·  Legal News, Analysis, & Commentary


Are Surrogate Markers Too Low a Bar for FDA Approval?

— October 31, 2014

The recent approval of a drug for use in combating leukemia by the US Food and Drug Administration has shed light on the relatively controversial, albeit common practice by that organization of using surrogate markers of efficacy for determining the benefit of a given drug or therapy.  Some believe this constitutes a low bar for FDA approval.

According to, “The drug caused severe reactions in the brain and nervous system, and a small clinical trial found that in more than 75% of children it did not produce the desired response. … Indeed, there was no proof that the drug, Arranon, kept children or adults alive any longer or that it improved their quality of life.”

This leukemia drug, Arranon, originally approved for other uses in 2005, was approved for leukemia last year based on “a surrogate measure, contingent on a follow-up study to determine if it improved survival.  But nine years after its approval, that study by manufacturer GlaxoSmithKline is not complete. Results are not expected until the end of 2016.” (Medpagetoday)

To be clear, this drug was approved using secondary (surrogate) markers – the FDA did not evaluate whether or not patients lived longer after using these compounds, or that the spread of tumors slowed.  This is understandable, for data on longevity was unavailable for Arranon, and standing in the way of a potentially helpful drug would be reprehensible, if not a breaking of the hippocratic oath – as long as the drug in question is safe.

As I noted, the use of surrogate markers in the approval of drugs is common.  Heart drugs are sometimes approved based on data that shows their use lowers lipid levels (rather than use decreases the rate of adverse cardiac events), and diabetes drugs have been approved for lowering blood sugar, rather than upon end-game markers of decreases in amputations and heart attacks.

This presents a dilemma: Should a drug be approved if it hasn’t been shown to address fundamental and important consequences of a disease?  Maybe.  If sufficient research demonstrates a drug is safe – that is, free of unreasonable side effects and does not exacerbate a pre-existing condition, and effective in combating an aspect of a disease, I believe it should be approved.

Heart disease drugs approved for lowering lipid levels but not for decreasing absolute heart attack risk on their own can be a part of a patient’s therapy, the same goes for the above-described diabetes and leukemia drugs.  With proper patient consent, safe drugs that have some efficacy should be administered in cases of last resort.  While the FDA is obligated not to approve dangerous drugs and maintain public safety as its first priority, it is important that doctors be allowed to provide patients with the full range of drugs and therapies that can provide relief for any given condition.

Join the conversation!