Latest Drugwonks' Blog
And now a cry for “mandatory rebates.”
Really? Why don’t we just call it what it is – a tax. More precisely, an excise tax imposed by Uncle Sam on drug sales to dual eligibles (based on the price difference between Medicaid prices and those of the private market).
But wait, it gets worse. The revenues from this tax don’t lower costs for a single patient. Not one. The cash would go into the general fund. It’s not a “rebate” – it’s a tax, plain and simple. A levy imposed on price.
And it’s a tax with a hidden purpose – the introduction of backdoor price controls. And price controls equal cost controls – with or without IPAB.
Forewarned is forearmed.
Editorial from today's edition of The Washington Post:
Editorial Board Opinion
High court highlights a gap in drug safety regulation
GLADYS MENSING’S doctor prescribed the brand-name drug Reglan to treat a gastrointestinal problem. When the Minnesota resident went to fill the prescription, the pharmacist — as he was compelled to do in Ms. Mensing’s state — dispensed a cheaper, generic version of the drug.
Ms. Mensing now suffers from tardive dyskinesia, an irreversible neurological condition linked to the drug and characterized by “grotesque involuntary movements of the mouth, tongue, lips, and extremities, involuntary chewing movements, and a general sense of agitation.” Ms. Mensing sued the manufacturer under a state law for failing adequately to warn of this potentially severe side effect.
Last month a 5-4 majority of the Supreme Court threw out her case. The reason: She used the generic version of the drug. Had Ms. Mensing suffered the same harm after consuming the brand-name drug, her case would have been allowed to proceed.
The majority, led by Justice Clarence Thomas, had valid reasons for its decision, but even Justice Thomas admits the result “makes little sense.” We would go further: The result is a dangerous one that exempts some 75 percent of the drugs dispensed in this country from essential safeguards. This situation should be rectified — and quickly — through federal regulation.
Risks associated with long-term use of Reglan and its generic version were long known, but neither the brand-name nor the generic version carried a “black box” warning — the most serious kind — until years after Ms. Mensing began using the product. Ms. Mensing sued the generic’s manufacturer under a Minnesota law that dictates that “where the manufacturer . . . of a product has actual or constructive knowledge of danger to users, the . . . manufacturer has a duty to give warning of such dangers.” She argued that the generic drug’s maker should have changed its label to reflect heightened risks.
But federal law foreclosed this possibility. Brand-name producers are typically the first to be alerted to adverse affects of their products and are allowed to — and in some instances are obligated to — make unilateral changes to warning labels. Generics producers, on the other hand, do not enjoy such flexibility — or responsibility — and are tasked only with parroting the brand-name’s warning labels. The court concluded that federal law required dismissal of Ms. Mensing’s suit since it was “impossible” for the manufacturer to comply simultaneously with the state and federal rules.
Writing for the four dissenters, Justice Sonia Sotomayor correctly noted that “as a result of today’s decision, whether a consumer harmed by inadequate warnings can obtain relief turns solely on the happenstance of whether her pharmacist filled her prescription with a brand-name or generic drug.”
This should not stand. The Food and Drug Administration should require manufacturers of generic drugs to track adverse effects and reach out to the FDA to initiate label changes to reflect new or heightened dangers. A fair right to sue is important, but even more so would be compelling full disclosure so that patients are not harmed in the first place.
Never express yourself more clearly than you are able to think.
--Niels Bohr
Think regulatory headaches about FaceBook is a hot topic?? Here are some communications issues that make social media guidance pale in comparison.
Today Eli Lilly, Johnson & Johnson, Novartis, Novo Nordisk, Pfizer, and Sanofi-Aventis will file a Citizen Petition with the U.S. Food and Drug Administration (FDA) asking the agency to clarify its policies on how truthful, non-misleading scientific information not included in approved product labeling can be communicated.
The petition will state that communicating accurate scientific information about new research would enhance health care quality and potentially lead to better patient outcomes, but that companies lack precise guidance on how to communicate such information.
Specifically, the companies requested that FDA issue clarifying regulations or guidances on four issues:
* “Scientific exchange”
* Sharing information with formulary committees and payers
* How to provide independent third-party clinical practice guidelines
* Responding to unsolicited requests for information
“Scientific exchange,” broadly defined, is the sharing of research and clinical information about investigational medical products or new information on approved products without representing the product as safe and effective for that use. FDA said in a 1963 regulation that it does not intend to restrict “scientific exchange.” The concept of “scientific exchange” however, is not precisely described in FDA’s regulations and
therefore leaves ambiguity about the limits of what is permitted.
Managed care formulary committees and other payers make important coverage and reimbursement determinations based on clinical evidence and other data. FDA has not issued a formal policy with respect to what information manufacturers can provide to formulary committees about new uses of approved medical products so that patients can be promptly reimbursed.
Third-party clinical practice guidelines are produced by leading medical organizations or the government to inform and guide diagnosis, management and treatment decisions. These guidelines are based on the most up-to-date clinical evidence and data and are intended to guide health care professionals in improving quality of care and optimizing clinical outcomes. There is no formal FDA policy on when and how it is appropriate
for companies to disseminate third-party guidelines that mention off-label uses of their products.
“Unsolicited requests” are unprompted questions from physicians or patients about the off-label uses of medical products. For years FDA has not taken enforcement action when companies respond to unsolicited requests for off-label information in a balanced and scientific manner. However, there is no written regulation or policy providing a comprehensive description of FDA’s policies on unsolicited requests.
The absence of alternatives clears the mind marvelously.
--Henry Kissinger
Sometimes profound change happens so swiftly that is unrecognized and unappreciated. Such is the case with the response to the Food and Drug Administration advisory committee’s decision to withdraw the agency’s approval for using Avastin to treat metastatic breast cancer. After the FDA Oncological Drug Advisory Committee declared Avastin to be unsafe and ineffective for women suffering from that incurable form of the disease the headlines and pundits spun the decision – and the discussion – as one where science triumphed over emotional and desperate women. Gary Schwitzer, a self-styled expert on objective medical reporting quoted the representative from the National Breast Cancer Coalition who at the ODAC hearing: "This decision can't be driven by anecdotes. It must be driven by science."
This is an unfair and lazy characterization of the debate over Avastin. The ODAC panel was stacked with members who already voted against Avastin’s use in MBC. The conflict was over the interpretation of clinical information and whether the FDA can pull an approval because, as it said in December of last year, Avastin doesn’t provide “a sufficient benefit in slowing disease progression to outweigh the significant risk to patients.” But several other groups that looked at the same evidence came to a different conclusion including The National Comprehensive Cancer Network and the European Medicines Agency (Europe’s FDA) that expanded approval Avastin based on the same “science” ODAC used in rescinding the drug’s FDA endorsement.
In any event, the speed with which both the Obama administration and private health plans announced they would still cover the cost of Avastin for the use the FDA rejected was stunning. When the FDA decided to yank Avastin’s approval in December 2010, several healths plans and regional Medicare reimbursement contractors told women that Avastin would no longer be covered. (Such decisions were reversed only after the FDA said it would review its revocation.)
Last week the same organizations – along with the Obama administration – rushed to distance itself from the FDA and assure women it would cover the drug.
The difference in response is a result of the rapid organization of patients through social media. While it culminated in the presence of hundreds of women at the ODAC hearing, that participation was only a part of an extensive, sustained and scientifically informed movement.
The FDA officials and the interest groups urging Avastin’s revocation were outgunned by individual patients who joined together much as HIV patients did in the 1990s and MS patients did in pushing for the return of Tysabri to the market a few years ago. This time however, the use of social media to share clinical information, organize support and express opinions was rapid, sustained and, above all surprising. The cancer advocacy ‘establishment’ was outgunned and reduced to irrelevancy. This also happened after the Obama administration’s recommended not to cover mammograms for women under 50. The National Breast Cancer Coalition sided with the administration and cancer patients, oncologists and radiologists everywhere told them go stick it. That decision, like the FDA’s rendition of Avastin, is being ignored in practice.
We see in this recent uprising against the Avastin decision a clear shift in power from the Beltway groups that claim to represent patients to individuals organizing on their own and in their own best interest. More to the point, this movement is well informed and shaped by what the science says. The attempt to demean or diminish it as purely anecdotal and emotional reflects the arrogance of bloggers and pundits who have but a thimble full of the clinical understanding of the movement’s participants. And it suggests contempt for any use of social media that does not seek to spread fear or skepticism of innovation.
Companies who develop new products will have to contend with consumers that demand credible and substantive clinical information. Health plans and the government will have to expect ongoing challenges to their ‘expertise’ and claims that it is using the best evidence in determining what to cover. In particular the apparatus and funding supporting comparative effectiveness research will find that consumers will be skeptical of one-size fits all judgments made by so-called ‘experts.’
The Avastin Spring suggests that resistance against the use administrative means to tell the rest of us what treatments we can and cannot use will only grow. We don’t know how it will all play out. But we do know that it will lead to more individual choice and less authority for self-styled advocacy groups, government and corporate entities who claim that only they have science on their side en route to restricting access to innovations.
What I didn't expect, but should have, was how quickly the Obama administration would make that decision and how it distanced itself from the FDA ODAC vote to revoke Avastin's indication. From Reuters:
"The FDA decision, when it comes, does not affect CMS," Don McLeod, a spokesman for the Centers for Medicare and Medicaid (CMS), said on Thursday."The drug will still be on the market, doctors will still be prescribing it, and we will continue to pay for it," he said, adding that CMS often pays for off-label uses of drugs." www.reuters.com/article/2011/06/30/roche-avastin-cms-idUSN1E75T17U20110630
Gee, what happened to the effort to coordinate reimbursement decisions and FDA approvals in order to "bend the cost curve."
The comparative effectiveness crowd must be comparing in their pants..
And if that wasn't enough, Team Obama trotted out Donald Berwick to extol the virtues and value of Provenge, a drug it delayed paying for by 18 months. Here's what Berwick said in a prepared statement that sounded like a forced confession from the lover of Britain's single payer health system.
“We are optimistic that innovative strategies may improve the experience of care for our beneficiaries who have cancer,” said CMS Administrator Dr. Donald M. Berwick. “CMS is dedicated to assuring that these patients can seek the treatments they need in accordance with their wishes.”
www.latimes.com/health/boostershots/la-heb-prostate-cancer-provenge-medicare-20110701,0,7641053.story
Here's Berwick in 2009:
"We can make a sensible social decision and say, “Well, at this point, to have access to a particular additional benefit [new drug or medical intervention] is so expensive that our taxpayers have better use for those funds.” We make those decisions all the time. The decision is not whether or not we will ration care — the decision is whether we will ration with our eyes open. And right now, we are doing it blindly."
www.ncbi.nlm.nih.gov/pmc/articles/PMC2799075/
Every time a new cancer drug is approved in Britain, the NHS gets hammered for rationing care. But what happens in Britain is tee-balll compared to what CER types and the institutions that will produce or use CER will go through every time it tries to restrict or delay access to treatments that benefit a segment of the population.
Trying to go up against innovation in the US? It could be compared -- if the Avastin and Provenge sagas are any indication -- to trying to challenge St. Louis Cardinal pitcher Bob Gibson, know for his take no prisoner attitude against any hitter. What Hank Aaron said in that regard might explain Team O's response to the FDA decision:
'Don't dig in against Bob Gibson, he'll knock you down. He'd knock down his own grandmother if she dared to challenge him. Don't stare at him, don't smile at him, don't talk to him. He doesn't like it. If you happen to hit a home run, don't run too slow, don't run too fast. If you happen to want to celebrate, get in the tunnel first. And if he hits you, don't charge the mound, because he's a Gold Glove boxer.' I'm like, 'Damn, what about my 17-game hitting streak?' That was the night it ended."
Don't dig in against innovation.
The Public Policy
FDA Decision Dooms Cancer Patients
Opponents of medical progress are celebrating the decision of a Food and Drug Administration panel to revoke approval of the use of Avastin in treating advance breast cancer.
Not so fast.
As Scott Hensley, a health care reporter for NPR, wrote:
The day after a panel of experts advised the Food and Drug Administration to go ahead with plans to revoke approval of Avastin to treat breast cancer, European authorities moved in the opposite direction.
The European Medicines Agency (EMA) gave the OK to an expansion of Avastin's approval to include using the drug in combination with Xeloda, a chemotherapy drug, to treat metastatic breast cancer, Genentech parent company Roche said Thursday.
The Europeans considered the same information that hasn't proved persuasive to U.S. regulators. Among other things, a study called RIBBON 1 found Avastin plus Xeloda increased progression-free survival or PFS -- (living longer without tumor growth) of women by 2.9 months over women getting Xeloda alone.
This improvement seems small but is actually quite significant. Gains in PFS among patients with cancers that spread through the body are hard to achieve because when the disease spreads it is considered incurable. And over time, the small victories over incurable cancers extend and improve life.
The EMA believes 2.9 months is a great beginning. The FDA sees nothing less than 6 months to be worth it and worked hard to make sure Avastin would never hit that mark.
The FDA's Richard Pazdur, who heads up FDA's Office of Cancer Drugs, had approved Avastin's use in breast cancer on the condition that future studies confirmed the improvement in PFS. Genentech conducted three studies that hit that mark. But then Pazdur claimed that PFS was not enough. He wanted evidence that median overall survival increased.
While an increase in overall survival has been considered the gold standard for cancer drugs, progression-free survival has been used as a benchmark for longer and better quality of life.
That's because a standard like overall survival only tells you what the median survival is for all patients -- it doesn't take into account individual differences in response based on genetic, clinical and other factors.
Yet when results of additional studies this summer concluded that Avastin doesn't extend life on average, an FDA advisory committee suddenly decided that Avastin should be measured by overall median survival -- not progression-free survival.
Before this measurement switch, the FDA admitted that the new studies showed a statistically significant improvement in PFS with Avastin. But then it said, "the magnitude of treatment effect, as commonly assessed by clinicians based on differences in median PFS, was marginal."
Pazdur seems to want to toughen standards based on a one-size-fits-all measure that requires longer and more expensive clinical trials. In doing so he has been supported by such left-leaning and anti-innovation entities as the Center for Science in the Public Interest's Merrill Goozner and Public Citizen, a Naderite group that has warned against most new medicines for cancer and diabetes since the 1970s. These and other Avastin opponents -- who have long regarded the drug as a symbol of corporate greed -- have lobbied for median survival as the key standard. They know that applying that standard would harm the perception of Avastin's effectiveness.
Goozner -- who has no medical background -- was appointed to an FDA advisory committee on pharmaceutical science. Two senior Public Citizen operatives, Peter Lurie and Larry Sasich, now set policy for the FDA. Fran Visco, the head of the National Breast Cancer Coalition, applauded the FDA decision after lobbying for it over the past year. Visco, a Democrat, is also on Experts Advisory Panel for the Universal Health Insurance Program at the New America Foundation, a left-wing think tank supporting Obamacare. The NBBC also supported the administration's decision not to cover mammograms for women under 50 though many breast cancers grow faster and earlier in African-American women.
To these groups, the FDA decision was a triumph. But their effort to manipulate the FDA will backfire. The EMA and every major group of cancer providers support Avastin's use. Cancer patients moblilized spontaneously to keep Avastin's label. They will take on the anti-innovation establishment and the FDA with greater intensity and vigor.
Medicare and some health plans will try to stop paying for Avastin. But Congress will hold oversight hearings on the Avastin decision en route to amending FDA's statute through one of many bills calling for faster access to new treatments.
The administration will have to respond to show it's not using FDA to ration care or slow innovation.
In the long term this is all well and good. But meanwhile many women dying of breast cancer will have to go to Europe to get a drug that could keep them alive.
Robert M. Goldberg is vice president of the Center for Medicine in the Public Interest and founder of Hands Off My H ealth, a grass roots health care empowerment network. His is new book, Tabloid Medicine: How the Internet is Being Used To Hijack Medical Science For Fear and Profit, was published last month by Kaplan.On CNBC this Tuesday, I called on HHS Secretary Sebelius to promise that CMS would continue to pay for Avastin as a treatment for breast cancer.
(The complete CNBC interview can be viewed here.)
And, late yesterday, Medicare confirmed it would do just that. According the CMS spokesman Don McLeod, “The label change will not affect our coverage.”
At least for now. As Andrew Pollack reports in today’s New York Times, “Mr. McLeod’s statement could allay those concerns, at least for women covered by Medicare. He said that Medicare commonly paid for off-label use of cancer drugs.”
McLeod said that while there were no plans for one right now, he could not totally rule out that Medicare might one day undertake a national coverage determination to decide whether to pay for Avastin. That process would take at least a year and involve public input.
In other words, the administration understands that, had CMS withdrawn reimbursement for Avastin’s use in breast cancer, it would have become a front-and-center election issue. Proof positive that ObamaCare equals denial of care.
A unique situation (at least as of late) where the right public health decision is also the savvy political move.
And hopefully it won’t be the last.
(Can you say “Adieu IPAB?")
I’ve just returned from the big BIO bash, where I was honored to moderate the panel discussion, "Lessons From In-Licensing Partnership: Biotech Company Partners with Global Pharma to Deliver Cutting-Edge Follow-On Biologics.” I was joined on the podium by joined by Arun Chandavarkar, Chief Operating Officer of Biocon Ltd.; Stephen Hoge, Principal at McKinsey & Co.; and Diem Nguyen, General Manager, Biosimilars, Pfizer.
Here’s how I opened the discussion:
Woody Allen said that, “Change should always be expected – except from vending machines.” But management guru W. Edwards Deming hits closer to the mark, “Change is not required. Survival is not mandatory.”
Many believe that the age of the blockbuster is over. Cost concerns are more challenging than ever. And we are struggling with what “personalized medicine” really means.
We are now in the era of post-patent medicine where advances in manufacturing, incremental innovation, and molecular diagnostics are as important as new molecular entities, and safety is as important (and as improvable) as efficacy.
The era of post-patent medicine is also the epoch of biosimilars. But will biosimilars really be as important an element of change as many believe. Will it be a game changer?
I believe the answer is “yes,” but I am not sure whether or not all the changes will positively affect the advancement of the public health. I fear the expectations that biosimilars will radically reduce costs are overstated. I fear that safety concerns are being understated and that the risks to innovation are real.
As Eli Lilly & Co. CEO John Leichleiter said, "Creating and maintaining the conditions for innovation to flourish is challenging and complicated work - work that is never finished.”
Case in point -- there seems to be general consensus that, with a clear FDA pathway still off in the future, BLAs are the way to go. Hence a redefinition of BLA as “Beat Legislative Ambiguity.” No aBLA biosimilar.
EMA and FDA recently announced that they are setting up a "cluster" on biosimilars to increase communications between the two agencies on the topic and the two agencies will discuss harmonization of regulatory requirements. Yet fundamental differences in the laws they administer make harmonization difficult.
Beyond a standardized regulatory pathway, there are many issues on the table:
* The role of “next generation biologics” (or, if you prefer, “biobetters”)
* Bioequivalence, interchangability, and therapeutic substitution
* The debate over distinguishable names and robust post-marketing surveillance
* GMP standards
* Reference products and clinical trial requirements and design
* And, last but not least, Patent Life vs. Data Exclusivity
And that’s not even considering PDUFA V. Nobody said it was going to be easy.
This morning’s panel won’t answer every question – and it is very likely to raise a few more. Our hope is that the panel will provide useful and timely insight on how global pharma and biotech companies can collaborate to develop, gain authorization, and globally commercialize cutting-edge follow-on biologics.
(And I believe we succeeded in delivering a thoughtful and thought-provoking discussion.)
Avastin Fight Highlights Limits Of Big, Random Trials
An FDA advisory panel on Wednesday unanimously rejected arguments from Genentech that its anti-cancer drug should continue as an approved therapy for... View Enlarged Image
A Food and Drug Administration special advisory panel voted 6-0 on Wednesday to withdraw approval of the drug Avastin for treating late-stage breast cancer, sticking to its usual scientific standards despite some patients' pleas to disregard them.
The recommendation was based on the best scientific evi dence currently available, but the controversy highlights the limits of the science the FDA uses to determine drug effectiveness.
"Large, randomized-controlled trials are the 20th century," said Peter Pitts, president of the conservative Center for Medicine in the Public Interest. "The 21st century is the age of personalized medicine, where we need better molecular diagnostics to determine which subpopulation reacts to which treatments."
Avastin blocks the growth of new blood vessels to tumors, and is already FDA-approved for late-stage colon and lung cancer.
In 2008 the FDA granted accelerated approval of Avastin for use in late-stage breast cancer based on one randomized trial that found it slowed the progression of late-stage breast cancer.
In late 2010, the FDA withdrew approval based on two trials that found Avastin did little to slow progression, did not improve overall survival from late-stage breast cancer, and that it posed serious health risks, including death.
Randomized-controlled trials often involve large samples of patients. Such studies determine if a drug has a widespread benefit. But this is also a limitation. A treatment may work for a subpopulation in the sample, but since it doesn't work for most people in the sample, the average shows that the treatment is ineffective.
"The concept that you're looking for one magic bullet that cures a ton of patients at once is the wrong idea," said Terry Kalley, who founded Freedom of Access to Medicines in response to the FDA's 2010 decision on Avastin. "Cancer is likely to be cured by several therapies that target different subpopulations."
Kalley says his wife Arlene has been taking Avastin, along with chemotherapy, for 27 months.
Roche asked the FDA to extend its approval of Avastin until it conducts a study that "would include a biomarker component to identify patients who may be more likely to derive a more substantial benefit from Avastin."
But that is in the future.
"Unfortunately, the data we have right now (don't) allow us to know if there is such a subpopulation," said Karuna Jaggar, executive director of Breast Cancer Action.
Jaggar is concerned that Roche is using this as a stalling tactic to keep Avastin on the market. The Swiss drug giant could lose nearly $1 billion in sales, analysts say.
"We must insist that breast-cancer patients are receiving drugs that have been demonstrated to work," Jaggar added.
Others say regulators should keep Avastin approved for now.
"The FDA should say the evidence isn't there right now, but we will work with Genentech and patient groups to develop the appropriate diagnostics," said Pitts. "But the FDA needs to leave the indication on the label so people can still use it and be reimbursed for that."
If the FDA rescinds Avastin for late-stage breast cancer, at least until subpopulations are studied, then Genentech/Roche cannot market the drug for that purpose.
Doctors could still prescribe Avastin for the off-label use. But it's unlikely that government programs like Medicare and Medicaid or private insurance will cover Avastin — which costs $80,000 or more per year — for breast cancer.
An estimated 17,500 women suffer from late-stage breast cancer.
Many people like Terry testified at the hearings about Avastin. But without better data, such stories are little more than anecdotal.
The flip side is that if it turns out that Avastin does help some subpopulations, such women today will suffer as long as the FDA does not approve the drug for late-stage breast-cancer treatment.
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.
