Generic Drugs Savings? Orrin not so Oral

03/05/2012 07:54 AM |

Generic Drugs' Effect on Health Costs Unclear, GAO Says

By Emily P. Walker, Washington Correspondent, MedPage Today

WASHINGTON -- Generic drugs were substituted for brand-name drugs 93% of the time in 2010, but whether increased use of generics is actually saving money is up for debate, according to the Government Accountability Office (GAO).

Studies looking at cost savings from use of generic drugs "had mixed results regarding the effect of using these generics, in that some found they raised healthcare costs, while others found they led to cost savings," wrote the authors of a GAO report released Thursday.

The GAO report was requested by Sen. Orrin Hatch, co-author of the 1984 Hatch-Waxman Act, which paved the way for a major increase in the number of generic drugs. In the early 1980s, there were generic versions of just 35% of the top-selling drugs with expired patents; by the late 1990s, almost all of them had generic versions.

Prescription drug spending more than tripled from 2001 and topped $307 billion in 2010, making up 12% of all healthcare spending in the country, the GAO researchers wrote.

However, the growth has slowed markedly since the early 2000s when an increasing number of generic versions of brand-name drugs hit the market. On average, the retail price of a generic drug is 75% less than the retail price of its brand-name equivalent.

The report summarized the findings of peer-reviewed articles, government reports, and studies by national organizations -- including trade and nonprofit organizations -- on the cost effects of increased utilization of generic drugs.

The report authors identified three general groups of studies. The first group estimated the cost savings from relying more on generic drugs. One group of studies in that pool -- sponsored by the generic drug lobby -- estimated the use of generics to have saved the U.S. healthcare system $1 trillion from 1999 through 2010.

Another report, by the Congressional Budget Office (CBO), found that dispensing generic drugs rather than their brand-name counterparts reduced total Part D prescription drug costs in 2007 by about $33 billion.

A second group of reports focused on the potential to save even more through greater use of generics. For instance, the CBO estimated that if generics had always been substituted for brand-name drugs in Medicare Part D, $900 million would have been saved in 2007.

A third group of studies estimated the effect on healthcare costs of using certain generic drugs in cases where questions have been raised about how medically similar they are to the brand-name version. That group of studies compared the lower cost of the drug with the higher cost of increased hospitalizations from using a potentially less effective generic drug.

One study in that group found that depressed patients on selective serotonin reuptake inhibitors (SSRIs) who started on a brand-name SSRI and switched to a generic ended up experiencing an increase of $881 in total healthcare costs because of increased hospitalization rates and emergency department visits.

However, another study found those who began treatment on generic SSRI's had significantly lower costs than patients using brand-name antidepressants.

Another study in that group, done among renal transplant patients, found that total healthcare costs one year following transplantation were about $4,000 higher for patients who started therapy with generic immunosuppressants compared with those using brand-name drugs. That difference was attributed to "the cost associated with needing higher doses of the generic drug or additional immunosuppressants needed to maintain the transplanted kidney in patients using the generic," the report said.

Overall, the studies on whether generic drugs save money were a mixed bag, the GAO said.

Generic drugs must have the same active ingredients, route of administration, strength, and intended use as their brand-name counterparts. They also must be absorbed into the bloodstream at the same rate. Generic drugs are allowed to have different inactive ingredients, such as binding materials, dyes, preservatives, or flavoring agents compared with brand-name drugs.

At the end of the GAO report to Hatch, which was dated Jan. 31, the agency mentioned that it agreed not to publish the results of the report for 30 days. In the meantime, Hatch could have publicized the results, but did not. Requests for comment from Hatch's office did not bring a response.

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Peggy to Liz: "Stop acting and get on with it!"

03/05/2012 07:47 AM |

Bravo.

Dear Colleagues,
 
I am thrilled to announce the permanent appointment of Elizabeth Dickinson as the Chief Counsel of the Food and Drug Administration, effective Monday, March 12, 2012.
 
As many of you know, Liz has had a long and distinguished history at the Agency; she joined the Office of the Chief Counsel in 1994.  Over the years, Liz has served as legal counsel to the Center for Drug Evaluation and Research and the Office of the Commissioner on innovator and generic drug review issues, orphan drug development, and biosimilars; has implemented pediatric exclusivity and pediatric drug development programs; has worked closely with the Department of Justice on dozens of cases addressing Waxman-Hatch issues and preemption; and has coordinated the development of the Office of the Chief Counsel’s flexible workplace program.
 
A graduate of the University of Massachusetts and Northeastern University School of Law, Liz is highly regarded by both her internal colleagues and those across the food and drug bar.  Over the years, Liz has received numerous awards for distinguished service, leadership and her outstanding legal skills.
 
Liz has been serving as Acting Chief Counsel since August 2011, and we have been grateful for her hard work and dedication each day that she has been on the job.  It is terrific to know that she will be serving the Agency in this role permanently as we move forward.  Please join me in congratulating Liz.
 
Sincerely,
 
Margaret A. Hamburg, M.D.
Commissioner of Food and Drugs

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Guidance Missles

03/02/2012 08:16 AM |

Two important stories from BioCentury:

FDA to hold hearing on biosimilars guidance

FDA will hold a public hearing on May 11 to discuss three recently published draft guidance documents on biosimilars. FDA said the hearing's purpose is to obtain public comment on the drafts, as well as receive input on topics to be included in the development of future biosimilar policies. The guidance documents, released early last month, indicate the agency hasn't settled some important biosimilars policy questions, including requirements for demonstrating interchangeability of a biosimilar with a reference product and terms for establishing the exclusivity period for pioneer biologics.

EC seeks to reduce duration of reimbursement decisions

The European Commission proposed a Transparency Directive that would reduce the time limits for member states to make pricing and reimbursement decisions for medicinal products. States would be required to issue a decision within 120 days of approval for an innovative drug and within 30 days for a generic. Current regulations require a decision for all drugs within 180 days. Member states that review the relative efficacy of a product via a health technology assessment would still be subject to the 180-day limit.

Under the proposal, member states would be required to designate an enforcement body with the power to award damages and impose penalties for delayed pricing decisions. Member states would also be required to regularly report to the EC on the time required for individual pricing decisions. The new directive is slated to begin implementation in 2014. EC said pricing and reimbursement decisions can take as long as 700 days for new drugs and up to 250 days for generics. The EC began public consultation on the proposed changes last year.

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Joint Custody

03/01/2012 07:58 AM |

On March 12^th, the FDA’s Arthritis Advisory Committee will meet and discuss the anti-nerve growth factor (Anti-NGF), a drug class that is currently under clinical hold because of the threat of joint damage.  Clinical trials for Pfizer’s tanezumab were suspended in 2010, at the FDA’s request, when some patients’ arthritis worsened to the point of needing joint replacement – and a class-wide clinical hold followed.  (Similar treatments are in early stage development at Johnson & Johnson, Regeneron, Sanofi, Abbott, and AstraZeneca.

Anti-NGF therapies are being developed for the treatment of a variety of chronic painful conditions including osteoarthritis, chronic lower back pain, diabetic peripheral neuropathy, post-herpetic neuralgia, chronic pancreatitis, endometriosis, interstitial cystitis, vertebral fracture, thermal injury, and cancer pain.  And if the fact that, according to Professor Thomas Schnitzer of Northwestern University, “We’ve had over a hundred years without having a major new pain drug,” isn’t enough – Anti-NGF’s are non-opioids.

FDA has tasked the adcomm to determine whether reports of joint destruction represent a safety signal related to the Anti-NGF class of drugs and whether the risk/benefit balance for these drugs favors continued development as analgesics.

Why a clinical hold? While a Phase II, 450-patient proof-of-concept study showed that tanezumab relieved knee pain when compared to a placebo, a Phase III study (published in the New England Journal of Medicine) showed 16 patients experienced progressively worsening osteoarthritis associated with a form of bone damage known as necrosis, which required total joint replacements.

In an accompanying NEJM editorial, John Wood a researcher at University College, London and a visiting professor at Baylor College of Medicine (a post funded by Pfizer), wrote the joint failure “was most likely caused by excessive wear and tear in the absence of joint pain. Pain has an important role in the avoidance of self-harm, but chronic inflammatory pain has generally been considered to be wholly undesirable.” The tanezumab study “suggests that a complete quenching of pain in patients with osteoarthritis may not necessarily be a good thing.”

In other words, according to a report in the Wall Street Journal:

“Some researchers are suggesting that an experimental Pfizer drug may have liberated arthritis sufferers to such a degree that they became more physically active — and that the subsequent wear and tear on their joints led to joint replacement surgery.”

The drug made people feel “better than [they] ever felt before, and I have a feeling they just overused their joints,” Nancy Lane, a rheumatologist and bone-health specialist at UC Davis Health System in Sacramento. She suggests the drug could still play a role as long as doctors “counsel patients not to overuse their joints.”

What happens when a drug … works too well?  Lane says she has seen this pain-masking situation before, including with the nonsteroidal anti-inflammatory drug (NSAID) indomethacin. “Because this is a new chapter in controlling pain, we didn’t realize we needed to counsel our patients in using their joints that were still diseased. Now we need to figure out how to use it so the risks don’t outweigh the benefits.”

And so the issue of patient education becomes crucial. What happens when a class of drugs is so effective, patients forget they have the underlying condition and behave contrary to their best medical interests? (In plain English – what happens when a therapy is so effective patients over do it and then suffer the consequences?) Hopefully the 3/12 adcomm will spend some quality time discussing this important social science question. Perhaps this issue should be taken up, um, jointly with the agency’s Risk Communications Advisory Committee? Anti-NGF drugs require not only a discussion of benefit/risk – but also the risk of benefit.

Those are, after all, precisely the kind of thorny scientific propositions FDA advisory committees are held to address.

Welcome to 21^st century medicine.

Ladies and Gentlemen, start your engines.

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Depressed About Statin Scare? There's a Pill For That...

02/29/2012 10:57 AM |

Kim Painter of USAToday's healthy perspective blog has a funny take on the statin scare and how dreding the same data in a different way produces contradictory results:

Statin risks and benefits: People who take statin medications to lower cholesterol might also lower their risk of depression, a study suggests. That finding might cheer up patients who just learned that the Food and Drug Administration is adding new warnings about elevated blood sugar and memory loss to statin labels.

Epidemiology of this type is to science what Sparknotes is to writing a novel. 

Kudos Kim!

http://yourlife.usatoday.com/health/healthyperspective/post/2012-02-29/concussions-in-kids-and-kobe-statin-risks-and-benefits-selenium-and-health-safe-airport-scanners-condoms-that-check-in/637023/1
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The Accidental (Medical) Tourist

02/29/2012 09:15 AM |

According to news reports, Sonia Gandhi, the leader of India’s governing Indian National Congress Party, has left the subcontinent for a medical check-up. She made a similar departure from India in August.

Where is she? Thailand? Brazil? Pakistan? Turkey? Or one of the many other nations touting their medical tourism credentials? Top of that list, of course, is India.

We wish Mrs. Gandhi well and assume she is currently being treated in a nation that has an up-to-date pharmacopeia of innovative treatments. That list of countries, it is interesting and disturbing to note, does not include the above-mentioned locations.

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Sleeping Pill Risk Study (and Reporting) Is a Nightmare

02/28/2012 02:58 PM |

Why do a study that looks at the "link" between sleeping pill use and risk of death that does not control for the diseases associated with higher risk of death such as depression, heart problems, anxiety and the impact insomnia has on all?

Why report on such a study with blaring headlines and warnings and bury all the caveats at the end of the study?

Maybe someone who reads this blog can explain why medical journals publish such garbage and why reporters can't take 5 minutes to look at previous research on the subject?

http://abcnews.go.com/Health/Sleep/sleeping-pills-linked-times-increased-death-risk/story?id=15803687#.T00wPMzu6Uo


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What Republicans Should Be Saying About Healthcare Part 1

02/28/2012 11:10 AM |

Here's a piece I wrote on the last Republican debate.  I plan a second installment on what the GOP candidates should be talking about and, to be fair and balance, what the President should say to defend Obamacare beyond the usual platitudes about not denying coverage for pre-existing conditions. 


Republicans Rock the Airwaves

By Robert M. Goldberg on 2.24.12 @ 6:08AM

http://spectator.org/archives/2012/02/24/republicans-rock-the-airwaves

So why didn't Rick Santorum take advantage to explain his real views on prenatal testing?

The most recent installment of the reality TV series, known as the Republican Presidential Debates, drew more cable viewers than The Jersey Shore or any of the cable channels' tributes to Whitney Houston. Never before have so many Americans been directly engaged in political discourse. (There were as many tweets, Google searches, etc. for the Arizona debate than for any other show on TV the other night!)

If you are like me, you were channeling the candidates and thinking of things they should have said but didn't. Why didn't Romney just say that Romneycare's individual insurance mandate was a mistake just as was Santorum's support for No Child Left Behind? Why not add that much of Romneycare -- individual buying at group rates, reforming Medicaid, and having insurance plans add a health savings account to their offerings -- are things Republicans support.

I hoping CNN's John King would have asked Rick Santorum about his views regarding prenatal testing. Santorum could have restated, without the left's media filter, that he doesn't want to ban contraception or prenatal screening.

Instead, he is concerned that prenatal screening, to detect for so-called birth "defects" such as Down's Syndrome, spina bifida, cystic fibrosis and Fabry's Disease, will be used in combination with abortion to place limits on neonatal care to control health care costs for high risk infants.

He is right to be concerned and talk about it. The health systems of Britain, Canada, the Netherlands and Australia discourage life-sustaining treatment for extremely premature or low birthweight babies. In 2005, the Royal College of Obstetrics and Gynaecology (RCOG) announced that "very premature babies were taking up intensive care space that could be used for healthier babies" and suggested that those born at very low gestations should not be intensively treated but rather allowed to die.

It said such infants were "bed blocking" and that due to better medicines and devices, "[t]here has been a constant need to expand numbers of cots to cover the increasing tendency to try and rescue babies at lower and lower gestations."

A review of neonatal intensive care units in Canada found "the majority of medical staff members do not recommend NICU care for an infant born at 24 weeks' gestation…" The review concludes that in some Canadian NICUs, preterm infants are not considered to be persons and, thus, are not treated in the same way as a larger patient. It doesn't help that Canada has severely limited growth in the number of NICUs. But that's by design. Indeed, to keep their babies alive, Canadian parents go to U.S. hospitals. In recent years hundreds have done so. U.S. doctors try to do what their Canadian colleagues cannot or will not, as in the case of Michelle James. Her doctors in Canada could not halt her labor when it began at 24 weeks and were not optimistic about the viability of her pregnancy. In the U.S., doctors succeeded in stopping labor for three weeks, improving her daughter's ability to survive and avoid a disability.

Could the cold calculus of cost-effectiveness be paired with prenatal screening under Obamacare? It already is.

The Agency for Healthcare Research and Quality and a senior advisor to the Patient-Centered Outcomes Research Institute -- the two agencies responsible for producing comparative effectiveness findings -- are already issuing guidance that would ration care to sick, vulnerable infants based on cost consideration and one-size fits all research.

Jean Slutsky -- who works for both AHRQ and PCORI -- heads up a committee that decides what technologies PCORI will examine. Here's what she and two colleagues said about prenatal screening: "Compelling stories of children who died from very rare metabolic disorders that might have been detected with newer, more expensive equipment have created powerful momentum for expanded screening of newborns. But in an era of constrained budgets, state policymakers need to weigh the benefits and costs of new screening programs against those of other equally important programs. Nonetheless, it remains politically risky to frame a health policy decision as being based primarily on cost or cost-effectiveness." That's compassion for you.

AHRQ and PCORI were established to obscure the fact that health policy decisions based on cost are politically cheap. AHRQ claims that there is no benefit for routine use of inhaled nitrous oxide to oxidate the lungs of pre-term infants. Yet dozens of studies demonstrate that newborns with iNO in combination with continuous airway pressure saves the lives of those with severe respiratory failure and pulmonary hyperplasia. It has been shown to save the lives of infants with premature rupture of the membranes (before 24 weeks of gestation). And it is looking at whether spending so much money on care for at risk babies is "cost-effective."

America spends more on at risk infants than any other nation. More babies that once died because they were too sick or small after birth are alive and part of loving families. We lead the world in life sustaining therapies for newborns. Santorum is standing up against the monstrous moral certainty of Obamacare. Amen to that.  Read More & Comment...

IPAB adieu via H.R. 452?

02/28/2012 10:29 AM |

Polly Toynbee, a very left-of-center columnist for the Guardian, writes that, “The NHS was always rationed. What matters is whether it is done rationally or haphazardly, nationally or by postcode, in public or secretly …More treatments are denied without a national or rational debate. A Doctors.net.uk survey of GPs shows most are deeply concerned at rationing by stealth.”

Sound familiar? It should -- it’s a fast-forward look at where we’re going through IPAB.  But maybe not.

Tomorrow, at 10AM in Rayburn 2123, the Committee on Energy and Commerce will meet in an open markup session to consider doing away with IPAB via the Medicare Decisions Accountability Act of 2011.  AKA H.R. 452, this piece of legislation would repeal Sections 3403 and10320 of PPACA – the sections that established and empowered the IPAB.

And Senator John Cornyn has introduced S. 2118, a bill that would similarly eliminate the Independent Payment Advisory Board.

As we enter into election season, it’s time for our elected representatives to go on the record about their positions on healthcare rationing – of which IPAB is Exhibit A.  As Ms. Toynbee writes, Better by far to make these painful choices in the full glare of open public debate.”

Ladies and Gentlemen of Congress -- it's time to stand up and be counted.
 

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The Sharp Tip of the Lancet

02/27/2012 07:52 AM |

According to the World Health Organization, “Counterfeit drugs may erode public confidence in health care systems, health care professionals, the suppliers and sellers of genuine drugs, the pharmaceutical industry and national Drug Regulatory Authorities.” And, in an editorial, the editors of the Lancet ask, “So what should be done to tackle the growing problem of counterfeit medicines?”

The Lancet makes a strong and straightforward case for action. “The consequences of counterfeit drugs are diverse, as are the solutions, which lie in collective involvement, responsibility, and responses of all interested parties: health professionals, drug regulatory authorities, judicial entities, and drug companies at both national and international levels. Critical to this effort is strengthening of drug regulatory authorities, which should not only be responsible for improving drug standards, but also provide effective recognition of counterfeit drugs and assist other agencies in stopping their trade. This is especially needed in those countries that have either no drug regulation at all or an impaired or corrupted system. Additionally, enactment and enforcement of new laws for prohibiting counterfeit drugs is vital.”

And the editors ask the obvious and troubling question, “So why is there not yet an international fake drug treaty?”

We all know the answer.

The Lancet tells the often uncomfortable and undiplomatic truth that “the Indian and Brazilian Governments and some non-governmental organisations … believe it would confuse quality and intellectual property rights issues and thus undermine access to legitimate and much lower-cost generic medicines consumed mostly in poor areas.”

As Prashant Reddy opined in Spicy IP, “Every time an intellectual property issue is brought up by an international organization in the context of public health we presume that there is an 'imperialist/blood thirsty East India type corporation' conspiring against India. The level of paranoia is simply unbelievable. It is time India started acting like a responsible, confident nation before it decides to torpedo international negotiations. It would also be nice if the Government could start articulating its concerns in the language of public health and not in the language of the generic drug industry.”

Amen.

It’s time to actively and aggressively pursue FDA Commissioner Peggy Hamburg’s call for a regulatory Marshall Plan to help build, nation-by-nation, global systems for both quality and safety.

Working together to raise the regulatory performance of all nations will help all nations create sound foundations to address a multitude of quality and safety dilemmas such the manufacturing of biosimilars, the control of API and excipient quality, pharmacovigilance and, yes, even counterfeiting.

And here’s the sharp tip of the Lancet, “The fight against counterfeit drugs must be strengthened without further delay. It needs consensus among all countries and interested parties, and requires wise and bold leadership from WHO. An indispensable goal of the campaign is ensuring the availability of genuine and affordable essential medicines in developing countries.”

Memo to New Delhi and Brasilia – get with the program … or get out of the way.

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Counterfeit Avastin: Assad State of Affairs

02/24/2012 08:39 AM |

According to a report in the Wall Street Journal -- About three years before counterfeit copies of Roche Holding AG's cancer drug Avastin surfaced in the U.S., a case in Syria involved fakes of the same drug, showing the company has been grappling with bootlegging of the product for some time.

In 2009, Syrian authorities seized a haul of phony Avastin at a warehouse there, a Roche document shows. The company confirms the case, and acknowledges it has encountered other "individual cases" of counterfeit Avastin in recent years. Until now, the only other known case of Avastin counterfeits, other than the recent U.S. case, was a 2010 incident in Shanghai.

According to officials in law enforcement and the pharmaceutical industry, at least three smugglers were jailed as a result of hauls in Egypt and Syria in 2009 that netted the fake Avastin and other counterfeits drugs. These people said the trio -- who officials said were part of the same counterfeiting network -- were released from Syrian and Egyptian jails last year.

It's unclear whether the Middle East currently produces fake drugs, acts as a transit corridor, or both. Evidence suggests many counterfeits that transit through the Middle East are produced in China. In the same Syrian raids that netted the fake Avastin in 2009, officials found other fake drugs packaged in Chinese-language bags. Authorities also found Chinese-manufactured equipment that the criminals were using to produce fake drugs.

In the 2010 case of counterfeit Avastin that surfaced in Shanghai, 116 patients were given a fake version of the drug. In addition to being used against cancer, Avastin is prescribed to treat an eye disease that causes blindness. The Chinese patients received injections in the eye, and some suffered complications, according to a report on the incident published last year in the New England Journal of Medicine.

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A pox on all their houses

02/23/2012 12:21 PM |

Dr. Marc Siegel recently appeared on Fox news with Megyn Kelly to discuss the danger posed by Chicken pox parties.
 
Watch the interview here:


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Qnexa: A Weight Off Of FDA's Shoulders

02/23/2012 10:44 AM |

Qnexa,  the weight loss drug developed by Vivus, was backed 20-2 by the FDA Endocrine and Metabolic Disease Advisory Committee.   Almost all patients on Qnexa lost about 10 percent of their baseline weight over a year compared to placebo.   Qnexa was rejected last year because of Avandia stoked worries about cardiovascular risks, particularly high blood pressure.   This time around, Vivus did an additional study and focused on cardiovascular endpoints and markers among various subgroups.   The study found among many groups that blood pressure and inflammatory markers declined along with a loss of weight. "  Effects of treatment on biomarkers of cardiovascular disease risk, such as hs-CRP, adiponectin, and fibrinogen, were measured in study OB-303. Treatment with QNEXA Top and Mid dose resulted in statistically significant mean changes in hs-CRP, adiponectin, and fibrinogen. The magnitude of reduction in hs-CRP appears to be comparable to those observed in the JUPITER trial with rosuvastatin."    And Vivus will closely evaluate how people respond to Qnexa in the real world. 

The emphasis on sub-group analysis to establish which patients would benefit most from Qnexa -- with an emphasis on collecting data from everyday patients -- reflects both a shift in the Vivus strategy and a change in FDA's outlook.   I think going forward a Steve Nissen will not be able to trash drugs of companies that he doesn't work for to the advantage of products from firms that he does with a sloppy meta-analysis.   (As as aside, Nissen's  use of a meta-analysis to attack Eric Topol's research on the value of using gene tests to select drugs for stenting procedures was recently laughed off and ridiculed.)  And companies that want to move a new product to market would do well to seek approval based on those sub-groups where the benefits exceed the risk.  And to be able to monitor disease progression and treatment response after market with simple blood tests would advance approval even more.   The more risk can be defined and measured at the subgroup or individual level, the less chance anti-innovation forces will have to block new devices and drugs that have clinical utility. 

That's what The Critical Path was supposed to do.  It sounds like the Qnexa decision was made consistent with that mission.

http://www.fda.gov/.../Drugs/EndocrinologicandMetabolicDrugsAdvisoryCommittee/UCM292317.pdf  Read More & Comment...

Bad News about Counterfeits -- "Over There" is now "Over Here"

02/22/2012 08:42 AM |

How did counterfeit Avastin enter the American drug supply? One reason is that profiteers masquerading as pharmacists are selling unsafe, unregulated, mislabeled, repacked, and co-mingled drugs to unsuspecting consumers – in Europe. “Over there” the cause of this malaise is known as parallel trade. Here at home we call it by another name -- drug importation. Whatever the moniker, its bad medicine. European parallel trade is the weak link in the western world’s supply chain – and the direct cause of our current misadventures with Avastin.

Last year over 140 million individual drug packages were parallel imported throughout the European Union — and a wholesaler repackaged each and every one. This means that, literally, parallel traders open 140 million packets of drugs, remove their contents and repackage them. But these parallel profiteers are in the moneymaking business, not the safety business. And mistakes happen. For example, new labels incorrectly state the dosage strength; the new label says the box contains tablets, but inside are capsules; the expiration date and batch numbers on the medicine boxes don’t match the actual batch and dates of expiration of the medicines inside; and patient information materials are often in the wrong language or are out of date.

This means that drugs purchased from a British pharmacy to an unknowing American consumer could come from European Union nations such as Greece, Latvia, Poland, Malta, Cyprus, or Estonia. In fact, parallel traded medicines account for about 20% (one in five) of all prescriptions filled by British pharmacies. In the EU there is no requirement to record the batch numbers of parallel imported medicines, so if a batch of medicines originally intended for sale in Greece is recalled, tracing where the entire batch has gone (for example, from Athens to London through Canada to Indianapolis) is impossible. Caveat Emptor is bad health care practice and even worse health care policy. Safety cannot be compromised, even if the truth is inconvenient.

Surprised about the path of counterfeit Avastin?  You shouldn’t be. There is ample evidence linking parallel importation with the growing threat of counterfeits. In August 2004 counterfeit medicines were found in the legitimate British supply chain after a patient complained of a crumbling tablet. The UK’s Medicines and Healthcare products Regulatory Agency (MHRA) issued an immediate alert. Only days later, the MHRA had to issue another alert after a different counterfeit medicine was found in Great Britain’s legitimate supply chain. Pharmaceutish Weekblad, a respected pharmacy journal in the Netherlands, recently reported that counterfeit medicines found in the Netherlands at the end of last year entered the legitimate supply chain through parallel importers. Stubborn facts.

Danish parallel trader, CareMed, said it was the link in the journey of fake Avastin from Switzerland to Britain. The fake has been traced back as far as Egypt before entering a complex supply chain that ended in California. (Roche does not make Avastin in Egypt.)

CareMed has admitted to sourcing the drug from fully licensed Swiss distributor Hadicon, and the 167 vials of Avastin 400mg were sold from a transit warehouse in Switzerland directly to a transit warehouse in Britain.

"In fact under our distribution license -- for patient safety reasons -- as a distributor, we are not even entitled to open the packages and check that, for example, batch numbers of the vials correspond to the batch numbers of the packages."

CareMed sold the drugs to a "highly valued and experienced customer" in Britain, which informed it at the end of November that the batch numbers on the vials did not match the packages.

The World Health Organization (WHO) estimates that 8-10% of the global medicine supply chain is counterfeit — rising to 25% or higher in some countries. The largest counterfeit market with close proximity to the EU free trade zone is Russia, where the generally accepted estimate is that 12% of drugs are counterfeit. Now that the Baltic nations of Latvia, Lithuania, and Estonia have joined the European Union, WHO has warned that an increase in the risks of counterfeits entering the EU supply chain is “obvious.”

Facts are stubborn things.

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A Timely Coincidence

02/21/2012 04:55 PM |

Just before the end of 2011, the FDA approved an adult indication for Prevnar 13 Prevnar 13 -- a conjugate containing a pneumococcal bacteria bound to a protein to help the body’s immune system recognize the bacteria and will have a longer lasting immune response. (Currently the only vaccine for pneumococcal bacteria approved in the United States for adults 50 years of age or older is Pneumovax which is only effective against invasive pneumonia and not effective on the more common, pneumococcal pneumonia.)

But at the ACIP meeting (that begins tomorrow and runs through Thursday), there is only a discussion of the 13-valent pneumococcal conjugate vaccine. Just a discussion.  While that’s important, a positive recommendation is crucial.  Otherwise it is, in many unfortunate respects, just talk.

Coincidentally, today a new study in JAMA (just released today) points to not only the therapeutic benefit of this new adult indication – but also to its cost effectiveness.

A computer-based cost-effectiveness analysis in the February 22/29 issue of JAMA suggests that use of the 13-valent pneumococcal conjugate vaccine (PCV13) might prevent more pneumococcal disease compared with the current 23-valent pneumococcal polysaccharide vaccine (PPSV23) vaccination recommendations -- while remaining economically reasonable.

Kenneth J. Smith, M.D., M.S., of the University of Pittsburgh School of Medicine, and colleagues conducted a study to estimate the effectiveness and cost-effectiveness of pneumococcal vaccination strategies among adults 50 years of age and older. Using various modeling techniques, simulations were performed in hypothetical groups of U.S. 50-year-olds.

(Note: FDA gave pneumovax 50 years and older indication, ACIP recommendation is for 65 years old or older.)

With no vaccination, the estimated lifetime risk from age 50 years onward for hospitalized NPP was 9.3 percent, for IPD was 0.86 percent, and for death due to pneumococcal disease was 1.8 percent. Among the different vaccination strategies compared in the analysis, those using PPSV23 were estimated to prevent more IPD than strategies using only PCV13, while strategies using 2 scheduled PCV13 doses were estimated to prevent more NPP.

Regarding cost-effectiveness, in the base case scenario, administration of PCV13 as a substitute for PPSV23 in current recommendations (i.e., vaccination at age 65 years and at younger ages if co-existing illnesses are present) had an estimated cost of $28,900 per quality-adjusted life-year (QALY) gained compared with no vaccination and was more cost-effective than the currently recommended PPSV23 strategy.

With routine vaccine administration at ages 50 and 65 years, it was estimated that PCV13 costs $45,100 per QALY compared with PCV13 substituted in current recommendations. Administration of PCV13 at ages 50 and 65 years followed by PPSV23 at age 75 years was estimated to cost $496,000 per QALY gained.



The authors’ write that, “There are no absolute criteria for cost-effectiveness, but in general, interventions costing less than $20,000 per QALY gained are felt to have strong evidence for adoption, interventions costing $20,000 to $100,000 per QALY have moderate evidence, and those costing more than $100,000 per QALY have weaker evidence for adoption.”

In an accompanying editorial, Eugene D. Shapiro, M.D., of the Yale University School of Medicine, writes that this analysis provides a reasonable framework with which to approach this issue. “What does seem clear is that improvements in vaccines against pneumococci and increased rates of immunization likely will result in continued reductions in the incidence of infections due to this common pathogen.”

Any further questions?

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Intent Dissent

02/21/2012 08:11 AM |

What makes Bob Temple so endearing (and his opinions so enduring) is his blunt truth telling. Alas, he is often the Cassandra of White Oak.

Recently Temple stated his belief that regulations on product promotion should not impede companies from rebutting findings from comparative effectiveness research involving their products.

This may not sound like a big deal – but it’s a clarion call for those who understand the imperative to systematically and scientifically counter the counter-detailing efforts coming thanks to the tens of millions of tax dollars earmarked for such efforts by the Patient Protection and Affordable Care Act (PPACA). 

According to the Pink Sheet, “The subject of asymmetry in the reporting and commenting on CER findings has been a key point of discussion for NPC as CER has taken on a more visible role within the health care debate. Some suggest manufacturers of products subject to CER might have difficulty discussing the findings of the research given FDA restraints on commercial speech.”

Perhaps not.

Speaking at the February 9^th conference, Asymmetry in the Ability to Communicate CER Findings: Ethics and Issues for Informed Decision Making (hosted by the National Pharmaceutical Council and cosponsored by the National Health Council and WellPoint), Temple said there is “no FDA view … that drug companies are condemned to silence about their products outside of formal promotion or perhaps published articles. If there’s something published that seems wrong, is based on poorly designed meta-analysis and so on, I don’t see any impediment to answer that and companies do answer that all the time."

Indeed, Bob seemed surprised and displeased that industry has sat by while the grand poobahs of comparative effectiveness share their questionable conclusions.

According to Dr. Temple, “A recent example might be newspaper assertions that antidepressants have no long-term benefit and really don’t work. This has been published repeatedly, and I’d like to see a rebuttal from the people who make antidepressants, because I think the published reports … are wrong. [FDA] may get around to rebutting, but somebody else might want to, and I don’t think there is any impediment to doing that."

Pedal to the metal?  Not so fast. Bob qualified his remarks by saying (appropriately) that companies should be mindful of how FDA regulates speech when (and if) they decide to rebut wrong or misleading information from a comparative effectiveness research (whether or not it’s government-funded). “It is clear to me that a sponsor could correct or dispute a CER statement by a payer, or even the government, as long as the correction was not itself promotional."

And there’s the rub.  Just what does “promotional” mean – and who is to judge?

Temple gives a good example of how to avoid such a problem:

“In recent months, we’ve seen companies disagree publically with meta-analyses, with epidemiologic conclusions they considered unsupported on methodologic grounds, and that’s OK, although making their own [conclusions] probably would not be."

In other words, it’s not “promotional” to point out a comparative effectiveness study’s design flaws and, therefore, the errors of its conclusions. If such an approach is “compliant,” it opens up tremendous opportunity in countering so-called “academic” detailing.

Or does it? Temple’s is a powerful voice inside the FDA – but it is only one voice. If Secretary Sebelius’ interference in the agency’s Plan B decision is any indication – might not his view be similarly overturned by the mandarins in the Humphrey Building?  After all, the comparative effectiveness studies under debate are funded by PPACA and fielded by the Agency for Healthcare Research and Quality (AHRQ). And, to put it bluntly, the current administration has not looked kindly on those who question either its philosophical motives or legislative methods. Industry is deemed guilty until proven guilty. The current modus operandi seems to follow Franz Kafka’s statement that, “My guiding principle is this: Guilt is never to be doubted.”

Which brings us back to the question, what does promotional mean?

A recent paper by Coleen Klasmeier (a former FDA attorney and currently the head of Sidley Austin’s FDA regulatory practice), addresses this issue head on. She points out that “The FDA approach is one of delicate balance – of forbidding off-label promotion without undue incursion into the ability of physicians to obtain information about off-label uses from manufacturers.”

This issue of “undue incursion” seems to dovetail nicely with Bob Temple’s notion of focusing on design flaws and incorrect conclusions. But what of intent?

Well – intent is in the eyes of the beholder.  Where one person might see a robust discussion of study design, another might see promotional intent.  The foundational problem, as Klasmeier eloquently points out, is the FDA’s reliance on “multifactorial tests rather than bright-line standards.”

Plainly stated, regulators at the FDA (and particularly those who must address thorny First Amendment issues) embrace ambiguity over predictability. It gives them almost limitless power. Industry, on the other hand, wants and needs an evidence-based regulatory framework that provides predictable standards for their communications efforts. Bright lines. Predictability is power in pursuit of the public health. Minus such an effort, we get the troubling example of Par Pharmaceuticals.

In a pending First Amendment suit against the FDA, Par contends 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.

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

If a company can be challenged when it discusses strictly on-label uses of a product, how much more convoluted, challenging and intimidating will it be to challenge a government-funded and government-detailed comparative effectiveness study?

Disputing comparative effectiveness studies – or any research for that matter -- need not fall into the chasm of promotion (off-label or otherwise). To lump scientific discourse into this slippery silo is to court both agency action and political attention. Alas, as Klasmeier writes, “The off-label problem reflects the accretion of administrative interpretations over the years.”

“Accretion” – otherwise known as mission creep.

Klasmeier continues, “… the commercialization of an investigational new drug is not to be construed to interfere with a manufacturer’s entitlement to engage in scientific exchange.”

And isn’t debating the flaws of a research study scientific exchange -- even if (and especially when) such exchanges raise questions about conclusions that are contrary to any given company’s marketing and sales objectives?  How does the issue of intent play into compliance when legitimate scientific exchanges also impact promotional considerations?

On which side should regulators err?

The answer is as easy as it is difficult – regulators should err on the side of the public health. And perhaps the best precedent is FDAMA Section 401, which expressly permits companies to provide reprints of peer-reviewed medical journal articles on off-label studies (as long as they have a pending supplemental application with the agency).

But – as a word to the wise – let’s remember the astute observation of William Blake that, “A truth that’s told with bad intent, beats all the lies you can invent.”

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Obama's Nurse Ratched

02/17/2012 11:05 PM |

Obama's Nurse Ratched

By Robert M. Goldberg on 2.16.12 @ 6:07AM
The American Spectator

Behind every powerful health care mandate under Obamacare is a power-hungry woman named Kathleen Sebelius. As the Health and Human Services Secretary, she has unprecedented power under Obamacare to control health care decisions, the approval of medical products and the national biomedical research agenda. The Secretary is not only the key player; she is the only one on the field. "The Secretary shall…" is mentioned more than 1000 times in the new health care law.

Sebelius is using that power to promote a liberal agenda and Obama's re-election.

She pushed the contraception edict. Her staff wrote the rules that decided Catholic hospitals and charities are not religious institutions. And she was the one who came up the with the "accommodation" in response to resistance to the mandate: just make the health plans pay for it even if the customers of the plan don't want it.

It is clear Sebelius cares only about imposing a worldview and policies to win support for Obamacare. A reporter asked Sebelius: "If a Catholic nonprofit is paying for your insurance coverage, isn't it paying for contraception if you are getting the coverage through that same insurer?"

Sebelius: "The federal employees health plan… costed this as no cost, free, no cost, because adding contraception and having some employees take advantage of that coverage lowers the overall cost of the health plan."

Free? She will tell insurers to suck up the cost and still force religious organization to offer the benefit. Or else.

This is not an aberration. It is quintessential Kathy: She rules by fiat and if you cross her she will crush you. And when she rebukes and bullies, Sebelius, like Nurse Ratched, claims she is doing so for our own good. As the Big Nurse said: "We do not impose certain rules and restrictions on you without a great deal of thought about their therapeutic value."

In 2002 Sebelius was the insurance commissioner in Kansas and campaigning for governor. She blocked the sale of Blue Cross Blue Shield to Anthem Health because she "thought" doing so would raise premiums. In 2003 when Sebelius was elected, Anthem decided against the merger. (Meanwhile, from 2000-2009 premiums in Kansas rose nearly 100 percent.)

Her use of power during the last days before a congressional vote on Obamacare was also Ratched-like in nature: Sebelius told the Association of Health Insurance Plans: "You can choose to continue your opposition to reform. If you do and reform goes down in defeat, we know what will happen." She threatened insurers that if they continued to blame their rate increases on the new health overhaul they could be excluded from health insurance exchanges.

Sebelius subsequently hauled in health plan execs in 2010 to explain why premiums were going up by 10-20 percent in certain states. And she tried to censor one health plan altogether when it sent a letter to Medicare customers about premium increases. She explained she was only doing this in ensure everyone gets basic care. Or a Nurse Ratched would say: "I tell you this hoping you will understand that it is entirely for your own good that we enforce discipline and order."

Last year Sebelius appeared at several fundraisers for Democrat congressional candidates and the 2012 re-election effort. Sebelius broke all campaign spending records in the 2006 re-election bid and she is regarded as a fundraising machine. In part this is due to the fact that the used the power of her office to punish enemies and reward pals. As HHS Secretary she has the power to mandate coverage, exclude health plans, reject payment for new technologies. She has shown she's not afraid to use this power to shake down and intimidate groups holding views contrary to her own and reward her allies. And since the Independent Payment Advisory Commission reports to her, she has absolute control over what Medicare and Medicaid will pay for in the years ahead.

Which is why Sebelius (who attacked Super PACs in 2010) is one of Obama's most important surrogates in the effort to raise outside money for his re-election. She has spoken at Planned Parenthood and the National Abortion Rights Action League events. Sebelius has attended fundraisers for several politicians over the past two years. And in the process she will use Obamacare as both carrot and stick to get her way.
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The Fighting Illini

02/17/2012 12:24 AM |

Illinois legislators introduce bill to limit biosimilar substitution

Illinois State Reps. Ann Williams (D) and Edward Acevedo (D) introduced a bill in the state's General Assembly that would limit the substitution of a biosimilar for a prescribed product by Illinois pharmacies. The bill (HB5581) would permit substitution only when five criteria are met: the biosimilar has been determined by FDA to be interchangeable with the prescribed product; the prescribing physician does not specifically prohibit substitution; the patient provides written consent for the substitution; the pharmacist notifies the prescribing physician in writing within 24 hours after the substitution; and the pharmacy and the prescribing physician retain a written record of the substitution for no less than five years.


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Cancer Patients Fume Over Counterfeit Avastin

02/16/2012 11:15 PM |

By KATIE MOISSE (@katiemoisse) Feb. 15, 2012
ABC News

Cancer patients are furious that a counterfeit version of the drug Avastin has landed in U.S. clinics.

Avastin, which is made by the California-based company Genentech, is used in combination with chemotherapy to treat cancers of the colon, brain, kidneys and lungs. But the counterfeit lacks the tumor-starving ingredient some patients need to survive.

"It's an outrage," said Diane Barraza, 48, who takes Avastin for stage IV colon cancer. "For a company to sell this drug, put it in our blood, it's an outrage."

The U.S. Food and Drug Administration announced Tuesday that 19 clinics in California, Texas and Illinois may have purchased the phony Avastin from Quality Specialty Products, an "unapproved" foreign supplier also known as Montana Health Care Solutions. The counterfeit vials are labeled "Avastin" but indicate "Roche" as the manufacturer. Roche is the parent company of Genentech.

"The counterfeit contains no Avastin, no generic Avastin, no active ingredient whatsoever," Genentech spokesman Ed Lang told ABC News. Lang said the contents of the vials are still under investigation.

For patients like Barraza, a fake cancer drug would be the cruelest con.

"To sit in the chemo chair and watch that stuff drop into my veins," said an emotional Barraza, who lives in Fullerton, Calif., with her 6-year-old daughter. "It's all I've got. And it might just be water?"

Avastin is expensive, costing upwards of $650 for a small vial. But Montana Health Care Solutions sold the counterfeit vial for $480, according to one of the clinics -- a cost savings of 25 percent.

"Obviously it makes good business sense to try to get the drug at a reduced cost," said Dr. Jack Jacoub, a medical oncologist at Orange Coast Memorial Medical Center in Fountain Valley, Calif. "But when you start to get drug pricing that's markedly different from that of the standard distributor, it should raise a red flag."

Only four U.S. distributors are authorized to sell Avastin to doctor's offices; another four can sell the drug wholesale to hospitals. Montana Health Care Solutions is not an authorized Avastin distributor. Jacoub, who treats Barraza, said his clinic buys Avastin in bulk from an approved distributor for $593.20.

Montana Health Care Solutions claimed to be based in Belgrade, Mont. But the company's recently disconnected phone number has a New Brunswick, Canada, area code. It's unknown whether Montana Health Care Solutions knew the Avastin was counterfeit. They also sold other cancer drugs, including Neulasta and Faslodex, at a significantly discounted price.

The FDA was alerted to the possible counterfeit in December 2011 by the Medicines and Healthcare Products Regulatory Agency in the U.K., according to Genentech's Lang. In a Feb. 10 letter, the agency urged the 19 clinics known to have purchased through unapproved distributors to "retain and secure" any unused drugs. The counterfeit Avastin vials have the lot numbers B86017, B6011, B6010, and the labels are slightly different.

Counterfeit or illegally imported drugs are rare in the U.S. but not unheard of. In 2008, heparin (a blood thinner) imported from China killed 81 Americans.

"Counterfeit drug makers have reached a level of sophistication where the real and fake products look almost identical," said Peter Pitts, president of the Center for Medicine in the Public Interest and former associate commissioner for the FDA. Pitts estimated that counterfeit drugs generated $75 billion in 2010, a figure expected to grow by 20 percent annually. "It's a low risk, high reward proposition. It's almost a perfect crime -- people aren't getting the drugs they need and they end up dying."

For Barraza, who will have four more Avastin treatments over the next two months, the thought of criminals profiting from her disease is sickening.

"I wish they could understand what it feels like to be a cancer patient, to take a drug and to suffer," she said. "I'd do anything to stay alive, but I need the right medication."

Read the full article here.
 
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Cough Medicine and Consumer-Centered Health Care

02/16/2012 12:46 PM |

Sometimes you need to state the obvious to make a point.   Or as Steve Martin once said:  "A day without sunshine is like, you know, night."

Such it is with cough and cold medicines.   A survey CMPI conducted on consumer use of such medications confirmed what we likely think we already know:

• Two-thirds (66%) of surveyed adults and 70% of surveyed parents rely on OTC cough medicines to treat their own and their children’s symptoms.
• Over the past year more than half of U.S. adults (57%) have taken cough medicines and 71% of parents have administered these medicines to their children aged four and older.
• 75% of consumers agree that OTC medicines provide relief of their cough symptoms so they can get a good night's rest.
• 68% of consumers agree that OTC medicines allow them to stay productive at work or school when they are not feeling well.
• 61 million consumers in the past 12 months have avoided missing work, school, or other scheduled appointments due to illness because they had access to OTC cough medicines to alleviate their symptoms (based on census data).

Not suprisingly, consumers like the freedom to get such medicines without waiting or paying for a doctor:

o 78% of consumers believe that it would place a burden on them and their family because they would need to visit a doctor.
o 74% of consumers believe that it would place a burden on them and their family because they would need to take time away from other responsibilities, such as work or school.
o 71% of consumers believe that it would limit their ability to provide care for their children.
o As such, 76% of consumers believe OTC cough medicines should remain available over-the-counter without restrictions.

The vast majority of Americans use cough and cold formulations because they are a save, convenient and affordable way to stop coughing.  And when you cough you -- or your children and people around you -- are uncomfortable, can't sleep, can't work.  And if we had to run to the doctor and get a prescription for every time we coughed or were stuffed up we would be spending a lot more money treating symptoms that, more often than not, resolve are their own.   Then again, running to the doctor, especially a pediatrician is just a figure of speech.  These days running to the doctor is like, well, not getting an appointment for days, sitting in an office with other parents and really sick kids, reading magazines that are so old they still have Mel Gibson on the cover. 

We did the survey for four reasons:  At a time when people are struggling to make ends meet, it's important to remember that OTC medicines save time and money.   Second, to show at a time when the government and nanny-crats are cracking down on school lunches brought from home, seeking to make sugar a controlled substance and telling us that contraception has to be free but we can't have access to new cancer drugs and vaccines that still have control over what we can do to take of ourselves and families might be -- given the times -- a precious liberty.   Third,  that there is wisdom in the crowd.   That the benefits of consumer empowerment outweigh the risks and that the risks themselves can be managed mostly by we-the-people by educating ourselves and each other.  Finally,  in the future turning more prescription medicines in OTC products is consistent with consumer-centered medicine, will save time and money and increase the number of people who take medicines in a routine and safe manner. 

These things may be obvious.   But too often they appear to be under assault.  Alerting so-called opinion leaders, experts, etc., that Americans value the freedom they have value to buy cough and cold medicines when they are coughing and have cold symptoms may be alerting them to the obvious.   But everything is obvious after the fact or when it's gone.

You can access the entire report, highlights and a press release on the CMPI website:  http://www.cmpi.org  Read More & Comment...