Latest Drugwonks' Blog
"FDA Approves First-Ever Treatment For Scorpion Stings."
The FDA is reorganizing it’s Office of Generics Drugs (OGD) to “improve coordination, communication, efficiency and to enhance the Office’s ability to assure that all generic drugs are safe, effective, high quality and interchangeable to the brand name drug product/reference listed drug.”
“Interchangable?” Hm.
OGD adds another Division to both the Bioequivalence and Chemistry programs, and converts the Microbiology and Clinical Review Staffs into Divisions. It also formalizes the position of Deputy Director for Science and Chemistry. Here is the new structure.
OFFICE OF GENERIC DRUGS 
Division of Bioequivalence I 
Division of Bioequivalence II 
Division of Labeling and Program Support 
Division of Microbiology 
Division of Clinical Review 
Division of Chemistry I 
Division of Chemistry II 
Division of Chemistry III 
Division of Chemistry IV
On a biosimilar note, BioCentury reports that the FDA reiterated plans for a two-step regulatory process for biosimilars that includes evaluating similarity and then interchangeability, according to an article published in the New England Journal of Medicine on Wednesday.
The agency will first review the similarity of a biologic to an FDA-approved reference product using a "totality-of-the-evidence" approach, which includes a review of comparative analytic data and in vitro data. Based on the initial review, FDA will determine if additional animal or human studies are required for approval as a biosimilar.
To meet the higher hurdle of interchangeability with a reference product, a manufacturer must demonstrate that the biosimilar is expected to produce the same clinical result in patients, and that switching between the two products does not increase a patient's risk compared with continued use of the reference product.
Earlier this year, senior FDA officials began outlining plans for the two-step process. The agency expects to issue a series of guidance documents on the process
According to the Pink Sheet, FDA has amassed a large reserve fund throughout PDUFA IV, but will likely be forced to spend most of it in the next fiscal year as application volume declines and more personnel move to the agency's new headquarters.
FDA ended FY 2010 with more than $150.6 million in the carryover account, a 252% increase from the $42.8 million in the account as of June 30, 2006. The agency said aside from excess fee collections during PDUFA III, the fund also included fees saved for the agency relocation to its White Oak campus that were allocated during PDUFA IV and a reserve for refunds.
Spending the carryover funds will allow FDA to reduce the size of the user fee the upcoming fiscal year, although that will probably feel like a small comfort to sponsors facing a more than 19% increase in FY 2012, which brings the total fee for a full application requiring clinical data to $1.842 million.
Two of the largest carrover balance expenses will be personnel-related. The agency said in the notice it expects to spend about $37.9 million to move the Center for Biologics Evaluation and Research to its White Oak campus in Silver Spring, Md. by FY 2014. CBER now is located in nearby Rockville, Md.
The General Services Administration already approved the project and President Obama allocated $23.68 million in his FY 2012 budget request to complete the lab and ensure it is ready for use by FY 2014. FDA said without the investment, it would be forced to pay rent for a new lab it cannot use and for an old lab it cannot vacate.
FDA also plans to spend $29.8 million from the carryover balance in FY 2011 and FY 2012 to pay for 53 new full-time equivalent employees. The hires were authorized in FY 2009 to handle additional work created by the FDA Amendments Act's drug safety provisions.
Another $2.5 million of the carryover fund must be reserved for refunds, the agency said in the notice.
FDA also is obligated by PDUFA rules to use some carryover money to offset industry fee overpayments made from FY 2002 and FY 2007. That nearly $31 million payment lowered the revenue target and, subsequently, the fees sponsors will pay. The agency said in the notice fee payments from FY 2008 through FY 2011 will be more than $27.2 million less than the amounts appropriated, which would not require an offset payment.
The agency also will be forced to cover two years of shortfalls with the carryover balance that were caused by slumping submissions. The agency projected an $8.4 million revenue shortfall in FY 2011 and an $8.7 million shortfall in FY 2012, according to the notice.
After receiving 17 fewer full paid applications in 2010, the agency adjusted its assumptions for annual volume to be 5.5 submissions fewer in FY 2011 and FY 2012, which caused the shortfalls. FDA received 118.4 fee paying full application equivalents in FY 2010 and estimated it would receive 102.5 through the end of FY 2011. Both were near record lows since PDUFA was implemented in FY 1993.
The shortfalls also likely influenced an FDA decision to lower its revenue target for operational reserves in early FY 2013. The agency is allowed to add three months of operating expenses to its fee calculations for the final year of a PDUFA cycle so it can "assure sufficient operating reserves" at the start of the next fiscal year, which would be the first for PDUFA V.
Three months of revenue at that time would be $169.2 million. When the remaining $32.4 million in the carryover balance is subtracted out, the agency would need another $136.9 million.
But FDA decided it would "assume more risk" and only require two months of operating expenses for the reserve, lowering the required amount to $80.4 million. The agency said including the full three months in FY 2012 "poses a substantial burden on the regulated industry at a time when it is undergoing significant financial strain," according to the notice.
The decision will save sponsors of applications requiring clinical data about 8% in fee payments. The fee would have been about $1.99 million if FDA demanded a three-month reserve.
When the House approved the FY 2012 Agriculture/FDA appropriations bill in June, it gave the agency a miniscule $3 million budget increase. User fee revenue increases were used to offset a $285 million cut in federal funding.
For more discussion of PDUFA, have a look (and bookmark) www.modernmedicines.com. It’s an important and useful site from the folks at Eli Lilly & Co on all-things PDUFA.
Remember “SiCKO?” That was the Michael Moore “documentary” that showed how, if the US would adopt the NHS model, our own healthcare problems would vanish.
Well, as this article from the British newspaper, “The Independent,” shows – well, reality bites.
(Can you imagine President Obama or any member of Congress telling parents that their kids can't have their tonsils out until they have had seven -- that's right seven -- bouts of tonsillitis?)
Cataracts, hips, knees and tonsils: NHS begins rationing operations
Almost two-thirds of trusts affected as cuts bite
Hip replacements, cataract surgery and tonsil removal are among operations now being rationed in a bid to save the NHS money.
Two-thirds of health trusts in England are rationing treatments for "non-urgent" conditions as part of the drive to reduce costs in the NHS by £20bn over the next four years. One in three primary-care trusts (PCTs) has expanded the list of procedures it will restrict funding to in the past 12 months.
Examples of the rationing now being used include:
* Hip and knee replacements only being allowed where patients are in severe pain. Overweight patients will be made to lose weight before being considered for an operation.
* Cataract operations being withheld from patients until their sight problems "substantially" affect their ability to work.
* Patients with varicose veins only being operated on if they are suffering "chronic continuous pain", ulceration or bleeding.
* Tonsillectomy (removing tonsils) only to be carried out in children if they have had seven bouts of tonsillitis in the previous year.
* Grommets to improve hearing in children only being inserted in "exceptional circumstances" and after monitoring for six months.
* Funding has also been cut in some areas for IVF treatment on the NHS.
The alarming figures emerged from a survey of 111 PCTs by the health-service magazine GP, using the Freedom of Information Act.
Doctors are known to be concerned about how the new rationing is working – and how it will affect their relationships with patients.
Birmingham is looking at reducing operations in gastroenterology, gynaecology, dermatology and orthopaedics. Parts of east London were among the first to introduce rationing, where some patients are being referred for homeopathic treatments instead of conventional treatment.
Medway had deferred treatment for non-urgent procedures this year while Dorset is "looking at reducing the levels of limited effectiveness procedures".
Chris Naylor, a senior researcher at the health think tank the King's Fund, said the rationing decisions being made by PCTs were a consequence of the savings the NHS was being asked to find.
"Blunt approaches like seeking an overall reduction in local referral rates may backfire, by reducing necessary referrals – which is not good for patients and may fail to save money in the long run," he said. "There are always rationing decisions that have to go on in any health service. But at the moment healthcare organisations are under more pressure than they have been for a long time and this is a sign of what is happening across many areas of the NHS."
According to responses from the 111 trusts to freedom-of-information requests, 64 per cent of them have now introduced rationing policies for non-urgent treatments and those of limited clinical value. Of those PCTs that have not introduced restrictions, a third are working with GPs to reduce referrals or have put in place peer-review systems to assess referrals.
In the last year, 35 per cent of PCTs have added procedures to lists of treatments they no longer fund because they deem them to be non-urgent or of limited clinical value.
Some trusts expect to save over £1m by restricting referrals from GPs.
Chaand Nagpaul, a member of the British Medical Association's GPs committee, said he was concerned about PCTs applying different low-priority thresholds and rationing access to treatments on the basis of local policies.
He said the Government needed to decide on a consistent set of national standards of "low priority" treatments to help remove post-code lotteries in provision. "Patients and the public recognise that with limited resources we need to make the maximum health gains and so there needs to be prioritisation. What is inequitable is that different PCTs are applying different thresholds and criteria," he said.
A Department of Health spokesman said: "Decisions on the appropriate treatments should be made by clinicians in the local NHS in line with the best available clinical evidence and Nice [National Institute for Health and Clinical Excellence] guidance. There should be no blanket bans because what is suitable for one patient may not be suitable for another."
Bill Walters, 75, from Berkshire, recently had to wait 30 weeks for a hip operation instead of the standard 18. "I believe that the Government is doing this totally the wrong way," he said.
Case study: 'They changed the rules to save money'
Anne Ball, 71, is a retired business consultant who used to work in electronics
"I have bilateral cataracts and under the original NHS criteria I was entitled to have at least one of mine treated – but then the West Sussex health authorities decided to change the threshold level to save money.
"It's like looking through gauze. Everything is foggy, and I've got quite a large 'floater' in my left eye. The consultant was as distressed as me, having to tell me, and he thought with my eyesight he wouldn't be able to function.
"I've appealed because the cataracts are having a significant impact on my quality of life and it's left me depressed and fearful about my low vision, which will continue to deteriorate. The new guidelines mean that people who fall below the standard set by the DVLA still do not qualify to have surgery. My vision is not good enough to drive at night.
"I'm not a cranky old lady. I'm the chair of a local village charity and I do a lot of computer work that is affected.
"It will just store up costs for future years, putting a strain on resources as more patients will end up in falls clinics. The longer you put it off the more complex the operation becomes and the riskier it is for the patient."
According to FDA Commissioner Peggy Hamburg there is “a lot of energy” spent by industry and FDA on DTC issues … I think it’s a missed opportunity to do something much better if we’re going to be talking about drugs and health to the public at large. Certainly one of the discussions that I’ve been engaged in with industry is how can we use some of the time and money that they’re putting into this to really address broader public health concerns and broader education with the public about important health issues.”
I agree! Have a look at this article from Health Affairs for more on this issue.
The article’s conclusion –
“Working together with industry, we can make a difference. We can make DTCA a more potent, precise, and persuasive tool on behalf of the public health. And rather than rubbing the lamp and wishing, we need to burn the midnight oil and work harder to make it a reality—because an educated consumer is our best customer.”
There came a time w hen the risk to remain tight in the bud was more painful than the risk it took to blossom. ~Anaïs Nin
Just back from the ePharma West conference where I was pleased to give a keynote address on the future of social media.
Some snippets:
Social media is communications at the speed of life. As Marshall McLuhan wrote, “"At electric speed, all forms are pushed to the limits of their potential."
(Replace “electric” with “digital” and it’s amazing how prescient McLuhan was. That’s genius.) That’s a wonderful challenge, to be pushed to the limits of our potential. But wait, it gets more complicated.
Healthcare social media has precious few rules. But there’s only one Golden Rule -- transparency. 100% transparency. 100% of the time. You can’t airbrush social media.
Social media for regulated industry is a wonderful green field of opportunity. But to maximize the opportunity, we must accommodate the reality of a messier world. Social media, almost by definition, is messy – and the regulatory framework (or lack thereof) is equally so. And it’s not likely to get much better. Get used to it.
Embracing social media means embracing regulatory ambiguity. And that’s a paradigm shift for an industry that has (in a post-Vioxx world) been going in precisely the opposite direction.
Social media (and its game-changing opportunities) demands a move away from the cautious tactics of the Vioxx Populi towards a better understanding of the digital Vox Populi. And that means more than sponsored Google links and branded Facebook pages with the interactivity turned off.
It means mixing it up with real people in real time. And when it comes to FaceBook, it means – turn the interactivity on!
It’s not going to be easy, or risk-free, or inexpensive. And whatever social media “marketing models” companies build will have to be elastic – just like the media environment in which they are designed to operate.
Benjamin Franklin once said: “Every problem is an opportunity in disguise.” While Facebook strategies and approaches have to be reexamined, Mr. Zukerberg’s medical mandate provides pharmaceutical marketers with an excellent opportunity to finally acknowledge and embrace the full capabilities of two-way social communication writ large.
FaceBook’s changes represent an opportunity for regulated industry to learn, understand and embrace the three key tenets of Pharmaceutical Marketing 3.0:
1. The Rise of the “Face of Pharma”
For the past 20 years, the overwhelming majority of pharmaceutical marketing budgets were dedicated to promoting specific products.
Now, due to both a less robust drug development pipeline and an increase in the rates of patent expiry, the next era of pharma marketing will put the company – and it’s corporate reputation – front and center.
When you think about it (if you allow yourself to think about it), its a perfect match for social media where transparency is the most urgent, non-negotiable and magnificent mantra.
Not third party groups, not KOLs (although these traditional avatars have their place) – but the company speaking on behalf of itself and its products. What a concept!
2. The Role of Social Media in the Era of Post-Patent Medicine
I believe that the blockbuster era of the pharmaceutical industry will be replaced by the Era of Post-Patent Medicine. To compete in an era of generics and biosimilars, Pharma companies will need not only a robust portfolio of lower cost medications, but an army of brand loyalists.
Communications programs, supported by social media must be one tool. Why? Because it’s where the people are.
3. Social Media Can Help Increase Patient Education and Prescription Compliance
You know the numbers. It’s estimated that Pharma loses $30 billion a year in patient non-compliance. True two-way social media has the potential to serve as a new and puissant health education platform by helping to keep patients informed of the dangers of non-compliance by earning their trust through transparent dialogue. And that’s twice as true when it’s mobile-based.
As another conference presenter, Dr. James Fowler, of the University of California at San Diego opined, “Pharma must realize their own network power.”
Amen.
PS/ I am also pleased to announce that I have joined the board of the Digital Health Coalition - a nonprofit corporation - seeks to promote responsible innovation via digital marketing and communications in a connected world. Their first initiative is focused on the rapidly evolving space of social media and seeks to promote a world where patients, physicians, and brands can connect, empower, and drive positive health outcomes. Individuals interested in learning more about the Digital Health Coalition are encouraged to visit:
http://www.digitalhealthcoalition.orgwww.digitalhealthcoalition.org
To Burr, with Love
BioCentury reports that Senator Richard Burr (R-N.C.) threatened Thursday to delay reauthorization of medical device and prescription drug user fee legislation unless FDA implements steps to improve and speed product reviews. Speaking at a Senate committee on Health, Education, Labor and Pensions hearing, Burr said user fees, especially for medical devices, have not improved FDA performance and expressed skepticism that increasing user fees would improve the situation. He said reauthorization will become "a very slow and laborious process" unless the new legislation has measurement tools to track whether a fee system produces better outcomes
HELP committee Chairman Sen. Tom Harkin (D-Iowa) pushed back, saying that safety and efficacy are more important than speed to market. He also said FDA is understaffed and underfunded, so more money could improve its review performance.
They’re both right.
PhRMA wants dedicated biosimilars funding
The merits of creating a dedicated appropriation for biosimilars reviews has emerged as a point of contention in closed door FDA-hosted biosimilars user fee stakeholder discussions. In a July 24 letter from the Pharmaceutical Research and Manufacturers of America (PhRMA) to FDA, the trade association came down solidly on the side of creating a funding stream for biosimilar reviews that is separate from PDUFA-funded drug reviews.
PhRMA also called for a separate biosimilars user fee "trigger," or minimum amount Congress must allocate for biosimilars reviews to enable FDA to spend user fees. A trigger was built into PDUFA with the goal of making user fees supplement, not replace, federal funding. The law creating a biosimilars pathway called for FDA to fund biosimilars reviews from PDUFA funds until October 2012, when biosimilars user fees are expected to kick in. Applying PDUFA to biosimilars past October 2012 would drain resources from reviews of innovative medicines, according to the PhRMA letter.
Lack of money is the root of all evil.
-- George Bernard Shaw
This week the mainstream media discovered patent expirations and the headlines rang, “drug prices plummet!”
But they missed the real story.
From JAMA:
Implementation of Medicare Part D and Nondrug Medical Spending for Elderly Adults With Limited Prior Drug Coverage
1. J. Michael McWilliams, MD, PhD;
2. Alan M. Zaslavsky, PhD;
3. Haiden A. Huskamp, PhD
Author Affiliations
1. Author Affiliations: Department of Health Care Policy, Harvard Medical School (Drs McWilliams, Zaslavsky, and Huskamp); and Division of General Internal Medicine and Primary Care, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School (Dr McWilliams), Boston, Massachusetts.
Abstract
Context Implementation of Medicare Part D was followed by increased use of prescription medications, reduced out-of-pocket costs, and improved medication adherence. Its effects on nondrug medical spending remain unclear.
Objective To assess differential changes in nondrug medical spending following the implementation of Part D for traditional Medicare beneficiaries with limited prior drug coverage.
Design, Setting, and Participants Nationally representative longitudinal survey data and linked Medicare claims from 2004-2007 were used to compare nondrug medical spending before and after the implementation of Part D by self-reported generosity of prescription drug coverage before 2006. Participants included 6001 elderly Medicare beneficiaries from the Health and Retirement Study, including 2538 with generous and 3463 with limited drug coverage before 2006. Comparisons were adjusted for sociodemographic and health characteristics and checked for residual confounding by conducting similar comparisons for a control cohort from 2002-2005.
Main Outcome Measure Nondrug medical spending assessed from claims, in total and by type of service (inpatient and skilled nursing facility vs physician services).
Results Total nondrug medical spending was differentially reduced after January 1, 2006, for beneficiaries with limited prior drug coverage (−$306/quarter [95% confidence interval {CI}, −$586 to −$51]; P = .02), relative to beneficiaries with generous prior drug coverage. This differential reduction was explained mostly by differential changes in spending on inpatient and skilled nursing facility care (−$204/quarter [95% CI, −$447 to $2]; P = .05). Differential reductions in spending on physician services (−$67/quarter [95% CI, −$134 to −$5]; P = .03) were not associated with differential changes in outpatient visits (−0.06 visits/quarter [95% CI, −0.21 to 0.08]; P = .37), suggesting reduced spending on inpatient physician services for beneficiaries with limited prior drug coverage. In contrast, nondrug medical spending in the control cohort did not differentially change after January 1, 2004, for beneficiaries with limited prior drug coverage in 2002 ($14/quarter [95% CI, −$338 to $324]; P = .93), relative to beneficiaries with generous prior coverage.
Conclusion Implementation of Part D was associated with significant differential reductions in nondrug medical spending for Medicare beneficiaries with limited prior drug coverage.
http://jama.ama-assn.org/content/306/4/402.full.pdf+html
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.
