2004N-0181 - Critical Path Initiative; Establishment of Docket
FDA Comment Number : EC13
Submitter : Dr. Robert Beall Date & Time: 08/02/2004 06:08:41
Organization : Cystic Fibrosis Foundation
Consumer Group
Category :
Issue Areas/Comments
GENERAL
GENERAL
CF Foundation Submission - Part 2 of 3, also see Part 1 and attachment

Clinical Trial Design
The CF Foundation believes the product development process must be revitalized with ingenuity and innovation if we are to cure this disease. To facilitate this, in 1998 we established a network for clinical trials, called the Therapeutics Development Network (TDN), specifically to work with industry to pursue new treatments for CF. The network, which links key CF clinical research centers with a centralized coordinating center, is a critical enticement for industry to focus on CF, as its leaders provide expert advice on trial design and its very structure facilitates patient recruitment. Expanded twice, the network now includes 18 centers across the country. The network also features centralized data management and analysis and a coordinated system of data safety monitoring with disease-specific expertise for protection of patients. Since the launch of the TDN, nearly thirty clinical trials have been completed or are underway. Any of these products in clinical trials could have a major impact on the disease or provide an ultimate cure.

The CF Foundation, with its active research community and Therapeutics Development Network Coordinating Center, champions efficient clinical trial design, and identification of appropriate endpoints for effective trials in CF. Determining proper endpoints is a critical decision in product development. The FDA must make a concerted effort to meet with development teams to identify and accept more appropriate clinical endpoints. These endpoints can make all the difference in product development.

We encourage the FDA to meet with the CF Foundation to reach early agreement on trial design and develop consensus on appropriate biomarkers and surrogate endpoints that are most promising for CF, and to replicate this outreach with other nonprofit research organizations. The FDA's acceptance of such endpoints could reduce the risk of failure in late stage trials by bringing greater certainty to the process sooner, as well as minimizing the number of patients required for trial participation. The FDA must clearly identify its standards for accepting clinically relevant endpoints that have been recommended by leading researchers, clinicians, and disease advocates.

In the case of products that may affect the lung functioning of people with CF, FDA should accept results from imaging tests to measure progress toward a trial endpoint. New imaging techniques can help to identify potentially important changes in lung architecture, a leading indicator that the product will positively affect lung function. Imaging is particularly important for pediatric trials where typical measures of improved lung function using pulmonary function tests are not obtainable. If a trial must show improved organ function as the endpoint, drug development could be stymied.

For orphan diseases, the number of patients required for clinical trials make it imperative to perform some trials overseas. We encourage the FDA to accept more clinical trial data from outside the U.S., including Europe. Increasing international harmonization on safeguards, processes and data collection for clinical trials is critical for efficient, timely drug approval, particularly for orphan diseases.

End part 2, see part 3