Latest Drugwonks' Blog
From today’s Wall Street Journal:
FDA spokeswoman Sandy Walsh said there's "no systemic change in how the FDA is approaching drug approvals."
From Albert Einstein:
Insanity: doing the same thing over and over again and expecting different results.
And onwards to PDUFA V.
Hyperbole and misdirection aren’t going to solve the problem of the slippery slope towards government-run health care – it’s going to hasten it.
No – not “death panels” (although this Palinian shibboleth certainly falls into this category) but rather statements to the effect that the FDA’s decision to remove Avastin’s breast cancer indication was “a crude cost calculation.” Not true. Not helpful.
In today’s Wall Street Journal, David Rivkin and Elizabeth Foley write that, “The FDA made a crude cost calculation; as everyone in Washington knows, it wouldn't have banned Avastin if the drug cost only $1,000 a year, instead of $90,000.”
“Everyone?” Not really. For those who understand what actually goes on at the Food & Drug Administration it’s not about “cost” as much as it is about “choice.” And on that note Rivkin and Foley get it right:
“The Avastin story is emblematic of the government's broader agenda to ration care based on cost and politics. Once ObamaCare comes into full force, such rationing will be pervasive. When the government sees insufficient benefit, all but the wealthiest and most politically connected will have to go without.”
We are being railroaded down the tracks towards Uncle Sam, MD – but the FDA’s ruling on Avastin (whether you agree with it or not) was based on the agency’s reading of the science. Trying to tag the FDA with a decision based on cost may be convenient – but it’s wrong.
Such hasty proclamations trivialize the urgent and legitimate arguments against the current cost-versus-care direction of American health care – and makes it all the more difficult to counter and correct.
Per the new HHS regulation that pays for “voluntary” end-of-life counseling as part of seniors' annual physicals – just what makes it voluntary? Does a person need to ask for it? Will there be a discussion guide? If so, who will prepare the talking points? When are such conversations "appropriate?" And since physicians are being incentivized to provide this service, where are the "best practice" guidelines? These are only a few of many unanswered questions.
The Wall Street Journal reports that:
The office of Oregon Democrat Earl Blumenauer, the author of the original rider who then lobbied Medicare to cover the service, sent an email to supporters cheering this "victory" but asked that they not tell anyone for fear of perpetuating "the 'death panel' myth." The email added that "Thus far, it seems that no press or blogs have discovered it, but we will be keeping a close watch.
The Journal continues,
The affront is that Medicare needs to sneak around in order to offer a type of care that is routine in private insurance. If the medical experts in Congress haven't decided that some treatment or service is worthy of the fee schedule, then the program won't pay for it even if it is in the best interests of patients.
Set your TiVo for CSPAN.
DDMAC is conducting a study of how consumers and physicians understand the information in print ads and drug labels. But it’s got a fatal flaw – it’s not double blind.
In comments on the proposed study design, Merck suggested removing statements from the draft physician questionnaire that the drug is fictitious on the grounds that this might bias the results and instead label it a "potentially new drug." FDA rejected this idea for physicians, though it agreed to a bit of deception on the consumer questionnaire. And they’re right. Alas, the FDA disagrees.
"FDA had many internal discussions regarding this issue and decided that because of the particular [physician] sample, it is necessary to be upfront with them about the nature of the drug," the agency states in a notice scheduled to be published in the Federal Register on Dec. 23.
"Physicians will be more savvy about the particulars of the chemical entities and the realism of the clinical benefits and we do not wish to make them skeptical of our purposes," FDA states. "We agree that this approach is preferable for consumers and so we will inform them that this is a potentially new drug in that part of the study."
The consumer survey will present identical safety information under one of two randomly chosen headlines - "Important Safety Information" or "Important Risk Information" - to see whether that makes a difference in the respondents' understanding.
General practitioners will be asked to look at a label for one of the fictitious drug and answer questions designed to show how they use the prescribing information - which sections of the label they choose to read, for how long, and in what order. They will be asked how they perceive the drug's efficacy and how well they can recall the claimed benefits, and their answers will be compared with those of the consumers.
In other words, the GPs will know this is a test. Isn’t it likely then, that they will pay closer attention to the details? Isn't it just as important to learn how much (or how little) physicians really understand the information presented in the P.I.? In fact -- isn't it more important since they are the "learned intermediaries?"
Comments from Eli Lilly & Co. suggested that benefits and risks be viewed together and in a similar format so as not to bias the results. FDA agreed that "the benefits and risks should be evaluated together and [we] have several measures to investigate both. ...[but] because of the complexity of DTC ads, we cannot manipulate both benefits and risks at the same time."
Hm.
Alas, the editorial buried the lead in the final paragraph:
"Genentech plans to request a hearing with the F.D.A. to argue the case for retaining Avastin’s status as an approved breast cancer treatment. It should focus on proposing ways to identify the subset of women who can really benefit from Avastin."
The full editorial can be found here.
Burying the lead is one thing. Prematurely burying patients is something altogether different.
A Double Edged Sword for U.S. Healthcare
By Paul Howard
The U.S. is in the midst of a quiet drug crisis - an unprecedented shortage of critical generic medicines affecting everyone from cancer patients to patients waiting for routine surgeries. The shortage has everyone from regulators to companies scrambling to find solutions, while industry critics are calling for the FDA to mandate that companies keep making some medicines, even when they lose money on them.
Their sense of alarm is understandable, but forcing companies to act against their bottom-line interests will only make things worse. A better solution would focus on improving communications between regulators and stakeholders and strengthening market incentives for companies to keep producing high quality generic drugs.
Ironically, the shortage is the result of America's highly competitive, highly efficient system for rewarding both drug innovation and generic competition. In the long run, the system works well: Americans benefit from having a thriving, innovative biopharmaceutical industry and widespread access to inexpensive, high-quality generics.
As patents expire and generic competitors enter the market, once expensive, brand-name drugs plummet in price, to the great benefit of patients and payers - generic drugs saved the U.S. $121 billion in drug costs in 2008 alone. Today, according to IMS Health, about 75 percent of all U.S. prescriptions are for generics, up from just 57 percent in 2004 - and companies like Wal-Mart offer 30 day supplies of hundreds of generic drugs for just $4 a month. Meanwhile, companies with drugs losing patent protection also have powerful financial incentives to invest in new research to develop newer and better medicines for patients, and to make up for lost revenue.
In the short run, however, problems can crop up as pricing competition drives generic drug prices to rock-bottom levels, forcing less efficient producers to exit the market.
This may lead to just a few (two or three) companies producing important generic drugs. In this situation, with hospitals or pharmacies reluctant to keep large quantities of drugs in stock they don't immediately need, shortages can crop up quickly when there are sudden spikes in demand. Also, as price competition intensifies, some companies may decide that profit margins or demand for a given medicine is too thin to justify continuing production.
The "short run" can be a matter of life and death for patients waiting on critical drugs for diseases like lung cancer or leukemia. Today, some cancer drugs are in short supply in some regions of the U.S. - including carboplatin, cisplatin, doxorubicin, etopiside, and leucovorin. In many cases, physicians or pharmacists can substitute other drugs, but for some cancers "there are no equivalents, no work arounds," says ASCO president-elect Michael Link.
Whatever the cause of the shortages, they appear to be growing worse over time. A particular problem appears to be occurring with complex drugs known as sterile injectables, which the FDA says have experienced "severe and frequent shortages in recent years," accounting for 46% of total drug shortages in 2009.
Sterile injectables require a relatively complex manufacturing process with a substantial "lead time" compared to other drugs. This limits the number of companies that have the capacity to make them.
One example is the fast-acting anesthetic propofol, first approved by the FDA in 1989, and which lost patent protection in 1998. By 2009, just three companies were making generic propofol for the U.S. market: Teva Pharmaceuticals, APP Pharmaceuticals, and Hospira. Last October, both Hospira and Teva had to recall propofol due to FDA-identified contamination in their product lines. By May 2010, Hospira was still off-line and had to recall all of its customers' inventory, according to the FDA.
In the meantime, Teva announced that it would not be returning to the market, a decision perhaps motivated by a massive ($500 million) punitive-damage award against the company as a result of patients contracting Hepatitis from contaminated propofol vials. Explaining the decision, Teva said that it made "little or no profit from the drug," which is complex to manufacture. That left APP Pharmaceuticals as the last firm manufacturing propofol, and they haven't been able to keep up with demand.
Critics have long blasted the pharmaceutical industry for focusing too much on "profits", and called for empowering the FDA to force companies to continue making generic drugs, even when they are unprofitable. This move would of course be a disaster, and it would potentially reduce the incentives for companies to make complex generic drugs on the assumption that exiting the market would be costly. It would also give payers even more power to slash prices, knowing that companies could never refuse to produce the drug, even if they had to sell it at a loss.
A better approach is for regulators, manufacturers, and health systems to work harder to identify potential shortages as early as possible, allowing hospitals and pharmacists to develop plans to better manage or reallocate existing drug supplies before the shortages occur. Hospitals and health systems might also want to consider long-term purchase agreements or paying a few pennies extra per pill to reward suppliers with a track record of making complex, high-quality generic products. Rewarding quality and long-term reliability with a slightly higher price (or longer term contracts) should give producers better incentives to stay with generic product lines and invest in continuously improving their manufacturing processes.
More can certainly be done as well on the FDA side, including better monitoring to ensure that companies are in compliance with current Good Manufacturing Processes, along with upgrading the FDA's ability to provide meaningful oversight inspections. This would include increased funding for more frequent FDA inspections of high-risk manufacturing facilities, and adequate staffing to conduct inspections outside the U.S.
Should the FDA do more? "More is always better," said former FDA Associate Commissioner Peter J. Pitts. "But the agency must spend its money where it can get the biggest bang for the regulatory buck. More focus should be put on those who present the highest risk -- particularly overseas. A handful of FDA inspectors in China and India just doesn't cut it."
The problem of drug shortages comes at a time when the drug market is changing significantly. In the next several years, the market between generic and branded drugs will blur as innovative companies expand into the generics and biosimilars markets.
While no company is immune from manufacturing problems (and many generic firms produce high-quality products), the greater manufacturing experience and scientific expertise available to large, established pharmaceutical companies may help to smooth out at least some of the reliability issues with complex drugs like sterile injectables. And competition works both ways in the pharmaceutical industry. As more traditional drug companies are moving into generic markets, generic drug companies in places like India are trying to move upstream and develop a drug-discovery capacity of their own - believing that they can produce new drugs better and less expensively than U.S. and European companies.
In the long run, supply and quality problems are likely to smooth out as the industry restructures to meet new market and competitive realities. But that's cold comfort for patients facing drug shortages today.
The challenge for health systems, industry, and regulators right now is to find a way to overcome existing supply challenges without dampening incentives to innovate, even for older generic products. Creating better market incentives, improving communications between stakeholders, and bolstering the FDA's ability to conduct risk-based inspections are the best ways to prevent the next shortage before it happens.
Drug Industry Dismayed by FDA Delay on Digital Marketing Guidelines
Three-Month Pushback Frustrates Industry Digging into Social Media and Internet Advertising
The agency released a statement Tuesday night to the EyeonFDA blog that read: "The Division of Drug Marketing, Advertising and Communications (DDMAC) has been researching draft-guidance topics on the following issues related to internet/social-media promotion of FDA-regulated medical products: Responding to unsolicited requests; fulfilling regulatory requirements when using tools associated with space limitations; fulfilling post-marketing submission requirements; online communications for which manufacturers, packers or distributors are accountable; use of links on the internet; correcting misinformation."
It continued: "Our goal is to issue one draft guidance that addresses at least one of these topics during the first quarter of 2011, but we cannot comment any further at this point as to exactly when any draft guidance will issue or any specific order in which the topics will be addressed. The public will be notified officially when any guidance is issued via Federal Register announcements."
The FDA was expected to announce online guidelines by the end of this year after holding two-day public hearings in November of 2009. Delaying that potentially for three more months -- and guaranteeing draft guidance on only one of those topics -- is not sitting well. "It's infuriating," said one health-care-centric ad agency president. "On one hand, you want FDA to get it right. On the other hand, the (public hearings) were last November. They've had more than a year to get it right. It's bullshit."
But Paul Machado, CEO and founder of New Jersey-based Health Innovation Partners, said the delay is not such a bad thing. "If you think about it from the FDA's perspective and the challenges they're dealing with regarding health-care reform, why come out with a position? There's not a need right now. Why bother?"
Mr. Machado added that the industry will "continue to meander through the forest and see what happens, be conservative, see what others do and slowly create a position for themselves. Even if they do come out with guidance, it will take companies a long time to react to it. The reality is, you can only do so much anyway. "
At the November 2009 hearings, more than 60 people spoke, including representatives from Google, drug-makers and ad agencies. A month later the FDA published its Guidance Agenda for 2010, and the "Guidance on the Internet and Social Media" was listed -- meaning, at some point this year, the FDA expected to issue those guidelines.
One of the first inklings that it was going to be delayed came earlier this month when the FDA issued its Guidance Agenda for 2011 and "Guidance on the Internet and Social Media" was again listed.
Asked in an email why the agency would delay its online guidance, former FDA associate commissioner Peter Pitts replied: "Lack of knowledge. Lack of urgency. First Amendment angst."
Ironically, as the pharmaceutical industry itself begs for online/social-media guidance in order to pursue marketing in the new media, the first documented enforcement letter stemming from the FDA's new "Bad Ad" program was online-related.
The Dec. 3 letter from the Division of Drug Marketing, Advertising and Communications (DDMAC) to Hill Dermaceuticals claimed the company's web pages for its Derma-Smoothe product "are false or misleading because they omit and minimize the risks associated with the use of Derma-Smoothe Body Oil, overstate its efficacy, present unsubstantiated superiority claims, broaden and inadequately communicate the indication, and present unsubstantiated claims for the drug product. Thus, the webpages misbrand the drug in violation of the Federal Food, Drug and Cosmetic Act."
The "Bad Ad Program," instituted in May, urges the medical community to report ads and sales pitches that violate FDA rules. Ostensibly, the program was designed primarily to catch what the FDA can't see -- the behind-office-doors pitches from pharmaceutical sales reps to physicians. But the broad definition of the program allows doctors and medical professionals to report false or misleading ads to the FDA, and to do so anonymously.“It really is getting to the point where decision making at FDA is really becoming a major obstacle to VCs committing more money to the life sciences sector,” said Jack Lasersohn, general partner at The Vertical Group.
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.
