Latest Drugwonks' Blog
In Friday’s Washington Post, the editorial page opines that, “… not every problem can or should be solved by federal regulation, and there is still a decent chance that the balance between regulation and liberty that the Affordable Care Act struck will work. If it does, the more rational health-care system that results will have been well worth the price in expanded government intervention in the health-care market.”
That’s the conclusion, but the body of the piece reads like an introduction to a manifesto about why what we really need is a single-payer system. A "rational health-care system" is the the global code phrase for "one-size-fits-all" care. Have a look here and judge for yourself.
Here’s my view on some of the same problems from a different angle (as seen in yesterday’s Des Moines Register).
The devil is in the details.
From: A Message from the Commissioner
Sent: Wednesday, December 11, 2013 02:05 PM
To: FDA-Wide
Subject: Personnel Announcement
Dear Colleagues:
I am deeply saddened to announce that John M. Taylor, Counselor to the Commissioner and Acting Deputy Commissioner for Global Regulatory Operations and Policy (GO), will be leaving the Food and Drug Administration in January 2014 to pursue other opportunities. John has accomplished so much during his two stints at the Agency (from 1991 to 2005 and from 2009 to present) as he served in various ways and touched many lives. From his early days in the Office of Chief Counsel, to his senior roles in the Center for Drug Evaluation and Research, the Office of Regulatory Affairs, and the Office of the Commissioner, John has brought leadership, sound advice, and most of all, good humor to his work. We will all miss his expert knowledge, his innovative thinking, and his uncanny ability to remain calm during times of adversity and matters of urgency. John has proven himself as a leader who epitomizes integrity, dignity, kindness and compassion, and he is widely respected by his colleagues.
Most recently, John has been wearing two hats – Counselor to the Commissioner and Acting Deputy Commissioner for GO. In these two positions over the past year, John has demonstrated flexibility, creativity, and decisiveness that has enabled us to make important forward progress on key matters. John has always stepped up in the times when I have needed him most to take on specific tasks that represent my highest priorities, including those related to globalization, FDASIA, and pharmacy compounding. John has been a catalyst for organizational progress and change while handling and managing the high demands of the Office of the Commissioner. And notably, John agreed to serve as the Acting Principal Deputy Commissioner during a time when the Agency was in a period of transition, for which I am extremely grateful.
I know I speak for all of us when I say that John will be sorely missed. Please join me in thanking him for his distinguished service to FDA and wishing him the very best in his future endeavors.
Margaret A. Hamburg, M.D.
Commissioner of Food and Drugs
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.
This careful balance is now 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.”
First let’s consider the rhetoric. Was the approval “controversial?” Well, for starters, the FDA approved the medicine notwithstanding a negative adcomm vote. Is that what makes it “controversial?” No. Adcomm votes are recommendations and the advice (while generally followed by the agency) is in no way binding and there’s plenty of precedent for the FDA going its own way.
No, 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? The AGs who are petitioning the FDA see abuse and seek to minimize access to opioids as the solution.
That’s a law enforcement solution. They mean well, but are behaving like a bull in a china shop. Arbitrarily limiting choice is not generally associated with the scientific method. Should regulation be shaped by factors other than science? Or should advances in medicine and digital information be used to right size regulation reduce the excessive reductionism that leads to regulatory overreaction and promote resilience rather than ever increasing regulation.
Which brings us to the second objection raised by the “Opioid-28,” that Zohydro lacks “an abuse-limiting formula.”
Per Doug Throckmorton,
Another important step towards the goal of creating safer opioids, and one that is a high public health priority for FDA is to encourage the development of formulations of these drugs that deter their abuse. This relatively new science of abuse deterrence is exciting and evolving and showing encouraging promise. To guide drug development in this new field, we also issued a draft guidance for industry in January, announcing a flexible, adaptive approach to encourage the development of abuse-deterrent opioids. We believe abuse deterrent products have promise to help reduce prescription drug abuse and improve public health.
The FDA has its eye on the prize. But what’s the game for the AGs? They refer to an “epidemic.” That’s a powerful word. But does it qualify in the case of opioids?
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.
And the “Opioid 28” wants fewer pain medications on the market?
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 (such as those proposed by the 28 AGs), we 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.
There is no expedient to which a man will not go to avoid the labor of thinking.
– Thomas Edison
As we inch closer to biosimilars in the US, we need to remember that similar does not mean identical – and that means paying close attention to bioequivalence.
MedPage Today reports that FDA-funded studies are underway that may lead the FDA to stiffen its bioequivalence rules for generic anti-epileptic drugs (AEDs) and others with so-called narrow therapeutic indices.
These studies examine drug pharmacokinetics in epilepsy patients and under chronic dosing -- could show that some current generic AEDs vary enough to put patients at risk. My eldest son has Juvenile Myoclonic Epilepsy (JME), and I can attest to the problems with therapeutic substitution from personal experience.
The FDA has shown a willingness to modify its rules if, indeed, the evidence is there, said Barry Gidal, PharmD, of the University of Wisconsin, at a press briefing held at the American Epilepsy Society (AES) annual meeting. "We're bringing the evidence."
Current bioequivalence regulations allow some variation in generic drug pharmacokinetics relative to the original branded drug. In particular, the lower boundary for 90% confidence intervals in measures of bioavailability can be as low as 80% of the mean for the branded drug, and the upper boundary can be as high as 125% of the branded drug mean.
Under current FDA rules, single-dose studies in healthy volunteers are adequate to show bioequivalence. He said that this poses two problems: drug availability and metabolism may be different in patients than in healthy people, and it may also be different with chronic dosing.
The issue of real-world generic equivalence is not confined to AEDs. Immunosuppressants are another drug class with narrow therapeutic indices, and an FDA-funded study of tacrolimus bioequivalence is also underway.
Another view of the bioequivalence issue was provided by another University of Cincinnati study led by Lisa Garrity, PharmD -- a survey of Cincinnati-area pharmacists about their knowledge and experience with generic AEDs.
Garrity and colleagues obtained responses to a one-page questionnaire from 30 retail pharmacists who had a mean of 15.6 years in practice (SD 8.8). Of these, 20 reported having no specific education about possible issues with generic AEDs when switching from one manufacturer to another.
Responses indicated that 22 believed that switching from a branded version to a generic could cause problems, but only 18 said that issues could arise when switching between generic versions of the same drug. Per Garrity, "I think these [types of switches] should be equally concerning.”
Another problem with the current system is the lack of transparency regarding generic drugs' pharmacokinetics. Data from manufacturers' FDA submissions are not readily available.
Can you say INN?
Today's FTC hearing on biosimilars cancelled because of safety concerns (snow day in DC).
A good name is better than precious ointment.
-- Ecclesiastes vii. 1.
U.S. approval of biosimilars promise to be a very good thing, but the devil is on the details. Unfortunately, we’re seeing a disturbing trend relating to one of those key details – naming nomenclature.
Advocates for nonproprietary names across innovator reference product biologics and the biosimilars associated with them dangerously miss the mark on the pivotal issues relating to naming. A new editorial in Nature Biotechnology demonstrates such misguided thinking. Wither their usual good sense?
Obviously much education remains to be done on this issue in the time between now and when FDA issues final draft guidance on naming. Because where FDA winds up on this issue -- nonproprietary names, nonproprietary names + identifier codes, unique names or somewhere in between – will significantly impact patients, providers, manufacturers, pharmacists, safety experts and others. We need to all side firmly with what's best for patients.
If you’re for patient safety, you can’t be against distinguishable naming. The WHO established the International Nonproprietary Names (INN) system in 1953 before biologics were a figment of anyone’s imagination. Through the INN system, innovators and generics that share the same active ingredient also share the same generic name, also called the INN. It’s worked pretty well for chemical compounds but, as has been acknowledged by WHO and regulatory bodies of every developed nation, biologics are not chemical compounds – they’re infinitely more complicated.
We need to learn from these market-based experiences of nonproprietary names in the EU and Thailand, and distinguishable names in places like Japan and Australia. We can also take valuable lessons from how approaches specific to naming of biologics lend themselves to more effective safety monitoring, pharmacovigilence, data collection, clarity and transparency.
While the U.S. National Drug Code system will continue to serve a purpose for both small and large molecules, we can’t count on it to be the be-all-end-all solution for safety monitoring for biologics. Not even close. Payers don’t universally use NDC codes, they are rarely present in patient records and they are often inaccurately entered when they are. Distinguishable names provide a necessary safeguard to maximize safety and credibility. It’s really that simple.
The FTC is holding a hearing on the topic of biosimilar naming on Tuesday. They have stacked the deck (with exceptions) and no one is expecting anything other than the susual cost-centric care-verse-patient-safety drivel. I’ll be there all the same trying (from the audience) to interject occasional bouts of patient-centric sanity.
When it comes to biosimilars, we need to be extremely thoughtful about how we set policy relating to these promising medicines and strike a balance that promotes health and safety, rather than forcing a binary response that is driven by profits rather than patients.
Here’s a non-biosimilar quote (with apologies to Mr. Shakespeare):
He that filches from me my good nameRobs me, enriches him,
And makes patients poor indeed
Pfizer has announced an update of its clinical trial data access policy that will “simplify and broaden access to information gathered in Pfizer-sponsored clinical trials. The updated policy builds upon and expands the company’s established methods of clinical trial information sharing, including Pfizer’s long track record of submitting for publication results from all interventional clinical trials in patients and its pioneering efforts to provide clinical trial results and data to study participants.”
Key elements of Pfizer’s expanded policy (effective January 1, 2014) are:
* Pfizer’s INSPIIRE public web portal for investigator-initiated research (iirsubmission.pfizer.com) will offer qualified researchers a standard form and process for requesting access to anonymized patient-level data from Pfizer-sponsored trials of approved (or discontinued) products/indications posted on clinicaltrials.gov that have been complete for 24 months.
* An external Independent Review Panel will consider all requests denied or only partially approved by Pfizer and make a final decision.
* Pfizer will publish (on Pfizer.com) synopses of clinical study reports (CSRs) filed with regulatory agencies for approved products for which basic results are posted in the clinicaltrials.gov registry (dating back to September 2007). These CSR synopses will include summary results for all primary and secondary endpoints; any data that could be used to identify individual patients will be removed.
* Pfizer will produce and distribute lay-language summaries of clinical trial results to trial participants who wish to receive them, starting with trials that begin enrolling in 2014, in countries where regulations permit.
* Pfizer is piloting the use of “Blue Button™” technology (launched by the U.S. Departments of Veterans Affairs and Health and Human Services) to enable Pfizer trial participants to download their own electronic clinical data collected in the trial.
According to Pfizer, their expanded clinical data access policy “also reinforces the company’s current practice of submitting for publication manuscripts for all interventional clinical trials in patients, regardless of outcomes, within 18 months of study completion, and the company’s commitment to register and post summary results for interventional human clinical trials to clinicaltrials.gov in the United States and to registries outside the United States as required.”
The full version of Pfizer’s expanded policy, the clinical data request form, the searchable CSR database, the Independent Review Panel membership roster and charter, and more information, including Frequently Asked Questions, are available at http://www.pfizer.com/TrialDataandResults.
According to the American Medical Association, cost estimates of inefficient health care claims processing, payment and reconciliation are between $21 and $210 billion. In the physician practice, the claims management revenue cycle consumes an unsustainable 10–14 percent of practice revenue.
The current system is all too often manual. It must be replaced by automated, transparent, unambiguous, real-time health care transactions.
The full AMA white paper on this issue can be found here.
A new article by Robert Oscar, RPh,President and CEO of RxEOB, furthers that argument. According to Oscar:
Prior authorization (PA) is a complex process that is often daunting and monotonous for medical practice managers. It is also costly in terms of economics and human life, in particular when PA requirements lead to patient medication needs “falling through the cracks,” as some patients abandon their prescriptions due to the confusion and delay of the approval process.
Some other important points from Oscar:
The original goal of PA was to save money, requiring physicians to justify to health plans the need for medications, diagnostic tests and procedures, but it has led to pharmacists having to spend an average of five hours per week handling PA requests. This is non-reimbursable time that is better served on direct patient care.
A nationwide physician survey indicates that more than 69 percent of physicians typically wait several days to receive a PA from an insurer for a prescribed drug, while 10 percent wait more than a week. While more than 52 percent of office-based prescribers utilize electronic prescribing methods, most of them continue to use paper-based methods for obtaining PA of medications from health plans, causing unnecessary delays for patients.
The good news is that a growing number of physicians and office managers are taking proactive steps to solve these issues by taking advantage of electronic PA (ePA), a technology that enables them to submit an authorization request through hand-held devices or via a web portal prior to pharmacy adjudication.
ePA speeds up health insurer response time, minimizes resources associated with manual processes, and helps to enhance the quality and utility of the PA process.
For physicians and office practice managers who want to reduce manual PA workflow, improve the quality of the PA enforcement process, automatically document all activities, reduce the PA approval response time, and increase their understanding of lower-cost therapeutic alternatives, ePA technology is the way to go. The best solution can enable physicians and their staff assistants to submit the PA request online via EMR or e-prescribing workflow, thereby mitigating unnecessary delays, improving the quality of patient care and enhancing the patient’s overall experience with care delivery process.
Oscar’s complete analysis can be found here.
Yesterday I participated in a conference on Content Marketing. (The complete program agenda can be found here.)
Content marketing?
As my sister (a mental health professional) asked me, “Content marketing? As opposed to what, bullshit marketing?”
Not a question I was prepared for over the Thanksgiving table but, from someone who we generically refer to as “a provider,” an honest and relevant one.
Rhetoric counts. Maybe a better phrase is “content management” – because then we can compare it to something more tangible – such as “financial management.” We certainly know what that is. You take a certain about of money (the “content”) and through a savvy understanding of the marketplace and using the legal tools and compliant instruments you seek to increase the value of your portfolio.
When it comes to healthcare, is it content marketing or content management – or is it yet something else?
Maybe a better way to ask the question is, if it’s content marketing, what is the content and to whom are we marketing it – and why?
Content marketing, as a business proposition, is about maximizing awareness, reputation, sales, market share – and the advancement of the public health. (And it needn’t be in that order.) Indeed, the purpose of content marketing is to maximize the potential of important, accurate and timely information.
So maybe we should be talking about content maximization – and a more three-dimensional agenda – that is to say, beyond sales acquisition to driving patient outcomes.
(Another reason to alter the nomenclature is to help recalibrate the corporate compass.)
Some important questions:
How can content maximization address the adherence/compliance quandary?
How can content maximization help healthcare communicators advance the use of new platforms and media?
Most importantly, how can content maximization help define healthcare communications in a post-blockbuster environment, specifically as it pertains to orphan diseases and the rise of personalized medicine?
Let’s consider how the goal of content maximization through the strategy of content management and the tactics of content marketing can help advance sales, corporate, and public health goals. (And, again, not necessarily in that sequence.)
The heart of content marketing is story telling. Savvy healthcare marketers need to move from ABC (“Always Be Closing”) to ABT (Always Be Telling).
In the world of 21st Century healthcare, companies must share their content from their own mouths – because in the ultra-transparent world of social media, you can't separate the story from the storyteller. And we shouldn't even want to.
Rhetoric counts. As Kurt Vonnegut wrote, we need to “transcend the bullshit.”
Amen.
It’s fast becoming an n of 1 world. A world where every disease is an orphan disease and success is measured by individual outcomes rather than large population studies such as CATIE or ALLHAT or the multitude of programs being funded by PCORI.
Small is the new Big means that we must also think differently about pharmacovigilance. While we must continue to capture adverse event data (and do a better job at that through social media channels and mobile apps), we must also strive to capture Substandard Pharmaceutical Events (SPEs). SPEs occur when a pharmaceutical 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. Small is the new Big.
And when it comes to drug development, adaptive clinical trials and companion diagnostics further define the outsized urgency of small-scale thinking. Demonstrating outcomes on an n of 1 level is crucial not just for 21st century healthcare technology assessment (think “value-based reimbursement”) but also for physician pay-for-performance measures and, last but not least, for the benefit of actual patients
There’s a lot of lip service paid to the comment that “the era of the blockbuster is over.” Now consider that statement from the perspective of another industry – in the 21st Century would you rather be Blockbuster or Netflix?
Small is the new Big. And that means a focus on individual patient outcomes, which means a focus on the individual patient rather than the general population and on long term care rather than short term cost.
And it’s about time.
Center for Medicine in the Public Interest is a nonprofit, non-partisan organization promoting innovative solutions that advance medical progress, reduce health disparities, extend life and make health care more affordable, preventive and patient-centered. CMPI also provides the public, policymakers and the media a reliable source of independent scientific analysis on issues ranging from personalized medicine, food and drug safety, health care reform and comparative effectiveness.
