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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
| Adolescent | 270 | 36 | 1805 | 138 |
| Toddler | 385 | 33 | 2793 | 105 |
| Infant | 447 | 36 | 3429 | 271 |
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
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.
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Key Part of Drug-Counterfeiting Bill Dies in Congress
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.”
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.
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.
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.
Here is a final summary of the House/Senate conference report.
No REMS nonsense either.
Onwards.
"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.
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
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.
Center for Medicine in the Public Interest is a nonprofit, non-partisan organization promoting innovative solutions that advance medical progress, reduce health disparities, extend life and make health care more affordable, preventive and patient-centered. CMPI also provides the public, policymakers and the media a reliable source of independent scientific analysis on issues ranging from personalized medicine, food and drug safety, health care reform and comparative effectiveness.
