If you skip to the very end to see their conclusion: “In the next few years, evidence will accumulate to indicate how well the new breakthrough-therapy designation improves the options of patients with serious and intractable diseases and to what extent it facilitates the market entry of treatments that promise more than they can deliver.”—then you’d guess that they are pretty wishy-washy about the new category of “breakthrough therapy” that Congress enacted in 2012. A close reading shows that you’d be wrong; if you check out all the fine print you’ll see that the authors are very negative about this new FDA category aimed at hastening new drug approval.
Why the negativity? The points they make are:
- There’s really no good evidence that currently, patients suffer as a result of slow FDA approvals. FDA approval times are steadily decreasing.
- There’s some evidence at least that unsafe drugs are getting onto the market because of current FDA approval practices. The authors mention among other examples the leukemia drug, ponatinib, approved on an accelerated basis in 2012, then temporarily suspended in 2013 when it was shown that nearly half of patients on the drug followed for 2.7 years developed serious blood-clotting events like heart attacks and strokes.
- Before Congress enacted this new “breakthrough” category, there were already several pathways for “fast track” approvals.
- In the first year after the “breakthrough” category was approved, the FDA received 92 new drug applications for this designation. As I noted in HOOKED and previously on this blog, in recent years, sober appraisals of new drugs have shown repeatedly that no more than a small percentage of new drugs qualify as significant advances over existing therapies. If this many drugs are seeking approval under the new designation, it is certainly being used for drugs that aren’t “breakthroughs” in any meaningful sense of the term. (The FDA approved only 27 of those applications.)
- We’ve seen many times here how a good way to approve a useless or a harmful drug is to look only at surrogate endpoints and not at meaningful patient outcomes. Under previous rules, a drug had to show activity first against a “well-established surrogate endpoint,” and then later, it was all right to address a “less-than-well-established surrogate endpoint,” whatever that is. Apparently even that was not loosey-goosey enough for Pharma, so this “breakthrough” category allows approval based on “an effect on a pharmacodynamic biomarker(s) that does not meet criteria for an acceptable surrogate endpoint, but strongly suggests the potential for a clinically meaningful effect on the underlying disease.” (And here I would have thought that would be the definition for an “acceptable surrogate endpoint”—shows how much I know.)
When the industry lobbies for a slicker greased pathway through FDA approval, it never comes to Congress by itself; it always comes along with “consumer” lobbyists supposedly representing patients desperate for cures. We’ve also seen numerous times how often those “consumer” groups are actually bankrolled by Pharma, so that pretty much disposes of that argument—but Congress laps it up nonetheless.
I explained in HOOKED how back around 1972, some brilliant Pharma lackey invented the “drug lag,” the claim that people were dying like flies in the U.S. because wonder drugs approved years ago in Europe were being held up by a stodgy, unresponsive FDA. I there compared the “drug lag” to John F. Kennedy’s famous “missile gap.” There are two analogies. One, the “lag” and the “gap” both turned out on investigation to be purely mythical. Two, once given voice, they refused to die, no matter how much proof was amassed on the other side. And so today we still operate under the myth that the FDA is too slow to approve marvelous new wonder drugs and somehow we have to speed up the process. Or at least Congress operates under that myth when huge piles of Pharma lobbying cash are spread around along with it.