A new report from the President's Council of Advisors on Science and Technology (PCAST) has recommended the Agency for Healthcare Research and Quality (AHRQ) receive funds above and beyond the $1.1 billion earmarked in the President’s initial stimulus package to develop a test network for comparative effectiveness research.

The report notes that if patient progress and outcomes are routinely captured in data and made available in near real time, "partial data can be used in sophisticated ways to assign treatments to new patients in optimal ways. These data also could be used to personalize treatment for patients already enrolled in a study."

“Assign treatment?” Perhaps “help a physician decide” or “provide important clinical information”  -- but … “assign?” Sounds rather top-down, don’t you think?  Alas, as this report was drafted by experts who understand the importance of precise language, we have to assume what they wrote is what they meant.

And that’s frightening.

Sounds like a good topic for a Congressional hearing.

The Council’s report can be found here.

This Sunday on "BioCentury This Week" TV

Broadcast on WUSA Channel 9 in Washington, D.C.
and Fox affiliate WFXT Channel 25 Boston
8:30 - 9:00 a.m. EST

Dec. 12 broadcast investigates
POLITICAL COMMUNICATIONS
Finding Biotech's Voice in a Divided Washington

continuous webcast at
www.biocenturytv.com

Biotech avoided the eye of the storm during the bruising healthcare reform debate. In the newly divided Washington, the question is whether the industry can afford to stay under the radar on its hot button issues, such as PDUFA, as other interest groups join the fray. On Sunday, Dec. 12, BioCentury This Week examines this political communications landscape.

I spent the last two days chairing the Social Media for Pharma conference and boy are my arms tired.

Actually, it’s my brain that’s tired – because it got a lot of exercise.

Some speaker comments that resonated:

Julie Zawisza (CDER’s Director of Communications):  “If we don’t tell our own story – others will.”

So true.  And not just for the FDA.  The same is equally relevant for pharmaceutical and medical technology companies.  Perhaps even more so.  In fact, definitely more so.

Paul Buckman, the FDA’s new Dean of Digital, revealed that there is an FDA employee who is (in real time) posting responses to queries generated on the agency’s FaceBook page.  This is surprising considering that such a thing would certainly constitute an FDA “written response.” More on this as it develops.

Ambre Morley and Alpesh Patel (product communications and regulatory affairs at Novo Nordisk respectively) discussed their much-ballyhooed Twitter campaign (for Levemir) with IndyCar driver Charlie Kimball.  At the beginning of the presentation, Alpesh said that when Ambre first discussed the idea with him, he said, “Let me think about it.” To which Ambre replied, “Actually, you said no.”  Success, as they say, has many fathers.

J&J’s always-insightful Marc Monseau shared some gems, discussing the need for well-developed social media “policy, process and guardrails.”  The most important pharmaceutical company asset for success in social media?  “A cultural willingness to try.”  Amen.

Shwen Gwee and Zach Barber (Vertex) discussed their company’s foray into Twitter – and the interesting correlation between number of tweets and number of followers.  Shwen also shared their concern over “proactive following.”  Add that one to things that make you go hmm.  (FYI – current Vertex Twitter guidelines can be found here.)

Both the Novo Nordisk and the Vertex presentations raised questions about retweets – especially those with a hotlink.  All present agreed that all links should be carefully vetted before being retweeted.  (Here’s a brainteaser – what about retweeting an FDA tweet with a product-specific hotlink that doesn’t one-click to the P.I.?  Once again – hmm.)

Relative to FDA tweets and the aforementioned FDA FaceBook – and as if things weren’t ambiguous enough – what happens when you have the federal agency in charge saying (for all intents and purposes) “do as I say, not as I do.” And, of course, this is made even worse since the FDA isn’t saying much.

But I digress.

During one of the breaks, I participated in a very entertaining conversation with three regulatory types from three different companies. We decided there is an unmet need for “regulatory emoticons.” The consensus opinion was for an emoticon representing arms crossed across the chest. We felt that a more, shall we say, digit-based representation was overly confrontational.

Nancy Buono Cartwright (Kaiser Permanente) discussed using social media as an internal communications tool. Much smart thinking and nifty program elements.  Her suggestion for engagement --“Play in traffic.”  Not the best way to encourage an already skittish audience. Auto de fé indeed!

The omega presenter was Dennis Urbaniak (sanofi-aventis) and he had a keen observation about pharma and social media, “It’s not if anymore – it’s when and how.”

He also pointed out that social media (as part of an integrated marketing strategy) is unlike other, more traditional component – such as advertising.  Social media programs are the gift that (properly understood and harvested) is the gift that keeps on giving.

What does that mean?  Well, a DTC television commercial doesn’t generate anything once it’s been aired.  Social media, on the other hand, generates awareness, interaction, a call to action (when appropriate), and robust metrics that supply real-time competitive intelligence.

Need I say more?

There were many excellent presenters who I have not mentioned.  The complete program agenda can be found here.

Fascinating and informative BioCenutury cover story on a 21t century regulatory pathway for diagnostics.  Penned by the always informed Steve Usdin, here are some snippets:

FDA and members of Congress are putting the finishing touches on different proposals to create a new regulatory pathway for diagnostics, making it almost certain that major changes will be unveiled in 2011. The question is which approach will prevail — and whether either approach solves the problem of value-based reimbursement.

Top FDA officials and lawmakers have concluded that the current oversight system for diagnostics, which imposes premarket review requirements for in vitro diagnostics (IVDs) but not for the vast majority of laboratory-developed tests (LDTs), is not sufficient to protect the public or to support the development of innovative tests that are at the heart of hopes for widespread adoption of personalized medicine.

The only option that is off the table is the status quo.

Senator Orrin Hatch (R-UT) is lining up bipartisan support — and his staff is trying to build consensus among labs, diagnostics companies and investors — on draft legislation that would preempt FDA’s efforts. His approach would create a new regulatory category encompassing both LDTs and IVD tests.

Under the Hatch bill, IVDs would no longer be regulated as medical devices. Also, FDA would for the first time routinely regulate tests performed in labs, although lab services and operations would continue to be regulated by the Centers for Medicaid and Medicare Services (CMS) under the Clinical Laboratory Amendments (CLIA) (see “BETTER at a Glance”).

Hatch hopes to use a new regulatory system to go even farther, as a platform for launching reform of diagnostics reimbursement policies, and shifting Medicare from a payment system based on the complexity of test procedures to one based on the value of tests, according to diagnostics.

FDA has clearly signaled that in the absence of legislation, it intends to regulate LDTs, fitting them into a structure that many labs and IVD manufacturers argue is ill-suited for diagnostics.

Indeed, according to Alberto Gutierrez, director of FDA’s Office of In Vitro Diagnostic Device Evaluation and Safety (OVID), laboratory directors who hope FDA will back off from its plans to regulate their tests are like “ostriches which have their heads in the sand.” Gutierrez, who made the comment at a Nov. 22 meeting organized by ACLA, said the agency is writing a guidance document outlining a proposed diagnostics oversight framework. While he declined to say when the guidance will be released, FDA has already begun recruiting staff to implement it. At the same time, FDA has indicated that it will move slowly, leaving room for Congress to intervene before the agency implements any major changes.

“The success of personalized medicine depends on having accurate diagnostic tests that identify patients who can benefit from targeted therapies.”

(From July NEJM commentary jointly authored by FDA Commissioner Peggy Hamburg and NIH Director Francis Collins.)

The complete BioCentury article can be found here.

Mr. Read said, “I am honored to lead an organization with outstanding and dedicated colleagues on the front lines of medical innovation. We have a broad portfolio that spans the entire spectrum of human and animal health, from vaccines to biologics to primary care, specialty care, oncology, consumer products, nutritionals and beyond.  I have great confidence in the strength of our company and our leaders and will be looking at the performance and potential of all of our businesses to ensure we are delivering value to our customers and shareholders. We have all the elements for success -- financial strength, global reach, a disciplined focus on the therapeutic areas with the strongest growth potential and a talented and dedicated workforce.”

Since 2006, Mr. Read has led Pfizer’s Worldwide Biopharmaceutical Businesses which now comprises five global business units – Primary Care, Specialty Care, Oncology, Established Products and Emerging Markets – and accounts for approximately 85 percent of Pfizer’s annual revenues.  He was responsible for more than 40,000 Pfizer colleagues.  His leadership team consisted of senior executives directing Pfizer development and commercial operations in 180 nations.

Mr. Read joined Pfizer in 1978 and quickly assumed positions of increasing responsibility in Latin America.  In 1996, he was appointed President of Pfizer’s International Pharmaceuticals Group, with responsibility for Latin America and Canada. He was named Corporate Vice President in 2001, and assumed responsibility for Europe in addition to Canada.  Mr. Read later added the Africa/Middle East and Latin American regions to his leadership responsibility.

The Board will elect a non-executive Chairman from its current membership at its next regularly scheduled meeting that will take place within the next two weeks.

The saga continues …

NEW YORK (AP) - Momenta Pharmaceuticals Inc. said Thursday it is suing rival Teva Pharmaceutical Industries Ltd. in a patent dispute over generic versions of the anti-clotting drug Lovenox.

The Cambridge, Mass., company said it filed a patent infringement lawsuit against Teva, alleging the Israeli company violated two patents held by Momenta that are related to its generic version of the drug. Lovenox, or enoxaparin, is used to prevent dangerous blood clots, including clots in the veins of the thigh or leg, or in patients who are having a heart attack or chest pain. The original version of the drug is made by Sanofi-Aventis SA, and it was approved in the U.S. in 1993..

Nice article by Matthew Arnold in the December edition of Medical Marketing & Media.  “Eye of the Storm,” provides a nice overview of what we might expect in 2011 on a range of issues.

Here’s the section discussing the future of PCORI (the Patient Centered Outcomes Research Institute):

Healthcare reform rematch

Ex-FDA communications chief Peter Pitts says the board “provides the grease on the slippery slope towards formularies.” Three of its 21 seats are dedicated to pharmas, with execs from Pfizer, J&J and Medtronic among the initial appointees. Congress could also pull the $1.1 billion allocated to the Agency for Healthcare Research and Quality for comparative effectiveness research by the law.

“That money will be radically reduced if not eliminated altogether,” predicts Pitts. Pitts also expects “a very colorful season for healthcare hearings on the hidden codicils of healthcare reform.”

The full article can be found here.

Talk about a doc fix!

News from the AMA. But not really “news,” in the sense that everyone knew this already.  Nevertheless …

 New AMA Survey Finds Insurer Preauthorization Policies Impact Patient Care

Chicago – Policies that require physicians to ask permission from a patient's insurance company before performing a treatment negatively impact patient care, according to a new survey released today by the American Medical Association (AMA). This is the first national physician survey by the AMA to quantify the burden of insurers' preauthorization requirements for a growing list of routine tests, procedures and drugs.

"Intrusive managed care oversight programs that substitute corporate policy for physicians' clinical judgment can delay patient access to medically necessary care," said AMA Immediate Past President J. James Rohack, M.D. "According to the AMA survey, 78 percent of physicians believe insurers use preauthorization requirements for an unreasonable list of tests, procedures and drugs."

The AMA survey of approximately 2,400 physicians indicates that health insurer requirements to preauthorize care has delayed or interrupted patient care, consumed significant amounts of time, and complicated medical decisions. Highlights from the AMA survey include:

·         More than one-third (37%) of physicians experience a 20 percent rejection rate from insurers on first-time preauthorization requests for tests and procedures. More than half (57%) of physicians experience a 20 percent rejection rate from insurers on first-time preauthorization requests for drugs.

·         Nearly half (46%) of physicians experience difficulty obtaining approval from insurers on 25 percent or more of preauthorization requests for tests and procedures. More than half (58%) of physicians experience difficulty obtaining approval from insurers on 25 percent or more of preauthorization requests for drugs.

·         Nearly two-thirds (63%) of physicians typically wait several days to receive preauthorization from an insurer for tests and procedures, while one in eight (13%) wait more than a week. More than two-thirds (69%) of physicians typically wait several days to receive preauthorization from an insurer for drugs, while one in ten (10%) wait more than a week.

·         Nearly two-thirds (64%) of physicians report it is difficult to determine which test and procedures require preauthorization by insurers. More than two-thirds (67%) of physicians report it is difficult to determine which drugs require preauthorization by insurers.

Preauthorization policies deliver costly bureaucratic hassles that take time from patient care. Physicians spend 20 hours per week on average just dealing with preauthorizations. Studies show that navigating the managed care maze costs physicians $23.2 to $31 billion a year.

"Nearly all physicians surveyed said that streamlining the preauthorization process is important and 75 percent believe an automated process would increase efficiency," said Dr. Rohack. "The AMA is urging health insurers to automate and streamline the current cumbersome preauthorization process so physicians can manage patient care more efficiently."

See these two new papers from Health Affairs:

Peering Into The Black Box: Billing And Insurance Activities In A Medical Group

Strombeek-Bever, Belgium, November 30, 2010 – Reliable Cancer Therapies (RCT) is a Swiss non-profit organization that provides research-based information on cancer therapies and selectively funds the development of promising therapies.

RCT today launched a global online database (www.reliablecancertherapies.com) that provides scientifically checked information on cancer treatments. With this online database, RCT hopes to broaden the reliable treatment options for cancer for patients.

 “Our online database provides patients and medical professionals with free and qualitative information on cancer treatments, guidelines and clinical trials s” states Lydie Meheus, PhD, executive director of RCT: “This website is an answer to the growing need for a comprehensive repository of reliable, trustworthy information on cancer treatments and investigational drugs. We give specific, verified information on as well conventional as non-conventional cancer therapies, and we want to focus on the resulting patient outcomes. We hope that this database will help people find their way through overwhelming, confusing and way too often unverified information. However, it should be emphasized that RCT does not provide medical advice and that our website does not replace a medical consultation.”

“Defensive REMS” May Be Needed To Appease Advisory Committees

Sponsors facing an FDA advisory committee should be prepared to discuss Risk Evaluation and Mitigation Strategies, even if FDA tells a company that a REMS need only have minimal elements or is not necessary, to avoid a negative vote, industry experts say.

Egrifta Approval Suggests Evolution In FDA Thinking On Role Of REMS

FDA’s decision not to require a Risk Evaluation and Mitigation Strategy for Theratechnologies’ HIV lipodystrophy drug Egrifta (tesamorelin) suggests the agency is becoming more circumspect in how it applies its drug safety powers under the FDA Amendments Act more than two-and-a-half years after they took effect.

Wither predictability?

Maybe PDUFA should stand for the Predictability Deposit User Fee Act.

As negotiations for PDUFA V get serious, there seems to be a widening gap between what FDA wants (more resources) and what industry wants (more predictability). 

Of course there are many, many other things – all of them important (and the devil is certainly in the details), but it’s the conjoined issues of resources and predictability that is driving the debate.

PDUFA V is turning into a battle over First Principles.  And it’s about time.

Industry has (IMHO) turned the corner relative to a well-funded FDA.  Regardless of whether or not some members of the 112^th Congress believe that the agency should receive less funding, a well-funded FDA is in the best interest of the both the public health and a robust biopharmaceutical industry.

A properly funded FDA will be able to do more things with greater ability and alacrity. And this will (among other things) help to further bolster the agency’s reputation with the public, thought leaders and elected officials.  And, as research has demonstrated, a well-regarded FDA leads to greater trust in the safety and efficacy of the products it regulates. A properly funded FDA will be able to more aggressively pursue the 21^st century regulatory science so essential for 21^st century drug development.  The Critical Path doesn’t come cheap – but it’s worth it.

Better, more current and predictable scientific research and standards must be developed and devoted to streamlining the critical path. Investment in basic research is not enough. Specifically new development tools are needed to improve the predictability, speed and quality of the drug development cycle and, on the flip side of that coin, lower the cost of research by helping industry identify product failures earlier in the clinical trials process.

25 years ago, the success/approval rate for a new drug was about 14%. Today, a new medicinal compound entering Phase 1 testing—often after more than a decade of preclinical screening and evaluation—is estimated to have only an 8% chance of reaching the market. For very innovative and unproven technologies, the probability of an individual product’s success is even lower. We have got to work together to turn that around.

When Thomas Edison was asked why he was so successful he responded, “Because I fail so much faster than everyone else.” Consider the implications if FDA could help companies to fail faster. Using the lower end of the Tufts drug development number ($802 million):

* A 10% improvement in predicting failure before clinical trials could save $100 million in development costs.

* Shifting 5% of clinical failures from Phase 3 to Phase 1 reduces out of pocket costs by $15-$20 million.

* Shifting of failures from Phase 2 to Phase 1 would reduce out of pocket costs by $12-$21 million.

What the FDA can do with more money is a long list. But nothing's going to happen unless recognition on the part of the agency that times are changing.

Industry cannot accept, as Abba Eban famously said, “We give and they take,’ as a negotiating strategy.

There are different dimensions when it comes to “predictability.” Of course there’s the “PDUFA Date” deliverable – the driving force behind the user-fee concept in the first place.  That’s broken. Then there’s the predictable and reportable allocation of funds. That’s absent. There’s a lack of consistency in agency decisions within the same therapeutic category. A poverty of best science practices that can be used to both develop and review drugs. A frightening lag relative to best practices in qualified methodologies. And a dearth of common data elements and standards. 

That’s for starters.

Other items include biomarkers, REMS, a less byzantine diagnostics development and approval pathway, social media guidance, DTC and DDMAC issues, a non-BLA FOB pathway, generic bioequivalence, clinical trial design, development and use of non-US data, safe use, early safety signal communications and building an effective and proactive safety surveillance system, pediatric exclusivity, orphan disease drug development, paperless labeling, stakeholder engagement, EU harmonization, enhanced transparency and communications, etc.

It’s in this context that you have to consider the FDA’s proposed four-stage review cycle that would allow the agency to suspend the review clock in mid-review to address application problems and amendments (the infamous “time out” provision) and, if you’re still counting, the issue of “non-binding advice.”

It would be useful for the 112th Congress to clarify some of the limitations on FDA’s authority to command the payment of user fees.  For example, CDER has interpreted the system to allow requests for user fees according to the number of data sets rather than applications/supplements, contrary to its own guidance. 

There are some rogue elements within industry that are ready to at least (or at last) discuss the “nuclear option” – no PDUFA fees at all. Why pay for the privilege of regulatory ambiguity? Why reward a lack of consistency? After all, they say, how much worse could it get? Well – the answer is “a lot worse.” But the fact that this is even being discussed points to the need to return to First Principles.  And the very first principle of PDUFA is predictability.

Industry seeks clarity. They want bright lines. They want to know the rules. They want predictability. This may sound simple and fair, but inside the FDA it has proven to be a fractious bureaucratic kulturkampf.  “Change is not required,” as management guru W. Edwards Deming once said. “Survival is not mandatory.”  And that doesn’t mean change for show, for politics – it means thoughtful, timely, strategic change that enhances the public health.  And that kind of change requires not walking on egg shells – but breaking them. 

Without a PDUFA “Predictability Deposit,” there’s not going to be much public health return. It’s a long road to September. Predictability is power in pursuit of the public health

Terry Vermillion, head of the FDA’s Office of Criminal Investigations (OCI) is “retiring” after the latest round of criticism directed at his department by congressional investigators.

The truth is that he’s taking a bullet for the team. And the public is not better off for it.

"I hope that with new leadership, this office will contribute more to the FDA's overall mission of protecting public safety," said Senator Charles Grassley (R, IA) in a statement Tuesday evening.

That’s a shameful comment.

When politics trumps public health, we are going in the wrong direction.  Terry is an unfortunate sacrifice to a political agenda.

OCI pursues cases that present a danger to the public health and have an FDA nexus. The diverse background of OCI agents gives the FDA the ability to aggressively address issues ranging from mail and financial fraud, to smuggling, forfeiture, and counterfeiting.  OCI agents do this with talent, devotion, skill – and success.

OCI is a career destination of choice for the cream of the crop of Federal law enforcement agencies such as the FBI and the Secret Service – and they come to the FDA with an average of 12.5 years of Federal law enforcement investigatory experience.  That’s why Terry Vermillion, the director of OCI and a former Secret Service agent himself, refers to his agents as “a taskforce of talent.” And they play a crucial role in protecting the safety of America’s prescription medicines and food supply.

In a typical year, FDA's Special Agents will investigate about 1,000 criminal cases resulting in the arrests of hundreds of suspected violators of public health laws.

On average, 200 criminal suspects are convicted each year as the result of OCI investigations. From 1993 to present, OCI has made 4,593 arrests that resulted in 3,546 convictions and more than $5.7 billion in fines and restitutions.

Consider the words of Teddy Roosevelt:

“It is not the critic who counts; not the man who points out how the strong man stumbles, or where the doer of deeds could have done them better. The credit belongs to the man who is actually in the arena, whose face is marred by dust and sweat and blood, who strives valiantly; who errs and comes short again and again; because there is not effort without error and shortcomings; but who does actually strive to do the deed; who knows the great enthusiasm, the great devotion, who spends himself in a worthy cause, who at the best knows in the end the triumph of high achievement and who at the worst, if he fails, at least he fails while daring greatly. So that his place shall never be with those cold and timid souls who know neither victory nor defeat.”

Stand tall Terry.

A three-judge panel of the U.S. Court of Appeals for the 2nd Circuit said Vermont’s law that restricts companies' use of information about the drugs doctors prescribe is unconstitutional on free speech grounds.

In a 2-1 ruling, the New York appeals court said the law doesn't achieve what Vermont wants to achieve and that a more limited restriction would be better.

"The state has not demonstrated that its interests in protecting public health and containing health care costs could not be as well served by a more limited restriction on speech," the majority opinion said.

But there’s more to this issue than Free Speech. There’s also a crucial safety component.

When FDA-directed safety warnings are issued, they're communicated via "Dear Doctor" letters to the physicians who have prescribed the drug in question. This is accomplished quickly and precisely because the industry has access to accurate data. And when safety issues arise, that same data helps define the scope of the problem. Because of this data, for example, the FDA can determine how many patients were taking a specific drug and for how long each patient had been taking it.

Further, FDA-mandated risk management plans - developed for physicians who prescribe higher-risk therapies - are physician-targeted through the use of prescribing data. These records are also an important tool in clinical trial recruitment, allowing doctors who are treating targeted patient populations to focus their efforts.

According to the American Medical Association (AMA), "Restrictions on the use of prescription information will disrupt health care research and its corresponding benefits for patients, government agencies, health planners, academicians, businesses and others."

Relative to physician concern that their prescribing data will be used for aggressive marketing campaigns, the AMA has a web-based program specifically designed to address physician concern over inappropriate use of prescribing information. Known as the Prescribing Data Restriction Program (PDRP), the program also ensures that prescribing-data remains available for all the reasons previously mentioned. In fact, all companies that purchase data from the AMA will be contractually required to adhere to the PDRP program.

The safeguards offered by the AMA's program offer a much more reasonable and targeted approach to protecting both patients and physicians from unwanted disclosures. And those safeguards come with far fewer unintended consequences than any ill-considered state legislation.