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



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.


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.


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 
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 
    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 
     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 
    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 

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 
    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 
    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]