Response to FDA Early "Warning" of Drug Problems is So Predictable

09/08/2008 12:46 PM |

The really, really early warning requirement for new drugs has prompted the predictable response from the usual suspects. The goal of course is to focus post market detective work on which groups of people respond best to which drugs.  But that's not how it's playing out. PhRMA fears people will worry unnecessarily and safety-uber-alles zealots like Diane Zuckerman, president of the National Research Center for Women and Families, worries "It's not going to say how many reports there were. It's not going to say how many died and how many were hospitalized."  

Oh.  And just how high a body count would Diane like?  I have a clue.

Diane, has also said that  anti-depressants don't work and that she knew better than I did because she is an epidemiologist,  When I told her that certain members of my family had responded well to SSRIs she said, "Well, good for you. "   I could feel the love. 

http://ap.google.com/article/ALeqM5jLeef2T5nlybcAAzF3Fe1qqDEaqgD930MUEG0

Like I said, predictable.
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AERS Apparent II

09/05/2008 06:13 PM |

Per the earlier question, "Will the FDA advise a pharmaceutical company in advance if one of their products is to be be included in a quarterly AERS report?" -- the answer is "yes."

According to my source inside the agency, "For all our communications we endeavored to communicate 24-48 hours in advance."

As far as today's inaugural report, sponsors were notified yesterday.

Question:  why not sooner?
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AERS Apparent

09/05/2008 03:28 PM |

The FDA announced today that it will post, quarterly, a report of drugs that are being evaluated for potential safety problems.  The FDA will base this list on adverse events reported through the agency’s Adverse Event Reporting System (AERS). The first report will be posted today.

This reporting mechanism is a requirement of FDAAA.

Ultimately, based on these evaluations, the FDA can require next steps ranging from (1) nothing – if the adverse events are determined not to be drug-related, (2) a risk management plan (REMS), (3) a label change, up to and including (4) a Phase IV clinical trial. It's important to note that all of these options can now, per FDAAA, be mandated by the agency.

This news was presented by Paul Seligman, MD (Associate Director of Safety Policy and Communication, CDER) and Gerald Dal Pan, MD (Director, Office of Surveillance and Epidemiology).  Both commented on the need to keep these warnings in perspective and both spoke to the issue of unintended consequences and that the agency would strive to communicate the information in the manner designed to avoid misinterpretation by patients and overreaction by the media.

(If you disagree that the media overreacts, let's see what happens tomorrow.)

One way to help modulate the unintended consequences (aka, "general hysteria") these things tend to generate is to make sure drug companies have some advance warning of these postings so they can be prepared to communicate their perspectives to patients, physicians and payers.  Will the FDA be advising companies that a given product will be included in the report?  It wasn't discussed during the press briefing.

Inquiring minds want to know (1) if "yes," how far in advance will a company be notified and, (2) if "no," why not?

More as more develops.

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Will Mr. Ross be home for Christmas?

09/05/2008 12:58 PM |

Last night John McCain came out strongly against healthcare reform that would have  “bureaucrats” telling doctors how to practice medicine. 

And he’s right. 

Many people, who disagree with the GOP nominee, echo the empty rhetoric of SiCKO and are calling for healthcare “like in Europe – where it’s free.” 

Well, it ain’t free.  Government-controlled healthcare is funded through (gasp!) taxes.

Consider Canada, while the percentage of taxes used to provide healthcare varies, it is estimated that 22 percent of taxes collected go towards funding of their health system.

Then consider the United Kingdom, so often held up by advocates of "universal" healthcare.

Citizens of the UK pay 11 percent of each pound they make in weekly income between £100 - £670 for the NHS, plus an addition 1 percent of income over £670 a week.

But it’s not only what you pay – it’s what you get (or don’t get) for the money. Consider this story from today’s edition of the British newspaper, The Independent:

“A cancer sufferer whose primary care trust refused to pay for a drug which could extend his life by up to three years has launched an 'end of the road' legal challenge to the decision. If Colin Ross continues to be denied the drug, Revlimid, he will die within a few months, experts say.

Mr. Ross, 55, said his doctors had requested funding for up to four courses of Revlimid at £5,000 a time. "If I don't win and I get no further treatment, I won't be here for Christmas. It's as simple as that," he said.

He was diagnosed with multiple myeloma, a cancer of the blood cells, in May 2004. Doctors at the Royal Marsden Hospital in London deemed Revlimid to be his last chance after side-effects forced him to give up the other life-prolonging drugs he was taking.

Revlimid is readily available to patients in Europe and the US but has yet to be approved by the National Institute of Clinical Excellence. 

In May, West Sussex Primary Care Trust blocked an emergency application for NHS funding for Revlimid for Mr. Ross, saying it was too expensive and his circumstances were not sufficiently exceptional for him to qualify.”

Yes – that’s what the “bureaucrat” said – “his circumstances were not sufficiently exceptional …” 

Yes, by all means, let’s put bureaucrats in control of health care.

Is this the sort of healthcare “reform” we want? 

Is that the sort of “change” we want?

For those who call for “free and universal” healthcare, remember the words of Benjamin Franklin, who said:

"All human situations have their inconveniences.  We feel those of the present but neither see nor feel those of the future; and hence we often make troublesome changes without amendment, and frequently for the worse."

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CME: An Evidence-Based Evaluation

09/04/2008 12:10 PM |

On September 22 in Washington DC, the Center for Medicine in the Public Interest is hosting a half-day conference on pharmaceutical industry support of continuing medical education.  We'll address some key questions such as:

* Is it "true" that industry-sponsored CME helps neither physicians nor patients because it is "biased?"

* Would CME be "better" if industry just gave the same dollars to academic medical centers and hospitals?

* Does barring industry support dampen intellectual freedom and drive talented people out of academic medicine?

We'll be joined by experts such as Tom Stossel, MD (Professor of Medicine, Harvard Medical School), Roger Meyer, MD (Clinical Professor of Psychiatry, Georgetown University), Jack Lewin, MD (President, American College of Cardiology), Gary Puckrein (National Minority Quality Forum), Michael Weber, MD (Professor of Medicine, Downstate Medical Center) and others.

We hope to see you there.  Here's a copy of the complete agenda. 

If you would like to attend (there is no cost), please contact Mario Coluccio at (212) 417-9169 or mario.coluccio@cmpi.org
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The Palin Health Care Record: Results You Can Count On

09/03/2008 01:14 PM |

I will write more about Sarah Palin later, particularly contrasting her decision to have her child Trig while Barack Obama was voting against a bill that made it illegal to deny medical treatment to babies that survived abortions and ghouls like the despicable Howard Brody who root for both aborting and witholding life sustaining care for infants with Down's Syndrome...

The%20healer%27s%20power%20-%20Google%20Book%20Search.webloc

For now it is worth mentioning that when campaigning for governor Palin promised to come up with a plan to provide all Alaskans with the opportunity to purchase affordable healthcare. She did. She established the Alaska Health Care Strategies Planning Council which in turn came up with a proposal to promote transparency of health care costs, deregulation in the formation of health care businesses to promote competition and expanded tax beneftis to support health savings accounts. The Palin plan also redirected state health spending towards electronic medical records, expansion of community health clinics in rural areas and increasing eligibility of the SCHIP program to 200 percent of poverty level. Further, Palin had instructed Alaska's Dept. of Health and Human Services to develop a goal-oriented action plan to improve the quality of care in nursing homes, increase foster care monitoring and quality, reduce child abuse, increase the amount of preventive care covered and paid for by Medicaid, reduce the incidence of SIDS in Alaska which is three times the national average due to a combination of genetic and risk factors unique to the Alaskan-Indian population. Last time I checked, that is called a record of accomplishment and action...

A news account and a copy of the final report of the Planning Council can be found here and here:

Read here

http://www.hss.state.ak.us/hspc/

The HHS goals can be found here: http://www.gov.state.ak.us/omb/09_omb/budget/HSS/  Read More & Comment...

The Truth Hurts

09/03/2008 12:32 PM |

As difficult as it is for parents who have lost children to suicide, the truth is the truth and cannot be ignored.

Consider today's story in the Wall Street Journal:

Elevated Rate Of Teen Suicide Stirs Concern

 
Trend Is Linked to Drop in Use Of Antidepressants After FDA Raised Worries About Risks

By SARAH RUBENSTEIN

A new study may bolster the argument that a drop in the use of antidepressants has led to an increase in teen suicides. Researchers said an analysis that included 2005 data -- the latest available -- shows that a surprising rise in the youth suicide rate in 2004 was largely sustained into the next year. While the rate dropped somewhat in 2005, researchers said, it remained higher than expected. The rise in suicides coincided with Food and Drug Administration advisories about antidepressants that led to an October 2004 decision to require strong "black box" warnings on all antidepressants' labels.

MAKING SENSE OF TEEN SUICIDE

How a trend changed direction.

1990-2003: The suicide rate for people 10 to 24 years old slid more than 28%.

2003-2004: The FDA issued advisories on antidepressants and required 'black box' warnings on labels.

2003-2004: The suicide rate for young people rose 8%.

2004-2005: The teen suicide rate slipped but remained elevated.

Last fall, the U.S. Centers for Disease Control and Prevention said the suicide rate for 10-to-24-year-olds rose 8% from 2003 to 2004 -- after a cumulative drop of more than 28% from 1990 to 2003. The CDC cautioned at the time that it didn't know if the rise was "short-lived" or the "beginning of a trend."

The CDC has monitored the data since then but hasn't come to a conclusion, saying several years of data are needed. But the new analysis by outside researchers suggests the increase "was not a single-year anomaly" and may reflect "an emerging public health crisis," according to a paper being published in Wednesday's Journal of the American Medical Association.

"We're seeing [more than] 600 more suicides in this two-year period than we would have expected, and that is cause for concern," said JeffreyBridge, an epidemiologist at the Research Institute at Nationwide Children's Hospital in Columbus, Ohio, and lead author of the study. A co-author was Joel Greenhouse, a statistician at CarnegieMellon University in Pittsburgh.

The latest analysis could rekindle controversy over the FDA's decision to require the "black box" warnings, which link the drugs to suicidal thoughts and behavior in young people. The warnings, along with the agency's concerns about antidepressants, contributed to a drop in prescriptions of the drugs for children and adolescents. The thorny question for doctors and patients: Are concerns about antidepressants scaring people away from medicines that could help them?

"We've seen this increase as soon as these warnings started, and it is what we were most worried about," said Kelly Posner, a researcher in ColumbiaUniversity's psychiatry department who has helped the FDA collect data on antidepressants and suicide and who says she doesn't have any financial ties to drug companies. "If you look at the whole evidence puzzle, it points in one direction -- antidepressants save lives."

Still, it's unclear whether a drop in antidepressant use is what caused the rise in the suicide rate. The suicide rate pertains to the entire population and doesn't indicate who took antidepressants and who didn't.

Other factors possibly contributing to the rise in the teen suicide rate include alcohol use, access to firearms, the influence of Internet social networks and suicides among U.S. troops, some of whom are older adolescents, Dr. Bridge wrote in the JAMA paper. His study was funded by the U.S. National Institute of Mental Health.

However, responding in part to concerns about avoidance of antidepressants in cases where they're needed, the FDA in 2007 called for an update to the boxed warning, adding that depression and certain other serious psychiatric disorders are themselves the most important causes of suicide. "It is our intent to fully inform prescribers about the risks and benefits of antidepressant prescribing -- not to discourage appropriate prescribing," FDA spokeswoman Sandy Walsh said.

Still, Ms. Walsh said, while the FDA continues to monitor data around the issue, it remains "confident the data support warnings" about suicidal thoughts and behavior in young people, and "it's still good advice to monitor patients starting treatment."

Suicide rates are calculated per 100,000 people. The rate for 10-to-19-year-olds was 4.49 per 100,000 in 2005, down from 4.74 per 100,000 in 2004. However, if the 2003-2004 rise were indeed a fluke, the 2005 figure would have been around 3.8 per 100,000, Dr. Bridge said. In 2003-2004, the increase in the suicide rate among people 10 to 19 was much sharper than the rise in the rate for 20-to-24-year-olds.

Still, the CDC is approaching the data cautiously. Alex Crosby, a medical epidemiologist at the CDC's InjuryCenter, said that in addition to watching the suicide figures, the agency is analyzing data from its National Youth Risk Behavior Survey of high-school students conducted every two years and its National Violent Death Reporting System, which includes details on the circumstances of suicides in 17 states.

The CDC has ramped up efforts aimed at Hispanic adolescents, who report a greater percentage of suicide attempts than other groups, and at Native Americans, who have the highest suicide rate among adolescents and young adults.

Now let's wait and see what the anti-SSRI mafia has to say.  You can bet it'll be vitriolic pharma-bashing with a heaping measure of junk science.

The truth hurts.

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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.
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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.

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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.

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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.

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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.

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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


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