Since issuing its Critical Path white paper in 2004, FDA has helped form numerous public-private partnerships (PPPs) with
industry, academia, patient groups, and other government agencies. These collaborations support research on new biomarkers,
disease models, data analysis methods, and data tracking systems such as FDA's Sentinel network. The aim of these partnerships
is to modernize FDA's research standards and approval criteria.
Biomarkers under study
In addition, CPI is updating clinical research methods. The Clinical Trials Transformation Initiative (CTTI), a collaboration
involving FDA, Duke University, and other partners, seeks to establish national standards for research functions, new review
models for multi-site trials, accreditation programs for investigators and sites, and improved data management systems.
Janet Woodcock, director of the Center for Drug Evaluation and Research (CDER), says it's time to shift CPI from concept to
implementation. The goal is to replicate the massive investment in research and flexible regulatory approaches that stemmed
the tide of the AIDS epidemic 20 years ago. That effort produced new surrogate markers and accelerated approval processes
to spur development of new treatments, recalls Mark Harrington of the Treatment Action Group. Yet that achievement was an
exception, and has not been extended to research and regulation for treatment of other infectious diseases.
Establishing those initial PPPs took months of negotiations involving data standards, information sharing, access to results,
and protection of proprietary information. Lawyers had to work out approaches for dealing with conflicts of interest and intellectual
property protections, as well as ensuring that collaborative groups complied with federal statutes. Neutral third parties—such
as the Critical Path Institute in Arizona and the National Institutes of Health [see sidebar]—provided venues for creating
partnerships that meet legal and technical requirements.
The good news is that better biomarkers and clinical trial methods may yield new treatments. An FDA initiative, the Analgesic
Clinical Trials Project (ACTP), aims to spur R&D on novel painkillers by developing new efficacy endpoints, and by evaluating
innovative study designs likely to improve the success rate of clinical studies for these products. Bob Rappaport, director
of CDER's Division of Anesthesia, Analgesia and Rheumatology Products, has received internal funding to re-analyze data from
failed analgesic trials to assess ways to maintain study sensitivity and to explore high placebo response rates. A broader
PPP will expand the scope of the project to address analgesic use in preventing chronic post-surgical pain.
Novartis scientists are hopeful that new biomarkers for detecting liver damage from drugs could lead to market approval for
its Cox-2 inhibitor Prexige. The drug is highly effective but has an "Achilles heel" of severe hepatoxicity in certain patients,
explained Timothy Wright, head of translational science at Novartis, at a September DIA workshop on CPI. Last year, FDA rejected
the drug, calling for additional safety data. A genetic marker that identifies patients most likely to develop liver damage
from the drug might warrant additional clinical trials to support approval, Wright suggested.
FDA has advanced these efforts to link postmarket adverse events back to clinical trials, establish biomarker data warehouses,
build a knowledge base of product quality, and establish a bioinformatics platform for data standards—all with just a $20
million investment in CPI, Woodcock points out. The agency's goal over the next five years is to obtain sufficient resources
to build on this expanded understanding of disease and pharmacology to ensure product quality and safety.
"Drug development tomorrow will not look like drug development today," Woodcock predicts.
Jill Wechsler is Pharmaceutical Executive's Washington correspondent. She can be reached at