Latest Drugwonks' Blog

FDA's Seven Year Itch

  • 08.31.2016
  • 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 The FDA listened -- and then waited until June 2014 to issue draft guidance.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?

ICERs Sins of Omission

  • 08.30.2016
  • 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. 

JAMA's Pizza Principle

  • 08.30.2016
  • 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.
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. 

Bee Smart About Drug Pricing

  • 08.29.2016
  • 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.

EpiPen 'Outrage' Update

  • 08.25.2016
  • 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.

Why Is The Media Sticking It to the EpiPen

  • 08.24.2016
  • 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.


 
 
 
 

Mylan's "Perfect Storm of Stupidity"

  • 08.24.2016
  • 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.
 
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.
 

Embracing Satan's PDUFA

  • 08.16.2016
  • 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.
CMPI

Center for Medicine in the Public Interest is a nonprofit, non-partisan organization promoting innovative solutions that advance medical progress, reduce health disparities, extend life and make health care more affordable, preventive and patient-centered. CMPI also provides the public, policymakers and the media a reliable source of independent scientific analysis on issues ranging from personalized medicine, food and drug safety, health care reform and comparative effectiveness.

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