By Mark Thornton
On Tuesday, President Barack Obama announced a massive initiative against cancer. “Our recovery plan will launch a new effort to conquer a disease that has touched nearly every American, including me,” he said in his speech to the nation, “by seeking a cure for cancer in our time.”
Specifically, the president was referring to a provision in his stimulus bill that will direct a tranche of funding to the National Cancer Institute (NCI). The money will come from the $10 billion that’s being steered to the National Institutes of Health, and it will, for the next two years, match the surge in spending on cancer that occurred between 1999 and 2003.
But despite the lofty goal set by Mr. Obama, it appears that the NCI is not mapping out a specific plan or strategy on how to most effectively use its new money. It is simply going to pour more money into the cancer research community.
Before that is allowed to happen, however, it is essential that we assess what happened the last time the NCI was entrusted with a spending surge — and what can be done this time to produce a better outcome.
In 1998, a new day was dawning in cancer research. The genomic codes of cancer were being broken, and an explosion of new vulnerabilities was being discovered that had the potential to reveal hundreds of new “drugable” targets. The hope then was that this would quickly produce a cure.
A wave of newly minted cancer-patient advocates, having learned lessons from the AIDS activists of the 1980s, scored a major victory in 1998 with a massive march on Washington that forced Congress to increase NCI’s funding by 100%. The dream was that this dramatic funding increase would break the back of cancer.
It didn’t. Now that the money has disappeared, the diagnosis of cancer is no less fearful in 2009 than it was in 1999. I recall having a conversation on this topic in 2005 with one leader of the march. She lamented that the billions Congress gave at her prodding to the cancer research community “seems to have gone down a thousand rat holes.”
Her point was that although a mini-explosion of research occurred during the 1999-2003 surge, she couldn’t point to a single meaningful accomplishment from the expenditure that had reduced the number of people killed by cancer.
More optimistically, I would today cite others who say this period led to a great ocean of fascinating discoveries that have the potential to make progress. But this ocean seems to be dammed up at one critical choke point — the inability to quickly perform the clinical trials necessary to determine whether cures that work in test tubes will also work in humans.
Clinical trials in oncology today are a painfully slow enterprise, testing the ability of a new therapy to keep a cancer patient alive longer than the comparative standard of care. Trials are necessary, but can they be done more quickly while also providing the same standard of safety and efficacy we have now? Is there a single nut that a single surge of new funding could crack to make dramatic progress against this foe?
The answer to these questions comes to us from a Brookings Institution conference on the subject held last September. One of the guests was former Food and Drug Administration Commissioner David Kessler. He honed in on the single greatest obstacle blocking a potential flood of progress, comparing where we are now in the fight against cancer to where we were in the fight against AIDS in the 1990s.
AIDS research was then at a crossroads. Much was known about the disease, but the clinical-trials process was agonizingly long, as studies into the survival rate of patients taking experimental drugs dragged on.
Dr. Kessler personally led the charge to streamline AIDS drugs approvals through the “validation” of new “surrogate endpoints” that evolved to test promising new AIDS drugs. One such “surrogate” for a prolonged trial was a blood test that measured the amount of HIV virus. The theory here is that if the virus count was down because of a new drug, it was possible to validate the finding that the patient would live longer.
A change in a simple blood test thus replaced a process that involved waiting years to see if an AIDS patient lived longer from a new drug. The law allows the FDA to use surrogate endpoints when evaluating drugs for approval for use against life-threatening diseases, if those end points have demonstrated eventual clinical benefit.
At the Brookings conference, Dr. Kessler and the cancer experts proposed using “progression-free survival” (PFS) as a surrogate endpoint for cancer clinical trials. PFS is not a blood test. It measures the progression of the disease in a patient receiving an experimental therapy. It helps determine whether a cancer has slowed down in response to treatment.
By measuring time to progression rather than time to death, oncology clinical trials would take months instead of years. Indeed, Dr. Kessler commented that if he were FDA commissioner today he would sit all parties down, develop an encompassing national plan, and promise political “cover” from the same naysayers who said a universal surrogate endpoint was impossible for new AIDS therapies.
Dr. Kessler’s proposal deserves attention and action by whoever becomes the next FDA commissioner. But acting on the proposal would take political courage and money. That gets us back to President Obama. Streamlining cancer clinical trials would be a perfect use for some of the money he is directing to the NCI.
Let’s learn from our recent history, and use the gift to the NCI wisely. By all means, increase funding for academic cancer research. But let us also focus resources and energy on breaking the single biggest obstacle that holds back real progress. Funding a national effort to fully validate PFS as a universal FDA approval standard across all cancer drug trials needs to be a high priority use of the NCI monies now available.
If the dam holding back rapid clinical trials can be broken, there will be new hope of having, in our lifetimes, new drugs speeding toward a cure for cancer, or at least for slowing down death from this disease. We will have only ourselves to blame if, in 2015, we stare at our No. 1 killer and look back incredulously on the surge of 2010-2012 to wonder where all that money went.
Dr. Thornton served six years as a medical officer at the Food and Drug Administration and is the president of the Sarcoma Foundation of America. He is also employed in the biotechnology industry.