Latest Drugwonks' Blog
The study group, METABRIC (Molecular Taxonomy of Breast Cancer International Consortium), reports its findings in the 18 April online issue of Nature. The Cancer Research UK-funded study is the largest global gene study of breast cancer tissue ever conducted, involving a large team of researchers, primarily in the UK and Canada.
Led by Professor Carlos Caldas from Cancer Research UK's Cambridge Research Institute and Professor Sam Aparicio from the British Columbia Cancer Centre in Canada, the team uncovered crucial new information about breast cancer. The researchers analyzed the DNA and RNA of breast tumor samples from nearly 2,000 women who had been diagnosed between five and 10 years ago, and for whom information about the tumor characteristics had been meticulously recorded. They compared this with the women's survival, and other information, like their age at diagnosis. Because the study was able to look at many tumors with rich data on each, it identified new patterns and "clusters" in the data not spotted before. In the study, the team classified breast cancer into at least 10 different subtypes: each characterized by common genetic features that link to survival. This suggests we need to rethink what we call breast cancer and start looking at it as at least 10 different diseases, each with its own molecular fingerprint and pattern of weak spots.
Dr Harpal Kumar, chief executive of Cancer Research UK, told the press the study will completely change the way we look at breast cancer. Caldas, who is also Professor of Cancer Medicine at Cambridge's Department of Oncology, said "breast cancer" should be regarded as an umbrella term for a range of diseases. The findings could change the way drugs are tailored to treat individual women with breast cancer. The team also discovered several previously unknown genes that drive breast cancer. Each of these is a potential target for new drugs, and should boost worldwide efforts to discover and develop new treatments. The study also reveals the relationship between these breast cancer genes and known signalling pathways, the networks that control cell growth and division. This invaluable knowledge will help identify how variants of these genes cause cancer by interfering with cell processes.
Over decades, the METABRIC project has produced a "goldmine" of data, says Caldas. The process is not unlike that of cartography. At first, intrepid explorers discover new continents, defined by outlines and some rough impressions of terrains and landscapes. Then gradually, as mapping techniques improve, the data becomes more detailed and more precise. The METABRIC team now has a detailed "map" of thousands of individual tumors that have been analyzed and re-analyzed in many different ways and linked to detailed information about the fate of the women they came from.
Not only has the team performed all kinds of analysis on the DNA of the tumors (for instance the map is now annotated with copy number changes and single letter variations or SNPs, for each tumor), it has also conducted a detailed analysis of their RNA so they can tell which genes were active in each sample. Altogether they did this for more than 30,000 types of RNA, each corresponding to the activity of a single gene. "We've drilled down into the fundamental detail of the biological causes of breast cancer," said Caldas, "we've moved from knowing what a breast tumour looks like under a microscope to pinpointing its molecular anatomy". "Our results will pave the way for doctors in the future to diagnose the type of breast cancer a woman has, the types of drugs that will work, and those that won't, in a much more precise way than is currently possible," he added.
Aparicio said: "The new molecular map of breast cancer points us to new drug targets for treating breast cancer and also defines the groups of patients who would benefit most." Caldas said these results will not affect women diagnosed with breast cancer today, but he envisages future breast cancer patients will receive treatments tailored specifically to the genetic fingerprints of their tumors. From this huge leap forward, the next step is to find out how the tumors in each of subgroup behave.
Caldas had this to say to the patients behind the study: "I want to stress, this study wouldn't have been possible without the breast cancer patients who donated their samples and agreed to take part in the study. None of this would have happened without them, and I'm so grateful for their participation." For an excellent account of how we have increased our understanding of breast cancer, plus a table showing the 10 disease subtypes, see Henry Scowcroft's post in the Cancer Research UK Science Update blog.
Transparency (via social media) is leading to erosion in trust of once sacrosanct gurus such as physicians, corporations, their avatars and other “experts” (not the least of which is the mainstream media).
It’s been a painful and swift denuding of influence. Rather than being slowly disrobed, yesterday’s unquestioned experts have been roughly stripped of their gravitas and authority. Some have behaved badly, the majority has ignored it. Too few have gotten the message – adapt or die. You can’t airbrush social media.
Perhaps (and hopefully) this isn’t so much a downward spiral as it is (in the words of Schumpeter) “creative destruction.”
As Schumpeter writes in Capitalism, Socialism and Democracy, “The fundamental impulse that sets and keeps the capitalist engine in motion comes from the new consumers, goods, the new methods of production or transportation, the new markets, the new forms of industrial organization that capitalist enterprise creates.”
He would have loved social media.
While various “emperors” are being exposed as having no clothes, the void is being filled with robust and real-time peer-to-peer communications. Alas, there are also many ascendant false prophets. The Internet is full of them. Some are well-meaning (but still dangerous) idiots (such as the anti-vaccine crowd), others pure charlatans ("Cure your cancer in Mexico!").
As Don Draper once said, “I'm enjoying the story so far, but I have a feeling it’s not going to end well.”
Social media is a wonderful “green field of opportunity.” But to maximize the opportunity, we must accommodate the reality of a messier world. Social media, almost by definition, is messy – and the regulatory framework (or lack thereof) is equally so. And it’s not likely to get much better. Get used to it.
All this doesn’t mean that social media is a bad thing. Nobody said it was going to be easy. If we want to change the healthcare paradigm (and for some that’s a big “if”), then changing the way people learn, discuss and address healthcare issues is a crucial element. And, unlike other aspects of healthcare change – it is happening with great rapidity.
Impact and influence happen when what you have to share is to the benefit of the seeker — not to you. And that requires a level of focus, acumen and honesty that is always hard and often lacking – especially when it comes to healthcare marketing. As the saying goes in our nation’s capital, “if you’re not at the table, you’re on the menu.”
In the words of Winston Churchill, “Ease is relative to the experience of the doer.”
We’re still looking to healthcare professionals for technical solutions (physicians are no longer the first and last word, but the first among equals). When it comes to practical advice, it’s an increasingly peer-to-peer proposition. Today (for better or worse) we are all “learned intermediaries.” (But some as more learned than others – a fact we need to recognize and advocate.)
Welcome to the new world of P2P Healthcare where social media holds the keys to the portals of power. And as Dr. James Fowler of the University of California at San Diego, opined, “Pharma must realize their own network power.”
Social media is communications at the speed of life. As Marshall McLuhan wrote, “At electric speed, all forms are pushed to the limits of their potential."
(Still think you can wait for more precise and directive FDA regulations?)
The PDUFA "primary season" is almost over
Today, BioCentury reports, the Senate HELP Committee will deliberate on a PDUFA reauthorization bill that would relax conflict-of-interest restrictions on advisory committee members, and enact new provisions intended to improve risk-benefit decision-making, facilitate global harmonization of clinical trials and promote regulatory science.
The PDUFA reauthorization manager's amendment would eliminate limits on the numbers of conflict-of-interest waivers FDA can issue for advisory committee members. It would require FDA to "implement a structured risk-benefit assessment framework in the new drug approval process to facilitate the balanced consideration of benefits and risks, a consistent and systematic approach to the discussion and regulatory decision-making, and the communication of the benefits and risks of new drugs." It also would instruct FDA to work with international regulators and industry to "encourage uniform, scientifically-driven clinical trial standards" that would facilitate simultaneous global development of new medical products. Another new provision would require FDA to identify regulatory and scientific gaps that impede product reviews and approvals and draft plans with specific milestones for addressing the gaps.
The House Energy and Commerce Subcommittee on Health will mark up its version of the FDA user fee reauthorization legislation on Thursday.
Is the final vote a sure thing? Probably.
But is any election ever a sure thing?
When it comes to drug shortages, pounding Big Pharma isn’t the answer. Finally someone is focusing on the perverse economic incentives of Average Sales Price (ASP) as a key factor behind the problem. And that someone is Senator Orrin Hatch (R, UT.)
His Patient Access to Drugs in Shortage Act is out for comment through April 25, 2012. This proposed legislation is the only bill dealing with the economic causes of the shortages.
Some important codicils include:
* Price Stability — The draft would change the Medicare reimbursement rate for generic injectable products with 4 or fewer active manufacturers from Average Sales Price (ASP) + 6% to Wholesale Acquisition Cost (WAC) in order to achieve market price stability.
* Medicaid/340B Rebate Exemption — The draft exempts generic injectable products with 4 or fewer active manufacturers from Medicaid rebates and 340B discounts in order to achieve market price stability.
* Extended Exclusivity — Manufacturers who hold an approved application for a drug that would mitigate a shortage can extend by 5 years any period of exclusivity, even if the drug is eventually moved from drug shortage designation.
* Drug Shortage Database — The Secretary would establish a mechanism by which health care providers and other third-party organizations may report evidence of a drug shortage.
This last point may sound innocuous – but it’s crucial. There are many players in the drug shortage game – not just innovator pharmaceutical companies and the FDA. There are generics manufacturers, hospitals, Group Purchasing Organizations (GPOs), and physicians. (For more on the GPO issue, see this new op-ed in today’s Washington Examiner).
As the Japanese say – don’t fix the blame; fix the problem.
Earlier this week the Supreme Court heard arguments as to whether representatives of pharmaceutical companies are entitled to overtime. The answer, it seems, turns on whether those visits are actually sales calls.
According to Paul D. Clement, lawyer for the defendant, the pharmaceutical sales representatives plaintiffs, “ … were hired for a sales job. They were given sales training. They attend sales conferences. They are assigned to sales territory, and they are evaluated and compensated as salespeople.”
But, commented Chief Justice John G. Roberts Jr, “They don’t do sales. Your long list sort of stopped one step short. They don’t make sales.”
As the New York Times accurately reports, industry reps “do not sell products in the strict sense of the term. Rather, they encourage doctors to write prescriptions for patients to buy drugs from pharmacies.”
Interesting semantical and practical questions and it’ll be interesting to see how the Supremes rule. In the meantime here’s a related question – depending on the final judgment – will government detailers (aka “academic detailers”) qualify overtime pay? They’re not supposed to be “selling” anything either.
I like BIO CEO Jim Greenwood's proposal to give FDA a chief innovation officer who who would examine whether the number of drug rejections is reasonable, or whether it is stunting innovation and causing unwarranted delays.
“People who die because a product is not approved quickly enough are just as dead as those who die because a product is not safe,” Greenwood said. “It’s not just the job of the FDA to protect us, it’s also to promote innovation.”
My pick for the position: Janet Woodcock. No one (except for Bob Temple) could and has balanced these two missions better. And no one has done more to promote personalized medicine, which allows products to more efficiently embody safety and innovation.
There are a lot of important bi-partisan ideas to accelerate the innovation process. A chief innovation officer should not be a ceremonial add-on or be limited to reviewing product development after the fact. That official could report to the Commissioner, search out and encourage companies with innovation products for fast track approval, be in on the development of products from the beginning. That's something Dr. Woodcock would and could do effectively.
But the way to change FDA to promote those broader objectives is to hold it accountable to new standards for product approval and oversight reflecting dramatic changes in the science sustaining innovation. Congressman Rogers and others can help the FDA by getting them out of the comparative effectiveness business. Reauthorization of PDUFA will give the agency more resources and more direction with regard to increasing the predictability in the development process for drugs, devices, diagnostics and combination products. However, the FDA would get a boost if legislation stipulated that any products that use biomarkers or other tools to target treatments and improve the ability to monitor disease progression or response would be automatically approved for use in Medicare, Medicaid, etc.
The more we can defang what is an increasingly worthless CER enterprise the more FDA can achieve the mission the Congressman Rogers wants the agency to carry out. CMPI will be releasing a study, supported by the Kauffman foundation, that estimates how much innovation and health value our nation will forfeit if CER becomes the focus of commercialization instead personalized medicine. The estimates, even with conservative assumptions built in, are staggering.
Every time someone at FDA has to pay lip service to CER it is a signal to companies that all the work put in on diagnostics, combination products and targeted treatments will go to naught because they have to wait for a bunch of underachieving health economists and other professionals to conduct systematic reviews or horizon scams, I mean scans, or clinical trials. Then again, as I noted in my last post, it looks at though PCORI will be handing out dough to to figure out how to conduct patient-centered research and how to engage patients, though the last time I checked no one -- except the stakeholders who will also get the PCORI cash -- was asking for such government help.
You want to make medicine patient-centered? Produce patient-centered medicine. Tools and treatments that reduce hassles, improve life, increase health.
That's something FDA can, should and is trying to do in collaboration with companies. If you asked people should we spend $3 billion on medical decision making or the same amount making better medicines more quickly available to people who need them, I don't have any doubt that faster approvals would win.
The FDA could do a lot with $3 billion over the next decade and do much more for our health and nation than PCORI ever will. Just a suggestion if Congressman Rogers wants to amend his bill....
Yesterday the HELP Committee released a draft version of PDUFA legislation and plans a April 25 PDUFA mark-up.
The Senate draft creates a new pathway for review of "breakthrough" therapies, requiring FDA to work with sponsors to expedite approval of products to treat serious or life-threatening diseases based on "preliminary clinical evidence indicating that the drug may demonstrate substantial improvement over existing therapies on one or more clinically significant endpoints."
On the other side of the Capitol, the House Energy and Commerce Committee released a discussion draft of PDUFA reauthorization legislation on Wednesday. Both the House and Senate bills incorporate the Generating Antibiotic Incentives Now (GAIN) Act, which would extend market exclusivity by five years for drugs that treat antibiotic-resistant pathogens. The E&C version includes an additional six month extension for drugs approved along with a companion diagnostic; this provision has been deleted from the Senate version.
The House draft also seeks to permanently reauthorize two laws that create incentives for conducting clinical trials in pediatric populations, the Best Pharmaceuticals for Children Act and the Pediatric Research Equity Act. Similar legislation, the Better Pharmaceuticals and Devices for Children Act, was introduced with bipartisan sponsorship in the Senate on Tuesday; it is likely to be incorporated into the Senate PDUFA reauthorization bill.
House lawmakers said they were optimistic that any outstanding issues in the GOP draft would be resolved in the coming days, and full committee Chairman Fred Upton (R, MI) said he was convinced the panel is on track to meet his goal of approving the legislation by the end of June.
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.
