Stagnation vs. Innovation: FDA's Critical Path Initiative

Americans born in the 1940s marvel at the advances made in modern medicine since their birth. Vaccines, penicillin, antibiotics, CAT scans, the unraveling of the human genome and cancer drugs have led the march of medical progress into the 21st century. And with so many achievements in medicine during the last 70 years, it is not surprising that Americans expect this trend to continue. But such expectations may be unrealistic. The high costs of drug and medical device development are hampering the industry. New drug approvals have flattened in recent years, in spite of statistics that cite expenditures of the public and private sectors in excess of $100 billion for medical research.

Recognizing the disconnect between funding and outcomes, in 2004 the FDA launched the Critical Path Initiative to stimulate and facilitate a national effort to modernize the sciences through which FDA-regulated products are developed, evaluated, and manufactured.

"We all agree that moving candidate products from discovery into the practice of medicine is a long and costly process", says Dr. Rachel Behrman, director of the Office of Critical Path Programs in the office of the FDA commissioner. Dr. Behrman has been in charge of the Critical Path Office since 2004 and has helped spread the Critical Path message about the need for a nationwide effort to build on recent achievements in biomedical research.

"In 2004, we recognized that the tool kit we use for evaluating drug and medical device development is from the last century. Previously, no one was thinking about the shape of the tool kit that underpins drug and device development. It was time to fix the kit", she says, "to update the predictive tools we need and to incorporate our achievements into clinical practice.

We all know that clinical trials have evolved dramatically over the last 30 years", she adds, "We need to rethink our development processes and bring them into the 21st century."

The Challenge of Innovation and Stagnation
The FDA thinks the Critical Path Initiative is the touchstone for bringing these processes forward. The program began in March 2004, with the release of a report entitled: Innovation/Stagnation: Challenge and Opportunity on the Critical Path to New Medical Products []. The report addressed the reasons for the decline in the number of innovative medical products submitted for approval.

The report also called for a modernization of the scientific tools (i.e., computer models, in vitro tests and innovative study designs) used to develop new medical products.The report states that ,"In the FDA's view, the applied sciences needed for medical product development have not kept pace with the tremendous advances in the basic sciences. The new science is not being used to guide the technology development process in the same way that it is accelerating the technology discovery process. For medical technology, performance is measured in terms of product safety and effectiveness. Not enough applied scientific work has been done to create new tools to get fundamentally better answers about how the safety and effectiveness of new products can be demonstrated, in faster time frames, with more certainty, and at lower costs. In many cases, developers have no choice but to use the tools and concepts of the last century to assess this century's candidates. As a result, the vast majority of investigational products that enter clinical trials fail. Often, product development programs must be abandoned after extensive investment of time and resources. This high failure rate drives up costs, and developers are forced to use the profits from a decreasing number of successful products to subsidize a growing number of expensive failures".

Dr. Behrman says the entire landscape of clinical trials has changed.  "Trials are no longer limited to a group of subjects at one site", she says.  "Now trials are conducted globally, on an international scale, with results captured electronically. The entire process is different. Therefore, FDA is working hard to make sure trials are conducted as efficiently and safely as possible."

She says that it's not enough to collect data from a trial's results.  "If something bad happens during the trial, we need treatment questions answered right away. We need to focus on the protection of human subjects in case of adverse events." This is another area the FDA is addressing under the Critical Path Initiative. Dr. Behrman adds that there is a great deal at stake in the development process for developers and for patients.  "What the Critical Path Initiative is doing is tackling issues that cannot be addressed during clinical trials due to the nature of the process, issues like optimal dosing and potential subpopulation-related concerns.

Concerns extend across the medical spectrum. According to FDA's report, the year 2000 marked the beginning of a decline in new drug and biologic submissions to regulatory bodies worldwide. Medical device submissions slowed, too. The result is that fewer new products and treatments are available to patients who need them. It's a losing situation for everyone in product development and for patients who are hoping for cures that haven't materialized.

One solution is industry collaboration. Collaboration is a key component of the Critical Path Initiative. The FDA is working with other federal agencies, patient groups, academic researchers, and industry experts to identify areas for improvement and solutions to product development impediments. More than 40 collaborations and scientific projects were initiated during 2006, and more are in planning.

In March 2006, the FDA published the second of two reports on the Critical Path to medical product development. This Critical Path Opportunities Report and List ( presented 76 specific activities that, if begun, would help modernize the Critical Path sciences. The activities are organized into six key topics:

  • Better Evaluation Tools
  • Streamlining Clinical Trials
  • Harnessing Bioinformatics
  • Moving Manufacturing into the 21st Century
  • Developing Products to Address Urgent Public Health Needs
  • Specific At-Risk Populations ? Pediatrics

The Critical Path Initiative is not limited to science that affects human medical product development. The Initiative has expanded to include all FDA-regulated products."My fascination with the Critical Path Initiative is that it is having a real impact on public health," says Dr. Behrman.  "As a physician, I can't think of anything more important than improving public health."

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