Why Does the FDA Approve Cancer Drugs That Don’t Work?


A new study in JAMA Internal Medicine finds that two-thirds of cancer drugs considered by the US Food and Drug Administration (FDA) over the past five years were approved without evidence that they improve health outcomes or length of life. (This study closely corroborates and acknowledges the findings published last year by John Fauber of The Milwaukee Journal Sentinel and Elbert Chu of MedPage Today.) Follow-up studies showed that 86 percent of the drugs approved with surrogate endpoints (or measures) and more than half (57%) of the cancer drugs approved by the FDA “have unknown effects on overall survival or fail to show gains in survival.” In other words, the authors write, “most cancer drug approvals have not been shown to, or do not, improve clinically relevant end points.”

The use of surrogate endpoints in the approval process is at the heart of this issue. Drug companies argue that these alternative measures permit smaller, cheaper and faster clinical trials, allowing desperately needed drugs to get to market faster. Demonstrating efficacy with “harder” measures like overall survival – whether someone actually lives longer as a result of the drug – is a higher bar that requires more time and resources.

Many drug company representatives argue that the shortcut is not only acceptable but desirable. A 2011 Genentech white paper on oncology endpoints opens with this headline:

“…such surrogate endpoints as objective response rate and progression-free survival have been employed because they can be reached faster and may offer important benefits in evaluating therapies.”

“May offer important benefits” is the operative phrase here. The problem arises when positive surrogate measure performance is not reflected in better health outcomes or longer life. A common example is progression free survival (PFS), a widely-used surrogate measure of how long the tumor remains dormant before beginning to grow again. While many studies of drug performance use PFS to measure impact, there typically is only spotty correlation between longer PFS and health or survival improvements. Surrogate measures can also mask complications that detract from improved results. So, as the FDA data show, positive performance on a surrogate measure may have no bearing on whether the drug works meaningfully for patients, and using surrogate measures may in fact be detrimental to patient care.

Of course, once FDA approval has been achieved, drug companies benefit. There is no discount associated with the compromise of using surrogate measures. The Journal Sentinel/MedPage Today investigation found that drugs approved by the FDA during the study period averaged about $10,000 per month. Four were priced at $20,000 per month and one was $40,000 per month.

This revelation – that most FDA cancer drug approvals lack evidence and don’t work – begs whether the FDA is so deeply influenced by pharma that it has abrogated its mission of ensuring safe, effective drugs for the American people. Some part of the move away from rigor and toward haste can probably also be assigned to trying to accommodate patient advocacy groups, who campaign for rapid new drug development.

Most importantly, the Kim-Prasad article raises hugely important questions of safety, credibility and trust for health care regulators. Even with follow-up, almost 9 of 10 drugs using surrogate endpoints approved by the FDA don’t or haven’t been shown to improve clinical results. FDA approval wrongly conveys that products work when they don’t, greenlighting them for use (to little or no positive effect) by American cancer patients, paid for at exorbitant rates by governmental, corporate and individual purchasers.

This is an epic regulatory failure. An inability to address this would be open acknowledgement that, at least with respect to cancer drugs, the FDA has been fully captured by the interests it is intended to regulate.

Brian Klepper is a health analyst and Principal of Health Value Direct.

Categories: Uncategorized

5 replies »

  1. As a non doctor, if not fully tested why not use regular chemo, which its side effects are well studied and known. There is nothing that enrages the medical establishment like B17 and it became, in their view, as the hallmark of Quackery. The arguments against it: it does not work, if it does it may end up with grave side effects, which have not been investigated. Yet it seems to be okay to quickly approve these new drugs. Please see also a presentation “FDA approves flawed cancer drugs” by Professor Zajieck on youtube.

  2. Paul @ Pivot Consulting,

    If you’ll read the quote from Fauber/Chu article carefully, you’ll note that the subset of 26 drugs in the 2nd part of their study each had at least 2 years of follow-up data, presumably enough time to demonstrate efficacy. In the Kim/Prasad article in JAMA, 86% of the FDA approved drugs either failed in follow-up or were unable to show benefit, even after follow-up studies.

    It is conceivably possible that these drugs could ultimately prove beneficial. It is also possible that these drugs both don’t improve the condition in question and have harmful side effects that seriously detract from quality of life. Part of a regulatory agency’s responsibility is to protect us from these kinds of problems.

    A secondary problem is the FDA’s recently documented failure to ensure follow-up studies on some 30% of surrogate endpoint-based approvals.

    Your argument is for open availability of agents that have not been proven. Perhaps those drugs should be available, but certainly not with the full approval rating that the FDA now provides, and not at the pricing of agents that have demonstrated effectiveness. Finally, because they are effectively experimental, they should not covered by third parties. Using them would then become an arrangement between the patient/end user and the manufacturer, outside the sanctioning and protections that are provided for more proven agents. A policy corollary to this would be that therapeutic treatments of the negative impacts associated with these unsanctioned agents should not be covered under coverages either.

    Hope this clarifies the issue.

    • Good points. I certainly don’t argue for full approval within appropriate validation, and I have not considered the important issue you raise of who pays.

  3. It is a bad thing that so many medical treatments (drugs, surgical etc) are common with no good randomized control trials that show they work.

    However, I think the author overstates the case. Here is a quote from the linked article:
    “only three of those 26 drugs have been proven to increase survival. One increased survival 10 months; one by eight weeks and another increased the three-year survival rate to 70% from 61% compared with those who got a placebo”…..with the other 23 the jury is out….they may turn out to be effective.

    The surrogate measures that allow release include things like tumor size reduction….. If I have a terminal kidney cancer I should have access to these drugs…..as long as my physician prescribes and informs me that these have yet to have RCT validation. To keep these drugs off the market for years….maybe decades…..until we have RCT validation ….as seems to be the suggestion of this piece……is bad policy.

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