Fwd: Pharma Marketing Tactics Threaten Public Health and Wealth

[Guest guest]

ALLIANCE FOR HUMAN RESEARCH PROTECTION Promoting Openness, Full Disclosure, and Accountability http://www.ahrp.org and http://ahrp.blogspot.com FYIAmid much fanfare, on Sunday, November 9, AstraZeneca announced the resultsof its  drug trial, Justification for the Use of Statins in Prevention: anIntervention Trial Evaluating Rosuvastatin (JUPITER). The results wereannounced at the American Heart Association conference and simultaneouslypublished in The New England Journal of Medicine (Nov. 9). The study washailed as a watershed event in heart disease prevention: "In this trial ofapparently healthy persons without hyperlipidemia but with elevatedhigh-sensitivity C-reactive protein levels, rosuvastatin [Crestor]significantly reduced the incidence of major cardiovascular events."Current treatment algorithms for the prevention of myocardial infarction,stroke, and death from cardiovascular causes recommend statin therapy forpatients with established vascular disease, diabetes, and overthyperlipidemia. Last year Statins command a $34 billion market share. http://www.forbes.com/2008/10/29/cholesterol-pharmacuticals-statins-biz-cx_mh_1030cholesterol.htmlNot satisfied with selling pharmaceuticals to the sick, drug manufacturersseek to expand the market for prescription drugs to healthy people. Theypromote drugs as though they were toothpaste-disregarding the drugs'hazardous effects. Companies do this by persuading an unsuspecting publicabout the need to take drugs as a preventive measure against presumed risksof future illness. And, more importantly, drug companies set out to convincedoctors-providing cash incentives-to prescribe drugs for healthy peopledespite documented--even life-threatening risks. Doctors have adopted a specious corporate rationale to justify prescribingdrugs for healthy people as "preventive therapy."  All-too-often, doctorsaccept findings from company-controlled, biased studies, ignoring theindicators for potential serious hazards posed by drugs. In the case of theJUPITER study, there was "a higher incidence of physician-reported diabetes"in the group exposed to Crestor.To their credit, the NEJM, published an editorial by Mark A. Hlatky, M.D.who took a more critical view of the study design, its reliance on a singlebiomarker, CRP, and he raises doubts whether the findings warranted expandeduse of statins. Dr. Hlatky points to other flaws in the JUPITER studydesign: "the study provides only limited and indirect information about the role ofhigh-sensitivity C-reactive protein testing in clinical management, sincethe trial did not compare subjects with and those without high-sensitivityC-reactive protein measurements, nor did it compare the use ofhigh-sensitivity C-reactive protein with the use of other markers ofcardiovascular risk.""The relative risk reductions achieved with the use of statin therapy inJUPITER were clearly significant. However, absolute differences in risk aremore clinically important than relative reductions in risk in decidingwhether to recommend drug therapy, since the absolute benefits of treatmentmust be large enough to justify the associated risks and costs. Theproportion of participants with hard cardiac events in JUPITER was reducedfrom 1.8% (157 of 8901 subjects) in the placebo group to 0.9% (83 of the8901 subjects) in the rosuvastatin group; thus, 120 participants weretreated for 1.9 years to prevent one event.""On the other side of the balance, of concern are the significantly higherglycated hemoglobin levels and incidence of diabetes in the rosuvastatingroup in JUPITER (3.0%, vs. 2.4% in the placebo group; P=0.01). There arealso no data on the long-term safety of lowering LDL cholesterol to thelevel of 55 mg per deciliter (1.4 mmol per liter), as was attained withrosuvastatin in JUPITER, which is lower than in previously reported trials.Long-term safety is clearly important in considering committing low-risksubjects without clinical disease to 20 years or more of drug treatment.Finally, the cost of rosuvastatin (roughly $3.45 per day or $1,250 per year)is much higher than that of generic statins."The cost-for the drug alone--of treating 120 people for 1.9 years to preventone serious cardiac event would be $ 285,000.Dr. Hlatky further notes: "Ridker et al. suggest, from their meta-regressionanalysis, that the risk reduction observed in JUPITER was greater than thatexpected on the basis of previous trials. Meta-regression is not a reliabletechnique, however, and the early termination of JUPITER owing to theefficacy data probably exaggerated the results to some degree."Which brings us to the issue of conflicts of interest:AstraZeneca funded the JUPITER study in order to justify prescribing itscholesterol-lowering statin, Crestor for people with normal cholesterollevels.  Needless to say, a favorable result would exponentially increasethe sales of the drug. The potential profit is in the trillions of dollars. The research objective had a built-in bias, and the sponsor and principleinvestigator had a strong stake in a desired outcome. Furthermore, in lightof the increased incidence of diabetes among the group prescribed Crestor(3.0%, vs. 2.4% in the placebo group), the trial's early suspension raisesred flags about the extent of that (and other risks) that are known to occurmostly after extended exposure.Not disclosed in the NEJM, is the discovery by Merrill Goozner:  "the firstthing you need to know about this trial is that its lead investigator, PaulRidker of Brigham and Women's Hospital in Boston, owns a patent on the $20test that measures CRP."  http://www.gooznews.com (posted below)The JUPITER trial screened nearly 90,000 people to find the 17,800 withelevated CRP measures who were eligible for the trial.  If 10 million peopleare tested to find the estimated two million with elevated CRP levels, "it's$200 million in test sales, which, if the royalty is only 1 percent, amountsto a hefty $2 million a year in extra income for Dr. Ridker."  IfAstraZeneca can get two million more "apparently healthy men and women" onrosuvastatin, it's an additional $2 billion-plus in sales."  In light of AstraZeneca's record of corrupt practices, [1] the followingauthors' statement should taken with a high degree of skepticism. "The trial was financially supported by AstraZeneca. The sponsor collectedthe trial data and monitored the study sites but played no role in theconduct of the analyses or drafting of the manuscript and had no access tothe unblinded trial data until after the manuscript was submitted forpublication."American medicine has been derailed from its therapeutic focus and ethicalprinciple, "first, do no harm," into a commercially driven enterprise sinceit aligned itself with the pharmaceutical industry.  Industry'sunconscionable marketing strategy-promotes the use of drugs for healthypeople-is accomplished with assistance from professional medical societiesand influential physicians at prestigious academic centers.  Doctors at the American Heart Association, lent legitimacy to prescribingstatins for long-term use in healthy people, simply on the basis of ascreening test that showed they had elevated levels of CRP, a biomarker forinflammation.  They predicted that the JUPITER study might lead as many as 7million more Americans to consider taking cholesterol-lowering statin drugs,such as: Crestor, Lipitor, Zocor, Similarly, the prescribing practices of US psychiatrists are driven byindustry's marketing agenda with no scientific-medical evidence to supportthe widespread prescribing of psychotropic drugs. Dubious screeningtests-such as DISC, TeenScreen, KiddieSADS, TRAYY-provide the basis for"diagnosing" mental disorders in millions of otherwise healthy Americanchildren who are then exposed to harmful toxic drugs that interfere withnormal physiological and neurological development. Even as these drugs'labels now carry black box warnings, the most severe drug warnings mandatedby the FDA-including the increased risk of suicide-prominent psychiatristspromote the use of these drugs in children. Financially compromisedpsychiatrists regularly pen their name (for hefty fees) toindustry-generated clinical trial reports and clinical practice guidelineswhose prescription drug recommendations have propelled the most toxicpsychotropic drugs into blockbuster sellers.  *AstraZeneca in the news:Nov. 6, 2008: Astra Zeneca Reps Told To Use Disney Characters In SeroquelMarketingHow is this for creative selling? .the idea was conveyed at a national salesmeeting and on field rides with sales reps, who were told to use Tigger as abipolar patient and Eeyore - the down-in-the-mouth donkey - as a depressedpatient. The reps were allegedly encouraged to use Tigger dolls asgiveaways." See:http://www.pharmalot.com/2008/11/tiggergate-using-disney-icons-to-sell-seroquel/June 19, 2008: Judge Price of the Montgomery County Circuit Court upheld thefraud verdict obtained by the State against AstraZeneca in the Medicaid drugpricing suit.  Judge Price upheld the compensatory damage award of $40million and,  pursuant to the statutory cap on punitive damages, cut thepunitive damages from $175 million to $120 million, making the total verdict$160 million.  AstraZeneca has stated they will appeal, so the AlabamaSupreme Court will be looking at it.  For more information, follow the linkto an article entitledhttp://www.forbes.com/feeds/ap/2008/06/19/ap5134622.html May 6, 2008: AstraZeneca released limited performance data for a trial usingits antipsychotic, Seroquel for depression. The company released the dataduring a poster session at the American Psychiatric Association'sconvention. The data has not been published yet in a peer-reviewed journal,so no information on drop out rates or whatever statistical methodology mayhave been used. The expanded use of antipsychotics for depression wouldrepresent a "huge tectonic shift" in treating depression-and a huge influxof profits. AZ hadn't released any efficacy data for Seroquel XR'sperformance versus placebo in treating depression (or Major DepressiveDisorder, as AZ has it). See: Furious Seasonshttp://www.furiousseasons.com/archives/2008/05/astrazeneca_releases_limited_seroquel_data_for_depression.html April 6, 2007: AstraZeneca, 'Bucket of Money' Group of 7 Whistleblowers Allege Off-Label Campaign for cancer drug,Faslodex, "There is a big bucket of money sitting in every office. Everytime you go in, you reach your hand in the bucket and grab a handful. Themore times you are in, the more money goes in your pocket. Every time youmake a call, you are looking to make more money." See:http://www.brandweeknrx.com/2007/04/az_bucket_of_mo_1.html  andhttp://tinyurl.com/5sjuq7 June 21, 2003: AstraZeneca, the large pharmaceutical company, pleaded guiltytoday to a felony charge of health care fraud and agreed to pay $355 millionto settle criminal and civil accusations that it engaged in a nationwidescheme to illegally market a prostate cancer drug. The government said thecompany's employees had given illegal financial inducements to as many as400 doctors across the country to persuade them to prescribe the drug,Zoladex. Those inducements included thousands of free samples of Zoladex,worth hundreds of dollars each, which the physicians then billed to Medicareand other federal health care programs, prosecutors said. The company alsogave doctors financial grants, paid them as consultants and provided freetravel and entertainment, the government said. See: AstraZeneca Pleads Guilty In Cancer Medicine Scheme By MELODY PETERSEN,The New York Timeshttp://query.nytimes.com/gst/fullpage.html?res=9C07E7D8163BF932A15755C0A9659C8B63  Contact: Vera Hassner Sharavveracare212-595-8974http://www.gooznews.com   November 09, 2008 CRP -- The Next Chapter in Medical Waste?The latest study on statins and heart disease, which appeared in the NewEngland Journal of Medicine website yesterday and in all the major papersthis morning, is worth a second look, not because of what it says aboutheart disease, which is mildly interesting at best, but because of what itreveals about profit-driven medical research and how it contributes tomaking the U.S. health care system the most bloated and wasteful in theworld.The randomized clinical trial, code-named Jupiter, involved giving a statindrug or placebo to 17,802 "apparently healthy men and women" (their words)with normal cholesterol but elevated levels of a biomarker for inflammationcalled C-Reactive Protein (CRP). Did it reduce CRP levels, and did thatreduce heart attacks, strokes and, most importantly, sudden death fromcardiovascular disease?The answer to both those questions is yes. But before we go to the data, thefirst thing you need to know about this trial is that its lead investigator,Paul Ridker of Brigham and Women's Hospital in Boston, owns a patent on the$20 test that measures CRP, and the trial was funded by AstraZeneca, whose$3.45-per-day or $1,250-per-year statin (rosuvastatin or Crestor), was usedin the trial. If they can get two million more "apparently healthy men andwomen" on rosuvastatin, it's an additional $2 billion-plus in sales forAstraZeneca. If they can test 10 million people to find the estimated twomillion with elevated CRP levels (they had to screen nearly 90,000 people tofind the 17,800 eligible for the trial), it's $200 million in test sales,which, if the royalty is only 1 percent, amounts to a hefty $2 million ayear in extra income for Dr. Ridker.I don't mention these conflicts of interest to cast doubt on the validity ofthe data presented in the NEJM paper. Rather, it puts me, as it should allanalyzers of this trial, on guard to see if there were any flaws in itsconstruction, biases in its analysis, or slants in its presentation. Theanswer to all three of those questions is yes.First let's take a look at these "apparently" healthy people (men over 50and women over 60). The median body mass index for the group was 28.3, whichmeans more than half were significantly overweight. Indeed, a third werecategorized as obese, which isn't surprising since 41 percent had metabolicsyndrome, a suite of conditions that suggests the person is well down theroad to developing Type II diabetes. This profile raises some disturbing questions about the ethical oversight ofthis trial. Were these trial participants offered counseling about lifestylechanges necessary to avoid developing diabetes, which is recommended forpeople with metabolic syndrome? The methods section suggests they were onlyoffered the right to participate in the trial, which involved taking a drugthat might prevent a heart attack because they had heightened levels of CRP.The data monitoring committee overseeing the trial stepped in to halt itonce it became apparent there would be a statistically significant reductionin cardiovascular events. Where were they when the protocols were beingwritten? Why didn't they step in at the beginning to insist that the at-riskportion of this patient population be offered the best available treatment(diet and exercise counseling) for their condition (metabolic syndrome)?This oversight becomes even more glaring when we look at one of the moredisturbing findings of the trial, noted in an accompanying editorial but"not adjudicated" by the study's endpoint committee. The group onrosuvastatin developed diabetes at a higher rate than the group given aplacebo, 3.0 percent versus 2.4 percent, an increase of six-tenths of apercentage point.Keep the size of that percentage in mind as I now turn to the actualbenefits of giving the statin for elevated CRP. While the overall rate ofcardiovascular incidents fell from 2.8 percent to 1.6 percent by giving thestatin, the number of so-called hard events -- heart attacks and strokes,including those that were fatal -- fell from 1.7 percent in the placebogroup to 0.9 percent in the statin group, a drop of eight-tenths of apercentage point.In other words, for every person who didn't get a serious cardiovascularevent, three-quarters of a person got diabetes.We can look at the benefits another way -- in terms of the number of peoplewho need to be treated to avoid a serious event. In this trial, 120 patientshad to be treated for 1.9 years to prevent one serious cardiac event.Remember what rosuvastatin costs? $1,250 a year. That's $285,000 per eventprevented just for the statin pills. The physician visits, CRP tests and labwork add additional thousands more. Can you imagine how many heart attacksand strokes could be prevented if that money were targeted at people who aretruly at risk of heart disease (the obese, smokers, hypertensives,diabetics) to help them modify their lifestyles and get treatment for theirunderlying conditions?There's one other curious element in the trial data. In table 4, Ridker andhis fellow authors report that the number of "serious adverse events" inboth arms of the trial was almost exactly equal: 15.2 percent in the statinarm versus 15.5 percent in the placebo arm. Presumably, all cardiovascularevents (2.8 percent and 1.6 percent, respectively) were included in thistotal.On the one hand, I'm not surprised that one in seven trial participantssuffered a serious health event during the two years of this trial. Themedian age of this predominantly overweight group was 66, with some as oldas 90.But what were those other serious events? Alas, the study is silent on thispoint. I, for one, would like to have seen that data published since the rawnumber suggests that at the end of the day, both of these groups faredalmost exactly the same. In other words, giving a statin to people withelevated CRP did nothing to improve this population's overall health. So there you have it. A possibly unethical trial with marginal results getstrumpeted in the media as showing "wide benefit" (New York Times). Based onthe laudatory quotes coming from the leaders of the American College ofCardiology, this off-label use of statins will quickly find its way intoclinical practice guidelines and drug compendia. Within a few years, healthcare payers will be forking over billions more dollars to the statin drugmakers in the name of preventing heart disease.Meanwhile, our health care outcomes -- including cardiovascular disease --will still rank somewhere between Romania and Poland. Health care costs willstill be rising at twice the rate of overall inflation. And those truly atrisk of heart disease still won't be getting the counseling that might savetheir lives. FAIR USE NOTICE: This may contain copyrighted (C ) material the use of whichhas not always been specifically authorized by the copyright owner. Suchmaterial is made available for educational purposes, to advanceunderstanding of human rights, democracy, scientific, moral, ethical, andsocial justice issues, etc. It is believed that this constitutes a 'fairuse' of any such copyrighted material as provided for in Title 17 U.S.C.section 107 of the US Copyright Law. This material is distributed withoutprofit.  =====In accordance with Title 17 U.S.C. Section 107, this material is distributed without profit to those who have expressed a prior interest in receiving the included information for research and educational purposes.