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As a former member of the FDA’s Counterfeit Drugs Taskforce I am pleased to report that the agency continues to tell it like it is. And it’s serious — despite what some members of Congress may think.
Speech before
Parenteral Drug Association’s Pharmaceutical Counterfeiting Conference
Remarks by
Scott Gottlieb, MD
Deputy Commissioner for Medical and Scientific Affairs
March 3, 2006
I want to thank you all for coming today to share your ideas and views on how we can do as effective a job as possible of keeping the American drug supply safe and secure. The United States has a very safe prescription drug supply, and FDA is working hard to keep it that way.
This is not something that we can take for granted. If you look around the world, in many countries a quarter or even a half or more of the prescription drugs that people take are not legitimate products. They may not work as intended, and that’s a real public health concern.
Studies by the World Health Organization estimates counterfeit drugs to be a $32 billion-a-year business. Counterfeit drugs have found their way into developed and developing countries alike.
In developed countries, counterfeiters target brand name drugs that are used in high volume and are high priced. In developing countries, the counterfeiters also target generic drugs that are used in high volume for widespread diseases that plague the public health in those countries.
It has been estimated in the press that 8 to 10 percent of the global medicine supply chain is counterfeit — a figure that rises to 25 percent or higher in some countries. Quantifying the problem is difficult because the counterfeiters do such a good job copying the genuine product and hiding their tracks, that it is hard to identify what is real and what is fake.
Here in The U.S., counterfeiting of drugs is much less common. Part of that stems from our closed drug supply system, which makes our borders less porous to the counterfeit medicines.
Our high confidence that we and the American public have about the integrity of the distribution system for U.S. drug products also stems from an intricate web of federal and state laws that protect our drug supply.
But despite our confidence, FDA has been concerned that the drug supply is under increasing threat of attack from more sophisticated and well financed counterfeiters. We know that there have been increased efforts to introduce counterfeit drugs into the U.S. market.
The Agency has also witnessed an increase in counterfeiting activities and a greater capacity to introduce finished dosage form counterfeits into legitimate drug distribution channels. Illicit wholesale drug diverters and others in the supply chain provide the window through which most counterfeit drugs have historically entered legitimate distribution channels.
To deal with these concerns, we have been engaged in an increasing number of anti-counterfeiting activities here in the U.S. and at FDA. The number of newly initiated counterfeit drug cases has risen sharply from just a few years ago, although still preliminary data from fiscal year 2005 suggest a decline relative to the peak reported for fiscal year 2004.
In fiscal year 2004, for example, FDA’s Office of Criminal Investigations initiated 58 counterfeit drug cases, a significant increase from the 30 cases initiated in fiscal year 2003 and up sharply from an average of less than 10 in the four years before 2001. Even more worrisome, we are seeing an increase in the sophistication, the cleverness, and the technical capabilities of counterfeiters that are trying to get drugs into the U.S. distribution system.
Let me stress that these are estimates of the number of newly initiated counterfeit drug cases being investigated. And since these are ongoing cases, we have no estimate of the volume of counterfeit drugs involved in each case — it could vary from dozens to thousands.
The increasing number of cases we’re involved in is a poor proxy to suggest that more counterfeit drugs are actually making it into the U.S. market. We believe that the unusually high number of cases in 2004 is in part due to an increased awareness and vigilance at all levels of the drug distribution chain. Moreover, we believe that one factor contributing to this increased awareness and vigilance is the Counterfeit Drug Report that FDA issued in February 2004. A second is increased referrals from, and coordination with other state and federal law-enforcement agencies, such as the DEA and the FBI, and communications with drug manufacturers.
And fortunately, most of the counterfeit drugs at issue did not reach consumers because we focused our resources and developed proactive investigations. We believe that this strategy enabled us to identify components of counterfeit products and interdict finished counterfeit drug products before they entered retail distribution.
But make no mistake — the prevalence of drug counterfeiters around the world presents a real public health threat, and the rising number of cases weç©©e getting involved in should be taken as an unmistakable sign of our resolve in the face of that threat. As we have seen from the counterfeit cases that we’ve already encountered and in many cases that we’ve solved and where we have put people in jail, counterfeit drug products may contain only inactive ingredients, they may contain incorrect ingredients, improper dosages, sub-potent or super-potent ingredients, or they may be contaminated.
The result is risks to patients’ health — either risk to their safety directly if the products are dangerous, or risks from people suffering from complications from the many diseases that prescription drugs can treat today. So this is a serious concern at FDA and it is a serious public health threat.
At FDA, we recently re-convened the Counterfeit Drug Task Force. This internal task force originally assembled to explore the use of modern technologies and other measures such as stronger enforcement to make it more difficult for counterfeit drugs to get distributed with — or deliberately substituted for — safe and effective drugs.
More than three years ago, when we first convened this task force, it culminated in a report that laid out a number of goals for making the drug supply more secure.
One of our proposed remedies was to strengthen our system for tracking drugs from the assembly line to the dispenser, by replacing the paperwork that now certifies who has had the drug at all times with an electronic track and trace system that cannot be easily forged or forgotten.
Electronic track and trace technology can include tiny chips that go on the individual drug packages, also known as radio-frequency identification (RFID), or it can include certain types of barcodes. New technology would allow for less costly compliance, and better controls.
We gave manufacturers time to deploy this kind of technology, and put a stay on a rule that would effectively require some kinds of tracking measures in order to give people opportunities to move from paper pedigrees which would not provide the same kinds of protections to electronic pedigrees, which would.
I was at FDA, working as a senior advisor to then Commissioner Mark McClellan, when that first report was issued, and I think it is fair to say that since that first report was released, the progress that has been made toward the implementation of an electronic pedigree has been disappointing. It has certainly been far slower than many envisioned when we set out on this original course.
I know there are many complicated reasons for this. For one thing, there is still no agreement about who would pay for what parts of the new RFID system, and who would own the data and provide it to other parties under what circumstances. And practical realities, including the diversity and sheer number of establishments involved in handling drugs as they move through the supply chain, as well as the cost of deploying new systems for electronically tracking medicines, have all remained factors.
But I think time is short to get such a system in place. The original pedigree rule is written broadly enough so that electronic track and trace could be used in place of paper pedigree. We plan to make a decision soon on this stay, which is in place until December 2006, and we could reach a decision well before that.
The bottom line is this: To continue to ensure the safety of the U.S. drug supply in the face of the mounting threats I talked about here today and the increasingly sophisticated criminals, we must pursue these new measures. This must be a public health priority for all of us.
To these ends, FDA held a two day workshop and vendor display in February 2006 solely dedicated to the use of radio-frequency identification (RFID) to combat counterfeit drugs. More than 400 registrants were in attendance to hear both Acting Commissioner Dr. von Eschenbach and Assistant Secretary for Health, Dr. Agwunobi discuss RFID as a way of fighting counterfeit drugs.
There were three main goals of this meeting:
The first was to identify incentives and obstacles for widespread adoption of RFID throughout the U.S. drug supply chain, as well as to discuss ways of overcoming any impediments to the adoption of these tools.
The second was to solicit comment on the implementation of the pedigree requirements of the Prescription Drug Marketing Act. The current provisions of that law were written largely with a paper pedigree, but I think we’d all agree, we need to be moving toward the adoption of a fully electronic, e-pedigree.
And the third was to learn about the state of technology development related to electronic “track and trace” and e-pedigree technology solutions.
During the public meeting we heard that vendors, wholesalers, and some manufacturers agree that the RFID pilot projects conducted to date showed that providing real-time electronic pedigrees is already feasible in a production environment with single wholesalers. But no pilot projects were presented that provided a pedigree for a drug product sold by one wholesaler to another before being sold to a retail pharmacy.
As our colleagues at other agencies who are also experts on counterfeiting technology have told us, there is no single magic bullet. Instead, we need layers of technology, much like paper money has many different technologies embedded in it to thwart counterfeiting.
Our money supply, just the paper money, has more than 20 embedded technologies, both overt and covert and some that are only known to the Treasury Department. We need multiple layers like that to build more safety and security in prescription drugs as well, and we’re going to be working to bring forward proven technologies, and to develop the proof for these other technologies. RFID is the most promising, and most advanced of these technologies, but we still need to continue to pursue other remedies.
To these ends, we also heard some vendors describe hybrid technologies, such as two-dimensional bar codes combined with RFID that might provide both identification and electronic pedigrees even without RFID being universally adopted.
We have also seen new applications of bar code labeling, new approaches to doing track and trace technology so that we can reliably — in ways that cannot easily be fraudulently faked — identify whether a product really is a legitimate one, whether it comes from a legitimate source and has not been tampered with along the supply chain.
We’ve seen new technologies for packaging, new color-based technologies that embed multiple different layers of protection. We’ve seen new anti-tampering technologies for drug packaging. Even the tops of injectable drugs that can help keep the product secure. And we’ve seen new technologies that can be used on the drugs themselves, from new color technologies to embedded bar codes embedded — not just unit-dose packaging but actually on the drug. And we have seen other “taggant” and chemical technologies that are not harmful for patients but that can make it very easy to determine whether a product is safe or not.
As a result of the information garnered from this workshop, as well as the information we gathered from comments placed in the workshop’s public docket, at FDA we’re in the process of preparing a summary report and we expect to have that publicly available in May 2006.
That report will address whether or not we issue another stay on implementation of the pedigree rule. But as I said, we have already waited a long time for this technology to come along, since the stay was issued at the time of our first task force report on drug counterfeiting. We believe that we can take steps, working with technology developers and all of those involved in the supply chain, to accelerate the development, the feasibility testing and the adoption of many of these technologies that are in development today. And as we are trying to do in other areas of FDA activities where there are new technologies that can be valuable, we want to bring them to benefit patients as soon as possible.
While some of these technologies do seem just a short time away from widespread application, others have not been fully developed yet and demonstrated to be feasible. We will continue to work with the private sector to foster advances in this field. Not only do many of these technologies need to go through some further developmental steps, counterfeiters are very sophisticated today, so this is a moving game.
Finally, it’s clear that despite the promise that these security technologies offer, electronic track and trace, including RFID, alone is not the solution to combating counterfeit drugs. A multi-layer approach, using other technologies to secure the product and packaging, increased vigilance and awareness, increased penalties and State efforts, just to name a few, are also important in this effort.
We constantly need to be finding ways to update our technologies. We constantly need to be thinking about whether we’ve got enough layers in place. We need to think simultaneously about a coordinated approach that involves tracking and tracing and product packaging and product-embedded technologies and others. In short, we need multiple layers to keep our drug supply safe.
One of the things that are evidenced to us in this work is that all of the participants in our drug distribution system, from manufacturers to wholesalers and distributors, to pharmacies, to patients, have a responsibility to help us prevent and detect the introduction of counterfeit drugs into our drug supply. In particular, the businesses that are involved in the pharmaceutical manufacturing and distribution industry can help by adopting and adhering to secure business practices.
We think from what we’ve seen so far that some of the business practices in existence today can be improved as a means of deterring and detecting counterfeit drugs.
We’ve heard from and we’ve gotten a lot of feedback out to wholesaler organizations, for example, that are moving forward with developing more secure business practice models as a standard for their industry. And we’re looking forward to working with all of the other stakeholders in the prescription drug distribution system to make sure that we have identified and are doing all we can to encourage the adoption of secure business practices to minimize vulnerabilities to counterfeit drugs.
It is also important that we rapidly receive and are able to disseminate information on counterfeit drug introductions when they do occur. As I said, the number of cases of counterfeiting is on the increase, and an important part of an effective anti-counterfeiting strategy is to be able to identify and limit the damage from counterfeit drug introductions when they do occur.
Our task force has recognized the need to strengthen the systems that are used for reporting suspected counterfeits and for alerting stakeholders and the public when these counterfeit drugs do enter the drug supply. We have partnered with health professional, trade, and consumer organizations to create FDA’s Counterfeit Alert Network. These partners agree to disseminate important information about confirmed counterfeit incidences in a timely manner and to disseminate educational messages about counterfeit drugs.
It is also essential for consumers, pharmacists, and other health care professionals to know how to identify counterfeit drugs and what to do when they believe that they’ve encountered a counterfeit drug. This includes recognizing knowing the warning signs for identifying suspect counterfeit drugs. We are working on tips for pharmacists and other health professionals on how to identify counterfeits, how to counsel patients who suspect that they have a counterfeit drug, and where to report if a counterfeit drug is suspected. FDA’s MedWatch system is the mechanism that should be used these reports.
Finally, counterfeit drugs are a global problem. We’re seeing an increasing number of cases that involve not just a few people manufacturing a fake product in their garage, but well-organized international criminal operations that are trying to make use of the latest technologies for making a product that looks like the real thing but isn’t. We work with international law enforcement, health and regulatory authorities, as well as private stakeholders internationally to help us address this problem effectively.
To those of you who are working on ways to combat the growing traffic in counterfeit drugs, at FDA we want to thank you for your contribution to dealing with this significant emerging public health threat. We’re confident that working together we can stay ahead of those who are out to make a fast buck at the expense of the health of Americans.
And we are sure that we will be able to work together to keep our drug supply safe and secure and the safest in the world if we do remain vigilant through steps like this.
Thank you all for your contributions.
I am not making this up.
Merck exec. acknowledges market pressure
ATLANTIC CITY, N.J. — A Merck & Co. marketing executive acknowledged Tuesday that the company was under pressure in 1998 to get its arthritis drug Vioxx on the market ahead of rival Pfizer’s drug Celebrex, with the company forecasting millions in lost sales if it did not win the race. Under questioning he did acknowledge that his pay was pegged to Merck’s sales and profits.
Next revelation — Merck scientist admits that drugs have risks!
An important, timely, and on-target editorial from today’s edition of the Washington Times. Attention must be paid.
Today, an advisory committee to the Food and Drug Administration will review information and hear from patients about whether to permit a medicine for multiple sclerosis called Tysabri back onto the market after a year’s absence. The FDA approved Tysabri in November 2004 after only year of clinical trials.
The agency did so because the drug worked extremely well in stopping what are known as “relapses,” a diplomatic term for describing the loss of memory, the inability to walk and permanent disability that occurs when the protective insulation of the nerves necessary for healthy brain function, and then the nerves themselves, are slowly destroyed. And compared to other MS drugs, Tysabri appeared to have few side effects.
Last February, Tysabri was voluntarily withdrawn from the market after someone taking it in combination with Avonex, another MS drug, died from progressive mulitfocal leukoecephalopathy (PML), a rare neurological disease. Another patient suspected of having PML at that time was later confirmed. An exhaustive study of all patients who took the drug found no new cases of PML. Overall, there is a 0.1 percent risk of contracting PML if you use Tysabri. That’s half the risk of dying from aspirin. Meanwhile, MS causes about 53,000 relapses yearly and 5 percent of relapses cripple or kill their victims.
Too often, in the wake of Vioxx withdrawal, pundits have ignored the health risks of not making a medicine available. Those risks cannot be ignored in this case. All the information about Tysabri’s benefits and risk are available. A plan is in place to reduce risk further and determine the best treatment strategy for every patient. MS patients have taken a page from HIV/AIDS activists and are descending on the hearing en masse. Their message: Our lives, our choice. Let’s hope the FDA and its advisory committee listen with open hearts and minds.
If a pharmaceutical company funds a well-constructed double blind clinical trial designed, overseen and reported on by highly respected medical researchers are the results relevant?
Not necessarily.
Consider the IDEAL (Incremental Decrease in Endpoints through Aggressive Lipid Lowering) trial, a multicenter, open-label study with blinded endpoint evaluation involving 8888 patients with coronary heart disease, an LDL of 122 mg/dl — and costing big money. Nobody can find any fault in the trial design and the results address a crucial global public health issue. But you can read all about all of the good news elsewhere.
Or can you?
Unfortunately, that task won’t be easy, because news reports on the study focus less on its critical findings than on the fact the study was (don’t faint) funded by Pfizer. Can you imagine that? A clinical trial funded by a big bad pharmaceutical company! How was that allowed to happen!
It’s a horrible (and horribly predictable) outcome of the on-going demonization of the pharmaceutical industry led by the media-political complex. And while not surprising, it’s dangerous for three main reasons:
FIRST: It casts aspersions on important and relevant health care information that could save lives.
SECOND: It gives governments worldwide political cover to avoid revising antiquated reimbursement guidelines (even though they would save significant money in the long term by addressing chronic conditions earlier and more aggressively).
THIRD: It lends unwarranted credence to those who would call for government being the sole source of medical research.
In those less than ideal circumstances we’d all end up paying — and in more ways than one.
Comrade Goldberg recants? Not.
The effort to regard any research conducted with industry support as defacto discredited, regardless of scientific principles, is the new Lysenkoism and will have the same consequences. Lysenkoism justified and rationalized all science that comported with government run farms and factories in the Soviet Union and regarded any other science as conducted to sustain capitalism. It lead to massive human suffering. Now we are in a time and place where any science not conducted by academics free of any funding save for government support (no bias there of course!) or the Ford or Rockefeller Foundation is considered propaganda.
Respected researchers don’t have the propaganda machine working on their behalf. Note the striking parallels between how Lysenko, who’s untested theories about agriculture and his attacks on the bourgeois research of geneticists, were trumpted by The Party and today where honest researchers are attacked by The Journals for carrying out research according to strict canons of study.
Today what passes for science from the new Lysenkoists boils down to surveys (the negative impact of DTC ads) or data dredging (demonstrating that millions likely suffered from Vioxx rather than conducting the careful pharmacogenomic research to establish biological causality) that can be easily conducted and quickly published, digested by the media, and regurgitated by politicians. Rarely is the question asked: have they proved their theories using the scientific method? Have they demonstrated that all research conducted with or by industry is flawed or biased by proving that the results of such research — new medicines, technologies, biological understanding of disease mechanisms — do not exist? Does that mean because Pasteur received funding from wine and beer companies in France that his theories about bacteria and fermentation are to be discredited?
According to the Jerusalem Post, “The timing of Austria’s conviction and imprisonment of David Irving for denying the Holocaust could not have been worse. Coming after the deaths of at least 30 people in Syria, Lebanon, Afghanistan, Libya, Nigeria and other Islamic countries during protests against cartoons ridiculing Muhammad, the Irving verdict makes a mockery of the claim that in democratic countries freedom of expression is a basic right.”
What does this have to do with DrugWonks.com? Actually, quite a lot.
I’ve just returned from London where I had the opportunity to speak with various European think tanks and pharmaceutical companies on the issue they call “information-to-patients” (ItP). That’s what we “on the other side of the pond” refer to as “direct-to-consumer-communications.” In Europe they choose to abstain from using the “A” word — “Advertising.”
But rhetoric counts. “Information TO patients” seems quite paternalistic when compared to the more New Worldly “DIRECT to consumer” moniker.
I learned a lot about the very restrictive national and EU laws that make it illegal for pharmaceutical companies to do almost any kind of “information-to-patients” programs and how the pharmaceutical industry’s representatives in Brussels are trying to, politely, inch towards incremental change. Unfortunately (at least as far as I could see) there are no go-forward ideas, no white paper, no consensus as to what more progressive European ItP policy might look like. Right now the only position is that it shouldn’t be the American model. That’s not a plan, it’s the pharmacrats dancing with the eurocrats. And the music is atonal, sounding more like a dirge than a motion-oriented Vienna waltz. It should really be more of a tango or passo double.
On the one hand europharma wants to have more options in the ItP arena, but on the other they don’t want to unduly upset the apple cart. And they CERTAINLY don’t want “American-Style” advertising. Heavens no. THAT’S off the table entirely. It’s also not based on any knowledge of how DTC advertising has impacted the American health care debate.
But facts are stubborn things. I felt obligated to point out to my European colleagues that DTC advertising drives patients to visit their physicians, creates an environment for more robust doctor/patient conversations, enhances compliance, destigmatizes diseases such as depression, and does NOT increase prices.
As Julian Morris of the London-based International Policy Network quipped, “Europe is running out of failed alternatives.”
But what caused the most noticeable discomfort was my pointing out that there is a larger issue at play — that of Free Speech. And having theses conversations at a time when Europe is regularly parsing what “Free Speech” means (David Irving, Ken Livingston, etc.) made these chats even more, shall we say, stimulating.
They are, after all, called “First Principles” for a reason.
And that brings me back to the Jerusalem Post article. While Brussels sprouts restrictions on all kinds of speech, much of europharma is content to demurely request an audience to obliquely begin a quiet and polite conversation on incremental change
Which is fine. But starting that conversation by stipulating that Free Speech can (and indeed should) be limited (i.e., by stipulating that direct-to-consumer advertising should now and forever be off the table) is, de minimus, strategically negotiating from a position of weakness.
The Danish prime minister recently said (in the wake of the cartoon scandal) that “Freedom of Speech is absolute. It is not negotiable.” That’s a good place to start when discussing ItP with the folks in Brussels.
Yielding the moral high ground may result in short-term success, but please consider that this is the same excuse that Yahoo and Google are using when they allow the People’s Republic of China to block search terms like “democracy.” After all, it’s just business, right?
According to the Jerusalem Post, “The timing of Austria’s conviction and imprisonment of David Irving for denying the Holocaust could not have been worse. Coming after the deaths of at least 30 people in Syria, Lebanon, Afghanistan, Libya, Nigeria and other Islamic countries during protests against cartoons ridiculing Muhammad, the Irving verdict makes a mockery of the claim that in democratic countries freedom of expression is a basic right.”
What does this have to do with DrugWonks.com? Actually, quite a lot.
I’ve just returned from London where I had the opportunity to speak with various European think tanks and pharmaceutical companies on the issue they call “information-to-patients” (ItP). That’s what we “on the other side of the pond” refer to as “direct-to-consumer-communications.” In Europe they choose to abstain from using the “A” word — “Advertising.”
But rhetoric counts. “Information TO patients” seems quite paternalistic when compared to the more New Worldly “DIRECT to consumer” moniker.
I learned a lot about the very restrictive national and EU laws that make it illegal for pharmaceutical companies to do almost any kind of “information-to-patients” programs and how the pharmaceutical industry’s representatives in Brussels are trying to, politely, inch towards incremental change. Unfortunately (at least as far as I could see) there are no go-forward ideas, no white paper, no consensus as to what more progressive European ItP policy might look like. Right now the only position is that it shouldn’t be the American model. That’s not a plan, it’s the pharmacrats dancing with the eurocrats. And the music is atonal, sounding more like a dirge than a motion-oriented Vienna waltz. It should really be more of a tango or passo double.
On the one hand europharma wants to have more options in the ItP arena, but on the other they don’t want to unduly upset the apple cart. And they CERTAINLY don’t want “American-Style” advertising. Heavens no. THAT’S off the table entirely. It’s also not based on any knowledge of how DTC advertising has impacted the American health care debate.
But facts are stubborn things. I felt obligated to point out to my European colleagues that DTC advertising drives patients to visit their physicians, creates an environment for more robust doctor/patient conversations, enhances compliance, destigmatizes diseases such as depression, and does NOT increase prices.
As Julian Morris of the London-based International Policy Network quipped, “Europe is running out of failed alternatives.”
But what caused the most noticeable discomfort was my pointing out that there is a larger issue at play — that of Free Speech. And having theses conversations at a time when Europe is regularly parsing what “Free Speech” means (David Irving, Ken Livingston, etc.) made these chats even more, shall we say, stimulating.
They are, after all, called “First Principles” for a reason.
And that brings me back to the Jerusalem Post article. While Brussels sprouts restrictions on all kinds of speech, much of europharma is content to demurely request an audience to obliquely begin a quiet and polite conversation on incremental change
Which is fine. But starting that conversation by stipulating that Free Speech can (and indeed should) be limited (i.e., by stipulating that direct-to-consumer advertising should now and forever be off the table) is, de minimus, strategically negotiating from a position of weakness.
The Danish prime minister recently said (in the wake of the cartoon scandal) that “Freedom of Speech is absolute. It is not negotiable.” That’s a good place to start when discussing ItP with the folks in Brussels.
Yielding the moral high ground may result in short-term success, but please consider that this is the same excuse that Yahoo and Google are using when they allow the People’s Republic of China to block search terms like “democracy.” After all, it’s just business, right?
Henry Miller minces no words about the current direction of the Lancet and precarious slip/sliding towards the Precautionary Principle.
THE LANCET PRICKS ITSELF
Henry I. Miller
The term “medical journals” elicits automatic respect from most people. Not from me: I read them. I’ve found the editors to be increasingly hubristic and anti-business; and even worse, not to know what they don’t know.
The British journal The Lancet is a case in point. Having previously erred by publishing an obviously flawed paper purportedly showing toxicity of gene-spliced potatoes, another containing wild and irresponsible (but damaging) speculation about the possible dangers of the insecticide DDT, and a commentary about a link between autism and vaccines that contain the preservative thimerosal, The Lancet again has gone off the deep end. This time the issue is the regulation of chemicals in Europe. (What this has to do with medicine isn’t entirely clear, but it illustrates the expansive, do-gooder mindset of the editors.)
The Lancet’s biases are unmistakable: Chemicals bad, regulation good. Therefore, REACH (Registration, Evaluation, and Authorization of Chemicals), the EU’s sweeping plan, which The Lancet believes is “designed to reign in an industry that for decades had placed chemicals on the market with, at best, only irregular government oversight,” is laudable; while any attempts to introduce rigorous scientific and economic analysis into regulation can only be the product of cynical, self-serving interference.
According to The Lancet, REACH was right on track until “European lawmakers met The Lobby. In what some European Commissioners say is the largest lobbying effort in the modern history of the EU, European and American chemical manufacturers orchestrated a multilayered and multipronged lobbying campaign that encompassed all the original 15 EU member states plus the 10 new ones, as well as countries outside the continent such as Japan, Mexico, and the USA.”
In spite of the bad rap that lobbying has gotten recently on this side of the pond, however, all lobbying is neither negative nor motivated by special pleading. At its best, it is a means to educate policymakers about important and sometimes arcane issues.
The Lancet’s sanguine view of REACH is demolished by the meticulously argued, “Europe’s Global REACH,” released last November by the Hayek Institute in Brussels. It concludes that REACH will harm Europe and its trade partners economically — without any convincing evidence of health or environmental benefits.
REACH would extend to all chemicals produced in or imported into Europe the bogus “precautionary principle,” which holds that if the evidence about a product, technology or activity is any way incomplete, it should be prohibited or at least stringently regulated.
Potential risks should be taken into consideration before proceeding with any new activity or product, to be sure, whether it is the siting of a power station or the introduction of a new flame retardant. But what is missing from precautionary calculus is an acknowledgment that even when technologies and products introduce new risks, most confer net benefits — that is, their use reduces other, far more serious hazards. Vaccines have occasional side effects, for example, but they confer net benefits. The danger in the precautionary principle, Â which in concept is centuries old, is that it focuses exclusively on the risks — often purely hypothetical ones, at that— and diverts consumers and policymakers from seeking possible solutions to known, significant threats to human health. Its overall impacts may be overwhelmingly net-negative.
The costs of REACH’s precautionary approach will be prodigious. The European Commission’s own estimates range up to 5.2 billion euros, but according to a study produced by the Nordic Council, the price tag could be as much as 28 billion. This higher estimate includes both direct and indirect costs, and assumes that the latter may amount to as much as 2.5 times the former.
REACH’s supporters maintain that businesses can absorb this high price tag easily, but the Hayek Institute analysis offers a very different view. Its author, public policy scholar Angela Logomasini, points out that cost estimates that are favorable to REACH are incomplete, fail to consider a host of direct costs, and often completely neglect the indirect costs.
Moreover, REACH’s advocates ignore its disproportionately harsh impact on small businesses and businesses in the newer EU member nations. A study conducted by consulting firm KPMG on behalf of the European Commission concludes: “The heaviest burden will be on SMEs [small and mid-sized enterprises] which cannot consistently fulfill the REACH requirements and so it is predicted that most of them may face financial troubles, may be taken over by bigger ones, or even shut down.”
These prospects should raise serious concerns for Europeans. Small and mid-sized firms represent more than 99 percent of EU businesses, and account for two-thirds of the jobs. The imposition of REACH will increase unemployment and diminish competition — which will lead to less innovation and higher prices.
The Lancet’s take on these monumental costs? “While EU regulation involves unpleasant upfront costs, it also provides predictability and efficiency.” The Hayek Institute’s analysis suggests that REACH will offer few predictable benefits to offset the potentially devastating costs. In a review of the benefits claimed for REACH, Logomasini shows that the “studies” that purport to demonstrate benefits depend more on unsupported assumptions and wishful thinking than on science or logic. The European Commission’s only study of likely benefits from REACH, conducted by Risk and Policy Analysis Limited (RPA) in 2003, addresses occupational exposure to chemicals and attempts to estimate the extent to which REACH would reduce health problems among workers. However, it is based on sketchy, incomplete, and inconsistently collected data assembled from a handful of member governments that is of questionable relevance to REACH.
The RPA report explicitly assumes that problems related to currently known chemical causes will be addressed by existing laws, while REACH will prevent currently unknown health problems from chemicals. But if these cases are unknown, how can we know they are caused by chemicals or are even work-related? Obvious errors and insufficient documentation in the report only compound problems with the study, which makes no mention of having been peer reviewed.
REACH’s presumed benefits are based on the assumption that testing chemicals, filing paperwork, and pursuing politically correct product bans will somehow reduce cancer rates. But as the Hayek Institute analysis makes clear, the vast majority of cancers are not related to chemicals. According to the World Health Organization, the major preventable causes are tobacco use, diet, and infections, which account for 75 percent of cancer cases worldwide. WHO bases these findings on a landmark study conducted by scientists Sir Richard Doll and Richard Peto, which concluded that all environmental pollution might amount to only as much as two percent of cancers.
In the interest of free markets and economic growth, we need global regulatory policies that make scientific sense and that encourage innovative research and development. But by promoting the precautionary principle, EU politicians are performing a disservice. The only winners will be the European regulators, who will enjoy additional power, and the anti-science activists who will have succeeded in erecting yet more barriers to the use of superior technologies and useful products.
The Lancet should narrow its focus and stick to what it does well, assuming that something in that category can be identified.
CMPI advisory board member Henry Miller on the troubles with Tysabri …
WALL STREET JOURNAL
March 2, 2006
COMMENTARY
Paternalism Costs Lives
By HENRY I. MILLER
Decisions about drug safety and efficacy are far from easy. Tysabri, a multiple sclerosis (MS) drug that was voluntarily withdrawn from the market last year after the appearance of a previously unknown side effect, illustrates some of the conundrums.
In advance of the publication of three critical new studies on Tysabri in this week’s issue of the New England Journal of Medicine, a major news organization recently asked me, as a physician and former FDA official, whether I knew of examples of prescription drugs that have “efficacy but [also] serious safety issues.” That is, I responded, the rule rather than the exception.
Obvious examples include the antimetabolites used for traditional chemotherapy. Because these drugs are no more than poisons administered in a way intended to be more toxic to cancer cells than normal ones, it is not surprising that their side effects are often serious and even life-threatening. When I was a medical resident three decades ago, hospital gallows humor included referring to BCNU, an experimental cancer drug, as “Be seein’ you.” Approved in 1977, it is still widely used.
A more recent example is aldesleukin, a drug that has offered new hope to victims of kidney cancer and malignant melanoma. It is highly effective in a small proportion of patients but exhibits significant toxicity. The patient information booklet warns that those taking the drug “frequently experience serious, life-threatening or fatal adverse events,” including dangerously low blood pressure and reduced organ perfusion, impaired function of infection-fighting white blood cells, disseminated infection and autoimmune disease.
Antibiotics are another class of wonder drugs that sometimes manifest significant toxicity. Chloramphenicol, a drug that is effective against a wide spectrum of bacterial infections, causes rare cases of fatal aplastic anemia, so it is used only sparingly. The potent antibiotic gentamicin is often lifesaving but can cause damage to the kidneys, nerves and ears. And significant numbers of patients are allergic to other important antibiotics, including the penicillins and cephalosporins.
But let us return to Tysabri, only the sixth medication approved — and the first in several years — for the treatment of MS, a common and debilitating autoimmune disease that affects the central nervous system. The impressive results of the drug’s testing in clinical trials — the frequency of clinical relapses reduced by more than half — induced the FDA to grant accelerated approval in 2004. By the time that several thousand patients were being treated with Tysabri, however, three had contracted progressive multifocal leukoencephalopathy (PML), a rare neurological disorder caused by a virus. (Because the drug suppresses certain components of the immune response, regulators, clinicians and the product’s developers had from the beginning been sensitive to the possibility of infections as a side effect.) Immediately — some would say prematurely — the manufacturers of the drug voluntarily halted production and distribution and withdrew Tysabri from the market. MS patients and many neurologists were bitterly disappointed.
The three clinical studies reported this week in the New England Journal of Medicine bolster our confidence about the safety and efficacy of Tysabri. In a study of almost a thousand patients that compared Tysabri to placebo, the drug cut the rate of clinical relapses by 68% (to 0.24 from 0.75), reduced by 83% the number of new or expanding brain lesions found on MRI, and slowed the clinical progression of disease. (The other currently used drugs for MS lower the occurrence of acute relapses by roughly one-third.) Similar results were obtained in a second trial which compared two-drug therapy with Tysabri plus interferon beta-1a to the interferon alone.
Finally, a third study found no additional cases of PML in more than 3,000 patients (exposed to an average of 17.9 monthly doses) who had participated in clinical trials of Tysabri. The investigators concluded that the incidence of this serious side effect is approximately one in a thousand patients treated with the drug. However, it should be noted that all three of the original cases of PML occurred in patients treated with interferon beta or other immunosuppressive agents in addition to Tysabri, so the risk might be significantly lower in patients treated with Tysabri alone.
The “safety” of a drug is a relative thing. Safety and efficacy, the two criteria required for marketing approval of a drug, are inextricably linked. The judgments of regulators (and practicing physicians) require a global and often difficult calculation of risk and benefit, including consideration of what alternative therapies are available. For a given drug, we are willing to tolerate greater uncertainty and more severe side effects for a potential cure for pancreatic cancer or AIDS, for example, than for a new drug that treats heartburn. When FDA grants marketing approval, the drug is deemed to be sufficiently safe and effective to be used for the conditions on the label.
In light of the just-published data — to which the FDA should have had access months ago — it is clear that this drug belongs back on the market, probably with new warnings about PML in the labeling.
The notion that the FDA should “err on the side of safety” sounds like a tautology but is an affront to patients with incurable or poorly treatable diseases: For them, there is no safety in the status quo, and we only damage them further with paternalistic public policy that prevents individuals from exercising their own judgment about risks and benefits. If the FDA must err, it should be on the side of patients’ freedom to choose.
Mr. Miller, a physician and fellow at the Hoover Institution, headed the FDA’s Office of Biotechnology from 1989 to 1993.
Dr. Bob Goldberg on risk, benefit, patients rights, FDA policy, politics … and Tysabri …
As Steve Usdin the Washington Editor of BioCentury (www.biocentury.com) points outs, “there has been very little debate about the risks associated with delaying or denying access to therapies or who should be empowered to make risk/benefit calculations.” Given the growing transparency of the drug development process, the rapid dissemination of post market information and intense and ongoing involvement patients have in both the clinical trial of medicines and managing an illnesses, the real question is, who should have the right to choose which drugs to use: the political class and their allies in the media, or patients, families and physicians?
Next week when an FDA advisory committee reviews evidence about whether to reintroduce a drug for multiple sclerosis called Tysabri back to market after it was removed in the wake of safety concerns, patients will demand that the FDA take ! into account not only the data about Tysabri’s risks, but the relative risks of taking other medicines such as aspirin or existing MS drugs and the benefits of the new drug itself. Ironically, Tysabri’s safety problems emerged the day when Senator Charles Grassley was holding hearing that sought to blame the problems associated with Vioxx on an incestuous relationship between Merck and FDA regulators. Back then, no one was paying attention to the pain of patients who had to live without Tysabri after taking the drug gave them back their lives.
Now, reminescent of HIV activists, MS patients have taken to the Web to organize en masses to pressure the FDA to respond. They are unwilling to let the political class and the professional fear mongers and those who warn against approving Tysabri because it is not a cure take the right to get the drug from them. Lack of access to Tysabri has caused nearly 8000 relapses — loss of movement, sight, independence — in 28000 patients over the past year. 1300 had relapses so severe that they are now permanently disabled. (Will Chuck Grassley or anyone in Congress hold a hearing on that?)
The FDA’s decision about Tysabri will be it’s most important all year. Jeff Krasner’s excellent piece in the Boston Globe provides a great perspective on all the issues surrounding Tysabri, and his coverage from the very start has, along with Usdin’s, been essential for anyone wanting to get up to speed on how the risks and benefits of medicines debate ought to be addressed. I also urge folks to log into MS Patients for Choice www.mspatientsforchoice.org
It will be interesting to see how the media covers this story.
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.
