This Article Extract Full Text (PDF) Purchase Article View Shopping Cart Alert me when this article is cited Alert me if a correction is posted Services Email this article to a colleague Similar articles in this journal Alert me to new issues of the journal Download to citation manager Rights & Permissions Citing Articles Citing Articles via Google Scholar Google Scholar Search for Related Content

An Interview With Richard Pazdur, MD

RP: We've continued many projects initiated earlier. These include workshops conducted with ASCO, the AACR [American Association for Cancer Research] and the ASH [American Society of Hematology] examining end points used in regulatory trials. These workshops examine end points that can potentially be used for drug approvals. In addition, a workshop goal is to identify areas where further clinical development is needed for validation of future end points. In the past, the FDA has conducted workshops on lung, prostate, and colorectal cancers. This year, we had workshops on brain tumors and acute leukemia. A workshop on ovarian cancer is slated for the spring. These workshops serve as a forum for discussion of measurements of clinical benefit. The resulting recommendations are communicated to the ODAC [Oncology Drug Advisory Committee], which can then advise the FDA.The new office has also begun regular meetings with the European Medicines Agency [EMEA], our counterpart in Europe. These activities include exchange of staff for meetings, exchange of guidances under development, and discussion of protocols and pending regulatory decisions. We have monthly teleconferences with this regulatory agency and also conduct a regulatory workshop during the annual ASCO meeting for drug regulators from Europe, Australia, Canada, and Japan.The office has made a concerted effort to work with companies on expanding patient access to promising unapproved agents for which NDAs [new drug applications] have been filed.

JOP: Have any expanded access programs been implemented?

RP: Yes. Many sponsors have initiated expanded access trials, called "treatment INDs [investigational new drugs]," to bridge the timing of the submission of a potentially successful application to its actual approval. These programs have availed promising drugs to thousands of patients. We have encouraged sponsors to collaborate with the OSHI [Office of Special Health Issues] and our Office of Oncology Drug Products to coordinate these expanded access protocols. In addition to treatment INDs, our office continues to support single-patient INDs and single-patient exemptions to ongoing clinical trials. These efforts bring investigational drugs to individual patients.

JOP: What new steps have been taken to speed evaluation of new drugs and technologies?

RP: Most promising oncology applications are reviewed as "priority reviews" within a 6-month review time. Frequently, these priority applications are completed before this 6-month deadline. Significant changes to expedite the evaluation of new drugs and technologies will probably be accomplished through a greater scientific understanding of oncology diseases and the mechanism of action of our drugs.The Oncology Biomarker Qualification Initiative, a collaboration between FDA, NCI, and CMS [the Centers for Medicare & Medicaid Services] announced this year, will assist in developing and evaluating biomarkers. These biomarkers may serve not only as potential clinical trial end points, but also as tools to select patients who may preferentially benefit from a therapy. Frequently, we observe modest response rates or minimal improvements in time-to-event end points, such as time to progression or survival, in conventionally defined histological categories, such as lung cancer or colon cancer. With biomarkers, we may identify populations within these categories who may be more likely to respond to a therapy. Hence, a larger therapeutic effect would be observed in a smaller population. If a therapy could target a population likely to respond, patients who have little or no likelihood of responding would not be subject to an ineffective therapy and could be directed to other therapeutic alternatives.Our office has also been active in the Critical Pathway Initiative, identifying and examining projects with our external stakeholders to expedite drug development. A recent example of this is a project examining FDG-PET [fluorodeoxyglucose–positron emission tomography] scanning in evaluating lymphoma therapy.

JOP: One of the missions of your office is to collaborate with other agencies. How are you collaborating with the NCI?

RP: The Office of Oncology Drug Products has a close professional relationship with the NCI to develop oncology therapeutics. A monthly meeting with the NCI examines specific drugs being developed by the NCI and reviews general regulatory issues. These meetings include collaboration with NCI investigators in the cancer therapeutic and prevention divisions. We work with the NCI to avoid unnecessary delays in reviewing protocols. Our end points meetings ... have included NCI representatives. These meetings also assist the NCI in identifying areas of future clinical research.

JOP: What initiatives or programs will your office undertake in the coming year?

RP: As I said, one major effort of our office will be to work closely with FDA's Critical Path Initiative. This initiative aims to identify and prioritize the most pressing medical product development problems and the greatest opportunities for rapid improvement in public health. The agency has realized that to reduce the time and resources expended during early drug development on candidate drugs that are unlikely to succeed, we need tools to distinguish those candidate drugs that hold promise from those that do not earlier in the drug development process. In oncology, this initiative will examine opportunities to improve the methods of evaluation of our therapies, including imaging projects, and methods to improve new and existing therapies, including biomarker utilization in clinical trials.We are also committed to expediting pediatric oncology drug development. Our office has instituted regular meetings of a pediatric subcommittee of ODAC to discuss and evaluate challenges of pediatric oncology drug development.From an internal FDA perspective, the office has organized regular meetings of representatives from other FDA centers, including the CDRH [Center for Devices and Radiological Health] and the Center for Biologics Evaluation and Research [CBER]. Since many drug development plans include the use of a biomarker diagnostic tool, these interactions between the FDA centers are clearly a priority of our office. These meetings attempt to ensure consistent regulatory advice within CDER and throughout the other FDA centers in the development of oncology therapeutics.

JOP: Are there opportunities for ASCO to partner with the FDA in accomplishing these initiatives?

RP: Yes. Since my arrival here at the FDA nearly 7 years ago, I have been committed to working with our external stakeholders, including ASCO, AACR, ASH, other professional groups, patient groups, and academic centers. Our previously mentioned end point project is a prime example of this interaction. Recently, we participated in a workshop conducted by ASCO and the National Coalition for Cancer Survivorship [NCCS] examining expanded access programs. Our office has had and plans to continue to present regulatory programs at both the ASCO and AACR Annual Meetings. In addition, the FDA oncology review staff has participated in numerous ASCO-sponsored workshops on drug development. Collaboration with all professional societies and academic investigators ensure that new regulatory principles are optimally developed. These interactions provide a forum to inform the American public of our regulatory decision-making process.

JOP: What do you foresee in the more distant future for development of cancer therapeutics?

RP: True advances will occur with a more thorough understanding of the oncology disease process and how therapeutics interact with these processes. We need a marriage between drug development and our understanding of carcinogenesis and cancer progression. Traditional pharmaceutical companies have a great deal of expertise in developing drugs, but not necessarily at initiating and fostering an understanding of the molecular basis of our diseases. This approach will occur most effectively with the collaboration between small and large pharmaceutical and biotechnology companies, government agencies—including FDA, CMS, and NCI—academic investigators, and patient groups. No matter how technologically sophisticated we may become, we must ultimately translate these findings to a benefit to cancer patients by improving the quality of life.

	Notes

 
Richard Pazdur, MD, was appointed in April 2005 to lead the new Office of Oncology Drug Products within the Center for Drug Evaluation and Research (CDER) at the U.S. Food and Drug Administration (FDA). The office consolidates review of most FDA oncology- and hematology-related drugs, biologics, and imaging; coordinates oncology activities across the FDA; and ensures outreach and collaboration between the FDA, the National Cancer Institute (NCI), and other cancer-related organizations, including ASCO. JOP spoke with Dr. Pazdur about the new office's accomplishments in the last year and his vision for the future.

This Article Extract Full Text (PDF) Purchase Article View Shopping Cart Alert me when this article is cited Alert me if a correction is posted Services Email this article to a colleague Similar articles in this journal Alert me to new issues of the journal Download to citation manager Rights & Permissions Citing Articles Citing Articles via Google Scholar Google Scholar Search for Related Content