Latest Drugwonks' Blog
Two new articles on the issue of off-label promotion.
The first, courtesy of Bloomberg.com, is far from courteous or unbiased. Consider this quote from Jerry Avorn, a professor at Harvard Medical School and regular critic of the industry:
“Marketing departments of many drug companies don’t respect any boundaries of professionalism or the law.”
Untrue and unfair. That’s a pretty broad brush – but Dr. Avorn has never worried about the unintended consequences of hyperbole.
The Bloomberg article continues, “The widespread off-label promotion of drugs is yet another manifestation of a health-care system that has become dysfunctional.”
That’s outside of any citation – that’s just the reporter talking. Bad journalism.
And then back to Jerry Avorn:
“It’s an unbearable cost to a system that’s going broke. We can’t even afford to pay for effective, safe therapies.”
Now the article is confusing the issue of off-label promotion with off-label use. And that’s a much clearer articulation of the article’s broader agenda.
The complete Bloomberg article can be found here.
A much better omnibus discussion of off-label promotion can be found in the November issue of Nature Biotechnology. An excerpt:
“… on October 2, Allergan, in Irvine, California, filed a lawsuit against the FDA seeking to challenge off-label regulations. Allergan contends that agency rules stop them from sharing safety information about off-label use of approved drug Botox (Clostridium botulinum toxin). The company contends that Botox is effective for as-yet unapproved uses in spasticity, and given that physicians are already using it for that purpose, it is important to communicate information to reduce the risk of adverse events. Indeed, Allergan claims the regulations violate the right to free speech under the First Amendment of the US Constitution. But it also stands to reason that if the information it seeks to communicate was in the literature, Allergan would not have needed to file the suit.”
The complete Nature Biotechnology article can be found here.
Also quoted in the Bloomberg article newbie FDA employee Peter Lurie, who makes an important point, “Most physicians don’t keep track of FDA-approved uses of drugs.”
All the more reason for a robust and expanded “safe use” program by the FDA.
Label detailing aids anyone?
From today's New York Times:
F.D.A. Fighting False Online Claims About Swine Flu Treatments
You can buy healing gels that “create a barrier between you and the potentially deadly virus now spreading across the globe.” Or “ionic silver” that kills every known pathogen, germ, bacteria, virus or fungus within six minutes. “Spray Swine Flu . . . Gone . . . with ionic silver on your hands,” one ad claims.
Now that the White House has declared swine flu a national emergency, and with the H1N1 vaccine in short supply, many Web sites have been peddling swine flu nostrums.
The Food and Drug Administration has identified 140 different dubious products sold online and has sent letters to 75 manufacturers. It is violation of federal law to market products that claim to prevent or treat H1N1 and that have not been approved by the F.D.A.
The agency has gone after sellers of gloves, inhalers, masks, shampoos, herbal extracts, air fresheners and an array of vitamins that make claims about fighting swine flu. Some of the Web sites were fly-by-night operations that have since closed down.
The complete New York Times story can be found here.
Food for thought for those who continue to foolishy call for risky drug importation schemes.
The first is that, of 12,500 measured patient-doctor conversations in 2008, the research firm found only 23 requests for specific drugs.
That’s somewhat counterintuitive considering all the punditry and political bloviation about DTC advertising driving “unnecessary” prescribing. But it’s not at odds with studies (including those done by the FDA) that show that about 6% of all doctor visits in the United States are a direct result of a patient (also known as a consumer) having seen a DTC ad. Taken together, these results demonstrate that DTC ads drive patients to visit their doctors (a good thing) and that those visits do not result in inappropriate pressure to prescribe.
The other Verilogue item of interest is that the most frequently cited drug by patients was Boniva. The Boniva DTC campaign, features actress – and honest-to-goodness osteoporosis sufferer -- Sally Field.
Supportive data, via IMS Health, shows that prescriptions for Boniva were up 11% last year, and sales of the drug grew 25%, to $675.6 million. The message, according to Richard "Erik" M. Gordon, assistant professor at the University of Michigan's Ross School of Business, is “authenticity.” Gordon says that, "People want to believe a celebrity isn't just doing this because they were paid a pile of money."
Maybe so. But, in the 21st century, solid healthcare communications is a lot more complicated than finding a celebrity sufferer -- it’s about moving from “Gidget” (the role that initially made Ms. Fields a household name) to “Widget” (social media tools that communicate healthcare messages – pharmaceutical and otherwise – in more immediate, trusted, peer-to-peer ways). Friends and neighbors. Now that’s star power.
Bouquets to Boniva for doing it right. And brickbats to Senators, such as Minnesota's Al Franken, who believe that DTC is deliterious to the public health despite mountains of evidence to the contrary.
FDA Unveils Safe Use Initiative that Targets Preventable Harm from Medication Use
Agency also releases drug dosage guidance for measuring devices included with OTC medications
The U.S. Food and Drug Administration today announced the Safe Use Initiative, a program aimed at reducing the likelihood of preventable harm from medication use.
“Too many people suffer unnecessary injuries from avoidable medication misuse, errors and other problems. The FDA is launching the Safe Use Initiative to develop targeted solutions for reducing these injuries,” said FDA Commissioner Margaret A. Hamburg, M.D.
Millions of people are harmed every year from inappropriate medication use. Many injuries occur as a result of incomplete access to information about a drug, a patient, or the patient’s condition.
Other preventable sources of harm include unintentional misuse of medications, medication abuse, and attempts at self harm. Unintended exposure to prescription medications such as opioid drugs can cause harm, even death, in a single dose, if taken by someone other than the patient who was prescribed the medication.
“Only through coordinated interventions across all sectors of the health care system can we substantially reduce preventable injuries from using medications,” said Janet Woodcock, M.D., director of the FDA’s Center for Drug Evaluation and Research. "All participants in the health care community have a role to play in reducing the risks and preventing injuries from medication use.”
More detailed information on the new program was contained in a report, titled, “FDA’s Safe Use Initiative – Collaborating to Reduce Preventable Harm from Medicines.” The report was released by Drs. Hamburg and Woodcock at FDA’s annual Science Writers Symposium at the agency’s White Oak Campus in Silver Spring, Md.
As outlined in the report, the FDA intends to collaborate with health care professionals and other stakeholders to identify drugs and drug classes that are linked to preventable harm. A list of specific problems, cross-sector interventions for reducing harm from these problems, and the metrics for success will be developed.
The report highlights several risk-reduction projects that may benefit from Safe Use collaborations, including evaluating consumer medication information, communicating about the risk of inadvertent overexposure to acetaminophen, implementing safeguards against surgery fires caused by alcohol-based surgical preps, and avoiding contamination of multiple use medication vials.
To further advance the Safe Use Initiative, the FDA intends to hold a series of public meetings to gather feedback as the candidate list is being developed and will open a public docket to receive comments on the report and proposed candidate cases.
The agency also today made public new FDA guidance for companies that manufacture, market, or distribute over-the-counter liquid medications packaged with dosage delivery devices such as calibrated cups, droppers, syringes and spoons.
The guidance document, titled “Dosage Delivery Devices for OTC Liquid Drug Products,” was posted for advanced viewing in the Federal Register today.
Accidental overdoses can be caused by dosage delivery devices that are unclear or are inconsistent with the labeled dosing instructions.
"This new drug dosage guidance document is an example of steps that can be taken to ensure safer medication use,” said Woodcock. “Many accidental overdoses result from confusion about exactly how much of a drug to take. Better measuring devices will help patients, parents, and other caregivers use the right amount of these medications – the safest and most effective dose – especially for children.”
WHY YOU CAN'T GET SWINE FLU VACCINE
The shortage of swine-flu vaccine results not from drug- company greed or outsize demand but almost entirely from the government's decision to pander to unfounded and unscientific fear.
As The Wall Street Journal reported last week, the US government set out to have the H1N1 vaccine produced largely in single-dose syringes -- a demand that has set back production considerably, because multidose vials are far easier to make.
And the only reason to seek single-dose production was to please people needlessly worried about the preservative thimerasol, which is used to provide multiple doses of the vaccine. The fear -- utterly groundless and repeatedly debunked is that thimerasol can cause autism and other neurological disorders in infants and other young children.
If not for that decision, we'd have more than enough vaccine. Instead, because the government yielded to pressure from antivaccine fringe groups, we're behind the curve on protecting millions of children from swine flu.
It's a tribute to the effectiveness of pandemic planning and the introduction of new technologies that the nation will likely have plenty of H1N1 vaccine within a month.
Flu strains don't show up when expected. H1N1 was supposed to arrive along with the "regular" seasonal flu, but it began three months early. Using genomic technologies, public-health officials and such vaccine developers as Novartis and Sanofi-Pasteur isolated the H1N1 strain and identified antibodies for production in record time.
Yet, despite this technological ability to adapt quickly to a pandemic threat, our system has been hamstrung by pseudoscience evangelists.
The thimerasol scare, disproved time and again, persists in part because the same public-health entities that encourage immunizations have made significant concessions to small, persistent fear-mongering activist groups.
In 1999, the Food and Drug Administration and the Centers for Disease Control called for the maximum removal of thimerasol from vaccines -- even though both stated there was no scientific evidence of side effects.
Beyond pressuring the government, antivaccine activists have had an indirect effect on the private sector's ability to meet the need for vaccines. Lawsuits in the '80s claimed that DTP (diphtheria, pertussis, tetanus) vaccine caused brain damage; the court actions scared off investment in production facilities using the new recombinant technologies.
As a result, the number of firms producing DTP and other vaccines plummeted. In 1980, 18 companies made vaccines; by the end of the decade, only four were left.
The loss of innovation, investment and profitability in the vaccine industry means we have a gene-based development process for the 21st century -- but a production process that hasn't changed in the last 100 years.
We reap the consequences of that antiquated production process today -- visible on signs posted outside local drugstores and clinics across the country: "Out of H1N1 Vaccine."
But production hasn't been the only casualty of antivaccine hysteria. Since the 1980s, many children have been left unprotected against diphtheria, pertussis and tetanus. How many hundreds of thousands of American children have suffered, from pertussis or other diseases, because of a crackpot minority? How many more will suffer during the current shortage?
By bowing to the unfounded concerns of a few, our government has compromised the safety of many. It's done an admirable job, so far, of communicating with the public about the H1N1 threat and boosting immunization rates. But perhaps its most important job moving forward is to properly align policy with established scientific opinion and the public's best interests.
Twisting the canons of science endangers the public's health and exposes our children to real harm.
Robert Goldberg is vice president of the Center for Medicine in the Public Interest. rgoldberg@cmpi.org
According to Andrew Dawson, staffer for the House Ways and Means Committee, “The final CER product - whatever comes out of the Senate, whatever comes out of the House - they are different enough that where we end up in a conference report will be somewhere in the middle."
When Mr. Dawson refers to "CER," he means Comparative Effectiveness Research -- aka cost effectiveness, aka clinical effectiveness, aka healthcare technology assessment. But it's important to recognize that these are not all synonyms. (For example, in the long ago and forgotten stimulus package, $1.1 billion was set aside for clinical effectiveness research.)
The Senate Health, Education, Labor and Pensions Committee's reform package would create a new center in the HHS Agency for Healthcare Research and Quality to oversee CER. The melded House health reform bill, unveiled Oct. 29 would also create a center within AHRQ, though supported by a combination of public and private funding and receiving advice from an independent stakeholder commission.
Another key pending issue is how research data generated by CER may be used. The House has previously added language stating explicitly that data "may not be used to deny or ration care." The Senate Finance Committee version lets CER data be used in Medicare coverage decisions, though only providing several criteria are met and a single CER study is not the only basis for a decision.
The Congressional Budget Office has scored the CER provisions of the revised House bill as lowering Medicare outlays by $100 million from 2010 through 2019, but increasing non-Medicare outlays by $1.2 billion during the same period.
How can CBO score CER studies – that (1) according to the revised House bill aren’t supposed to be used “to deny or ration care” and (2) don’t exist yet? Hmm.
And the list of those testifying is also a guarantee of better-than-usual fare. That list (subject to change) can be found here.
Pharmaceutical marketers and the FDA are in a tough spot when it comes to social media. On the one hand, both recognize the importance of and opportunity in it. It's where the people are. It's where the action is. On the other hand there are those pesky regulatory concerns.
To quote that well-known FDA pundit -- Buffalo Springfield -- "There's something happening here. What it is ain't exactly clear."
And clarity (qua predictability) is the key to success for social media to become a powerful tool in advancing both marketing aims as well as the public health. Not mutually exclusive goals -- and not necessarily in that order.
Regarding Harry
The public option diverts attention from the legislation's real faults.
By KIMBERLEY A. STRASSEL
You couldn't swing a cat this week without hitting a discussion of the public option. Somewhere, in some Capitol office, Senate Majority Leader Harry Reid is grinning.
Two weeks ago, the subject of a government-run insurance plan was a sore point with the Nevadan. He didn't have the votes for it, his base was bitter, and he didn't want to talk about it. This week, a transformed Mr. Reid devoted an entire news conference to it. Americans support the public option! His caucus supports a public option! He supports a public option! The public option is in! No problem!
In the real world, this kind of behavioral shift lands you in a psych ward. In Washington, the press just marked it down to forces bigger than Harry. The majority leader had been pushed into a public option by his liberal members, we were told. Chuck Schumer was scarier than Ben Nelson. The Huffington Post was even scarier than Chuck Schumer. Poor Mr. Reid, clucked observers, had been backed into a corner.
Maybe. Then again, maybe he is majority leader for a reason. Maybe Mr. Reid didn't just wander out of the Nevada desert. Maybe he has a plan. Maybe, just maybe, he sees a big upside in turning the public option into the centerpiece of the health-care debate. After all, what does he have to lose?
Up for re-election next year, Mr. Reid is facing Nevada polls that suggest he's lost most voters outside his base. His base too, was slipping, with Moveon.org making him a punching bag for not embracing the public option. With this week's announcement, he is once again the hero of the left, and has that baboon off his back.
Who knows? It might even work. Mr. Reid included the fig leaf of an "opt-out" for states that don't want the public option. It's a ruse, but it might provide cover for votes. If not, he's got room to maneuver. There's the "opt-in" alternative, which even some Republicans claim to like. There's the fall-back "trigger," which re-earns him Olympia Snowe.
And if it doesn't fly, well, is that so bad? Mr. Reid can still say he gave it the varsity try. He'll get it to the floor and let those swing-state Democrats amend the public option away. Not his fault! What he also knows, even if the press doesn't, is that for all the big talk of his liberal members, they are the more likely to give way. Even without a public option, this bill is a big step toward a single-payer system. And it isn't as if any of them risk losing their seats by voting "only" for a $1 trillion health expansion.
Better yet, by turning the public option into the big, bad bogeyman, he makes it more likely he'll snag those swing-state votes in the end. Nebraska's Mr. Nelson, Arkansas's Blanche Lincoln, Indiana's Evan Bayh—they can all claim victory for stripping the bill of a national insurance plan, then feel comfortable voting for all the tax hikes and Medicare cuts that remain.
Speaking of tax hikes, premium jumps and Medicare cuts, notice how nobody is today talking about them? Mr. Reid surely has. The public option might be controversial in D.C., but the majority leader knows most of the country doesn't understand it, or assumes it doesn't apply to them. Most Americans already have health care that they like, and polls show their real fear is that this experiment will leave them paying more for less. This, not the public option, is ObamaCare's exposed jugular.
The insurers get this, which is why (as they now try to bottle the genie they helped loose) they are issuing reports on how "reform" will double or triple premium prices. It is why America's Health Insurance Plans, the lobby group, has run ads in swing states warning about huge cuts to Medicare Advantage. Some of the grass roots get it, too, which is why Americans for Tax Reform is now live on TV in Nebraska noting Sen. Nelson has signed its taxpayer pledge and that he'd violate it by voting for the bill's nearly $500 billion in tax increases.
If Mr. Reid had pulled the plug on the public option, these highly unpopular policy issues would be front and center. As it is, the public-option sideshow is sucking up all the air, and will continue to. It even overshadowed liberal divisions, such as union pushback on Cadillac-plans taxes. Maybe, just maybe, Mr. Reid likes it that way.
Granted, this is the cynic's view of Democrats' health-care strategy. Mr. Reid did, after all, goof last week, failing to round up the votes to pass his party's proposed "fix" to Medicare reimbursement rates. Maybe he doesn't know which way is up. Maybe he is taking a flier.
Then again, anyone who has watched this debate has earned the right to cynicism. Democrats are determined to get a health bill, and Mr. Reid is no rube. His opponents—those trying to save the country from this wreck of a bill—would be wise not to forget it.
PETER J. PITTS is president of the Center for Medicine in the Public Interest and a former FDA Associate Commissioner.
The following testimony delivered by Paul Offit in 2006 about how an outbreak of Asian flu was prevented in 1957 provides a perspective on how well we are doing today. Now if only CDC would tell the anti-vaccine and thimerasol scaremongers to go shove it!
www.fas.org/irp/congress/2006_hr/biodefense.html
PHILADELPHIA
Dr. Offit. Good morning, Senator. My name is Paul Offit. I am Chief of Infectious Diseases at Children's Hospital in Philadelphia and a former member of the Advisory Committee on Immunization Practices to the CDC.
I would like to talk briefly today about an event that occurred 50 years ago in 1957, the only time in our history that we have made influenza vaccine in advance of a pandemic, because I think there are several lessons that can be learned from that event. On April 17, 1957, Maurice Hilleman, a scientist working at the Walter Reed Army Medical Research Institute, read an article in the New York Times titled ``Hong Kong Battling Influenza Epidemic.'' The article stated that 250,000 people, 10 percent of the entire population of Hong Kong, had suddenly come down with the flu.
Hilleman found that this outbreak signaled--feared that this outbreak signaled the start of the next pandemic. So the next day he sent a telex to the Army's 406th Medical General Laboratory in Zama, Japan, asking them to send him specimens from people infected with the virus. The first specimens arrived 1 month later on May 17, 1957.
For 5 days and nights, Hilleman worked to determine whether the influenza virus circulating in Hong Kong could be a pandemic strain. He tested sera from members of the American military and adults in the general population, but could not find anyone whose immune systems had seen this virus before. Hilleman then sent the virus for testing to the United States Public Health Service, the Commission on Influenza of the Armed Forces Epidemiological Board, and the World Health Organization. They found that only a handful of people in the United States and the Netherlands had antibodies to the virus. Because few people in the world had antibodies to stop it, the influenza virus circulating in Hong Kong in 1957 could spread from one country to the next unchecked.
Hilleman then sent the virus, now called Asian flu, to six American-based companies. He figured that if he were to have any chance of saving lives companies would have to make and distribute tens of millions of doses in only 4 months. Hilleman sped up the process by ignoring the Division of Biologic Standards, the Federal agency responsible for regulating vaccines.
He also asked vaccine makers to advise chicken producers not to kill their roosters, even though it was late in the hatching season. He knew that production of tens of millions of doses of vaccine would require at least 200,000 eggs a day.
As predicted, in September 1957 Asian flu entered the United States from both coasts. The first laboratory-proven cases occurred aboard naval vessels in Newport, Rhode Island, and San Diego, California. The first outbreak was triggered by a San Diego girl who carried the virus to an international church conference in Grinnell, Iowa. The second occurred in Valley Forge, Pennsylvania.
Companies made the first lots of Asian influenza vaccine in June 1957 and vaccination began in July. By late fall, 40 million doses were distributed in the United States. Within a few months, influenza infected 20 million Americans. 70,000 died from the disease. Worldwide, the pandemic killed at least 4 million people.
The Surgeon General of the United States, Leonard Burney, later said, quote: ``Many millions of persons we can be certain did not contact Asian flu because of the protection of the vaccine.'' For his efforts, Maurice Hilleman won the Distinguished Service Medal from the American military.
Several features of this outbreak and our response to it are instructive. First, Hilleman had to rely on reading an article in a newspaper to know what was happening in Southeast Asia and he had to wait 1 month before he received samples of the virus. Today the international community of scientists, clinicians, and public health officials, armed with sophisticated virological techniques, are much better at surveillance of outbreaks and characterization of possible pandemic strains.
Second, Hilleman called on six U.S.-based influenza vaccine makers. Today no U.S.-based companies make the inactivated vaccine. Sanofi Pasteur has a manufacturing facility in Swiftwater, Pennsylvania, but is not a U.S.-based company.
Third, Hilleman had to rely on eggs to produce vaccines. Recognizing that egg production is unreliable, the President's pandemic flu plan has effectively encouraged vaccine makers to gear up facilities to grow influenza virus in mammalian rather than avian cells. For example, GlaxoSmithKline recently purchased a manufacturing facility in Marietta, Pennsylvania, and MedImmune, the makers of a live attenuated influenza vaccine, will manufacture vaccine in mammalian cells in Maryland. Given that the influenza vaccine is generic and inexpensive, it is unlikely that vaccine makers would have done this without financial encouragement.
Fourth, Hilleman completely ignored the Division of Biologic Standards, the Federal agency responsible for regulating vaccines. At the time vaccine regulation was in its infancy, regulated by a small division within the National Institutes of Health. Today vaccines are regulated by the Food and Drug Administration and they do an excellent job. Vaccine regulation I think has helped to make vaccines arguably the safest and best-tested products that we put into our bodies. But the process is slow and if we are to make vaccine quickly the regulatory process would have to be streamlined significantly.
Fifth, Hilleman was a committee of one. He took responsibility for shepherding each step of the process. It would be impossible for him to do that today, but it would certainly be of value for one central agency to be held accountable for making sure that vaccine was made, tested, and distributed quickly and efficiently.
Sixth, Hilleman never considered liability protection for vaccine makers. In 1957 pharmaceutical companies were not held liable if they were not negligent in the production or design of their product. Ironically, the birth of liability without negligence for pharmaceutical companies began with a jury verdict against a vaccine maker, Cutter Laboratories, only a few months later. However, it is clear that vaccine makers would not make a pandemic flu vaccine today without substantial protection from frivolous litigation.
Thanks for giving me an opportunity to speak before this committee.
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.
