From Buproion to Biosimilars

10/10/2012 08:13 AM |

According to an article in BioWorld Today:

The FDA’s decision last week that an approved generic bupropion wasn’t comparable to GlaxoSmithKline plc’s antidepressant Wellbutrin XL 300 mg (bupropion) raises questions about the hurdles biosimilar developers may face along the new regulatory path.

Those challenges likely would be exacerbated when developing biosimilars to drugs such as antidepressants, which fall into a narrow therapeutic index, according to Pitts. In April 2010, the Pharmaceutical Science and Clinical Pharmacology Advisory Committee voted unanimously, with one abstention, that critical dose drugs constitute a distinct group and that the FDA should develop a formal list of those drugs, he pointed out. In an 11-2 vote, the committee also concluded that existing bioequivalence standards were not sufficient for drugs in the narrow therapeutic index group.

“The issue with biosimilars is interchangeability,” Pitts told BioWorld Today. Differences between small-molecule drugs like Wellbutrin and biosimilars are iteratively more complicated than they are with generics because they involve not just the chemical composition of the product but also the manufacturing process.

“When it comes to biosimilars, you’re talking about molecules that are between 5,000 and 20,000 atoms,” he added. “The question is whether a 5,000-atom biosimilar is less difficult than a 20,000-atom biosimilar. Of course it is.”

Thus, biosimilars developers must prepare to contend with “many, many more ways to cut safety and efficacy” data, Pitts added.

The Budeprion/Wellbutrin decision indicated the FDA now realizes that issues of similarity exist even with small molecules, Pitts said. “With biosimilars, it’s going it’s going to be a billion times more complicated,” he cautioned.

Still, the fact that the FDA is feeling its way along the biosimilars regulatory pathway and potentially revisiting its general approach to extrapolation should give biosimilars developers pause, Pitts suggested.

“Ten years from now, when the FDA has more experience dealing with this, [the pathway] will be more predictable,” he said. “But now, every biosimilar that comes before the FDA for review is going to be a de novo experience. It’s going to be a very difficult, very risky and very problematic process. From a business standpoint, you have to ask yourself: Is this a worthwhile proposition?”

Tough questions with no easy answers.

The complete Bioworld Today article can be found here (bottom right, page one).

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Signal-to-Noise Toys

10/09/2012 09:18 AM |

In case you think that, by avoiding more active engagement in social media, adverse event reporting isn’t going to catch up with you – think again.

The Wall Street Journal reports that, “Scientists are sifting through massive quantities of freely available data scattered across the Internet, aiming to catch potentially deadly problems with prescription drugs more quickly—even ahead of federal regulators.”

Researchers from the University of Virginia and West Virginia University have developed mathematical recipes that computers use to filter billions of pieces of data from patient comments in online chats, websites and news stories to detect serious adverse drug reactions.

They then catalog the complaints and determine when they rise to a level that deserves medical or regulatory attention. Similar techniques have been used to detect bioterrorism threats, study crowd and consumer behavior and map out how infections spread.

The goal is to be able to alert the medical community about possible negative drug reactions much earlier so they can use it their clinical practices, as well as to warn the FDA about potential new adverse reactions.

The challenge for researchers, they say, is to sort through tons of "noise," the reams of information that aren't relevant, accurate or important, and to recognize useful signals. Researchers hope to use continually improving computer algorithms—programs that detect key patterns or relationships between words—to make recognition of important signals more accurate, says Ahmed Abbasi, a professor of information technology at the University of Virginia's McIntire School of Commerce in Charlottesville.

In preliminary data, they found that 80% of the time, their formulas detected potential adverse event patterns three months earlier than the FDA issued warnings, said Dr. Adjeroh, a computer science professor at West Virginia University in Morgantown. In some cases, they were years ahead of the FDA's warnings. The researchers were recently awarded a $130,000 grant from the National Science Foundation Smart Health and Wellbeing program to launch a bigger project in this area.

Such big-data approaches move away from a reliance on voluntary reporting and clinical intuition. "There's always been this struggle between intuition and data," says Dr. Abbasi. "There's a paradigm shift where data-driven decision-making is being increasingly adopted."

Note to industry:  Lead, Follow, or Get Out of the Way.

Suggestion to industry:  Lead.

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All Partners, Foreign and Domestic

10/09/2012 09:01 AM |

You can use all the quantitative data you can get, but you still have to distrust it and use your own intelligence and judgment.

-- Alvin Toffler                                             

Last week (October 1 at the at the Center for Strategic and International Studies), FDA Commish Peggy Hamburg noted that the recently enacted FDA Safety and Innovation Act provides the agency with new authorities surrounding information-sharing with foreign regulators, as well as user fees to pay for some of those activities.

Information-sharing “makes complete sense. There’s too much work to be done, you have to do it together across nations with an agreed-on set of standards and outcome measures. But if we rely on an inspection done by another country and then there’s a problem, everybody’s going to say, ‘How could you possibly have let that happen?’ So I think we do have to be realistic about that.”

If FDA takes action based on information collected by other regulatory authorities “and something goes wrong, there’s going to be a price to pay. So I think that there’s going to be a pendulum that’s going to go back and forth as we move towards systems that hopefully will work in a more enduring way.”

In other words, there has to be political accountability for domestic regulatory decisions. No argument there. But that doesn’t mean the use of non-US data should be verboten. And it doesn’t mean there shouldn’t be a predictable way the agency uses such data in domestic regulatory matters.

That is both “realistic” and “enduring.”

No foreign policy, no matter how ingenious, has any chance of success if it is born in the minds of few and carried in the hearts of many.”

-- Theodore Roosevelt

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High V

10/08/2012 09:10 AM |

From PDUFA V to Pangea V. 

FDA is ordering operators of about 4,100 websites to immediately stop selling unapproved medications to U.S. consumers.

It also follows the FDA’s launch last Friday of a campaign to warn consumers that the vast majority of online pharmacies do not follow laws or pharmacy industry standards and their products could harm or even kill people. The campaign includes a new website, www.fda.gov/BeSafeRx, that explains the risks of fake online pharmacies and how to tell the difference between those websites and legitimate ones.

The FDA has sent warning letters to three companies behind most of the 4,100 websites it identified as illegally selling potentially dangerous, unapproved drugs. It’s also seized some illegal medicines, filed civil and criminal charges against companies and individuals, and contacted Internet registrars and service providers, asking them to suspend the 4,100 websites.

According to the FDA one business, called CanadaDrugs.com, operates 3,710 of the targeted websites. Another company, identified in the warning letter as Eyal Bar Oz, runs more than 200 sites. A third company, called Arkadiy Kisin/White Forest Solutions, also operates more than 200 sites.

The drugs include various versions of the erectile dysfunction drugs Viagra, Levitra and Cialis, as well as an unapproved contraceptive called Norplant, an unapproved generic version of the influenza treatment Tamiflu, an unapproved antibiotic called Baycip TZ, and a drug for stomach disorders that also increases production of breast milk but is not approved because it’s been linked to irregular heartbeats, cardiac arrest and sudden death.

The warning letters say that the websites have been offering unapproved drugs to U.S. consumers. The letters, sent to the companies between Sept. 18 and 21, order them to reply within 10 business days.

As yet -- no reported replies.

The warning letters to the three companies are part of a simultaneous crackdown on online sellers of counterfeit and illegal medical products, involving police and regulators in 100 countries around the world. The fifth annual campaign coordinated by Interpol, the international police agency, is known as the International Internet Week of Action, and also as Operation Pangea V.

Let's hope that, in the case of Pangea, "V" also stands for "Victory."

 

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Washington Didn't Sleep Here

10/05/2012 11:28 AM |

Last night in Seattle I was honored to speak at a dinner sponsored by the Washington Policy Center (where I am an adjunct scholar). The attendees were physicians, hospitalists, representatives of the biotech industry, provider organizations, and state legislators. The topic was:  Biosimilars: The Precarious Struggle Between Cost-driven Health Care Policy and Patient-centered Care.

Why a “precarious struggle?”

Because physicians live in a world where cost concerns of patients, insurance companies and the government chaff against the freedom to practice the art and science of patient-centered care.

At the same time, legislators are constantly bombarded with public policy schemes that claim to solve the problem of providing more health care dollars at a time of historic belt cinching. To paraphrase H.L. Mencken, for every complex problem there is a simple solution — and it is usually wrong.

These are the tensions that exist in the world of health care reform and biosimilar medicines that will cause problems in examination rooms and legislative chambers nationwide because they prevent people from having a clear understanding of what biosimilar drugs are and how they impact patient treatment.

A policy of forcing the use of “cheaper” medicines also has a chilling effect on medical innovation and economic investment.

Wanting something to be true (whether a “magic pill” for a state’s budgetary woes or a “risk-free” way to reduce a patient’s medical expenses) should not cloud the judgment of lawmakers or physicians. Careful consideration of the advantages and disadvantages of biosimilar drugs should be the guiding principle for both physicians and legislators to ensure we “first do no harm.”

Policymakers must seek out the counsel of physicians, medical and disease organization and, yes, also patient groups as they consider ways to address and implement health care reform. Biosimilars are but the most recent addition to that complicated and highly political conversation. When it comes to biosimilars, partisanship must be put aside because a legislative misstep based on a misunderstanding of the science (or the blinders of party loyalties) could have significant unintended consequences not just for budgetary reform, but for patient health and safety.

My remarks were based on a new paper, a primer on biosimilar drug policy for both policymakers and physicians. It can be found here.

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Conservative Case For Obamacare: A Post Debate Perspective

10/04/2012 02:40 PM |

If you are part of the small circle of people who lay claim to being a health policy "expert" then you have read and commented on J. D Kleinke's NYT op-ed, The Conservative Case For Obamacare.   JD ( who I have known for at least 20 years) asserts that Obamacare is really based on conservative principles and but for the fact that it covers contraception and that the credit went to the President and not Republicans, conservatives would like the new law.  

Conservative health policy types have written op-eds or posted blogs refuting Kleinke's claim.  Tom Miller, also of AEI,  sums up the response of Kleinke's critics when he writes that Kleinke's op-ed:

"Recycles a fact-challenged rewriting of health-policy history and combines flawed analysis with wishful thinking.
Kleinke argues that the individual mandate and health exchanges of the Affordable Care Act (ACA) were, and should remain, sound conservative ideas meriting Republican support. He imagines that, but for crass political calculations, Republican leaders would be taking credit for what President Obama borrowed from them."

I am not going to pile onto Kleinke.  I woud only add that he wrote nothing new.   The claim that Obamacare is based on conservative proposals and ideas -- and it a carbon copy of 'Romneycare' is a standard Democratic talking point.    Indeed, President Obama stated as much in last night's debate.  

 The New York Times published his piece for three reasons:

1.   He is a resident fellow at AEI, a conservative think tank.  If Jonathan Livingston Gruber had written the article, it would have seen the light of day, which by the way, is a fitting final destination for all of Gruber's work. 
2.   In the article he made the ad hominem assertion that social conservatives want the government to tell women they can't have abortions.  
3.   He endorsed the liberal's view that conservatives made up things like death panels to scare people. 

Without attempting to put words into JD's mouth or op-ed,  I think what he was really trying to say is Obamacare uses the rhetoric of the marketplace, retains in a half-baked way reforms such as HSA and uses tax credits to pay for private coverage, many on the left still dislike the new health law because it's not single payer.   That's the true measure of how market driven Obamacare is and, as a result, conservatives should claim ownership
Indeed, the last line in his NYT piece states: 

"The real problem with the health care plan — for Mr. Romney and the Republicans in general — is that political credit for it goes to Mr. Obama. Now, Mr. Romney is in a terrible fix trying to spin his way out of this paradox and tear down something he knows is right — something for which he ought to be taking great political credit of his own."

Let's grant Kleinke his argument for a moment, that the use of exchanges, tax credits and an individual  mandate to reform healthcare are conservative ideas.   He ignores the most important conservative objections to Obamacare:

1.   It uses price controls to cut spending in Medicare, takes about $60 billion from Social Security and eliminates market choices for seniors to pay for Medicaid for the middle class.   
2.   It uses and creates agencies that will, decide what all health plans should cover,  tell doctors what procedures are "best",  and will 'control'  Medicare spending by deciding what new technologies and treatments to pay for.  

Finally,   conservatives object to Obamacare because it imposes new taxes on most Americans and compells them to buy a product, the price and composition of which is determined by the government.   

The Soviet Union used market mechanisms for it's 5 year plans.   It set prices, decided upon both the array of goods to be produced as well as where they would be sold and at white price.   One year Soviet factories made a lot of shoes for left feet only.   

And all of this would be nearly laughable if people were not compelled to buy the products at the prices set.   But that's in fact what Obamacare is (and Romneycare isn't):  a government created market that only functions because it taxes people and forces them to buy only government developed and subsidized insurance products.  As Grace Marie Turner noted:  "According to a research arm of Congress, the Congressional Research Service, over time, “families will both pay higher penalties and reach the cap at lower income amounts.” This new ObamaCare tax will, like the Alternative Minimum Tax, hit more and more people over time as incomes rise."

I don't know if JD doesn't understand that how a market is organized is more important than calling something a market or if he just using the rhetorical stance to suck up to the NYT.   One thing I do know:  JD has always been an articulate supporter of making consumers more responsible for health care decisions.  In 2003 I sponsored a Manhattan Institute forum where he said: 

"We have come to expect that health insurance should pay not just for disease, but also for impairment, discomfort, and vanity. Why shouldn’t it? Everyone wants something for nothing. It’s human nature. That’s the real problem. The problem isn’t how much better we are getting at finding new medications as a society. The problems is the fact that the health insurance enterprise is gargantuan and ever expanding, along with being inefficient and generating incredibly archaic and bizarre rules.

What’s the solution for this? It’s the simplest thing in the world. Reform the tax code. If people are going to insist on buying everything, down to the $200 deductible with their employer’s money, which is really their money, they should simply continue to do so - but direct that spending personally. It should fall outside of the health insurance premium. Deductibles should be raised to something resembling what we had decades ago, when insurance was involved only when someone got really sick. The premiums for this type of coverage are much lower. And the difference can be set aside, pre-tax, for all that routine spending. This way, for a great deal of the health care entereprise generally, we get consumers far more involved and bureaucrats far less involved."

That's one of the most concise and thoughtful summation of a new health care payment model I ever heard.   JD is not only as smart as the people criticizing him, he has also run and set up health care companies.   That's the JD I know and learned from.    

I disagree with his NYT op-ed and think his characterization of Obamacare as market-driven is either misguided or misleading.  And I believe this attack on the pro-life community was a cheap shot.   

But as Mitt Romney showed in his deft defense of the Massachusetts health reform, there's a grain of truth and insight in what Kleinke wrote.   Tax credits, market competition and increase consumer responsibility are the core of conservative health proposals  have become mainstream, the leading health systems are far and away more efficient and consumer-driven then, say, the VA where delay and sub-substandard care for wounded warriors is the norm.    And as the President demonstrated, liberals see any market-driven changes in our health care system as a threat to a single payer government run system like those in Canada or Great Britain.  Why would the president repeatedly defend a government panel established to decide what new technologies and treatments should be used and whether to pay for them?    Repealing Obamacare means shutting down a government run marketplace and expanding consumer choice.

As JD notes: It's the simplest thing in the world.  



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"D"lightful

10/04/2012 09:28 AM |

A new poll sponsored by Medicare Today (an initiative of the Healthcare Leadership Council) shows that 90% of seniors are satisfied with Medicare Part D -- and approval has constantly risen since the plan came on line in 2006.

"Nearly seven years later, 9 in 10 Medicare beneficiaries have prescription drug coverage," says the poll. "Satisfaction among those with Medicare Part D has grown 12 points from 78% to 90%. Most are very satisfied with their coverage and say their plan offers excellent value, reasonable costs, and convenience."


Seniors "feel peace of mind" with the prescription drug program, and regard it as "a safety net."



Among other poll findings show that without Part D:

-- 84% report that out-of-pocket drug costs would be higher.

-- 61% would be unable to fill all of their prescriptions.

-- 53% would be more likely to cut back or stop taking medicine altogether.



Cooperation and partnership between the free market and Uncle Sam works.

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Regretting Obamacare

10/04/2012 06:56 AM |

He voted for the law.

Former US Senator Evan Bayh on the disastrous consequences of the looming medical device tax:

The Supreme Court decision in June upholding the Affordable Care Act leaves in place a tax on medical devices that threatens thousands of American jobs and our global competitiveness. It will also stifle critical medical innovation in the industry that gave us defibrillators, pacemakers, artificial joints, stents, chemotherapy delivery systems and almost every device we depend on to save lives.

The 2.3% tax will be charged to manufacturers on each sale and takes effect in January. Many U.S. device companies, in response, have already announced layoffs, canceled plans for domestic expansion and slashed research-and-development budgets. This month, Welch Allyn—a maker of stethoscopes and blood-pressure cuffs—announced that it will lay off 10% of its global workforce over the next three years, but all of the jobs being cut are in the U.S.

Given the fragile state of the U.S. economy, Congress must move quickly to redress the harm from this tax before it becomes irreversible.

The medical-device industry has been a great American success story. More than 400,000 U.S. workers are employed in this sector directly, and another two million, including those involved in supply and distribution, benefit indirectly. At a time when the economy struggles to produce good jobs, medical-device positions pay well. Average compensation is $58,188 annually compared with a national average of $41,673 annually for all employment, a 2010 Lewin Group report found.

Click here for the full WSJ piece.


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Number of Uninsured Will Soar Under Romney Plan, Report Says

10/03/2012 08:36 PM |

From Medscape Medical News

Number of Uninsured Will Soar Under Romney Plan, Report Says

By Mark Crane
 
October 2, 2012 — The number of individuals with out health insurance could soar to 72 million nationwide by 2022 under Mitt Romney's plan to repeal the Affordable Care Act (ACA), compared with 27 million uninsured if the law remains intact, according to a report released by The Commonwealth Fund, a liberal health policy advocacy group.
 
The report, "Health Care in the 2012 Presidential Election: How the Obama and Romney Plans Stack Up," is based on assumptions that Romney would replace the healthcare reform law with block grants to states for Medicaid, institute a premium support program for Medicare to provide beneficiaries with a specified sum of money to buy the plan they choose, and enact new tax incentives to encourage people to purchase insurance on the individual market.
 
Although some details of Romney's proposals have not been specified, economist Jonathan Gruber from the Massachusetts Institute of Technology, Cambridge, used a set of assumptions based on similar proposals advanced in the past. Specifically, to equalize tax treatment of health insurance, he assumed that premiums for individual market insurance can be deducted from income on an "above the line" basis, meaning a deduction available to all, not just those who itemize taxes.
 
Almost 18 million children younger than 19 years are estimated to be uninsured by 2022 under Romney's plan, compared with 6 million under President Barack Obama's plan to implement the law. Under Romney's plan, another 18 million middle-income Americans — with incomes between about $32,000 and $58,000 a year for a family of four — are estimated to be uninsured by 2022 (more than one third of this income group). By comparison, 3.3 million middle-income families are estimated to be uninsured under the ACA. Among families of four with incomes under $32,000 a year, 38.7 million people are estimated to be uninsured under Romney's plan and 17.2 million under the ACA.
 
"There are stark differences between what each candidate has proposed for our healthcare system, and this report shines a light on how Americans might be affected, based on their age, their income, and where they live," lead report author Sara Collins, vice president for affordable health insurance at The Commonwealth Fund, said during a news conference yesterday. "The report finds that repealing the Affordable Care Act would significantly increase the number of Americans without health insurance, limiting their ability to get the healthcare they need and exposing them to burdensome medical bills and debt."
 
Effect of Repeal?
 
What effect would repeal of the law have on physician practice? "The ACA has provisions to improve the kind of team practice envisioned by designers of the law, such as promoting medical homes and coordinating care," Stuart Guterman, another Commonwealth vice president, said during the press conference. "Accountable care organizations put primary care at the center of that model, allowing providers to be rewarded for cost savings. The ACA also raises Medicare and Medicaid fees for primary care physicians. If the law is repealed, a lot of those provisions would be eliminated. It's hard to see how to achieve the same goals relying only on market forces."
 
The report finds that young adults and baby boomers would also have better access to secure health insurance coverage under the ACA, with an estimated 7.2 million young adults aged 19 to 29 years remaining uninsured in 2022, compared with more than 18.6 million estimated to be uninsured under Romney's plan. Among older adults aged 50 to 64 years, 4.9 million are estimated to be uninsured in 2022 under the ACA, whereas nearly 11.8 million would be uninsured under Romney's plan.
 
Under Medicare, Romney's plan would eliminate the phasing out of the "doughnut hole" in the prescription drug benefit, beneficiaries' free annual wellness visit, and preventive care with no cost-sharing. Converting Medicare to a premium support program, as Romney has proposed, might raise beneficiaries' out-of-pocket costs if the premium allowances failed to keep pace with growth of healthcare costs. Without the reform law's provisions, the Medicare Hospital Insurance Trust Fund would be depleted by 2016, rather than 2024, as currently projected under the ACA, the report said.
 
In addition, according to a news release from The Commonwealth Fund, the law "imposes sweeping new rules on insurers to protect consumers. Some of these rules have already been implemented, including a ban on rescissions (insurers cancelling coverage when a beneficiary gets sick), bans on lifetime benefit limits, a phased-in ban on annual benefit limits, no longer allowing insurers to turn away children with preexisting conditions, and requiring insurers to cover preventive care without copayments from beneficiaries.... Romney's plan to repeal the ACA would rescind all of these protections. Romney has said that he would prevent discrimination against people with preexisting conditions who maintain continuous coverage."
 
False Assumptions?
 
Opponents of the ACA were quick to criticize the report, saying it uses false assumptions to bash Romney's plan by ignoring several of his proposals. They add that polls have consistently shown that most Americans favor repeal of the law.
 
"In a word, this 'study' is nonsense," Grace-Marie Turner, president of the Galen Institute, told Medscape Medical News. "Commonwealth made up a health plan they attributed to Gov. Romney in order to shed the worst possible light on an alternative to Obamacare. The result is nothing more than a political news release for the Obama campaign.
 
"The real effort here is to try to get the American people to forget how much they despise the law, which will cost at least $2.6 trillion and still leave 30 million people uninsured," she said. "Seniors are still exposed to the independent payment advisory board's ever deeper cuts to Medicare spending, compromising their access to care. The ACA did nothing to reform the out-of-control Medicaid program, which ill serves our most vulnerable citizens while threatening to bankrupt many states."
 
Robert Goldberg, vice president of the Center for Medicine in the Public Interest, agrees. "This report assumes a Romney proposal to turn Medicaid into block grants will lead states to limit coverage" and result in greater numbers of uninsured, he told Medscape Medical News. "That's because the vast majority of Americans would be forced into Medicaid under Obamacare. So Gruber is assuming the massive expansion in Medicaid is the only way to insure people.
 
"Romney's plan gives millions of Americans tax credits to buy insurance, allows states to use Medicaid to target those in greatest need and combine federal dollars with their own revenues to allow people to choose and keep coverage even if they lose or change jobs," Goldberg said. "Gruber doesn't measure the impact of the 'real' Romney proposals. Hence, he ignores that they will stop the diversion of $716 billion from the soon-to-be-bankrupt Medicare program to pay for Obamacare."



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Captain Renault Reports

10/03/2012 09:50 AM |

"I'm shocked, shocked to find that gambling is going on in here”

-- Captain Renault

Dozens of weight loss and immune system supplements on the market are illegally labeled and lack the recommended scientific evidence to back up their purported health claims, government investigators warn in a new review of the $20 billion supplement industry." The report, which is "being released Wednesday" by HHS' Office of Inspector General, found that "20 percent of the 127 weight loss and immune-boosting supplements investigators purchased online and in retail stores across the country carried labels that made illegal claims to cure or treat disease." Notably, Federal regulations do not require the FDA to "review supplement companies' scientific evidence for most of their products' purported health benefits before they hit the market"; and the OIG "found that in numerous cases, when companies did submit evidence to back up their health claims, it fell far short of government recommendations."

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Flawed Studies

10/03/2012 05:33 AM |

Grace-Marie Turner on the Commonwealth Fund’s study comparing Obamacare to the Romney health plan:
 
The liberal Commonwealth Fund is at it again, releasing today a new study, “Health Care in the 2012 Presidential Election: How the Obama and Romney Plans Stack Up.” But the “study” is, in a word, nonsense.

The crucial sentence in the publication is this one: “Because Romney has not yet fleshed out the details of [his health reform] proposals, a set of assumptions was made.” That is a significant understatement.

The work regurgitates a similar “study” by the liberal FamiliesUSA last week, which devised its own assumptions about what a Romney plan would look like.

Read the full piece here.
 
Avik Roy took apart the Families USA study here.


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Trevor Butterworth Calls Out Nick Kristof For Scientific Illiteracy

10/01/2012 03:23 PM |

http://www.forbes.com/sites/trevorbutterworth/2012/08/26/why-nick-kristofs-scientific-illiteracy-threatens-us-all-2/?commentId=comment_comment.id This is a great piece by one of smartest science writers around...  Read More & Comment...

Why doctors are depressed

10/01/2012 12:17 PM |

Dr. Marc Siegel explains why physicians are pessimistic about the future of medicine in the country:

President Obama and Congress should have checked with the country’s physicians before passing a law that relies on our efforts to handle health insurance expansion to more than 30 million more people.

A new on-line survey by the non-profit The Physicians Foundation, one of the largest doctors surveys ever performed, confirms that over two thirds of physicians are pessimistic about the future of medicine, over 84 percent feel that our profession is in decline, and a majority would not recommend it as a career for their children. (The survey was sent to over 600,000 doctors and over 14,000 responded).

If you ask my three children you will find that neither my wife or I (also a physician) are recommending a medical career to them despite the fact that we still manage to find ways to enjoy what we do.

Read the full piece here.



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The FDA's Drug Shortage Czar

09/28/2012 10:26 AM |

Dear CDER Staff:

On September 6, 2012, CDER Center Director Janet Woodcock informed you that she would be proposing important organizational changes within the Center to sharpen the Center’s focus and strengthen resources around pharmaceutical quality.

As part of these organizational changes, we will also be proposing that the Drug Shortages Staff (DSS) be moved from the Office of New Drugs and be elevated to the Office of the Center Director under the leadership of Deputy Director for Regulatory Programs, Dr. Doug Throckmorton.

On July 9, 2012, President Obama signed into law the Food and Drug Administration Safety and Innovation Act (FDASIA) of 2012.  In this new law, Congress provided FDA with new authorities to combat shortages of drug products in the United States and imposed new requirements on manufacturers regarding early notification to FDA of issues that could lead to a potential shortage or disruption in supply of a product.

Drug shortages can occur for many reasons, including manufacturing and quality problems, delays, and discontinuations.  They have reached crisis proportions for many healthcare systems and are creating personal crises for many patients.  Fortunately, the Agency has been able to prevent a significant number of drug shortages. In 2011, FDA helped prevent 195 drug shortages; as of August 2012, FDA prevented close to 100 shortages.

FDA places tremendous value on the Center’s efforts to curb drug shortages.  In addition, with the new authorities brought by FDASIA, we look forward to an ever-increasing focus on this crucial program. 

The proposed elevated placement for DSS -- with its greater visibility and prominence within the Center -- reflects how important the work of the DSS is to ensuring that patients in need have critical and life-saving drugs available to them. Undoubtedly, this work is paramount to the Center’s mission to guarantee that safe, effective, and high-quality drugs are available to the American public.

Doug Throckmorton

Deputy Director for Regulatory Programs, Office of the Center Director

John Jenkins

Director, Office of New Drugs

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Another Doc Fix!

09/28/2012 07:44 AM |

The doctor is in … trouble.

Each year, physicians in America conduct over 1.2 billion patient visits, treating illnesses ranging from the minor to the life-threatening.

With A Survey of America’s Physicians, the Physicians Foundation has endeavored to provide a “state of the union” of the medical profession. What are physicians thinking about in the year 2012: about the practice of medicine, about their career plans, and about the current state of the healthcare system?

The survey was sent to over 630,000 physicians – or over 80 percent of physicians in active patient. One thing is clear -- it is a challenging and uncertain time to be a doctor.

The results of the survey reflect uncertainty and should be taken in the context of current events.

Key findings include:

* Over three quarters of physicians – 77.4 percent – are somewhat pessimistic or very pessimistic about the future of the medical profession.

* Over 84 percent of physicians agree that the medical profession is in decline.

* The majority of physicians – 57.9 percent -- would not recommend medicine as a career to their children or other young people.

* Over one third of physicians would not choose medicine if they had their careers to do over.

* Over 52 percent of physicians have limited the access Medicare patients have to their practices or are planning to do so.

* Over 26 percent of physicians have closed their practices to Medicaid patients.

* Over 62 percent of physicians said Accountable Care Organizations (ACOs) are either unlikely to increase healthcare quality and decrease costs or that that any quality/cost gains will not be worth the effort.

* Over 59 percent of physicians indicate passage of the Patient Protection and Affordable Care Act (i.e., “health reform”) has made them less positive about the future of healthcare in America.

What’s wrong with this picture?

The complete study can be found here.

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Longtime Companion (Diagnostics)

09/27/2012 08:18 AM |

A companion’s words of persuasion are effective.

-- Homer

Diagnostic test quality may not be something that pharmaceutical and biotechnology companies have had a lot of experience dealing with, but shortfalls in a diagnostic development program can undercut efforts to streamline clinical trials for personalized medicines.

The Pink Sheet reports that the need for a high-quality diagnostic test development program was a key message delivered by a representative from FDA’s devices center at a September 14th conference on drug/diagnostic co-development.

The conference, sponsored by the Friends of Cancer Research and Alexandria Real Estate Equities Inc., served as a discussion forum for a multi-stakeholder draft proposal aimed at enabling late-stage clinical development of drugs with companion diagnostics by quickly identifying a patient subset most likely to benefit from treatment while minimizing exposure of patients least likely to benefit.

FDA officials were generally receptive to the draft ideas put forward. However, they highlighted the threshold need for a well-characterized, high-quality diagnostic that can accurately distinguish between those patients well-suited for treatment and those unlikely to derive any benefit.

The draft conference paper presented at the meeting was developed with the goal of guiding design of Phase III trials to evaluate a drug and companion diagnostic in situations where prior studies do not provide a clear definition of the diagnostically selected population and sufficient evidence to restrict development.

The draft is intended to fill some of the stakeholder-identified gaps in FDA’s July 2011 draft guidance on vitro companion diagnostic devices. In that 12-page guidance, FDA explained how it defines a companion diagnostic and its expectations for simultaneous development and approval of a drug with the accompanying test.

However, the guidance left many in the drug and device industries wanting more details, such as the regulatory ramifications for drug/diagnostic combinations that are not developed and reviewed in parallel fashion and how laboratory-developed tests fit into the agency’s paradigm for companion diagnostics.

“Patients have to be protected by appropriately balancing the strength of the diagnostic hypothesis with the need for thorough data generation and evaluation,” the draft paper states. “We believe the appropriateness of including marker-negative patients primarily depends on the strength of the science in support of the diagnostic hypothesis (including but not limited to mechanism of action, pre‐clinical efficacy and, if known, class effect), the potential for risk to patients, and clinical data available to date,” the draft paper states.

FDA Office of Hematology and Oncology Products Director Richard Pazdur highlighted several basic principles that FDA considers when evaluating the use of biomarkers in applications submitted to the agency.

The first among these is that the companion diagnostic must be essential for use of the drug, Pazdur said. “It’s not like we’d like to have it or it might be nice to have it or we might in the future need it. It should be essential for the use of the drug when it is licensed.”

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Premature Evaluation

09/26/2012 07:46 AM |

The U.S. should implement policies that will double the output of new, innovative medicines for important unmet medical needs within 15 years, according to a report released yesterday by the President's Council of Advisors on Science and Technology. The report on "Propelling Innovation in Drug Discovery, Development, and Evaluation" said this goal could be met through increasing funding for basic, translational and regulatory science and creating a broad-based partnership bringing together government, industry, academia and other stakeholders to improve the discovery, development and evaluation of new medicines.

The report recommends creating a new "special medical use" pathway to approve drugs for narrow populations. It also recommends strengthening FDA's postmarketing surveillance capacity by appropriating $40 million per year for the agency's Sentinel electronic safety surveillance system. PCAST said FDA should explore the creation of an adaptive, or progressive, approval system, but it concluded that legislation creating an adaptive approval system "would be premature at this time."

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Calumniatory PCORI

09/25/2012 07:57 AM |

A “trust problem” indeed.

The Patient-Centered Outcomes Research Institute’s draft methodology report contains discussions and language choices that could (per Pink Sheet reportage) “tarnish” the institute’s approach to research on pharmaceuticals.

Rust never sleeps.

Both PhRMA and BIO express consternation about what they see as the draft report’s implication that the public should be suspicious of the results of drug industry-sponsored trials.

Their views are contained in recent comments on a draft methodology report written by PCORI’s Methodology Committee. The methodological standards contained in the report will be part of funding review criteria for future applicants for the institute’s research grants.

The idea that manufacturer-sponsored trials may be untrustworthy is mentioned in the report’s introductory chapter, which contains a section labeled “A trust problem.”

PhRMA, in its written comments, responds that the “implication that physicians are willing to subject patients to potential harm as a result of financial interests is troubling and should be deleted.”

BIO’s written comments agree that the passage is “unduly biased against industry-sponsored research” and “presents a skewed view of research conducted by biopharmaceutical companies.”

The Association of Clinical Research Organizations takes an even stronger stance, saying that for the Methodology Committee “to make such assertions of manipulation or bias without any supporting evidence is highly problematic and calls into question the objectivity and integrity of the committee.” It adds that the discussion “impinges on PCORI’s credibility as a research organization by exposing its own potential bias.”

And then there’s the issue of cost in the draft report’s Chapter Five. It says: “The committee’s view is that in the context of PCOR, cost, like other aspects of the health care delivery system, can be a factor in the effectiveness of care if it influences choices made by patients and clinicians. Cost can be an incentive for delivering inappropriate care, not just a barrier to appropriate care. Providers may have incentive to favor more costly treatments under the common belief that ‘more is better’ in healthcare.”

BIO contends that identifying cost as a potential endpoint “is in direct conflict with the authorizing statute’s specific prohibition of PCORI from considering cost effectiveness in studies of comparative effectiveness.”

PhRMA asserts, “While cost undoubtedly can influence the quality and patient-centeredness of care that individuals receive, research that includes cost as an element of analysis or endpoint of measurement is outside the scope of PCORI’s mandate.”

Industry commenters also say the report is trying to do too much by addressing issues that lie outside of research methodology, in particular the report’s discussions of setting research priorities – the topic of an entire chapter – and disseminating research results.

BIO observes that ACA assigns two responsibilities to the methodology report: provide recommendations for PCORI on methodological standards and develop a translation table to guide researchers in applying the standards to specific studies. The “diversity of other subjects the report discusses,” in particular the discussions of the dissemination of research results and developing research priorities, “distracts from the mandated focus on scientifically-derived methodological standards for PCOR and the framework underpinning the development of a translation table,” BIO says.

PhRMA joins in calling for PCORI to cut these non-mandated subjects from the report, saying that given the resources demands of providing comprehensive standards for PCOR, “we recommend PCORI focus its report on standards for research, rather than important but ancillary issues like research priority-setting and results dissemination.”

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Studies 'Proving' Soda Programs Genes To Make Us Fat Fizzle Out

09/24/2012 02:56 PM |

Here's the AP the story on the evils of sugared soft drinks....  


Studies more firmly tie sugary drinks to obesity

By MARILYNN MARCHIONE - AP Chief Medical Writer - Associated PressFriday, September 21, 2012 
New research powerfully strengthens the case against soda and other sugary drinks as culprits in the obesity epidemic.

A huge, decades-long study involving more than 33,000 Americans has yielded the first clear proof that drinking sugary beverages interacts with genes that affect weight, amplifying a person's risk of obesity beyond what it would be from heredity alone...

This means that such drinks are especially harmful to people with genes that predispose them to weight gain. And most of us have at least some of these genes.

In addition, two other major experiments have found that giving children and teens calorie-free alternatives to the sugary drinks they usually consume leads to less weight gain.

Collectively, the results strongly suggest that sugary drinks cause people to pack on the pounds, independent of other unhealthy behavior such as overeating and getting too little exercise, scientists say.

That adds weight to the push for taxes, portion limits like the one just adopted in New York City, and other policies to curb consumption of soda, juice drinks and sports beverages sweetened with sugar.


Now what's wrong with the article and the studies that make this claim? 

1.  The article on genetics and soft drinks did not control for other forms of sugar or interaction with other behaviors.  Or other genes for that matter.  For instance, there are other genetic mutations that appear regulate obesity which interact with the amount of fiber in one's diet.   

2.  Even if gene-soft drink association (let's just say sugar) is established,  the contribution of the genetic factor may be -- and has been reported to be -- quite small.   For instance, most of us have genetic mutations that increase the risk of diabetes or cancer.   But the relative contribution of those genes and their mutations to winding up with either disease is very, very small in most of us.   Other factors and genetic interactions trigger disease and influence it's progression.   Getting a virus or infection, or having high levels of inflammation, etc. can lead to epigenetic changes that shape disease risk.   Shame on the report and the researchers for not qualifying their message in this way. 

3.  Similarly, the reporter asserts that sugary drinks are the biggest source of calories in the American diet.   Wrong.   The USDA's  Dietary Guideline Advisory Committee gives the breakdown for most Americans...  

  Yeast breads (129 calories per day)
• Chicken and chicken mixed dishes (121 calories per day)
• Soda/energy/sports drinks (114 calories per day)
• Pizza (98 calories per day)

Soft drinks are not even the biggest source of sugar among many age groups.  (Snacks are)  Nor are they problem.  What is?  We don't eat enough plant-based fiber, we take in too much saturated fat..  And we don't exercise.  The DGAC again:

Several distinct dietary patterns are associated with health benefits, including lower blood
pressure and a reduced risk of CVD and total mortality. A common feature of these diets is an
emphasis on plant foods.  Fiber intake is high and saturated fat is typically low. When
total fat intake is high, that is, more than 30 percent of calories, the predominant fats are
monounsaturated and polyunsaturated fats. Carbohydrate intake is typically in the range of 50 to 60
percent of calories, but these often include whole grain products with minimal processing, as well as
cooked dry beans and peas. The totality of evidence documenting a beneficial impact of plant-based
dietary patterns on CVD risk is remarkable and worthy of recommendation.  

The so-called 'empty' calories don't come from soft drinks but the food we eat with them.   But soft drinks are a sweeter target and feed into the narrative that corporations process food to kill us for the sake of profits.   The same capitalism = pollution story that has been applied to energy, chemicals and pharmaceuticals is being applied to food.

When you think about it, the professional critics and their recording secretaries (the media) are attacking the four human innovations that have made life on t his planet better and healthier.  





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Reshaping Breast Cancer

09/24/2012 07:45 AM |

And what role will the FDA play? 

Study Divides Breast Cancer Into Four Distinct Types

By GINA KOLATA

In findings that are fundamentally reshaping the scientific understanding of breast cancer, researchers have identified four genetically distinct types of the cancer. And within those types, they found hallmark genetic changes that are driving many cancers.

These discoveries, published online on Sunday in the journal Nature, are expected to lead to new treatments with drugs already approved for cancers in other parts of the body and new ideas for more precise treatments aimed at genetic aberrations that now have no known treatment.

The study is the first comprehensive genetic analysis of breast cancer, which kills more than 35,000 women a year in the United States. The new paper, and several smaller recent studies, are electrifying the field.

“This is the road map for how we might cure breast cancer in the future,” said Dr. Matthew Ellis of Washington University, a researcher for the study.

Researchers and patient advocates caution that it will still take years to translate the new insights into transformative new treatments. Even within the four major types of breast cancer, individual tumors appear to be driven by their own sets of genetic changes. A wide variety of drugs will most likely need to be developed to tailor medicines to individual tumors.

“There are a lot of steps that turn basic science into clinically meaningful results,” said Karuna Jaggar, executive director of Breast Cancer Action, an advocacy group. “It is the ‘stay tuned’ story.”

The study is part of a large federal project, the Cancer Genome Atlas, to build maps of genetic changes in common cancers. Reports on similar studies of lung and colon cancer have been published recently. The breast cancer study was based on an analysis of tumors from 825 patients.

“There has never been a breast cancer genomics project on this scale,” said the atlas’s program director, Brad Ozenberger of the National Institutes of Health.

The investigators identified at least 40 genetic alterations that might be attacked by drugs. Many of them are already being developed for other types of cancer that have the same mutations. “We now have a good view of what goes wrong in breast cancer,” said Joe Gray, a genetic expert at Oregon Health & Science University, who was not involved in the study. “We haven’t had that before.”

The study focused on the most common types of breast cancer that are thought to arise in the milk duct. It concentrated on early breast cancers that had not yet spread to other parts of the body in order to find genetic changes that could be attacked, stopping a cancer before it metastasized.

The study’s biggest surprise involved a particularly deadly breast cancer whose tumor cells resemble basal cells of the skin and sweat glands, which are in the deepest layer of the skin. These breast cells form a scaffolding for milk duct cells. This type of cancer is often called triple negative and accounts for a small percentage of breast cancer.

But researchers found that this cancer was entirely different from the other types of breast cancer and much more resembles ovarian cancer and a type of lung cancer.

“It’s incredible,” said Dr. James Ingle of the Mayo Clinic, one of the study’s 348 authors, of the ovarian cancer connection. “It raises the possibility that there may be a common cause.”

There are immediate therapeutic implications. The study gives a biologic reason to try some routine treatments for ovarian cancer instead of a common class of drugs used in breast cancer known as anthracyclines. Anthracyclines, Dr. Ellis said, “are the drugs most breast cancer patients dread because they are associated with heart damage and leukemia.”

A new type of drug, PARP inhibitors, that seems to help squelch ovarian cancers, should also be tried in basal-like breast cancer, Dr. Ellis said.

Basal-like cancers are most prevalent in younger women, in African-Americans and in women with breast cancer genes BRCA1 and BRCA2.

Two other types of breast cancer, accounting for most cases of the disease, arise from the luminal cells that line milk ducts. These cancers have proteins on their surfaces that grab estrogen, fueling their growth. Just about everyone with estrogen-fueled cancer gets the same treatment. Some do well. Others do not.

The genetic analysis divided these cancers into two distinct types. Patients with luminal A cancer had good prognoses while those with luminal B did not, suggesting that perhaps patients with the first kind of tumor might do well with just hormonal therapy to block estrogen from spurring their cancers while those with the second kind might do better with chemotherapy in addition to hormonal therapy.

In some cases, genetic aberrations were so strongly associated with one or the other luminal subtype that they appeared to be the actual cause of the cancer, said Dr. Charles Perou of the University of North Carolina, who is the lead author of the study. And he called that “a stunning finding.”

“We are really getting at the roots of these cancers,” he said.

After basal-like cancers, and luminal A and B cancers, the fourth type of breast cancer is what the researchers called HER2-enriched. Breast cancers often have extra copies of a gene, HER2, that drives their growth. A drug, Herceptin, can block the gene and has changed the prognosis for these patients from one of the worst in breast cancer to one of the best.

Yet although Herceptin is approved for every breast cancer patient whose tumor makes too much HER2, the new analysis finds that not all of these tumors are alike. The HER2-enriched should respond readily to Herceptin; the other type might not.

The only way to know is to do a clinical trial, and one is already being planned. Herceptin is expensive and can occasionally damage the heart. “We absolutely only want to give it to patients who can benefit,” Dr. Perou said.

For now, despite the tantalizing possibilities, patients will have to wait for clinical trials to see whether drugs that block the genetic aberrations can stop the cancers. And it could be a vast undertaking to get all the drug testing done. Because there are so many different ways a breast cancer cell can go awry, there may have to be dozens of drug studies, each focusing on a different genetic change.

One of Dr. Ellis’s patients, Elizabeth Stark, 48, has a basal-type breast cancer. She has gone through three rounds of chemotherapy, surgery and radiation over the past four years. Her disease is stable now and Dr. Stark, a biochemist at Pfizer, says she knows it will take time for the explosion of genetic data to produce new treatments that might help her.

“In 10 years it will be different,” she said, adding emphatically, “I know I will be here in 10 years.”

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