Latest Drugwonks' Blog
Once again into the abyss. This time the issue is Guidant defibrillators. Solid reporting by Barry Meier of the New York Times raises some troubling and important matters. The first, of course, is what did Guidant know, when did they know it, and why did they delay reporting important adverse events to the FDA? The second, more troubling question, isn’t when the FDA knew — it’s why didn’t they act sooner. Or, to be more precise, how long did the report reside in a CDRH in-box before it was read and acted on. The first set of questions raise the specter of disquieting corporate shenanigans. But the issue of CDRH timeliness is, in the broader scope of the public health, more important, more troubling and, believe it or not, easier to address and remediate. The “front end” of CDRH functions well enough. The “back end,” the part that deals with post-market surveillance issues, not as well. The dedicated career staff at CDRH, under the respected leadership of Dan Schultz work hard — but they (like the rest of FDA) are under-funded and under-staffed. Let me be clear. There is no excuse for delay — but human beings can only do so much. Minus an increase in funding (which doesn’t seem to be in the cards any time soon) something else must be done, from a process perspective, to eradicate delays of potentially life-saving information. Even if Guidant had submitted its report on time, it’s likely the FDA would have taken the same amount of time to read it, digest the implications and issue the same public health advisory. The question isn’t confidentiality. That’s not even relevant. The issue is timeliness. And the answer is for the FDA to take a hard look at its existing processes and make them better. The New York Times, editorializing on its own report, recommends an interesting option — separate the wheat from the chaff. Ask device companies to provide a separate “hot sheet” that directs the FDA’s attention to the most crucial information — rather than burying it deep within the bowels of a more lengthy report. Drugs have risks and devices fail — that’s the world in which we live. And it’s all the more reason for device manufacturers to step up to the plate and be a more senior partner in protecting the public health. But corporate behavior is no excuse for an FDA process issue. A problem has been identified and a solution suggested. Now it’s time for the dedicated public servants at the FDA to solve it — and fast.
When asked why he robbed banks, Willy Sutton, the depression-era desperado replied, “because that’s where the money is.” And, as my former boss Mark McClellan used to say, if Sutton were alive today he’d be selling counterfeit prescription drugs. The bad news is that international prescription drug counterfeiting is on the rise. The worse news is that pending US legislation could make it even worse. Two news items crossed the wire late this week that illustrate this growing problem — and its truly global nature. The first story, from China, tells of eleven Chinese nationals and one American arrested in a counterfeit medicine scheme that spanned eleven countries, 440,000 bogus pills and $4.3 million US dollars. The drugs being peddled were Lipitor, Viagra, Cialis and Levitra. The nations involved were the US, Great Britain, Switzerland and Israel. (Note to Senators Dorgan and Vitter: Drug importation from the EU is dangerous.) The second, more frightening news item comes from Hamilton, Ontario where a registered pharmacist, Abadir Nasr, was charged with selling counterfeit Norvasc (a medicine used for the chronic treatment of hypertension and angina). Congressman Bernie Sanders (I, VT) and others, when asked about the dangers of drug importation are fond of quipping, “Show me the dead Canadians.” Well, the regional coroner in Hamilton is currently investigating the deaths of five people who filled prescriptions for Norvasc at Mr. Nasr’s pharmacy. All five died of a heart attack or stroke. (Note to Governors Pawlenty, Blagoevich and Doyle — and a big red warning to Governor Perry: Drug importation from Canada is dangerous.) Attention must be paid to this very serious problem and the way to make it better is not to make it worse by opening up American borders to medicines not under the jurisdiction of the FDA. Here’s another question — why haven’t either of these news stories been reported by any major American media. (Note to The Washington Post and the New York Times: Google “Hamilton, Ontario.”)
In 2006 the Center for Medicine in the Public Interest (www.cmpi.org), estimated that counterfeit drug commerce will grow 13% annually through 2010. The CMPI study is cited by the WHO on its updated counterfeit pharmaceuticals fact sheet.
Counterfeit sales are increasing at nearly twice the rate of legitimate pharmaceutical sales and they are a money machine. In 2010 CMPI estimates that fake drugs will generate $75 billion in revenues — a 92% increase from 2005. And the risks of detection and prosecution are low.
Our original estimates were made based on conservative projections of counterfeit medicines manufacture and sales issued by the WHO, the FDA, the EU Commission and other global bodies.
But we now feel these numbers are too low – because an entirely new criminal enterprise has emerged – counterfeit ingredients. While counterfeit API (active pharmaceutical ingredient) isn’t a new issue, there is a new and frightening manifestation. In the past, counterfeit API was purchased by criminals making counterfeit drugs. Today a new, significantly more dangerous and difficult to fight enterprise is underway – the sale of counterfeit (“tainted”) ingredients to legitimate pharmaceutical manufacturers. The most high profile example of this is the deadly case of Heparin.
It is impossible to believe that the case of Heparin was an unfortunate mistake – a quality lapse, a one-time and unique circumstance. The facts speak otherwise. This was a case of fraud. Criminal fraud. So let’s call it by its proper name -- counterfeiting.
Counterfeit medicines, according to the WHO are “deliberately and fraudulently mislabeled with respect to identity or source. Counterfeiting occurs both with branded and generic products and counterfeit medicines may include products with the correct ingredients but fake packaging, with the wrong ingredients, without active ingredients or with insufficient active ingredients.”
It’s time to rethink and broaden that definition to include the potential for fake ingredients (“tainted” is both too polite and too inaccurate a term) that insidiously find their way into legitimate pharmaceutical manufacturing.
And, unfortunately, it means that CMPI must recalculate its global estimates for counterfeit medicines and their profits upwards.
Senators Stabenow (D, MI) and Vitter (R, LA) both need better staff work and a remedial course in patent law. Both are offering up H.R. 2862 (aka the Northup amendment). Purpose — “To prevent the United States Trade Representative from negotiating future trade agreements that prevent the United States from changing United States patent law to allow the importation of pharmaceutical products.” It’s a familiar canard — and a dangerous one, as intellectual property rights of US companies are under attack across the globe. Their position, that the USTR shouldn’t have the authority to negotiate agreements that enshrine US patent law, is half-baked and benighted since that’s precisely what Congress instructed the USTR to do in the Bipartisan Trade Promotion Authority Act! Debbie and David are fixated on the recent agreements USTR negotiated with Australia, Singapore and Morocco — and name these three accords specifically in their loony legislation. But the truth is that the provisions in these agreements apply to ALL patented products. It’s also especial peculiar since Australia already has its own law prohibiting the export of pharmaceuticals (Hello Byron!) and neither Senator Stabenow nor Senator Vitter have included Singapore or Morocco as recommended nations of export on drug importation bills they’ve either authored or co-sponsored. H.R. 2862 is a clear choice between truth or consequnces. And,as the saying goes, results are what you expect, and consequences are what you get.
Huh? Jerry Avorn raises some interesting and valid arguments in his September 8th Perspective in the NEJM. But, unfortunately, he swiftly devolves into the bizarro world of Marcia Angell. In discussing FDA’s clinical measurements of “safe and effective” he posits that the public health would be better served if the agency also required, “consideration of a drugs efficacy and safety as compared with alternative therapies.” Dr. Avorn argues that such clinical evidence would make better prescribing information more readily available. But since every patient is unique, how relevant is this really? Just as there is no such thing as a “me-too” medicine (as any sober chemist will tell you), neither is there such a thing as a “me-too” patient. Patients (otherwise known as “people”) respond differently to different drugs — even drugs within the same therapeutic category. Asking FDA to recalibrate “safe and effective” to “as safe mostly but not as effective in some circumstances but somewhat more effective in others” is a poor public health course. Dr. Avorn, chief of the Division of Pharmacoepidemiology and Pharmacoeconomics at Brigham and Women’s Hospital should know better. There are a lot of places that FDA belongs — but subjective intermediary between patient and doctor is not one of them.
Well, my wife prevailed upon me to see The Constant Gardener this weekend. How can I say this gently: Don’t waste your money. A new tuberculosis strain is wreaking havoc across Africa, you see, and a corrupt pharmaceutical firm has developed an effective treatment that, sadly, has the unfortunate side effect of killing many of those taking the drug. We know this because UN aid workers in Kenya, using only the most rigorous of statistical analytic tools, say so. And so the poor Africans killed by this drug are secretly buried in lime pits, while the official records of their lives are expunged. Only Soviet-style airbrushing of photos failed to have been included. Meanwhile, the starlet—-Ms. Rachel Weisz, aka Tessa Quayle in the film—-learns that the evil pharmaceutical firm, aided by some corrupt British officials, is covering up the obvious evidence of the drug’s deadly effects because fixing the formula would cost millions and take considerable time during which the firm’s competitors could create their own effective drugs that would not kill people, thus cutting into the corrupt firm’s profits, etc., etc. And this perfidy makes sense because the epidemic is likely to spread worldwide, creating a large demand for the drug, and suppression of the deadly side effects will guarantee a huge market in Asia and the West. It’s all about the money, you see.
Got that? Anyway, the evil pharmaceutical firm through its allies in Kenya arranges for the murder of the fair Tessa and her ally, a Kenyan doctor both humanitarian and seemingly the only man in the country both unpoor and uncorrupt, before they can expose the plot. After all, that is not the kind of direct-to-consumer advertising that sells medicine. And so Tessa’s loving husband Justin picks up the torch, exposes the evildoers for what they are, and then allows himself to be murdered by the same nefarious forces so that he can be together again with his beloved Tessa in heaven. Who says that Hollywood is not religious?
Well, if Big Pharma is motivated only by money, why would they expose themselves so crudely to the plaintiff’s bar in the West? After all, people would start dying in the West also; can we even imagine the sums that the juries would award in such cases? And would the FDA and the other regulatory agencies in Europe simply accept the results of such African “clinical trials?” And what about the brand name capital of the offending pharmaceutical firm? Does it not have a profit motive to protect it by marketing only drugs the benefits of which justify the downside risks?
This flick is so silly—-so Michael Moore-like in its excess and mendacity—-that the pharmaceutical industry has little to fear from it in terms of adverse p.r. It’s good thing, as Martha might put it, when those out to destroy capitalism prove themselves so crude.
Just for a minute put aside your feelings about emergency contraception and rather than thinking about Plan B, consider Plan E. That’s E like in Ephedra. During my tenure at FDA, one of the agency actions I was most proud of was the banning of dietary supplements containing Ephedra. All the scientific evidence supported the decision. Politicians and the media were laudatory. There was broad public support — especially among parents of high school athletes — some of whom had tragically died because of these dangerous snake oil supplements. I am convinced that lives were saved because of the FDA’s decision. And then, in April of this year, a federal judge in Utah — Ground Zero for the dietary supplement industry, overturned the agency’s ban. The judge’s ruling was based on the legal argument that FDA hadn’t really proven Ephedra was dangerous. Yes, that is absurd. But sometimes the law really is an ass. That’s why it’s so important that FDA decisions be based not only on sound science but also on a sound legal foundation.
Which brings me to Plan B. Considering the highly charged environment surrounding female reproductive issues, legal maneuvering to overturn a potential “behind the counter” decision wouldn’t be based on science, but rather on the agency’s authority to make such a split decision. And making public health decisions through litigation is not in the best interests of the public health. An action on Plan B, absent a definitive and public rule making process would, rather than making emergency contraception more widely available, very likely delay OTC availability due to prolonged and protracted legal actions. And if legal action is the most effective route, you can be sure it will be pursued.
Almost every year during Sweeps Week (when networks try to boost viewership for their annual Nielson ratings) there is a health-related horror story. This year almost every network news program, both local and national, ran stories on how FDA-approved vaccines are causing autism in previously normal, happy, healthy young children. One the one side (the side with about 95% of the airtime) are parents (mostly mothers) whose children developed autism after being vaccinated for childhood diseases. On the other side (and for only the briefest of sound bites) is a nerdy looking doctor saying that every single third-party research study over the past ten years shows absolutely no correlation between autism and childhood vaccines. Who do you think the average viewer believes? And this fear-over-facts tabloid journalism was even more effective this year than usual with the FDA on its heels over drug safety. And to prove to us, once again, that irresponsible actions often have dire unintended consequences, Governor Pataki just signed into law a bill that (effective in 2009) would prohibit children three years of age or younger from being inoculated with vaccines that contain the mercury preservative thimerosal. Another action in the growing litany of public opinion rather than hard science driving public health policy. According to the American Academy of Pediatrics, “This legislation represents very bad public health policy that is based on junk science and mass hysteria, not on the evidence of science.” The AAP continues to say that such a ban has the very real danger of scaring parents away from getting their children vaccinated. Whenever a child develops a horrible condition parents want someone to blame. But the hard truth is that bad things do happen to good people for reasons that cannot be determined. But a worse fate is to reintroduce into society childhood diseases that were the scourge of previous generations. Governor Pataki has incautiously adopted the Precautionary Principle — and put at risk the youngest generation of the Empire State.
Attention Senators Dorgan and Vitter: Here’s some info from a recent AP story that you might find interesting …
MEXICO CITY. In just eight years Farmacias Similares, or Similar Pharmacies, has grown from a single store in Mexico City to 3,329 across Mexico and is spreading throughout Central America as well as Argentina, Ecuador and Chile. A pharmacy opened in the Peruvian capital of Lima on July 29. Colombia is next. And it’s made Victor Gonzalez a rich man.
His catchy advertising — a cartoon doctor and an army of scantily clad models — has made 58-year-old Gonzalez a household name. His slogan is “The Same, Only Cheaper.”
Now the recovering alcoholic and self-professed womanizer wants to translate his popularity into a run for president, though the law is against him, as is most conventional wisdom.
Gonzalez refuses to divulge his net worth, joking in an interview, “If I tell you, they’ll come kidnap me.” But his eight companies, manufacturing, transporting or selling pharmaceuticals, generated around $400 million in sales last year. His group claims to control one-quarter of Mexico’s $9 billion drug industry.
AARP announced today it would spend $5.5 million on a campaign to get seniors signed up for Part D. Bravo. Quixotically, this is the same AARP that just spent millions of dollars on an anti-pharma, pro-foreign drug importation jihad. Will the real AARP please stand up?