Article today in the Wall Street Journal on the persistent and quiet revolution going on inside the FDA to implement the Critical Path even as the brickbats from Grassley, Waxman, Hinchey and other media hounds come up with 19th approaches for evaluating 21st century medicines.

WSJ(7/10) FDA May Be Open To `Shifting’ Drug Trials
Jul 10, 2006 (From THE WALL STREET JOURNAL)
By Anna Wilde Mathews

CLINICAL TRIALS of medicines are traditionally performed in a “blinded” fashion so that the findings will remain secret until the studies are completed. But regulators and the pharmaceutical industry are increasingly interested in starting to use a very different model that lets studies change as they go along, based on early results.

Drug companies have begun to perform such adaptive trials for their new medicines, hoping for more efficient tests that could save millions of dollars. The Food and Drug Administration, meanwhile, is sending increasingly encouraging signs that it is open to considering the results of such trials. In a move that could lay the groundwork for greater future use of such studies, Scott Gottlieb, an FDA deputy commissioner, is set to announce today plans to develop regulatory guidelines for adaptive trials. The FDA has also put together an internal team to work with its drug-review divisions on the adaptive designs, which are statistically complex.

It’s clear what adaptive trial designs can help accomplish: As Peter notes, “Adaptive trial designs represent a major advance in drug safety because the best kind of safety is better understanding of how a drug works *
and who it works best for.”

How? Adaptive trial designs allows researchers to tailor the
study of the drug and its dosing to what they learn about the medicine and
the patient in real time. It’s another tool for personalizing medicine
that the 21st Century Task Force endorsed in is report.

As we pointed out in our recent Washington Times op-ed, the best post market safety is good pre-market surveillance through the use of critical path tools. The battle over FDA reform — and the real end game — how to use user fees — will come down to whether to invest in 21st century or 19th century tools. Spending dough on the status quo won’t cut it.

And speaking of NICE, have a look at Heinz Redwood’s new paper, “The Use of Cost-Effectiveness Analysis of Medicines in the British National Health Service: Lessons for the United States.”

Here’s the link:

http://www.phrma.org/files/Nice%20Report.pdf

The lessons learned are important ones and once again the phrase that pays (or, rather, doesn’t) is price controls = choice controls.

What do Madame Curie, Albert Einstein, Jonas Salk, George Hitchings, Joshua Ledeberg, Gertrude Elion and Sir James Black all have in common? They are Nobel Prize winners who have transformed the 20th century for the better through the contributions to science and medicine. And, according to the Wall Street Journal’s Thomas Burton, their research has, uh, “limitations” because they all did consulting or received honoraria from pharmaceutical firms. I guess by extension Louis Pastuer’s findings on pathogenesis are limited or have in Burton’s tart terms, “shading and nuances” because he received funding for the work from French beer and wine producers.

Burton wasn’t talking about Nobel prize winners in his article, of July 6, 2006 in the The Wall Street Journal Europe , “Antismoking drug from Pfizer shows promise in research “

He was writing about Chantix, a new Pfizer drug that helps suppress smoking by smoothing out the production of dopamine (not blocking as Burton states) involved in creating the craving for nicotine. There is less binging or withdrawal as a result. I know a little bit about the drug since I had the chance to talk to the Pfizer pharmacologists who designed the drug to produce the biochemical effect. In any event, the drug uses a different pathway and novel approach so the robust results are not surprising one respect.

What is suprising is that Burton decides to regard the fact that the researchers source of money is somehow a limitation on the drug’s effectiveness equal to that of the study’s exclusion critieria….

“Despite the positive findings, there were several limitations to the research. One is the fact that people with pre-existing conditions such as depression, alcohol or drug abuse, and diabetes requiring insulin were excluded from some of the studies. Another stems from the fact that the majority of authors of the three studies, which were published in the Journal of the American Medical Association, either have done consulting work or received honoraria or research grants from Pfizer and other drug companies, or are Pfizer employees or shareholders.

Such apparent conflicts of interest won’t normally change the major findings of research. But they can affect nuances and shadings of the way they are presented. “All of these papers were rigorously peer-reviewed,” says the University of Wisconsin’s Douglas E. Jorenby, who headed one of the studies. (He has received research funding from Pfizer but not consulting fees or honoraria.) A Pfizer spokeswoman says, “Regarding consultation fees, Pfizer follows standard protocols for consulting agreements and provides adequate disclosure.”

As one of my friends who works for a drug company noted, “Based on the logic presented here every commercially conducted/funded research project has a built-in âlimitationâ. Seems easier just to add some standard warning label - like on cigarettes - to every commercially supported study and be done with it.”

But it’s worse. This approach slimes the good work of every good and great researcher who in any way associates with private companies. It disqualifies and discredits pivotal work and deprives the public of pathbreaking research that cannot be duplicated anywhere else. Let’s be clear: not only is the commercialization of science not bad. Commercialization of science, it’s industrialization is critical to advancing the public health. Those purists who want science to be conflict or profit free want the medicine THEY can control, plain and simple.

That’s a sure-fire recipe for medical Lysenkoism.

Scott Gottlieb’s statement on why the FDA is not going to go down the road of comparing medicines prompted CMPI’s Chairman, Michael Weber, MD — one of the world’s experts on heart failure and hypertension — to submit this post about the trend towards states using cost-effectiveness studies to limit access to certain drugs. Setting aside questions of genetic tests that suggest high response to one drug compared to the one deemed “cost effective” by a bunch of second rate economists engaged in data dredging, Dr. Weber writes about the impact this approach has on the quality of care:

Most patient visits to the doctorâs office result in a prescription being written. Physicians depend heavily on the availability of appropriate drugs, and particularly the flexibility of choice to provide medicines that best fit the needs of individual patients.

For this reason, lists of drugs available to be prescribed - typically called formularies - should include an array of agents that optimize patient care. This selection of drugs can affect local prescribing, as in a typical health plan, or it can have broad-based implications, as in a national or governmental formulary.

Cost-effectiveness as a basis for choosing drugs for a formulary sounds beguiling; it implies a rational process that provides benefits to the patient and value to the healthcare system. But this approach is more complex than it appears.

Consider the two components of cost-effectiveness. Strange as it may seem, cost is hard to figure since it involves not only the price of acquiring drugs, but also â among other things — providing for additional doctor visits, extra tests, and adjustments to other drugs being taken. These all contribute to the overall expense.

Effectiveness is equally hard to define. After all, this is not just a simple measure of drug efficacy, but must also take into account acceptability, tolerability and ease-of-use for patients and doctors. Difficulty in achieving true effectiveness is highlighted by the fact that by 12 months of taking life preserving drugs with proven long-term benefits, only 50% of patients are still refilling their prescriptions.

So, simply put, cost-effectiveness is a term that compounds the inaccuracies of two difficult-to-define variables. When all is said and done, we are dealing with a euphemism that has become popular with government agencies and health insurers. In their jargon, the term cost-effectiveness in essence means that they will usually select drugs for formularies that offer them the best financial deal.

Underlying this selection process is the assumption of so-called class effect: if drugs are similar to each other chemically they should work in similar ways, so why not choose the cheapest? But consider these brief examples of common clinical conditions that argue against this approach.

A class of drugs that is widely used for the common problem of clinical depression is known as the SSRIs. Ever since Prozac, these agents have been widely accepted. Yet there are important differences among the several members of this group in their performance; sometimes clinicians find it necessary to work through three or even four different drugs before finding one that works best for a particular patient. These drugs also differ in their safety profiles, so again it is critical to have a broad selection available.

Commonly used pain killers, NSAIDs like ibuprofen, naproxen, aspirin and celecoxib also - on average - share similar benefits in patients with arthritis or other painful conditions. Even so, individual patients can get different degrees of pain relief from one drug as compared with another. There are also issues of convenience: some drugs can be taken once daily, others need multiple doses. And there are also differences among these agents in safety issues, including their propensity to cause gastrointestinal upsets or ulcers, to raise blood pressure or have other effects that necessitate switching to alternative members of the class. Having choices is imperative.

Consider a broader issue. Suppose, at first sight, there doesnât seem to be much meaningful difference among drugs within a particular class. There is still a compelling argument â old-fashioned competition — for including a variety of these drugs on formularies. Most obviously, manufacturers of rival brands will recognize the need to keep their prices within bounds, thus driving down costs across the class.

But there is an even stronger need to stimulate competition. Look, for instance, at what happened with classes of drugs called ACE inhibitors or angiotensin receptor blockers that are now used for treating hypertension, heart failure and a variety of other life threatening conditions related to the heart, strokes and the kidney. As manufacturers were compelled by competitive needs to demonstrate that their particular products could provide special advantages or differentiation, they undertook a wide variety of innovative clinical trials that created truly major advances in improving the quality and length of lives across a wide spectrum of patients.

Without the breakthroughs fueled by this competition, important new therapeutic indications would have remained undiscovered and we would still be using these drugs in a limited fashion, a tragic loss of opportunity to improve many lives. In fairness, manufacturers could hardly be expected to take the major financial risk of investing in large multi-year clinical trials if they were not able to earn at least some revenues during this prolonged and expensive process.

In the short term, cost-effectiveness as a basis for formulary selection may save money for government agencies and may increase profits for health plans. But for the well-being of many individual patients, as well as for critically needed medical progress, the price of drugs cannot be the only criterion for their availability. We should remember that drugs represent only a small fraction of total health care costs and we should not lose sight of our overall health care objectives when deciding on access to drug products.

Here’s an important global public health story that deserves wide attention (and, one might argue, words of praise from certain members of the United States Congress).

Major kudos are due to Mark McClellan (in his previous life as FDA Commissioner) and current FDA Deputy Commissioner Scott Gottlieb for navigating through the many obstacles to expedited FDA approval.

(I am proud to have played a very small role in helping make this a reality.)

Here’s the rest of the story …

The Food and Drug Administration has approved the first 3-in-1 antiretroviral pill for use by the American-sponsored plan for AIDS treatment. The pill, made by an Indian generic drug company, is for patients in countries helped by the President’s Emergency Plan for AIDS Relief.

Under that plan, the United States is now the largest provider of antiretroviral drugs in the world, paying for treatment for 561,000 patients in Africa, Asia and the Caribbean.

The Global Fund for AIDS, Malaria and Tuberculosis, the second-largest provider, pays for about 541,000 patients. (The United States also pays one-third of the Global Fund’s budget.)

The new pill, made by Aurobindo Pharma of Hyderabad, India, combines three common first-line drugs, AZT, 3TC and NVP, which are also known as zidovudine, lamivudine and nevirapine and sold in the United States as Retrovir, Epivir and Viramune.

Geeta Anand had another sob story about the high price of biotech drugs. This time it was about Revlimid, Celgene’s drug for treating multiple mylema, Myelodysplastic syndrome (MDS) an illness associated with the underproduction of blood cells and possibly ALS if the results with transgenic mice are replicated in human trials. Geeta is upset that Revlimid retails for about $6400 a month. Mind you, that’s for a drug which appears to extend for a year or more the lives of about 6000 people who are facing certain death. The cancer stopped progressing in most patients after seven treatments and they were disease free 9.6 months after followup. People with multiple myeloma can live disease free for years. A true breakthrough. Is that worth $6400 a month. A house in the Hamptons is. So is a month at Harvard for the matter.

Revlimid is also approved to treat patients with transfusion-dependent anemia due to low- or intermediate-1-risk myelodysplastic syndromes (MDS) associated with a deletion 5q cytogenetic abnormality with or without additional cytogenetic abnormalities. That is, it’s a genetically targeted therapy for MDS which itself affects about 10000 people a year.

Both diseases are devastating, either fatal or life crippling. But they are not blockbuster in size. They are orphan diseases. Revlimid is a medicine that will control them with specific regimens and in specific quantities. As it is studied further, funding for which will come from Celgene’s well deserved profits and not any idiotic Cracker Jack prize competition suggested by Jamie Love or Bernie Sanders in lieu of real rewards (let’s divide .5 of our GDP by the contribution of the increase to the quality of life years divided by the number of patients, less the total cost of care, less the NIH investment which equals the reward less the 90 percent tax rate…) and in the wake of patent seizures, we might see even wider and newer uses, including ALS.

And one more thing. What if Celgene is a one hit wonder? Celegene now has a full pipeline of products in development. What if none of them get approved? Revlimid might have a 97 percent gross margin but that goes to pay for all the other research. That’s the company’s venture capital for future biomedical discovery activity. You can’t finance the future of medicine on WSJ criticism or Jamie Love’s Cracker Jack prizes. And by the way, isn’t worth $72k to beat back cancer?

You know how we feel about “evidence-based medicine” — that quotation marks are required since what it really means is “cost-based medicine.” Here at Drugwonks.com we are firm believers in patient-centric medicine with no quotes required because that’s what it means — putting the patient at the center of the health care equation.

We are also apostles of the Critical Path, of personalized medicine, of the Biomedical Century. And so it is with great interest that we recommend an article from The New York Times, “Imperfect, Imprecise But Useful: Your Race,” by Denise Grady. Here’s the link:

http://www.nytimes.com/2006/07/04/health/04opin.html?_r=1&oref=slogin

The article addresses the question, “Is race medically relevant?” According to Dr. James P. Evans, director of adult genetics at the University of North Carolina, “The question remains, does any of the differential distribution of gene forms have potential medical significance. I think the answer is sure. There may be differentially distributed genotypes that put a group, in aggregate, at increased or decreased risk for certain diseases or affect their responses to certain medications.”

Yes indeed. More information is better.

Are we there yet?

Ms. Grady writes, “Ideally, he said, doctors would like to know precisely which genes in each individual explain susceptibility to disease. But for most diseases the science is not there yet.”

No better argument exists for the need to accelerate down the Critical Path.

“In the meantime,” says Dr. Evans, “If we can glean some hint from someone’s ancestry, we should use it if it can help us treat them better.”

Drugwonks Exhibit A: The urgent need to aggressively identify and exploit biomarkers.

Yes — there are Luddites. Consider the statement of one editorialist, “In medicine there is only one race — the human race.” Nice sound-bite but, as the NEJM reports, important racial differences exist in the way people react to various medicines, including drugs used to treat high blood pressure, heart failure, depression, and pain.

How does this relate to patient-centric medicine? Ms. Grady writes, “The differences could affect the dose a person needed, or whether a particular drug should be used at all.”

The battle for using “continent of ancestry” (the PC term used in place of “race”) is similar in tone and temperament to the “evidence-based” versus patient-centric debate. Just as “cost” must not be the only issue in determining the most appropriate treatment for an individual patient, so too must race (pardonnez-moi — continent of ancestry) not be excluded because of political considerations.

Patient-centric, n’est pas?

Ms. Grady writes, “As a patient I would like to know about this kind of thing. More important, I would really like my doctor to know about it. If information linked to race could help somebody even a little, it would seem worth having. But it could be lost if researchers become wary of studying this subject or even talking about it.”

Is there even a debate here? Do we want doctors to use all relevant information so that their recommendations can be as targeted, effective and safe as possible? Or do we want them to close their eyes and write the prescription?

This just in about the dangers of taking high doses of Tylenol, especially if you are knocking a couple back this holiday week. I fully expect the new darling and David Graham of the media, FDA Drug Safety numbers cruncherRosemary Johann-Lang, who complained “How does one justify balancing the risk of fatal liver failure against one day less of ear pain?” about Ketek — the last line of defense for many against community acquired pneumonia — to rise up and leak a memo claim “how does on justify balancing the risk of fatal liver failure against one day less of fever?” which in turn will be interpeted by members of Congress and the media as a call to take Tylenol away from everybody… (More on Rosemary’s obsession with insignificant safety signals in other areas in another post)

High Tylenol doses linked to liver woes

By CARLA K. JOHNSON, Associated Press Writer

Healthy adults taking maximum doses of Tylenol for two weeks had abnormal liver test results in a small study, researchers found, raising concerns that even recommended amounts of the popular painkiller might lead to liver damage

Lots of polls and pols are reminding us almost daily that confidence in the FDA is on the decline. How much of this is caused by posturing and putting politics in front of the public health? A lot. But the numbers don’t lie.

So what can the FDA do to regain the confidence of the American public? I think that a large part of the answer is to tell the truth — that the agency is the world’s gold standard — and they’ve got the proof to back up that statement. As a mentor of mine once opined, “He that tooteth not his own horn, that horn shall go untooted.”

As Dizzy Dean said, “It ain’t bragging if you can do it.”

Just doing the right thing, day after day isn’t enough. Just addressing some of the most difficult and important regulatory issues of the day isn’t enough. Just working likes dogs for government pay isn’t enough. FDA must go on the offensive, knocking down untruths, mistruths, and half-truths one-by-one everytime they are floated in the media, in press releases, in public statements by grandstanding public officials, by vendetta-driven “whistle blowers.”

All of the research that I’ve seen makes it clear that the pubic wants to have faith in the FDA. They are willing to believe the FDA. But the FDA must go out and get it. Mix it up. Engage in the debate. The FDA has the bona fides while those basking in the Splendor in the Grassley are but paper tigers.

And the time is now. With the pending release of the Enzi/Kennedy bill and PDUFA reauthorization, now is the time to set the agency on an aggressive, accelerated Campaign of Confidence.

What better way to commence the FDA’s second hundred years.

I am still recovering from Wednesday evening. The ever gracious Grace-Marie Turner (of Galen Institute fame) hosted a memorable launch party for the Center for Medicine in the Public Interest (the public policy home of drugwonks.com.)

Memorable for so many reasons but mostly because of those who attended — FDA Deputy Commissioners Janet Woodcock and Scott Gottlieb, NCI Deputy Director Anna Barker, Julie Goon, the new White House health care policy guru, along with my former FDA colleagues Dan Troy and John Taylor, former NIMH director (and CMPI board member) Dr. Fred Goodwin — and our keynote speaker, Dr. Mark McClellan — the hardest working man in health care. Here are some of the kind things Mark had to say:

“… CMPI is focusing on the right issues at the right time. And with the right people.”

“… CMPI is about great ideas and effective communication. CMPI begins at the right time, promoting ideas that make a difference in medicine that is personalized, predictive, preventative, and therefore effective in the 21st century.”

“… It’s nice to see ideas, communicated effectively, that translate into policies that change the way healthcare is being delivered in this country. That is happening because of what Peter and Bob and all of you here tonight are doing day in and day out, tirelessly, often thanklessly — but it is making a huge difference.”

“… I’m certain that CMPI will be an important new force in health care policy — a force that will help to get better healthcare for all Americans.”

Well golly.

That’s a lot to live up to — and we intend to exceed expectations.

Here’s a press release from the Office of Senator Chuck Grassley which, along with the Senator, a edging towards a complete disconnect with reality when it comes to Ketek….

Sen. Chuck Grassley issued the comment below in response to the
announcement today about Ketek and a new bold warning label. Sen.
Grassley has been investigating allegations about the FDAâs handling of
Ketek and failure to ensure the integrity of a pivotal study about the
benefits and risks of this drug. The FDA continued to cite the study in
safety information despite its own determination that the study was
riddled with fraudulent information.

Grassley comment —-

âThere are questions about whether this drug should stay on the market,
and thereâs great legitimacy to those questions. Ketek is another
example where the FDA accommodated a drug maker and turned a blind eye
to serious safety concerns. …..â

Is there anyone who questions whether Ketek should stay on the market? Who are they and what are there reasons? Does Senator Grassley have sources? And if he does, will he provide them or will we at drugwonks have to send someone over to his over to demand them?

We hope to have answers soon.

New op-ed, “Putting Clinical Trials in the Dock.”

Have a read:

Putting clinical trials in the dock
The Roanoke Times
June 27, 2006

BY: Peter Pitts

Pitts, a former Food and Drug Administration associate commissioner, is director of the Center for Medicine in the Public Interest.

“One size fits all” rarely does. From clothes to shoes to hats, few people find that items carrying that label work with their individual bodies. So why do we entrust the health of our bodies — one of the most important assets we have — to a one-size-fits-all mentality?

Unfortunatly, that’s exactly what the influential movement known as “evidence-based medicine” does. It sounds like a good thing, does’t it? Of course we want our health care based on evidence. But the phrase is misleading. As it turns out, “evidence-based medicine” often ignores the most critical evidence of all — the individual patient.

Advocates of EBM urge doctors to base their clinical decisions on research findings. Randomized clinical trials become crucial under this regime: The results of these trials are what doctors overwhelmingly base their suggested treatment on.

The problem is that clinical trials aren’t the only thing doctors need to take into account when making decisions. Evidence-based medicine emphasizes just one aspect of the clinical pie over all the others. This model, which began taking shape in the 1970s, is now broken and outdated.

EBM is stuck in the past. For the most part, it is a retrospective look at clinical studies and head-to-head comparisons of medicines and medical procedures. EBM may involve a careful look at the science. But in practice, it’s very limited. All of these studies are population-based, have rigid exclusion criteria and can’t integrate new information or innovations.

The result is decidedly and transparently a narrow one: to eliminate “practice variation.” Indeed, that’s one of the primary aims of EBM — to standardize medicine around what is known to work.

Practice variation is any treatment that varies from the norm that EBM prescribes. The canard of evidence-based medicine is the belief that practice variation is bad and that one-size-fits-all medicine is good. EBM presupposes that all people respond precisely the same way to all medicines. But that’s simply not true. Disease varies by individual, and selection of treatment must be driven by diagnostics, not just guidelines.

Today, the science of genomics is ushering in an age of personalized medicine. Clinical outcomes can be monitored with increasing precision. Computers can control for hundreds of variables to help doctors and researchers identify what treatment steps matter most in improving care.

People can be screened with a variety of molecular diagnostics to reduce side effects, increase compliance, improve outcomes, and even prevent various forms of cancer, depression, hypertension, Alzheimer’s and immune disorders.

This is 21st-century evidence-based medicine — patient-centric and cost-efficient.

The triumph of modern medicine is that it can be so precisely targeted to a single patient’s needs. It is a dramatic leap forward from EBM’s sweeping approach, which sees only through the broad lens of population-based studies, and the individual patient is kept out of focus.

Unfortunately, EBM continues to enjoy broad support in the policy community. Why? Because at its core, evidence-based medicine is cost-based rather than patient-based. In other words, its standardized approach supposedly saves money. But this is extremely short-sighted.

Evidence-based medicine may provide transitory savings in the short term, but the same patient who takes the cheapest available statin today may very well be the patient costing you — the taxpayer, the policymaker, the thought-leader, the sister, the spouse — big bucks when that patient ends up in the hospital because of improperly treated cardiovascular disease.

The repercussions of choosing short-term thinking over long-term results and cost-based medicine over patient-based are pernicious to both the public purse and the public health.

We need a new approach. The health care community must work together to develop new cost-efficient programs that account for modern genomics and individual screening. Because “one size fits all” treatments are dangerously outdated in this era of patient-centric medicine.

Some people, like Senator Schumer, thinks it is wrong for drug companies to reduce their prices and co-market generic version of products nearing the end of patent life. As is Hatch-Waxman is a law that turns Para 4 challenges into an annuity. Sorry. That’s not what the law or the federal court says. And moreover, more competition means lower prices over the life cycle of the drug. As for the idea that Merck has “forced” managed care companies to impose a higher copay on generic Zocor, an allegation that Schumer served up, the fact is HMOs use higher copays to drive people to lower priced drugs all the time. I don’t like the practice because drug choice should be based on what’s best but that’s the game. Whining about it won’t change a thing and it shouldn’t.
Ultimately, the opposition to the Zocor price shift is just an effort to protect the generic drug “industry” and not consumers. It is ironic that the same people who belittle Rx and bio industry arguments about the impact of price controls on incentives for future investment are now arguing that the Zocor price shift and authorized generic movement —which is temporal and depends on blockbusters by the way — will undermine the long term incentive of generic companies to….initiatie patent challenges. What a loss. Fewer lawsuits.

The FDA has decided to shelve its plans of opening an Indian office to help expedite regulatory clearances for Indian drug exporters to US.

Sources said Dr David Lepay, the FDA’s Senior Advisor for Clinical Science and Director, GCP Programs revealed at a session on Asian clinical trials at the 42nd annual meeting of the Drug Information Association (DIA) in Philadelphia, USA, that the US food and drug regulator was not planning to set up offices neither in India or anywhere else in Asia, at present. The announcement from the FDA official came in the presence of Dr Ashwini Kumar, Drug Controller General of India (DCGI), who was also a speaker at the program.

Pharmabiz had reported about two years ago that the FDA was planning to start its Indian office at New Delhi with an initial investment of about $5 million, considering the fact that India has the maximum number of FDA-approved facilities outside the US. This office was to facilitate Indian companies with the procedures of filing for marketing approval for products to be launched in US, application for site inspection and other procedures dealing with the FDA. The office was envisaged to facilitate the exchange of communication between Indian companies and the US authorities, thereby saving a lot of time and resources, sources had told Pharmabiz.

Dr Leepay told the seminar, attended by a good contingent of Indian participants, that it was not mandatory that a new drug marketing application in the US be supported by a US study and there had been instances of marketing applications wholly supported by non-US studies. However, the FDA had criteria that non-US studies were expected to meet US standards and that non-US data was reviewed to the same standards as data from the US. Though the FDA had a long history of inspection of clinical trials outside the US, its experience in the Asia/Pacific region was limited, and the region currently accounts for only 5 per cent of FDA’s international inspections. He also clarified that the FDA does not certify clinical investigators, clinical sites, sponsors or ethics committees, nor does it approve study protocols or informed consent documents.

Here’s one of CMPI’s Scientific Adviser Peter Hotez, (and recipient of a Gates grant for his work on the development of a vaccine against hookworm) on how the Bill and Melinda Gates Foundation does it’s good work…

http://abcnews.go.com/Video/playerIndex?id=2121626

The latest broadside against the FDA is by Congressman Waxman who argues the FDA is doing a lousy job by not prosecuting and attacking companies who are producing inferior products, engaging in mislabeling or selling suspicious goods. This is the sort of after fact enforcement activity that pols love since it gives them something to hold hearing about. I call it regulation by body count since it requires people to die or be harmed in order for a regulatory or enforcement act to take place. In contrast, since Mark McClellan became commissioner in 2003, the FDA has sought to improve overall product quality through manufacturing efficiencies, risk management programs and other quality improvement efforts that are not politically sexy and often take years and millions of dollars to implement. (Not to mention cooperation. ) Indeed manufacturing is part of the Critical Path lest anyone forgets.

Of course, the drive by media ignores all of this. And the FDA has not done enough to get the message out about these important initiatives. One more thing: Why does Gardiner Harris refer to the ‘conservative’ American Enterprise Institute and the ‘watchdog’ Public Citizen? Public Citizen is nothing but ‘liberal’ and as for watchdog, that is a matter of opinion, not absolute truth. Even a Rockefeller can figure that one out.

Report: Many Americans Too Willing To Ask For Help
June 26, 2006 | The Onion, Issue 42*26

BETHESDA, MD — A National Institutes of Health study released Monday revealed that Americans are excessively, almost pathologically eager to seek help for various personal, psychological, financial, organizational, and sartorial problems. “American citizens are four times more likely to seek counseling than Canadian citizens, eight times more likely than the British, and 900 times more likely than Germans,” said the NIH’s Dr. Anne Hanratty, who authored the study. “In addition, they seek help an average of seven times faster than citizens of other nations, sometimes only a few hours after they undergo any emotion or experience that could be interpreted as negative or problematic.” A related study showed that Americans are nine times less likely to seek help for medical matters, such as high cholesterol or colon cancer screenings, but 85 times more likely to ask for second helpings.

At a time when the social scientists are telling us that post 9/11 Americans are more safety-conscious/risk-averse then ever before — while at the same time looking to medical science for ways to live longer, healthier lives at lower costs — the announcement that the FDA is going to lead the charge towards a 21st century model for clinical trials is good news — very good news.

Here’s the announcement. Further detail can be found at www.fda.gov.

FDA Announces New Initiative to Modernize the Regulation of Clinical Trials and Bioresearch Monitoring

The Food and Drug Administration today announced a series of new policy and regulatory developments to strengthen the Agency’s oversight and protection of patients in clinical trials and the integrity of resulting data in an effort to modernize the agency’s approach to bioresearch monitoring as part of the Critical Path Initiative. The Human Subject Protection and Bioresearch Monitoring (HSP/BIMO) Initiative will facilitate the modernization of the regulation of clinical trials and bioresearch monitoring, specifically the protection of human subjects and the integrity of data in clinical trials, and encompasses devices, foods, human drugs, biological drug products and veterinary medicine.

The new effort is part of an HHS-wide initiative to employ recent advances in basic science, including genomics and molecular analysis, in order to bring about more effective development and review of therapies, and to enable increasingly targeted and individualized care management for patients.

“As clinical trials continue to evolve, in particular becoming increasingly large, decentralized and global, the FDA’s approach to bioresearch monitoring and human subject protection must also evolve and modernize,” said Janet Woodcock, FDA Deputy Commissioner for Operations at this year’s Drug Information Association annual meeting. “BIMO will help FDA modernize biomedical research monitoring making the most efficient use of its resources to help ensure the safe conduct of clinical trials, including taking appropriate opportunities to leverage existing oversight done by private entities to accomplish the Agency’s risk minimization goals.”

Clinical trials have evolved dramatically since FDA first began inspecting them in 1977. In an effort to protect the rights and welfare of human subjects and to verify the quality and integrity of data submitted for review, FDA established over time a bioresearch monitoring program that included the development and implementation of compliance programs to provide guidance for inspections of investigators, sponsors, contract research organizations, institutional review boards and bioequivalence facilities. With the expansion of clinical trial studies and sites, electronic record-keeping in the studies, and greater participation by vulnerable subjects in clinical trials, the role of FDA’s bioresearch monitoring compliance programs must expand and evolve as well. The HSP/BIMO Initiative addresses that need.

Over the past year and a half, FDA has carefully inventoried its programs and identified issues to launch the HSP/BIMO Initiative. As this initiative moves forward, FDA will continue to gather additional issues for the initiative and related information from internal and external stakeholders, e.g., industry, academic, and government activities and programs, and intends to conduct workshops and create other opportunities for public input.

Janet Woodcock, M.D., Deputy Commissioner for Operations, will chair the HSP/BIMO steering committee which is comprised of representatives from the Center for Biologics Evaluation and Research (CBER), Center for Drug Evaluation and Research (CDER), Center for Food, Safety, and Nutrition (CFSAN), Center for Veterinary Medicine (CVM), Office of Regulatory Affairs (ORA), and the Office of the Commissioner (OC).

Caution needed in helping the FDA
By Boston Herald editorial staff
Sunday, June 25, 2006

The top Republican and Democratic members of the Senate committee dealing with health, Sens. Michael Enzi of Wyoming and our own Ted Kennedy, have begun preparing a bill that would give the Food and Drug Administration new powers over drug safety.

Some new powers are needed, but we fear Congress may go too far.

Senators are reacting to the withdrawal of Vioxx and similar drugs after the discovery that these stomach-friendly painkillers increased the risk of heart attack when taken for 18 months.

The FDA would get the ability to order changes in a drug label after it goes on sale and the power to force manufacturers to live up to any promises to conduct post-approval safety studies. Experience shows these are needed improvements.

But the bill reportedly (a text is not yet available) sets up dispute resolution procedures and requires the FDA to publish formal plans for evaluating and mitigating risks of every new drug, complete with schedules and timetables. All this would just augment the agency’s “avoid mistakes” culture. Its bureaucrats know they will be pilloried for approving a drug that later reveals problems, but will be left alone if overcaution delays the sale of something useful.

Caution has costs. Approval of Erbitux, a new treatment for colon cancer, was withheld in 2001 because not all the study patients had failed conventional therapy. The drug was approved 27 months later. Colon cancer strikes about 8,700 people every month; Erbitux (used with another drug) halts tumor growth for 4.1 months. The delay thus cost about 80,000 person-years of tumor arrest.

The FDA has improved its once-draggy performance. Average time to approval of new drugs fell from 22 months to 14 from 1993 to 2003; time to approval for promising drugs in fast-track review fell from 13 months to six. Congress should do nothing to slow it down.

Frank Lichtenberg of the Columbia Business School has estimated that on the average each new drug approved in 1970-1991 saved 11,200 person-years of life in 1991 alone, and presumably each year thereafter. New drugs yielded a return to society of 40 percent per year on the cost of development, he calculated.

All drugs have side effects. The senators would do well to encourage the taking of worthwhile risks, perhaps by mandating the use of sound cost-benefit analysis in surveillance of drug safety.

Great piece today in the NY Post by Dr. Marc Siegel about how the fearmongering by the media and certain members of Congress is driving his patients away from taking medicines that can keep them alive. Marc has written well about how we should use science — not fear — to guide policy and medical decisions.

Here’s the entire article:

POLARIZED PILLS
By MARC K. SIEGEL

June 23, 2006 — MEDICINES are too often portrayed as either life savers or killers - a polarization of our pills that serves neither science nor health care.

Thanks to two high-profile lawsuits, my patients are now asking me if Lipitor - the cholesterol-lowering drug - is still safe. With the suits claiming that Lipitor can cause brain and nerve damage, my old comeback - “I take the drug myself” - is no longer sufficient to calm fears. One patient tells me that I’m blindly ignoring the risks of serious side effects.

In fact, Lipitor, the country’s top-selling prescription drug, has been shown to prevent the progression of coronary plaques in patients with heart disease, and is likely to be as useful in patients who are at risk for heart attack and stroke from these same plaques.

The most potent drug in the class known as statins, Lipitor has been successfully administered to millions. In very rare cases, it can trigger a severe muscle breakdown known as rhabdomyalysis. It has never been proven to cause memory loss or nerve damage, and I and most other physicians believe it to be a safe and effective drug.

So why the worry? Part of the problem is the way the drug industry hypes its products, setting them up as some kind of panacea. But if it’s sold as a magic elixir, the discovery of any flaw rings alarm bells.

Not all drugs that are victims of the pendulum swing from panacea to panic are as famous or as successful as Lipitor. This month, an FDA safety panel also cancelled a study where 4,000 children were to receive the antibiotic Ketek, an effective treatment for bronchitis and sinus infections. Why stop the study? Ketek, a new drug, has been prescribed to over 5 million people over the past two years, but 12 have sustained liver failure (in four cases, fatally), while 23 others have suffered damaged livers.

Should Ketek be restricted, labeled with ominous warnings or taken off the market entirely? Not without much better evidence of danger. At a time when few new antibiotics are being developed, drug-resistant bacteria continue to emerge, drugs like Ketek are important tools.

Unfortunately, when the media and the lawyers target a drug, they overlook the fact that the side effects are rare, and/or alternative treatments more problematic. Sober statistics-based analysis gets tossed aside. The drug-maker’s stock price and the number of prescriptions written plummet.

Decisions on drug safety should be based on real facts - a weighing of the real risks and benefits. Hysteria doesn’t belong in the drug-safety equation.

Dr. Marc K. Siegel is an internist at NYU Medical Center and associate professor at the NYU School of Medicine.