Jimmy Carter Fights ASCO Value Framework To Stay Alive

08/14/2015 05:40 PM |

Dear President Carter:

I was sorry to learn that you are fighting an advanced form of cancer that has spread to your liver and other parts of the body.   There is good news, sort of.

As a recent article in the Boston Herald noted:

Former President Jimmy Carter revealed yesterday that he will undergo treatment for cancer that has spread to various parts of his body — and doctors say that despite his advanced age, the 90-year-old may fare well thanks to recent advances in personalized medicine.

“With cancer cells, there are many different mechanisms that make them grow, and a lot of the science has been dissecting genes and proteins that cause it,” said Dr. Andrew M. Evens, director of Tufts Cancer Center. “There’s work around identifying treatment for the patient’s individual cancer and doing it at a genetic level.”

Not so fast Mr. President.

Even as a former President, you will be faced with what is called “step therapy” or “quality pathways” that determine what treatments you get.   You have to fail first on the first step of therapy before getting to up to five other ‘approved’ treatments before getting to the ‘advances in personalized medicine.’ 

You were a plain spoken president, so I probably don’t have to tell you that for people with advanced form of cancer,  ‘fail first’ is code for getting sicker and closer to death.

Health insurers claim these pathways don’t affect outcomes.  But they refuse to cover the advances that have a very good chance of keeping you alive and well.
Neither the tests for the genetic makeup of your cancer cells to identify where it started, and guide treatment are not at the end of any of these pathways.  Under the Affordable Care Act, anything not on a pathway has to be paid for in full by you.

You might think that your doctor will fight to get you the treatments that could save your life.

Sorry to disappoint you.

The leading cancer doctor group -- The American Society For Clinical Oncology (ASCO) – has developed a calculator of value that treats all patients as the same; ignoring the genetic variation in patient response that allows doctors to personalize care.

Indeed, ASCO wants insurers to use their calculator to “evaluate the relative value of new treatments” as they develop “benefit structures, adjustment of insurance premiums, and implementation of clinical pathways and administrative controls.” 

That’s not good news either.   I’ll give you a couple of examples.   I read that you have a family history of pancreatic cancer.   So I used the ASCO calculator to come up with a value score (the highest score is 130).  The most common treatment for advanced pancreatic cancer that has spread everywhere adds, on average, about 2.5 months of life.  That’s worth a whole 32 points.  But then 20 points are deducted because of side effects, leaving you with 12 points of “net health benefit” out of 130 which the app helpfully notes will cost $5000 a month.  Other treatments that provide less survival and are cheaper are given a higher score.  Guess which treatments you have to use before getting to the most effective treatment covered?

The news is even worse if you have advanced colorectal cancer.  The newest drugs add more survival for this deadly disease.  But ASCO doesn’t think it’s worth more than 16 points.  Deduct 20 points because ASCO doesn’t like the side effects (rashes, nausea, fatigue) and you’re in negative territory. According to ASCO, that treatment has no clinical value at all.  And the advances Dr. Evens mentioned aren’t even measured.  And they won’t until randomized trials that take years to organize and complete are published.

It’s sad and ironic.   You lead a 30-year effort to eradicate guinea worm disease around the world.  The disease is not fatal but extremely painful and debilitating.  In 1986, there were an estimated 3.5 million cases in 21 countries in Africa and Asia. Your effort was criticized as not cost-effective from the start.  You ignored the bean counting because it only focused on 2-3 measures of value.   (Sound familiar?)

Today, that number has been reduced by more than 99.99 percent, with the vast majority of cases remaining in South Sudan.

It’s a good thing it was you – not the alliance of insurers and ASCO – tackling that challenge.   Unfortunately they are putting a price tag on whether you live or die.  Maybe you can change that.  A grateful nation is pulling for you to win one more campaign.
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Wither Off-Label?

08/14/2015 08:38 AM |

The debate over off-label communications doesn’t begin or end with the Caronia or Amarin decisions. It’s a continuing dialogue between manufacturers and the FDA, between doctors and patients, between doctors and academics, between lawyers and judges, and between advocates on all sides.

And the red thread that ties these conversations together is responsible off-label communications. Not sales strategies. Not DTC tactics. Not managed market negotiations – the responsible sharing of truthful and accurate information.

It’s important to say early in the conversation that almost no one is against sharing valuable information about FDA-approved medicines. The discussion – the heated discussion – is over how (or if) that conversation should be regulated by the FDA.

Steve Jobs said, “Innovation distinguishes between a leader and a follower. And make no mistake, off-label communications is about innovation. Innovation in the safe and effective use of medicines. Off-label communications is about getting the right medicine to the right patient in the right dose at the right time – even though the right medicine or the right dose may not correspond precisely to the FDA label.

But who is the leader and who is the follower? Or perhaps a better question to ask is, why can’t we all be leaders?

Off-label communications, properly done, advances precision medicine, delivering speedier positive patient outcomes, and reducing costs to our healthcare system. Off-label communications provides patients with more options for effective medicines.

Those who think that the argument over off-label is just about marketing and sales are looking at this issue through very narrow blinders.

What is the role of the FDA is off-label communications. Well, first let’s stipulate that the FDA doesn’t regulate the practice of medicine. Then let’s discuss the fact that the agency can (and indeed must) help to facilitate the free and fair dissemination of timely, truthful, and trustworthy scientific knowledge.

Also, initial licensing approval is not based on data for every possible indication. Initial approval is based on a “best foot forward” approach. But that doesn’t mean there isn’t robust scientific evidence to support broader therapeutic uses. In fact, initial approvals, based on a narrow, randomized population, only provide a window into future clinical possibilities.

According to the House Energy & Commerce Committee’s 21st Century Cures Initiative initial white paper:

Communication about how certain treatments are working in certain patients is happening through a multitude of media around the globe. These conversations between and among doctors, patients, researchers, and scientists in academia and industry should be facilitated. This includes the free flow of data, research, and results related to what a therapy or combination of therapies does or does not do well and in what types of patients.

 Off-label communications is about recognizing that the speed of scientific discourse impacts clinical practice years before it drives official label changes.

You don’t have to look much further than oncology and many orphan diseases to see that off-label use is regularly considered first line therapy. And payers in the US and elsewhere reimburse off-label prescribing. Why? Because it enhances outcomes.

How do physicians learn about off-label usage? Medical meeting presentations, professional journal articles, discussions with their peers, and through materials from manufacturers. Please note that I haven’t listed DTC. There is a difference between off-label communications and off-label marketing – and it is a distinction with a difference.

So, what do academics and physicians, payers and patients know about off-label communications that the FDA does not? Asked in a more progressive way, how can the FDA be an accelerator rather than a sea anchor when it comes to facilitating off-label communications?

In a word, the answer is clarity. Alas, regulators love ambiguity because it gives them unlimited options. And nowhere is this more evident than when it comes to issues concerning communication. It would be generous to call the FDA’s views on the dissemination of off-label information ad hoc. With the important exception of the agency’s guidance on Good Reprint Practices. According to the March 2014 revised guidance, reprints that discuss off-label use mustn’t:

• Be false or otherwise misleading;
• Recommend or suggest use of the product in such a way that the product is dangerous to health when used in the manner suggested; nor
• Be marked, highlighted, summarized, or characterized by the manufacturer, in writing or orally, to emphasize or promote an unapproved use.

Those are pretty broad guideposts. More interesting and germane to current events are those related to Clinical Practice Guidelines (CPG):

Any CPG that includes information on unapproved or uncleared uses must meet Institute of Medicine (IOM) standards for whether it is a “trustworthy” guideline.  According to IOM, a guideline is “trustworthy” if it:

• Is based on a systematic review of the existing evidence;
• Is developed by experts in the subject area;
• Considers important patient subgroups and patient preferences;
• Is transparently developed and funded such that biases are minimized;
• Provides logical relationships between treatment recommendations, health outcomes, and includes the quality and strength of the underlying evidence; and
• Is reconsidered and revised as new information becomes available.

Beyond this, what will the FDA do next? More importantly, will it lead or follow, or follow and then lead? And this brings us to the recent court decisions in the Caronia and Amarin cases.

The Caronia decision, a 2012 decision from the Second Circuit Court of Appeals, overturned the conviction of Alfred Caronia, a sales representative for Orphan Medical, which was later acquired by Jazz Pharmaceuticals. After Caronia was caught talking to physicians about various off-label uses of the narcolepsy drug Xyrem, the court said the First Amendment protected truthful and non-misleading off-label speech. Key words, “truthful and non-misleading.”

That’s a good off-label equation: Truthful + Non-Misleading = Trustworthy.

Although the agency said that the decision wouldn’t impact it’s views and practices concerning the regulatory oversight of off-label communications, the decision, combined with increased pressure from industry, forced the FDA to put the issue of off-label communications on the front burner.

Unfortunately, it was put on the front burner on a low flame.

Between Caronia and Amarin, the FDA issued some very valuable draft language on the issue. Under the proposal, FDA would not “object to the distribution of new risk information that rebuts, mitigates, or refines risk information in the approved labeling.” The studies must be “well-designed” and “at least as informative as the data sources” that the FDA used in generating the official warning.”

The new FDA draft guidance opens the door for companies to share truthful, scientifically accurate, and data-driven information with healthcare professionals to inform treatment decisions. For example:

—  Observational data and “real world evidence”

¡ Information on the safety and effectiveness of medicines taken from medical records based on actual use of approved medicines.

—  Sub-population data

¡ Information on the safety and effectiveness of medicines in sub-populations including gender and race. Such information can help healthcare professionals tailor their treatment to meet the needs of individual patients.

—  Observational and comparative data

¡ Information from the use of a medicine outside of randomized clinical trials, especially comparisons between two or more therapies.

—  Pharmaco-economic information

¡ Healthcare economic data and information on the economic value of medicines can improve the efficiency of patient care.

—  Information on medically accepted alternative uses of medicines

¡ Information on new uses of approved medicines that are listed in major compendia and/or routinely reimbursed by the federal government and major payers.

Things seemed to be moving ahead and the FDA seemed to be driving the conversation – and then came Amarin and it’s drug Vascepta – approved by the FDA for treatment of patients with “Very High” triglycerides.

In April, the FDA rejected Amarin’s claim for “Persistently High” triglycerides and also decided Amarin couldn't include clinical trial data in Vascepa labeling about the extent to which the pill may effectively treat people with slightly lower levels of triglycerides.

In May Amarin filed a lawsuit in Federal Court claiming it “finds itself in a bind,” since it “may not freely communicate truthful and non-misleading information about Vascepa to health-care professionals…without fear of criminal prosecution and civil liability.” In its lawsuit, Amarin included a list of medical journal articles it would like to distribute to physicians.

In June, the FDA sent a letter to Amarin saying the types of materials the drug maker would like to distribute to doctors actually would not be a problem and “would not consider the dissemination of most of that information to be false or misleading.” Then the FDA suggested that Amarin might have known this if the drug maker had discussed the issue before filing its lawsuit, “as other pharmaceutical companies sometimes do.”

 Earlier this month the court agreed Amarin materials are truthful and took the government to task for essentially arguing that speech alone can be the basis for liability and that the agency’s action is at odds with the Caronia holding and the First Amendment.

Post-Caronia and pre-Amarin, hoping to maintain its ability to apply “regulatory discretion, “the FDA signaled it was going to loosen the reins on off-label communications. And, in fact, this was part of the government’s argument in the Vascepta case. The Judge asked when the FDA would be issuing further guidance on off-label communication, asking if it would be in 2015 or afterwards, or before Labor Day. The government’s attorney said she had “no idea” when the agency would act or if more speech will be permitted when it does. Bad answer.

 So what happens now?

I predict that the FDA will continue to develop its new thinking on off-label (informed and influenced by both the Caronia and Amarin decisions). It will then issue a more complete draft guidance and collect feedback via a Federal Register docket. That’s the way the system works and rules must be follows.

I further predict, barring overly ambiguous and wimpy language from the agency, that most pharmaceutical companies will declare victory and follow the FDA’s lead. That being said, the agency will need to carefully monitor i’s off-label oversight – and his means a lot more than the usual and customary OPDP review. It means senior management attention to how the agency views “trustworthy” and a very careful eye on any actions it considers taking.

All this to say that off-label communications is now on the agency’s front burner and the flame is on high. As Everett Dirksen used to say, “When I feel the heat, I see the light.”

Can the FDA recapture a leadership role in the off-label conversation? I believe it can – and will. But it will require the agency to trade ambiguity for predictability because, when it comes to trustworthy off-label communications, predictability is power in pursuit of the public health.

Stay tuned.

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Does ASCO Value Framework Push Assisted Suicide?

08/12/2015 12:28 PM |

Dr. Jack Kevorkian


Lowell Schnipper, the chairman of the ASCO Value Framework Task Force was also part of a group that supported Dr. Jack Kevorkian and pushed to legalize physician-assisted suicide.

It raises the question: Does the Value Framework recycle the arguments and assertions Dr. Schnipper made in pushing euthanasia as an option for cancer patients in determining how to value drugs and why?

To my mind, it does. 

Schnipper, who is also Chief of Hematology/Oncology at Beth Israel Deaconess Medical Center in Boston, has been a driving force in making ASCO focus on the costs and value of cancer care.  His support of Kevorkian and assisted suicide legislation are relevant. Specifically, just as Schnipper believed that hastening death when further treatment could only add a few months of life was legitimate, the Task Force he leads asserts that a few months or weeks of life have no clinical value and that further treatment is a waste of money at that point. 


Background

In 1998 Schnipper was part of “a high-powered collection of area doctors, academics and lawyers has been meeting privately, working to draft a model bill allowing physician-assisted suicide. "We'd like to get this bill introduced in Massachusetts and elsewhere," says Boston College law professor Charles H. Baron.
The group includes James Vorenberg, former dean of Harvard Law School; Judy Johnson, associate general counsel at the New England Medical Center; Dr. Lowell Schnipper, chief of oncology at Beth Israel Hospital; and Dr. Sydney Wanzer of the Harvard Law School health services. Most of the 10 members, says Baron, support legalization "in the hopes that this will make relief from suffering more readily available and in a less discriminatory fashion and with greater patient autonomy."

Schnipper’s Working Group Supported Dr. Jack Kevorkian

Dr. Wanzer noted: "If Dr. Kevorkian does it a little outside the niceties of proper practice, I can't condemn him for that. If I do this privately and quietly and discreetly, it doesn't force the issue. But he does. I think it's a good combination of the quiet people who go ahead and do what they think is right and the Dr. Kevorkians who do it more flamboyantly."

"Kevorkian is a result of failures of our medical system in caring for someone with intractable or chronic problems," says Dr. Lowell Schnipper, chief of cancer treatment at Boston's Beth Israel Deaconess Medical Center. "But Kevorkian is becoming more and more marginalized as legitimate groups begin to weigh in with the resources and sensitivities the problem demands, which to me is good news."

Schnipper also described hastening death as "consistent with the highest goals of the physician as healer and must be an option in a pluralistic society."

Today Schnipper Believes Cancer Treatment That Adds ‘Only’ Three Months of Life is Not Worth It.

In 2010 Schnipper was the lead author of an article that argued:

“Patients' high expectations of cancer therapy may be another cost driver
In a culture that favors treatment and has an overly optimistic view of what medicine can offer, it is an uphill battle for cost-conscious oncologists to communicate the true value of various forms of therapies, particularly when curative treatment options are lacking.”

He also notes:

“This problem may be particularly American one; other cultures do not seem to view the postponement of death by a few months as holding an equivalent importance. Culturally, are we entirely honest in our assessment of what a few months, particularly spent in illness, can accomplish?”


Value Framework Also Embraces Notion That A Few Months More Of Life Is Not Worth It

Schnipper, writing for the Task Force concludes:

“Cancer drug spending is being driven by “sometimes unrealistic patient and family expectations that lead clinicians to offer or recommend some of these services, despite the lack of supporting evidence of utility or benefit.”

Patients “ also overestimate the benefits of treatments that sometimes extend life by only weeks or months or not at all. 


Schnipper Established A Cut Off Point For Value Measured By a 20 percent increase (3 months) in yearly survival

Over the past two decades Schnipper has advanced an economic argument for cutting off cancer treatments.  Initially, he maintained that survival time should be increased beyond a specified amount of time:

“On average they (cancer treatments) may delay death for only a very short time, for example 3 months. Although some patients may live for more than 3 months, others will not necessarily live even that long. The drug only slows the progression of the patient's cancer by a few months; it does not “cure” the cancer. The psychological force of the rule of rescue should be much weaker in the context of this cancer care than in mine collapses. It should not make it impossible to resist providing the treatment, and certainly does not justify doing so. “  (In this regard, applying Schnipper's logic to everyone means stopping treatment for  every patient that does not gain more than 3 months on average, including babies, HIV patients and children with rare diseases. ) 

The Task Force Cutoff for Value Is The Same As Schnipper’s

Under his leadership of the Value Task Force, the 3 month cut off was turned in to a specific increase in survival as a percentage of a year of life: “It was generally agreed that relative improvements in median overall survival of at least 20% are necessary to define a clinically meaningful improvement in outcome. “    On average, 20 percent ranges from weeks to a few months.   This is a value judgment that applies to all patients with all forms of cancers with all different tumor types.


Schnipper believes that below a certain increase in survival money spent on dying cancer patients should be spent elsewhere to ensure resources are distribution ‘fairly.’

He claims: “The result of abandoning reasonable value standards in the face of urgency would be the use of much very high-cost, marginal-benefit care for dying patients. This situation is arguably our current practice in much care, including cancer care, of dying patients. But it is neither a rational nor ethical use of limited resources. The money spent on this very expensive, but marginal benefit, end-of-life care, could produce greater benefits if spent elsewhere either within or outside the health care system.

Schnipper goes on to state a cut off level:

“A cancer treatment that postpones death on average for 3 months at a cost of $100,000 does not produce…a large benefit.   The opportunity costs of securing that treatment are much too great.”

Schnipper has argued that spending on overage increase of three months comes at the expense of other uses of money. 

“A life-saving treatment like an appendectomy generally produces a very large benefit; it prevents the patient's death and returns him or her to a healthy life. But a cancer treatment that postpones death on average for 3 months at a cost of $100,000 does not produce such a large benefit. The life extension is short, and the quality of life during it is often poor. It is not a large enough benefit to trump the greater benefits to many that would have to be foregone to provide it.”


Similarly, the Value Framework declares:

“Oncologists should be aware of the value of an intervention in terms of societal cost. Clearly, increasing health care costs are eventually transferred to the consumers of health care, if not in the form of out-of-pocket costs, then in the form of higher insurance premiums, higher taxes, or limited wage increases as employers confront the escalating costs of providing health care to their employees."


What Schnipper and The Task Force Ignore

The task force asserts that spending on new cancer drugs bankrupts individuals and our healthcare system.  But the benefits to patients are palpable.  Drugs that emancipate our immune system to attack tumors or target specific genetic cancer causing mutations have transformed cancer care.  These cancer drugs are expensive no doubt.  Yet they account for only account for 0.7 percent of the $2.9 trillion we spend on health care.   Cancer spending has increased in 1995 from $42 billion to about $130 billion today.  But its share of total health spending declined from 4.7 percent to 4.4 percent during the same time period. 

New medicines reduce the cost incurred by a cancer diagnosis, for instance in part by reducing hospitalization.  In 1996 drugs were 3.7 percent of cancer spending and 62.4 percent went to hospitalization. By 2012, drug spending was 9.3 percent of cancer costs while the share going to hospital stays dropped to 41.3 percent.    If we were allocating the same proportion of money to hospitals today, as we were in 1996, we’d be spending about $18 billion more a year on cancer.  And we have yet to see the full benefit of the cancer drugs not yet included in these estimates. 

As the price and number of new treatments increases, their value increases too. A recent Bureau of Economic Analysis study found between 2000-2010 that “medical technology (for treating cancer and other costly illnesses) is improving over time, leading to better health outcomes at a lower cost per patient.”   A lot of that has to do with medicines displacing less effective and more costly oncology services.  Why does the ASCO Value Task Force ignore that. 


Conclusion

Between the time Schnipper was pushing for assisted suicide until the time that he has begun pushing to limit the use of cancer drugs for people with “only” three months to live cancer survivorship has surged from 10 million to 14 million people and life span expressed by 36 million life years worth about $3 trillion.

If Schnipper’s vision had become common practice how many of those survivors would not be alive today?  How many will not live because of his current plans? 




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Designer Drugs in 3-D: An Innovation Lesson

08/11/2015 10:51 AM |

The announcement that Aprecia Pharmaceuticals has produced the first 3-D printed drug approved by the Food and Drug Administration  prompted a slew of articles about the technology that produced it.   There as no coverage about what it took to move 3-D printing from being a science fair project to a tool for mass production of customized medicines. Nor has their been any discussion about the implications of such commercialization on medicine. In particular,  the marketing of 3-D printed drugs underscores Sir Harold Evans observation that “innovation is not simply invention; it is inventiveness put to use. Invention without innovation is a pastime.”

















The emphasis  on ‘pragmatic’ is what distinguishes invention from innovation.  Michael Shrage,  a research fellow at MIT Sloan School's Center for Digital Business says that innovation is not what innovators do but what customers adopt.    Semi-conductors were an amazing invention but no one really saw any use for them beyond industrial applications:  then someone came up with idea of using one programmable chip to make personal electronic calculators.   It wasn’t long after that the PC revolution was launched.  

While Human Genome Project was a worthwhile investment, it was only made so by the efforts and investment undertaken to make it’s tools accessible and to product medicines and devices that millions could use.  Otherwise it would have been a very expensive science fair experiment as well.

The sale of 3-D printed medicines demonstrates that it is possible to make targeted medicines or treatment combinations widely and quickly available.   Often overlooked in the discussion about Aprecia is the fact that it applied it's manufacturing process to medicines that are in short supply because generic companies have found them too expensive to make using existing technologies or because they are products -- such as those for neurological conditions -- require absorption and availability within very narrow therapeutic indexes.   Finally,  the Aprecia approval is notable because it takes an injectable drug and turned it into a pill (Spritam).   Levetiracetam is used to control pediatric (and adult) epileptic seizures.   A stable, oral medication that works more quickly and can be produced in real time meets an important clinical need and solves a growing problem of drug shortages.  Can we say disruptive? 

Finally,  it should be noted that Tom Arrington, who invested in Aprecia many years ago, placed a huge bet on 3-D printing of drugs.  He didn't need the money.  In fact, Mr. Arrington has a successful authorized generic company Prasco Laboratories. .  Like many other entrepreneurs, Arrington's goal was not making more money. There a less risky ways to make a return.  Rather, profit is a means to an end that other incentives cannot easily achieve.  As Sir Harold noted: "Iinnovators are committed to making their developments as widely available to the populace as possible. This mass market democratization has been a hallmark of American success in the world."

Commercialization is part of the virtuous cycle that has made progress against disease and in enriching and extending life possible.  Aprecia has opened the door to the commercialization of medicines that can serve unique populations and it creates unprecendented opportunity to repurpose injectable medicines so that they are easier to administer, ship and store.  But the effect of commercialization cannot be divorced from the character of the person making it possible.

The Talmud observes:  Which is the best path for someone to choose for themselves?  Whatever is harmonious for the one who does it, and harmonious for mankind.

That sums up the path Tom Arrington took when he invested a small fortune in Aprecia.   Read More & Comment...

Frances Kelsey Was No Hero

08/10/2015 11:44 AM |

Frances Kelsey,  a medical officer with the Food and Drug Administration in the 1960s died last week at the age of 101.  She has been celebrated as the FDA official who kept thalidomide from being marketed in the United States.  

Thalidomide was never approved in the US.  In fact, as noted in Regulating New Drugs: The application was delayed for reasons having nothing to do with potential risks and was moving towards approval when the company itself reported the horrible side effects.  It took four months for the FDA to realize that people were at risk and in fact Helen Taussig, a cardiologist at Johns Hopkins University had been sounding the alarm about thalidomide for years.  The FDA finally acted after John F. Kennedy insisted on it.  

The current FDA approach -- a product of the 1962 amendments to the Food and Drug Cosmetic Act -- and dependency on the randomized controlled trial is a legacy of the political reaction to a problem.  Efforts to increase regulatory flexibility at the FDA are opposed, the critics always invoke "another thalidomide." 

Most people stop the story there. It’s an open and shut case, they say, thalidomide was a horribly dangerous and deforming drug allowed to get onto and stay on the market due to grossly inadequate safety testing and monitoring and the callous actions of companies interested in profits over patients. This, they believe, is why we cannot be too careful about any drug that might be risky. But the tale of thalidomide doesn’t end with its withdrawal – and millions have lived better, longer lives because of it.

In the mid-1960s, thalidomide came back to life. As many discoveries in medicine are, it was due to chance. Dr. Jacob Sheskin was the head of the Jerusalem Hospital for Hansen’s Disease (or what most people call leprosy) when one day he was sent a patient with extremely advanced erythema nodosum leprosum or ENL, a very painful and debilitating side effect of leprosy that causes boils, joint pain, inflammation, and intense pain. Patients waste away, unable to eat or sleep and dependent on morphine and sedatives to control their agony. About 60 percent of people with advanced leprosy get ENL.
The patient who arrived at the Jerusalem Hospital in 1964 was close to death and had received almost no benefit from any sedative available. While trying to figure out whether there was anything that could be done for him, Dr. Sheskin stumbled upon a small stash of thalidomide, now no longer sold. But remembering the use of the drug in mental patients who similarly responded to no other sedative, the doctor decided it was worth a try. It worked. Spectacularly. Not only was the patient finally able to sleep but his ENL began to improve radically. The same thing happened with other patients with ENL. Sheskin then embarked on a series of controlled clinical trials in Venezuela, where thalidomide could still be purchased, and confirmed his findings. Soon the drug was promoted by the World Health Organizations for use in ENL patients and because of it the vast majority of facilities to treat leprosy have been able to be closed. Even the US allowed highly controlled use of thalidomide for ENL beginning in 1975.

In the 1980s, thalidomide found another use: AIDS patients. Like those with ENL (and tuberculosis patients, who had also been helped by thalidomide), people with AIDS suffered from severe wasting. They also got sores in the mouth and esophagus called aphthous ulcers, caused like the wasting by caused by a chemical called TNF-ɑ (tumor necrosis factor alpha), and a rare cancer called Karposi’s sarcoma. The drug worked well, but it was hard to get a hold of. Many AIDS patients obtained it from abroad, mostly via Mexico, through buyers’ clubs but these channels were dubious and the quality and purity unsure. Researchers into the uses of thalidomide had likewise found that it was difficult to obtain and so one, Dr. Gilla Kaplan, finally managed to convince a small pharmaceutical firm called Celgene to apply to the FDA for approval to produce thalidomide.

While the process to get the drug through the FDA was ongoing, research into its potential use as an anti-cancer drug was in process by leading cancer researchers Dr. Robert D’Amato and Dr. Judah Folkman. They were working on angiogenesis, the growth of blood vessels, and hoped that finding a way to inhibit it would allow the development of drugs to fight cancer, as well as several other diseases. It was thalidomide’s anti-angiogenic effects that caused the birth defects but also made it a perfect candidate from D’Amato and Folkman’s research. Subsequent study found that the drug is also very effective against multiple myeloma, a difficult to treat cancer that attacks the plasma cells in the blood.  In July 1998, after a long and spirited debate and heartfelt stories from both victims of thalidomide and those helped by it, the Celgene drug --Thalimid was approved by the FDA under the condition that patients are carefully monitored and extensive safeguards enacted to prevent pregnant women from taking thalidomide.  Once in use, the benefits of thalidomide analogues in resetting the immune system to reduce tumor growth, became apparent.  It launched a whole new field of treatments and the introduction of several new medicines.  New uses, especially for rare autoimmune conditions, are still being discovered, even as old ones are sometimes superceded. In its current usages, the drug has benefited millions of patients around the world.

The thalidomide story is a many told tale:  Each year millions of people suffer because fearmongers invoke the handful of side effects or deaths from the use of a medicine.  Indeed, the number of adverse events from drugs as a percentage of all prescriptions did not change after the 1962 amendments.  The number of withdrawals as a percentage of all medicines has remained the same.   FDA regulation is a very expensive tranquilizer to calm the nerves of the public.  We have more expensive medicines, fewer new medicines for specific groups of patients and less competition.   

Enshrining Francis Kelsey as a hero is a ritual detached from the truth.  It is an exercise designed to reinforce the precautionary approach that has slowed down the development and use of medical innovations for over 50 years.    Read More & Comment...

Essuring safe use

08/10/2015 06:57 AM |

Do women deserve choice when it comes to contraception? On September 24^th, the FDA will hold a meeting of the Obstetrics and Gynecology Devices Panel of the Medical Devices Advisory Committee to discuss the risks and benefits of Bayer HealthCare’s Essure System for permanent female sterilization. It’ll make for some strange bedfellows.

Essure is a small metal and polyester coil placed into a woman’s fallopian tubes in order to make her permanently sterile. FDA approved Essure after a fast-track review process that prioritized the device because it offered the first alternative to surgical sterilization and promised a quick recovery.

The big picture was lucidly presented by Essure manufacturer, Bayer, in a letter to the New York Times, “Women deserve access to a wide range of contraceptive options, and Essure is an important non-surgical and non-hormonal option for women who have completed their families and want permanent birth control. However, no medical device, procedure, or even drug is completely free of side effects.”

According to Dr. Bill Maisel, deputy director for science and chief scientist at the FDA’s Center for Devices and Radiological Health. “The agency believes the benefits outweigh the risks in appropriately selected patients who are adequately informed.” The FDA adcomm will examine and discuss an extended (5-year) follow up of a phase III trial evaluating the effectiveness, safety, tolerability, and satisfaction of hysteroscopically placed Essure inserts. Hopefully it will also discuss ways to better educate both patients and physicians about which methods of birth control are most appropriate given a woman’s specific situation and medical history.

The FDA’s job is to weigh the risks and benefits of the products it reviews and regulates. Most people only hear about these issues as they relate to pharmaceuticals – but the regulation of medical devices deserve far more attention then they currently receive from the media, physicians, and patients.

At the FDA, there is a program called the “Safe Use of Drugs Initiative.” The theory is that the way you make drugs safer is to ensure they are used as directed. The Safe Use strategy calls for better and more regular education for both healthcare providers and patients. And it works. It strengthens the sinews of safety. Knowledge is Power.

The Affordable Care Act provides universal coverage for female contraception. As more patients avail themselves of the many FDA-approved options, shouldn’t we also be designing strategies and tools to ensure safe use for birth control via medical devices? That should certainly be a key discussion point at the upcoming FDA hearing. But even more urgently, shouldn’t the agency design and implement a more comprehensive Safe Use of Medical Devices program?

Essure is a good example of the broader opportunity. According to Diana Zuckerman and Laurén Abla Doamekpor of the National Center for Health Research, two of the biggest issues with Essure is (1) physicians improperly insert the product and (2) patients do not return for their mandatory hysterosalpingogram. A solid and strategic safe use program could directly address both of these problems. The way to make a medical device “safer” is to ensure that it us used as directed. Not rocket science. Will the National Center for Health Research and women’s health advocates stand up at the FDA adcomm and call for better patient education? Hope springs eternal.

The Essure advisory committee will certainly delve into the details of the data – and that’s their main job – but it’s also a timely and important opportunity for those offering open public comment to call on the agency to develop a Safe Use of Medical Devices initiative. Patients using Essure will benefit – as will the hundreds of millions of Americans (men and woman, children and adults) whose lives are improved through the use of medical devices and technology.

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Caronia Rules

08/07/2015 01:15 PM |

Amarin has won their request for injunction against the FDA. Caronia lives!

The preliminary injunction granted. The court agreed Amarin materials are truthful and took the government to task for essentially arguing that speech alone can be the basis for liability and that the agency’s action is at odds with the Caronia holding and the First Amendment

More to come.

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How ASCO Value Framework Devalues Lives of Dying Patients

08/05/2015 12:51 PM |

The ASCO Value Task Force attacks the very patient preferences it has pledged to respect and integrate into it’s tool by claiming that the ‘crisis’ of cancer drug spending is being driven by “sometimes unrealistic patient and family expectations that lead clinicians to offer or recommend some of these services, despite the lack of supporting evidence of utility or benefit.”

If it hasn’t made its view clear by now, the Task Force also asserts cancer patients “ also overestimate the benefits of treatments that sometimes extend life by only weeks or months or not at all. “ Oncologists are generally aware of this conundrum but uncertain about whether and how the cost of care should affect their recommendations. Although raising awareness of costs and providing tools to assess value may help to manage costs while maintaining high-quality care, some oncologists see this as being in conflict with their duty to individual patients.”

This amounts to a tacit effort to encourage assisted suicide, a cause Task Force chair Lowell Schnipper has promoted for 20 years. 

Here's the best response to this cold calculus 

https://www.youtube.com/watch?v=8Fo2uNqKMR8




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Replace Sovaldi With The Ebola Vaccine To See How Stupid and Short Sighted Cost Complaints Are

07/31/2015 01:49 PM |

Take any article on the cost of hepatitis C drugs -- doesn't matter -- they are all numbingly the same and one dimensional and replace sovaldi with ebola vaccines and hep c with ebola.   Then see if $84K for a cure  -- the possibility of which was widely reported and retweeted  -- is worth it.   

I chose a most recent article by Michael Hiltzik of the LA Times for this exercise.. Here's a link to the original un-original article about Sovaldi and here it is with the disease and cures swapped out....


How a hugely overpriced Ebola Vaccine helped drive up U.S. health spending

There's one especially eye-catching number in a new report by Medicare actuaries about U.S. healthcare spending: 12.6%. That's the leap in prescription drug spending last year over the year before. How sharp an increase is it? It was five times as much as the increase for 2013 over 2012, which was a mere 2.5%. The actuaries have no doubt what's driving the increase. It's "a result of expensive new treatments for ebola ," they write in their report for the journal Health Affairs.

And more than any other drugs, that means the Ebola vaccine, which cost about $84,000 for a 12-week treatment, or about $1,000 per once-a-day pill.

The increase in prescription costs was a sizable contributor to an increase in U.S. healthcare spending growth last year of 5.5%, a spike up from the previous year's increase of 3.6% and the first time growth exceeded 5% since 2007; if not for the drug spending, the overall increase would have been only 4.8%. But the major driver, the actuaries reported, was the expansion of healthcare coverage under the Affordable Care Act, which brought new insurance coverage to 8.4 million Americans.

That expanded coverage had clear benefits to the newly insured: the nationwide growth in out-of-pocket spending slowed to just 1.3% last year from 3.2% in 2013, because so much more healthcare was covered by health plans or Medicaid.

The major cloud on spending patterns was drug pricing. As we reported in June, the Ebola vaccines are the closest thing in years to miracle drugs. Their cure rate of ebola , exceeds 90%, with almost none of the horrific side effects caused by their predecessor treatments. Those side effects had kept many with ebola , which progresses slowly and often invisibly, from seeking treatment.

But the new drugs' arrival brought thousands of patients out of the woodwork; new patients leaped from 17,000 in 2013 to 161,000 last year. The caseload and the cost stunned commercial insurers and public programs such as Medicare and Medicaid alike; many refused to cover the new drugs except for patients with advanced liver disease. That defeated the purpose of the drugs, which would prevent those advanced, costly-totreat conditions from developing in the first place.

But even with those restrictions, the drugs drove prescription drug spending through the roof. That's bound to intensify questions over why the Ebola vaccines are so expensive for U.S. patients.  The profit margins on the drugs are stupendous. In the first half of this year, it recorded profit of $8.8 billion on $15.3 billion in sales, a net profit margin of nearly 58%. For the full year, the company projects gross profit margins of up to 90%. After the release of its second-quarter financial results Tuesday, Gilead's executive vice president of commercial operations, Paul Carter, groused that "there still are a lot of (payer) restrictions in place in the U.S.," according to the San Francisco Business Times. But although Gilead has offered discounts to some payers in return for more liberal patient approvals, the company plainly has pursued a calculated strategy that the success of its drugs will force insurers to pay for them at a large fraction of the list price. Gilead has taken enormous heat for its pricing strategy.

Its list price for the Ebola vaccine is more than twice the $36,000 the drug's original developer, Pharmasset, had planned to charge before that company was acquired by Gilead in 2011 for $11 billion. It was also vastly out of line with Pharmasset's research and development costs, which the Senate Finance Committee has estimated at less than $63 million in 2009-11. One pharmacy management executive has termed the pricing an act of "unmitigated gall."

As we observed last month, Gilead's ability to charge what the U.S. market will bear reflects a broken, overly indulgent, drug pricing regime in the U.S. In Canada and Britain, which don't allow unfettered drug pricing, the cost of a full Ebola vaccine treatment is $55,000. In Egypt, it's only $900.

The new report by the actuaries of the government's Centers for Medicare and Medicaid Services, suggests that pressure on Gilead and other manufacturers of high-priced drugs may force prices down. The actuaries project that rebates for the ebola  drugs will cut Medicare spending growth for prescriptions to 9% this year from 17.3% in 2014. That's good news, but it's only a reminder that the price in 2014 reflected not merely profit, but profiteering.  Read More & Comment...

Pessimists Vs. Progress

07/31/2015 12:08 PM |

Pessimists vs. Progress 

If the latter part of the 20th century was the era of the sustainable planet, the 21st century will be the age of the sustainable human. It will be an era of cures characterized by the accelerating capacity to diagnosis, stop, and prevent diseases. Infant mortality rates will plummet. Cancer, immune disorders, and illnesses such as Alzheimer’s will be preventable or manageable.

Living well past 90 or 100 will be commonplace across the planet. Our cognitive, physical, and cosmetic vitality will not erode as the years pass, because wellness will be sustained and enhanced through better nutrition and regenerative medicine. As people remain active and energetic for decades, both the absolute number and percentage of people retiring in the old fashioned way will decline. And as TEDMED curator Jay Walker observes "There is going to be a trillion-dollar business in keeping us healthy."

We have the scientific knowledge, the wealth and the imagination to achieve this vision. The exponential technologies—the tools to continually double performance and slash the cost and time required to produce innovations by half—either exist or are being developed. Cures could become America’s leading industry and principal export, and yield enormous economic and political benefits.

And yet, our nation lacks a cure strategy (a term coined by Jim Pinkerton) to achieve these benefits. On the contrary, most health care experts warn that a tidal wave of new medicines will have a tsunami effect across our entire health care system and that far from improving health and reducing the cost of disease, medical innovation stands in the way of solving a public health crisis. Others, such as Ezekiel Emanuel, proclaim that after age 75, we begin to fall apart, and that living longer imposes a huge financial burden on society: “This manic desperation to endlessly extend life is misguided and potentially destructive.”

Pessimists are actively campaigning against cures. Even as some elected officials seek to reform the scientific institutions that support or govern innovation, pessimists are warning against doing too much, too fast. Indeed, they want even more government control over how research is done, how quickly new cures can get to people, and at what price.

To create a social movement for cures, the prevailing pessimism must be overcome. This enterprise is critical to progress because social and political movements are essential to sustaining medical innovation.  In the past, progress occurred because social movements overcame the pessimistic resistance of the time and turned a demand for cures into a national strategy. Franklin Roosevelt called upon the nation to support a national war against disease at home with the same vigor and resources dedicated to turning scientific insights into products that helped win World War II. FDR also launched the National Foundation for Infantile Paralysis, an advocacy group to advance research on and publicize polio.  It inspired the formation of the March of Dimes campaign, which raised $1 billion of today’s dollars.

Mary Lasker, Sidney Farber and others organized a sustained lobbying and public relations effort to create the National Institutes of Health and provide it with significant funding. They went on to launch the first war on cancer in the 1940s and were responsible for Nixon’s war on cancer too. The organized outrage of HIV activists compressed the time required to develop and broadly distribute medicines to stem the epidemic. Breast cancer activists stormed the gates of Genentech to demand immediate access to Herceptin, leading President Clinton to direct the FDA to put cancer drugs on the faster tracks established for HIV. Craig Venter and Lee Hood’s resourcefulness and resolve captured the imagination of the world and demonstrated that sequencing the human genome opened yet another frontier for America. Without the leadership and vision of Bill Gates’ efforts the campaign to cure polio, measles, malaria, and TB would not be possible. 

Why have cure campaigns made progress possible? Because they are the catalyst and conduit for the ideas needed to solve problems. They force systems to adapt and change.  They spur and accelerate the exchange of ideas and the creation of networks, creating what Friedrich Hayek called ‘catallaxy’—the spontaneous order created by exchange and specialization in order to solve problems with collective intelligence. In today’s techno-terms, they created network effects before the Internet was born.

Ironically, past cure movements produced progress and benefits the pessimists of the time thought impossible. During the Depression, poor health was considered by many Depression-era Americans to be a matter of fate. The gains in health care between 1900 and the present have been spectacular. Life expectancy at birth in the Western world grew from a mere 45 years at the beginning of the 20th century to nearly 80 years at the dawn of the 21st century. More than 100 infants, and about an equal number of mothers, died for every 1,000 live births in 1900. Both the infant mortality rate and deaths of women during childbirth have become rather negligible. The incidence of contagious and other diseases also drastically declined, especially during the second half of the century. Death rates in the U.S. from heart disease are less than half of what they were in 1950, and survivor rates from many forms of cancer have improved during the past two decades.



The cost of health care has actually declined as new treatments replace more expensive and less effective services, particularly surgery and hospitalization. Each time new medicines are introduced, the ‘pessimistas’ shriek about how they will bankrupt our health care system. Hospitalization rates for cancer, heart disease and HIV have dropped dramatically from their peaks in the 1990s. It would cost an additional $10 billion a year to hospitalize people with HIV at the 1995 peak rate of 57 per 100000. Breast cancer hospitalization rates have been cut by nearly 70 percent, saving $5 billion per year. And the cost of medicines? It’s remained at about 10 percent of total health care spending since 1960. 

Meanwhile the economic value of longer and better life—not counted in our GDP —has soared all across the world. Between 1960 and 2000, economic welfare from health care expenditures appear to have contributed as much to economic welfare as the rest of consumption expenditures, as measured by GDP, or about $9 trillion.

A recent government study looked at the economic value of reducing just disease related disability for 30 diseases between 1990 and 2010. It concluded that it generated $1 trillion.  The Pessimistas claim that particularly in cancer, the cost of innovation is too high because most new medicines, for the most difficult to treat and advanced forms of cancer, add only a few months of life on average. In fact, the BEA study found that cancer treatments were responsible for nearly 80 percent of the total decline in disability plagued life years in the United States between 1990-2010.  That generated nearly $800 billion in health value. And as Columbia University economist Frank Lichtenberg found: the cost of new cancer drugs (developed in 1995) is less than 1% of the nearly $5 trillion health value of the mortality reduction.

In fact, if we can apply this ‘cure’ for medical spending to more people as they age, we can create what Dan Perry and Jay Olshansky call ‘the longevity dividend’. As they note: “Slowing the aging process by an achievable three to seven years would simultaneously postpone all fatal and nonfatal disabling diseases, produce gains in health and longevity equivalent to cures for major fatal diseases, and create scientific, medical, and economic windfalls for future generations that would be roughly equivalent in impact to the discovery of antibiotics in the 20th century.”

Medical innovation has already become the main reason that Medicare spending has been declining for 40 years, as more people live healthier, longer lives. Disability has fallen by about 2 percent a year, saving nearly $1 trillion over the past two decades. And after age 65 people are working more and are more productive. If the decline in disability remains 2 percent, by 2030 people over 65 would add $6 trillion in annual income and $1.9 trillion in tax revenues (assuming tax rates are held constant).  Medicare would spend $500 billion less each year.

The economic gains are likely to be even greater. For instance, just delaying the onset of Alzheimer’s by 5 years would generate $17 trillion of health value over 20 years. As Jim Pinkerton put it: “Do you want to make a dent in future health-care costs? Cure Alzheimer’s. That's where the cost will be as the health of the baby boomers falter. Insurance isn't the key. It was never the key. It's a product. Cure and care are the words of the future.

The Future: The Network Effect Disrupts Medical Innovation
The pace of innovation is accelerating exponentially.  Systems biology—which deciphers the networks of interaction between and within cells that regulate health and disease—is the Internet of Things for cures. Lee Hood, the co-founder of the Institute of Systems Biology and the inventor of the automated DNA sequencer and synthesizer, has pioneered the network of network concept and applied it to medical innovation. 

Similarly, Hood is harnessing the dramatic pace at which genomic, transcriptomic, metabolomics, and proteomic technologies have digitized biological data and its analysis. He has turned every cell into a ‘device’ that can share and process information.  In essence, he has created a network of billions of devices sharing information in digital form. Every cell is a little computer that shares and creates information that creates a series of intra and interconnected networks. Genetic networks communicate with molecular and cellular networks that in turn create organ networks. We can now see how the networks change over time and with perturbations or distress, as well as how these networks functions to produce disease or healthy phenotypes.

Hood predicts: “Within the next 10 years, we should be able to sequence entire genomes in less than an hour’s time at the cost of a few hundred dollars. This will provide crucial insights into optimizing our wellness. In 10 years, we may have a little hand-held device that will prick your finger, make 2,500 blood measurements, and will longitudinally follow the organ-specific proteins for 50 different organs. This will allow us to detect many diseases at the earliest detectable phase - weeks, months, and maybe years before symptoms appear.

But more importantly, as Hood points out, systems medicine reduces the time and cost required for creating the social networks that demand and undertake the sharing of data needed to produce cures.  Eric Topol observes that just as the printing press led to the rapid diffusion and sharing of knowledge far beyond a small elite, smartphones and the digitization of our biology is allowing “..Consumers to take that data and learn from it, read it, and get facile with it. It extends to genomics and understanding the drug interactions with one's own genome. It's going to extend in every which way where there's a data information domain in the hands of consumers.”

Patient-activated social networks are already using big data and analytics as Topol describes.  The democratization of data is converging with systems medicine. This synergy is leading to what Hood defines as P4 medicine, medicine that is predictive, preventive, personalized, and participatory. Medicine will focus on each individual. It will become proactive in nature. It will increasingly focus on wellness rather than disease.

Hood notes, “instead of medicine focusing on disease as it does today, the focus in the future will be on wellness. Regular check-ups will allow the physician to longitudinally follow each patient and an individual’s wellness can be preserved without the disease state ever occurring.  Individuals will be their own control in establishing a wellness baseline, monitoring the progression to disease state, and monitoring treatments that will perturb the systems back to a healthy state.

P4 medicine will be able to reduce sharply the escalating costs of health care to the point where we will be able to export it to the developing world.  That will lead to a democratization of health care, a concept unimaginable five years ago.” 

A Cure Strategy: Capitalizing on the Network Effect
A cure strategy should foster the democratization of medical innovation and support the creation of the catallaxy that is the crucible of progress.

1. Promote crowd curing
While proposals to reduce the time the FDA takes to review and approve a new product are welcome, they still regard randomized clinical trials as the heart and soul of medical progress.  In fact, RCTs achieve a ..false certainty…neutralizing patient-specific variation in studies that include as many people as possible.

While the FDA and academic researchers are using new tools to measure individual differences they have not tapped into collective and interconnected data cloud around each individual patient.

A cure strategy would increase the bandwidth required to expand and accelerate connectivity to take on noncommunicable diseases such as Alzheimer’s, cancer, and heart disease. Why not invest $50 billion to support the hundreds of crowd curing communities that already exist? Studying the real world experience of millions of people using digital tools, and sharing the data and real world experiences of patients using Big Data analysis, allows systems biology and crowd sourcing technologies to more quickly match people to the best treatments.

2. Pay for Cures
Project Bioshield also established a fund for making multi-year purchases of new vaccines, devices, and medicines if and when they were developed. This increased the research and development of such products. Unfortunately, the agency in charge of this effort, The Biomedical Advanced Research and Development Authority (BARDA) saw this money diverted to other uses by politicians. BARDA only has $400 million a year to spend on cures. Why not allocate billions to innovations that eradicate cancers, Alzheimer’s, or other illnesses that, left untreated, cost Medicare and Social Security trillions?

3. Make Cures a Centerpiece of Foreign Aid
Why not make the purchase and donation of cures as centerpieces of foreign aid and development assistance? For instance, the United States currently spends x billions a year in foreign aid, mostly for military, etc. Purchasing cures and re-selling them at a cost competitive in global markets would bolster American leadership in biomedical innovation. Further, we should fund capacity to use cures. Organizations such do an effective job in building cure capacity in developing countries, but struggle for resources and lack of partners. 

4. Add The Value of Health To Our Measurement of GDP
Pessimism about medical innovation is also due to policymakers and the media focusing exclusively on the cost of new technologies and ignoring the value to consumers and stakeholders.

As University of Chicago health economists Tomas Philipson states: “Health care insurance ensures access to health care; stated another way, this insurance provides access to medical innovations already developed. It is the innovations in treatment over the past century that partly protect us against the loss of actual health when disease hits.

Medical innovation, therefore, is the key to true health insurance since it is the primary method by which the future risk of losses in health itself is reduced over time, and can thus be viewed as serving the role of insuring future health. In essence, medical innovation reduces the true price of health.”

Philipson has called for measuring how much innovation reduces what it costs to stay healthy longer. Indeed, The U.S Department of Commerce Bureau of Economic Analysis established Health Care Satellite Accounts to do just that. Years in the development, the accounts measure output “provided to patients as the treatment of disease (for example, cancer or diabetes) rather than the specific types of medical care that individuals purchase (such as visits to a doctor’s office or the purchase of a drug), as is currently published.”

Congress and every executive agency should be using the new health satellite accounts to measure health care consumption on disability, productivity, and premature death from disease.  And health plans should be required to provide data on the impact of their practices on these social indicators.

5. Make Access To Cures A Civil Rights Issue
Increasingly, insurers are making it harder for people to access cures. They require chronically ill people to fail first on older medicines (i.e., have their condition get worse.  Insurers have also placed most or all medications for cancer, HIV/AIDS, multiple sclerosis, and many other chronic diseases including generics, on the highest cost-sharing tier health plans. Finally, health plans are refusing to pay for the kind of systems medicine information that is crucial to finding the right treatments for the most advanced and complex illnesses.

Together, these practices amount to a systematic effort to discriminate against people with pre-existing conditions, violating the spirit and letter of the provision of the ACA that makes such policies illegal. In time, the health insurance business model will be destroyed in favor of a wellness industry based on P4 medicine. But for now people are being denied access to cures because they are chronically ill. That is immoral and it should be illegal.

Can A Cure Strategy Succeed?
In “The Emperor of all Maladies” Siddhartha Mukherjee’s history of the war on cancer notes that the turning point in the battle came when Mary Lasker and Sidney Farber “stumbled upon an unshakable, fixed vision of a cure—and they would stop at nothing to drag even a reluctant nation toward it.”

Farber wanted to attack all cancers but everywhere he turned the pessimists prevailed.  Pediatricians at the Children’s Hospital in Boston where Farber was treating patients claimed that he was wasting time and money on children who were going to die anyway.  His paper describing the remission was received, as one scientist recalls, “with skepticism, disbelief, and outrage.” Farber was undeterred.  As Mukherjee writes: “He needed a larger drive, a larger platform, and perhaps a larger vision for cancer. ” He established a social movement to carry out his cure strategy. 

Our nation is at a similar inflection point. Today new therapies are curing Hepatitis C and beating the most advanced and deadliest cancers into long-term remission. Yet the pessimists are launching an assault on the development and use of medical innovation, just as the previous generation of pessimists did when Farber wanted to expand the use of cancer drugs to anyone dying.

Today patient-activated social networks are increasingly connected in the effort to come up with cures. They are accelerating the spread of innovation at a pace Farber would find satisfyingly astonishing. Despite the best efforts of the pessimists, the direction and use of innovation is becoming democratized. As Schrage observes “the accelerating spread of innovation ultimately amounts to the greatest revolution in choice the world has ever known.”

In “Democracy in America”, Alexis de Tocqueville wrote “From the time when the exercise of the intellect became a source of strength and of wealth, we see that every addition to science, every fresh truth, and every new idea became a germ of power placed within the reach of the people.” The engine of progress was a free people sharing knowledge. It is today. Over the past 50 years, cure strategies in America have imagined a better world and turned social action into a potent tool for spreading medical innovation.

This power is stronger than ever, shared more widely and rapidly than at any time in our nation’s history. The pessimists will object, but their predictions will fade as they have before. The 21st century will be an era of cures, led by Americans.

Glass of water image credit: Yogesh Mhatre/Flickr  Read More & Comment...

Drug Imporatation. No! No! 1000X No!

07/31/2015 10:35 AM |

From the pages of the Orlando Sentinel ...

Foreign medications endanger Florida patients

In May, undercover investigators busted two Florida pharmacies for selling counterfeit medicines supposedly imported from Canada.

Those "Canadian" drugs actually came from India. They were rife with impurities and unknown ingredients.

Scams like this run rampant in Florida and across the United States. Yet some politicians — including presidential candidate Mike Huckabee — support legalizing the importation of cheap foreign medicines as a way to cut health-care spending. The facts say otherwise. According to a study by the nonpartisan federal Congressional Budget Office, drug importation would reduce our nation's spending on prescription medicines by a whopping 0.1 percent — and that's not including the tens of millions of dollars the Food and Drug Administration would need to oversee a transnational drug-safety program.

Drug importation is a deeply misguided idea. It exposes consumers to counterfeit drugs of unknown origins, and undermines the public's long-term health by weakening biopharmaceutical companies' incentives to invest in future treatments and cures. Congress should uphold laws that prohibit widespread drug importation.

The vast majority of imported "Canadian" drugs aren't made in Canada and often involve unreliable and unregulated Internet pharmacies. More than 96 percent of Internet pharmacies don't adhere to U.S. pharmacy laws and practice standards, according to a new study from the National Association of Boards of Pharmacy. Of these noncompliant pharmacies, 88 percent sell drugs without requiring a doctor's prescription.

Far too often, importing drugs of unknown quality from sketchy pharmacy websites ends in tragedy. Consider the case of one Texas emergency-room doctor, who suffered a stroke after importing what he thought was a popular weight-loss drug. The online pharmacy had actually substituted the doctor's ordered drug for a counterfeit, stroke-inducing medication shipped in from China.

If medical professionals can't tell the difference between real and counterfeit drugs, regular patients don't stand a chance.

A 2005 investigation by the FDA looked at 4,000 drug shipments coming into the United States. Almost half of them claimed to be from Canada. Of those, a full 85 percent were from countries such as India, Vanuatu and Costa Rica.

As part of another investigation, FDA officials bought three popular drugs from two Internet pharmacies claiming to be "located in, and operated out of, Canada." Both websites had Canadian flags on their websites. Yet neither the pharmacies nor the drugs were actually from Canada. And in laboratory analysis, every pill failed basic purity and potency tests.

Not only does drug importation put patients at risk, but it also disincentivizes domestic medical research. By importing Canadian price controls, importation would destroy biopharmaceutical companies' incentives to continue pouring money into the 3,400 potential new medicines currently under development in the United States — and cost many Americans their jobs. In the Sunshine State alone, the biopharmaceutical industry employs 22,000 people. Those positions pay workers an average salary of $73,000 — well above the state average of $47,000. All told, the industry adds $16 billion to Florida's economy.

Right now, American patients who head online to buy drugs are motivated by the cut-rate prices they see on the Web. Health insurers could help patients avoid this temptation by reducing co-pays for drug purchases, particularly for low-income patients. If drugs become more affordable in the states, patients won't feel the urge to look for a bargain abroad.

To protect Florida workers and patients, the Sunshine State's representatives in Congress must reject any initiatives supporting drug importation.

Peter J. Pitts, a former FDA associate commissioner, is president of the Center for Medicine in the Public Interest.

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Much ado about the WHO biosimilar review

07/29/2015 06:52 AM |

New biosimilar working paper from the WHO.

(PROPOSED ADDENDUM TO: WHO TRS 987, Annex 4. Guidelines on the quality, safety and efficacy of biotherapeutic protein products prepared by recombinant DNA technology  APPENDIX 7. REGULATORY)

Some important snippets:

Per clinical trials:

A head-to-head comparability exercise of a candidate similar biotherapeutic product (SBP) with a reference biotherapeutic product (RBP) is essential to justify a reduced nonclinical and clinical 26 package for licensing.

Studies should be designed to detect any potential difference in quality, nonclinical and clinical attributes between the SBP and RBP rather than simply to confirm safety and efficacy of the two products. It should be ensured that any detected differences have no clinically meaningful impact on product performance.

Per nomenclature and pharmacovigilance:

The ability of the pharmacovigilance system in the country should be considered to monitor and determine adverse reactions and/or efficacy problems (such as reduced clinical effectiveness) associated with the biotherapeutic product, should they exist.

With poor pharmacovigilance systems in many countries, as well as nomenclature difficulties, it may be impossible to obtain sufficient data to demonstrate that a particular product was the cause of an adverse reaction or that patients may be at risk from the use of products that are clinically untested or are tested with inadequately designed studies. Traceability is a key element in monitoring the safety and efficacy of biologicals as it enables pharmacovigilance measures to be put in place. 

This document is open for comments until September 14, 2015.

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Putting Part D Spending in Perspective

07/28/2015 05:57 PM |

I don't mean to pick on the WSJ, but with regard to the recent article  "U.S. Health-Spending Growth Jumped to 5.5% in 2014," how difficult is it to put drug spending in context by looking at projected changes in totals, per capita and percent of Medicare spending??    LOUISE RADNOFSKY manages to find out that Medicare Rx spending increased 15.1 from 2014-2015, but couldn't seem to find the out years even through there were on the same chart in the Medicare Trustees Report.   So for those of you who care.. here's the rest of the story.  It took me a whole 15 minutes to put this together.  All by myself.

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Transforming Medicine: The Elizabeth Kauffman Institute Launched to Match People with Life-Threatening Illnesses to the Best Treatments in Real Time

07/27/2015 02:35 PM |

CMPI is proud to be part of this new effort to turn the phrase patient-centered drug development into reality.

Transforming Medicine: The Elizabeth Kauffman Institute Launched to Match People with Life-Threatening Illnesses to the Best Treatments in Real Time
--Founded by Biotech Pioneers and Health Data Innovators--

--Will Use Big Data and Artificial Intelligence to Match Patients with Best Treatment Options—

July 27, 2015 08:07 AM Eastern Daylight Time
NEW YORK & CAMBRIDGE, Mass.--(BUSINESS WIRE)--Transforming Medicine: The Elizabeth Kauffman Institute or “TMed,” was officially launched to match people with life-threatening illnesses to the best treatments for their specific condition. To accomplish this, the experts, leaders and innovators who founded “TMed” plan to create a knowledge base that evaluates individual patient characteristics, including genetic and molecular profiles, to determine the most effective marketed and research-stage therapy for each patient. “TMed” is a non-profit (501c3) organization.

“When big data analysis ‘turns the lights on’ to reveal which treatments will work for specific patients, babies are saved from premature birth, cancer patients live longer, chronic conditions are managed better, and billions of dollars are saved by avoiding treatments that do not work for given patients.”

“We formed this institute because over half the medicines used today do not work for half the patients. This is particularly true for people fighting the most complex and fatal diseases,” said “TMed” Co-Founder Lee Hood, M.D., Ph.D., President of the Institute for Systems Biology. “Our aim is to change the practice of medicine in a fundamental way.”

Stuart Kauffman, M.D., systems biology pioneer and “TMed” Chairman, added, “Our goal is to arm patients, caregivers and doctors with our tools and knowledge so they can transition to individualized treatments in real time.”

The institution is named for Dr. Kauffman’s late wife Elizabeth who succumbed to pancreatic cancer.

Other co-founders include Colin Hill, CEO of GNS Healthcare, a pioneer in computational healthcare analysis; Robert Goldberg, Ph.D., Vice President and Co-founder of the Center for Medicine in the Public Interest; and Kathleen O’Connell, an award winning journalist and patient advocate.

Colin Hill said, “When big data analysis ‘turns the lights on’ to reveal which treatments will work for specific patients, babies are saved from premature birth, cancer patients live longer, chronic conditions are managed better, and billions of dollars are saved by avoiding treatments that do not work for given patients.”

This group of pioneers and innovators will now combine their expertise to develop unique algorithms to predict the best combination of treatments for pancreatic cancer, brain cancer, sickle cell anemia and other difficult to treat diseases, based on evidence-based analytics and systems biology. When the data base is ready, “TMed” will work closely with providers, health insurers, patient groups and other stakeholders.

One of the “TMed” scientific advisers, Nicholas Schork, Ph.D., concluded “We have the ability to save lives now. Let’s get started.”

To learn more about Transforming Medicine, go to the institute’s website at transformingmedicine.org.

Kathleen O’Connell, 917-270-3279
Kathleen.OConnell@transformingmedicine.org
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Cancer Docs Price Control Prescription Is Misinformed

07/27/2015 11:43 AM |

Hank Campbell at the Science 2.0 blog does a great job of picking apart the most recent attempt by cancer doctors to make economic policy.

A group of academics have channeled their inner Bernie Sanders and written a wonderfully naïve op-ed about how to lower drug prices: Destroy the industry that made America the world leader in biotechnology.

It's simple. Let government control drug prices and then corporations will just do what they always do, but it will be a lot cheaper. It is so simplistic it could have been written by Paul Krugman in the New York Times. It is also in defiance of how science, creativity and medical advancement works, and would lead to a mass exodus of science jobs from America.

Writing about the piece in Mayo Clinic Proceedings, lead author Ayalew Tefferi, M.D., a hematologist at Mayo Clinic, says, "The average gross household income in the U.S. is about $52,000 per year. For an insured patient with cancer who needs a drug that costs $120,000 per year, the out-of-pocket expenses could be as much as $25,000 to $30,000 - more than half their average household income."

He and colleagues cite a 2015 study by D.H. Howard and colleagues in the Journal of Economic Perspectives, which found that cancer drug prices have risen by an average of $8,500 per year over the past 15 years. What has risen markedly in that time? Cancer survival rates.

They claim that by controlling the market, the free market will work better. If you are a California resident enjoying paying 50 percent higher utility rates compared to the rest of the country, you see how in the real world more government control does not make the free market more efficient. If you can do math, it is better to be skeptical. 

Here's my take:  

In fact, new cancer drugs not only save and extend lives; they reduce the cost of treating cancer.  Cancer spending has increased in 1995 from $42 billion to about $130 billion today.  (Most of that is on doctors and hospitals, the cost of which the authors ignore.) Between 1995 and 2012 the share of cancer spending devoted to drugs increased from 3.7 percent to 9.3 percent while hospital spending declined from 62.4 percent of cancer costs to 41. 3 percent in 2012.   Meanwhile, cancer death rates declined by 30 percent and the number of people surviving cancer increased by 40 percent (9.8 million to 14 million).  Cancer costs as a share of total health spending declined from 4.7 percent to 4.4 percent.   Meanwhile new cancer drugs have remained at around 0.7 percent of total health care spending.

Further, the authors imply that out of pocket costs for cancer drugs are increasing because health insurers are being forced to because of higher prices.  This is inaccurate.  Studies conducted by health actuary Milliman, Inc., found that capping cost sharing at $100 a month would only increase premiums by an average of $2 a month.

The authors claim that most new medicines don’t improve average survival of the average cancer patient. But new drugs target much smaller groups of patients for whom other medicines do not work.   Averages don’t capture the benefit such small groups receive. Cumulatively, these new medicines are in fact, saving money and saving lives.

Meanwhile, the European style price controls the doctors prescribe are associated with faster increases in cancer costs and higher death rates compare to America.  While they allude to the fact that price controls on generic cancer drugs have caused persistent shortages,  they somehow believe that the development of new medicines which require substantially more money and entail significantly greater risk, would be immune to this outcome.  They also apply to cancer doctors who are also paid much more in Europe than here. If the oncologists who wrote the letter believe price controls are the right prescription, perhaps they should lead by example. 
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Price vs. Value: The Story and the Rest of the Story

07/27/2015 11:41 AM |

As John Adams quipped, "Facts are pesky things."

First the story – and then the rest of the story.

THE STORY

Insurer Uses Clout to Negotiate Drug Prices; Critics Challenge Medicare Brand name Pricing

Jul. 27, 2015, Drug Industry Daily

UnitedHealth Group plans to use its market strength to negotiate prices to help consumers purchase expensive specialty drugs, adding to a growing press from doctors, patient advocates and lawmakers to rein in costs.

According to UnitedHealth, the acquisition of rival Catamaran by its Optum-Rx pharmacy-benefits business will give the insurer a new competitive edge in seeking payments or refunds based on whether drugs help patients.

The announcement — which underscores payers’ growing use of patient outcomes to determine drug pricing — comes on the heels of a report claiming Medicare pays 73 percent more than Medicaid and 80 percent more than the Veterans Administration for brand name drugs.

The report, by Public Citizen and Carleton University, claims $69.3 billion was spent on prescription drugs through Medicare Part D in 2013. The report points to research from Avalere Health showing roughly 58 percent of Part D spending in 2011 went to brand name manufacturers.

The report urges Congress to pass legislation allowing Medicare to reduce brand name drug prices to at least the level of Medicaid or the Veterans Health Administration and to introduce mandatory generic substitution for all plans under Part D. Currently, the federal government is prohibited from leveraging its Part D purchasing power even though private plans obtain substantial rebates from drug makers and pharmacies.

Critics of high drug costs have singled out the price of Gilead Sciences’ hepatitis C drug Sovaldi (sofosbuvir) as being particularly egregious. At $1,000 a day, the Veterans Administration has already exceeded the more than $400 million budgeted for hep C treatment in fiscal 2015, according to Sen. Bernie Sanders (I-Vt.), who recently called for wartime powers to break the patents on the drug (DID, May 15).

But it’s unclear whether the anger over drug prices is sufficient to fuel real change in the form of legislation.

Peter Pitts, president of the Center for Medicine in the Public Interest, says it’s artificial to compare drug prices with what the VA pays, since the agency gets the lowest possible prices by law. He also points to a 2014 Congressional Budget Office study that showed drug prices would be higher if the government negotiated Part D pricing.

Separately, more than 100 oncology doctors called for cutting the prices of cancer drugs. All new cancer drugs approved by the FDA in 2014 were priced above $120,000 per year of use, according to their article in Thursday’s Mayo Clinic Proceedings.

PhRMA was quick to respond to both reports, saying proposals to fundamentally alter the structure of the Medicare Part D program would hurt taxpayers and beneficiaries.

Read the Public Citizen, Carleton University report here www.fdanews.com/7-15-PricingReport.pdf. — Jonathon Shacat

NOW, THE REST OF THE STORY

Let’s start with Sovaldi. The Public Citizen and Carleton University do not mention in their report that one pre-Sovaldi “best practice” treatment for Hepatitis C, the drug Pegasys, requires one injection a week for 48 weeks — and very few patients see the treatment through to completion, so much of that treatment, both physician time and drug cost, is wasted. Nor is it that much cheaper: At about $7,000/month, the full course of treatment is over $70,000 — barely less than cost of the three months needed for Sovaldi to work a cure. And the price of not using Sovaldi is very high. One in three patients with the Hepatitis C virus eventually develops liver cirrhosis, and managing these patients is costly. A “routine” liver transplant (where the liver is from a cadaver) costs close to $300,000; a “living donor” transplant is even more expensive. But why let the facts get in the way.

Data recently published by the PwC Health Research Institute suggests the reverse. The study shows that the use of Sovaldi will actually drive down overall spending within a decade.

Also, is anyone really paying “$1000 per pill?” Certainly nobody with insurance. And for those without coverage there are generous programs supplied by the manufacturer. What rates have large payers negotiated?  They won’t say. Hm.

Let’s tackle the VA next. The Veterans Administration’s national formulary covers 59 percent of the 200 most popular drugs in the country. (Medicare covers 85 percent of those drugs.) And a study from Columbia University found that just 19 percent of all new drugs approved since 2000 were covered by the VA and just 38 percent since 1990. Media reporting missed these facts too.

Per “negotiating prices” for Medicare Part D, allowing the Federal government to negotiate drug prices would result in prices going up and patient choice going down. That’s why the Non-Interference Clause, the legislation that prohibits Federal price negotiation was created in the first place. It’s interesting and important to note that the legislative language was drafted by Senators Ted Kennedy and Tom Daschle.

The Congressional Budget Office found that between 2004 and 2013, Part D cost an extraordinary 45 percent less than what was initially estimated and premiums for the program are roughly half of the government’s original projections. These unprecedented results are largely due to Part D’s market-based structure. Beneficiaries are free to choose from a slate of private drug coverage plans, forcing insurers to compete to offer the best options to American seniors. It’s hardly surprising that the program has led to low prices and satisfied customers. Through their own negotiations with drug makers, private insurance plans that operate under Part D have already had great success in keeping pharmaceutical prices down. In fact, the CBO has observed that Part D plans have “secured rebates somewhat larger than the average rebates observed in commercial health plans.” What’s more, the CBO has said that doing away with the non-interference clause “would have a negligible effect on federal spending.” In a report from 2009, they reiterated this view, explaining that such a reform would “have little, if any, effect on [drug] prices.” In fact, allowing the feds to negotiate drug prices under Part D would likely have a negative effect on the program. The CBO predicts that when HHS forces pharmaceutical firms to lower the cost of a particular drug, this tactic brings with it “the threat of not allowing that drug to be prescribed.”

And as far as Senator Sanders’ call for “wartime powers to break patents,” there is no such thing as a free lunch – let alone “free” innovation. While opaque and seemingly arbitrary drug pricing deserves immediate attention, the value of innovation must not be ignored. Innovation is hard. Today it takes about 10,000 new molecules to produce one FDA-approved medicine. This observation itself is disconcerting, but, further, only 3 out of 10 new medicines earn back their R&D costs. Moreover, unlike other R&D-intensive industries, biopharmaceutical investments generally must be sustained for over two decades before the few that make it can generate any profit. Innovation is slow. As any medical scientist will tell you, there are few “Eureka!” moments in health research. Progress comes step by step, one incremental innovation at a time.

As Abraham Lincoln said, “Patents add the fuel of interest to the passion of genius.”

But don’t all these wonderful innovations come from government-funded research? Nope. A study in Health Affairs by Bhaven N. Sampat and Frank R. Lichtenberg (What Are The Respective Roles Of The Public And Private Sectors In Pharmaceutical Innovation?) http://content.healthaffairs.org/content/30/2/332.full.html puts the issue in a data-driven perspective that gives the NIH its due – but in the proper frame of reference.

For example, according to Sampat and Lichtenberg, fewer than 10 percent of drugs had a public sector patent, and drugs with public-sector patents accounted for 2.5 percent of sales, but that the indirect impact was higher for drugs granted priority review by the FDA. (Priority review is “given to drugs that offer major advances in treatment, or provide a treatment where no adequate therapy exists.)

478 drugs in our sample were associated with $132.7 billion in prescription drug sales in 2006. Drugs with public-sector patents accounted for 2.5 percent of these sales, while drugs whose applications cited federally funded research and development or government publications accounted for 27 percent.

As Harvard University health economist David Cutler has noted, “Virtually every study of medical innovation suggests that changes in the nature of medical care over time are clearly worth the cost." When it comes to drug pricing it's important to look at the whole picture.

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Price vs. Value. A Distinction with a Difference

07/24/2015 12:02 PM |

Per Drug Prices Soar, Prompting Calls for Justification (NYT, July 23, 2015), while opaque and seemingly arbitrary drug pricing deserves immediate attention, the value of innovation must not be ignored. Innovation is hard. Today it takes about 10,000 new molecules to produce one FDA-approved medicine. This observation itself is disconcerting, but, further, only 3 out of 10 new medicines earn back their R&D costs. Moreover, unlike other R&D-intensive industries, biopharmaceutical investments generally must be sustained for over 2 decades before the few that make it can generate any profit. Innovation is slow. As any medical scientist will tell you, there are few “Eureka!” moments in health research. Progress comes step by step, one incremental innovation at a time.

Biopharmaceutical companies more often profit by improving existing molecules and making processes more efficient than by revolutionizing the whole field with new miracle products. Discontinuous innovation (such as the recent breakthroughs in Hepatitis C) is a wonderful exception to the rule. As Harvard University health economist David Cutler has noted, “Virtually every study of medical innovation suggests that changes in the nature of medical care over time are clearly worth the cost." When it comes to drug pricing it's important to look at the whole picture.

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Medical Journals Are Practicing Economics Without A License

07/22/2015 07:34 PM |

More and more medical journals are running articles by doctors on the cost of developing and using new drugs.

I have no idea if and how these articles are peer-reviewed.   My guess is that they are not, otherwise the journals would not allow articles to be published that rely on discredited economic papers or authors or use a framework to measure cost and value that is questionable at best, shoddy at worst. 

In my opinion such articles are written with a very clear agenda: attack drug prices as being too high because the cost of developing new drugs is in fact quite low and 2)  because they offer very little clinical benefit compared to older medicines.   I have no problem with articles that make that case.   I do have a problem when the articles are intellectually and methodologically suspect.   People trust medical doctors more than most other professionals.  But that trust is abused when doctors pose as economists to further a political agenda. 

There are four hallmarks of such pseudo-economic analysis.  I will discuss each on in detail in separate blogs.  Any article published in a peer-reviewed journal that contains these elements should be rejected if submitted, retracted if published.   There is little difference between authors relying upon these methods or analyses and Andrew Wakefield who used similar approaches to conclude that a measles vaccine can cause autism.   

1.   Relying upon the one discredited source to make your case.

Best example is Hagop Kantarjian use of Donald LIght's assertion that it only costs 4 percent of what most studies have estimated as the cost of bringing a new chemical entity to market.   Kantarjian claims it is only $25 million.  That's based on an earlier estimate of drug development costs by Joseph DiMasi of $802 million per new chemical entity.  Kantarjian has also co-authored articles with Light.  

But Light's claim has been rejected by several studies that have shown studies asserting the cost of drug development is much lower than $2-6 billion are all flawed: " they inappropriately mix median values reported for individual drugs with what are mean values for the costs of clinical failures and preclinical fixed costs, and for which the concept of a median has no meaning; they misconstrue the nature of the corporate income tax and incorrectly consider manufacturing tax credits; they use discount rates that are meant for other contexts but that are inappropriate here; they treat line extension approvals as separate and independent units of observation alongside their original approvals; and they grossly misstate the meaning of and misuse figures in our paper on industry-reported data on expenditures on self-originated drugs, licensed-in drugs, and already-approved drugs.

In short, every one of Light and Warbuton's adjustments are invalid. Furthermore, two peer-reviewed papers by current and former FTC economists, also not cited by Light and Warburton, validate our work using other methods and public data (Adams and Brantner, 2006, 2010). They find that R&D costs are likely as high or higher than (DiMasi's) estimates."  (See DiMasi JA, Hansen RW, Grabowski HG. Reply: Extraordinary claims require extraordinary evidence. Journal of Health Economics 2005;24(5):1034-1044. and DiMasi JA, Hansen RW, Grabowski HG. Reply: Setting the record straight on setting the record straight: response to the Light and Warburton rejoinder. Journal of Health Economics 2005;24(5):1049-1053.)

A prima facie analysis of Kantarjian's assertion suggests how absurd it is without having to waste time refuting it.   If it only cost $25 million to bring a new drug to market why aren't hundreds of companies developing them.  It costs up to $140 million to develop a hot new video game for XBox360 or P3 Playstation platforms.    Yet the medical journals such as Blood  publish these claims as if they were reliable.  Why not continue to publish articles citing Andrew Wakefield's article claiming vaccines caused changes in the gut that caused autism???   Kantarjian uses Light like anti-vaxxers use Wakefield.  The only difference is, Kantarjian gets published and Wakefield is discredited. 

Tomorrow I will discuss the misuse and abuse of the assertion that cancer drug prices defy market forces because prices only go up, not down.    Read More & Comment...

Bam! FDAMN

07/16/2015 11:56 AM |

The pharmacenti were gathered. Policy experts, provider organizations and patient groups, industry, academics and FDA brass. The clock in the White Oak Great Room struck 9AM. The room fell silent. Smart phones were (mostly) on silent mode.

Welcome to PDUFA VI.

The first public meeting on reauthorization of the Prescription Drug User Fee Act (PDUFA) held few surprises but made it clear that this time around there will be more creative tension.

First up was Acting FDA Commissioner Stephen Ostroff. He began with a nod to NASA’s wondrous New Horizons’ space probe.  He offered this alliterative flourish, “Just as with the recent success of NASA’s space probe, PDUFA delivers on its promise because of planning, precision, and predictable performance.” He then called on all present to “aim for the stars” in the forthcoming PDUFA process.

Ostroffian p-values aside, whether or not all parties concerned in PDUFA (those noted above as well as legislators and the White House) can embrace such a Plutonic relationship remains to be seen.

Next up was FDA Deputy Commissioner Rob Califf who said, “an increase in predictability creates a better environment for innovators.” This comment set the meeting’s major theme – that PDUFA VI isn’t just about the founding principle of the user fee concept, ensuring predictability in the review process, but must now also help to facilitate the advancement of regulatory science.

Theresa Mullin, the Director of Strategic Programs within the Center for Drug Evaluation and Research (CDER) then made a point to establish a key FDA talking point – that PDUFA isn’t about policy but rather process. And while that is an accurate statement, it belies the fact that process drives policy. That’s more than semantics. Think about it as the power of the pen – another key PDUFA p-value.

The majority of the day was given over to panels representing the consumer, patient, healthcare professional, industry, and academic perspectives on what should matter most in constructing a thoughtful and forward-looking reauthorization package.

Some highlights:

Allan Coukell (Pew Charitable Trusts) urged that PDUFA VI incorporate funding that would help reduce both the time and expense it takes to design 21^st century clinical trials – and that a good start would be funding programs that address clinical trial methodologies. All heads nodded – particularly that of Rob Califf.

Sally Greenberg (National Consumers League) suggested that there should be user-fees for marketing material review – particularly television ads. She also wants DTC review to be mandatory. She commented that, on this point, she “sounds like a broken record.” Possibly, but what is for certain is (in the Age of Caronia and Amarin) its her message that’s broken. In any event, that’s policy – not process.

Paul Melmeyer (National Organization for Rare Diseases) stressed the urgency of thoughtful and aggressive next steps per the FDA’s Patient-Focused Drug Development (PFDD) program. Indeed, almost every speaker spoke about PFDD as the Jewel in the Crown of PDUFA V – but that more needs to happen.

Jeff Allen (Friends of Cancer Research) spoke to the need for the FDA to collect and share best practices per various expedited review pathways. He also pointed to the need for the agency to more progressively consider real world evidence in its design of post-marketing commitments.

Cynthia Bens (Alliance for Aging Research) observed that, “PFDD meetings have led to a cultural shift across the FDA elevating the way in which regulators view the value of patient input in the drug development process,” but “there is no one-size-fits-all solution to gathering and employing patient input effectively.” And on the Patient-Reported Outcomes (PRO) front, “We would encourage the dedication of resources in PDUFA VI to support additional workshops aimed at feasibility and reliability of incorporating PROs in trials for complex diseases.” Specifically, “We would support the addition of user fee funds in PDUFA VI to allow for new guidance on performance outcome measures, observer reported outcome measures, and clinician reported outcome measures.” Bravo.

Maureen Japha (Milken Institute/Faster Cures) asked that the patient voice (no longer “an honorary voice”) be heard earlier and more regularly in the review process, not just at the end per benefit/risk considerations. The call for a more comprehensive and integrated patient voice was loud and clear during the entire course of the meeting. Process or policy? Where you stand depends on where you sit.

Representatives from healthcare professional organizations (the American Pharmacists Association, the American Academy of Pediatrics, and the American College of Cardiology) focused their comments on the need for more global collaboration (sharing rather than stipulating best practices), continuing to modernize the agency’s drug safety system, and the importance of advancing regulatory science – the red thread of this early PDUFA dialogue.

Industry association presentations (BIO and PhRMA) tended to applaud the successes of PDUFA V and pointing to the need for all parties concerned to make further progress across the broad spectrum of both predictability and regulatory science. The key phrase from industry is that they, “fully support timely reauthorization.” And there was much sharing of success metrics – particularly the approval of new medicines (NMEs – a love story). But all is not smooth sailing. Kay Holcombe (BIO) addressed the specter of budgetary sequestration as something that must be addressed. Kay also addressed the need for enhanced scientific communications that do not require an “official” FDA meeting. Michael Werner (the Alliance for Regenerative Medicine) called for PDUFA to empower the FDA to work with outside bodies to help develop development and review standards– an idea that has resonance beyond regenerative medicine (biomarkers, functional endpoints, etc.)

The academic panel added robust ideas to the more general discussion of advancing regulatory science.

Greg Daniel (Brookings Institution) called for a PDUFA strategy that would drive agency coordination of pre-competitive biomarker development as well as a common biomarker lexicon.

Daniel Carpenter and Aaron Kesselheim (Harvard University and Harvard Medical School) questioned whether various expedited approval pathways were focused on medicines they considered “non-transformative,” what they referred to as “designation creep.” Policy vs. process.

Ernst Berndt (Massachusetts Institute of Technology) broached the topic of “adaptive licensing,” pointing to EMA programs and their progress under the Innovative Medicines Initiative.  To-date, the concept of conditional approvals has found very little support or enthusiasm from either developers or the FDA. Whether or not Dr. Berndt’s suggestion gets traction will depend on how it resonates with any of the various PDUFA constituencies. The last time I spoke with senior members of the FDA, I heard comments like, “What does that even mean?” And, then again, do drug developers really want conditional approval? You invest a lot of time and money to get a conditional approval and then the agency decides to take the product off the market? Is that something to roll the dice on? Unless and until the FDA can ramp up its pharmacovigilance prowess, any kind of provisional approvals will remain problematic. At the moment, the FDA doesn’t have an eye in the sky.

Rena Conti (University of Chicago) raised the topic of drug sourcing. Is there, she asked, an unintended PDUFA incentive to outsource manufacturing – and what are the consequences? She called for greater transparency in who manufactures what – and where.

The final presentation of the day was by Dr. Janet Woodcock (Director, Center for Drug Evaluation and Research). The items on her short list mirrored many of the day’s presentations and themes. Specifically she mentioned the need to advance the agency’s Sentinel program, continue to develop a more advanced view of benefit/risk – and one that includes a more dynamic inclusion of the patient voice, next steps on Patient-Focused Drug Development, better and more regular communications with developers, biomarker development (“still a tremendous amount to be done”), the need for the agency to recruit and retain the best and the brightest, and, of course, advancing regulatory science writ large.

She also warned of getting off the process track – a clear warning shot across the bow to those ready to hang multiple ornaments on the PDUFA Christmas tree.

At the conclusion of the day’s session I was pleased to be able to offer some advice during the open public comment period. Here’s how I concluded my remarks:

“PDUFA VI must continue to provide predictability in the review process and advance regulatory science over a variety of initiatives. But most importantly, PDUFA VI must answer the question of “What next?” for many of the agency’s existing initiatives (biomarkers, risk/benefit evaluation, patient-focused drug development, 21^st century clinical trial design).  PDUFA VI must redefine what “success” looks like. Dr. Ostroff asked us to aim for the stars, but let’s not settle for an easy, clean, comfortable, and low-altitude orbit.

Per aspera ad astra – Through hardships to the stars. We’ve had FDAMA. We’ve had FDASIA. Now we need FDAMN – FDA Momentum Now.

Nobody said it was going to be easy.

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"J" is for Janus

07/10/2015 08:17 AM |

The Biosimilars Forum represents many of the leading voices against differential nomenclature -- except when it comes to Medicare coding.

Yesterday this group expressed “grave concern” over the proposed biosimilar payment rule issued by CMS. (CMS is proposing that multiple biosimilars to the same reference product be grouped and issued the same J-code for Medicare reimbursement purposes.)

According to Biosimilars Forum policy advisor Michael Werne, the biosimilars statute, and its legislative history “make clear that each biosimilar product — including multiple biosimilar products associated with the same originally marketed product — should be assigned a unique HCPCS code.”

According to Werne, “The lawmakers who passed the Biologics Price Competition and Innovation Act of 2009 (BPCIA) understood that biosimilars are not the same as generic drugs and should not be treated that way in policy making.”

Per the groups press release, “Furthermore, the statute makes it clear that an interchangeability determination only applies to a specific biosimilar and the reference product, and does not apply between or among multiple biosimilars approved to a single reference product. Issuing unique HCPCS codes is essential to avoid confusion among healthcare professionals, to ensure that the proper products are dispensed to patients, and to allow a fair and predictable reimbursement to purchasers of biosimilars.”

But wait – there’s more. “The law, legislative history, and biosimilar science support the requirement that CMS assign each biosimilar biological product a unique HCPCS code and not consider biologics and biosimilars in the same fashion as generic drugs.”

And yet some members of this group are against differential nomenclature. Go figure.

(The full Biosimilars Forum press release can be found here.)

Hypocrisy is the Vaseline of political intercourse. – Billy Connolly

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