Notice Number: NOT-HL-06-132

Key Dates
Release Date: July 13, 2006
Response Date: August 14, 2006

Issued by
The National Heart, Lung, and Blood Institute (NHLBI), (http://www.nhlbi.nih.gov/)
U.S. Food and Drug Administration (FDA), (http://www.fda.gov/)

The NHLBI, in cooperation with the FDA under its Critical Path Initiative (http://www.fda.gov/oc/initiatives/criticalpath/), is soliciting comments from pharmaceutical companies, as well as academic investigators, biotechnology firms, and other health research-oriented organizations, regarding the value, design, feasibility, and operation of a possible study of subjects with chronic obstructive pulmonary disease (COPD) intended to (1) identify pathogenetically homogeneous subpopulations of subjects with COPD on the basis of their genomic, genetic, biomarker, and radiographic characteristics; and (2) identify and validate intermediate outcome measures for use in future clinical trials.

Background

COPD affects approximately 15 million people in the U.S. and is now the fourth leading cause of death.  There is no cure, and treatments are only moderately effective at relieving symptoms.  Many novel treatments have been proposed, based on advances in pathogenetic research, but few clinical trials are currently being performed.  This is mainly due to the large sample size and long duration required for clinical trials in COPD as a result of:  (1) the heterogeneity of the disease, possibly indicating the operation of different pathogenetic mechanisms in different patients; and (2) the absence of validated and responsive outcome measures that can be evaluated in studies of reasonable size and duration. 

To overcome these barriers, the NHLBI is considering a plan to obtain phenotypic data appropriate for the identification of subpopulations and intermediate outcome measures in COPD.  It is anticipated that this research program will involve analysis of the following data from several thousand subjects with COPD: (1) baseline characterization by historical, clinical, physiological, biomarker, CT radiological, genomic, and genetic examinations; (2) follow-up measurements of CT images, biomarkers, and gene expression profiles, possibly at 1 year after enrollment; and (3) long-term follow-up over 3 or more years using conventional measures of COPD progression (rate of decline in FEV1, exacerbation frequency, decline in quality of life, and mortality).  Putative subpopulations will be identified by cross-sectional analysis of the radiological, biomarker, genomic, and genetic data obtained at baseline.  Measures with spontaneous changes over 1 year that correlate with long-term outcomes will be identified as possible intermediate outcome measures.  Data collected through this program will be made available to qualified investigators for additional analyses in accordance with the NHLBI Policy for Distribution of Data (see http://www.nhlbi.nih.gov/resources/deca/policy_new.htm).

Information Requested

The NHLBI and FDA solicit general comments regarding the significance, approach, and utility of the research study described above.  Specifically, we seek answers to any or all of the following questions:

1. Would a study similar to that described above yield information that would be of significant value for improving the efficiency of future clinical trials in COPD?  What study design would be optimal?  What sample size is needed?
   
   
2. Would it be feasible to obtain data for this study from control subjects of future clinical trials that voluntarily conform to a uniform protocol for subject characterization and follow-up?  Are trials anticipated in subjects with COPD which could perform extensive subject characterization and long-term follow-up and contribute appropriate data and specimens to this program?
   
   
3. Describe the personnel, facilities, and organization that would be required to carry out this program.  Would there be a need for an advisory panel; a network of clinical centers; a data coordinating center; centralized laboratories for biomarker, genomic, and genetic assays; and core centers for the analyses of CT image, genomic, and genetypic data?  Comment on the availability and costs of these resources and services.

Responses

This request for information is for planning purposes only and shall not be construed as a solicitation for applications or as an obligation on the part of the government.  The government will not pay for the preparation of any information submitted or for the government’s use of that information. 

Please send comments (and include the Notice number HL-06-132 in the subject line) to [email protected] by August 14, 2006.  Responses may also be sent by letter or FAX to the following address:

Tom Croxton, Ph.D., M.D.
Two Rockledge Centre, Room 10208
6701 Rockledge Drive
Bethesda, MD  20892-7952
Telephone: (301) 435-0202
FAX: (301) 480-3557
Email: [email protected]

Acknowledgement of receipt of responses will not be made, nor will respondents be notified of the government’s assessment of the information received.  No basis for claims against the government shall arise as a result of response to this request for information, or in the government’s use of such information as either part of our evaluation process or in developing specifications for any subsequent announcement.  Responses will be held in a confidential manner, but the general content of responses may be shared anonymously with the NHLBI Board of Extramural Advisors and the NHLBI Advisory Council.  Any proprietary information should be so marked.