Latest Drugwonks' Blog
Per a new PhRMA white paper, FDA guidance on the supporting evidence drug companies need for the health care economic data they send to formulary managers should specifically allow for use of a range of data sources, not limited to adequate and well-controlled clinical trials.
The white paper urges the agency to develop formal regulatory guidance on Sec. 114 of the FDA Modernization Act of 1997, which allows drug companies to proactively disseminate health care economic information to formulary committees within certain limitations.
In the 15 years since FDAMA was passed, FDA has yet to issue formal guidance on Sec. 114. As a result, “many biopharmaceutical companies are reluctant to engage in these communications,” PhRMA points out, and “the promise of FDAMA Sec. 114 has not been fully realized.” A recent analysis of FDA enforcement actions over the past 10 years supports the premise that drug companies have been slow to engage in promotional activity under Sec. 114.
Sec. 114 requires that economic information be supported by “competent and reliable scientific evidence,” which was intended as a more flexible standard than the “substantial evidence” standard for drug approvals, PhRMA maintains. The “competent and reliable” standard was drawn from the Federal Trade Commission’s standard for supporting promotional claims.
The white paper outlines a number of data elements that should satisfy the competent and reliable scientific evidence standard. They include: methods for establishing economic costs and consequences that are widely accepted by experts in the field using a clear, pre-defined study protocol; an “accurate and balanced assessment of the economic consequences of a drug therapy, consistent with the current weight of credible evidence”; a representative study population; and information that allows the reader to determine how the research was conducted.
PhRMA recommends that FDA allow the competent and reliable standard to be satisfied with data obtained through a number of different methods, including observational study designs, database reviews and other economic modeling techniques. “There should be no pre-specified number or type of study required to substantiate a claim."
For example, “a claim that a drug is more cost-effective than a competing drug may be made where the cost savings are due to reduced resource utilization resulting from improved efficacy outcomes, decreased administration or monitoring costs, or where the difference in cost is due to the drug causing fewer adverse events, as long as these differences are supported by competent and reliable evidence.”
PhRMA argues that FDA should not consider such a statement a comparative clinical claim, which would trigger the “substantial evidence” requirement involving clinical trials.
Companies should be permitted to disseminate data on the “real world” economic implications of a therapy on health outcomes, according to the white paper. For example, “if a manufacturer conducts a competent and reliable study investigating the impact of a drug indicated for the treatment of diabetes mellitus on costs associated with cardiovascular care, the manufacturer should be permitted to proactively disseminate such data to appropriate audiences.”
Or is just just because rent-seeking behavior, especially in health care, is all about making money by charging admission fees to show up to conferences where the usual talking points about CER, value-based purchasing, etc are shared? Is Don Berwick actually being paid to talk about Medicare activities that consist of charging people to talk about Medicare? Yes.
So here's a refreshing point of view. Enough of using social media to just talk and spread the fertilizer around.. how about using it to take action against disease more quickly..
http://www.forbes.com/sites/ashoka/2012/10/12/lets-move-from-breast-cancer-awareness-to-collaboration-around-solutions/
Senator Joe Biden voted against the Medicare prescription drug benefit (Part D). Vice President Biden warned said that a Romney Administration would take it away.
This proves one thing -- Part D is a big success.
No up-for-reelection veep, on a nationally televised debate during a tight race is going to be against a program with approval ratings above 90%, universally acknowledged as improving the health of seniors, and is regularly coming in below budget estimates.
What neither Vice President Biden (not surprisingly) nor Congressman Ryan (surprisingly) mentioned is the reason Part D is so successful -- its design as a public/private partnership.
Vice President Biden mentioned (although not by name) the Non-Interference Clause – and that we should do away with it. Wrong. He did not mention it was designed by then Senator Tom Daschle and the late Senator Ted Kennedy during the debate over ClintonCare.
The first question to ask is, what did Senators Tom Daschle and Ted Kennedy know that President Obama does not? The answer is that allowing the Federal government to directly negotiate for Medicare drug prices is a bad idea. That’s why they (Daschle and Kennedy) drafted the original language for the Non-Interference Clause.
Politics aside, consider the facts:
"It is not obvious that allowing the government to negotiate with pharmaceutical companies will lead to lower prices than those achieved by private drug plans. Private plans like Kaiser or United are able to negotiate deep discounts with pharmaceutical companies precisely because of the plans' ability to say no – the ability to include some drugs and to exclude others, allowing the market to judge the resulting formulary. On the other hand, when the government negotiates, its hands are tied because there are few drugs it can exclude without facing political backlash from doctors and the Medicare population, a very influential group of voters. Neither economic theory nor historical experience suggests government price negotiation will achieve lower drug prices. Congressional Democrats need to be careful in making the logical leap from market share to bargaining power. Empowering the government to negotiate with pharmaceutical companies is not necessarily equivalent to achieving lower drug prices. In fact, neither economic theory nor historical experience suggests that will be the outcome. Members should think carefully before jumping on the bandwagon – this promise may bring just the opposite of what was ordered."
Stanford Business School's Alain Enthoven and Kyna Fong
And in the words of the American vox populi (aka, USA Today):
"Both the non-partisan Congressional Budget Office and Medicare actuaries have said they doubt the government could negotiate lower costs than the private sector. The theory behind Part D is that market forces and competition among drug plans, overseen by government, can achieve better results than a government-run program. The multitude of plans allows seniors to pick one that best meets their needs. Government price negotiation could leave people without drugs that manufacturers decide aren't sufficiently profitable under the plan. Medicare recipients account for half of all drug prescriptions. With that kind of clout, government might try to dictate prices, not just negotiate them. This could leave people without drugs that manufacturers decide aren't sufficiently profitable under the plan. The VA plan illustrates the point. It offers 1,300 drugs, compared with 4,300 available under Part D, prompting more than one-third of retired veterans to enroll in Medicare drug plans."
Many of the President’s men and women are ready with the following talking point, “Look at how successful direct Federal negotiation works for the Veteran’s Administration,” suggesting that allowing the feds to directly negotiate for Part D is no different from the current VA scenario. But suggesting that the Veteran’s Administration “negotiates” prices for prescription drugs is a false premise.
Under rules set by Congress, to sell drugs to the VA, companies must offer each drug at a price that “represents the same discount off a drug’s list price that the manufacturer offers its most-favored nonfederal customer under comparable terms and conditions.” The medication must be offered “at a discount of at least 24 percent off [the] nonfederal average manufacturer price (NFAMP). An excess inflation rebate is also required, equal to the percentage by which the price increase for [the] drug has exceeded the consumer price index (CPI) in the prior period.” The manufacturer must make all of its drugs available through the Federal Service Schedule for any of its drugs to be eligible for reimbursement under the VA and Defense Department health systems, the Public Health Service (including the Indian Health Service), the Coast Guard, and the various state Medicaid programs.
A study by Professor Frank Lichtenberg of Columbia University found that the majority of the VA formulary’s drugs are more than eight years old and more than 40 percent are 16 years old or more. Just 19 percent of all prescription drugs approved by the FDA since 2000 are available to veterans; only 38 percent approved during the 1990s are.
There’s a big difference between negotiating and mandating – and it’s not a thin line. A negotiated Part D plan is but the first step towards a more strident program of government price controls.
The bottom line here is that Part D is a tremendous success – due in no small part to the Non-Interference Clause.
Say it is so, Joe.
Ditto this claim that market forces and pay for performance will save Medicare tons.
Here's the lede about the results of yet another Medicare demonstration project that saved no money...
Medicare penalty fails to curb hospital-acquired infections
By Karen Cheung-Larivee
Four years after the Centers for Medicare & Medicaid Services discontinued payments for preventable hospital-acquired conditions (HACs), new research finds that the policy had no effect on curbing infections, published today in The New England Journal of Medicine.
In October 2008, CMS discontinued additional payments for preventable HACs, according to the American Society for Healthcare Risk Management:
Vascular-catheter-associated infection
Catheter-associated urinary tract infection
Pressure ulcers (stage III and IV)
Falls and trauma
Surgical site infection after bariatric surgery for obesity
Certain orthopedic procedures
Bypass surgery (mediastinitis)
Administration of incompatible blood
Air embolism
Foreign object unintentionally retained after surgery
Although the policy only cut back an average of six-tenths of a percent of Medicare revenue, according to The Boston Globe, it was a high-profile policy change toward a pay-for-performance approach to reimbursement.
Researchers looked specifically at data from 2006 through 2011 on central catheter-associated bloodstream infections and catheter-associated urinary tract infections and compared infection data against rates of ventilator-associated pneumonia, which is not under the nonpayment policy.
The result: Researchers found "no evidence that the 2008 CMS policy to reduce payments for central catheter-associated bloodstream infections and catheter-associated urinary tract infections had any measurable effect on infection rates," study authors wrote.
Still, researchers acknowledged that hospital infection rates are falling overall.
Although infections rates have generally dropped since 2006, it wasn't because of the Medicare penalties, U.S. News and World Report's HealthDay reported.
"It had really nothing to do with the CMS policy," Grace Lee, associate professor at Harvard Pilgrim Health Care Institute and Harvard Medical School, told The Boston Globe.
The downward trend was happening well before policy implementation, due to hospitals taking charge of infections. Hospitals may already haven taken big steps to control infections in the years prior, Lee said.
The overall improved infection rates also may have more to do with rigorous coding procedures, in which case, the improved rates demonstrate better administrative skills rather than better quality, HealthDay noted.
The research strengthens some providers' discontent with the federal agency's "stick" approach, in which CMS halts reimbursement for what it deems preventable or avoidable events.
American Hospital Association Vice President Nancy Foster told The Wall Street Journal the study should make policy makers "take a step back and say, 'Are payment penalties the right way to go; do they actually add to the efforts?' on reducing infections and other hospital-acquired conditions?"
Post-election, the $10 billion or so in new money for all these demonstration projects should be ripe for elimination.
The best way to stop an infection from spreading is to get at the underlying cause....
As previously reported (‘Heavy Meddle,” May 3, 2012), when our tax-payer funded government detailers call to schedule an appointment with a “high-volume” prescriber, one of the enticements they offer are free CME credits.
Who accredits those CME credits? Here’s how Barry Patel, CEO of Total Therapeutic Management (the company contracted by the AHRQ to handle it’s so-called “academic detailing” program) responded:
“One of AHRQ’s contractors, PRIME, Inc., coordinates accreditation for the CE/CME modules presented during the visits. PRIME works with the appropriate accrediting bodies for the different types of clinicians taking part in the visits, including doctors, nurses, pharmacists, physician assistants, and others.”
I shared Mr. Patel’s response with ACCME and asked how they felt about free CME being offered as an enticement to a physician. Here is the response I received:
“Questions about credit should be asked of the credit systems."
Punt!
When I pressed for an answer, this is what I was sent:
"You are welcome to refer to our Web site for information about our accreditation requirements and accredited providers. We do not comment on specific accredited providers or activities and we do not have any further comments to make at this time."
That’s the nadir of ACCME.
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.
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.
