September 2013 Archives



I grew up, as did many people, believing that government agencies protected us in many ways. It seemed obvious that an agency named the Environmental Protection Agency protected the environment from would-be polluters and the Department of Education advanced the educations of Americans. As an aside, the government has long been acutely aware that names matter, which is why bills are named the Affordable Care Act and the Clean Water Act. Who could be against affordable care or clean water?

As I got older and went to college and then graduate school, I took economics and public policy classes and learned the problems with government agencies and the benefits of freedom, decentralization, spontaneous order, and self-regulating free markets. I changed my views and saw government agencies, such the U.S. Food and Drug Administration, in a new, more critical light. My perspective changed again, slowly and largely imperceptibly, when I went to work in the pharmaceutical industry. I was so busy dealing with my new responsibilities that I virtually stopped thinking about public policy issues. Then, one day, I noticed that I again believed in the FDA. If we didn't have the FDA, I thought, what menagerie of dangerous and inefficacious drugs would be on the market? Without the FDA, Americans could be dying. My thinking had come full circle, largely in the background and on automatic pilot.

This didn't mean that I liked or even respected the FDA, as I heard all the damning stories of the FDA's internal workings. I think at this point, however, my views were pretty consistent with many employees in the pharmaceutical business: The FDA was a messed up government bureaucracy that still performed a critically important function.

These days I think and write more about drug regulation and the FDA and my views have continued to evolve. I'm excited because I'm thinking about these issues more clearly than before, but I keep coming back to the same question: Do we really need the FDA?

I'd like to hear the stories of others. Have you always had the same view of the FDA and drug regulation? Has it changed over time? If so, why? What triggered the change? If it hasn't changed, when did you first become aware of your view?



As Milton Friedman once said, "I don't think the state has any more right to tell me what to put into my mouth than it has to tell me what can come out of my mouth." Of course, the state doesn't agree and the FDA's whole raison d'ĂȘtre is to tell us what we can put into our mouths.

Now consider Andrea Sloan, a vibrant woman fighting advanced ovarian cancer. She has been through countless therapies that have kept her cancer in remission, but it has returned once more. Now her doctor informs her that she has run out of options. "We had the conversation where he told me to get my affairs in order." In other words, prepare to die.

In the midst of this despair, she learned of an experimental drug, named BMN 673, which is being developed by the California biotech company, BioMarin. According to Dan Spiegelman, chief financial officer: "As a phase two small patient study goes, it's as good as it gets. We think our numbers stack up well at this level. The drug is clearly the most potent of the compounds we're talking about." BMN 673 may yet help Sloan with her ovarian cancer.

Of course, any drug, even an approved and marketed drug, has risks. Sloan understands these risks and still wants to try BMN 673. "I just want a chance to live a long and healthy life and I'll continue fighting until I get it." In other words, she's going to die anyway, so why not try a drug that might possibly work? A chance of living is always better than no chance.

There's one big problem. The FDA has not approved BMN 673 and BioMarin is not offering BMN 673 under a so-called compassionate use program. Now, you might blame BioMarin for not offering this new drug to Sloan and perhaps BioMarin deserves to be rebuked. But BioMarin is only a player in the drug development game and it is the FDA that wrote the rules. The FDA does allow companies to give experimental drugs to people in certain life-or-death situations. However, if Sloan suffered some sort of problem or, worse, died while taking BMN 673, it could preclude the subsequent development and FDA approval of BMN 673.

Companies know how difficult and dangerous the FDA's drug approval process is and they respond rationally by behaving conservatively. This is an example of that behavior. If Milton Friedman got his way and the state didn't tell us what we could put into our mouths, I have no doubt that Andrea Sloan would already be on BMN 673 therapy. This is just another example of how the FDA's policies kill Americans, all the while presenting BioMarin as the bad guy who says "no."


The cardiovascular benefit of statins is anything but news. But a very large retrospective study from Taiwan may bring the utility of these drugs to an entirely new level--it appears that the use of high dose statins cut the risk of senile dementia in older people. And by a lot.

And if there is one area where medical progress is sorely needed, it's Alzheimer's Disease. Because, despite being the target of vast amounts of research, all we really have is a vast amount of failures.

Treating Alzheimer's is bad enough (and the treatments for it are plenty bad). But preventing it? With the exception of taking steps to reduce vascular dementia (due to strokes)--forget it. Every vaccine, therapeutic or preventative, has been a total bomb.

Statins have been suspected of both increasing and decreasing dementia. Ironically, one reason that this study was conducted was to see whether cognitive dysfunction was a possible side effect of statins.

It didn't exactly turn out that way.

In a presentation to the 2013 meeting of the European Society of Cardiology, Dr. Tin-Tse Lin and Dr. Min-Tsun Liao of the National Taiwan University Hospital reported that not only didn't statins adversely impact cognitive function, but they had a significant protective effect .

Lin and colleagues used a database of one million people covered by Taiwan's national health insurance program. From this sample, about 57,000 people (aged 65+) with no history of senile dementia were selected during the period of 1997-1998. About 15,000 of these participants were taking statins.

During the 4.5 year follow-up period, about 5,500 people developed non-vascular senile dementia (not caused by strokes or blockages). And the data from this group are fascinating.

As shown in Figure 1, there was a substantial and dose-dependent difference in the number of dementia cases for participants who took statins--the higher the dose, the lower the risk of dementia. Also, the more potent statins showed a larger effect than the less potent, which in effect, strengthens this dose response trend (which is already impressive).

Screen Shot 2013-09-11 at 10.42.50 AM.png
Figure 1: Dose Response of Statins (Source:http://www.theheart.org/article/1578833.do). For clarity, hazard ratios (given in the report) were converted to percent reduction: 1.0 minus HR times 100 = percent reduction.

For example, for rosuvastatin (Crestor), the low, medium and high dose groups showed a reduction in the incidence of dementia by 63, 87, and 87(!) percent, respectively.)

The relationship between the potency of the particular statin and protection against dementia is similarly interesting (Figure 2, below).

There is clearly a relationship between the inherent potency of the statins (at equivalent doses) and their effect. For comparison, the low-dose group is used as an example). The potent statins (atorvastatin and rosuvastatin) clearly outperform the less potent statins (e.g., lovastatin) in reduction of dementia.
Screen Shot 2013-09-06 at 12.38.55 PM.pngFigure 2. Correlation of statin potency (low dose) with percentage of dementia reduction . Rosuvastatin is arbitrarily assigned 100 for reference purposes.

Of course, as a retrospective study (albeit a very good one), there are built-in limitations. It cannot prove that statin use will protect you against senile dementia--only that there is a strong association between the two. Cause and effect can only be determined by a prospective controlled study--something that will surely be done now.

This is far from definitive, but given the huge number of participants, the robust dose response, and the relationship between the strength of the statin and the magnitude of the response, it would seem that they are onto something here.

And when you add the fact that non-vascular-related dementia was excluded from the data, suggesting that the is more going on here than statins acting as lipid-lowering agents, it gets even more intriguing.

It is doubtful that high dose statin therapy for seniors will become standard practice anytime soon, but these results are certainly intriguing. Anything that can help combat Alzheimer's--perhaps the most devastating of all diseases--would be an enormous medical advance.



I gave a "Making Great Decisions" talk with my coauthor, David Henderson, to a successful mortgage lending company in late September 2006. Coincidentally, that was right around the start of the subprime mortgage crisis. Little did they know that they would be filing for bankruptcy in less than three years. Before you start faulting any advice we might have given them, you should be aware that the all-day meeting didn't go well and our clients exhibited a strange combination of disinterest, obtuseness, and belligerence. We were paid for our time and then sent away, but certainly never invited back.

What struck me as interesting was how this company set its mortgage rates. Everything was based on statistical analysis. The company had good computerized data which it analyzed thoroughly to set its rates and decide who to lend to. The first problem is that this good data hadn't been available for very long, so most of the history being analyzed had occurred during a period of low interest rates, economic growth, and stability. The second problem is that statistical analysis, while powerful, is equivalent to driving by looking in the rearview mirror. Statistics is concerned primarily with what has already happened, not what may happen. Decision analysis, on the other hand, focuses primarily on what may happen in the future. Decision analysis is the study of decision-making within uncertain and sometimes risky situations, and is inherently forward-looking.

How does all this relate to health care? Simple. The American health insurance market is about to undergo significant upheaval with the rollout of the Affordable Care Act (aka Obamacare). Here's what a recent Wall Street Journal article reported about the trouble facing insurers: "But because the marketplace created by the law is new, he says, there is no previous pricing or demographic information to help calculate rates. 'There is no experience,' Mr. Whisler says."

Exactly. Insurance companies are in the same position today that mortgage lenders were in circa 2005. Those companies that rely heavily on statistics are hereby forewarned that the future will not be like the past. The precise analysis of a market that no longer exists will not prepare them for a new world. What these companies need to do, instead, is use the techniques of decision analysis and think about what may happen, not focus on what has happened. The future isn't written in any book--we are actively creating it.


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