Vytoringate: A Failure to Communicate with Doctors

May 19, 2008

Video clip: Scene from the Oscar winning 1967 Movie “Cool Hand Luke” starring Paul Newman

Background

Vytorin sales have dropped dramatically, billions of dollars of shareholder value have vanished from Merck and Schering-Plough, and everyone appears confused about how to spin the Vytorin/ Zetia tale. With almost daily scandalous “Vytoringate” headlines, it’s becoming more difficult for the public and the media to determine what’s fact, what’s hyperbole and what’s speculation. The Vytorin controversy refuses to go away because it raises many fundamental and emotional issues about potential abuse and ethics violations by the two huge pharmaceutical companies possibly trying to delay release of clinical trial information by two years to fatten their bottom lines at the expense of millions of patients’ health and pocket books, and the possibility that 20 year old theories linking statins and elevated cholesterol with vascular disease may be off-target. The Wall Street Journal blog by Jacob Goldstein chronicles the story in more detail, but the media failed to probe the most interesting issue: the communications failure between pharmaceutical companies and doctors.

Role of Doctors

What are the doctors who prescribe cholesterol-lowering drugs to thousands of patients thinking? How has the American College of Cardiology expert cardiologist panel influenced them? How have the media reports influenced them? These doctors are the ones dispensing the medications, and literally controlling the spigot of pharma revenues through their prescriptions. They are the ones making life and death decisions for their patients. Why has so little been said about physicians’ perspectives? It’s bizarre that the media and legislators are shouting so loudly, yet the expert doctors charged with prescribing the medication, the doctors who literally control the sales results and stock price hardly have a voice. How do doctors feel about their relationship to the two pharmaceutical giants? Have doctors sent a tacit message to these companies reflected in the sales figures, stock prices and market share? Has this eroded the partnership between doctors and Merck and Schering-Plough, and perhaps all pharmaceutical companies? Was there a failure to communicate with all doctors who prescribe cholesterol lowering drugs?

The American College of Cardiology expert cardiologist panel ruled in late March 2008 that Vytorin and Zetia should be avoided since they are no better than a statin alone. But this panel does not represent the voice of most doctors who prescribe the medication. Also, their decision is a no risk decision whether wrong or right, but there is huge risk if they had supported the effectiveness of Vytorin and Zetia. This panel appears to have abandoned Merck and Schering-Plough. Was there a failure to communicate with the most distinguished doctors?

What Doctors Think Market Research Plan

As a public service, WhatDoctorsThink.com decided to probe the role doctors played in Vytoringate, an issue the media ignored. “What Doctors Think” performed healthcare market research on the Vytorin/ cholesterol controversy using two randomly selected groups of physicians. The online surveys queried cardiologists, internists and general practitioners–the leading prescribers of Vytorin and other cholesterol lowering drugs. The first survey was conducted in January 2008, shortly after the release of the ENHANCE study and its ensuing controversy. The second survey was conducted in late April to early May 2008 after the American College of Cardiology statements had been digested by the media and doctors who prescribe these medications.

The surveyed doctors have arguably more clinical experience with cholesterol lowering drugs than anyone; this experience spans two decades and millions of patients. We wanted to compare physicians’ changing perspectives on these issues to better understand the impact of the news and their prescribing regimens. We already know prescriptions for these drugs had dropped from sales reports by Merck and Schering-Plough, we wanted to know what rationale these doctors used to change their prescribing habits. We believe there are lessons here for pharmaceutical companies who rely on these doctors for revenue, and for the media, for their lack of in-depth analysis of the role played by the most critical group in Vytoringate: doctors who prescribe the medication.

Probing Strategy

Here is a list of key issues the surveys probed:

Did the ENHANCE study select the appropriate test subjects? Did it use appropriate measurement tools for the test markers, and did it have significant endpoints?
Was the interpretation of the ENHANCE study carried out in a fair and balanced manner?
Was the release of the ENHANCE study results delayed for appropriate reasons?
Was Vytorin marketed properly to physicians and the public in view of the delayed ENHANCE results?

What benchmark should the FDA use to approve cholesterol-lowering drugs? Is it sufficient for the drug to just lower cholesterol, or should trials demonstrate stabilization of artery plaque, or reduction of artery plaque, or should the FDA insist on the highest standard: reduction of heart attack and stroke incidence?

What We Learned

From analysis of the before and after surveys, here are highlights of what we learned:

Doctors were as confused as everyone else as to whether the ENHANCE study was designed, implemented and interpreted properly. When doctors are confused, their patients become even more confused. As a result, about half the doctors either reduced or stopped their Vytorin prescriptions. Doctors are the conduit through which pharma dispenses drugs, so this failure to communicate has cost Merck and Schering-Plough dearly. Vytorin sales have been about $5 billion in the last few years. Analysts expect about a 50% reduction in future sales–consistent with the survey results. Is this doctors’ way of punishing Merck and Schering-Plough for their failure to communicate?
Doctors seem to be roughly equally split about the conflict of interest issue—delay in publishing ENHANCE data. Astonishingly, the surveys found doctors are as influenced by media reports as by the findings of a respected panel of experts and key opinion leaders. The media has the power to control the fate of the pharmaceutical industry, especially when there is a failure to communicate between pharma and doctors.
Doctors are not sure of the cause for the delay of the ENHANCE results, but many are skeptical enough that they want an answer and feel that congressional hearings are warranted. The vast majority of cardiologists favored discontinuing marketing of Vytorin to the public. This is not a good sign for Merck and Schering-Plough since loss of trust by prescribing physicians points to further market share erosion and out of control PR.

The obvious lesson for pharma is that billions spent on detailing has not fostered the essential communications that would have averted this precipitous drop in trust, sales and stock price.

Doctors are split with regard to what the FDA criteria should be for approving cholesterol-lowering drugs. Until recently, lowering cholesterol was assumed to lower heart attack risk based on previous studies on Mevacor, Lipitor and other drugs. Mevacor and Lipitor were FDA approved years before their corresponding clinical outcome trials were completed, which proved reduction of heart attacks. Should the FDA adjust benchmarks for future cholesterol drugs? Is a sliding benchmark fair for future drugs and companies? Will it delay benefits from possibly better drugs because the clinical outcome trials (incidence of heart attacks) take many years to complete? For example, the Vytorin IMPROVE IT trial will not be completed until 2012. Will everyone criticize the FDA for dragging its feet on new drug approvals? Apparently, Vytoringate has hardened the FDA’s stance on approval of new statins since it has rejected Cordaptive and Mipomersen, two new cholesterol drugs, in recent weeks.

Despite the suspicion by doctors of inappropriate behavior by the two pharmaceutical companies, surprisingly the surveys reveal that a vast majority of doctors still believe in the effectiveness of Vytorin, or Zetia plus a statin. This must astound any pharma marketing observer since it appears as if pharma has managed to antagonize its most powerful ally, and its main conduit to millions of patients. If pharma can’t communicate with its most important customers, it has no chance with the media.

Summary of More Interesting Findings

Here are some more interesting findings:

Before release of the Vytorin-ENHANCE study in January 2008, the four most commonly prescribed cholesterol drugs were Lipitor: 51%, Simvastatin (generic Zocor): 25%, Vytorin: 12%, and Crestor: 12%. Based on their clinical experience, 84% of doctors believed that Vytorin, or Zetia plus a statin, lowered cholesterol more than a statin alone. After release of the ENHANCE study, 48% of doctors reduced their prescriptions for Vytorin and Zetia, and this is confirmed by sales results.
72% of doctors believed that the ENHANCE study group of patients were not appropriate to test Vytorin on. Another indication that expert doctors side with the two drug companies, but because of the communications failure, the companies failed to leverage this to their advantage. A source of confusion by prescribing physicians: 24% of doctors said that carotid artery plaque thickness was not an important endpoint, and that lowering cholesterol was the more important endpoint; 27% of doctors said that carotid artery plaque was the significant endpoint and cholesterol lowering alone was not; 20% said that they didn't know if the ENHANCE study findings were significant or not, and therefore would not change their Vytorin and Zetia prescriptions; 17% said that they didn’t know if the ENHANCE study findings were significant or not and therefore would reduce their Vytorin and Zetia prescriptions. Yet despite this confusion, 33% of doctors advised their patients not to switch from Vytorin, even though the patients asked to be switched.
50% of doctors ignored the American College of Cardiology expert panel recommendations and didn’t change their Vytorin prescriptions, and 50% heeded the recommendations and reduced their prescriptions. One respondent said: “ The ACC panel was an embarrassment to the ACC. It was NOT a scientific discussion, it was a diatribe by one member who attempted to thrust his strong opinions on all. It was a great disservice to the cardiology community and resulted in unnecessarily scaring [of] many patients . ” Yet 52% of doctors said they reduced Vytorin prescriptions as a result of media reports, and 47% of doctors said they were not letting media reports on the Vytorin controversy affect their prescribing of Vytorin. So it appears that the missed communications from Merck and Schering-Plough has elevated the media’s influence on par with the distinguished American College of Cardiology expert panel.
Prior to the American College of Cardiology expert panel recommendations, 70% of doctors would have prescribed Vytorin and Zetia for themselves or a family member. After the American College of Cardiology expert panel recommendations, 50% of doctors would have prescribed Vytorin and Zetia for themselves or a family member.
43% of doctors said that they thought there were conflicts of interest in the ENHANCE study and interpretations of its results. But there is some hope because 13% of doctors said that Merck and Schering-Plough delayed release of the ENHANCE study because the data was confusing and difficult to analyze. However, 37% of doctors said that Merck and Schering-Plough purposely delayed release of the ENHANCE study to prevent reduced sales of Vytorin; and 52% of doctors didn’t know why the release of ENHANCE study results were delayed.
67% of doctors believe that Congress should investigate “Vytoringate”
With regard to the ongoing Vytorin IMPROVE IT clinical trials, 29% of doctors believe that Vytorin will reduce heart attack and stroke incidence as compared to simvastatin/ Zocor alone, and 16% of doctors believe that Vytorin will not reduce heart attack and stroke incidence as compared to simvastatin/Zocor alone, and 55% were not sure what the results will be.
Our January 2008, post ENHANCE release survey revealed that 83% of cardiologists favored discontinuing Vytorin television DTC ads, and 53% favored discontinuing print ads.

Conclusion

Trust is like a vase… once it's broken, though you can fix it, the vase will never be same again. Old Proverb.

A communications failure can be repaired, but it will require a new attitude by pharma towards doctors. Doctors should not be viewed as targets for free dinners, pizzas and pens, doctors want to be respected for the role they play in society, their rare clinical expertise and their healing powers. Doctors resent being bypassed with DTC ads. Doctors don’t just want detailers to visit and promote their products, doctors want a voice, and pharma needs to listen to their voice because doctors have first hand knowledge of the end customers (the patients), and doctors can have a powerful influence on pharma market performance. Although doctors are not as unified as they’d probably like to be, in the age of the Internet, it does not take much to usurp their rightful power. Pharma needs to mend fences with all doctors (not just elite medical panels or prestigious medical schools) before it can gain the respect of the public and the media, because a failure to communicate with doctors is surely a recipe for failure to communicate with the media, and the result of that is Vytoringate.

To view the detailed survey results for the surveys discussed here and other surveys of interest to the medical community, please visit What Doctors Think.