Alleged Off-Label Lipitor Marketing--Further Details

In the previous blog post, I tried to summarize some of the background information about the evidence in favor of prescribing drugs for cholesterol. I am now able to relate the recent allegations against Pfizer, in the whistleblower lawsuit, to this body of information. I was very kindly sent a copy of the complaint filed with the US District Court for the Eastern Circuit of New York in the case of United States of America et al., ex rel. Dr. Jesse Polansky v. Pfizer, Inc. from which the rest of the information is taken.

Dr. Polansky, a former Pfizer manager, claims that the company engaged in a deliberate and sustained marketing campaign to encourage physicians to prescribe Lipitor for patients for whom the drug was not indicated according to the FDA label. According to these allegations, what, exactly, did Pfizer do?

The basic goal of the campaign (remember that this is all allegation, not demonstrated fact) was to greatly increase the number of patients with elevated cholesterol levels for whom Lipitor would be prescribed, beyond the limits suggested by the recent practice guidelines issued by the NIH National Cholesterol Education Project (NCEP). Now, this is already a tall order because many people claim that the guidelines themselves are overly generous in recommending statin therapy--I discuss this at some length in HOOKED. We'll see later why that may be so, as the vast majority of members of the NCEP panel are engaged in conflicts of interest and receive funding from Pfizer and associated entities.

However, even NCEP had to admit that for some moderate-risk patients, the evidence favored using diet and exercise to manage one's cholesterol, rather than drugs. Dr. Polansky now claims that Pfizer's marketing team set out to convince doctors, patients, managed care entities, and anyone else who would listen that most of these patients really needed drugs, not lifestyle changes. The claim alleges that Pfizer's off-label prescribing was so blatant that the company virtually admitted this transgression to its investors, bragging about how the campaign would drive up sales.

The centerpiece of this marketing campaign was a set of materials that was designed to create the clear impression that the viewer was seeing a summary of the NCEP guideline recommendations. But the Pfizer version deviated from NCEP in important ways. The most significant change was substituting one key number for another so as to favor drug prescribing.

The NCEP guidelines feature threshold values of cholesterol (specifically, LDL or "bad" cholesterol) that are supposed to be triggers for prescribing a drug if the patient's lab values exceed that number. Once a patient is placed on a statin drug, the guidelines then suggest target levels. This is the lab value you are supposed to be trying to reach with your drug, and you should adjust the dose of your drug and choice of drug to try to reach that target, according to NCEP. (I explained in my previous post that these "targets" are really based on no good evidence, according to my colleagues Jim Wright and John Abramson; but put that aside for now as we are discussing what NCEP actually claims and then what Pfizer construes NCEP as claiming.)

The allegations are that Pfizer's materials fail to mention the threshold values and instead focus exclusively on the target levels. The entire focus of the marketing campaign is to get the patient to achieve the target. Let's take an example of what this means. For some risk categories, the LDL level that provides the threshold for prescribing drug treatment is 160, and the target you then try to reach with the drug therapy is 130. The Pfizer materials ignore the 160 and only talk about the 130. What if you have a patient in that risk category whose LDL is 150? According to NCEP, that person does not need drug treatment. According to what Pfizer wants you to think NCEP says, this patient has not yet reached target and so you need to prescribe a drug (ideally Lipitor of course) to get the LDL down another 20 points.

But, one might say, why not use diet and exrcise to bring the LDL down that much? Pfizer's marketing materials are ready with the answers. Diet and exercise simply don't work the vast majority of the time, they emphasize. All they do is make patients feel guilty when they fail. You wouldn't want to do that terrible thing to your patients, now would you? So of course the best bet is to start off with the drug right from the get-go. Again, this advice is quite contrary to NCEP guidelines.

The allegations proceed to shine a light on two other questionable marketing practices. First, the complaint alleges that while the FDA is relatively strict about policing drug advertising that comes in the form of journal and TV ads (acually they are not, but save that argument for another time), they are very lax about other media such as web-based and hand-held computer calculators. So Pfizer created a number of computer decision calculators designed to be used by docs to figure out which patients needed to be put on drugs. The complaint alleges that these calculators use inaccurate numbers, not consistent with NCEP, to magnify the numbers of patients who end up "needing" drugs. If your friendly Pfizer rep gives you a nice handheld PDA with this calculator loaded onto it, and you use it to prescribe for your patients, your patients get more drugs than indicated and Pfizer gets more profit.

Second, the complaint goes into details about how Pfizer allegedly channeled a lot of money to support continuing medical education (CME) programs through three front organizations--National Lipid Education Council (NLEC--notice how easy it is to confuse with NCEP); Emerging Science in Lipid Management; and Vascular Biology Working Group. These impressive sounding entities could sponsor CME programs and spread the Pfizer marketing materials and messages while allowing the drug company to remain in the background.

Now we come to the conflict of interest matter--the complaint provides a nice table that lists all the big-time scientists who staff the NCEP guideline writing panel, along with their various roles in each of the three Pfizer-controlled and -funded "educational" organizations. The result is a nice checkerboard pattern with every one of the NCEP docs having at least one tie to another organization, and many having numerous ties. Assuming that these are paid consultantship-type relationships, it illustrates how members of NCEP all get some sort of drug company money, and in turn, how they make that money by "educating" physicians to prescribe more and more statins--even beyond what NCEP guidelines call for.

I am not a lawyer and so I cannot comment on any of the legal merits of this suit. Just looking at this list of allegations, I am worried. It seems that the case that is being made depends very heavily on a thorough understanding of the epidemiological data about heart disease risks and drug treatment. This is a tough enough task for a medical school classroom. What will it be like trying to teach an epidemiology course for non-epidemiologists in a courtroom? I will be very interested to see how this all unfolds.

NOTE ADDED 1/2/08: As I should have said as part of my analysis of Pfizer's marketing strategy: this example also shows how a drug company that positions itself properly can sell as many drugs by selling a lab test as it can by selling the drugs directly. Given that an awful lot of Americans have high cholesterol levels, once Pfizer has been successful in redirecting physicians' attention away from the threshold values for starting drug treatment and instead toward the target levels (as explained above), the best way to sell more Lipitor is to make sure that more and more people get their cholesterol checked. Hence the support for "health fairs" and other means by which lab tests will be "sold" to either the general public or to docs. John Abramson, in his Overdosed America, provides similar examples of how osteoporosis drugs are "sold" by encouraging more women to get bone-mineral-density testing. According to our cultural mythology, anyone who urges more and more people to go out and get tested for something "preventive" is a public health hero and so is immune from criticism--even if the motive and the result are higher profits pure and simple rather than any real patient benefit.