Latest Drugwonks' Blog
Sent: Thursday, November 03, 2011 11:17 AM
To: CDER-ALL-HANDS
Subject: FY2011 Innovative Drug Approvals
CDER Staff:
You may have seen news reports or statements by industry that we are not “innovative,” or that we make it too hard for companies to get a new product on the market. But these broad-brush statements are, in most cases, inaccurate and unfair. They often lack important context that would explain our intentions and the work we do.
To help correct these misimpressions, CDER recently collaborated with the Commissioner’s Office, CBER, and many others throughout FDA on a report that highlights the innovative products approved by the agency in Fiscal Year 2011.
The report, released today, shows that in FY 2011, for CDER and CBER combined, FDA approved 35 new molecular entities (NMEs). These include innovative therapies for hepatitis C, late-stage prostate cancer, lupus, drug resistant skin infections, pneumonia, and other serious and life-threatening diseases.
The speed and efficiency with which these products were approved speaks directly to our staff and our high-quality reviews. It also demonstrates our willingness to exercise regulatory flexibility and creative approaches to help industry meet our standards—without lowering them.
FDA expedited the approval of many of these products by streamlining clinical trial requirements to permit smaller, shorter, or fewer studies wherever possible.
Here are a few highlights of the report:
FDA approved nearly half -- 16 -- of the innovative drugs under the agency’s “priority review” program for drugs that may offer major advances in treatment; priority reviews carry a six-month target date for review.
FDA approved all but one of the 35 products on or before the target dates for approval agreed to with industry under the Prescription Drug User Fee Act.
FDA approved the majority of these innovative drugs on the “first cycle,” that is, without requests for additional information that would trigger a second review cycle.
Continuing to enhance our efficiencies remains important, and in the near future I will be sharing with you some ideas on this topic. The positive messages highlighted in this report are a direct result of the combined hard work of all of us at CDER. Thanks to all of you! I am proud and appreciative to be part of the CDER team!
To view today's press release and the report, please visit http://www.fda.gov/NewsEvents/Newsroom/PressAnnouncements/ucm278383.htm
FY2011 Innovative Drug Approvals Page: http://www.fda.gov/AboutFDA/ReportsManualsForms/Reports/ucm276385.htm
Please join the Center for Medicine in the Public Interest (www.cmpi.org) and some of the nation’s top experts in PDUFA and FDA reform for an interactive panel discussion of “Defining the Future of the FDA: PDUFA V and Beyond.”
When: 12:00 – 1:30PM, November 29, 2011
Where: RM.2168 Rayburn House Office Building
Who:
Peter J. Pitts (Moderator), Former FDA Associate Commissioner, President of the Center for Medicine in the Public Interest
Vincent J. Ventimiglia, Jr, Former Assistant Secretary for Legislation at the US Department of Health and Human Services, Senior Vice President in the Health and Life Sciences Practice at B&D Consulting, a division of Baker & Daniels LLP.
Paul T. Kim, Former Deputy Staff Director for health policy for Senator Edward M. Kennedy, Partner at Foley Hoag LLP in the Government Strategies practice.
Michele J. Orza, Former Assistant Director of the Health Care Team at the Government Accountability Office, Principal Policy Analyst at the National Health Policy Forum.
Tim Franson, Former Vice President, Global Regulatory Affairs, Eli Lilly & Co., President, USP Convention, Senior Vice President, Health and Life Sciences Sector, B&D Consulting.
RSVP: mcoluccio@cmpi.org
From today’s edition of The Washington Examiner:
Who watches the watchdogs of government prescription detailing?
Misguided political philosophy and tens of millions of taxpayer dollars are behind one of the least transparent aspects of Obamacare, government-funded pharmaceutical "detailing."
Known by those who support it as "academic detailing," it is an effort by Uncle Sam to change the prescribing habits of America's physicians. So what's the problem?
Well, that change is driven by the largest health care insurance company in the country to lower costs rather than improve patient care. And that insurance behemoth is the government of the United States.
Specifically, the verbatim goal is to change prescribing habits that are "not in accord with the recommendations" of studies commissioned by the Agency for Healthcare Research and Quality.
The long and the short of it is that our government is spending tens of millions of tax dollars to tell our doctors how to practice medicine based on studies that are commissioned without any public input or transparency.
And the term "academic detailing" isn't accurate -- because the work isn't being done by academics. The AHRQ hired a firm, Total Therapeutic Management, and is paying it $11,680,060 to recruit and train physicians, pharmacists, nurses and physician assistants.
That's not academic detailing. That's government detailing. And the devil is in the details.
Will physicians be required to be visited by this new battalion of government agents? Will physicians be given incentives to spend time with AHRQ's angels and punished if they do not (via Medicare and Medicaid restrictions)?
And how will Uncle Sam decide which doctors are to be visited? Will "high prescribers" of on-patent medicines be on a priority list? Barry Patel, the CEO of Total Therapeutic Management, said its top priority is "high volume" practices.
Rather than focusing on offices with disproportionately high negative patient outcomes, Uncle Sam is directing its efforts against those doctors who are high prescribers -- which is a pretty good indicator about what government detailing is all about -- decreasing cost rather than improving care.
And what safeguards are in place to certify that physicians are being presented information that is unbiased? Previous government detailing efforts have often focused on demonstrating their own value by highlighting the cost-effectiveness of initiatives through savings generated from the increased utilization of generics and other low-cost therapies.
The repercussions of choosing short-term savings over long-term results, of cost-based choices over patient-centric care, of "fail first" policies over the right treatment for the right patient at the right time -- are pernicious to both the public purse and the public health. Skimping on a more expensive medicine today but paying for an avoidable hospital stay later is a fool's errand.
And how can an "academic detailing" program funded by our nation's largest payer (Uncle Sam) be considered neutral? Just like detailing programs run by pharmaceutical companies, there is an inherent "interest."
And that's OK -- as long as that "interest" is transparent. Who will be the arbiters of transparency? Who will decide what these detailers can say or not say? Will these government "reps" have to play by the same rules as their pharmaceutical counterparts?
And, importantly, what is the oversight mechanism? If academic detailers stray into off-label conversations, to whom does the FDA complain? Whom does the Department of Justice investigate? Who pays the fine? Quis custodiet ipsos custodes?
As currently designed, government detailing is a tool to increase government control over the practice of medicine and is a slippery slope towards the introduction of health care rationing and price controls.
Congressional oversight must be required for the $42.3 million that AHRQ has already awarded for public and physician outreach.
As Rudyard Kipling said to the Royal College of Surgeons in London in 1923, "Words are, of course, the most powerful drug used by mankind. ... They enter into and colour the minutest cells of the brain."
We allow them to be usurped and corrupted at our own peril.
Peter J. Pitts, a former Food and Drug Administration associate commissioner, is president of the Center for Medicine in the Public Interest.
I had the honor and pleasure of chairing the 4th Annual Risk Management and Drug Safety Summit. Here are my opening remarks from Day One (today):
Risk management cannot exist without a more holistic understanding and acceptance of the Responsibility of Risk.
Risk management means more than REMS strategies and tactics, more than validated methodologies and therapeutic registries. It’s not about the management of risk -- it’s about assuming the mantle of responsibility.
Risk management can’t just be about doing what’s necessary to get a product approved and abiding by prehistoric adverse event reporting mechanisms. It’s got to be more than MedWatch and MedGuides. Accepting the responsibility of risk means that we must stop being translucent and start being transparent. It’s more than just doing what we’re told, of being in compliance. Because we know better.
The responsibility of risk a shared responsibility. It must be more than what the FDA expects from industry and more than what industry expects from the FDA. It’s what all parties to the public health conversation must expect from themselves. And that goes far beyond anything to do with marketing or sales or stock price or legislative authority. It means doing what’s right in addition to what is required.
"The fault, dear Brutus, is not in our stars, but in ourselves.”
Let me repeat -- the responsibility of risk means doing more than what is in compliance. The responsibility of risk means doing what’s in the best interest of the patient fully and completely and beyond what is required – even when it is contrary (or viewed as such) to short term sales and marketing objectives. When we allow either profit or politics to trump what’s in the best interest of the public health – we might as well be selling air conditioners.
Principles, as my father taught me, don’t count until they hurt.
Abraham Lincoln said that patents “add the fuel of interest to the passion of genius.” Well, to paraphrase, accepting the responsibility of risk adds the fuel of interest to the passion for serving the public health.
The responsibility of risk means appreciating and actualizing the philosophy of the safe use of drugs. For example, the responsibility of risk means not just detailing – but detailing the label.
Traditional risk management means finding ways to avoid risk, to mitigate it. That’s important, but its tactical – and very 20th Century. In the 21st Century we have to invent new strategies. And that starts with embracing risk just as we embrace benefit. There should be a journal dedicated to the science of risk – a medical Kabala of Contingency. Otherwise all we’re left with is the anemic and feeble compost of early safety signal communications.
And the responsibility of risk is global. Acknowledging the responsibility of risk means embracing the urgency for harmonized global pharmacovigilence.
Other than that, it’s pretty easy and straightforward.
Thank you.
Letter Urging Rejection of Florbetapir F18 Injection (Amyvid), Experimental Procedure for Diagnosing Alzheimer’s Disease
Letter Opposing Approval of Rivaroxaban (Xarelto) for Anticoagulation Therapy in Patients With Atrial Fibrillation
The ABC News stories ignore context. But so do the press releases and studies from the CDCP triggering this anxiety. The CDC fails to note that the increase is concentrated among young adults in rural areas who are also abusing other prescription painkillers and medications in combination with cocaine. That's not a good thing but it's not an epidemic affecting everyone.
The Wolfe inspired panic is par for the course. For instance, Sid Wolfe opposed the approval of every oral diabetes drugs since the 1970s.
And speaking of scares: Remember when Steve Nissen spread fear about the cardiovascular risks of using meds for ADHD. The cardiologist who knows next to nothing about treating ADHD said he wants doctor's pen to quiver before the write a scrip for a drug Nissen believes is overprescribed. He continued the assault earlier this year when an observational study that Nissen (who specializes in running small observational studies for money) trashed as too small showed no CV risk. http://www.cbsnews.com/8301-504763_162-20063572-10391704.html
Now a large FDA sponsored study finds no risk.
Everything we worry about, especially when it's a risk hyped by those who are anti-innovation like Wolfe and Nissen , has to be placed in the context of previous studies, other risks, variations unique to individuals or groups. If a risk is not discussed with such parameters in place, it is not a risk..it's a false alarm.
"The order offers drug manufacturers and wholesalers both a helping hand and a gloved fist in efforts to prevent or resolve shortages that have worsened greatly in recent years, endangering thousands of lives."
(A gloved fist? Ouch. I hope that this isn't the President's low cost alternative to PSA screening...)
It instructs the F.D.A. to do three things: broaden reporting of potential shortages of certain prescription drugs; speed reviews of applications to begin or alter production of these drugs; and provide more information to the Justice Department about possible instances of collusion or price gouging.
Price gouging? Harris may have overlooked some of the findings of the administration's own report on the economics of drug shortages? Economic Analysis of the Causes of Drug Shortages (HHS) http://aspe.hhs.gov/sp/reports/2011/DrugShortages/ib.shtml
Harris summarizes the study: "the administration will release two government reports that mostly blame a dysfunctional marketplace for drug shortages, directly contradicting assertions by some commentators that government rules are to blame."
In fact the HHS report does more than blame a 'dysfunctional market', it explains what is behind the problem:
"...drugs that subsequently experienced a shortage are those in which the volume of sales was declining in the 2006-2008 period prior to the shortages."
It goes on to note in AppendixB : "Analysis of average sales prices shows that shows that oncology sterile injectable drugs that experienced shortages since 2008 decreased in price from $56.17 per unit in Q1 2006 to $37.88 per unit in Q1 2011. Oncology sterile injectable drugs that have not experienced shortages have had relatively stable prices over this period."
In plain English: artificially low prices caused the decline in the drugs that are now in shortage.
Ezekiel Emanuel zeroed in on the cause of the low prices in a NY Times oped back in August:
"The Medicare Prescription Drug, Improvement and Modernization Act of 2003...required Medicare to pay the physicians who prescribed the drugs based on a drug’s actual average selling price, plus 6 percent for handling. And indirectly — because of the time it takes drug companies to compile actual sales data and the government to revise the average selling price — it restricted the price from increasing by more than 6 percent every six months.
The act had an unintended consequence. In the first two or three years after a cancer drug goes generic, its price can drop by as much as 90 percent as manufacturers compete for market share. But if a shortage develops, the drug’s price should be able to increase again to attract more manufacturers. Because the 2003 act effectively limits drug price increases, it prevents this from happening. The low profit margins mean that manufacturers face a hard choice: lose money producing a lifesaving drug or switch limited production capacity to a more lucrative drug."
The result is clear: in 2004 there were 58 new drug shortages, but by 2010 the number had steadily increased to 211. (These numbers include noncancer drugs as well.)
http://www.nytimes.com/2011/08/07/opinion/sunday/ezekiel-emanuel-cancer-patients.html
For some reason Harris extolls the public spiritedness of generic drug companies who will pay about $300 million in one time user fees to break the logjam of approvals at the FDA's Office of Generic Drugs:
"The (generic) industry recently agreed to provide the F.D.A. with nearly $300 million annually to bolster inspections and speed drug applications. That amounts to about 1 percent of the industry’s revenues and about 5 percent of its profits in the United States, an extraordinary vote of confidence in the government’s ability to improve the situation. "
If the point is to show how this agreement will be used to resolve the current shortages, Harris is in error. The user fee agreement is designed to start accelerating approval of both new and backlogged generic drug applications by 2017. It has no bearing on the current shortage. But mentioning it is a nice way to divert our attention from the price controls that have lead to an underproduction of injectible cancer drugs and anti-biotics as well as a reluctance to invest in new facilities or production lines. As Emanuel notes:
"You don’t have to be a cynical capitalist to see that the long-term solution is to make the production of generic cancer drugs more profitable. Most of Europe, where brand-name drugs are cheaper than in the United States, while generics are slightly more expensive, has no shortage of these cancer drugs. " (Though it would be interesting to see if that is also a function of treatment patterns in Europe.
The administration's proposal to launch an attack on 'price gouging' will make companies reluctant to even attempt to raise prices. At the same time Team Obama is seeking to impose price controls on all Part B injectible drugs and Part D Medicare drugs. If you like shortages, just wait till these controls kick in.
On August 26th, in a Washington Times op-ed on the drug shortages, I wrote, “It is time not to fix the blame, but to fix the problem. Let’s start with the FDA.”
Today, Health and Human Services Secretary Kathleen Sebelius and FDA Commissioner Peggy Hamburg will join President Obama at the White House where he will sign an executive order instructing the FDA to take a series of actions to address the issue of drug shortages.
Thank you Mr. President.
The agency tries to do the best it can with limited authority, spare resources, and shared staff. In 2010, there were 178 drug shortages reported to the FDA. Is that a solid number? It’s hard to say, because current regulations do not require companies to notify FDA of shortages. The only requirement is that companies inform the agency six months in advance of discontinuing sole-source, medically necessary drugs.
President Obama will announce his support for House and Senate legislation that would require drug makers to notify the FDA six months ahead of a potential shortage, the official said. Under current regulations, drug manufactures are only required to notify the FDA if medically necessary drugs are being discontinued. Notification of shortages is strictly voluntary.
Thank you Mr. President.
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 facilities to help resolve shortages of medically necessary drugs.
The FDA says major causes of drug shortages are quality or manufacturing problems, or delays in receiving components from suppliers. Drug makers also discontinue certain drugs in favor of newer medications that are more profitable. The FDA does not have authority to force drug makers to continue production of a drug.
The executive order instructs the FDA to speed reviews or alter production of drugs that face critical shortages.
Thank you Mr. President.
But what will surely get the most attention is the executive order’s instruction for the FDA to provide more information to the Justice Department about possible instances of collusion or price gouging.
Mr. Obama should say “thank you” to the Institute for Safe Medication Practices who had previously identified that, relative to drug shortages, the top three problems of fall squarely within the zone of appropriate FDA attention and action:
* Little or no information available about the duration of a drug shortage (85 percent).
* Lack of advanced warning from manufacturers or the FDA to alert practitioners of an impending drug shortage and suggested alternatives (84 percent).
* Little or no information about the cause of the drug shortage (83 percent).
But – the President isn’t giving the FDA any additional funding to bolster its efforts in surveillance or to expedite regulatory applications to address them.
Mr. President, show me the money.
My August op-ed concluded as follows:
“Should the issues of both authority and funding for the FDA's efforts to mitigate drug shortages be hung on the Prescription Drug User Fee Act Christmas tree … or addressed in separate legislation? Either way, it’s an issue that must be addressed with alacrity before it becomes a question of American lives.”
Thank you Mr. President for keeping the issue of funding on the front burner.
Today, the media is skeptical of claims that vaccines cause autism or any change in mental or physical status not supported by a testable hypothesis as well as plausible biological cause. But it still swallows Wakefieldism in large doses without reading the fine print or learning from experience.
This week the authors of “Impact of Early Life Exposure to BPA” the journal Pediatrics concluded that exposure to bisphenol-A (the most common chemical used in everything from cash register receipts to computers to condoms) was associated with “worse behavior, especially among girls” at age 3. In doing so, they relied on nanoparticle of science and a significant amount of Wakefieldism, kept alive once again by a pliant media.
The easiest way to know if a so-called scientist is scamming you is to look at how rigorously they are actually testing the hypothesis they claim to prove. Wakefield never tested a hypothesis, he claimed to find an association between bowel inflammation in kids, autism and MMR vaccination. In the case of the BPA paper the authors claim there’s an association between BPA exposure and bad behavior in three-year-old girls. Our intrepid scientists should have been “testing this hypothesis directly in a cohort of pregnant women by daily monitoring of serum total BPA and BPA over an extended period of time would seem to be a logical next step.” In plain English: they should have been taking urine samples from women every day during their pregnancy.
So what did the researchers who claim at BPA- developmental damage link do? “Three maternal spot urine samples were collected between March 2003 and January 2006, twice during pregnancy, at _16 and _26 weeks of gestation, and within 24 hours after birth. Children’s spot urine samples were collected at 1, 2, and 3 years of age. “
I am not a real scientist but even I can tell you that does not add up to having women pee into a cup every day.
Second, a hallmark of Wakefieldism is to divert attention from pesky issues such as how MMR actually caused autism by hyping the association and not explaining how the probable cause came into being.
Similarly, the authors never tell us where the BPA comes from. I can tell you that: Most BPA comes from what we eat. So one way of establishing whether BPA has any effect on anything at all is to directly compare “urinary concentrations, dietary exposure, and internal exposures to inactive and bioactive BPA.” Oh yes, there are two forms of BPA too. But you won’t find a reference to that distinction in “Impact of Early Life BPA Exposure”. That’s because the bioactive form of BPA can only be detected through blood tests of which the total number taken by the researchers is zero.
Because this is the first study to actually look at BPA exposure in utero and in early life these are precisely the questions you would want answers to. You would also want to know if the fetal/neonatal blood concentrations of BPA of mothers and little girls in the study are much higher than studies of adult men.
Then there is the determination that the girls who had been exposed to higher levels of BPA were more likely to be anxious, have ADHD, be emotionally disruptive, etc. They too were only measured once. At age three. Let’s set aside the fact that diagnosing ADHD in preschoolers is best left to experts. The most important factor predicting ADHD and other disorders is the parent’s own emotional background and behavior.
The authors of the paper have overstated their conclusion by hyping the dangers and avoiding real science. And the media has failed once again to dig deeper to help us determine whether we should worry more about the kind of parents we are then what kind of lunchbox our kids bring to school. Wakefield was discredited but his methods live on.
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.
