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The New York Times’ breaking news on cheerleaders as pharmaceutical detailers and the Wall Street Journal’s hard-hitting expose on professional medical writers both appeared on the front-pages of these national newspapers of record. Today’s story on a Pfizer-funded $100 million, 20,000 patient study on Celebrex (headed by the Cleveland Clinic’s well-respected cardiologist, Dr. Steven E. Nissen) appeared on pages C3 and D5 of the New York Times and the Wall Street Journal respectively. What is wrong with this picture?
I am queried by a DrugWonks reader as to whether any of the medical ghostwriters vilified in the below-referenced WSJ article have at any point also been cheerleaders.
Here’s the most recent example of why facilitating FDA’s Critical Path initiative is so crucial. FDA has granted initial clearance to AcryMed Inc. for a nanotechnology that can render existing medical devices impervious to infection-causing bacteria. The successful application of nantechnology is big news. The product, SilvaGard, can be used to treat virtually any medical device and its use does not alter the device’s original properties. The Centers for Disease Control estimates that 2 million U.S. patients a year acquire hospital-related infections. These infections cost an average of $47,000 per patient to treat and cause 90,000 deaths each year. The added cost to hospitals is $4.8 billion annually in extended care and treatment. The initial FDA clearance was given for marketing regional anesthesia delivery catheters. These devices are treated with a silver nanoparticle antimicrobial coating that protects against the formation of infection-causing biofilm. The devices can be treated to provide effective antimicrobial protection for days, weeks, or even months, depending upon application requirements.
Dr. Bob Goldberg on much ado about data …
In another example of how the once respected and objective medical journals have become both caricatures of their former selves and tools of a political agenda, the editors of the New England Journal of Medicine has weighed in with a non-peer reviewed and unscientific piece of second guessing about an article Merck researchers submitted regarding the VIGOR (Vioxx Gastrointestinal Outcomes Research Study). The editorial, written in a near breathless fashion makes a big deal about three heart attacks associated with Vioxx that were omitted from the study which itself was designed to see if Vioxx was better for the tummy than Aleve. Merck says the heart attacks came after the study occurred, should not have been included and were therefore deleted. The NEJM editors who never explain how they came upon the missing data (it was just discovered, ya see, one night by accident) but you would think that that given the front-page coverage afforded this discovery that the editors had discovered that John Lennon is really alive.
In fact, it is hard to see if the charts cooked up by Drazen and company actual overestimate the relative risk of a heart attack since we do not know (though the FDA does) the actual source, cause and timing of the incident nor whether even at the relative risk they assigned it would have caused the FDA any greater concern about Vioxx labeling than it had expressed at the time. Indeed, the FDA had plenty of data from Merck and other sources about the cardiovascular risk associated with Vioxx, particularly among seniors with rheumatoid arthritis. The question was, and is, at what point and at what dose was it problematic? But the same question can be raised about ANY painkiller. The deletion of three cases was statistical small potatoes back then. It did not stifle concerns. On the contrary, the complex issues about the relative risks and benefits of COX-2 drugs are now being sorted out at a molecular level.
I am not sympathetic to a company that aggressively markets a product beyond what prudent science suggests. But to suggest that Merck deliberately hid data or even imply it in a once reputable medical journal is another form of aggressive marketing and self-promotion that endangers lives as well. Too many people are now not taking important medicines for pain, depression and other illnesses because the NEJM, JAMA, The Lancet and the British Medical Journal have allowed their political love fest with the leftists in the media and their hatred of drug companies to pollute their ability to remain objective. These publications and their editors fancy themselves as rebels with a cause, as insurgents who will stand up against the pharmaceutical industry with hit and run editorials, after the fact articles like Topol and Nissen’s second guessing of the FDA’s review of a diabetes drug and half baked ideas for FDA reform, all the while ignoring more substantive and transformative scientific research that will truly make medicines safer and more effective. Their agenda driven publications are steadily losing credibility. There are many in the scientific community who are fed up with their tyranny and arrogance as well as the damage they are inflicting upon patients.
From Day Two of FDA’s Part 15 Hearing on communicating risk information.
Day 2 was more energized and useful than Opening Day. This is due in no small part to the panelists acting more like engaged health care advocates rather than website designers. Having a website does not replace having insight. To wit:
Alan Goldhammer (PhRMA) made the point, echoed by many other panelists over the course of the day, that FDA and industry can do a better job communicating risk information by working together rather than (a) covering the same ground separately (which eats up both precious time and spare resources), or (b) acting in an adversarial fashion (which causes messages to be either inappropriately magnified or dangerously ignored). Alan made the very excellent point that it’s very easy to frighten people — and that leads to dangerous unintended consequences.
John Wolleben (Pfizer) commented that risk communication must begin with the thought, “What do patients need to know?” He also verbalized the quandary that it’s hard to turn drugs “on and off” at the right times in the right ways. He suggested that the FDA’s goal should be to develop standardized tools for both agency and industry and suggested a working group to design and test such instruments.
Cherif Bennattia (APhaRC) said that the FDA should learn from the the pharma industry’s success in communicating benefit to better understand how to communicate risk. A good point. Dr. Nancy Ostrove (a member of the FDA panel on the second day) commented that FDA really couldn’t move forward with any industry learnings without supporting data. My comment — boy is that the pot calling the kettle black. Cherif also made the point that as the agency moves forward they need to define their goal — something like “what is the goal of successful risk communications.”
Joe Cranston (AMA) had the most specific recommendations of the day relative to helping docs receive and communicate risk information. His list included: finalize the new physician labeling rule; work more closely with specialist organizations on relevant risk communications issues; use post-market surveillance information for data mining opportunities; and increase funding for same. He also made the point that the big issue for MDs is TIME. How can the FDA help physicians prioritize and deliver relevant risk information to their patients? His other specific suggestions included: a CME initiative on risk communications; a standardized FDA website icon by specialties; more user-friendly “Dear Doctor” letters; electronic “Dear Doctor” letters; having pharma firms incent their sales force to “detail” risk information; and most interestingly — interfacing with (yet-to-come) e-prescribing technologies.
Joe is The Man.
Susan Winckler (APhA) suggested that the debate be about quality rather than quantity — that an increase in volume has resulted in the unintended consequence of pharmacists not being as alert to PIS and medguide issues.
Tom Lawlor (NACDS and Walgreen’s) pointed out that Walgreen’s research shows that volume of risk information reduces compliance among patients, docs, and pharmacists. He also very smartly noted that the debate shouldn’t be about “risk communications” but rather “risk management communications” — and that’s a lot more than just a finesse.
Focusing on prescription drug counterfeiting as international health care terrorism is often trivialized by pols and pundits as “just another scare tactic of Big Pharma.” That argument has never held up under the facts (stubborn things those facts) — and here’s a new truth that should further force those who deny the threat of counterfeits to reconsider their position — efforts to control the spread of bird flu in poultry in Southeast Asia are being hampered by the use of ineffective and often fake agricultural vaccines. This according to Robert Webster, a British virologist, animal flu specialist, and director of the World Health Organization’s Collaborating Centre for Studies on the Ecology of Influenza in Animals and Birds. As a result the threat of the virus evolving and being able to pass to humans, triggering a potentially catastrophic pandemic grows. It’s time to wake up and address prescription drug counterfeiting as what it is — international health care terrorism.
Literally. I’m blogging to you from deep beneath L’Enfant Plaza at Day One the FDA’s two-day Part 15 hearing on “Communication of Drug Safety Information.”
In announcing the meeting in the Federal Register, FDA posed six questions about how to better communicate drug safety information, but it really only boils down to one (posed by me, not the FDA): When the agency’s motive (a better informed consumer) is good, but it’s methods (or lack thereof) are bad — what should be done?
In typical government fashion, the answer is “seek comment.” Herewith some of what was presented today:
Ruth Day (Duke University) gave a very good presentation on why FDA’s communications on drug safety issues create (are you ready for a new term?) “Cognitive inaccessibility.” That means the information is disseminated in a way that is not only not understood by consumers but, worse, is misunderstood leading to unintended consequences. She reckons that only 20% of the information put out by FDA is properly comprehended. Her suggestion (among others) is that FDA initially focus on communicating better with health care providers (read “doctors and pharmacists”).
Michael Wolf (Northwestern University) gave a similar presentation. His take-away point was that 90 million adult Americans are functionally health-illiterate, meaning that 90 million adult Americans misunderstand FDA information and this leads to unintended consequences.
Diana Zuckerman (National Research Center for Women & Families) pointed out that FDA’s attempts to communicate safety information is neither clear nor clearly focused to specific user groups with the result being unintended consequences.
Ray Bullman (National Council on Patient Information and Education) spoke to the point that incomplete and emerging information can result in unintended consequences. He also called for the development of an FDA research agenda (with request for comments in the Federal Register) so that the agency can design a communications platform based on sound social science that would drive how they communicates drug safety with and to various constituencies.
When your motives are good and your methods are bad (causing cognitive inaccessibility and unintended consequences) what you should do (beyond “seeking comment”) is “first do no harm.”
It’s gonna take a lot more than just fixing how the FDA uses its website.
PS/I should also add that Sid Wolfe was one of the panelists, but he mumbled his way through his presentation and I wasn’t paying attention.
Bob Goldberg’s bark is as sharp as his bite as is illustrated below:
And the Award for Least Curious Journalist Goes To …
Take your pick when it comes to inconsistency on following the so-called conflict of interest issue as it pertains to the FDA. Here’s how it works. If you have “ties” to industry by virtue of talking to companies for nine months or if your wife has ties to a big drug company or if you work for the FDA and your kid babysits for someone who works for a big drug company you are conflicted and therefore should not be allowed to work for the FDA or any issue coming before the FDA according to Charles Grassley and Maurice Hinchey or those eager reporters who define conflict of interest in similar terms. But what if you work at the FDA and happen to also have part ownership in a company that markets products that compete with a drug that you happen to review? No problem! That is, unless you are the company that raises an objection about a possible conflict and then of course you are accused, as was Wyeth, of “targeting” an FDA reviewer of animal medicines. Then the mainstream media (MSM) is all over the issue as yet another example of how big drug companies — who get but 8 percent of all the drugs they develop approved — manhandle the FDA.
To sum up: it’s a conflict and worth reporting if you consulted for a drug company or had lunch with a drug company representative or someone from a drug company attended your kid’s Bar Mitzvah. But if you run business that sells products in direct competition with those you are reviewing, that’s ok because the direct competition is a BIG DRUG COMPANY.
An invitation to babysit for any MSM journalist who can explain their inconsistency on this one or at least has the guts to respond to me at firstname.lastname@example.org
In July 2003 the FDA’s Consumer Health Information for Better Nutrition Initiative announced, as its central focus, the twin goals of making available better, easily understood, up-to-date scientific information about how dietary choices can affect health, as well as encouraging companies to compete based on health and nutrition consequences, in addition to such non-health-related features of products like taste and ease of preparation. According to the press release (which I helped to draft), “A better-informed public — aided by science-based health information — would be able to choose foods that are more nutritious, potentially addressing such urgent public health problems as the rise in obesity and overweight.”
But that was way back in 2003. Today the FDA turned down a request by General Mills to label cereal, bread and other products as a “good source” or “excellent source” of whole grains. Noting that the government’s new dietary guidelines do say that consumers can benefit from increased consumption of whole grains, the FDA said it wants to further consider what the term “whole grain” should include.
In a lengthy petition filed in May 2004 General Mills asked the FDA to define what it means for a product to be described as “made with” whole grain or an “excellent source” of whole grain or a “good source” of whole grain. It suggested that the FDA use the amount of fiber in a product to determine if it is, indeed, a good source of whole grain. The FDA, in its recent letter, refused.
But the agency has permitted the food makers to declare on the label that eating whole grains can reduce the risk of heart disease and certain cancers, if the foods contain more than 51% of whole grain and the required amount of fiber. Food companies also can make statements, such as “10 grams of whole grains” and “100% whole grain oatmeal.”
The FDA must not be pulled, spiraling downwards, by the dangerous gravitational pull of the Precautionary Principle. Rather than being seen as Dr. No, FDA should step up to the plate (so to speak) and do the right thing — promote good health. And whole grains is a no-brainer.
Some non placebo-coated comments from CMPI advisory board member, Henry Miller — especially timely as we approach the two day Part 15 hearing on communicating drug safety (this Wednesday and Thursday). I will be at this meeting and report on what I encounter. In the meantime — heeeeeeere’s Henry!
Overhaul of Unwieldy Labels on Drugs Isn’t Thorough Enough
By Henry I. Miller
Have you ever tried to read the official FDA-approved labeling for a drug? It’s tough going even for physicians who are trying to find something in a hurry, and almost impossible for non-experts. Although there is a standard format for the subheadings, it is without rhyme or reason, and there is a lack of consistency in fonts and spacing. Both common sense and focus groups tell us that crucial information such as the drug’s uses, warnings and dosage should be up front, but instead it’s buried in the middle of the labeling — and in impenetrable small print.
Consider, for example, the antibiotic Cipro, whose labeling in the
Physicians’ Desk Reference runs to five full, large pages of tiny print. The first paragraph of the first section, “Description,” contains this gem” “Ciprofloxacin hydrochloride, USP, a fluoroquinolone, is the monohydrochloride monohydrate salt of 1-cyclopropyl-t-fluoro-1, 4-dihydro-4-oxo-7-(piperazinyl) — 3 quinolinecarboxylic acid. It is a faintly yellowish to light yellow crystalline substance …”
Just the info you need at your fingertips! And the second section,
“Pharmacology,” is equally unhelpful, discussing absorption, distribution within the body, metabolism, excretion and so on.
It’s not until the third page of the labeling that we finally get to
critical information, “Indications and Usage.” After that follows a
series of discrete sections whose contents overlap significantly (and
problematically): “Contraindications,” “Warnings,” “Precautions,” and
During a recent advisory committee meeting, FDA officials outlined proposed new labeling, which is expected to be published soon. Information will be organized logically and in order of importance: boxed warnings (the most forceful caution that FDA can require), what the drug is used for, and then the dosage and administration. Any major changes in the label will also be prominently featured, and the old sections on contraindications, warnings, precautions and adverse reactions (that is, side effects) will be consolidated. There will also be, we are told, “more clarity in the adverse reaction section.”
The FDA also intends to introduce DailyMed, “an electronic repository of … the most current labeling, vetted, approved, the gold standard of drug information.” I am looking forward to it; the Physician’s Desk Reference on my office bookshelf is the 2004 edition, which means that the data was compiled at least two years ago.
These initiatives will be a marked improvement over the current antiquated system of drug labeling. However, not all of the FDA’s innovations are so inspired.
Much criticized lately for supposed deficiencies in the surveillance and reporting on the safety of drugs, the agency is implementing a wrong-headed scheme for releasing data on drugs’ adverse reactions.
In May, the FDA announced its new Drug Watch program, which will make
“emerging safety information” publicly available. According to the FDA, this program “is intended to identify drugs for which the FDA is actively evaluating early safety signals. The Drug Watch is not intended to be a list of drugs that are particularly risky or dangerous for use; listing of a drug on Drug Watch should not be construed as a statement by the FDA that the drug is dangerous or that it is inappropriate for use. Rather, inclusion on the Drug Watch signifies that FDA is attempting to assess the meaning and potential consequences of emerging safety information.”
FDA further “clarifies” in the same document that Drug Watch is intended “to share emerging safety information before we have fully determined its significance or taken final regulatory action so that patients and health care professionals will have the most current information concerning the potential risks and benefits of a marketed drug product upon which to make individual treatment choices.”
However, it is difficult to fathom how physicians and other health care providers — let alone members of the public — can make good use of such preliminary data, which will be available on the agency’s Web site. There is a difference between indiscriminate data and useful information, and Drug Watch seems destined to provide far more of the former than the latter. Moreover, given the current fervor at FDA for ensuring drug safety, and the difficulty of proving a negative, one wonders how a “suspect” drug could ever clear its name and get off the Drug Watch list.
As FDA Deputy Commissioner Scott Gottlieb has said, “Information that
could influence clinical medical practice needs to be made available more quickly, and more widely, after it has gone through a deliberative scientific process that firms up its meaning and the magnitude and the veracity of its conclusions.” DailyMed, which will provide up-to-the-minute labeling information, meets these criteria, while Drug Watch fails miserably.
Surely, it would be better to rely on what the FDA considers to be
information that is “vetted, approved, gold standard” than on what
Gottlieb himself has dismissed as data “still unscrubbed by scientific rigor.”
My advice to the FDA: Take two aspirin, get a good night’s sleep, and
perform a Drug Watch-ectomy in the morning.