Federal Register / Vol. 65, No. 128 / Monday, July 3, 2000 / Notices 41073

Budget, New Executive Office Building,

Room 10235, 725 17th Street, NW.,

Washington, DC 20503.

Comments may also be sent to

Cynthia Agens Bauer, OS Reports

Clearance Officer, Room 503H,

Humphrey Building, 200 Independence

Avenue SW., Washington, DC 20201.

Written comments should be received

on or before August 2, 2000.

Dated: June 15, 2000.

Dennis P. Williams,

Deputy Assistant Secretary, Budget.

[FR Doc. 00–16669 Filed 6–30–00; 8:45 am]

BILLING CODE 4150–04–M

DEPARTMENT OF HEALTH AND

HUMAN SERVICES

Office of National AIDS Policy; Notice

of Meeting of the Presidential Advisory

Council and HIV/AIDS and Its

Subcommittees

June 27, 2000.

Pursuant to P.L. 92–463, notice is

hereby given of the meeting of the

Presidential Advisory Council on HIV/

AIDS scheduled for September 21–22,

2000 at the Madison Hotel, Washington,

DC. The meeting of the Presidential

Advisory Council on HIV/AIDS will

take place of Thursday, September 21,

and Friday, September 22 (8:30 a.m. to

6 p.m. on Thursday and Friday) at the

Madison Hotel, 1177 15th Street, NW,

Washington, D.C. 20005. The meetings

will be open to the public.

The purpose of the subcommittee

meetings will be to finalize any

recommendations and assess the status

of previous recommendations made to

the Administration. The agenda of the

Presidential Advisory Council of HIV/

AIDS may include presentations from

either of the Council’s subcommittees,

Services or Prevention.

Daniel C. Montoya, Executive

Director, Presidential Advisory Council

on HIV and AIDS, Office of National

AIDS Policy, 736 Jackson Place, NW,

Washington, DC 20503, Phone (202)

456–2437, Fax (202) 456–2438, will

furnish the meeting agenda and roster of

committee members upon request. Any

individual who requires special

assistance, such as sign language

interpretation or other reasonable

accommodations, should contact

Vanessa Vaughn at (301) 986–4870 no

later than August 25, 2000.

Daniel C. Montoya,

Executive Director, Presidential Advisory

Council of HIV and AIDS.

[FR Doc. 00–16779 Filed 6–30–00; 8:45 am]

BILLING CODE 3195–01–M

DEPARTMENT OF HEALTH AND

HUMAN SERVICES

Office of the Secretary

Human Subject Protection and

Financial Conflict of Interest:

Conference

AGENCIES: OASPE, OPHS, NIH, FDA,

and CDC, HHS.

ACTION: Notice of conference; request for

comments.

SUMMARY: A Conference on Human

Subject Protection and Financial

Conflict of Interest will be held at

Natcher Auditorium, NIH Campus on

August 15–16, 2000. The issue of

financial conflict of interest is one of the

5 main issues identified by the Secretary

of Health and Human Services in her

announcement of steps being taken to

strengthen human subject protection

during clinical trials. In that

announcement, the Secretary stated that

there would be a public process to

review this issue. She said that HHS

would undertake an extensive public

consultation to identify new or

improved means to manage financial

conflicts of interest that could threaten

the safety of research subjects or the

objectivity of the research itself.

Emphasis will be placed on the

informed consent process and how it

might be clarified and enhanced in

dealing with issues related to financial

conflict of interest.

The Conference will review the

current regulatory requirements and

guidance, serve as a forum for

presentations of current approaches

being taken for dealing with real and

potential financial conflict of interest at

the institution, IRB, and clinical

investigator levels. This conference will

help the government refine its current

guidance and may lead to other changes.

NIH has developed a set of issues to

consider related to its regulations which

is now available as background for the

conference. Further guidance will be

issued based on the responses to

questions posed in this Notice and the

conference deliberations.

To facilitate review of current

policies, regulations, and guidance

documents, these documents are cited

as references at the end of this Notice.

The references cited are also available

electronically at the OASPE Website

(http://aspe.hhs.gov/sp/coi/index.htm).

To maximize the efficiency of this

process, six questions (see below) have

been developed. Please address these in

writing by August 1, 2000. This will

help in organizing the plenary and

concurrent work group sessions. There

will be a public session where brief

comments on these topics can be

addressed during the conference.

DATES: Conference on Human Subject

Protection and Financial Conflict of

Interest: The Conference will be held on

Tuesday August 15, 2000 from 8:30 AM

to 5:30 PM and Wednesday August 16,

2000 from 8:30 AM to 1:00 PM.

Although the entire conference is open

to the public and there will be no

registration fee, it is requested that all

those who wish to participate in the

conference register by August 1, 2000.

This will allow us to prepare an

adequate number of conference

background materials and to make

appropriate assignments for the

breakout sessions.

Request for Comments: Written

responses to the six questions are

requested by all parties, whether or not

they will be attending the conference,

by August 1, 2000 as described below.

Opportunity for Public Comment

during the Conference on August 15,

2000, 2:15–3:30 PM. There will be an

opportunity to make brief presentations

during this session set aside for public

comments. The comments should be

responses to any or all of the six

questions listed below. Anyone wishing

to make comments should file a written

Notice of Participation as described

below by August 1, 2000. You will be

contacted after all the requests are

reviewed and given information about

the time of your presentation and other

details.

ADDRESSES: The Conference will be held

at Natcher Auditorium, Building 45,

NIH Campus, 9000 Rockville Pike,

Bethesda, MD 20892.

Registration Information: To register

for the conference please contact Mr.

Mark Brown, CMP, MasiMax Resources,

Inc., phone 240–632–5618, FAX 240–

632–0519, e-mail:

Mbrown@masimax.com. Please register

by August 1, 2000.

Comments and Notices of

Participation in Public Session: Written

or electronic responses to the six

questions as well as submissions of

written or electronic Notices of

Participation to speak during the Public

Session of the Conference should both

be addressed to: Stuart L. Nightingale,

M.D., Office of the Assistant Secretary

for Planning and Evaluation,

Department of Health and Human

Services, 200 Independence Avenue,

SW, Washington, DC 20101, Fax: 202–

205–8835 email: COI@aspe.dhhs.gov

Notices of Participation to present

during the Public Session should

include name, affiliation, (whether

person is from an IRB, an institution,

41074 Federal Register / Vol. 65, No. 128 / Monday, July 3, 2000 / Notices

industry, is a clinical investigator, etc.),

main points of presentation, how much

time requested (no more than 5

minutes), and telephone number and

other contact information.

FOR FURTHER INFORMATION CONTACT:

Stuart L. Nightingale, FAX 202–205–

8835, e-mail: coi@OSASPE.dhhs.gov.

SUPPLEMENTARY INFORMATION:

A. Background

In recent years, clinical research has

generally become ever more complex—

which, in turn, has engendered a new

degree of complexity in accompanying

ethical and conflict of interest

considerations. Financial conflict of

interest in clinical trials has been of

concern for a number of years, both

from the perspective of research

objectivity and human subject

protection. Both the PHS and FDA have

requirements/regulations and guidance

in place relating to financial conflict of

interest. Recently, financial

arrangements between commercial

interests and institutions have become

more common and some institutions

have arrangements with the same

commercial organizations as

investigators. This has been highlighted

in the area of gene transfer research.

Additionally, although IRBs are

required to deal with conflict of interest

issues, these have been understood to be

directed more toward members’ own

conflict of interest rather than those of

investigators or institutions. There is

little guidance to IRB’s and a recent

HHS Inspector General’s Report found

that only 25 percent of IRBs review

these issues and consider them for

inclusion in the informed consent

document.

B. The Secretary’s Initiatives To

Strengthen Human Subject Protection

Notwithstanding the many successes

over the years in protecting human

research subjects from undue and

undisclosed risks, we recognize that the

protection system itself needs to be

enhanced. In this regard, we agree with

the finding of the HHS Inspector

General that Institutional Review Boards

(IRBs)—the central element of the

system—often have difficulty fulfilling

even their fundamental responsibilities

because many of them are overworked

and few have been accorded adequate

resources by their parent institutions.

These findings have been reinforced

over the last two years by a series of

inspections by the HHS Office for

Protection from Research Risks (OPRR).

Several inspections resulted in complete

or partial cessation of human subjects

research until the institutions involved

took appropriate actions.

In response to these developments,

Secretary Shalala recently announced

five initiatives designed to enhance

protection for human research subjects.

First, HHS will take steps to require

that clinical investigators and IRB

members and staff undergo continuing

education in issues relating to human

subjects.

Second, HHS will issue guidance

making clear that research institutions

and clinical trial sponsors are expected

to take stringent continuing review

actions, such as audits of research

records, to promote compliance with

current informed consent requirements.

Third, HHS will expand its

requirements for study monitoring—

thereby improving the oversight of even

small-scale clinical trials. Large-scale

phase III clinical trials, already have the

requirement to have data and safety

monitoring.

Fourth, HHS will undertake an

extensive public consultation to identify

new or improved means to manage

financial conflict of interest that could

threaten the safety of research subjects

or the objectivity of the research itself.

The insights gained from this process

will be expressed in new guidance for

the research community regarding what

information about the financial interests

of investigators and research institutions

should be disclosed to research subjects

and others. The objective of this

guidance will be to make current

conflict of interest regulations more

effective.

Fifth, HHS will seek new legislation

to enable FDA to level civil money

penalties for violation of informed

consent and other important regulatory

requirements so that they can be applied

to clinical investigators and institutions.

This new authority would fill a

significant gap in the current spectrum

of sanctions against those who fail to

obey Federal regulations for protection

of human research subjects.

C. HHS/PHS Grant Award

Requirements for Dealing With

Financial Conflict of Interest

In 1995 the Public Health Service

promulgated regulations establishing

standards and procedures to be followed

by institutions that apply for research

funding to ensure that the design,

conduct and reporting of research under

PHS grants, contracts or cooperative

agreements would not be biased by any

conflicting financial interest of those

investigators responsible for the

research. These regulations require that

investigators disclose to an institutional

official a listing of significant financial

interests (and those of his/her spouse

and dependent children) that would

reasonably appear to be affected by the

research. The institutional official must

review the disclosures and determine

whether any of the reported financial

interests could directly and significantly

affect the design, conduct or reporting of

the research and, if so, the institution

must, prior to any expenditure of funds,

report the existence of any conflicting

interests to the PHS awarding

component and assure that the conflict

of interest has been managed, reduced

or eliminated in accordance with the

regulations.

D. FDA Regulations Requiring

Financial Disclosure by Clinical

Investigators

On February 2, 1998, FDA published

a final rule requiring that financial

interests and arrangements of clinical

investigators that could affect the

reliability of data submitted to FDA be

identified and disclosed to FDA by the

applicant. Clinical research data provide

the basis for FDA’s assessment of

whether a product is approvable under

statutory requirements. It is essential

that these data be reliable and that steps

be taken to minimize possible effects on

the data resulting from potential bias on

the part of any investigator. This

regulation, which became effective on

February 2, 1999, applies to any

applicant who submits a marketing

application or reclassification petition

for a human drug, biological product, or

medical device and who submits any

clinical study of a drug or device in

humans that the applicant or FDA relies

on to establish that the product is

effective, or any study in which a single

investigator makes a significant

contribution to the demonstration of

safety. The regulation requires

applicants to certify to the absence of

certain financial interests of clinical

investigators or to disclose those

financial interests. If the applicant does

not include certification and/or

disclosure, or does not certify that it was

not possible to obtain the information,

the agency may refuse to file the

application. On December 31, 1998,

FDA published an amended final rule

that reduced the need to gather certain

financial information for studies

completed before February 2, 1999.

E. Purpose of This Conference

As discussed above, the issue of

financial conflict of interest in research

is one of the 5 main areas identified by

the Secretary of Health and Human

Services in her announcement of steps

being taken to strengthen human subject

protection during clinical trials. In that

Federal Register / Vol. 65, No. 128 / Monday, July 3, 2000 / Notices 41075

announcement, the Secretary stated that

HHS will hold public discussions this

summer to find new ways to manage

conflicts of interest so that research

subjects are appropriately informed, and

to further ensure that research results

are analyzed and presented objectively.

In addition, these public discussions

also will focus on clarifying and

enhancing the informed consent

process.

This Conference Will:

Implement one of the Secretary’s five

initiatives to strengthen human subject

protection in clinical research.

Remind participants of current PHS/

FDA regulations, guidelines and

guidance through documents and

presentations.

Present examples of how the issue of

financial conflict of interest is dealt

with at the level of: Institutions, IRBs,

and Clinical Investigators (including

Sponsor/Investigators), and Industry/

Sponsors.

Receive public comments on

questions posed in the Federal Register

announcing the conference.

Provide information for the

Department of Health and Human

Services to develop more useful and

detailed guidance to implement current

regulatory requirements.

Who Should Attend?

Institutional Officials, IRB staff and

members, Clinical Investigators,

Industry/Sponsors, National

Organizations/Health Professionals,

Patient and Advocate groups, Patients

and Research Participants.

General information about the

conference, the conference Program is

available on the ASPE Website (http://

aspe.hhs.gov/sp/coi) and at the Website

of MasiMax Resources, Inc.

(www.masimax.com/coi/index.html).

F. Questions for Comment

Members of the Public who wish to

respond to the following questions,

should send their comments by August

1, 2000 or comment at the Conference

during the public session (To comment

at the conference during the session for

Public Comment, a Notice of

Participation should be submitted).

1. For each group listed below, what

types of financial interests are

associated with human subjects research

funded or regulated by HHS agencies?

Clinical investigators (including

sponsor/investigators)

IRB members and staff

Awardee institutions

2. Is there empirical evidence that

informing research participants about

financial relationships or financial

conflict of interest of the investigator,

the institution, or the IRB:

Can cause or prevent real or perceived

harm (physical or psychological) to

human research subjects?

Can compromise the objectivity of the

associated research?

Can adversely or positively affect

participation in the trial?

Can enhance the informed consent

process by more fully informing

potential participants?

Can be understood by and is

meaningful to the potential research

participant?

3. If information about financial

interests is disclosed to potential

participants in clinical trials, what

information should be disclosed and at

what level of detail?

Should potential participants be told

of all of the financial interests of

investigators, IRB members, or

institutions, or only those financial

interests which constitute a financial

conflict of interest or might constitute a

financial conflict of interest? Should

potential participants be told what

protections are in place and are working

to ensure that financial conflicts are

managed, reduced, or eliminated to

promote objectivity and enhance human

subject protection in the trial? Are the

financial limits set forth in current PHS

regulations covering awardee

institutions still appropriate for clinical

researchers? What are appropriate levels

of reportable financial relationships for

IRB members and institutions?

4. If information about financial

interests is disclosed to potential

participants, when and how should

information about financial conflict of

interest be provided to them?

If information about financial

interests/conflict of interest involving

institutions, IRBs, and investigators

should be provided, what is the optimal

point in the process for disclosure?

Should information be provided by

the institution, the research investigator,

the IRB, or a third party?

Should disclosure information and

institutional policy be provided in the

informed consent document or in an

entirely separate document?

5. What are appropriate roles for the

institution, the IRB, the clinical

investigator (including sponsor/

investigators), and perhaps other

entities in dealing with financial

interests or financial conflict of interest?

What are the responsibilities and

obligations of each entity?

How should each entity relate to the

other entities?

Should disclosed information on

which determinations are made

(including deliberations) be shared with

the other entities? If so, what

information should be shared and how

and when should the disclosures be

conducted?

What confidentiality protections are/

should be in place to safeguard the

privacy and confidentiality of the

investigator, IRB member, and

institution?

6. Other than those at the Federal

level, what protections exist to ensure

that the financial conflicts are managed,

reduced, or eliminated to promote

objectivity in the trial and to enhance

human subjects protection?

References

HHS NEWS, U.S. Department of Health

and Human Services, May 23, 2000:

‘‘Secretary Shalala Bolsters

Protections for Human Research

Subjects’’

HHS FACT SHEET, U.S. Department of

Health and Human Services, May 23,

2000 ‘‘Protecting Research Subjects’’

Code of Federal Regulations, Title 45,

Part 46, Subpart A. Federal Policy for

the Protection of Human Subjects

(Basic DHHS Policy for Protection of

Human Research Subjects).

Code of Federal Regulations, Title 42,

Part 50, Subpart A. Responsibility of

PHS Awardee and Applicant

Institutions for Dealing With and

Reporting Possible Misconduct in

Science

Code of Federal Regulations, Title 42,

Part 50, Subpart F. Responsibility of

Applicants for Promoting Objectivity

in Research for Which PHS Funding

Is Sought

Frequently Asked Questions Concerning

the Department of Health and Human

Services’ Objectivity in Research

Regulations and the National Science

Foundation Investigator Financial

Disclosure Policy, Federal Register:

July 3, 1996 Volume 61, Number 129,

p. 34839.

Required Education in the Protection of

Human Research Participants. NIH

Guidance, June 5, 2000

Financial Conflict of Interest and

Research Objectivity: Issues for

Investigators and Institutional Review

Boards. NIH Guidance, June 5, 2000.

FDA Information Sheets, Guidance for

Institutional Review Boards and

Clinical Investigators, 1998 Update,

Revised February 1999. Also available

at www.fda.gov

Code of Federal Regulations, Title 21,

Part 50. Protection of Human Subjects

(FDA)

Code of Federal Regulations, Title 21,

Part 54. Financial Disclosure by

Clinical Investigators (FDA)

41076 Federal Register / Vol. 65, No. 128 / Monday, July 3, 2000 / Notices

Code of Federal Regulations, Title 21,

Part 56. Institutional Review Boards

(FDA)

Code of Federal Regulations, Title 45,

Part 76. HHS Debarment Regulations

Dated: June 27, 2000.

William F. Raub,

Deputy Assistant Secretary for Science Policy,

Office of the Assistant Secretary for Planning

and Evaluation, Department of Health and

Human Services.

[FR Doc. 00–16760 Filed 6–30–00; 8:45 am]

BILLING CODE 4151–05–P

DEPARTMENT OF HEALTH AND

HUMAN SERVICES

Centers for Disease Control and

Prevention

[Program Announcement 00095]

Cooperative Agreement for Birth

Defects Surveillance, Research, and

Prevention Activities; 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 the University of South

Alabama Birth Defects Surveillance,

Research, and Prevention Activities.

B. Eligible Applicants

Single Source: Assistance will be

provided only to the University of South

Alabama. No other applications are

solicited.

This authority is granted under the

Consolidated Appropriations Act 2000

(Public Law 106–113), which states:

‘‘* * * under section 1509 of the Public

Health Service Act * * * $1,000,000

shall be for the University of South

Alabama birth defects monitoring and

prevention activities.’’

C. Availability of Funds

Approximately $800,000 is available

in FY 2000 to fund this award. It is

expected that the award will begin on or

about September 30, 2000, and will be

made for a 12-month budget period

within a project period of only 1 year.

Funding estimates may change.

D. Where To Obtain Additional

Information

If you have questions after reviewing

the contents of all the documents,

business management technical

assistance may be obtained from:

William A. Paradies, Grants

Management Specialist, Grants

Management Branch, Procurement and

Grants Office, Centers for Disease

Control and Prevention, 2920

Brandywine Road, Room 3000, Atlanta,

GA 30341–4146, Telephone number

(770) 488–2721, Email address:

WParadies@cdc.gov.

For program technical assistance,

contact: Larry D. Edmonds, State

Services, Birth Defects and Pediatric

Genetics Branch, Division of Birth

Defects, Child Development, Disability

and Health, National Center for

Environmental Health, Centers for

Disease Control and Prevention (CDC),

4770 Buford Highway NE., Mailstop F–

45, Atlanta, GA 30341–3724, Telephone

number (770) 488–7171, E-mail address:

LEdmonds@cdc.gov.

Dated: June 27, 2000.

John L. Williams,

Director, Procurement and Grants Office,

Centers for Disease Control and Prevention

(CDC).

[FR Doc. 00–16719 Filed 6–30–00; 8:45 am]

BILLING CODE 4163–18–P

DEPARTMENT OF HEALTH AND

HUMAN SERVICES

Centers for Disease Control and

Prevention

[Program Announcement 00105]

TB Epidemiologic and Operational

Research; Notice of Availability of

Funds

A. Purpose

The Centers for Disease Control and

Prevention (CDC) announces the

availability of Fiscal Year 2000 funds for

a new cooperative agreement to enhance

the capabilities of recipients of state and

local tuberculosis (TB) elimination and

laboratory agreements to conduct TB

epidemiologic and operational research.

This program addresses the ‘‘Healthy

People 2010’’ focus areas of

Immunization and Infectious Diseases.

For the conference copy of ‘‘Healthy

People 2010’’, visit the internet site

http://www.health.gov/healthypeople

The purpose of this cooperative

agreement is to build capacity at state

and local health departments to conduct

and implement protocol-driven

epidemiologic and operational research.

Such actions are consistent with

recommendations issued by the

Advisory Council for the Elimination of

Tuberculosis (ACET) calling for decisive

actions to: Better understand the

changing epidemiology of TB to rebuild

the public health infrastructure; identify

challenges and opportunities for TB

control in an era of changes in health

care organizations and delivery;

recognize the interdependence of global

TB and TB in the United States; and

develop and evaluate new tools for TB

diagnosis, treatment and prevention.

This new cooperative agreement will be

awarded to successful applicants from

state and local health agencies to

support health department-based

investigators with access to patients

with tuberculosis, latent tuberculosis

infection, or recent exposure to persons

with active tuberculosis (‘‘contacts’’) in

the implementation of protocols for

epidemiologic and operational research.

Recipients of this award will be

expected to conduct site-specific

epidemiologic and operational research

activities in TB which rely upon the

implementation of common, agreedupon study protocols. Award recipients

will be expected to successfully

compete for one or more of the specific

TB research projects listed below.

Eligible applicants may request support

for activities under one or more of the

following three separate focus areas. See

Attachments 1–3 in the application kit

for details under each focus area:

1. Development of Contact

Investigation Self-Evaluation Tools: (See

Attachment 1): Assist local TB control

programs in building local-level

capacity for evaluation of contact

investigation processes by providing

them with a package of self-evaluation

tools. These tools will enable programs

to systematically assess contact

investigation processes and target

programmatic revisions accordingly.

The package will include economic

evaluation tools to show how program

changes will impact resource use and

outcomes, thus enabling programs to

plan strategically. The package of tools

will be pilot tested to ensure usefulness

and feasibility. These funds will give

state and local health departments the

ability to develop practical evaluation

tools, based on the CDC’s

Recommended Framework for

Evaluation, that can be used by local TB

programs to use local data to evaluate

contact investigation processes. They

will also provide for the development of

educational support materials to enable

local level program staff to understand

evaluation principles and conduct selfevaluations.

2. Improving Contact Investigations in

Foreign-Born Populations: (See

Attachment 2) Improve contact

identification for foreign-born (FB) TB

cases. Improve completeness and

timeliness of screening for identified

contacts to FB TB cases. Improve the

interpretation of screening results for

contacts to FB TB cases in [a] the

context of screening results for US-born

contacts to the same cases and [b] using

serum immunologic profile (IFN-gamma