Keeping the Bay State at Bay

04/08/2014 04:13 PM |

Governor Deval Patrick wants to ban Zohydro in Massachusetts.

That's what he wants, but what he needs is an intro level course in federal jurisdiction -- and he's about to get one.

US District Court Judge Rya W. Zobel would not grant an immediate restraining order as requested by drugmaker Zogenix, but scheduled a followup hearing for Monday, saying it appeared that Zogenix would have a likelihood of winning the case.

 “I think, frankly, the governor is out of line on this,” Zobel said..”

 She urged both sides to discuss the issue before Monday.

 “I do not expect this to be a very long hearing,” he said.

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Channeling Patty Delaney

04/08/2014 07:05 AM |

Returning to the subject of expanded access to developmental medicines (When Compassion Isn’t Enough), I want to be clear that it wasn’t me who coined the term “expanded access.” As one of my former FDA colleagues commented, “In March 1990 the IOM Roundtable for the Development of Drugs and Vaccines Against AIDS held a workshop “Expanding Access to Investigational Therapies for HIV Infection and AIDS.”  FDA staff, including me, participated in the Keystone national policy dialogue (Expanded access to promising therapeutic drugs for HIV infection and AIDS with implications for other life-threatening diseases) in the early 1990s.  Also in the early 90s, FDA used the term expanded access at advisory committee meetings and at meetings of the National Task Force on AIDS Drug Development.”

Naming issues aside, this remains a highly contentious issue – and for all the wrong reasons. A new paper from the Goldwater Institute, “Everyone Deserves the Right to Try: Empowering the Terminally Ill to Take Control of their Treatment,” points the finger at the FDA as a roadblock to access, “Sadly, over half a million cancer patients and thousands of patients with other terminal illnesses die each year as the bureaucratic wheels at the FDA slowly turn.”

Nothing could be further from the truth.

What the paper presents a libertarian platform, “The burdens imposed on a terminal patient who fights to save his or her own life are a violation of personal liberty.” Maybe so, but the Supreme Court has ruled otherwise. In January 2008, the U.S. Supreme Court, without comment, opted not to accept an appeal of Abigail Alliance v. von Eschenbach. In other words, the federal appeals court ruling that patients do not have a constitutional right to experimental drugs stands

The paper continues, “Such people should have the option of accessing investigational drugs which have passed basic safety tests, provided there is a doctor’s recommendation, informed consent, and the willingness of the manufacturer of the medication to make such drugs available.”

I don’t think that anyone of those constituencies has any argument on that point. But should the FDA be cut out of the process? According to the paper, “… bureaucratic impediments violate an individual’s fundamental right to try to save his own life.”

But that’s consistent with the author’s libertarian philosophy. She believes that the “vast new granting of power (of the Kefauver-Harris Amendments) “was unwarranted.” So, consider the source of the argument.

Alacrity is important, certainly. But process is important too, as is collecting data on expanded access use.

The paper does raise important questions, such as at what point in the drug development process should an investigational product be available to patients? The author argues for Phase I. That’s an aggressive position, but one worth debating.

One item that paper ignores is that for the FDA to address single patient INDs with both more careful attention and speed is funding. That’s more than the 800-pound gorilla sitting in the room – it’s the 800-pound gorilla sitting on the chests of desperately ill patients who want access to investigational medicines.

The author quotes Patty Delaney. Patty (who passed away in 2008) was the FDA’s main liaison to the cancer community and a tireless soldier for “doing the right thing.” She was a pit bull on behalf of patients.

According to the paper, “As Patty Delaney, the former director of the FDA’s cancer liaison program explained in 2007, “the patient has a right to be heard, but in the end, it’s the data that matters. FDA opinions about safety and efficacy are always based on data.”

I’ll side with Patty.

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One of these things is not like the other

04/07/2014 07:25 AM |

Much chatter about Janet Woodcock’s Energy & Commerce Subcommittee on Health testimony last week.  Much of it ill-informed.

Dr. Woodcock stood firm that separate labeling for generic drugs will advance the public heath by advancing 21^st century drug safety. Subcommittee Chairman Joe Pitts (no relation) didn’t agree. His comment, “The only outcome I see is confusion,” demonstrates his own confusion.

“I’d like to dispel the notion that labels are the same now with respect to safety information,” said Janet. Representative Pitts was not mollified, moving on to suggest the agency’s motives were other than for advancing the public health – specifically that “trial lawyers” were to blame for the agency’s actions.

Trial lawyers? Clearly he’s met with representatives of the GPhA.

Janet made it clear that the decision to move forward on the labeling change rule was CDER and no one other than CDER. “The personnel in the Center for Drugs did not meet with the trial layers.”

Mr. Pitts’ suspicions were not assuaged. Whatever.

(PS/Representative Waxman commented that he found the GPhA’s report that distinct labeling would increase consumer spending on generic drugs by $4 billion annually “highly invalid.”)

Dr. Woodcock also clarified that the discussion about generics labeling did not extend to biosimilars.

Per Janet, “This rule does not apply to that because those would be under the Pubic Health Service Act – and they’re not considered generics, so that’s a separate issue.”

Much consternation over this last remark. Some see it as a nod and a wink that the agency is going to allow biosimilars to have the same name and labeling language as innovators. I disagree for two reasons:

(1) Janet was precisely correct in stating that generic drugs and biosimilars are two distinct things. Biosimilars are not generic drugs.

(2) The fact that the FDA has made distinct generic drug labeling such an important policy initiative certainly does not send a signal that they will view biosimilars in a more laissez faire manner. Au contraire.

So, for people trying to read too much into Janet’s statement that generic drug labeling is different from biosimilar naming and labeling, relax. If anything, the news is good.

Prediction is very difficult, especially about the future. – Niels Bohr

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The Hamburg Manifesto

04/04/2014 07:05 AM |

As a wise man once said, “He who tooteth not his own horn, that horn shall go untooted.

This is a valuable lesson that the FDA has learned to be true. And it couldn’t have happened at a better time. Specifically, I refer to opioids.

The FDA has taken the bit out of its mouth and taken hold of the reins of pain.

While scene-stealing members of Congress, some governors, and a gaggle of state attorneys general are trying to run roughshod over science-based regulation to great attention from the media, the FDA has been quietly doing the right thing without anybody noticing.

But when you do the right thing and don’t tell anyone about it, the assumption is that you’re not doing anything. That began to change with FDA Commissioner Hamburg’s aggressive testimony in front of the Senate HELP Committee defending the agency’s October approval of Zohydro ER.

And it continued yesterday with the agency’s approval of EVZIO™ (naloxone hydrochloride injection) for the emergency treatment of known or suspected opioid overdose. Smartly, the FDA used the approval to speak, more broadly, to the topic. There was a lot to say – and it’s about time the FDA said it.

Peggy’s complete remarks can be found here.

During the stakeholder teleconference the Commissioner laid it all on the table. It turns out that the FDA is doing a lot to mitigate opioid risk after all! Most importantly, they are doing so while understanding the need to ensure appropriate access for the tens of millions of Americans suffering from chronic pain.

She got specific:

Combatting the serious public health problem of misuse, abuse, addiction and overdose from opioid analgesics is a high priority. Since 2001 the FDA has taken a number of actions designed to help address prescription opioid abuse and to encourage the development of new drug treatments for pain. These actions include:

Revising the labeling for opioid medications to foster their safe and appropriate use, including recent changes to the indications and safety warnings of extended-release and long-acting opioids.

Requiring that manufacturers conduct studies of the safety of long-term use of prescription opioids.

Improving appropriate prescribing by physicians and use by patients through educational materials required as a part of a risk mitigation strategy for extended-release and long-acting opioids.

Using the agency’s expedited review programs to advance development of new non-opioid medications to treat pain with the goal of bringing new non- or less-abusable products to market.

Working with other federal agencies and scientists to advance our understanding of the mechanisms for pain and how to treat it, including the search for new non-opioid medications for pain.

Recommending that hydrocodone-containing combination products have additional restrictions on their use by rescheduling them from Schedule III to Schedule II.

Strengthening surveillance efforts to actively monitor the changing nature of prescription opioid abuse and to identify emerging issues.

And, importantly, encouraging the development of medications to treat opioid abuse, such as buprenorphine for use in medication-assisted treatment, and to reverse opioid overdoses, such as naloxone.

I can’t say I agree with all of these things. (Upscheduling impacts appropriate access), but it’s a pretty powerful list.

And, it seems, recalling drugs that are currently on the market isn’t on the agenda.

In the immortal words of Don Draper, “If you don't like what is being said, then change the conversation.

Peggy returned again and again to the role the FDA must play in facilitating physician education, not only through labeling language but physician education. She specifically mentioned CME and working to develop (with a broad constituency) validated tools for physicians to use in determining which patients may be more prone to slide into abuse so they can choose their therapeutic recommendations more precisely.

“It all comes back to provider education,” she said. Amen.

Provider education – the Hamburg Manifesto.

That’s not regulatory mission creep; it’s the appropriate application of the agency’s Safe Use of Drugs initiative. The way you make a drug “safer” is to ensure that it is used by the right patient in the proper manner.

Importantly, the Commissioner regularly referred not to “abuse” but to “misuse and abuse.” That’s more than a rhetorical flourish since it recognizes that misuse is a gateway to abuse.

Joining Dr. Hamburg on the call were Michael Botticelli, Acting Director, Office of National Drug Control Policy, Douglas Throckmorton, M.D., Deputy Director for Regulatory Programs, Center for Drug Evaluation and Research, FDA, Melinda Campopiano, M.D., Senior Medical Officer, Center for Substance Abuse Treatment, Substance Abuse and Mental Health Services Administration, and Wilson Compton, M.D., Deputy Director, National Institute on Drug Abuse, National Institutes of Health.

Oh, and HHS Secretary Kathleen Sebelius, who never mentioned the word “recall” either. It looks like the specter of Secretarial interference is off the table. Kudos to Secretary Sebelius for making it clear this is a cross-departmental priority.

The take away message was loud and clear –misuse and abuse of opioids is a serious issue that must be addressed in an appropriate manner.

And, per today’s teleconference, “appropriate” means science-based and patient-centric.

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Peggy on Opioids

04/03/2014 12:09 PM |

For Immediate Release: April 3, 2014
Media Inquiries: Sandy Walsh, 301-796-4669, sandy.walsh@fda.hhs.gov
Consumer Inquiries: 888-INFO-FDA

FDA Commissioner Margaret A. Hamburg Statement on Prescription Opioid Abuse

For more than a decade, the U.S. Food and Drug Administration has been working to address the important public health problems associated with the misuse, abuse, addiction and overdose of opioid analgesics, while at the same time working to ensure continued access to effective and appropriate medications for millions of Americans currently suffering from pain. I firmly believe that these goals are compatible, and that actions to address one should not be at the expense of the other.

Tragically, the most recent data shows that more than 16,000 lives are lost each year due to opioid-related overdoses. In fact, drug overdose deaths, driven largely by prescription drug overdose deaths, are now the leading cause of injury death in the United States – surpassing motor vehicle crashes. We know that the illegal diversion, misuse, and abuse of prescription opioids are often fueled by inappropriate prescribing, improper disposal of unused medications, and the illegal activity of a small number of health care providers. This highlights the important role that education of prescribers and patients can play in addressing this epidemic. The FDA has taken steps to address this but more work remains to be done.

Combatting the serious public health problem of misuse, abuse, addiction and overdose from opioid analgesics is a high priority. Since 2001 the FDA has taken a number of actions designed to help address prescription opioid abuse and to encourage the development of new drug treatments for pain. These actions include:

Revising the labeling for opioid medications to foster their safe and appropriate use, including recent changes to the indications and safety warnings of extended-release and long-acting opioids.

Requiring that manufacturers conduct studies of the safety of long-term use of prescription opioids.

Improving appropriate prescribing by physicians and use by patients through educational materials required as a part of a risk mitigation strategy for extended-release and long-acting opioids.

Using the agency’s expedited review programs to advance development of new non-opioid medications to treat pain with the goal of bringing new non- or less-abusable products to market.

Working with other federal agencies and scientists to advance our understanding of the mechanisms for pain and how to treat it, including the search for new non-opioid medications for pain.

Recommending that hydrocodone-containing combination products have additional restrictions on their use by rescheduling them from Schedule III to Schedule II.

Strengthening surveillance efforts to actively monitor the changing nature of prescription opioid abuse and to identify emerging issues.

And, importantly, encouraging the development of medications to treat opioid abuse, such as buprenorphine for use in medication-assisted treatment, and to reverse opioid overdoses, such as naloxone.

Today’s FDA approval of Evzio (naloxone autoinjector) provides an important new tool in our arsenal to more effectively combat the devastating effects of opioid overdose, which is one part of our comprehensive work to support opioid safety. Reflecting the FDA’s commitment to encouraging important new therapies, the FDA’s review of Evzio was granted priority status, and the application was reviewed by the FDA in just 15 weeks.

This product is the first auto-injector designed to rapidly reverse the overdose of either prescription or illicit opioids. While the larger goal is to reduce the need for products like these by preventing opioid addiction and abuse, they are extremely important innovations that will help to save lives.

The FDA will continue to work to reduce the risks of abuse and misuse of prescription opioids, but we cannot solve this complex problem alone. A comprehensive and coordinated approach is needed; one that includes the White House Office of National Drug Control Policy, the Drug Enforcement Administration and many of our sister agencies within the Department of Health and Human Services, as well as state and local governments, public health experts, health care professionals, addiction experts, researchers, industry, and patient organizations.

I am confident that this can be accomplished, but we will all need to work together to invest in strategies and responsible approaches that deter or mitigate the effects of abuse while preserving access to pain medicines for the patients that need them the most.
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You can call me Al ... Jazeera

04/03/2014 07:36 AM |

On Tuesday I appeared on Al Jazeera America program, “The Stream.” The episode was titled “Inside the medicine cabinet,” and here’s how it was described:

Nearly 70% of Americans are on at least one medication. But for millions, combining too many of them could lead to dangerous consequences – even with safeguards in place to protect patients. We’ll explore what you need to know about your medicine cabinet.

Hosted by Lisa Fletcher, my fellow panelists were

Michael Carome 
Director, Health Research Group at Public Citizen 

Dr. Natalie Boulware 
Naturopathic Physician, Tulsi Holistic Living 

Dr. Caleb Alexander  
Co-Director, Johns Hopkins Center for Drug Safety and Effectiveness

David S.H. Lee 
Assistant Professor, Oregon State University College of Pharmacy

Good topic. Good panelists.

Click here for the full video.

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Adherence 'Appens

04/03/2014 06:53 AM |

According to a new study from Adherent Health, a mobile health engagement advisory focused on medication safe-use, adherence, and health outcomes attainment, nearly three-quarters of prescription-takers use mobile apps, including most older adults and seniors.

Mobile app adoption rates are high across all medication-taking adult age groups: 93% (age 18-24), 90% (age 25-34), 88% (age 35-44), 80% (age 45-54), 66% (age 55-64), and 50% (age 65+).

Among other study findings, prescription-taking patients using mobile apps were similar to their non-app using counterparts in terms of annual income, education level, and geographic region.

Conducted in the first quarter of 2014, the 2014 Patient Preference Study surveyed the mobile app behaviors and medication support preferences of 2,216 prescription-taking patients aged 18-65+.  

"This is a high rate of mobile app use among prescription-taking patients of all ages, including those 65+" remarked Michael A. Weber, MD, Professor of Medicine at the SUNY Downstate College of Medicine in Brooklyn, and Editor-In Chief of the Journal of Clinical Hypertension. "Apps represent an attractive communications medium to better support patient understanding, medication adherence, and medication safe-use."

Approximately half of America's 187 million prescription-takers are non-adherent, meaning they do not take their medications as prescribed.

App-using patients prefer a privacy-protected single app (such as Adherent’s Mobile Health Library system) by a factor of 11 to 1 over email programs often offered by medication manufacturers.  This high preference for a privacy-protected single app, customized to a user's needs for medication education and support services, was observed across all adult age groups.

"I'm not surprised that most patients would prefer a single privacy-protected app that supports medication dosing reminders, ongoing education, and co-pay and affordability needs" said Amy C. Sidorski, MS, CRNP, BSN, RN of Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University, and member of the ONS:Edge Oncology Nurse Experts Panel.  "Especially one they receive from their physician or nurse."

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When Compassion Isn't Enough

04/01/2014 09:38 AM |

A very important series of stories in this week’s issue of BioCentury (authored by Steve Usdin) addressing the thorny, urgent (and too frequently ignored) topic of expanded access to experimental medicines. The articles generally refer to “compassionate use” and “compassionate access.” That’s the wrong terminology – and a good place to begin the conversation.

In January 2008, the U.S. Supreme Court, without comment, opted not to accept an appeal of Abigail Alliance v. von Eschenbach. In other words, the federal appeals court ruling that patients do not have a constitutional right to experimental drugs stands.

This is a tough, emotional issue and, with such heated rhetoric on both sides, it's easy to lose sight of the fact that everyone wants the same thing -- expanded access to drugs under clinical investigation.

For me this issue began (when I was Associate Commissioner for External Affairs at the FDA) during a meeting with Theresa Toigo (then the Director of the agency’s Office of Special Health Issues) and Frank Burroughs (founder of the Abigail Alliance for Better Access to Developmental Drugs). The meeting centered on Frank’s assertion that the FDA could do more to expand its parameters for patient access. We all agreed more could be done. Frank left. Terry stayed – and I asked her why we (the FDA) used the term “compassionate use.” Her answer was simple – “It’s what we’ve always called it.”

I said, “Let’s change what we call it." Allowing desperately ill patients into clinical trial programs shouldn't be an act of noblesse oblige it should be an act of civil society. We decided to work towards changing the term to “expanded access.” And we did. It’s one of the things I am most proud of accomplishing during my time at the FDA.

But it has to be more than rhetoric. The words have to mean something – and what they have to mean is that more patients get more access to more experimental medicines more expeditiously. In many cases it is, literally, a life-or-death situation.

When it comes to pharmaceutical safety, pure libertarianism isn't in the best interests of the public health. Expanded access to experimental drugs simply can't and shouldn't morph into total, unfettered access.

That doesn't mean the status quo is working. What it means is that the FDA needs to figure out a way to dramatically broaden and facilitate expanded access to experimental drugs under its review. And the Abigail Alliance and its supporters need to keep up the pressure to improve the current system.

This is best done in a spirit of collegiality rather than a confrontational courtroom or in Congress. Should expanded access design and development planning discussions be binary conversations between a sponsor and the FDA? What about the patient community? Perhaps, as part of the FDA’s current initiatives to enhance both the timeliness and weight of the patient voice, expanded access plan development and execution should involve patient organizations.  

In the BioCentury articles, Usdin speaks to the phenomenon of social media and the pressures it can (and does) bring to bear on sponsors. Maybe it’s time to harness that power to make the process both more inclusive and better.

It’s time.

The BioCentury articles can be found here, here, and here.

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Unfulfilled Expectations

03/31/2014 09:17 AM |

A new analysis by the Alliance for Integrity and Reform of 340B indicates that a substantial portion of hospitals enrolled in the 340B program provide only a minimal amount of charity care; as such, they may not be fulfilling Congress’ expectations. 

The study, compiled from newly available public data analyzed by Avalere Health, noted that the 340B drug discount program was designed by Congress to help safety net providers improve access to prescription medicines for uninsured, vulnerable patients in the outpatient hospital setting. Yet, the analysis shows, most hospitals that benefit from the program provide less charity care than the national average for all hospitals, and charity care in about a quarter of all 340B hospitals represents 1% or less of total patient costs.  A small number of 340B hospitals provide the lion’s share of all charity care delivered by 340B hospitals.

The analysis raises questions about whether the current 340B eligibility criteria specifically used for DSH hospitals are serving the spirit and intent of the law in that they may be overly broad and not just target those entities that serve high numbers of vulnerable, uninsured patients.  Specifically, the new research shows:

•       More than two-thirds of hospitals that receive 340B drug discounts provide less charity care as a percent of patient costs than the national average for all hospitals, including for-profit hospitals which do not qualify for 340B under current eligibility criteria.

•       For approximately a quarter (24%) of 340B hospitals, charity care represents 1% or less of the hospitals’ total patient costs.

•       Approximately one-fifth (22%) of 340B hospitals provide 80% of all charity care delivered by 340B DSH hospitals.

Currently, hospitals that qualify for the program claim 340B discounts for most outpatient prescription drugs, for both insured and uninsured patients.  And while the 340B program lowers outpatient drug costs for qualifying hospitals on the presumption that it will help significant numbers of vulnerable, uninsured patients, participating hospitals currently see no restrictions on the way they spend the revenue generated if they charge both insured and uninsured patients higher prices than the 340B-discounted price. 

This stands in contrast to many other covered entities that participate in the 340B program as a result of a specific grant (often referred to as “grantees”) from the U.S. Department of Health and Human Services.  The grant-approval process typically requires these providers to demonstrate that they provide services to certain specified vulnerable populations, at times based upon the patients’ “ability to pay”, and that the entities reinvest resources into services for those populations.

340B's broad eligibility criteria for hospitals have led to an explosion in the number of hospitals that have come into the 340B program. Today, one-third of all hospitals in the country participate in the 340B program and get 340B discounts; that number is expected to grow, particularly absent an effort to tighten eligibility requirements. Drug purchases through the 340B program will almost double, from $6 billion in 2010 to $13.4 billion by 2016, though little of the billions of dollars in discounts has been directly tracked to or linked with charity care for vulnerable indigent patients.

The complete report, “Unfulfilled Expectations,” can be found here.

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Delta Force

03/27/2014 10:15 AM |

BioCentury reports that NICE is seeking input on proposed changes to its health technology assessment methodology that the agency said would more explicitly take into account the burden of a person's illness and the wider impact of a disease on people's ability to be part of society. NICE is proposing to measure burden of illness as the proportional shortfall in quality-adjusted life years (QALYs) for those with a disease compared with the expected QALYs for those of the same age and gender without the disease. NICE said evaluating burden of illness as a proportional difference "recognizes the position of those patients who stand to lose the greatest proportion of their remaining health expectancy." The agency noted that the measure "is not particularly sensitive to the age at which people are diagnosed."

What NICE calls "societal impact" would be measured as the absolute difference between the expected QALY in a patient with a disease and the expected QALY in people of the same age and gender without the disease. The agency noted that for an absolute shortfall, "the larger the shortfall, the larger the effect" on society. Comments on the proposed methodology changes are due June 20, with NICE planning to introduce the changes this fall.

In 2010, the U.K. government proposed to establish a system under which NICE would have assessed the value of a new drug and assigned a value-based price. But the 2014 Pharmaceutical Price Regulation Scheme (PPRS) agreement essentially marked the end of value-based pricing as it was originally proposed, with NICE instead shifting toward a "value-based" assessment process.

It’s important to consider VBID in the broader conversation of clinical effectiveness and more specifically HTA modeling a la QALY – because that brings you into the direct path of VSLY – the value of a statistical life year.  According to Dr. Frank Lichtenberg of Columbia University, for a healthcare technology assessment scheme (such as the NICE model) to yield valid decisions in practice, it is necessary to have reliable estimates of:

ΔCOST
ΔQALY
and VSLY (Value of a Statistical Life Year)

and his main point is that the devil is in the details.

Lichtenberg believes that incorrect estimates of some or all of these key inputs are often used:

ΔCOST is frequently overestimated
ΔQALY and VSLY are frequently underestimated

And due to these estimation biases, health technologies that are truly cost-effective may often be rejected as cost-ineffective.

Per the recent debate over the utility of new cancer treatments, he makes a very interesting point -- that even though, over the past 30 years, the U.S. Mortality Age-Adjusted Rates for cancer have remained relatively constant -- (leading to such mainstream media headlines as Fortune Magazine's "Why have we made so little progress in the War on Cancer?” and NEJM articles like "The effect of new treatments for cancer on mortality has been largely disappointing” -- the often ignored reality is that 5-year relative survival rates, for all cancer sites, have increased from 50.1% in 1975 to 65.9% in 2000.

Lichtenberg cites two crucial studies, pointing out how health care economists must seriously reconsider the outdated estimates of a QALY:

Viscusi and Aldy: The value of a statistical life for prime-aged workers has a median value of about $7 million in the United States

Viscusi, W. Kip and Joseph E. Aldy, “The Value of a Statistical Life: A Critical Review of Market Estimates Throughout the World,” The Journal of Risk and Uncertainty, 27:1; 5–76, 2003.

and

Murphy and Topel: The value of a life year is $373,000.

Murphy, Kevin M., and Robert H. Topel, “The value of health and longevity,” Journal of Political Economy, 2006.

If the devil is in the details (and it is) -- it's time for a deep dive beyond simplistic and self-serving "comparative effectiveness."

Attention must be paid. Are you listening PCORI?   Read More & Comment...

Is Off Label on the Table?

03/26/2014 08:59 AM |

From the pages of the Wall Street Journal ...

Pharma and the First Amendment: A Proposal From the FDA

By Ed Silverman

On one hand, the agency is being praised for trying to move the ball forward, given ongoing uncertainty over disseminating material that contains off-label uses. Although physicians may prescribe a drug as they see fit, many drug makers have been fined for promoting their medicines for uses not approved by the FDA.

Yet at the same time, the FDA is being criticized for being overly restrictive concerning some materials and for also failing to specifically address First Amendment issues that have figured prominently in some recent court rulings about drug marketing.

“The fact that they’re starting to pay attention and open up off-label communications indicates they know they have to do a better job of defending the limits they have, and specifying what can and can’t be used and how that’s done,” says John Kamp, executive director for the Coalition for Healthcare Communication, a trade group for medical publishers and advertising agencies. “There are steps forward here. But in some cases, baby steps.”

One portion that was welcomed by industry representatives pertains to clinical practice guidelines, the official recommendations for patient treatment that are issued by professional medical societies. Until now, the FDA had not addressed these guidelines, which are closely tracked by doctors and may include off-label uses. The guidance says that CPGs must be distributed separately from promotional information and should display a statement that some of the products described might not approved or cleared by the FDA, among other things.

By devoting a portion specifically to clinical practice guidelines, the agency has now carved out a separate road map for distributing these missives to physicians.

“They’ve brought some clarity to this issue, which is very important,” says Alan Bennett, an attorney who represents more than a dozen drug makers that last fall filed a citizen’s petition (PDF) with the FDA in hopes of gaining clarity on distributing materials that contain references to off-label uses. The drug makers include Eli Lilly, Novartis, Sanofi, Genentech, Purdue Pharma, Pfizer and Johnson & Johnson.

But the FDA raised some hackles with its other dictums. For one, the agency did not add much understanding to an earlier guidance from 2009 that was devoted to medical and scientific journal reprints containing off-label information. This time around, though, the FDA noted that it does want companies to limit reprints to “adequate and well-controlled clinical” studies.

The earlier guidance also mentioned pharmacokinetic, pharmacodynamics and meta-analysis studies.

This would appear to preclude almost anything other than a double-blind, placebo-controlled study, according to Richard Samp, chief counsel at the Washington Legal Foundation, a nonprofit that frequently agitates for commercial free speech rights. “Against the great weight of medical opinion, FDA continues to insist that other types of studies have no scientific validity,” he says.

There was also disappointment that the FDA did not address the simmering debate over distribution of off-label materials that may be protected by the First Amendment. One closely watched case involved the 2008 conviction of a former pharmaceutical sales rep, who was prosecuted for encouraging doctors to prescribe a drug on an off-label basis.

A federal appeals court, however, overturned the conviction in late 2012 after agreeing that his First Amendment rights were violated because the federal government failed to prove his remarks were false or misleading. But the FDA did not discuss free-speech issues in its guidance at all. “They were silent on this and at some point they’re going to have to address it,” says a disappointed Bennett.

For now, the guidance may be sufficiently restrictive to discourage drug makers from taking many chances. “The hurdles for any meaningful dissemination of peer-reviewed information on off-label uses are very high,” says Arnie Friede, a former FDA associate chief counsel and former senior corporate counsel at Pfizer, who is now at Sandler, Tavis & Rosenberg, a law firm based in Miami.

And he notes that many drug makers may already be gun shy due to Corporate Integrity Agreements. These stem from settlements relating to off-label promotion, and many already regulate the dissemination of this material. “In theory,” he says, “a company subject to a CIA will have to run a dual gauntlet – compliance with the CIA and compliance with the draft guidance. So it becomes a fair question to ask: why bother?”

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Clinical Trial Data: Will the EU go Open Kimono?

03/24/2014 12:51 PM |

The Wall Street Journal reports that, “Drug companies and researchers will no longer be able to withhold the results of unfavorable clinical trials, if changes to European law are passed as expected next month.”

The new law would require the results of all trials plus a full clinical-study report to be published within a year of the trial ending. The European Parliament is expected to vote on the new legislation April 3, and it would come into force in 2016.

What the Journal did not report was that in May 2013 the General Court of the European Union prohibited the Euro­pean Medicines Agency from releas­ing data from two AbbVie and Inter­mune trials in an interim ruling, part of a challenge by the two drugmakers to the agency’s decision to grant access to information the companies provid­ed as part of their market approval ap­plications. The challenge is the first to be made to the EMA’s three-year old access-to-documents policy.

The Journal, “Around half of all trial results go unpublished, according to current estimates, including a 2009 paper that looked at 677 studies conducted in different countries. A 2012 paper found just 45% of 635 U.S. National Institutes of Health-sponsored trials were published within 30 months of completion.”

Unreported is that in 2000, the National Institutes of Health (NIH) launched ClinicalTrials.gov to provide public access to information on clinical studies.  Although it initially contained information primarily on NIH-funded research, it has been expanded to include both publicly and privately supported clinical research. 

Since the launch of the site, it has been enhanced to significantly increase data sharing. The ClinicalTrials.gov database includes information on nearly 140,000 clinical trials in all 50 states and 182 countries. 

Is anyone accessing this wealth of information? Yes!  The NIH reported last year that ClinicalTrials.gov “receives more than 95 million page views per month and 60,000 unique visitors daily.

At the July 2013 Clinical Trials Disclosure and Transparency Summit, Sir Alasdair Breckenridge, former Chairman of the MHRA and currently the Chair of United Kingdom’s Department of Health Emerging Science and Bioethics Advisory Committee, noted that transparency is “a process without a beginning or an end. It is a continuum.” And, “Transparency is like feeding a hungry dog – you more you give it, the more it wants.”

Sir A. suggested four key questions:

(1) Should the public have access to data on which regulatory decisions are taken?

(2) What are the advantages and disadvantages of increased transparency?

(3) What are the key distinctions between transparency and communication (specifically the issue of public health literacy and numeracy – and the “road testing” of released information)?

(4) Will increased transparency lead to increased trust in regulators and industry?

On that last point, Dr. Breckenridge points out that increased transparency does not lead to increased trust. Trust depends on perceptions of honesty and competence, and transparency may expose inherent inefficiencies in a system. And that’s a good thing – if we really mean to make the most of transparency.

Transparency cannot be “for thee but not for me.”

And he offers five keystones for moving forward:

(1) Agreement on timing of release of information

(2) Agreement on nature of information to be released

(3) Standards of protection of personalized data

(4) Standards for meta-analyses

(5) Rules of engagement for observational studies

Per the European Parliament vote, some policy issues to consider:

* Should transparency be a government dictate or a working collaboration between interested parties both private and public – and what role should patients play.

* Should there be formalized transparency consortia? Should it be global?

* What are the implications for intellectual property and the connected question of incentivizing (or dis-incentivizing) investment in innovation? Is transparency a Trojan horse to attack patents and intellectual property rights?

* Can transparency become a competitive advantage as well as a public health imperative?

After all, good things happen when everybody wins.

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The Not-So-White Coat Effect

03/18/2014 09:49 AM |

According to Reuters, “Some U.S. doctors are becoming concerned about the quality of generic drugs supplied by Indian manufacturers following a flurry of recalls and import bans by the Food and Drug Administration.”

"I'm just beginning to realize the gravity of the problem," said Dr. Steven Nissen, head of cardiology at the Cleveland Clinic. "It's terrible and it is starting to get a lot of traction among physicians."

(Maybe he can do a meta-analysis.)

India's drugmakers, a $14 billion industry, reject any criticism that their products are inferior to drugs made in other countries.

"We have heard doctors making generalized statements, without being specific on any product or company," said D.G. Shah, Secretary General of the Indian Pharmaceutical Alliance, a trade group representing large Indian drugmakers. "This is a deliberate and serious campaign to malign the Indian generic industry."

Denial, it seems, is more than just a river in Egypt.

"We are losing control over what people are swallowing," said Dr. Harry Lever, a cardiologist at the Cleveland Clinic who is trying raise awareness of the matter among U.S. lawmakers. "Now, when a patient comes in who is not doing well, the first thing I do is look at their drugs and find out who makes it."

FDA is addressing these concerns by establishing an Office of Pharmaceutical Quality to improve the agency’s scrutiny of brand-name, generic and over-the-counter drugs. The agency is talking with the industry to develop data that may signal which manufacturing plants are straying from standards and need inspection, she said.

FDA now collects such information only during inspections. The thrust of the effort would be to head off potential concerns before the agency wields penalties such as banning products from troubled factories. According to CDER Director, Dr. Janet Woodcock, “We want to use leading indicators. These people aren’t in trouble yet but they could be.”

And, per Commissioner Peggy Hamburg, “All companies must understand that quality is the basis for the public’s trust and confidence in their products and maintaining high quality standards is part of the cost of doing business.” Hamburg said the new office will “improve our oversight of quality throughout the lifecycle of a pharmaceutical product.”

Some Indian physicians do not share these concerns.

"Our drugs are being sold in many countries and being accepted, so we have no issues," said Narendra Saini, Secretary General of the Indian Medical Association, a voluntary body of 215,000 doctors. "How do I know that Western drugs are better than our drugs?"

Not so. The truth is that nation’s across the globe are uncovering serious issues with products manufactured in India. This is particularly true for generic oncology medicines -- where there isn’t room for error.

It’s too simplistic to call these “quality” problems. There’s a range from sub-standard API and manufacturing issues, to excipient changes and, most importantly, bioequivalence and bioavailability standards.

Dr. Joel Zonszein, director of the Clinical Diabetes Center at Montefiore Medical Center in New York, said he is concerned about the quality of generic drugs in general, not just those from India. He cited, as an example, his experience with the diabetes drug metformin.

"When patients open the bottle of medication it smells like dead fish," he said. Zonszein did not know which company made the foul-smelling drug.

Dr. Richard Kovacs, who heads a number of American College of Cardiology committees and sits on its board of trustees, said doctors may need to play a greater role monitoring the medications prescribed by their practices.

"The average U.S. cardiologist has been able to assume that the drugs were safe and effective. It now appears we need to be more vigilant as a profession, and assist the FDA by reporting cases where we are concerned about irregularities in the drugs supplied to our patients," he said.

FDA’s recent draft guidances on bioequivalence for both generic and innovator products, as well as the move towards independent labeling for generic products are additional steps the agency has recently taken to address the issue of drug quality beyond safety and efficacy. And the implications for biosimilars is obvious

(Something else to consider is for the FDA to report BE and BA and PK data in generic labels.)

Small is the new Big means we must think differently about pharmacovigilance. While we must continue to capture adverse event data, we must also strive to capture Substandard Pharmaceutical Events (SPEs). SPEs occur when a product does not perform as expected—perhaps because of API or excipient issues. SPEs can arise because of an issue related to therapeutic interchangeability. When it comes to 21st-century pharmacovigilance, we have to both broaden and narrow our views about bioequivalence to the patient level.

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Who "lost" Abuse Deterrence?

03/17/2014 11:36 AM |

Google “opioid abuse deterrence” and you’ll find a lot of hits from lawyers and elected officials. What you won’t find is a lot of expert thinking from the FDA.

That needs to change.

FDA Commissioner Hamburg’s recent comments (and, in particular, her testimony in front of the Senate HELP Committee) hopefully represent a more aggressive stance by the agency. That’s good. But there needs to be more. The FDA must be the leading voice on the issue of abuse deterrence and the safe use of opioids.

At present, politicians and pundits (not to mention trial lawyers) own the conversation. They're the ones talking about it. They're the ones the media goes to when they write about it. Have a look at a sampling of the press coverage surrounding Zohydro and see who's quoted and what they're saying.

The struggle over control of the opioid abuse deterrence story is, shall say, not going the right way for the agency.

Peggy got it right when she testified that (per Zohydro), “We recognize that this is a powerful drug, but we also believe that if appropriately used, it serves an important and unique niche with respect to pain medication and it meets the standards for safety and efficacy.”

In short – not all opioids are the same and not all patients respond to all opioids in the same way. Further, it’s important to remember that “safe” doesn’t mean 100% safe. Never has. Never will. Not for any medicine. It’s always about the benefit/risk balance.

This is not a new topic. Americans woke up the morning after the Vioxx recall and were amazed to discover that drugs have risks. Good lord. Who let that happen! Avandia, in that respect, was Son of Vioxx. And, like any sequel, new actors were brought in to spice up the story. Now it’s about opioids.

Relative safety is an important conversation. It’s an opportunity for the FDA to help educate the public about the safe use of drugs.

(The foundational proposition of the FDA’s “Safe Use” initiative is that the way to make a drug “safer” is to better educate prescriber, dispenser, and user about the product.) And nowhere is “safe use” a more important issue than opioids.

Dr. Hamburg’s testimony continued, “It doesn’t do any good to label something as abuse deterrent if it isn’t actually abuse deterrent, and right now, unfortunately, the technology is poor.”

As with safety, “abuse deterrent” doesn’t mean that an opioid can’t be abused. “AD” doesn’t mean “100% abuse deterrent” just as “safe” doesn’t mean 100% safe.

Who does that and how it is done is where the rubber meets the road. After all, as the saying goes, everything you read in the paper is true except for those things you know about personally. Such is the case for the drug safety imbroglio currently surrounding opioids.

The FDA must take the lead. And that means more than finessing the label. It means working with CME providers to develop better curricula. It means more targeted REMS. It means enhanced and validated reporting tools for post-marketing surveillance. It means better tools for using that data for better social science in developing tools that can assist prescribers in determining which patients are likely to abuse. “Abuse deterrence” isn’t just a formulation question – it’s a systems question.

Unfortunately complex systems make for bad media coverage, while simplistic, dramatic demagoguing makes for sexier headlines. And when Bloomberg reporter Drew Armstrong notes that “FDA pain drug czar Bob Rappaport has already said the agency would consider jerking Zohydro from the market if an abuse-resistant version become available,” it reinforces the erroneous concept of “100% abuse deterrence.” Dr. Rappaport certainly knows better. The general public does not.

There’s an apt Japanese proverb that bears repeating, “Don’t fix the blame. Fix the problem.” Unfortunately, the recent bashing of opioids (and the FDA’s regulatory decision-making and oversight thereof) isn’t helping. It's time for the grown-ups to step forward and take charge of the debate on drug safety.

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A Manchin on the Hill

03/14/2014 10:28 AM |

What ever happened to “politics has no role at the FDA?”

Yesterday, Senator Joe Manchin (D, WVA) introduced a bill to overturn the FDA’s approval of the opioid Zohydro ER.

That certainly sounds like legislating science.

As a part of his rationale, Senator Manchin noted that the agency approved the drug last year over the objections of an advisory experts that had voted 11-2 to recommend rejection of the drug.

Yes, Senator, that’s why it’s called an advisory committee. Would he make such votes binding on the agency? That’s a pretty radical shift in regulatory policy.

To her credit, FDA Commissioner Peggy, in testimony before the Senate Health, Education, Labor and Pensions Committee on Thursday, defended the agency’s October approval of Zohydro ER.

"We recognize that this is a powerful drug, but we also believe that if appropriately used, it serves an important and unique niche with respect to pain medication," Dr. Hamburg testified.

Senator Joe isn’t alone in his well-meaning but misguided attempts to legislate science. Senator Charles Schumer (D, NY) is urging Health and Human Services Secretary Kathleen Sebelius “to overturn the government’s approval of a new powerful prescription opioid, Zohydro ER” (hydrocodone), “until it has been made abuse-proof.” According to reports, Schumer “believed there was a ‘decent chance’ that” Sebelius would revoke the FDA approval.

In “Personalized Medicine and Responsible Access to Pain Medication” (a white paper based on the Center for Medicine in the Public Interest’s September 2013 Capital Hill conference), Dr. Douglas Throckmorton, CDER’s Deputy Director, for Regulatory Programs and the FDA’s point person on opioids, writes,

We understand that for the millions of Americans experiencing an acute medical need or living with chronic pain, opioids, when prescribed appropriately, can allow patients to manage their pain as well as significantly improve their quality of life. However, we have also become increasingly concerned about the abuse and misuse of opioids. We are challenged with determining how to best balance the need to ensure continued access to patients who need these medications while addressing concerns about abuse and misuse.

FDA must walk a difficult public health tightrope, balancing patient need, medication safety, and (in the case of opioids), the dangers of abuse.

In addition to Senator Manchin’s call for legislation and Senator Schumer’s call for Secretarial interference, this careful balance is also being called into question by 28 state attorneys general who, in a letter to FDA Commissioner Margaret Hamburg, ask the agency to “reconsider its controversial approval of the powerful new narcotic painkiller known as Zohydro.” The attorneys general are concerned that the medicine lacks “an abuse-limiting formula.”

Was the approval “controversial?” Well, it depends what you mean by “controversial.” It’s controversial because the issue of opioid abuse is controversial. And that’s an important difference. Nobody said the FDA’s job was easy.

Noble Prize winner Joshua Lederberg once observed that the failure of regulatory legal and political institutions to integrate scientific advances into risk selection and assessment was the most important barrier to innovation in public health. Lederberg noted that in the absence of such changes, “The precedents affecting the long-term rationale of social policy will be set not on the basis of well-debated principles, but on the accidents of the first advertised examples.” And there isn’t a better perspective-setting proposition when it comes to the issue of Zohydro than that quotation.

Policies and regulations that seek to limit risk are often shaped by the immediate fear of sensational events. This perspective is commonly referred to as the Precautionary Principle, which, in various forms asserts that unless innovators can demonstrate that a new technology is risk free, it should not be allowed into the marketplace. Moreover, any product that could possibly be dangerous at any level should be strictly and severely regulated. But precaution is not always safer than the alternatives.

Pierre Trudeau once said, “There’s no place for the state in the bedrooms of the nation.” But what’s the appropriate place for the state in our nation’s pharmacies and medicine chests? Should regulation be shaped by factors other than science?

According to the CDC in 2008, there were 14,800 opioid overdose deaths. Half of those, the CDC has claimed, involved opioids and other illicit substances, whether it’s cocaine or heroin, or alcohol. They also mentioned that alcohol was involved in many of those deaths but they don’t actually tell us the numbers. So conservatively, half or 7,400 deaths occurred in 2008 from opioid overdose. The same year from CDC’s own statistics, there were 36,500 suicides. There also were 24,000 alcohol-induced deaths and that doesn’t count other related alcohol deaths like drunk driving. The bottom line is that the opioid numbers do not even come up in the CDC’s list of the top 15 causes of death of Americans

It’s important to add to this “epidemic” perspective, the fact that people suffering from chronic pain are under-served by existing therapies. A recent IOM report that was issued in June of 2011 found that 100 million Americans are now living with chronic pain. That’s a third of the U.S. population. Ten million of those have pain so severe that they are disabled by the pain. The report also said that pain costs the U.S. economy about 600 billion dollars a year in lost productivity and healthcare cost.

The vast majority of people who use opioids do so legally and safely. A subset, approximately four percent, use these medications illegally. In fact, from 2010 to 2011, the number of Americans misusing and abusing opioid medications declined from 4.6% to 4.2%.

And the FDA’s decision was “controversial?” Really?

Rather than dealing with the problem of abuse with sledgehammer solutions, Senators’ Manchi and Schumer, and the various state AGs should focus on potential solutions such as:

* The structure and impact of programs such as the recently instituted by CVS initiative (detailed in a recent New England Journal of Medicine perspective piece) where, through the use of “Big Data”, the chain pharmacy identified outlier prescribers and took appropriate and responsible action.

* The role of the 21st century pharmacist in improving drug safety and medication adherence via more proactive and remunerated patient education?  How can pharmacists become better integrated beyond Med Guides into the FDA’s Safe Use of Medicines initiative?  When will pharmacy synchronization really kick into gear, and how will states help to jump-start these important initiatives? 

* Government and legislative initiatives such as the Stop Act (H.R. 486), which focuses on tamper-deterrent formulations and the continued development of those.  Also, Senate Bill 1277 (sponsored by Senator Barbara Boxer, D/CA) which would establish a commission to bring all of the stakeholders together to have discussions about how to approach this issue so that law enforcement, providers, patients, and pharma can debate the issues and reach common ground.     

* The appropriate role of tamper-resistant technologies. They are part of the solution, but they’re not the whole solution. We need to develop policy options that focus on the prescriber/patient relationship, and a professional assessment of what’s the risk involving this patient. Is the patient is going to tamper with the medication and potentially expose themselves or others to some danger. We have to do a better job (via CME and other methods) of training physicians and other prescribers on how to do these kinds of assessments. 

And, most importantly, we need to keep the needs of patients front and center.

Whatever your position on the issue of opiods, the proper venue for this decision is not the office of the Secretary of HHS or the halls of Congress or the courts -- but rather the office of the FDA Commissioner.

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"Wiggle" my Aunt Fanny

03/12/2014 05:15 PM |

OPDP reminds us that it's not the platform -- it's the content. (Or in this case, the lack thereof.)

According to an article in Medical Marketing & Media,

The latest proof that the FDA is not giving social media outreach wiggle room, even though communications guidelines are not due out until this summer, is an untitled letter to Institute Biochimique and US partner Akrimax Pharmaceuticals over a Facebook page for its hypothyroidism drug Tirosint.

Not so fast MM&M.

It seems that, per OPDP, the FaceBook page failed to “communicate risk information” and omitted material facts.

There should never be “wiggle room” for that. Not ever – especially for a drug with a boxed warning.

“Wiggle Room?” Hardly.

How about “proper oversight?”

Well done, OPDP.

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Marilyn's Graceful Retreat

03/11/2014 08:42 AM |

On January 6th, CMS issued a proposed rule that would result in foundational changes to Medicare Part D and negatively impact America’s seniors, and other constituencies. Most disturbingly (if not surprisingly) it reveals the Administration’s authentic view of Part D by attempting an unprecedented level of government interference with what was intended to be a competitive, market-based proposition.

On Monday, CMS Administrator Marilyn B. Tavenner said the agency would not pursue the proposal. “Given the complexities of these issues and stakeholder input, we do not plan to finalize these proposals at this time.”

Translation -- The draft rule is dead.

Senator Mitch McConnell said he was “pleasantly surprised to see the Obama administration backtracking on a number of proposals that would undermine the highly successful Medicare drug program.”

Senator Ron Wyden also welcomed the administration’s decision to drop some of the Medicare proposals. In a letter to Ms. Tavenner last month, Mr. Wyden and 19 other committee members said the proposals would “disrupt care for millions of beneficiaries and unnecessarily interfere with a successful program.”

For a more detailed look at the now moribund CMS proposals, see Bizarro Part D.

Congratulations are due to Administrator Tavernner for acknowledging that the proposed CMS rule was a mistake – and to shelve it.

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The Politics of Innovation

03/10/2014 03:21 PM |

BioCentury reports that “President Obama has again proposed to shorten the exclusivity period for innovator biologics in his FY15 budget proposal. According to HHS's summary, the president's budget request includes a proposal to cut the exclusivity period to seven years from the current 12 years. Obama proposed the same change in his FY14 budget request.”

It’s hugely disappointing that the same man who (as a United States Senator) once said that …

“Realizing the promise of personalized medicine will require continued federal leadership and agency collaboration; expansion and acceleration of genomics research; a capable genomics workforce; incentives to encourage development of genomic tests and therapies; and greater attention to the quality of genetic tests, direct-to-consumer advertising and use of personal genomic information."

 … is now advocating a policy that would result in precisely the opposite.

 After speaking (and in a widely quoted op-ed in the Wall Street Journal) about the need for America to embrace innovation – President Obama is trying to make it more difficult, specifically when it comes to the desire to invest in pharmaceutical innovation – a sure bet under no circumstances.

Patent exclusivity funds an innovator company’s research and development efforts. If the President’s proposal becomes law, the US would provide less data protection for innovative biologics than Europe.

12 years of exclusivity also gives hope to those suffering from rare diseases or conditions. If innovator companies think they will have a short time before a follow-on versions of their products hit on the market, they will likely only focus on drugs for major diseases and conditions -- potentially ignoring ailments that are less common, but equally as serious, to those suffering.

If innovation is one of the key answers to our national economic recovery, then the President should abide by what he said, “Our economy is not a zero-sum game. Regulations do have costs; often, as a country, we have to make tough decisions about whether those costs are necessary. But what is clear is that we can strike the right balance. We can make our economy stronger and more competitive, while meeting our fundamental responsibilities to one another.”

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Statin Down the Hatches

03/07/2014 08:33 AM |

OTC Statins: More Questions than Answers

Much news lately about Pfizer’s desire to move Lipitor into the OTC category.

OTC statins. Not a new conversation, but certainly a timely one as we continue to face not just Hyperlipidemia – but medication adherence (and particularly for chronic, asymptomatic conditions).

Are statins “safe enough” to be available without a prescription? Well, with the appropriate caveat that no drug is 100% safe, it’s pretty fair to say that their safety profile is excellent – for Rx products. But is the same true if they were available OTC?

Here’s some history.

In 2005, an FDA advisory panel voted down a bid by Merck & Co. and Johnson & Johnson to sell lovastatin (Mevacor), without a prescription. Several panel members said the FDA should consider establishing a behind-the-counter system that would allow consumers to purchase lovastatin from pharmacists much like the British are allowed to purchase simvastatin (Zocor), another cholesterol-lowering drug. Most panel members said that, if such a system existed in the U.S., they would have voted to allow Mevacor to be sold without a prescription.

(Other countries with behind-the-counter status include Australia, Canada, New Zealand, Denmark, Germany, Italy, the Netherlands, Sweden and Switzerland.)

Then, in 2007, another proposal to offer lovastatin over-the-counter was rejected by an FDA panel, primarily due to the fear consumers might not select the drug appropriately.

“It is not clear that the benefits to patients of lovastatin being over-the-counter outweigh the risks, although the risks are small,” Arthur Flatau, PhD, said during a joint meeting of the Nonprescription Drugs Advisory Committee and the Endocrinologic and Metabolic Drugs Advisory Committee. “Clearly, there are a lot people who are not on statins and should be on statins; putting the drug over the counter will not increase the number of patients who take it.”

The vote was 10-2 against over the counter approval of lovastatin with one abstention. The majority of panel members who voted against lovastatin over the counter felt consumers were unable to make a decision regarding whether they should be taking a statin.

Can a patient self-diagnose and self-dose?  Do symptoms hide another, potentially more serious, underlying condition?  And what of safety concerns? 

Per a New England Journal of Medicine written by the chair of the FDA advisory committee, "Some docs argue that increasing access to statins could prevent heart attacks and strokes, which in turn would lower health care costs. Overall, a study of an OTC Mevacor (Merck's statin) showed 30 percent of patients who thought they should take the drug actually had less than a 5 percent risk of a heart attack or other cardiovascular event in the next 10 years, and were therefore unlikely to benefit."

Does this open the door for a so-called “behind the counter” (BTC) category? CDER Director Janet Woodcock has spoken out in favor of such strategies since they would allow switch candidates with greater self-selection obstacles to be available without a prescription.

This is an important debate as well as a "teaching moment" for American pharmacists to communicate the crucial role they play in 21st century American health care.

Pfizer recently started a 1,200-patient clinical trial to test if consumers taking OTC Lipitor and getting their own blood tests improve their cholesterol levels and then make the right decisions based on the results of a second blood test. (These blood tests, in the real world, would be administered at the pharmacy.)

What additional questions should be asked when it comes to the OTC statin debate? Here are a few:

* Should any chronic medications be available OTC? (This is a very big “beyond statins” question that hasn’t been widely discussed … yet.) Most Rx-to-OTC switches have been for the treatment of acute, transient symptoms of allergies, heartburn, etc.

* Isn’t this a de facto BTC play? After all, the pharmacist will have to advise, test, and dispense. Isn’t that beyond the scope of FDA’s existing regulatory authority?

* Is an OTC “Drug Facts” label up to the task of properly communicating the most important benefit/risk information about statins (or, for that matter, about any OTC product)?

* Even at a 10mg dose?

* Per that second blood test, what does “success” look like?

* What if the patient doesn’t come back for a second blood test?

* What about the financial burden on the consumer? Rx products are reimbursed. OTC products are not.

* And, to that point, when there is an increased financial burden on the patient (i.e., raised co-pays) – adherence declines. Would OTC statins further exacerbate the problems with statin adherence?

* If, after the second pharmacist-implemented blood test, the patient is told to see their physician – why shouldn’t they just have gone to see their physician in the first place?

* If Pfizer is granted the OTC designation for Lipitor and then other statins follow suit (a pretty safe supposition), how are patients supposed to choose which statin is “best for them” minus a physician's “clinical experience?”

* What about prospective patient (aka “consumer”) education? Pfizer says it hopes to persuade regulators to approve OTC Lipitor by using "new and creative ways" to communicate instructions for use.

All this to say that it’ll make for an interesting and important conversation.

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The Big Lie of ObamaCare gets bigger

03/06/2014 08:35 AM |

The visionary lies to himself, the liar only to others.                                                                                                                                                 -- Friedrich Nietzsche

You can fool some of the people all of the time and all of the people some of the time. But what about when it comes to election time?

The Big Lie of ObamaCare is “If you like you’re insurance you can keep it.” And it’s the lie that keeps on giving.

Here’s the latest from the pages of Modern Healthcare – a magazine without an agenda that plays it straight.

Extension of policies that don't comply with ACA called ploy

By Virgil Dickson

The Obama administration's decision Wednesday to allow people to keep insurance plans that don't comply with the Patient Protection and Affordable Care Act for an additional two years was quickly criticized by ACA opponents as a midterm-election-year ploy, even as administration officials were denying politics was involved in the decision.

Regardless of the motivation, the change likely will irk insurers hoping to sign up as broad a spectrum of the public, especially healthy people, as possible in compliant plans offered on exchanges.

“Plans need to know the parameters in which they have to work so they can make the best decisions for the consumers they serve moving forward,” said Jeff Drozda, CEO of the Louisiana Association of Health Plans, which counts both large payers and small regional plans as its members.

Last month, during an earnings call, Humana expressed disappointment in the number of enrollees it had from the exchanges at that point and blamed the company's woes on the transitional policy, for example.

“We believe this change will result in an overall deterioration of the risk pool and ACA-compliant plans as more previously underwritten members have stayed with their current carriers rather than enter the exchanges,” Humana President and CEO Bruce Broussard said.

Administration officials Wednesday, confirming media reports that started surfacing early this week, announced insurers could renew noncompliant policies that begin on or before Oct. 1, 2016. That means some customers can stay on these plans into 2017.

This is an extension of a decision made in November when the president gave states the ability to allow noncompliant policies to continue. Originally these plans were only meant to last until October 2014, right before midterm elections in November.

High-ranking administration officials who spoke on background to reporters Wednesday insisted multiple times that the potential backlash of thousands of people receiving policy cancellation notices right before heading to the polls played no part to the extension.

Instead, they said, the extension gives 500,000 consumers in these plans time to make the choice of staying in their current policy a little longer or joining a new marketplace plan. They added that it's likely all of these consumers will make the switch to a compliant plan by 2016, but if they do not, HHS now has the discretion to extend the transitional policy for a third year.

The more than 20 states that chose not to allow consumers to keep noncompliant plans will now have another opportunity to do so as long as the plans are still active, they said. People now in compliant plans can't go back to ones that don't meet the standards.

Beyond any administration concern about midterm elections, concern about the tax penalty these individuals were facing likely also played a role in the decision, said one ACA observer. Before the new extension, if a person didn't have a compliant ACA plan by the end of the enrollment period in 2015, he or she would have been hit with a levy worth up to 2% of income when filing taxes in 2016.

“Without the extension, a lot of people may get hit with the tax penalty and that could lead to a political fallout,” said Ning Liang, co-founder of a new website that helps people compare and sign up for ACA-compliant plans on HealthCare.gov.

The change is likely to provide scant political cover to Democratic congressional candidates facing broad attacks over the administration's healthcare policy, some said.

“I think, at this point, consumers have wised up and are asking some demanding questions,” said Peter Pitts, president of the Center for Medicine in the Public Interest. “This extension further demonstrates the disingenuous nature in how certain political candidates are presenting the Affordable Care Act to their constituents”

“The problem is you can't unshoot the gun,” said David Hogberg, a healthcare policy analyst at the National Center for Public Policy Research. “People are going to remember that the administration violated a very serious promise that people could keep their plans and I suspect Republicans will use that to no end this November.”

The extension gives Republicans one more change to the Affordable Care Act to criticize. Grace-Marie Turner, president of the Galen Institute, a conservative research organization, noted that her organization has tracked at least 19 changes made, most by executive order, to the ACA since it became law.

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