WASHINGTON, D.C.-A report recently released by the Association of American Medical Colleges (AAMC; www.aamc.org), in cooperation with the Food and Drug Administration (FDA; www.fda.gov), calls for new and increased collaboration among pharmaceutical companies, academia, and regulators to help overcome obstacles to developing innovative diagnostics and therapeutics.

Citing a decline since 1996 in the introduction of novel drugs, even in the face of increased drug discovery funding by the biopharmaceutical industry, the report concurs with a recent FDA white paper that acknowledges that many processes in product development are inefficient, redundant and costly.

The report, a summary of findings from a two-day conference held earlier this year and involving leading researchers and executives from industry, academia, and the National Institutes of Health, cites a fundamental problem in drug development is “a lack of sufficient understanding of the complexities and diversity of whole animal and human biological systems and their relation to disease mechanisms; that is, to the initiation and maintenance of diseases.”

Specifically, the report says that “it is increasingly recognized that many animal models do not predict human biology with enough accuracy to define the balance of benefit and risk of a potential therapeutic agent….far more valuable would be validation of responses in humans, or…better understanding of the limits of extrapolation of the animal models to human studies.”

Other issues that hinder drug validation, as cited by conference attendees:

• An inadequate number of physician and veterinary scientists with significant understanding of human diseases and drug interventions are being trained to lead research initiatives. “Overcoming the hurdles in drug development requires substantial judgment and expertise, particularly for researchers conducting early clinical studies in man,” the report says.
• Genomic targets that fail to deliver: “A huge amount of potential genomic information is being captured by the pharmaceutical industry, but much of that is for product profiling during development and occurs before there is a successful product. There is a great need to expand the number and diversity of carefully phenotyped populations in order fully to realize the promise of the human genome project.”
• New target platform technology development is stagnant “largely because venture capitalists no longer are interested in funding such research,” thanks in part to “lack of confirmation that past large investments…have fundamentally improved the selection of drug candidates that become successful drugs.”
• Some pharmaceutical R&D programs focus on quantity vs. quality and “companies count the number of new targets introduced per year rather than the quality of the targets identified. Moreover, target selection is often driven by the size of the potential commercial market instead of the strength of scientific evidence that demonstrates the ability of the target to impact disease.”

The report’s participants then identified several immediate opportunities for enhanced collaboration among industry, academia and regulatory agencies, including:

• Developing mechanisms that facilitate learning from failed drug tests;
• Creating collaborative systems that enable sharing of toxicology data across the industry and FDA;
• Establishing joint models for biomarker validation;
• Establishing a consortium to analyze and learn from failed clinical trials;
• Identifying, and proposing to Congress, new regulatory incentive policies for small-market drugs;
• Developing model agreements for sharing information now restricted as intellectual property or proprietary.

According to Dr. David Korn, senior vice president of AAMC’s Division of Biomedical and Health Sciences Research, “By seizing the opportunities identified in the report, with the repeated emphasis on the need to facilitate more collaborative research among FDA, NIH, industry and academic medicine, we can accelerate the rate at which scientific discoveries give rise to novel products that improve the health of the public.”

A complete copy of the report can be found at: www.aamc.org/publications.