FDA's Woodcock Sends Patients Strong Message With Exondys 51 Approval

09/19/2016 01:19 PM | Robert Goldberg

The FDA's press release announcing the accelerated approval of Exondys -- the first drug for Duchenne muscular dystrophy -- sends a very important message.


The prose is PR-speak 101.  The meaning is in the messenger:

"The U.S. Food and Drug Administration today approved Exondys 51 (eteplirsen) injection, the first drug approved to treat patients with Duchenne muscular dystrophy (DMD). Exondys 51 is specifically indicated for patients who have a confirmed mutation of the dystrophin gene amenable to exon 51 skipping, which affects about 13 percent of the population with DMD.
“Patients with a particular type of Duchenne muscular dystrophy will now have access to an approved treatment for this rare and devastating disease,” said Janet Woodcock, M.D., director of the FDA’s Center for Drug Evaluation and Research. “In rare diseases, new drug development is especially challenging due to the small numbers of people affected by each disease and the lack of medical understanding of many disorders. Accelerated approval makes this drug available to patients based on initial data, but we eagerly await learning more about the efficacy of this drug through a confirmatory clinical trial that the company must conduct after approval.”

Why is this release different from all other releases?

In most FDA releases about new drug approvals, the director of the division that reviewed the drug is quoted.  

In this release, Janet Woodcock, who runs the whole show is quoted.  

Woodcock has been publically involved in taking the FDA's good intentions about involving patients in the design of clinical trials and in defining study endpoints as well as encouraging scientifically rigorous alternatives to randomized clinical trials that can bring medicines to market faster as well as allow more patients to participate in a study without randomization.  

After the FDA committee initially rejected Sarepta's application for accelerated approval,  virtually attacking the patient community for not supporting a randomized trial.  

So of course so-called patient advocacy organizations that attack and question new medicines at every turn hailed the first denial.   The expertly and eternally ignorant Diane Zuckerman, president of the National Center for Health Research sums up the anti-innovation tunnel vision: "If this drug is approved — on the skimpiest, most pathetic data I’ve ever seen — then it is going to set a precedent that is very uncomfortable." 

Woodcock stepped in at that meeting to note that too often the FDA focuses on not approving drugs because they are relatively safe and effective but that it often engages in "little consideration of another error, which is failing to approve a drug that actually works”. But most of this consequence is borne by patients who have little say."

Patients had a lot to say about the study design and basis for Exondys 51's  approval.  The FDA's bureaucrats and it's supporters among the handful of elites used the initial denial to derail such involvement.  How ironic that these individuals, who pontificated about using data, not emotion, to determine drug approvals, made extreme and factually false statements (See, Zuckerman, Diane) before and after the denial.

 Exondys 51 is now approved.   So too is a pathway that allows patients who bear the risk of clinical trials and the burden of disease to have a say in how medicines should be measured and used.  DMD advocate Christine McSherry, Executive Director of the Jett Foundation, stated that the DMD community’s involvement in drug approvals “will change the way people confront barriers to justice in society. This will be historic not just in Duchenne, not just in rare disease, but for every ordinary individual who has felt the need to change a broken system but never knew how to do it.”


Christine McSherry and her son Jett

Increasingly medical advances determine not only whether we live or die, but how we will live and die.  Ordinary citizens, like Christine McSherry who are potential patients and the friends and relatives of such patients have as much to say on these innovations as any so-called expert. 

That's what Janet Woodcock's announcement means.     Read More & Comment...

Sarepta and the Value of Adaptive Clinical Trials

09/19/2016 12:28 PM | Peter Pitts

Here’s a new op-ed from the Cleveland Plain Dealer. It speaks directly to today’s FDA approval of Sarepta.

Consider what the editor chose to add to my attribution at the bottom of the article:

“Peter J. Pitts, a former FDA associate commissioner, is the president and co-founder of the Center for Medicine in the Public Interest. CMPI receives some funding from biopharmaceutical firms, which could benefit from adaptive trials.”

I suggested that he also add that adaptive trials benefit patients. He declined.  I wonder what the parents of children with Duchenne muscular dystrophy would say?

Build better drugs faster with nontraditional, adaptive clinical trials

Breast cancer surgeon Dr. Laura Esserman of San Francisco sings to her patients as they go under anesthesia. She tackles any song request, whether it's a top 40 hit or a Broadway ballad. This same patient-centric attitude drove Dr. Esserman to participate in adaptive clinical trials, a game-changing way to test new medications.   

It's past time that other researchers think beyond traditional clinical trials.

Adaptive trials can make drug testing both more efficient and accurate. If regulators were to encourage greater use of adaptive trials and facilitate sharing of electronic health record data, researchers could deliver better drugs to patients, faster. 

In a traditional clinical trial, researchers plan out every element of the trial -- from the number of participants to the type of data to be collected -- before they begin testing. They stick to this rigid master plan until the trial is complete. 

But in an adaptive trial, researchers preplan certain modifications that they can make partway through the trial, based on the results they've uncovered so far.  

Think of it in terms of mapping a run. A runner might look at a map and realize that at one point, the road will fork. Instead of deciding whether to go left or right before he ever begins jogging, he might choose to postpone the choice until he actually reaches the fork. Perhaps he'd like to observe which path is muddier or which path has less traffic -- and he'll only know when he gets there.

Similarly, researchers administering adaptive clinical trials can modify their tests as they make observations. Like the runner, they have to preplan what choices they'll make and when. But the more flexible trial formula enables them to alter the trial in response to real-world results. 

The staff at the Case Western Reserve University/University Hospitals AIDS Clinical Trials Unit is using a new video, brochures and other community outreach efforts to invite women without HIV to participate in HIV-related studies.

Dr. Esserman's trial, for example, personalized testing by splitting breast cancer patients into different groups depending on various measurements of their health. She tested a combination of therapies on these patients -- and only continued testing those that were found initially effective. By not having to run a dud treatment through the course of a standard clinical trial, the adaptive design reduced the cost, time, and number of patients needed for the trial. 

Similarly, a group of Florida physicians used an adaptive trial to test and quickly identify the most effective dosage for a drug that relieves post-operation pain. 

By not having to run a dud treatment, adaptive design reduced the cost, time, and number of patients needed.

The U.S. Food and Drug Administration (FDA) currently permits adaptive trials in limited instances. Letting researchers use this model more often would improve the drug development process. 

Another way to improve the process is to enable doctors, insurers, and drug companies to share data on patients' health outcomes after they take new FDA-approved medicines. By analyzing this data, they could uncover patterns that can't be detected even in the largest clinical trials.

Companies like Explorys are pioneering Big Data in the health care realm, raising prospects of a Cleveland niche in an emerging industry. For instance, a clinical trial for a diabetes drug might include 1,000 participants, ten of whom are Native American. Perhaps 60 percent of all patients respond well to the drug, but all ten Native Americans get their blood sugar under control thanks to the medicine. 

It's impossible to tell from such a small sample size whether the medicine really is vastly more effective for Native Americans, or whether those ten patients just got lucky.

The real world offers much larger sample sizes. Assume a million patients take the drug after the FDA approves it, and 10,000 are Native American. If doctors, insurers, and research firms had access to those patients' electronic health records -- with names and other identifying information stripped away, of course -- they'd be able to determine if the drug should be the go-to prescription for Native Americans with diabetes, or if the promising results from the clinical trial were a fluke.

Changing regulations to permit greater sharing of such data would help researchers unveil rare side effects, complications, or "miracle" results that crop up. That would make drugs safer and ensure that the right patients receive the best treatments possible.

Adaptive trials and increased data sharing would deliver better medicines to patients faster and with greater safety. That's something to sing about. 

Peter J. Pitts, a former FDA associate commissioner, is the president and co-founder of the Center for Medicine in the Public Interest. CMPI receives some funding from biopharmaceutical firms, which could benefit from adaptive trials.  Read More & Comment...

When is access not access?

09/17/2016 08:52 PM | Peter Pitts

From the current edition of Newsweek …

There Is a Sure Cure, but It’s Not Covered by Your Health Insurance Plan

When 41-year-old New Jersey resident Amy Speicher was diagnosed with advanced skin cancer, she feared the disease as well as the hair loss, vomiting and crippling fatigue that usually come with cancer treatment.

None of that came to pass. Speicher sailed through her treatment, balancing parenting and a full-time job. How? Her insurance paid for a groundbreaking immunotherapy, which has far fewer side effects than run-of-the-mill chemo.  

Unfortunately, her story is the exception. Throughout the country, insurers increasingly shun the most advanced cures, treatments and tests because they don't want to foot the bill. This short-term focus on profits is callous—and counterproductive. Denying patients the best health care leaves them sicker, ultimately raising insurers' expenses.

In recent years, insurers have replaced fixed co-pays—say, $20 at the pharmacy—with "co-insurance," where patients are asked to pay a percentage of an advanced medicines' total cost. Insurers know many patients can't afford these payments and will ask their doctors for less expensive—and often, less effective—medicines.

Insurers have also embraced "fail first" policies to limit patients' access to cutting-edge treatments. Such policies require patients to use cheaper treatments first. Only if those treatments fail—and patients get sicker—do insurers pony up for cutting-edge drugs.

Increasingly, insurers are also refusing to pay for some treatments unless a doctor first seeks permission before writing a prescription. Most drug regimens should begin immediately, so waiting days or even weeks for an insurer to approve a doctor's prescription simply isn't tenable.  

Consider the case of Angela and Nate Turner, both addicted to opioids. Their doctor sought insurer permission to prescribe a treatment that lessens drug cravings. As the insurer delayed, precious time passed. Angela became violently ill from withdrawal after waiting for three days. After waiting five days, Nick succumbed to his urges and used heroin.  

Insurers are even reducing coverage of preventive care.

For instance, insurers in New Jersey, Tennessee and North Carolina have stopped covering the only genetic screening test approved by the Food and Drug Administration. Such tests scan for genetic mutations that often lead to hereditary breast or ovarian cancer. The insurers now cover only cheaper, lower-quality genetic tests, none of which have proved to be as accurate.

The less-precise tests could raise a woman's risk of receiving a false positive, a test result that incorrectly concludes she's likely to get cancer and should undergo expensive preventive surgery. Worse, lower-quality tests could also lead to false negatives. Women would incorrectly think they have little risk of cancer and opt out of preventive surgeries that could save their lives.

Subpar insurance harms patients' financial health too. Using a better medicine or genetic test from the start prevents lost productivity and needless hospitalizations. In fact, for every dollar spent on newer advanced medicines, non-drug medical spending drops by more than $7.

Insurers know that better preventive care is ultimately cost-effective. But they hesitate to make large up-front investments in patients' health since people frequently switch insurers. Companies don't want to spend heavily—and jeopardize their sacred quarterly results—to save their rivals money a few years down the road.

But this short-term thinking won't save them in the long run. If the overall pool of insured people becomes sicker, insurers' expenses will increase. Year-to-year fluctuations obscure the fact that insurers are just recruiting each other's sick people.

Under the Affordable Care Act, insurers can't resort to their old practice of flat-out denying people coverage. And their new strategies of restricting access to the best treatments only make people sicker, delaying the inevitable expense of covering their care.

Health care economists tout "precision medicine"—the strategy of giving patients treatments and tests uniquely suited to their health and genetic backgrounds—as a way to ultimately prevent and cure illnesses and curb health care spending. But precision medicine works only if insurers pay for the treatments doctors recommend.

If insurers want to help their customers, and their own bottom lines, they need to think long term and cover treatments that prevent and wipe out diseases.

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

Amundsen turns frosty on biosimilars

09/16/2016 02:24 PM | Peter Pitts

When it comes to biosimilars, where is True North?

An interesting new paper on the value of biosimilars from the folks at Amundsen Consulting. The paper is appropriately titled, “Who Saves?” The answer isn’t what patients want to hear.

Per the report:

“It may be difficult for patients, physicians, and advocates to understand the value of biosimilar therapies: Because patient costs are not likely to decline, use of biosimilars may be especially difficult to rationalize for those patients who are already gaining clinical benefits from innovator therapies. Without the realization and effective communication of how payers will use savings to support patient care or reduce cost, the value of biosimilars to the U.S. healthcare system will be limited ... Therefore, it is critical that the savings recognized by other parties translate into meaningful improvements in access or new pro­grams/initiatives that advance patient care. Moreover, they need to be communicated to patients and plan sponsors effectively."

The complete paper can be found here.
   Read More & Comment...

UN Panel Proposes To Stifle Medical Progress

09/15/2016 01:51 PM | Robert Goldberg

My colleague Peter Pitts has penned an eloquent response to the UN Secretary General’s High Level Panel on Access to Medicines Report. 

The Report is entitled: Promoting Innovation and Access to Health Technologies.  But that’s false advertising.  The report recommends shredding patent protection for new medicines and claims that the cost of medical innovation should have nothing to do with prices.  

I am not surprised.  The recommendation has nothing to do with the facts.  Rather, the panel claims that there is "policy incoherence between the justifiable rights of inventors, international human rights law, trade rules and public health.”

Really?   Seems to me that the thousand-fold improvement in public health worldwide is the result of the commercialization of medical inventions.  As Nobel Prize winning economist Angus Deaton has observed: “Progress in health has been as impressive as progress in wealth. In the past century, life expectancy in the rich countries increased by thirty years, and it continues to increase today by two or three years every ten years. Children who would have died before their fifth birthdays now live into old age, and middle-aged adults who once would have died of heart disease now live to see their grandchildren grow up and go to college. Of all the things that make life worth living, extra years of life are surely among the most precious.”

But the UN panel breezes through how this progress has been achieved – and how countries such as Venezuela has starved its people -- to argue that inequalities of access require redistribution and confiscation of private property.    

To be sure, progress has opened up inequalities as new medicines originated in America (for the most part) and were consumed there first at launch prices that put such drugs out of reach for much of the world. As Professor Deaton notes: “These “health inequalities” are one of the great injustices of the world today... (But) when new inventions or new knowledge comes along, someone has to be the first to benefit, and the inequalities that come with waiting for a while are a reasonable price to pay. “

That is, eliminating inequality is less important than eliminating disease or poverty. And in my opinion the UN panel’s ideas and ideology should be judged by whether or not it will increase absolute well-being not whether it makes Paul Krugman happy. 

The idea that letting rogue states violate IP will somehow increase well-being should have died with Venezuela, Argentina Brazil, India or Thailand.  There is no empirical evidence that state regulation promotes betterment.  On the contrary, the countries pushing for greater government control over private ideas are also societies where the extreme inequality of power strangles growth, including Russia and China. 

Not surprisingly, in such countries the confiscation of IP is just another tool for rewarding rich and powerful interests.  Government production of medicines through compulsory licensing with contracts to produce and counterfeit US developed innovations.  As Deaton notes: “Powerful and wealthy elites have choked off economic growth before, and they can do so again if they are allowed to undermine the institutions on which broad-based growth depends.”

The UN Panel is not simply assaulting patent protection.  It is attacking, as the brilliant economist Deirdre McCloskey observes, two levels of ideas: the ideas in the heads of entrepreneurs for the betterments themselves (the electric motor, the airplane, the stock market); and the ideas in the society at large about the businesspeople and their betterments (in a word, that liberalism).

The UN Panel on Patent Expropriation is, to paraphrase McCloskey “obsessed with first-act changes that cannot much help the poor, and often can be shown to damage them grievously, and are obsessed with an angry envy at the consumption of the very rich. They are willing to stifle, through the generation and commercialization of ideas that lead to greater well-being the trade-tested betterments that in the long run have gigantically helped the poor.”

This assault on health innovation is not only an attack on American productivity, it is a direct hit on the access to medicines the panel professes to promote. 


   Read More & Comment...

Forrest Gump for UN Secretary-General

09/14/2016 03:49 PM | Peter Pitts

Just when you thought it was impossible for the United Nations to be less relevant comes The Report of the United Nations Secretary-General’s High-Level Panel on Access to Medicines.

What’s the UN’s answer to broader access to medicines? Doing away with patents. Disregarding intellectual property. Compulsory Licensing. A triple-play of nonsense and unintended consequences. But we’ve heard it all before.

The UN is living proof of HL Mencken’s famous maxim that, “For every complex problem there is an answer that is clear, simple, and wrong.”

The focus of the UN report is on new, on-patent medicines, but the report ignores the WHO’s model Essential Drug List. Why? Because it doesn’t fit the narrative of “Big Pharma as the enemy.” After all, very few of the 400 or so drugs deemed essential are new, or patented or were ever patented in the world’s poorest countries.  In category after category, from aspirin to Zithromax, in almost every case and in almost every country, these medicines have always been (or have been for many years) in the public domain.  That is, the medicine is fully open to legal and legitimate generic manufacture.

And yet, they are not readily available.

There are important implications for the world’s poorest patients. If these patients had reliable and affordable access to these several hundred essential medicines, all available theoretically as multi-source, that is from generics companies, then global mortality and morbidity might be cut as much as 10-20% — a huge gain for populations around the world. Given the potential hugely positive impact on access to medicines, any reasonable person might ask why doesn’t a body that largely represents the needs and desires of the Developing World address this issue?

The UN report isn’t a serious attempt to address access. It’s just another political broadside against patents and intellectual property. For shame.

Perhaps the next Secretary General of the United Nations should be … Forrest Gump.

Neatly timed to coincide with the UN’s screed comes Colombia’s Declaration of Public Interest to impose additional price cuts on the Novartis’ Gleevec. This decision has the potential to result in higher spending on lower-quality generics. Here’s how PhRMA’s Brian Toohey directly addresses the issue,

“There continues to be no legitimate reasons for Colombia to enforce a declaration of public interest for the product in question. This medicine is being provided to all Colombian patients who need it and almost half of the patients needing the drug are taking a generic version. In addition, the medicine has been sold in Colombia at a price negotiated and agreed to by the Colombian Government under its existing pricing system and there is no apparent shortage or evidence of other access issues. The Colombian Government’s actions are therefore without merit.

“Biopharmaceutical innovators support strong national health systems and timely access to quality, safe and effective medicines for patients who need them. Ad hoc price cuts are not effective or sustainable ways to improve access or achieve other critical public health goals. Pricing systems should be based on transparent rules and fair processes that provide business certainty for pharmaceutical innovators.

“The enforcement of a declaration of public interest as a mechanism to impose superfluous price controls sets a harmful global precedent, undermining the incentives that enable high-risk research and development investments in life-saving medical innovation and a host of other cutting-edge industries.

“The way to achieve access to medicines is not through compromising incentives for innovation but by leveraging the collective abilities, strengths and resources of all stakeholders to improve health outcomes.”

Bravo.  Read More & Comment...

Allergan's Social Contract: Replace Rebates With Increased Patient Protection From Drug Prices

09/08/2016 01:41 PM | Robert Goldberg

Allergan CEO Brent Saunders published a social contract with patients on his corporate blog.   In doing so, Saunders demonstrates that the first question for a leader always is: 'Who do we intend to be?' Not 'What are we going to do?' but 'Who do we intend to be?

Saunder's begins by noting that large price increases undermine the mission of medical innovation:

“Basically, in this social contract patients understood that making new medicines required significant investment.   At the same time companies, doing the hard, long and risky work of bringing new medicines to market, understood that they had to price medicines in a way that made them accessible to patients while providing sufficient profit to encourage future investment.  It was designed to be a win-win-win.  New medicines for patients.  Lower overall cost or damage of disease.  An appropriate return on capital for those taking risk by investing time and talent in the arduous and uncertain task of developing new treatments.

Those who have taken aggressive or predatory price increases have violated this social contract!

I don’t like what is happening, and despite the fact that it is hard to speak out publicly on this, now is the time to take action to spell out what this social contract means to me.  By doing so, I am conveying to my Allergan colleagues that we must keep this social contract in mind as we make business decisions that ultimately improve wellbeing, and as a result, address the hopes others place in us.”

Saunders first observes that “large payers making decisions that may limit patient access to our medicines in favor of a competitor based on the latter’s willingness to pay more rebates.  In order to ensure that patients and physicians have access to a full array of medical options, we believe that these intermediaries should have open access to formularies whenever possible. “

In the main however, he discusses what his company will do to reinvigorate the social contract with patients: 

We commit to these responsible pricing ideals for our branded therapeutics.
•    We will price our products in a way that is commensurate with, or lower than, the value they create by mitigating or avoiding the need for other treatment modalities or providing better quality of life to those patients without other treatment options.
•    We will enhance access to patients.  This means that Allergan will enhance our patient assistance programs in 2017 to match the current industry leader(s).
•    We will work with policy makers and payers to facilitate better access to our medicines.
•    We will not engage in price gouging actions or predatory pricing.
•    We will limit price increases.  Where we increase price on our branded therapeutic medicines, we will take price increases no more than once per year and, when we do, they will be limited to single-digit percentage increases.  Our expectation is that the overall cost of our drugs, net of rebates and discounts, will not increase by more than low-to-mid single digits percentages per year, slightly above the current annual rate of inflation. 
•    We will not engage in the practice of taking major price increases without corresponding cost increases as our products near patent expiration. While we have participated in this industry practice in the past, we will stop this practice going forward.  Where new regulatory requirements impose added costs, we will seek to reflect those costs in our pricing.
•    We commit to providing an aggregate view of the net impact of price on our business at least annually.

Three quick observations:

1.    Every biopharmaceutical company should take or make the same pledge.   Failing to do so is tantamount to siding with price gouging. 
2.    To limit out of patient of pocket costs Allergan will consider taking the rebates now pocketed by PBMs and insurers and give them directly to patients in the form of increased patient assistance. Other biopharma companies should make the same pledge.
3.    The Allergan social contract includes ensuring that the increased cost of government regulation not be passed on to consumers whenever possible and to limit price increases net of rebates.  See point 2 for how this will be done. 

If most drug companies adopt and live up to the Allergan social contract it would be the most disruptive and positive step the industry has ever taken to establish its value.    

Ultimately, biopharmaceutical companies will need to replace the current business model in which hundreds of billions in rebates go to corporate profits, not patients and in which so-called drug value framework builders are focused on driving down drug prices to increase rebates under the guise of making drugs affordable to patients.   

Hence, the social contract developed by Brent Saunders is also a call to replace a business model that has become financially and morally unsustainable.  To increase and accelerate access now, companies have to reward insurers and PMBs less and help patients more by reducing the cost (and increase in cost) of medicines.  Otherwise any social contract with patients will be an exercise in hypocrisy.    Read More & Comment...

FDA's Seven Year Itch

08/31/2016 08:05 PM | Peter Pitts

Almost seven years to the day of the FDA's November 2009 two-day Part 15 hearing on social media, a new Part 15 meeting on off-label communications, Manufacturer Communications Regarding Unapproved Uses of Approved or Cleared Medical Products; Public Hearing

The 2009 affair was "The Super Bowl of Part 15 hearings." Attended by hundreds of interested stakeholders, many of who were skilled communications professionals. The FDA listened as speaker after speaker (including me) offered timely comments on the new frontier of social media. The FDA listened -- and then waited until June 2014 to issue draft guidance.

The big difference between that meeting and the November 2016 version is that there are already a slew of lawsuits that have seriously undercut the agency's authority in regulating off-label speech. Another important difference is that industry already has released its own guidelines. It's also important to note the meeting will take place immediately after national elections. If the folks at White Oak think this will deter attention, they are mistaken.

The agency is soliciting comments as to the ways communications from drugmakers regarding off-label use information are distinct, and whether they provide unique benefits compared to other sources. The announcement lays out eight lengthy sets of questions. Some specific ones are:

* What are the benefits for clinical decision making, research, coverage, reimbursement or other purposes if firms communicate to health care professionals, payers, researchers and patients information about off-label uses? Are there risks, and ways to mitigate these risks?

* To what extent do changes occurring in the health care system that give payers and formulary committees more influence on prescribing decisions provide incentives for firms to generate the necessary high-quality data demonstrate safety and effectiveness for off-label uses?

* What processes do firms use to determine whether information is scientifically appropriate to communicate to health care professionals about a product?

* What information should firms communicate to make audiences aware that the medical product is not indicated for a certain use and to distinguish between the approved uses of the medical product and the unapproved use?

The agency is asking a lot of excellent questions, but they've had a lot of time to ponder all of them already. The only thing that is clear is that no guidance on the topic will be forthcoming until well after a new President takes office -- and that could have profound implications on the direction of both agency thinking and timing.

It will surely be worthwhile, but can the sequel live up to the original?  Read More & Comment...

ICERs Sins of Omission

08/30/2016 05:47 PM | Robert Goldberg

An article in The Huffington Post and the Global Living Healthy Foundation's blistering response to ICER’s defense against against criticism that I and others made about how anti-patient and pro-rationing it is, makes my planned second post about the organization unnecessary.  As Patient Rising’s Jonathan Wilcox put it in the HuffPo piece, ICER claims it is objective because it uses:
 
“…mathematical calculations known as “value frameworks” to justify the nonprofit’s preference to target certain drugs. But this is no unbiased test or dispassionate statistical measurement. It’s a Catch-22 in which patients can’t win because the ICER process determines they have a lesser quality of life than a healthy person – forever. “
 
Similarly, the Global Health Living Foundation had this to say about ICER’s zealous defense of the quality adjusted live year as a perfectly ethical and rigorous measure of what patient’s truly value from medical care:
 
“The QALY was ultimately found to be so offensive and contradictory to the beliefs surrounding patient care in the U.S. that its use in computations was disallowed (outlawed) by the Affordable Care Act. The ban on using cost-per-QALY thresholds also seems to reflect longstanding concerns that the approach would discriminate on the basis of age and disability. The worry is that the metric unfairly favors younger and healthier populations that have more potential QALYs to gain.”
 
Ouch.   ICER continues to evade this important question.  Apart from some soft promise to look at QALYs going forward, it continues to double down on their use in determine access to and price of medicines.  And despite the legitimate ethical and methodological  questions about ICER’s work,  JAMA is willing to be ICER’s seal of medical approval. 
 
Case in point: JAMA’s recent publication of “Cost-effectiveness of PCSK9 Inhibitor Therapy in Patients with Heterozygous Familial Hypercholesterolemia or Atherosclerotic Cardiovascular Disease.”   This is a recycling of ICER’s blacklisting of the two PCSK9 inhibitors that reduce high cholesterol in people who – because of a specific mutation or side effects – don’t respond to statins. 
 
 I am not surprised that JAMA would publish a high speculative and poorly constructed comparative effectiveness article.   That’s because in general most CER work winds up in medical journals where – to put it gently – the reviewers of articles have little or no expertise in econometrics or best practices for health economic studies. I even wonder if the reviewers even read the article or did more than check for typos.  For instance, in the JAMA article on the authors conclude:
 
“The results of multiple scenario analyses suggest that reducing the price of PCSK9 inhibitors remains the primary approach to improving the value of these therapies.”
 
The article goes on to say that “If ongoing clinical trials demonstrate that the drugs do not improve clinical outcomes as predicted by their effect on LDL-C, this model will have overestimated their cost-effectiveness.”
 
The authors completely ignore the other possibility: that studies will show increased cost-effectiveness.  This violates a cardinal principle of HTA research:
 
“All data are imperfect point estimates of underlying distributions that incorporate a variety of errors. All analytical methods are subject to biases and limitations. Thus, extensive sensitivity analyses are required to determine the robustness of HTA findings and conclusions. The limitations of the analysis should always be acknowledged.”
 
The JAMA/ICER study also violate best practice principles for cost effectiveness analysis proposed by the International Society for Pharmacoeconomics and Outcomes Research (ISPOR) Drug Cost Task Force Report:
 
“The task force recommended discouraging studies from claiming that they are taking a true societal perspective when they are not. “
 
Yet ICER continually claims that their studies and recommendations consider ‘societal choices’ even though the costs and benefits of such choices are never formally modeled. 
 
Further, ISPOR the task force suggests that studies state “that using some fraction (e.g., 40–60%) of net acquisition drug cost (i.e., cost net of discounts and rebates) would be an appropriate proxy for opportunity cost for a societal CEA for marketed products, but that a limited societal or a health systems perspective is more relevant and useful for current decision-makers.”
 
ICER ignores this modest proposal claiming it is too hard to estimate net drug costs (even as it has no problem estimating for patients how much their lives are worth.)  This speaks to the fact that ICER gets most of its money from insurers and PBMs.  That’s not a problem so long as all the exceptions to best practices are identified and limitations of ICER studies with regard to measure societal value are highlighted. 
 
 As a I have mentioned elsewhere, ICER uses list price to establish how much drug prices should be cut to be cost effective.  It ignores the fact that the discounts and rebates to reach that price would go right to insurers, employers and PBMs, not patients whose QALY hangs in the balance.  It fails to acknowledge that the choice of list price will affect it’s analysis or that it reflects the perspective of the health system.
 
ICER can get away with recycling it’s biased research in JAMA.  The publication’s reviewers of HTA are about as effective in policing violations of basic HTA practices as the UN Peacekeeping Force in Lebanon is in preventing Hezbollah from threatening Israel.
 
But ICER’s day of reckoning is coming. Patients, researchers, real economists and others are beginning to challenge the role of ICER specifically (and pre-determined value frameworks in general) in making life changing decisions on behalf of everyone else.   Read More & Comment...

JAMA's Pizza Principle

08/30/2016 12:55 PM | Peter Pitts

From today’s edition of the Detroit News …

Doctor-industry lunches are good for you

Drug firms have discovered a powerful new mind-control technology that threatens to topple our healthcare system: a free slice of pizza. That’s the implication — but not the actual findings — of a new study in JAMA Internal Medicine.

The report finds that physicians who accept complimentary meals of under $20 in value from pharmaceutical representatives are more likely to prescribe certain brand-name medications to Medicare patients. The more frequent — and more expensive — the meals, the greater the effect on doctors’ prescribing rates.

Is the drug industry corrupting America’s medical practitioners through a cunning use of appetizers? Not quite. The study fails to mention that doctors voluntarily attend these meetings to stay informed about new medicines — not new recipes.

What’s more, the article never bothers to ask a basic question: are doctor-industry interactions bad for the health of patients? To date, there is no evidence to suggest that they are.

In reality, meals are often provided as part of educational events hosted by drug companies. The point of these meetings is to convey technical information to doctors about a particular drug. Doctors who attend the meeting and learn about a medicine’s clinical effectiveness are obviously more likely to prescribe that drug than physicians who didn’t go to the meeting and have never heard of the medicine. Similarly, doctors who already prescribe a company’s medicine are more likely to receive lunch invites than doctors who aren’t in sales reps’ rolodexes.

In other words, it’s hardly surprising or scandalous that doctors who meet with salespeople are more likely to use what they’re selling — once they’ve learned about the value of the medicines being discussed.

Complaints about drug-company influence would be a lot more credible if researchers could show it harmed patients’ well-being. For instance, do free meals compel doctors to prescribe a brand-name drug when a cheaper generic would suffice? Do they persuade physicians to use one particular treatment when a different therapy would be more effective?

There’s simply no way for physicians to stay current on every pharmaceutical product at their disposal. By one estimate, some 1,700 articles are published on the top 25 medicines each year. Drug producers use a variety of promotional efforts to cut through this information glut.

Dennis Ausiello, chief of medicine at Massachusetts General Hospital, and Thomas Stossel, a professor at Harvard Medical School, have made this point. According to them, “company salespersons complement physicians’ information derived from many sources. They tell physicians about a limited range of products about which their employers train them under strict FDA regulations.”

Since when did transmitting accurate medical information to doctors become a bad thing?

To be sure, pharmaceutical firms are motivated by profit. But improving patient health and boosting sales aren’t mutually exclusive ends — especially when the product in question addresses a genuine public health need.

Moreover, it’s simplistic and insulting to assume that highly-educated doctors are selling out their patients for the price of a slice. In a 2008 survey of physicians conducted by KRC Research, only 11 percent reported being greatly influenced by pharmaceutical representatives. Clinical knowledge, a patient’s specific circumstances, and insurance restrictions all played a larger role in determining prescribing practices.

Let’s hope misinterpreted studies and manufactured media outrage don’t lead to further restrictions on these meetings. If that were to happen, doctors might go without a free lunch — but patients would go without the best treatment plans possible.

Peter Pitts, a former FDA associate commissioner, is president of the Center for Medicine in the Public Interest.  Read More & Comment...

Today's Mylan Moment: Drug Prices Are Rigged By PBMs and Insurers

08/29/2016 12:07 PM | Robert Goldberg

From  Drugchannels:  “Ronny Gal, Ph.D., a senior analyst at the investment bank Sanford C. Bernstein & Co., just published a great client note on the Mylan EpiPen pricing brouhaha.”  
 
Gal’s note should be read and memorized by every reporter, editorialist, talking head so that it is seared into their frontal cortex when writing about drug prices.  I have helpfully italicized and placed the critical indights in bold.  And I have given these important observations their very own paragraphs.
 
Thus spake Gal:
 
 
“We received multiple questions from investors about Mylan rolling back price increases.
 
The problem is that this would not necessarily help consumers much.
 
 The price charged to consumers is set by payors.  
 
(NB  Repeat silently to yourself: The price charged to consumers is set by payors.  The price charged to consumers is set by payors.  The price charged to consumers is set by payors. )
 
Thus, to reduce consumer prices, Mylan would have to renegotiate increases, discounts and rebates to the payors; this will take some time and we suspect payors are not too unhappy seeing Mylan swinging in the wind a bit. Further, they will demand some steep discounts to help Mylan off the hook."
 
(NB: Note that in order to reduce prices to consumers, Mylan would have to also pay PBMs and insurers a discount, just because)
 
My next post will explain why Mylan’s authorized generic strategy, while risky, is also inspired and could launch a movement of companies who will refuse to payoff PBMs, insurers, hospitals and government agencies and use the money to cover drugs at point of care.  

But for now, I hope everyone takes Ronny Gal's insights to heart and applies them when writing, talking or debate about drug prices.  

Failing to do so is tantamount to lying.   Read More & Comment...

Bee Smart About Drug Pricing

08/29/2016 11:13 AM | Peter Pitts

From today’s edition of the Sacramento Bee …

Rising drug prices the fault of insurers, not drug companies

By Peter J. Pitts
Special to The Bee

Republican voters hate Obamacare, but they hate high prescription drug prices even more. Health care scholar Avik Roy recently pointed to the polls as a reason the GOP must develop a “clear plan to tackle the high and rising price of branded prescription drugs.” He proposed a number of measures aimed at reining in supposedly greedy pharmaceutical firms.

But Roy, like many others who have weighed in on the cost of medicines, overlooks two key points. First, the very real financial pain many Americans feel at the pharmacy counter is the fault of insurers – not drug companies. Second, the obsessive focus on cost obscures the vastly higher value of new drugs.

For most Americans, the price of drugs means the co-pays or co-insurance they fork over when picking up prescriptions. Insurers, not drug manufacturers, set those rates and they’ve been increasing cost-sharing requirements for years. Of those who buy individual health plans through their jobs, a record 46 percent must pay their first $1,000 of medical expenses.

The insurance industry has managed to pull the wool over Americans’ eyes and convince them that drug prices aren’t tied to the pharmaceutical industry’s investments in research and development. That’s intuitively and factually wrong.

Since 2000, drug firms have spent more than $500 billion developing new medicines. Research costs last year alone totaled almost $59 billion, up from $15.2 billion in 1995. The pharmaceutical sector spends five times more on R&D than aerospace, and two and a half times more than the software industry.

Much of this money goes toward the hundreds of potential treatments that never make it to market. Of those few medicines that enter human testing, just 12 percent win federal approval. The high failure rate is why creating just one FDA-approved medicine costs nearly $2.6 billion.

Drug companies don’t have “infinite pricing power,” as critics claim. Just look at the fierce competition among the makers of hepatitis C treatments. Gilead, the first company to enter the market, priced its two cures, Sovaldi and Harvoni, at $84,000 and $94,500 for full courses of treatment.
Soon other firms entered the market, sparking a fierce price war that led to 50 percent discounts for insurers. Hepatitis C drugs now cost less in the U.S. than in Europe.

Most patients don’t know this – and how would they? Insurers largely pocketed the discounts instead of passing them along to consumers.

Critics’ single-minded focus on drug prices ignores the immense value that modern medicines deliver to patients. Pegasys – the previous “best practice” treatment for hepatitis C – required weekly injections for as long as 48 weeks. Since few patients completed treatment due to severe side effects, much of the drug was wasted. The newer treatments are vastly more effective, curing 90 percent of patients in just 12 weeks, with mild side effects.

And let’s not forget the price of not using these drugs. One in three patients with the hepatitis C virus eventually develops liver cirrhosis, which can require a transplant. A “routine” liver transplant costs close to $300,000.

New and better drugs aren’t a problem; they’re the solution to America’s worsening chronic disease burden. Demonizing the creators of these medicines will do nothing to bring down patients’ skyrocketing co-insurance payments and deductibles. But it would sap investors’ enthusiasm to pour money into expensive research that ultimately saves lives.  Read More & Comment...

EpiPen 'Outrage' Update

08/25/2016 02:33 PM | Robert Goldberg

Great article by Elura Nanos of Law Newz capturing the various viewpoints and thoughts about EpiPens.  (She quotes me in the piece) 

What's Behind the Outrageous Cost of EpiPens

It’s back-to-school time, and for many parents, that means stocking up not only on #2 pencils and pocket-folders, but also replenishing their EpiPens. Parents of children with allergies face the exhausting tasks of obtaining and filling prescriptions, complying with school rules, checking expiration dates, monitoring schools’ use and storage of this medication, and of course, sending their reaction-prone children to school without much more than anxiety-filled hopes that they’ll return home without having an anaphylactic incident. Mylan Pharmaceuticals, the company that produces the EpiPen, makes over $1 billion a year from this life-saving product; but apparently, that’s just not enough. Mylan has now raised the price of a dual-pack of EpiPens to over $600. For those of you keeping score at home, that’s a 500% increase since 2004. Last year alone, Mylan raised the price of EpiPens by over 30%.

Deborah Solomons, Food Allergy Awareness Activist spoke with LawNewz today:

“1 in 13 children suffer from allergies – many of them facing potentially fatal reactions if allergens are ingested. Right now, EpiPen is our best insurance against a life-threatening reaction. We rely on our children’s having access to multiple EpiPens at all times – including in school, at sporting events, and when traveling. Paying hundreds of dollars out of pocket is just not an option for all families.”

Solomons, who is also a licensed clinical social worker, continued on to discuss the global impact such pricing has on families: “It’s stressful enough to deal with the allergies, and the financial burden just compounds the stress.”

The price hike might not feel so offensive had it not come on the heels of Mylan CEO Heather Bresch’s having taken a 600% pay increase, bringing her grand total to $44.7 million over the past two years. There’s also more to hate: Mylan recently did what’s commonly called a “corporate inversion.” The basic concept is that Mylan purchased a smaller pharmaceutical company that is headquartered in the Netherlands; as a direct result of that acquisition, the company is now taxed primarily as a foreign corporation. It will pay taxes at a lower tax rate on some income, and skip out completely on taxes for other income.  Bresch’s take on squeezing Mylan through this tax loophole has been “it’s not me, it’s the tax code;” in the competitive pharmaceutical marketplace, Mylan had no choice but to minimize its tax exposure.

Other companies have attempted to take their place within the epinephrine market, but have failed.   Most recently, Sanofi voluntarily recalled their Auvi-Q, leaving Mylan with an effective monopoly. Whether Mylan has had a hand in squelching its competition remains to be seen – but is certainly the suggestion made by a variety of media outlets and political critics.

Heather Bresch herself has also been involved with a scandal or two – like the time when she got an MBA from West Virginia University, only to have it revoked after an investigation concluded that her transcripts had been falsified by school officials. At the time, Bresch’s father, Joe Manachin, (who was then the governor of West Virginia, and who is now a U.S. Senator) and the family had close ties to the university’s administration; two top-ranking members of which promptly resigned on the heels of the scandal.

The EpiPen pricing issue has even united political foes against Mylan. Senator Chuck Grassley (R-Iowa), the chair of the Senate Judiciary Committee, began an inquiry into Mylan’s pricing earlier this week. Senators Amy Klobuchar (D-Minn) and Richard Blumenthal (D-Conn.) have also been active in demanding a price reduction. Even infamous pharmaceutical gauger Martin Shkreli described Mylan as a group of “vultures.”

Food Allergy Research & Education (“FARE”) released the following statement today:
 

“For the millions of Americans at risk for anaphylaxis, epinephrine is a lifeline. It is the only drug that can counteract a potentially life-threatening allergic reaction. FARE believes no individual in need of epinephrine should ever be without this life-saving drug due to a lack of affordable access to the drug. Even a single life lost due to lack of access to this drug is one life too many. We are deeply concerned about the challenges our community face related to the accessibility and affordability of epinephrine, which have become increasingly difficult for various reasons.”    
 
And let’s not be naïve about the radius of impact here. Mylan’s pricing doesn’t affect only allergy sufferers. As Senator Grassley pointed out, with 40 percent of children publicly insured. “taxpayers are picking up the tab for this medication.”

 It’s certainly tempting to blame Big Pharma for business practices motivated by greed at the expense of children’s health. But after speaking with Robert Goldberg, Vice President for the Center for Medicine in the Public Interest, I think there may be a far more complex web of avarice at play. According to Goldberg, pharmaceutical companies have little choice but to consistently and drastically increase the list prices for drugs; the combination of government-imposed price controls and drug shortages (resulting from the increasingly small pool of generic drug manufacturers willing to take the financial risk of producing certain medications) effectively mandates companies like Mylan to charge sky-high list prices for its products. Context is important too. Goldberg pointed out that the cost of other drugs, such as Albuterol and commonly-used antibiotics, have gone up as much as 3500%.

Goldberg shared with me his take on the underlying reason for EpiPen pricing having suddenly become a controversial issue:

“Mylan didn’t do anything illegal. This is pre-election hoopla. Mylan is in the hotseat because it ran ads endlessly during the Olympics. At times, I didn’t know whether I was watching an EpiPen documentary or women’s gymnastics.”

But media hype or no, $600 is a lot to spend on this product.   If it’s not Mylan’s fault, what’s the real cause of the outrageous cost of EpiPens? According to Goldberg, this is a “great example of crony-capitalism. Everyone knows the joke –you raise prices, you get beaten up, but then everyone pockets the money. If you lift up the rock on the rhetoric, you find a series of incestuous relationships between manufacturers, insurers, and the government that focus on dividing up discounts and cash rebates and passing the cost onto consumers.”

The outrageous pricetag on EpiPens, after all, is the “list price.” That means that when the manufacturer issues “rebates” (which is standard practice), those rebates are lining the pockets of pharmacies and health insurers – but not those of consumers.   The EpiPen issue can be framed as “Big Pharma and the Government Watchdogs Trying to Protect Us” as easily as “The Predatory Tale of Healthcare Companies and the Politicians Who Enable Them” – it’s all in the telling. While we, the consumers, are left to sort it all out, the prices of EpiPens will likely continue to rise.
  Read More & Comment...

Why Is The Media Sticking It to the EpiPen

08/24/2016 04:08 PM | Robert Goldberg

Now a few words about the outrage over EpiPen prices. 
 
The EpiPen’s list price has increased before.  And the list price of other generic drugs had been increasing even more.  A lot more as the chart below (courtesy of the wise and charming Adam Fein from his wise and charming blog Drugchannels) shows. 
 


In general, these list price hikes reflect increased cost of production and the fact that the only way to increase revenue is to increase prices to account for federal price controls on Medicaid prices, rebates, discounts, etc.
 
EpiPen’s price hike was modest compared to others on the list.
 
Meanwhile, the spike in generic prices have abated as the FDA cleared the backlog of generic drug approvals. 
 
So why the outrage now? And why Mylan’s EpiPen?
 
First, last November Sanofi ($SNY) pulled the main competitor for EpiPen--Auvi-Q--from the market, a turn of events that at time looked as if it “should keep Mylan dominating the epinephrine injection field.”
 
Mylan already had 85 percent market share.
 
It’s been running ads for EpiPen ever since.  In fact, Mylan ran so many EpiPen commercials during the Olympics I started to wonder if self-injection was a new competitive sport.  (It’s not.) 
 
Meanwhile CVS and Express Scripts removed another competitor, Andrenaclick, from it’s formularies.   Andrenclick retails at $141 while EpiPen retails at around $600.  You tell me why Express Scripts and CVS tossed it from it’s formularies.
 
At the same time, CVS and Express Scripts moved EpiPen from the lowest cost sharing tier to the highest cost sharing tier most likely to extract rebates from Mylan.   Mylan could have said no, which led the PBMs to retaliate.  Mylan could have responded by just increasing the amount of money going to patients directly to reduce out of pocket costs. And for the most part, it did as Consumer Reports points out:
 
“Such is the case for Tracy Bush, of Pfafftown, N.C., whose 14-year-old son relies on EpiPen for his allergies to nuts, eggs, and other foods. Bush has watched the price of EpiPen increase over the past nine years from $146 for a two-pack to more than $600. The total cost of Bush's recent prescription for three EpiPen two-packs came to $1,819.08.  Fortunately for Bush, her insurance along with the co-pay coupon she gets through the drug's manufacturer, Mylan, covers a large portion of the costs.”
 
So what changed was the out of pocket cost of the EpiPen vs the acquisition price of the injectable which can be as low as $240 per two pak (the federal Medicaid price limit).   
 
Mylan offers a coupon that reduces co-pays for insured patients by up to $100 per prescription (for up to a maximum of three two-pack cartons per prescription). Patients without insurance can apply to get EpiPens for free through Mylan’s patient assistance program.
 
So why the outrage?  And why is it only directed at Mylan.
 
Because it fits the narrative, which is: Big Pharma has monopoly power to jack up prices as a high as they want and force people to go without life saving medicines. 
 
 And we are in a season of silliness in which economic illiterates propose price controls and patent seizures to cut costs.  (See the incredibly stupid article in JAMA by a bunch of doctors masquerading as real economist entitled The High Cost of Prescription Drugs.  There is a reason such crap is published by JAMA and other medical journals.  Because the research and approach is so shoddy that it could never pass a peer-review threshold in a real journal of economics.  But then again, the media is not interested in differentiating between real economics and propaganda. )
 
The truth is the EpiPen was probably priced too low to increase capacity fast enough to handle the fact that it’s main competitor’s product tanked.   (I think many medicines are price too low given the unmet medicical needs and the huge investment it will take to tackle diseases with innovative medicines. ) And it was price too low in 2007 ($60) for value it delivers, namely saving a child from a potentially fatal anaphylactic shock.   The prevention is a bargain for insurers too who otherwise would be required to pay for 1000 times more than the cost of an EpiPen 2-pak in hospital, rehab services. 
 
Further, Mylan is now in the innovator pharma space.  In 2014 Mylan invested in a Theravance Biopharma product called Revefenacin, a once-daily, nebulized long-acting muscarinic antagonist (LAMA) to treat chronic pulmonary obstructive disorder. 
 
You see, the improved quality of treatment via EpiPens, reducing the use of high cost medical services and sparing parents the terror of seeing their child choke to death before their eyes.  And some of the profits have gone to executive bonuses.  So what?  Most of it is going into new medicines.
 
Meanwhile, competitors have seen the market for injectable ephrinefrine explode.  Other companies are developing products to compete with Mylan.  FDA regulation is a bitch, requiring time and money.  But eventually there will be more than one EpiPen competitor.
 
All this is truth.  But it conflicts with the evil Pharma narrative that can be recycled again and again without any originality to generate clicks.  The increasingly banal and predictable reporting at Forbes, Bloomberg, the New York Times and WSJ are cases in point.  And the reporting is banal and predictable because it is not truthful.   As Jonah Goldberg once observed: Journalists define the powerless and powerful based on their own preferred narratives. When the truth interferes with the narrative, the truth must be bent or jettisoned.


 
 
 
   Read More & Comment...

Mylan's "Perfect Storm of Stupidity"

08/24/2016 03:53 PM | Peter Pitts

It’s as though Turingfreude never made it to Mylan HQ.

Dramatically raising prices on Epipen during a political cycle?  Really? That’s the new dictionary definition of (among other things) being tone deaf.
And to make matters even worse, the head honcho at Mylan, Heather Bresch is the daughter of US Senator Joe Manchin (D, WVA). That’s gotta be embarrassing.

The naivity is … Breschtaking.

Have a look at my comments during CNBC’s Power Lunch.

Folks -- you just cannot make this stuff up.
   Read More & Comment...

If you’re taking a biologic, you’ve got a friend in Pennsylvania

08/17/2016 11:06 AM | Peter Pitts

When it comes to protecting and advancing the public health, some states are leaders, others laggards. Consider biosimilars.

On July 20, Pennsylvania Governor Tom Wolf signed into law Senate Bill 514, which allows pharmacists to substitute for a brand name biological product a less expensive biosimilar product that has been deemed interchangeable by the FDA. Pennsylvania is one of 25 states and territories to enact such a law.

Under the Pennsylvania law, a pharmacist may substitute a biosimilar for a prescribed biologic product only if (1) the biosimilar has been determined by the FDA to be interchangeable with the prescribed product, (2) the prescriber does not designate verbally or in writing on the prescription for that product that substitution is prohibited, and (3) the person presenting the prescription receives notification of such substitution. 

A pharmacist must also communicate the substitution to the prescribing physician, unless it is a refill prescription of the same previously dispensed interchangeable biosimilar. 

It’s important to note that none of the biosimilars currently approved by the FDA have been approved as “interchangeable.” At least not yet – but as soon as the FDA completes its regulatory pathway, there will be – and there will be many. Those states with Pennsylvania-like legislation in place will recognize larger savings and sounder patient safety faster. That’s a potent public health double play that the folks in Harrisburg have already figured out. It’s time for every state to pay attention.
   Read More & Comment...

Embracing Satan's PDUFA

08/16/2016 08:23 AM | Peter Pitts

Yesterday’s public meeting on the FDA’s PDUFA VI Commitment Letter was a love-fest (mostly) – but as Theresa Mullin, Director of CDER’s Office of Strategic Programs, wisely noted, “the devil is in the details. Indeed.

The meeting was in three panels: Pre-Market Review and Post-Market Safety, Regulatory Decision Tools, and Administrative Enhancements.

A few highlights and comments.

Opening up the day, CDER Director Dr. Janet Woodcock commented that, since the introduction of the first PDUFA in 1993, “It’s a brave new world.” That’s certainly true, but some have been braver than others. As Aldous Huxley wrote in his novel, A Brave New World, ““Most human beings have an almost infinite capacity for taking things for granted.”

Janet (and later on others) spoke about PDUFA VI building a Patient-Focused Drug Development (PFDD) “Bridge.” In other words, moving from holding meetings to developing “fit-for-purpose tools to better reflect the benefit/risk calculus of patients.” A key point, via Janet, is that by doing this the FDA will not be the PFDD “bottleneck." The devil is in the details.

She also pointed to a fully operational and funded Sentinel program as a linchpin not just for advancing safety (specifically pharmacovigilance) more broadly, but also for accelerating the ecosystem of Real World Evidence. RWE was a major focus of the meeting. More to follow. Albeit to say – the devil is in the details.

The factoid of the day was that in FY2015 (to date), the FDA has held over 3000 PDUFA meeting requests. Don’t even bother doing the math, because that doesn’t include the intense meeting preparation division staff must undertake prior to any actual face-to-face (or teleconference) encounters. This is a highly significant statistic insofar as there was much discussion on enhancing sponsor-agency communications. Is more always better? It depends. As Walter Gropius said, “Less is more. But more tastes better.” Communications must now be more about quality than quantity but, from a PDUFA perspective, how can that be measured?

In a small but important improvement, the FDA will provide 72-hour notice to all manufacturers whose products will appear in the quarterly FDAAA-mandated Public Notification of Emerging Postmarket Medical Device Signals (921 Safety Notices).

Per Sentinel, it was mentioned a number of times (including on an FDA slide) that it will be used to “inform important regulatory decisions.” Does this mean Sentinel data will be used “beyond risk” to also “inform” FDA thinking on potential new benefits? Will Sentinel become a tool for validating Real World Evidence? That was not discussed – but maybe it’s time for it to be put on the table, perhaps at one of the RWE meetings promised in the agency’s commitment letter.

As promised, the FDA will publish an updated version of its Structured Approach to Benefit/Risk Assessment in Drug Regulatory Decision-Making. It’s been an arduous journey. It’s important to remember that the key tenet of the PDUFA philosophy isn’t speed, but predictability, and the ability to understand regulatory decision-making (and, ultimately reproducibility) is crucial. This is important for many reasons, not the least of which is the ever-increasing costs of drug development.

There was (Finally! At last!) much discussion about “staff capacity.” Not just more, but better. Not just quantity, but quality. One specific conversation focused on the need for better reviewer understanding of and training in adaptive clinical trial design models. Let’s face it, there aren’t a lot of people inside the FDA considered expert in (among other things) Bayesian statistical design. Better MAPPS and SOPPS (Manual of Policies & Procedures, Standard Operating Policies & Procedures), that were promised and they will help. There have to be internal rules of the 21st century regulatory road as well as external guidance but – the devil is in the details.

Some positive forward motion on biomarker prequalification. Among other things, the FDA will create a website listing the biomarkers it’s working on. Per the agency's presentation, this is designed to help stimulate further development. It’s a start and more needs to be done. (More, always more!) But without the internal expertise, how is the FDA to parse its expert resources? Maybe it’s time for a more serious discussion of intramural cooperation. FDA needs adequate resources – beyond PDUFA funding -- to provide advice and oversee review and decision-making. One solution is to partner with an external entity (perhaps an Intramural Biomarker Consortium-IBC) to develop early advice and serve as an expert sounding board for nascent biomarker efforts.  The IBC could be a required or voluntary resource in the review process, especially for initial data package reviews. This approach would allow FDA staff to focus on their primary role of product review and regulatory oversight.

PDUFA is an important path, but it isn’t the only one.

All present (FDA staff, patient groups, industry representatives) were very excited about the opportunities of PFDD next steps and Real World Evidence. But how to get there? As BIO’s Kay Holcombe said, “We cannot put anecdotes on the drug label.” Real World Evidence is the new star on the precision medicine horizon. But the tool set for using this treasure trove of healthcare information is nascent and the tasks as are daunting as the opportunities. Patient passion is important to share. When combined with data and a more dispassionate understanding of regulatory paradigms, a patient-driven pathway can and must evolve into a tool used to impact regulatory decision-making. The devil is in the details.

The most decidedly unsexy but most honest and important part of the meeting came last – a discussion of “administrative enhancements” including electronic submissions and data standard activities, hiring capacity, and financial management. It’s important to note that PDUFA VI is the first time that “hiring capacity” has been directly addressed – and it’s about time. The FDA must have the firepower to not only retain but to aggressively recruit the best and the brightest. Again, it’s not just about body count (quantity) but quality. Quality is not what you put in. It’s what you get out. “Staff capacity” means more (a lot more) than PDUFA-measurable hiring numbers. We need a PDUFA quality metric.

In the immortal words of Admiral Hyman Rickover, “The devil is in the details, but so is salvation.  Read More & Comment...

Why ICER Can't Be Trusted

08/15/2016 11:31 AM | Robert Goldberg

ICER has come out with a response to what it defines as myths about it’s funding, approach and mission.  The rejoinder is an excellent example of President Kennedy’s observation that “the great enemy of the truth is very often not the lie, deliberate, contrived and dishonest, but the myth, persistent, persuasive and unrealistic.”

ICER wants to be perceived as trusted non profit organization that is identifying the best medicines at prices patients can afford.  As ICER puts it: “How can we make sure that we can afford the innovation we want for patients in the future?” 

And it believes, led by Steve Pearson, ICER’s believer in chief, tha unless ICER rolls up their sleeves to determine the prices of new medicines and who should get them  drug spending “would contribute to an increase in overall health care costs at a rate greater than growth in the overall national economy, (and) health system value would be diminished.”

ICER’s publication takes issue with several so-called myths. Some of them address criticism about their belief that an additional year of life is at maximum worth $150K.  Another deals with how little ICER includes patient perspectives of health value.  I will deal with those in another post. 

For now,   I will deal with the criticisms I have raised about ICER that it has tried to refute 

Myth #5: ICER wants to take money from dying patients in order to “fix potholes.”

 ICER claims “much of the more recent criticism has been fueled by a lack of knowledge about ICER or even willful mischaracterization by those who oppose a move toward pricing in alignment with the added value for patients.  Some of these distortions have taken on a life of their own, threatening to make it more difficult for patient groups and others to engage constructively in our report development and in the broader debates now going on about value assessment and drug pricing.”

In particular, ICER is ticked off  that I claimed that ICER wants to take money from dying patients in order to “fix potholes.”  Let’s give Pearson and ICER the floor:

Truth:

This is one of the more remarkable and malicious mischaracterizations of our intentions.
In introducing the broader social and ethical questions that ICER reports are supposed to help address through public dialogue, we have shown data from the state of Massachusetts demonstrating that state spending on health care has risen nearly 60% in the last decade. We also show data on where that money came from: steep reductions in spending on every other major type of social service, including education, fire and police protection, housing, public health, and infrastructure.  The same story is echoed in state houses around the country: health care costs are growing rapidly, severely impinging on the ability of states to maintain other services.  This obviously does not imply that ICER wants dying patients to be denied treatment in order to fix potholes.  What it does mean is that we hope that our reports and the public meetings we convene can lead to a more robust and honest discussion about the real choices and trade-offs that are being made in spending at the state and national level.  If the shared hope is to be able to provide innovative drugs for all patients with serious illness, and to be able to also afford good education for our children and other services, then we believe that transparent discussions about whether prices for drugs and other health care services are reasonably aligned with the value they bring to patients are an important way to help us get there.”


It is true that I posted a blog  “ICER's Moral Vision: Repair Potholes Instead of Rescuing Lung Cancer Patients”

I used that title because it seemed to capture Pearson’s moral vision. Here’s what he said about lung cancer treatments in article he wrote in 2012 entitled "Which Orphans Will Find a Home":

“Considering…the marginal impact on the length and quality of life, and the implicit opportunity costs of this level of expenditure, our framework would suggest that public and private insurers would be justified in refusing to pay for cetuximab (a lung cancer drug).”

Of note, Pearson claims that lung cancer patients aren't really that sick.  They are just louder than other groups.  Pearson claims just because an advocacy group creates awareness of a specific disease or need, that's no reason to cover new  medicines.  In the case of lung cancer drugs Pearson writes: demand is" driven largely by the heightened public consciousness" and that there is "no..obligation to rescue identifiable rare disease patients based on a duty of rescue within personal morality."

Which ties into another charge I have raised that ICER seeks to rebut: the use of QALY’s discriminates against the sickest patients is a myth. (So-called)  It claims:

“In fact, starting out with a lower quality of life, whether through a serious illness or disability, offers more “room” for improvement, giving treatments for patients with serious conditions more opportunity to show improvement compared to treatments for patients whose baseline condition is already near perfect health.”

But that is NOT how QALY is applied.  Pearson has stated “a sickest-first principle might require allocation of resources even when only minor gains can be achieved and the cost is very high, which is obviously inefficient…coverage decisions must not only incorporate consideration of the benefits gained but the opportunity costs incurred when covering expensive orphan drugs.”

And contrary to Pearson’s claim about not considering cost in recommending what drugs to use, he and ICER are clearly targeted what they believe are “ the growing number of expensive therapies that offer benefit only to small populations” to “ensure that an undue burden is not
placed on others for the sake of a few.” 

In addition, ICER and Pearson regards living longer, the result produced cumulatively by new drugs, as a cost which, if it exceeds a specific amount of spending per drug estalblished by ICER, would diminish health system value.  

Indeed, as ICER points out it's measurement of QALY is conducted " from a health system perspective, and so does not incorporate costs and effects that might be relevant from a societal perspective, such as productivity, transportation, or caregiver costs."

Moreover,  ICER measures costs as the combination of "new treatment on top of existing treatment, as is the case for multiple myeloma drugs.." That "means that to reach standard cost-effectiveness levels the entire regimen, including the older, existing drugs that are part of the regimen, would need to be deeply discounted, or certain costs must be considered “unrelated” and excluded from the economic evaluation.
Pearson's response: "At current wholesale acquisition costs, the estimated long-term cost-effectiveness of these regimens exceeds commonly-cited thresholds."  

In other words, myeloma treatments surge about the ICER QALY cap of $150K because people are living longer and have more options to increase survival.  They are therefore, from ICER's perspective (and the insurer's perspective a noted above) new drugs that extend life will NEVER be cost-effective. 

With regard to the pothole vs dying patient “myth" I was simply writing based on a FAQ that ICER had posted on it’s website until recently but is no longer available:

“When we’re paying for drugs and don’t know the drug’s value, individually, we may pay more out of pocket and more for insurance. While if we’re covered at work and our employer is paying more in premiums, we may not get as big a raise as we otherwise would have. We also pay more in taxes as the government (Medicare, Medicaid, and federal employees) has to pay more for health care.  We’re siphoning off resources for other things we need like better schools and more resources for local police, roads and bridges.”

But the claim that spending money on drugs drains money away from other services is an outright falsehood.


Source: National Assoc. of State Budget Officers

As the chart above demonstrates, state Medicaid spending has increased slightly, while other expenditures have remained stable or increased slightly.  (Transportation being an exception.)  Doesn't look like a siphon to me. 

And here’s a look at the Massachusetts budget ICER claims is being savaged by the use of drugs that are expensive and not very valuable (like drugs for dying lung cancer patients, as Pearson suggested.) 


Source: Massbudget.org

Turns out Medicaid spending in Massachusetts declined as a percentage of total state spending from 2004-2014.


Finally, let me show that for all of ICER’s deception and spin, Medicaid spending on drugs has remained about the same percentage of total Medicaid spending for the past decade.   



(Source, CMS) 


Ask yourself this question: If we can't trust ICER to present accurate data about the impact of drug spending on our economy or governent expenditures, can we trust it, as it wants us to do, to determine patient access to new medicines?



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Bayer exonerated per Essure. Where's the MSM coverage?

08/12/2016 02:13 PM | Peter Pitts

Judge dismisses 1,225 cases against Bayer Healthcare

Fairfield County Business Journal

By Bill Heltzel

August 11, 2016
 
A federal judge in White Plains has dismissed 1,225 lawsuits against Bayer Healthcare Pharmaceuticals that were filed by women who claimed that the company’s contraceptive device injured them.

U.S. District Court Judge Cathy Seibel concluded that the absence of expert testimony made it impossible to prove that the device can injure women after it was inserted.

“No reasonable jury could find in favor of plaintiffs because there is no evidence in the record from which a jury could find that secondary perforation exists and is capable of causing plaintiffs’ injuries,” Seibel wrote in a July 28 opinion.

“The court reaches this conclusion reluctantly, knowing that it will doom hundreds of cases,” she said, “but in the court’s view it is compelled by the law.”

The U.S. Food and Drug Administration approved Bayer’s Mirena intra-uterine contraceptive device in 2000.

The small, plastic T-shaped IUD releases a continuous dose of a hormone that reduces the chances of pregnancy. A trained health care provider implants the device.

Mirena has been marketed as a convenient form of birth control. It is meant to last for up to five years and it can be removed if a woman wanted to become pregnant.

Women who sued Bayer complained of side effects, such as perforation of the uterus, pelvic inflammatory disease and ectopic pregnancy. Many said the device shifted and caused internal injuries.

The legal issues, Seibel said, are when perforations occur and whether the label adequately warned of all risks associated with perforation.

The Mirena label went through a few versions. For years, it said “perforation or penetration of the uterine wall or cervix may occur during insertion.” In 2014, the label said perforation “may occur most often during insertion.”

Bayer argued that the scientific consensus was that perforations cannot occur after the device is implanted. The plaintiffs contended that secondary perforations can occur.

In March, Seibel barred testimony from seven expert witnesses for the women, concluding that they were unqualified or unreliable to offer expert opinions on clinical issues, causation or regulatory issues.

A biomedical engineer, for example, had no experience with IUDs or hormonal contraception devices like Mirena and no particular familiarity with the anatomy of the uterus. His only experience with the hormone used in Mirena came from reviewing articles that the plaintiffs’ counsel gave him and that he copied and pasted into his expert report.

“This is not the level of rigor an expert in the field would apply and does not pass muster,” Seibel concluded.

A professor of physiology presented a theory on secondary perforation “without confronting scientific literature that refutes this notion,” casting doubt on her reliability.

The plaintiffs’ attorneys tried to salvage their cases by arguing that other evidence could prove their cases. But Seibel ruled that allowing such admissions to substitute for expert testimony would defeat state laws that require experts and would leave the jury to speculate about the cause of injuries.

In 2013, when about 40 cases were pending in 17 federal districts, the Judicial Panel on Multidistrict Litigation consolidated the lawsuits.

The cases shared common factual issues on the alleged risks of perforation and migration and on the adequacy of the product label, the panel said. Placing all cases under one judge would make it easier to accommodate everyone in the pretrial proceedings.

The panel chose the Southern District of New York because it is near Bayer operations in Connecticut, New Jersey, New York and Pennsylvania, where the primary witnesses and documentary evidence would likely be located. The district also is easy to reach for plaintiffs around the country.

Bayer Healthcare once operated a facility in Tarrytown. The operations were moved in 2013 when the Bayer subsidiary opened a new U.S. headquarters in Whippany, N.J.

The panel chose Seibel because she was already presiding over three related cases, “and she is an experienced transferee judge who we are confident will steer this litigation on a prudent course.”
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Danger in drugs from Canada

08/11/2016 02:27 PM | Peter Pitts

Via The Washington Times:

Danger in drugs from Canada

Clinton and Trump are both wrong on importation


ANALYSIS/OPINION:

When it comes to health care reform, Hillary Clinton and Donald Trump have something in common — and it’s dangerously wrong. They support drug importation “from Canada.” It’s a sound-bite solution that won’t offer lower prices but will result in a public health calamity.

Importing drugs from Canada is exceedingly dangerous for a number of reasons. For starters, many internet pharmacies based up north are stocked with drugs from the European Union. And while many people wouldn’t hesitate to take medicines purchased from countries like France, Germany and Great Britain, there’s plenty of risk involved.

The EU currently operates under a system of “parallel trade,” which allows products to be freely imported between member countries. This means that any drugs exported from the United Kingdom to Canada could have originated in an EU country with significantly less rigorous safety regulations, like Greece, Portugal, Latvia or Malta.

Just last year, EU officials seized more than 34 million fake pills in just two months. And in May, Irish drug enforcers confiscated over 1.7 million pounds of counterfeit and illegal drug packages. So if American customers start buying drugs over the internet from Canadian pharmacies, they could easily wind up with tainted medicines of unknown European origin.
It’s also important to note that drugs from anywhere in Europe aren’t even legal for sale in Canada. So when politicians say we can get “the same drugs” that Canadians get, they’re just plain wrong.

Even more worrisome is outright fraud — many “Canadian” pharmacies are actually headquartered somewhere else. 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 Food and Drug Administration (FDA) looked at 4,000 drug shipments coming into the United States. Almost half of them claimed to be from Canada. Of those, fully 85 percent were actually 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.

The on-the-ground reality of state and local importation schemes has been dismal and politically embarrassing. Remember Illinois’ high profile “I-Save-RX” program? During 19 months, only 3,689 Illinois residents used the program — that’s .02 percent of the population.

Programs like this wouldn’t do any better on a national basis. A study by the nonpartisan Congressional Budget Office showed that importation would reduce our nation’s spending on prescription medicines a whopping 0.1 percent — and that’s not including the tens of millions of dollars the FDA would need to oversee drug safety for the dozen or so nations generally involved in foreign drug importation schemes. And generic drugs (which represent more than 85 percent of the medicines dispensed in the U.S.) are cheaper here at home than in Canada.

Calling foreign drug importation “reimportation” is a clever way to sell the idea to the American people. But the term simply doesn’t fit with the facts. In reality, in addition to importing foreign price controls, Americans would end up jeopardizing their health by purchasing unsafe drugs while not saving money.

A better policy for both candidates would be to focus on the issue of increasing insurance company co-pays. American patients who head up north or online are motivated by the cut-rate prices they see on the web. Health insurers could help patients avoid this temptation by reducing their 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.

Dropping drug co-pays would also help patients stick to their prescribed treatment regimes. All too often, people skip a dose, don’t get a refill, or stop taking their drugs prematurely in order to save money. In the long run, though, not adhering to a drug regimen leaves patients less healthy — and increases national medical expenses by an estimated $300 billion annually.

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