Latest Drugwonks' Blog
How important is the issue of opioids? Well, important enough that it was the very first panel offered at the 2014 BIO Convention’s regulatory affairs track. And it didn’t disappoint.
Moderated by yours truly, I was joined by three experts (Douglas Throckmorton, MD, Deputy Director of Regulatory Programs, FDA’s Center for Drug Evaluation and Research, Richard C. Dart, MD, PhD, Director of the Rocky Mountain Poison and Drug Center, and J. David Haddox, DDS, MD, Vice President of Health Policy for Purdue Pharma, L.P.) and a room full of engaged and inquisitive attendees. The session began with a question – Who lost opioids?
I reminded the audience of the old public relations maxim that, “Everything you read in the newspaper is true – except for those things you know about personally.” And today that means the preeminence of social media. Google “opioid abuse deterrence” and you’ll find a lot of hits from lawyers and elected officials in the mainstream media -- but you have to know where to look (or who to ask) to access expert thinking from the FDA.
There’s certainly no dearth of verbiage and suggested solutions from the law enforcement community. Alas, those fixes rely on the general philosophy that the only good opioid is a recalled opioid. And that results in strategies that require strict prescribing limitations, and severely limited access. Punishing the legitimate pain patient, all the panelists agreed, is the wrong way to go.
Then there’s the legislative solution – but what this really means is allowing politics to drive the agenda. The posturing and hyperbole that has surrounded the issue of opioids pain medicines hasn’t resulted in a single workable solution. And the premature promptitude of many attorneys general and chief executives such as Massachusetts Governor Deval Patrick has led to numerous headlines but, in the end, nothing but fruitless lawsuits.
As Mark Twain quipped, “For every complex problem there is usually a simple answer – and it is usually wrong.” What those seeking to solve the problem with one-shot solutions have ignored is that pain in America is a medical problem of enormous proportion.
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 the pain disables them. Pain costs the US economy about $600 billion dollars a year in lost productivity and healthcare cost. And lawsuits, recalls, and police actions won’t change those dire statistics.
But just as opioids aren’t the problem, neither are they a panacea. Yet payers often implement barriers to the use of branded, on-label non-opioid pain medicines, relegating these treatments to second line options. 52% of patients diagnosed with osteoarthritis receive an opioid pain medicine as first line treatment, as do 43% of patients diagnosed with fibromyalgia, and 42% of patients with diabetic peripheral neuropathy.
Aren’t abuse deterrent opioids the magic bullet we’ve all been looking for? Not really. First of all, what does “abuse deterrence” even mean? As FDA Commissioner Peggy Hamburg testified to Congress, “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.” Abuse deterrence is a goal. And at present, it’s an elusive one.
Abuse deterrence also raises some very important and difficult regulatory questions for the FDA. What type of 21st regulatory science will be required to review abuse deterrent applications? How will the agency approach the approval of non-abuse deterrent generics? What about more sophisticated pharmacovigilance programs? And, last but not least, how can the FDA better protect the public health while simultaneously preserving innovative development programs?
Dr. Throckmorton’s presentation noted that both FDA and other government epidemiologists are working to improve the surveillance databases and tools used to assess impact of abuse deterrent formulations in US market. He specifically mentioned the “DAWN” (Drug Abuse Warning Network) database replacement, measuring appropriate access to opioids by pain patients. The development and broad adoption of successful abuse-deterrent formulation remains an important priority for FDA. But we’re in the early days of the science, with much important work to be done.
But what else can be done?
As former Canadian Prime Minister 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 – particularly for opioids? As CDER Deputy Director (and the FDA’s point-man on opioids) Dr. Douglas Throckmorton said, “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.”
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. In the immortal words of Don Draper, “If you don't like what is being said, then change the conversation.
The FDA must play a lead role in facilitating physician education, not only through labeling language but physician education. The FDA has, of late, repeatedly discussed enhancing continuing medical education (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.
In the words of FDA Commissioner Hamburg, “It all comes back to provider education.” 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.
Abuse deterrence is a worthy goal and will evolve when all the players work together in a more regular and synchronistic fashion. Fortunately, all panelists agreed this was the reality.
As the Japanese proverb goes, “Don’t fix the blame, fix the problem.”
The Massachusetts Senate has passed legislation to allow pharmacists to substitute a biosimilar for a biological medicine when the United States Food and Drug Administration has determined that the two biological products are interchangeable and the prescriber has not instructed otherwise.
Following a substitution, the bill requires pharmacists to notify the prescribing practitioner and the patient. The bill will now go to the Governor for his signature.
Sounds good, right? Physician notification. But the bill was obviously drafted before the FDA expanded the types of biosimilars it will consider. Once upon a time there were two categories: biosimilar and interchangeable. But today there are four: not similar, similar, highly similar or highly similar with a fingerprint-like similarity -- depending on the type, nature and extent of any structural and functional differences revealed.
The reality is that “interchangable” is a thing of the past – even before it was a thing of the present.
In keeping with the spirit of the Massachusetts legislation (as well as that in many other states), the nomenclature should be reconsidered to reflect the realities of the evolving regulatory science.
First-Ever Patient-Initiated “Guidance for Industry” for Duchenne Muscular Dystrophy Submitted to FDA
Parent Project Muscular Dystrophy-led guidance seeks to address unmet clinical needs of individuals with Duchenne muscular dystrophy and accelerate development of safe and effective therapies
Washington, DC–June 25, 2014 -- Parent Project Muscular Dystrophy (PPMD) and a broad coalition of stakeholders today submitted the first-ever patient advocacy-initiated draft guidance for a rare disease to the U.S. Food and Drug Administration (FDA) to help accelerate development and review of potential therapies for Duchenne muscular dystrophy (Duchenne).
“This landmark guidance represents a major milestone for the Duchenne community and may open the way for other rare disease groups to incorporate the patient perspective in a well-documented and quantifiable way, moving beyond any one family’s experience,” said PPMD President Pat Furlong. “By working closely with the FDA to provide industry and other clinical trial sponsors with clearer guidance from the patient perspective, we will increase the likelihood that clinical trials will be designed to better match the unique needs of Duchenne patients. It is our profound hope that this, in turn, will lead to the approval of much needed treatments for all people living with Duchenne muscular dystrophy.”
Duchene, the most common lethal genetic disorder diagnosed in childhood, is a progressive and degenerative condition with no cure or disease-modifying treatments available in the United States.
Clinical trials for rare diseases like Duchenne are difficult to design and implement because of challenges such as small study populations, incomplete and evolving understanding of rare diseases, and effective ways to measure clinical impact of therapies being studied. Last year, FDA collaborated with PPMD and its scientific advisors to convene a policy forum that informed the process for developing the Duchenne community’s suggested guidance.
“The U.S. Food and Drug Administration is appreciative of the input of Duchenne patients and patient advocates. Their input will enhance the essential data-driven process and evaluation of new therapies,” said Janet Woodcock, M.D., Director of the Center for Drug Evaluation and Research at the U.S. Food and Drug Administration.
About The Suggested Guidance
More than 80 representatives of the Duchenne community - including parents and patients, medical experts, academics, and biopharmaceutical industry representatives -- participated in seven working groups that met over the past six months to draft the guidance.
The cornerstone of the guidance encourages the FDA and trial sponsors to engage patients and their families at all stages of trial development and to take into account what they consider acceptable risk in clinical trials. A recent PPMD study published in the journal Clinical Therapeutics* shows that parents of children with Duchenne will accept substantial risk when balanced with noncurative slowing or stopping of the progression of muscle weakness, even with no improvement in life expectancy. The results came from the first-ever scientific survey of benefit/risk perspectives that PPMD conducted last year involving 120 Duchenne parents.
“As the FDA evaluates new drug applications for Duchenne therapies, it is imperative to take into consideration the value that parent decision makers place on even moderate benefits to function and mobility, and their tolerance for considerable risk and uncertainty,” said Furlong. “Parents and caregivers of Duchenne children know firsthand that every day without treatment is another day closer to their child losing essential activities of daily living such as walking, feeding oneself, and eventually, breathing. When your child is living with Duchenne, you find yourself willing to take significant risk for even the hope of modest benefit. Parents can make these decisions thoughtfully and the FDA must recognize that. They cannot protect us from what we think is important in the drugs we need now.”
Each section of the guidance includes extensive published or in-press peer-reviewed articles and focuses on six areas aimed at overcoming the challenges in trial design and implementation:
* Benefit/Risk Assessment – providing a community-centered approach for the benefit-risk framework fundamental to the regulatory process and reflecting the community’s tolerance of potential risks or uncertainty of benefit associated with new treatment options.
* Diagnosis – referring sponsors to guidance produced by the American Academy of Pediatrics (AAP) on a diagnostic algorithm, as well as, providing context on diagnostic delay and importance of genetic analysis using modern technologies, including access to genetic testing.
* Natural History – accurately characterizing the clinical course of Duchenne to reflect the timing of the loss of certain abilities based on current medical management practices, including how Duchenne affects cardiac and pulmonary function.
* Clinical Trial Designs, Outcome Measures and Considerations – ensuring that trials – to the degree possible – are inclusive of Duchenne patients of all ages and disease stages.
* Muscle Biopsy-Based Biomarkers – addressing key considerations when performing muscle biopsies, including the ethical imperative to perform them only when needed and precautions to assure usable specimens; sponsors are also referred to an international effort to standardize methodologies and emerging technologies.
* Non-Muscle Biopsy-Based Biomarkers – exploring the ability to bring non-invasive imaging techniques to replace biopsy (e.g., MRI/MRS skeletal muscle imaging) and eventually reach the goal of being a surrogate endpoint for treatment trials.
PPMD-Led Efforts
The suggested FDA guidance represents the culmination of PPMD’s 20 year history of improving care and developing urgently needed therapies for Duchenne. PPMD led the effort to pass the MD-CARE Act, which created the Senator Paul Wellstone Muscular Dystrophy Cooperative Research Centers. The draft guidance builds on PPMD’s effort to shape federal policy that reflects the needs of families living with Duchenne, including the release of “Putting Patients First” which calls on the FDA to act more flexibly when reviewing applications for Duchenne therapies. PPMD also ensured that the FDA Safety & Innovation Act of 2012 (FDASIA) responded to the needs of the community; recently published a groundbreaking benefit/risk study which documented the willingness of families to live with risk; and held a national PPMD-FDA Duchenne Policy Forum where the community made its needs and preferences in drug development known to the Agency.
*[EDITOR’S NOTE – Peay H.L. et al: A community-engaged approach to quantifying caregiver preferences for the benefits and risks of emerging therapies for Duchenne muscular dystrophy; Clinical Therapeutics, Vol. 36, No. 5, 2014; available for access: http://www.clinicaltherapeutics.com/article/S0149-2918(14)00209-4/abstract.]
The New York Times has written quite a lot lately on the cost of drugs – without a word on either the value of new medicines or the cost of investing in innovation. On the up side, the Gray Lady has finally discovered the cost of poor medicines quality.
For years, Dr. Harry Lever, a cardiologist at the Cleveland Clinic, has been warning nearly anyone who would listen of his growing suspicions about generic versions of a widely used heart drug, Toprol XL.
Patient after patient, he said, would visit his office complaining of chest pains or other symptoms after switching from the brand-name version, made by AstraZeneca, to a generic product, often one made in India. When he switched them back to the brand — or to another generic — the symptoms disappeared, he said. Dr. Lever wrote a letter outlining his concerns to the Food and Drug Administration in 2012, and this year, he traveled to Washington to try to get the attention of Congress.
Dr. Lever could not prove that the generic drugs were to blame. “You see enough people and you get a feel, but it’s anecdotes,” he said in an interview Monday. “It’s not science.”
This is in keeping with a March Reuter’s story on the same topic:
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."
Hopefully the Times story will provide further traction because, as Dr. Lever said (in the Reuter’s story),
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."
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.
Bioequivalence does not always equal therapeutic equivalence – and that’s as true for Toprol XL as it is for Wellbutrin. According to the Times story, Two large Indian manufacturers, Wockhardt and Dr. Reddy’s Laboratories, have announced recalls over the last two months totaling more than 100,000 bottles of Toprol XL because their products were not dissolving properly — therefore probably not working as they should. The drug is a beta blocker that treats high blood pressure and heart ailments. Not good.
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.
Where's the Times editorial on that?
My bags are packed. I’m ready to go.
As many of us head out to San Diego for BIO, it’s important to put the gathering in the proper perspective. It’s not just about business. It’s not just about networking. It’s about advancing the public health. It’s about protecting and advancing innovation.
Attached is a letter that Pfizer honcho Ian Read just sent to Representative Fred Upton. Mr. Upton, as you are likely aware, is the Chairman of the House Committee on Energy & Commerce and has been leading a series of hearings on 21st Century Cures.
Ian also attached a more complete thought piece on a series of innovation priorities. Innovation? Read all about.
While at BIO I’ll be participating in two panels.
Panelists
Peter Pitts, Moderator, President and co-founder, Center for Medicine in the Public Interest
Douglas Throckmorton, MD, Deputy Director of Regulatory Programs, FDA’s Center for Drug Evaluation and Research
Richard C. Dart, MD, PhD, Director of the Rocky Mountain Poison and Drug Center
J. David Haddox, DDS, MD, Vice President of Health Policy for Purdue Pharma, L.P.
WHERE: San Diego Convention Center Room 31 B
WHEN: Tuesday, June 24 2014, 9:00 am –10:00 am
The second: Thriving Again in 2014: Preparing for Success, Not Just Survival at FDA Advisory Committee Meetings
Panelists
David Schull, president of Russo Partners
Penny Daniels, strategic communications consultant at 3D Communications
Craig Audet, Ph.D., senior vice president, operations and head of global regulatory affairs with Arena Pharmaceuticals, Inc.
Peter Pitts, president and co-founder of the Center for Medicine in the Public Interest and former FDA associate commissioner of external affairs
Silvia Taylor, senior vice president, investor relations, public relations, and corporate communications at Sucampo Pharmaceuticals, Inc.
WHERE: San Diego Convention Center Room 31B
WHEN: Tuesday, June 24 2014, 3:00PM – 4:00PM
In addition, the Center for Medicine in the Public Interest will have a booth. It’s #5642. And we’ll be talking about innovation.
Hope to see you there.
Urban legend attributes the following quote to Albert Shanker, the very outspoken past president of the American Federation of Teachers:
“When school children start paying union dues, that’s when I’ll start representing the interests of children.”
As always, it’s a question of priorities – and whose priorities. Today that same issue has arisen in the debate over biosimilar nomenclature.
The issue for drug compendia stakeholders (among other things) is interoperability.
According to Inside Health Policy:
“While some say an easy solution is to simply add a suffix to distinguish a biosimilar from the innovator product, the compendia group told FDA any change is a change, and regardless of the simplicity of the change, the associated coding would also have to shift. First data bank and two other databanks are sold to stakeholders who assemble them and put overlays on them and then the data are used for different purposes, including for reimbursement.”
Yes, well unfortunately change is not always easy. But as management guru W. Edwards Deming warned, “Change is not required. Survival is not mandatory.”
Assigning differential naming to biosimilar products will certainly prove challenging to the various constituents of the drug compendia community – but it will be crucial for pharmacovigilance. In the real world, how can we not have separate names when there are going to be four categories of products?
Based on comparative analytical data, FDA will characterize its assessment of biosimilarity into one of four levels -- not similar, similar, highly similar or highly similar with a fingerprint-like similarity -- depending on the type, nature and extent of any structural and functional differences revealed.
Additional pharmacologic studies would be required to show that the identified difference is "within an acceptable range to consider the proposed biosimilar product to be highly similar to the reference product." FDA said only products in the top two tiers would meet the statutory requirement for analytical similarity under the Biologics Price Competition and Innovation Act of 2009. Products in the top two tiers would then only require "targeted and selective animal and/or clinical studies to resolve residual uncertainties" to demonstrate biosimilarity. In addition, these data could be used to extrapolate clinical data for additional indications.
Giving credit where credit is due, the good people at the USP understand that interoperability is important, but that naming is more of a philosohpical issue. That's why they support differentiation via discrete numerical suffix.
Per Inside Health Policy:
The drug compendia stakeholders told a group of 13 FDA drug policy experts, including drug center chief Janet Woodcock, that changing the traditional naming process would require that each piece of the compendia process be individually rebuilt in order to ensure patient safety and restore functionality to the system. Doing so, while possible, would be difficult and could lead to confusion, errors and misunderstanding, creating a "very real risk to patients," according to slides presented at the May 2 meeting and a June 6 follow-up letter, obtained by Inside Health Policy.
The argument that differential naming is bad for patient safety is pure Orwellian Newspeak -- specifically “blackwhite,” The ability to accept whatever "truth" the party puts out, no matter how absurd it may be.
When it comes to biosimilar nomenclature, it’s urgent that we keep our priorities straight. And that means keeping patient safety, not interoperability challenges, at the top of the agenda.
Fortunately, White Oak trumps blackwhite.
Per FDASIA: By July 9, 2014, FDA must issue guidance describing FDA policy regarding Internet promotion, including social media, of medical products regulated by FDA.
Well, ahead of schedule we now have two draft guidances:
And:
First let’s discuss “Social Media Platforms with Character Space Limitations.
Perhaps the biggest leap forward for the agency is that is beginning to differentiate between social media platforms, recognizing that different rules must apply for different types of platforms. Obviously, when it comes to platforms such as Twitter the main issue is character limitations. The agency also points out that the same is true for advertising venues such as banner ads on Google (shades of the FDA’s first batch of warning letters from 2009).
So, to the FDA’s credit, it only took the agency about five years to develop draft guidance. Not a badge of honor.
Still, there are some interesting things to be gleaned from the draft guidance. The agency writes:
Risk information should be comparable in content and prominence to benefit claims within the product promotion (i.e., a balanced presentation). Achieving a balanced presentation requires firms to carefully consider the desired benefit claims and risk profiles for their products when choosing a promotional platform.
That’s good advice – choose the platform that best suits any given communications need. But, it’s not really any communications need – it’s any promotional program. That’s important because promotional speech is regulated speech. And that’s not just regulatory rhetoric. And this begs a crucial question not covered in the draft guidance – What it the intent of the communications?
Don’t wait for the FDA to offer guidance on that. They will not and should not. That’s a question only the communicator can answer. And it needs to be done honestly and early in the communications development process.
The agency writes:
FDA acknowledges that Internet/social media platforms associated with character space limitations may pose challenges for firms in providing a balanced presentation of both risks and benefits of medical products, as discussed above … The firm should also provide a mechanism to allow direct access to a more complete discussion of the risks associated with its product.
In a likely unintended nod to self-deprecation, the agency offers potential examples of how this could be done for the fictitious product NoFocus.
The agency writes:
A firm is considering promotion of its prescription drug NoFocus on Twitter … NoFocus is indicated for mild to moderate memory loss.
The draft guidance suggests that the tweet contain the following 40 characters:
NoFocus for mild to moderate memory loss
The agency writes:
The benefit information for NoFocus that is communicated within the first 40 character spaces of this tweet is accurate and non-misleading and includesmaterial facts about the indication and limitations to the use of NoFocus.
So, the agency is also suggesting that these 40 characters be the first 40.
The agency then proceeds to discuss paid search advertising for the fictitious product Headhurtz. (This is likely the product in development for legal and regulatory review departments at pharmaceutical and medical device companies.)
The agency suggests that information on limitations and appropriate use as well as a link to the product website be included. Specifically:
Headhurtz [www.headhurtz.com] For severe headache from traumatic brain injury
It’s not Brief Summary, it’s Tweet Summary.
The agency’s most important advice appears on Page 12 of the draft guidance:
In communicating risk information on Internet/social media platforms with character space limitations, firms should consider the following points:
1. Risk information should be presented together with benefit information within each individual character-space-limited communication (e.g., each individual message or tweet).
2. The content of risk information presented within each individual character - space-limited communication should, at a minimum, include the most serious risks associated with the product.
3. A mechanism, such as a hyperlink, should also be provided within each individual character-space-limited communication to allow direct access to a more complete discussion of risk information about the product … the Agency recommends that a direct hyperlink to a landing page that is devoted exclusively to comprehensive risk information about the product be initially included within the original character-space-limited communication.
Not rocket science, but urgently important to remember when considering both the design and appropriateness of a limited-character platform. Also, the use of hyperlinks is crucial – and will be even more so as we move on to a discussion of the second of the agency’s newly minted draft guidances. (Note – the agency makes it clear that a link’s name should also be considered. Specifically, it shouldn’t be a claim (i.e., www.bestcancercuredrug.com).
Per the new “Tweet Summary,” the agency writes:
Since benefit information was provided within the tweet (example 1A), the firm should communicate, at a minimum, the most serious risks associated with NoFocus within the same tweet. The firm should also include within the same tweet a direct hyperlink to a more complete discussion of risk information about NoFocus. Additionally, the prominence of risk information should be comparable to the benefit information contained within the tweet, taking into consideration any formatting capabilities that may be available. The firm considers including the following benefit and risk information within the tweet:
NoFocus for mild to moderate memory loss; may cause seizures in patients with a seizure disorder www.nofocus.com/risk
And, as a further build:
… the firm should also communicate the brand and established names within the tweet. The firm considers including the following product information, together with benefit and risk information about NoFocus, within the tweet:
NoFocus (rememberine HCl) for mild to moderate memory loss-May cause seizures in patients with a seizure disorder www.nofocus.com/risk
As it turns out, the Tweet Summary takes up quite a bit of the available characters – and this is for a non-Black Box product. For those of you keeping count, it’s now up to 134 characters – leaving only six characters for Hi Mom.
Later on Pages 12-13 the agency spells out how verbiage and hyperlinks can be compliantly used for promotional speech such as sponsored Google links. Its well a well thought out and developed template. And it’s more restrictive – as it should be. After all, there are rules for advertising. Five years in the making. Headhurtz indeed!
Now let’s move on to a far more important public health issue: Correcting Independent Third-Party Misinformation About Prescription Drugs and Medical Devices.
For those of you not currently on NoFocus therapy, you will remember the 2009 Part 15 hearing on social media – the “SuperBowl of FDA Part 15 hearings.” One of the key questions the agency wanted to discuss was how to correct erroneous product information. All they got were blank stares and request for FDA guidance. Five years later – voila!
The agency writes:
This draft guidance is intended to describe FDA’s current thinking about how manufacturers, packers, and distributors (firms) of prescription human and animal drugs (drugs) and medical devices for human use (devices) should respond, if they choose to respond, to misinformation related to a firm’s own FDA-approved or -cleared products when that information is created or disseminated by independent third parties on the Internet or through social media or other technological venues (Internet/social media), regardless of whether that misinformation appears on a firm’s own forum or an independent third-party forum or website.
Key take-away is that the decision to correct errors is purely voluntary. (But, then again, technically so are all product recalls.) Where that becomes more complicated is how companies may choose to cherry-pick where they interceded for corrective purposes. This is not an issue addressed by the FDA in this draft guidance. One thing this all means is more work for legal and regulatory review.
This draft guidance is all about user-generated content. The agency writes:
The Internet and Internet-based technologies have made it easier for third parties who are independent of firms to disseminate information about drugs and devices. Information created by third parties (which for purposes of this guidance is user-generated content (UGC)) might appear on an interactive portion of a firm controlled website or other interactive Internet/social media platform, or information might appear on a website or other Internet/social media platform that is independent of, or not under the control or influence of, a firm.
Many Internet/social media platforms allow for real-time and continuous communications and interactions (e.g., blogs, microblogs, social networks, online communities, and live podcasts) while other platforms do not provide a means for interactive content to be posted. Whether a forum is interactive may affect the means by which a firm is able to respond to information.
And, the agency stipulates, “UGC might not always be accurate and may be dangerous or harmful to the public health.” Well, yes. What’s a manufacturer to do?
Five years later, some helpful advice from the good people at White Oak.
Specifically:
If a firm voluntarily corrects misinformation in a truthful and non-misleading manner and as described in this draft guidance, FDA does not intend to object if the corrective information voluntarily provided by the firm does not satisfy otherwise applicable regulatory requirements regarding labeling or advertising, if any.
From a regulatory perspective, that’s a lot of wiggle room and should provide significant food for thought in erring on the side of more rather than fewer voluntary corrective actions.
But:
If a firm chooses to respond to misinformation about its products using non-truthful or misleading information or in a manner other than that recommended in this draft guidance, however, FDA may object if the information provided by the firm does not comply with applicable regulatory requirements related to labeling or advertising, if any.
Certainly. But what this also harkens back to is the agency’s previous guidance where it warns against using company-generated (sponsored) UGC relative to other companies’ products. That 12/11 guidance warns:
If a firm chooses to respond to public unsolicited requests for off-label information, the firm should respond only when the request pertains specifically to its own named product (and is not solely about a competitor's product).
Forewarned is Forearmed. Don’t get to cute.
This draft guidance isn’t about sponsored communications. The agency writes:
This draft guidance does not apply when a firm is responsible for the product communication that contains misinformation. A firm is responsible for communications that are owned, controlled, created, or influenced, or affirmatively adopted or endorsed, by, or on behalf of, the firm.
A firm is thus responsible for communications on the Internet and Internet-based platforms, such as social media, made by its employees or any agents acting on behalf of the firm to promote the firm’s product, and these communications must comply with any applicable regulatory requirements.
Specifically:
… this draft guidance applies when a firm is not responsible for a product-related communication that appears on the firm’s own forum, an independent third- party website, or through social media, and the firm chooses to correct misinformation about its own product contained in that communication. In such cases, we recommend that the firm do so as described in this draft guidance.
More detail is provided here relative to the nuance of “control” and “sponsorship (pages 7-8) and are worth reading.
Here are the agency’s eight ground-rules for “appropriate corrective information;”
* Be relevant and responsive to the misinformation;
* Be limited and tailored to the misinformation;
* Be non-promotional in nature, tone, and presentation;
* Be accurate;
* Be consistent with the FDA-required labeling for the product;
* Be supported by sufficient evidence, including substantial evidence, when appropriate, for prescription drugs;
* Either be posted in conjunction with the misinformation in the same area or forum (if posted directly to the forum by the firm), or should reference the misinformation and be intended to be posted in conjunction with the misinformation (if provided to the forum operator or author);
* Disclose that the person providing the corrective information is affiliated with the firm that manufactures, packs, or distributes the product.
Truthful. Accurate. Transparent. Three good rules of thumb. But what about “timeliness?” No advice from the agency on this one – but something crucial for manufacturers to consider since the goal here is to protect the public health.
Again, the agency offers important nuance on how to correct. For example, don’t just correct one mistake when multiples ones appear. The draft guidance also offers absolutely critical commentary relative to the depth and breadth of responsibility when correcting one piece non-sponsored UGC, “The firm is not expected to correct misinformation that appears on other webpages of the website.”
Those sweet sixteen words address a world regulatory angst.
Further:
Once a firm undertakes the correction of misinformation, FDA does not expect the firm to continue to monitor the website or communication that previously included UGC containing misinformation.
This does, however, point to the need for individual companies to develop their own policies in this regard. More work for legal/regulatory review teams!
And, for those of you who are thinking a little too hard, consider this important caveat:
… if a firm chooses to correct only misinformation that portrays its product in a negative light in a third-party communication but does not address misinformation that overstates the benefits of its product in that same clearly defined portion of the communication, the firm’s actions do not meet the recommendations in this draft guidance.
Voluntary corrective action isn’t just about “bad” information.
And, importantly:
FDA recognizes that a firm cannot control whether an independent third party refuses to correct the misinformation, or corrects only a portion of the misinformation even though the firm provided complete corrective information, or declines to include the respective required labeling, or declines to remove misinformation, or does not correct all the misinformation in one clearly defined part (if the firm sought to correct more than one piece of misinformation). Accordingly, FDA will not hold a firm accountable for an independent third party’s subsequent actions or lack thereof.
The perfect shall not impede the public good.
And, lastly:
FDA does not expect firms to submit corrections to the Agency when correcting misinformation pursuant to this draft guidance; however, FDA recommends that firms keep records to assist in responding to questions that may come from the Agency. The records should include, for example, the content of the misinformation, where it appeared, the date it appeared or was located, the corrective information that was provided, and the date the corrective information was provided.
Good guidance has been provided. Now it’s time for industry to do the right thing.
U.S. Healthcare: Most Expensive and Worst Performing
In a new international ranking, the United Kingdom ranks first, while the U.S. performs poorly across almost all health metrics.
This study -- or rather a version of it conducted by the World Health Organization -- has been thoroughly shredded by Scott Atlas in his Commentary article: The Worst Study Ever?
As Atlas points out: "researchers divided aspects of health care into subjective categories and tailored the definitions to suit their political aims. They allowed fundamental flaws in methodology, large margins of error in data, and overt bias in data analysis, and then offered conclusions despite enormous gaps in the data they did have."
All to make the case for single payer health systems.
In this case, the Commonwealth Fund measures everything except the quality of care. It measures lots of process measures that are easily skewed by bias. So for instance, in measuring "efficiency" CW ranks countries based on percentage of GDP spent on health and percent of health care spent on administrative services. Of course the US is destined to be the worst.
Next, it ranks countries on access. Again the US is trashed. And the UK is number 1. Don't laugh. CW used "having access to basic medical care the same or next day." Apparently wait times for cancer care, hip replacements, by-pass surgeries, etc. don't count. Indeed, CW ignores the explosion in outpatient same day surgery and walk-in clinics in the US.
The US is also slammed for unfairness. CW claims -- surprise! -- that the UK does the best on providing the same great care to everyone rich and poor. Apparently, despite the exhaustive research CW did, the group failed to come across the Marmot report calling health inequality in the UK a ticking time bomb. Here's the link in case CW wants to update it's study:
Meanwhile, CW ignores the following (courtesy of Scott Atlas again!):
"American cancer patients, both men and women, have superior survival rates for all major cancers. Removing “lead-time bias,” where simply detecting cancer earlier might falsely demonstrate longer survival, death rates from prostate and breast cancer from the early 1980’s to 2005 declined much faster in the US than in the 15 other OECD nations studied (Australia, Austria, Canada, Finland, France, Germany, Greece, Italy, Japan, the Netherlands, Norway, Spain, Sweden, Switzerland, and UK)."
What about heart disease?
"A comparison of the US to ten Western European nations (Austria, Denmark, France, Germany, Greece, Italy, Netherlands, Spain, Sweden, and Switzerland) showed that 60.7 percent of Americans diagnosed with heart disease were actually receiving medication for it, while only 54.5 percent of Western Europeans were treated (a statistically significant difference)."
Also...
"Another comparison study showed that fewer Americans than UK residents die (per capita) from heart attack despite the far higher burden of risk factors in Americans for these fatal events. In fact, the heart disease mortality rate in England was 36 percent higher than that in the US. These superior outcomes from US medical care are particularly impressive, considering that American patients have far more risk factors (diabetes, obesity, chronic kidney disease) that worsen outcomes and death rates after heart attack and after heart surgery.
The US shows a far greater reduction in death rates from stroke, the third leading cause of death and the leading cause of disability in adults in the US and most Western European nations, than almost all Western European nations and the European Union overall."
So why did CW ignore outcomes like mortality and survival and focus on income inequality and how universal a health care system was.
You have to take into account CW's frame of reference. If someone told you time again that the VA health system is a model of excellence, would you take their study on health care performance seriously?
And boy does Commonwealth love the VA.
Here's CW president Stephen Shoenbaum gushing over the VA in an interview with Managed Care magazine:
MC What parts of the health care system are working?
SCHOENBAUM: There are some examples of excellence within the U.S. health system. If we pick any given area, such as quality or driving down costs, we find examples of excellence. Some large systems are doing very interesting things. Kaiser Permanente and the Veterans Administration are managed systems that are trying to improve performance and reduce costs by using a primary care-based system and using information technology creatively. Another example is Geisinger Health System in Pennsylvania.
And here's a CW study of the VA, which it claims is a high performing health system. I take that to mean it meets the standards CW set in the report dumping on US health care. The study celebrates how the Memphis and Lincoln, Nebraska VA systems shortened wait times, reduced emergecny room vistis and reduced blood sugar levels in some patients.
Hmm.. Memphis VA.. where have I heard that before..
VA Hospital Axed Veteran Programs While Approving $1 Million In Bonuses
The Memphis Veteran Administration (VA) Medical Center approved over $1 million in bonuses months before closing a therapeutic aquatic pool citing a lack of funds.
The Memphis VA Medical Center handed out $1,005,644 in bonuses for its approximately 2,000 employees in fiscal year 2010, according to data provided to The Daily Caller by Sandra Glover, the communications officer for Veteran Integrated Services Network (VISN) 9, which includes the Memphis VA Medical Center.."
And this:
Memphis Veterans Affairs Medical Center Flagged in Audit
The CW study is an exercise in confirmation bias, which is the " tendency to search for or interpret information in a way that confirms one's preconceptions, leading to statistical errors. Confirmation bias is a type of cognitive bias and represents an error of inductive inference toward confirmation of the hypothesis under study."
It was designed to reinforce the meme that goverment run health systems are better, fairer and cheaper. This blog was a modest effort to speak truth to bias.
Here's a story from The Pharma Times on how NICE is searching for multiple ways to say "no". That will of course lead to delays in access, during which time people will die. Now that's a way of reducing the "drain on healthcare resources."
NICE asks for more data on Sovaldi
WORLD NEWS | JUNE 17, 2014Tweet
SELINA MCKEE
NICE asks for more data on Sovaldi
Cost regulators for National Health Service treatments in England and Wales have raised an eyebrow or two by asking Gilead for more information on its hepatitis C wonder drug Sovaldi (sofosbuvir).
In draft guidelines the National Institute for Health and Care Excellence (NICE) said it is minded not to recommend Sovaldi, despite the drug being linked with cure rates of over 90% in just 12 weeks.
While the Institute conceded that available evidence shows Sovaldi is an effective treatment for chronic hepatitis C in certain patients, "evidence is lacking for some subgroups of patients with chronic hepatitis C, and there are also substantial uncertainties in the evidence base presented by the manufacturer", it said, explaining its current stance.
"The Committee has therefore requested further information from the manufacturer before it can decide whether sofosbuvir is a cost-effective use of NHS resources".
Move unexpected
The move came as somewhat of a surprise given that, in April this year, NHS England approved funding for Sovaldi in England and Wales significantly at risk of dying or needing a liver transplant, while the Scottish Medicines Consortium cleared its restricted use on NHS Scotland.
The drug was approved for use in Europe in January this year, but has been in the spotlight globally for some time because of its widely-perceived high price tag as much as its stellar effectiveness. With a 12-week course costing just shy of £35,000 in the UK, there are concerns that the drug could prove to be a devastating drain on healthcare resources.
On the other hand, the price of not using Sovaldi is could run much much higher; one in three patients injected with HCV eventually developing liver cirrhosis and managing these patients is costly.
Charles Gore, chief executive of the Hepatitis C Trust, said the drug's high price "should not put off commissioners because price is not supposed to be the determinant – cost-effectiveness is".
"If NICE OK Sovaldi, it should be prescribed to anyone who wants it. We have the Pharmaceutical Price Regulation Scheme (PPRS) to cap the drugs budget," he noted.
The closing date for comments on the draft guidance is 4 July 2014.
New combo shows 100% response rates
Meanwhile, Gilead also unveiled Phase III data showing that the fixed-dose combination of the NS5A inhibitor ledipasvir and sofosbuvir achieved 100% sustained virology response in hepatitis C patients in Japan.
The cure rates observed "are impressive because they were achieved without the need for interferon or ribavirin, both of which involve more complex dosing requirements and may be associated with significant side effects,” said Norbert Bischofberger, Gilead’s Chief Scientific Officer.
The results suggest that the once-daily pill "has the potential to be an efficacious and well-tolerated regimen" for many patients in Japan, he added.
Recently Allison Bell, a blogger for LifeHealthPro.com, a newsletter focusing on how insurance companies can maximize revenue posted on CMPI's effort to focus on the value of new cancer treatments from the patient's perspective.. Here's her post and my reply.
On the Third Hand: Drugs Opinion
Thanks Allison,
You raise important questions that need to be answered.. unfortunately until now no one has wanted to check the math.
Here's some math: According to IMS the number of targeted has increased from 11 percent of all cancer drugs to 46 percent of all drugs over the past decade. The average price of drugs has doubled. Meanwhile, cancer drugs as a percent of healthcare spending has actually declined. The rate of hospitalization for cancer has fallen by 20 percent during the same time period. Cancer mortality rates have declined 20 percent. Productivity gains of people living cancer free are conservatively estimated at $68 billion a year, or 2.5 times more than what was spent on new treatments.
New drugs and diagnostics are responsible for 90 percent of these gains.
I would argue that the way to make a system sustainable is to increase productivity (which leads to more people paying premiums and taxe) and reduce the use of more labor intensive services like hospitals. Without new cancer drugs there would be 6 milion fewer people alive today. Without 'expensive' HIV drugs that are also being rationed by health plans, there would be 3-5 milion fewer people alive today. If you cut the work force and tax base by 20- 30 percent by denying access in ways AHIP wants, what happens to the financial support everyone seems to worry about.
The greatest gains will come when more cancer care is personalized and is matched the right time, the first time to patient tumor variability. Yet the ASCO and AHIP plan guidelines discourage and delay the adoption of such innovations.
The fact is, no one with ASCO or AHIP has discussed this math. I offered several times to be part of such discussions. No response. Lowell Schnipper who runs the ASCO value task force has written it’s not worth treating patients if it ‘only’ adds three months of life because “it is not a large enough benefit to trump the greater benefits to many that would have to be foregone to provide it.” Indeed, he believes the problem (of wanting to live longer) “ may be a particularly American one; other cultures do not seem to view the postponement of death by a few months” as important as Americans.
Has anyone covered the fact that the Wellpoint bonus program for cancer doctors measures value in the same way ASCO will measure it: efficacy, toxicity and cost. No mention of quality of life from the patient's perspective. Or how about that both Lee Newcomer and Schnipper said that the way to herd people into pathways that save money for health plans is to have the doctors develop the guidelines so that the plans are not accused of being self-serving (Schnipper and Newcomer's words, not mine). Shouldn't this be a subject of journalistic, if not congressional investigation? Shouldn't such cooperation -- with patients left on the sidelines -- be a source of concern?
Also, ask yourself: Should we take AHIP and critics of drug prices at their word because they don't get funding from pharma and ignore what I and others say because we get support from pharma? Does that mean that groups getting money from AHIP or health plans are to be believed? Is truth a function of where you get funding? Paul Offit did work for Merck on the rotavirus vaccine.. Does that mean that what he said about vaccines NOT causing autism should be discounted whereas Jenny McCarthy should be accepted.
When people attack where CMPI gets it support rather than engaging on the substance, it's a sign of desperation. I expect more of the same as the untenable and discriminatory assault on chronically ill patients continues.
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.
