Envisioning 2.0

Today I moderated a panel at the Healthcare Blogging Summit, which is being held in Las Vegas. John Mack, author of the Pharma Marketing Blog, released the details of a new survey he conducted focusing on pharmaceutical-related blogs. Respondents to his poll believe that blogs that are critical of the industry are more credible.

During his presentation, Mack speculated that his data may be influenced by the composition of his survey sample. Specifically, most respondents to the survey may be industry critics.  It will be interesting to see how the statistics change when he fields the survey in the future. To learn more about the study, please click here.

This morning the New York Times reported that the Food and Drug Administration is investigating a preliminary Zyprexa study Eli Lilly conducted in 2000 that indicated the drug increased blood sugar.  From the Times:

“The F.D.A. has questions about a Lilly document from February 2000 in which the company found that patients taking Zyprexa in clinical trials were three and a half times as likely to develop high blood sugar as those who did not take the drug. That document was not submitted to the agency. But a few months later, Lilly provided data to the F.D.A. that showed almost no difference in blood sugar between patients who took Zyprexa and those who did not.”

Eli Lilly said it “had rechecked its database and found errors in the original statistics. The data submitted later was accurate.”

Interestingly, the Times’ reporting is based on documents it received in violation of a protective order sealing the materials from public view.  The reporter who wrote this and other Zyprexa-related stories, Alex Berenson, was blasted by a New York judge for engaging in “reprehensible” activities and for being “deeply involved in the effort to illegally obtain the documents.”

The saga continues . . .

Healthcare communicators and others have long urged pharmaceutical companies and non-profits to forge partnerships in order to educate the public and improve health. Clearly, these cause alliances have been very successful for all involved, which is why they remain popular.

Today however, the landscape is changing. As already reported on several blogs, including Pharmalot, new research from my firm, Envision Solutions, indicates that the public is skeptical of the pharmaceutical industry’s motives for supporting non-profits. According to a national survey commissioned by Envision Solutions, 43% of US adults believe that pharmaceutical companies fund groups like the American Heart Association and the National Kidney Foundation in order to get more people to buy their products or medicines.

This suspicion, coupled with increasingly negative media coverage of these alliances cries out for action on the part of communicators and non-profit/pharmaceutical executives. The first step is recognizing that we have a problem. The second is taking appropriate steps to ensure the public understands how these partnerships are structured and why they are independent and valuable. If we don’t take action, we face the prospect of increased government regulation and other unpleasant consequences.

A new report available for purchase on my firm’s Website, “Preserving the Power of Pharma-Non-Profit Partnerships,” outlines the problem and illustrates one way we can move forward. Click here to learn more about it.

The Wall Street Journal reported today on new legislation that would place sharp limits on direct-to-consumer (DTC or DTCA) advertising.  From the Journal:

“The goal [of the legislation], supporters say, is to ensure medicines are safe before allowing industry to promote them to consumers in the hopes they will request prescriptions from doctors.  But a reduction in TV and print advertising, which helped transform medications for heartburn and arthritis into blockbusters, would be a serious financial blow to drug makers. According to one study, every $1 spent on pharmaceuticals advertising often adds more than $2 in sales.”

As the debate over DTC advertising once again heats up in Congress, we’ve recently seen a flurry of data focusing on the impact of the commercials.  Specifically:

-According to a Harris Interactive poll commissioned by the Pharmaceutical Safety Institute: “Fifty one percent of adults believe that DTCA encourages them to ask additional questions when visiting their physician . . .  [and] [f]orty two percent believe that DTCA provides useful information on the risks of using prescription medications.”

-On the other hand, Consumer Reports conducted a survey indicating that “three-quarters of consumers (75 percent) agreed that drug ads lead to over-prescribing, with 38 percent ‘strongly agreeing.’ And 59 percent agreed that the government should restrict advertising by pharmaceutical companies, with 26 percent strongly agreeing to such restrictions.”  However, Consumer Reports also found that 63 percent agree that they find the ads useful when speaking with their physicians.

-The consultancy Booz Allen Hamilton conducted a study showing that consumers “trust their physicians [for health content] and have a dim view of information from employers, the government and pharmaceutical companies” – especially drug advertising.

With all of this data flying around, it’s hard to figure out what figures to trust.  Of course, as anyone involved in designing polls will tell you, one can get very different answers to questions depending on how they are asked.

Despite the data supporting DTC advertising, Democrats (and their Republican allies) are determined to place limits on it.  Everyone will be watching to see how the latest chapter in this long-running debate pans out.

In keeping with my promise to follow the development of Vertex’s new hepatitis C drug, VX-950, here’s the latest on the product from Dow Jones.

“Vertex Pharmaceuticals Inc. (VRTX) on Saturday said interim study data showed its investigational hepatitis C drug may shorten the duration of treatment time for patients.  Of 175 hepatitis C patients given telaprevir, or VX-950, in combination with pegylated interferon and ribavirin, 70% achieved a rapid viral response rate at 12 weeks of dosing, compared with 39% of patients who received a placebo in combination with the two medicines, Vertex said in a statement.”

Recently, the mainstream media and bloggers have been paying a lot of attention to Pfizer’s new Celebrex advertisement. Some have called it confusing, while others have praised Pfizer for taking a leadership position and candidly discussing the risks associated with prescription medications.

Sidney Wolfe, however, is not very pleased with the commercial. He asked the FDA to “immediately stop [Pfizer’s] dangerous, misleading 2 ½ minute television advertisement for Celebrex.” He said that the commercial suggests “the cardiovascular dangers of Celebrex are not greater than those of any of the other NSAID painkillers.” He also says that the “ad violates FDA law and regulations because it contains several false or misleading statements that will lead many viewers to underestimate the cardiovascular and gastrointestinal risks of Celebrex and use it in preference to equally effective, safer alternatives such as OTC naproxen.”

Pfizer, of course, defended the commercial. According to Bloomberg News the company said the “ad refers to its safety profile and other prescription drugs in its class, nonsteroidal anti-inflammatory drugs. It does not compare Celebrex to over-the-counter medications, as stated in the Public Citizen letter.”

I think that the Celebrex commercial is certainly interesting. Most importantly, it seems to be an attempt to respond to criticism of direct-to-consumer advertising by presenting lots of information upfront about side effects. However, from a communications perspective the commercial falls flat because it has too much information. Health literacy is notoriously low in this country. With all of the high-level language in the commercial it’s a wonder anyone can follow it.

We can’t really blame Pfizer for this. The FDA requires companies to present side effect information in this fashion and has not yet developed “plain English” guidelines for adverse event communications. Maybe we should focus on answering the question most people ask when they take a medication: “What’s MY risk of suffering from a side effect?” Personally, I think percentages work well, e.g., your risk of suffering from a heart attack is .0005 percent.

Right now we don’t have a good way to communicate risk when it comes to prescription medications. Pfizer’s taken a great stab at it, but we have a long way to go.

Last week, Peter Rost, author of the popular blog Question Authority, highlighted the statements of an AstraZeneca sales executive about how to sell oncology drugs. Mike Zubillaga said:

“There is a big bucket of money sitting in every office. Every time you go in, you reach your hand in the bucket and grab a handful. The more times you are in, the more money goes in your pocket. Every time you make a call, you are looking to make more money.”

Executives at AstraZeneca were appalled by Zubillaga’s remarks, promptly fired him and launched an investigation into how the newsletter got through its screening process.

Many commentators have asked whether Zubillaga’s comments represent the thoughts of many sales executives at pharmaceutical companies. Ed Silverman, who writes the blog Pharmalot has examined this issue very closely and received a number of interesting comments to his post. Here is one from a pharma exec:

“In my experience sales reps who are successful financially break down in two ways. The first is one who is all about the sale first and foremost with no real feeling for the people afflicted or the physicians who care for them. . . . The second group understands the suffering of the patient and the amount of time and energy that is needed to treat the disease especially cancer, HIV, and heart disease. These reps will be successful because they have good science and a willingness to reach out beyond themselves and the money they will make.”

Clearly, sales representatives are under a lot of pressure to “make the numbers” each and every quarter. It’s a pressure that those of us involved in pharmaceutical marketing understand very well. However, many also focus on the need for balance. That it’s about patients first and satisfying shareholder’s demands for profits second.

Art Caplan, who directs the Center for Bioethics at the University of Pennsylvania, said this to Silverman: “I’m not sure this person who got fired was some kind of outlier. At the end of the day, the sales force is rewarded for how much they sell. When you have Wall Street exerting enormous pressure on pharma to perform, the pressure to deliver profit is the overriding mandate, and that becomes the #1 goal.”

In 2002, the National Institutes of Health stopped a Women’s Health Initiative (WHI) study because it found that post-menopausal women taking hormones were at higher risk of a suffering from a heart attack. In 2004, another WHI study was halted because it indicated women taking estrogen had an increased risk of suffering from a stroke.

Today, the Wall Street Journal (subscription required) and other publications reported the results of a JAMA study that represents a giant flip-flop by government researchers. New data indicates that hormone replacement therapy is not as dangerous to the heart as earlier research indicated. What?!

Yes, now the Journal is reporting that “women who use hormones in the first five years after the arrival of menopause are not at increased heart risk.” Here’s the catch. While the study meets the normal test of statistical significance (p = .05), it does not satisfy a newer, more conservative standard set after the data was reviewed by JAMA.

According to the Journal: “At issue is something called the P value, an index that measures how strong the evidence really is. Traditionally a P value of 0.05 is acceptable, showing that there is only a 1-in-20 chance that the result isn’t real. That is the standard used in most WHI analyses. The analysis easily met this test of significance, coming in with a P value of 0.02. But once the paper started being reviewed, a decision was made to further lower the standard for statistical significance — to 0.01. ‘Both the internal reviews and the journal reviews drew attention to the need to be cautious and recommended this,’ Dr. Rossouw said. A more conservative approach was needed, he says, because the data had already been subjected to a number of statistical analyses, a process that statisticians agree increases the likelihood of a false positive.”

In this case, researchers were concerned that women could be at increased risk for coronary heart disease when the data indicated they weren’t (under the old standard). Under the new statistical test, they can now conclude that women taking hormones five years after menopause may still be at risk. However, scientists usually set the significance level at the beginning of a study. Changing it mid-stream is very, very unusual and increases the possibility of statistical error.

The ongoing debate about the WHI study illustrates why science is almost never an exact . . . science. Results of clinical trials should be interpreted and communicated with caution. However, because research is always ongoing, we can never be sure if we have the full story.

The FDA announced last week that it has asked Novartis to suspend sales and marketing of its irritable bowel treatment Zelnorm because patients taking it are at risk of suffering from adverse cardiovascular events. From the FDA press release:

“Throughout February and March 2007, Novartis reported to FDA the results of a new analysis of 29 short-term (1 - 3 months) randomized, controlled clinical trials of Zelnorm. FDA has concluded, based on these data, that for most patients the benefits of this drug no longer outweigh the risks. The analysis included more than 11,600 patients treated with Zelnorm and over 7000 patients treated with placebo. The data showed that the risk of serious cardiovascular adverse events (e.g., angina, heart attacks, and strokes) associated with use of Zelnorm is higher than with placebo treatment. Thirteen Zelnorm-treated patients (or 0.1%) had confirmed cardiovascular ischemic events, and only 1 placebo-treated patient (or 0.01%) with an event.”

This is certainly a setback for Novartis, but it is a testament to the need for aggressive post-approval monitoring of new medications to identify potentially dangerous side effects.

Interestingly, an independent expert retained by Novartis to review the Zelnorm data, Dr. Jeffery Anderson, said that he does not believe the data indicate there is a “causal” relationship between Zelnorm and the “cardiovascular events observed in clinical trials.”  About 500,000 people are currently taking the product.

New Class Of Hypertension Drug

In other news, Novartis’ new antihypertensive renin inhibior Tekturna reduced blood pressure when added to Diovan, an angiotension receptor blocker. Novartis’ work on Tekturna is important because it is the first new type (or class) of blood pressure medication approved by the FDA in a decade. This is significant because critics of the pharma industry have complained that drug firms spend a lot of money working on “me-too” drugs – i.e., new formulations of existing medications. The Diovan/Tekturna combination is also important because most patients will require more than one medication to reach their blood pressure goals.

Although the loss of Zelnorm is not good news for Novartis, the evolution of Tekturna should be interesting to watch, as newer, more effective blood pressure medications are desperately needed.