Scott Gottlieb: Hope Over Hate

04/27/2017 11:18 AM | Robert Goldberg

Today (we hope) the Senate HELP Committee will vote to confirm Dr. Scott Gottlieb as the next FDA commissioner.

Three things stand out about his nomination:

1.    Dr. Gottlieb has garnered the support of a wide range of patient organizations and medical associations.  The same coalition supported Dr. Rob Califf’s nomination in 2016.
2.    The same groups and individuals who oppose Dr. Califf’s nomination are opposing Scott.  Apart from the Senators who opposed both individuals to demonstrate frustration with the FDA’s response to the opioid addiction problem, the critics are the self-important and self-serving hacks from Public Citizen along with smug academics whose names I will not repeat. 
3.    Both Dr. Gottlieb and Dr. Califf are deeply committed to changing the paradigm of FDA approval by working with talented individuals inside the agency.  

Dr. Gottlieb’s nomination reflects a bi-partisan consensus about the role of the FDA that originated with President Obama and the nomination of Dr. Peggy Hamburg:   When it comes to evaluating the risk and benefit of innovations that determine not only whether we live or die but how we live and die, patients and their loved ones have as much of say on the basis for approval and regulation as any expert.  

Dr. Gottlieb will carry on that tradition.  His opponents want to destroy that tradition.  Hope vs. hate. Remember that the next time you see a hateful, angry tweet about the next FDA commissioner.  
  Read More & Comment...

Making Drug Manufacturing Great Again

04/21/2017 01:25 PM | Peter Pitts

From the pages of Investor’s Business Daily …

Making Drug Manufacturing Great Again

President Trump wants to lower drug prices and reinvigorate domestic pharmaceutical manufacturing.  Bravo. But standing in the way is the inside-the-Beltway gospel that preaches that regulators love ambiguity.

As a former FDA associate commissioner, I can affirm that's true. Vagueness gives the agency almost unlimited authority to do whatever it wants.
But, when it comes to the FDA, it's predictability in pursuit of the public health that's important. And nowhere is this truer or more timely than when it comes to the oversight of drug manufacturing.

Drug manufacturing isn't sexy to the general public and rarely makes headlines — unless something goes wrong. Recalls make headlines. Adherence to current good manufacturing practices (GMPs) do not.

A few years ago I had the chance to visit Pfizer's Kalamazoo production facility. What impressed me more than the gee-whiz production aspects of the facility (of which there were plenty) was the dedication of the people who work there — top to bottom.

It actually reminded me a lot of the FDA. Long-term employees dedicated to serving the public health through dedication to quality. And they all took it very personally. Just like at the FDA, the Pfizer folks were on personal missions of quality. There was a lot of pride on display.

Mr. President — there hasn't been an exodus of pharma manufacturing to foreign shores. In fact, when I visited the Kalamazoo facility they were exporting (among other things) the active pharmaceutical ingredient (or API, the actual drug substance) for methyl prednisolone (a corticosteroid long off patent) to both China and India.

A U.S. manufacturing facility of an innovative biopharmaceutical company that exports drugs to China and India for profit?  What's wrong with this picture? Well, as it turns out, it's what's right — innovation through manufacturing prowess, organic chemistry smarts and green technology. Better. Faster. Cheaper.

Pharma's always bragging about its ever-growing investment in R&D. But when was the last time you heard about investments in domestic manufacturing? Probably never.

And when was the last time you read about enhanced drug safety through good manufacturing processes and cooperation between industry and the FDA? Not recently. That's a shame because they're both important stories.

The president's nomination of Dr. Scott Gottlieb to be the next FDA commissioner likely portends a more holistic view of drug regulation. I served with Scott for two years at the agency. Not only is he a voice for greater regulatory predictability, he's also a silo-buster.

Having previously served as deputy commissioner, he understands the need for greater interdepartmental cooperation. In other words, it's not just about better utilization of expedited review pathways or better use of real-world data, or enhanced post-market surveillance, or more robust off-label communications. It's about making the process work for patients.

But manufacturing is all about process. Modernized pharmaceutical manufacturing isn't only about ensuring and enhancing quality for finished medicines, it's also about making America's pharmaceutical factories globally competitive players in the production of API (like Pfizer's plant in Kalamazoo) and excipients (the ingredients other than the API that are included in the manufacturing process or are contained in a finished pharmaceutical product.)

And the more complicated the drug, the more complicated the active pharmaceuticals and other ingredients. American know-how and dedication to GMPs present a wonderful opportunity for our domestic facilities to thrive. Quality manufacturing is our unique proposition vis-a-vis less expensive operations overseas.

FDA regulation of medicine manufacturing is also a crucial piece of the solution to preventing future drug shortages. According to a 2012 report from the House Committee on Oversight and Government Reform, by hastily ramping up manufacturing enforcement actions, the FDA "effectively shut down 30% of the total manufacturing capacity at four of the country's largest producers of generic injectable medications."

Resolving this problem will require the FDA to work with manufacturers to find practical, science-based solutions to quality-control issues that neither compromise safety nor slow down production. Regulatory discretion is often the better part of valor.

Enforcement of savvy manufacturing quality control is crucial, but an equally important (and often ignored) aspect of the FDA's mission is to advance America's pharmaceutical production acumen by being both regulator of and partner with industry.

That's a winning combination: the best and the brightest from industry and government together with the best production capabilities in the world. The keys to the kingdom are on the table.

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

DTC Fair Balance ... for Lawyers!

04/17/2017 09:19 AM | Peter Pitts

House Judiciary Committee Chairman, Rep. Bob Goodlatte (R/VA.) wants drug side-effect ads that are run by lawyers to include a warning that patients should talk with their doctors before adjusting medication, the Wall Street Journal reports. Along with the American Medical Association and some drug companies, he contends the ads are to blame for patients suffering harm or even dying after dropping treatment.
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PDUFA Reauthorization. Discuss.

04/14/2017 05:54 PM | Peter Pitts

House, Senate Health Committee Leaders Release Discussion Draft of FDA User Fees Reauthorization

WASHINGTON, DC – The leaders of the Senate and House health committees today released a discussion draft of bipartisan legislation reauthorizing the Food and Drug Administration user fee agreements.

The Food and Drug Administration (FDA) Reauthorization Act of 2017 renews FDA's authority to collect user fees from the makers of prescription brand drugs, medical devices, generic drugs and biosimilars, and several vital programs at the FDA. The 2012 prescription drug user fee amendments (PDUFA), medical device user fee amendments (MDUFA), generic drug user fee amendments (GDUFA), and biosimilar user fee amendments (BsUFA) all must be updated and reauthorized by Congress before the current user fee agreements expire on September 30.

If the agreements are not reauthorized before the August work period, the agency will be forced to send layoff notices to more than 5,000 FDA employees. A delay in reauthorizing these agreements would delay the reviews of critical drugs and devices.

“We are fully committed to a timely reauthorization of the agreements and are well on our way,” said Energy and Commerce Committee Chairman Greg Walden (R-OR). “This represents another opportunity to help expedite the review and approval of new cures and treatments for patients, and we must prioritize it. As this process proceeds, I look forward to continued discussions with my colleagues in the House on other member priorities that could strengthen this important legislation.”

"The swift reauthorization of these user fee agreements is critical to making sure FDA has the resources and personnel it needs to ensure timely review and approval of safe and effective medical treatments,” said Energy and Commerce Committee Ranking Member Frank Pallone, Jr. (D-NJ). “These carefully negotiated agreements encourage innovation, improve our regulatory review process, and provide certainty to both patients and industry. I look forward to working with my colleagues to move this legislation through Congress and to the President's desk.”

“If we do not move quickly to reauthorize these agreements, in late July, the FDA will be forced to begin sending layoff notices to more than 5,000 employees to notify them that they may lose their job in 60 days,” said Senate Health, Education, Labor and Pensions Committee Chairman Lamar Alexander (R-TN). “The sooner we reauthorize the agreements, the better – to give patients, reviewers, and companies certainty. In addition to harming patients and families that rely on medical innovation, a delay in reauthorizing the user fees would threaten biomedical industry jobs and America’s global leadership in biomedical innovation.”

“I’m encouraged by our bipartisan work to reauthorize these agreements to advance safe, effective, and innovative medical products,” said Senate Health, Education, Labor and Pensions Committee Ranking Member Patty Murray (D-WA). “Patients and families nationwide are relying on us to ensure FDA can continue its vital work without interruption. I hope that we can continue to put partisanship aside and advance this important legislation.”

The FDA Reauthorization Act of 2017:

Updates and reauthorizes the user fee programs, which, in Fiscal Year 2016, accounted for 70 percent of the brand drug review budget, 36 percent of the medical device review budget, 75 percent of the generic drug review budget, and 29 percent of the biosimilar review budget.

Reflects the recommendations sent by FDA to Congress in January, which were based on over a year of negotiations and discussions with industry, Congress, patients, and other stakeholders.

Implements the four user fee agreements authorized by FDARA, which support the goals of the 21st Century Cures act and advance key bipartisan priorities:

Prescription Drug User Fee Amendments (PDUFA VI): Enhances patient-focused drug development, supports biomarker development and qualification, dedicates staff to assist in the development and review of rare disease drugs, sets clear timelines and improves guidance for drug and device combination products, and evaluates ways to modernize the clinical trial process.

Medical Device User Fee Amendments (MDUFA IV): Enhances the patient voice in the device development process, supports the collection of real world evidence on the safety and effectiveness of devices, and improves the review process for  “de novo” devices—low- to moderate-risk devices that are the first of their kind.

Generic Drug User Fee Amendments (GDUFA II): Improves the fee structure to support small businesses, provides goal dates for all outstanding generic applications, and establishes priority review timelines.

Biosimilar User Fee Amendments (BsUFA II): Continues to build the biosimilars program, and supports guidance for product developers.

CLICK HERE for the text of the discussion draft, HERE for a section-by-section summary of the discussion draft, and HERE for a one-pager. Health committee leaders ask that stakeholders who wish to comment on the contents of this draft please submit to FDAuserfees2017@help.senate.gov by April 28th.  Read More & Comment...

PIE Day

04/12/2017 07:47 AM | Peter Pitts

It's time to go beyond FDAMA 114.

Representative Brett Guthrie (R/KY) introduced the Pharmaceutical Information Exchange (PIE) Act of 2017 (H.R.2026). The bill incorporates the multi-stakeholder consensus recommendations developed during a forum sponsored by the Academy of Managed Care Pharmacy. The legislation would allow biopharmaceutical manufacturers to proactively share clinical and economic information with population health decision makers on emerging therapies in advance of Food and Drug Administration (FDA) approval, an area that is significantly restricted by current federal laws and FDA regulations.
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Expediting Complex Geneics

04/06/2017 09:18 AM | Peter Pitts

It's not about speed, it's about predictability.

The way to expedite complex generics is by making the process predictable. Predictability = more development programs = competition = lower prices.
   Read More & Comment...

PV in the EU: Can the Doctor See You Now?

04/06/2017 06:57 AM | Peter Pitts

European, national, and regional authorities should invest in awareness-raising campaigns to increase public knowledge about medicinal safety and adverse drug reaction (ADR) reporting.
 
This is one of the main findings of the study “Pharmacovigilance in the European Union: Practical implementation across Member States” from the University of Duisburg-Essen which assesses the functioning of EU pharmacovigilance legislation.
 
The report focuses on adverse drug reaction (ADR) reporting of biologicals in six EU Member States - the UK, Finland, France, Poland, Portugal, and Germany. Since the 1990s, legislation at the EU level has strengthened medicinal safety in general, and particularly the reporting of ADRs. However, transposition problems remain in some EU Member States when it comes to medicinal safety.
 
ADRs account for 5% of all hospital admissions, cause around 200,000 deaths per year in the EU, and cost roughly €80 billion.
 
Almost 85% of EU rules are not transposed on time, and occasionally come with a delay of more than two years. Although patients are given a strong role within the new EU pharmacovigilance legislation, they lack awareness, and this leads to ADRs going unreported.
 
The report argues that ADR reporting should be viewed as a key responsibility for healthcare professionals and not as a failure or lead to reputational damage. They should also be properly trained and targeted by awareness-raising campaigns to ensure they are aware of the importance of medicinal safety to public health and feel comfortable in reporting ADRs without fear of liability and/or failure.
 
Patients also have a critical role to play, and Member States should enable patients to report ADRs online, and connectivity of IT systems between general practitioners, hospitals, pharmacies, and the national competent authority should be improved.
 
A key solution identified by the report is to put in place awareness raising programmes aimed at both patients and healthcare professionals to increase knowledge about medicinal safety and highlight the role it can play to ensure public health.
 
The report will be shared with EU Member States, the EU Institutions, and key stakeholders, with the aim of ensuring the recommendations are taken up by governments, and that the EU legislation can be properly implemented across Europe.  Read More & Comment...

Scott STAT!

04/05/2017 10:05 PM | Peter Pitts

“I think Scott is very much for good regulation, and very much against bad regulation,” Pitts said. “Importantly, he recognizes where FDA core mission stops, and where mission creep begins — and that’s an important finesse he’d bring to the commissioner’s chair.”
 
Via STAT News:
 
 Gottlieb’s pledge to uphold ‘gold standard’ raises red flags
 
When Dr. Scott Gottlieb pledged at his confirmation hearing to uphold a “gold standard of safety and efficacy” at the Food and Drug Administration, he raised an important question:

What exactly does he mean by that?
 
Traditionally, “gold standard” refers to robust, randomized controlled clinical trials. But there’s enormous pressure on the FDA — from pharma companies and Congress, for starters — to accept other kinds of evidence, perhaps even patient anecdotes, to determine whether experimental drugs work. And President Trump is promising to speed drug approvals.
 
So when Gottlieb said: “I think there are ways to modernize clinical studies without sacrificing the gold standard,” he raised red flags.
 
“I don’t think he was using the phase ‘gold standard’ in the way that most of us who think about the agency for a living understand it,” said Rachel Sachs, an associate professor of law at Washington University in St. Louis.
 
“I think he views adaptive clinical trial design as in keeping with that gold standard,” Sachs said.
 
And that’s the rub, because modifying clinical trial standards has many people concerned. Reshma Ramachandran, co-chair of the National Physicians Alliance’s FDA task force, says she, too, doesn’t know what Gottlieb meant by “gold standard” — but isn’t optimistic about his interpretation.
 
She pointed out that Gottlieb has criticized the use of adequate and well-controlled Phase 3 trials in the past, saying they’ve needlessly delayed access to important drugs.
 
“That seems to indicate that his idea of ‘gold standard’ means sacrificing safety and efficacy you’d expect from FDA in favor of expediting an approval pathway,” Ramachandran said.

Joshua Wallach, a research fellow at Yale’s Collaboration for Research Integrity and Transparency, had similar worries.

“I’m concerned: I don’t want a complete erosion of the quality of clinical trial evidence that’s required from industry,” Wallach said. “There’s definitely a movement still toward deregulation — and lowering of evidentiary standards.”
 
Wallach is afraid, in particular, of changes to clinical trial endpoints. Modernizing the clinical trial process might force trials to lean on surrogate endpoints. That could mean assessing an experimental drug based on whether it has some interim effect (like improving a dementia patient’s performance on a memory test) rather than whether it meets more significant long-term goals (like prolonging that patient’s ability to complete daily tasks). It could also open the door to pharma companies scouring their clinical trial data to find metrics that look good — and presenting those to the FDA, even if the trial was originally designed to answer an entirely different question.
 
“I’m worried about seeing more small, crappy trials that don’t actually tell you anything about efficacy and safety — which are extremely important before drugs can be approved or marketed,” Wallach said.
 
Part of upholding the FDA’s gold standard could involve respecting and keeping on career staff, Sachs said. And for that, she gives Gottlieb high marks.
 
“I think he understands the importance of a strong, well-resourced FDA,” Sachs said. “I don’t think he will burn it all down. I don’t think he’s inclined to destroy the agency from within.”
 
Peter Pitts, president of the nonprofit Center for Medicine in the Public Interest, saw another glimmer of good news in the confirmation hearing: He said he thinks Gottlieb’s definition of “gold standard” includes keeping FDA funding strong.
 
“The president and his team understand that you can’t get more for less — and that’s especially true on staffing,” said Pitts, who was a former associate commissioner of FDA and worked with Gottlieb at the agency for two years. “And Scott came pretty close to saying he was against a reduction of budget.”
 
Pitts added that he was impressed by Gottlieb’s performance at the hearing.
 
“I think Scott is very much for good regulation, and very much against bad regulation,” Pitts said. “Importantly, he recognizes where FDA core mission stops, and where mission creep begins — and that’s an important finesse he’d bring to the commissioner’s chair.”  Read More & Comment...

Arizona and Off-Label. Heart in the right place. Brain -- not so much.

03/30/2017 10:11 AM | Peter Pitts

Arizona is first state to pass a law allowing drug makers to promote off-label uses

Ed Silverman @Pharmalot

In what some observers are calling a misguided effort, Arizona has become the first state in the nation to pass a law allowing drug makers to promote their medicines for so-called off-label uses — so long as the information given doctors is truthful.

Interestingly, the law was hatched by the Goldwater Institute, the same think tank that spearheaded the controversial Right to Try laws designed to give patients early access to experimental medicines. And the think tank is vowing to duplicate that campaign by introducing off-label bills around the country.

This move comes amid rising pressure on the Food and Drug Administration to loosen regulations for off-label promotions, which is one of the most contentious issues to roil both the agency and the pharmaceutical industry. At issue is a fierce debate over patient safety and free speech.

Doctors can prescribe a medicine for an off-label — or unapproved — use, but drug makers have battled restrictions on their ability to distribute such information, such as reprints of medical studies. The companies believe free speech is being curtailed and have lobbied Congress and the FDA to loosen regulations. For its part, the FDA worries public health can be jeopardized by promotions that go too far.

Significantly, drug makers were emboldened by a pair of court rulings in recent years that determined companies can disseminate off-label information, so long as it is truthful and not misleading. However, one of those decisions, which was issued by a federal appeals court, only extends to Connecticut, New York, and Vermont, creating uncertainty about whether the issue would be tested elsewhere.

The FDA, meanwhile, has not yet taken any action.

In fact, the agency held a two-day, public meeting last November. But two months ago, the FDA issued a memo that, instead of suggesting possible solutions, simply summarized key points framing the long-running debate and carefully rebuffed many of the suggestions made by drug makers and others that support expanding pharmaceutical marketing.

And so the Goldwater Institute is trying to force the issue with the Free Speech in Medicine Act.

“Curbing the exchange of information about off-label treatments by those with the most knowledge about the drug’s uses, risks, and side effects not only prevents patients from receiving the best possible care; it violates the constitutional right to free speech,” said Christina Sandefur, the executive vice president of the Goldwater Institute, in a statement.

While the Goldwater Institute plans to take its “model law” to other state legislatures, so far, similar bills have not yet been introduced elsewhere, according to Richard Cauchi, health program director at the National Conference of State Legislatures.

Meanwhile, though, one former FDA official, who has publicly urged the FDA to loosen its regulations, believes such state laws would be useless, because they would be preempted by federal law that allows the FDA to issue guidance documents and rules about various activities and requirements.

“It’s nice that the Arizona legislature thinks disseminating off-label information is a good thing, but it’s not their jurisdiction to say so,” said Peter Pitts, a former FDA associate commissioner who heads the Center for Medicine in the Public Interest, a think tank that is funded, in part, by the pharmaceutical industry. “I don’t think a challenge in court would last more than five minutes.”

Nonetheless, one consumer advocate, who opposes widening the ability of drug makers to promote off-label uses, fully expects the Goldwater Institute to persist.

“I don’t think the law will change the landscape, but they’re seeking to gin up public attention and become a stepping-stone to try to get Congress to pass laws that would accomplish the same thing on a national level,” said Michael Carome, who heads Public Citizen.  “I suspect that’s the ultimate goal.”

As for the Right to Try campaign, 33 states have so far passed such laws and, recently, bills were introduced in the US House and the Senate. Critics say these bills are wrongheaded for trying to cut the FDA out of the process, since regulatory oversight would be removed and drug makers are actually the ultimate gatekeepers for deciding access to their drugs.
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STAT News Tangled Treatment of Scott Gottlieb

03/29/2017 12:29 PM | Robert Goldberg

STAT News is one of my favorite sites for medical and health news.   The reporting is great and the journalists are open, thoughtful and smart.   

Every once in a while there will be clunker like the following article about Scott Gottlieb:

Trump’s FDA nominee pledges to untangle his ties to 25 biopharma companies

"President Trump’s pick to lead the Food and Drug Administration has promised to recuse himself from agency decisions on more than 25 companies to which he has ties.

Dr. Scott Gottlieb, who is deeply entrenched in the industry he may soon regulate, plans to resign from his roles in investment banking, venture capital, and as a consultant to drug companies within 90 days of his Senate confirmation. At the same time, he’ll sell off his shares in a host of biotech companies.

And for one year after those resignations, Gottlieb will stay out of any FDA deliberations related to those companies, which include GlaxoSmithKline, Bristol-Myers Squibb, and Vertex Pharmaceuticals."

Deeply entrenched?  Untangling of ties?  From 25 -- count em, 25 -- companies? Sounds suspicious.  Should we ask Carrie Matheson to get to the bottom of Gottlieb's consulting activities?  

A less breathless and narrative driven article could have noted that Scott's recusals and divesting of industry related investments and associations are no different than what any other nominee for FDA commissioner has done, including Rob Califf and Peggy Hamburg.   And no one was keeping score of how many companies they consulted for or held stock in.  Or that Gottlieb has made increasing the number of generic drugs that compete against medicines made by companies he advised a top priority? 

To be fair,  when I wrote to STAT News editor Rebecca Robbins raising my belief that the article was more narrative than reporting she responded that the intent was not to reinforce a narrative peddled those who regard Dr. Gottlieb as a pharma pawn.  

But there is this as well: "The 44-year-old physician has traced an unusual career path, pivoting from Wall Street to a role at the FDA and then embarking on a lucrative career as an investor and adviser." 

Who else thinks that this article will spur more attacks and spawn similar pieces from other news outlets that will include quotes from anti-industry critics such as Public Citizen who have already smeared Scott?


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ICER Devalues People With Rheumatoid Arthritis

03/28/2017 01:05 PM | Robert Goldberg

 

ICER recently had a meeting to discuss its latest study: "Targeted Immune Modulators for Rheumatoid Arthritis: Effectiveness & Value." It is no different than any other ICER report:  It concludes no medicine is cost effective and it uses methodology that no economist can replicate.   ICER reports are the cold fusion experiments of health care economics. 

I have released a report discussing the impact of ICERs approach on patients.  It concludes that applying ICER's cost-effectiveness standard to all biologics developed for RA since 2000 (none are cost-effective according to ICER) would have harmed a lot of people with RA.

Between 1999 and 2014 there would have been 46689 more deaths under an ICER regime.   Additionally, research suggests that since 1999 the life expectancy of people with RA who used new medicines could expect to live 10 years longer than those not treated.   Hence under an ICER regime people with RA would have 466894 fewer life years (46689 x 10).  

Going forward, ICER claims new RA drugs are not cost effective either.  

ICER estimates that only 97000 people year for five years (486000) with RA would get two new drugs it reviewed: baricitinib and sarilumab.  Both medicines were tested in people with RA whose disease didn’t respond to any other treatments or couldn’t tolerate any other medicines.  

ICER fails to disclose how they arrived at the estimate that 97000 people a year would use new drugs. Further, it assumes – without any support – that 70% of new users on baricitinib would come from patients using sarilumab and 30% would come from another biologic -- adalimumab--that it claims isn't cost effective either. 

In doing so, ICER assumed that 50% of these patients were moderate-to-severe cases, and 50% of this subset had failed initial treatment with non-biologic RA drugs such as methotrexate.  ICER states: "Applying these proportions to the projected 2016 US population resulted in an estimate of approximately 486,000 patients in the US over a five-year period.”

But this assumption is flawed. A recent study found that 50 percent of all RA patients failed to respond to their second-line biologics. Further, many other patients will stop responding to any therapy.   Finally, ICER did not consider that many people with RA do not benefit from any other medicines.  So, there is little basis to assume that two new medicines would not be used more widely as well as claim that one would replace the other.  

If the 97000 limit is applied, 398000 people with RA a year would be denied medicines that improve their condition and could likely increase their life expectancy. ICER limits would cost RA patients up to 250900 life years over that time. 

You can access the entire study here.   Read More & Comment...

Limpid Lipids

03/28/2017 10:25 AM | Peter Pitts

Nothing is more illustrative of the price/value discussion than PCSK9s. Just what are they worth? What's innovation worth?

At a recent Galen Institute forum, cardiologists, patient organizations, and policy wonks sat down to discuss the relative merits of PCSK9s both as a therapeutic choice and a reimbursement imbroglio. Issues ranged from physicians’ frustration with pre-authorization, to best practice beyond familial hyperlipidemia. What value should be assigned to PCSK9s for patients who are non-compliant with their statin therapy? Providers want to have the freedom to deliver the best clinical outcomes. How can payers become a more symbiotic part of that therapeutic journey?

Galen Institute President Grace-Marie Turner commented, "As I travel the country, I have become increasingly concerned as doctors say that their hands are being tied by bureaucrats who second-guess their clinical decisions. At this critical moment in the health care debate, I believe policymakers need to hear the physician point of view." She noted that, typically, physicians are so busy caring for patients that they do not have much opportunity to take part in discussions of health care policy. "For this reason, we decided to bring this group together to begin a national conversation about this crisis in the medical profession, and ensure that policymakers and patients alike understand the barriers doctors are facing as they attempt to deliver the best care possible to their patients."

According to Dr. Seth Baum, fellow of the American College of Cardiology, the American Heart Association, the American College of Preventive Medicine, the National Lipid Association, and the American Society for Preventive Cardiology, "Patients should not have to wonder who is deciding which medicines they take -- their doctor, or their insurer … In my case, I am forced to complete intricate, 17-page documents so that insurers will allow my patients access to lifesaving new cholesterol medications, only to see them turned down, repeatedly."

Baum also pointed to "fail first" policies, which require doctors to prescribe older, cheaper medicines for patients until those patients "fail" on those drugs, before being allowed to prescribe breakthrough treatments that would be more effective. "These decisions are best made between doctor and patient, not by bureaucrats," he added. "Insurance should help ease health care worries, not tie doctors and patients up in red tape."

Another speaker at the conference, Dr. Hal Scherz, a pediatric urologist, said, "Third-party interference has become endemic in the U.S. health care system, and is increasingly destructive to the patient-physician relationship. A recent survey by the Physician's Foundation found that 53.9% of physicians surveyed claim that some of their decisions are compromised due to their current level of clinical autonomy. I am glad to take part in this discussion, and hope it will increase public awareness of the restrictions doctors encounter in their daily work."

Disease is the enemy. Practicing physicians know this, but their professional association -- the American Medical Association -- seems in need of some education. The AMA's new program, "truthinrx.org," is entirely silent on the actual metrics of healthcare spending and the value of pharmaceutical innovation. Ignorance is not bliss.

Medicines lower health care costs by improving patient health and warding off more serious complications, government interventions that discourage drug development will increase health care spending, not cut it.

The current inquisition of the pharmaceutical industry is meant to justify government restrictions on drug pricing. If facts still matter, free-market competition will be exonerated and upheld as the best way to contain health care spending while delivering quality care. If they don't matter, and legislators insist on imposing innovation-killing price controls, future health care savings will go up in smoke.

Healthcare innovation saves lives, saves money, promotes economic growth, and provides hope for hundreds of millions of people (both patients and care-givers) in the United States and around the world. It deserves respect -- or at least honest reportage.

Does this sound naïve? Perhaps, but as Schopenhauer said, "All truth passes through three stages. First, it is ridiculed. Second, it is violently opposed. Third, it is accepted as being self-evident."

How’s that for a tweet?  Read More & Comment...

Fake DTC news mustn't drive the healthcare debate

03/27/2017 09:57 AM | Peter Pitts

Policy development by sound bite is becoming a chronic disease. Exhibit A: “Pharma spends more on marketing and sales than on R&D.”

The Washington Post wrote about it.

John Oliver talked about it.

Legislators are fixated on it.

Letters to the Wall Street Journal complained about it.

Let’s look at the record – because the devil is in the details – and it starts with what “sales and marketing” means.

When pundits, politicians, and policymakers speak about “sales and marketing,” the picture they are painting is of direct-to-consumer pharmaceutical advertising – the public face of Big Pharma. So, let’s set the record straight on that straight away. In 2016 $5.6 billion was spent on DTC. Same period R&D spending is roughly $70 billion. Amorous middle-aged couples in claw foot bathtubs are a lot sexier than excel spreadsheets, but facts are pesky things. Surprised?

Here’s another eye-opener, the category of “marketing and sales” also includes product sampling and communications to physicians, legal and accounting fees, salaries, rent and utilities, and all post-licensure programs deemed necessary by the FDA. Nuts and bolts aren’t cheap. It’s also important to understand that the R&D reported investment is only for pre-approval investment and doesn't take into consideration post approval R&D expenditures, which were $20 billion in 2011 and most likely, much higher today.

But let’s address the elephant in the room – DTC advertising. Yes – it’s good for business (otherwise it wouldn't exist) but it’s also good for the public health. And, no, it doesn’t make medicines more expensive.

The good news is that an informed healthcare consumer is a healthier citizen.  And while information comes from many sources outside of the physician’s office – one of the most pervasive channels is through direct-to-consumer advertising.

Properly done, pharmaceutical advertising helps to de-stigmatize certain diseases and encourages people to talk with their doctors about problems previously considered taboo -- like depression. Other research demonstrated little or no correlation between a brand's DTC spending and it's cost. In other words, brands that spend more heavily on DTC advertising do not necessarily cost more than their less-advertised competition.

FDA research, of patients who visited their doctors because of an ad they saw, and who asked about that prescription drug by brand name, 87 percent actually had the condition the drug treats. And in 6 percent of those DTC-generated visits, a previously undiagnosed condition was discovered. Why is that so important? Because earlier detection combined with appropriate treatment means that more people will live longer, healthier, more productive lives without having to confront riskier, more costly medical interventions later on.

Only 7 percent of doctors said they felt "very pressured to prescribe" a particular advertised drug. When the FDA panel probed into the question of "pressure to prescribe," what we found out was that the real pressure was time pressure. More patients are coming in armed with more questions. A study in Health Affairs arrived at a similar conclusion. According to the study, ad- inspired doctor visits resulted in the advertised medicine being prescribed in only about 47 per cent of cases. Put another way, patients didn't get a prescription for the medicine they came in to discuss on more than half their visits. Even with advertising, doctors exert appropriate judgment when they prescribe drugs.

According to the FDA study, a majority of doctors feel that DTC advertising increases patient awareness and involvement, improves compliance, and enhances the overall doctor-patient relationship. But we can - we must - do better. Health care information is the consumer's Rosetta Stone, and the FDA, public policy institutes, pharmaceutical firms, communications professionals, health care providers, disease organizations, patient advocates, academics along with state and federal legislators must help design 21st century DTC advertising that not only helps to sell product, but also advances the public health.  Read More & Comment...

De-Commissioning Drug Importation

03/17/2017 07:35 AM | Peter Pitts

Yesterday, four former FDA commissioners warned that proposals to allow importation of pharmaceuticals would create serious risks for consumer and patients, and would produce only minimal savings.

While importation proposals are intended to "make lower-cost but genuine, safe and effective drugs available to U.S. consumers," in practice they would "harm patients and consumers and compromise the carefully constructed system that guards the safety of our nation’s medical products," the former commissioners wrote in an open letter to Congress. Robert Califf, Margaret Hamburg, Mark McClellan, and Andrew von Eschenbach signed the letter.

The former commissioners note that in exceptional circumstances, limited importation has been permitted, but wrote that when they were in office, none of them was "able to conclude that a wider policy of routine importation would increase access to safe and effective drugs for the American public."

The letter directly addresses legislation that seeks to assure the safety of imported drugs by limiting importation to drugs made in FDA-inspected plants. "Allowing importation of drugs purported to be manufactured overseas in FDA-inspected facilities and drugs purported to be manufactured domestically for export to other countries and re-imported from those countries to the United States can not meet the requirements under the existing closed drug manufacturing and distribution system because the drugs could not be tracked and certified by the manufacturer."

Sales of illicit, ineffective, or adulterated products are a lucrative business for organized crime, the letter warns. It would be practically impossible to screen and verify the authenticity of massive quantities of imports, the group wrote, adding that "if spot-checking discovered a dangerous or counterfeit product, in the absence of the closed system currently in use, there would be no way to trace that product to its origin or intervene to protect other consumers before irreparable harm occurs."

The letter also challenges assumptions about cost savings from importation, noting that drugs are allotted to countries based on the needs of their populations, leaving little extra inventory for export to the U.S. It states that importation "would likely have only a small, incremental effect on cost and access for drugs in the U.S. market; further, these small savings might not be passed on to patients, even if consumers are able to obtain a legitimate imported drug."

The letter concludes: "We urge Congress and the many others concerned about the cost of drugs to deal directly with the issues driving the cost of medicines and not to place false hope in measures that will place patients who need treatment at risk and jeopardize public health.  Read More & Comment...

The Worst Drug Cost Article of the Year

03/16/2017 10:31 AM | Robert Goldberg

Liz Szabo wrote what I predict will be the worst (as in most deceptive and inaccurate) article on prescription drug costs to be published by a so-called mainstream media outlet in 2017.  

"As Drug Costs Soar, People Delay Or Skip Cancer Treatments" claims that high drug prices are causing cancer patients to go bankrupt.  To make that point distorts and omit facts in ways that let PBMs and health plans off the hook for imposing high out of pocket drug costs on a small group of patients.

Szabo overstates the problem and then fails to support her claim: 

"We're talking about huge numbers of patients," says Dr. Scott Ramsey, director of the Hutchinson Institute for Cancer Outcomes Research at the Fred Hutchinson Cancer Center in Seattle. "It's an epidemic. And it's not going away."

While a huge problem for anyone in that situation, the good news is that the percentage of patients that must pay thousands of out of pocket is very small.  Nearly 95 percent of  cancer patients are not exposed to high out of pocket cancer costs.   The other 5 percent often have supplemental insurance or receive cost sharing assistance.  

Szabo claims that between 168,000 to 405,000 ‘ration’ their prescription use because of cost.    This a sloppy use of the word made even sloppier because Szabo defines rationing as delaying the use of cancer drugs.  Moreover, the studies she relies on to generate her guesstimate looks only at the small group of patients that –because of a low income or lack of insurance coverage – cite cost as a barrier to care.

The burden of out of pocket cost is not a small matter to those who must bear it.   But to address the problem you have to identify the cause.  Szabo strenuously avoids doing so. 

She insinuates that the most important factor is the price of medicines. In fact, it is extreme drug cost sharing imposed by PBMs and insurers on the sickest 1 percent of patients with cancer, MS, rheumatoid arthritis, cystic fibrosis and other rare diseases.   

Further,  PBMs and insurers systematically target people with these conditions particularly in Medicare Part D and commercial plans provided under the Affordable Care Act.  In those plans, insurers and PBMs have placed most or all new cancer drugs on the highest cost-sharing tier of drug benefit programs. 

Net drug prices have been declining so the excuse that cost sharing has to increasse in step with increasing prices won't wash. 

A Kaiser study recently found that “Payments for deductibles and coinsurance have outpaced increases in costs paid by the health plans themselves.  Average payments toward deductibles more than tripled, rising 256 percent, and average payments toward coinsurance more than doubled, rising 107 percent. This is while average payments by health plans themselves only increased 58 percent. “

The real reason for the cost sharing discrimination Szabo ignores is that is where the money is.

The one percent of patients and the 1 percent of the drugs that are dispensed to them generate about $150 billion in drug sales at list price.    PBMs and insurers extract $30-40 billion from drug companies in the form of rebatres.  These rebates reduce the actual cost of drugs.  But those savings are not fully passed on to patients. 

Instead, most of these drugs are placed in the highest cost sharing formulary tier and patients then pay up to 50 percent of the list -- not rebated -- price of drugs.  On average, the cost sharing is about 35 percent of the retail price of drugs.   That's another $45 billion insurers and PBMs collect.    Generating $75 billion on sales of $150 billion is a nice haul.  But Ms. Szabo seems to think it's not such a big deal. 

Did I mention that this practice is systematic? 

A recent study found that insurers are increasingly designing benefits to maximize profitability and turn patients into revenue centers.  The analysis notes for example that patients being treated for cancer or multiple sclerosis will cost an average of $61,000 but only generate $47,000 in revenue after accounting for the large risk adjustment and reinsurance transfer payments.  The difference is made up by squeezing more profits out of drugs.

The researchers said this creates a large incentive to place such drugs on specialty tiers, where patients face high out-of-pocket costs and where drugs generate the most rebates. 

This is certainly what has happened to cancer drugs.  Since 2011 net price increases have declined for cancer medicines.  Yet list prices have increased.  The difference between net and list prices goes to rebates pocketed by health plans and insurance companies even as they hike cost sharing.  

Further, even as rebates increase, more health plans are putting all cancer drugs in higher cost-sharing tiers, generic or not:

As a recent American Cancer Society study concludes: “Plans continue to place most or all oral chemotherapy medications on the highest cost-sharing tier, creating transparency and cost barriers for patients. The two generic oral cancer drugs we studied regularly appeared on the most expensive tier (41 and 62 percent of the time). The effect may be to inappropriately discourage enrollment by cancer patients.”

This is both unfair and inefficient.  the use of new medicines lower treatment costs over time as well as substantially improving health over time.  

In some case,  insurers have recognized the dynamic contribution new medicines make to health and health systems and have protected  cancer patients from high-cost sharing.  A study of coverage for targeted drugs treating chronic myeloid leukemia found that their use of “was associated with lower spending on other types of healthcare services. CML patients on such targeted drugs ..”had roughly $12,000 less in nonpharmaceutical medical costs than did patients on alternative forms of therapy. This translated into a decline of more than 30% in medical spending and offset roughly 40% of the cost of the drugs...This result is consistent with prior work that suggested changing generosity for one healthcare service has both short- and long-term implications for spending in other areas.” 

Instead, Szabo ignores the qualitative improvement in new cancer drugs and advantage of eliminating cost barriers for the most innovative treatments:

Spending on cancer has remained about 4 percent of health care spending since 1960 because drugs have been displacing hospitalization, which is more expensive.  For instance, if people were being hospitalized for cancer in 2014 at the same rate they were in 1995, total hospital costs would be $60 billion a year more.   

Additionally, whereas there were only 4 million cancer survivors in 1975, there are 14 million survivors today. The cancer death rate for men and women combined fell 25% from its peak in 1991 to 2014.  

New cancer medicines have reduced health care spending and increased well-being and capacity to work.  So, my question is: if the use of new medications makes cancer care more effective and affordable, why are health plans and PBMs making them more expensive? 

Maybe another reporter will write an article about that.   Read More & Comment...

Wyden the PBM Investigation

03/15/2017 08:47 AM | Peter Pitts

Politico 3-15-17: TODAY: WYDEN INTRODUCES BILL TARGETING PBMs — The ranking member of the Senate Finance Committee will roll out a proposal today to lower drug costs by targeting prescription benefit managers (PBMS) — middlemen who negotiate discounts on drugs with pharma companies and administer prescription drug coverage for health insurance companies.

According to an email obtained by POLITICO, the bill would mandate that patient co-pays or co-insurance for drugs in Medicare Part D are based on the negotiated price of the drug, not the higher list price. The bill also requires more transparency by mandating that PBMs publicly disclose aggregate rebates and the amount of those rebates passed on to health plans, as well as the difference between what a PBM pays a pharmacy for a drug and what the PBM charges a health plan for the drug.  Read More & Comment...

Scott Gottlieb: The Patient's FDA Commissioner

03/14/2017 11:17 AM | Robert Goldberg

Dr. Scott Gottlieb

I have worked with Scott Gottlieb for over a decade on making drug development swifter by making it more scientific and increasing patient access to medical innovations.   Scott played an important role in developing the Critical Path Initiative that has been the FDA's roadmap for moving the agency -- and our health care system -- towards predictive, personalized and participatory medicine.  None of the advances in expediting approval of important new medicines would have been possible in the absence of The Critical Path Initiative. 

I could discuss his accomplishments in the post.  But many others will write about Scott's ability and experience in support of his nomination to be FDA commissioner.  A handful will attempt to demonize him for that very experience.  

So let me tell you what I know about the human being who has been nominated to be FDA commissioner. 

 I know of Scott's calm courage after his cancer diagnosis, his devotion to his family and his dedication to the practice of medicine.  For years (until he had children) he was an internist and hospitalist, seeing and healing patients on weekend, evenings and holidays, all the while performing his duties at FDA and CMS.   He loves medicine and that emotion shapes his view about how to best use advances in science to improve the safety and effectiveness of medical technologies.    He is not an ideologue.  He is data-driven and his views and decisions are informed by the kind of robust discussion and debate that is increasingly rare in our public sphere.  

Finally, Scott has never let the intricacies of policy or statistical hair splitting deter him from thinking about the FDA as an institution that has more control over life and death -- as well as how well we live -- than any other agency on earth.   He knows that patients and their families have as much a right to weigh in on FDA decisions as any so-called expert.  The great medical reformer, William Osler once noted: "The good physician treats the disease; the great physician treats the patient who has the disease."  

Scott is a great physician and will be a great FDA commissioner who puts patients first. 

   Read More & Comment...

Fighting Opioid Abuse with Regulatory Clarity

03/14/2017 08:41 AM | Peter Pitts

At the recent abuse deterrent opioids summit, CDER Deputy Director for Regulatory Programs Dr. Doug Throckmorton presented the FDA’s position. He said, “We must move on from older to newer technologies. Amen. But how?

Per Dr. Throckmorton, “Ongoing and planned activities reflect the commitment by FDA to integrate the use of all of our available tools to achieve our goals related to the safe use of prescription opioids.” Two crucial aspects of moving forward are smart policy initiatives and regulatory clarity. We are inching our way forward on both. We can and must do better.

A key part of the FDA’s Opioid Action Plan is “Expand access to abuse-deterrent formulations (ADFs) to discourage abuse.” In order to achieve this worthy goal, the agency has issued numerous guidance’s – but actions speak louder than words – and the FDA’s actions have been, at times, confusing. When it comes to the development of new therapies to prevent opioid abuse and addiction, predictability is power in pursuit of the public health.

One of the FDA’s stated goals is to “Incentivize the development of opioid medications with progressively better AD properties and support their widespread use.” Bravo. But the devil is in the details. One area of regulatory clarity that could be improved is the agency’s views on differentiation between extended-release and long-acting (ER-LA) and immediate release (IR) opioids and how new products are tested for abuse-deterrent properties.  This is a critical concern as IR opioids, with over 240 million scripts annual, represent nearly 96% of the entire opioid market. They are the “gateway” drug of prescription opioid abuse and do not have a single approved ADF formulation.

Believe it or not, abuse deterrence is largely defined and determined by how admitted opioid abusers “like” the product.  (Abuse of IR opioid drugs is attractive to abusers because bypassing intestinal absorption and metabolism can lead to a higher Cmax and faster Tmax resulting in a more intense and more immediate high.)

Not surprisingly, abusers prefer immediate release products because they get their highs faster. But, as far as regulatory review is concerned, that also means that IR products under review by the FDA are determined to be less abuse-deterrent.

It’s an apples-to-oranges comparison that is resulting in an uneven ER-LA/IR regulatory playing field. And the unfortunate result is that it’s harder for immediate release opioids to pass FDA muster. Since IR opioids are designed to release “immediately” and last for a short duration (3-4 hours), measurements of drug exposure and “liking” should be taken at earlier, more IR-relevant intervals (when measured against existing, non-abuse deterrent comparator drugs).  Measuring IR products by ER-LA standards is not a real world proposition. (When ER-LA’s are compared to IR’s by abusers – of course they like the immediate “high” better).  The “clinic” experience needs to be reflective of real-world abuse.

Regulatory ambiguity and common sense are not allies. In fact, the agency has identified one of its major challenges as assessing the impact of individual formulations. Admitting the problem is important. Addressing it is urgent.

It’s time for the FDA to reflect on a more nuanced approach in measuring and determining appropriate standards for demonstrating abuse-deterrent properties of immediate release opioid.  Small differences can lead to big benefits in the real world of deterrence.  The key question remains not unanswered, but unaddressed – are the endpoints suggested in FDA’s “Guidance for Industry: Abuse-Deterrent Opioids—Evaluation and Labeling” the most relevant for demonstrating abuse-deterrent properties of an IR opioid?

While the public health imperative must drive the regulatory agenda, another important issue is how agency actions impact continued robust research and development. Minus more up-to-date and predictable FDA review criteria for abuse deterrent opioids, investment in their development is already becoming less attractive. Can we really afford to leave these decisions in the hands of admitted drug addicts? Actions (or inactions) have consequences.

As Dr. Throckmorton said at the recent meeting of the Agency’s Science Board: “FDA will act within its authorities in support of our public health mission to help defeat the epidemic of opioid abuse through a science-based and continuously evolving approach by improving the use of opioids through careful and appropriate regulatory activities, improving the use of opioids through careful and appropriate policy development, improving the treatment of pain through improved science, and improving the safe use of opioids through communication, partnership and collaboration.”

The time to focus on this issue is now. Lives are at stake.
   Read More & Comment...

Scott Gottlieb in the Pink (Sheet)

03/13/2017 10:18 AM | Peter Pitts

Some snippets from an excellent article in the Pink Sheet.

Gottlieb Nomination As US FDA Chief Could Signal Changes To Generic Approval Process

Michael Cipriano
 
Former deputy commissioner will also likely push increased use of biomarkers and more flexibility in off-label communication, among other reforms. President Donald Trump's choice of Scott Gottlieb to head the US FDA could signal efforts to bring reforms among a variety of fronts, perhaps none more notable than how the agency approves generic drugs.
 
Peter Pitts, president of the Center for Medicine in the Public Interest and a former FDA associate commissioner, touted Gottlieb as "a great choice." Pitts, who worked with Gottlieb for nearly two years at the agency, tells the Pink Sheet that he "knows the people, he knows the process, and he understands how to make both work harder and smarter."

"He understands the need to bring generic drugs to the market faster," Pitts said. "He understands the importance of addressing the single-source generic issue from a competitive perspective. He also understands, probably most importantly, the need not just for things happening faster, but things happening with greater predictability."
 
Public Citizen, however, was not so rosy about Gottlieb's selection, citing his close ties to industry, as it similarly did when Robert Califf was tapped to head the agency under President Obama.
 
In a statement, Michael Carome, director of Public Citizen's Health Research Group, noted that Gottlieb is currently serving or has recently served on the boards of five pharmaceutical companies, including that of  GlaxoSmithKlein, and that he received at least $413,000 from multiple drug and medical device companies for mainly consulting and speaking fees. Carome called on the Senate to reject his nomination.
 
"When Gottlieb served as FDA deputy commissioner, he was recused from many key meetings and decisions due to his close relationship with industry," Carome said. "If the Senate does not reject Gottlieb, he will have to be recused from key decisions time and time again, otherwise there is no way to be sure he will put the public’s health over industry profits."
 
Pitts, however, contended that close ties to industry "are incredibly important."

"FDA has to be both a regulator of and ally with industry," Pitts said. "And I think Scott is the right guy to practice that nuanced relationship."  Read More & Comment...

The Drug Pricing Ecosystem -- A NY State of Mind

03/09/2017 07:53 AM | Peter Pitts

Governor Cuomo’s budget aims to control drug pricing through price controls . While this is a good political sound bite, it’s bad public policy with dangerous unintended consequences – the worst of being that it won't lower prices but will reduce patient choice.

Have a look at this interview I did yesterday on Capital Tonight for a robust conversation on PBMs, the value of innovation, the role of the FDA in lowering drug costs, and other timely topics.

   Read More & Comment...