Some may remember when Zerhouni, prior to his time served at Sanofi, directed the NIH. There are some rumors that he may yet be recruited back to that same job (if Peter Thiel's efforts are thwarted—taking the path Thiel has proposed would be akin to taking Ron Johnson and putting him in charge of a bank; I think the results of that approach can be seen in the near death spiral that Johnson put JCPenney's into).

In any case, Zerhouni has an observation that some of us have been noting for many years. Not all acquisitions should be integrated into a parent pharmaceutical company, and not all promising pharma start-up have value as acquisitions.

Dylan Distasio writes:

Tangentially, Thiel's pick of Jim O'Neill would be one of the best things ever to happen at the FDA. I, for one, am hoping Thiel's efforts are NOT thwarted!

If O'Neill was able to successfully roll back the Kefauver Harris Amendment to the Food, Drug, and Cosmetics Act of 1938, my assertion is that we could get back to a cheaper, quicker NDA process that would benefit everyone outside of power hungry government bean counters. IMO, efficacy should have never been added as a requirement to the drug testing and approval process. Getting rid of it could potentially usher in a golden age of treatment options and save many lives in the process.

David Lillienfeld responds: 

1. It is impossible to assess safety information in the absence of efficacy data.

2. In the absence of randomized trials, implemented principally to meet K-H Amend requirements, many adverse events due to the underlying disease would likely have been attributed to the drug with the result being a lack of use by the medical community and a withdrawal from the market.

The best example of the need for K-H Amend is laetrile. Wonderful drug. No efficacy. Lots of toxicity. Lots of criticism of FDA (for more than two decades that I'm aware of) for not allowing the drug on the US market and consigning hundreds (if not thousands) of patients to certain death. The laetrile hastened the deaths of many, and there is no data to suggest any benefit. (I'll leave aside the oral contraceptive story—1st and 2nd generations. Or clozapine.)—I've got other examples for off-list discussion.

I have all sorts of problems with the spontaneous reporting system institutionalized by KH Amend. But the need to show efficacy I don't quarrel with. You would be absolutely shocked to see what would have been unloaded into the marketplace in the absence of a need to demonstrate efficacy. I might not like the cost of the new HepC drugs, but they are cost-effective—they do cure HepC. Compare that with Panalba.

 The notion that you would have an outpouring of new drugs in the absence of the FDA is a myth. One of the biggest problems that we have in the US is that de facto cutbacks at the NIH and CDC have not only reduced the R&D workforce available to the US pharmaceutical industry (limiting its ability to produce the drugs need to address today's unmet medical needs) but also the lack of understanding of the pathophysiology of diseases. That's the single biggest problem, for instance, with Alzheimer's, Parkinson's (which is no longer just a movement disorder), and sepsis. There have been lots of drugs for sepsis put forward. Only one was allowed onto the market, with lots of concerns registered within FDA and by the medical community. While efficacy wasn't great, FDA argued that there was nothing else available that held any potential benefit approaching this drug's. The drug was a commercial flop and Lilly subsequently withdrew it from the market. Or aerosolized insulin—but that's a pretty involved story.

Alternative stories in which drugs that might otherwise never have made it to market in the absence of the FDA are Tracleer and thalidomide. (Yes, FDA facilitated re-introducing it back in 2000.)

I suggest looking into the history of the Biologicals Control Act (see my paper: The first pharmacoepidemiologic investigations: national drug safety policy in the United States, 1901-1902. Perspectives Biology Medicine 2008; 51:188-98) for an example where the industry begged for the FDA (actually its predecessor—see the paper) to implement regulations to assure the public of the safety of its nostrums.

If you prefer, you might think of it in terms of surgeries. Was every CABG in the 1970s and 1980s (and 1990s, for that matter) efficacious? No; there's pretty good data that single and double were not beneficial and probably resulted in lots of deaths, and not a small number of strokes (~5%). There are lots of other surgical examples, whether they be radical mastectomies (vs simple mastectomies), internal-external carotid bypasses, and some forms of bariatric surgery just as starters. Just because some surgeon figured out a way to cut doesn't mean it was beneficial to the patient, and it's not as though the surgery is without its own risk.Substitute therapeutics for surgical procedures, and one gets the same result. I've been offered surgical procedures many times that I have declined in the absence of data indicating that it was efficacious.

My father (chair of epidemiology at Johns Hopkins) declined to have a triple CABG until the data indicated that there was a benefit at least commensurate with the stroke risk (did you know that when the Cleveland Clinic first started CABGs, the post-op ICU was nicknamed "the stroke ward"?), never mind death.

There are lots of issues present at FDA, especially on the food side. But the notion that FDA is the reason why more life-changing drugs haven't ben introduced in the US is more a case of political philosophy trumping scientific data in the presence of asymmetry of information (Ackerlof's lemons come to mind). The biggest challenge in getting more drugs to market in the US has been the slowness in the development of our understanding of how disease happens. The NIH funded the work that indicated there may be a role for statins—the work on the HMG receptor. The industry took the risks in discovering and developing statins, not the NIH. But in having the NIH budget as a political football, the creation of new drugs has been retarded.

Little understood in all of this is that the pharmaceutical industry is one of the net exporters (big time) from the US, that the effects of the drugs that it does develop are usually cost-effective (despite the assumed to be outrageous prices for them (generics don't merit some of the pricing that they are allowed, though)—and save the economy lots of money, that 2% of the US GDP is now the pharmaceutical industry (not a small number of jobs or wealth production) or that the rate of return on investments in NIH/CDC research is pretty significant.

Bottom line: I don't think KH Amend are the problem they are often held up to be. The data simply aren't there to support the argument. Of course, if you want to oppose them on philosophical grounds, that's a different story.

There's lots of stuff that one can criticize the government for in regard to the health care system. The health care provided by the military and the VA is a great example—they've been underfunded for years and the result is some horrific health care being delivered (though it's better than it was 5-10 years ago). I could go on and on, even insofar as the effect that the way we fund medical education in revving up the use of procedures, like endoscopies or surgical procedures, of questionable need. But that's a different discussion.

But if one assumes homo economicus and no information asymmetries, then maybe the KH Amend might be superfluous. But that world exists only in the minds of economists—even the one-armed ones.





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