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"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.
“Generic” does not equal “identical.” That’s why the FDA wants to tighten certain bioequivalence standards.
Generic-drug makers will have to meet tighter standards to prove that “critical dose drugs” such as blood- thinners and anti-seizure treatments, work as well brand-name products. And it’s about time.
The FDA, responding to complaints that some copies don’t work as well as the originals, is writing guidelines for limits companies must follow that include how fast active ingredients are absorbed in the bloodstream.
Critical dose drugs have a narrow therapeutic index, meaning that small changes in blood concentration have the potential to result in serious therapeutic failures and/or serious adverse drug reactions.
The FDA is outlining its plans to companies after patients and employees of generic-drug makers complained to regulators that some of the medicines don’t work as well as the originals.
And, according to Lawrence Yu, deputy director for science and chemistry in the agency’s Office of Generic Drugs, “Ideally, they should start using them now.”
Currently, the "sameness" of a brand product and a generic version is evaluated based on two-treatment crossover study to prove bioequivalence, the aim being to show that the 90 percent confidence intervals of the geometric mean test/reference ratios for both maximum plasma concentration and the area under the plasma concentration-time curve fall within a range of 80 percent to 125 percent. The agency is now requiring a rate between 90 percent and 111 percent for narrow therapeutic index drugs.
A generic drug’s potency will also have to fall within 95 percent and 105 percent of the original. Currently, drugs can fall within a range of 90 percent to 110 percent.
The FDA plans to release guidelines on the stricter standards, Yu said, declining to say when. Well, the sooner the better -- because a confused public wants to know.
A Consumer Reports poll of 1,226 adults in June showed 39 percent of respondents had concerns or misconceptions about generics while 21 percent thought the copies weren’t as effective as brand-name products. Twenty-one percent didn’t trust generics as much as brand-name drugs and 14 percent said they didn’t think the products were as safe.
Pharmacists “hope that FDA tightening the standards does in fact help alleviate some consumer skepticism about generics,” said Chrissy Kopple, a spokeswoman for the National Association of Chain Drug Stores.
Rx-to-OTC switch questions that FDA asked advisory committees over the past 10 years can help guide future sponsors to success, says the lead researcher in an analysis of the agency's switch actions.
The journal SelfCare has published "an essential blueprint for designing and implementing any Rx-to-OTC drug development program," says lead author Bill Soller, professor and executive director of the Center for Consumer Self Care at the University of California, San Francisco, School of Pharmacy. Well, maybe not essential -- but certainly intriguing.
Soller and his colleagues list questions - "OTC Considerations" - based on switch principles FDA set in 1990 and 1998 and questions to post-2002 advisory committees that evaluated first-in-class switches.
The analysis recommends 11 primary questions about the Rx fundamentals of a drug, its "OTCness" and overall risk vs. benefit.
1- Has the Rx product been on the market for a sufficient time and extent to enable full characterization of the drug's safety profile?
2- Can the condition be adequately self-diagnosed or is there a need for physician diagnosis?
3-vIs the minimally effective dose known?
4- Are there efficacy studies needed to support the intended OTC use of the switch candidate?
5- What are the patterns of diagnosing, prescribing and patient use in the Rx setting related to OTC intended use?
6- Are the studies supporting OTCness generalizable to the intended OTC target population?
7-Do consumers understand key communication objectives of the label, relating to directions for use, contraindications, in-use warnings and precautions?
8- Do consumers show they would be likely to be able to assess and take action on the treatment effect (e.g., take appropriate action if the drug is not working, serious side effects emerge, or self-monitoring is needed)?
9- Do consumers demonstrate successful self-selection and de-selection of the product under conditions (or simulated conditions) of actual use?
10- Does the pattern of actual use support that the label can be successfully used in practice?
11- Do the benefits of OTC availability outweigh the risks?
The list reflects materials FDA provided advisory committees and presented at meetings on first-in-class switches from 1992 to 2011. The latest was in 2007.
The authors say FDA "uses its discretion to select areas of concentration for advisory committee discussions on switch." Factors influencing the agency's questions for advisory committees include the novelty and uniqueness of a proposed OTC indication or Rx active ingredient; intrinsic and extrinsic toxicity of a switch candidate; and robustness of published and NDA-derived data and worldwide post-marketing surveillance evaluations, according to the article.
The analysis in SelfCare comes a month after FDA published a draft guidance on designing self-selection studies in support of OTC switches. The draft states FDA's interest in greater insight into consumers' thought processes and says study sponsors should follow up with medical history questions and additional open-ended queries.
What about the potential of Behind-the-Counter (BTC) arrangements? Well, according to Eric Brass, a physician, director of Harbor-UCLA Center for Clinical Pharmacology and a professor at David Geffen School of Medicine at UCLA, "The statement that a company will voluntarily impose such a restriction cannot influence the regulatory decision, as the second company to market could not be held to the same restriction.” Good point. And, further, “If pharmacist assessment is required for safe and effective use by the consumer, I think that the drug would not be appropriate for OTC status today." Brass added that no public health benefit from expanding consumers' access to medicines through pharmacists has been established.
Maybe it’s time for the pharmacy community to step up to the plate and commence that conversation.
Bloomberg reports that Eli Lilly & Co., which has spent $135 million since 2003 training seven generic drugmakers to make treatments against drug-resistant tuberculosis, plans to spend $30 million over the next five years helping patients to get access to the pills.
Lilly plans to work on improving availability of treatment for people in China, India, Russia and South Africa, and to train health-care workers from 2012 until 2016.
There were about 9.4 million cases of tuberculosis globally in 2009, according to the World Health Organization. Of those, almost 4 percent were a form of the disease that isn’t cleared by the two frontline drugs used against it, requiring treatment with costlier medicines. Lilly’s funds will help make second-line medicines available to those who need it, Chief Executive Officer John Lechleiter said. He traveled to western China in March to observe the Lilly Foundation’s work.
“The impression that that left me with is the scarcity of resources available to health-care providers,” Lechleiter said. “By that I mean simple things like posters and brochures that would make people aware of the disease, how to prevent it, how to seek treatment.”
That’s a consistent message. On September 16th, at the Washington Post’s “Sharing the Responsibility” event on non-communicable diseases, Lechleiter commented, “There is no substitute for the power of partnership.”
Amen.
With the Food and Drug Administration Amendments Act (FDAAA) of 2007 barely in the rear view mirror and the Prescription Drug User Fee Act V reauthorization rapidly approaching, drug safety, risk evaluation and mitigation strategy (REMS), and pharmacovigilance in the United States are about to undergo significant changes.
Meanwhile, the United Kingdom is forging ahead with its most significant pharmacovigilance legislation since 1995, with serious implications for applicants and holders of European Union marketing authorizations.
What will these changes mean for the pharma industry worldwide?
Please join the Center for Medicine in the Public Interest (www.cmpi.org) and FDA News for the 4th Annual Risk Management and Drug Safety Summit: Building an Effective Global Risk Management and Drug Safety Program, scheduled for Nov. 1–2, 2011, in Washington D.C.
Keynote speakers:
• Peter Pitts, co-founder, president, Center for Medicine in the Public Interest (chair)
• Edward Fotsch, M.D., CEO, PDR Network LLC (chair)
• John Lechleiter, Ph.D., CEO, Eli Lilly & Co.
• Janet Woodcock, M.D., director, Center for Drug Evaluation and Research (CDER), FDA
• Sir Alasdair Breckenridge, chairman, Medicines & Healthcare Products Regulatory Agency, UK
• Ravi Deshpande, vice president, McKesson Specialty
• John Jenkins, M.D., director, Office of New Drugs, CDER, FDA (invited)
• Ankur Makadia, PharmD, risk management plan leader, Global Clinical Safety & Pharmacovigilance, UCB
• Jane Axelrad, associate director for policy, CDER, FDA (invited)
• Deborah Autor, deputy commissioner, Globalization & Regulatory Operations, OC, FDA
• Josephine Torrente, director, Hyman, Phelps & McNamara (invited)
• Vaishali Patadia, Ph.D., director, head, Pharmacoepidemiology, Astellas Pharma (invited)
• Timothy Franson, M.D., senior vice president, health and life sciences sector, B&D Consulting; president, U.S. Pharmacopeia Board of Trustee; former vice president, global regulatory affairs, Eli Lilly & Co. research laboratories
Click here to see the full agenda.
But setting aside the dislocations deep recessions, burst bubbles and depressions cause in household income (the right metric for measuring disparity in my opinion) is the gap between rich and poor – in America and elsewhere – has been declining over the past two centuries, not increasing. By any measure, the Gini ratio in particular, the gap between rich and poor declined from 1967 to 2010. And the cause for this change in which everyone’s incomes rise is mainly medical innovation that allows billions of people to live longer and healthier lives. Nobel Prize winning economist Robert Fogel comments on the effect of what he calls the “technophysical evolution” of the human race on inequality:
“In every measure that we have bearing on the standard of living, such as real
income, homelessness, life expectancy, and height, the gains of the lower classes have been far greater than those experienced by the population as a whole, whose overall standard of living has also improved. If anything sets the twentieth century apart from the past, it is this huge increase in the longevity of the lower classes.
The fact is that government transfers were incapable of solving the problems of beggary and homelessness during the eighteenth and much of the nineteenth centuries, because the root cause of the problems was chronic malnutrition.
Even during the most generous phases of the relief program, the bottom fifth of the English population was so severely malnourished that it lacked the energy for adequate levels of work (It was the huge increases in English productivity during the later part of the nineteenth and the early twentieth centuries that made it possible to feed even the poor at relatively high caloric levels. Begging and homelessness were reduced to exceedingly low levels, by nineteenth century standards, only when the bottom fifth of the population acquired enough calories to permit regular work. The principal way in which government policy contributed to that achievement was through its public health programs. By reducing exposure to disease,more of the calories that the poor ingested were made available for work.”
http://www.ekh.lu.se/seminar/presentation/Fogel.pdf
In our time, longer life and the increased participation of women in the workforce have contributed an increase in income and wealth among married households who are 45 and older. By contrast, households headed up by a single women are likely to be poorer and experience slower growth in income.
Income inequality is a function of education and life expectancy. The healthier people are the more they are likely to think about the long term and as a result, more likely to invest time and money in education and health care. Much of the inequality in income – over the decades -- is still due to barriers to regular work. Education can remove many of those obstacles, but reducing exposure to mental and physical diseases will be required to achieve greater growth and productivity. Thus the key to reduce disparities and promoting prosperity is consumption of new medical products.
http://www.census.gov/compendia/statab/cats/income_expenditures_poverty_wealth.html
My guiding principle is this: Guilt is never to be doubted. – Franz Kafka
Will Par Pharmaceutical Inc.’s First Amendment suit against FDA result in a new approach to battling government allegations of off-label marketing?
Par contends that the government is criminalizing it’s speech to healthcare professionals about the on-label use of its appetite suppressant Megace ES (megestrol acetate) in settings where doctors prescribe the drug for both approved and unapproved uses.
Par’s complaint, filed Oct. 14 in the U.S. District Court for the District of Columbia, seeks a preliminary injunction against government enforcement of FDA labeling regulations on the grounds they are harming Par’s First Amendment rights by chilling protected speech.
Par’s suit states that physicians more frequently prescribe the drug to treat wasting in non-AIDS geriatric and cancer patients and that the majority of prescriptions for the drug are for off-label uses.
Par also seeks a declaratory judgment that it may speak about the approved use to physicians who could prescribe it for that use, even if they are more likely to prescribe the drug for off-label uses.
“Common sense dictates that the government cannot justify censoring a broad swath of truthful and valuable speech regarding lawful activity out of a desire to prevent other lawful activity,” a memorandum in support of the motion for preliminary injunction states. “And it is absurd to think that the government may imprison a person for engaging in truthful speech about a lawful activity that the government itself subsidizes.”
At issue in Par’s suit are provisions in the Food, Drug, and Cosmetic Act concerning “intended use” of a drug and misbranding.
“If a manufacturer speaks about the on-label use of its drug in a setting where the manufacturer knows that physicians prescribe the drug off-label, the government interprets the FDA’s ‘intended use’ regulations to deem the manufacture to be expressing an ‘objective intent’ that physicians prescribe the drug off-label,” Par’s memorandum states.
Par says the government has advised the company that manufacturers should only talk to physicians in an off-label setting if there are “a sufficient number of patients being treated for whom the drug could be prescribed on-label,” but that the government has not provided any guidance as to what would constitute a sufficient number of on-label patients.
“The regime is also Kafkaesque. Manufacturers have no way of knowing whether, under the FDA’s regulations, they may speak to physicians who, for instance, prescribe the drug 20% on-label and 80% off-label, or to physicians with the reverse prescription ratio.”
In a press release announcing the suit Par said it hoped to “elicit tailored and constitutionally permissible regulatory guidance to ensure that physicians may be kept abreast of valuable, on-label information about prescription drugs to aid in their provision of quality and informed patient care.”
Atlas was permitted the opinion that he was at liberty, if he wished, to drop the Earth and creep away; but this opinion was all that he was permitted. – Franz Kafka
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.
