The Learned Disintermediary

04/30/2012 08:18 AM |

Patient, diagnose thyself -- and then reach a little deeper into your wallet.

Physician, step aside.

Pharmacist, step up to the plate.

Maybe.

The FDA may soon permit Americans to obtain some drugs used to treat conditions such as high blood pressure and diabetes without obtaining a prescription.

The FDA says over-the-counter distribution would let patients get drugs for many common conditions without the time and expense of visiting a doctor, but medical providers call the change medically unsound and note that it also may mean that

Under the changes that the agency is considering, patients could diagnose their ailments by answering questions online or at a pharmacy kiosk in order to buy current prescription-only drugs for conditions such as high cholesterol, certain infections, migraine headaches, asthma or allergies.

By removing the prescription requirement from popular drugs, the Obama administration could ease financial pressures on the overburdened Medicare system by paying for fewer doctor visits and possibly opening the door to make seniors pay a larger share of the cost of their medications.

The change could have mixed results for non-Medicare patients. Although they may not have to visit a doctor as often, they could have to pay out more money for medications because most insurance companies don't cover over-the-counter drugs.

How will this impact patient compliance?  How will this effect one condition masking another, more serious one?

How will this change the role of the pharmacist?

Comments on the FDA proposal are due by May 7.

  Read More & Comment...

PDUFA -- If and When and How

04/30/2012 07:12 AM |

“Cozy Deal” (New York Times, April, 29, 2012) argues,

“The best approach would be for the government to fully finance the F.D.A. That is unlikely to happen. So before it ratifies any new deal on user fees, Congress must ensure that patient safety is the first priority.”

Sure, but unlike the Gray Lady we must all live in the real world. User fees are the cost of predictability -- not just for innovators who wants to know if and when they can commence marking new products but also for patients and physicians who want to know if and when these new treatments will be available.  Predictability is also an issue of how. And this rests on the ability of the FDA to create and communicate a thoughtful and patient-centered model of risk/benefit analysis. Thankfully this is a central part of the current reauthorization debate.

  Read More & Comment...

A Methodology to PCORI's Madness

04/27/2012 07:49 AM |

Talk about positive outcomes!

It pays to have friends on PCORI’s Methodology Committee.  Five of the seven grantees selected for PCORI funding are directly affiliated with members of that panel. In dollar terms its even more lopsided. Of the $799,524 awarded, $721,940 went to institutions with direct representation on the conclave.

If those committee seats are pro bono somebody should ask -- Cui bono?

  Read More & Comment...

Celebrating Israel's Independence and Existence

04/26/2012 03:18 PM |

Zach On Patrol Near Gaza 2012




Today is Yom Haatzmaut  (Israel Independence Day) and Peter Beinart will be celebrating it by giving a lecture at a synagogue about his anti-Israel book, “The Crisis of Zionism.”  In doing so, Beinart joins Gunter Grass and the producers of the 60 Minutes segment (blaming Israel for the withering away of the Palestinian Christian community) in proposing that Israel can only be purified if it ceases to exist as a Jewish state.

Victor Davis Hanson points out that the new anti-Semitism regards the creation of the Jewish state as a manifestation of the Western hegemonic impulse.  It  barely concedes that  Israel is democratic and protects human rights in a way unlike its autocratic neighbors.   It’s proponents ignore the systematic persecution of Christians in Arab countries, the torture and extortion of Hamas, the ongoing slaughter in Syria, the resurgence of the Islamic Brotherhood.

Rather, they are focused on forcing Israel to give up what the Economist calls the  “Auschwitz Complex.” accrued from the Holocaust, a pathology which they say its unwillingness to  “to give up its empire” (by crawling back into the 1949 borders of the state and absorbing millions of Palestinians).

The remembrance of the Holocaust is a searing reminder of the necessity of Israel.   Yom Hashoah is recalled by a two minute siren -- invoking the shofar – that turns all moving things and people into standing monuments.. The moment stretches on, the wail growing tighter and thinner, like a taut thread, binding all together, until it unwinds.

But Yom Ha-Shoah is only the tragic beginning of the story, not the end.  Seven days after,  Yom Ha’atzmuat (Israel Independence Day) is celebrated.  The day preceding that holiday, Israel observes Yom Ha-Zikaron ( Memorial Day)  to reaffirm (as written in the Israel Defense Force manual) “that establishing the State of Israel was intended to provide an answer to the problem of the existence of the Jewish people, in view of the fact that all other solutions had failed.  The Holocaust proved, in all its horror, that in the twentieth century, the survival of Jews is not assured as long as they are not masters of their fate and as long as they do not have the power to defend their survival.”

The movement from Yom Hashoah, to Yom Ha-Zikaron to Yom Ha'atzmaut reminds people, as Rabbi Irving Greenberg notes, that the “ State of Israel is not a reward or a product or an exchange for the Holocaust; it is a response. The Jewish people responded to the total assault of death by an incredible outpouring of life.”

And with an enduring sense of purpose.  When my son immigrated to Israel in 2007 and joined the IDF he was repeatedly asked why he did so.  He could never fully explain to others or to himself until his unit was called into battle during 2008 Operation Cast Lead against Hamas. 

He was in an APC with his brothers in arms.  He looked around at his comrades with who he shared the cramped space. 

Zach writes:

“To my right was the sharpshooter, an Ethiopian by the name of Redit Mullah. His parents were thrown onto Israeli chartered planes and saved from political instability and war in the 1991 Solomon Operation, when Israel rescued and integrated thousands of Ethiopian Jews into its growing populace. 

To my left was my friend Avichai Galilee, of Yemenite descent, whose grandparents were similarly rescued from persecution and vehement Arab violence by a massive and unprecedented Air-Evac operation known as ‘Operation Magic Carpet’ in 1950.
In back of me were two soldiers, of Russian and Iraqi descent.  They both shared the same legacy of being rescued and welcomed by the Jewish state when they had no place else to live as Jews.   It did not matter that the Israeli economy was anemic at the time and that we had few resources to spare. We did it anyways.

It then finally made sense to me: The state of Israel is there for us, and so should we be there for the state of Israel. Riding away in our APC’s it was us who was thanking Israel and paying a debt of gratitude for all it had done for us. “

Tomorrow Israel celebrates this spirit.  So do most Americans, who know that a democracy can achieve great things only if the citizens believe it is worth defending.   Only people like Beinart want to strip the Jewish state of this eternal essence.
  Read More & Comment...

10 More Reasons Why PCORI and CER Are Obsolete

04/26/2012 03:01 PM |

Breast cancer is at least 10 different diseases, each with its own genetic signature and pattern of weak spots, according to a new landmark study that promises to revolutionize diagnosis and prognosis, and pave the way for individualized, tailored treatment.

The study group, METABRIC (Molecular Taxonomy of Breast Cancer International Consortium), reports its findings in the 18 April online issue of Nature.  The Cancer Research UK-funded study is the largest global gene study of breast cancer tissue ever conducted, involving a large team of researchers, primarily in the UK and Canada.

Led by Professor Carlos Caldas from Cancer Research UK's Cambridge Research Institute and Professor Sam Aparicio from the British Columbia Cancer Centre in Canada, the team uncovered crucial new information about breast cancer. The researchers analyzed the DNA and RNA of breast tumor samples from nearly 2,000 women who had been diagnosed between five and 10 years ago, and for whom information about the tumor characteristics had been meticulously recorded. They compared this with the women's survival, and other information, like their age at diagnosis. Because the study was able to look at many tumors with rich data on each, it identified new patterns and "clusters" in the data not spotted before. In the study, the team classified breast cancer into at least 10 different subtypes: each characterized by common genetic features that link to survival. This suggests we need to rethink what we call breast cancer and start looking at it as at least 10 different diseases, each with its own molecular fingerprint and pattern of weak spots.

Dr Harpal Kumar, chief executive of Cancer Research UK, told the press the study will completely change the way we look at breast cancer.  Caldas, who is also Professor of Cancer Medicine at Cambridge's Department of Oncology, said "breast cancer" should be regarded as an umbrella term for a range of diseases. The findings could change the way drugs are tailored to treat individual women with breast cancer. The team also discovered several previously unknown genes that drive breast cancer. Each of these is a potential target for new drugs, and should boost worldwide efforts to discover and develop new treatments. The study also reveals the relationship between these breast cancer genes and known signalling pathways, the networks that control cell growth and division. This invaluable knowledge will help identify how variants of these genes cause cancer by interfering with cell processes.

Over decades, the METABRIC project has produced a "goldmine" of data, says Caldas. The process is not unlike that of cartography. At first, intrepid explorers discover new continents, defined by outlines and some rough impressions of terrains and landscapes. Then gradually, as mapping techniques improve, the data becomes more detailed and more precise. The METABRIC team now has a detailed "map" of thousands of individual tumors that have been analyzed and re-analyzed in many different ways and linked to detailed information about the fate of the women they came from.

Not only has the team performed all kinds of analysis on the DNA of the tumors (for instance the map is now annotated with copy number changes and single letter variations or SNPs, for each tumor), it has also conducted a detailed analysis of their RNA so they can tell which genes were active in each sample. Altogether they did this for more than 30,000 types of RNA, each corresponding to the activity of a single gene. "We've drilled down into the fundamental detail of the biological causes of breast cancer," said Caldas, "we've moved from knowing what a breast tumour looks like under a microscope to pinpointing its molecular anatomy". "Our results will pave the way for doctors in the future to diagnose the type of breast cancer a woman has, the types of drugs that will work, and those that won't, in a much more precise way than is currently possible," he added.

Aparicio said: "The new molecular map of breast cancer points us to new drug targets for treating breast cancer and also defines the groups of patients who would benefit most." Caldas said these results will not affect women diagnosed with breast cancer today, but he envisages future breast cancer patients will receive treatments tailored specifically to the genetic fingerprints of their tumors. From this huge leap forward, the next step is to find out how the tumors in each of subgroup behave.

Caldas had this to say to the patients behind the study: "I want to stress, this study wouldn't have been possible without the breast cancer patients who donated their samples and agreed to take part in the study. None of this would have happened without them, and I'm so grateful for their participation." For an excellent account of how we have increased our understanding of breast cancer, plus a table showing the 10 disease subtypes, see Henry Scowcroft's post in the Cancer Research UK Science Update blog.  Read More & Comment...

P2P Healthcare & the Portals of Power

04/26/2012 07:54 AM |

Transparency (via social media) is leading to erosion in trust of once sacrosanct gurus such as physicians, corporations, their avatars and other “experts” (not the least of which is the mainstream media).

It’s been a painful and swift denuding of influence. Rather than being slowly disrobed, yesterday’s unquestioned experts have been roughly stripped of their gravitas and authority. Some have behaved badly, the majority has ignored it. Too few have gotten the message – adapt or die. You can’t airbrush social media.

Perhaps (and hopefully) this isn’t so much a downward spiral as it is (in the words of Schumpeter) “creative destruction.”

As Schumpeter writes in Capitalism, Socialism and Democracy, “The fundamental impulse that sets and keeps the capitalist engine in motion comes from the new consumers, goods, the new methods of production or transportation, the new markets, the new forms of industrial organization that capitalist enterprise creates.”

He would have loved social media.

While various “emperors” are being exposed as having no clothes, the void is being filled with robust and real-time peer-to-peer communications. Alas, there are also many ascendant false prophets. The Internet is full of them. Some are well-meaning (but still dangerous) idiots (such as the anti-vaccine crowd), others pure charlatans ("Cure your cancer in Mexico!").

As Don Draper once said, “I'm enjoying the story so far, but I have a feeling it’s not going to end well.”

Social media is a wonderful “green field of opportunity.”  But to maximize the opportunity, we must accommodate the reality of a messier world.  Social media, almost by definition, is messy – and the regulatory framework (or lack thereof) is equally so. And it’s not likely to get much better. Get used to it.

All this doesn’t mean that social media is a bad thing. Nobody said it was going to be easy. If we want to change the healthcare paradigm (and for some that’s a big “if”), then changing the way people learn, discuss and address healthcare issues is a crucial element. And, unlike other aspects of healthcare change – it is happening with great rapidity.

Impact and influence happen when what you have to share is to the benefit of the seeker — not to you.  And that requires a level of focus, acumen and honesty that is always hard and often lacking – especially when it comes to healthcare marketing. As the saying goes in our nation’s capital, “if you’re not at the table, you’re on the menu.”

In the words of Winston Churchill, “Ease is relative to the experience of the doer.”

We’re still looking to healthcare professionals for technical solutions (physicians are no longer the first and last word, but the first among equals). When it comes to practical advice, it’s an increasingly peer-to-peer proposition. Today (for better or worse) we are all “learned intermediaries.” (But some as more learned than others – a fact we need to recognize and advocate.)

Welcome to the new world of P2P Healthcare where social media holds the keys to the portals of power.  And as Dr. James Fowler of the University of California at San Diego, opined, “Pharma must realize their own network power.”

Social media is communications at the speed of life. As Marshall McLuhan wrote, “At electric speed, all forms are pushed to the limits of their potential." 

(Still think you can wait for more precise and directive FDA regulations?)

  Read More & Comment...

PDUFA Update

04/25/2012 11:07 AM |

The Energy and Commerce Health Subcommittee PDUFA Reauthorization Markup scheduled for tomorrow has been postponed.  The Health Subcommittee Markup will occur on Tuesday, May 8.  The Full Committee may have opening statements on the user fee bills Wednesday, May 9 and possible Full committee mark-up Thursday, May 10.  The Chairman cited continued staff negotiations for the reason for the postponement  Read More & Comment...

Endgame for PDUFA Primaries

04/25/2012 06:55 AM |

The PDUFA "primary season" is almost over

Today, BioCentury reports, the Senate HELP Committee will deliberate on a PDUFA reauthorization bill that would relax conflict-of-interest restrictions on advisory committee members, and enact new provisions intended to improve risk-benefit decision-making, facilitate global harmonization of clinical trials and promote regulatory science.

The PDUFA reauthorization manager's amendment would eliminate limits on the numbers of conflict-of-interest waivers FDA can issue for advisory committee members. It would require FDA to "implement a structured risk-benefit assessment framework in the new drug approval process to facilitate the balanced consideration of benefits and risks, a consistent and systematic approach to the discussion and regulatory decision-making, and the communication of the benefits and risks of new drugs." It also would instruct FDA to work with international regulators and industry to "encourage uniform, scientifically-driven clinical trial standards" that would facilitate simultaneous global development of new medical products. Another new provision would require FDA to identify regulatory and scientific gaps that impede product reviews and approvals and draft plans with specific milestones for addressing the gaps.

The House Energy and Commerce Subcommittee on Health will mark up its version of the FDA user fee reauthorization legislation on Thursday.

Is the final vote a sure thing?  Probably.

But is any election ever a sure thing?

  Read More & Comment...

Creating a Patient Centered Path To Innovation

04/24/2012 06:08 PM |

I attended the Value Driven Engineering conference sponsored by The Austen Bioinnovation Institute of Akron ( http://www.abiakron.org/vde-home) and ABIA's CEO, Dr. Frank Douglas. The meeting brought together a combination of engineers, entrepreneurs, doctors, patients, government officials to discuss ways to make innovation sustainable by making it patient centered. The shift in perspective brings about a shift in how both value and cost are defined and measured as well as how new medical products are developed. Peter Drucker once observed: “Quality in a product or service is not what the supplier puts in. It is what the customer gets out and is willing to pay for. A product is not quality because it is hard to make and costs a lot of money, as manufacturers typically believe. This is incompetence. Customers pay only for what is of use to them and gives them value. Nothing else constitutes quality.” Value (from the patient perspective) is defined as what benefits end users look for and get from a new technology. This is not a new concept, but it's application in the design and purchase of medical innovations is indeed, innovative and in many ways radical. It means that elegant technology has to enhance experience and solve problems. It means that consumers of products will have to be involved in the design of products in some meaningful manner. And it means that product design must be refined by real time, real world experience. Does it mean that new products have to be cheaper or reduce the cost of treating patients. Sometimes, and likely more often than not. But that shift does not mean giving up quality. Indeed, a Johns Hopkins University engineering students are developing a fetal heart monitor that is ten times cheaper than the state of the art machine used in America and is less invasive and more precise. It's also a product anyone can use. Often they are products that have a higher price but reduces the complexity of care, makes it more convenient and frees people up to work more and be more independent, not less. And they also fill an unmet clinical need. A growth factor in heart stem cells can be injected in minutes to help repair left ventricles and save lives. The biggest hurdle to VDE is, the conferees agreed, was reimbursement requirements, especially those that require CER as another step to adoption. VDE uses and depends upon real work use and reworking of products to improve performance and reduce cost. Companies can complete this virtuous cycle more frequently and with less interference offshore. Which is why innovation is leaving America. The choice is between VDE, a prospective partnership that designs products based on reducing cost and consumer value and CER, an after fact hurdle that patients must scale to access innovation.   Read More & Comment...

Gasp -- ASP!

04/23/2012 07:45 AM |

When it comes to drug shortages, pounding Big Pharma isn’t the answer. Finally someone is focusing on the perverse economic incentives of Average Sales Price (ASP) as a key factor behind the problem.  And that someone is Senator Orrin Hatch (R, UT.)

His Patient Access to Drugs in Shortage Act is out for comment through April 25, 2012. This proposed legislation is the only bill dealing with the economic causes of the shortages.

Some important codicils include:

* Price Stability — The draft would change the Medicare reimbursement rate for generic injectable products with 4 or fewer active manufacturers from Average Sales Price (ASP) + 6% to Wholesale Acquisition Cost (WAC) in order to achieve market price stability.

* Medicaid/340B Rebate Exemption — The draft exempts generic injectable products with 4 or fewer active manufacturers from Medicaid rebates and 340B discounts in order to achieve market price stability.

* Extended Exclusivity — Manufacturers who hold an approved application for a drug that would mitigate a shortage can extend by 5 years any period of exclusivity, even if the drug is eventually moved from drug shortage designation.

* Drug Shortage Database — The Secretary would establish a mechanism by which health care providers and other third-party organizations may report evidence of a drug shortage.

This last point may sound innocuous – but it’s crucial. There are many players in the drug shortage game – not just innovator pharmaceutical companies and the FDA. There are generics manufacturers, hospitals, Group Purchasing Organizations (GPOs), and physicians.  (For more on the GPO issue, see this new op-ed in today’s Washington Examiner).

As the Japanese say – don’t fix the blame; fix the problem.

  Read More & Comment...

Depth of a Salesman

04/20/2012 07:38 AM |

Earlier this week the Supreme Court heard arguments as to whether representatives of pharmaceutical companies are entitled to overtime. The answer, it seems, turns on whether those visits are actually sales calls.

According to Paul D. Clement, lawyer for the defendant, the pharmaceutical sales representatives plaintiffs, “ … were hired for a sales job. They were given sales training. They attend sales conferences. They are assigned to sales territory, and they are evaluated and compensated as salespeople.”

But, commented Chief Justice John G. Roberts Jr, “They don’t do sales. Your long list sort of stopped one step short. They don’t make sales.”

As the New York Times accurately reports, industry reps “do not sell products in the strict sense of the term. Rather, they encourage doctors to write prescriptions for patients to buy drugs from pharmacies.”

Interesting semantical and practical questions and it’ll be interesting to see how the Supremes rule.  In the meantime here’s a related question – depending on the final judgment – will government detailers (aka “academic detailers”) qualify overtime pay? They’re not supposed to be “selling” anything either.  

  Read More & Comment...

My Pick For FDA Chief Innovation Officer

04/19/2012 11:53 AM |

http://www.bizjournals.com/boston/news/2012/04/18/bio-ceo-jim-greenwood-on-innovation.html

I like BIO CEO Jim Greenwood's proposal to give FDA a chief innovation officer who who would examine whether the number of drug rejections is reasonable, or whether it is stunting innovation and causing unwarranted delays.

“People who die because a product is not approved quickly enough are just as dead as those who die because a product is not safe,” Greenwood said. “It’s not just the job of the FDA to protect us, it’s also to promote innovation.”

My pick for the position:  Janet Woodcock.   No one (except for Bob Temple) could and has balanced these two missions better.  And no one has done more to promote personalized medicine, which allows products to more efficiently embody safety and innovation.

There are a lot of important bi-partisan ideas to accelerate the innovation process.  A chief innovation officer should not be a ceremonial add-on or be limited to reviewing product development after the fact.  That official could report to the Commissioner, search out and encourage companies with innovation products for fast track approval, be in on the development of products from the beginning.   That's something Dr. Woodcock would and could do effectively.



  Read More & Comment...

Empower FDA By Eliminating CER

04/19/2012 11:39 AM |

My heart is with Mike Rogers and other members of Congress who want to expand FDA's mission to include  job creation and economic growth.   And I get the message they are trying to send to the public and the FDA about what's important.  CMPI has consistently made the case that medical innovation is the primary source of longevity and prosperity.  

But the way to change FDA to promote those broader objectives is to hold it accountable to new standards for product approval and oversight reflecting dramatic changes in the science sustaining innovation.   Congressman Rogers and others can help the FDA by getting them out of the comparative effectiveness business. Reauthorization of PDUFA will give the agency more resources and more direction with regard to increasing the predictability in the development process for drugs, devices, diagnostics and combination products.  However, the FDA would get a boost if legislation stipulated that any products that use biomarkers or other tools to target treatments and improve the ability to monitor disease progression or response would be automatically approved for use in Medicare, Medicaid, etc. 

The more we can defang what is an increasingly worthless CER enterprise the more FDA can achieve the mission the Congressman Rogers wants the agency to carry out.   CMPI will be releasing a study, supported by the Kauffman foundation, that estimates how much innovation and health value our nation will forfeit if CER becomes the focus of commercialization instead personalized medicine.   The estimates, even with conservative assumptions built in, are staggering.  

Every time someone at FDA has to pay lip service to CER it is a signal to companies that all the work put in on diagnostics, combination products and targeted treatments will go to naught because they have to wait for a bunch of underachieving health economists and other professionals to conduct systematic reviews or horizon scams, I mean scans, or clinical trials.   Then again, as I noted in my last post, it looks at though PCORI will be handing out dough to to figure out how to conduct patient-centered research and how to engage patients, though the last time I checked no one -- except the stakeholders who will also get the PCORI cash --  was asking for such government help. 

You want to make medicine patient-centered?  Produce patient-centered medicine.   Tools and treatments that reduce hassles, improve life, increase health. 

That's something FDA can, should and is trying to do in collaboration with companies.  If you asked people should we spend $3 billion on medical decision making or the same amount making better medicines more quickly available to people who need them, I don't have any doubt that faster approvals would win.

The FDA could do a lot with $3 billion over the next decade and do much more for our health and nation than PCORI ever will.  Just a suggestion if Congressman Rogers wants to amend his bill....



  Read More & Comment...

And Rounding the Club House (and Senate) Turn ...

04/19/2012 08:05 AM |

Yesterday the HELP Committee released a draft version of PDUFA legislation and plans a April 25 PDUFA mark-up.

The Senate draft creates a new pathway for review of "breakthrough" therapies, requiring FDA to work with sponsors to expedite approval of products to treat serious or life-threatening diseases based on "preliminary clinical evidence indicating that the drug may demonstrate substantial improvement over existing therapies on one or more clinically significant endpoints."

On the other side of the Capitol, the House Energy and Commerce Committee released a discussion draft of PDUFA reauthorization legislation on Wednesday. Both the House and Senate bills incorporate the Generating Antibiotic Incentives Now (GAIN) Act, which would extend market exclusivity by five years for drugs that treat antibiotic-resistant pathogens. The E&C version includes an additional six month extension for drugs approved along with a companion diagnostic; this provision has been deleted from the Senate version.

The House draft also seeks to permanently reauthorize two laws that create incentives for conducting clinical trials in pediatric populations, the Best Pharmaceuticals for Children Act and the Pediatric Research Equity Act. Similar legislation, the Better Pharmaceuticals and Devices for Children Act, was introduced with bipartisan sponsorship in the Senate on Tuesday; it is likely to be incorporated into the Senate PDUFA reauthorization bill.

House lawmakers said they were optimistic that any outstanding issues in the GOP draft would be resolved in the coming days, and full committee Chairman Fred Upton (R, MI) said he was convinced the panel is on track to meet his goal of approving the legislation by the end of June.

  Read More & Comment...

PCORI's Maximum Feasible Participation (Of Consultants)

04/18/2012 06:38 PM |

I am sure that I will be one of the few that doesn't laud PCORI for focusing so much on patient-centeredness.  But I have two questions:  Just what is PCORI (and all the CER cronies they will pay through AHRQ to consult) doing? 

That PCORI was able to get JAMA to publish two fluffy and self congratulatory editorials that explain how patient-centered reflects the extent to which PCORI, AHRQ and the consultants it funds will be able to disseminate about any crap that it produces through the 'major' medical media outlets.   AHRQ, PCORI and cronies are able to get anything it produces published in medical journals.  It is spending hundeds of millions of dollars peddling CER to doctors who in exchange get CME credit just for clicking on to a website.   And PCORI will be spending hundreds of millions of dollars holding conferences, webinars, etc  to explain to 'stakeholders' how patient-cetered they are.

But what exactly is PCORI producing?

In the JAMA puff piece, Joe Selby and colleagues note:

"The institute's first funding announcement solicited projects focused on methods for engaging patients and other stakeholders in all aspects of the research process. "

They conclude that "The proposition that greater involvement of patients, clinicians, and others in the research process could help reorient the clinical research enterprise, reduce clinical uncertainty, and speed adoption of meaningful findings holds great promise, but remains to be tested. PCORI will test this hypothesis. The underlying imperative is to improve patients' care experience, decision making, and health outcomes. Patients as well as the physicians and other health care professionals who care for and about them are invited and encouraged to join in this effort. "
http://jama.ama-assn.org/content/307/15/1583.full?ijkey=2UlGCXlTXheck&keytype=ref&siteid=amajnls

This sounds alot like maximum feasible participation encouraged in community action programs during the 1960s.   In his book "Maximum Feasible Misunderstanding,"  Daniel Patrick Moynihan noted that the "war on poverty was not declared at the behest of the poor.  It was declared in their interests by persons confident in their judgment on such matters." 

The War on Poverty was not a war and did not do much about poverty.  But it did employ and give out grants to the policy entrepreneurs who conceived the War on Poverty in the first place.  That consisted of professional economists, professional social scientists, government officials and professional philanthropists.

Similarly,  PCORI was not created in response to an outcry from patients about the lack of inclusion of their "voices" in medical decision making.  It was a product of the same said professionals who supported PPACA and who believe that spending $3 billion on making sure the CER they produce is marketed and used is in the nation's interest.

The article by the Methods Committee on how it plans to spend money on grants reflects a similar disconnect between the needs of patients and the myopic goals of the CER community.  See if you can figure out the punchline of this paragraph:

"Ms M is a 45-year-old woman with depression (Box 2), whose situation similarly highlights the gap between existing research and the characteristics and concerns of patients. Little evidence exists about which sequence of treatments is optimal for Ms M's constellation of symptoms, adverse effects, or initial response. Despite more than 1000 trials on antidepressants and related treatments, most studies include patients with narrowly defined characteristics who are followed up for short periods, do not take place in settings in which care is routinely delivered, and include a limited spectrum of comparators, including drugs and other therapeutic approaches.^11​ How can clinical research focusing on much larger, long-term issues trials yield more personalized guidance for patients like Ms M?¹²"

http://jama.ama-assn.org/content/307/15/1636.full?ijkey=419QnSMR.MBDU&keytype=ref&siteid=amajnls


The Methods Committee presumes that since all manner of studies have never been able to identify what treatment is right for Mrs M that the solution is to spend more  money on methodologies that will be larger and more long term but at the same time yield more personalized guidance.  

Does anyone believe that bigger studies that take longer to produce will,  especially at a time when medical information is becoming digitized and atomized, yield personalized guidance that patients will abide by and obey?    Am I the only one who sees a social science scam in all this?  Is this too cynical on my part?

More later. 
  Read More & Comment...

Survival of the Most Compliant

04/18/2012 08:24 AM |

They’ve got a list.  And they’re checking it twice.

The giant PBM Express Scripts is launching ScreenRx, a program that uses a computer to sift through hundreds of factors that affect patients and forecast who is most likely to forget a refill or simply stop taking their drugs. The company then plans to contact those patients to help them stick with their doctor's orders.

It’s estimated that about $317 billion in additional medical expenses were incurred by the U.S. health care system last year because people didn't comply with prescriptions. These additional expenses might include a heart attack for someone who stops taking cholesterol medicines or an amputation for someone who doesn't adhere to diabetes treatment.

The analysis, called predictive modeling sorts through more than 400 variables that could affect a patient to see which people have enough red flags to warrant concern.

Once a patient has been flagged, they receive a phone call. An Express Scripts representative will talk to the person to see if they need help. The PBM then might send the patient a pillbox if they have a hard time remembering their prescriptions or a special beeper that goes off when it's time to take medicine.

If the patient struggles to pay for the drugs, Express Scripts will provide information on assistance programs.

According to a report in the Washington Post, “Analysts say predictive modeling programs that aim to forecast patient behavior and improve care have been evolving in health care over the past few years, and the Express Scripts product is the latest evolution.”

Survival of the most compliant. Would Darwin have approved?

  Read More & Comment...

Towards a Sustainable Innovation Ecosystem

04/17/2012 07:35 AM |

Eli Lilly’s John Lechleiter believes that the biopharmaceutical industry exists in an “innovation ecosystem.” A new study by the Tufts University Center for the Study of Drug Development (funded by PhRMA) confirms that notion by exploring the breadth and nature of partnerships between biopharmaceutical companies and academic medical centers (AMCs).

The full study can be found here.

The Tufts study examines a subset of public-private partnerships – more than 3,000 grants to AMCs from about 450 biopharmaceutical company sponsors. The Tufts report describes the various types of partnership models that exist, and recent trend as well as identifies next generation academic-industry collaboration models emerging from the public-private-partnership paradigm.

To add to Lechleiter’s phrase, the report discusses the importance for and a model of a sustainable innovation ecosystem. This is in keeping with the ethical and pragmatic policy of the American Association of Clinical Endocrinologists (AACE) and the American College of Endocrinology (ACE) regarding the disclosure of conflicts of interest:

“There is no inherent conflict of interest in the working relationships of physicians with industry and government.  Rather, there is a commonality of interest that is healthy, desirable, and beneficial.  The collaborative relationship among physicians, government, and industry has resulted in many medical advancements and improved health outcomes.”

Some findings from the Tuft’s study:

The partnerships examined in this report fall into three primary categories: joint clinical trials (75%), studies targeting public health priorities (14%), and health research and education projects (11%).

* 72 percent of the joint clinical trials are for pharmaceuticals.

* Studies targeting public health priorities cover a range of topics, including breakthrough-investigations involving multiple disciplines.

* Joint health research and educational activities ranged from basic medicine to translational research to new technologies, particularly nanotechnology and pharmacogenomics.

Tufts found that these relationships often involve company and AMC scientists and other researchers working side-by-side on cutting-edge science with advanced tools and resources, enabling the U.S. to rise to the challenge of various biomedical opportunities, such as personalized medicines and a growing understanding of rare diseases.

The report outlines the 12 primary models of academic-industry collaborations and highlights emerging models, which reflect a shift in the nature of academic-industry relationships toward more risk- and resource-sharing partnerships.

* Unrestricted research support has been one of the most widely used models. While these models have generally represented the most common form of academic-industry collaboration, Tufts research found that they are becoming less frequently used.

* The report found a range of innovative models emerging, from corporate venture capital funds to pre-competitive research centers to increasingly used academic drug discovery centers.

Examples of emerging academic-industry partnership models include:

* The Coalition Against Major Diseases, a consortium under the Critical Path Institute, involves biopharmaceutical companies, academic institutions, and others working together to facilitate the development of effective treatments for Alzheimer’s and Parkinson’s disease.

* Eli Lilly and Company launched the Open Innovation Drug Discovery program to facilitate research on molecules around the world that have the potential to ultimately be developed into medicines by allowing academic and other researchers to submit molecules for free screening as potential drug candidates.

* Sanofi has a strategic alliance agreement with the Massachusetts Institute of Technology’s (MIT’s) Center for Biomedical Innovation focused on advancing knowledge in the area of human health through basic and applied research and promoting scientific exchange between MIT and Sanofi researchers to support the development of health care solutions for patients.

The report highlights the mutual benefits of partnerships:

* Both academia and industry are facing increasingly complex scientific challenges. According to the report, as the scope of some of the scientific challenges is so large, collaboration is viewed as increasingly important to making significant progress.

* Partnerships benefit both industry and academia by providing the opportunity for the leading biomedical researchers in both sectors to work side-by-side to explore the promising new technologies and scientific discoveries that have the potential to treat the most challenging diseases and conditions facing patients today.

The report finds that the nature of collaboration occurs across all aspects of drug discovery. According to Tufts, companies are funding and working collaboratively with the academic component of the public sector on basic research that contributes broadly across the entire spectrum of biomedical R&D, not just for products in their portfolios.

The report concludes that academic-industry partnerships are growing in number and importance as “the translational gap between discovery and clinical development has become increasingly difficult to bridge.” The complementary nature of partnerships involving AMCs and biopharmaceutical companies increases synergies between the two sectors, ―enabling the nation’s R&D enterprise to tackle the most complex and challenging diseases and conditions.

How’s that for sunshine?

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Wanted: Clarity on Biosimilarity

04/16/2012 09:08 AM |

The official comment period is over and it's pretty clear that FDA’s February 9^th biosimilar draft guidance has sparked resistance among some industry players – specifically over certain definitions and requirements. No surprises there.

Stakeholders sent criticisms over the suggested protocols as well as several recommendations for change. The draft guidance, contained in three documents, represent FDA’s interpretation of the Biologics Price Competition and Innovation (BPCI) Act of 2009.

Biosimilarity

Two drug developers said that the agency should tighten its proposed biosimilarity standards. While commending FDA for “an excellent job drafting guidance on quality considerations for demonstrating biosimilarity to a reference product,” Genentech took issue with FDA’s proposed wording that manufacturers “should” thoroughly assess the analytical similarity of their biosimilars to their reference products, and  “should” perform in-depth chemical, physical, and bioactivity comparisons with side-by-side analyses of “an appropriate number of lots of the proposed biosimilar product and the reference product.” FDA also suggested that “where available and appropriate,” manufacturers compare their products with the reference standard for specific suitable attributes such as potency.

The assessment of the analytical similarity of a biosimilar product and the robustness of these methods are fundamental requirements for a biosimilarity assessment, and use of the word “should” implies that it does not necessarily need to be done, Genentech noted. “Please replace ‘should’ with ‘is expected to’ or ‘needs to,’” Genentech stated in a letter transmitted to the agency by Earl Dye, director of technical regulatory policy and strategy.

Novo Nordisk urged FDA to define biosimilars as products that are as similar as scientifically possible to their reference products, at least through sharing the same amino acid sequence, without exception, as their reference products. The company cited FDA’s emphasis on the importance the 3-D structures of proteins play in their biological functions and the ability of post-translational modifications to alter the proteins’ functions.

“FDA should never permit biosimilar applications for products that cannot be adequately characterized,” Novo Nordisk stated in its letter, signed by James C. Shehan, Novo Nordisk’s corporate vp, legal, government, and quality affairs.

Biosimilar producer Biocon counter-suggested that FDA should expect that the expression construct and/or the processing of a proposed product would result in the same primary amino acid sequence as the reference product. Some expression constructs may give a precursor protein that only after modification in the process will yield the same amino acid sequence as that of the reference product, Biocon noted in its letter, submitted by Siriam Akundi Ph.D., associate vp, quality, and regulatory.

Demonstrating Safety

Novo Nordisk also believes that biosimilar applicants “should always submit the results of comparative animal toxicity studies.” It added, “In the current state of science, some form of comparative safety and effectiveness testing will be necessary for almost all biosimilars.

“All biosimilar applicants should conduct at least one comparative clinical pharmacokinetic study and, where there is a relevant pharmacodynamic marker, at least one comparative clinical PD study,” Novo Nordisk added. “Similarly, a biosimilar applicant should always conduct at least one comparative clinical immunogenicity study.”

Two patient groups also called for FDA to promote greater safety. The Colon Cancer Alliance asked FDA to require “extensive” clinical testing of biosimilars, with a system capable of rigorously tracking and tracing them back to their product of origin. “It is critical to the safety of patients that these drugs be submitted to open and robust clinical studies and are marked with a unique and transparent product labeling system that will facilitate robust pharmacovigilance,” Global Healthy Living Foundation (GHLF) president Seth Ginsberg wrote in GHLF’s letter.

Interchangeability

Ginsberg noted that it is difficult to designate a biosimilar as interchangeable with their innovator products unless there is sufficient data. He expressed concern that decisions on interchangeability could be made by pharmacists or insurers through states’ automatic substitution policies. “We believe that the choice of product should be decided only by patients and physicians, who are ultimately responsible for patient care and have the full spectrum of a patient’s medical history,” Ginsberg added.

Novo Nordisk urged FDA to confirm that it would not designate a new biosimilar delivery device or container closure system as interchangeable with its reference product “where additional training on the new device or system is necessary to guide safe use, or where the proposed delivery device or container closure has inequivalent performance or critical design features.”

And miles to go before …

“The keys to success for the biosimilar pathway are informing and educating patients and physicians on the benefits and safety challenges of replicating biologic drugs, providing a unique and distinctive naming and labeling system, and understanding that the FDA’s approval of a biosimilar as a standalone therapy does not mean that it is interchangeable with its biologic counterpart,” the Colon Cancer Alliance stated in its letter to FDA written by CEO Andrew Spiegel.

The alliance urged FDA to adopt a system that uses individual nonproprietary names for biologics and biosimilars, enabling physicians, patients, and regulators to differentiate between products easily—a suggestion also made by Novo Nordisk and the National Association of Chain Drug Stores.

Biocon took issue with FDA’s requirement that sponsors provide “sufficient scientific justification” for extrapolating clinical data to support biosimilarity determinations for each condition of use for which a license is sought. “Once biosimilarity is established, and product is approved for one indication, no additional clinical studies should be expected for obtaining approval for other approved indications,” Biocon stated. “If the route of administration, dosing frequency, and dosage amount of the proposed biosimilar is identical to the reference product for each indication, any additional clinical studies should not be expected.”

Novo Nordisk also urged FDA to publish product-class specific guidance for biosimilar and bioequivalent applications for complex proteins, like the EMA has done. With all the discord that FDA’s draft biosimilar guidance has created, the agency will have to work to balance the interests of innovators, biosimilar developers, and patient groups. The agency will have to ensure that it does not tilt its final guidance toward developers of new drugs by rules that unduly impede biosimilars. Nor should it tilt its requirements toward biosimilar makers seeking less rigorous review. It won’t be easy, but balancing competing interests will ultimately benefit companies, researchers, and especially patients, by finally providing a biosimilar pathway in the U.S. 

And that's assuming the law that makes biosimilars possible remains on the books after the Supreme Court ruling.

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'Choosing Wisely' Replaces Hippocratic Oath With The Ethos of The Hunger Games

04/13/2012 12:23 PM |

http://spectator.org/archives/2012/04/13/obamacares-medical-mercenaries  Read More & Comment...

In Vitro Veritas

04/13/2012 07:24 AM |

In Vitro Veritas

A renegotiation of the EMA (European Medicines Agency) medical devices directives is imminent.  Our spies tell us that, for in vitro diagnostics, a line will be drawn between tests used as companion diagnostics -- where clinical evidence of their applicability will be required -- and other in vitro tests such as PSA for prostate cancer -- where no such evidence will be required.

Uneasy lies the head that wears a crown

Eric Abadie, the chair of CHMP (The Committee for Medicinal Products for Human Use) has resigned -- another victim of L’Affaire Mediator (the French anti diabetic /anti obesity drug remained questionably available in France and killed somewhere on the order of 5000 patients from pulmonary valve disease). The French Agency sacked him and the EMA opted not to pick up his salary.

Meanwhile on our own placid shores

Here’s an excellent article from the April edition of Nature Biotechnology on some of the key policy questions facing the US biotech sector pending PDUFA and presidential politics.

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