The Dumbing Down of Healthcare

04/07/2008 09:19 AM |

I have great respect for the work of John Wennberg and Elliot Fisher at Dartmouth. Their work has underscored that some clinical practices which are entrenched by tradition or local relationships between doctors and hospitals are not the most effective compared to others. But there is a bit of hubris creeping into their more recent analyses which presume that if we standardized care to cheapest providers of care to those who die within 2 years of a subjectively determined time we could save 20 percent of Medicare spending.

First, as a patient I would like to know which care is associated with not dying within the two year time frame. And as a methodological issue, the failure to compare cost of patients receiving the same care for the same disease without adjusting for severity of illness is a big one. Accordingly, recommending ways to reduce overuse of acute hospital care without knowing what works to improve outcomes -- not always a cut and dried answer -- is probably beyond the data delivered by the Dartmouth group.
http://www.dartmouthatlas.org/


Second, Wennberg and Fisher have also looked at gaps in providing effective care that contributes to longer life. If those gaps were filled it would cost more money. And if people lived longer they would ultimately wind up with a disease that could be expensive to treat. More people receiving better care, more preventive screenings, etc. all adds up. They should be more persistent in coupling that message with their other "magic bullet" solutions.

Finally, to claim that more choices lead to higher costs as an article in the WSJ suggested perhaps mistates what the Dartmouth group concludes. The Dartmouth Atlas suggests that regional variations in utilization have nothing to do with better outcomes. But in fact not even the Dartmouth folks presume to tell everyone what sets of practices would work in all situations. Genomic and clinical insights suggest that tailoring treatments and prevention to individual variations improves outcomes. So how could choice be bad?



http://online.wsj.com/article/SB120752201349093441.html  Read More & Comment...

TRIPS: The Light Fantastic

04/07/2008 07:13 AM |

I don’t know about you, but I get about 30+ e-mails a day from Jamie Love and his buddies telling me all about the public health benefits of compulsory licensing. If you buy the bunk, then you probably believe in the Easter Bunny. (Apologies to those of you who believe in the Easter Bunny.)

Nowhere has the Love-Line rhetoric been more omnipresent than at the recent session of the WHO’s Intergovernmental Governmental Working Group (IGWG).

Not that it was an even-playing field. The IGWG discussions were completely void of innovators -- with pharmaceutical researchers relegated to the sidelines. In their place were activists who are unwilling (and seemingly unable) to engage in any discussion that does not begin and end with removing systems of intellectual property (IP) protection for innovative medicines.

As with many of their ilk, these activists believe in freedom of speech – as long as what you say supports their position. Otherwise you’re a capitalist tool. Their grasp on the truth is questionable and, to their minds, the end justifies the means.

So it comes as no small relief that a comprehensive new study debunks the myth that TRIPS-related pharmaceutical patent protection is somehow contrary to enhancing the health of the developing world. The opposite is true – and truth speaks louder (if not more frequently) than rhetoric.

“Investments in Pharmaceuticals Before and After TRIPS: Property Rights and New Drug Development” (Authors: Margaret Kyle, assistant professor, London Business School and Anita M. McGahan, Professor, Rotman School of Management, University of Toronto) examines the impact of TRIPS on investments in pharmaceutical R&D – with important and significant implications to the ongoing discussions at IGWG, regarding the benefits IP brings to the effort to enhance health in developing and less-developed countries.

Some extracts:

“TRIPS was central in the development of foundational pharmaceutical capabilities in least-developed and developing countries.”

“TRIPS had a strong, consistent, and major impact on general and corporate investment at every phase of research on global disease.”

But all is not rosy:

“There appears to be a gap that prevents the immediate efficacy of TRIPS in promoting the introduction of new drugs on poverty diseases.”

They continue: “On the other hand, TRIPS has encouraged research on disease that are present but not dominant in least-developed and developed countries, such as cardiovascular diseases and cancers.”

And they conclude by saying, “This research suggests an opportunity to implement policies that are complementary to TRIPS for filling this gap to promote research on poverty diseases immediately.”

So let's move forward. Let's work together. Let's leave the rhetoric aside.

(And sorry about the Easter Bunny.)  Read More & Comment...

LiveSmart via Drugwonks

04/06/2008 03:47 PM |

Pleased to report that the LiveSmarter blog has named Drugwonks one of its 100 top Academic/Medical blogs -- and first in our category (Drugs/Medicine).

The full Top 100 list can be found at:

http://www.ondd.org/the-top-100-academic-medical-blogs/


And, as the man says, thank you for your support.  Read More & Comment...

Toasted Bagel. Coffee. And Preemption.

04/04/2008 03:22 PM |

My sources tell me that Sunday’s New York Times will feature a front-page feature on FDA preemption by Alex Berenson and Gardiner Harris. And, considering the authors, you know what that means – among other things much use of the “Z” word.

Certainly the piece will be fair and balanced -- as all pieces are in our national newspaper of record -- but whether or not adequate provision will be given to the facts remains to be seen.

To wit, a few pieces of information that may or may not make the final cut of the story.

When product manufacturers provide fraudulent information to FDA, or deliberately withhold information about safety problems associated with their products, preemption doesn’t offer them protection and they can and should be held accountable.

The problem is that the current liability system doesn’t reward lawyers who focus on these real public health concerns. Instead, the most experienced and well-financed law firms know that the biggest payouts regularly go to those who take advantage of the FDA’s best efforts to promote the safe and effective use of medications and medical technology. More and more often, these “mass tort” firms specialize in taking a new product warning label or withdrawal decision by the FDA, and view it as a signal to go forward with all guns blazing. Their bullets, unfortunately but not unpredictably, hit multiple innocent targets and result in a wounded American health care system.

As Dan Troy has written:

“Judgments concerning the need for and formulation of statements in drug labeling and advertising are squarely within FDA’s statutory authority and expertise, and they deserve deference from courts and juries applying state tort law. The agency carefully considers the scientific evidence relating to a proposed warning, as well as the public health consequences of including or omitting particular language from drug labeling or advertising. FDA should not have to act to safeguard its control over the label each time a plaintiff brings a state law action challenging the absence of a particular warning in drug labeling. Where FDA repeatedly has reviewed particular drug labeling and advertising content, state courts and juries should not second-guess the agency’s scientific determinations.

FDA’s legal authority over drug labeling and advertising is broad, and its expertise is unmatched. The agency’s decisions on the content of these communications deserve substantial deference from courts applying state tort law in product liability cases that challenge the adequacy of drug warnings.”

Amen.

It should also be noted that the FDA has consistently stood behind the concept of preemption through both Republican and Democratic administrations – so any mention of “the Bush FDA pushing preemption” is just bad reporting.

Recently, the 3rd U.S. Circuit Court of Appeals ruled that federal law bars a suit alleging false-advertising claims under state law because the U.S. Food and Drug Administration has "exclusive authority" to regulate prescription drug advertising.

"To allow generalized state consumer fraud laws to dictate the parameters of false and misleading advertising in the prescription drug context would pose an undue obstacle to both Congress' and the FDA's objectives in protecting the nation's prescription drug users," U.S. Circuit Judge D. Brooks Smith of the Western District of Pennsylvania, wrote in his 51-page opinion in Pennsylvania Employees Benefit Trust Fund, et al. v. Zeneca Inc.

Further, U.S. Solicitor General Paul Clement issues an opinion to the U.S. Supreme Court supporting federal preemption, saying that FDA-approved drug labeling preempts state law.

Specifically, Clement disagreed with the Vermont Supreme Court’s ruling that a patient could sue Wyeth over the labeling of its anti-nausea drug Phenergan (promethazine). In the case of Wyeth v. Diana Levine, Clement opined that the state court, “erroneously interpreted” the law by saying the FDA’s approval of a drug label is only a “first step.” He also noted that federal law prohibits a company from unilaterally changing the FDA-approved label.

Clement writes, “If manufacturers were free to make unilateral changes to labeling the day after the FDA’s approval, based on information that was previously available to the FDA, the approval process would be greatly undermined and the agency’s careful balance of risks and benefits thwarted.”

I don’t think it’s a stretch to predict that the Berenson/Harris piece will not be a ringing endorsement for the principle of FDA preemption. And if the Gray Lady follows precedent, there will be a same-day editorial supporting the general view of the article -- that FDA preemption should be struck down as a general principle because of, among other things, the evil pharmaceutical industry and an agency that is “in the pocket” of same.

Who does this help? Consumers? No. Trial lawyers? Yes. (And we all know that Alex Berenson has many of these folks on speed dial – and visa-versa.)

So on Sunday, brew your coffee, toast your bagel – and count how many times trials lawyers are quoted in the article.  Read More & Comment...

Mission ACCOMPLISHed or ALLHAT is Old Hat

04/04/2008 07:46 AM |

While everyone was posturing around the ENHANCE study another, perhaps more important piece of research was published without any fanfare about treatment of hypertension.

"New data from the Avoiding Cardiovascular Events in Combination Therapy in Patients Living with Systolic Hypertension (ACCOMPLISH) trial were presented today at the American College of Cardiology 2008 Scientific Sessions [1]. They showed that a single-tablet dual-mechanism therapy initiated in high-risk hypertensive patients significantly reduced the risk of morbidity and mortality by 20% compared with conventional therapy.

ACCOMPLISH, a major morbidity and mortality trial, compared the effects of two forms of antihypertensive combination therapies on major fatal and nonfatal cardiovascular events. It was stopped early because treatment with antihypertensive combination therapy — the angiotensin-converting enzyme (ACE) inhibitor benazepril plus the calcium-channel blocker amlodipine — was more effective than treatment with the ACE inhibitor plus diuretic."

As in more effective than a diuretic alone or a diuretic in combo with something else. As in ALLHAT, the foundation for Jerry Avorn's campaign to become FDA commissioner and the so-called gold standard of comparative effectiveness research....

"If you use the combination of a calcium-channel blocker with an ACE inhibitor, you get exquisite blood-pressure control," said Jamerson, who added that similar control was observed with the ACE inhibitor and diuretic. Despite the similar blood pressure, the combination with the calcium-channel blocker and ACE inhibitor reduced cardiovascular morbidity and mortality 20%.

During a press conference announcing the results, Jamerson told the media that the findings are "paradigm-shifting" and the data are a clear win with a clear message. He said the ACCOMPLISH findings challenge the guidelines, especially in terms of starting with a one-drug strategy and the use of diuretics in combination with ACE inhibitors."

This will be an acid test to see just how evidence-based people who are pulling the comparative effectiveness bandwagon really are....Will such studies be rejected if they are not conducted or approved as "kosher" by a Comparative Effectiveness Institute? Will patients have to wait months or years to get access to better or tailored therapies while a bunch of economists sit in judgment?

Science moves way too fast for such an institute to have any real relevance. There are better ways to produce better medical information....A look back without looking ahead means retreating into the past as disease advances...
http://www.medscape.com/viewarticle/572341  Read More & Comment...

Hard Pill To Swallow

04/04/2008 07:43 AM |

Here's my review of Melody Petersen's new book, "Our Daily Meds."
http://www.nypost.com/seven/03302008/postopinion/postopbooks/hard_pill_to_swallow_104120.htm?page=0


March 30, 2008 -- Melody Petersen has a drug problem. Not illicit ones, mind you, but prescription drugs. According to her new book "Our Daily Meds," the marketing of medicines has led people to swallow pills that do not work, that they do not really want or need, for diseases that they do not have. The "drug companies chain of influence is so complete that there are few people left to look objectively at the effects of their products on the nation's health or at the consequences of their power for society," she claims.

I don't know what Petersen means by "few" but she counts herself among this vanishing breed of the uninfluenced. Which raises a question - one of many - that Petersen fails to answer: If the chain of influence is "so complete" why is the image of drug companies as marketing machines so firmly etched on the American psyche?

Petersen claims slick marketing drives the sale of expensive and needless meds at the expense of cheaper treatments. Yet over the past three years drug spending has slowed and most new prescriptions are written for generic versions of brand medications.

It goes without saying that the pharmaceutical industry has done dumb and illegal things in an effort to increase sales. Yet Petersen is so intent on ascribing absolute power to drug companies to bamboozle doctors and patients that she never acknowledges the benefits of medicines. She complains that the "$2 billion that Iowans spent on prescriptions filled at pharmacies was approaching the $2.7 billion they spent at all the state's fast-food joints, restaurants and bars." Better liquor than Lipitor according to her.

Petersen asserts that companies focus on ways to "medicate consumers on a daily basis" at the expense of "cheap medicines that actually cure disease." She cites Glaxo's promotion of Zantac, the acid-blocker used to treat ulcers, even as two researchers in Australia were trying to prove that a bacterium, H. pylori, was the underlying cause and therefore could be treated with antibiotics.

What Petersen leaves out is the fact that the bacteria hypothesis was being tested in the late 1980s while Zantac and other drugs like it had been on the market since 1970, well before the infection route was explored. Meanwhile, Zantac was replacing surgery for the treatment of ulcers; a transformation Petersen apparently missed. When it became clear that antibiotics could cure many ulcers, guess who fought for and obtained approval for using such drugs for that purpose? Drug companies of course. And because of aggressive marketing and physician education, today antibiotic therapy is the standard treatment for ulcers.

She quotes Dr. Allen Roses, who helped run drug development at Glaxo, who noted, accurately, that "the vast majority of drugs - more than 90 percent - only work in 30 to 50 percent of the people" as if this were a deliberate act of omission on the part of drug companies. But she fails to quote Roses about his contention that in the future companies will develop personalized medicines that work well for smaller groups of patients based on genetic variations. Most drugs are being rejected by the FDA because they do not work in most people. So why would companies want to persist in that path?

In the same vein, she criticizes companies for "introducing dozens of copycat medicines that were barely distinguishable from one another." Yet, such "me-too" drugs allow the 50 percent of people for whom one medicine won't work to get something that does. So which is it? Are drug companies evil for developing medicines that are not targeted in the first place or evil for marketing many variations of the same medicine to address the hit or miss nature of prescribing?

Petersen's prescription for better health is simple: End the marketing and the need - along with the diseases - will disappear. Childhood depression and suicide? A trumped up myth the screening for which does more harm than good. She quotes a doctor who says: "Kids need to be loved and supported and they'll turn out OK."

Except that in recent years, child suicides have increased as prescribing of antidepressants has declined, reversing a decade of fewer deaths. I'm wondering if Petersen and others who share her view will accept much blame for this tragedy as they have assigned to the big bad drug companies. I doubt it. Self-righteousness is a disease for which there is only one cure: ignoring the source.

Our Daily Meds

How the Pharmaceutical Companies Transformed Themselves into Slick Marketing Machines and Hooked the Nation on Prescription Drugs

by Melody Petersen

Farrar, Strauss & Giroux  Read More & Comment...

Medicaid Grace Period

04/03/2008 06:39 AM |

Grace, that is, as in Grace-Marie Turner, a member of the President's Medicaid Commission and herself President of the Galen Institute.

Yesterday, in front of the House Energy and Commerce Committee's Subcommittee on Health, Grace-Marie presented cogent and important testimony on the Protecting the Medicaid Safety Net Act of 2008 (H.R. 5613).

She made many valid, technically savvy comments and recommendations, but it was her conclusion that should strike at the best bipartisan angels of our legislative nature.

"The president and CEO of the Mayo Clinic, Dr. Denis Cortese, spoke in Washington recently about health reform. Mayo is renowned worldwide for its expertise in medical diagnosis, and Dr. Cortese drew on these capabilities to help policymakers think more strategically about health reform. He said in medical care and in public policy, change must focus on putting the needs of the patient first. Patients want personal, high-value health care, and we need to provide better incentives for programs and providers to provide that care.

Micromanagement of the system through rules and regulations is not putting the patient first. Instead, we need to focus on new financial incentives to encourage patients, providers, program administrators, and the states to make sure they are getting the best value in health spending. Rethinking Medicaid’s financial structure, I believe, is needed.

Our commission heard many, many witnesses testify that patients want a medical home. The worst place to get routine medical care is in a crowded hospital emergency room, but too many Medicaid recipients have no other choice. Having a medical home would mean that someone is working on their behalf to coordinate care. Medicaid doesn’t support the kind of coordination that would lead to better care and more efficient spending.

After hearing hours and hours of testimony during my service on the Medicaid Commission, I believe we must begin the process of transforming this fragmented, procedure-oriented program to one that is focused on coordinated care, results, and outcomes. Quality of care for Medicaid recipients will be improved when health care providers are responding to patients’ needs and not to bureaucratic program rules and regulations.

For Medicaid to become more patient-focused and to more effectively meet the distinctive needs of populations with different needs, Medicaid programs must begin funding health care in a new way. Achieving better quality of care is integrally connected to creating new incentives to achieve better outcomes. This means that new funding mechanisms should be tied to the success of providers and health plans in coordinating patient care, gathering sharable information on the patient’s medical care, and giving patients more information and responsibility to be partners in managing their health.

Focusing on these goals and on putting patients first would assure taxpayers, states, and most importantly, patients, that the system is supporting quality care."

Words well put -- and worth heeding.

Here's a link to Grace-Marie's complete testimony:

Download file

And if you want to consider yourself in the know, my suggestion is this -- read it.  Read More & Comment...

Iguard my Drug Safety, Do You?

04/02/2008 01:39 PM |

Pharmalot blogs on the Consumer's Union report that one out of six people have had a bad enough reaction from a drug that they went to the hospital.
http://www.pharmalot.com/
Which raises the question: are people and doctors taking enough responsibility for how they take their medicines? Another question: are companies doing enough to treat consumers of medicines as customers, resolving problems, addressing side effects on an individualized basis instead of behind a battalion of lawyers..

My guess is the answer is no. Therefore simply dialing up the FDA to complain about one own's sloppy behavior is no way to resolve the issue. A better way would be to get patients with similar meds, conditions and characteristics to report and share information about their experience with all drugs, OTC, prescription, supplements within a virtual community. Then that information can be scrubbed and reviewed for trends and safety signals.

Which is why CMPI is a proud sponsor of http://www.iguard.org the first patient created and patient centered source of information on how drugs are affecting people like you and me.

The Consumers Union recommendation is well intentioned but old school. The way and wave of the future is http://www.iguard.org  Read More & Comment...

Why Doctors Hate Big Pharma

04/02/2008 01:15 PM |

Peter Huber notes that new medicines replace what Lewis Thomas termed as half-way technology or palliative care and eliminates jobs and buildings along the way..

"Diagnosis used to be almost all doctor; now it's almost all lab--and the lab technicians rely on higher-caliber dipsticks, assays and reagents developed and mass-produced by the same teams of top-tier doctors, research hospitals and big drug companies.

When drugs get good enough, they displace hours of ineffectual (but remunerative) human monitoring and palliative care. Drugs displace doctors, nurses and hospital beds because they really work and because they often work long before bad chemistry morphs into clots, plaques, lumps and other symptoms that require scalpels and beds. In the first half of the 20th century almost all medically supplied gains in health and life expectancy came from germ-killing vaccines and antibiotics. All the important gains since have come from arrays of drugs that target clogged arteries, strokes, cancer and other diseases rooted in our own human chemistry. Human eyes can't see and human hands can't handle most of the things that make us sick--bacteria, viruses, white blood cells, antibodies, proteins, enzymes, fats and genes."

This is a variation of Lewis Thomas wrote over 30 years ago: "A multiplicity of new variants of antibiotics and chemotherapeutic agents has appeared on the market, but one would not expect that the rational use of this technology, even allowing for the high cost of development and marketing, would have proven to be anything like the previous cost of hospital care in the absence of such a technology..typhoid was a 12 to 16 week illness; meningitis often require several months of care through convalesence; these and other common infectious diseases can now be aborted promptly, within just a few days..."

Thomas concludes: If our society wishes to be rid of the diseases, fatal and non-fatal, that plague us the most, there is really little prospect of doing so by mounting a still larger healthcare system at still greater cost for delivering essentially today's kid of technology on a larger scale....The harvest of new information from the biological revolution of the past quarter century is just now coming in, and we can probably begin to figure out the mechanisms of major diseases which were black mysteries a few years back as accurately and profitably as was done for the infectious diseases earlier in the century."

In the 30 years or so since Thomas wrote that, his prediction has come to pass. We still have more to harvest however. And as Huber points out, to think we can do it without commercializing research reflects a hostility to capitalism and protectionism of the worst sort.

Read Full Article


  Read More & Comment...

Listening to the Infinite (Mind)

04/02/2008 05:04 AM |

Being on a program called "the Infinite Mind" is humbling -- especially when the host is Dr. Fred Goodwin -- and on NPR no less.

Here are the program notes:

In the wake of new high-profile violent acts by people taking anti-depressant medications, including the recent Northern Illinois University shootings, and new research on antidepressant medications and their possible link to "suicidality," we look at the science on the connection between antidepressants and violent behavior.

Is there a link between antidepressants and suicide?

The answer may surprise you.

Joining us are Nada Stotland, president-elect of the American Psychiatric Association; Peter Pitts, a former FDA official who participated in the administration’s labeling of antidepressants as dangerous; and Andrew Leuchter, Director of the Laboratory of Brain, Behavior, and Pharmacology and Senior Research Scientist at UCLA, who has studied how press coverage and public alarm about antidepressants affects the nation’s health and willingness to be treated for real, life threatening illnesses.

And here's a link to the actual program:

http://www.lcmedia.com/mind524.htm


In addition to the program, this link also provides some very good commentary on the topics of depression and SSRIs.  Read More & Comment...

Schering Stupidity

04/01/2008 10:30 AM |

Two wrongs don't make a right. So while Schering's behavior appears to mimic that of Steve Nissen and Atherogenics when it came to fiddling with imaging data or at least sitting on it, this is no way to win, earn, retain, build the trust of doctors and consumers in your products.

It won't be enough for Schering and Merck to launch a $5 million PR campaign on the product. This sullies the reputation of all other companies and calls into question the integrity of the conduct of clinical trials in general. Just as the blockbuster era is over, so too is the closed door approach to clinical trials at an end. The need for collaboration, transparency, sharing of data -- particularly about what doesn't work and for who -- is paramount. Further, we need to move beyond the "bet-the-farm" mentality where the fate and fortune of a drug hinges on the outcome of one large trial. ENHANCE was a study of the impact of a specific drug for a selective population. It raised more questions than it answered, as much of scientific research does. There are better ways to get at such information, which is what the Critical Path is all about.

I don't think Schering did anything wrong...it is likely given the advances in imaging technology and shifts in opinion about the reliability of intravascular scans (pro and con) an independent data monitoring board would have come to the same conclusion. But when faced with the complexities it should have handed it over to an independent panel. No one was thinking about the larger repercussions of not doing so. Or maybe they were and made the wrong choice. Now heads will roll and rightly so.  Read More & Comment...

Warfarin and Peace

04/01/2008 07:33 AM |

Have you seen the article by Darlene Elias and Eric Topol (European Journal of Human Genetics)?

The title says it all, "Warfarin Pharmacogenomics: A big step forward for individualized medicine: enlightened dosing of warfarin."

Here's a link:

http://www.nature.com/ejhg/journal/vaop/ncurrent/full/5201945a.html

They applaud advances in genetic testing ... and ask some tough questions:

"In the meantime, however, a real dilemma exists for treating physicians and patients taking warfarin. Who to test and how to manage? What dosing nomogram to use? The clinical availability of the genetic testing is limited but presumed soon to be expanding. How or will the genotyping be reimbursed, given these commercially available tests are quite expensive for both CYP2C9 and VKORC1. And should all this be coordinated centrally, since studies have shown that warfarin monitoring can be improved and INR is more frequently in range with the adverse event rates lower when a centralized anticoagulation service is used compared to usual individual physician care."

We must all face these and similar issues and commence our difficult journey down the Critical Path. The future of the public health demands no less.  Read More & Comment...

Lilly Has The Last Laugh on Prasugrel

03/31/2008 01:32 PM |

Remember the media assault on Eli Lilly for suspending it's study of prasugrel last year, assuming malfeasance, substandard results, etc? Let's roll the tape from Matt Herper's dark commentary entitled "Lilly's Scary Silence":

"It's hard to see how that could be any comfort to investors. As is often true, there is a big downside risk to investors ahead of the data release on Nov. 4. But investors should be equally concerned about whether or not Lilly is giving straight answers about its data. If these studies do bode badly for prasugrel, investors have a right to know now. If they don't, Lilly still needs to give a clearer explanation. If the company can't do that, the safest thing is probably to assume the worst and sell the stock."

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

Science doesn't just snap to the whims of investors and reporters...but in case anyone cares here's an update from http://www.fiercebiotech.com




Study Results Show Investigational Drug, Prasugrel, Cuts Risk of Stent-Related Clots by More than Half Versus Clopidogrel
March 29, 2008

Reductions seen as soon as three days and out to 450 days in patients who received either bare metal or drug-eluting stents
CHICAGO, March 29, 2008 /PRNewswire-FirstCall via COMTEX News Network/ -- The investigational antiplatelet drug prasugrel plus aspirin produced a marked and highly statistically significant reduction in the risk of coronary stent thrombosis (ST) - a major concern for physicians and patients with potentially fatal consequences - in patients who received a stent as compared to standard therapy with clopidogrel (Plavix®) plus aspirin (1.13 percent vs. 2.35 percent, p<0.0001), according to a stent analysis from the head-to-head TRITON-TIMI 38 trial.

The findings were presented today by Dr. Stephen Wiviott, an assistant professor of medicine at Harvard Medical School and investigator with the Thrombolysis in Myocardial Infarction (TIMI) Study Group, at the Society for Cardiovascular Angiography and Interventions Scientific Sessions with the American College of Cardiology's Innovation in Intervention: i2 Summit, in Chicago. In addition, the manuscript was simultaneously published online by the British medical journal, The Lancet.

In the TRITON-TIMI 38 trial, whose overall results were previously published, 12,844 of the 13,608 enrolled patients received at least one intracoronary stent. Of those patients, 6,461 received a bare metal stent (BMS), 5,743 patients received a drug-eluting stent (DES), and 640 patients received both BMS and DES at the time of enrollment. Stent thrombosis was a pre-defined secondary endpoint in the trial.

Prasugrel reduced the relative risk of coronary stent thrombosis (a new clot at the implanted stent site) over clopidogrel by 52 percent (1.13 percent vs. 2.35 percent, p<0.0001). In patients who received drug-eluting stents (DES), treatment with prasugrel reduced relative risk by 64 percent over clopidogrel (0.84 percent vs. 2.31 percent, p<0.0001), and by 48 percent in patients who received bare metal stents (BMS) (1.27 percent vs. 2.41 percent, p=0.0009).

In the analysis, prasugrel was consistent in reducing stent thrombosis, compared to clopidogrel, whether assessment occurred early or late (<30 days and greater than or equal to 30 days, out to 450 days, the median duration of therapy), regardless of the type of stent used (bare metal or drug-eluting), and regardless of which academic research consortium (ARC) definition of stent thrombosis was used - definite/confirmed stent thrombosis, definite/confirmed plus probable stent thrombosis, and definite/confirmed plus probable plus possible stent thrombosis. Definite/probable stent thrombosis was reduced by 59 percent in prasugrel-treated patients within 30 days of stent placement (0.64 percent vs. 1.56 percent, p<0.0001), and by 40 percent after 30 days (out to 450 days, 0.49 percent vs. 0.82 percent, p=0.03).

"Stent thrombosis is very serious, given the high risk of mortality. In TRITON, among 210 patients with definite or probable stent thrombosis, 186 (89 percent) either died or experienced an MI as a result of the event," said Francis Plat, M.D., vice president, clinical development, Daiichi Sankyo Company, Limited. "We were excited by the results of this study and the possibility that prasugrel may someday provide an alternative treatment for ACS patients undergoing PCI and receiving coronary stents."

A 19 percent reduction in risk was observed with prasugrel compared with clopidogrel among all patients receiving a stent (9.7 percent vs. 11.9 percent, p=0.0001) in TRITON's primary endpoint of cardiovascular death, non- fatal heart attack, or non-fatal stroke. A 20 percent relative reduction favoring prasugrel was observed in the primary endpoint in patients who received only a bare metal stent (10.0 percent vs. 12.2 percent, p=0.003), and in patients who received only a drug-eluting stent, results showed an 18 percent relative reduction in the primary endpoint favoring prasugrel (9.0 percent vs. 11.1 percent, p=0.019). Fatal stent thrombosis occurred in 18 (0.28 percent) patients treated with prasugrel and 29 (0.46 percent) patients treated with clopidogrel (p=0.10). Of note, of the 210 patients with stent thrombosis, 89 percent either died or had a myocardial infarction associated with the event.

The rate of major bleeding was higher in all patients receiving a stent treated with prasugrel vs. clopidogrel (2.4 percent vs. 1.9 percent, p=0.06). Major bleeding in both DES and BMS prasugrel-treated groups when compared to clopidogrel-treated patients was 3 percent vs. 2 percent (p=0.34 DES) and 2 percent vs. 2 percent (p=0.09 BMS).

In addition to a reduction in the primary endpoint (CV death, non-fatal heart attack, or non-fatal stroke), a significantly lower rate of the composite endpoint of cardiovascular death, heart attack or urgent target vessel revascularization (UTVR) was observed with prasugrel vs. clopidogrel for both bare metal stents (10 percent vs. 12 percent, p=0.009) and for drug- eluting stents (9 percent vs. 11 percent, p=0.004). A significant reduction was also seen in heart attack alone (8 percent vs. 10 percent, p=0.003, BMS and 7 percent vs. 9 percent, p=.006, DES). In DES-implanted patients, regardless of those receiving only sirolimus-eluting or paclitaxel-eluting stents, there was a similar magnitude of event reduction with prasugrel compared to clopidogrel.

For the entire cohort, sub-acute stent thrombosis (24 hours to 30 days) was 0.36 percent in prasugrel-treated patients vs. 1.19 percent in clopidogrel-treated patients (p<0.0001). DES-implanted patients had lower rates of stent thrombosis compared to BMS-implanted patients, and prasugrel was shown to significantly reduce stent thrombosis in DES-implanted patients within the first three days compared to clopidogrel (0.14 percent vs. 0.63 percent, p=0.003) as well as for thromboses that occurred >30 days following the DES implantation (0.42 percent vs. 0.91 percent, p=0.04).

"The reduction in risk seen in patients in this analysis treated with prasugrel over patients treated with clopidogrel is encouraging for high-risk patients with acute coronary syndrome being managed with PCI," said J. Anthony Ware, M.D., Lilly vice president for cardiovascular/acute care.  Read More & Comment...

Vapid Vytorin Coverage Part 2

03/31/2008 11:59 AM |

And speaking of vapid coverage, an accompanying article in the NEJM that claims the higher use of Vytorin in the US was due to DTC provides no evidence of cause and effect or association. Rather, it does put it's finger on the real reason: Canada health system delayed and restricted access:


"Vytorin has been available in the United States since July 2004 but is still not available on the Canadian market. The use of ezetimibe-containing products in the United States increased sharply with the introduction of Vytorin. Some U.S. clinicians may have adopted the combination cholesterol-lowering product to improve adherence to dual therapy, but this option was not available in Canada. Third, in Canada, publicly funded provincial drug formularies have been conservative in their coverage of ezetimibe. Two of the three provincial government-funded formularies that serve three provinces (Ontario, Quebec, and British Columbia), in which approximately 75% of Canada's population lives, list ezetimibe with prescribing criteria that limit its use to patients in whom the target level of LDL cholesterol has not been achieved with a statin and patients who cannot tolerate or have a contraindication to statins; a third formulary does not even list ezetimibe as a benefit, although it is currently under review. These formulary criteria appear to be consistent with guideline recommendations that favor medication classes for which data on outcomes are available. Public formulary listings often influence medication coverage in private Canadian drug plans.

Oh.

But watch how many media articles cite DTC as the culprit. This is typical of the the quality of the case against DTC.
http://content.nejm.org/cgi/content/full/NEJMsa0801461  Read More & Comment...

Vapid Vytorin Coverage

03/31/2008 11:35 AM |

It would great if, just once, coverage about clinical trials focused on the unpredictability of science and the inherent difficulty of designing "real world" studies of the effect of drugs that produce desired results, particularly a measurable reversal in biochemistry that contributes to death.

That will not happen with Vytorin, except in the breach. To be sure the original:" these findings plus future biologic and clinical evidence could confirm that the benefits of lowering LDL cholesterol may depend not only on "how low you go" but also on "how you get there."
http://content.nejm.org/cgi/content/full/NEJMe0801608


This is a point that Eric Topol has been making since the first wave of ENHANCE data was released. See Eric's video on his blog:
http://blogs.theheart.org/posts/temple-of-the-ldl-cholesterol

In the end, Vytorin use will fall but for the wrong reasons. Absent information about "how to get there" before prescribing, LDL treatment will still be hit or miss. That's all the ENHANCE study showed. We know that reducing LDL is important but we still lack targeted treatments.  Read More & Comment...

Doctor, Reveal Thyself

03/31/2008 07:49 AM |

As many in this country are calling for a ban on the sharing of physician prescribing data -- our regulatory cousins in the United Kingdom are moving aggressively in precisely the opposite direction.

According to a report in the Financial Times,

The government is considering making public the full details of 700m prescriptions issued by general practitioners each year.

Publication could provide valuable new statistics to help improve treatment, fight "postcode prescribing" and hold GPs more accountable.

The proposal is sensitive, however, following embarrassing losses of personal information by government agencies in recent months. Medical specialists warn that detailed prescription data could also threaten patient confidentiality and undermine existing research databases.

The aim was "to determine whether it would be possible to make practice-level prescribing data more accessible to the private sector", the government said in an answer to a recent parliamentary question.

Sue Sharpe, head of the Pharmaceutical Services Negotiating Committee, which represents pharmacists, said, "I have concerns about patient and prescriber confidentiality" if the data were released more widely. She also commented that it could also lead to "aggressive promotion of prescriptions" by drug companies.

Here's a link to the complete article:

http://www.ft.com/cms/s/0/dea53df6-feba-11dc-9e04-000077b07658.html?nclick_check=1

Same issues as here at home, but a completely antipodal policy design.  Read More & Comment...

The Virtual House Call

03/31/2008 07:27 AM |

Dr. Marc Siegel, a senior fellow at the Center for Medicine in the Public Interest, is a practicing internist, an Associate Professor at the New York University School of Medicine and a fellow in the Master Scholars Society at New York University. Dr. Siegel is also a columnist for The Los Angeles Times and a frequent contributor to the Washington Post, USA Today, Slate, and many other publications. He is the author of False Alarm; the Truth About the Epidemic of Fear (top 20 books of 2005 - Discover Magazine) and Bird Flu: Everything You Need to Know About the Next Pandemic. Dr. Siegel appears regularly on CNN, the NBC Today Show, and the Fox News Channel. Dr. Siegel was a contributor to the U.S. Senate Finance committee investigation of the 2001 bioterror crisis.

In his essay, "The Virtual House Call," Dr. Siegel discusses many of the challenges facing the 21st century physician in the United States. Here is a free sample (yes, we here at drugwonks are still giving away free samples) of his discourse:

"I have a litmus test to check on my humanity. I call it the virtual house call. It isn’t an actual house call but it relies on similar notions of inconvenience in order to help a patient. Rarely do we have time these days to travel to a patient’s home. We must extend ourselves beyond our offices and our blackberries in caring for our patients in order to become truly empowered as physicians. This extension of self is the virtual house call.
Here is my litmus test: Every day I leave my office for a cup of coffee when I get restless. The coffee shop is one block south of where I practice. I ask myself what I would do if one of my patients, on his or her way to see me, suddenly collapsed right outside that same coffee shop I frequent and called my office from his cell phone while gasping for air.

Would I instruct my nurse to call 911, or would I run the same block I always walked?

Would I at least show as much commitment to my patient as I show to my caffeine habit?


I’ve never had to face this particular litmus test, but I certainly hope I would pass it. And each time I pick up the phone to check in on one of my patient, I’m conscious of a similar kind of litmus test. As I listen over the phone to the telling sounds of fast breathing or nervous coughing, I make determinations that my nurse or secretary could never make. I try to remain available, to not set strict limits. I’m convinced that continuity of care makes me a better doctor.

Dr. Siegel's entire composition can be found at both at the top of this page and at http://www.cmpi.org under the "Report" heading. The larger paper is titled, "The Hazards of Harassing Doctors."  Read More & Comment...

Flooding the Safety Zone

03/28/2008 12:59 PM |

The FDA is ramping up it's effort to monitor the safety of drugs through its Early Alert and REMS program. It could be that the constant release of information on safety will do two things:

First neutralize the fear mongering and it's impact of people like Steve Nissen (more on him later) by getting ahead of the curve early and often. Second, get people and doctors to think more generally about the risks and benefits of medicines as well as their proper use. Finally, maybe it will prod companies and insurers to offer genetic tests to increase safer and more tailored dosing and drug selection right off the bat...

Genomas for instance is developing a genetic test to predict and compare an individual's risk of getting muscle pain among atorvastatin, simvastatin and rosuvastatin. I have used the protoype for my statin selection. http://www.genomas.net

I was pretty critical about the Early Alert program at first, regarding it as not being science based. But maybe (is it possible?) I was wrong. I think that flooding the safety zone with information is useful. It would be great as part of the Alerts to note that incidence of safety problems as a percentage of total scrips to put things into perspective. Along those lines, we encourage everyone who cares about the safety and impact of their meds to sign up for Iguard.org, a patient community that shares information about the benefits and side effects of their drugs. You can enroll at www.iguard.org  Read More & Comment...

Just what we need, an even Dentzer Health Affairs

03/28/2008 11:40 AM |

No, really.

Health Affairs has announced that the NewsHour's Susan Dentzer will become the journal’s new editor-in-chief on May 1, 2008.

“It’s a great honor to be taking the reins at Health Affairs after John Iglehart and Jamie Robinson have done so much to make it the preeminent health policy journal of our time,” Dentzer said. “I’m delighted to become part of Project HOPE, and I look forward to working with the journal’s talented staff to continue to bring the best thinking and writing to bear on the top domestic and global health issues confronting us all.

Dentzer also serves on the Kaiser Commission on the Future of Medicaid and the Uninsured, and she is a member of the national advisory committee for the Robert Wood Johnson Foundation’s Investigator Awards in Health Policy Research. From 1993 to 2004, Dentzer was a member of the board of trustees for her alma mater, Dartmouth College, and she chaired the board from 2001 through 2004. As a Nieman Fellow at Harvard University in 1986 and 1987, Dentzer studied political economy, health economics, and business at the John F. Kennedy School of Government, Harvard Business School, and the Harvard School of Public Health.

Good luck Susan.  Read More & Comment...

A new FDA story? Fill in the blanks.

03/28/2008 08:21 AM |

Why even bother having an FDA reporter when writing an FDA “expose” story is as easy as, well, Mad Libs.

New Report by (proper noun) Accuses FDA of (adjective) Oversight

Today (adjective) Citizens for (adjective) Health, a not-for-profit organization, released a (adjective) meta-analysis that (adverb) concludes the FDA, “is in the (noun) of (adjective) Pharma.”

“Our research of (number) concerned (plural noun) points (adverb) to an agency that has once again (verb past tense) the American public. It’s a (adjective) indication that the FDA places (noun) over (noun) and cannot be trusted to (verb) or (verb) – and certainly not (verb) in the public interest,” said the author’s report Dr. Sidney (type of animal).

“I find this new report both (adjective) and (adjective) – but (adverb) not (adjective),” commented Representative Henry (proper name).” “And I intend to hold televised (plural noun) on the matter.”

“This is just another (adjective) example of the FDA’s lack of (adjective) (noun), added Dr. Steven (name of automobile company). If I were the FDA Commissioner this (adjective) circumstance would never have occurred.”

In an embargoed editorial, the New (place name) Journal of Medicine opined that the (adjective) problem “is caused by the Prescription (noun) User-Fee Act and made even (adjective) by the agency’s continued (verb) of direct to (noun) advertising.” The editorial also points to the need for (adjective) importation of prescription (plural noun) from (name of country).

Supporting this notion, the AAR(letter) added that (adverb) high (plural noun) for drugs are a result of the (type of shrub) Administration's (adjective) program known as Part (letter) and supports (adjective) government (verb).

The FDA had (adjective) comment.  Read More & Comment...