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No Safe Haven for FDA


By John Russell

July 29, 2010 | The Russell Transcript | Is it time for the U.S. Food and Drug Administration (FDA) to relinquish its role as the sole arbiter of drug efficacy and to focus instead on its original role as the enforcer of safety? Is it even possible for FDA to retain its primacy position in efficacy given today’s crushing economic pressures, advancing technology, and the growing imperative for comparative effectiveness-driven reimbursement (CER)?

This isn’t my idea. It’s an idea that’s percolating in many quarters. I’m not sure if it’s a good idea. There are many downsides but it doesn’t matter. The pharmaceutical industry’s snail paced output can’t sustain the size of the industry’s R&D enterprise. It has to change. CER and powerful tools like next gen sequencing will force biopharma behavior changes and FDA will have to adapt.

Let’s look at the scary numbers (again):

  • In 2009, FDA approved 26 new drugs, precisely one more than in 2008.
  • During the recent recession, perhaps the worst since the Great Depression, U.S. drug companies spent roughly $65 billion (‘09) and $63 billion (‘08) on R&D.
  • “The United States spends over $2.2 trillion on health care each year—almost $8,000 per person. That number represents approximately 16 percent of the total economy and is growing rapidly. If we do not act soon, by 2017, almost 20 percent of the economy—more than $4 trillion—will be spent on health care.”
          —2010 Office of Management and Budget (OMB) report
  • It’s generally conceded that major classes of drugs only work in 30-60% of patients and OMB has estimated that $250-325 billion is spent annually on unwarranted care.
  • Despite adaptive trial approaches, the basic five-year clinical trial paradigm seems unlikely to shorten substantially any time soon.

Off-Label Prescribing and Sequencing

It’s no secret the current system is in trouble. What’s changing is the diminished ability and desire to pay for the status quo. Indeed the American Recovery and Reinvestment Act of 2009 has targeted $1.1 billion to push CER forward. Payers (commercial and government) want to mine more effectively their vast stores of outcomes data for what works and in which sub-populations. The rise of next gen sequencing and the realistic prospect of payers picking up the bill to sequence essentially everyone—perhaps as soon as 3-to-5 years—is a key piece to the puzzle.

One can imagine payers subsidizing real and “virtual” clinical trials for new indications for existing, proven safe compounds by combining outcomes data and sequence data to look for what works and in which sub-populations. Informatics and data mining tools would play a huge role in such activity. Biopharmas certainly want to develop drugs that will be prescribed and paid for and could become partners in that effort, or at a minimum, take more of their direction directly from payers. FDA would lose sway.

No doubt off-label prescribing certainly has dangers and drawbacks and many legal questions. That said, a sizeable portion of oncology drugs are already used in off-label fashion. This “unapproved” use could extend to diagnostic and prognostic testing, as well, such as the K-RAS test for EGFR mutations, which was not FDA approved but which many payers decided to reimburse.

In this case, the test indicates which patients are unlikely to benefit from the drug. It is estimated that between 30-40% of patients with colorectal cancer have a KRAS mutation that would ultimately render them ineligible for EGFR-targeted therapy. Since 2009, the test has been added by FDA to the labels for Vectabix and Erbitux (see, “Amgen’s Personalized Medicine Story,” Bio•IT World April 2008).

The inherent slowness and high cost of clinical trials along with FDA resource constraints imposes seemingly hard limits on the number of drugs that can be moved to market through FDA. Maybe that’s OK or unavoidable for new medical entities (NMEs) but it seems increasingly likely, in order to sustain itself, the pharma industry will be forced to take cues from payer organizations and align more closely with them, jointly undertaking drug discovery and development. An alternative route for drug efficacy determination could emerge.

What the new R&D effort will look like remains unclear and many questions persist around the ownership and use of patient data. But one can imagine a substantial shift of pharma R&D away from chasing elusive NMEs and toward searching for alternative indications for existing compounds. The FDA does an excellent job on many fronts—ensuring safety by and large, for example—but the time to yield ground on determining efficacy may be forced upon it.


This article also appeared in the July-August 2010 issue of Bio-IT World Magazine. Subscriptions are free for qualifying individuals. Apply today.


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