Federal Register, Volume 74 Issue 8 (Tuesday, January 13, 2009)

[Federal Register Volume 74, Number 8 (Tuesday, January 13, 2009)]
[Notices]
[Pages 1695-1697]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: E9-450]

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DEPARTMENT OF HEALTH AND HUMAN SERVICES

Food and Drug Administration

[Docket No. FDA-2009-N-0674]

Participation of Certain Population Subsets in Clinical Drug
Trials; Request for Comment

AGENCY: Food and Drug Administration, HHS.

ACTION: Notice; request for comments.

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SUMMARY: The Food and Drug Administration (FDA) is seeking information
and comments on issues related to the enrollment of certain populations
in clinical drug trials. Particularly, we are requesting information
and comments from medical product manufacturers, institutional review
boards (IRBs), patient groups, universities, researchers, community
groups, and other interested parties. This request is related to FDA's
implementation of the Food and Drug Administration Amendments Act of
2007 (FDAAA) section 901, which requires recommendations be included in
a report to Congress addressing best practice approaches on increasing
the participation of elderly populations, children, racially and
ethnically diverse communities, and medically underserved populations
in clinical drug trials. FDA requests that those with information on
possible approaches to increase participation of these groups in
clinical drug trials submit comments.

DATES: Submit written or electronic comments by February 27, 2009.

ADDRESSES: Submit electronic comments to http://www.regulations.gov.
Submit written comments to the Division of Dockets Management (HFA-
305), Food and Drug Administration, 5630 Fishers Lane, rm. 1061,
Rockville, MD 20852.

FOR FURTHER INFORMATION CONTACT: Brenda Evelyn, Office of Special
Health Issues, Office of the Commissioner, Food and Drug
Administration, 5600 Fishers Lane, Rockville, MD 20857, 301-827-4460.

SUPPLEMENTARY INFORMATION:

I. Background

Section 901 of FDAAA requires that FDA submit a report to Congress
that includes ``recommendations regarding impediments to the
participation of elderly populations, children, racially and ethnically
diverse communities and medically underserved populations in clinical
drug trials'' and recommendations that address ``best practice
approaches for increasing the inclusion of such subsets of the general
population'' in clinical drug trials (FDAAA, section 901(d)(5)). In
developing this report, FDA seeks comments that may help to develop
these recommendations.
Participation of all segments of the population in medical research
is critical to public health. The ability to develop drugs that are
safe and effective for diverse groups hinges on the availability of
clinical drug trial participants from these same groups. Some
researchers and public health experts argue that inconsistent
representation of certain communities can potentially lead to health
disparities and insufficient data for risk assessment. FDA has
previously identified the need for inclusion of children, both sexes,
the elderly, racially and ethnically diverse communities, and other
populations in clinical trials so that data are available to evaluate
the potential differences among these subgroups (63 FR 6854, February
11, 1998). According to the Department of Health and Human Services
(HHS) Office of Minority Health, in a recent prostate cancer study,
only 8 percent of the 18,000 participants were minorities
(www.omhrc.gov/templates/content.aspx?ID=5147). Increased participation
from all of these sub-groups may help assure that data relevant to the
entire treatment population are obtained.
In addition, statutory mandates and incentives such as the
Pediatric Research Equity Act (PREA) (Public Law No. 108-155 as amended
by FDAAA) and the Best Pharmaceuticals for Children Act (BPCA) (Public
Law No. 107-109 as amended by FDAAA) require and encourage medical
research to consider implications for pediatric populations.
For over 20 years, FDA has worked to encourage broad participation
of all groups in clinical drug trials. Under FDA regulations (21 CFR
312.33), all investigational new drug (IND) applications must include
in annual reports the number of patients tabulated by age, gender, and
race, and under 21 CFR 314.50(d)(5)(v) and (d)(5)(vi), new drug
applications (NDA) are required to include analyses of efficacy and
safety by demographic subgroups. Biologics license applications
typically include analyses of efficacy and safety by demographic
subgroups. The International Conference on Harmonization (ICH) guidance
on the common technical document also calls for such analyses (see M4E:
The CTD--Efficacy (August 2001) available at http://www.fda.gov/cber/gdlns/m4ectd.pdf.).
FDA has issued labeling recommendations for specific sub-
populations (Guidance for Industry: Content and Format of the Adverse
Reactions Section of Labeling for Human Prescription Drugs and
Biological Products, January 2006, available at http://www.fda.gov/cber/gdlns/cfadvers.htm) and guidelines for studying gender differences
in clinical drug studies (Guideline for the Study and Evaluation of
Gender, July 1993, available at http://www.fda.gov/cder/Guidance/old036fn.pdf). FDA has made recommendations for minimum standards for
the collection and use of race and ethnicity information to assist in
the reporting of the summary of safety and effectiveness data by
demographic subgroups (age, gender, race), as well as an analysis of
whether modifications of dose or dosage intervals are needed for
specific subgroups. (Guidance for Industry: Collection of Race and
Ethnicity Data in Clinical Trials, September 2005, available at http://www.fda.gov/CBER/gdlns/racethclin.htm; see, also ICH E-7 Guideline for
Industry, Studies in Support of Special Populations: Geriatrics (August
1994) available at

[[Page 1696]]

http://www.fda.gov/cder/guidance/iche7.pdf and Reviewer Guidance:
Conducting a Clinical Safety Review of a New Product Application and
Preparing a Report on the Review (February 2005) available at http://www.fda.gov/cder/guidance/3580fnl.pdf.)
Other agencies have also issued guidelines for the participation of
diverse groups in clinical trials. For example, the National Institutes
of Health (NIH) requires the inclusion of women and minority groups in
NIH-funded trials unless an exception is warranted (NIH Policy on the
Inclusion of Women and Minorities as Subjects in Clinical Research as
amended October 2001, information is available at http://grants.nih.gov/grants/funding/women_min/guidelines_amended_10_2001.htm). NIH also has issued guidelines for inclusion of children as
research subjects (March 1998 NIH Policy and Guidelines on the
Inclusion of Children as Participants in Research Involving Human
Subjects, available at http://grants.nih.gov/grants/guide/notice-files/not98-024.html).
Currently, healthcare professional organizations, various
universities, foundations, and industries are taking steps to encourage
broad participation of all populations in clinical drug trials.
Since 1998, the National Medical Association has administered
Project IMPACT, a program initially funded by HHS designed to train
African American physicians on being clinical investigators and to
increase knowledge and raise awareness about clinical trials among
African American physicians and consumers. (Information is available at
http://www.omhrc.gov/assets/pdf/checked/Project%20IMPACT_
Increasing%20Minority%20Participation%20and%20Awareness%20of%20Clinical%
20Trials.pdf.) The program is currently being funded by AstraZeneca and
has expanded to include the Interamerican College of Physicians and
Surgeons, an Hispanic health professional organization. (Information is
available at http://www.astrazeneca-us.com/community-support/?itemId=1338629.) Further, some foundations have supported studies and
programs designed to increase participation (e.g., the Lance Armstrong
Foundation's support of the Education Network to Advance Clinical
Cancer Trials, intended ``to foster awareness about cancer clinical
trials, enhance their acceptability and improve access to them.''
Information is available at http://www.livestrong.org/site/c.khLXK1PxHmF/b.2662065/k.C0D9/ENACCT.htm). Industry has partnered with
academia to fund similar programs (e.g., Genentech's and Baylor College
of Medicine's research initiative with the Intercultural Cancer
Council, ``Project addresses underrepresentation of minorities,
underserved patients in clinical studies.'' Information is available at
http://www.bcm.edu/news/item.cfm?newsID=420).
We are seeking information to determine if additional approaches
are necessary to increase participation of certain subsets of the
general population (elderly populations, children, racially and
ethnically diverse communities, and medically underserved populations)
in drug clinical trials.

II. Request for Comments and Information

In providing comments, we are particularly interested in responses
to the following questions regarding the participation of certain
population subsets in clinical drug trials.

A. Communication and Knowledge Barriers

1. To what extent do differences in native language, educational
level, and literacy interfere with members of some populations'
participation in clinical trials:
Finding out about the existence of trials and how to
enroll
Understanding informed consent documents and procedures
Adhering to clinical trial instructions and drug regimens
Completing clinical trials
2. To what extent do limitations in access to technology and to
medical care in general decrease the chance that members of some
populations will know about the existence of clinical trials and how to
participate in them?
Are these subsets of populations aware of
www.ClinicalTrials.gov?
3. What proven methods, i.e., best practices, are available to
address the impact of these potential barriers to communication about
the existence of, and how to participate in, clinical drug trials?
4. To what extent are health care providers aware of
www.ClinicalTrials.gov?

B. Trust and Cultural Sensitivity

1. To what extent do culturally-bound beliefs or traditions, or
trust or stereotypes about the medical research community, interfere
with group members' willingness to participate in clinical drug trials?
Are particular populations significantly more or less
trusting of those who conduct medical research?
2. What approaches to address cultural sensitivity and trust
issues, including increased collaboration with community-based
organizations, have been shown to increase successful clinical trial
participation?
3. To what extent do the beliefs of clinical trial personnel about
the commitment or ability of members of some populations to follow
through with a protocol influence willingness to recruit and enroll
such individuals in clinical drug trials?
4. What approaches, i.e. best practices, have been shown to improve
trust between potential participants and clinical drug trial
researchers and healthcare providers who can provide referrals?

C. Costs of Clinical Trial Participation

Note: The term ``cost'' may vary from participant to participant
and is intended to include time lost (i.e. wages, childcare, etc),
effort expended, and other sacrifices that may be necessary to
participate in clinical drug trials.
1. To what extent do data show that the ``costs'' of participation,
to either potential participants or to those who conduct clinical drug
trials, prohibit participation or enrollment of particular populations?
2. To what extent do data address the following?
Do particular populations understand the potential public
benefit from participating in clinical drug trials as compared to the
``cost'' to the participant?
Is the belief that there is a public benefit from
participating in clinical drug trials a sufficient incentive for
participation for some populations?
3. To what extent do data show that limited health insurance
coverage is an impediment to clinical drug trial participation?
4. To what degree is the geographical accessibility to clinical
trials a significant cost that affects the participation of some
populations?
5. What are the ``costs'' of participating in clinical drug trials
that are most relevant to some populations? How might these be reduced?
6. What approaches, i.e. best practices, have been shown to
decrease ``costs'' with resulting increased participation in clinical
drug trials?

D. Other

1. Please describe any other barriers, or best practice approaches,
that HHS should consider in striving to increase participation of
certain population subsets in clinical drug trials.

[[Page 1697]]

III. Comments

Interested persons may submit to the Division of Dockets Management
(see ADDRESSES) written or electronic comments regarding this document.
Submit a single copy of electronic comments or two paper copies of any
mailed comments, except that individuals may submit one paper copy.
Comments are to be identified with the docket number found in brackets
in the heading of this document. Received comments may be seen in the
Division of Dockets Management between 9 a.m. and 4 p.m., Monday
through Friday.
Please note that on January 15, 2008, the FDA Division of Dockets
Management Web site transitioned to the Federal Dockets Management
System (FDMS). FDMS is a Government-wide, electronic docket management
system. Electronic comments or submissions will be accepted by FDA only
through FDMS at http://www.regulations.gov.

Dated: January 6, 2009.
Jeffrey Shuren,
Associate Commissioner for Policy and Planning.
[FR Doc. E9-450 Filed 1-12-09; 8:45 am]
BILLING CODE 4160-01-S