Latest Drugwonks' Blog
From today's Wall Street Journal:
An ObamaCare Drug Preview in Germany
By John C. Lechleiter
Germany was in many ways the birthplace of the pharmaceutical industry. But today, German policies place the industry's future progress at risk.
More than a century after Eli Lilly's founding, many of us still trace our company's greatest "spark" to Germany, and to a scientist born in 1877 named George Henry Alexander Clowes. An Englishman, Clowes was determined to become a great chemist and was dedicated to improving human health. In the late 19th century, such a goal meant one thing: Go to Germany. Clowes left Germany not only with a Ph.D. in chemistry but also with a conviction that breakthroughs against disease depended on the collaboration of industry, academia and medicine.
Twenty-six years later in 1922, Clowes had crossed the Atlantic and become the head of research at a small company in Indianapolis. He helped to spearhead the commercial manufacture of insulin for the treatment of diabetes—turning what was once a death sentence into a manageable condition.
Today in Germany, it's doubtful that George Clowes would find much inspiration. The ethos of hard work certainly still exists, but intrusions of bureaucracy, misunderstandings of science, and an exaggerated emphasis on short-term cost savings are jeopardizing the country's legacy as a pharmaceutical powerhouse.
Of particular concern is a new law passed last year that imposes a complex new assessment mechanism to determine the added benefit of new pharmaceutical products, which in turn is used to set prices. The situation in Germany bears close scrutiny in the U.S., as health-technology assessment processes grow in significance under the recent health-care overhaul.
Our concerns begin with the timing of Germany's assessment: at the point of launch. Pharmaceutical companies invest hundreds of millions of dollars into clinical trials to prove the efficacy and safety of new medicines—but efficacy and safety are not the same things as added benefit. We introduce products into the market with well-founded hypotheses about their unique benefits, but rarely with definitive evidence. By insisting that we provide such evidence before a single patient has used a medicine in regular medical practice, German authorities are devaluing the final and arguably most important stage of pharmaceutical development.
Contrary to popular mythology, so-called blockbuster medicines are not the result of slick marketing campaigns but of demonstrated success in the actual practice of medicine. At Lilly, we wonder how many of our earlier blockbusters—which might have appeared very similar to existing medicines at their launch but proved more effective in practice—would have survived the requirements of Germany's new early assessment requirement. Similarly, we wonder if incremental innovations in the treatment of cancer, for example, or new medicines that limit side effects and improve patient compliance with doctors' orders in diabetes care, will be considered beneficial under Germany's new system.
Even that bleak conclusion assumes that the early assessments will be carried out in a fair and transparent manner, which is far from assured based on what the industry has seen so far. Companies such as Lilly are looking at the all-important "comparators" being assigned to our new molecules in the assessment process. In many cases, German authorities appear to be comparing cutting-edge products with decades-old generic products and still pricing the new products just pennies above the generics. Our conclusion is that we are being set up for negative decisions on added benefit and ruinous price controls as a result.
The wisest decision that a company can make in such circumstances may be to delay the launch of a new medicine in Germany until evidence can be generated elsewhere. The other alternative may be to keep new drugs off the German market entirely to prevent the global reputational damage of a slap from the German authorities.
Meanwhile, the broader uncertainties created by the new German law—literally any product can be drawn into the new evaluation process without advance notice—wreak havoc on our industry's business planning.
Now is the time to step back and consider the unintended consequences of Germany's new law, and make sure we don't repeat the same mistakes in the U.S. We share Berlin's goals of generating value and limiting unnecessary costs in health care. We see ways of harnessing and improving health-outcomes research.
Most of all, we believe that dialogue between government and industry is the only way to ensure that the cradle of the pharmaceutical industry remains a nurturing environment for new medicines in the 21st century.
Mr. Lechleiter is chairman and CEO of Eli Lilly & Co.
http://archpsyc.ama-assn.org/cgi/content/full/archgenpsychiatry.2011.76#YOA15046T2
Which begs this question: Since so many of the likely 'environmental' factors alleged to be linked to autism (, inflammatory diseases, mitochondrial disorders, vaccines, water supply, chemicals) have been discredited, how reliable is a study -- one that is at odds with every other genetic association study regarding autism -- that claims environmental factors are twice as likely to trigger autism than genes? How good is a model that predicts things at odds with what experience demonstrates?
Of course the media never examines this question, never puts this study into context and never looks at the toxicological studies showing that certain toxins some swear cause autism, impotence, cancer, etc. are not even present in concentration levels necessary to cause of biological reaction (benign or not). Not suprisingly, BPA is now being held up as the next new culprit causing autism. Thus the recent EPA review of BPA levels in humans will go unmentioned:
EPA Study Findings:
· Consistent with previous human and animal studies, this new study confirms that human exposure to BPA is extremely low, and BPA is efficiently metabolized and rapidly excreted in urine. Of particular importance, these results confirm the validity of the controlled human volunteer pharmacokinetic studies that have been used by regulators in BPA risk assessments.
o Based on how much total BPA (after hydrolysis of metabolites) was found in urine (average exposure was 21% greater than the 95th percentile exposure determined by CDC’s population-scale urine biomonitoring data), the authors concluded that “BPA exposures in this study can therefore be viewed as representative of, or exceeding, the high end of the U.S. BPA exposure distribution.”
o Total BPA was detected in only 14% of the 320 blood samples, only one of which was above 1 ppb. Total BPA was below the sensitive limit of detection (0.3 ppb) for 86% of the samples.
o Estimates of peak BPA levels in the blood were 1 to 3 orders of magnitude below levels associated with potentially adverse health effects in the most sensitive experimental rat models.
o Free BPA was below the limit of detection in all 320 blood samples analyzed by the CDC lab, even for samples with detectable total BPA. Based on their results the authors note that reported high levels of BPA in blood are unlikely to be valid. (“Furthermore, the current results obtained using analytical methodology 10-45 times more sensitive than the previous human study by Voelkel et al. suggest that reported BPA concentrations in human blood of 1.4-19.2 nM [~0.3-4.4 ppb] (Vandenberg, Chahoud et al. 2010) are highly unlikely in the general population exposed orally to amounts as much as ~4 times greater than the 95th upper percentile of aggregate exposure in the general U.S. population.”)
o While subjects of this study did not include pregnant women, the authors also add that “recently reported mean urine concentrations in pregnant women are low enough that blood and serum levels are likely to be below current detection limits.”
o Samples with detectable total BPA were further analyzed in the FDA lab to confirm the findings. Very low but detectable levels of free BPA were found in 3 of these samples, but further analysis revealed that contamination was most likely the source of the free BPA. The authors note, “the evidence presented here and elsewhere for low-level contamination (Markham et al., 2010; Twaddle et al., 2010), even in the face of extraordinary attention to this problem, suggests that these infrequent positive determinations near the detection limit should be suspect” and “Thus, some attributions of high blood BPA concentrations from oral exposure seem implausible.”
24-Hour Human Urine and Serum Profiles of Bisphenol A During High Dietary Exposure tinyurl.com/3efsdw8
Will we -- and the media -- unlearn the lessons of Wakefieldism?
Blame innovation!
According to an editorial in today’s New York Times, “A prime driver of our escalating health care costs is the advance of medical technology …”
Indeed.
The driver of the Gray Lady’s oration is the decision by Medicare to pay for both Provenge (advanced prostate cancer) and Avastin (for breast cancer – even if the FDA removes this as an on-label indication).
The Times objects to both treatments “staggering high cost” and “modest help to the typical patient.”
Are these treatments “too expensive?” Well, as they say inside the Beltway, where you stand depends on where you sit.” Too expensive for whom? And there lies the rub.
When our nation’s biggest health insurance provider – Uncle Sam – is footing the bill, the real payer is the American tax payer. You and me.
That being the case, how do we feel about spending our tax dollars on end-of-life care for our fellow citizens? After all, these treatments aren’t cures. They extend patient life. Some gain months, others years.
This is a tough and timely question for both public and private debate – and not just amongst policy wonks and editorialists. Do we want a health care system that is cost-based or patient-centric? Should end-of-life care be rationed? If so, by whom and by what measure?
And if we decide not to pay for new medicines, the clear signal to the pharmaceutical industry is “cease research and development for new treatments for killer diseases."
Blame innovation? Consider:
Innovation is slow. As any medical scientist will tell you, there are few "Eureka!" moments in health research. Progress comes step-by-step, one incremental innovation at a time.
Innovation is hard. Today it takes about 10,000 new molecules to produce 1 FDA-approved medicine. And if that's not frightening enough, only 3 out of 10 new medicines earn back their research and development costs. And here's the kicker -- unlike other R&D-intensive industries, pharmaceutical investments generally must be sustained for over two decades before the few that make it can generate any profit.
Innovation is expensive. In 2003, researchers at Tufts Center for the Study of Drug Development estimated the costs to bring a new medicine to market to be $802 million, and others suggest that the total cost is closer to $1.7 billion
Innovation is under attack. From accusations of the “me-too” variety, to crackpot schemes to replace pharmaceutical patents with a “prize” system, life for innovator pharmaceutical companies is rough and tough.
But innovation is important – and not just for pharmaceutical industry profits. Increases in life expectancy resulting from better treatment of cardiovascular disease from 1970 to 1990 have been conservatively estimated as bringing benefits worth more than $500 billion a year. In 1974, cardiovascular disease was the cause of 39 percent of all deaths. Today it is about 25 percent. Cerebrovascular diseases were responsible for 11 percent of deaths back then. In 2004 they caused 6.3 percent of deaths. Kidney diseases were linked to 10.4 percent of deaths and now they are associated with 1.8 percent. And that’s just for the United States.
As Harvard University health economist (and Obama healthcare advisor) David Cutler has noted: "The average person aged 45 will live three years longer than he used to solely because medical care for cardiovascular disease has improved. Virtually every study of medical innovation suggests that changes in the nature of medical care over time are clearly worth the cost."
Blame innovation – because now we are living long enough to suffer in larger numbers from cancer and Alzheimer’s disease. Diseases that cannot be cured (at least not yet) and are expensive to treat.
And what of the “typical” patient? The current gold standard of drug testing, the randomized controlled clinical trial, isn’t specifically designed to identify patient subpopulations who might benefit from a treatment that does not aid the general population. According to the folks at our nation’s newspaper of record, Avastin “provides almost no benefit for the typical woman with advanced breast cancer.” Well – true, except for the subpopulation of women for whom it does. The problem isn’t that Avastin “doesn’t work,” it’s that we have no way of identifying which women it will work for.
The solution isn’t to carp on cost – it’s to develop better diagnostics to help physicians identify the “four rights” – the right drug in the right dose for the right patient at the right time. We need to focus not on cost effectiveness but on clinical effectiveness.
But nowhere in the Times’ editorial is there a call for increased FDA funding for the development and regulation of molecular diagnostics – something that is urgently needed and, alas, rarely discussed.
Rather the Times’ editorial ends as follows, “Whether the drug is worth its high price is a question our health care system is currently unprepared to answer.”
Really? It seems that Medicare is not only prepared to answer the question – but that, via their decision to reimburse for both Provenge and Avastin, they have.
At least for now. After all, we're entering into a Presidential election cycle.
Of course many experts weighed in on the study:
"Critics say this new review is based on just seven studies that were not designed to test the effects of sodium reduction interventions on CV events and mortality and is therefore unreliable. "
One physician, Lawrence Appel, was particularly harsh: "The authors truncated the best set of trials, TOHP1 and TOHP2, which has extended follow-up of >10 years, to just the trial period, 1.5 years for TOHP1 and three years for TOHP2. This set of trials, with extended follow-up, documented a significant reduction in CVD events."
This is the same Lawrence Appel who continues to push ALLHAT and a diuretic alone as the gold standard for treating hypertension to the exclusion of several new, large studies demonstrating that a combination of blood pressure meds reduce the risk of death from stroke and other ailments more effectively.
A little more consistency in how medical studies are evaluated and applied would be helpful. The totality of evidence matters. But what matters more is moving away from population based conclusions towards individualized and mechanism specific approaches to care.
Epidemiology, the foundation of comparative effectiveness research, is so 19th century.
See: Advising people to eat less salt is not best approach to reduce CVD at theheart.org
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.
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.
