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BioCentury reports that the FDA has dentified eight priorities in the Strategic Plan for Regulatory Science: preclinical toxicology; personalized medicine; manufacturing; evaluation of emerging technologies; using information sciences to improve health outcomes; food safety; medical countermeasures; and communication with consumers and professionals.
The agency is seeking to improve the prediction of product safety through new animal models that consider both disease progression and co-morbidities. The plan also calls for FDA to collaborate with academia, industry and global regulatory agencies to develop and refine clinical trial designs. Such a collaboration would identify and evaluate improved endpoints and related biomarkers for areas where "optimal" endpoints are lacking, such as for osteoarthritis, gene therapy, ophthalmic indications, tumor vaccines and stem cell-derived therapies
Read More & Comment...CDRH has released two draft documents on approval process and guidance on its evolving approval process and planning clinical trials.
The first document explains the Center’s procedures for approving diagnostic and therapeutic devices -- how it weighs benefits and risks, judges the seriousness of a disease or condition, estimates how many people would use a device, and gauges availability of other devices for the same condition.
“Availability of other devices?” Really? Shouldn’t Shuren and Company stick to safety and efficacy? Where’d this third leg come from?
Sounds like insidious mission creep of the comparative effectiveness variety.
The second document explains the agency's expectations for medical device clinical trials, and suggests companies pre-submit protocols for the design of pivotal studies. Both drafts are open to public comment for 90 days, beginning August 15.
Read More & Comment...The IRS has "released what it's calling “temporary regulations” under which brand-name drugmakers must pay fees "to help fund" health-reform law provisions.
This was, as you will recall, part of “the deal.”
The regulations request payments of $2.5 billion in 2011 and are due by September 30th. Additionally, IRS calls for $2.8 billion in each of '”fee years” of 2012 and 2013; $3 billion for fee years 2014 through 2016; $4 billion for fee year 2017; $4.1 billion for fee year 2018; and $2.8 billion for fee year 2019 and thereafter.
So what’s “temporary?” And what about those who are pounding the podium about rebates for dual eligibles?
Just asking.
According to reporting in Congressional Quarterly, although pharmaceutical companies have to "pay fees," they will garner "far more sales as millions of the uninsured gain coverage."
The requirement applies to companies with annual drug sales of "$5 million or more" to Medicare "Parts B and D"; Medicaid; and Veterans Affairs, and Defense Department and TRICARE programs.
Read More & Comment...All of a sudden the Mainstream Media (highlighted by a much ballyhooed New York Times Week in Review op-ed by Zeke Emanuel) has discovered the problem of drug shortages.
Except it’s not a new problem.
According to a recent analysis, the frequency and impact of drug shortages have risen to critical levels, more than tripling since 2005, and affecting all segments of the healthcare community. In 2010, over 240 drugs were either in short supply or completely unavailable and more than 400 generic equivalents were backordered for greater than five days. In most instances, these did not progress to critical shortages, but point to instabilities in the supply chain that cause national concern. Many of the drugs identified in 2010 remain unavailable or in short supply in 2011.
Seventy-seven percent of drugs in short supply in 2010 were sterile injectable products, critical in the acute care setting. Recent media coverage highlights the plight of patients and physicians faced with shortages for cancer drugs, anesthetic agents, and critical care medications that have contributed to delays in treatment and surgery, or changes in care plans. Drug backorders cause patients to receive substitute therapies that add expense to patient care.
A major reason for shortages is quality/manufacturing issues. However there are other reasons such as production delays at the manufacturer and delays companies have experienced receiving raw materials and components from suppliers. Discontinuations are another factor contributing to shortages. (The FDA can't require a firm to keep making a drug it wants to discontinue.)
It is time not to fix the blame – but to fix the problem.
Let’s start with the FDA.
In 2010, there were 178 drug shortages reported to the FDA. Is that a solid number? Hard to say, because current regulations do not require companies to notify FDA of shortages. The only requirement is that companies inform FDA six months in advance for discontinuations of sole source, medically necessary drugs.
(In 2010, for example there were 38 shortages prevented due to companies notifying FDA voluntarily of potential issues that could lead to shortages and FDA was able to work with the company to avoid a shortage.)
Inside the FDA’s Center Drug Evaluation and Research (CDER) resides the agency’s Drug Shortage Program (DSP). The DSP was established to address potential or actual shortages of drugs that have a significant impact on public health. Through communication, facilitation and negotiation, DSP works with pharmaceutical manufacturers, review divisions, compliance and other components of FDA to manage product shortages.
For example, when the drug shortage is for a generic product (as it often is), the FDA works with other firms making the drug to help them ramp up production if they are willing to do so. Often they need new production lines approved or need new raw material sources approved to help increase supplies. FDA can and does expedite review of these to help resolve shortages of medically necessary drugs.
But the FDA can't require the other firms to increase (or commence) production.
The agency tries to do the best it can with limited authority, spare resources and shared staff. In addition to direct communication with industry, the DSP also gets reports from healthcare professionals, patients/individuals, or professional organizations using the e-mail address drugshortages@fda.hhs.gov.
But, as you can imagine, there is not a lot of e-mail traffic. And there is no social media effort to promote either its purpose or existence.
It’s a good start – but it’s not enough. And you know what they say about good intentions.
The FDA’s Drug Shortage Program is a good start. But it’s not getting the job done. The problem is getting worse. The FDA needs both more authority and greater resources. In short, more needs to happen.
The Institute for Safe Medication Practices reports that, according to survey of 1800 healthcare practitioners, more than half of respondents frequently or always encounter difficulties associated with drug shortages.
The top three problems fall squarely within the zone of appropriate FDA attention and action:
* Little or no information available about the duration of a drug shortage (85%)
* Lack of advanced warning from manufacturers or FDA to alert practitioners to an impending drug shortage and suggested alternatives (84%)
* Little or no information about the cause of the drug shortage (83%)
Survey respondents felt “unsupported by the FDA and are perplexed regarding why the US is experiencing drug shortages of epic proportion that are often associated with third-world countries.”
(More detail on the ISMP survey can be found here.)
And before it becomes a question of American lives.
Read More & Comment...
The EU Innovative Medicines Initiative (IMI), the world’s largest public-private partnership in health R&D, is calling for proposals across seven new health care areas.
The areas of focus are linking patients’ data to develop more targeted therapies; using knowledge management of experimental data for translation into drugs for patients; complications of obesity; predicting Alzheimer’s disease and other dementias; drug delivery by nanocarriers; sustainability of chemical drug production; investigating stem cells for drug discovery; and understanding the behavior of drugs in the human body.
The EU has agreed to contribute up to €105 million ($150 million) to this latest step in IMI's evolution, a figure that will be matched by "in kind" contributions – staff, access to databases and research activity and equipment – from the European Federation of Pharmaceutical Industries and Associations.
The new project phase comes weeks after IMI signed a Memorandum of Understanding with the U.S.-based Critical Path Institute, aimed at increasing collaboration between the two bodies. They have agreed to foster increased information sharing regarding each other’s programs and create a mechanism to exchange knowledge and develop scientific consensus regarding research and testing methods.
But, as our European cousins step up to advancing 21st century medicine, wither our own domestic efforts? What’s become of the Critical Path? Where’s the Reagan/Udall Center?
Funding for the FDA’s Critical Path program and the Reagan/Udall Center is generally considered a “Christmas Tree” issue relative to PDUFA V. That’s a mistake. Beyond the agency’s request to fund it’s Advancing Regulatory Science Initiative (ARSI), we are all talk and no action.
For many involved in the reauthorization process, one statement that keeps coming up is -- ”The FDA is broken.” But what does that mean? Rather than making blanket statements that cause friction and promote areas of disagreement, one thing everyone can agree to is that the FDA’s must be both ally and accelerator in the advancement of innovation.
And that must be within the confines of PDUFA V – and it cannot be accomplished without moving forward the FDA’s Critical Path program and funding the Reagan/Udall Center.
Read More & Comment...Sander Flaum, the grand master of pharmaceutical marketing asks, “If you put the world’s top CEOs together in a room and asked them what challenges kept them up at night, what do you think you’d hear?”
The answer is shocking if not surprising/
According to the Conference Board’s CEO Challenge 2011 Survey – Fueling Business Growth with Innovation and Talent Development, most CEOs in the U.S. and Europe listed Business Growth as their top challenge.
According to Flaum there’s an even bigger concern. “Look down the list of the top challenges. Where did these leaders consistently rank Innovation? #3! And guess what U.S. CEOs collectively viewed as an even more pressing challenge than the need for innovation– Government Regulation!”
Flaum continues, “A CEO who is more worried about being handcuffed by regulations than coming up with the next big idea needs a priority readjustment. Sure, regulations can be a pain. But they can also be simply an excuse for failure. In Pharma, we’re always contending with the FDA in the struggle to bring innovations to market. And it’s not easy. But doesn’t the need for Innovation come first? If we don’t have something new and important to bring to market, then why complain about the regs?
Top 5 Global Challenges by Region
Rank | U.S. | Europe | Asia |
1 | Business Growth | Business Growth | Talent |
2 | Government Regulation | Cost Optimization | Business Growth |
3 | Innovation | Innovation | Innovation |
4 | Talent Cost Optimization (tied) | Customer Relationships | Corporate/Brand Reputation |
5 |
| Government Regulation | Sustainability |
Wither innovation? This crucial question becomes even more problematic when you consider the issue of “disinvestment” -- the processes of (partially or completely) withdrawing health resources from existing healthcare practices, procedures, technologies, or pharmaceuticals that are deemed to deliver little or no health gain for their cost, and thus do not represent efficient health resource allocation. “Disinvestment” is a more honest (and frightening) term for “comparative effectiveness.”
And leading the disinvestment charge (not surprisingly) is NICE.
Over the past 10 years NICE has identified over 800 clinical interventions for potential disinvestment. But, in the July 27th edition of the British Medical Journal, Sarah Garner and Peter Littlejohns (both of NICE) report that although disinvestment will increase the opportunity for cash saving is unlikely to provide ways of controlling costs without cutting quality of care.
The authors write:
There is general agreement that stretched health services budgets should not be used to fund low value services. However international experience has shown that identifying and removing those services can be problematic and controversial.
Are you listening AHRQ?
Many suggestions for total disinvestment are based on a “social judgment” about whether it is appropriate for the NHS to fund the intervention rather than evidence of poor clinical or cost effectiveness. Others relate to “experimental” use of technologies outside their indications and evidence base.
Are you listening Dr. Berwick?
Opponents of a total disinvestment approach highlight the methodological flaws of using average estimates of effect drawn from populations; they argue that an intervention may be beneficial for an individual patient and should be an option, even if a last resort. An alternative strategy is optimal targeting: identifying subgroups in which an intervention is most clinically and cost effective.
Are you listening Dr. Pazdur?
Disinvestment is part of a broader agenda to improve efficiency and quality focusing on public health and prevention and ensuring that patients receive the right care at the right time in the right way.
Are you listening PCORI?
Although this approach releases resources in the long term, it may entail investment in the short term. It is very important to make the distinction between improving the efficiency of care and saving money.
Aha!
Without data, it is also difficult to identify the subgroups necessary to fully understand variation in care and therefore determine realistic potential savings.
Did somebody say “personalized medicine?” Did somebody say, “more and more targeted molecular diagnostics?”
The author’s conclude, “However, current evidence suggests that disinvestment is unlikely to achieve the huge savings required to meet tightened NHS budgets.”
We would be wise to learn from honesty of our transatlantic cousins.
Read More & Comment...Avastin Spring helps spur a resistance against bureacracy
By Dr. ROBERT GOLDBERG
Times Guest Columnist
Sometimes, profound change happens so swiftly it’s unrecognized and unappreciated. Such is the case with the response to the Food and Drug Administration advisory committee’s decision to withdraw the agency’s approval for using Avastin to treat metastatic breast cancer.
After the FDA Oncological Drug Advisory Committee declared Avastin to be unsafe and ineffective for women suffering from that incurable form of the disease, the headlines and pundits spun the decision — and the discussion — as one where science triumphed over emotional and desperate women.
Gary Schwitzer, a self-styled expert on objective medical reporting quoted the representative from the National Breast Cancer Coalition who at the ODAC hearing: “This decision can’t be driven by anecdotes. It must be driven by science.”
This is an unfair and lazy characterization of the debate over Avastin. The ODAC panel was stacked with members who already voted against Avastin’s use in MBC. The conflict was over the interpretation of clinical information and whether the FDA can pull an approval because, as it said in December of last year, Avastin doesn’t provide “a sufficient benefit in slowing disease progression to outweigh the significant risk to patients.”
But several other groups that looked at the same evidence came to a different conclusion, including the National Comprehensive Cancer Network and Europe’s equivalent of the FDA, the European Medicines Agency (EMA). Indeed, the EMA expanded approval Avastin based on the same “science” ODAC used in rescinding the drug’s FDA endorsement.
In any event, the speed with which both the Obama administration and private health plans announced they would still cover the cost of Avastin for the use the FDA rejected was stunning. When the FDA decided to yank Avastin’s approval in December 2010, several health plans and regional Medicare reimbursement contractors told women that Avastin would no longer be covered. Such decisions were reversed only after the FDA said it would review its revocation.
Last week, the same organizations — along with the Obama administration — rushed to distance itself from the FDA and assure women it would cover the drug.
The difference in response is a result of the rapid organization of patients through social media. While it culminated in the presence of hundreds of women at the ODAC hearing, that participation was only a part of an extensive, sustained and scientifically informed movement.
The FDA officials and the interest groups urging Avastin’s revocation were outgunned by individual patients who joined together, much as HIV patients did in the 1990s and MS patients did in pushing for the return of Tysabri to the market a few years ago.
This time however, the use of social media to share clinical information, organize support and express opinions was rapid, sustained and, above all surprising. The cancer advocacy “establishment” was outgunned and reduced to irrelevancy. This also happened after the Obama administration recommended not to cover mammograms for women under 50. The National Breast Cancer Coalition sided with the administration — and cancer patients, oncologists and radiologists everywhere told them go stick it.
That decision, like the FDA’s Avastin rendition, is being ignored in practice.
The uprising against the Avastin decision could signal a clear shift in power from the Beltway groups that claim to be patient or consumer “advocacy” groups - but are beholden to a particular party or just staying in favor with the powers that be — to individuals organizing on their own and in their own best interest.
More to the point, such movements are well informed and shaped by what the science says. They are often funding research to accelerate better treatment and detection of illnesses. The attempt to demean or diminish such movements as the expression of anecdotal experience and emotions reflects the arrogance of bloggers and pundits who have but a thimble full of the clinical understanding of the movement’s participants. And it suggests a contempt for any use of social media that does not seek to spread fear or skepticism of innovation.
Most immediately, the Avastin Spring has undermined the legitimacy of the effort to use comparative effectiveness research to delay access or payment for new technologies. Health plans and the government will have to expect ongoing challenges to their ‘expertise’ and claims that it is using the best evidence in determining what to cover. Consumers will be skeptical of one-size fits all judgments made by so-called “experts.”
Similarly, companies who develop new products will have to contend with consumers demanding credible and substantive clinical information.
The Avastin Spring suggests that resistance against bureaucrats telling the rest of us what treatments we can and cannot use will only grow. This is not an anti-science enterprise. Rather, these are movements that regard individual choice as an imperative as the science of personalized medicine advances. It means less authority for those claiming only they have science on their side en route to restricting access to innovations. Both changes bode well for our well being.
Dr. Robert Goldberg is co-founder and vice president of the Center for Medicine in the Public Interest. He is also author of the book, “Tabloid Medicine: How the Internet is Being Used To Hijack Medical Science For Fear and Profit.”
Metrics for monitoring prescribing patterns to identify changes in access to opioid products may not be in place when FDA approves REMS for individual products.
The missing element is the methodology.
“It will take a number of months to develop detailed methodology with a research organization,” the Industry Working Group told the FDA in a communication seeking guidance on the agency’s expectations for the REMS. IWG is developing the shared implementation program for the risk management plan and has met with the FDA several times to clarify the agency’s expectations.
The access analysis is one of seven components of the assessment plan The FDA imposed when in April it unveiled its requirements for the opioid REMS. “The IWG has already proposed a high-level overview of the [prescriber pattern] methodology in the proposed REMS, with more detailed methodology to be developed after the REMS is approved,” IWG said.
The FDA seems willing to accept a staggered launch of the program. While the methodology may be only in draft form in the sponsors’ REMS submissions, they should provide a schedule “for expeditious completion of the methodology,” according to the agency.
Class-wide REMS and shared REMS assessment program do not eliminate the need to look at whether individual products are being used more safely.
The agency clarified that its request for drug-specific information does not refer to the active drug substance, dosage form or delivery method. Rather, the agency wants “as much detail as possible for each individual product, including each unique dosage form/delivery system.”
Industry is concerned about “providing comparative data on competing products and would prefer to perform general surveillance, looking at the changes in adverse events for the class or at the level of active drug substance, rather than for specific products.”
Read More & Comment...Watchdogs bark as FDA relaxes rules on conflicts of interest
An FDA move to relax conflict-of-interest rules governing advisory panels is meeting with heated opposition from watchdog groups and medical societies.
FDA commissioner Margaret Hamburg recently told Public Citizen that the agency may loosen a three-year-old policy aimed at keeping industry-funded physicians off FDA advisory panels because the resulting vacancies are gumming up the approvals process.
An FDA spokesperson told MM&M: “The new conflict of interest rules have, in some cases, made it more difficult for FDA to find expert advisors. In most cases, FDA has been successful in finding experts to meet our needs. However, in a few cases it has been necessary to delay holding advisory committee meetings in order to allow more time to contact and screen more experts for consideration or to begin the screening process with many more experts. This increases the work requirement for advisory committee preparation.”
As of March, 23% of the agency's advisory committee seats – 138 of them – were vacant.
FDA CDER director Dr. Janet Woodcock said at a conference in May: “There is no doubt it is difficult finding highly experienced people who do not have conflicts.”
Bull, said the Project on Government Oversight (POGO), arguing that the number of conflict-of-interest waivers granted FDA advisory members has never exceeded 5% and that the percentage of seats vacant is falling, having sunk from 30% in 2009.
“These rules do create an additional hurdle, but that is exactly the point,” said POGO head Danielle Brian in a letter to Dr. Hamburg. “We want expert advice that is as free as possible from the influence of industry.”
Like POGO, the National Physicians Alliance pointed to lists of conflict-free physicians.
“We understand and decry the increasing entanglement of many researchers and clinicians with industry and understand that finding reviewers without conflicts can be a challenge,” said National Physicians Alliance president Valerie Arkoosh, MD, who noted that almost half of the cardiologists who develop clinical practice guidelines for the American College of Cardiology and the American Heart Association do not have conflicts of interest.
In the FDA's corner on the topic is House Energy and Commerce Committee chair Rep. Fred Upton (R-MI), who said in July: “The rigid and unrealistic conflict of interest provision has prevented FDA and its advisory committees from utilizing some of science's best minds and left advisory committee slots unfilled,” and suggested that the rules have slowed approvals.
Another voice in favor of relaxing the rules is that of Peter Pitts, an industry PR man and generally pro-industry think tanker who, as FDA associate commissioner, was in charge of advisory committee oversight, in which role he had final say on what would-be panelists with conflicts made the cut and were granted conflict of interest waivers.
“Many did not,” wrote Pitts, “but those who did received their waivers because FDA professional career staff made a strong case that these people weren't just important to the advisory committee but critical. And we should all pay attention to the nomenclature. It's not about ‘conflict of interest' – it's about (as HHS Secretary Sebelius correctly says) ‘interest.' And having an ‘interest' is not necessarily a bad thing as long as you're transparent about it.”
“If we allow FDA adcomms to become the realm of the second best and the almost brightest,” continued Pitts, “What have we done to the advancement of America's health?”
Drug Companies Spend an Average $13,000 per Patient on Comparative Effectiveness Research in Phase IV
RESEARCH TRIANGLE PARK, NC -- (Marketwire) -- 08/09/11 -- The cost of running a comparative effectiveness trial is $13,087 per patient during Phase IV, according to a study by Cutting Edge Information.
Comparative Effectiveness Research (CER) compares drugs, devices or other medical tests and procedures to determine the most effective outcomes for patient populations. Drug companies often use CER studies to compare their products head-to-head against competitors. The study found that CER studies make up the second largest portion of the average Phase IV development program, at 29%. Data generated from CER studies can prove invaluable. Favorable results from a registered Phase IV comparator trial is a powerful marketing and sales tool and can eventually alter disease treatment patterns.
Cutting Edge Information's study, "Phase IV Clinical Trials: Best Practices in Post-Marketing Study Management," found that in the U.S., CER studies typically cost drug companies $14,924 per patient. But companies that conduct these studies in Europe can see a substantial savings. According to the research, European CER studies run an average $9,873 per patient.
"Comparative effectiveness research studies are some of the more costly Phase IV trials that companies can invest in," said David Richardson, research team leader at Cutting Edge Information. "They can also prove risky for companies when their drugs don't compare favorably. However, the risks may be worth the gamble as product teams face reimbursement challenges by payers who are unwilling to cover more costly treatments for unclear patient benefit."
CER presents an opportunity for drug companies to prove that their products are not only more effective than their competitors, but could also prove better patient outcomes -- such as longer life spans -- and more cost-effective in the long run.
"Phase IV Clinical Trials: Best Practices in Post-Marketing Study Management," available at http://www.cuttingedgeinfo.com/research/medical-affairs/phase-iv-clinical-trials/, contains per-patient cost benchmarks on comparative effectiveness studies, patients-per-site, patients-per-investigator and other key metrics for five types of Phase IV studies. It includes metrics covering the U.S. and Europe as well as major therapeutic areas.
Read More & Comment...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.
Read More & Comment...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.
Read More & Comment...
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.
Read More & Comment..."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.
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"FDA Approves First-Ever Treatment For Scorpion Stings."
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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
Read More & Comment...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.
Read More & Comment...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."
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