Latest Drugwonks' Blog
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).
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.
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
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."
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.
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.
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.
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.
From Medscape Medical News
Number of Uninsured Will Soar Under Romney Plan, Report Says
By Mark CraneOctober 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."
"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."
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.
