Those issues (adverse events, off-label discussions, fair balance presentation, no meaningful FDA guidance) hardly need rehashing here, and despite the barriers, progress has been made on the digital front, as evidenced by – if nothing else – pharma’s willingness to invest in smaller-scale social media efforts not directly tied to product sales. In the digital sphere, ROI means “hitting the primary endpoint,” and that endpoint could be data collection, engagement with widgets or functionalities on a page or within an app, or the number of visitors (or likes) on a Facebook page. “The ROI of social media is that your business will still exist in five years,” a quote from Socialnomics author Erik Qualman that surfaced in one of the presentations, speaks to the accepted necessity – in some quarters – of social media participation and customer engagement.

“Advertising has already largely shifted to what people say about your brand,” as opposed to the magazine, television and radio ads that people consume, said Martin Husar, customer strategy and innovation at Sanofi Canada. In Canada, DTC isn’t allowed, but last October Sanofi tapped the Toronto-based agency MediResource for an interactive Facebook campaign around atrial fibrillation (A-fib). The business objective, said Husar, was to “own the primary venues for Canadian patients and caregivers to learn about AFib.” By his measure, the company’s Afib at Heart | La fibrillation auriculaire à coeur Facebook campaign has been a success – one need not “like” the page to access the content, and thousands have clicked on tabs like “Ask the Expert,” or “Don’t Skip a Beat,” a Simon-inspired memory game.

A Janssen Canada educational campaign around psoriasis goes a step further, offering a list of available treatments, and a dermatology locator that returns only those dermatologists who “agree that they will use biologics” – Janssen markets Stelara, an immunomodulating biologic – and who have voluntarily signed up to be listed on Janssen’s Living Well With Psoriasis website, according to Spilios Asimakopoulos, director of marketing technology, Janssen Pharmaceuticals Canada. The site also offers a shareable psoriasis “severity calculator,” which is available online or as an app for download.

South of the Canadian border, others agree that the educational/disease awareness space is a good place for experimentation. John Patten, a sales rep for Facebook, told ePharma attendees that “Facebook makes sense in terms of initial support groups [for rare diseases], and locating others with the disease.” He also singled out Bayer’s Walk for Hemophilia and Sanofi Pasteur’s Voices of Meningitis as good examples of Facebook educational campaigns. “Pharma is more powerful in the unbranded, open wall pages” on Facebook, said Patten. Whitelisted brand pages, or pages with the comments function disabled, will be “de-prioritized in the news feed,” and they go against Facebook’s model, which Patten defined as “a distribution platform that promotes authentic sharing.” Perhaps as an added nudge to discourage whitelisted pages, Patten announced that by the end of February, “admins can drill down into individual commenters, and message them directly,” to help deal with “your drug turned my arm blue” adverse events comments.

A couple of hours before Patten’s presentation, however, a regulatory affairs director from a major pharmaceutical company was on a panel griping about the fact that while Facebook allows blocking of comments on the wall, “we can’t turn off sharing or commenting” on the actual brand image. Asked whether the company responds to such comments on the branded Facebook page, the panelist said no: “once you do that, where do you stop?”

Allergan CEO David Pyott

Allergan CEO David Pyott is bullish on Botox’s potential as a salve for chronic migraine. He’s also betting on a next-gen dihydroergotamine (DHE) – Levadex – from MAP Pharmaceuticals.

It’s hard to know whether migraine sufferers will get behind Botox as a treatment; migraine patients are notoriously allergic to doctor visits, and many go undiagnosed. But for the worst kinds of migraines, particularly those that don’t respond to triptans or currently marketed DHEs, patients will probably be willing to try just about anything. Allergan CEO David Pyott, and MAP Pharmaceuticals CEO Tim Nelson, see headroom for growth in the category.

In 2009, the migraine market slipped into a steady decline after Imitrex, the go-to member of the triptan class, lost its patent (and blockbuster sales). Many of Imitrex’s classmates – Maxalt, Amerge, Zomig, and others – will face generic competition this year, if they aren’t facing it already. That makes Botox for migraine a difficult sell – it’s for chronic migraine, firstly, and it costs exponentially more than generic Imitrex – but during a 4Q earnings call yesterday Pyott said the migraine indication is performing “better than planned.” Around 4,600 physicians have been trained to give the injection, to date, said Pyott. “The vast majority of neurologists will inject for as long as three injection cycles,” even if they’re skeptical about the drug’s efficacy for migraine,” he Pyott. He’s hoping they’ll be convinced after that.

Branded print ads for Botox migraine will launch in women’s magazines this month, and an unbranded disease awareness campaign on television “has worked – the click-through on the website is positive,” said Pyott, adding that Allergan’s internal consumer surveys have shown “a high level of satisfaction” among patients.

After an upfront payment of $60 million last February, MAP Pharmaceuticals scored a $20 million milestone payment last August, when it filed Levadex with FDA. The company could receive up to $97 million more from Allergan if all goes well with the regulatory process; the PDUFA date on Levadex is March 26. Levadex, like Valeant Pharmaceuticals’ Migranal, is a DHE, but Migranal is a nasal spray, while Levadex is inhaled. The benefit with inhalation means that the drug sidesteps first pass metabolism en route to the brain – it avoids the GI tract, and potential dilution. At JP Morgan’s 30^th Annual Healthcare Conference in January, MAP CEO Tim Nelson said that Levadex “works faster, and has fewer side effects, than the triptans.” He added that 29 million scripts for migraine were written in 2008, and close to half of them were written off-label. After triptan, “41 percent of the scripts were for opioids, and 28 percent were anti-depressants,” said Nelson. MAP will hire 50 specialty sales reps if Levadex gets the FDA go-ahead, and will expand the drug into pediatrics and other neurological conditions later on, he said.

Levadex won’t compete directly with Botox for migraine; the former is for acute migraine, the latter for chronic migraine. Nelson said Allergan’s expertise in managed care, reimbursement and experience with FDA, makes it a good partner for Levadex. MAP is also looking for “a partner in Asia, and in ex-US in general,” said Nelson.

At $40 to $80, with a ceiling at $100 per dose, though, Levadex may be as tough a sell as Botox. But then again, migraine sufferers only want one thing when the pain sets in: for it to be gone.

Responses on the value of eDetails compared with in-person details differed significantly across the four practice areas covered – family medicine, oncology, cardiovascular and allergy/immunology – and suggest that biopharmaceutical companies have an opportunity to adjust the promotional mix for stronger returns.

Over the last two years, in-person visits to oncologists decreased by 14%, but eDetails for the group only increased by 4%. Allergy/Immunology docs saw a 5% decrease in rep visits, but eDetailing grew by 8%. Still, allergy/immunology docs only received 1.8 eDetails per week, on average, but would like to see 3.3 eDetails per week, according to the survey results.

In terms of perceived value, in-person reps ranked higher across the board. However, oncologists and family medicine practitioners said they were better educated by eDetails, whereas cardiologists and allergy/immunology docs said in-person reps provided a better education.

Regardless of whether a physician prefers eDetails or traditional sales calls, the kinds of material preferences included in a detail also vary by practice area. “If you go into a cardiology detail without referencing clinical trial data, they’re going to feel like something’s missing,” says Kevin Olson, CEO at Industry Standard Research, publisher of the survey. Oncologists, on the other hand, “don’t tell us the same thing” about clinical trial data, says Olson. Oncologists (39%) cited the ability to answer product-related questions as the most important aspect of a detail, followed by the inclusion of information that is “sufficiently patient focused,” at 30%. Fifty percent of cardiologists said clinical trial data is most important.

Samples remain a critical part of the in-person detail experience, according to survey results, despite the fact that many eDetailing platforms provide an easy way to request samples. Asked what is lost when in-person details go the way of the dodo bird, Olson says that distribution of samples was “one of the biggest results,” although it’s “pretty clear in our data that physicians do receive value” from the opportunity to dialogue with a human being. Asked about some of the more surprising results of the survey, Olson says one question asked about the importance of key opinion leader (KOL) content; he was surprised to learn that it did not rank highly in comparison to other aspects of the detail.

The 130-page report, titled eDetailing vs. In-person Detailing: A head-to-head comparison of Volume, Time, Value, and Outcomes, surveyed 118 practicing U.S. physicians during the fourth quarter of 2011. Participants completed a 15-minute web-based quantitative survey.

A magazine ad for Boniva, fronted by actor Sally Field, generated the DDMAC (now the Office of Prescription Drug Promotion, or OPDP) Untitled Letter last year due to following phrase: “After one year on Boniva, 9 out of 10 women stopped and reversed their bone loss.” That didn’t jibe with the scientific data, DDMAC said in the letter, before requesting that all ads containing the phrase be removed from the campaign.

Genentech went a step further. In September of last year, the company began running corrective magazine ads addressing the overstated claim. The corrective ad states that the violative ad “may have given you the wrong impression.” It goes on to state that “Boniva has not been proven to stop and reverse bone loss in 9 out of 10 women and is not a cure for postmenopausal osteoporosis.” The corrective ads will run though April 2012.

Unlike their mild-mannered, Untitled Letter cousins, Warning Letters are considered more severe, and they typically mandate corrective ads to clear up any overstated claims or minimized risk information. Given that Genentech received the former communique and not the latter, it’s notable that the company chose to run corrective ads without a mandate.

After speaking with DDMAC about the Untitled Letter, Genentech worked with the agency to create and then “voluntarily” launch the corrective ads last September, according to Chris Vancheri, director, public affairs, at Genentech.

In a statement, Genentech said that in addition to the corrective advertisements – which are running in several women’s magazines, including Weight Watchers and this month’s WebMD the Magazine – “our clinical specialists have reached out to health care providers” to inform them about the corrective ads, which intend to “clarify the benefits and risks of Boniva in women suffering from post-menopausal osteoporosis.”

Sally Field was the face of Boniva beginning in 2006, but Vancheri says Field is “no longer engaged” on the campaign. GlaxoSmithKline signed a co-promotion deal with Roche on Boniva in 2001, but the companies broke the partnership in 2010.

In response to off-label inquiries about a drug, biopharma companies can use the kind of boilerplate they’ve been inserting on social media sites for years – thanks for your comment, here’s our contact information, call us for more information – but they cannot address the question publicly, where it appears, a privilege many hoped would be included in FDA’s long-promised and long-awaited social media guidelines. Companies must also include a “mechanism for providing readily accessible current FDA-required labeling,” but cannot include a link to anything that could be construed as promotional, like a “product website, product promotional materials, firm websites, or third-party websites.” Guidance on responding to unsolicited requests for off-label information was published in the Federal Register a few days before the end of 2011.

Responding to an unsolicited off-label question/comment is only appropriate when a specific brand is named, and if the question is “broad in nature,” drug companies should “appropriately narrow the question.” FDA recognizes the fact that companies are “capable of responding to requests about their own products in a truthful, non-misleading, and accurate manner,” and that companies probably know more about their own products than other self-appointed responders:

It can be in the best interest of public health for a firm to respond to unsolicited requests for information about off-label uses of the firm’s products that are made in public forums, especially since other responders may not provide or have access to the most accurate and up-to-date medical product information.

Unlike other forum responders, who can comment publicly in response to any question, manufacturers must wait for the original commenter to respond to the boilerplate message with contact information, before providing “any substantive communication about off-label uses for the product, in response to the original unsolicited off-label question,” and that communication must occur “solely between the firm and the individual who made the request…the firm should not make its detailed response with off-label information publicly available within the same forum.”

FDA’s guidance on industries’ social media interaction with patients, at least with respect to off-label inquiries, seems to be: Don’t participate publicly. According to the guidance document, this sentiment reflects a concern that publicly posted off-label information – in response to an unsolicited query – would be available for an indefinite period of time, and would also reach the eyes of readers who have not requested such information. Even if the drug information is accurate when it’s posted, it may not be accurate next month. For viewers who didn’t ask about an off-label use, but are still party to a public response, the information itself, regardless of its scientific merit, “may promote a product for a use or condition for which FDA has not approved or cleared.”

Those companies that would like to respond to an individual with a question, assuming that person has called or emailed the company in response to the provision of contact information – contact info that leads to a firm’s medical or scientific department, not a marketing department, the guidance clearly states – should include the following materials, according to the document:

• FDA—required drug label
• A prominent statement saying the product has not been FDA approved
• A prominent statement disclosing approved indications, if any
• A prominent statement of all important safety info, including box warnings, if any
• A complete list of references for all of the information disseminated in the response (firms should use peer-reviewed articles whenever possible)

Companies should also maintain the following records about off-label responses:

• The nature of the request for information, including the name, address and affiliation of the requestor
• Records regarding the information provided to the requestor
• Any follow-up inquires or questions from the requestor

The guidance is open for comment for 90 days. Here’s the Federal Register entry.

On November 17, FDA’s Risk Communication Advisory Committee (RCAC) will convene to discuss the best ways to take a drug’s complex clinical data, and present it to doctors and patients in an understandable way. The stated goal is to improve healthcare decision-making by clinicians, patients and consumers.

At issue is the implementation of a drug facts box or table, which would appear in a drug’s promotional labeling and print advertising. Research shows that a drug facts box, or a “table quantifying [health] outcomes with and without a drug,” as described by Dartmouth Medical School profs Lisa Schwartz and Steven Woloshin, could do a better job presenting the benefits and risks of a particular medicine, which facilitates a more informed decision about treatment. It would also dramatically change the way drugs are currently promoted, at least in print. (For a facts box mock-up, click here)

Woloshin says he has not looked into broadcast media applications for the facts box, but suggests that certain warnings, such as approval on the basis of a surrogate outcome, or the main efficacy finding for a drug, could be easily inserted into broadcast spots. For broadcast, “we imagine the primary goal would be to point people to a drug [facts] box, either in print or online…we have not tested these ideas, but hope to in the future,” says Woloshin.

On facts boxes in print, however, Woloshin and his colleagues have conducted extensive research, and have published a substantial body of literature. In fact, three years ago, FDA’s RCAC – then chaired by Baruch Fischhoff, of Carnegie Mellon University – gave the facts box a unanimous recommendation. Speaking to PharmExec about the facts box, Fischhoff calls it “a sound design, both analytically and empirically…it follows the theories of risk communication, it has demonstrated efficacy in its field trials, and is clearly much better than what we have out now.”

So what’s the hold-up on implementation, you may be wondering. Unsubstantiated suspicions abound, and a request for comment from HHS – which received a mandate via the Patient Protection and Affordable Care Act (Section 3507) to review the evidence for or against a quantitative summary of a drug’s risk and benefit, “such as a table or drug facts box,” and to make a judgment – went unanswered. A report filed to Congress by HHS in March requested at least three more years for additional research.

“It’s crazy that people – doctors, patients, tax-payers – don’t have ready access to summaries of [a drug’s efficacy and risks] in a way that we’ve shown can help them make better decisions,” says Woloshin. “FDA is supposed to be interested in transparency, getting information out to people in the most transparent form; that’s exactly what the facts boxes are meant to do.” Asked about possible reasons for foot-dragging at HHS, Woloshin says he’s “completely baffled by the delay,” an opinion he made known in the editorial pages of the New York Times last July. Fischhoff agrees: “Given the amount of work that’s gone into the fact box and the evidence that supports it, it’s hard for me to believe that [alternate design studies conducted by HHS/FDA] would justify a delay of a couple of years.”

RCAC is unlikely to make any bold decisions on Thursday; the discussion is primarily geared toward whether or not substantial gaps exist in the literature around a standardized risk/benefit format, and if data exist to shed light on how to select and present information for clinicians, patients and consumers. Interested parties can sit in on the RCAC meeting remotely, here.

In an exhaustive review of the literature on using quantitative summaries for the presentation of drug benefit and risk information – published on August 15^th – FDA admits that “numeric presentation of risk/benefit information appears to have had a positive impact on several outcomes relative to non-numeric presentation,” (non-numeric presentation means using words like “often” or “rare,” in place of numeric statistics). But the report insists that important gaps exist in the literature, such as “insufficiently investigated actual behaviors” versus theoretical behaviors, and a “focus only on risk information rather than on both risk and benefit information.” The report also cites differences in “a person’s numeracy or literacy levels” as a point against standardized, quantitative summaries.

Note: Apologies for the lack of a facts box quiz, alluded to in PharmExec‘s weekly newsletter. The quiz unfortunately died from editorial and technical complications. -BC

Asked whether DTC ads on television should be retired, Read answered unequivocally – “No” – and noted the difficulty of educating patients when “so many warnings are required that [a drug ad] scares more people than it helps.”

Robert Bazell, NBC’s chief science and health correspondent – and Read’s interlocutor during a lunch session at the Cleveland Clinic’s annual Medical Innovation Summit – picked up on Read’s comments about excessive warnings on televised drug ads, noting Pfizer’s 2007 Celebrex ad that lasted over two minutes, almost all of which was spent on the recitation of warnings (Celebrex, along with its fellow NSAIDs, picked up a black box warning in 2005).

Responding to the question of why Pfizer decided to go ahead with Celebrex DTC ads, post black box warning, Read said “the trials that gave rise to [black box] labeling in Celebrex, the data, if one patient had gone the other way, there would have been a different statistical result.”

Asked by Bazell about the issue of trust: “What is your perception of the public’s perception of Pfizer and the rest of the industry?” Read said Big Pharma’s reputation could use some improvement. “We’re above Congress and tobacco, and slightly below physicians and hospitals…there is blame on [industry’s] part for that.” Read said increasing transparency in clinical trials and other areas could ameliorate industry’s reputation. “We don’t sell a pill, we sell data. If you believe the data, there must be transparency,” he said.

Read emphasized the importance of incremental innovation to society, the need to protect industry’s intellectual property, and called for an explicit risk/benefit profile for drug development. He called the U.S. tax rate “uncompetitive,” citing tax rates in Europe “as low as 15%.” Industry “can’t work with one hand tied behind our back,” said Read. “Elites have lost faith in innovation as a social benefit…it’s a cost only conversation.”

“Perception of value drives the willingness to pay, and those perceptions vary from country to country,” said Adam Woodrow, vice president of Pfizer’s specialty care business unit, at a marketing and strategy forum hosted by Simon-Kucher & Partners. “We need to do a much better job communicating value to payers, and that means knowing what turns the payer on,” said Woodrow.

In a global environment where “a simple slip up in one country” can mean losing “half a billion dollars overnight,” – due to the widespread adoption of cross-country reference pricing in Europe, Asia and elsewhere – drug companies need to send a consistent message to stakeholders, said Woodrow. Payers often speak with physicians, for example, when evaluating a product for reimbursement; if sales reps are out saying one thing to doctors, and payers are hearing something else, that disconnect could translate into a less than ideal reimbursement decision.

Patient groups and associations represent another way to boost the perception of value on a given drug, said Woodrow. “Patient groups can be incredibly powerful” in gaining reimbursement, he said, citing the World Federation of Hemophilia as one particularly strong organization. “Hemophilia drugs are reimbursed almost across the board,” due in no small part to governments being pressured by patients, said Woodrow. “We have to be very careful about how we interact with patient groups.”

Woodrow, who jokingly referred to the UK’s National Institute for Health and Clinical Excellence (NICE) as NICER – “No, I Can’t Expect Reimbursement” – said Big Pharma has “failed to communicate value properly, but let’s be real: half the drugs are me-too, so there is no value. We have to begin [the clinical process] with a truly different value proposition” that recognizes the payer’s needs and perception of value, and brings patient advocacy groups on board.

The New York City Life Sciences Marketing & Strategy Forum was held yesterday in Manhattan.

In a letter to the Joint Select Committee on Deficit Reduction – otherwise known as the Super Committee, a bipartisan body tasked with cutting $1.5 trillion from the federal budget over the next 10 years – the Pharmaceutical Care Management Association (PCMA) talked up PBMs’ use of pharmacy networks, home delivery, utilization management and formularies to bring down costs. The letter goes on to describe seven ways to save:

• Medicaid: the program’s pharmacy benefit should use more generic drugs, and pay drugstores less, in keeping with the prices that Medicare and private insurers pay.
• Medicare Part D: maximize generic and therapeutic interchange, by “shifting spending from the most expensive single source drugs to equally effective lower cost options.”
• Reduce biologic exclusivity periods.
• Allow Part D health plans to negotiate prices on all drugs.
• Remove the DTC advertising tax credit.
• Remove Medicare’s restrictions on home delivery, and encourage the use of mail order for maintenance medications.
• Ban pay-for-delay drug settlements, to provide quicker access to low-cost generics

Mark Merritt, President and CEO at PCMA (and a former PhRMA strategist), said in a statement that “Everyone in the pharmacy community: drugstores, pharmacy benefit managers, drug companies, drug wholesalers, and others have a responsibility to offer cost-saving solutions to this committee.” Merritt was honored by the Generic Pharmaceutical Association (GPhA) earlier this year, in recognition of his “aggressive advocacy for lower cost prescription medications,” according to the PCMA website.

Many of the PCMA’s recommendations to the Super Committee fly in the face of PhRMA’s efforts to protect things like biologic exclusivity, price negotiations in Part D, rebates for Medicaid/Medicare dual eligibles and the DTC tax credit. All of those are viewed as necessary revenue streams that facilitate the development of innovative new treatments.

A spokesperson for PhRMA declined to comment on the specific proposals laid out by the PCMA. “Regarding the Super Committee, PhRMA’s focus is on communicating the success of the Part D program, and any proposal that would weaken the program should not be considered,” the spokesperson said.

But the idea that innovation requires a big budget is being increasingly challenged, particularly in light of the political debate around the deficit and government’s budgetary capacity for so-called entitlement spending. While the PCMA letter is surely one of many letters hoping to bend the Super Committee’s ear – PBMs stand to gain financially from an increased use of mail-ordered drugs and generic utilization, or course – it remains unclear where the biggest cuts will come.

In early August, Gene Sperling, Director of the National Economic Council and Assistant to the President for Economic Policy, wrote in the White House blog that “Everything is on the table, as it should be,” with respect to the Super Committee’s mandate. If the pharmaceutical industry hopes to convince the Super Committee, and the American public, that innovative drug prices are justified, it will need to speed up efforts to align positive health outcomes with expensive new products.

The companies listed above – Abbott and GSK, on the one hand, and Danone and Nestlé, on the other – represent two distinctly different industries that are beginning to step on each other’s toes.  Consumer packaging goods (CPG) companies are skilled at developing and marketing consumer products, while pharma’s expertise is more science-oriented, in terms of product development and marketing requirements. Both industries have taken notice of a snowballing consumer interest in so-called nutraceuticals and functional foods, or products that don’t necessarily involve active pharmaceutical agents, but have marketable, science-based ingredients.

While Abbott, GSK, Sanofi and other pharmas have shown an interest in building a nutraceuticals or science-tempered nutritionals business around areas like heart disease, Alzheimer’s, diabetes and gastrointestinal disorders, others have shied away from the prospect of low margin consumer products, and the marketing efforts they require. Pfizer, for example, put Wyeth’s baby formula business up for sale in July; Nestlé and Danone are reportedly the leading bidders.

Given the pipeline gap, pharma can’t afford to cede the nutraceuticals market to CPGs like Nestlé, a company that is actively climbing over the fence into pharmaceuticals. Pharma companies are “gun shy” about aggressive consumer marketing, and less willing to take risks, says Leonard Fuld, CEO of Fuld & Company, a competitive intelligence firm, and host to the aforementioned war games. Pharma’s FDA regulatory funambulism is the source of its reticence, whereas CPGs are willing to risk obtrusiveness (and legal grey areas) in the attempt to dominate a market. You won’t see embedded video advertising for a pharma brand placed against pirated television shows hosted offshore, for example.

Fuld says the war game discussions also revealed that pharma companies are nervous about partnerships with CPGs, believing that brand identity or intellectual property could be usurped after handing over a product. While Nestlé in particular could “break the mold” – the company has walled off its high-science division, separating disciplines like genomics, biochemistry and human cell biology, from say, innovations in foam-boosted cappuccinos – Fuld says pharma companies need to make a public health case for nutraceuticals, since they don’t know how to educate consumers the CPG way: by creating and exploiting a broad, populist market need. CPGs like Nestlé and Danone are pushing into new, science-based products that don’t require a prescription. Fuld says pharma should be more willing to collaborate, and recognize the nutraceuticals and “designer foods” market for what it is: an opportunity for new revenue that bypasses a decade-long testing phase and an increasingly hostile payer environment.

Participants representing the four companies in the war game were culled from Dartmouth’s Tuck School, MIT Sloan, Northwestern’s Kellogg School, and the Yale School of Management. Actual company representatives observed and made comments.