Pharma Needs to Step Up & Help Develop a Universal Flu Vaccine

Recently, I've been reading a lot about a "universal flu vaccine." A Bloomberg View piece, for example, points out that the greatest breakthrough in the fight against the Flu, which each year kills as many as a half-million people, including 3,000 to 49,000 Americans, would be "a universal flu vaccine that would protect against all viral strains, eliminating the need for annual and pandemic inoculations. Researchers are experimenting with parts of the virus that don’t mutate in the hope of creating vaccines offering lifelong, or at least years-long, protection."

This is of great interest to me because (1) I am getting older and more prone to die from the flu, (2) I just learned that current flu vaccines are not as effective as I thought they were or I was lead to believe (see "Does the Flu Vaccine Work? What 62% 'Effective' Really Means"), and (3) I was involved tangentially in the research to develop a universal flu vaccine way back in the early 80s!

Regarding my involvement: I once made a living building molecular models of complex proteins for life science researchers. One such model was of the influenza flu coat protein, which I built for Dr. Ian Wilson, who is now Chairman of the Department of Integrative Structural and Computational Biology at The Skaggs Institute for Chemical Biology, which is part of the Scripps Research Institute. The model is still on display in the lobby of the Scripps Research Institute! Below is a recent photograph that was sent to me by Mika Elizabeth Ono, Scripps Research Institute Director of Communications.

(The model looks as if it were built yesterday! Damn, am I a good craftsman or what? Kudos to Scripps for the excellent maintenance -- it must require dusting every week, I imagine.)

This protein is the key for looking for "parts of the [flu] virus that don't mutate."

Ian Wilson’s group has been studying the rare antibodies produced in some people that bind to regions of the virus coat protein that do not change as quickly as the typical targets. "The hope is that these antibodies will be able to recognize many different strains of the virus," reports MIT Technology Review (see "Why the Flu Is So Relentless, and How Technology Might Help"). "Over the last few years, different research groups have shown that such antibodies can recognize multiple flu strains, and a study from Wilson’s group and the Crucell Vaccine Institute in September 2012 showed that one antibody can recognize strains from both major subtypes of seasonal influenza, more than had been previously shown."

Back in the 80s, when I built this model, computer graphics were not good enough to help scientists like Wilson visualize the detailed structure of proteins. Here's how Dr. Wilson describes my tiny contribution to his research:

"We decided we would have a go at building a trimer so we co-opted John Mack from New York who was a model builder. He came up to Harvard [I built a model there first] and we constructed a dimer as one unit. This was a three-dimensional plastic model, 1 angstrom per cm. We could actually look at this thing to see what it really looked like and we could obviously trace it out. There were some limited computer-graphics programs that you could use to trace out the molecule, but it was really hard to get a feel for what it was all like without seeing everything at once. So that (three-dimensional) model turned out to be extraordinarily useful for trying to understand the structure. The third monomer was also built and we thought we would be able to assemble and disassemble the trimer, but they were so intertwined that it was impossible" (see "A Discussion with Ian Wilson").

It's great to be a small part of the history of virology, but it would be even better if that history eventually includes the successful development of a universal vaccine for the flu. And this is where the drug industry needs to step in according to Bloomberg View:

"[T]he government has limited means and little product-development experience. Making a new vaccine typically takes a decade and can cost $1 billion. A project of that size is better suited to large pharmaceutical companies. Most, however, have been loath to seriously invest in new vaccines, which offer low returns.

"Given this market reality, the U.S. government should design incentives to get the industry more deeply involved, and it should encourage other countries with manufacturing capability to follow suit. The National Vaccine Advisory Committee should begin by asking industry leaders what it would take. Among the possibilities they should consider: tax credits for research and development costs, fast-track procedures for product approval, extensions for patents and periods of market exclusivity, and financial prizes for scientific breakthroughs.

"By engaging Big Pharma in creating future flu vaccines, governments can ensure that a market failure doesn’t lead to a public health catastrophe."

In a Pre-emptive Strike, Amgen & Genentech (Roche) Lobby States to Block Biosimilars

No doubt you've heard of how Amgen essentially paid off U.S. Senators to sneak a provision in the "fiscal cliff" bill that delays price restraints on a class of drugs used by kidney dialysis patients, including Sensipar, a drug made by Amgen (see "Big Pharma buys off the Senate"). That "richly embroidered loophole" will cost taxpayers a half a billion dollars.

Although a bill was proposed to close the Amgen loophole in federal law, Amgen and Genentech, which is owned by Roche, are lobbying (i.e., paying) state lawmakers to block generic versions of their products according to the New York Times (see here). Specifically, these companies are proposing bills that would restrict the ability of pharmacists to substitute generic versions of biological drugs for brand name products. "Bills have been introduced in at least eight states since the new legislative sessions began this month," reports the Times. "Others are pending. The Virginia House of Delegates already passed one such bill last week, by a 91-to-6 vote."

These crooks, er... biotech companies, claim they are doing this in the name of "patient safety" because the generic versions of biological drugs (so-called "biosimilars") are not identical to the originals. NOTE: Biosimilars are unlikely to be available in the United States for at least two more years. So, these Biotech lobbying efforts are pre-emptive strikes.

Three of Genentech's biologics -- Rituxan, Herceptin and Avastin -- and one of Amgen's -- Enbrel -- are among Forbes' list of "Best Selling Drugs of All Time" (see chart below and here):

"These are really complex, highly sensitive molecules," said REPUBLICAN State Senator Patricia Vance of Pennsylvania, who plans to introduce a bill. "We want to make sure we are not hurting people." Sure, especially let's not hurt the Amgen, Genentech, and Roche stockholders.

Lipitor & Plavix: The Last of the Small Molecule Best Sellers?

Forbes just published a list of "Best Selling Drugs of All Time" (see here). I created the following chart from the data cited (click on it for a larger view):

"Tellingly," notes the Forbes author, Simon King, "each of the products in the list above best positioned to record an increase in peak annual sales over the next five years is a biologic; Humira, Enbrel, Rituxan, Herceptin and Lantus being the chief candidates. This is driven by a number of factors – the later launch of certain brands, for example – but also illustrates the robustness of leading biologic franchises that do not face direct substitutable generic competition."

But I have another take on the ascendancy of biologics in terms of dollar sales. Many of these drugs are so damn expensive that relatively few sales are required to reach the annual sales numbers heretofore reached by small molecules such as Lipitor and Plavix.

However, even some "small molecules" may command high prices in the future. Pfizer's Xalkori (crizotinib), for example, is a small molecule drug that was recently approved to treat a rare form of lung cancer. Pfizer plans to charge $115,200 a year per patient for treatment with Xalkori. At that rate, Pfizer needs only about 9,000 patients worldwide to generate $1 billion in annual sales of Xalkori. In comparison, 1,671,000 Lipitor patients are required to generate the same sales figure (see chart here).

Will Novo Air a Super Bowl Commercial?

Yesterday, on my way to the NJ Turnpike, I passed by the BMS R&D facilities in Hopewell, NJ and noticed a sign announcing that Novo Nordisk will build a site directly across the road from BMS. I couldn't help commenting to Mrs. Pharmaguy, who prefers the Route 1 path to the NJT, that "diabetes has been very good to Novo" because it seems to be growing rapidly. Not too long ago Novo built a new mega site on the Route 1 path to NJT. Gone are the days when Novo had only a smallish U.S. presence (and building) further south on Route 1 near Princeton.

So, it seems Novo is betting big on the U.S. diabetes market and well it should. As we all know from recent reports, currently 26 million people in the U.S. have diabetes and about a quarter of them do not know it (see this infographic) and by 2020 it is estimated that nearly half of U.S. adults will suffer from diabetes (I didn't just pull that factoid of my you-know-what; see here).

Most of those cases will be diabetes type 2 for which Novo has treatments. To promote its diabetes franchise, Novo has hired celebrities of questionable cache such as Paula Deen (see "Novo Nordisk Defends Choice of Paula Deen Over Anthony Bourdain (for example) as Celebrity Chef Spokesperson").

Lately, it seems that Novo is focused on athlete celebrities. Novo Nordisk in Europe, for example, recently launched an all-diabetes professional cycling team to compete as part of "Team Novo Nordisk" (see "Team Novo Nordisk: Insulin 'Doping' Difficult to Prove"). With Lance Armstrong's "fall from grace," however, cycling is now again an EU sport with little hope of reaching as wide a U.S. audience as before.

No problem.

Novo U.S. has open-wheel racecar driver Charlie Kimball as a U.S. sports celebrity spokesperson (see here). Open-wheel racing, however, is not as popular as NASCAR racing in the U.S. Also, Kimball is a type 1 diabetic.

So, it's no wonder that Novo U.S. has launched yet another diabetes campaign featuring a sports "celebrity" with a little more "oomph" in the U.S. sports scene and focuing on type 2 diabetes. That celebrity is two-time NFL Super Bowl Champion and NovoLog® patient Kendall Simmons (see "Novo Nordisk Launches New Program To Recognize People With Type 2 Diabetes Who Give Back To Their Communities"; see here). Simmons will "encourage people to get involved" in the first NovoLog® Community Star contest.

Which leads me to ask: Will Novo air a commercial for the NovoLog® Community Star contest during this year's Super Bowl? "There are so many big companies with ads featuring big name stars debuting during Super Bowl XLVII that it can all get a bit confusing," says the author of a Super Bowl ad preview list (find that list here).

Novo is not on the list just cited, but that doesn't mean it won't run a commercial sometime during, before, or after the Super Bowl. What better audience to reach out to about type 2 diabetes than the "typical" NFL fan and Super Bowl watcher who is gorging him or herself on sugary and high calorie snacks while sitting on the couch watching the game?

On one hand, if Novo does NOT run an ad during the game, it will miss the best possible opportunity this year to raise awareness about type 2 diabetes to the largest U.S (and worldwide) TV audience ever! On the other hand, Novo may agree with former Pfizer exec John LaMattina that TV advertising is bad and should be "dropped" (see here). But LaMattina is/was an R&D guy, not a marketing guy.

Also, TV ads -- especially Super Bowl TV ads -- are very expensive and will probably not be well-received by the public IF it shilled an Rx product. Some currently-employed pharma execs are worried bout the cost and negative effects of pharma marketing and, like Novartis Chief Joseph Jimenez, they suggest that pharma should "spend less money on sales & marketing" (see here). However, even Jimenez might not piss on "disease awareness" marketing, especially in the area of diabetes for which Novartis also has treatments and celebrity spokespersons (see here).

Addendum: I received a comment via email from Sarah Spielvogel, Novo Nordisk Product Communications Manager, who said: "you will not be seeing us during half-time next Sunday." That still leaves upon the possibility that Novo will air a commercial in a less expensive Super Bowl slot such as during the pre-game show or during the first or second half of the game. I'll have to record/watch the whole thing to find out!

An Attempt to Exhume the "Ethical Drug Industry"

When was the last time you heard "ethical" and "drug industry" in the same sentence? These days, you are more likely to see "unethical" linked closely with the drug industry that during the time of its birth during the Civil War in the U.S. used "ethical" to distinguish its products from quack medicines. Here's a piece of drug industry history from "The Evolution of Pharmaceuticals in the United States," which I found by Google search:

"Frederick Stearns was [an] important industry pioneer. He started a manufacturing facility in Detroit in 1855 and it was an important supplier of medicines during the Civil War. Stearns also became a reactionary against the medical quackery that was rampant at that time, so he put his products into popular-sized packages bearing full directions for their use plus a plain statement of the names and quantities of the ingredients in the package. He thus pioneered the phrase 'ethical specialty' for his products, and that was the origin of the phrase 'ethical pharmaceuticals' that survives to the present day. (Frederick Stearns and Company was acquired by Sterling Drug in 1944.)"

I am not sure when this bit of history was written, but as I said, in the "present day" we no longer hear the phrase "ethical pharmaceuticals." We all know why. The industry has been found guilty of unethical and even unlawful practices that include hiding clinical trial data (see "GSK's Coverup of Avandia's Heart Risk Data: Is This How the Entire Industry Views Its Responsibility to Patients?") and illegally marketing drugs. In recent years, the industry has paid huge fines and instituted corporate integrity agreements to settle DOJ cases (see, for example, "Transparency Vs. Translucency in Reporting Physician Payments").  The industry's low esteem among the general public is a direct result of this bad behavior and not, as some industry defenders claim, due to skewed media reports and anti-industry books like "Bad Pharma" (see here).

So it was with great interest that I read about a new effort to improve the drug industry's reputation: the establishment by a bioethicist of an accreditation rating system (read all about it on Pharmalot: "Good Housekeeping Seal For Pharma?"). "Jennifer Miller, a fellow at the Edmund J Safra Center for Ethics at Harvard University and president of Bioethics International, a non-profit that advises educational programs on ethical issues on medicine and healthcare, is trying to develop the industry equivalent of a Good Housekeeping Seal of Approval," reports Pharmalot.

"The standards [for the rating system] have been compiled and developed by a council that I put together," said Miller. "It includes input from two former FDA commissioners – Mark McClellan and Andrew von Eschnebach, and some executives in the pharmaceutical industry, patient advocates, physicians."

Her choice of former FDA commissioners leads me to believe Miller's system is "fixed" so that no pharma company would get a bad grade. As one Pharmalot commenter pointed out "The credibility of this plan will depend on who the judges are. The fact that the 'committee' already includes an FDA Commissioner who himself resigned because of ethical trouble makes one wonder."

Andrew von Eschenbach, famous for resigning as FDA commissioner and leaving the agency leaderless on the very day that Obama was inaugurated (see Eschenbach Announces Resignation, FDA Staffer Throws Shoes in "Farewell Kiss"), is now employed as chairman of conservative think tank Manhattan Institute's Project FDA initiative. If von Eschenbach has his way, FDA will be out of the business of approving new drugs based on efficacy, but will merely rubberstamp any drug that won't kill humans outright (see here)! In essence, the entire U.S. population will become non-volunteer experimental subjects. A drug's efficacy will be proven (or not) in the marketplace. That would not be how the general public would want an "ethical" drug industry to operate.

Meanwhile, Mark McClellan was allegedly involved in the decision to bar Barr's Plan B OTC conversion. McClellan resigned after a very short term. According to a story in the NY Times, the FDA deleted or threw out all of McClellan's e-mail and written correspondence on the subject (see "Plan B FDAgate").

Is it any wonder that no pharma company will touch Miller's proposed plan with a 10-foot pole and become a "pilot" case?

Is Pharma Too Big to Succeed?

You've heard of investment banks being "Too Big To Fail" as an excuse for government intervention. After reading the book "Devalued and Distrusted" by John LaMattina, former Pfizer president of R&D, I've come up with a new twist on corporate bigness and failure: Pharma is Too Big to Succeed; well, succeed alone.

LaMattina does says that “industry consolidation of the last 15 years has resulted in less competition, less investment in R&D, and a gradual decrease in the approval of new medicines…such a trend should be alarming,” according to LaMattina.

LaMattina cites M&A’s disruptive consequences, such as cost-cutting, site closures, shifting of people and projects, etc. However, a few pages on, LaMattina points out that big pharmaceutical companies cannot meet a glaring unmet medical need for new antibiotics because the “commercial return on a new antibiotic would pale in comparison to a new treatment in areas like cancer or Alzheimer’s Disease. This is attributed to the fact that an antibiotic is generally used acutely,” says LaMattina, “not chronically, and so profits are diminished by short-term use. . . This narrow use. . . [makes] it unattractive for a big [my emphasis] company.” La Mattina suggests that fulfilling such unmet medical needs is “ideally suited to the expertise of biotech companies.”

These musings and others in the book seem to undermine LaMattina’s goal, which is to correct the public’s perception of the drug industry – a perception that has been distorted by the media such as The Dr. Oz Show where he made a fateful guest appearance. Much to LaMattina’s chagrin, the show was titled “The Four Secrets that Drug Companies Don’t Want You to Know.” His book is in many ways an attempt to rebuff the premise of that one show by addressing the “four secrets,” which are:

1. Drug companies underestimate dangerous side effects
2. Drug companies control much of the information your doctor gets
3. You’re often prescribed drugs that you don’t need
4. Drugs target symptoms, not the cause

I’m not going to get into all of LaMattina’s thoughts on these issues. You’ll have to read the book yourself. Unfortunately, as I mentioned in a previous post, the paperback version costs $29.95, which means most of the American public will never buy it. Even if they did buy it, I doubt they would read it because it is pretty technical and seems to be written more for physicians than for the lay public.

Back to the “secrets.” I’d like to focus on LaMattina’s rebuff of “secret” #4 and how it relates to the topic of this post; that is, Pharma is Too Big to Succeed.

IMHO, LaMattina, fails to convince me that Big Pharma focuses on the causes of diseases rather than the symptoms. When he waxes on about the benefits of “targeted therapies,” for example, he says we are “not far from the time when a cancer diagnosis” will be one “of a chronic disease, one that might not necessarily be cured but rather treated with a variety of medications that will keep one’s cancer in check. . . what a wonderful situation for patients,” says LaMattina. Obviously, postponing death – a major “symptom” of cancer – is wonderful for many patients. It’s also wonderful for Big Pharma, which currently has about 1000 “novel anticancer agents” in clinical development.

LaMattina suggests he may be “naïve” when he assumes expensive targeted cancer drugs when used in combinations can be delivered at a “reasonable cost.” It’s only this hope that he cites to counter the point he makes earlier that paying for all these new cancer treatments “will become unsustainable.” Treatments are not so “wonderful” when they are not sustainable, IMHO.

LaMittina also points out that Big Pharma spends only about 15% of its R&D budget on “R”; i.e., basic research. Research is much better left to NIH, academia and other government funded labs. LaMittina gives the public sector credit for this basic research and points out that “a successful academic-industry partnership is crucial in discovering new medicines.” In those cases where NIH is “diverting” hundreds of millions of dollars to do “drug discovery,” LaMittina suggests this is “clearly better done by industry,” which is responsible for 90% of new drugs approved for marketing by the FDA.

So, it’s clear that Big Pharma cannot succeed on its own and should not lay claim to all advances in “curing” diseases such as cancer.

Despite the economic realities of Big Pharma companies mentioned above, LaMattina on one hand says that “Big Pharma can gain a lot of good will, something it desperately needs, by fully committing to rare diseases…” On the other hand, LaMattina suggests that Big Pharma needs to be happy with a “niche blockbuster” model whereby instead of having a “few $10 billion-selling drugs,” it has “many billion dollar products.”

As I pointed out in a previous blog post, it is possible to have billion dollar “orphan drugs” targeted at rare diseases IF the price is right. One such drug is Pfizer's Xalkori (crizotinib), a newly approved for a rare form of lung cancer, for which Pfizer plans to charge $115,200 a year per patient. LaMattina cites Xalkori many times in his book as a wonder drug, but does not mention the price Pfizer wants to charge for it. At that price Pfizer only needs 9000 patients to reach a billion dollars in sales! (see “New Big Pharma Economies of Scale: Less Patients Needed to Reach Blockbuster Sales”).

Drop TV Ads, Says John LaMattina, Former Pfizer President of R&D

It's been a long, long time since anyone has seriously suggested a "moratorium" or complete halt to direct-to-consmer (DTC) drug TV advertising in the U.S. But that's just what was suggested by John LaMattina, former Pfizer president of Research and Development. In a Forbes opinion piece titled "Pharma's Reputation Continues to Suffer -- What Can Be Done To Fix It" (find it here), LaMattina offered 4 "fixes," including "Drop TV Ads" as #4 on his list.

The other 3 fixes LaMattina put on a par with dropping TV ads are

1. Transparency of payments to healthcare professionals, 
2. Transparency of clinical trial data, and 
3. Stop the illegal detailing of drugs 

These fixes are not nearly as controversial as #4. #1 is already being dealt with thanks to the Physician Sunshine law -- although complete implementation has not yet occurred (read this). #2 is also in the works, although there seems to be some push back from the industry (see "A Voluntary Industry Code For Releasing Trial Data?" here). #3 is self-evident; I mean "duh!"

Drug TV ads, says LaMattina, "may be doing more harm than good. The litany of side-effects that must be discussed is numbing and probably doesn’t provide a sense of the true risk-benefit for that medication. Plus, the public views these ads to be a waste of funds that could otherwise be invested in R&D or in lessening drug costs."

The last time I wrote about banning drug TV ads was in August 2009 when I wrote a piece that appeared in the NY Times (see "The New York Times, DTC, and Me"). In it I said "the industry pushes the envelope by overstating benefits and playing down the risks. That has got to stop."

LaMattina is also the author of a new book published by Wiley: "Devalued and Distrusted: Can the Pharmaceutical Industry Restore Its Broken Image?" You can get a Kindle edition on Amazon for an astounding $23.99 ($29.95 for the paperback version)! This book, IMHO, is not likely to get a wide readership among the general public for that price! Luckily, LaMattina sent me a review copy at no charge.

In his book, LaMattina closes the section on dropping TV ads with this paragraph:

"If the pharmaceutical industry is really concerned about being better valued by the public, it might do well to drop TV ads completely. However well-intended they are, the negatives have always [my emphasis] outweighed the benefits. If the members of the Pharmaceutical Research and Manufacturers Association agreed to halt TV ads, my guess is that the public's response would be overwhelmingly positive. My sense is that they wouldn't miss the commercials either."

But I know a few influential people who WOULD miss the ads: pharmaceutical brand managers and their DTC advertising agencies. After all, these ads generate a 2:1 return on investment (ROI) according to DTC experts (read this, for example) and the agencies surely enjoy and, in these trying economic times, need their portion of the $2.4 billion that LaMattina says is spent on TV ads each year by the industry.

So will pharma ever "drop" TV ads? It's like the old Woody Allen joke: a guy walks into a psychiatrist's office and says, hey doc, my brother's crazy! He thinks he's a chicken. Then the doc says, why don't you turn him in? Then the guy says, I would but I need the eggs!

P.S. In his book, LaMattina admits he was part of the problem when he was employed by "Big Pharma." "I was sympathetic to these ads," he says. Perhaps LaMattina could have spoken out against TV Ads when he was president at Pfizer, but as an R&D person it wasn't his place to do so. However, at least ONE currently employed Big Pharma executive has suggested that pharma marketing spending has gone too far, at least relative to R&D. In a video interview with Wall Street Journal, Joseph Jimenez, the CEO of Novartis, said "The industry needs to spend more money on R&D and less on sales and marketing" (read more about this here).

I'll have more to say about LaMattina's "fixes" in a review of his book to be published in an upcoming issue of Pharma Marketing News.

Does the Flu Vaccine Work? What 62% "Effective" Really Means

JAMA has posted today a Viewpoint titled “Influenza Prevention Update: Examining Common Arguments Against Influenza Vaccination.”

In this Viewpoint, the authors (from the Vanderbilt University School of Medicine) provide perspective to some of the reasons why people refuse the flu vaccination, including:

• The vaccine does not work
• The vaccine causes the flu
• I have an allergy to eggs
• I cannot get the vaccine because I am pregnant or have an underlying medical condition or because I live with an immunocompromised person.
• I never get the flu/I am healthy 

I was disappointed when Dr. LaPook on a recent CBS Evening News program said that this year's Flu vaccine was 62% effective in preventing the flu. First of all, I would have liked it to be 100% effective in preventing the flu. And I'm pretty sure LaPook specifically said "preventing" without qualifying what "preventing" actually means. Now I learn from the JAMA viewpoint cited above that there is a qualifier:

The Centers for Disease Control and Prevention's midyear assessment of this season's influenza vaccine's effectiveness is 62% (95% CI, 51%-71%) for the prevention of medically attended acute respiratory illness [my emphasis].

Also: "CDC typically presents vaccine effectiveness (VE) as a single point estimate: for example, 60%. This point estimate represents the reduction in risk provided by the flu vaccine. CDC vaccine effectiveness studies commonly measure laboratory confirmed flu illness that results in a doctor’s visit or urgent care visit as an outcome. For this outcome, a VE point estimate of 60% means that the flu vaccine reduces a person’s risk of developing flu illness that results in a visit to the doctor’s office or urgent care provider by 60%" (see "How does CDC present data on flu vaccine effectiveness?").

The authors note "A prevention measure that reduced the risk of a serious outcome by 60% in most instances would be a noted achievement."

Back on January 11, Vanderbilt University's Dr. William Schaffner (not an author of the Viewpoint cited above) was interviewed on "CBS This Morning" (listen here) where he "anticipated" that the vaccine is "able to prevent 60 to 70 percent of all infection." He, like Dr, LaPook, did not mention prevention in terms of preventing a "serious outcome" (i.e., medically attended acute respiratory illness).

I've taken the vaccine. So I guess I can still get the Flu, but not serious enough that I will end up in the emergency room -- at least a 60% chance that I won't end up there! I think I'm feeling slightly sick. Can it be the flu?

Pharma Sets Record: Number of "Pay-for-Delay" Deals Hits 40 in 2012 Says FTC

According a new Federal Trade Commission (FTC) staff report, in Fiscal Year (FY) 2012, the number of "potentially anticompetitive patent dispute settlements" (aka, "Pay for Delay" deals) between branded and generic drug companies increased significantly compared with FY 2011, jumping from 28 to 40 (find the report here).

Here's a plot of the data showing the trend over the past 9 years:

The study also found that in nearly half of these settlements, branded firms may have used the promise that they would not develop or market an authorized generic (AG) as a payment to stall generic drug firms from marketing a competing product.

Why the big jump in these deals? It's another indicator that pharma has fallen off the patent expiration cliff and is using these deals to ensure "soft" landings. I thought, however, that such deals would have declined in the face of recent FTC challenges such as the complaint against Solvay Pharmaceuticals. According to the FTC, Solvay paid generic drug makers to delay generic competition to its branded testosterone-replacement drug AndroGel (see "FTC Sues Drug Companies for Unlawfully Conspiring to Delay the Sale of Generic AndroGel Until 2015"). Now that there's Androgel 1.62%, a whole "new" formulation approved for marketing by the FDA, any previous pay-for-delay deal is beside the point.

Aside from developing new formulations, drug companies have other ways to avoid costly and public image busting pay-for-dealy deals. You might recall, for example, that Pfizer tried to extend the marketing life of Lipitor by implementing an innovative "Save the Lipitor Cash Cow" battle plan, which included:

• keeping marketing at a high level instead of the typical two-thirds dropoff during the final year of patent protection, 
• offering insured patients a discount card to get Lipitor for $4 a month, 
• paying pharmacies to mail Lipitor patients offers for the $4 copay card and to counsel patients about the benefits of Lipitor, 
• negotiating unusual deals with some insurance plans and prescription benefit managers

The plan, however, failed (read more about it here and here). Perhaps Pfizer should have been less "innovative" and stayed with the tried-and-true "pay-for-dealy" deals.

Study Reveals Inaccuracy of Smartphone Health Apps

Performance of smartphone applications in assessing melanoma risk is highly variable and 3 of 4 applications incorrectly classified 30 percent or more of melanomas as unconcerning, according to a study published in JAMA Dermatology ("Diagnostic Inaccuracy of Smartphone Applications for Melanoma Detection"; jamadermatol.2013.2382). The authors suggest that reliance on these applications, which are not subject to regulatory oversight, and not seeking medical consultation can delay the diagnosis of melanoma and potentially harm users.

This is the first example I have seen of a study evaluating the accuracy of health apps, but it may not be the last. Sooner or later, apps developed by pharma companies will also be subject to such scrutiny by academics, and also by the FDA.

I myself have reviewed several health apps developed by pharma companies that may be "buggy" and deserve to be rigorously tested for accuracy (see "Some Unregulated Physician Smartphone Apps May Be Buggy"). Some pharma apps may be collecting personal information without adequately notifying users (see "Checking Under the Hood of Pharma Mobile Apps") or may be performing diagnostic calculations using undocumented and uncertified algorithms (see "FDA Promises Still More Guidance! This Time It's Mobile. Janssen's Psoriasis iPhone App May Need It").

The authors of the study cited above looked at 4 apps that are designed to help consumers evaluate photographs of skin lesions and provide the user with feedback about the likelihood of malignancy. Three of the apps studied used an automated analysis algorithm to evaluate images. These apps were free or very inexpensive (e.g., $4.99) and allowed unlimited evaluations at no additional charge. The fourth app required images to be sent to a board-certified dermatologist for evaluation and an assessment is returned to the user within 24 hours (for a fee).

Although the authors did not identify the apps, I used one of their search terms ("skin cancer") in the Apple App Store and quickly found two representative apps, which are displayed in the image below:

The authors used the apps to evaluate photos of 60 melanoma and 128 benign control lesions. It's no surprise that human experts were much better at correctly evaluating skin lesions. Whereas the 3 apps that used algorithms evaluated 30% or more of melanomas as "unconcerning," the remote dermatologist app incorrectly evaluated only 1 of the 53 melanomas as typical (ie, benign).

The authors note that "more than 13,000 health care applications marketed to consumers are available in the largest online application store alone... Two-thirds of physicians use smartphone applications in their practice. Some [my emphasis] of these applications have been evaluated in the peer reviewed literature,...However, this type of evaluation is not common for applications marketed directly to consumers," noted the authors. And I wouldn't say this type of evaluation is "common" either for apps marketed directly to physicians by pharma.

The FDA may regulate some medical apps, but it is unclear which apps will be subject to regulation and what the regulatory review will entail. Sooner or later, IMHO, Congress is going to be investigating mobile health apps to see if more stringent regulations are required.

IMHO, the pharmaceutical industry should differentiate itself from "wild west" apps developers by being pro-active in issuing Guidelines for Mobile Health Apps Developed by the Pharmaceutical Industry in much the same manner as it developed other self-regulatory guidelines such as PhRMA's DTC Guiding Principles and Code on Interactions With Healthcare Professionals.

What Do You Think?

The Regulation of Pharma Health Apps Survey asks whether or not you agree that it is in the drug industry's best interest to police itself and develop best practices or self-regulatory guidelines for developing trustworthy health/medical apps for consumers and physicians.

It also asks if you agree or disagree with the following specific suggestions:

• Apps must include full disclosure regarding the company that has created the app or the sponsoring pharma company. This includes contact information. BRANDED apps MUST include ISI (important safety information) up front in an easily accessible manner (e.g., on start-up screen).
• Apps that are BRANDED (i.e., mention drug brand names) must be available ONLY from the appropriate U.S. app site (e.g., Apple App Store) even if all the FDA-required ISI (important safety information) is included.
• Apps intended to be used by healthcare professionals in the U.S. must be HIPAA compliant.
• If an app collects personal information, it should include a privacy policy that explains how such data is protected (security), who owns the data, how users can access the data, where data is stored (on device or on remote web site) and instructions for opting out of data collection.
• The pharmaceutical industry has to police itself with regard to development of all health apps regardless of what regulations FDA may impose.
• The app should include appropriate disclaimers and terms of use that the user MUST agree to before the app will run.
• All health/medical apps should be certified by third parties such as Happtique.
• If an app relies on algorithms or formulas, it must be validated through rigorous testing and documentation to ensure it works properly (i.e,. calculations are correct).

Please take a few minutes to respond to this survey here. The summary of results will be published in a future issue of Pharma Marketing News. You may remain anonymous or you may provide your name and contact information if you wish to be quoted in the published summary. If so, I may contact you for more details and allow you to review your responses prior to publication.

Bad Pharma: A Cherry Picked NON Evidence-based Critique of Pharma Marketing?

I finally finished reading the 400 plus page book Bad Pharma™ by BenGoldacre, a British physician, whose previous book, Bad Science, was a best seller in the "non-fiction" realm.

As the name suggests, Bad Pharma is a no-holds-barred critique of practically every aspect of the pharmaceutical industry from drug development to marketing. Chapter titles include reiterations of the "bad" theme such as "Bad Trials" and "Bad Regulators." The chapter on marketing, which comprises about 25% of the book, is merely titled "Marketing." Goldacre summarizes the raison-d'etre of pharma marketing as existing for "no other reason than to pervert evidence-based decision making in medicine" and proceeds to "take a look at this mysterious world."

Of course, pharma marketing is not "mysterious" to me. I am familiar with most of Goldacre's criticisms, having written about the same subjects for many years. I was surprised, therefore, when none of my posts to this blog was referenced by Goldacre!

For example, when Goldacre states unequivocally that "tens of billions of pounds are spent each year, $60 billion in the US alone, on medicines marketing," he might have referred to my post that disputed this number ("Promotion vs. R&Deja vu all over again!"; also, see my analysis below).

I'd like to focus on this issue again here because it illustrates how Goldacre "cherry picks" data to buttress his argument despite his claim otherwise ("this book is based on systematic reviews, which summarise all of the evidence ever collected on a given question") and his claim that the pharma industry does the same; e.g., fails to report negative trial data, which is the focus of the first chapter of his book, "Missing Data", and which is "key to the whole story."

How much money the drug industry spends on marketing vs. research and development is a contentious issue, as Goldacre points out. "Marketing spend is a contested area, as the industry is keen to play it down," says Goldacre in the Notes section of the book where he could have referenced my post above, but did not. Nevertheless, he summarizes the issue this way:

"A quarter of the pharmaceutical industry's revenue is spent on marketing, twice as much as it spends on research and development, and this all comes from your money, for your drugs. We pay 25% more than we need to, an enormous mark-ip in price, so that tens of billions of pounds con be spent every year producing material that actively confuses doctors and undermines evidence-based medicine." 

"This is a very odd state of affairs," says Goldacre.

It's also "odd" that Goldacre's math does not add up. The value of the global pharmaceutical market was estimated to be US$880 billion in 2011 according to IMS Health (see "Pharmerging Markets to Continue Strong Growth"). One quarter of that would be over US$200 billion. All of this, of course, is not spent in US marketing, which Goldacre pegged as US$60 billion. However, I cannot imagine that the difference (US$140 billion) is spent in other countries. US marketing spend must be about 75% of the total in line with the overall size of the US market compared to the rest of the world. Even if it's only 50% that would mean US$100 billion spent on pharma marketing in the US, which is quite a bit more than the US$60 billion that Goldacre cited a few pages earlier in his book.

OK, that's a math error. But Goldacre also cites conflicting numbers for pharma marketing spending in the US. While he cites US$60 billion on page 246, on page 317 he says "we know that $30-40 billion is spent by the industry on drug marketing in the America" (aka "US").

I don't want to nitpick, but which is it: $60, $100, or $30 billion? Obviously, whatever the number, it's big. But is it twice as big as the R&D spend? That's the main thing Goldacre and other critics of the drug industry want people to believe in order to blame marketing for the high cost of drugs.

Let me revisit my critique of the $60 billion number that Goldacre cited and thus debunk the notion that pharma spends twice as much on marketing as it does on R&D.

The study that Goldacre cited for the $60 billion estimate was done by two Canadian authors: "The Cost of Pushing Pills: A New Estimate of Pharmaceutical Promotion Expenditures in the United States," which was published in PLoS Medicine.

Their conclusion: The pharmaceutical industry spends almost twice as much on the marketing and promotion of drugs than on research and development (see the story here).

"For the last 50 years, say the authors, there has been an ongoing debate as to which image [see left] of the drug industry is most accurate. The industry promotes a vision of itself, say the authors, as 'research-driven, innovative, and life-saving,' but the industry's critics contend that the drug industry is based on 'market-driven profiteering.'"

To prove this, the authors use data from 2 different sources: IMS and CAM as shown in this table:


Is anyone troubled by the methodology of the authors?

I mean, what could be easier than cherry picking which data to use and to make sure to always use the highest estimate to prove your point, which you obviously believed was true before you even did the "analysis?"

In essence, the authors place more value on the CAM data then on the IMS data. I'm not sure why, since both companies provide services for a fee to the pharmaceutical industry. The main difference between the two company's methodology is that IMS surveys the industry whereas CAM surveys doctors.

If you ask me, one methodology (IMS's) overestimates R&D costs and underestimates promotional costs, while the other (CAM's) is prone to exactly the opposite.

The biggest differences between the datasets involve cost of samples, cost of detailing, and "unmonitored promotion."

Cost of Samples
There is a large difference between the IMS (US$15.9 billion) and CAM (US$6.3 billion) estimates for cost of samples. Essentially, IMS bases its estimate on the retail value of samples, whereas CAM bases it on the Average Wholesale Price.

Which number would you use?

The PLoS authors use the IMS retail cost estimate because that is how the drug industry itself estimates the value of free samples it gives away! This is just another case where the industry shoots itself in the foot. It's hard to argue with the PLoS authors' statement that "it is inconsistent for donations to be reported in terms of retail value and samples in terms of wholesale value."

Cost of Detailing
The authors point out that "There is a significant discrepancy between the two sets of data in the cost of detailing: US$7.3 billion for IMS and US$20.4 billion for CAM."

IMS only considers the "cost to field the rep" and doesn't include in its estimate--as CAM does--indirect costs like costs for the area and regional managers, the cost of the training, and the cost of detail aids such as brochures and advertising material.

The authors claim that "relying on physician-generated data to estimate the amount spent on detailing [which is CAM's data collection method] is likely to give a more accurate figure than using figures generated by surveying firms [which is IMS's method]. Companies may not report some types of detailing, for example, the use of sales representatives for illegal off-label promotion, whereas doctors are not likely to distinguish between on- and off-label promotion and would report all encounters with sales representatives."

I dunno. If it were up to me, I would use a number somewhere in between the IMS and CAM estimate--say $10 billion.

"unmonitored promotion"
I am especially troubled by the $14.4 billion estimate for "unmonitored promotion." All that the PLoS authors have to say about this is:

"We believe that it is appropriate to correct for unmonitored promotion and that the figure we used is a reliable estimate. The 30% correction factor is based on a direct comparison that CAM is able to make between the data it collects through its surveys and the amount reported by companies."

May I say that this hardly rises to the level of objective analysis of available data? My analysis would completely discount this number as something that cannot be known and therefore should not be used. Besides, the same could be said for R&D spending and the two estimates would cancel one another.

My "NEW NEW" Estimate
Instead of the estimate of $57.5 billion that the PLoS authors use for promotional spending in the US, my NEW NEW estimate is $32.7 billion, which is pretty close to the $29.6 billion the PLoS authors use for the R&D estimate. This would lead me to conclude that--within the sampling margin of error, the US pharmaceutical industry spends about as much on R&D as it does on promotion. There! Everyone's happy!

Of course, I don't expect Goldacre to be happy with my NEW NEW estimate. He is a doctor and therefore would tend to favor physicians' anecdotal estimates vs industry's estimates of how much is spent on pharma marketing. That is, he favors a distinctly NON evidence-based approach when it suits his goal.

What is your estimate of the ratio of global pharma spending on marketing vs R&D?
	Marketing Spend = R&D Spend (about same)
	Marketing Spend = 2 X R&D Spend (twice as much)
	Marketing Spend = 0.5 X R&D Spend (about half)
	I prefer to avoid the issue altogether

Team Novo Nordisk: Insulin "Doping" Difficult to Prove

Novo Nordisk has a penchant for teaming up with athletes to help promote its diabetes franchise. You might recall that in the U.S. Novo Nordisk's Levemir insulin brand team sponsors Charlie Kimball, a racecar driver who has diabetes (see here). Just recently Novo Nordisk in Europe created the first all-diabetes professional cycling team to compete as part of "Team Novo Nordisk."

Auto racing and cycling are two sports that are heavily sponsored by corporations. Brand and company logos are plastered all over the machines and the uniforms worn by the athletes. Kimball is a Levemir-branded billboard that must comply with FDA regulations because he displays the Levemir logo and is known to use the drug to treat his diabetes. Therefore, the back of his uniform must include fair balance (seriously!).

Pharma companies, however, cannot sponsor branded ads in Europe. Consequently, the uniforms worn by the cyclists of Team Novo Nordisk only sport the corporate logo and the tag line "Changing Diabetes" (see the photo on the left, which is the one used by the @TeamNovoNordisk Twitter home page; see more photos here).

In order for this sponsorship to work, Novo has to be EXTREMELY careful about "doping," which as we know from Lance Armstrong et al is (or was) rampant in the professional cycling circuit. Artificial insulin (e.g., Levemir) is reportedly being used by a growing number of athletes in an effort to boost performance illegally (see here). The International Olympic Committee banned the use of this hormone by non-diabetic athletes in 1998 and Team Novo Nordisk has announced that they will set up a zero-tolerance doping policy; presumably doping with performance enhancing drugs OTHER than Levemir (see here).

It is perfectly legal for Team Novo Nordisk members -- all of whom have diabetes -- to use Levemir while racing. Does it give them an advantage similar to the "advantage" that some people claim runners with high-tech prosthetic limbs have (see here)?

"We don't want riders who have ever been convicted of doping, and there will be immediate consequences, if one uses illegal means,” Jacob Riis, senior vice president at Novo Nordisk, told the Ritzau news agency. “Otherwise, we rely on the initiatives taken by the international cycling union UCI has begun."

"The World Anti Doping Agency (WADA) is currently seeking a test for insulin abuse," according to the article cited above. That agency may have a technique that can discriminate metabolites of lantus insulin (a long-acting synthetic insulin) from naturally produced human insulin. "However, this method doesn’t seem to work for the urine samples from diabetic patients who have been treated with recombinant human insulin or Levemir, two other commercially available long-acting insulins. This is obviously a major drawback when trying to establish a reliable test to detect insulin abuse."

So, it may be impossible to determine if Team Novo Nordisk members are engaging in "insulin abuse" and if that would be "illegal."

I may be cynical, but it seems that whenever there's an incentive to commit a crime that cannot be easily detected, the odds are good that the crime will be committed. Hopefully, Novo will be able to eliminate the incentive for Team Novo Nordisk members to "abuse" Levemir and make sure the team focuses on the goal: "be an inspiration for people with diabetes."

Some "Off-Label" Speech is No Longer Politically Correct

The Supreme Court has ruled that corporations are people protected by the U.S. Constitution and Bill of Rights just like us ordinary folk. That means, for one thing, the government cannot limit the freed of speech of corporations. This issue has been much discussed since last month's U.S. Court of Appeals 2-to-1 split decision to throw out the conviction of a sales representative for promoting off-label use of a prescription drug (see here).

This decision is already having an impact on speech, but not the speech of drug companies. It could be making the word "off-label" politically incorrect for use by the U.S. Department of Justice (DOJ), whose motto is "who prosecutes on behalf of justice."

"What will be different in ... future off-label cases," says Erika Kelton in a Forbes article, "is the vocabulary used [by DOJ] in describing the violations. Expect to hear the term “misbranding” being emphasized more than “off-label,” and “intended use” replacing “promotion” in supporting the misbranding charges brought by the government."

"This shift in vocabulary," says Kelton, "is already evident in the DOJ’s recent press releases announcing misbranding (née off-label) settlements. Justice chose its words carefully in its post-Caronia announcement of the Amgen settlement on Dec. 19 and navigated around the First Amendment decision. In describing Amgen’s wrongdoing, the government press release [here] explained that 'it is illegal for drug companies to introduce into the marketplace drugs that the company intends will be used ‘off-label,’ i.e., for uses or at doses not approved by the FDA.' [my emphasis]

"Compare that to the Justice Department’s pre-Caronia announcement of GlaxoSmithKline’s $3 billion settlement just six months ago. Like Amgen, Glaxo also was charged with criminal misbranding and civil False Claims Act liability. But the Justice Department release described the basis of illegality somewhat differently: 'Promotion by the manufacturer of other [unapproved] uses – known as ‘off-label uses’ – renders the product ‘misbranded.' [my emphasis]"

That's an interesting observation. However, further down in the DOJ press release is this: "The federal civil settlement agreement encompasses allegations that Amgen: (1) promoted [my emphasis] Aranesp and two other drugs that it manufactured, Enbrel and Neulasta, for “off-label” [my emphasis] uses and doses that were not approved by the FDA and not properly reimbursable by federal health care programs..."

More important than what the DOJ says in press releases is what it says in allegations brought before the court. We'll have to wait for future cases to see how that wording may change. The new motto of DOJ may also need revision as in "who prosecutes on behalf of political correctness."

AbbVie's "Drive for Five" Campaign: Innovative, Derivative, and Conflictive?

In reviewing what pharmaceutical trade publications had to say about the industry in 2012, I came across MM&M's "All-Star" winners of the year. Sanofi, for example, was MM&M's "All-Star Company of the Year." What caught my attention, however, was the "All-Star Marketing Team of the Year: Androgel." That team is AbbVie - Abbott Laboratories's recently spun-off independent biopharmaceutical company - and its agencies, which include Digitas Health for consumer and AbelsonTaylor for professional ads.

Androgel is a treatment for "low testosterone"; i.e., Primary hypogonadism and Hypogonadotropic hypogonadism. Or, as marketers like to call it, "Low T," which is much less scary than "Hypogonadotropic hypogonadism" (see "When It Comes to 'Low T' Treatment, Which Does Your Gut Trust: Axiron or Androgel 1.62%?").

I didn't realize that Low T drug sales in the U.S. reached nearly $2 Billion a year (ending October 2012) and that the $1.37 Bn in sales of Androgel represent about 70% of that total. In fact, Androgel sales increased 19% over that period thanks no doubt to direct-to-consumer (DTC) marketing coupled with physician marketing. No wonder MM&M gave Androgel marketers a rave review!

One of the marketing "initiatives" that MM&M highlighted was the “Drive for Five” campaign, which urges men to know their testosterone (T) levels, in addition to lipid, BP, blood sugar and PSA numbers. On the website (http://www.driveforfive.com; "Mens Health | Learn about 5 risks to mens health") is an animated "gear box" that shifts from high cholesterol (first gear) to high blood pressure (second gear) to high blood sugar (third gear) to high PSA (four gear) and, finally, to low testosterone (fifth gear).

Perhaps first gear -- the LOW gear -- would have been a better choice for LOW testosterone (it also would have been depicted FIRST in the animation). But, what do I know? I'm not an award-winning pharma marketer.

What I AM, however, is a representative member of the target audience for the "Drive for Five" campaign, except that I am not comfortable driving a stick shift -- in fact, I don't think I ever drove a stick shift car in fifth gear! I guess I don't "measure up" as a good target for Androgel advertising after all :-(

It seems that "driving" is a theme used by many pharmaceutical marketers. Recall, for example, Boehringer Ingelheim's "Drive for COPD" campaign (see "Danica Patrick: NASCAR Driver, Super Model, Superbowl Lingerie Ad Model, & COPD Spokesperson All Rolled Into one!") and Novo Nordisk's "Drive with Insulin" campaign, which posted the branded tweet heard round the world (see here).

So I'm not giving the "Drive for Five" campaign many kudos for being innovative. In fact, it's a bit "derivative" in that "Drive for Five" is a campaign slogan used by many other brands as evidenced by these images found via a Google search:

Shell, Pepsi, New York Islanders, and Nike have all used that service/trade mark. I'm not a trademark lawyer, but Shell may contest AbbVie's registration of the "Drive for Five" trademark. Shell registered this mark in August, 2011, whereas Abbott Labs registered it in April 2012.

Lastly, urging men to know their testosterone levels is another example of how pharmaceutical companies manipulate numbers to suggest that more of us require treatment than would otherwise be the case. How do they do this? By influencing treatment guidelines recommended to physicians by their professional societies such as the Endocrine Society Clinical Practice Guideline for Testosterone Therapy in Adult Men with Androgen Deficiency Syndromes (find it here). Here's a screen shot of the financial disclosure page of that guideline (click on it for a larger view):

Six out of the seven task force members have received payments from Abbott Laboratories and other pharma companies. According to the Institute of Medicine (IOM) Standards for Trustworthiness of practice guidelines, none, or at most a small minority, of guideline development group members should have conflicts, including services from which a clinician derives a substantial proportion of income. In particular, says IOM, the chair and co-chair should not have conflicts. Shalender Bhasin, M.D. -- the task force chair for the Endocrine Society Clinical Practice Guideline for Testosterone Therapy -- received consultation fees from GSK and Merck and research grants and "Other Research Support" from Abbott Laboratories, Ligand, and Merck.

This, no doubt, is a "conflict of interest" regarding when physicians should "measure up" their male patients; i.e., perform a test to measure their testosterone levels. In the recent past, another conflict of interest may have been at play because Abbott both marketed Androgel and supplied the testosterone testing services. Now that Abbott Labs and AbbVie are separate companies, there is no conflict of interest between Androgel promotion (handled by AbbVie) and testosterone testing (handled by Abbott Labs, I assume).

BTW, I notice that the "Drive for Five" gearshift does not have "reverse." I can only guess why the marketers omitted it. There must have been some "cons" and "pros" expressed by the team. One "con" may have been that "reverse" connotes negativity. A "pro" argument could have been that "reverse" could signify a reversal in the aging process -- like regaining energy, libido, etc. Oh wait, that might been interpreted by the FDA as overstating efficacy or promoting "off-label."

"Spend Less Money on Sales & Marketing," Says Novartis Chief Joseph Jimenez

In a video interview with Wall Street Journal, Joseph Jimenez, the CEO of Novartis, said "The industry needs to spend more money on R&D and less on sales and marketing. In the past two decades, a lot of the value creation came from sales and marketing muscles for new drugs. And now there is probably less investment by some companies to ensure that there is going to be a continuous flow of innovation." Find a partial transcript of that interview and the video here.

I modified an image of the famous "Welsh Wanker" to illustrate the "muscle" analogy suggested by Jimenez. The "S&M Arm" of the "Pharma Wanker" represents the overspending on sales and marketing, whereas the  "R&D Arm" represents the underspending on research and development.

"Wanker," BTW, is a pejorative term of British origin. It initially referred to "one who masturbates" but has since become a general insult commonly meaning wasting time or, in this case, money.

According to Cegedim Strategic Data, Novartis is among the top 10 (maybe #4 or #5) direct-to-consumer (DTC) spender -- not a shabby "Pharma Wanker" as far as Sales & Marketing muscle goes. The chart below shows the top 10 DTC spenders between July 2011 and April 2012.

I don't have data on R&D spending, so I can't judge the relative muscle size of Novartis's "R&D Arm" compared to its "S&M Arm." It remains to be seen, however, whether Novartis will let the latter atrophy a bit and step up development of the former.

In a previous post, I predicted that DTC spending by the pharmaceutical industry in general will decrease agin in 2013 (see "Some Interesting Pharma Predictions for 2013"). When a CEO of a major pharma company says the industry should spend less on sales and marketing, it signals that my prediction may come true in spades!

A "New" New Year's Resolution: Keep on a Few Extra Pounds

Almost everyone makes this New Year's resolution: lose weight! I also resolve to lose weight this year. But after seeing the results of a new study published in JAMA, I am modulating that goal: remain "overweight" by keeping on a few extra pounds.

The study (see here), which was performed by the Centers for Disease Control, was a meta-analysis of 97 studies that provided a combined sample size of more than 2.88 million individuals and more than 270,000 deaths. The researchers found that "overweight" and even slightly "obese" people had a 5-6% lower risk of death than people of normal weight.

In the U.S. approximately 30% of people are classified as "overweight" as determined by a well-known and widely used "health risk" indicator: Body Mass Index (BMI). According to the National Heart, Lung, and Blood Institute (NHLBI), BMI is a "measure of body fat based on height and weight that applies to both adult men and women." NHLBI defines these BMI categories:

• Normal weight = 18.5-24.9
• Overweight = 25-29.9 
• Obesity = BMI of 30 or greater

At least one pharmaceutical company with a product that treats a weight-related illness such as type 2 diabetes includes a BMI calculator on its drug.com website. Sanofi Diabetes goes so far as to use "BMI Calculator" as a keyword to serve up search ads such as the following:

Loss Leader Search Ad
This visible URL of this ad (www.rapid-acting-insulin.com) actually takes you to the Apidra branded website home page (www.apidra.com), not directly to the BMI calculator, which is among the tools on the site. I call this a "loss leader" search ad, meaning it entices you into the "store" (drug.com website) with a free offer (e.g., health risk calculator), but forces you to search through the site for the calculator while being bombarded with promotional messages for an expensive product; i.e., Rx drug.  In this case the drug is Apidra, a rapid-acting insulin for adults with type 2 diabetes.

NOTE: The above ad is also an example of "URL redirection," which is a technique for making a web page available under many URLs. This technique is generally not allowed in Google Adwords, but the pharmaceutical has a "free pass" from Google to use redirection to avoid including the brand name in the visible URL of the ad and thus avoid FDA regulation. For more on that, see "Should Google Allow Pharma an Exception to Its Ban on Redirect URLs?"

I eventually found the BMI calculator on the apidra.com site and calculated the weight I would have to maintain in order to be in the "sweet spot" with the lowest risk of death. According to the study mentioned above, that "sweet spot" is a BMI between 25 and 29.9, which is associated with a "hazard ratio" of all-cause mortality equal to 0.94 (compared to 1.00 for normal weight people with BMI below 25). In my case, I need to weigh at most 195 lbs to be in that sweet spot:

The Right Thing to Do Viz-a-Viz Online Risk Calculators
BMI calculators and similar "health risk" tools promoted by pharma marketers often do not indicate the source of the algorithm used to calculate the results (see here, for example). I am sure that the Sanofi BMI calculator is based on the same algorithm used by NHLBI, which is fine. Sanofi and other pharma companies, IMHO, should follow best ehealth ethical practices such as the eHealth Code of Ethics and disclose what sources the site has used for its risk calculators, with references or links to those sources.

According to an editorial accompanying the research cited above, "Not all patients classified as being overweight or having grade 1 obesity, particularly those with chronic diseases, can be assumed to require weight loss treatment. Establishing BMI is only the first step toward a more comprehensive risk evaluation." One of the "chronic diseases" mentioned is diabetes. "The presence of a wasting disease, heart disease, diabetes, renal dialysis, or older age are all associated with an inverse relationship between BMI and mortality rate, an observation termed the obesity paradox or reverse epidemiology. The optimal BMI linked with lowest mortality in patients with chronic disease may be within the overweight and obesity range."

All this brings into question the appropriateness of BMI as and indicator of mortality (the JAMA editorial is titled "Does Body Mass Index Adequately Convey a Patient's Mortality Risk?"). One might even question the appropriateness of using BMI calculators as "loss leaders" to promote diabetes Rx drugs such as Apidra.