Drug Shortages: Discretion, yes. Expediency, no.

06/22/2012 07:48 AM |

Despite what you might have read in a recent Congressional report, drug shortages are neither the exclusive fault of the FDA, nor does the FDA represent the entire solution.

Monday, at the big BIO bash, I spoke on a panel about the issue.  My complete remarks can be found here.  The gist of my comments is that, while the FDA has an important role to play – the role of economics (ASP, 340B rebates, Group Purchasing Organizations) are the primary reasons we find ourselves in the fix we’re in.

A few points:

* Market price stability is crucial. A US government analysis of average sales prices shows that oncology sterile injectables 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 same period.

* Safety is non-negotiable.  Alleviating a shortage by shorting GMPs is a bad and dangerous pathway. Expediency causes as many problems as it solves.

* That being said, regulatory discretion must be part of the solution.  With 30% of production capacity off-line because of FDA issues, the agency must work with manufacturers to find creative, science-based solutions. My fellow panelist, Gerry Migliaccio (senior vice president of network performance at Pfizer) said his experience with other regulators around the world is that if you create a "science- and risk-based action plan," industry can often address quality issues without disrupting supplies of essential drugs.

* The FDA might allow some temporary fixes that fall in line with that thinking, explained the FDA’s Jouhayna Saliba (senior regulatory program manager at the FDA's Drug Shortage Program). If a company discovers impurities that could be filtered out, the agency might allow the product to be shipped along with filters and explanations of how they are to be used in order to avoid a shortage, she said.

* Who inspects the inspectors? Per that 30% of manufacturing capacity off-line due to FDA issues, I challenged Jouhayna to undertake an agency audit to see why there’s been such a jump in GMP issues. It’s hard to believe that year-over-year, production quality control has suffered such a significant lapse. Is there something wrong in the way FDA inspectors (many of them still wet behind the ears and eager to please) are doing their jobs? It’s a question worth asking – and answering.

For a brief 5-minute BIO-produced video on the topic, see here.

As Saliba said, "This is not a problem that is going to go away soon."

But the sooner the better.

Richard Feynman said, “The worthwhile problems are the ones you can really solve or help solve.”

Drug shortages are a worthwhile problem to solve – and we need to keep our collective eyes on the prize.   Read More & Comment...

CDC Thinks Exposing Babies To Meningitis is More Cost-Effective Then Immunizing Them

06/21/2012 01:41 PM |

I'm not making that up..

CDC -- through the Advisory COmmitee on Immunization Practices -- which recommends what vaccines will be covered by the government and health plans under the new health law -- has decided that new vaccines for meningitis that prevents thousands of cases where children are maimed and hundreds of deaths each year isn't worth it.   A study by the Dr. Chris Stomberg of Bates-White Economic Consulting entitled:  Policy Priorities and the Value of Life raises some disturbing questions that Congress should focus on.  

Dr. Stomberg writes:

"In contrast to its Medicare program, the government makes life and death decisions at the other end of the age scale, guided in part by cost considerations. In fact, the CDC has come to explicitly consider cost-effectiveness studies when setting nationwide childhood immunization policy. 

When the first meningococcal vaccine for adolescents (ages 11 to 55) was approved by the FDA in 2005, CDC promptly included it on the routine vaccine schedule. ACIP’s recommendation at that time was supported, in part, by information found in a cost-effectiveness study (Shepard et al. 2005)
that was led by a team of investigators from the CDC and published in the journal Pediatrics.

                                                                   Cases            Deaths        QALYS                  Cost per 
                                                                    Averted         Averted       Gained                  QALY Gained

This study estimated the benefits in terms of deaths averted, cases averted, and QALYs gained if the meningococcal vaccine were administered to three different populations: adolescent, toddler and infant.....the study actually found that the greatest benefits would be accrued by
administering a meningococcal vaccine to the infant population, and the lowest cost per QALY would the fact that prior studies In early 2010, after it reviewed the results of a cost-effectiveness study of meningococcal vaccine for infants, ACIP continued to hold its position against including any of the forthcoming infant vaccines in its routine recommendations once approved by FDA.

In Aril 2011, the FDA approved the first meningococcal vaccine for infants, with other products on the horizon for this age group as well. A
routine recommendation for infant use of meningitis vaccines has not yet been made.What this example highlights is the importance of cost in the CDC’s deliberations over its infant meningitis immunization recommendations. It provides an interesting counterpoint to Medicare’s decision to continue coverage of Avastin. While Medicare has elected to continue covering the use of a drug for which the FDA has withdrawn approval, CDC has refrained from recommending (and paying for) the use of an FDA-approved vaccine. Whether intentional or not, there is apparently a deep divide in how the government thinks about healthcare spending at the two ends of the age spectrum. With no consistent method for evaluating health programs, this is to be expected. "

You can read the entire paper here. 

http://www.bateswhite.com/events.php?EventID=106  Read More & Comment...

The Dawn of Eurosimilarity

06/21/2012 07:49 AM |

Perhaps we should call them "Eurosimilars."

According to the Pink Sheet, European Health Commissioner John Dalli has announced that the EU would be prepared to accept applications for biosimilar products with data from original biologic medicines that are not sourced from within the Union. The move, while expected, will breathe new life into a stagnant industry sector with few EU authorizations each year and is likely to send pharmaceutical manufacturers the surest signal yet that this is time to jump quickly onto the bandwagon.

Speaking at the European Generic medicines Association (EGA) annual meeting, Dalli acknowledged that while Europe had lit the touch paper of biosimilars development by coming up with the first regulatory framework, the explosion of biosimilars across the globe was gathering pace at an impressive rate. “I believe that this is a natural and positive trend, but I realize that the application of the EU rules on biosimilars do not fully match this trend,” he said. He added that the EU was ready to rectify this situation.

While Dalli’s announcement represents a significant boost for biosimilars manufacturers, the real icing on the cake is that EU acceptance of third-country comparability data could happen very quickly. This is because the commission now says that such a move only requires a re-interpreting the law, rather than a full-fledged legislative process, which could take up to five years. This would be accompanied by an update of the overarching guideline.The global development concept is also gathering pace in the U.S., where draft guidance suggests that “under certain circumstances” a sponsor might use data from studies comparing a proposed product with a non-U.S.-licensed product. FDA has confirmed in writing that an EU-referenced product could be used in comparative trials for application in the U.S. (Please note the use of the conditional “could.”)

The complete Pink Sheet story can be found here.   Read More & Comment...

A Missed Opportunity on Track-and-Trace

06/20/2012 04:18 PM |

Key Part of Drug-Counterfeiting Bill Dies in Congress

By Barnini Chakraborty

A key provision in a bill designed to track medication and protect the country’s supply chain from the threat of fake or stolen drugs was killed this week in Congress. Instead, House and Senate lawmakers agreed on a watered-down version that creates penalties against drug counterfeiters but does not include the track-and-trace system the U.S. Food and Drug Administration says is needed to stop dangerous -- sometimes lethal -- drugs from reaching Americans.

“It’s unfortunate that the process is moving forward without track-and-trace at this point,” said Sen. Michael Bennet, D-Colo., adding that both Democrats and Republicans came close to a consensus during the conference process but ultimately could not reach a compromise.

Public health advocates and the FDA have pushed for a system that tracks each individual drug bottle through the supply chain using electronic barcodes. The system is already being used in Belgium and Sweden. Lawmakers said Tuesday they were unable to bridge disagreements over the system and instead dropped the provision. 

While industry groups say they will continue their fight for a federal track-and-trace program, realistically it’s unlikely to happen anytime soon. Trying to resurrect the measure as a stand-alone bill later this year would face big hurdles in both chambers.

The risks and realities of counterfeit drugs were highlighted earlier this year when the FDA reported two separate batches of a fake cancer drug making its way into doctors' offices in the U.S.

In April, a new batch of counterfeit cancer drug Avastin was discovered. The 120 phony vials were purchased in Turkey under the name Alzutan and shipped through Britain by U.K.-based middlemen in a strikingly similar shipment pattern as the fakes that first hit U.S.
doctors' offices in February.

The repetition of the crime exposes vulnerabilities in the global medicine supply chain and the need to track medicine coming into the country.

Big profits and low penalties have made the drug counterfeit industry attractive for criminals in the U.S. and abroad. Current penalties for peddling fake prescription pills are about the same as selling knockoff Prada bags on the street.

Once relegated to poor countries with weak regulations, the industry has turned into a multi-billion dollar one. According to The Center for Medicine in the Public Interest, activities related to counterfeit drugs generated about $80 billion in 2011. Former FDA Associate Commissioner Peter Pitts tells FOX Business that number could reach the $100 billion mark in the next decade.

So what are counterfeit drugs and how are regulators trying to stamp out the trade?

Simply put, a counterfeit drug is fake medicine. It may be contaminated, contain the wrong active ingredient, a toxic ingredient, or none at all. Or it could have the right ingredient but the wrong dose. Either way, the result poses both a direct and indirect threat to public health.

The drug counterfeiting industry has grown globally at a break-neck pace as pharmaceutical supply chains stretch across continents with the help of the Internet. In some countries, counterfeit prescription drugs make up 70% of the drug supply and are linked to thousands of deaths. The problem also extends to non-pharmaceutical medical products like faulty electronic medical equipment and syringes. In places like India and China, fake drugs have crowded out real drugs in marketplaces.

Massive free trade zones have also been used by counterfeiters to create toxic pipelines that enable middlemen to smuggle fakes into the country. In 2007, a sting operation revealed that large amounts of counterfeit drugs were supplied through a complex six-country arrangement using a free-trade zone in Jebel Ali, Dubai. The drugs were manufactured in China, sent through Hong Kong to the free-trade zone in Dubai to Britain then the Bahamas and back to Britain where the products were mailed to customers with United Kingdom postage.

They were then sold on a website that made American customers believe they were buying medicine from a Canadian website.

The incident illustrated how counterfeit drugs moved in a global economy and the difficulties behind regulation.

Here at home, the pharmaceutical industry has shifted a large part of its manufacturing operations and supply sourcing overseas. Nearly 40% of the drugs Americans take are imported and nearly 80% of the active ingredients in the drugs on the American market come from overseas sources.

The proliferation of additional handlers, suppliers and middlemen creates “new entry points through which contaminated, adulterated and counterfeit products can infiltrate the drug supply,” said FDA Commissioner Margaret Hamburg at the Partnership for Safe Medicines Interchange annual conference. “As a result, the supply chain – from raw material to finished product – has become more complex and mysterious involving a web of repackagers and distributors in a variety of locations.”

Prosecuting cases, which has been slow in the past, is finally gaining traction.

Last year, Manuel Calvelo, a Belgian citizen, was sentenced to 48 months in federal prison on charges of operating an Internet pharmacy that sold $1.4 million worth of misbranded and counterfeit drugs as well as controlled substances. Calvelo, who was extradited from Costa Rica to Kansas, admitted to setting up web-based pharmacies, including allcheapdrugs.com, allcheappills.com, allnaturalpharmacy.com.

Calvelo operated a customer service call center in the Philippines and issued payments to employees through wire transfers via Western Union in the Philippines, Costa Rica and the United States.

Calvelo’s sites, which operated from 2005 to 2008, offered more than 40 prescription drugs including brand names Zoloft, Lipitor and Viagra. Controlled substances for sale included Alprazolam (sold under the brand name Xanax), Lorazapam (Ativan) and Clonazepam (Klonopin).

Calvelo’s alleged co-conspirator, Canadian citizen Jeffrey Westmoreland, remains on the lam.

In February 2011, a federal jury in North Carolina convicted Awni Shauaib Zayyad on five counts related to the sale and possession of counterfeit Viagra and Cialis pills. Zayyad sold more than 500 counterfeit Viagra pills at a Charlotte, N.C., convenience store that was being investigated by law enforcement.

And in Denver, Shenyang Zhou, a Chinese national, was sentenced to 7 years in prison on charges of trafficking and attempting to smuggle in counterfeit versions of the weight-loss drug known as “Alli.”

  Read More & Comment...

AMA: Open wide and say "no."

06/20/2012 04:12 PM |

From today's edition of the Los Angeles Times:

Soda taxes endorsed by AMA as a way to fight obesity

By Mary MacVean

The American Medical Assn. voted Wednesday at its annual meeting to adopt a policy that recognizes soda taxes as one way to pay for anti-obesity programs, and that says any such tax revenue should go to programs to treat obesity and related conditions.

“While there is no silver bullet that will alone reverse the meteoric rise of obesity, there are many things we can do to fight this epidemic and improve the health of our nation,” AMA board member Dr. Alexander Ding said in a statement. “Improved consumer education on the adverse health effects of excessive consumption of beverages containing added sweeteners should be a key part of any multifaceted campaign to combat obesity.”

In its statement, the AMA noted that studies have shown sugar-sweetened beverages to be “strongly and consistency associated with increased body weight and a number of health conditions like type 2 diabetes.” Sugar-sweetened beverages account for about 46% of Americans’ added sugar intake.

“Where taxes are implemented on sugar-sweetened beverages, using revenue for anti-obesity programs and educational campaigns explaining the adverse effects of excessive consumption of these beverages will help to reduce the consumption of these caloric beverages and improve public health,” Ding said.

The AMA is holding its annual meeting in Chicago this week. Proposals at previous AMA annual meetings about taxes on sugary beverages failed.

The American Beverage Assn., an industry group, issued a statement saying it supports efforts to reduce obesity, but funding such programs with a tax on sugar-sweetened drinks is “discriminatory” and “misguided.”

 “The body of science proves, and real world evidence demonstrates, that taxes on sugar-sweetened beverages will not have a meaningful impact on obesity.  History also shows that revenues from existing soda taxes are not being used to improve public health. Americans can't trust that new taxes would be used any differently,” the beverage group said in its statement.

Conversation about soda has heated up in the last several weeks. Among the voices has been that of New York Mayor Michael Bloomberg, who proposed banning the sale of sodas bigger than 16 ounces at theaters, arenas and other spots starting next spring.

The public policy organization Center for Medicine in the Public Interest, a nonprofit group dedicated to free-market healthcare reform, says the mayor’s heart is in the right place. But the idea is wrong-headed, just like Prohibition was, the group says.

“It reeks of nanny-statism and diverts attention away from the issue. Plainly speaking, it trivializes the problem. Prohibition doesn't work. How many times do we have to learn this lesson?” the group said in a statement.

CMPI’s president, Peter Pitts, a former associate commissioner of the federal Food and Drug Administration, said by phone that taxes are a better idea – if the money funds public education programs.

People need to take responsibility for their health, and the government needs to mount efforts to help them – “not just carrots but sticks,” Pitts said.

“It’s not about punishing the people who make the products. It’s about people who have choices not using those choices wisely,” he said.

Taxing sugar-sweetened beverages is one of the more controversial proposals in the public debate. Opinions are sharply divided about whether taxes work.

The AMA’s Council on Science and Public Health recommended Wednesday’s vote, saying that current research models predict that a tax of a penny an ounce on sweetened drinks would lead to a 5% reduction in the prevalence of overweight and obesity and reduce medical costs by $17 billion over 10 years.

The report says such taxes alone are unlikely to have a significant effect on obesity and related conditions. But it says that a penny per ounce excise tax would be imposed on producers and wholesalers. Such a tax is estimated to reduce sugary drink consumption 10% to 25%, which one analysis cited in the report says could reduce premature death by 26,000 instances over 10 years, the report says.

Federal dietary guidelines advise people to drink water instead of sugary drinks and to limit added sugars to 100 calories or less for women, 150 for men. Twelve ounces of most sugary drinks contain 130 to 150 calories of added sugars, the report says.

Supporters of taxes on sweetened drinks cite the role of tobacco and alcohol taxes in reducing rates of smoking and alcohol consumption; opponents question whether sugary drinks should be singled out among contributors to obesity and whether taxes would work.

  Read More & Comment...

Our Friend John Vernon

06/20/2012 01:43 PM |

It is written in the Talmud that "The highest form of wisdom is kindess."

Our friend and colleague John Vernon, who passed away suddenly on June 19th, was very wise.

The health policy community is well aware of John's brilliance as an economist and his contribution to the literature on thevalue of biomedical
innovation.  That legacy will endure.  And we are honored to have worked alongside him on several publications, particularly in the area of comparative 
effectiveness research, which he pursued with passion and intellectual precision.

But we knew John best for his gentle determination in the face of incredible personal tragedy,  his genorosity and dedication, his open heart and devotion to his friends, his family and his son.  

His death is truly tragic.  He was to begin a new position and a new health policy program at Purdue, close to his son.  We had talked at length about Indiana being a great place to live and raise a family.   It seemed that the one person who deserved a blessed existence was getting his due, plus interest.

Now we can only remember by continuing his work and following his example of kindness, courage and unconditional love. 

The Talmud also observes:

“There are stars who's light only reaches the earth long after they have fallen apart. There are people who's remembrance gives light in this world, long after they have passed away. This light shines in our darkest nights on the road we must follow.”

So too will our friend John Vernon's kindess light the way for us, now and in the the future, no matter how dark the days ahead.   We will miss him greatly but will honor him even more. 

  Read More & Comment...

Bloomberg's Big Gulp on Biosimilalrs

06/20/2012 07:07 AM |

The channel -- not the mayor.

Biosimilar Drug Development is a Challenging Proposition
Insights from a Bloomberg Panel Discussion

On June 12th, inThought co-hosted a Bloomberg Industries Biosimilars Panel Discussion with Owen Fields, vice president of Worldwide Regulatory Strategy at Pfizer and Peter Pitts, president and co-founder of the Center for Medicine in the Public Interest.

Discussion centered on the commercial viability of biosimilars, focusing on pricing, the increasing influence of payors, and various life cycle management strategies being implemented as barriers to biosimilar adoption.

Panelists also debated key issues of interchangeability, extrapolation, naming, and use of foreign reference data.

The panel discussion continually highlighted the uncertainties and difficulties facing companies seeking to develop biosimilars, whether through the FDA biosimilar pathway or the traditional BLA approval process.

With the requirement for significant upfront investment, uncertain regulations, potential for huge litigation costs, and an uncertain degree of acceptance by physicians and patients, the development of differentiated biosimilars (“biobetters”) may ultimately be the more compelling business model for companies wishing to participate in the biosimilar market.

A more detailed review of the panel discussion can be found here.

  Read More & Comment...

PDUFA Consensus

06/19/2012 03:34 PM |

Almost home.

Here is a final summary of the House/Senate conference report.

No REMS nonsense either.

Onwards.  Read More & Comment...

Entrepreneurs Will Empty the Hospitals By Personalizing Medicine

06/19/2012 11:22 AM |

In an interview with The Guardian,  former CMS administrator Donald Berwick told a reporter:

"When you invite entrepreneurial private sector investors into the delivery of care, under most payment systems, they will be very interested in volume. They will be very interested in doing more things to people and you may find that you lose control of that level of discipline to the disadvantage of patients. When more things are done, more unnecessary things get done and more hazard enters the system – not just cost.

"You want hospitals that seek to be empty, doctors that seek to be idle, machines that are few. In healthcare you want to find the way to help that is the least invasive of the person's life and body. A volume-based system does not have that incentive structure."

Berwick misunderstands of the motivations of entrepreneurs and investors in health care and the role that government plays in skewing incentives.   He also ignores how Moore's Law is remaking medicine, a subject I write about in the just released Scientific American Worldview   (My article begins on page 88.)  The rapid decline in the cost of the even more rapid digitization of health information is being combined with genomic knowledge to create low cost point of care diagnostics,  accelerate the shift to same day surgery,  permit the development of targeted oral therapies for illnesses that once required transplants or infusions,  create treatments tailored to specific groups of individuals so as to avoid miss and hit type medicine.  All the things Berwick claims he believes entrepreneurs are against.  

One obstacle is reimbursement.  That's shaped by government and private insurers who follow the government's lead.   So Medicare will pay more for injectible drugs than oral treatments for MS or cancer and more for treating congestive heart failure than preventing it.    Health plans will pay less for same day surgery for hip replacements if the surgeon is out of network than it will for the traditional form of the procedure even though it costs as much and the recovery time is twice as long.   Both want to use CER to determine whether or not to pay for a product based on cost, not the "least invasive of the person's life and body."    Otherwise, why would have Medicare rejected gene testing for warfarin?  Is it better to keep sending people to hemotologists to have blood drawn? 

Entrepreneurs should have a passion for achieving what Berwick envisions: less intensive and complex care and better health.   But the obstacles to achieving that are not the entrepreneur's vision nor the technology.   They are the design of the products, the resistance of physicians and 'stakeholders' to adoption and a reimbursement system that discourages innovation in favor of stepwise incrementalism.   I bet Berwick would agree on that score...

CMPI pulled together entrepreneurs who have a passionate capacity for change, a record of accomplishment and a commitment to accelerating the commercialization of personalized medicine.   The result was The Personalized Medicine Acceleration Working Group and a report: From Promise to Performance: Commercializing Personalized Medicine.

I think you will find the report and it's recommendations timely.    PPACA is -- whether it's ruled unconstitutional or not -- constructed as if current trends in health and health care delivery will continue for decades with nothing changing.  Nothing will be further from reality.   The design of new products that embody technological progress will create value for millions of people around the world.   The problems of health care seem large because the tools we currently have for solving them are inadequate.   As the tools get better, the tasks will become simpler and perhaps many will disappear.  I's the entrepreneurs and companies who made up our working group -- and the Kauffman Foundation who supported it's efforts -- that is making it possible. 

  Read More & Comment...

The other Supreme Court healthcare ruling

06/19/2012 06:48 AM |

In a 5-4 decision the Supreme Court has ruled that pharmaceutical sales reps are not entitled to overtime pay because their job is to … sell drugs.

Yes folks, it took our nation’s highest court to decide that the job of a rep is “not merely to make physicians aware of the medically appropriate uses of a particular drug. Rather, it was to convince physicians actually to prescribe the drug in appropriate cases.”

And now back to our regularly scheduled programming.

The obscure we see eventually. The completely obvious, it seems, takes longer.

-- Edward R. Murrow

  Read More & Comment...

More On Generic PDUFA Politicking

06/18/2012 01:02 PM |

I want to continue my discussion of Section 1131 of the Senate version of PDUFA (S. 3187) that would compel an innovator company that has a REMS in place to sell "samples" of their product to potential generic competitors.   PDUFA POLITICS: GENERICS SEEK PROFITS AND FORSAKE SAFETY

My colleague and tireless crusader for free market healthcare Grace Marie Turner has a concise post at NRO's Critical Condition health blog that raises an important point I did not address:

"This provision also faces a potential constitutional challenge.  Such FDA intrusion into the marketplace would be unprecedented because the government would be compelling a commercial transaction between companies that does not involve a willing seller and willing buyer."

Grace-Marie's point is grounded in both the FDA statutory authority and previous Supreme Court rulings that anti-trust claims are not grounds for forcing a company to share it's intellectual property with it's competitors.   In the past, when Congress enacted statutes requiring innovator companies to share IP or data absent an exclusivity period or protections they did so in stand-alone bills (Hatch-Waxman and biosimilars) and not as amendments that, as Grace Marie notes, are "tucked" into another bill.  (Though the biosimilars measure was folded into PPACA)

Further, the exclusivity granted to innovator companies extends, in particular cases, to REMS programs.  Specifically 10 percent of all REMS require elements to assure safe use (ETASU) that include training, websites, track and trace technology to link companies, wholesalers, pharmacists, physicians and patients,  software systems that integrate prescribing information with data collected to monitor safe use.   These are proprietary systems without which a drug is considered unsafe.  It's a criminal activity to sell knowingly sell unsafe drugs.   Companies can incur criminal and civil liability even for selling such drugs with the understanding that they will be used in a 'safe' manner if the drug winds up being mis-used or harming someone.  Will generic companies assume the cost of litigation and damages?   What safeguards are in place to assure that both the administration of a REMS and product testing are done overseas where Congress has raised concerns about FDA's oversight? 

Grace Marie also notes that the "REMS provision is expected to save the government at least $100 million over ten years (for reasons that are unclear even to careful observers). The risks to innovation and patient safety are incalculably larger."

That's an understatement.  Just as the original estimates of the savings from biosimilars were vastly overstated and unreliable, so too are the estimates of hundreds of millions of dollars in savings from generic versions of drug with REMS.   REMS, especially those with hard-wired systems to assure safe use, are expensive to develop, maintain and update.   The cost of REMS will be passed on to consumers in the form of higher prices.  My guess is CBO and the sources it relied on to develop the cost-saving estimates did not take into account the requirement that generic companies will need to create a REMS for the drugs they want to get outside of REMS.    

And I also bet they did not look at the impact this amendment might have on drug shortages.   Maintaining an ETASU program is an expensive proposition.  Most of them are required of cancer drugs or drugs used in treating cancer patients.   What's the point of accelerating generic development of products only to create shortages of the drugs down the road?   The PDUFA bill has a whole section on addressing drug shortages.  Not a word on how the cost of REMS might affect that problem.  

Finally, In a previous post I wrote:  "And now, because the Supreme Court ruled that innovator companies are liable for harms done to patients by the administration of a generic version of their drug  (Wyeth v. Levine)   any screw up because of a sloppy REMS or the purchase of a product outside the REMS or even an adverse event could be grounds for suing an innovator. "  

I failed to also note that a more recent Supreme Court ruling could also put innovator companies in more legal danger.  In PLIVA Inc. v. Mensing, 131 S.Ct. 2567 (2011) "the Court ruled that FDA’s regulations preventing generic drug manufacturers from changing their labeling except to mirror the label of the brand-name, Reference Listed Drug (“RLD”) manufacturer (whose drug product is approved under an NDA) preempt state-law failure-to-warn claims against generic drug manufacturers, because generic drug manufacturers are unable to comply with both federal and state duties to warn. Since the Court issued its decision, scores of court decisions have been issued dismissing litigation against generic drug manufacturers on Mensing grounds. "

So that might mean innovator companies will still be on the hook for updating REMS well after it stops manufacturing a drug.   It's one reason Roche has pulled out of making Accutane and the iPLEDGE program.   

There's another wrinkle to the liability issue.  As the FDA Law Blog notes:  Two months ago, Senator Leahy noted that the Mensing decision “creates a troubling inconsistency in the law with respect to prescription drugs.” This is a reference to the U.S. Supreme Court’s March 2009 decision in Wyeth v. Levine, 555 U.S. 555 (2009), in which the Court held that state-law tort actions against a brand-name drug manufacturers for failure to provide an adequate warning label are not preempted.  

Leahy has introduced The “Patient Safety and Generic Labeling Improvement Act.” The bill would amend the FDC Act to add new section 505(w): "Notwithstanding any other provision of this chapter, the holder of an application approved under subsection (j) may change the ‘Warnings’ section of the labeling of a drug so approved in the same manner as the holder of an approved new drug application under subsection (b), unless the Secretary prescribes by rule another manner.

Section 1131 could open up another double standard of tort liability.  At the very least, it complicates Leahy's effort to develop a stand-alone bill.  

It is an ill-considered amendment that was rejected once before because it was considered extreme to force a company to sell a product to a competitor who wants to make money by copying it.    Because it also threatens patient safety, exposes innovator companies to unknown liability and may contribute to drug shortages, another approach to reconciling REMS with generic drug approvals is needed.   Read More & Comment...

Contraception, who cares?

06/18/2012 06:25 AM |

From the June edition of MedAd News:

Contraception, who cares?
By:  Peter J. Pitts

During an episode of “Mad Men,” someone asks (apropos of an advertising campaign for pantyhose), “What do women want?” Strolling by, agency principal Roger Sterling quips, “Who cares?”

Who cares, indeed?

There’s been a lot of news lately about pharmacists not wanting to be forced to dispense medicines about which they have moral objections, specifically Plan B, “the morning after pill.” A thorny topic, to say the least. Yet, despite all the hoopla from the usual suspects, there has been total silence from an important voice in the debate – the pharmaceutical industry.

On the one hand, that’s not surprising. Why, after all, would anyone want to interject themself into such a no-win, high stakes, high profile battle? But doesn’t a manufacturer who makes a product have a responsibility to stand up and be counted when their product is under attack?

(And, let’s face it, contraceptives are under attack. No value judgment here – just a fact.)

What? Pharma take a stand? Not only is this not unheard of, it is regular and accepted practice when scientific questions are raised. It is regular and accepted practice when safety and efficacy are debated.  It is regular and accepted practice when legislative questions arise.

Here’s a relevant example – pseudoephedrine. When many state and federal legislators wanted to ban (or severely restrict) the availability of many OTC products in order to address the scourge of methamphetamine (pseudoephedrine is a common ingredient, or “precursor,” in the manufacture of methamphetamine) both manufacturers and their trade association (the Consumer Health Products Association) went on the offensive.

But, then again, there’s no pro-meth lobby.

When it comes to pharmacists not wanting to dispense Plan B – there’s nothing but silence from the manufacturer. Has Planned Parenthood approached Teva (the maker of Plan B) to enlist its support? If so, what explains the company’s silence? And, if not – why not? Doesn’t Teva have the courage to speak out in favor of its own product? When the initial Rx-to-OTC switch debate was raging, Barr Labs (subsequently purchased by Teva) was quite vocal in its support of Plan B as an avatar for reproductive rights. Today – silence. Qui tacet consentire videtur? Not likely. So why is mums the word?

Could it be that leveraging reproductive rights at FDA was in Barr’s financial interest but that debating it “in the streets” isn’t? Is Teva afraid (should they side with Planned Parenthood and other such organizations) that there might be a boycott against many of its other products? 

Mums the word? Consider this couplet from Piers Plowman:

Thou mightiest beter meten the myst on Malverne hulles
Then geten a mom of heore mouth til moneye weore schewed!

That translates as, “You may as well try to measure the mist on the Malvern Hills as to try and get her to speak without first offering payment,” or, in more modern parlance, “Show me the money.”

Why the silence from Teva?  

It’s a shame and a sham that a principled stand on reproductive rights was silenced when it became associated with potential commercial risk – just as Secretary Sebelius’ recent reversal of FDA on further Plan B access was done to mitigate potential political repercussions. When politics and profit come before the public health – bad things happen.

As my father used to say, “A principle doesn’t count until it hurts.”

Ouch.
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PDUFA POLITICS: GENERIC SEEK PROFITS AND FORSAKE SAFETY

06/15/2012 03:32 PM |

The passage of the Prescription Drug User Fee Act (PDUFA) has stalled.   The generic drug industry, along with AARP, trade unions and some other organizations support a provision that they claim would simply require " brand-name drugmakers to provide samples of their medicines, including biologics. Generic drugmakers and their allies, including some insurers and pharmacy benefit managers, complain that brand-name drugmakers have been using the strict distribution provisions of the Risk Evaluation and Mitigation Strategies ( REMS) regulation as an excuse not to provide samples for development and testing."  

And the generic industy says that as a result drug companies are costing consumers and taxpayers billions.

That's the spin.   It's not about the samples.   It's about getting around REMS.  Generic companies never guarantee that they will replicate the REMS system that an innovator comany uses.    Anyone who has seen the citizen's petitions of the generic companies knows that.   So does the FDA.   Take the the case of Accutane (the acne drug that goes by the generic name of isotretinoin):  Despite a  program designed to limit fetal damage from the drug called iPLEDGE there were 122 pregnancies just in its first year.   And that was with just one program. 

By allowing "samples"  the provision would force FDA to approval countless versions of REMS programs that were designed for a single drug for a single use for a specific group of patients.   And now, because the Supreme ruled that innovator companies are liable for harms done to patients by the administration of a generic version of their drug  (Wyeth v. Levine)   any screw up because of a sloppy REMS or the purchase of a product outside the REMS or even an adverse event could be ground for suing an innovator.  

Finally,  it's not just giving samples.  Especially when it comes to the little things, like say, permanent birth defects, maybe we want to be a bit more careful.  Perhaps we want to be extra cautious about passing around samples without having a good reason to go outside a tightly controlled method of distributing and administering a specific group of drugs that has protected infants from damage up till now?   REMS are not one size fits all to be sure.  But take a look at this video about the effects of thalidomide before assuming that there's no risk in giving generic companies every sample of every drug they want.   I find it ironic that the same interests who demand more regulation of innovator companies for the sake of safety are willing to let safety slide for the sake of generic industry profits... 


http://www.youtube.com/watch?v=FK-RuOqdZ1M



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Hard to Swallow

06/15/2012 07:48 AM |

Let’s give credit where credit is due – Mayor Bloomberg’s heart is in the right place. Obesity (especially of the childhood variety) is an epidemic that is going to sink us all unless we can address it immediately and aggressively.

But we have to address it smartly.

The media circus surrounding the Mayor’s call to ban large sodas is just silly. It reeks of nanny statism and diverts attention away from the issue. Plainly speaking, it trivializes the problem.

Prohibition doesn’t work. How many times do we have to learn this lesson?  What works is personal responsibility and adherence to the Aristotelian Mean  (aka – moderation).

In the immortal words of Nucky Thompson, “First rule of politics, kiddo: Never let the truth get in the way of a good story.”

It’s time to put headlines behind us and move on to addressing the real story.

And we start right here with a short video --  “Big Gulp Empire.” Have a look and pass it on.

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Big Apple's Big Appetite For Food Control

06/14/2012 11:05 AM |

Not content to stop at keeping people from 20 oz bottles of Mountain Dew (but unlimited refills are fine) the Board of Health started coming up with other food items that it should portion control:  

“The popcorn isn’t a whole lot better than the soda,” said Bruce Vladeck, a senior adviser at Nexera Consulting  and one of the mayor’s appointees to the 11-member board. The board yesterday agreed to put Bloomberg’s big-soda ban up for a public hearing July 24, but also talked about the merits of limiting other high-calorie treats.  A large tub of movie-theater popcorn has up to 1,650 calories.


 Bruce Vladeck (center in photo) 

But why stop at regulating popcorn?

“There are certainly milkshakes and milk-coffee beverages that have monstrous amounts of calories . . . and I’m not so sure what the rationale is not to include those,” said member Dr. Joel Forman, a pediatrics professor at Mount Sinai.    (Milkshakes have calories?  Coffee coolattas too?  Shocking.) 

So wait.. I thought the enemy was sugar.  Or is it calories?  Or is it portions?  Or is it food?

Perhaps we should just wait until the Board of Health comes out with a government approved menu that we all have to buy from.  Scary thing is, as this poll shows,  there are enough social control freaks out there who would agree the government should regulate what we eat and drink:  



 And here's an enthusiastic defense of the nutritional police state by someone that calls herself "the portion teller."  (Oy)

http://portionteller.com/size-matters-at-least-in-nyc/



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FDA Approves Treatment for Rosa Nervosa

06/14/2012 07:21 AM |

Rosa Nervosa and Full Speed Ahead

BioCentury reports that the Reagan-Udall Foundation received $900,000 from FDA to support FY12 operations and infrastructure. The funds are the first from FDA since Congress created the foundation in 2007 as a public-private partnership to oversee and fund precompetitive research to advance drug development and regulation. FDA funding was previously blocked by the U.S. House of Representatives, led by Rep. Rosa DeLauro (D-Conn.), who claimed that the foundation could prompt FDA to lower its approval standards.

The FDA Amendments Act of 2007 authorized $500,000-$1.3 million annually from FDA to support the foundation, and also gave Reagan-Udall authority to accept private sector funding. The specific amount from FDA is determined annually between the foundation and the agency, but the foundation's Executive Director Jane Reese-Coulbourne said she does not expect further funding roadblocks.

Reagan-Udall has received $1.3 million in grants and donations to fund research, including a $60,000 grant last year from Susan G. Komen for the Cure to support a project on cardiotoxicity associated with tyrosine kinase inhibitors. By year end, the foundation expects to have a publicly-accessible database of genes and pathways associated with cardiotoxicity. Last May, the foundation also received a $1 million grant from the Bill & Melinda Gates Foundation to serve as a facilitator among global tuberculosis stakeholders in the Critical Path to TB Multidrug Regimens Project (CPTR), an initiative to test and seek approval for combinations of individual investigational TB drug candidates.

Huzzah!
 

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Mitt Earns a Gentlemen's D

06/14/2012 07:01 AM |

Part D that is.

On Tuesday Governor Romney discussed an alternative to the ACA (aka, “ObamaCare”) that would make the health insurance system more like a “consumer market” -- applying free-enterprise principles to the nation’s health-care system (letting competition drive down prices and increase choice and quality) rather than operate it like a “government-managed utility.”

In other words, precisely the model that has made Medicare Part D such a resounding success among seniors (as measured by participant satisfaction pushing 90%), below budget costs (the price of Part D over the next decade is expected to be nearly $120 billion less than originally estimated) and lower than expected premiums (in August 2011, HHS announced that premiums would be slightly lower in the drug program in 2012).

Smart partnership between government and the free market works.

It works at keeping costs low and – most importantly – improving care. As JAMA reported,  “Implementation of Medicare Part D was followed by increased use of prescription medications, reduced out-of-pocket costs, and improved medication adherence.” And this, in no small measure, significantly reduces more drastic medical interventions -- which in turn reduces our overall national health care spending.

It’s time for many on the left to address their PDDD (Part D Deficit Disorder) and embrace a free market solution to health care reform.

Governor Romney also wants to divert federal Medicaid money and other federal funding to state governments, making them responsible for covering the uninsured. He correctly recognizes that states are the laboratories of invention. (And that some labs are more successful than others – witness the success of “Healthy Indiana” vs. the albatross of the Bay State’s “Commonwealth Care.” The Governor speaks from personal experience.)

If the Supreme Court doesn’t entirely repeal the ACA, Governor Romney said he would work to repeal whatever remains of it on his first day as president by granting a waiver to all 50 states to opt out of the legislation’s restrictions.

 “We can get health care to act more like a consumer market, and if we do that and we stop making it like a big government-managed utility, we’re going to see better prices, lower costs and better care,” Romney said. “It’s happened everywhere we’ve applied consumer-market principles. Free enterprise is the way America works. We need to apply that to health care.”

Amen.

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CMPI: Scientific Group Recommends Steps to Promote American Competitiveness in Medical Innovation

06/13/2012 03:22 PM |

Scientific Group Recommends Steps to Promote American Competitiveness in Medical Innovation
New report calls for value-driven collaboration for design
and reimbursement of personalized medicine 

New York, NY (June 13, 2012)

A new report calls for greater collaboration and replacing comparative effectiveness research with value-driven design of new products in order to preserve American leadership in medical innovation and personalized medicine.

“From Promise to Performance: Commercializing Personalized Medicine” was produced by The Personalized Medicine Acceleration Working Group. The working group is a project of The Center For Medicine In The Public Interest and was established to recommend new pathways for the faster commercialization of tools and technologies that deliver personalized medicine. The report and the working group were supported with a grant from the Ewing Marion Kauffman Foundation (www.Kauffman.org).

Robert M. Goldberg, PhD, a working group member and author of the report notes: “Medical progress has been a source of economic growth and prosperity for the United States. Personalized medicine, because of its capacity to extend life and prevent illness, will be a source of future value and wealth. However, the nation’s ability to commercialize such products has declined even as the capacity to do so has grown in countries such as China, India, and Brazil.”

The working group focused on how to design and reimburse new products that reflect increased value to consumers.

The working group recommends adopting a value-driven approach to the design and development of personalized medicine. Simply put, that means investing in design elements that make medicine easier and more effective for consumers or end-users and ensuring that proof-of-concepts and prototypes achieve that goal.

To do so, it recommends the refinement and use of a value-driven equation to measure improved patient-centricity and reduced complexity relative to the cost of using a new technology. Such an equation can take into account the preferences of health plans, consumers, and doctors prior to both FDA review and adoption. It is, therefore, an approach to measuring value for reimbursement purposes built into the design of products.

It also recommends that two institutions involved in the working group – The Scripps Translational Research Institute and the Austen Bioinnovation Institute of Akron – collaborate to create a usability lab that would use the value-driven equation and help entrepreneurs engage in value-driven design and engineering.

The working group recommends replacing the current approach government and health plans use to decide whether to pay for personalized medicine. Reimbursement processes come after FDA approval and do not measure the value of new personalized technologies to add to the value of health and increase simplicity. Value-driven design would build the needs and preferences of patients, health plans and physicians into the design of products.

A separate paper developed for the working group estimates that comparative effectiveness research (“CER”) may reduce the number of new medicines by 57 over the next 10 years and cause the United States to forgo nearly $10 trillion in health value.
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The report – “From Promise To Performance: Commercializing Personalized Medicine” – can be downloaded here: http://cmpi.org/reports-newsletters/reports/from-promise-to-performance

The second report -- "Uncertain Innovation: The Effect of Comparative Effectiveness Research (CER) On Personalized Medicine" -- can be downloaded here: http://cmpi.org/reports-newsletters/reports/uncertain-innovation 

Reporters interested in scheduling an interview with the authors of the report should contact CMPI Vice President Bob Goldberg at rgoldberg@cmpi.org or 212-417-9169.

About CMPI
The Center for Medicine in the Public Interest, a non-profit public policy group dedicated to research-based free market reforms for the health care industry.



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Government Detailing by Number

06/13/2012 10:18 AM |

It's do-it-yourself detailing!

Total Therapeutic Management (TTM) is the company chosen by AHRQ to develop the agency’s so-called “academic detailing” program.

(“Academic” in quotations since the majority of detailers are pharmacists. It’s really government detailing – in every sense of the word.)

Barry Patel, TTM’s CEO, has made available the materials that his reps are using to re-educate America’s doctors (particularly the high prescribing ones).

Those non-FDA reviewed detail aids can be found here.

Slides cover the therapeutic areas of Breathing Conditions, Cancer, Developmental Delays, ADHD, Autism, Diabetes, Digestive System Conditions, Gynecology, Health and Blood Vessel Conditions, Infectious Diseases, HIV/AIDS, Mental Health, Muscle, Bone, and Joint Conditions. And there’s the promise of more to come!

 

For a more, um, detailed discussion of government detailing and TTM’s remunerative involvement therein, see this new paper from the May edition of the Drug Information Journal.

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CMPI: Personalized Medicine Placed at Risk by Comparative Effectiveness Research

06/12/2012 05:41 PM |

Personalized Medicine Placed at Risk by Comparative Effectiveness Research, says Center for Medicine in the Public Interest
CMPI says requirements under federal health care reform would deprive Americans of medical innovation worth trillions over 10 years

New York, NY (June 12, 2012) --- Personalized medicine – treatments targeting individual risk of disease -- can increase life expectancy and generate $13 trillion in health value – but comparative effectiveness research would reduce investment in such innovations according to a report released today by the Center for Medicine in the Public Interest (CMPI), entitled: “Promoting Innovation and Health: Personalized Medicine or Comparative Effectiveness Research?”

"Our analysis shows that personalized medicine can increase life, well-being and the social value of health but also demonstrates that CER increases the cost and uncertainty of investing in such innovation," said John A. Vernon, Ph.D., a professor at the Purdue University, Krannert School of Management and co-author of the study. "CER will deny our nation better health and much needed biomedical investment."

The federal health reform law requires government-run comparative-effectiveness research, which will purport to evaluate the costs and benefits of different treatment options -- and use these studies to decide what medical innovations government and health plans should pay for and to limit what technologies doctors and patients can choose.

Proponents of CER claim it can increase investment in personalized medicine. But the CMPI study, conducted for its Personalized Medicine Acceleration Working Group, found that CER will reduce the level of investment in biomedical research by $75 billion over 10 years. There would be 60 fewer new personalized medicines available over the next decade if CER is required before marketing.

“We need to build upon the promise of personalized medicine,” said Robert Goldberg, Ph.D., Vice President of CMPI and co-author of the study. “Commercialization of innovations that reduce cost and extend life contribute to our nation’s prosperity and our global competitiveness. Policymakers should find ways accelerate the adoption of personalized medicine rather than adding regulatory requirements that increase the cost and risk of innovation.” 

The study was conducted for The Personalized Medicine Acceleration Working Group, a CMPI project focusing on actionable steps that can be taken to speed up the commercialization and adoption of personalized medicine. The study and the working group were supported with a grant from the Ewing Marion Kauffman Foundation (www.Kauffman.org)
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The report -- "Uncertain Innovation: The Effect of Comparative Effectiveness Research (CER) On Personalized Medicine" -- can be downloaded here: http://cmpi.org/reports-newsletters/reports/uncertain-innovation

Reporters interested in scheduling an interview with the authors of the report should contact CMPI Vice President Bob Goldberg at rgoldberg@cmpi.org at 212-417-9169.

About CMPI
The Center for Medicine in the Public Interest, a non-profit public policy group dedicated to research-based free market reforms for the health care industry.
 
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