The FDA Commissioner Scott Gottlieb, MD, recently tweeted that his agency is winning accolades from cancer docs.
— Scott Gottlieb, M.D. (@SGottliebFDA) June 2, 2017
He was referring to an editorial in The Oncologist by Dr. Bruce Chabner, a cancer researcher, which shoveled praise onto the FDA for its “thoughtful analysis and reinvention of the cancer drug approval process” — which involves speeding up approvals of so-called “breakthrough” therapies based on lower-quality evidence. Meanwhile, the “naysayers,” Chabner writes, “fail to acknowledge the benefits of the vast majority of new drugs that reached market” under the accelerated approval designation. Claiming that the new drugs deliver “life lengthening benefits for so many patients formerly bereft of hope,” Chabner’s praise also comes with lots of dissing for the “highly toxic and modestly effective chemotherapies” that are being replaced with “much more effective targeted therapies and/or intermittent immunotherapies.”
It’s not surprising to see Commissioner Gottlieb, a consummate pharma insider who collected about $145,000 from drug companies in 2016, waxing poetic about the benefits of faster drug approvals. Nor is it unexpected that Chabner, who has spent a career in drug development, would extol the benefits of relaxed FDA standards, which are very good for the drug business. Chabner
strongly suggests that these standards are also good for patients.
But when such pronouncements from authoritative voices substantially misrepresent the true situation for patients and the public, we think it’s time for some corrective mythbusting to bring the conversation back to reality. Here are five claims made in the editorial that simply don’t square with the evidence:
Not really. As Chul Kim of the National Cancer Institute and co-author Dr. Vinay Prasad, (one of the noted “naysayers”) reported in JAMA Internal Medicine: “36 of 54 (67%) cancer drug approvals from 2008 to 2012 were made on the basis of surrogate markers — either tumor response rate or progression-free survival, in about equal frequency. But over a median follow-up period of 4.4 years, only five of those 36 drugs were shown, in randomized studies, to improve overall survival.” Eighteen drugs failed to improve survival and 13 were never tested. There are many reasons why surrogates like progression-free survival may not translate to clinical benefit. Tumors that shrink in one area may progress undetected elsewhere. Drugs that hold tumors back for a period of time may ultimately encourage a more aggressive rebound.
Do you mean “proven effective” by good quality science? If that’s your bar, then a systematic review in the BMJ suggests more of us should be skeptical of the claims of both the FDA commissioner and cancer drug cheerleaders. They found that when novel drugs (including cancer drugs) are approved by the FDA on limited evidence, “few proper studies after approval actually confirmed the original FDA approval indication.” When the approval was based on a surrogate, for example, less than 10 percent of the drugs had a post-approval trial that confirmed a benefit on clinical outcomes (like longer duration of life or quality of life). The upshot? Drug companies have a very strong incentive to get their drugs on the market, at any cost, because they know it’s unlikely anyone will come after them later to prove the drug actually works as claimed.
A previous analysis from the Government Accountability Office found that even when the FDA demanded a post-approval study as a condition of approval of drugs based on surrogate markers, approximately 30 percent of 400 requested studies hadn’t been completed or were terminated. Did the FDA order the companies to take an unproven drug off the market? Nah. The analysis showed that the FDA “has never exercised its authority” to remove those products from the market. (Since the 1970s about three dozen approved drugs have been “voluntarily withdrawn” from the US market due to health risks, typically at the FDA’s request.)
Chabner and the drug industry would like to claim credit for falling cancer mortality that they attribute to faster approval of new drugs. However, the American Cancer Society says cancer rates are falling due mainly to societal changes and better screening. The major contributions are fewer cancers of the lung due to fewer people smoking, better prevention/detection through colon cancer screening, and better treatment of childhood leukemias. The fact that cancer death in children dropped 20 percent from 1999 to 2014 (see image here), due at least in part to new therapies, is certainly worth celebrating. Prostate cancer diagnoses have also dropped, thanks to the recognition of overdiagnosis due to the PSA test, though the levels of prostate cancer deaths (shown by this graph) have barely budged in 30 years.
It’s a comforting thought — the idea that exorbitant drug prices are ultimately going to help fund research on lifesaving new medicines. But a study by Tito Fojo and colleagues in JAMA Otolaryngology – Head & Neck Surgery suggests that expensive new cancer drugs, instead of jump-starting fruitful research as claimed by the drug industry, are actually “stifling progress.” They note that the current approaches are “encouraging enormous expenditures of time, money, and resources on marginal therapeutic indications and promoting a ‘me-too’ mentality that is stifling innovation and creativity.” Instead of setting their sights on the achievement of meaningful outcomes like longer life, researchers are investing in therapies that make a small impact on outcomes like tumor shrinkage that don’t really prove a benefit.
Unfortunately, that hope is often dashed. As Kaiser Health News excellently reported on the experiences of patients: “for every cancer patient who wins the lottery, there are many others who get little to no benefit from the latest drugs.” Only a very small minority of patients have cancers that are potentially treatable with immunotherapy. And only a minority of those potentially treatable cancers will respond to the latest drugs. Moreover, these drugs have harms that are underappreciated, and their high cost can help send patients into bankruptcy.
There is no arguing that new cancer drugs have improved the outlook for some cancer patients very dramatically. But those actual advances, which apply to few, are being leveraged to mislead many more desperate patients who have no hope of being helped. They’re also a tool for the drug industry to maintain an unsustainable status quo on pricing. People with cancer understandably want a shot at treatment that will extend their lives and offers the possibility of a cure. But in many cases we simply don’t know whether the drugs work as claimed. The policies advocated by the drug industry, and embraced by the FDA, will ensure that we never know. This is unethical when the treatments are exorbitantly expensive and can also cause serious harm.
We all have a stake in better drug therapies that can deliver on improvements in quality and quantity of the lives of our citizens. Unfortunately, the apologists for high prices, quick approvals, and “innovation” make up a trifecta that continues to require skeptical analysis.