When it comes to problems with pharmaceutical policy, everyone is at fault

It’s either a slow news week, or I’ve touched a nerve, I’m still getting a lot of email and comments about the piece from earlier this week on Abbott Labs and Tricor. So let me expand on that a bit and make this explicitly clear: no one is blameless here. It’s easy to make it all about Abbott, and they did any number of things that make my blood boil, but what they engaged in is standard practice in the pharmaceutical industry. It’s called “evergreening“, and it’s not uncommon. But let’s not stop there. Let’s make sure everyone gets their fair share of the blame:

1) Pharmaceutical Companies – This is where it has to start. Abbott may have broken no laws, but what they did is still hard to justify outside of “making money”. They licensed the drug originally, so they can’t claim that they had to recoup research and development costs. There were almost no costs to develop Tricor-2, Tricor -3, or Triliplix. And the $300 million in lawsuit settlements is a trifle; sales of fenofibrate reached $1.4 billion in 2011 alone. Again, no moral judgement here. This is a company, and its job is to make money for its shareholders. They are doing that. But at some point, it’s important to remember that that job doesn’t always align with the needs of the health care system. When those needs are opposed, it’s sort of silly to rely on industry to do things like “reduce health care spending”.

2) FDA Policy – Can we agree that the 30 month moratorium anytime a patent infringement suit is brought is a complete moral hazard. When sales of a drug are often above a billion dollars a year, what company wouldn’t always  bring such a suit forward in order to get a near-automatic extra 2.5 years of exclusivity? The economic incentive is simply massive. Moreover, sometimes exclusivity is given for ludicrous reasons. We don’t need to reward “delayed release” or “indoor allergies” with years of protection.

3) Pharmacy Policy – Pharmacists can now often substitute generic drugs for name brand drugs if the doses are exactly the same (ie 50mg generic fenofibrate  for 50mg branded fenofibrate). But if the doses are slightly off, they can’t do it. This was the genius behind Tricor-2. By making that drug a slightly different dose, pharmacists could not substitute the 67mg generic for the 54mg branded drug. But here’s the thing. Abbott got approval for the 54mg tablet by showing it was bioequivalent. In other words, they proved to the FDA that the new dose worked the same way as the old one. If that’s the case, then pharmacists should be allowed to reach the same conclusion as the FDA. If they’re the same for approval, they’re the same for treatment.

Now, I’m not saying that this is true for all drugs. Some need to be very fine tuned. But in this case, they specifically proved that the new dose was the same as the old one. We’re leaving $700 million on the table by not allowing switches to generics.

4) The Research/Practice/Guideline Pipeline – Maybe you can tell I don’t know exactly whom to blame here. But someone needs to be able to explain to practicing physicians what’s going on. Moreover, someone needs to get the word out that this drug isn’t even as good as it was first thought. From the accompanying editorial to the article (emphasis mine):

Therapeutic enthusiasm for lipid-lowering treatments, fueled by expanding use of statins, spilled over to fibrates in general and to fenofibrate in particular, likely aided by aggressive marketing of the Tricor brand in the United States. Professional society guidelines were perhaps enthusiastic as well. In 2001, the Adult Treatment Panel characterized elevated serum triglyceride levels as an independent risk factor for coronary disease based on prospective observational findings. Both therapeutic lifestyle changes and drug treatments, including fibrates, were recommended. In the 2004 update, Grundy and colleagues acknowledged that “Although the evidence base to support fibrate therapy is not as strong as that for statins, fibrates may have an adjunctive role in treating patients with high triglycerides/low HDL [high-density lipoprotein], especially in combination with statins.”4(p231) Fenofibrate was singled out as less likely to increase the risk of statin-related myopathy.

Recent evidence should have dampened enthusiasm for triglyceride-lowering drugs with fenofibrate. In a large placebo-controlled trial among patients with diabetes mellitus, fenofibrate did not significantly reduce the risk of coronary events (hazard ratio, 0.89; 95% CI, 0.75-1.05). In a second large trial among patients with diabetes, fenofibrate as add-on therapy to statins did not differ from placebo in terms of cardiovascular events (hazard ratio, 0.92; 95% CI, 0.79-1.08). Indeed, in a prespecified subgroup analysis, fenofibrate was associated with benefit in men but with harm in women.

High levels of triglycerides, defined as levels between 200 and 500 mg/dL, are a weak asymptomatic risk factor for cardiovascular events (to convert triglyceride level to millimoles per liter, multiply by 0.0113). Although triglyceride-related pathways may be important in causing coronary heart disease, epidemiological associations between risk factors and events do not necessarily predict the effect of drug treatments in preventing cardiovascular events. The original formulation of fenofibrate was approved on the basis of triglyceride lowering, without any clinical outcomes data. Favorable effects on surrogate markers do not necessarily mean favorable effects on clinical outcomes, hence the need for large, long-term trials. Drugs that target a risk factor may or may not influence the incidence of clinical events and the occurrence of off-target adverse events. Drug treatments of an asymptomatic risk factor for the prevention of future cardiovascular events should be shown to have a favorable clinical risk-benefit profile before they are widely used. The lack of such evidence makes the popularity of fenofibrate in the United States puzzling. The increased use started well before supportive evidence and continued to increase after the null results that have repeatedly emerged from the large trials among patients with diabetes. Abbott’s approach to pharmaceutical innovation, together with therapeutic enthusiasm on the part of physicians, exposed many patients to a drug with high costs, known risks, and little or no clinical benefit.

And yet, $1.4 billion in sales in 2011. Those same professional societies should probably work just as hard to stop what they started.

5) Physicians – I left docs for last, not because I don’t think they’s culpable, but because they actually have to power to make all the other things moot. Let’s face it – any doctor should be able to read this manuscript and immediately recognize what’s going on. They should be able to understand that any of the Tricors are interchangeable, let alone the generics. Still, they write gazillions of dollars of branded prescriptions each year. Why? My friends know me well enough by now not to tell me what drugs they are on. I simply become apoplectic when I see a Nexium prescription when Prilosec will do. Focalin instead of Ritalin. Clarinex instead of Claritin. If you really want my blood to boil, Sarafem instead of Prozac.

If docs didn’t write the scripts, none of this would be necessary. I’d like to hear a really good explanation for why someone wrote for Tricor-3 instead of Tricor-2, let alone the generic substitute.

The authors had some similar ideas (and others) in the original manuscript.


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