[Federal Register Volume 66, Number 98 (Monday, May 21, 2001)]
[Notices]
[Pages 27984-27985]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 01-12625]


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DEPARTMENT OF HEALTH AND HUMAN SERVICES

Food and Drug Administration

[Docket No. 01N-0197]


Clinical Development Programs for Drugs, Biological Products, and 
Devices for the Treatment of Ankylosing Spondylitis (AS) and Related 
Disorders; Request for Assistance

AGENCY: Food and Drug Administration, HHS.

ACTION: Notice.

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SUMMARY: The Food and Drug Administration (FDA) is requesting 
assistance in developing guidance for industry on issues related to 
drugs, biological products, and devices for the treatment of AS and 
related disorders. Once finalized, the guidance would aid sponsors and 
others interested in developing new agents to treat AS and related 
disorders.
    Before the agency can develop such guidance, a critical appraisal 
of certain fundamentals of the science related to AS is needed. FDA is 
interested specifically in identifying a party, or parties, willing to 
take the lead in coordinating this critical appraisal.

DATES: Submit written comments on this notice by July 20, 2001.

ADDRESSES: Submit written comments to the Dockets Management Branch 
(HFA-305), Food and Drug Administration, 5630 Fishers Lane, rm. 1061, 
Rockville, MD 20852.

FOR FURTHER INFORMATION CONTACT: Mary Jane Walling, Center for Drug 
Evaluation and Research (HFD-105), Food and Drug Administration, 5600 
Fishers Lane, Rockville, MD 20857, 301-827-2268.

SUPPLEMENTARY INFORMATION: Because of the positive response to the 
agency's guidance on rheumatoid arthritis, the agency has recognized 
the need for more information on the development of drugs, biological 
products, and devices for the treatment of AS and related disorders. 
FDA intends to put the information received in response to this notice 
in a public docket so that interested parties can learn of each other 
and coordinate these activities.
    Specifically, the agency is interested in identifying an interested 
group or consortium of interested groups from academia, industry, 
practitioners, and patients and their representatives willing to take 
the lead in a critical appraisal of certain fundamentals of the science 
related to AS. Initially, the parties may want to organize a public 
meeting to discuss relevant questions (a number of which are noted 
below). The agency hopes this meeting will lead to conceptual advances 
now not present and their expression in a series of concept papers. 
Subsequent workshops would then be able to fully discuss these concept 
papers, soliciting feedback from all quarters including regulators from 
the United States and elsewhere. Emphasis should be on debating the 
rationale for various approaches to key issues. The agency welcomes 
other suggestions of activities that could be undertaken as part of 
this guidance development effort.
    To provide a starting point for discussion, the agency has 
developed a list of some key concepts that the interested parties may 
want to consider at the meeting:
    1. Scope: Should the guidance discuss AS alone, or a broader 
spondyloarthropathy rubric? What about the clinical subgroups and 
pediatric expressions of the disorder(s)?
    2. Claims: What type of claims structure is optimal to encompass 
the types of clinical benefit a therapeutic product might have on 
patients with AS? What type of evidence would be needed to support each 
proposed claim?
    3. Measures of disease activity: Are currently available 
instruments for measuring disease activity adequate or are new measures 
required? Which disease activity should be measured in clinical trials 
in AS, and on what basis: (1) A consensus approach, which aims for 
agreement (clinicians, patients, and others) based on a blend of an 
observer-driven approach and performance characteristics; (2) a 
decision based on the comparative statistical characteristics of each 
measurement using concepts such as random measurement error; or (3) a 
fully data-driven approach where each measurement is tested in a 
standard venue to assess its predictive capacity.
    4. Overall trial design: Are longitudinal comparison of means 
optimal? Because longer trials inevitably have substantial dropouts, 
would a survival analysis be more appropriate?
    5. Intrinsic trial design: Which measures should be included in the 
primary analysis of the clinical trial to assess whether the 
therapeutic product is associated with a clinical benefit? Do all 
measures need equal-weight in the primary analysis? Can they be 
unequally weighted? Is the use of composites justified? Are outcomes of 
secondary endpoints essential for determining the success of the trial?
    Interested persons should submit to the Dockets Management Branch 
(address above) comments and

[[Page 27985]]

expressions of interest in taking a lead in a critical appraisal. Two 
copies of any comments are to be submitted, 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 
are available for public examination in the Dockets Management Branch 
between 9 a.m. and 4 p.m., Monday through Friday.

    Dated: May 11, 2001.
Margaret M. Dotzel,
Associate Commissioner for Policy.
[FR Doc. 01-12625 Filed 5-18-01; 8:45 am]
BILLING CODE 4160-01-S