A Day That Will Live in Regulatory Infamy

01/12/2012 08:41 AM |

Will December 7th, 2011, be a day that will live in regulatory infamy?

That’s when Secretary of Health and Human Services Kathleen Sebelius overruled a decision of the Food and Drug Administration (FDA) on the over-the-counter (OTC) status of emergency contraception.

By reversing an FDA decision, the Secretary set a dangerous precedent for all-comers to lobby Congress, the Department of Health and Human Services and the White House on any and all FDA decisions—directly inserting politics into what must be a scientifically driven process.

"Should the HHS Decision to Overrule FDA on Plan B be Reversed?" is addressed head on in the latest issue of the Food and Drug Law Institute’s Policy Forum (Volume 2, Issue 1, January 11, 2012).

I think it’s a timely and provocative read.  (After all, I wrote it.)

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FDA in the Pink?

01/11/2012 09:10 AM |

Statistics are like a bikini.  What they show you is interesting, but what they conceal is essential.

Nevertheless, someone at the FDA owes the Pink Sheet a thank-you note.

The Pink Sheet reports that:

The agency has been trumpeting the 30 new molecular entity and new biologic entity approvals from CDER in 2011 – the most since 2004 and a welcome sign of recovery after the approvals doldrums in between – but it also deserves recognition for achieving an unprecedented, near-perfect rate of PDUFA review goal compliance (96.7%) while maintaining healthy rates of first-cycle approvals (63.3%), and time to approval (an average of 15 months)

CDER Review Performance In The PDUFA IV Era
Year	Approvals (average time to approval)	User fee compliance	First-cycle review share	First-cycle share, Standard	First-cycle share, Priority
2011	30 (15 mo.)	96.7%	63.3%	43.8%	85.7%
2010	21 (15.1 mo.)	86%	76.2%	75%	77.8%
2009	25 (17.3 mo)	72%	58%	47%	66.7%
2008	24 (17.9 mo.)	70%	67%	53.3%	88.9%

Consistency is becoming a hallmark of FDA’s review activity, with nearly identical average times to approval in the two years following the adjustment period for implementation of the FDA Amendments Act. The striking difference between 2010 and 2011 is the number of approvals, not the parameters of the reviews – showing FDA can deliver the same performance with a higher volume.

Innovative drugs drove the positive review trends, with 12 first-in-class agents among the CDER NMEs and NBEs, representing 40% of calendar year 2011 approvals.

First-in-class status correlates closely but imperfectly with priority review status, another marker of innovation that incorporates not only pioneer mechanisms but also unmet medical needs. By the metrics, the 2011 class did not vary significantly from the level of innovation in recent years, though the significance of some of the innovative products cleared in 2011 certainly makes the class notable.

The difference in time to approval between the first-cycle and second-cycle approvals is stark. On average, the penalty for going to the second review cycle was 19.6 months, the difference between the 7.8 month average time to approval for all NMEs and novel BLAs (CDER and CBER) approved in one review cycle and the 27.5 month average for products requiring two review cycles.

FDA could not have posted a good year for new drug approvals without plentiful applications based on well-constructed clinical programs – an aspect in the hands of industry. But the agency can also make its own luck. The case studies of drug approvals published each month by Pharmaceutical Approvals Monthly suggest that the agency will show great creativity and flexibility in analyzing and acquiring data for new products that address unmet medical needs.

The Pink Sheet ends it’s analysis with the comment, “As the agency heads into PDUFA reauthorization, FDA’s review success will be a powerful argument that the agency knows what it is doing. Just look at the numbers.”

Just so, but as Vince Ventimiglia, Former Assistant Secretary for Legislation at the US Department of Health and Human Services, commented at a recent Center for Medicine in the Public Interest conference on PDUFA, numbers are very much determined by who provides them.  He called one myth about PDUFA, “Lie to Me." When it comes to numbers, he asks, “Are they always true? And the answer is no. It behooves you to look very carefully at FDA numbers, Department of HHS numbers, and OMB numbers as a package. They’re not always in sync with each other."

As Mark Twain said, “Facts are stubborn things, but statistics are more pliable.”

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My tribute to Tony Blankley in the American spectator

01/10/2012 03:07 PM |

IN MEMORIAM Tony Blankley: A Man in Full By ROBERT M. GOLDBERG on 1.10.12 @ 6:06AM A conservative in Washington who made a difference.  Tony Blankley was one of the kindest people I have ever known. I am sure he will be memorialized for his other unique qualities and for the impact he had on the nation's political culture. He was wise, funny, and thoughtful. He was a gifted writer and political tactician whose contribution to America is enduring. But above all, at least to me and when I met or dealt with him over the years, I remember Tony Blankley as a generous, kind person. When Tony became editor of the editorial page editor of the Washington Times my friend Ed Kutler -- who worked with him for Speaker Newt Gingrich -- sent him a note suggesting that I should write op-eds for him on a regular basis. I received a letter from Tony inviting me to send ideas and article along as I saw fit. He added, "The pay per article isn't great. Enough for some cheese and a glass of port. But maybe we can make difference." During his tenure at the Washington Times he encourage me to write about more than health care. I was able to write about Israel, popular culture, do book reviews, and even the unsigned editorials under the paper's masthead. When we met I would try to thank him for the opportunity he had given me but he would have none of it and turn the conversation to politics or movies. I should have tried harder. When he left the paper to become Senior Vice President at Edelman we stayed in touch. At one meeting he suggested that I should write more regularly and that The American Spectator -- which at the time was building the online presence it has now -- would be a great place to do so. When my son was in the Israeli Defense Forces he would ask about him and his well-being. Tony was a willing source of advice and gentle guidance. There are many more people he supported and kept in touch with in the same way. He will and should be remembered for his two important books The West's Last Chance: Will We Win the Clash of Civilizations and American Grit: What It Will Take to Survive and Win in the 21st Century. In the latter work he asserted a strong America was essential to human freedom and doing what we must to "protect and strengthen this providential nation" was more important than ideology. It was a theme and worldview that has influenced me greatly. Because he was so much to the many people whose lives he touched, there will be as many ways to recall and pay tribute to Tony. Here's mine: I saw him the past two summers at the Steamboat Institute freedom conference. When he wasn't moderating panels he was strolling gracefully arm-in-arm with his wife Lynda under the cloudless Colorado skies. That is how I will always remember Tony Blankley.   Read More & Comment...

Anything you can do I can do (bio)better

01/10/2012 08:35 AM |

According to executive director Guido Rasi, the European Medicines Agency will issue final guideline on biosimilar monoclonal antibodies in March or April with draft guidelines on the approval process for copies of other drugs to follow in May or June. (These will include low molecular weight heparin and modern analogues of insulin.)

Rasi said he believed biosimilars would play an important role in future European healthcare and also noted that many pharmaceutical companies are developing next-generation versions of medicines.

Rasi, "I don't really have concern about the level of safety. What is a question-mark is efficacy, since many biotechnology products are now being improved."

“Biobetters” anyone?

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Board of ... Education?

01/09/2012 08:28 AM |

BioCentury reports:

CDER creating medical policy board

FDA is creating a medical policy board at the Center for Drug Evaluation and Research to enhance the consistency of medical policies, CDER Director Janet Woodcock told BioCentury. Woodcock, who announced the initiative to CDER staff on Friday, said the new board is a response to complaints from drug sponsors that review divisions often take different, sometimes contradictory, approaches to similar issues.

Examples of issues the board will work on include creating a CDER-wide policy for obtaining approval based on a single trial, and the types of evidence that can be used to supplement a single trial. The board also will establish standards for use of the Animal Rule to obtain approvals of bioterrorism countermeasures based on efficacy studies in animals, Woodcock said.

In addition to consistency, the new body will also examine whether approval standards are infeasible, and if they are, establish new standards. The board's conclusions will be published and will be subject to public comment procedures, Woodcock said. It will be headed by Rachel Sherman, director of CDER's Office of Medical Policy

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Drug Shortages and the Free Market: Problem or Solution?

01/06/2012 08:51 AM |

Is the free market the cause or the solution to the problem of drug shortages.?

Yes.

According to a story in today’s Detroit Free Press:

“The most common causes are manufacturing violations, production delays, shipping problems or ingredient shortages … Shortages grow as generic manufacturers have consolidated and fewer plants are left making certain drugs.”

All of these issues can be addressed and resolved through smart free market solutions and the helping hand of economic incentives.

As Scott Gottlieb commented in front of the Senate Finance Committee:

The is a clear correlation between price and availability – with many of the cheapest infused medicines also being the ones that seem most likely to be in shortage. These drugs are often sold for very low prices, sometimes just several dollars for a single dosage vial of a medicine. As a result, the cost of manufacturing ends up comprising a sizable proportion of the overall price of the finished medicine. In some cases, these drugs are being sold at a loss to their manufacturers once all the production and distribution expenses get fully loaded into the cost. The economic problems are widespread, and deeply embedded in the markets for these drugs.

We should consider policy constructs that would give manufacturers a financial incentive to develop intellectual property that improved the manufacturing characteristics of generic medicines even if these changes it didn’t alter the clinical properties of a drug.

Let’s adopt a free-market solution and free American physicians, pharmacists, and patients of the problem of needless drug shortages.

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A Positive/B Negative

01/05/2012 10:55 AM |

What do Avastin and Plan B have in common?

The answer is that both products received attention from both the FDA and HHS. One was a policy decision, the other a political.

During the FDA’s hearing on Avastin, HHS announce that “The label change will not affect our coverage.” (Actually, he should have said “potential label change,” but neither here nor there.)

That “Yes from HHS” was a policy decision that was also a savvy political one (had CMS withdrawn reimbursement for Avastin’s use in breast cancer, it would have become a front-and-center election issue).

On the other hand, Secretary Sebelius’ override of the FDA’s decision to allow unfettered OTC access for Plan B was a political decision thinly (and awkwardly) couched as a policy decision.

That’s the difference between policy and politics.

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PCORI keeps low profile as it preps markers

01/04/2012 06:08 PM |

PCORI keeps low profile as it preps markers

The institute is trying to advance the cause of CER without creating a political flashpoint.

By BRETT NORMAN | 12/29/11 9:32 AM EST

So far, the new institute that’s supposed to run comparative effectiveness research has avoided the harsh political rhetoric of health care rationing and “death panels” — but its supporters worry that its luck could be about to change.

The Patient-Centered Outcomes Research Institute, set up by the health care reform law, is walking a fine line, trying to advance the cause of comparative effectiveness research without creating a political flashpoint. And that means getting as much buy-in as possible from stakeholders throughout the health care sector.

In January, PCORI will lay down two markers — its draft research agenda and its national principles — outlining the framework of a national program for comparative effectiveness research. And a lot of people are watching closely.

“They are really operating under the shadow of the death panel crazies,” said Jerry Avorn, professor at Harvard Medical School and author of "Powerful Medicines." “There’s still a lot of fear that even the most reasonable and necessary research — say, the best approach to lowering blood pressure or cholesterol, for instance — will be demagogued and demonized by those on the right.”

But tempers have cooled at least somewhat since the arguments flared in 2009 after the stimulus bill included $1.1 billion for CER. The calmer environment is leading supporters to be guardedly optimistic that PCORI will be able to proceed — albeit cautiously — without excessive political distraction.

“My belief is that much of the storm has subsided — not to say it can’t come back,” said Robert Dubois, chief science officer of the National Pharmaceutical Council. Dubois wrote a paper this month in Health Affairs with advice for how PCORI should prioritize treatments for study — transparently and based on explicit evidence, with input from all stakeholders.

“The combination of the way the legislation was written, the board of governors and the tone that they have set has satisfied most people,” he said.

The point of comparative effectiveness research is to compare two or more different ways of treating the same condition to see which one works best. The idea is that if definitive best practices can be established, they will be widely adopted by providers and may be preferentially reimbursed by payers.

Cheaper treatments that are effective would be favored.

It may sound harmless — like common sense, even, to the uninitiated — but it’s a menacing prospect to some pharmaceutical companies and medical device-makers who are concerned that their products may wind up on the wrong side of the ledger.

For this reason, Michael Cannon, director of health care studies at the Cato Institute, says good comparative effectiveness research is almost suicidal.

“The whole point of [comparative effectiveness research] is to find out what doesn’t work,” Cannon said in an email. “Every time the government has tried to do CER, the guys who provide the stuff found not to work successfully lobby to have the offending agency defunded. I see no reason to think this time will be any different. The moment it produces useful CER, PCORI is toast.”

And that’s just one source of opposition. The other includes general foes of the Affordable Care Act, who have seized on elements like the Independent Payment Advisory Board, and end of life counseling, suggesting that health reform will lead to government “pulling the plug on grandma.”

Betsy McCaughey, former lieutenant governor of New York and author of “Obama Health Law: What It Says and How to Overturn It,” fueled some of the most heated claims in 2009 about threats of government health care rationing.

McCaughey said she won’t prejudge PCORI’s agenda, but that generally “there’s an intense politicization of medical research to support an agenda that wants to save money by denying care to the elderly and sick. … The term ‘comparative effectiveness’ is code for giving care based on age and life expectancy of the patient.”

Supporters say that objection is off base, and that the research is designed to find the most effective treatment for every population.

But even the institute’s name bears the imprint of the red-hot controversy the subject fuels. During the health care reform debate, the very term “comparative effectiveness research” was abandoned in favor of “patient-centered outcomes research.” The latter has an explicit emphasis on the wishes of the patient, rather than hinting that the true goal is cheaper care.

And the ACA specifically states that PCORI will have no authority to mandate coverage or reimbursement, although it doesn’t forbid public or private payers from using the research to inform their coverage decisions, John McDonough, who worked as an aide to Sen. Ted Kennedy, reports in his book "Inside National Health Reform."

PCORI is led by Joe Selby, a widely respected former executive at Kaiser Permanente, who is well aware of the delicate political balance he has to strike.

“Everyone at PCORI, our board and our staff, recognizes the great need for research that compares different prevention, diagnosis or treatment options to see which ones work best for different people with a particular health problem,” Selby said in an emailed response to questions. “That’s at the heart of PCORI’s mission, to provide patients and those who care for them with the information they need to support health care choices.”

After the release of its draft agenda in January, PCORI will award 40 grants totaling $26 million that will fund methodological and agenda-setting research. Selby said PCORI will award another $100 million in primary research funds by the end of the year. The majority of funds will go to comparative effectiveness research studies, he said.

The ACA established a trust fund for PCORI, so it isn’t subject to the annual appropriations process, which provides a measure of security. It’s funded by the government but is independent of it, and so far, in the various debt reduction negotiations this year, it has not emerged as a target.

But laws can change, and even PCORI foes suspect the agency will tread lightly next year.

Robert Goldberg, vice president of The Center for Medicine in the Public Interest, believes that money being spent on PCORI would be better spent elsewhere. “I don’t think there’s any hard evidence that comparative effectiveness actually improves health at a reduced cost,” he said.

He co-authored a paper with John Vernon, an economist at the University of North Carolina, arguing that if a comparative effectiveness standard were built into the FDA’s premarket approval process, the impact on innovation would be severe. “To the extent that it’s just another link in the chain from the time a product is developed 'til the time it’s approved, it’s going to delay access and discourage innovation,” Goldberg says.

Harvard’s Avorn calls this “crying wolf,” because comparative effectiveness has never been a part of FDA review and including it is not in the cards.

And Goldberg acknowledges it is a purely hypothetical scenario — one that can’t be allowed to become reality.

Despite his suspicions, though, he thinks of PCORI as mostly harmless.

“I don’t see PCORI as a real threat. I think they’re more interested in shoving the money out in a neutral way not to upset anybody and see if they can build support for it after 2012,” Goldberg said. “Depending how the elections go, they could be an early target, so they’d like to build some consensus.”

Supporters agree on the last part — the need for consensus — and generally applaud the efforts to bring as many people to the table as possible. Consensus is needed, they believe, not just to keep political foes at bay, but also to advance the cause of comparative effectiveness research beyond the institute.

Large-scale comparative effectiveness studies are extremely expensive. Despite PCORI’s substantial funding, it will never be able to tackle all of the clinical issues that need to be studied.

The goal is to set up a framework that will allow others — insurance companies, research institutes and others — to build on the experience and carry out studies of their own, Dubois said.

Rita Redberg, a comparative effectiveness expert and professor at the University of California San Francisco, said she believes PCORI is doing great work under very trying circumstances.

“I think they’re going to move the needle in terms of what we need to know,” Redberg said. “They’re really doing great with the restrictions they have, but there are a lot of masters to please.”

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Proscribing Prescribing?

01/04/2012 09:11 AM |

According to a new report by University of Southern California researchers in the American Journal of Managed Care," "Though some doctors stick to a few highly advertised medications, only a few physicians prescribe them exclusively.”

No surprise there, but useful and timely as we enter into the New Year with the specter of government detailing (aka “academic detailing”) hovering over both patient choice and the overall ability of physicians to practice medicine as they see fit.

"Narrow prescribing patterns may be optimal when one drug is clearly superior to the others, or if all the drugs in the class act in a similar way."

“Superior” in individual patient performance (clinical performance) to be sure. 

The researchers also noted “although most physicians have a favorite drug, they are not reluctant to try new therapies.”

Which begs the question – how and from whom are physicians to learn about new treatments?

A tough and important question for 2012.  And it’s not, strictly speaking, academic.

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Unnecessary Necessities & the Denizens of Inertia

01/03/2012 08:22 AM |

Civilization is a limitless multiplication of unnecessary necessities. -- Mark Twain

According to the FDA’s Karen Mahoney, the recent draft guidance regarding Unsolicited Requests for Off-Label Information About Prescription Drugs and Medical Devices is "the first of multiple planned guidances that respond to testimony and comments from the Part 15 public hearing that FDA held in November 2009."

In the meantime, we’ll see if these promised “multiples” will reinvigorate the denizens of inertia who believe regulated industry needs to “wait” for further agency instruction before embracing a more holistic approach to social media.

Here is the source of the FDA quote:

FDA's Social-Media 'Guidelines' Befuddle Big Pharma
After Two-Year Wait, Guidance Addresses Only Off-Label Uses of Drugs

By: Rich Thomaselli

After a two-year wait that included the fanfare of a two-day public hearing, the Food and Drug Administration this week quietly announced new social-media marketing guidelines for pharmaceutical companies.

Well, sort of.

The FDA on Tuesday posted its "Guidance for Industry Responding to Unsolicited Requests for Off-Label Information About Prescription Drugs and Medical Devices" in the Federal Register, an under-the-radar move neither announced by press conference or press release. And the guidance seems to fall a bit short of what a legion of pharma-industry and healthcare-agency marketing execs anticipated.

"What everybody was expecting was actual guidelines around social media," said Jim Dayton, senior director of emerging media for Overland Park, Kan.-based InTouch Solutions, a pharma-centric digital-marketing agency. "I still think it's monumental," he added. "The FDA finally addressed the digital channel in a specific way by mentioning Twitter and YouTube in the document, and those have never been mentioned before. But this is an industry that wants specific instructions and rules, and that didn't happen here."

"We understand the level of interest and wanted to get out what we had available to provide guidance," said FDA spokeswoman Karen Mahoney, who added that this was just "the first of multiple planned guidances that respond to testimony and comments from the Part 15 public hearing that FDA held in November 2009."

The 15-page FDA guidance addresses only off-label information, laying out instructions for pharma companies on how to respond to consumers seeking information for a prescription drug other than what it is indicated for. That is, in a very rudimentary example, if a consumer asked a question on Facebook or called a pharma company's 800 number asking whether it was safe for men over the age of 50 to use Botox, a representative for Botox-maker Allergan could certainly answer the question. However, if the consumer asked whether the use of Botox also helped grow hair on balding men, the representative should refer the consumer to the Allergan website on use and safety information.

"Firms may choose to respond to unsolicited requests for information about off-label uses of their approved or cleared products in a manner other than that recommended in this draft guidance. Such activity would not constitute a per se violation of the law, but could potentially be introduced as evidence of a new intended use," the FDA wrote in its guidance.

"FDA recognizes that 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 addressed to a public forum, as other participants in the forum who offer responses may not provide or have access to the most accurate and up-to-date information about the firm's products. … Statements that promote a drug or medical device for uses other than those approved or cleared by FDA may be used as evidence of a new intended use. Introducing a product into commerce for such a new intended use without FDA approval or clearance would, under these requirements, generally violate the law."

But for some, that still leaves things ….."ambiguous," said one pharma company digital director who asked not to be identified. "It leaves a lot open to interpretation."

Big Pharma, which spent $1 billion in online promotion last year and was expected to reach $1.52 billion in spending by 2014, has been somewhat inhibited by the lack of guidance and ambiguity on social-media use.

But that's the best the industry can expect right now, said Peter Pitts, former FDA associate commissioner and now the president of the Center for Medicine in the Public Interest. "What everybody was looking for was never going to happen. If you're waiting for divine guidance, you're still waiting," said Mr. Pitts.

Both Messrs. Pitts and Dayton said pharma should embrace this first leg of social-media guidelines. "On the face of it, you can look at it and say 'This is nothing,'" Mr. Pitts said. "In reality, I doubt there is ever going to be definitive rules for social media-marketing like there are for TV and print. And there's a reason for that. FDA has made it very clear they were not going to make platform-specific guidelines, like how to use Facebook, how to use Twitter, because social media evolves every day. How can you write guidelines for something that shifts in 90 days? Social media is unpredictable. If industry wants to use social media, they have to embrace ambiguity. The key element here is to use your judgment. If you wouldn't say it offline, don't say it online."

Added Mr. Dayton: "However ambiguous some might see this, I do not think this document should stop anybody from using social media for marketing purposes. We should use this document to show us how the FDA is thinking when it comes to social media. This is indicative of future guidelines around social media. It's going to have to be something we interpret, which is typical of a government agency. We're not ever going to be like Nike or Apple and say whatever we want in social media. The rules haven't changed for us -- it's the same rules this industry has for traditional media."

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Mary, Mary -- Not so contrary

01/02/2012 08:05 AM |

Mary Pendergast, former Deputy Commissioner) and an architect of FDA's call for emergency contraceptives during the Clinton administration) and I find ourselves in violent agreement over the outrageous decision of HHS Secretary Kathleen Sebelius to overrule the FDA on Plan B.  Here are three links to our recent discussion (expertly moderated by Steve Usdin) on BioCentury This Week.

Part 1:  Is there a Secret FDA in the Secretary's Office?

Part 2: The Differences Between Politics and Policy

Part 3: What’s Next?

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What's your Plan B for 2012?

12/30/2011 08:40 AM |

Sunday, January 1

BioCentury This Week kicks off the election year dissecting the Obama administration's decision to overturn FDA's plan to authorize OTC access to the Plan B contraceptive to all women, regardless of age. Did HHS compromise FDA's scientific integrity to avoid a campaign fight over the morning-after pill?

Debating the public health and social consequences:

Jeanne Monahan of the Family Research Council

Kirsten Moore of the Reproductive Health Technologies Project
  
Cynthia Pearson of the National Women's Health Network

Analyzing the political calculus:

Mary Pendergast, former Deputy Commissioner and an architect of FDA's call for emergency contraceptives during the Clinton administration

Peter Pitts of the Center for Medicine in the Public Interest, and former Associate Commissioner at FDA during the Plan B debate in the Bush administration

Watch the Broadcast
8:30 - 9:00 a.m. EST
WUSA Channel 9
in Washington, D.C.

Watch on the Web
www.biocenturytv.com
Continuously available
starting at 9:00 a.m. EST  Read More & Comment...

Pharma, Guide Thyself

12/29/2011 08:36 AM |

The December 27^th Draft Guidance, “Responding to Unsolicited Requests for Off-Label Information About Prescription Drugs and Medical Devices” offers sound counsel but not much in the area of direct guidance. Nevertheless, there are valuable lessons to be learned -- if you are willing to read between the numerated lines.

The draft guidance doesn’t address many of social media’s (referred to in the document as “emerging electronic media”) regulatory red flags such as adverse events, the question of property owner vs. property user, and a more precise discussion of what “sponsored” means.

But the giant regulatory bugaboo, not only of social medi but of regulated speech writ large, is off-label communications. So those who are complaining this document isn’t “comprehensive enough” don’t understand what it has to offer. 

Lesson #1: The agency is saying (in so many words) “if you wouldn’t say it off-line, don’t say it on-line.” It isn’t a question of platform-specific guidance (regulatory rules for YouTube or FaceBook or Twitter). Rather, the FDA is asking industry to use their best judgment in this new and, well, emerging media. That’s the good news.  The bad news is many folks in pharma find that frightening.

Consider the following verbiage from the draft guidance:

FDA has long taken the position that firms can respond to unsolicited requests for information about FDA-regulated medical products by providing truthful, balanced, non-misleading, and non-promotional scientific or medical information that is responsive to the specific request, even if responding to the request requires a firm to provide information on unapproved or uncleared indications or conditions of use.

The agency recognizes companies are already responding to unsolicited requests for off-label information.  That means the current procedures companies have in place to address these requests are (when properly followed) FDA compliant.

Lesson #2: When trying to create processes and procedures for social media communications – draw parallels to existing communications processes and procedures.

That’s not, however, a get-out-of-jail-free card by any means.  Just as with traditional communications, there’s a great deal of regulatory ambiguity and use of the FDA’s favorite tense -- the conditional tense:

Statements that promote a drug or medical device for uses other than those approved or cleared by FDA may be used as evidence of a new intended use.

In other words, the role of legal and medical in the review of social media communications (relative to off-label issues and beyond) is still crucial.  This draft guidance doesn’t lighten the regulatory burden – it just makes it more feasible.

What it also says (IMHO) is that responding to unsolicited off-label communications is, indeed, in the best interest of the public health:

FDA recognizes that 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 addressed to a public forum, as other participants in the forum who offer responses may not provide or have access to information about the firm’s products.

The agency has, importantly, made a clear distinction between “solicited” and “unsolicited” off-label questions:

Unsolicited requests are those initiated by persons or entities that are completely independent of the relevant firm.  (This may include many health care professionals, health care organizations, members of the academic community, and formulary committees, as well as consumers such as patients and caregivers).  Requests that are prompted in any way by a manufacturer or its representatives are not unsolicited requests.

Lesson #3: The message being sent here is, “don’t get too cute.”  And that’s worth remembering. Using social media for marketing is okay – but using it to advance the public health takes precedence.

One key area that requires greater clarification (on the part of the FDA) is the definition of an unsolicited off-label request.” Does it have to actually be a question or could it also be a non-interrogative incorrect statement about the off-label use of a product?  Independent third parties who make erroneous statements about off-label use generally are ignorant of the fact that they are making factual misstatements.  Shouldn’t a company be able to respond to factual errors that aren’t in the form of a question?  Isn’t the whole idea here not to play Jeopardy with the public health?

The draft guidance makes it clear that misinformation is an important issue (one that also came up at the November 2010 FDA’s Part 15 hearing on social media):

The Internet has also spawned a variety of social media tools that host online content primarily created and published by users other than the intellectual property owner or product manufacturer.  In some cases, this online content may not be accurate.

Agency clarification is necessary so that companies can regularly and aggressively correct on-line misinformation about their products.

Lesson #4:  It is the responsibility of every company to correct product misinformation that it discovers not only in social media -- but it all media.  After all, what would a company do if a factual mistake about one of its products appeared in the pages of the New York Times?

The draft guidance also offers some very sound and practical tactical advice.  For example, when dealing with off-label questions:

Information distributed in response to an unsolicited request should be provided only to the individual making the request directly to the firm as a private, one-on-one communication.

And:

If a firm chooses to respond to public unsolicited requests for off-label information, the firm should respond only when the request pertains specifically to its own named product (and is not solely about a competitor’s product).

Lesson 5: Take conversations about off-label use (and, IMHO, adverse events) off line and into existing processes and procedures.

The FDA requires some additional assistance in understanding social media.  Specifically:

FDA is also concerned about the enduring nature of detailed public online responses to off-label questions because specific drug or device information may become outdated (e.g., new risk information may become available).

While it’s good to be concerned, it’s also important to recognize that any piece of information ever written on social media (generally speaking) is going to be available forever for those who know how to find it.  Perhaps a better way to address this concern is:

Lesson #6:  Companies who respond to posts on independent third party sites should continue to regularly monitor those sites for future legitimate interventions.

Another questionable statement in the draft guidance concerns the use of “brand.com” sites as an inappropriate way to address unsolicited public off-label questions:

The public response should include a direct link to the current FDA-required labeling, if any, but should not include links to any other information (e.g., product websites, product promotional materials, firm websites, third-party websites).

Why shouldn’t a product website, assuming that every word on the site is appropriately compliant, be used?  Isn’t this where the most comprehensive, up-to-date, and accurate product information resides? If the agency is concerned about the legacy of “old” on-line information, they should support options that are regularly (and factually) updated – such as brand.com sites.

The draft guidance also raises the issue of communications with health care professionals and formulary committees. For both of these constituencies, seeking a regulatory parallel is useful. For healthcare professionals, the current guidance on Good Reprint Practices is as clear (and useful) for a social media interaction with a physician (or nurse-prescriber) as it is for a one-on-one office visit by a pharmaceutical company representative.

For formulary committees it’s more complicated. Coincidentally, on the same day the draft guidance on off-label communications was issued, the FDA also issued a Federal Register Notice requesting input, “with respect to manufacturer responses to unsolicited requests; interactions with formulary committees, payors, and similar entities; and the dissemination of third-party clinical practice guidelines.”

Coincidence?  I don’t think so. But certainly timely.

Lesson #7:  Social media means more than marketing products. It means using this “emerging electronic media” to advance the public health by communicating factual and timely information.  In short – sharing knowledge with those who want it, when they want it, where they want it.

Lesson #8:  Not just when a company marketer wants to. 

Lesson #9:  It’s about judgment. If a company can make a strong case (internally and honestly) that a social media engagement truly advances the public health, it’s a strong foundation for ensuring compliance. 

Lesson 10: Pharma, Guide Thyself.

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When is science not science? When it's promotion. Maybe.

12/28/2011 08:49 AM |

Just when you thought it might be safe to go on vacation -- something to think about for the remainder of 2011, the free and fair dissemination of scientific and pharmacoeconomic data.

According to a notice in the Federal Register:

The Food and Drug Administration (FDA) is announcing the establishment of a docket to assist with our evaluation of our policies on communications and activities related to off-label uses of marketed products, as well as communications and activities related to use of products that are not yet legally marketed for any use, we would like to obtain comments and information related to scientific exchange.  FDA is interested in obtaining comments and information regarding scientific exchange about both unapproved new uses of products already legally marketed (“off-label” use) and use of products not yet legally marketed for any use. 

And the issue of “scientific exchange” comes front and center. According to the FR notice, To assist with our evaluation of our policies on communications and activities related to off-label uses of marketed products, as well as communications and activities related to use of products that are not yet legally marketed for any use, we would like to obtain comments and information related to scientific exchange.

The FR notice puts this request into perspective:

On July 5, 2011, a citizen petition was submitted by Ropes & Gray and Sidley Austin LLP on behalf of seven product manufacturers (Petitioners):  Allergan, Inc.; Eli Lilly and Co.; Johnson & Johnson; Novartis Pharmaceuticals Corp.; Novo Nordisk, Inc.; Pfizer, Inc.; and sanofi-aventis U.S. LLC under 21 CFR 10.30.  The citizen petition requested that FDA clarify its policies for drug products and devices governing certain communications and activities related to off-label uses of marketed products and use of products that are not yet legally marketed for any use.  Specifically, the petition requests clarification in the following areas:

1.  Manufacturer responses to unsolicited requests; 

2.  Scientific exchange; 

3.  Interactions with formulary committees, payors, and similar entities; and

4.  Dissemination of third-party clinical practice guidelines.

For some time, FDA has been considering these issues and is currently evaluating our policies on sponsor or investigator communications and activities related to off-label uses of marketed products and use of products that are not yet legally marketed for any use.  We have been considering what actions to take in the areas specified by the petitioners with respect to manufacturer responses to unsolicited requests; interactions with formulary committees, payors, and similar entities; and the dissemination of third-party clinical practice guidelines.

Specifically, the FDA asks:

• How should FDA define scientific exchange?  

• What types of activities fall under scientific exchange?

• What types of activities do not fall under scientific exchange?

• Are there particular types and quality of data that may indicate that an activity is, or is not, scientific exchange?

• In what types of forums does scientific exchange typically occur?  Should the use of certain forums be given particular significance in determining whether an activity is scientific exchange or an activity that promotes the drug or device?  If so, which forums?

• What are the distinctions between scientific exchange and promotion?  What are the boundaries between scientific exchange and promotion?

•  Generally, who are the speakers involved in scientific exchange, and who is the audience for their communications?

• Should the identity of the participants (either speakers or audience) be given particular significance in determining whether an activity is scientific exchange or an activity that promotes the drug or device?  If so, which participants would be indicative of scientific exchange and which would be indicative of promotion?

• How do companies generally separate scientific roles and promotional roles within their corporate structures?

• How should the Agency treat scientific exchange concerning off-label uses of already approved drugs and new uses of legally marketed devices? Please address whether there should be any distinctions between communications regarding uses under FDA-regulated investigation (to support potential approval) and communications regarding uses that are not under express FDA-regulated investigation.

• How should the Agency treat scientific exchange concerning use of products that are not yet legally marketed (that is, products that cannot be legally distributed for any use outside of an FDA- or institutional review board (IRB)-approved clinical trial)?

• Should investigational new drugs and investigational devices be treated the same with respect to scientific exchange? Why or why not? 

• Under 21 CFR 812.7(b), an investigational device is considered to be “commercialized” if the price charged for it is more than is necessary to recover the costs of manufacture, research, development, and handling.  Similarly, FDA considers charging a price for an investigational drug that exceeds that permitted under its regulations (generally limited to cost recovery) to constitute “commercialization” of the drug (see 74 FR 40872 at 40890, August 13, 2009; 52 FR 19466 at 19467).  What other actions indicate the commercialization of drug and/or device products?  If there are differences in the steps taken to commercialize drug products and the steps taken to commercialize device products, either before or after approval, please explain these differences.

A lot of questions and, it seems, a lot of potential regulatory mission creep.

Relative to, “Interactions with formulary committees, payors, and similar entities,” the door is now also open for debate on FDAMA Section 114 and health economic data.

There is no on-the-books draft or final guidance on Section 114. It’s been 14 years since the initial language. Health-related quality of life claims are considered under the established "adequate and well-controlled trials" standard.

Some background to put this into perspective:

To address concerns that FDA regulations were limiting the dissemination of outcomes research, Congress added Section 114 to set a new, less stringent standard applicable to promotional dissemination of health care economic information to MCO formulary committees: "competent and reliable scientific evidence."

Even though there is no FDA guidance to explain the agency's understanding "competent and reliable scientific evidence,” PhRMA developed a draft guidance, which was submitted to the FDA in June 1998. In its draft, PhRMA sought input from the International Society for Pharmacoeconomics and Outcomes Research, the Society for Medical Decision Making, the Academy of Managed Care Pharmacy, the American Pharmaceutical Association, and other groups.

In its submission to the FDA, PhRMA explained the history behind Section 114 and proposed guidance on the following terms used in the new law:

• Health care economic information.
• Managed care or other similar organizations.
• Formulary committee or other similar entity.
• Directly related to an approved indication.
• Competent and reliable scientific evidence.

The PhRMA proposal took an approach to interpretation consistent with Congress's intent that Section 114 would increase the dissemination of outcomes research information by product manufacturers to MCOs. PhRMA concluded that the term "health care economic information" should include all forms of economic analysis so the guidance could adapt to new and evolving outcomes research methods.

One of the phrases in Section 114 that is difficult to interpret is that promotion must involve a claim that "directly relates to an indication approved [by the FDA]." In the draft guidance, PhRMA proposed that extrapolation from data included on labeling would be appropriate at least under the following circumstances: from duration of use in labeling to actual duration of use found in pharmacy databases, from dosages included in labeling to actual dosages found in pharmacy databases, and from controlled trial settings to actual practice settings.

The standard set by Section 114, "competent and reliable scientific evidence," is the same standard used by the Federal Trade Commission (FTC) when assessing the adequacy of substantiation for manufacturer claims involving OTC drugs and products affecting environmental health. That standard requires transparency of methods and use of methods accepted by experts in the field. In its proposal, PhRMA recommended that the FDA follow long-established FTC interpretation of the competent and reliable scientific evidence standard.

The full FR Notice on "Communications and Activities Related to Off-Label Uses of Marketed Products and Use of Products Not Yet Legally Marketed; Request for Information and Comments" can be found here.

It’s more than a notice – it’s a broadside and it’s required reading.  The docket should be interesting.  Folks – it’s time to step up to the plate.

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Happy Hannukah! At Long Last FDA Social Media Guidance. (Well, Sort of.)

12/27/2011 01:58 PM |

In time for the last night of Hanukkah – some long awaited (draft) guidance on social media.  Well, sort of.

According to the FDA:

This draft guidance is intended to describe the Food and Drug Administration’s (FDA or Agency) current thinking about how manufacturers and distributors (firms) of prescription human and animal drug products (drugs) and medical devices (devices) can respond to unsolicited requests for information about unapproved or uncleared indications or conditions of use (off-label information) related to their FDA-approved or cleared products. This draft guidance updates and clarifies FDA’s policies on unsolicited requests for off-label information, including those that firms may encounter through emerging electronic media.

“Emerging electronic media.”  You gotta love the lingo.

Further:

The rapid growth of the Internet, including social media tools and other emerging technologies, has made it easier for both consumers and health care professionals to quickly seek information about medical conditions and treatments.  Many firms have also used emerging electronic media to disseminate product information.  As a result, firms may encounter requests for off-label information about their products through product websites, discussion boards, chat rooms, or other public electronic forums that they maintain and over which they have full control.  In addition, third-party sites (i.e., websites and other venues that are either entirely independent of a firm’s control and influence or not fully controlled by a firm) also may reveal questions about off-label uses of a firm’s products.  These questions about off-label uses are typically directed to users of the site at large, rather than directly and privately to firms.  Such posted information is likely to be available to a much broader audience than just the original requester, especially because communication threads (i.e., questions and replies) are often available for an indefinite period of time.

This draft guidance provides FDA’s recommendations to firms wishing to respond to unsolicited requests for off-label information, including both requests made directly and privately to firms and requests made in public forums, including through emerging electronic media.  FDA recognizes that firms are capable of responding to requests about their own named products in a truthful, non-misleading, and accurate manner.  Furthermore, as these firms are regulated by FDA and have robust and current information about their products, FDA recognizes that 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 addressed to a public forum, as other participants in the forum who offer responses may not provide or have access to the most accurate and up-to-date information about the firm’s products.

Now here’s the important part:

If a firm responds to unsolicited requests for off-label information in the manner described in this draft guidance, FDA does not intend to use such responses as evidence of the firm’s intent that the product be used for an unapproved or uncleared use.  Such responses would also not be expected to comply with the disclosure requirements related to promotional labeling and advertising.  Firms may choose to respond to unsolicited requests for information about off-label uses of their approved or cleared products in a manner other than that recommended in this draft guidance.  Such activity would not constitute a per se violation of the law, but could potentially be introduced as evidence of a new intended use.

(Note: Bolded remarks throughout this discussion are my own emphasis.)

So, what’s the difference between “unsolicited” and “solicited?”  Here’s the FDA view:

Unsolicited Requests

Unsolicited requests are those initiated by persons or entities that are completely independent of the relevant firm.  (This may include many health care professionals, health care organizations, members of the academic community, and formulary committees, as well as consumers such as patients and caregivers).  Requests that are prompted in any way by a manufacturer or its representatives are not unsolicited requests.  Two types of unsolicited requests are addressed in this draft guidance: non-public unsolicited requests and public unsolicited requests.  Responses to unsolicited requests can likewise be non-public (private) or public.

Non-public unsolicited requests

A non-public unsolicited request is an unsolicited request that is directed privately to a firm using a one-on-one communication approach.

Example 1: An individual calls or e-mails the medical information staff at a firm seeking information about an off-label use.  In this case, neither the request nor the response would be visible to the public.

Public unsolicited requests

A public unsolicited request is an unsolicited request made in a public forum, whether directed to a firm specifically or to a forum at large.

Example 2:  During a live presentation, an individual asks a question, directed to a firm’s representative but heard by other attendees, regarding off-label use of a specific product.  This request is a public request. Similarly, a response by the firm that is conveyed to the same audience as the original question would be considered a public response.

Example 3: An individual posts a question about off-label use of a specific product on a firm-controlled website (or a third-party discussion forum) that is visible to a broad audience.  The request could be directed to a firm specifically or posed to users of a discussion forum at large.

This request is a public online request. Similarly, a response by the firm that is visible to the same audience as the original question would be considered a public online response.

Solicited Requests

FDA considers requests for off-label information that are prompted in any way by a manufacturer or its representatives to be solicited.  Such solicited requests may be considered evidence of a firm’s intent that a drug or medical device be used for a use other than that specifically approved or cleared by FDA. Although not exhaustive, the following examples illustrate what FDA generally considers to be solicited requests for off-label information.

Example 4:  If a firm’s sales representative mentions a use of a product that is not reflected in the product’s approved labeling and invites a health care professional to request more information, resulting requests would be considered solicited requests.

Example 5:  If a representative of a firm, such as a medical science liaison or paid speaker (e.g., key opinion leader), presents off-label use data at a company-sponsored promotional event (e.g., a dinner) and attendees then ask or submit requests for more information, these requests would be considered solicited requests.

Example 6:  If a firm issues to health care professionals business reply cards that are intended for use in requesting off-label information, presents statements or contact information in promotional pieces in a manner that solicits requests for off-label medical or scientific information (e.g.,  “Product X continues to be evaluated in more than 50 trials in a broad range of conditions and patients” and “Call 1-800-… for more information”), or displays a commercial exhibit panel suggesting a new indication (e.g., a sign that reads “Coming Soon, a new use for Product X”), requests made in response to these types of prompts would be considered solicited requests.

Example 7:  If a firm provides a phone number, e-mail address, uniform resource locator (URL), or username that is a word, alpha phrase, or alpha representation implying the availability of off-label information for its product, requests using this phone number, e-mail address, URL, or username would be considered solicited requests.

Example 8:  A firm asks or otherwise encourages users to post videos about their own uses of its product on third-party video-sharing sites (e.g., YouTube), which may result in video postings about an off-label use of its product.  If the firm’s initial request for posting of videos results in any questions about off-label uses, or if any off-label video posting made in response to the firm’s encouragement of video postings results in questions about the product’s off-label use, these questions would be considered solicited requests.

Example 9:  If a firm sends out packets of information to known bloggers or online consumer reviewers and encourages them to write about an off-label use of its product on third-party sites and this then provokes a discussion about that off-label use, any requests inquiring about the product’s off-label use as a result of these blogs, whether posted as comments to the third-party site or directed to the firm, would be considered solicited requests.

Example 10:  If a firm announces results of a study via a microblogging service (e.g., Twitter) and suggests that an off-label use of its product is safe and effective, any comments and requests received as a result of the original message about the off-label use would be considered solicited requests.

Example 11:  If a firm sets up a website that enables viewers to read prepared standard responses for the firm’s products that are generated from prefixed pull-down menus naming various disease states, including any standard responses related to off-label uses for the firm’s product, resulting requests for off-label information would be considered solicited.  Moreover, if this website makes it possible to use search terms to generate standard responses that go beyond the scope of the product information being requested, including off-label use information, resulting requests for and responses to such a search would be considered solicited requests.

For all of you out there who thought the FDA was going to answer all your questions and solve all your problems relative to social media and regulatory ambiguity, sorry. Here’s what the agency is telling you – just do what makes sense.

Or, put another way:

FDA has long taken the position that firms can respond to unsolicited requests for information about FDA-regulated medical products by providing truthful, balanced, non-misleading, and non-promotional scientific or medical information that is responsive to the specific request, even if responding to the request requires a firm to provide information on unapproved or uncleared indications or conditions of use. If responses to unsolicited requests fall within these parameters, FDA has not expected those responses to meet regulatory requirements for promotional labeling or advertising and has not considered these responses as evidence of intended use.  This draft guidance sets forth FDA’s current thinking on this topic, consistent with the Agency’s past policy statements about responding to unsolicited requests.

Now, here’s the fun stuff –

RESPONDING TO PUBLIC UNSOLICITED REQUESTS FOR OFF-LABEL INFORMATION, INCLUDING THOSE ENCOUNTERED THROUGH EMERGING ELECTRONIC MEDIA

While it certainly isn’t news, here’s the conclusion the FDA has reached regarding “the Internet” – The Internet has revolutionized communication, information-sharing, information exchange among systems, and collaboration, enabling consumers to become more proactive about their health and safety. Consequently, the Internet has become a widely used medium for manufacturers and distributors of FDA-regulated medical products to disseminate information. 

So stipulated.  Now here’s the interesting part

The Internet has also spawned a variety of social media tools that host online content primarily created and published by users other than the intellectual property owner or product manufacturer.  In some cases, this online content may not be accurate.  Because consumers increasingly use the Internet to search for information about medical conditions and treatments, firms may receive public requests for off-label information about their products through, for example, product websites, discussion boards, chat rooms, or other public electronic forums that they maintain and over which they have full control. Firms may also encounter requests for off-label information on third-party sites (i.e., websites and other venues that are either entirely independent of a firm’s control and influence or not fully controlled by a firm).  Questions about off-label use may be directed to the website users at large, rather than specifically to a firm.

FDA recognizes that firms are capable of responding to requests about their own named products in a truthful, non-misleading, and accurate manner.  Moreover, because firms usually have robust and current information about their products, 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.

However, because product information posted on websites and other public electronic forums is likely to be available to a broad audience and for an indefinite period of time, FDA is concerned that firms may post detailed public online responses to questions about off-label uses of their products in such a way that they are communicating unapproved or uncleared use information about FDA-regulated medical products to individuals who have not requested such information.  In this circumstance, communications to persons who have not requested information may promote a product for a use or condition for which FDA has not approved or cleared.  FDA is also concerned about the enduring nature of detailed public online responses to off-label questions because specific drug or device information may become outdated (e.g., new risk information may become available).

Here comes the “guidance” part of the draft guidance:

FDA makes the following recommendations to a firm that chooses to respond to public unsolicited requests for off-label information about its product(s), including those encountered through emerging electronic media.

If a firm chooses to respond to public unsolicited requests for off-label information, the firm should respond only when the request pertains specifically to its own named product (and is not solely about a competitor’s product).

The level of specificity of the question posed in a public forum is important in determining the appropriateness of a firm responding to the unsolicited request.

Example 13:  An individual poses the specific question “Can Drug/Device X be used for Condition Y” in a public forum (and this question is not prompted by or on behalf of the firm).  It may be appropriate for the firm to respond as outlined below because the question is unsolicited and specific to the firm’s named drug or device.

However, if an individual poses the non-specific question “What drug/device can be used for Condition Y” in a public communication thread and the firm manufactures or distributes Drug/Device X, which is not FDA-approved or cleared for Condition Y, the firm should not respond to the request because the question is not specific to Drug/Device X.

A firm's public response to public unsolicited requests for off-label information about its named product should be limited to providing the firm’s contact information and should not include any off-label information.

The firm’s public response should convey that the question pertains to an unapproved or uncleared use of the product and state that individuals can contact the medical/scientific representative or medical affairs department with the specific unsolicited request to obtain more information.

The firm’s public response should provide specific contact information for the medical or scientific personnel or department (e.g., e-mail address, telephone number, facsimile) so that individuals can follow up independently with the firm to obtain specific information about the off-label use of the product through a non-public, one-on-one communication.

In other words, a post along the lines of, “Hi Bob.  My name is Susan and I work for DRUG COMPANY NAME.  I saw your post regarding NAME OF PRODUCT.  That is an off-label use of the product.  For FDA-approved indications, here is a link to the official FDA label. If you would like to discuss this product at with our medical personnel, please call this toll-free number”

Not rocket science folks. The draft guidance continues:

After an individual has privately contacted a firm for more information regarding an off-label use of the firm’s product, the firm should provide a detailed response and maintain records following the parameters outlined in Section V of this draft guidance.  Therefore, any substantive communication about off-label uses for the product, in response to the original unsolicited off-label question, should occur solely between the firm and the individual who made the request.  Regardless of the fact that the original, unsolicited off-label question may have been available to a very broad audience, the firm should not make its detailed response with off-label information publicly available within the same forum.  For example, after the requestor has contacted the firm and provided a personal e-mail address to obtain an answer to the off-label question, the firm’s detailed off-label response, within the parameters outlined in Section V of this draft guidance, should be e-mailed to the requestor since this resulting communication will occur solely between the firm and the specific individual making the unsolicited request for the off-label information.

3. Representatives who provide public responses to unsolicited requests for off-label information should clearly disclose their involvement with a particular firm.

FDA recommends that a representative who responds to a public request clearly disclose in his/her public response that he/she is a particular firm’s representative and inform the requestor of the name of the firm representative or department to contact should the individual choose to follow up directly with the firm in a non-public forum for detailed information about the unsolicited request for off-label information.

4.  Public responses to public unsolicited requests for off-label information described in numbers 2 and 3 should not be promotional in nature or tone.

In addition to a firm’s contact and disclosure information, a public response should include a mechanism for providing readily accessible current FDA-required labeling, if any, for the product  (e.g., FDA-approved package insert and, if the response is for a consumer, FDA-approved patient labeling or, for new animal drugs, FDA-approved client information sheet).  The public response should not provide any promotional information.  For example, a public online response should include a direct link to the current FDA-required labeling, if any, but should not include links to any other information (e.g., product websites, product promotional materials, firm websites, third-party websites). Furthermore, the uniform resource locator (URL) or web address where viewers are directed to obtain the FDA-required labeling, if any, should not itself be promotional in tone or content (e.g., should not be www.bestcancercure.com).

If a firm responds to public unsolicited requests for off-label information, including those encountered through emerging electronic media, in the manner described above, FDA does not intend to use such responses as evidence of the firm’s intent that its product be used for an unapproved or uncleared use. Such responses also would not be expected to comply with the disclosure requirements related to promotional labeling and advertising.

What can we learn from this draft guidance?  Well, the most important lesson is that if we just follow our own common sense, social media is a greenfield of opportunity to help market products but – more importantly – to help advance the public health.

If you were waiting to be led by the hand by the "emerging social media" savants at the FDA -- sorry.

The full draft guidance is worth studying and can be found here.

And Happy Hanukkah!

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Ocean's 2011

12/22/2011 08:21 AM |

Well, it certainly has been an eventful 2011.

But the good news is -- you ain't seen nothin' yet.  (Or is that the bad news?)

In either event, thank you for your attention, comments and criticisms during the past year.  And here's to a healthy, happy and successful 2012.

See you all on the other side.

Cheers.

Peter

Peter J. Pitts  Read More & Comment...

Paul's Christmas Epistles

12/21/2011 08:43 AM |

Once upon a time, Paul Kim worked for both Congressman Henry Waxman (on the Energy & Commerce Committee) and Senator Ted Kenendy – giving him the honor of negotiating with FDA on the original PDUFA package and then, subsequently on the reauthorizations both on the House and Senate side.

As a panelist at CMPI’s PDUFA without the Politics conference, he had a lot to say.  (A video of his full comments can be found here.) Specifically, when it came to ornaments to hang on the PDUFA Christmas Tree he had two – both aimed at enhancing and incentivizing innovation.

There are bills that even in a very partisan environment find a lot of bipartisan support and interest in a bicameral way. And there were two I just felt I had to call out. They go to the innovation gap -- an issue and a set of concerns that are so much more resonate now in this economy and the role that the agency plays in promoting innovation. There are two proposals. The first is called the Gain Act. It’s sponsored by Congressman Gingrey - Dr. Gingrey, here in the house – and Senator Blumenthal in the Senate. Wonderful bipartisanship, bicameral support there. It would enhance incentives in terms of exclusivity for sponsors that are trying to generate and create and innovate on microbials. And given the enormous challenge that microbial resistance presents to public health, this is an area where it seems like there’s a classic market failure. There aren’t enough players in the field. The marketing incentives are not strong enough to draw interest, to draw investment. So, that’s a proposal that already has bipartisan support in both chambers. I think it’s the subject of a lot of discussions in the committees of jurisdiction. So, do look out for the GAIN act as a possible ornament somewhere in the upper branches of the PDUFA Christmas tree.

The second proposal is one that has also received bipartisan support, sponsorship and interest on both sides, Senate and House. And that’s to reform the humanitarian device exemption or HDE process.

Little known, it’s kind of the lesser known sibling to the Orphan Drug Act, which has promoted and really generated tremendous innovation for diseases, rare diseases and disorders affecting 30 some million Americans. When it was originally enacted in 1990, there was a profit cap. It said if you develop a device for a very, very small population, you can only charge for cost. It was intended as a safeguard, but instead what’s happened is it’s blocked and chilled interest in using that pathway to market.  The consequence is that we’ve had some 54 HDEs or Humanitarian Devices approved since 1990. In contrast, literally hundreds of orphan drugs have been approved since the enactment of that act. Again, it’s an issue that has bipartisan interest and support, a very small change to existing laws. It’s not overturning the apple cart, but I think you’ll see some significant changes in the marketplace among sponsors, investors, investigators, and scientists as a result of any federal change like that.

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Finally! A Congressional Action to Lower Healthcare Costs!

12/20/2011 08:14 AM |

Some important items courtesy of the good folks at BioCentury:

Finally – a Congressional action that will lower healthcare cost:

IPAB budget slashed

The appropriations bill passed last week by Congress cut 2012 funding for the Independent Payment Advisory Board by $10 million to $5 million. The Patient Protection and Affordable Care Act created IPAB and gives it authority to recommend steps to cut Medicare costs if spending exceeds specific triggers. The recommendations would go into force automatically unless Congress overruled them by a two-thirds vote and enacted other cuts of equivalent size.

IPAB has been criticized by members of both parties. Republicans said IPAB would lead to healthcare rationing. Democrats said they oppose IPAB because it usurps congressional authority.

Understanding the importance of medical technology after-the-fact

Senators introduce device bill

Sens. Chuck Grassley (R-Iowa), Richard Blumenthal (D-Conn.) and Herb Kohl (D-Wis.) introduced the Medical Device Patient Safety Act, which would allow FDA to require postmarketing studies for medical devices approved via the 510(k) process. The proposed legislation would give FDA the authority to revoke a device's approval if postmarketing studies are not conducted. Grassley said the legislation should be included in the reauthorization of MDUFA next year.

And prepare for March Madness

Supreme Court sets March date for healthcare challenges

The U.S. Supreme Court scheduled three days in March to hear challenges to the Patient Protection and Affordable Care Act, including the constitutionality of the law's individual insurance mandate. The court allocated five and a half hours spread across March 26, 27 and 28. On March 26, the court will consider a procedural question on whether the mandate challenge is barred by the Anti-Injunction Act. On March 27, the court will hear arguments on the mandate's constitutionality. On March 28, the court will consider whether the mandate, if found to be unconstitutional, can be severed from the rest of PPACA or if the entire law must be struck down. Later that day, the court will hear a challenge to PPACA's expansion of Medicaid to cover individuals with income of up to 133% of the federal poverty level.

The challenges are taken from three separate cases: National Federation of Independent Business et al. v. Sebelius, et al.; Florida, et al. v. U.S. Department of Health and Human Services, et al.; and U.S. Department of Health and Human Services, et al. v. Florida, et al.

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PDUFA Christmas Tree Ornament for Children

12/19/2011 08:54 AM |

O Tannenbaum, o Tannenbaum,
wie treu sind deine Blätter!

At CMPI’s PDUFA without the Politics conference, each panelist was asked to bring one ornament to hang on the reauthorization Christmas Tree.  Tim Franson (President of the USP Convention and one of the “Fathers of PDUFA”) offered a little lifeboat.

What can we do for those with life threatening unmet needs? One thing, as was done in PDUFA IV, is adding renewal of the Best Pharmaceuticals for Children’s Act. That piece of legislation has done more for pediatric drug development than anything in the past. It’s been good for American children and it should be made permanent. I think the better policy argument is to make it permanent, because companies don’t invest in five-year cycles. (Note to reader: The Act is currently renewable every five years.)

If I’m looking for a return on an investment, I need certainty well in advance of five years on types of studies I should be conducting and I need to know the benefit I’m getting at the end. I think five years is far too short a period of time.

Here’s what Vince Ventimiglia (a former Assistant Secretary for Legislation at the US. Department of Health and Human Services) had to say when asked about renewal vs. permanent authorization:

The argument I heard when we first set the five-year term, and that I heard again when we tried to make it permanent in subsequent years, was that we want to hold these guys accountable. It’s more to use it as a tool against industry -- and hold out the prospect that it could be removed.

To which Father Franson replied:

There’s an accumulated body of evidence, of companies fulfilling their commitments. Maybe its time we make it permanent. I think this point of holding up renewal like the Sword Damocles isn’t very persuasive even to sponsors.

O Tannenbaum, o Tannenbaum!
Das soll dein Kleid
mich lehren.

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Lead or follow?

12/16/2011 09:16 AM |

On August 18th, I wrote that pharmaceutical manufacturers should agree to voluntarily notify the FDA when they become aware of circumstances (manufacturing and otherwise) that might result in drug shortages,

(When I served at FDA we signed an MOU with PhRMA that required its member companies to inform the agency when instances of counterfeit medicines came to the attention of manufacturers. It got the job done – minus additional federal regulation.)

Shortly afterwards, Senators Amy Klobuchar (D, MN) and Bob Casey (D, PA) introduced legislation to require drug manufacturers to give “proper prior notification” to FDA when there is going to be a drug shortage.

Watch the Federal Register on Monday for an interim final rule from the FDA that requires manufacturers that are the only producers of critical drugs to report to FDA all interruptions in manufacturing processes, regardless of whether a drug shortage occurs. Previously, such manufacturers were only required to notify the agency when a drug shortage occurred. The rule goes into effect 30 days after being published.

This would have been a better and more interesting story if industry had taken the initiative rather than being directed to change its behavior.   Read More & Comment...