Megan McArdle's article on why there are fewer drugs approved is well taken and is actually not new, just lost in the stupid way the media reports on the FDA. I also take strong exception to the claim that conservatives blame the FDA. Five years ago I chaired a task force, established by the late Joshua Lederberg, to look at how the FDA was using regulatory science based on new genetic and clinical insights used to discover new targets to change medical product development. The Critical Path initiative was established to create a new set of tools for this purpose, tools that would help individualize risk and benefits. Those who use Big Pharma to attack commercialization have sought to undermine the Critical Path because it eliminates unexpected fear as a political weapon. Those who attack "biomarkers" as another way companies can market new, ineffective drugs willfully fail to grasp the fact that the principal barrier to approval is the absence of well validated markers. And the attack comes from the right and the left.
The report can be found here: www.manhattan-institute.org/pdf/CMP_FDA_Task_Fo...
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Interesting story in yesterday’s edition of the St. Louis Post-Dispatch about Express Scripts and its president, George Paz (who is referred to in the article as a “former accountant").
Mr. Paz -- “The cheapest drugs is (sic) where we make our profits.” To that end, the article points out that in 2008, “Express Scripts agreed to pay $9.3 million to 28 states and $200,000 in reimbursement to consumers to settle lawsuits that accused the company of deceptive business practices in allegedly overstating the economic benefits to consumers of switching to certain drugs.”
And yet:
“Express Scripts would like to extend its influence further. Plans are in the works to put information kiosks in doctor's offices to advise patients about cheaper alternatives to brand-name drugs.”
Not “better.” Not “more effective.” Not “safer.” “Cheaper.” Can you imagine what would happen if a pharmaceutical company wanted to try something like this? Can you say “congressional investigation?”
And just who is “cheaper” better for?
"Our whole model is switching people to lower-cost drugs," Paz said. "The more money my shareholders make, the more money I make."
(According to the Post-Dispatch article, Mr. Paz’s compensation, including bonuses and other incentives, totaled $10.6 million in 2009.)
This is sadly reminiscent of the Blue Care Network of Michigan program (now discontinued) that sent letters out to their participating primary care physicians offering a $100 payment “for each member in their panel with a BCN pharmacy benefit who fills a prescription for a generic lipid lowering agent.”
Per an ABC News investigative report, “Blue Care Network in Michigan paid 2,400 doctors $2 million to switch their patients from Lipitor to a generic version of its competitor, Zocor. They were paid $100 for each patient they switched from Jan. 1 through March 31, 2007.” In other words, we’ll pay you $100 to switch your patient to a generic statin that isn’t even a generic version of what they are currently taking.
When asked by the ABC reporter if patients knew their doctors were receiving payments from the insurance company in return for a service that helps to increase the profits of the insurance company, the response from BCN was “not specifically.”
A study fielded by the National Consumers League demonstrated that switching a patient to a generic medicine doesn’t always result in positive outcomes:
- 15% of general Rx users saying that they or a family member experienced therapeutic substitution
– Nearly half of Rx users (47%) were dissatisfied (or their family was) with how the process occurred and report that this substitution did not result in lower pocket costs.
– More than a third (40%) said that the new medication was not as effective as the original one, and nearly a third (30%) experienced more side-effects following the substitution.
– Large majorities of Rx users think that the potential side effects of the new medication, the patient’s medical history, how well the drug works and the prescribing physician's opinion are factors that are absolutely essential when decisions are made about therapeutic substitution.
Just as no two patients have the same biochemistry, no two medicines are exactly equivalent. But if your primary goal is to reduce short-term costs, that's an inconvenient truth.
The repercussions of choosing short-term thinking over long-term results, of short-term cost-based choices over patient-based care, of “me-too” medicines over the right medicine for the right patient at the right time—are pernicious to both the public purse as well as the public health.
http://content.nejm.org/cgi/content/full/NEJMp1006304?query=OF
The key paragraph is:
"The challenge is to deliver the benefits of this work to patients. As the leaders of the National Institutes of Health (NIH) and the Food and Drug Administration (FDA), we have a shared vision of personalized medicine and the scientific and regulatory structure needed to support its growth. Together, we have been focusing on the best ways to develop new therapies and optimize prescribing by steering patients to the right drug at the right dose at the right time."
Sadly not everyone shares their commitment. There are those in the agencies both of them lead who oppose their vision. I know since I have met and heard them speak. One of them -- from the NIH -- called the ALLHAT study the "gold standard" of evidence-based medicine. Must have received his MD from the Rosa Delauro School of Biomarker Science (Merrill Goozner, Dean of Academic Research).
At the same time, personalized medicine does not automatically translate into faster approvals. It would be easy to chalk this up to agency risk aversion across the board. Rather, I think it is more a matter of over time that the regulatory system has been able to become bloated and expensive because the way health care technologies have been paid for allowed both industry and government to pass the cost of oversight on to consumers, inefficiencies and all. Is the process of developing new medicines risky and expensive? You bet it is. But could it be less so and could industry made or demanded more efficiencies in product cycles and manufacturing? Absolutely. And will more of the fate and future of a produce be determined in the market rather than in the clinical period. That will be true as well. Especially when in comes to finding new uses based on the same pathways in different diseases or disease sites.
So faster approvals will still matter, but faster adoption or approvals for new uses will likely matter more. Which means getting to "no" faster in the early stages of development and finding multiple uses in the real world. And both will depend on personalized medicine as defined by Drs. Hamburg and Collins.
The recent 500-page IOM/National Research Council report on the state of FDA’s food regulatory shortcomings is 500 pages of stating the obvious. To conclude that the FDA needs to do more more efficiently does not, shall we say, provide a memorable “aha!” moment.
In July 2003 the FDA issued its Task Force on Consumer Health Information for Better Nutrition Initiative report.
According to the Task Force (on which I was honored to serve), “A better-informed public, supported by effective, science-based regulation of health information, would be expected to make better nutritional choices.”
A sound hypothesis and a noble mission. Unfortunately, the road to better health through better nutrition remains paved with only good intentions. That needs to change. Unfortunately, the IOM/NRC report doesn’t even give passing lip service to this important agenda. Instead, it goes off into the political nether Never Never Land of a “single food agency.” A docket item almost guaranteed to mire any action in political and bureaucratic in-fighting for the foreseeable future.
In 1990 Congress passed the Nutrition Labeling and Education Act, which established the FDA-regulated Nutrition Facts Panel (what most civilians refer to as “the food label) “to assist consumers with healthy dietary practices.” The fact that the “E” in NLEA remains silent continues to go sadly unrecognized, unreported -- and unaddressed. And that’s a real disservice to the public health.
The federal government is trying some humorous scare tactics in a new ad campaign to persuade men to get recommended checkups, today’s WSJ reports.
Experts warn that men’s reticence about going to the doctor — men are 24% less likely than women to have made a routine care visit in the last year — could translate into higher costs of care for a flood of aging Baby Boomers. “In the next 20 to 30 years we are going to see an increase in the population of men who have had virtually no preventive care,” says John Morley, an endocrinologist and geriatrics specialist at Saint Louis University School of Medicine in Missouri. “Men have to be much more aggressive about getting involved in their own health.”
The list of tests men should consider is based on recommendations from the U.S. Preventive Services Task Force, and is limited to screenings that evidence shows are effective for routine use. Those include blood pressure and cholesterol screening, as well as screening for depression and sexually transmitted diseases.
But experts say men also need to talk to their doctors about the risk of developing diseases that aren’t screened for using the recommended tests. For example, the death rate for skin cancers is steadily rising among middle-aged and older men, with white males over 50 making up nearly 50% of all melanoma deaths in the U.S. The USPSTF says there is insufficient evidence to recommend routine body checks for skin cancer, but a study last year in the Archives of Dermatology found that by delaying seeking care for melanoma, men more often present to doctors at a later stage when it is no longer treatable. Cancer groups and dermatologists have stepped up efforts to target men — especially less-educated, middle-aged and older men — to encourage self-exams of the skin to look for changes in moles, since early detection can improve survival.
Prostate cancer, meanwhile, is the second leading cause of cancer death in men after lung cancer, but the task force doesn’t recommend routine screening; for men younger than 75, it says, the benefits are uncertain and the balance of benefits and harms can’t be determined; for men over 75, there is moderate certainty that the harms of screening outweigh the benefits, according to the task force. The USPSTF recommends that doctors discuss the harms and benefits of prostate cancer screening with their patients before performing screening procedures.
The recommendations don’t necessarily affect coverage decisions. For example, for beneficiaries aged 50 or older, Medicare covers one test each year for the two most common tests to detect prostate cancer: the prostate specific antigen (PSA) blood test, and the digital rectal examination (DRE).
In addition to print and broadcast ads that portray Dad as doomed if he doesn’t get his preventive screening tests, the Agency for Healthcare Research and Quality has developed an “e-card” for people to send to their fathers to remind them to go get preventive care. It’s available on the AHRQ’s website by clicking on the button that says: “Get Dad to the Doc.CMPI President Peter Pitts interviews Former Governor George Pataki
No Refills - Magazine - The Atlantic
"India may send health officials to China to inspect manufacturing units of bulk drug suppliers to the South Asian nation to prevent cheap imports, the Press Trust of India reported, citing a government official it didn’t identify. Health officials want to verify drugs supplied to India are made at units certified by government agencies, the news agency said."
Much chatter about David Graham and his leaked Avandia report. It’s turning into a real whodunit. And it’s more complicated than it looks.
First, it’s important to understand that the FDA had already approved Dr. Graham’s request to submit his manuscript to JAMA. So the report (in the Wall Street Journal) that, “… Dr. Graham complained that senior FDA officials were holding up his efforts to publish his work,” is just completely wrong.
So why would Graham leak the report and torpedo his chances of getting it peer-reviewed and published? A few theories are being floated:
(1) The manuscript had been submitted and rejected by JAMA. So spurned, Dr. Graham took the next most expedient step and leaked his report.
(2) Same as above, except the leak came from a supporter inside JAMA either with or without the knowledge of Dr. Graham.
(3) JAMA accepted the paper but determined that it would also offer the FDA or GSK or both a chance for rebuttal. Dr. Graham or a JAMA editor felt this wasn’t fair and leaked the document.
(4) The report was leaked by some else inside the FDA.
Or, in the words of Sherlock Holmes, “When you have eliminated the impossible, whatever remains, however improbable, must be the truth.”...
Whatever the truth, “leaking” a confidential FDA report is not the act of a whistle-blower. Whistle-blowers have the courage of their convictions and are (appropriately) protected. Leakers, on the other hand, are just cowards with an agenda.
At the end of the day, the only thing that counts is that the FDA reach its conclusions based on sound science and not on media leaks – or politics.
It should be in a loose leaf folder.
The most recent example is the article in today's WSJ:
FDA Scientist Attacks Avandia Safety
By JEANNE WHALEN And ALICIA MUNDY
Medicare patients in the U.S. who took GlaxoSmithKline PLC's diabetes drug Avandia may have suffered as many as 48,000 heart attacks, strokes and other problems between 1999 and 2009 that could have been averted had they taken a different drug, a Food and Drug Administration scientist contends in a new study.
The unpublished study by outspoken Avandia critic David Graham, an FDA drug-safety official, echoes his earlier assertions and another study led by the Cleveland Clinic's Steven Nissen that linked Avandia to additional heart attacks and strokes.
The FDA is scheduled to review the drug's safety in a meeting next month. Dr. Graham and others have argued that Avandia should be withdrawn from the market. An FDA official said Thursday that Dr. Graham's study would be included in safety data to be reviewed for that mid-July meeting.
Why should it be included? Or rather, why, since it is just another example of assuming the worst based upon questionable data, is it being included at all.
Because the media and pols pressure the FDA to include it, whether it is crap or not.
Oh, but wait, this isn't just ANY study. This one was
"first published by the Pharmalot blog, which also posted a May 28 email from Dr. Graham to the FDA's senior leaders. In it, Dr. Graham said he wanted to submit the study to the Journal of the American Medical Association for publication. The Pharmalot blog is a respected blog covering the pharmaceutical industry written by Ed Silverman, an editor at large for the industry publication Med Ad News.
In the email, Dr. Graham complained that senior FDA officials were holding up his efforts to publish his work. However, an FDA official, who confirmed the email, said Thursday that the agency isn't suppressing the study and that it was subsequently submitted to the journal.
A JAMA spokeswoman said the journal doesn't ever confirm or deny receipt or acceptance of any manuscript until publication. Dr. Graham couldn't immediately be reached for comment."
We all know that respected peer-reviewed medical journal Pharmalot, which of course does not accept any advertising.
(Drugwonks is respected too but if we were part of such a stunt the Tabloid Medicine machine would rise up in anger and call us tools or something,)
In any event, the preceding is just fancy footwork around having to undergo peer-review (which for an article like this should not be a hard sell at JAMA) and to make all sorts of claims without having to answer serious questions. One of them being, if Nissen showed 43 percent increase risk cherry picking data even as he consults for Takeda, a company making a competitor product, how do you explain the 25 percent figure Graham came up with. Confidence intervals anyone? A second one, is this claims data (yes) and was it adjusted for severity of illness (no) and how many people were on multiple medications (many). Is there a dose effect. Perhaps and in my next blog I will take this on. Third, and the one the FDA will seek to address in adult fashion, do the risks of any of these medications (which all drugs carry) outweigh benefits with respect to controlling progression? The answer is likely no.
So here's the difference, traditional science is rapidly moving towards the personalization of medicine using biomarkers and real-time clinical data. In this new world, risks and benefits can be adjusted more precisely.
Meanwhile the Tabloid Medicine machine -- which includes Nissen, Graham, Mundy, Silverman, Grassley -- see risk everywhere and insist upon a system that seeks to anticipate every risk before it happens.
As Cass Sunstein has noted, the precautionary principle, with it's standard of not allowing any technology absent evidence of zero harm, carries it's own risks. One of them is that people will stop taking medicines that help, including Avandia. The other is that medical innovation will slow to a crawl and that personalized medicine in particular will be crushed by those who, because of cultural and ideological biases, will spread rumors about risk in a unscientific and unbalance fashion. More people will be harmed by adopting the slant of this most recent article in the WSJ.
Where you stand often depends on where you sit. Former Governor George Pataki supports repeal and reform. Some are for, others against. Judge for yourself via this recent interview with the former Empire State Chief Executive.
One thing he points out that we can all agree on is that this shouldn’t be a debate about politics – but rather about policy.
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.
