts. Without

accommodation, some tests may cease

to be available. Therefore, the Task

Force recommends that the proposed

Genetics Advisory Committee to CLIAC

explore means to simplify compliance

with CLIA without sacrificing quality,

just as accommodations have been made

for rare genetic disease testing within

the New York State Department of

Health laboratory permit process.

Recognizing current deficiencies under

CLIA in the assessment of genetic tests

(discussed above), the Task Force also

encourages CAP/ACMG to make its

clinical accreditation programs available

to low-volume laboratories that are

unaffiliated with a hospital, and modify

its procedures to accommodate such

laboratories.

Directories of laboratories providing

tests for rare diseases should indicate

whether or not the laboratory is CLIAcertified and whether it has satisfied

other quality assessments, such as the

CAP/ACMG program.

The recommendation made earlier,

calling on the CDC to expand its data

monitoring capabilities, is intended to

include rare diseases. Collecting data on

rare diseases will require coordinating

data from multiple sources. It is

particularly needed to validate tests,

describe the natural history of rare

diseases and determine the safety and

effectiveness of interventions to prevent

disease or ameliorate its severity.

(Catalogue of Federal Domestic Assistance

Program No. 93.172, Human Genome

Research.)

Elke Jordan,

Executive Secretary, National Advisory

Council for Human Genome Research.

[FR Doc. 97–2286 Filed 1–29–97; 8:45 am]

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