[Federal Register: August 3, 2005 (Volume 70, Number 148)]
[Notices]               
[Page 44660-44662]
From the Federal Register Online via GPO Access [wais.access.gpo.gov]
[DOCID:fr03au05-161]                         

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DEPARTMENT OF HEALTH AND HUMAN SERVICES

Food and Drug Administration

[Docket No. 2004N-0355]

 
Critical Path Initiative; Developing Prevention Therapies; 
Planning of Workshop

AGENCY: Food and Drug Administration, HHS.

ACTION: Request for Comments.

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SUMMARY: The Food and Drug Administration (FDA) is planning a 2-day 
workshop to explore approaches and potential obstacles to developing 
drugs, disease biomarkers, medical devices, and vaccines to prevent or 
reduce the risk of illness. The agency plans to hold the workshop as 
part of its Critical Path Initiative. Speakers at the workshop will be 
asked to discuss the challenges in developing chemoprevention therapies 
(i.e., prevention therapies other than lifestyle changes, dietary 
supplements, or dietary choices that could reduce the risk of certain 
illnesses such as cancer, diabetes, and obesity). Because prevention of 
illness is widely recognized to be an important goal and the possible 
scope of this workshop is very broad, FDA welcomes comments related to 
the scope of this workshop.

DATES: Submit written or electronic comments by November 1, 2005. 
General comments are welcome at any time.

ADDRESSES: The FDA invites you to submit written comments on the 
proposed scope of the workshop. Please submit comments to the Division 
of Dockets Management (HFA-305), Food and Drug Administration, 5630 
Fishers Lane, rm. 1061, Rockville, MD 20852. Submit electronic comments 
to http://frwebgate.access.gpo.gov/cgi-bin/leaving.cgi?from=leavingFR.html&log=linklog&to=http://www.fda.gov/dockets/ecomments.


FOR FURTHER INFORMATION CONTACT: Nancy Stanisic, Center for Drug 
Evaluation and Research (HFD-05), Food and Drug Administration, 5600 
Fishers Lane, Rockville, MD 20852, 301-827-1660, FAX: 301-443-9718, e-
mail: Stanisicn@cder.fda.gov.

SUPPLEMENTARY INFORMATION:

I. Background

    The development of methods to prevent disease has been the single, 
most effective advance in healthcare in the past century, particularly 
in developed countries. The widespread ravages of smallpox, infantile 
diarrhea, plague, cholera, typhoid, and polio are gone from the United 
States.
    The challenge that lies ahead is to prevent the diseases that still 
ravage our population, including: Heart disease, cancer, diabetes, 
Alzheimer's disease, and others. In recent decades, substantial effort 
has been made in the chemoprevention or early intervention for some of 
the top killers in the United States, notably cardiovascular disease 
and some cancers. Examples of effective preventive interventions 
include the aggressive treatment of hypertension to reduce the risk of 
stroke, statins to lower cholesterol and decrease the risk of a 
myocardial infarction, the use of low-dose aspirin and beta blockers to 
prevent death in patients after a myocardial infarction, tamoxifen to 
reduce the risk of recurrent breast

[[Page 44661]]

cancer, aggressive control of blood glucose to reduce the long-term 
consequences of diabetes, and flu and pneumonia vaccination programs to 
reduce morbidity and mortality.
    Significant advances have also been made in the early 
identification of healthy individuals at risk of developing disease. 
Examples of predictors include genetic markers, such as BRCA 1 and 2 
for malignancy; pap tests for identification of patients at risk for 
cervical cancer; genetic alpha-1-antitrypsin deficiency for lung 
disease; colonoscopy to identify polyps that predict an increased risk 
of colon cancer; and family history, obesity, and ethnicity for type II 
diabetes mellitus. Ongoing work in genomics and proteomics promises to 
identify additional markers to predict specific health risks and 
potential targets for intervention.
    Although markers have been identified, candidate therapies require 
prospective testing in clinical trials. The design and conduct of 
chemoprevention trials offer substantial challenges. For example, in 
the Women's Health Initiative, we learned that the epidemiologic study 
results of the use of conjugated estrogens to prevent heart disease 
could not be replicated in the randomized, double-blind clinical trial 
setting. The Celebrex trial gives another example that prevention 
studies, in this case polyp prevention trials, must be of sufficient 
duration to ensure that the risks of long-term use of drugs are 
captured. These risks may be unexpected and the Data Safety Monitoring 
Boards need to pay careful attention as signals arise.

II. FDA Critical Path

    On March 16, 2004, FDA published its Critical Path report,\1\ aimed 
at identifying potential problems and solutions to ensure that 
breakthroughs in medical science can be efficiently translated to safe, 
effective, and available medical products. In the report, FDA 
underscored the importance of FDA collaboration with academic 
researchers, product developers, patient groups, and other stakeholders 
to make the critical path more predictable and less costly. This 
workshop and any activities that result from the workshop are part of 
that broad effort.
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    \1\ For the complete report, see http://frwebgate.access.gpo.gov/cgi-bin/leaving.cgi?from=leavingFR.html&log=linklog&to=http://www.fda.gov/oc/initiatives/criticalpath
.

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III. Topics Related to Planning the Public Workshop

    Because the range of potential topics that could be discussed at 
such a workshop is so wide, we are seeking the public's input on what 
key topics should be addressed at this initial meeting.
    Although the prefix ``chemo-'' is often used in relation to 
treatments for cancer, we are using the term ``chemoprevention'' in 
this notice to describe prevention therapies other than lifestyle 
changes, dietary supplements, or dietary choices that could reduce the 
risk of certain illnesses. We welcome comments on the use of the term 
``chemoprevention.''
    What follows is a list of topics and questions we have identified 
for possible discussion at the workshop. We welcome comment on whether 
these topics and questions are appropriate for discussion at a workshop 
on chemoprevention therapies? Are there other related issues that 
should be discussed at the workshop? What are they? Currently, we 
envision a 2-day workshop, with the first day devoted to identifying 
hurdles and challenges in designing and implementing chemoprevention 
studies from a broad perspective. The second day may consist of 
breakout sessions devoted to specific diseases or disease categories. 
We welcome input on the format for the 2-day workshop.
    Does the following list of questions reflect the kinds of questions 
we should try to answer at a 2-day workshop on chemoprevention 
therapies? What questions would you be interested in having answered? 
In addition to the following topics, what other topics should be 
included in the scope of the meeting?
    1. What have our successes been so far, and what lessons have we 
learned from past experience with regard to the development of the 
following preventive therapies:
    a. Vaccines
    b. Cardiovascular disease
    c. Cancer
    i Breast
    ii Colon polyps
    2. Which diseases are the most promising with regard to development 
of chemoprevention therapies?
    3. What options are available now for identifying populations at 
risk for those diseases?
    a. Screening
    b. Genomics
    c. Other
    4. What techniques are available for assessing the risks and 
benefits of new therapies in prevention?
    5. How much risk from the candidate therapy is acceptable?
    6. Are there specific regulatory concerns in developing 
chemopreventions (e.g., Long trials, safety and efficacy issues, 
registries)? And what steps can FDA take to facilitate development in 
this area, such as the following?
    a. Mechanisms to streamline the regulatory process
    b. Mechanisms to facilitate the scientific process and clinical 
trials
    i. To better and more efficiently answer questions regarding 
product efficacy
    ii. To better and more efficiently answer questions regarding 
product safety
    7. What are some of the obstacles facing manufacturers who wish to 
develop new or existing compounds for chemoprevention? For example, are 
there specific industry perspectives that need to be considered?
    8. What patient perspectives are important to consider?
    We have proposed the following topics and questions for discussion 
on the second day during breakout sessions. Are these appropriate? What 
other issues would you be interested in discussing at these breakout 
sessions?
    1. Cancer prevention issues
    a. What characteristics of particular cancers make prevention 
promising?
    b. What characteristics from epidemiologic, early trials, or other 
models make particular drugs promising?
    c. What trial design issues should be addressed (e.g., endpoints, 
surrogates, population, adverse event data collection)?
    d. Are there obstacles to marketing prevention drugs?
    2. Cardiovascular prevention issues
    a. What characteristics of cardiovascular disease make prevention 
promising?
    b. What characteristics from epidemiologic, early trials, or other 
models make particular drugs promising?
    c. What trial design issues should be addressed (e.g., endpoints, 
surrogates, population, adverse event data collection)?
    d. Are there obstacles to marketing prevention drugs?
    3. Cerebrovascular prevention issues
    a. What characteristics of cerebrovascular disease make prevention 
promising?
    b. What characteristics from epidemiologic, early trials, or other 
models make particular drugs promising?
    c. What trial design issues should be addressed (e.g., endpoints, 
surrogates, population, adverse event data collection)?
    d. Are there obstacles to marketing prevention drugs?
    4. What other conditions should be discussed?

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IV. Submission of Comments

    Interested persons may submit written or electronic comments to the 
Division of Dockets Management (see ADDRESSES). Submit a single copy of 
electronic comments or two paper copies of any mailed comments, except 
that individuals may submit one 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. You can 
also view received comments on the Internet at http://frwebgate.access.gpo.gov/cgi-bin/leaving.cgi?from=leavingFR.html&log=linklog&to=http://www.fda.gov/ohrms/dockets/dockets/dockets.htm



    Dated: July 28, 2005.
Jeffrey Shuren,
Assistant Commissioner for Policy.
[FR Doc. 05-15282 Filed 8-2-05; 8:45 am]

BILLING CODE 4160-01-S