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, ­ 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.

Henry Miller on Susan Wood and revisionist history …

Susan Wood laments that “our federal health agencies seem increasingly unable to operate independently and that this lack of independence compromises their mission of promoting public health and welfare.” However, Ms. Wood is a fifteen-year veteran of the federal government, which makes one wonder where she spent the 1990’s.

Although there is no question that many of the Bush administration’s science-related appointments and its record leave much to be desired — witness the litmus tests for appointees to science-related positions, distortion of information to consumers about health and safety issues, antagonism toward embryonic stem cell research, and the FDA’s apparently politically motivated decision not to permit over-the-counter sales of the Plan B morning-after contraceptive — the Clinton administration’s blatant perversion of science was even more pervasive and egregious.

As President Bill Clinton’s science and technology czar, Al Gore was entrusted with choosing many top appointees to regulatory agencies, thereby obtaining the leverage to politicize the administration’s policies and decisions. There was no room for dissension or respect for data-driven policy in the Clinton administration, no participation in the marketplace of ideas unless you were a true believer and toed the party line. And on many environmental and public health issues, it was a very radical party line, indeed.

As to the politicization of decision-making, I was a senior FDA official at the time and, like many of my colleagues, was appalled at the willingness of then-FDA Commissioner David Kessler to take orders from above about which products should be expedited and which delayed by regulators. For example, the agency approved a dubious female condom after being informed by the secretary of HHS that it was a “feminist product,” and that delay was not acceptable; and FDA officials went to extraordinarily lengths to look for reasons not to approve biotech-derived bovine somatotropin, a veterinary drug, because the vice-president’s office considered it to be politically incorrect.

At a recent conference of biotech executives, frustration seemed to be the order of the day with venting the inevitable result. Both are understandable. The remarks (dutifully reported by Lisa Richwine of Reuters and reprinted below) show an industry and an agency engaged in a life-or-death battle. Actually, two life-or-death battles. The first is corporate survival, the second, patient survival. And while saving lives is more important than making money (is it even necessary to say that?) you can’t have one without the other. No biotech industry, no new lives saved, extended, or enhanced.

The general frustration is the on-going dichotomy of predictability versus ambiguity at the FDA. One reviewer deals with a sponsor one way while two doors down data is addressed in an entirely different manner. Predictability is power in pursuit of the public health. And while that’s always been true, today it’s become an urgent public health imperative.

Reform is crucial. Or should I say “critical” … like in Critical Path.

Here’s the Reuter’s article. Read beyond the frustration and the venting and you’ll see an opportunity for greater collaboration between regulators and regulated. A high-wire balancing act? Certainly. But one well worth the effort.

Business as usual is not an option.

Biotechs say FDA ranges from good to ‘horrifying’
By Lisa Richwine

BOSTON (Reuters) — Biotechnology companies trying to get new drugs to the market have had experiences with U.S. regulators that range from productive to “horrifying” as they craft early development plans, senior executives told Reuters this week.

Interactions can vary vastly between Food and Drug Administration divisions that review products and provide guidance to companies long before they seek approval to sell a drug, company officials said.

“We have some very good experiences and we have had some horrifying experiences, where you wonder, ‘Where did that come from?’” Genzyme Chief Executive Henri Termeer said at the Reuters Biotechnology Summit in Boston. “What is reasonable and what is not reasonable differs by individual … It’s quite frustrating,” he added.

FDA officials have acknowledged inconsistencies, or a lack of clarity, from some reviewers during early stages, when companies are seeking input on how to design clinical studies of experimental medicines. They have pledged improvements and launched major efforts to work with manufacturers earlier in the process to help more drugs make it to the market.

The agency holds more meetings than ever with drugmakers, more than 2,000 annually.

“We believe more and better interactions will lead to better outcomes and have invested a lot of resources in these efforts,” Scott Gottlieb, FDA deputy commissioner for medical and scientific affairs, said via e-mail. The FDA also is providing guidelines on how to develop better applications, he said. Officials will announce other measures to improve the review process soon.

Biotechs can face more challenges than traditional pharmaceutical companies. Many biotechs are small, inexperienced and testing their first product. Their technology may be new and unfamiliar to regulators.

Alnylam Pharmaceuticals Inc. CEO John Maraganore said his company has had “remarkably good” dealings with the FDA on efforts to develop treatments based on a new “gene silencing” technology.

“You can engage them in a science-based discussion … People that run into troubles don” engage them in that type of dialogue,” he told the Reuters Summit.

FDA staff are very responsive on potential breakthrough drugs, said Ariad Pharmaceuticals Inc. CEO Harvey Berger. Having “fast-track” status for promising medicines helps insure regular communication, he said. His company’s employees talk often with the agency in person and on the phone and get answers to questions within days. “I think the key is you have got to have a drug that they see a real opportunity for,” Berger said.

Cell Therapeutics Inc. CEO Jim Bianco agreed FDA staff will move quickly for drugs that are “sexy,” but said less exciting, though still important, medicines can get left behind. His company has been frustrated in its development of a cancer drug, Xyotax, which he described as a traditional chemotherapy medicine with fewer side effects.

European regulators are open to clearing the drug based on evidence it is equivalent to other chemotherapy, rather than superior, because it has less toxicity, but U.S. regulators are not, Bianco said.

FDA staff “are not equipped to handle that,” he said. To the agency, “standard chemo is not what moves the field forward,” he said.

Genzyme’s Termeer said it has become easier to deal with European regulators, who routinely approve his company’s products before the FDA does.

“The Europeans are willing to delegate much more of the process … to expert opinions. Much more of the work is done outside the bureaucracy,” he said.

Remember the January 30th Federal Register notice where FDA said they were going to investigate whether or not coupons in DTC ads were legit because they might “foster consumer misperceptions about the advertised prescription drug product.” Well, they’ve withdrawn it — quietly. When asked why the agency replied, “The agency withdrew the notice because the matter required additional consideration.” Well said. Translated that means (and this is my best guess) that cooler heads in the agency (most likely in the Office of Chief Counsel) pointed out that FDA has no authority to regulate this area.

Good decision. Good press statement. Face is saved.

Plastics.

It was good advice in “The Graduate,” but it’s bad news for internet profiteers masquerading as pharmacists.

Both Visa and MasterCard rules prohibit the processing of any illegal transactions such as those from illegal online pharmacies. Both card companies have issued fines for doing so. Several online pharmacy accounts, in fact, were recently terminated as a result of card Association and member bank pressure.

To do business with online pharmacies it is required that the member bank conduct an investigation for every online pharmacy. This will include providing a copy of the pharmacy’s license, a statement that the merchant’s sales activity is in compliance with all applicable laws, proof that valid prescriptions are required before medications are dispensed and proof that only prescriptions from licensed physicians are accepted.

Any questions?

The Ol Perfessor (in this case, the young and vibrant Dr. Bob Goldberg) tells it like it is …

The study put out by the Democrat minority staff of the House Government Reform committee, “Medicare Drug Plan Prices Are Increasing Rapidly,” is misleading and inaccurate in many respects.

It deliberately leaves out drug plans that allow patients to pay a fixed low price for all the drugs they survey. There are many drug plans that allow consumers to pay $30 for a month’s supply of each drug (or $25 a month if purchased through mail order). All these prices are substantially lower than any of the average prices cited by the Democrat staff. For example, the Democrat House staff quotes average prices of about $150 for a month supply for Aricept and Advair whereas most plans quote about $27.

Nor does the study does control for different co-pays and prices for drugs depending on its tier placement. Zocor, Prevacid and Lipitor have been shifted into higher co-pay and price tier by some companies and not others. At the same time, some companies have pushed Celebrex off their formulary and raised prices accordingly while others have kept it on formulary.

Even when these errors and oversights are taken into account, a significant number of companies offer drug prices lower than those quoted by House Democrat staff. In many cases the prices quoted by the various plans are about 75 percent lower than the average price cited by the House Democrat staff.

Like Casey said, you can look it up.

I recently had the privilege of a private meeting with Nobel Laureate Joshua Lederberg. The topic of conversation was the future of the FDA and the agency’s Critical Path initiative. We talked about the state of applied research and “the texture” of the agency, the prioritization of development science, biomarkers and a host of other future-oriented issues. He talked. I took a lot of notes. At the end of the meeting he put everything into perspective in a single sentence. He leaned over the table and said, “The real question should be, is innovation feasible?”

I hope so.

Smart thinking from Bob Goldberg, CMPI’s new Vice President for Strategic Initiatives …

Meet the challenge
By Robert Goldberg
Published February 21, 2006
The Washington Times

Democrats are gearing up to make health savings accounts and Medicare battering rams against the Republican Party in in the midterm Congressional elections. Liberal think tanks and congressional Democrats first attacked the Medicare drug benefit as a “a complex program that does nothing to bring down the costs of soaring drug costs.” Now, they are trashing health savings accounts as a tax shelter for the rich without offering an alternative of their own.

They don’t have to. The Bush administration and congressional Republicans have done a poor job responding to criticisms of the Medicare drug benefit and HSAs. Conservatives and think tanks have largely stood on the sidelines as the beating has taken place. Many think they are standing on principle, but in fact it reflects a lack of vision on their part.

The fact is, most conservative think tanks and conservatives frame Medicare and health insurance in terms of reducing health-care costs. As a result, they cede the moral high ground on the health-care issue that is all about coverage and quality of care. Similarly, as I have argued before, conservative griping about the cost of the Medicare drug benefit has blinded Republicans to the fact that Medicare modernization is counterweight to single payer health care.

Liberals complain that even if HSAs become the norm, they won’t slow health-care costs because 80 percent of all health-care spending is incurred after the high deductible ($2,100) is met and would still be generated by consumers using insurers’ money instead of HSAs. That’s true. Then again, the same thing is even more true about single-payer systems or managed care plans where the out-of-pocket cost are nearly hidden.

In either case, it’s the 20 percent of people with chronic illness that generates 80 percent of the cost. Medical progress, not administrative machinations, will reduce the cost of disease.

Conservatives are doomed to lose the HSA debate because they regard them largely as cost cutting tools. To the extent that anxiety about health care coverage is at the heart of uneasiness about a vibrant economy, it behooves the Republican Party to retool their health-care message in general and their HSAs policy in particular.

Republicans must commit to expanding and protecting medical insurance for all Americans. HSAs should be hailed as one way for achieving that goal. Last year, people with incomes of $35,000 or less per year were the fastest growing segment of HSA-eligible health insurance plan purchasers. Sales to this segment grew 104 percent over 2004. MIT economist Jonathan Gruber estimates that more than 1 million working class people will lose their insurance as a result of HSAs being offered. He doesn’t explain why. Maybe the 1.5 million lower-and middle-income people, who were previously without insurance were too stupid to follow an MIT economist’s theory. They actually obtained obtain insurance that included well baby visits, prescription drugs, ob-gyn care and other medical care for about $125 a month, less than what they paid last year.

To continue to boost and maintain insurance coverage among low and middle income Americans, the Republicans should introduce legislation that allows employers to put the full amount of the deductible into HSAs in order to eliminate any out of pocket cost. Working-class and poor families should receive pre-funded debit cards for HSAs with the full deductible amount as well.

The Department of Health and Human Services could help people comparison shop by posting Medicare prices for every single service. It could work with WebMd and other private health-information services to share news about who is doing a good job delivering medical care. Further, since most people rarely spend more than a small percentage of their account, the legislation should allow unused funds — as well as any additional monies contributed by the individual to be used tax free to pay for health care premiums during periods of unemployment as well as any deductibles or co-pays.

Third, HSAs must be compared to liberal efforts to prop up a single-payer and an employer-based health system that is providing less coverage for more money each year. Liberals are responsible for the loss of health care coverage in America. Now they shriek that HSAs would leave less money for subsidizing the increasingly expensive health insurance demands of labor unions, demands that send jobs overseas. Meanwhile, HSAs are giving more working class people more coverage they can keep and call their own for less money.

HSAs are not for everybody or a panacea. They’re only part of a long-term effort to expanding access to health insurance. But if Republicans frame the HSA debate in terms of coverage, they can stop playing defense on health care. First, they have to get passionate about the value of medicine and not what it costs.

Robert Goldberg is vice president for strategic initiatives for the Center for Medicine in the Public Interest.

According to an article in today’s edition of The New York Times, psychiatrists say they have been getting panicked phone calls from patients worried by an FDA advisory panel’s recommendation this month that drugs for attention-deficit disorder carry a prominent warning about heart risks.

Can you say “unintended consequences?”

The calls are coming not just from parents of children who take the drugs but from adult users, who the panel warned might be at the highest risk for heart problems.

Can you say, “irresponsible advisory committee causing increased non-compliance?”

“Every single adult patient I saw today, the first thing out of their mouth was, ‘Am I going to drop dead on this?’ Every single one of them,” said Dr. Timothy Wilens, a psychiatrist at Massachusetts General Hospital in Boston.

Can you say “fear replacing caution?”

Can you say “Precautionary Principle?”

Because if you can’t say it, you can’t fight against it.

And fight against it we must.

The just completed WHO meeting on counterfeit prescription medicines is over. And what took place in Rome should have a chilling effect on us all.

Consider these few facts (direct from WHO, so nobody can say they’re “industry” numbers) —

Between 1998 and 2004 there has been a 1000% increase in seizures of counterfeit prescription drugs

That is not a typo. A 1000% increase.

Between 2001 and 2004 there were 170 official cases of counterfeit medicines originating from an illegitimate supply chain

And most frightening …

Between 2001 and 2004 there were 27 official cases of counterfeit medicines that originated from the legitimate supply chain.

Sound frightening? It is.

Action is required.

While some in the US still don’t believe that counterfeit prescription drugs are a real problem (“Show me the dead Canadians!”) Europe is taking it dead serious.

On Wednesday, the Center for Medicines in the Public Interest (home to this blog) and the Brussels-based Centre for the New Europe co-sponsored a conference titled, “A False Sense of Security — The Growing Threat of Counterfeit Prescription Products.”

Shortly I will post all of the presentations from that event. A book will follow.

The next day (last Thursday) the World Health Organisation and the international pharmaceutical industry launched a global taskforce aimed at stemming “the growing epidemic” of counterfeit drugs that has become a magnet for organized crime.

Here’s what the Financial Times wrote on the subject …

On some estimates, fake drugs account for more than 10 per cent of the medicines market worldwide, worth nearly 40bn US dollars (34bn euros, 23bn pounds) a year. But in developing countries that proportion is more like 25 per cent and in some countries it may be as high as 50 per cent.

Howard Zucker, WHO’s top official on pharmaceuticals, said: “People donç©° die from carrying a fake handbag or wearing a fake t-shirt. They can die from taking a counterfeit medicine.”

The taskforce will focus on strengthening national laws and enforcement, raising awareness by consumers and health professionals, improving international co-operation and developing “innovative technology solutions” including electronic tagging to track fakes.

However, WHO is no longer pressing for work to start on an international treaty to tackle counterfeit medicines, which critics feared could simply serve as an excuse for delay and inaction.

“Clearly what’s needed here is action and we don’t need a convention to take some action,” said Harvey Bale, director general of the International Federation of Pharmaceutical Manufacturers and Associations (IFPMA), which is co-sponsoring the Rome conference.

The Centre for Medicines in the Public Interest has predicted that counterfeit drug sales could nearly double to $75bn by 2010. While the problem is worst in poor countries with weak regulation and enforcement, where counterfeiters fake medicines for life-threatening diseases such as malaria, tuberculosis and Aids, much of the growth is fuelled by internet sales into western markets.Counterfeiters are now focusing not just on “lifestyle” drugs such as hormones and remedies for erectile dysfunction, but also expensive treatments for cancer and drugs in high demand, most recently the anti-viral Tamiflu.

The absence of criminal laws against counterfeiting in many countries has encouraged organised crime rings to enter the business.

“Organised crime is gravitating towards the industry because the risks are a lot less than forging currencies or trafficking heroin,” said Mr Bale. “You can make a fortune, at no risk.”

Dr Zucker said: “International police action against the factories and distribution networks should be as uncompromising as that applied to the pursuit of narcotic smuggling.”

WHO said it planned to extend to more regions a web-based system for tracking the activities of drug counterfeiters it set up last year to link national health authorities and other agencies in the western
Pacific.

As I arrived back in the US my mobile phone rang. It was a radio station in South Korea wanting to interview me on the fact that North Korea is now in the business of counterfeiting prescription drugs for profit. The world is paying attention. So must we.

It’s time for US regulators to join this working group and address the problem from a truly transatlantic perspective.

The lives we save may be our own.

Rep. Gil Gutknecht (R-Minn) and Rep. Rahm Emanuel (D-Ill.), the dumb and dumber of Congressional voices calling for drug importation, demanded an explanation on Wednesday for increased government seizures of drugs mailed to U.S. customers by Canadian pharmacies.

They don’t want an explanation — because they know the answer — uninspected, unregulated foreign drugs are unsafe and illegal. This is a recording.

“We believe this unannounced policy of increased enforcement is irresponsible,” the two said in a letter to the Food and Drug Administration and to U.S. Customs and Border Protection.

“There is a growing chorus of outraged Americans concerned that access to affordable prescription drugs is being denied to them,” reads the letter.

It is a chorus of two backed up by a supportive media echo chamber. But the music is out of tune and increasingly out of touch.

Here’s what these two elected representatives of the people are complaining about — recently the FDA launched an investigation confiscating thousands of drug shipments headed for the U.S. Some of them were headed for Minnesotans who ordered them over the state’s Web site. When opened, nearly half claimed to be of Canadian origin but, according to FDA investigators, 85 percent of them were from 27 other countries such as China, Iran, and Ecuador. And 30 of the drugs were counterfeit.

Why did FDA do what they did? Because it’s their job and it’s the right thing to do.

This is a recording. If you are looking for media attention, please leave your name and congressional district at the sound of the beep.

Bob Goldberg on the price-tag for survival …

It is both remarkable and tragic that at a time when we are finally winning the war against cancer, actually reducing the numbers of deaths due to that dreaded disease, the New York Times is editorializing against the value and use of the very medicines that have made such advances possible. Do we really need enemy combatants against medical progress?

The NYT claimed recently that Avastin at a retail price of $8000 for a month of treatment is too expensive for an average of 6 months of more life, without pain or toxic side effects for cancer patients that have not responded to other forms of cancer care. Here’s how I would have put the question: Is it worth having your insurance company pay about $5000 to keep you alive for 6 months or longer? What’s it worth to have drugs like Avastin around to keep tens of thousands of cancer patients alive longer and longer so they can live free of caregivers, can go to work, parent their kids, etc? The Times never asks that question.

Similarly, medical journals are now abandoning real science and are simply becoming collections of editorials by Monday morning quarterbacks. Most recent is the assault on the right of multiple sclerosis patients to use Tysabri to treat the devastating relapses associated with the disease. The British Medical Journal published “Lessons for Clinical Trials from Natalizumab in Multiple Sclerosis” by Abhlijt Chaudhuri, a physician known for believing that no drug for MS should be used without any rebuttal.

Unfortunately, his “lesson” seems to “grin and bear it.” Not acceptable.

The term ‘relapse’ sounds innocuous. It means losing balance, one’s sense of taste, eyesight, memory, etc. without warning. It can make walking impossible. The attack on Tysabri is simply an old saw applied to a new drug: since the drug doesn’t actually stop MS from progressing the possible long term safety problems aren’t worth the risk of returning to market. The article spews the same accusations made of every drug that is experimental: we don’t know what the optimal dose should be and how long people should take it. The fact that only clinical experience can help answer that question is ignored in favor of a standard of evidence that, if applied to the early release of penicillin, the measles vaccine, HIV drugs, and other breakthroughs, would have cost millions of lives.

That is like saying that since some drugs don’t cure a disease, don’t make them available at all. Again, the value of these medicines to people and their ability to give them back lives of productivity, dignity and independence means nothing.

On 2/4, blogging on a report that there was a backlog of generic drug applications at the FDA, I suggested that the agency seriously consider user-fees for this important area of responsibility. And it looks like that’s going to happen.

Scott Gottlieb, the FDA’s feisty and forward-looking deputy commissioner for medical and scientific affairs plans to tell the generic drug industry today that it is time for the government to charge its member companies fees so the agency can hire more staff and exprdite the processing of applications to market new generic medications.

In a speech he is scheduled to deliver to the Generic Pharmaceuticals Association in Florida, Gottlieb plans to say that user fees — like those paid by the makers of brand-name drugs, medical devices and animal drugs — are needed to keep up with generic reviews.

“From our perspective at FDA, we have seen user fee programs applied to our medical device and new drug programs with great success,” a copy of his speech says.

Gottlieb is scheduled to say in his speech that raising funds from generic-drug companies would allow the agency to review applications faster, to have more scientific data analyzing whether proposed new generics are equivalent to established brand-name drugs, and to address potential safety issues once the drugs are on the market.

Per Scott, “It’s not fair to compare our work in our generic drug office to our work in the new drug office, as some have done, without acknowledging that our new drugs program has benefited from funding tools that are not available to us when it comes to generic drugs.”

Use of generic drugs — which must be equivalent to the branded products that they duplicate — has been growing steadily, with more than 53 percent of prescriptions now filled with generics. That percentage could increase
quickly because an unprecedented number of major branded drugs will lose their patent protection in the next few years.

In addition to raising the user-fee issue, Gottlieb is set to outline a number of agency initiatives to speed generic reviews. One is a formal lifting of a ban on direct telephone conversations between FDA reviewers and generic drug makers. Another involves grouping bioequivalence review applications for the same or similar drugs.

You tell em Scott.

Talk about being a Nabob of Negativism! Families USA (the political lobbying group that masquerades as a “citizens advocate”) is downright gleeful in it’s grossly premature burial of Medicare Part D. According to its new report (a love note to the Intelligensia of Interference issued on Valentine’s Day) the Bush Administration has “significantly lowered” its enrollment projections for the new drug benefit.

Really? I don’t recall anyone from the White House saying that? Maybe Ron Pollack, the Families USA “Godfather,” meant White Castle? And I certainly didn’t hear Mark McClellan say anything remotely like that during his recent, highly publicized congressional testimony. And I didn’t read it in a Robert Pear column. So could it really be true?

No. I think that the Godfather must be hearing voices — and that those voices are “interfering” with his cognitive processes.

Giving a new and draconian meaning to “family-friendly,” Godfather Ron also concludes that a vast majority of those enrolled in Part D already had drug coverage before the benefit began and that only “a very small fraction” of beneficiaries eligible for the low-income subsidy have entered the program.

Methinks that the Godfather would like the truth to sleep with the fishes. This new report is just another example of reality non-interference.

I suppose that Families USA expected 100% sign-ups with zero problems after almost a month and a half! Can’t this administration do anything right!

Proving that they are most decidedly living in a Pelosi-induced fantasyland, Godfather Ron commented, “It’s truly disappointing to see such a large number of seniors not get the benefits to which they are entitled.” He further added that the drug benefit has so far “produced rather meager results.”

I guess he thinks that if he keeps saying that enough times people may actually start believing him.

CMS spokesman Gary Karr politely suggested that Families USA spend its time and energies more productively by helping to expand the number of seniors enrolled in Part D instead of taking “ill-informed partisan potshots.”

Good for you Gary.

Karr then said that CMS has not downgraded their enrollment estimates. “The numbers that [Families USA] cite come directly from us. We’ve been open and above board about exactly what those numbers are and where we get our estimate of the 28-to-30 million.” Families USA, citing a January 28, 2005 CMS Federal Register notice, said that the administration had been projecting that 39 million beneficiarieswould enroll.

But it’s the Godfather of Garbage and his “Family” who are doing the projecting. For them it’s all about political spin and vituperative spittle. Anything for the cause.