Latest Drugwonks' Blog
On July 5th, Eli Lilly, Johnson & Johnson, Novartis, Novo Nordisk, Pfizer, and Sanofi-Aventis filed a Citizen Petition with the FDA asking the agency to clarify its policies on how truthful, non-misleading scientific information not included in approved product labeling can be communicated.
According to the petition, communicating accurate scientific information about new research would enhance health care quality and potentially lead to better patient outcomes, but that companies lack precise guidance on how to communicate such information.
“Scientific exchange,” broadly defined, is the sharing of research and clinical information about investigational medical products or new information on approved products without representing the product as safe and effective for that use. FDA said in a 1963 regulation that it does not intend to restrict “scientific exchange.” The concept of “scientific exchange” however, is not precisely described in FDA’s regulations and therefore leaves ambiguity about the limits of what is permitted.
We now have, thanks to those wonderfolks at DDMAC, some clarity when it comes to one kind of scientific exhange – open label trials.
DDMAC has cited Nycomed for a flashcard that based many of its claims on articles that “describe the preliminary and follow-up efficacy results of an uncontrolled, open-label study in patients with actinic keratoses."
"Results from a single open-label trial with no control group do not constitute substantial evidence or substantial clinical experience to support these, or any other, efficacy claims," DDMAC said, referring to graphs purporting to show how effective Solaraze is at "clearance of target lesions" of actinic keratoses.
This study also was not acceptable as a basis for a claim about the effectiveness of Solaraze in treating subclinical lesions, the letter adds. The company also cited an open-label study - it is unclear whether it was the same one - to claim that "the majority of patients were compliant with treatment," which also was unacceptable, according to DDMAC.
DDMAC has sent several sponsors (Arbor Pharmaceuticals, Hill Dermaceuticals, AMAG Pharmaceuticals) letters recently making it clear that open-label trials are not considered to be acceptable evidence of clinical efficacy.
You ask for clarity. You get clarity.
For a change.
If you compare Provenge to a Benlysta, the first new treatment for lupus in 50 years, you can't help but conclude that the beating Provenge took and the uncertainty that swirls around it's reimbursement still -- some might call it fear -- is so significant among community doctors that even the best sales force couldn't ovecome it. Benlysta was approved in March of 2011 and HHS issued a reimbursement code for the drug July 1. Provenge not only took a year, it was the subject of a Medicare technology review committee hearing. A big part of the difference is the beating Provenge took at the hands of Medicare and anti-innovation types.
Is Provenge a harbinger of how innovation will be handled? I don't have the answer to that. But there is a dramatic disconnect between what scientists are discovering and the ethos of most of the rent-seeking companies, regulators, health plans administrators, Commonwealth Fund/Soros funded researchers, etc. That ethos is organized what Aaron Wildavsky called "radical eqalitarianiasm:" the belief in the moral virtue of equalizing differences. Medical innovation is regarded as a source of inequality: the less we spend on new cancer drugs, the more we can spend on healthcare entitlements.
The contributions of medical technology are denigrated and the harms of innovations -- cancer, heart attacks, autism -- as part of a narrative depicting commercialization of science as a corrupt and corrupting enterprise the place profits above people. The healthcare stakeholders by and large are consumed with finding fault, imposing the precautionary principle, holding up each and every innovation to the benchmark of comparative effectiveness or tort action. They view innovation as a source or vector for inequality or injustice and treat marketing of any form as a potential criminal activity. And hence they regard all new technologies as expensive, potentially dangerous, while adding a teardrop of benefit to society at an enormous cost.
The prevailing cultural view of "the stakeholders" towards innovation is one of deep hostility. Opposing views of the relationship between humanity and medical innovation are hardly heard and barely represented. When they are, those who regard commercialization as inherently corrupt and regard themselves as the annointed visionaries who know what is best for the rest of us, invoke the canard of conflict of interest.
The radicals claim innovation won't wither because of requlation, it will only make companies more 'competitive.' In one sense they are right. Venture capital and IPO financing for medical technology and life science companies are at all time highs -- in China. That may be part of the effort to respond to the growing demand for healthcare services in emerging markets. But in China, new biotech and medical device companies are welcomed instead being treated as criminals or obstacles to human progress.
The gauntlet Provenge had to run through is a product of that hostility. And there's more to come.
Witness the prescient wisdom of Ralph Waldo Emerson who wrote, “Democracy becomes a government of bullies tempered by editors.”
Now consider the story of HHS v. Forest Laboratories.
When the Wall Street Journal pointed out the utter outrageousness of HHS threat of debarring Forest Labs CEO Harold Solomon (Kathleen Spitzer, 5/2/11), the department sent a BSD letter to the editor (if you don’t know what these letter to the editor restating, for all intents and purposes, “look out, there’s a new sheriff in town.” (PS/ If you are not familiar with the acronym “BSD,” please ask a friend to explain.)
But the Journal was right and the U.S. Department of Health and Human Services was wrong.
The gist of the Journal editorial can be summed up in these two excepted paragraphs:
HHS says its action is about holding corporate CEOs accountable, but it looks more like the Administration's latest bid to intimidate the health-care industry into doing its bidding on prices, regulations and political support for ObamaCare. This is the same agency that has threatened insurers with exclusion from new state-run health exchanges if they raise their premiums more than Mrs. Sebelius wants, or if they spread what she deems to be "misinformation" about the President's health bill.
The hammer on Forest Labs "reinforces everybody's worst fears—that this Administration won't do business with anybody that doesn't completely agree with its policy initiatives. Not only will it refuse to even have the argument, it will actively destroy these people," says Peter Pitts, a former Food and Drug Administration official who now runs the Center for Medicine in the Public Interest.
But, just like any other blustering bully, when you stand up for what’s right – the bully folds like a house of cards.
On Friday, HHS dropped its foolish efforts to force the resignation of Harold Solomon after protests from the company and major business groups.
In another letter, this time to Mr. Solomon, the office of the inspector general of the Department of Health and Human Services said, "Based on a review of information in our file, and consideration of the information your attorneys provided to us both in writing and in an in-person meeting, we have decided to close this case."
Oops. Sorry about that.
A statement from the HHS inspector general's office Friday said: "We remain committed to investigating and, when appropriate, sanctioning executives" who engage in health-care fraud. "This includes individuals who directly committed fraud as well as executives who were in a position of responsibility at the time of the fraud.”
As they should. And when the fraud is an attempt by the current residents of the Humphrey Building to cow healthcare companies into obsequious servitude – they should, equally and publically and aggressively, be called to task.
"Public health advocates and some mayors are sounding the alarm over Lazy Cakes, a brownie adorned with a lackadaisical cartoon character and laced with a powerful sleep aid that has sold millions nationwide.
“Children are attracted to brownies,” said Dr. Caroline Apovian, director of the Nutrition and Weight Management Center at Boston Medical Center. “I don’t think it’s appropriate to put herbal things that are actually drugs in brownies or food items that are attractive to children. I think that’s heinous.”
One Lazy Cake, which is wrapped in plastic with a photo of a smiling cartoon brownie, contains 8 mg of melatonin, a sleep-inducing supplement not regulated by the federal government. Apovian said 10 mg of melatonin would cause an adult to abruptly fall asleep."
Alarm? Heinous?To see the breathless coverage and comments from Nannystaters you would think that the FDA was racing to head off some terrorist plot. The contraband in question is lazycake brownie advertised as having "relaxation baked in". I mean they are brownies for goodness sakes, not ground turkey or Avastin...
Of course, all it took was one stupid grown up to spoil snack time for America's youth:
"Earlier this year, a 2-year-old Tennessee boy was hospitalized after a relative gave him a portion of a Lazy Cake, according to news reports."
The brownies have about 10 mg of melatonin in them. Melatonin pills have about 3 mg of the stuff. Apart from the toddler from Tenn this is no evidence that the the brownies harming kids or turning them into zombies. And it's not as if the Lazycake guys are the first to make something quasi-therapeutic taste good too: Flinstone vitamins anyone? Or how about fruit flavored zinc lozenges? Maybe we should ban making any medicine flavorful because that would make them "attractive".
I am trying to figure out what alarm is... Maybe some people believe that if you market brownies laced with melatonin and stress how relaxed they make you feel and well, the next thing you know they'll be selling Chips Ahoy cookies with Valerian root will become the next gateway snack.
Apparently the FDA will demand changes in the labeling and marketing of the product or else.. Maybe they should require Lazycake to be stored behind retail counters like cough medicines and the morning after pill. Oh wait, that's a serious proposal under consideration. So too, I bet, is a lawsuit sometime soon.
Maybe everyone should just.... chill. But not with a brownie. Unless there's some perspective and common sense baked into them.
"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."
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.
