If it’s Tuesday it must be a single nucleotide polymorphism

09/03/2008 12:00 PM |

Scientists have shown that they can use genomic analysis to pinpoint a person's geographical origins to within just a few hundred kilometers. Besides offering possibilities for the testing of genetic ancestry, the research could also have important implications for understanding the role of genes in complex diseases and other genomic-based health studies.

By plotting the differences between genetic variations of 3,000 Europeans in a two-dimensional grid, the researchers were able to reveal a pattern that looks remarkably like Europe. The scientists included researchers from CornellUniversity; the University of California, Los Angeles (UCLA); the University of Chicago; and the University of Lausanne, in Switzerland. The findings appear in this week's issue of Nature.

Here’s the full story. 

Fortunately the Critical Path does not require a visa -- but it does require funding -- now!

  Read More & Comment...

A New Drugwonks Voice

09/02/2008 02:55 PM |

As you can see from the blog entry “What Depression, Measles and Sir Isaac Newton have in common”, there’s a new voice on drugwonks – Dr. Tim Franson.

Recently retired after 22 years of service at Eli Lilly & Company (most recently as Vice President for Global Regulatory Affairs), Tim was one of the original architects of PDUFA.  He was also one of the first people the FDA recruited to discuss the nascent concept of the Critical Path.  He loved the idea but also helped to identify some of the problems.

Tim is a guy who, as the old Jewish joke goes, "knows where the rocks are."

His regulatory knowledge is nonpareil and his optimism is contagious.

It is therefore, with great honor and excitement, that we announce that Dr. Franson has joined the Center for Medicine in the Public Interest (the public policy home of drugwonks.com) as a senior fellow.

Among his many achievements, Tim has served on Drake University's Task Force on the College of Pharmacy and Health Sciences and is currently a member of the College of Pharmacy Dean's Advisory Board for Auburn University. Dr. Franson has authored over 50 articles and one text in the fields of infectious disease, epidemiology, pharmacoeconomics, and antibiotic utilization. He is board certified in Internal Medicine and Infectious Diseases.

We welcome his compassion, intelligence and commitment to the public health.

  Read More & Comment...

Statin Insanity

09/02/2008 02:21 PM |

At what point does the persistence in ignoring science and replacing it with conjecture become an alternative reality? Read the Alex Berensen article on Vytorin in yesterday's NY Times:

"When the Food and Drug Administration approved a new type of cholesterol-lowering medicine in 2002, it did so on the basis of a handful of clinical trials covering a total of 3,900 patients. None of the patients took the medicine for more than 12 weeks, and the trials offered no evidence that it had reduced heart attacks or cardiovascular disease, the goal of any cholesterol drug."

Read New York Times article

Neither did any of the other clinical trials for any of the other statins.... So does that mean statins have not reduced heart attacks or CV disease? And PS, the study also showed that there was no risk of cancer, but you don't find that out until the end of the story. And in any event, not one story has investigated the complex relationship between lipid levels and cancer which has confounded and confused researchers for decades. Check out:

Integr Cancer Ther. 2008 Mar;7(1):33-41

Read more here

Berensen then shifts to the Vytorin post market studies....which are focused on specific groups of patients, high risk groups that are genetically at risk for athersclerosis, aortic stenosis, etc.

The researchers in the SEAS study observe:

"The combination of simvastatin and ezetimibe resulted in an average reduction in LDL cholesterol of at least 50%, as compared with placebo. Despite this favorable effect over a minimum period of 4 years, there was no overall effect on aortic-valve stenosis and no significant overall effect on the composite primary outcome. The lack of any effect on the progression of aortic stenosis as seen on echocardiography supports the conclusion that the lack of effect on clinical valve-related events was real and not due to a lack of statistical power. The finding of increased numbers of incident and fatal cancers in the simvastatin–ezetimibe group, as compared with the placebo group, was unexpected and requires further exploration in trials of simvastatin and ezetimibe.

The lack of effect on aortic-valve stenosis is in agreement with the findings of the smaller Scottish Aortic Stenosis and Lipid Lowering Trial, Impact on Regression (SALTIRE) study, in which atorvastatin was used.³⁴ The results of the Rosuvastatin Affecting Aortic Valve Endothelium (RAAVE) study (ClinicalTrials.gov number, NCT00114491 [ClinicalTrials.gov] ) indicated a favorable effect on aortic stenosis, but the study had a nonrandomized and open-label design, with comparisons of various categories of patients with aortic stenosis.³⁹

Our study population did not represent all patients with aortic-valve stenosis, since high-risk patients with severe hyperlipidemia requiring active lipid-lowering treatment, known atherosclerotic disease, or diabetes mellitus were not included in order to allow for placebo treatment. This factor may explain the relatively low rate of progression of aortic-valve stenosis in our study, as compared with that in other studies."

http://content.nejm.org/cgi/content/full/NEJMoa0804602?query=TOC

So Berensen, Nissen and Furberg (see below) ignore the fact that Lipitor also failed to reverse aortic stenosis. Perhaps Lipitor should be removed from the market too?

Here's Nissen, who by the way received money from Pfizer but not from Merck or Schering Plough

“The F.D.A. set the bar too low on the initial approval,” said Dr. Steven Nissen, chairman of cardiology at the Cleveland Clinic. “It would have been a lot better if the agency had said, ‘Show us that you do more than lower LDL a little bit, show us evidence of effectiveness.’ ”

Further, when the F.D.A. approved Zetia, several statins were already on the market, giving patients other options to lower their cholesterol. So the agency’s decision to approve Zetia without requiring larger trials is especially puzzling, Dr. Nissen said.

Lower LDL a little bit?

"The combination of simvastatin and ezetimibe resulted in an average reduction in LDL cholesterol of at least 50%, as compared with placebo. "

How about lying a littlle bit?

Now of course a more measured and targeted reassessment of the LDL heart disease relationship does exist. It is ignored by Nissen (who has never done any basic or NIH funded research on CV disease and only does research when he can make money conducting clinical trials) and pursued by Eric Topol at Scripps Genomic Health:

http://content.onlinejacc.org/cgi/content/abstract/52/5/378

Topol is working on gene-based trials to develop new drugs and diagnostics to treat people at high risk of serious heart diseases in studies that actually measure disease progression.

But Topol, who did the heavy lifting on the Vioxx safety problem, only to be shoved aside by a media hungry Nissen, is too busy doing real science in the area of biomarkers. Unfortunately, the folks on the NY Time speed dial are bio-Luddites who prescribe longer, larger (wishful thinking on their part?) clinical trials for every new drug using whatever media trumped up danger de jour to justify this outmoded position:

'Dr. Curt D. Furberg, an epidemiologist and drug safety expert at Wake Forest University, said that before approving drugs the F.D.A. should require that drug companies conduct large trials on whether they reduce death and disease, except in rare cases where no alternatives exist. If the agency approves drugs without such data, that fact should be noted prominently on a drug’s label, Dr. Furberg said.

What he and others continue to willfully overlook is that the studies in question are designed to reduce particular types of heart disease in small groups of patients and when they miss the endpoint claim the drugs don't work at all, and use that as an argument for larger, longer trials for safety and effectiveness. Conjecture and opinion replaces solid science. Unless science moves faster to occupy the space the Bio-Luddites occupy on the Web, traditional scientific institutions and science-based approaches will continue to be under attack by the ignorant and angry elite.
  Read More & Comment...

What Depression, Measles and Sir Isaac Newton have in common

09/02/2008 02:05 PM |

On the surface, the disease states of depression and measles could not be more dissimilar. Measles, a viral infection usually afflicting children at an early age, is typically an acute, self- limited disorder with a striking skin rash easily recognized by trained health professionals, and effectively prevented by insidious conditions with periodic worsening which impact all ages   (though most frequent in adult females) which have no visible signs on physical examination and are not amenable to primary prevention.

What these two medical entities share are the risk of serious complications if not properly managed - and their plight in the health policy arena as byproducts of the "law of unintended consequences".

As a result of concerns about alleged overtreatment of depression  in adolescents and a suspected risk of suicidal ideation related to  therapy - fueled by congressional hearings and media attention, with resultant restrictive labeling additions by FDA several years ago - antidepressant therapy in this population has decreased.  Recent surveillance studies indicate that for the first time in a decade, the rate of adolescent suicide attempts has risen … whether this potential temporal relationship of "reduced use-to-increased suicide attempts" is valid does require more careful study to be validated, but it is tempting to speculate that some cause and effect link may be present.

Likewise, accusations of childhood vaccines (notably those containing mercurial preservatives) being associated with causing autism have frequently surfaced over the past few years. While  extensive studies by WHO and other authorities have found no evidence of vaccines being associated with autism, this concern continues to be highlighted by very vocal congressional and media sources -- and seemingly has created a "parental flinch" resulting  in the reduced prevalence of childhood vaccine use in some communities. In the past week, reports have come to light regarding an increased incidence of measles cases in the US and elsewhere compared to previous years - a distressing development in the eyes of those who remember the devastating complications which occurred  associated with measles outbreaks in years past. Cause and effect?

 In both situations, there is no question that the actions of those in Congress and the media were well-intentioned and taken based on their perspective of drug/vaccine safety issues being a priority concern.

However, as Sir Isaac Newton correctly observed centuries ago, "For every action, there is an equal but opposite reaction.” An undue focus on safety concerns, to the exclusion of a broader consideration of benefit-risk tradeoffs is fraught with disastrous, unintended consequences. Did the potential benefits of overall vaccine and antidepressant use get equal consideration in the conduct of these policy debates and decisions? Were voices raised about the importance of looking at long term as well as immediate impact of deliberations founded on "safety in isolation"? If so, those kind of tempered thoughts were not reflected in the accounts reaching the general public, which certainly can provide an incomplete, misleading basis for parents considering the upsides vs. risks for medical interventions proposed for their children.

The public health would be better served by policy decisions in which [1] no decisions are made based on safety alone, with a reinforcement of thoughtful benefit-risk assessments being the platinum yardstick (as they are done at the bedside of any patient) and [2] decisions are coupled with appropriate follow-up monitoring to ensure that unintended consequences do not surface as a result of such recommendations - and if such do occur, to promptly revisit such matters using careful reconsideration, with corrective actions as warranted (just as physicians do in managing a patient's conditions over time). Such approaches would not diminish the attention given to new safety findings, but would encourage more balanced actions. Our vision skills are best when employing both eyes, and monocular outlooks on life often lead to blind spots -- our vision of health policy deserves similar insight.

During my medical career, I frequently heard sage faculty admonish trainees to understand their limitations and not to fall into the trap of "doctors playing God" -- the converse also holds true, for when influential policy gods play doctor, power trumps knowledge … in both such scenarios, accountability is lost and Newton's Third Law cannot be appealed. Kids deserve better.

  Read More & Comment...

The Pied Piper Effect

09/02/2008 12:34 PM |

A new study out of Harvard debunks the canard that DTC advertising causes a “Pied Piper” effect of patients marching en masse to their physicians demanding drugs they don’t need.

Reuters reports that, “Expensive advertising of prescription drugs directly to consumers may do little to encourage sales, U.S. and Canadian researchers reported on Monday.”

According to the report, even though companies spent an estimated $3 billion in 2005 on such ads in the United States, they did not appear to result in more prescriptions.

"People tend to think that if direct-to-consumer advertising wasn't effective, pharma wouldn't be doing it," HarvardMedicalSchool's Stephen Soumerai said in a statement. "But as it turns out, decisions to market directly to consumers are based on scant data."

The nonprofit Kaiser Family Foundation has come to similar conclusions in reports on direct-to-consumer ads.

In an April report the foundation found that 91 percent of adults surveyed had seen or heard advertisements for prescription drugs, but just one-third spoke to a doctor about a drug they saw advertised, and 54 percent of them got a prescription for a different drug.

Among doctors, 76 percent said they sometimes recommend a different prescription drug to a patient who mentions a drug ad and 5 percent said they frequently gave patients the drug.

Here is the complete Reuters story.

Will this study stop the Congressional Pied Pipers who keep piping up about the dangers of DTC? 

Stay tuned.

  Read More & Comment...

Patients are a virtue

09/02/2008 12:19 PM |

From today's edition of the Wall Street Journal:

Pfizer Drops Celebrity Pitch in New Lipitor Spots

 
As Generics Catch Up, Dr. Jarvik Is Jettisoned
From Heart-Drug Ads

By JON KAMP

Pfizer is set to resume promotion of its blockbuster heart drug Lipitor on television -- this time without a celebrity endorsement or expert advice -- after a half-year hiatus following claims of misleading advertisements featuring Robert Jarvik, the inventor of an artificial heart.

The new television ad, set to debut Tuesday, features a testimonial from heart-attack survivor John Erlendson, a 58-year-old California talent agent. He didn't take a cholesterol-fighting drug before his heart attack last year despite a history of high cholesterol, and his ad urges people in similar situations to be more proactive.

In other words, they should talk to their doctors about Lipitor. The new campaign comes amid pressure on Pfizer's marquee drug from generic competition, and it follows criticism that prior Lipitor commercials featuring Dr. Jarvik were misleading. The New York-based company pulled the Jarvik ads in February amid criticism, and attention from a U.S. House committee, linked to the fact he isn't a practicing physician.

This time around, Pfizer felt that using an average guy, someone with a story similar to that of many other baby boomers, struck the right chord.

"When we did testing with consumers, what we found out was John really resonated with them," said Jim Sage, senior director and leader of the Lipitor marketing team at Pfizer.

Mr. Sage declined to say how much the drug company is spending on the new campaign but said it will have a wide presence on TV and in print. "This ad is going to run for a while on a national basis," he said.

Lipitor, the world's best-selling prescription drug, is a so-called statin drug that is typically taken once daily to block an enzyme in the liver that helps make cholesterol. The U.S. Food and Drug Administration approved Lipitor 12 years ago.

The drug had sales of $12.7 billion in 2007, a 2% decline from the prior year. Sales through the first half of 2008 were up 1%, with a strong overseas showing bolstered by the weak dollar.

Lipitor is feeling heat from health plans promoting the use of cheaper, generic versions of other cholesterol drugs. It stands to lose protection against generic copies in the U.S. in 2011, and has been facing a tough market without a big ad campaign for most of the year.

The new spot is visually similar to some of the Jarvik ads, in that it shows Mr. Erlendson in an outdoorsy setting, biking and picnicking by the water with his wife and son -- a notable ad with Mr. Jarvik showed a body double rowing a racing scull across a lake. But the new ad takes a different approach, relying on its star's experience rather than expertise, and his appeal for viewers to avoid his missteps.

"Talk about a wake-up call. I had a heart attack at 57," Mr. Erlendson says in the commercial's opening, in which he's filmed in close-up and black-and-white. "My doctor told me I should have been doing more for my high cholesterol. What was I thinking? But now I trust my heart to Lipitor." He had tried to tamp down his cholesterol with diet and exercise.

The commercial shifts to the color outdoor scenes -- while the drug's benefits and potential side effects are reviewed by a voice-over -- and closes with advice for viewers to discuss their risk and Pfizer's drug with their doctors.

The phrase "a Lipitor heart to heart" appears on screen near the beginning and end and will be a recurring theme in other ads.

While marking a departure from the Jarvik ads, which leaned on a figure with stature in matters of the heart, Lipitor's new pitch man is not a total outsider. The talent agent -- who will be paid a union scale rate -- said he learned of the ad campaign when news of Pfizer's search for a testimonial subject crossed his desk. They were looking for a heart-attack survivor who took Lipitor, and he knew one who fit the profile.

"I'm hoping my message can get out to people like myself," Mr. Erlendson said.

Future ads could follow the theme of the new spot and may feature other Lipitor users; Mr. Erlendson could also reprise his role.

  Read More & Comment...

The Scum Also Rises

09/01/2008 11:25 PM |

Why am I not surprised.... Just a matter of time before the Left began blaming the Down's syndrome condition of Governor Sarah Palin's son Trig on her being a bad mother...

http://michellemalkin.com/2008/08/31/palin-derangement-syndrome/
  Read More & Comment...

The Difference Between Good and Bad Post Market Pharma Analysis

08/29/2008 05:35 PM |

The good is today's article in the British Medical Journal that re-examines the association between use of antipsychotics in seniors and various forms of stroke.

The authors used a general practice research database which "contains information from over six million patients registered at over 400 general practice surgeries in the UK.¹¹ Continuous information is recorded for each patient, including a record of each consultation, any diagnoses made, all prescribed medicine, and basic demographic data. The geographical distribution and size of general practices represented in the database are largely representative of the population of England and Wales, and the individuals registered on the database are representative of the whole UK population in terms of age and sex.¹² The data held are rigorously checked and regularly audited and have been successfully used to conduct over 500 peer reviewed published studies. The information obtained from the database is entirely anonymous."

The authors were able to control for length of drug use, type of drug, and "measured the differential effects of typical and atypical antipsychotics among all patients and stratified by dementia status."

The most relevant results are here:

Any antipsychotic drug

Typical only

Atypical only

Patients with recorded dementia (n=1423)
No in group	1423	1208	85
Exposed v unexposed periods	3.50 (2.97 to 4.12)	3.26 (2.73 to 3.89)	5.86 (3.01 to 11.38)
Days after treatment:
1-35	4.03 (3.34 to 4.87)	3.74 (3.05 to 4.59)	5.70 (2.50 to 12.98)
36-70	3.04 (2.33 to 3.96)	2.92 (2.20 to 3.88)	4.41 (1.40 to 13.89)
71-105	2.71 (1.97 to 3.73)	2.40 (1.69 to 3.41)	3.50 (0.76 to 16.25)
106-140	2.14 (1.45 to 3.15)	2.16 (1.44 to 3.23)	2.21 (0.28 to 17.34)
141-175	1.53 (0.95 to 2.44)	1.49 (0.90 to 2.44)	2.40 (0.30 to 18.88)

The authors note that only a handful of patients even received an atypical so it is hard to extrapolate beyond what previous studies have suggested: that people 80 and older are much more likely to have a stroke than other groups of patients and that a small statistical association between stroke and atypicals exists. However, it is unclear from the data whether the association is a function of dose or duration. In any event, the research provides a much needed systematic assessment of an important clinical issue dealing with the treatment of dementia.

Not so the rigged and biased attack Curt Furberg launches on all oral diabetic drugs....

"We reported [in the journal Diabetes Care] in June 2007 that thiazolidinediones doubled the risk of congestive heart failure in patients with type 2 diabetes...The increased heart failure appears to be a class effect."

Well, appearances are deceiving, especially when you are reporting on a highly selective group of studies....

A random-effects meta-analysis of three randomized controlled trials showed an odds ratio (OR) of 2.1 (95% CI 1.08-4.08; P = 0.03) for the risk of heart failure in patients randomized to TZDs compared with placebo. Four observational studies revealed an OR of 1.55 (1.33-1.80; P < 0.00001) for heart failure with TZDs. A dose-time-susceptibility analysis of 28 published reports and 214 spontaneous reports from the CADRMP database showed that heart failure was more likely to occur after several months (with median treatment duration of 24 weeks after initiation of therapy). Heart failure equally occurred at high and low doses. The adverse reaction was not limited to the elderly, with 42 of 162 (26%) of the reported cases occurring in patients aged <60 years. CONCLUSIONS: Our teleo-analysis confirms the increased magnitude of the risk of heart failure with TZDs. We estimate the number needed to harm with TZDs to be approximately 50 over 2.2 years. Existing guidelines and package inserts may have to be revised to incorporate these risk characteristics of TZDs..

Furberg also uses the ACCORD and ADVANCE studies to justify yanking Avandia off the market. According to ScienceDaily, here is Furberg's logic:

"They said that results from three large randomized clinical trials published this past June all failed to demonstrate that intensive control of blood sugar reduces mortality or events from cardiovascular disease in patients with type 2 diabetes.

The three trials were ACCORD, ADVANCE, and the Veterans Affairs Diabetes study. In ACCORD, the patients who received intensive treatment to control blood sugar actually had more cardiovascular disease mortality than patients receiving standard treatment."

Uh, maybe because they were sicker to begin with.

In any event, what has that to do with Avandia's risks and benefits. Nothing. But Furberg is grasping at straws here and he knows it.

As noted by Kevin, MD: "RECORD, ADOPT, DREAM, ACCORD and VADT; there have been over 26,000 patients studied for over 3.5 years, of which more than 15,000 patients took Avandia and showed absolutely no difference in heart attacks or myocardial ischemia. I think it is clear based on the inherent limitations of Nissen's findings and the substantial evidence from the aforementioned studies that Avandia is not, and has never been associated with heart attacks or myocardial ischemia."

Yes, post market evaluation of meds is important. But it needs to be done right and honestly.
  Read More & Comment...

Obama's Deceptive Health Plan

08/29/2008 01:35 PM |

Barack Obama promised to reduce the health care premiums of all Americans who have health insurance (by $2500 per family according to his website) and provide those who don't have health insurance the same kind of coverage that members of Congress have.

Even the NY Times know when they are being jerked around.

First of all, the article points out, the $2,500 figure includes not only the portion of premiums paid by individuals, but also the large portion paid by employers and, in the case of Medicare and Medicaid, the government.

Given that caveat, what’s the source of the $2,500 figure? It comes from this memo, put out by three Harvard professors who are unpaid advisers to the Obama campaign. They cited RAND findings that investing in health IT could $77 billion a year, and improving management of chronic disease could save another $81 billion. Cutting administrative costs in the insurance industry could save up to $46 billion, the memo said, citing the Commonwealth Fund.

The memo points out that it’s impossible to predict actual savings, and cites a wide range of possible outcomes. But the authors say their best guess is annual savings of $200 billion.

They took that figure, divided it by the population of the U.S., multiplied to get a family of four, then rounded down to $2,500 to get a round number, the article says.

Whether all those savings estimates are realistic — and what time frame it would take to realize the savings — are both subjects of debate. Earlier this year, the Congressional Budget Office said stirred things up when it said that RAND may have overstated potential savings from investing in health IT.

And what about giving everyone else the same health care coverage members of Congress have? The plan would be paid for by cutting payments to doctors and hospitals. Obama's model for the national plan is not what his colleagues in Congress have but how states have tried to expand Medicaid to create universal health coverage.

Obama's National Health Exchange would set up a public planrequire all private insurers to accept everyone regardless of illness, pre-existing condition, etc. set premiums and then " require that all the plans offered are at least as generous as the new public plan and have the same standards for quality and efficiency. And that means price controls.

Obama claims this will eliminate bankrupcty from health care expenses and reduce uncompensated care expenses.

Not so. Rationing will force patients to sell off houses and pay out of pocket for services biggovhealth says no to. Just like in Canada and England. Allowing states to extend coverage to illegal immigrants and a new provision to provide health insurance to the children of illegal immigrants via SCHIP and Medicaid will see costs skyrocket and private hospitals will be forced to make up the difference between the federal reimbursement and what they have to spend on care, just as they do now.

Finally, "Obama will require that providers that participate in the new public plan, Medicare or the Federal Employee Health Benefits Program (FEHBP) utilize proven disease management programs. This will improve quality of care, give doctors better information and lower costs."

Is there any evidence of that? No. But we will have a government agency that will tell doctors what they can and cannot use based on one-size fits all and outdated studies of how to treat chronic illness. Such studies, because they ignore genetic, gender, racial differences will deepen health disparities. Combined with cuts in payments to doctors, care and coverage in the poorest areas will dry up.

Change. Yes we can.

  Read More & Comment...

Imagine No Fair Balance

08/29/2008 12:35 PM |

“Disease Awareness” ads are, by definition, advertisements for prescription drugs that discuss a disease, but not a specific medicine.  They educate the consumer about important health issues such as … how to quit smoking.

But here’s how Alicia Mundy, in today’s Wall Street Journal, begins her story about a disease awareness campaign on just this public health issue:

“Pfizer Inc. has found a way to encourage the use of its antismoking drug Chantix without detailing serious potential side effects through a commercial that doesn't mention Chantix at all.”

Okay class, is this going to be a story that praises Pfizer (the world’s largest pharmaceutical company) for educating people about how to quit smoking? Or is it a story about how Big Pharma is trying to hide the fact that (gasp!) drugs have risks?

Ms. Mundy continues:

“Under Food and Drug Administration rules, if an ad doesn't directly name the drug, it doesn't have to include the reading of possible side effects that can chew up expensive television time.”
True.  But consider the phrasing.  For Ms. Mundy, “disease awareness” is just another clever ploy to avoid fair balance/adequate provision.

And she lumps all disease awareness ads together:

“This unbranded approach has been used in the past to promote disease awareness and build markets for treatments for those disease. Bob Ehrlich of DTC Perspectives, which monitors direct to consumer advertising by drug makers, says the Ambien and Chantix promotions may be clever, but ‘There's a risk they could rouse congressional ire over cute commercials that don't emphasize medicine.’ “

Bob, there’s a difference between these two campaigns.  Check them out and judge for yourself.  One has to assume that Ms. Mundy did – and that she’s decided that all disease awareness ads are the same – meaning that they are equally devious.

But, in fairness, she gives Pfizer the chance to comment:

“Pfizer says it isn't pushing Chantix in its ads, or trying to circumvent FDA rules. "The goal of the My Time to Quit campaign is to encourage people to quit smoking," said company spokeswoman Sally Beatty. "My Time to Quit is designed to encourage people who are thinking about quitting to speak to their healthcare provider about the benefits of quitting smoking and available treatment options," she said.”

Isn't it refreshing when Big Pharma stands up for itself?

Perhaps the most astounding and important paragraph in the article is the following:

"With unbranded ads, you don't have the 'fair balance' requirement," said Rich Gagnon of the ad agency DraftFCB, part of Interpublic Group of Companies Inc., in New York. "Imagine paying millions to run that ad campaign, and having to use up 30 seconds to list all the problems," said Mr. Gagnon, who has several pharmaceutical clients.”

“Imagine” paying millions to talk about risk?  I should say its money well spent. Does Mr. Gagnon really believe that disease awareness ads are just a slick way to sidestep providing fair balance?  If he was misquoted or if his comment was taken out of context, he should strive to correct the record a pleine vitesse.

Ms. Mundy also goes to Ruth Day – with whom we often disagree on DTC issues:

“Ruth Day of Duke University, a frequent critic of direct to consumer ads, gave the commercial and website high marks for useful information. An expert in how medical ads work on consumers, Dr. Day said mytimetoquit.com is relatively easy and gets to lists of side effects quickly.”

And we’ll leave it at that.

  Read More & Comment...

The Strange Silence of Complete Response

08/28/2008 02:02 PM |

Do “complete response” letters offer more clarity or ambiguity?  It depends who you ask.

If you are privy to what the letters say, they offer greater clarity as to what needs to be done to gain FDA approval.  (At least that’s the theory.)

If you are a reporter or a financial analyst or a patient or a physician, you only know what the sponsor tells you.  And that’s not much.

But it never has been and a lot of people find that frustrating.

Well, life is full of frustrations.

Consider the media.  They have a job to do.  Will complete response letters help them write a more complete story?  No, because the letters are not public and it is highly unlikely (for many good reasons) that "commercial confidential" communications with the FDA will be shared with anyone outside the confines of the sponsor.  (For more on the issue of complete response letters and commercial confidentiality, see, “Public or Private,” from the Journal of Life Sciences.)  

Some companies will blame the FDA with excuses like, “The FDA won’t allow us to discuss the letter” or “The FDA will be upset if we release the letter.”  Hogwash.

Here it is straight from the Bob Temple:

“If I were a reporter, I would say, ‘if you don’t show me the letter I don’t even want to talk to you.’  That’s what I would say.”

Wisdom of Temple or Temple of Wisdom, no matter how you slice it, it equals the FDA’s strong support for transparency. Easier said than done? Sure. But let’s stop with the lame “We’ll make FDA angry” excuses.

The strange silence that generally accompanies FDA communications is a tough nut to crack.  If “more” is desirous by the media, but problematic from the legitimate viewpoint of the sponsor, what can be done?

One incremental step forward is to help clarify what is not in a complete response letter.  Recently Johnson & Johnson received a complete response letter for paliperidone palmate.  In addition to the usual and customary, “We’re looking forward to working with the FDA to bring this important new product to market,” J&J also added one important piece of information – that the FDA had not asked for any additional studies.

Rather than sharing what was in the letter, J&J shared what was not in the letter.  Smart.

For more discussion of the complete response issue have a look at this excellent article from the July/August 2008 issue of the RPM Report.

  Read More & Comment...

Don't be Bob

08/27/2008 01:25 PM |

Much discussion about 47 million uninsured.  Very little discussion about who they are. 

Always included in that much touted number are scores of healthy young people — close to 20 million, by some accounts — who elect not to buy health insurance even though they can afford it. They voluntarily choose not to have health insurance — which is quite different from not being able to get health insurance.

Invulnerable?  Not always.

Check out the new website, "don't be bob,"  that is trying to attract this segment of the uninsured population.  It's good for these uninsured adults.  It's good for the overall risk pool.

And it's a good start towards solving the problem with smart and savvy free-market solutions.

For more on that same sane notion of free-market solutions, have a look at the op-ed in today's Wall Street Journal by Grace-Marie Turner, president of the Galen Institute.  She writes:

"A new study by University of Minnesota economists Stephen Parente and Roer Feldman shows that Congress could boost by more than 12 million the number of people who have health insurance without spending taxpayer dollars.  The change required is to allow people to buy health insurance across state lines, so they can shop for less expensive policies ... For example, a typical health-insurance policy in heavily regulated New York costs more than three times as much as in less regulated Iowa ($388 a month versus $98 a month for the same coverage)."

But you won't hear any of that free-market hooey coming out of Denver.

  Read More & Comment...

Stanford's Sad CME Shakedown

08/26/2008 12:02 PM |

Ironic that Stanford Medical School is located at 300 Pasteur Drive.  Ironic, because Pasteur's transformational research on bacteria was financed largely by the beer and wine industry as were most of his writings, lectures and travels on the subject. 

Which  means that Dr. Pasteur would have been been banned from doing such research and promoting it's value by Stanford.  Instead, the funding would have gone to the dean of the medical school and a group of bureaucrats more interested in political correctness than medical progress.   According to the new Stanford medical school policy on industry support for medical education,  "the faculty, in conjunction with the office of CME, will decide the choice of topic and content for all Stanford CME activities, and curricula will be chosen based on the educational needs of our learner populations."

http://deansnewsletter.stanford.edu/#1

And as we all know, academics are free of any bias and never seek to steer money away from approaches they don't believe in and funnel cash to their own pet theories. 

Which means that Pasteur, whose original ideas were rejected and ridiculed would have been labeled as "corrupted" by industry funding and would never have seen the light of day.  CME would have gone instead to supporting treatments of disease based on spontaneous generation.  Pasteur's subsequent work on the anthrax and rabies vaccine would be similarily attacked for it too had industry funding.

Pasteur challenged the dogma of the time and challenged his critics to attack him not in terms of circular and self-justifying arguments but by engaging in their own experimental research. 

Attack my experiments," he challenged his critics. "Prove that they are incorrect instead of trying new ones that are merely variants of mine, but into which you introduce errors that then have to be pointed out to you."

Sadly today, that spirit is being extinguished by the new religion of politically correct science.  When the Dean of one of the finest medical schools in the country claims "the historical and traditional models of CME, based largely on lectures and discussion groups, have served a purpose, although their impact on truly enhancing medical knowledge that leads to improvements in health care outcomes is unresolved" he is parroting the catechisms of a anti-science caste who believe, without evidence, that commercial support of research, training and symposium have an adverse impact on public health.  

Simply handing the CME cash over to medical schools  is problematic particularly if the role of CME in health improvement is unresolved.  And if Dean Pizzo and others truly believe that, then they should be not responsible for the nearly $1 billion in industry support for such activities.   For all the prattle about lack of accountability in CME, their is no murkier moral or intellectual stew than an academic department at a major university or no entity better at siphoning dollars for overhead, salaries and indirect expenses. 

The larger issue, that men and women of insight and teaching talent might find themselves barred by universities of promoting ideas and interests they have researched remains.  So does the fact that medical schools have largely failed to serve the primary care and nonphysician workers who treat the  medically underserved, those health care providers who don't have the money or the luxury of an tony academic appointment or CME cash. 

As with all myopic ideological movements, the attack on industry support of CME has casualties.  Public health will be one.  Truth another.  As Pasteur put it, "In each of us there are two men, the scientist and the man of faith or doubt. The two domains are distinct, and woe unto him who seeks to make the one encroach upon the other in the current imperfect state of our knowledge."

http://www.people.fas.harvard.edu/~agoldham/articles/pasteur.htm


  Read More & Comment...

How does a Scotsman get his healthcare information?

08/26/2008 11:50 AM |

How does a Scotsman get his healthcare information? With difficulty.

Here's a new article from today's edition of The Scotsman:

Advertising rules stifle free market for prescriptions
By Peter Pitts

IN EUROPE, it is illegal for drug companies to advertise prescription-only drugs to consumers. But the European Commission (EC) recently announced that it will allow pharmaceutical firms to disseminate "information" on their products over the airwaves, on the internet, and in print.

I think this change can't come soon enough. For too long, European bureaucrats have put cost considerations before patient care, keeping patients in the dark about alternatives that may best address their needs. Officials have, I think, paid lip service to the idea of empowering patients with more information on treatment options.

James Copping, a principal administrator of the EC, said in 2006: "We want a system where patients can be empowered to take an equal part in healthcare decisions." But thus far, no such thing has happened.

Consider the European agencies tasked with weighing the effectiveness of various treatments, such as the UK's National Institute for Clinical Excellence (Nice) or Germany's IQWiG. These agencies exist to provide unbiased medical information to government.

But because they are operated by government, I would say they have a vested interest in keeping costs down and have an incentive to conclude that newer, more expensive medicines are no more effective than older, cheaper ones.

Nice offers an instructive example. In 2001, contrary to expert findings by licensing authorities in 65 countries – including Scotland – it cited "insufficient evidence" for recommending the use of Gleevec in leukaemia patients.

In 2002, US authorities approved Gleevec for the treatment of stomach cancer and it was deemed a miracle drug. It wasn't until 21 months later that Nice authorised the use of Gleevec for English victims of the disease.

IQWiG seems similarly set on depriving German patients of vital treatments. The agency has promoted an "efficiency frontier" as its governing methodology for evaluating treatments. But such jargon is smoke and mirrors, designed to cover for the government's preference for established – and generally less expensive – treatments, and by decreeing the most cost-effective option in a treatment category, these agencies effectively determine what a doctor must prescribe, irrespective of a patient's individual characteristics.

Obviously, pharmaceutical companies have products to sell. But, by allowing them to provide Europeans with medical information, they could serve as a counterbalance to the heavy-handed pronunciations of state-run comparative-effectiveness agencies.

Indeed, a great deal of evidence demonstrates that consumers benefit when drug manufacturers participate in healthcare decision-making.

In the US, for example, a 2002 study by the Food and Drug Administration found that direct-to-consumer advertising of pharmaceuticals improved both patient-doctor discussions and compliance with physician recommendations. The study also found that 88 per cent of patients who asked about a specific drug were afflicted with the condition in question.

A 2003 study in US health policy journal Health Affairs arrived at a similar conclusion. According to the study, ad- inspired doctor visits resulted in the advertised medicine being prescribed in only about 47 per cent of cases. Put another way, patients didn't get a prescription for the medicine they came in to discuss on more than half their visits. Even with advertising, doctors exert appropriate judgment when they prescribe drugs.

On other occasions, according to the study, previously undiagnosed medical conditions get treated – a good thing.

For European bureaucrats, there is reason for concern. If consumers can get additional information on drug options thanks to direct-to-consumer efforts, there's a good chance they'll start to ask the state-run health systems why they can't access certain treatments.

As European Parliament member Jorgo Chatzimarkakis recently argued: "Citizens cannot be deprived of information by their own governments on such crucial issues as one's health."

Government-run systems have demonstrated that they're not interested in spending more money, but armed with new information, consumers may be able to make the case to their leaders that the status quo of rationed, controlled care will no longer suffice.

  Read More & Comment...

Uncompensated care study: Case of Wishful Arithmetric

08/25/2008 09:55 PM |

Today's study in Health Affairs tries to suggest, once again, that  universal health care of some sort would cost only less than paying out for uncompensated care to the uninsured who receive most of this "free" care. 

The researches argue that neither health care spending or private premiums would go up that much because "hospital spending on uncompensated care has been relative stable.  That is partly because the public hospitals and clinics that most often care for the uninsured often don't have many privately insured patients to absorb the costs."

Translation: most uncompensated care is due to the fact that Medicare and Medicaid don't pay the full cost of medical expenditures.  Uncompensated spending has been stable because Medicare and Medicaid have held reimbursement rates steady and because in many cases the state match (to pay for the care of illegals) has skyrocketed with most of the money going to urgent care and maternal health, not complex medical procedures. 

GIve people a full blue plate entitlement and watch both government expenditures rise and uncompensated care increase as well.  In every state where a single payer plan has been enacted uncompensated care continues to go up.  The best example is the Oregon Health plan which ensures the uninsured by rationing access to cutting edge treatments and raising taxes.  The trend of uncompensated care since 1994 in that state is below.

Statewide Uncompensated Care by Year:
	Year	Charity Care	% Change from Prev. Year	Bad Debt	% Change from Prev. Year	Total Uncomp. Care	% Change from Prev. Year
	1994	74,653,735		90,272,616		164,926,351
	1995	55,645,120	-25.5%	90,262,052	0.0%	145,907,172	-11.5%
	1996	53,036,784	-4.7%	80,387,137	-10.9%	133,423,921	-8.6%
	1997	55,123,781	3.9%	83,974,361	4.5%	139,098,142	4.3%
	1998	58,291,332	5.7%	96,289,876	14.7%	154,581,208	11.1%
	1999	53,994,527	-7.4%	102,732,393	6.7%	156,726,920	1.4%
	2000	64,916,584	20.2%	128,914,104	25.5%	193,830,688	23.7%
	2001	77,772,655	19.8%	138,822,832	7.7%	216,595,487	11.7%
	2002	107,854,204	38.7%	164,629,911	18.6%	272,484,115	25.8%
	2003	183,626,444	70.3%	221,580,947	34.6%	405,207,391	48.7%
	2004	268,333,010	46.1%	269,741,864	21.7%	538,074,874	32.8%
	2005	374,330,244	39.5%	301,574,208	11.8%	675,904,452	25.6%
	2006	445,884,426	19.1%	305,343,908	1.3%	751,228,334	11.1%
	2007	524,707,945	17.7%	351,866,447	15.2%	876,574,392	16.7%

The same thing happened in Tennessee when Tenncare was enacted.  The idea that a single payer system will eliminate uncompensated care is bogus unless the single payer doubles what it pays providers, hospitals, etc.  Just the opposite takes place in a single payer system.   What will reduce uncompensated care -- apart from rationing which will drive up costs elsewhere --  are changes to the financial and technological structure of healthcare that reward saving and investment in personal health and staying healthy.   Indeed, as the percent of people in consumer directed plans increases and includes the uninsured, the amount of out of pocket spending has remained stable and as a RAND study last year shows, the consumer directed plans are associated with reduced hospital and physician visits and increased access to prescriptions.  This does not always "control" costs but does appear to improve quality by encouraging more management of costly chronic illnesses,

http://content.healthaffairs.org/cgi/content/full/hlthaff.27.5.w399/DC1
  Read More & Comment...

When is Off-Label not Off-Label?

08/25/2008 12:57 PM |

When is off-label not off-label?  When it's on-formulary and off-patent of course.

At least that seems to be the position of some state Medicaid plans.

Case in point, pregabalin (Lyrica) and Iowa (coincidentally, the state represented in the United States Senate by Charles Grassley).

Iowa Medicaid requires preauthorization for pregabalin -- which is FDA-approved for (among other indications) fibromyalgia.  In Iowa a patient with a diagnosis of fibromyalgia must first fail on at least two  of the State's "preferred" agents -- trycyclic anti-depressants, topical lidocaine, or gabapentin.  None of these three agents are approved by the FDA for the treatment of fibromyalgia.

But they are less expensive than the on-patent, on-indication product.  So what we've got here is step-therapy based on off-label usage.  Not unheard of, certainly , but it does start sending some interesting policy messages about the appropriateness of off-label use in various circumstances.  (And it's more than a little bizarre when you consider that Pfizer, the manufacturer of pregabalin, had to pay a $430 million fine for off-label promotion of gabapentin.)

The actions of the Hawkeye State Department of Human Services are even more peculiar considering that Senator Grassley (R, IA) asked the U.S. Government Accounting Office (GAO) to investigate off-label prescribing -- and not because he thought it was a valuable tool for patient care.

So here's where we stand:  Off-label use of on-patent medications is bad, but off-label use for generics is good.  Translation:  off-label use is good when it saves the payer money.

Is cost-based trial-and-error medicine really the path we want to take in the era of personalized medicine?

What about science?

What about relying on the professional judgment of the physician?

What about what's best for the patient? 



  Read More & Comment...

Patient-Centric Care? He knows it when he sees it

08/22/2008 11:45 AM |

John F.P. Bridges, Assistant Professor, Department of Health Policy and Management at the Johns Hopkins School of Public Health and Senior Fellow at the Center for Medicine in the Public Interest, is the featured interview in the current edition of DIA Today.

It's a Q&A.  Here's a sample:

DIA:  Do you think that the general public -- the average "patient on the street" -- would recognize the concept of patient-centered care?

JB:  "I think that if they experience it, they can tell the difference, but at the moment we're setting up barriers to patient-centered care.

To find out what that means, have a look at the compete interview here.  It begins on page 18.
  Read More & Comment...

Is It Worth Letting Women Get Cervical Cancer

08/21/2008 01:16 PM |

I guess if you take a "societal" (read government or HMO) perspective it does, especially if you believe that an additional yearl of disease free life for a women 21-26 is only worth $100K, which is an arbitrary numbe developed in 1985 that reflects a "societal perspective" on the cut off or rationing point...

"We adopted a societal perspective, discounted costs and benefits by 3% annually, and expressed benefits as quality-adjusted life-years (QALYs) gained. After eliminating strategies that were more costly and less effective or less costly and less cost-effective than an alternative strategy, incremental cost-effectiveness ratios were calculated as the additional cost divided by the additional health benefit associated with one strategy as compared with the next-less-costly strategy. Although there is no consensus on a cutoff point for good value for resources, we interpreted our results in terms of a commonly cited threshold of $50,000 per QALY gained, as well as an upper-bound threshold of $100,000 per QALY gained."

Hmm, and what does that cover...

"The routine vaccination of 12-year-old girls, in the context of current screening and assuming lifelong vaccine-induced immunity, had an incremental cost-effectiveness ratio of $43,600 per QALY gained, as compared with screening alone (Table 2). The addition of a 5-year catch-up program for girls between the ages of 13 and 18 years cost $97,300 per QALY, and extension to 21 years of age cost $120,400 per QALY. The extension of the catch-up program to 26 years of age cost $152,700 per QALY, as compared with the catch-up program to 21 years of age."

The extra $52 K is really society saying, we have decided after $100K  we will roll the dice and see if we have to pay for all the costs relateded to screening, treatting, etc. cevical cancer.   It does not even address what a 26 year old woman might think a catch up shot is worth....

Oh,  and the additional benefits. like avoiding screening and the worry or other illnesses were never counted either.

"when the potential benefits associated with preventing noncervical HPV-16–related and HPV-18–related cancers and HPV-6–related and HPV-11–related juvenile-onset recurrent respiratory papillomatosis were included, cost-effectiveness ratios were reduced"

So of course the NEJM runs an editorial claiming the vaccine is not cost effective, it's press department hypes that and not the guts of the study and the rest of the media takes the lead and will ikely cite (via misrepresentation) the study as proof that many new products are not worth their cost.  .

Still believe cost-effectiveness will certainily be a patient-centered and objective process taking into account all stakeholder concerns.  

http://content.nejm.org/cgi/content/full/359/8/821
  Read More & Comment...

Cost-effectiveness wars

08/21/2008 12:44 PM |

John F. P. Bridges, Assistant Professor at Johns Hopkins Bloomberg School of Public Health, a Senior Fellow at the Center for Medicine in the Public Interest and the Founding Editor of The Patient, comments on the new Hanover Consensus and the future of comparative effectiveness.

Here's what he has to say:

 
Peter Pitts’ depiction of the almost ten year old “cost-effectiveness” wars in Germany (See Uncommon Denominator) is just an introduction to the debate over economic evaluation of medicine in Germany, Europe and beyond. While it is commonly believed that Europe had long ago fallen to the dark forces of cost-effectiveness analysis, the German defiance referred to in Peter’s article has highlighted that this is not really the case (and there are plenty more counter examples out there). 

Two key issues central to the German debate over economic evaluation are, (1) what methods constitute “best practice” in the economic evaluation of health care, and (2) what type of evaluation is needed for a system that is based on a combination of employer and private health insurance, albeit a system that is subjected to an increasing government presence – along with calls for major reforms to create (attention Obama-ites) a national health care system.

The Hanover Consensus Group has consistently taken the line that “everyone else is doing it, so why aren’t we?” (Although a cynic might read “other health economists are profiting from it and we want too as well!”) While cost-effectiveness analysis is a regularly accepted rule, it’s wrong to consider it as accepted best practice.  Even for those who herald its use, it is often understood as a “necessary evil”.  Furthermore, in an evidence base world, there has never actually been a technology assessment performed on cost-effectiveness analysis, hence we don’t know if it does or does not lead to better health care investments or lowers overall expenditures. Anecdotal evidence in Ontario indicates that it failed to decrease -- and potentially increased -- the rate of medical inflation following its implementation.  Based on the experience in Australia, cost-effectiveness analysis can decrease total expenditures -- but by delaying reimbursement decisions -- a de facto shortening patent life on drugs – or through the negotiation of major price discount, and not by weeding out bad practice. 

The more subtle point in this debate relates to the compatibility of cost-effectiveness with the German health care system.  Created by Otto von Bismarck at the end of the 19^th century, the system of Social Health Insurance was based on the principles of solidarity and subsidiarity.  While Angela Merkel’s health care reforms have threatened the latter to promote affordability, the Germany health care system remains essentially employer and employee sponsored, with a limited role for government.  Furthermore, the Social Code Book that defines the German health care system calls for efficiency to maximize within each disease state, which is at odds with the “priority setting” approaches (a more genteel way of referring to health care rationing) implicit in cost-effectiveness analysis. 

Having been a regular IQWiG watcher since its inception, I have to congratulate Dr. Kolominsky-Rabas for his efforts in searching for an alternative approach to cost-effectiveness analysis.  While I might not agree with the current approaches presented by Caro and colleagues, I find it refreshing that we are now entertaining alternatives. American policy makers  should not only pay attention to this robust debate in Germany, but should be active participants given that we too might find ourselves with our own version of IQWiG in the near future. 

  Read More & Comment...

Is FiercePharma Becoming Bio-Luddite

08/20/2008 08:57 PM |

The latest synoposis about Merck suggests that whoever is writing Fiece Pharma is going over to the dark side:

"This is in addition to Merck's efforts to make the vaccine mandatory for young U.S. girls, with many wondering if the rise in cervical cancer vaccines are due to increased awareness or to Merck's aggressive, award winning and highly controversial marketing schemes. "

First of all, is the above an actual sentence written by a journalist whose first language is English or was it translated from the original Vulcan?

Second, given the increasing reliance on other blogs with a bias as a primary source instead of real background, it is obvious that FiercePharma believes that arsenic causes diabetes, all marketing is a ploy and vaccines are dangerous.

Third, the argumentation of the piece is consistent with tendency of bio-Luddites to use their belief than medical innovations are just an excuse to rape the public as evidence instead of a fearful emotional response.

Note the lack of clear deductive or inductive reasoning balanced with a complete lack of empirical information. For instance there is a problem with increased used through marketing but not public awareness....is there a difference? Or are those responding to Merck marketing brainwashed and the those that received it from on high enlightened? Does evidence of adverse events mean the vaccine should NOT be marketed. What is the marketing was less aggressive? And what about the trend towards not covering by insurance companies? Obviously sales are lagging so what good is awareness is the so-called health maintenance organizations won't pay for prevention? They cover chicken pox vaccines but not cervical cancer?

Previously Fiercepharma claimed a article relying upon memos redacted and provided by tort lawyers that was published in the Archives of Interna Medicine (or was it annals? Who cares, right?) alleging the Advantage study Merck conducted was primarily for marketing "proves" that it was so because it was run in a "peer reviewed journal." It is my humble opinion that the Advantage study was designed to assauge fears, but that is just my opinion and publishing it here or even in JAMA using documents from a biased source does not make it fact.

I am supposed to be on vacation.
  Read More & Comment...