It is getting hard to figure out what to panic about first: Lead in lipstick? Cough medicines for kids? The statin surge among adolescents? How about MRSA in the boysroom? Can anyone guess which is associated with more deaths: MRSA or influenza? The answer is (b) influenza with 36000 deaths a year with another 11000 deaths linked to respiratory infections linked to flu as well. MRSA, 85-90 percent which are hospital related and found among the elderly who are immunocompromised is linked to about 17000 deaths. Handwashing anyone?

Get your Halloween chills the old fashion way. In the meantime read CMPI Sr. Fellow Mark Siegel's calming piece on MRSA in today's NY Post. It's before the article on Joe Girardi.

http://www.nypost.com/seven/10312007/postopinion/opedcolumnists/rx_for_the_superbug.htm

Scott Gottlieb tells it like it is via this column in today's edition of The Wall Street Journal ...

Attack of the Superbugs
By SCOTT GOTTLIEB

One of the early morning television news shows recently staged a live feed from a suburban Maryland high-school. It was the latest to close after a student contracted a virulent and drug-resistant bacterium called methicillin-resistant staphylococcus aureus, or MRSA. Pronounced "mersa," it's become this season's equivalent of shark attacks, every day bringing new, terrifying reports, although the dangers of such bacteria are hardly new.

Researchers working at the Centers for Disease Control and Prevention reported this month that nearly 19,000 Americans died in 2005 from MRSA, and about 95,000 were infected. Doctors have been reporting for years that MRSA was cropping up with alarming frequency. The same is true for other bacteria. In Rochester, N.Y., doctors recently reported nine children stricken with a strain of the bacteria that causes ear infections -- streptococcus pneumonia -- that was resistant to all 18 antibiotics commonly used to treat the condition.

The real news isn't that these bugs exist, but how woefully unprepared we are to deal with them. As we make progress in fields like cancer, we are taking a U-turn on bacteria. Despite advances in drug development, the bugs have increased their IQ nearly as fast as research, outwitting our medicines. Efforts have turned to preventing bacterial spread and clamping down on antibiotic prescribing.

There's no question that poor hospital hygiene, overuse -- and sometimes misuse -- of antibiotics contribute to educating bugs at our expense. But preventative efforts alone won't solve our bacterial challenges. What we need most are better diagnostic tests and new medicines.

This is high-stakes science, but the pipeline isn't promising. Since 1998, just 10 new antibiotics have been approved by the the Food and Drug Administration, only two of which work in fundamentally new ways. Only 13 new antibiotics are in development inside big drug companies, compared to an average of 60 more than a decade ago. Since leaving the FDA this year as its deputy commissioner, I've advised a few biopharma firms making antibiotics and the venture investors supporting them. Regrettably, however, many big drug makers have followed the lead of Eli Lilly, a pharmaceutical company that once pioneered antibiotics, only to exit the business entirely.

The problem? There's not a lot of payoff for developing drugs aimed at infections. First, they last only days, or at most weeks, limiting sales. And the better the drug, the more likely doctors and hospitals are to keep it on the shelf as a last resort. Most hospitals require that doctors get special approval to prescribe the best new antibiotics. In that regard, what's good for public health isn't necessarily good for antibiotic development.

Capricious regulation is another problem, adding to uncertainty and, in turn, the cost of development. For drugs targeted to many common bacterial ailments, the FDA historically required so-called non-inferiority trials. This meant a new antibiotic needed to prove it was generally no worse than existing treatments in order to win regulatory approval. Otherwise, conducting trials to prove a new antibiotic was better than a sugar-pill placebo -- or superior to existing drugs -- would require huge trials and, in some cases, was simply unethical if it meant asking patients with potentially serious infections to risk treatment by placebo.

That changed just last year when a handful of FDA reviewers became miffed that companies would get drugs approved through these non-inferiority trials without proving the new drugs were better than older medicines, and then market the new drugs for broad upper respiratory indications. The reviewers brought their complaints to Congress, which has since leaned on the FDA, at one point asking the Government Accountability Office -- staffed with lawyers and policy analysts -- to opine on the nuanced scientific question of non-inferiority trial design. The political intrigue has pushed the FDA to raise its approval bar in some areas, jettisoning the non-inferiority approach for some ailments while leaving a mess of uncertainty for many others.

So how do we surmount these obstacles to get the drugs and diagnostic tests we need to stay ahead of aggressive bacteria like MRSA?

First, we need to recognize that developing drugs aimed at super bugs is not an ordinary pharmaceutical business, and requires unique incentives. If public-health policies compel doctors to hold the best new antibiotics in reserve, we need to compensate with incentives for developing those niche drugs.

One way would be to clarify the rules under the 1983 Orphan Drug Act to include drugs that target resistant bugs. That law provides special incentives for drugs that treat rare diseases, including patent protections and streamlined regulatory review. The FDA needs to create better opportunities for companies to target not only conditions -- such as pneumonia or skin infection -- but also specific bacteria, like multi-drug resistant staph.

The FDA's guidance on other aspects of antibiotic drug development is similarly murky due, in part, to fluid standards. Congress recently had to write into law a demand that the FDA produce guidance on antibiotics for acute exacerbations of chronic bronchitis and acute bacterial sinusitis (finally released yesterday). Merely issuing documents doesn't guarantee clarity, and one of the FDA's recent documents on an aspect of antibiotic development ran several pages, saying little.

The FDA should collaborate with the Infectious Disease Society of America (IDSA) to develop meaningful guidelines that provide clear pathways to new drug development. The IDSA's credible voice could also buttress the FDA against the maneuvering of a handful of staff who take their views to politicians when they lose internal scientific debates.

Finally, we badly need better tools for rapidly detecting resistant infections in blood, even screens for bacterial genes. Today it can sometimes take days to discover that a patient is infected with a resistant bug. If there were better diagnostics -- similar to the "rapid" strep test -- bacterial infections could be distinguished early and doctors could treat patients with confidence. Drug companies could also more easily develop drugs targeted to specific bugs, conducting clinical studies aimed at specific pathogens, and making sure the right patients got the right drug early in the course of their illness, when drugs can make the most difference.

But the diagnostics business has been a lower-margin affair for many years, steering product developers into other fields. There are complicated reasons for this, but Medicare has systematically tried to drive down prices for diagnostic tests, often refusing to pay for new tests altogether. In turn, the big companies that make the tests committed a fundamental mistake early on, by adopting a strategy of charging lower prices for the throw-away test kits and premium prices for the platforms they run on -- a reverse of the old razor-blade model.

The big diagnostic companies figured they would make most of their money off the platforms. They're regretting that now. The strategy may have worked if they had continued to innovate, but now many of the best ideas for new tests are coming out of small firms that have little ability to sell their own big platforms, and a hard time premium pricing diagnostic tests in a market conditioned by the big firms to expect cheap razor blades.

Most existing antibiotics are as old as the earth, screened out of nature where they resided, doing battle with bugs for centuries. We need to accelerate this evolution in our laboratories. Public policy mistakes are partly to blame for creating this inhospitable environment for new development, and it will take a concerted effort to improve it. The only sure way to stay ahead of bacterial evolution is by escalating this arms race.

Dr. Gottlieb, a practicing physician and resident fellow at the American Enterprise Institute, was previously a Deputy Commissioner of the Food and Drug Administration.

Seems as though John Edwards must have been absent during the law school lecture on the US Constitution – specifically the part that relates to Freedom of Speech. In a speech the other day he called for, among other things, mandatory FDA approval before drug companies launch major ad campaigns.

Must have tested well in focus groups.

Similar bloviation during debate over FDA reform was quickly dismissed because of some more educated members of Congress familiarity with the First Amendment.

But, as we all know, facts and reality have very little to do with Presidential campaigns.

Further proof of this was Senator Edwards’ remark that drug advertising misleads patients and drives up health care costs.

Neither of these statements is true. As to “misleads patients,” what DTC does do is send patients (aka – consumers) into the offices of their physicians were they have important dialogue about their health. In many of these DTC-initiated visits a previously undiagnosed condition is diagnosed. And earlier diagnosis and treatment decreases health care costs.

As to whether or not DTC increases the cost of medicines, consider this – when you compare the prices of medicines within a given therapeutic category along with their spending on DTC, there is no correlation. Also, when you compare the amount of money spent on DTC versus research and development – they don’t even have the same number of zeroes.

According to Edwards, "The excessive costs of prescription drugs are straining family budgets and contributing to runaway health care costs.”

Another nice sound bite that belies the truth. Only 11.5% of the US health care spend is on pharmaceuticals – the same pharmaceuticals that keep people out of the hospital (over 30% of our health care expense). Proper medication keeps people healthy, at work, and paying taxes.

But that’s not as popular a sound bite in Iowa and New Hampshire (where Senator Edwards shared his comments with primary voters).

"With such aggressive and often misleading drug company marketing, it's too easy for advertising -- instead of doctors or proven results -- to influence families' health decisions," Edwards' campaign quoted him as saying.

Often misleading? Really? Does he even know about “fair balance” and “adequate provision?” Does he even know about the research that shows how few people actually even try to read various brief summaries?

Probably not. And that would explain why the “Edwards Plan” also calls for drug advertising to disclose more information about side effects and comparisons of drugs against placebos and alternatives.

Someone should ask him about this during the next candidate debate. (And speaking of “comparisons,” someone should also ask him about his understanding of comparative effectiveness.)

Further, the Edwards plan would institute a two-year delay on consumer advertising of all new drugs.

So, not only do we not really need Freedom of Speech – we also don’t need new and timely information about new and timely medicines.

Gevalt.

Matt Herper and Robert Langreth have a good column about Lilly's hurry up and wait approach to releasing the results of a dosing study about prasugrel, which would not compete with but be an alternative to people who do not respond well to Plavix or aspirin.

Again, it's not the data so much as how it is presented to investors and the clinical community. The rules of the road have changed. People demand more data. And the genetic underpinnings that cause differences in drug response and dose response -- which is what at issue here -- are pretty much like open source software or operating systems.

I don't think anything nefarious is going on. If the science types have control of the process -- and Steve Paul who runs RD at Lilly is a straight shooter -- they are probably retooling and re-examining the data to see which dose works for which groups.

But that is not the end of the matter. Matt and Robert should know that Lilly is likely trying to figure how all this tailored treatment info pans out and whether or not -- in the safety uber alles environment -- even a drug that has diagnostic or gene-specific dosing limits ala warfarin could even get through the FDA these days.


Maybe Lilly is compiling a list of drug safety vigilantes it needs to hire as consultants to ensure they don't trash the drug to the trial attorneys and the media. Drug safety? More like a protection racket.

http://www.forbes.com/2007/10/25/pharmacuticals-prasugrel-lilly-biz-sci-cx_mh_1026lilly1.html?partner=alerts

Seems simple enough. Get rid of samples, pens, pizza. But then let's see just how much information about new medicines flow to doctors and whether that affects patients. Right now the claim that freebies adversely influence prescribing patterns and do not advance patient health is unsubstantiated. And who would decide who gets what information and how? The same group that supports government run comparative effectiveness trials? And the proposal to eliminate all private industry involvement in academic medicine will undermine medical progress. As if academic medicine would be free of bias, conflict, error and devious behavior if money was not involved. Right. See the piece from The Scientist below...

http://www.the-scientist.com/news/home/53709/

In the spirit of full and open dialogue, here are two letters-to-the-editor from today's on-line edition of the New York Times ...

Opinion

LETTERS

Testing New Drugs
Published: October 25, 2007

Re “A Test of Bad Health” (Op-Ed, Oct. 18):

To the Editor:

Peter Pitts’s criticism of the proposed Center for Comparative Effectiveness exemplifies the scare tactics used by the pharmaceutical industry to protect its interests.

While he cites one example of delayed drug approval in Britain, he doesn’t mention the many cases in which comparative effectiveness studies have fostered timely and appropriate decisions to adopt or not adopt new drugs and other medical advances.

The use of government-sponsored studies to inform drug coverage decisions by government agencies is not “an inherent conflict of interest,” but rather the judicious exercise of government resources to serve the public interest.

Sadly, the casualties of President Bush’s veto of the State Children’s Health Insurance Program bill include not only the millions of children left uninsured, but also the hundreds of millions of Americans and their doctors who need better information to make the best possible decisions about their health care.

Alan B. Cohen
Boston, Oct. 18, 2007
The writer is a professor of health policy and management and the executive director of the Boston University Health Policy Institute.

To the Editor:

Peter Pitts warns that a proposed Center for Comparative Effectiveness to test new drugs would be dangerous because “conducting these studies is so tricky, their findings are regularly overturned or modified by further research.” Yet he would have us accept the company’s clinical trials showing the drug to be safe and effective?

One wonders why it is so tricky for the government to do this research, yet so simple for his pharmaceutical financiers to do the same.

Kevin Carlsmith
Hamilton, N.Y., Oct. 18, 2007

After all, everyone's entitled to their opinion.

Who says sorry seems to be the hardest word? Here's a sample of some a Pete Stark's other gentle musings about those who differ with him on healthcare policy issues... From Jonathan Weisman of the Washington Post (get a look at the photo the WP selected for the article..)


2003: As Stark belittled House Ways and Means Chairman Bill Thomas (R-Calif.), then-Rep. Scott McInnis (R-Colo.) told him to "shut up."

"You think you are big enough to make me, you little wimp?" Stark taunted. "Come on. Come over here and make me, I dare you. You little fruitcake."

2001: At a Ways and Means subcommittee hearing on abstinence promotion, Stark referred to then-Rep. J.C. Watts (R-Okla.) as the "current Republican Conference chairman, whose children were all born out of wedlock."

1995: In a private meeting, Stark called then-Rep. Nancy L. Johnson (R-Conn.) a "whore for the insurance industries."

"He didn't call her a 'whore,' " defended Stark press secretary Caleb Marshall. "He called her a 'whore of the insurance industry.' "

1991: Stark singled out "Jewish colleagues" for blame for the Persian Gulf War, referring to then-Rep. Stephen Solarz (D-N.Y.) as "Field Marshal Solarz in the pro-Israel forces."

1990: Stark called then-Health and Human Services Secretary Louis Sullivan, who is African American, "as close to being a disgrace to his race as anyone I've ever seen."

http://www.washingtonpost.com/wp-dyn/content/article/2007/10/23/AR2007102302165.html

Gee, I wonder who leaked this to the WSJ...Let's see, when you don't have the science or the facts on your side, presenting the sort of observational data in public to defend your position that you derided as evidence in support of the safety of other drugs and when everyone else in the agency is pretty much responsible...my guess is David Graham and that it is part of a well-orchestrated effort. We know it's not the European Medicine Agency which just tighted prescribing data. Let's hope with better post market data we won't have this hysteria in the future. My guess is, with tort lawyers and web-based interest groups profiting from fear we will see more of this, not less.

http://online.wsj.com/article/SB119318921736669347.html?mod=health_home_stories

Here's the bottom line reason pediatricians love the decision to ban cough medicines: fewer 2 AM phone calls from parents about dosing, less anxiety about lawsuits...

Benjamin Brewer MD who blogs for the WSJ on medicine:

The dose provided some relief — the boy’s sniffles and cough abated long enough for the Brewers to get some shuteye. “I have found that the advice to hold off on a kid’s cold medicine is much easier to give than it is to heed,” Brewer writes.

The crackdown on cold medicines for kids may have an unintended benefit for the doctor. “With infant cold medications off the market, I won’t miss the parents calling in the middle of the night for recommendations on how much to use,” he writes. “I won’t miss meticulously documenting how many tenths of a milliliter I advised a person to give or the liability risks associated with my advice.”

Thanks for the dose of honesty doc.

I just wish the FDA experts were as freaked out about MRSA and diminishing antibiotics to treat them as they were about cough medicines. Ironically, the "safety uber alles" movement has made it likely kids will see fewer antibiotics for killer bugs or coughs. Reminds me of when I was a kid. It would make me feel a little bit better if Mickey Mantle were still batting clean up for the Yankees.

http://blogs.wsj.com/health/2007/10/23/a-taste-of-his-own-medicine/

For those who want to see Mantle's stats as opposed to the number of kids who died from infectious diseases in the 1960s...

http://www.baseball-reference.com/m/mantlmi01.shtml

Seichel. In Hebrew it means discretion and in Yiddish it means "common sense" or as Joseph Aaron puts it...good sense, street smarts, the kind of wisdom you don’t get from getting a Harvard diploma.

Seichel tells you what’s right and what’s smart better than any book or guide or intellectual.

Or any FDA panel.

Seichel tells you that when millions of parents over 40 years have used cough and cold medicines responsibly they have a better handle of their kids needs than the media seduced know it alls who gathered in Rockville.

Did any of them consider that, because of the ban, parents will simply water down or dose adult cough meds to help their kids stop coughing or sniffling? Or that they will turn to even less effective or untested "natural" remedies that may be even more dangerous?

No, because the panel and the American Academy of Pediatric were not guided by seichel but by the "safety uber alles" principles pushed by the trial lawyers (websites now coming to a computer near you) have pushed medicine past science and common and into the panic room.

The decisions we make out of fear and to eliminate risk completely will always lack common sense and reek of mob rule.